PL122152B1 - Process for preparing derivatives of 3-/thiomethyl/ cephalosporinsnov - Google Patents

Description

The subject of the invention is a method for preparing derivatives of 3-(thiomethyl)cephalosporins by substituting the acetoxy group in cephalosporanic acid with a sulfuric nucleophilic compound. Substituting the acetoxy group of cephalosporins with a sulfurous nucleophilic compound is a reaction known from United States Patent No. 3,278,531. the above patent description and other publications, for example J.D. Cocker J. Chem. Soc, 1965, 5015, it is stated that the reaction takes place only in an aqueous medium. Practically, substitution reactions use a salt of cephalosporanic acid in water and a nucleophilic sulfur compound or its salt, at a pH of 5-8. The combination of an aqueous environment, elevated temperature (35-70°C) and an almost neutral to alkaline pH usually has a destructive effect on many cephalosporin rings, and products obtained in this way often require long-term purification. Attempts to carry out the substitution reaction of cephaloacids - sporane in water at a lower pH of 2-3, lead to the formation of significant amounts of 1-actone in a side reaction, which significantly reduces the yield of the given product. It is known from German patent description No. 2344451 and British patent description No. 1368716 that research is carried out the action of replacing the acetoxy group of cephalosporins with a sulfur nucleophilic compound in an organic solvent, in a reaction system containing water. It has now been found that the substitution reaction of the acetoxy group, as well as other 3-acyloxy groups in cephalosporin acids, with a nucleophilic sulfur compound can be very advantageously carried out in organic solvents, but under anhydrous conditions. The reaction under such conditions is not complicated by the formation of lactone, the yields are generally higher, and the product can be isolated more easily. Some products even precipitate spontaneously from the reaction mixture. It is assumed that this process is general in nature and can be applied to practically every sulfur nucleophilic compound and every cephalosporanic acid. The method according to the invention is a new process in which 3-( thiomethyl)cephalosporins of the general formula 1, in which R13 is a group of the formula 2, in which each R4 is designated independently of a hydrogen atom, an alkyl group with 1-4 carbon atoms, an alkenyl group with 2-3 carbon atoms, cyclohexyl or phenyl, or R13 is a group of the formula 3, a group alkyl of 1-4 carbon atoms, a group of formula 4 or a group of formula 5, in which each R3 is independently an alkyl group of 1-4 carbon atoms, alkoxy of 1-4 carbon atoms, halogen, hydroxyl, nitro, cyano, methanesulfones - hydrogen or trifluoromethyl, q is 0, 1 or 2 and R6 is a moiety forming, together with the moiety of formula 14, an optionally substituted five- or six-membered heteroaromatic ring containing a total of 1-4 heteroatoms in the following combinations: 1 atomitrogen and 0 or 1 atom oxygen or sulfur, 2 nitrogen atoms and 1 oxygen or sulfur atom, 3 nitrogen atoms and 0 or 1 atom 122 152122 152 3 oxygen atoms or 4 nitrogen atoms, all remaining atoms in the ring being carbon atoms, or R6 is a moiety that collectively with the group of formula 14 it forms a 2-ben'unridazotillorva, 2-benzothiazolyl, 2-benzoxazolyl radical or a radical of formula 15, R1 is a hydrogen atom or a methoxy group, R2 is a phthalimide, succinimide group, a group of formula 6, in which L is a hydrogen atom or a nitroso group, or R2 is a group with the formula R3 -C(=0)-NH-, in which R3 is a hydrogen atom, an alkyl group with 1-6 carbon atoms, a -CEL-chloroalkyl group with 1 -3 carbon atoms in the alkyl part, -CH2-fluoroalkyl group with 1-3 carbon atoms in the alkyl part, cyanoaflulo group with 1-4 carbon atoms, hydroxyalkyl group with 1-4 carbon atoms, p-nitnobenzyloxy, tertiary .-butoxylpwa^ 2J2^^cVoroethoxy, or R3 stands for 4-keto-4-carboxybutyl group, 3-carboxypropyl group, group of formula 7, in which each a and ar is independently a hydrogen atom, grape alkyl with 1-4 atoms carbon, an alkoxy acid with 1-4 carbon atoms, a halogen atom or a hydroxyl group. -thienyl, 3-thienyl or grape fcnyl of the formula 8, in which a and a1 have the meanings given above, and Q denotes a hydroxyl, formyloxy, acetoxy, carboxyl group of the formula -C(=0)-O-A2, in where A2 is a diphenylmethyl, p-nitrobenzyl, benzyl, 2,2,2-trichlorcetyl, tert-butyl or p-neioxybenzyl group or Q which is a sulfonic acid group or a group of the formula Me-0-SO2- where Me is an alkali metal atom, or Q is an acylamino group with the formula —NH—C(=0)—T, in which T is an amino group, a group with the formula —NH—C(= «NH)—NHi, ^-N =0) -CH=CHR», a group of formula 9, 10, 11 or 12, in which R7 is a hydrogen atom or an alkyl group with 1-3 carbon atoms, R' is a phenyl, halophenyl, furyl, ethyleamine, dimethylamine group - va, ethylamino, diethylamino, methylcetylamine, methylpropylamino, dipropylamine, diisopropylammonium, phenylamino or diphenylammonium, R* means a hydrogen atom, an alkyl group with 1-4 carbon atoms or phenyl group, R means a hydrogen atom, an alkyl group with 1-3 carbon atoms or methylsulfoayl, R11 is an ethylene, trimethyl or vinylene group and p is the number 2 or 3, or R* is a group of the formula 13 or a group of the formula 13 in which the OH group is replaced by the group -OCHi or -O- C(=0)CHi, wherein P* in formula 13 has the meaning given above for P or represents a 2-furyl group; or R3 is a group of the formula V-S(0)-CHa-, in which V is a group of the formula -CFj or of the formula -CHi-X, in which X is a hydrogen atom, a methyl group, a group of the formula —CHa, —CN or ~-Nj group and n is 0,1 or 2, or R3 is a group with the formula Y—CHa—, in which Y is a 2-thieoyl, 3-thienyl, 2-furyl, 2- oxazolyl acid, 2-thiazolyl acid, 1-tetrazolyl acid, 1-benzotfrazolyl acid, 2-oxazolilic acid), 2-thiazolyl acid, 1,2,3-tetrazolyl acid, 5-thio-#lr3,4-triazolyl)-2 -yl, 1,3,4-thiadiazolyl-2-tic-, group 5-methyl-1J394-dadiazoyl-2-thio, 1r2,4-thiadiazoyl-5-thio, 3-methyl-1A4-thiadiazolium-5 -lio, 1,2,5-nadiazolyl-3-thio, 1,3A-oxadiazolyl-2-thio, 5-methyl-1,3,4-oxadiazolyl -2-4-thio, 1-methyl-5-tetrazolyl thio , pyridylthio, 4-cyano-1,2,3-triazolyl-1 or 3-cyano-1,2,4-triazolyl-1. The method according to the invention consists in the fact that the compound of formula 16, in which R1 and R2 have the above-mentioned meanings, and R denotes an alkyl group with 1-3 carbon atoms, a cyclo-alkyl group with 4-6 carbon atoms, an amino group, one- or two (alkyl)amine with 1-3 carbon atoms in the alkyl radical, a group of formula 17, 18 or 19, is reacted in the presence of an organic solvent with a sulfur nucleophilic compound with a rise V&*—S—R14, in which R "has the meaning given above and R" means hydrogen, or in the case where R13 is a methyleneamino group, and only then, R14 together with R13 forms thiourea, and the feature of the process according to the invention is that the reaction is carried out under anhydrous conditions. Products process carried out according to the invention have antibacterial activity, and many of them are intermediates for the production of other cephalosporins also having antibacterial activity, as shown, for example, in United States Patent No. 3,932,393. In the above In specific terms, the term alkyl group denotes various straight-chain and branched-chain alkyl groups. The term substituent* R3, as an alkyl group with 1-* carbon atoms, refers to groups such as methyl, ethyl, propyl, isopropyl, butyl, tertiary-butyl, amyl, isoamyl, hexyl, 2,3-dimethyl * butyl and the like. The term -CH2-chloroalkyl group with 1-3 carbon atoms in the alkyl part and the -CH2-fluoroalkyl group with 1-3 carbon atoms in the alkyl part refers to groups such as chloroethyl, fluoroethyl, 2-chlorocetyl, 2- chloropropyl, 3-fluoropropyl and 4-chlorobutyl. The term cyanoalkyl group having 1-4 carbon atoms means groups such as cyanomethyl, 2-cyanoxymethyl, 3-cyanopropyl and 2-cyanopropyl. The term hydroxyalkyl group having 1-4 carbon atoms means groups such as hydroxymeryl, 2-hydroxyethyl, 3-hydroxypropyl and 2-hydroxypropyl. It is desirable that the amino groups in the 3-(acyloxymethyl-cephalosporinino formula 161, as well as in the sulfur nucleophilic compound) are protected. Methods of protecting the amino groups are known, for example, from "Protective Groupe in Organic Chemistry", publisher J.T.W.McOmie , Pknum Press, London and New York, 1973. In general, the amino protecting group should be removable, but this is not necessary. The term halogen means fluorine, chlorine, methylene, or sodium. 90 The term alkoxy group with 1-4 carbon atoms means a group methoxy, etcoxy, isopropoxy, n-butcksylcyl and pedebne. The term alkali metal atom preferably means at 35. Examples of groups with the formula R3 - C (= 0) - NH - are groups such as: formcmidewa, aoetamidewa, prepicnemidewa, butyranium, «-methylcprcp:onfmidewa, walcramideva, o-methylbutyamideva, trimethylcacctE midcwa, pen-tanccarbenamidew*, htksLnckarbcn*' midcwa, 3-chloroprc- 40 pionamidewa, 3-chlorobuty?amidewa, 4-fluorobutyramide, 5 -chloridesEmldcwa, cyaBcace(amidcwa, 2-cyanoprop:onamidcwa, 3-cypnopropionaimdcwa, 4-cyao- butyramtdwa, hydraxylcetamidcwa, 2-hydroxyhydroxypionamideva, 3-hydroxybuCyramidcwa, p-nh*afr» 45 zylcksykaibcny lc^mincwa, lII- is.-butcksykaibcnyl£«H»122 152 5 new, (2,2,2-trichloroethoxy (carbonylamino, 5- (2,5- dichlorobenzamido) -5- carboxyval eramide, 5- -acetamido -5- carboxyvaleramide, 5 -carbomethoxy- -5- (2,4-dichlorobenzamido)valeramide, 5-carbo-n- -butoxy-5- (2,4-dichlorobenzamido)valeramide, 5- -carboxy -5- (2,4- dichlorobenzamido)valeramide , 5-(p-propionamido-5-carboxyvaleramide, 5-(3-chloropropionamido)-5-carboxyvaleramide, 5-benzamido-5-carboxyvaleramide, 5-keto-5-carbexyvaleramide and 4-carboxybutyramide. PF are examples of groups with the formula R*—C(=0)—NH—, in which R3 is a group with the formula 7, and may represent the number 0 * and groups such as phenylacetamido, 2-(p-methylphenylq)acetamido, 2-(m-ethylphenylAcetamido, 2-( p-iso-propylphenyl)acetamide, 2-(o-methylphenyl)acetamide, 2-(p-chlorophenylAcetamide, 2- (p-bromophenyl)acetamide, 2- (2,4-dichlorophenyl)acetamide, 2- -( m-bromophenyl acetamide, 2- (p-fluorophenyl acetamide, 2- (o-fluorophenyl acetamide, 2- (3,4-di- hydroxyphenyl)acetamide, 2- (p-hydroxyphenyl)acetamide, 2- (m -hydroxyphenyl)acetamide, 2-(2,6-dim5-thoxyphenyl)acetamide, 2-(m-methoxyphenyl)acetamido, 2-(p-isopropoxyphenyl))acetairudium, 2- - (m-ethoxyphenylAcetamido, 2-(p) -metho)cyphenyl)acetamide, 2-(3,4-dimethoxyphenyl)acetamido, 2- - (p-tertbutoxyphenyl)acetamidoval 2- [p- (acetamido-methyl)phenyl]acetamido, 2- [ p-(tert-butoxycarbonylaminommethyl)phenyl]acetamide, 2-[o-(tert-butoxycarbonylaminomethyl)phenyl]acetamide, 2-(m-butoxyphenylAcetamide and 2-(3- chloro-4-methylpheny- (o)acetamide. If in the above mol formula Z is an oxygen atom -O-, an example of such a group is the group phenoxyacetamide, 2-(p-methylfencksyAcetamide, 2-(m-ethyl-fencksyAcetamide, 2 - (p-isopropylphenoxyAcetamide, 2-(o-methylphenoxyAcetamide, 2-(p-chlorophenoxy)acetamide, 2-(p-bromophenoxyAcetamide, 2-(2,4-dichlorophenoxyAcetamide, 2-(m-bromephenoxyAcetamide) , 2- (p-fluorophenoxyAcetamide, 2-(o-fluorophenoxyAcetamide, 2- (2,6-dimethoxyphenoxyAcetamide?., 2- (m-ethoxyphenoxy)acetamide, 2-(p-methoxyphenoxyAcetamide, 2- (3,4 -dimethoxy-phenoxy)acetamide, 2-(p-III-butcksyfencksyAcetamide, 2-(o-butexyfencksyAcetamide, 2- (3-chloro-4-methylphenoxyAcetamide, 2- (3-hydroxy-4-methyl - phenoxyAcetamide, 2-(o-chloricfencksy)acete:midcwa, 2-(3-hydroxy -4-methylphenoxyAcetamide, 2-(o- -chlorophenoxyAcetamide, 2- (p-isopropoxyphenoxy)acetamide, 2-[o- (acetamidomethyl) phenoxy Jacetamide and 2-[p-(III-batoxycarboynlcaminomethyl)phenoxy]acetamide. When in the above formula m=l and Z is the sulfur atom —S—, an example of such groups is the 2-( phenylthioAcetamido, 2-(p-methylphenylthio)acetamido, 2-(m-ethylphenylthioAcetamide, 2-(p--isopropylphenylthioAcetamide, 2-(c-methylphenylthio)acetamido, 2-(p-chlorophenylthio)acetamido, 2- (p- - bromophenylthio)acetamide, 2- (2,4-dichlorophenylthio)acetamide, 2- (m-bromophenylthio)acetamide, 2- (p-fluorophenylthioAcetamide, 2-(o-fluorophenylthio)acetamide, 2- (3,4- dihydroxyphenylthio)acetamide, 2- - (p-hydroxyphenylthioAcetamide, 2- (m-hydroxyphenylthio)acetamide, 2- (2,6-dimethoxyphenylthioAcetamide, 2- (m-ethoxyphenylthioAcetamide, 2- (p-methoxy- 6phenylthioAcetamide) , 2-(3,4-dimethylphenylthioAcetamide, 2-(p-III-butoxyphenylthioAcetamide 2-(m-butoxyphenylthioAcetamide, 2-(3-chloro-4-methyl-phenylthioAcetamide, 2-(3,4- dimethylphenylthioAcetamide, 2-(3,4-dichlorophenylthio)acetamide, 2- - (2,5-dichlorophenylctioAcetamide, 2- (3-fluoro-4- -chlorophenylthioAcetamide, 2- (3-chloro-4-fluorophenes- 1 othioAcetamido, 2-(2,6-difluorophenylthioAcetamido, 2-(m-fluorophenylthioAcetamido, 2-[o-(acetamido-methyl)phenylthio[acetamido and 2-[p-(tert-butoxy-carbonylamincmethyl) phenylctic]acetamide. In the case where R3 is a group with the formula P— —CH(Q)—, an example of a group with the formula R3 —C(—0)— —NH— is the mandelamide group (phenylhydroxyacetamide), its derivative 0 -formyl and O-acetyl, 2-carboxy-2-phenylacetamide group, 2-sulfo-2-phenylacetamido group, protected 2-amino-2-phenyl acetamide, in which the protected amino group is, for example, carbonylamino group, tertiary .-butoxycarbonylamino, tricetoxycarbenylcamino or p-nitrobenzyloxycarbonylamino and 2-acylamino-2-phenylacetamido group. These groups also include 2-thienyl acetamide and 3-thienyl acetamide groups substituted in the 2-position, i.e. the above groups in which the phenyl group is replaced by a 2-thienyl or 3-thienyl group. ; An example of the above acetamide groups is mandeiamide(2-hydroxy-2-phenylacetamido), 2-hydroxy-2-(p-methylphenyl)acetamido, 2-hydroxy-2-(p-hydroxyphenylAcetamido, 2-hydroxy-2(m - -hydrolcyphenylAcetamide, 2-hydroxy-2- (p-methoxy-phenylAcetamide, 2-hydroxy-2- (m-bromophenyl)acetamide, 2-hydroxy-2-(p-chlorophenylAcetamide, 2- -hydrokay -2- (3-mctyl-4-fluorophenyl)acetamide, 35 2-hydroxy-2-(o-fluorophenyl)acetamide, 2-hydroxy- -2-(p-fluorophenyl)acetamide, 2-hydroxy-2- (p-isopro- pylphenylAcetamide, 2-0-formyl-2-(3,4-dimethyl-phenylAcetamide, 2-0-formyl-2- (p-chlorophenyl)acetamide, 2-0-formyl-2- (m-isopropoxyphenyl)acetamide - 40 dow, 2-0-formyl-2-(m-bromophenylacetamide, 2-0-formyl-2-phenylacetamide, 2-0-formyl-2-(3,4-di-methoxyphenyl)acetamide, 2-0 -acetyl-2-phenylacetamide, 2-0-acetyl-2-(p-hydroxyphenylAcetamido, 2-hydroxy -2- [(p-acetamidomethyl)phenyl [acetamido, 45 2,-0-formyl-2- (p - hydroxyphenyl)acetamide, 2-hydroxy-2-(thienyl-2)acetamide, 2-hydroxy-2-(thienyl-3-acetamide, 2-formyloxy-2-(thienyl ^acetamide), 2-acetoxy-2 -(thienyl-2Acetamide, 2-formyloxy-2-(thienIo-3)acetamide, 2-acetoxy-2-(thienyl-3Acetaamide, 2-(tert-butoxycarbonyl)-2-phenylacetamide , 2- (2t2,2-trichloroethoxycarbonyl)-2-(p-methyl-phenylAcetamide, 2- (benzyloxycarbonyl)-2- (p-hyoroxyphenylAcetamide, 2-(tert-butcksycarbonyl)-2- - ( p-hydroxyphenylAcetamido, 2-(p-nitrobenzyloxy--55carbonyl)-2-(m-hydroxyphenylAcetamido, 2-(p-methoxybenzyloxycarbonyl)-2-(p-methexyphenyl)acetamido, 2-(diphenylmethoxycarbcnyl)-2-( m-bromophenylAcetamide, 2-(tert-butoxycarbonyl)- -2-(p-chlorophenylAcetamide, 2-(2,2,2-trichlore-60 toxicocarbonyl)-2-(3-methyl-4-fluorophenyl) acetamide, 2- (benzyloxycarbonyl)-2- (o-fluorophenylAcetaamide, 2- (p-nitrobenzyloxycarbonyl)-2-(p-fluorophenylAcetamide, 2- (p~methoxybenzyloxycarbonyl)-2- - (p- isopropylphenylAcetamido, 2- (tert-butoxycarbonyl)-2- (3,4-dimethylphenyl)acetamido, 2-122 152 7 - (tert-butoxycarbonyl)-2- (m-isopropoxyphenyl)ace - tamide, 2-(diphenylmethoxycarbonyl)-2-(3,4-di-methoxyphenyl)acetamido, 2-(tert-butoxycarbonyl))-2-[ p-(2,5-dichlorobenzamidomethyl)phenyl] acetamide, 2- (m-butoxycarbonyl)-2-(thienyl-2)acetamide, 2- (IU-butoxycarbonyl)-2- (thienyl-3)acetamide, 2- (sodooxysulfonyl)-2-phenylacetamide, 2-(sodooxysulfonyl)-2- (p-methylphenyl)acetamide, 2-(potassiumoxysulfonyl)-2- (p-hydroxyphenyl)acetamide, 2-(lithoxysulfónyl)-2- (m -hydroxyphenyl)acetamide, 2-(sodooxysulfonyl) 2- (p- methoxyphenyl)acetamide, 2-(sodooxysulfonyl) -2- (m- bromophenyl)acetamide, 2- (sodooxysulfonyl)-2- (p -chlorophenyl)acetamido, 2-(sodooxysulfonyl)-2-(3-methyl-4-fluorophenyl)acetamido, 2-sodooxysulfonyl)-2-(o-fluorc-phenyl)acetamido, 2-(sodooxysulfonyl)-2- (p-fluorophenes! o)acetamido, 2-(sodooxysulfonyl)-2-(p-acetamidomethylphenyl)acetamido, 2-(sodooxysuTfcnylc)-2-(p-isopropylphenyl)acetamido, 2-(sodicoxysulfonyl)-2-{3,4 - dimethylphenylp)acetamide, 2-(sodooxysulfonyl)-2- (m- isopropoxyphenyl)acetainide, 2- (-sodooxysulfonyl)-2- (3,4- dimethoxyphenyl)acetamide, 2-(sodooxysulfonyl)-2- (thienyl-2)acetamide, 2-(potassiumoxysulfonyl -2- (thienyl]o-3)acetamide, 2-(p-nitrobenzyloxycarbonylamino)-2-phenylacetamide, 2-(tert-butoxycarboxycarbonylamino) -2- - (thienyIo-2)acetamido, 2- (benzyloxycarbonylamino)- -2-(m-hydroxyphenyl)acetamido, 2-CH-i.e. -butoxy-carbonylamino)-2- (p-hydroxyphenyl)acetamido, 2- -ureido - 2- phenylacetamide, 2-ureido -2-(thienyl- -2)acetamide, 2-(3-amidino-1-ureido) -2- phenylacetamide, 2-(3-methylaminocarbonyl -1-ureido) -2- phenylacetamide, 2-(3-dimethylaminocarbonyl-3-methyl-1-ureido)-2-phenylacetamide, 2-[N-(imidazolidinone -2-yl-1-carbonyl)amino]-2-phenylacetamide, 2- [N-(3-methylimidazolidinone -2- yl -2-carbc-nyl)amino] -2-phenylacetamide, 2- [N-(hexahydro- pyrimidinone -2- yl -1- carbonyl)amino [-2- phenylacetamide, 2-[N-(3-methylhexahydropyrimidinon-2- -yl -1- carbonyl)amino [ -2- phenylacetamide, 2- [N- (3- methanesulfonyl hexahydropyrimidinon- -2-yl -1- carbonyl)amino [-2- phenylacetamide, 2-(3-di-n-propylaminocarbonyl-1-ureido)-2- phenylacetamide, 2- [(4-ethyl -2,3- diketopiperazinyl-1)carbonylamino [- 2-phenylacetamide, 2- [(3-methylsulfonyl- -2-ketoimidazolidinyl -1)carbonylammo]-2-phenylacetamide, 2- [(2-keto -4-imidazolinyl-l)carbonylcamino] - 2 - phenylacetamide, 2 - [(4-keto 4H - thiopyranyl - 3) carbonylamino[-2- phenylacetamido, 2-(3-methyl-3- - (methylcarbonyl)ureido)-2- phenylacetamido, 2-(3-methyl -3- ( cynamoyloureido)) -2- phenylacetamido, 2-(3-methyl -3- (acryloyloureido)) -2-phenylacetamido, 2-[(4- ethyl -2,3- diketopiperazinyl- l)carbonylami- [ -2-thienylacetamido, 2- [(4-ethyl-2,3- diketopiperazinyl -l)carbonylamino [ -2- (p-hydroxyphenylacetamido, 2- [(4-ethyl -2,3-dicetopiperazinyl-l)carbonylamino [ -2-phenylacetamide, 2- [(2-ketoimidazole-lidinyl-1 (carbonylammo]-3- thienylacetamide and 2- - [(2-keto -3- (methylsulfonyl)-4- imidazolinyl -l)carbonylamino [ - 2-(p-hydroxyphenyl)acetamido. An example of groups with the formula R3—C(=0)—NH—, in which R3 is a group with formula 13, is the 2-(hydroxyimino)-2-phenylacetamide group, 2- (methoxyimino)-2-phenylacetamide, 2-(acetoxyimino)-2-phenylacetamide, 2- (hydroxyimino)-2-(thienyl-2)acetamide, 2-(hydroxyimino)-2- (furyl 2- )acetamide, 2-(methoxyimino)-2-(thienyl-3)acetamide, 2-(methoxyimino)^-(furyl-2)acetamide, 2-(methoxyimino)-2-(p-hydroxy-phenyl) acetamido, 2-(hydroxyimino)-2-[2-(2,2,2 - 5 tricMorc*toxycarbonyioainino)-4-thiazolyl]-acetamido (tautomeric with group 2-(hydroxyimino)-2-[ 2-(2, 2,2-trichloroethoxycarbonylimino)-4-thiazolinyl-4[acetamide), 2-(methoxyimino)-2-[2-(p-nitrobenzyloxycarbonylamino)-4-thiazolyl]acetamide (tautomeryl 2-(methoxyimino)-2- [2-(p-nitrobenzyloxy-carbonylimino)-4-thiazolinyl-4]acetamido) and 2* -(methoxyimino)-2- (4- chlorophenyl)acetamido. Examples of groups with the formula R3— G(=0)—NH—, in which R* is a group of the formula V—S(0)n—CH2— is a 2-(trifluoromethylthio)acetamido group, 2-(methylsulfonyl)acetamido, 2- (cyanomethylthio)acetamidovar 2-(azidomethylthio)acetamide, 2-(ethylsulfonyl)acetamide, 2-(2,2,2-trifluoroethylthio)aceUmidcwa, 2-(methylosulfinyl)acetamide and 2-(cyanomethylsulph^ 20 )acetamide. An example of a group of the formula R3—C (=0)—NH-, in which R* is a group of the formula Y—CH2— is the group 2-(thienyl-2)acetamide, 2-(thienyl-3)acetamide , 2-(furyl-2)acetamide, 2-(oxazolyl-2)acetamide, 2-(tJazc- & lilo-2)acetamide, 2-(tetrazolyl-1)acetamide, 2- - (benzotriazolyl-1) acetamidcwa, 2- (cksazoli! o-2-thio)acetamide, 2-(thiazolyl-2-thio)acetamide, 2-(1,2,3- -triazolyl -5-thio)acetamido, 2-(1,3,4 - triazolyl -2- -thio)acetamide, (1,3,4-thiadiazolyl -2-thio)acetamide, 30 2-(5-protected amino-1,3,4-thiadiazolyl -2-thio)acetamide, 2-(5- methyl-1,3,4-thiadiazolyl-2-thio)acetamide, 2-(1,2,4-thiadiazolyl-5-thio)acetamide, 2-(3-methyl-1,2,4-thiadiazolyl-5 - thio)acetamide, 2-(1,2,5 -thiadiazolyl -3-thio)acetamide, 2-(1,3,4 - oxadiazolyl -2-thio)acetamide, 2-(5-methyl- 1 ,3,4-oxadiazolium-2-thioacetamide, 2-(l-methyltetrazolyl-5-thio)acelamide, 2-(pyridylthio)acetamide, 2-(4-cyano-l,2,3-triazolylc--l )acetamide, 2-(3-cyano-l,2,4-triazolyl-l)acetamide and 2-(2-protected amino-4-thiazolyl)acetamide 40 tautomeric with 2-(2-imino-4-thiazolinyl -4)acetamide. Many of the cephalosporanic acids used as starting compounds in the process of the invention are known compounds and all are obtained by known methods, attention should be paid to "Cephalosporins and Penicillins, Chemistry and Biology", publisher Edwin H. Flynn, Academic Press, New York, 1972, especially chapters 3, 4 and 15 and the references cited therein, as well as United States Patent No. 3,914,157 and South Africa Patent No. 71/3229. 50 Favorable, sulfur nucleophilic compounds are those compounds of the formula R13—S—R14, in which R13 is a group of formula 5. The appropriate five-membered heteroaromatic rings of formula 5 include pyrrole, oxazole, isoxazole, thiazole, isofazole, pyrazole, imidazole, 1,2,3-cksadiazole, 1,2,4- -okradiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, 1,2,3-thiadiazole, 1,2,4-thiadiazole , 1,2,5-thiadiazcl, 1,3,4-thiadiazole, 1,2,3-triazole, 1,2,4-triazole, oxatriazolitetrazcl. The corresponding six-membered rings include 60 pyridine, pyridazine, pyrimidine, pyrazine, 1 ,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3,4-tetrazine, and 1,2,4,5-tetrazine. Some of the heteroarylthiols, alkylthiols and phenylthiols of the formula R»—S—R14, exist in the form of thions or tautomeric mixtures of thiols and tics. An example is 122 152 9 2-methyl-1,3,4-thiadiazolothiol-5 occurring in the form of tautomers with formulas 20 and 21. The reaction carried out according to the invention takes place with the mentioned groups of sulfur nucleophilic compounds, regardless of whether they occur in the following way: taci thiols cythions. Thus, within the scope of the invention is a process carried out using thiolones or thiol-thion tautomes of the specified compounds. Heteroarylthiols may be unsubstituted or substituted with one or more substituents. Generally, the type of substituent is not essential. For best results, the primary or secondary amine group should be protected. If the heteroaryl thiol contains more than one thiol group, the one that does not react should be protected. Methods for protecting thiols are known from the above-cited McOmie publication. If these groups are protected, the reaction proceeds regardless of the type of substituent. It is preferable to avoid excessively large substituents. Generally, preferred are those substituents whose molecular weight is not more than about 500. Most substituted heteroaromatic rings contain substituents with a total molecular weight of less than about 250. Suitable substituents include an alkyl group with 1-4 carbon atoms, an alkenyl group with 2-4 carbon atoms, an alkynyl group with 2-4 carbon atoms, a cycloalkyl group with 5-6 carbon atoms, a benzyl group, a phenylethyl group, an aryl group, such such as phenyl, a specified previously substituted phenyl group, a halogen atom, a —CFj, = 0, —OH group, a protected amino or alkylamino group with 1 to 4 carbon atoms, a —COOH, —COOA2, —CONH2 group, a protected aminomethyl or alkylamino-methyl with 1-4 carbon atoms in the alkyl part, group —CH2SO3 — alkali metal atom, group — —CH2C OOH, —CH2COOA* or —(CH2)2N (CHj)2. Examples of sulfur nucleophilic compounds with the formula R13 -S-R14 are thioureas such as allylthiourea, N,N'-di-n-butylthiourea, N,N'-di-tert-butylthiourea, N,N'-dicyclohexylthiourea, N,Nl-diisopropylthiourea, N^-dimethylthiourea, N-methylthiourea, N,N,N',N'-tetraethylthiourea, N,N,N',N'-tetramethylthiourea, thiourea, N-phenylthiourea, N, N'-diphenylthiourea and N,N-dimethylthiourea. Sulfur nucleophilic compounds also include thiobenzoic acid and alkynethiols such as motanethiol, ethanethiol, propanethiol-1 or -2, butanethiol-1 or -2 and 2-methylpropanoticl-1. Representative bonzenethiols with the above formula are bsazenethiol, 4-b:omo -3-methylbenzenethiol, p-bromobenzenethiol, p-chlorobenzenethiol, 2,5-dichlorobenzenethiol, 2,4-dichlorobenzenethiol, 4-fluorobenzenethiol, m-mstoxybenzenethiol, p-methoxybenzenethiol, p-nitrobenzenethiol and p- methylbenzenethiol. Further examples of sulfur nucleophiles are heteroarylthiols such as pyrrolothiol-2, pyrrolothiol-3, 2-methylpyrazolothiol-3, 2-methylimidazolothiol-4, imidazolothiol-2, oxazolethiol-4, isoxazolethiol-3, thiazole thiol-2, isothiazolothiol-3, 1-methyl-1,2,3-triazolothiol-5, 1-benzyl-1,2,3-triazolothiol-4, 2-methyl-1,2,3-triazolothiol-4 3,5-Dimethyl-1,2,3-triazolothiol-4, 1,2,4-triazolothiol-3, 4-methyl-1,2,4-triazolothiol-5, 3-methyl-1,2,4 -triazolothiol-5, 3,4-dimethyl-1,2,4-triazolothiol-5, 2-m3tyl-1,2,4-triazolothiol-5, 2-benzyl-1,2,4-triazolothiol-5 , 2,3-dimethyl-101,2,4-triazolothiol-5, 4-methyl-3-(trifluoromethyl)-1,2,4-triazolothioI-5, 3-carbamyl-4-methyl-1,2 ,4-Triazolothiol-5, 3-(carboxymethyl) 4-methyl 1,2,3-triazolothiol-5, 3- -(carboethoxymethyl) -4- methylIo-1,2,4-triazolothiol-5r 3- 5 -amino -4- methylIo-1,2,4-triazolothiol-5 with protected amino group, 3-hydroxy-4- methyl - 1,2,4-triazolothiol-5, 5-methyl - 1,2,3- oxadiazolothiol-4 , 1,2,4-oxadioazolo-thiol-3, 3-methyl-1,2,4-oxad.azolothiol-5, 3-methyl-l,2,5-oxad azolothiol-4, 2-methyl- 1,3,4-oxadiazolothiol-5, 3-10 methyl-1,2,4-thiadiazolothiol-5, 1,3,4-thiadiazole ol-5, 2-methyl-1,3,4-thiadiazolothiol-5 , 2- (N-methylacetamido)- -l,3,4-thiadiazoleTol-5, terrazolothiol-5, 1-methyltetrazolothiol-5, 1-benzyltetra:olot'ol-5, l-(carboxymethyl)tetrazolothiol -5, 1-[(sodooxysulfonyl)methyl[tetrazolothiol-5, 1-15-(2-dim5tylaminoethyl)tetrazolothiol-5, 1,2,3,4-oxatria-zolothiol-5, pyridinethiol-2, pyridinethiol-1-oxide -2, pyridinethiol-3, pyrimtdinethiol-2, pyrazinethiol-2, 1,2,3-triazinethiol-4, 1,2,4-triazinethiol-3, 4,5-dihydrogen-6- -hydr*oxy- 4-methyl-5-keto-1,2,4-triazonthiol-3, 1,3,5-triazinethiol-2, 1,2,4,5-tetrazinethiol,-3, benzimidazolothiol-2, benzothiazolothiol- 2, benzoxazolethiol-2 and tetrazolo(1,5-b)pyridazinthioI-6. Most of the sulfur nucleophilic compounds used in the process of the invention are known compounds, and all of them can be obtained by known methods. In the case of hetoroaryltiols, noteworthy are the numerous volumes of "Heterocycic Gompounds", publisher Robert C. Elderfield, John Wiley and Sons, Inc., N.Y. and various volumes dealing with particular heterocyclic systems, in the series "The Chcmistry of Heterocyclic Compounds", publisher Weissberger and co-workers, John Wiley and Sons, N.Y. An essential condition in the process of the invention is that the reaction is carried out in an organic solvent. 35 nym. However, the type of solvent is not of primary importance because large amounts of organic solvents have given satisfactory results. Generally, the following groups of solvents have been found to be suitable: aliphatic and aromatic hydrocarbons, alcohols, amides, ethers, ketones, carboxylic acids, carboxylic acid esters, halogenated hydrocarbons, nitro compounds, nitriles and thioethers. Since some nucleophiles are liquids, excess such a reagent can serve as a solvent. The solvent should be inert, in the sense that it cannot react with any of the reagents. Particular solvents suitable for carrying out the reaction include pentane, cyclopentane, and hexane. , heptane, octane, benzene, toluene, o-, m- or p-xylene, cumene, mecylene, p-cymer, pentene-1, diethyl ether, 50 butyl ethyl ether, diamyl ether, benzyl ethyl ether, acetone, methyl ethyl ketone , butanone-2, pentanone-3, methyl isobutyl ketone, cyclohexanone, acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, methyl acetate, ethyl acetate, 55 propyl acetate, isopropyl acetate, ethyl propionate, butyl acetate, isobutyl acetate, acetate Second-butyl, amyl acetate, isoamyl acetate, ethyl isovalerate, methyl benzoate, benzyl acetate, methyl butyrate, diethyl carbonate, dimethyl maleate, diethyl oxalate, ethylene glycol diacetate, diethyl malonate, fluorobenzene, chlorobenzene, bromobenzene, o-, m- or p-fluorotoluene, o-, m- or p-chlorotoluene, o-, m- or p-bromotoluene, 2-chloroethane, 1- or 2-chloropropane, 1- or 2-chlorobutane, l- chloro-2-methylpropane, 1,2- or 65 3-chloropentane, 1-chloronaphthalene, methylene chloride, chloroform, carbon tetrachloride, 1,1-dichloroethane, 1,2-dichloroethane, 1,1 ,1-trichloroethane, 1,1,2-trichloroethane, 1,1,2,2-tetrachloroethane, o-, m- or p-dichlorobenzene, nitromethane, nitroethane, 1- or 2-nitropropane, nitro-benzene, acetonitrile, propionitrile, butyronitrile, isobutyronitrile, valeronitrile, benzonitrile and phenylacetonitrile. Preferred solvents are hydrocarbons such as benzene, toluene, o-, m- or p-xylene, cumeri and mesitylene. Preferred solvents also include halogenated hydrocarbons such as chloroethane, 1- or 2- chloropropane, 1- or 2-chlorobutane, isobutyl chloride, 1-, 2- or 3- chloropentane, methylene chloride, chloroform, 1,2-dichloroethane, carbon tetrachloride, 1,1,1-trichloroethane, 1,1, 2-trichloroethane, l,ljl,2,2-tetrachloroethane, fluorobenzene, chlorobenzene, bromobenzene, o-, m- or p-fluorotoluene, O", m- or p-chlorotoluene, o-, m- or p-bromotoluene, o-, m- or p-dichlorobenzene. Also preferred solvents are acids such as oetic acid, propionic acid, butyric acid, isobutyric acid and valeric acid. Preferred ester solvents include methyl acetate, ethylene glycol diacetate, ethyl acetate , propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, tert-butyl acetate, peryl acetate, ethyl propionate, methyl butyrate, n-butyl mfformate, propylene carbonate and ethylene carbonate. Preferred solvents are furthermore, nitro compounds such as nitrobenzene, nitromethane, nitroethane and nitropropane, nitriles such as acetonitrile, propionitrile, butylnithyl, isobutyronitrile, valeronitrile, benzonitrile and phenylacetonitrile, as well as ketones such as methyl ethyl ketone and methyl isobutyl ketone. A particularly preferred solvent is acetonitrile , 1 ,2-dichloroethane, methylene chloride, propionitrile, nhrbmethane, nitroethane, acetic acid, isopropyl acetate, butyl acetate and methyl isobutyl ketone. The 3-(acyloxymethyl)cephalcsporins of the general formula 16 used are designated as acids. It is assumed that the reaction takes place in an acid because cephalosporin salts are generally insoluble in organic solvents. The exception is the solubility of cephalosporin salts in carboxylic acids such as acetic acid. The reaction can therefore be carried out by dissolving a 3-(acyloxymethyl)cephalosporin salt, such as an alkali metal salt, in a carboxylic acid. Regardless of the type of solvent, it is necessary to carry out the process under substantially anhydrous conditions. The reaction mixture should generally contain less than 5% water, preferably less than 1 µ water, and it is more preferred that the amount of water is less than 0.5%. If the commercial starting materials and solvents are not sufficiently anhydrous, the water may be removed by known methods such as azeotropic distillation and by the use of drying agents such as alumina, silica gel, anhydrous calcium sulfate and the like. The reaction proceeds over a wide range of temperatures. Generally, the reaction takes place over a wide range of temperatures. it is carried out at temperatures of 50-140°C, but better results are usually achieved at temperatures of 70-120°C. The reaction can be carried out at increased pressure, but no benefits are observed. Therefore, atmospheric pressure is usually preferably used for reasons of process simplification. The amounts of reactants are not critical. In general, an excess of sulfur nucleophilic compound of 1.0-5.0 molar equivalents of this compound per 12 molar equivalent of 3-(acyloxymethyl)cephalosporin is preferred. The method according to the invention is used in particular to introduce the following heteroarylthio groups into the 3-position of the cephalosporin: 5- methyl-1,3,4-thiadiazolyl-2-thio, 5 1-methyl-1H-tetrazolyl-5-thio, 1-carboxymethyl-1H-tetrazolyl-5-thio, 4-methyl-6-hydroxy-5- keto-1,2,4-triazyl-3-thio, 1-methyl-1,3,4-triazolyl-2-thio, 2-methyl-1,3,4-triazolyl-5-thio, 1 ,2-dimethyl-1,3,4-triazolyl-5-thio, 3-methyl-1,3,4-triazolyl-5-thio, 2,3-dimethyl-10-1,3,4-triazolyl- 5-thio, 1-methyl-2-trifluoromethyl-1,3,4-triazoyl-5-thio, 1-methyl-2-carbonamido-1,3,4-triazol! o~ -5-thio, 1-methyl-2-carboxymethyl-1,3,4-triazoles! o-5-thio, 1-methyl-2-carboalkoxy-1,3,4-triazolyl-5-thio, 1-methyl-2-(protected aminomethyl)-1,3,4-triazolyl-5-tfo, 1- 15 methyl-2-(protected amino)- 1,3,4-triazolyl-5-thio, 1-methyl-2-hydroxy-1,3,4-triazolIo-5-thio, 1H-tetrazolyl- - 5-thio, 1- (2-dimethylaininoethyl)-1H-tetrazolyl*5-thio, 1-(sulfomethyl)-1H-tetrazolyl-5-thio, its alkali metal salt, 5-methyllc-1,3,4- oxadiazolyl-2-thio, 1,3,4-20-thiadiazolyl-2-thio, 3-methyl-1,2,4-thiad:azolyl-5-thio and 2- - (protected aminomethyl)-1,3, 4-thiadiazolyl-5-thio. Important known cephalosporins of formula 1 that can be prepared by the synthesis according to the invention include cefamandole of formula 22,formylcefaman-25 and celazafluT of formula 26, SCE-963 of formula 27, BLS- 786 Formula 28, CS-1170 Formula 29, SQ-67590 Formula 30, SKF-75073 Formula 31, BBS-226 Formula 32 and SQ-14359 Formula 33. Products of the process of the invention, deblocked thereof derivatives and pharmacologically acceptable salts are used to combat infections in warm-blooded mammals, when administered parenterally in a non-toxic dose of 10-500 mg/kg body weight. Preparations containing the active compounds are prepared in a known manner. The examples given illustrate the method according to the invention. Example I. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)-thiomethyl]-7-[2-(thienyl- 2 (acetamido] - 40 cephemo-3-carboxyl-4 in acetonitrile. To 25 ml of lacetonitrile placed in a flask equipped with a condenser with a tube containing as a drying agent anhydrous calcium sulphate sold under the brand name Drierite, 2.2 g ( 5.5 mmol) 7-[2-(thienyl-2)acetamido[-cephalosporanic acid and 1.0 g (8.6 mmol) 1-methyl-1H-tetrazolothiol-5. The whole is stirred and heated in boiling point, monitoring the course of the reaction by thin-layer chromatography. After 90 minutes of heating, the chromatography shows the presence of about 2/3 of the starting cephalsporanic acid and 1/3 of the desired product. After three hours, the chromatography shows the presence of about 1 /3 of the starting cephalsporanic acid and 2/3 of the product. After 6 hours, according to the chromatographic results, the reaction is practically complete and then the mixture is cooled to room temperature and left overnight. The solvent is evaporated on a rotary evaporator and the remaining foam is dissolved in 10 ml of ethanol. After adding 1 ml of a solution of dicyclohexyl-60 amine in 10 ml of ethanol dropwise, a precipitate of the dicyclohexyl-ammonium salt of the product falls out, which is filtered off after stirring for 15 minutes. The product was washed with 15 ml of ethanol and dried under reduced pressure at 40°C for 2 hours. 2.50 g (76.1%} of product 65 with a melting point of 183-184°C (with decomposition) are obtained. 122 152 13 CSF and IR spectra and thin layer chromatography give results identical to those for the original sample of the product obtained by the previous method by substitution in an aqueous medium . CSF spectrum (DMSO-cUM: 3.52(mA2—CHO. 3.76(s,2,CH2CONH—), 3.92 (s,3, —CHi in tetrazole), 4.35 (s, 2, 3—CH2S), 5.00 (d, 1, Q—Hf J=5Hz), 5.55)q, 1, Ci—H, J=5Hz, J=»9Hz), 6.95(d, 2 , 3 and 4-^1 from thiophene, J=3Hz), 7.35 (t, 1.5—H from thiophene, J-3Hz) and 8.75 (d, 1,—CH2CONH—, J=9Hz) Example 2. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-[2-(thienyl-2-acetamido]-cefemo-3-carboxylic acid-4 in acetonitrile. 4.0 g (10 millimoles) of 7-[2-(uenyl-2)acetamido]-cephalosporanic acid and 5.8 g (50 millimoles) of 1-methyl-1H-tetrazolothiol-5 heated at reflux in 50 ml of anhydrous acetonitrile (stored above the resin containing the anhydrous acid sulfonic acid, sold under the brand name Amberlit 15), carrying out the reaction in an anhydrous atmosphere for 8 and 3/4 hours. Inspection by thin layer chromatography shows that the reaction is almost complete after 8 and 3/4 hours. The solvent is evaporated and the residue is added to 125 ml of chlorine. After administering a solution of 6 ml of dicyclohexylamine in 75 ml of water, the product is precipitated in the form of a bicyclohexylamine salt, washed and dried, 4.50 g of product are obtained; yield: 71.0%. IR and PMR spectra as well as thin-layer chromatography show that the product is identical 2 authentic samples of the product obtained by the substitution method in an aqueous medium. The CSF spectrum is the same as for product X, example I. Example III. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)methyl]-7-[2-(thienyl-2)acetamido]cefemo-3-carboxylic acid in 1,2-dichloroethane. 2.0 g (5 mmol) 7-[2-(thienyl-2)acetamido] - -cephalosporanic acid and 1.2 g (10 mmol) 1-methyl-1H-tetrazolothiol-5 in 25 ml 1.2 -dichloroethane, heated at reflux in an anhydrous atmosphere for 5.5 hours. The solvent is removed using a rotary evaporator and a solution of 2 ml of dicyclohexylamine in 25 ml of ethanol is added dropwise to the residue dissolved in 25 ml of ethanol. The product crystallizes in the form of a dicyclohexyl ammonium salt. The mixture is stirred for 20 minutes at room temperature, then filtered, the precipitate is washed with 25 ml of ethanol and dried at 40°C under reduced pressure. 2.34 g (73.8%) of a cream-colored precipitate are obtained. IR and CSF spectra are the same as for the sample obtained by substitution in an aqueous medium. The CMR spectrum is the same as for the product from Example I. Example IV. Preparation of 3-[1-methyl-1H-tetrazolyl-5)thiomethyl]-7-aminocefemo-3-carboxylic acid in 1,2-dichloroethane. 3.0 g (10 mmol) of 7-formamidocephalosporanic acid and 2.4 g (20 mmol) of 1-methyl-1H-tetrazolothiol-5 are stirred and heated for 7 hours at reflux temperature in 50 ml of 1.2 -dichloroethane. The mixture is cooled to room temperature and left at this temperature overnight. A red gummy precipitate forms. The 7-formyl group is removed from the product as follows. The solvent is evaporated using a rotary evaporator and the residue is dissolved in 25 ml of methanol and 2.8 ml of concentrated hydrochloric acid and left overnight at room temperature. The solution is diluted to 50 ml with water and the pH, initially 0.9, is raised to 3.6 by adding triethylamine dropwise. The obtained light-yellow crystals are filtered off, washed with water and dried. 2.10 g (64%) of product are obtained. 5 The CMR spectrum is identical to the product obtained by substitution in an aqueous medium. CSF spectrum (D20, NaHC03) <5:3.65 (q, 2.2—CH2, Jab=16.5Hz), 4.08) (s, 3, —CH3 in tetrazole), 4.16 (q, 2, 3—CH2S—, Jab=12.5Hz), 5.05 (d, 1, C«—H, J=5Hz) and 5.45 (d, 1, 10 Ci—H,J=5Hz). Example V. Preparation of 3-acid [(1-methylIo-1H-tetraiohlo-5)thiomethyl]-7-[2-(thienyl-2)acetamido]-ce-femo-3-kaiboxyl-4 in isopropyl acetate. 2.0 g (5 mmol) 7-[2-(thienyl-2)acetarnido]-cephalosporanic acid and 1.2 g (10 mmol) 1-methyl-1H-tetrazolothioIu-5 are boiled in 25 ml isopropyl acetate, while stirring for 23 hours. The reaction mixture is cooled to room temperature. Thin layer chromatography shows that some of the starting cephalosporanic acid remains. The light cream precipitate is filtered off, washed with isopropyl acetate and dried. 1.60 g (70.8%) of the product are obtained. The CSF spectrum confirms the identity of the product and the yield of 1% of the starting cephalosphomotto acid* FMR spectrum (DMSO-d*)*: 3.72(s) , 2, 2— ~CHaX 3*0(* 2, -^OLCONH-), 3.99& 3* -CH, from tetrazole), 4.30 2.3^Clk—S~), 5.10 (d , 1, C«—H, J-5Hz), 5.70(q, 1, Cr-«, J«5Hz, J=8Hz), 6.92(d, 2, 30 3— i 4-^H from thiophene, J«3Hz), 735 (t, 1, 5—H from thiophene, J ~3Hz) and 8.78 (d, 1, —CHiCONH—,J-8Hz). Example VI. Preparation of 3-[(1-methyl*1H-t3trazolyl-5)uomethyl]-7-[2-(thienyl-2(aortamido]*cefemo-3-carboxylic acid-4 in propionitrile. 35 2.0 g (5 mmol) acid 7-[2-(thienyl-2)acetamidol-cephalosporan acid and 1.2 g (10 mmol) of 1-methyl-1H-tetrazolothiol-5 in 25 ml of anhydrous propionitrile are heated at reflux temperature (97 °C ), until the complete disappearance of the starting cephalosporanic acid is determined by thin layer chromatography, which takes 4.5 hours. The reaction mixture is cooled to room temperature and the solvent is evaporated using a rotary cake (some of the product is lost in the process). due to entrainment of the solution). The residue is dissolved in 35 ml of warm ethanol and a solution of 2 ml of dicyclohexylamine in 10 ml of ethanol is added. A precipitate of the dicyclohexylammonium salt is formed. The whole is stirred for 10 minutes at room temperature, filtered, and the precipitate is washed with ethanol. and dried. 1.24 g (39.0%) of product are obtained, with no product lost in the rotary evaporator. The CMR spectrum is identical to the product from Example I. Example VII. Preparation of 3-[1-methyl-1H-tetrazolyl-5)thiomethyl]-7-[2-(thienyl-2)acetamido]-cefemo-3-carboxylic acid 4 in acetonitrile with the addition of 3,5-dichlorophenyl dihydrogenphosphate. 2.0 g (5 millimoles) 7-[2-(thienyl-2)acetamido]-cephalosporanic acid, 0.87 & (7.5 millimoles) 1-methyl-1H-tetrazolothiol-5 and 3.5 dihydrogen phosphate -dichlorophenyl (0.122 g 0.5 mmol), heated overnight (0 in 25 ml of anhydrous acetonitrile, at a temperature of about 70°C. The solvent is evaporated in a rotary evaporator to a volume of about 8-10 ml, and then crystallize the product. The whole mixture is stirred for half an hour and then 25 ml of isorno-propyl acetate are added dropwise within half an hour, which causes further crystallization. After half an hour of additional stirring, the precipitate is filtered off, washed with isopropyl acetate and dried. 0.98 g (43.4%) of the product are obtained, the CMR spectrum of which is identical to the spectrum of the product from Example V. P r 2, Example VIII. Preparation of 3-[(1H-tetrazolyl-5)thiómethyl]-7-[2 -(thienyl-2)acetamido]-cephem-3*carboxylic acid-4 in acetic acid. To 25 ml of glacial acetic acid, 2.0 g (5 millimoles) of 7-[2-(thienyl-2)acetamido]-cephalosporic acid are added ranic acid and 0.87 g (7.5 mmol) 1-methyl-1H-tetrazolethiol-5. The mixture is heated to 60°C and left at this temperature for one hour. Thin layer chromatography determines the presence of only product deposits. The reaction mixture is heated for 5 hours at 80°C, then left overnight and the product is filtered off, washed with acetic acid and dried. 0.71 g (31%) of the product are obtained, the CMR spectrum of which is identical to the spectrum of the product from Example V. Example IX. Preparation of 3-[(4,5-dihydro-c% hydroxy-4-methyl-5-keto-1,2,4-triazinyl-3)thiomethyl]-7-[2-(thienyl-2)acetamido acid ]-cefemo-3-carboxylic acid- in acetonitrile. To 25 ml of anhydrous acetonitrile, placed in a reaction flask immersed in an oil bath at a temperature of S4-85 °C, 2.0 g (5 mmol) of 7-acid are added [2-(thienyl -2)acetamido]-cephalosporan acid and 1.2 g (7.5 mmol) 4,5-dihydro-6-hydroxy-4-methyl-5-keto-1,2,4-triazinethiol-3 . The flask is equipped with a condenser with a tube containing anhydrous calcium sulfate as a drying agent, sold under the brand name Drierit. The whole is mixed gently with a magnetic stirrer for 16 hours, under the above-mentioned conditions. The product crystallizes from the hot solution. The mixture is cooled to room temperature, filtered, the precipitate is washed with acetate and acetone and dried under reduced pressure. 1.81 g (72.6%) of the product are obtained in the form of whitish crystals with a melting point of 161°C (with decomposition). After being held, the second portion of crystals falls out of the filtrate. After filtration, washing with acetonitrile and drying, 0.26 g (10.5%) of the product are obtained, also with a melting point of 161°C (with decomposition). The total yield is therefore 83.1%. Example 3-carboxylic acid-4 in 1,2-dichloroethane. Mixture of 2.0 g (6 mmol) 7- [2- (thienyl-2) acetamido [-cephalosporanic acid and 0.87 g (7.5 mmol) 5 -methyl-1,3,4-octadiazole 2 in 25 ml of 1,2-dioroethane is placed in a flask equipped with a magnetic stirrer and a condenser with a tube containing anhydrous calcium sulfate, sold under the brand name Drierit, as a drying agent. The flask is immersed for 8 hours in an oil bath at a temperature of 84-85°C and cooled within two days. Part of the product crystallized and was filtered off, washed with 1,2-dichloroethane and dried, obtaining 1.10 g (48.7%) of the product. The product is dissolved in 15 ml of water and filtered to remove insoluble parts. Then 75 ml of demineralized water were added dropwise and the precipitated product was filtered off and dried. 0.61 g of product with a melting point above 114°C (with decomposition) is obtained. After evaporating the filtrate, 0.23 g of a mixture of the product and both starting compounds is obtained. 16 Example XI. Preparation of 3-[(1-methyl-1H-tetrazolium-5)thiomethyl]-7-[2-(thienyl-2(acetamido]-cephemo-3-carboxylic acid-4 in nitromethane. To 25 ml of anhydrous nitromethane 2 are added .0 g of 5 (5 mmol) 7-[2-(thienyl-2)acetamido]-cephalosporanic acid and 0.87 g (7.5 mmol) of 1-methyl-1H-tetrazolethiol-5. Immerse the flask for a period of 4.5 hours in an oil bath at a temperature of 100-101 ° C, and then cooled to room temperature. Thin-layer chromatography shows that the reaction is complete. The solvent is evaporated in a rotary evaporator and the residue is dissolved in 75 ml warm ethyl acetate. The solution is filtered to remove a small amount of undissolved parts, and then extracted with two portions of 25 ml of a 5% aqueous solution of sodium bicarbonate. 50 ml of ethyl acetate are added to the combined extracts and acidified to a pH of approximately 1.0 70 % aqueous solution of methanesulfonic acid. The acetate layer is separated and the aqueous layer is extracted with 25 ethyl acetate. The combined acetate layers are dried over anhydrous sodium sulfate and concentrated to 25 ml using a rotary evaporator. After adding 50 ml of diethyl ether dropwise, the product crystallizes, which is filtered off, washed with diethyl ether and dried. 1.27 g (56.2%) of a creamy crystalline product with a melting point of 156-159 °C (decomposition) are obtained. Identity of the product is confirmed using PMR.Example XII. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethylJ-7-[2-(thienyl^2)acetamide]-30 cephemo-3-carboxylic acid-4 in methylene chloride. Mixture 11.9 g (30 millimoles) of 7-[2-2-(thienyl-2)acetamido]-cephalosporanic acid and 7.0 g (60 millimoles of 1-methyl-1H-tetrazolothiol-5 in 300 ml of cyclohexane-stabilized methylene chloride are placed in an acid-resistant autoclave with a capacity of 1 liter, equipped with a heater. The whole is stirred and heated at a temperature of 83-86°C for 16 hours, under a pressure of approximately 2.952-102 kPa. Then the mixture is cooled to room temperature. Thin-layer chromatography 40 shows conversion to the product with only traces of the starting cephalosporanic acid. The mixture is allowed to crystallize at room temperature. After concentrating to a volume of approximately 200 ml, the precipitate is filtered off and washed with methylene chloride. 7.37 g (54.3%) of white are obtained. - 45 of a crystalline precipitate with a melting point of 163.5-164°C (with decomposition). The filtrate is diluted with 100 ml of ethyl ether, the precipitate is filtered off, washed with ethyl ether and dried. A second portion of 1.40 g (10.3%) of the product is obtained in the form of light yellow crystals. 50 Third portions of 1.18 g (8.7%) are obtained after diluting the filtrate with isopropyl acetate. The total yield is therefore 73.3%. Example XIII. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethylc]-7-[2-(thienyl-2(acetamido]-55 cephemo-3-carboxylic acid-4 in fluorobenzene. Mixture 2.0 g (5 .04 mmol) 7-[2-(thienyl-2)acetamido]cephalosporant acid and 1.2 g (10 mmol) 1-methyl-1H-tetrazolothiol-5 in 75 ml of fluorobenzene (boiling point 85.1 °C), is stirred in a flask equipped with a condenser with a tube containing as a drying agent anhydrous calcium sulfate, sold under the brand name Drierite. The whole is heated to boiling point and the course of the reaction is monitored by thin-layer chromatography, using the ethyl acetate-acetic acid system 65 7:1. The mixture remains heterogeneous and the reaction is practically completed after 72 hours. The reaction mixture is cooled to room temperature, then the precipitated product is filtered off, washed with fluorobenzene and dried at 40°C, under under reduced pressure, within five hours. 2.13 g (93.4%) of the product are obtained in the form of cream crystals with a melting point of 161-162°C (with decomposition). The identity of the product is confirmed by CSF. Example XIV. Preparation of 3-[(1-m3tyl-1H-tetrazolyl-5)thiomethio]-7-[2-(thienyl-2)icetamido]-10-cefemo-3-carboxylic acid-4 in thiophene. Mixture 2.0 g (5 millimoles) ) of 7-[2-(thienyl-2)acetamido]-cephalosporanic acid and 0.87 g (7.5 mmol) of 1-methyl-1H-tetrazolothiol-5 are boiled in 25 ml of thiophene for 7 hours. During this time, the product crystallizes. The reaction mixture is cooled to room temperature, stirred for 30 minutes to complete crystallization, then the precipitate is filtered off, washed with 0.5 ml of thiophene and dried under reduced pressure for 2 hours. 1.82 g (80.2%) of the product are obtained in the form of 20 white crystals with a melting point of 162-163 °C (with decomposition). Thin layer chromatography shows the presence of an additional amount of product in the filtrate. Example 15. Preparation of 3-[(5-methyl-1,3,4-thiadiazc4yl-2)thiomethyl]-7-[1H-ietrazoiyl-1)acetamido]-cephcmo-3-carboxylic acid-4in acetonitrile. Mixture 0, 76 g (2 mOimole) of 7-[2-(1H-*etrazolyl)acetamido[-cephalosporanic acid and 0.33 g (2.5 mOimole) 5-mstyle-1,3,4-thiadiazolothiol-2 are heated at boiling point in 10 ml of pure acetonitrile for 30 two hours and forty minutes. The product crystallizes during this time. The reaction mixture is cooled in an ice bath and the product is filtered off, washed with 3 ml of acetonitrile and dried under reduced pressure at 40°C. 0.61 g (67%) of product is obtained, the identity of which is confirmed by PMR. PMRc spectrum: 2.68 (s, 3, -CH3 from tetrazole), 3.72 (s, 2, 2 -CH2) , 4.40 (q, 2, 3—CH2S—, Jab= 13 Hz), 5.12(d, 1, C6—H, J=5Hz), 5.38(s, 2, — CH2CONH—), 5.72(q, 1, C7—H,J=5Hz,J=9Hz), 9.00(s,l,5—H from thiophene) 40 4 9.17 (d, 1, —CH2CONH—). Example XVI. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-(2-formyloxy-2-phenyl-acetamido)-cefemo-3-carboxylic acid-4 in 1,2-dichloroethane. 45 To 25 ml of 1,2-dichloroethane are added 2.17 g (5 mmol) of 7-(2-formyloxy-2r-phenylacetamido)-cephalosporanic acid and 0.87 g (7.5 mmol) of 1-methyl- 1H-tetrazole-thiol-5. The whole was heated at reflux temperature for six hours, and samples were taken on a thin-50 layer chromatograph at 3 and 6 hours. The mixture is heated additionally for one hour and left to cool overnight. The solvent is evaporated and diethyl ether is added to the residue, forming a rubbery precipitate that solidifies. After filtration, washing with diethyl ether and drying, 1.90 g (77.0%) of the product are obtained. CSF spectrum (DMSO-d6) <$: 3.52(s, 2.2—CH2) 3.88 (s, 3, —CH3 from tetrazolium), 4.10(s,2.3—CH2S—), 4.92(d, 1 , C6—H), 5.62(q, 1, C7—H, J=5Hz, J=9Hz), 6.06(s,l, eo —CHCONH—), 7.26(s, 5, protons phenyl) and 8.28 (s, 1, -OC( =0)H). Example XVII. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-[5-carboxy-5-(2,5-dichlorobenzamido)-valeramido]-cefemo-3-carboxy-4 in acetonitrile (A) and 1,2-dichloroethane {B).A) A mixture of 2.9 g (5 mmol) of 7-[5-carboxy-5- (2,4-dichlorobenzamido)valeramido]-cephalosporanic acid and 1.2 g (10 mmol) 1-methylIo-1H-tetrazolothioIu-5 in 50 ml of acetonitrile, heated at reflux overnight (about 18 hours). Thin layer chromatography shows that the reaction is approximately 90% complete. The reaction mixture is evaporated and the residue is suspended in ethyl acetate and filtered to obtain 1.51 g (48.3%) of the product. B) A mixture of 2.9 g (5 mmol) of 7-[5-(carboxy-5-) (2,4-dichlorobenzamido)valeramido]-cephalosporan acid and 1.2 g (100 moles) of 1-methyl-1H-tetrazolothiol-5 in 50 ml of 1,2-dichloroethane are heated at reflux temperature for five and a half hours. Chromatography thin layer shows that the reaction is approximately 90%. The solvent is decanted and the remaining plastic precipitate is triturated in boiling ether and 2.83 g (89.3%) of the product is filtered off in the form of a dark yellow crystalline precipitate. CSF spectrum (DMSO-d65:1 .78i2.26(dvam,adipoyl side chain), 3.66(m, 2.2—CH2), 3.95/s, 3,—CHi from tetrazole), 4.30(m,2.3 —CH2S—), 5.08(d, 1, O—H, J=5Hz), 5.68(q,l,C7—H,J=5Hz), 7.50 and 7.62(two, 2 ,4-dichlorophenyl) and 9.00(m,2, two groups -CONH-).Example 18. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-[acid 2-(thienyl-2(acetamido)-phenK^-3-kboxyl-4w^dichlorothanation. Mixture A99 g (2.5 mmol) 7-[2-(thienyl-2)acetamido]- oephalosporaic 2-methyl-1H-tetrazolethiol-5 in 12.5 ml of 1,2-dichloroethane is heated to boiling point, removing the acetic acid formed as a by-product by passing the returning 1,2-dichloroethane through calcium oxide. After 5 3/4 hours of heating, the reaction mixture is cooled to room temperature and filters. The floccular precipitate in the form of needles was washed with 10 ml of 1,2-dichloroethane and dried, obtaining 0.77 g (68.1%) of the product. After evaporating the filtrate, an additional 0.04 g (3.5%) of the product is obtained. The identity of the product is confirmed by thin-layer chromatography and, in the case of the main product, by CSF analysis. The CSF spectrum is identical to the spectrum of the product from Example V. Example XIX. Preparation of 3-[(-5-methyl-1,3,4-thiadiazolyl)thiomethyl]-7-[2-(thienyl-2)acetamido]-cefemo-3-carboxylic acid-4 in acetonitrile. Mixture 2.0 g (5 mmol) 7-[2-(thienyl-2)acetamido]-cephalosporanic acid and 2.64 g (20 mmol) 5-methyl-1,3,4-thiadiazolothioIu-2 in 25 ml of acetonitrile - heats at a temperature of 79 ° C during the night. Thin layer chromatography shows only traces of the starting cephalosporanic acid. The reaction mixture is filtered to remove the oily residue and the solvent is evaporated on a rotary evaporator. The residue is crystallized from a 1:1 mixture of acetonitrile and isopropyl acetate, the precipitate is filtered off, washed and dried under reduced pressure. 1.59 g (33.9%) of product with a melting point of 166 °C are obtained. The identity of the product is confirmed by IR, UV, mass spectrum and elemental analysis. PMR ((DMSO- de)S: 2.68 (s, 3,—CH3 from tetrazole), 3.68 (s, 2.2—CH2), 3.76(s, 2, —CH2CONH—), 4 .38 (q, 2, 3—CH2S), J = =13Hz),5.10(d, 1, C6—H, J=5Hz), 5.70(q, 1, C7—H, J=5Hz , J=9Hz), 6.92(d, 2.3— and 4—H from thiophene), 7.37 (t, 1.5—H from thiophene) and 9.10(d, lt—CH2CONH-. , J=9Hz).122 152 19 Example XX. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-[2-(thienyl-2)acetamido]-cefemo-3-carboxylic acid-4 in 1,1,2-trichloroethane. Mixture 2 .0 g (5 millimoles of 7-[2-(thienyl-2)acetamido[-cephalosporanic acid and 1.2 g (10 millimoles) 1-methyl-1H-tetrazolothiol5 in 25 ml of 1,1,2-trichloroethane are heated in temperature of 100-101°C. The course of the reaction is monitored by thin-layer chromatography. After stirring at a temperature of 100-101°C for 4 hours, thin-layer chromatography shows no presence of the starting cephalosporanic acid. The whole is stirred and cooled to room temperature. The reaction mixture is seeded with a sieve and stirred overnight, during which time the product crystallizes. The solvent is evaporated and 25 ml of 1,2-dichloroethane are added. The product is filtered off, washed and dried under reduced pressure. 0.98 g is obtained ( 43.4%) 3-[(1-methyl-1H-tetrazolIo-5)thiomethyl]-7-[2-(thienyl-2)acetamido]-ce-femo-3-carboxylic acid-4 with a melting point of 158° C (with decomposition). Example XXI. Preparation of 3-[(1-methyl-1H-tetrazoiflo~5)thiomethyl]-7-[2~(thienyl-2)acetamido]-cefemo-3-carboxylic acid (A) and 1,1,2-trichloroethene (B.A) A mixture of 2.0 g (5 millimoles) of 7-[2-(thienyl-2)acetamphdo}-ocylsporanic acid and 1.2 g (10 millimoles) of 1-methyl-1H~ tetrazolothiol-5 in 25 ml of methyl ethyl ketone is heated at reflux temperature for 48 hours. Thin layer chromatography shows only traces of the starting cephalosporanic acid. The reaction mixture is washed with a solution of 2.5 g of sodium bicarbonate in 50 ml of water. 1 g of carbon and 50 ml of ethyl acetate are added to the aqueous layer, then the pH is lowered to 1.6 by adding 4 ml of methanesulfonic acid in 30 ml of water. The acetate layer is dried over sodium sulfate and the oily residue is evaporated on a rotary evaporator. The product crystallizes after adding 50 ml of ether. The product is filtered off, washed and dried under reduced pressure. 0.94 g (41.6%) of the product is obtained with a CMR spectrum identical to that of the product from Example V.B) The procedure is repeated using the same amounts of starting compounds as in point (A), but using 50 ml as a solvent, 1, 1,2-trichloroethylene. The reaction mixture is heated at reflux for 16 hours. Thin layer chromatography shows the disappearance of the starting cephalosporanic acid. The product is isolated as described in part (A). 0.47 g (20.8%) of a product with a CSF spectrum identical to that of the product from Example V are obtained. Example XXII. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-[2-phenylacetamido)-7-methoxy-cefemo-3-carboxylic acid in 1,2-diorcethane. Mixture 210 mg (0.5 mmol) 7-(2-phenyl-acetamido)-7-methoxycephalosporanic acid and 87 mg (0.75 mmol) 1-methyl-1H-tetrazoIothiol-5 in 15 ml of 1,2-dichloroethane, stirred is mixed and heated at reflux under nitrogen for 6 hours. Thin layer chromatography shows only traces of the starting cephalosporanic acid. An additional 29 mg (0.25 millimole) of 1-methyl-1H-tetrazolophiol-5 are added and the mixture is heated at reflux for a further three hours. Thin-layer chromatography shows no appreciable changes. The reaction mixture is washed four times with a saturated sodium bicarbonate solution. The carbonate layer is washed three times with ethyl acetate, then a fresh portion of ethyl acetate is added, cooled to 0°C, the pH is adjusted to 2.2.5 by adding 20% HCl. The separated and aqueous layers are washed with ethyl acetate. The combined acetate layers were washed with a saturated NaCl solution, dried over magnesium sulfate, filtered and evaporated. 199 mg (83.6%) of a light green foamy precipitate are obtained, the identity of which is confirmed by CSF spectrum and thin-layer chromatography. CSF spectrum (CDCb+ Id acetone-dtf5: 3.45(s, 3,— -OCHs), 3.55(s , 2, 2—CH2), 3.75 (s, 2, CoHsCHzCO—), 3.9(s,3,CH3ztetrazolium), 4.4(s,2, 3—CH2S—), 5.15(s , 1, C6—H), 7.35(s, 5, C6H5—), 8.0(8, 1, —CH2CONH—) in and about 11.2(s,l,J«OHz,—COOH). Example XXIII Preparation of 3-[(2-benzothiazolyl)thiomethyl]-7-[2-(thienIo-2)aoethamido]-cephem-3-carboxylic acid-4 in 1,2-dichloroethane. 1.0 g (2.5 mmol) of 7-[2-(thienyl-2)acetamido]-20 cephalosporanic acid and 0.625 g (3.75 mmol) of 2-mercapto-benzothiazole are placed in a flask, the air is removed with a stream of nitrogen, 25 ml are added 1,2-dichloroethane and the entire month and heated at reflux for 24 hours. The mixture is cooled and filtered to obtain 1.1 g. as (88%) of a creamy product with a melting point of 190.5-191 °C. Product it is dried overnight under reduced pressure at 40°C and analyzed. The identity of the product is confirmed by spectrum analysis. are CSF, DV, IR and mass spectra and elemental analysis. CSF spectrum (DMSO-d«V: 3.74(s, 2.2—CH2), 3.80(s, 2, —CH2COKH—), 4.58( q, 2.3—CH2S—, J=13Hz), 5.14(d, 1.0-H, J=5Hz), 5.73(q, 1, C7—H, J«5Hz J—8Hz) , 6.96, 7.43 and 7.96 (three m, phenyl ring 85 and thienyl), 9.10 (d, 1, —CH2COKH—, J=8Hz). Example XXIV. Preparation of acid u 3-[( N-methylacetamido)-1,3,4-thiadiazcl;lc-2)t'cmethyl]-7-[2-(thieny!o-2)acetamidc]-cefemo-3-carboxylic acid -4 in 1 ,2-dichloroethane. 41 A mixture of 2.0 g (5 mmol) 7-[2-(thienyl-2(a-cetamido)-cephalcspranic acid and 1.42 g (7.5 mmol) 5-(N-methylacelamidc^-1^^thiadiazoloticl ^ in 50 ml of 1,2-dichloroethane, heated at reflux temperature for 10 hours. The reaction mixture is cooled, filtered, the precipitate is washed with 1,2-dichloroethane and the product is dried under reduced pressure. 2.06 g ( 78.3)% of the product with a melting point of 178^179 CC. The identity of the product is confirmed by IR, TJV, CSF and mass spectrum analysis as well as 50 elemental analysis. CSF spectrum (DMSO-dtf5: 2.42(s, 3, —COCHa), 3.74(m,7.2—CH2,—CH3 from tetrazole and CH2CONH—), 4.35(q,2.3—CH2, J=13Hz), 5.10(d, 1, C«—H, J=5Hz), 5.70(q, 1, Ct—H, J-5Hz, J=9Hz), 6.96 and 7.36(two m,3,H from thiophene) and 9,10(d,l, -CH2 65 CONH-,J=9Hz).Example 25. Preparation of 3-[(1-methyl-1H-tetrazoyl-5)tphomethyl]-7-(N-tertium) acid .-butoxycarboxyl-1-2-phenylglycylamido)-cephemo-3-carboxylic acid-4 in 1,2-dichloroethane. So 45 ml of 1,2-dichloroethylene are heated at boiling point to remove the azeotreptive mixture with water, and then distill the solvent to a volume of 30 ml and cool it. 253 mg (0.5 mmol) of 7-(N-tert-butoxycarboxyl-2-phenylglycylmide)cephalic acid are added and the mixture is distilled and piped to a volume of 122 122 15 ml and cooled again. 87 mg (0.75 milliliters* mol) of 1-ntyl 1H-tetrasolothiol-5 are added and the mixture is heated at reflux temperature under nitrogen, monitoring the course of the reaction using thin layer chromatography. After 16 hours, chromatography shows only 5 traces of the starting compound. The reaction mixture is washed four times with a saturated sodium bicarbonate solution, the carbonate layers are combined and washed twice with ethyl acetate. A new portion of ethyl acetate is added to the washed carbonate solution, cooled to 0*C and the pH is adjusted to 2.4 by adding 20% HCl. The layer was blown out and the aqueous layer was washed with ethyl acetate. The acetate layers were poured off, washed with a saturated NaCl solution, dried over magnesium sulfate, filtered and evaporated. 224 mg (80%) of a white foam product are obtained, the identity of which is confirmed by IPMR thin-layer chromatography. CSF analysis shows the presence of a small amount (^ 0.10%) of the starting cephalosporanic acid. 20 The product is suspended in 10 ml of ethyl ether and ground for 1 hour. The ether is decanted, 10 ml of diethyl ether are added and the mixture is ground for another hour. The ether is decanted and evaporated to dryness to give the product as a white powder. ¦#.- & The identity of the product is confirmed by thin-layer chromatography and CSF. CSF spectrum (CDQ,M: 140(i»^ —COO-m-row. -C*H»), 3.6 (s, 2.2—CHa), 3.95 (s3, CHi from tetrazole)* 4.3(s, 2.3—CILS—), 4.9(d, 1, J-6H* Q—H), 5.4(d, 1, J-8H* C6H3CH—), 5.75 (q, 1, J- 30 -4Hz, Cr-H), 6.2(d, 1, J*=8Hz, OHsCH)—NH)—), 7.4 (s,5,C6Hs—), 7 .65(d,l,J=*8Hz,CONH) and about *.3(s,l,COOH). Example XXVI. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)t omethyl]-7- [N- (III-butoxycarbonyl)-2-(p- hyd:oc$yfeayl)glycylamido] - cefemo-3-carboxyl-4 in 1,2-dichloroethane. 45 ml of 1,2-dishlorootate are heated at reflux using an asotropic solution and 15 ml of the solvent are removed. After 30 ml, 30 ml are cooled, 260.5 mg of 40 (0.5 millimohm) 7-[N-(tert-butoxycarbonyl)-2-(p-hydroxy)glycylamido]-cephalosporan acid are added , distills the solvent to a volume of 15 ml and cools it again, then adds 87 mg (0.75 mmol) of 1-methyl-1H-tetrazobtiol-5 and heats it at a temperature of 65-70°C, monitoring the course of the reaction by means of thin-layer chromatography . After 3 hours, the initial compound has completely disappeared by chromatography. After 4 hours, the mixture is processed and the product is purified in practically the same way as in the previous 50 examples. 189 mg (65.5%) of the crude product and 46 mg (approximately 16%) of the purified product are obtained. CSF spectrum (CDCb+2d acetone-d6) <5: 1.45 (s, 9,—COO—III-C4H9), 3.35 (s, 2, 2—CH2), 3.85 (s, CH3 from tetrazolium), 4.3 (p. 2.3~CH2S—) 4.9(d, 1, J=*6Hz, 55 C6—H), 5.3 (q, 1, J=3Hz, Ci—H), 5.4( s, 1, HO— —CeHsCH—), 5.75 (d, 1, J=6Hz, HO—CaHsCH— —(—NH)—), 6.4(s, 1, COOH), 6.8( d,2, J=8Hz, group of formula 34) and 7.9 (d, 1, —CONH—). Example XXVII. Preparation of 3-[(1-&methyl-1H-tetrazolyl-5)thiomethyl]-7-(2-phenoxyacetamido)-cefemo-3-carboxylic acid-4 in 1,2-dichloroethany. 60 ml of 1,2-dichloroethane are heated to reflux using an azeotrope and 15 ml of solvent are removed. The remaining 45 ml are cooled, 5,406 ml (1 mmol) of 7-(2-phenoxyacetamido)HX-phalosporaic acid are added, the solvent is distilled to 30 ml and cooled again* and then 174 mg (1.5 mmol) of l-methyl are added -1H-tetrazolothiol-5 and heat the whole at reflux temperature under nitrogen for 12 hours. Thin layer chromatography, when developed with a mixture of 10 parts of ethyl ether and 3 parts of a 3:1 mixture of acetic acid and water, shows the presence of the product, an excess of thiol, a small amount of the starting cephalosporanic acid and an unknown compound. The reaction mixture is worked up in practically the same manner as described in the two previous examples. Chromatography of the final product shows that it is identical to the product obtained in a previously known manner. CSF spectrum (CDCb)*: 3.65 (s, 2 , 2—CHz), 3,*(s,3 CH3 from tetrazole), 4.35 (s, 2.3—CH2S—), 4.65 (s, 2, C*H,CH2—), 5, 1 (d, 1, J-4H*, C6^H), 5.9(q, 1, J - 4Hz C7—H), 7.l(m,5,C6Hs—), 7.6(d, 1, J=*10Hz, —CONH—) and approximately 9(s, 1, —COOH). Examples XXVIII—XXXI. Preparation* of 3-[(l-methyl-jlH- tetrazolyl -5)thiomethylJ-7*{2-(thienylT 2)Lcetamido]-cefemo-3* carboxylic acid-4 in fluorobenzone* Acid - 3Kl(l*iftsib -1H-t«tra3KliJo-5)toinetylJ' 1* K-a)acetamideQ1-cifemo-3-carboxylic acid-4 is prepared in four different reactions in which different cephalosporasic acids are used; ' XXVIII — 41 mg (0.1 mmol) 3-(propionyl- okymethyl (-7- [2-{thienyto-2)acetamido] -ccfemo-3-carbiD- oxytic acid-4, XXIX — 42 mg (0, 1 millimole) of 3-(2-methylpropionylpoxymethyl)-7* [2-(thienyl-2)acetamido]-cephemo-3-carboxylic acid"4, XXX —42 mg (0.1 millimole) of 3-(n-butyryloxymethyl) acid - methyl)-7-[2*(uenyl-2)acetamido]-cephem-3-carboxylic acid-, XXXI -43 mg (0.1 mmol) 3*(cyclobutyiocarbonyloxymethyl)-7- [2- In each case, the compound is suspended in 10 ml of fluorobenzene (dried over an aluminosilicate drying agent, sold under the name 4-A Linde molecular sieves). Nistepae is added in each case 18 mg (0.15 mmol) of 1-methyl-1H-teUazolothiol-5 and the reaction mixture is heated at reflux for approximately 24 hours. The precipitated product is filtered off and dried. Thin-layer chromatography in a mixture of ethyl acetate and acetic acid shows in each case the substitution is quantitative. The CSF spectra of each product are identical to the spectrum of the sample obtained by substitution in an aqueous medium. Example XXXII. Preparation of 3-[(3-methyl- Lo -1,2,4-oxad4azolyl-5)thiomethyl]-7-[2-(thienyl-2)acetamido]-cefemo-3-carboxylic acid-4 in 1.1, 2-tri-chloroethane. 396 mg (1 mmol) of 7-[2-(thienyl-2)acetamido]-cephalosporanic acid are suspended in 40 ml of 1,1,2-trichloroethane and 116 mg (1 mmol) of 3-methyl-1,2 are added ,4-oxa-diazolothiol-5. The reaction mixture is heated for approximately 3 hours at 113°C in an oil bath, then allowed to cool overnight and evaporated to the oil. To this residue are added ethyl acetate and a saturated sodium hydrogen carbonate solution. The acetate extract is washed with a sodium hydrogen carbonate solution. The carbonate layers are combined and washed with ethyl acetate. The aqueous layer is covered with a new portion of ethyl acetate, cooled in an ice bath and the pH is adjusted to 2.5 with the addition of 20% HCl. The layers are separated and extracted again. The acetate solution is washed, mixed with a saturated sodium chloride solution, dried over magnesium sulfate, filtered and evaporated. 1,1,2-trichloroethane is added to the residue and the product solidifies. 220 mg (48%) are obtained. The identity of the product is confirmed by CMR, IR and UV spectra and a bioautogram. CSF spectrum (DMSO- ót)5l 2.35(s, 3, CHr from oxadiazole), 3.7(q, 2, J=18Hz, 2—CHiK 3.8fe,2,—dfeCONH—), 4.4 (q, 2, J=14Hz, 3—CH2S—), 5.l(d,l,J=5Hz,Ctf—H), 5.6(q, 1, J=4Hz, Ct—Hft 69.7 .3(t,d, 39 Hz thiophene), 9.1 (d* 1, J-8Hz, -CHAGONH-).Example XXXIII. Preparation of 3-[(1H- 1,3,4-triazotilo -5)thiomethyl] -7- [2-(thienyl-2)acetairiido] ¦ cefemo -3- carboxylic acid-4 in 1,1,2-trichloroethane. 396 mg <1 mlimole) of 7-[2-(thienyIo-2)acetarnido]-cephalosporanic acid is suspended in 30 ml of 1,1,2-trichloroethane and 100 mg (approximately 1 millimole) of 1H-1A4-triazol-thiol-5 is added . The mixture is heated to 105°C. After 30 minutes, the product precipitates. The whole thing is heated at a temperature of about 100°C for about 6 hours and then cooled to room temperature; The product is filtered off and washed with 1,1,2-trichloroethane. Efficiency 388 m#M (87%). *¦ The identity of the product is confirmed by IR, CSF, UV and bioautogram. The autobiogram also indicates • the presence of the initial cephalosporanic acid, the amount of which according to high-pressure pressure chromatography is 6.8%. CSF spectrum (DMSO-KfcJS: 3, 7 (s,2, 2^CHi), S,8(«,2,—CHiCONH—), 4.2 (q, 2, J=5Hz, 3^GH2^S—), 5.l(d, l, J~5Hz, Ctf—H), 5.7(q, 1, J=4Hz,C7—H), 7.0( and 7.4(t,d,3,H from thiophene), 8, 45 (s,3, NHztriazole)i9,13(d,1, J=8Hz,— —CHiCONH—).Example 34. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl acid] - 7-(2-phenylacetamido)cephemo-3-cyrboxylic acid-4 in chloroform. 195 mg • (0.5 mmol) of 7-(2-phenylacetamido)-cephalosporanic acid are suspended in 75 ml of chloroform and 75 mg (0, 65 mmol) of 1-methyl-1H-tetrazolethiol-5. The reaction mixture is heated in a water bath at 0-85°C for 3 hours and 60 ml of the solvent are distilled off. Thin-layer chromatography shows the presence of very little quantity of product. 20 ml of 1,2-dichloroethane are added and heating is continued overnight. Chromatography shows the presence of a small amount of starting cephalosporin. After a total of 26 hours, the reaction mixture is cooled to room temperature. The product is processed as described in Example XXXII and 80 mg of purified compound (35%) are obtained. The identity of the product is confirmed by IR, UV and bioautogram, CSF (DMSO-d). <5: 3.6(s,2,2—CH2), 3.7(s, 2,—CH2CONH—), 4.0(s,3,CH3 from tetrazolium), 4.3(s, 2, 3-CH2S—), 5.1 (d, 1, J=5Hz, C6—H), 5.7(q, 1, J=4Hz,C7—H), 7.3(s,5,C« H5—) and 9.13(s, 1, J=8KHz, —CH2CONH-. Example 35. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl}-7-acetamidocefemo-3- acid carboxylic acid-4 in 1,2-dichloroethane. 24,314 mg (1 mmol) of 7-acetamidocephalosporanic acid and 98 mg (0.65 mmol) of 1-methyl-1H-tetrazolethiol-5 are mixed in 70 ml 1, 2-dichloroethane and then distilled off 50 ml of the solvent, then heated and refluxed for about 24 hours. The reaction mixture is processed as described in Example XXXII, obtaining 120 mg (32%) of the product, the identity of which is confirmed by CMR spectra analysis, IR, UV and bioautogram. CSF (DMSO-d65: 1.97 (s, 3, in CHsCONH—), 3.7 (s, 2—CH2), 4.0 (s,3, CHsconH—)* 4.35 (s, 2.3—CH2S—), 5.1 (d, 1, J-5Hz, O—H), 5.7(0^ 1, J=4Hz, C7—H) and 8.8(d , 1, J=8Hz, -CH2CONH-).Example XXXVI Preparation of 3-[(3-methyl-1,2,4-thiadiazolyl-5)thiomethyl[-7-[2-thienyl-2) acid acetami- 15 to]-cephemo-3-carboxylic acid-4 in 1,1-dichlorcetane. Mixture of 200 mg (0.5 mmol) 7-[2-(thienyló-2)acetamido]-cephalosporanic acid and 85 mg (0, 65 mmol) 3-methyl-1,2,4-tiad:azolothiol-5 in 50 ml of 1,2-dichloroethane, heated at 95°C in an oil bath. 10 The temperature of the bath is then maintained at approximately 90°C for approximately 19 hours. The reaction mixture is removed from the bath, cooled and chilled for one day, then three volumes of ethyl acetate are added and two 50 ml portions of saturated sodium bicarbonate solution are added. The combined carbonate extracts are extracted with ethyl acetate, covered with a fresh layer of ethyl acetate and cooled in an ice bath. The pH value is then adjusted to 2.0, the layers are separated and the aqueous layer is extracted once again with ethyl acetate. The combined ao acetate extracts were washed with saturated sodium chloride solution, dried over magnesium sulfate, filtered and evaporated to give 252 mg of a foamy solid. This precipitate is crystallized from acetone and ethyl ether, obtaining 153 mg (65%) of the product, the identity of which is confirmed by CMR, UV, IRibioautogram. CSF spectrum (DMSO-d65: 3.7 (s, 2.2 —CH2), 3.8 (s, 2^ —CH2CONH—), 4.5 (q, 2, J =15Hz, 3—CH2S—), 5.1 (d, 1, J=5Hz, C«— H), 5.7(q, 1, J=4Hz, C7—H), 6.96 and 7.38(t,d,3,H from thiophene) and 9.13(d, 1, J=8Hz ,—CH2 40 CONH—.Example XXXVII Preparation of 3-[(pyrimidinyl-2)thiomethyl]-7-[2-(thienyl-2)acetamido]-cefemo-3-carboxylic acid-4 in acetonitrile A mixture of 2.0 g (5 mmol) 7-[2-(thienyl-2)-acetamido]-cephalosporanic acid and 0.62 g (5.5 mmol) 2-mercaptopyrimidine in 25 ml of anhydrous acetonitrile is heated at boiling for about 16 hours with stirring. The thin layer chromatography shows complete conversion to the product. The reaction mixture is cooled to room temperature and the product is set aside, washed with about 50 ml of acetonitrile and dried at 50°C for 4 hours, under under reduced pressure. 1.86 g (83%) of cream crystals are obtained with a melting point of 217°C (with decomposition). 55 The CSF spectrum in DMSO-down shows no parent compound. The identity of the product is confirmed by IR, UV and PMR. CSF spectrum (DMSO-d6S: 3.55(q, 2, 2—CH)2,J=18Hz), 3.74(s, 2, —CH2CONH—), 4.28 (q, 2.3-CH2S ^, J=13Hz), 5.00(d, 1, C6—H, J=5Hz), 60 5.64(q,l, C7—H, J+5Hz, J=9Hz), 7.08 and 8.52 (m, d, 6, H from thiophene and pyrimidine) and 9.00 (d, 1, —CH2CONH—,.J=9Hz). Example XXXVIII. Preparation of 3-[(pyrimidinyl-2)thiomethyl]-7-[2-(thienyl-2)acetamido]-6S cephemo-3 carboxylic acid in acetic acid.122 152 25 Mixture 2.0 g (5 millimoles) of 7-[2-(thienyl-2)acetamido]-cephalosporanic acid, 0.6 g (5.4 millimoles) of 2-mercaptopyrimidine and 0.41 g (5 millimoles) of sodium acetate, in 25 ml of acetic acid glacial, heated at 85 °C for 4 hours. The product crystallizes when heated. The mixture is cooled to room temperature, the product is filtered off, washed with acetic acid and dried to obtain 1.58 g (70.5%) of a creamy, crystalline product with a melting point of 218 °C (with decomposition). The identity of the product is confirmed by IR, UV, CSF and elemental analysis. The CSF spectrum is identical to the spectrum of the product from Example XXXVII. Example XXXIX. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-[2-(thienyl*-2)acetamido]-cefemo-3-carboxylic acid-4 in acetic acid. Mixture 2, 0 g (5 mmol) 7-[2-(thienyl-2)acetamido}-cephalosporanic acid, 0.81 mg (7 mmol) 1-methyl-1H-tetrazolothiol-5 and 0.41 mg (5 mmol) sodium acetate , in 25 ml of glacial acetic acid, is heated for 8 hours at a temperature of 75-77°C. The course of the reaction is checked hourly using thin layer chromatography, confirming the completion of the reaction after an hour. The reaction mixture is cooled to 40-45 °C and the acetic acid is removed under reduced pressure. 50 ml of ethyl acetate and 50 ml of water are added to the residue. The aqueous layer is acidified to pH 1.5 with In H2SO4. The acetate layer is separated, dried over anhydrous sodium sulfate and the solvent is evaporated on a rotary evaporator. The remaining light oil is dissolved in 50 ml of ethanol and a solution of 2 ml (10.2 mmol) of dicyldohexylamine in 10 ml of ethanol is added. A precipitate of the dicyclohexyl ammonium salt forms almost immediately. The mixture is stirred for 15 minutes, the precipitate is filtered off, washed with ethanol and dried. A total of 1.2 g (37.8%) of a product with a melting point of 185-186 °C is obtained, identical according to IR, CSF and UV to the product obtained previously. Example XL. Preparation of 3-[(1-benzyl-1H-tetrazolyl-5)thiomethyl]-7-[2-(thienyl-2)acetamido]-cefemo-3-carboxylic acid-4 in 1,2-dichloroethane. Mixture 2.0 g (5 mmol) 7-[2-(thienyl-2) acetamido]-cephalosporanic acid and 1.44 g (7.5 mmol) 1-benzyl-1H-tetrazolothiol-5 in 25 ml 1,2-dichloroethane , heated and stirred at 85 °C overnight in an oil bath. Thin layer chromatography shows no initial cephalosporic acid. The solvent is evaporated in a rotary evaporator. The remaining foamy precipitate is dissolved in 25 ml of methanol and the mixture is heated in a steam bath until completely dissolved. The solvent is evaporated in a rotary evaporator. The product crystallizes. The mixture is stirred for 15 minutes, the precipitate is filtered off, washed with methanol and dried under reduced pressure. 1.6 g (60.6%) of product are obtained, melting point 171-171.5 °C. Example XLI. Preparation of 3-amidinothiomethyl-7-[2-(thienyl-2)acetamido]cephem-3-carboxylic acid in acetonitrile. A mixture of 3.12 g (8 mmol) of 7-[2-(thienyl- 2) acetamido]-cephalosporan and 912 mg (12 millimoles) of thiourea, in 15 ml of acetonitrile (dried over an aluminosilicate drying agent, sold under the name 4-A Linde molecular sieve), mixed and heated at 26 at 87°C in within 24 hours. After one hour, a precipitate begins to form from the mixture. After 24 hours, the product is filtered off from the hot reaction mixture and dried. 2.5 g (76%) of product are obtained. 5 Elemental analysis: calculated: C - 43.68, H -3.91, N -13.58, found: C -43.50, H -4.03, N -13.29. The CSF spectrum confirms the identity of the product. Example XLII . Preparation of 3-bcnzoyl-10thiomethyl-7-[(2-(thienyl-2)acetamido]-cefemo-3* carboxylic acid in isopropyl acetate. 1.0 g (2.5 mmol) of 7-[ 2-(thienyl-2)acetaminophen cephalosporanate and 510 mg (3.7 mmol) of thiobenzoic acid are suspended in 20 ml of anhydrous isopropyl acetate and heated at reflux temperature for 31 hours. complete dissolution of the reactants. The solvent is evaporated under reduced pressure. Thin-layer chromatography shows that the residue is a 60:40 mixture of the product and the unreacted starting material. A sample of the product is purified by preparative thin-layer chromatography on silica gel, using developing a 16:1 mixture of acetone and acetic acid. CSF spectrum (DMSO-d«5: 3.50(ABq, 2H, 2—CHa, 23 J^H* J«f9Hz), 3.82(g2H,^CH2CONH— ), 4.20(d, 2H, 3—GH*S—J-5Hz), 5.03 J-5Hz), 5.69 (d, 1H, Ct—H, J-5Hz), 6.89— 8.0 (m. 8H, H aromatic). -?.* < ' Example XLIII. Preparation of 3-(phenylthio)methyl-7-[2-(ticnyl-2)acetamidol-cefemo-3-carboxylic acid-4 in 1,2-dichloroethane. Mixture of 2.0 g (5 mmol) of 7-[acid 2-(thienyl-2)acetamido]-cephalosporanic acid and 0.75 ml (7.5 mmol) of benzenethiol in 25 ml of 1,2-dichloroethane are heated overnight at reflux temperature. Thin-layer chromatography shows no starting cephalosporanic acid. . The solvent is evaporated in a rotary evaporator and 25 ml of ethanol are added to the residue and heated, partially dissolving the precipitate. In order to completely dissolve the residue, 25 ml of methanol are added and the mixture is heated. The resulting solution is filtered through cotton wool, 2.0 g of carbon is added, stirred for 5 minutes and filtered through a filter aid. The solvent is evaporated in a rotary evaporator. The CMR spectrum of residue 45 shows the presence of some starting thiol. The residue is suspended in 125 ml of isopropyl acetate, filtered and cooled overnight. The filtrate is then diluted with 25 ml of ethyl acetate and washed with 25 ml of dilute sodium bicarbonate solution to remove the thiol. The acetate layer is added to 25 ml of water and the pH value of 8.5 is adjusted to 1.4 with sulfuric acid. The acetate layer is dried over magnesium sulfate, filtered and evaporated on a rotary evaporator. 0.92 g (19.4%) of a foamy precipitate are obtained. 55 CSF spectrum (DMSO-d65: 3.58 (m, 2, 2—CH2), 3.75 (s, 2, —CH2CONH—), 4.12(q, 2, 3—CH2S—, J = 13Hz ), 5.08(d, 1,C6—H,J=5Hz), 5.66(q, 1, C7—H, J=5Hz, J=9Hz), 7.15(m, 8, H z thiophene and benzene), 9,10(d, 1, -CH2CONH-, J=Hz). 60 Example -7- (2- phenylacetamido) -cefemo -3- carboxylic acid-4 in 1,2-dichloroethane. Mixture of 1.95 g (5 mmol) 7-(2-phenylacetamido)-cephalosporanic acid and 0.99 g ( 7.5 mmol) of 5-methyl-65-1,3,4-thiadiazolothiol-2 in 25 ml of 1,2-dichloroethane, 122-152 27 is heated at reflux temperature for 16 hours. Thin-layer chromatography shows the presence of traces of the starting acid ceftlosporan. During the reaction, the product crystallizes. The reaction mixture is cooled to 0-5°C, filtered, the product is washed with cold 1,2-dichloroethane and dried under reduced pressure. 1.82 g (78.8%) of the product are obtained. melting point 171-172°C. CSF spectrum (DMSOd*)*: 2.70(s, —CH3 from thiadiazole), S.58(^.2,—ClLCONH—), 3.70f wide s,2.2 —CH2), 4.40(q, 2.3—CH2S—, l*13Hz, 5.12 (d, 1, C6—Hf J- 5H*X S,72(ash Ci~to, J^5Hz,J -9Hz), 7.28 (s, 5, phenytic H), M&(dyi;--CteCONH—, J^9Hz. Example XLV. Preparation of 3-(methylthio-butyl)*?-¦ E2*(tphenyto-2)acetamido]-cefemo-3-carboxylic acid-1 in methylene chloride. Mixture of 24 g (60 milnol) of 7-[2- ( thienyl-2) acetornldol-cephalosporan, 7.0 ml of metaneHol and 600 mL of methylene chloride, are mixed and heated for 18 hours in an autoclave at a temperature of 84~-86°C. The reaction mixture is cooled to room temperature. A small amount of undissolved substances is filtered off and the filtrate is evaporated. Ethyl acetate and filtration are added to the residue. Approximately 150 ml of water are added to the filtrate, stirred and gradually add 1N NaOH solution to pH 5.5. The aqueous layer was separated and concentrated to a volume of approximately 75 ml, and then dissolved to a volume of 700 ml with water * glacial acetic acid was added to pH 3.8. An amorphous precipitate is formed and the mixture is stirred in the liquid for 3 hours in an ice bath and then cooled overnight. The precipitate is filtered off, 100 ml of ethyl vinegar are added to the filtrate and the pH is adjusted to 2.0 with concentrated hydrochloric acid. The organic layer is separated and extracted with 100 ml and then 159 ml of ethyl chloride. The combined organic layers are dried over magnesium sulfate and the solvent is evaporated. The amber pan-shaped precipitate is dissolved in 5 ml of ethical acetate, inoculated with the product and left to cool overnight. The crystalline precipitate is filtered off, washed with cold isopropyl acetate and dried under reduced pressure at a temperature of about 50°C. 32 g (14%) of the product are obtained, the identity of which is confirmed by the PMR spectrum. PMRJ spectrum: 2*00(s,3, 3^CH2SGH3, 3.74(m, 3—CH2S^,! 2—CH2i—CH2CONH —, 5.14 (d, 1, O—H, J-5Hz), 6.64(q,l,C7—H, J=5Hz, J=9Hz), 7.15(m,3, Hz thiophene ) and 9.12(d, 1, ^CHjCONH—, J=9Hz). Example ) thiomethyl-cefemo-3-carbexyl-4, as sodium salt, in benzene. Mixture of 2.17 g (4.65 mmol) of 7-(2-formyl-oxy-2*.phenytoacelamido)-cephalosporan acid and 0, 87 g (7.5mHimole) of 1-nrctyl-1H-tetrazolothioIu-5 in 25 ml of benzene, heated at boiling point (about £0°C) for 12 hours. During heating, sediments form on the walls of the vessel. ; a soft precipitate that forms a glassy precipitate upon cooling. Thin-layer chromatography shows that the filtrate contains only trace amounts of the product, while the precipitate on the walls contains mainly the product and some deformyl compound. The reaction mixture with the addition of acetone, you evaporate. The obtained sandy residue is dissolved in 35 ml of anhydrous acetone and 10 ml of a solution containing 1.25 g of sodium 2-ethylcaproate in vacetone are added. The sodium salt of the product precipitates. After one hour, the product is filtered off, washed with 20 ml of acetone and dried. 1.38 g (58%) of product* are obtained, the identity of which is confirmed by thin-layer chromatography and CMR spectrum analysis. 5 CSF spectrum (D2O)*: 3.48 (q,2,2—CH* J~18Ha,) 4.00(s,3, —-CHr % tctrazole), 410(m, 2; 3—CH2S— ), 5.05(d, 1, C6—H J«5Hz), 57©(d, U C7—H, J-5Hz), 6.24(s, 1, —CHCONH—, 7»5a(», 5, phenytic H) and 8.33 (s, 1, —O—CH)»0). 10 Example XLVII. Preparation of 7*(2-(bmy- looksy -2- phenyioacetamido)-3- [(I-methyl -1H- tetrazo-yl-1)thiomethyl]-cefcmo -3-carboxylic acid-4 in carbon tetrachloride. Mixture 2.17 g (4.65 mmol) 7-(2-formyl-15 oxy-2-phenyioacetamido)-cephic)sporaic acid and 0.87 g (7.5 mmol) I-methyl-1H- tetrazolothioca-5 in 25 ml of carbon tetrachloride, heated at boiling point (about 77°C), cooled to room temperature for 12 minutes and the supernatant was defrosted from the hardening semi-solid precipitate. 25 ml of 1,2-dichloroacetate are added to the precipitate and heated. The product crystallizes. Alo& is cooled to room temperature and stirred for about one hour, then the product is filtered off, washed with 100 ml of 1,2-dichloroethane and dried under reduced pressure at 45°C overnight. 1.54 g (65%) of white crystalline precipitate. The identity of the product is confirmed by CSF analysis and thin-layer chromatography, which shows the presence of 90 trace amounts of a deformyl compound. The CMR spectrum is identical to the spectrum of the product from Example XVI. Example XLVHI. Preparation of 3-methyl-1,2,4-oxadiazoloticl-5. 30 g (0.4 mol) of acetamide oxime, 100 ml (1.6 mol) of carbon disulfide and 56 ml (osmol) of triethylamine are mixed in 1 liter of pyridine. The carbon disulfide solution is bubbled with nitrogen. The mixture is heated in an oil bath at 70°C for three days and then evaporated. Ethyl acetate and a saturated sodium carbonate solution are added to the oily residue. The layers are separated and the organic layer is washed with a saturated sodium bicarbonate solution. The combined carbonate solutions are extracted with ethyl acetate and the acetate extract is discarded. The aqueous extract is covered with a layer of fresh ethyl acetate and cooled in an ice bath. The pH value is adjusted to 2.5 with 20% hydrochloric acid, and then sodium chloride is added to saturate the solution. The solution is extracted with ethyl acetate, washed with a saturated sodium chloride solution and dried over anhydrous magnesium sulfate. The solution is filtered and the filtrate is evaporated to 1/2 its original volume, then an equal volume of carbon tetrachloride is added and evaporated until crystallization begins. 24.8 g (52%) of product are obtained. Example XLIX. Preparation of 3-[(^mess tyl~1,2,4-cksadazolylc-5)thiomethyl]-7-[2-(thienyl^2)?cetamido]-cephemo-3-carboxylic acid-4 in 1 ,2-dichloroethane. 100 mg (0.25 mmol) of 7-[2-(thienyl-2)^cetami- to]-3- (carbamyloxymels:o)-cefcmo -3- carbexyl- 60 wegc-4 acid is suspended in 25 ml of 1, 2-dichloroethane and add, while stirring, 35 mg (0.30 μmol of 3-methyl o-1,2,4- oxadiazolothiol-5. The reaction mixture is heated in an oil bath at 110° C. and 5 ml of the solvent containing traces of it are distilled off water. The temperature of the bath oil is reduced to 90-95 °C, maintained for 122-152 29 19 hours. Then the mixture is cooled to room temperature, the insoluble parts are filtered off and washed with lt2-dichloroxoethane and ethyl ether. Thin-layer chromatography shows that this is unreacted starting material, containing only trace amounts of product. The filter is evaporated and a solution of sodium bicarbonate and ethyl acetate is added to the oily residue. The layers are separated and a new portion of ethyl acetate is added to the water, cooled in an ice bath and the pH is adjusted to 2.5 with 20% acid salt. The organic layer is separated and the aqueous layer is extracted with a new portion of ethyl acetate. The combined acetate extracts are washed with a saturated sodium chloride solution, dried over magnesium sulfate, filtered and evaporated. The oily residue is crystallized from a 1:1 mixture of hexane and ethyl ether. 13 mg (11.5%) of the product are obtained, the identity of which is confirmed by the CSF and IR spectra, identical to the compound obtained according to example XXXII. Example L. Preparation of 3-[( 1-methyl-1H-tetrazolyl-5)thiomethyl]-7-(2-tert.-butoxycarbonyl-2-phenylacetamido)-cefemo-3-carboxylic acid in nitromethane. Mixture of 490 mg (1 mmol) acid 7-(2-Hyrr.-butoxycarboxylate-2-phenylacetainióo) and 145 mg (1.25 moles) of 1-methyl-|H-tetrazolothiol-5 in 15 ml of anhydrous water, heating it at a temperature of -90°C* within 8 hours Thin-layer chromatography shows the presence of the product, excess thiol, decarboxylated product and the absence of the starting cephalosporanic acid. The nitrometam is evaporated and the remaining orange, foamy precipitate is dissolved in 10 ml of saturated sodium bicarbonate solution, then 20 ml of water are added and the mixture is washed with methyl acetate until a clear washing solution is obtained. The acetate solutions are combined, 20 ml of water are added, the mixture is cooled to 0°C and the pfl is adjusted to 2.2 with 20% hydrochloric acid. The layers are separated and the aqueous layers are washed with ethyl acetate. The combined acetate extracts are washed with a saturated sodium chloride solution, dried over magnesium sulfate, filtered and evaporated. 455 mg (83%) of a brown foamy solid are obtained. Thin-layer chromatography shows the presence of the product, traces of thiol and traces of decarboxylated product. 455 mg (0.833 mmol) of the product are dissolved in 7 ml of ethyl acetate and 0.833 ml of lithium acetate are added dropwise with stirring. A brown precipitate of the lithium salt is obtained, which is filtered off, washed with ethyl acetate and dried overnight under reduced pressure at room temperature. 368 mg (80%) of the product are obtained, the identity of which is confirmed by thin-layer chromatography, CMR spectra, bioautogram, elemental analysis and IR and UV spectra. Chromatography shows traces of a decarboxylated compound. CSF spectrum (CDClb)$: 1.4(s, 9, -COCMII- n.-COfc)* 3^(8.2,2^0%), 385 4.3(s, 2, 3—CHaS— ), 4.44 and 4.45(2s, 1, C«H*~-CH), 4fitór U J«=6Hz, C«^-H)v 5.8(fl, 1, J=6Hz, Ct— H), 7^5(sl5,C6H5—), 8.2 and 7,&(2d, Ir, J~9Hz, —CONH—) and 9.3 (s 1, —COOH). UL Example Preparation of 3-[(1-methyl-1H-tetrazolium-5)thiomethyl]-7-[N-(1,3-dimethylureidocarbonyl)-2-phthyrifogylcylamido]-eephemo-3-carboxylic acid-4 in nucometanife. 30 130 mg (0.25 mmol) of 7-[N-(1,3-dimethyl-ureidocarbonyl)-2-phenylglycylamido]-cephalcsporanic acid is suspended in 5 ml of mtromethane and 43.5 mg (0.375 mmol) 1 is added -methyl-1H-tetrazoctiol-5. Calcsc 5 is heated under nitrogen at 85°C for 12 hours and then left at room temperature over the weekend. The reaction mixture is filtered and the precipitate is washed with a small amount of nitromethane and then dried in a vacuum oven at 35°C. 10-83 mg (58%) of the product are obtained, the identity of which is confirmed by thin-layer chromatography, CSF, IR, TJV spectra as well as elemental analysis and bioautogram. CSF spectrum (DMSO-d*)*: 2.65(d, 3, J-4Hz , —CON HCHj), 3.15(s, 3, CONCHACO—), 3.6(s, 2, 2—CH2), *5 3.9 (s, 3, CHj from tetrazole), 4.3( s, 2, 3—CHAS—\ 5.0(d, 1, J=5Hz, Ce—H), 5.5(d, 1, J-=7Hz, CeH^CH^N- (HCOX 5.7 (q, 1, C7—H)„ 5.8 (q, 1, —CONHCH3, 7.4(s, 5, Ott —), 9.3(d, 1, J=8Hz, C6H5CHCONH—). 10 (o\M=8Hz,C«H5 -CH(NH-)—CO—). 20 Example LU. Preparation of 3-[(1-methyl-1H-tetrazolflo-5)thiomethyl]-7-[2-thienyl acid -2(acetamkk}- cefemo -3- carboxylic acid-4 in acetorritrile with the addition of tetrabutylammonium iodide. 25 Mixture. 2.0 (5 mflimoles) of 7-[2-(thienyIo-2) ac^tam^doj-celemo -3 - carboxylic acid-4, 1.2 g (10 milliliters) of 1-methyl^ -1H- tetrazolothipl-5^, 0.2 g of tetraburylammonium iodide and 25 ml of anhydrous acetonltrile, heated to reflux for 8 hours. 30 The reaction mixture is cooled to room temperature and the solvent is removed using a rotary evaporator. A hot mixture of 25 ml of isopropyl acetate and 5 ml of acetoncrylate is added to the residue, then filtered and left to cool slowly. The product crystallizing in the form of 35 cream crystals is filtered off, washed with isopropyl acetate and dried. 1.30 g (57.5%) of the product are obtained, the CSF spectrum of which is identical to that of the product from Example V. Example LHL Preparation of 3-[l-methyl-40 LH-tetrazoryl-5thiomethyl]-7- [2 - (thienyl-2)acetamidol-cefemo-3-carboxylic acid-4 in 1,2-dichloroethane with the addition of tetrabutylammonium iodide. The procedure from Example LU is repeated, except that 1,2-dichloroethane is used as the solvent. After adding 2 ml of dicyclohexylamine, 1.55 g (48.9%) of the dicyclohexylammonium salt of the product are obtained, the CMR spectrum of which is identical to that of the product from Example I. 50 Example LIV. Acid production. 3-(phenylthio)methyl-7-[2-(thienyl-2)acetamido]-eefemo-3-carboxylic acid-4 in 1,2-dichloroethane with the addition of 1-methyl-5-(methylthio)-1H -tetrazol. Mixture of 2.0 g (5 mmol) 7-[2-(thienyl-2)55-acetamido]-cephalosporanic acid, 0.75 ml (7.5 molimole) benzenethiol and 0.65 g 1-methylrS-methylthio -1H-tetrazole in 25 ml of 1,2-dichloroethane is heated to reflux. Thin layer chromatography after approximately 14 hours of heating shows that the reaction is complete. The solvent is evaporated on a rotary evaporator and the residue is extracted several times with ethyl ether. After removal of the solvent, 1.66 g of a yellowish-brown precipitate remain (74%). The IR and CSF spectra are identical to those of the product prepared according to the previous examples.122 152 31 Example LV. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-[2-(thienyl-2)acetamido]-cefemo-3-carboxylic acid-4 in isopropanol. Mixture 2.0 g (5 mmol ) 7-[2-(thienyl-2)acetamide o]-cephalosporanic acid and 0.87 g (7.5 mmol) 1-methyl-1H- tetrazolothiol-5 in 25 ml isopropanol are placed in a flask equipped with a condenser with a tube containing anhydrous calcium sulfate, sold under the brand name Drierite. The flask is immersed in an oil bath at a temperature of 84-85°C. The course of the reaction is monitored by thin-layer chromatography. After 40 hours of heating at 82-83 °C, only half of the cephalosporanic acid reacts. Example LVI. Preparation of 3-(2-oxazolyl-althiomethyl)-7-[2-(1H-tetrazolyl-1)acetamido]-cefemo-3-carboxylic acid-4 in nitromethane. Suspension of 0.38 g (lmillimol) of 7-[2- (1H-tetrazolyl-1)acetamido]-cephalosporan acid and 0.11 g (1.1 millimole) of oxazolothiol-2 in 5 ml of nitromethane are placed in an oil bath at a temperature of 90-91 °C. The reactions are carried out in an atmosphere of dry nitrogen. After 20 minutes all the reagents dissolve and after 35 minutes the product begins to crystallize. After 6 hours, the reaction mixture is cooled to room temperature, the product is filtered off, washed with 7 ml of nitromethane, dried in air and then dried under reduced pressure for 3 hours at 40°C. 0.36 g (85.7%) of a creamy crystalline product with a melting point of 196 °C (with decomposition) are obtained. The CMR spectrum shows that the product contains 70% of the desired compound and 30% of the starting cephalosporanic acid. The product is recrystallized from 5 ml of DMSO-d6 and 10 ml of water, filtered, washed with 5 ml of a 2:1 mixture of water and DMSO-de, and dried on air and then under reduced pressure at 50°C for 6 hours. 0.26 g of product is obtained, the CSF spectrum of which shows the content of 87% of the desired compound and 13% of the starting cephalosporanic acid. Recrystallization is repeated using 3 ml of DMSO and 6 ml of water and stirring for 1 hour. 0.21 g of product is obtained, the CMR spectrum of which (DMSO-down) shows that the cephalosporic acid content has decreased to 5% and confirms the identity of the desired compound. PMR 6: 3.75(s, 2, 2- CH2), 4.34(q, 2, 3—CH2—S, J=14Hz), 5.16(d, 1, Gs—H, J=5Hz), 5.76(q, 1, C7—H , J=5Hz, J=9Hz), 5.44(s, 2, —CH2CONH—), 7.28 (s, 1, C4-^-H zoxazole), 8.14 (s, 1, C3—H from oxazole), 9.37 (s, 1, H from tetrazole) and 9.53 (d, 1, _CONH—, J=9Hz). EXAMPLE LVII. Preparation of 3-(2-oxazolylmethyl)-7-(2-formyloxy-2-phenylacetamido)-cefemo-3-carboxylic acid-4 in 1,2-dichloroethane. 0.52 g (1 mmol) of 7-(2-formyloxy-2-phenylacetamido)-cephalosporanic acid solvate with methylene chloride and 0.12 g (1.1 mmol) oxazolothiol-2 in 20 ml of 1,2-dichloroethane, is heated at reflux temperature for about 16 hours and then cooled to room temperature. Thin layer chromatography shows clear conversion into the desired compound. The reaction mixture is concentrated in a rotary evaporator to approximately 10 ml. After some time, some crystalline, gelatinous precipitate falls out, which is filtered off, washed with 1,2-dichloroethane and dried, obtaining 0.12 g of a gray precipitate. After complete removal of the solvent from the filtrate, 0.45 of a light yellow foamy precipitate is obtained. This precipitate is triturated with 25 ml of ethyl ether and dried, obtaining 32 0.21 of a light yellow powder, the identity of which is confirmed by the CSF spectrum 6:3.56(m, 2, 2-CH2), 4.24(q, 2, 3— CH2S—, J =13Hz), 5.00(d,l,C6—H,J=5 H2), 5.70 (q, 1, C7—H.J=5Hz, J=9Hz), 6.14(s , 1, C6H5—CH—), 7.25 (s, 1.5 C4—H from oxazole), 7.45 (m, 5, H from phenyl), 8.12 (s, 1, Cs—H from oxazole ), 8.35 (s, 1, —CHO) and 9.40 (d, 1, —CONH—, J=9Hz). Example LVIII. Preparation of 3-[(4-phenylthiazolIo-2)thiomethIo]-7-[2-(thienyIo-2)acetamido]-cefemo-3-carboxylic acid-4 in acetonitrile. Mixture 2.0 g (5 millimoles) of 7-[2-(thienyl-2-acetamido[-cephalosporanic acid) and 1.44 g (7.5 millrools)-4-phenylthiazolothiol-2 in 35 ml of acetonitrile are heated at reflux temperature for 16 hours protected from moisture atmospheric tube containing as a drying agent anhydrous calcium sulfate, sold under the brand name Drierite. Thin layer chromatography shows clean conversion to the new product. After cooling the reaction mixture to room temperature and stirring for 2 hours, the product crystallizes, which is filtered off, washed with acetonitrile and dried. 2.25 g (85.6%) of the product are obtained, melting point 180°C (with decomposition). The CSF spectrum confirms the identity of the product. 25 Example LIX. Preparation of 3-[(5) acid -methyl-1,3,4-thiadiazolyl-2)thiomethylol -7-[2-(1H-tetrazolyl-1)acetamido]-cefemo -3-carboxylic acid-4 in nitromethane. To 25 ml of nitromethane from alumina peroxide is added 1.92 g (5 mmol) 7-[2-(1H-tetrazolyl-1)acetamido[-cephalosporanic acid and 0.79 g (6 mmol) 5-methyl-1,3,4-thiadiazolothiol- 2 and the whole mixture was stirred and heated at 95°C in an oil bath for 4 hours. Thin layer chromatography shows that only traces of the starting cephalosporanic acid remain (less than 2%). The reaction mixture is cooled to room temperature, filtered, washed with nitromethane and dried under reduced pressure. 2.11 g (92.5%) of product with a melting point of 183.5 °C (with decomposition) are obtained, the identity of which is confirmed by the CMR spectrum. 49 Example LX. Preparation of 3-[(5-methyl-1,3,4-thiadiazolyl-2)thiomethyl]-7-[2-(1H-tetrazolyl-1Acetamido]-cefemo-3-carboxylic acid in propionitrile. Up to 25 ml propionitrile from superneutral aluminum oxide, 1.92 g (5 mmol) of 7-[2-(1H-tetrazolyl-1)acetamido]-cephalosporanic acid and 0.99 g (7.5 mmol) of 5- methyl-1,3,4-thiadiazolothiol-2. The whole is heated and stirred at reflux temperature (97° C.) for 9 hours. Thin layer chromatography shows only traces of the starting cephalosporanic acid. The reaction mixture is cooled to room temperature , filtered, washed the precipitate with propionitrile and dried under reduced pressure. 2.04 g (89.5%) of the product were obtained, melting point 186.5°C (with decomposition). The identity of the product was confirmed by the CMR spectrum. 55 Example LXI. Preparation of acid 3-[(l-methyl-1H-tetrazolyl-5)thiomethyl]-7-(2-formyloxy-2-phenyl-acetamido)-cefemo-3-carboxylic acid from 7-aminocephalosporanic acid in 1,2-dichloroethane 26.25 g of trinutylsilyl acetamide (0.200 mol) are added to a suspension of 13.62 g of 7-aminocephalosporanic acid 60 (0.05 mol) in 100 ml of 1,2-dichloroethane. The reaction mixture is heated to 40°C, the reagents dissolve, forming a cloudy solution, which is then cooled to 20°C. A solution of 10.92 g (0.055 mol) of 122 152 33 34 2-formyloxy-2-phenylacetyl chloride in 25 ml of 1,2-dichloroethane was added dropwise to the solution over 20 minutes, raising the temperature to 30°C. The mixture is stirred for 2 hours, 100 ml of 1,2-dichloroethane are added, and the mixture is washed with three portions of 100 ml of water. The aqueous layers are combined and extracted with 2 x 50 ml of 1,2-dichloroethane, which is then washed for 40 minutes. ml of water. The organic extracts are combined and mixed for 20 minutes with 2.0 g of activated carbon, sold under the brand name Darco G-60, and mixed with diatomaceous earth, sold under the brand name Hyflo Super-Cel. The total volume of the solution is 375 ml, and it contains the desired 7-(2-formyloxy-2-phenylpacetamido)-cephalic acid. This solution is evaporated at a temperature of about 30° C. to a weight of 336 g, which corresponds, as tested, to 250 ml of 1,2-dichloroethane and 22 g of 7-(2-formyloxy-2-phenylacetamido) acid. -cephalosporin. To the above solution is added a solution of 6.39 g (55 mmol) of 1-methyl-1H-tetrazolothiol-5 in 250 ml of 1,2-dichloroethane and the whole is heated to boiling point. The water from the previous washes is distilled azeotropically using an azeotropic cap. Thin layer chromatography after 12 hours of heating at reflux shows an almost normal reaction*. The reaction mixture is cooled to room temperature and seeded to precipitate the product, 3-[(1-methyl-1Hrjetrazol-yl-5)thiomethyl]-7- acid. (2-formyloxy-2-phenylacetamido)-cefemo-3-carboxylic acid-4. After about 2 hours, the product is filtered off and washed with 63 ml of 1,2-dichloroethane. 13.90 g (56.7% in relation to 7-AC acid) of the product are obtained. Thin-layer chromatography shows the purity of the product and the CMR spectrum confirms that it is identical to the product produced according to Example XVI. Example LXII. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-(formyloxy-2-phenylacetamido)-3-cephem-carboxylic acid-4 in 1,2-dichloroethane. Up to 25 ml 1,2-dichloroethane are added 2.33 g (5 millimoles) of 7-(2-formyloxy-2-phenylacetamido)-cephalosporanic acid and 0.64 g (5.5 millimoles) of 1-methyl-1H-tetrazolothiol- 5, and the whole thing is heated at boiling point for 12 hours. The reaction mixture is cooled to room temperature, then heated again to the boiling point and 10 ml of the solvent are distilled off, then 10 ml of tetrachloride are added dropwise at a temperature close to the boiling point (77°C). The whole is cooled to room temperature and stirred for one hour, the product is filtered off, washed with 14 ml of a 40% solution of carbon tetrachloride in 1,2-dichloroethane and dried under reduced pressure at a temperature of 50°C. 2.12 g (86. 5%) of a product whose spectrum is identical to the CMR spectrum of the product produced according to Example XVI. Example LXIII. Preparation of 3-[(3-(benzyloxycarbonylamino)methyl)-1,2,4-triazolyl-5)thiomyl]-7-[2-(thienyl-2)acetamido]-cefemo-3-carboxyl- acid wego-4 in nitromethane. Mixture of 2 g (5 mmol) 7-[2-(thienyl-2)acetamido]-cephalcsporanic acid and 2 g (7.6 mmol) 3- (benzyloxycarbonylaminomethyl)-1.2 ,4-Triazolothiol-5, in 35 ml of nitromethane, is heated at 80-90°C with stirring for 6 hours. The reaction mixture is cooled and the product is filtered off. After recrystallization twice from an aqueous solution of acetone, 1.2 g of 16 20 (40%) of a creamy, crystalline precipitate with a melting point of 174-178 °C are obtained. Elementary analysis for the CasH^NeOeSs formula: calculated: C-49.99, H-4.03, N-13.99, S-16.01 1 found: C-50.20, H-4.03, N-13.76, S-15.68. Example LXIV. Preparation of 3-[(1-(carboxymethyl)-1H-tetrazolyl-5)thiomethyl[-7-[2-(thienyl-2)acetamido[-cefemo-3-carboxylic acid-4 in acetonitrile. 1.0 g (2.5 mmol) 7-[2-(thienyl-2)acetamido]-cephalosporanic acid and 0.61 g (3.8 mmol) 1-(carboxymethylmethyl)-1H-tetrazolothiol-5 in 75 ml of acetonitrile, heated to boiling and 35 ml of the solvent were distilled off. Then the whole thing was heated at reflux for 13 hours, cooled, filtered and the filtrate concentrated under reduced pressure. The residue is dissolved in ethyl acetate, washed with 1N hydrochloric acid and brine, dried over sodium persulfate, and then hexane is added. The precipitate was filtered off and triturated with ether to obtain 0.475 g (38%) of a brown-yellow precipitate. The identity of the product is confirmed by comparison with a sample of the product obtained by another synthetic route. Example LXV. Preparation of 3-[(5-methyl-13,4-thiadiazolyl-2)thiomethyl]-7-(3-chloropropionamido)- -cefemo -3-carboxylic acid-4 in nitromethane.Suspension 1.0 g (2.5 mmol ) 7-(3-chloropropionamido)-cephalosporanic acid and 0.4 g (3 mmol) 5-methylIo-1,3,4-thiadiazolothioIu-2 in 20 ml of nitromethane, Jp is immersed in an oil bath at 95-96°C. Thin layer chromatography shows that the reaction is complete after 3 hours. The reaction mixture is cooled to room temperature, filtered and evaporated under reduced pressure. The remaining light red oil crystallizes after two hours at room temperature. It is ground with 15 ml of ethyl acetate, filtered, washed with ethyl acetate and dried. 0.64 g (55.2%) of the product are obtained, the identity of which is confirmed by IR, UV, titration, microanalysis and CSF. 40 Elemental analysis for the formula C16H19CIN4O4S3: calculated: C - 41.51, H-4.14, N-12.10, S-20.78, Cl-7.66 found: C - 41.70, H - 4, 23, N - 11.84, S - 20.51 Cl - 7.88. 45 Example LXVI. Preparation of 3-[(1-ben" zyl-1H-1,2,3-triazolyl-5)thiomethyl]-7-[2-(thienyl-2)acetamido]-cefemo-3-carboxylic acid-4 in 1,2-dichloroethane. 200 mg (0.5 mmol) 7-[2-thienyl-2)acetamido]-50 cephalsporanic acid and 140 mg (0.7 mmol) 1-benzyl-1H-1,2 ,3-triazolothiol-5, in 15 ml of 1,2-dichloroethane, is stirred and heated at 65-70° C. for 21 hours. The solvent is removed under reduced pressure, 25 ml of a saturated bicarbonate-55 solution are added sodium hydroxide solution and the mixture is extracted with two portions of ethyl acetate. A new portion of ethyl acetate is added to the aqueous phase, the mixture is cooled in an ice bath and the pH is adjusted to 2.5 with 20% hydrochloric acid. The acidic product is extracted with two portions of acetate. The combined ethyl acetate extracts are washed with a saturated aqueous NaCl solution and dried over anhydrous magnesium sulfate. The magnesium sulfate is filtered off and the ethyl acetate is evaporated under reduced pressure. 76 mg of product are obtained, which, as determined by thin-layer chromatography, is a mixture of the starting compound and the product. For comparison, product and starting compound standards are used. Examples LXVII-LXXII. Substitution of 7-methoxy-7-[2-(1H-tetrazolyl-1)acetamido]-cephalosporanic acid with various thiols, in nitromethane.7-methoxy-7-[2-(1H-tetrazolyl-1)acetamido acid ] - cephalosporan is reacted with various thiols instantly. The procedure is practically the same as presented above, except that high-pressure liquid chromatography is used to isolate products from mixtures with unreacted starting compounds. The following compounds are obtained: acid 3- [(1-methyl -1H- tetrazolyl-5)thiomethyl] - 7- methoxy -7- [2- (1H-tetrazolyl-l)acetamido] -cefemo -3- car- boxyl-4, UV max (ethanol) 273 mu (e=9.082), acid«3- [(5-methyl-13,4-thiadiazolyl-2)thiomethyl] -7- mephoxy -7- [2-( 1H-terazolyl-1)acetamido]-cefemo -3- carboxyl-4, UV max (ethanol) 273 m# (Elemental analysis for GsHmNsOsS*: calculated: C - 37.18, H - 3.33, N - 23.13 found: C-36.99, H-3.31, N-22.86 acid 3-[(5-methyl-1,3,4-oxadiazolyl-2)thiomethyl] -7- methoxy -7- [2-(1H-tetrazolyl-1)acetamido]-cefemo -3- carboxylic acid-4. UV max (ethanol) 269 nv* (€=8.910). Elemental analysis for G5H16N1O6S2: calculated: C - 38.46, H - 3.44, N- 23.92. found: C - 38.58, H - 3.69, N - 23.91 3-[(l-carboxymethylolH-tetrazolyl-5)thiomethyl]-7-methoxy acid -7- [2-(lH-tetrazolium! o-l)acetamido]-ce¬ femo -3-carbpoxyl-4, UV max (ethanol) 269 m/i (c= 7669). Elemental analysis for G5H16N10O7S2: calculated: C - 35.16 H - 3.15, N - 27.33 found: C-35.42, H-3.38, N-27.39 acid 3-[(4,5-dihydro -6- hydroxy -4- mctyl-5-keto-1,2,4-tirazinyl-3)thiomethyl]-7- methoxy -7-[2-(lH-tetrazolyl-l)acetamido]-cefemo -3-carboxylic acid-4, UV max (ethanol ) 274 (c=11967). Elemental analysis for C16H17N9O7S2: calculated: C-37.57^ H-3.35, N-24.65 found: C-36.96, H-3.80, N- 27.63 acid 3- [(1A4- triazolIo-5)thiomethyl]-7-methoxy-7-[2-(1H-tetrazolyl-1)acetamido]-cefemo-3-carboxylic acid-4. Elemental analysis for G4H15N9O5S2: calculated: C - 37.08, H - 3.33, N - 27.80 found: C-36.98, H-3.43, N-27.79 Example LXXIII. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl[-7-[2-(4-ethyl-2,3-di-ketopiperazinyl-1-carbonylamino)-2-phenylacetamido]-cefemo-3 acid -carboxylic acid -4nitromethane. To 6 mL of nitromethane dried over aluminum oxide, 0.3 g (0.5 mmol) of 7-[2-(4-ethyl-2,3-diketopiperazinylcarbonylamino)-2-phenylacetamido] acid hydrate are added -cephalosporan acid and 0.0725 g (0.625 mmol) 1-methyl-1H-tetrazolothiol-5. The reaction mixture is heated at 85° C. under nitrogen for 12 hours. The nitromethane is evaporated and the remaining brown foam is redissolved in the sodium bicarbonate solution and washed twice with ethyl acetate. Fresh ethyl acetate is added, the mixture is cooled to 0°C and the pH is adjusted to 2.3. The layers are separated and the aqueous layer is washed with ethyl acetate. The acetate solutions are combined, washed with a saturated NaO solution, dried over anhydrous magnesium sulfate, filtered and evaporated. 130 mg (40% of theoretical yield) of a light yellow powder are obtained. The identity of the product is confirmed by the CMR spectrum. <5: 1.2 (t, 3, —NCHzCHj, J-7Hz), 3.65 (m, 6, N^CH2CH3 and H 5 piperazine), 4.0 (s, 3, —CHs from tetrazole), 4.4 (s, 2, 3—CH2S—), 5.1 (d, 1,C6—H,J-6Hz) and 5.8(d, 1, C7—H, J-8Hz), 6, 0(d, 1, GsHs—CH)—N)—, J=*6Hz), 7.4 (m., 5, phenyl H), 8.4(d, 1, -^CHCONH—, J=8Hz ) and 10.0(d, 1, —CH)—NH(CONH—, J-6Hz). 10 Example LXXIV. Preparation of 3-[(1-carboxymethyl-1H-tetrazolyl-5)thiomethyl]-7-[2-(4-ethyl-2,3-dioketopiperazinyl-1-carbonylamino)-2-phenylacetamido] acid -cefemo-3-carboxylic acid-4 in 1,2-di-chloroethane. 15 0.3 g (0.5 mmol) of 7-[2-(4-ethyl-2,3- diketopiperazinylcarbonylamino)-2-phenylacetamido-cefolotporate acid hydrate is dissolved in 45 ml of 1,2-dichloroethane dried over aluminum oxide and heats the solution at 95°C, removing water azeotropically. 20 After collecting 40 ml of the solvent, 10 ml of nitromethane and 0.160 g (1 millinnl) of 1-(carboxymethyl)-1H-tetrazolothiol-5 are added. The reaction mixture is maintained at 90°C, under nitrogen, for 12 hours. The solvent is then filtered and evaporated. A gummy residue is obtained, to which ethyl acetate and a saturated sodium bicarbonate solution are added. The mixture is washed twice with ethyl acetate, fresh ethyl acetate is added, cooled to 0°C and the pH is adjusted to 2.3 with 20% HCl. The layers are separated and the aqueous layer is washed with ethyl acetate. The acetate solutions are combined and washed with saturated HCl, dried over anhydrous magnesium sulfate, filtered, evaporated and dried at room temperature. 123 mg of product are obtained. 35 The identity of the product is confirmed by the CSF spectrum <5: 1.2 (t,3,—NCH2CH3, J=7Hz), 3.6(m,4,N—CH2CH3 and 5—H from piperazine), 4.1 (m, 2, 4—H from piperazine), 4.4 (s, 2, 3^CH2S—), 5.1 (d, 1, C8—H, J=5Hz), 5.3 (s, 2, 1— CH2COOH from tetrazole), 5 .75(d, 1, C7—H, J=6Hz), 40 5.9 (d, 1, CjHs—CH)N C (—), 7.4 (m, 5, H phenyl) and 9.9 ( d, 1, C6H5—CH(NH)—, J=7Hz).Example LXXV. Preparation of 3-[(4,5- dihydro -4- methyl -6- hydroxy -5- keto -1,2,4- triazinyl-3) thiomethyl] -7- [2-(4-ethyl -2) ,3-diaketopipe-45razinyl-1-carbonylamino)-2-phenylacetamido]-cefemo-3-carboxylic acid-4 in nitromethane. 0.3 g (0.5 mmol) 7-[2-(4-ethyl-2,3- diketopiperazinyl -1- carbonylamino) -2- phenylacetamido]-cephalosporanic acid hydrate and 0.111 g (0.625 mmol) 5- ke-50 to-l,2,4-triazinethiol-3 is dissolved in 10 ml of nitromethane under nitrogen at room temperature and the reaction mixture is heated at 85°C for 12 hours. The brown gummy precipitate that forms is discarded. The solvent is evaporated. slowly. Yellow 55 precipitates form. The residue is cooled, filtered and washed with diethyl ether. Two portions of a cream-colored solid product are obtained, identical after thin layer chromatography. The total yield is 80 mg (24%). The identity of the product was confirmed by the PMR spectrum: 1.1 (t, ^ 3, -NCH2CH3, J=6Hz), 3.3 (s, 3, CH3 from triazine), 3.65 (m, 4, N-CH2CH3 and 5H from piperazine), 4.0 (m, 2.6—H piperazine), 4.6 (s, 2, 3—CH2—S—), 5.1 (d, 1, Gj—H, J«5Hz), 5.75(m,2, GsH,—CH(N)—and C7—H), 7.45(m, 5, phenyl H), 9.5 (d , 1, —CHCONH—, J=8Hz) and 10.0(d, 65 1, OH,—CH(NH)-, J=Hz).122 152 37 Example LXXVI. Preparation of 3-[(5-methylthio-1,3t4-thiadiazolyl-2)thiomethyl]-7-[2-(1H-tetrazolyl-1)acetamido]-cefcmo-3-carboxylic acid-4nitro-methane. 15.0 g (39.2 mmol) 7-[2-(1H-tetrazoliumIo-1)5-acetamido]-cephalosporanic acid and 6.43 g (39.2 mmol) 5-(methylthio-1A4-thiadiazolothiol-2 suspend in 500 ml of nitromethane passed through a column of neutral aluminum oxide. The mixture is heated to 95 °C and maintained at this temperature for 6 hours. Then it is cooled overnight, filtered, washed with 250 ml of nitromethane and dried at 45°C for 4 hours, 18.08 g of product (94.9%) are obtained. This product is added to 150 ml of water and 4.0 ml of acetic acid. The pH is adjusted to 6.3 with In NaOH 15 (107 ml) and stirred for one hour. A solution of 257 ml of 60% sodium lactate and 65 ml of ethanol is added and the mixture is left for 45 minutes. Then it is stirred for 45 minutes, filtered, washed three times with ethanol and dried. 18.1 g are obtained. The product is resuspended in 300 ml of ethanol for 3 hours, filtered, washed with ethanol and dried. 14.85 g are obtained. The identity of the product is confirmed by high-pressure liquid chromatography. Example LXXVII— LXXXTV. Preparation of 3-[(5-methyl-1A4-thiadia2!oKIo-2)thiometyIoI -7-|2- (IH- » tetrazolyl-1)acetamido] -cefemo -3- carboxylic acid- in various solvents. 7-[ acid 2-(1H-tetrazolyl-1)acetamidol-cephalcsporate is reacted with 5-methyl-1,3,4-thiadiazolothiol-2 in various solvents. The basic reaction conditions are given in the table. Other reaction data are similar to the previous examples. 38 pouring acetic acid at a temperature of 84-86°C for 8 hours. The reaction mixture is cooled to room temperature and 0.4 g (1.6 mmol) of iodine are added to convert the unreacted thiol into the disulfide. The mixture is stirred for 20 minutes at room temperature, poured into 100 ml of ethyl acetate in 50 ml of water and removes excess J2 by adding sodium sulfite. The layers are separated and the acetate layer is washed with two 100 ml portions of water and once with 50 ml of 20% NaCl solution, and then dried over anhydrous sodium sulfate. Ethyl acetate is removed in a rotary evaporator and the residue is dissolved in 10 ml of methanol. Add 0.21 g (2 mmol) of acetanulite dihydrate and stir for 20 minutes at room temperature. The crystallized product is filtered off, washed with 5 ml of methanol and dried. 0.34 g (69.4%) of white crystals are obtained. The identity of the product is confirmed by the PMR spectrum: 3.50 (ABq, J = 17 Hz), 3.92 (s, -CH3 from tetrazolium), 4.20 (s , 3—CH2S—), 5.04(d, C«—H, J=5Hz), 5.24(s, GJL CHCONH—), 5.64 (d, C7—H, J=5Hz) and 7 .44(s, C6H5— —H). The CMR spectrum is identical to the spectrum of the original sample of the product obtained by substitution in an aqueous medium. Example LXXXVI. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-{2-[o-(tert-butoxycarbonylaminoinethyl)phenoyl]arc-3-caxhcyl-4wniti^methane . 0.2 g (0.386 mmol) 7-{2-[o-(Ul-butoxycarbonylaminomethyl)phenyl]acetamido}-cephalosporanic acid and 0.047 g (0.405 mmol) 1-methyl-IH-tetra- zolothiol-5 is reacted for 12 hours in 5 ml of nitromethane at a temperature of 85°C under nitrogen. Obtains Table Amount of cephalosporanic acid 1.91 g 0.96 g 1.96 g 1.26 g | 3.82 1.91 g 2.02 g* 1.928 Amount of thiol 0.86 g 0.363 g 0.5g 0.5g 1.98 g 0.99 g 1.0 g 0.79 g Solvent ' acetonitrile (dried semen) nitrobenzene 1:1 mixture of 1,2-dichloroethane and nitromethane nitroethane propylene carbonate ethylene carbonate acetic acid mixture of 52.5% nitromethane and 47.5% 2-nitropropane Temperature boiling point 85°Cil00°C 85°C 90°C 95°C 95 °C 85°C 95 °C Time 24 hours 16 hours 72 hours 14 hours 16 hours 8 hours 6 hours 5 hours 3 hours 50 minutes Efficiency % 87 83 88 84 68 22 55 | 89 Analysis I 190°C | 181 °C (with decomposition) | 182—183°C [ (with decomposition) I 177 °C 1 (with decomposition) [ — | — | — ( — [ * in sodium form Example LXXXV. Preparation of the lithium salt of 3-[(1-methylIo-1H-tetrazolyl-5)thiomethyl]-7-(2-hydroxy-2-phenylacetamido]-cefemo-3-carboxyl- ego-4 in glacial acetic acid, 0.48 g (1 mmol) of 7-(2-hydroxy-2-phenyl-acetamidocephalosporanic acid and 0.5 g (4.3 mmol) of 1-methyl-IH-tetrazolium-5 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-{2-60[o-(m-butoxycarbonylaminomethyl)phenyl]acetami-do} acid is reacted in 15 ml of -cefemo -3-carboxylic acid-4. The identity of the product is confirmed by the PMRS spectrum: 1.45 (s, 9, —C(CH3)0, 3.65 (s, 4, 2—CH* and —CHiCONH—), 3, 85(s, 3, —CH3 from tetrazole), 4^3 (m, 4, 3—CHaS— a and —CH2NHCOO—DJ-rz.—C4Hf), 5.0 (d, 2, C«—H,122 152 39 J=4Hz), 5.7(q, 1, Ci—H), 7.25(s, 5, Hphenyl and —CONH) and 8.9 (s, 1, —COOH). Example LXXXVII. Preparation 3-[(1-methyl-1H-tetrazolyl-5)thiometyIo]-7-(2-ureido-2-phenylacetamido)-cefemo-3-carboxylic acid-4 in nitromethane. 0.224 g (0.5 mmol ) 7-(2-ureido-2-phenyl-acetamido)-cephalosporanic acid and 0.061 g (0.525 mmol) of 1-methyl-1H-tetrazolothiol-5 are reacted in 8 ml of nithiomethane at 85°C for 12 hours. 10 3-[(1-methyl-1H- tetrazolyl -5)thio- methyl]- 7- (2- ureido -3- phenylacetamido)-cefemo -3- carboxylic acid-4 is obtained. The identity of the product is confirmed by the CSF spectrum <5: 3.5 (d, 2, 2-CHz, J=3Hz), 3.83 (s, 3, —CH3 from tetrazole), »5 4.17 (d, 2, 3—CH2S—, J =3Hz), 4.9(d, 1, C6—H, J=5Hz) 5.4(d, 1, —CH2CONH—, J=8Hz), 5.6(m, 3, C7—H and — NH2), 6.7(d, 1, C6H5CH(NH)—, J-8Hz), 7.25)(m, 5, Hz phenyl and 9.2(d, 1, —CH2CONH^, J=8Hz) .Example LXXXVIII Preparation of 3-[(1-2methyl-1H-tetrazolyl-5)thiomethyl]-7-(2-cyanoacetami-to)-cephem-3-carboxylic acid-4 in nitromethane. 0.339 g (1 mmol) 7-(2-cyanoacetamido)-cephalosporanic acid and 0.122 g (1.05 mmol) of 1-methyl-1H-tetrazolothiol-5 are reacted in 10 ml of nitromethane 2 at 85 °C, under nitrogen, for 12 hours. 3-[(l-methyl -lH-tetrazolyl-5)thiomethyl [-7- (2- cyanoacetamido)-cefemo -3- carboxylic acid-4 is obtained. The identity of the product is confirmed by the CSF spectrum <5: 3( 3.5 (s, 2, 2—CH2), 3.65 (s, 2, CNCH2CONH—), 3.95 (s, 3, —CH3 from tetrazolium), 5.35 (s, 2 , 3—CHiS—), 5.1 (d, 1, C6—H, J=6Hz), 5.75(q, 1, C7—H, J=4Hz), 7.8 (s, 1, — COOH) and 8.7 (d, 1, -CH2CONH-, J=9Hz). 3' Example LXXXIX Preparation of 3-[(1- * methyl-1H-tetrazoliumIo-5)thiomethyl]-7- [2- (m-chlorophenylthio)acetamido]-cefemo-3-carboxylic acid-4 in nitromethane. 0.390 g (0.855 mmol) of 7-[2- (m-chlorophenylthio)acetamido]cephalosporanic acid and 0.104 g (0, 9 millimoles) of 1-methyl-1H-tetrazolylthiol-5 are reacted in 10 ml of nitromethane under nitrogen at 85°C for 12 hours to obtain 3-[(1-methyl-1Htetrazolyl- 5)thiometyIo] -7- [2- (m-chlorophenylthio)acetami- doj -cephemo-3-carboxylic acid-4. The identity of the product is confirmed by the CSF spectrum <5 3.6(s, 2, 2—CH2) 3.75 (s, 2, —CH2CONH—), 3.9 (s, 3, —CH3 from tetrazolium), 4.4(s, 2, 3 —CH2S—), 5.0(d, 1, C6—H, J=5Hz), 5.8(q 1, C7—H, J=4Hz), 7.15(m, 4, ^ phenyl protons) , 7.7 (d, 2—CH2CONH—, J=8Hz) and 8.5(s,l,COOH). Example XC. Preparation of [(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-[2-(phenylthio)acetamido]-cefemo-3-carboxylic acid in nitromethane. 55 0.422 g (1 mmol) of 7-[2-(phenylthio)acetamido]-cephalosporanic acid and 0.122 g (1.05 mmol) of 1-methyl-1H-tetrazolothiol-5 are reacted in 10 ml of nitromethane, at a temperature of 85 ° G, under nitrogen for 12 hours. [(1-matyl-1H-tetrazolyl-5)thiomethyl]-7-[2-(phenylthio)acetamido]-cefemo 1-carboxylic acid is obtained. Identity the product is confirmed by the CSF spectrum <$: 3.7 sol), 4.35 (s, 2.3—CH2S—), 4.9(d, 1, C« —H, J=6Hz), 85 40 5.8(q, 1 , C7—H, J*=4Hz), 7.25(s, 5, phenyl H), 7.7(d, 1, —CH2CONH—, J=8Hz) and 9.4(s, 1, —COOH ).Example XCI. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-[2-(thienyl-2)acetamido]-cefemo-3-carboxylic acid in n-butyl formate. 3.96 g (10 millimoles) of 7-[2-(thienyl-2)acetamido]-cephalosporanic acid and 1.28 g (11 millimoles) of 1-methyl-1H-tetrazolothiol-5 are reacted in 98 ml of n-butyl formate, in temperature 84-86 °C for 43 hours. 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-[2-(thienyl-2)acetamido]-cephemo-3-carboxylic acid-4 is obtained, melting point 167 .5-168°C. The efficiency is 79.5%. The CSF spectrum is identical to the spectrum from Example V. Example XCII. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-[2-(thienyl-2)acetamido]-cefemo-3-carboxylic acid-4 in toluene. The reaction is carried out in the same scale as in Example XCI, except that 150 ml of toluene is used, the temperature is 84-86 °C and the reaction time is 136 hours. The melting point of the product is 163-183.5°C and the yield is 88.5%. The CMR spectrum of the product is identical to the CMR spectrum of Example V. Example XCIII. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)t'omethyl]-7-(HI-butoxycarbonylamino)-cefemo-3-carboxylic acid in nitromethane. 0.372 g (1 mmol) of 7-(HI-butoxycarbonylamino)-cephalosporanic acid and 0.122 g (1.05 mmol) of 1-methyl-1H-tetrazolothiol-5 are reacted in 10 ml of nitromethane at a temperature of 80 ° C for 12 hours. 3-((1-methyl -1H-tetrazolyl-5)thiomethyl]-7-(tert-butoxycarbonylamino)-cefemo-3-carboxylic acid-4 is obtained. The identity of the product is confirmed by the CSF spectrum <5: 1.45) (s, 9, —C(CH3)3), 3.7(s, 2, 2—CH2), 3 95(s, 3, —CH, from tetrazole), 4.4 (s, 2, 3—CH2S—), 5.0(s, 1, Cs—H). 5.6 (s, 2, C7—H and CH2CO—NH) and 13(s, 1, —COOH). Example XCIV. Preparation of 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl] -7- [2-(4-ethyl-2,3-di- ketopiperazinylcarbonylamino) -2- (p-hydroxyphenyl)acetamido] - cefemo-3-carboxylic acid-4. 0.180 g (0.306 mmol) 7-[2-[4-ethyl-2,3- diketopiperazinylcarbonylamino -2- (p-hydroxyphenyl)acetamido]-cephalosporanic acid and 0.0374 g (0.322 mmol) l-methyl -1H-tetrazolothiol-5 is reacted in 6 ml of nitromethane at 80°C for 12 hours. 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-[2-(4-ethyl-2,3-dioketopiperazinylcarbonylamino)-2-)p-hydroxyphenyl)acetamido]-cefemo acid is obtained -3- carboxylic acid-4. The identity of the product is confirmed by the CSF spectrum <5: 1.2 (t, 3, N—CH2CH3), 3.6 (m, 6, 2-CH2, 6—H and N—CH2 CH3 piperazine), 3.9 (m, 2, 5—H piperazine), 3.95(s, 3, —CH3 of tetrazolium), 4.4(s, 2.3—CH2S—), 5.0 (d, 1, G*—H, J=6Hz), 5, 6(d,l,C7—H,J=6Hz), 5.8 (d, 1, CHCONH— —, J=8Hz), 6.8 (d, 2, phenyl H, J=8Hz), 7, 3 (d, 2, phenyl H, J=8Hz), 8.3(d, 1, —CHCONH, J=8Hz) and 9.9(d, 1, —CH(NH)CONH—, J=6Hz) .Example XCV. Preparation of 3-[(1,3,4- thiadiazolyl-2)thiomethyl]-7-[2-(1H-tetrazolyl-1)acetami- to]-cefemo-3-carboxylic acid-4 in acetonitrile. 0.38 g (1 mmol) of 7-[2-(1H-tetrazolyl-1(acetamido]-cephalosporanic acid and 0.15 g (1.27 mmol) of 1,3,4-thiadiazolothiol-2 are reacted in 15 ml of acetonitrile, at reflux temperature under nitrogen for 24122 152 41 hours. 3-[(1,3,4-thiadiazolyl-2)thiomethyl]-7-[2-(1H-tetrazolyl- l)acetamido]-cefemo-3-carboxyl-4. The identity of the product is confirmed by the CSF spectrum <$: 3.74(m, 2, 2—CH2—), 4.48 (q, 2, 3—CH2—S, Jab=14), 5.16 (d, 1, C6—H, J= 5), 5.42 (s, 2, —CH3 from tetrazole), 5.76 (q, 1, C7—H, J6.7=5, J7NH=8), 8.87 (s, 1, ring, tetrazole), 9.40 (s, 1, starting thiadiazole thiol), 9.53 (d, 1 —CH2CONH—, J=8Hz) and 9.57 (s, 1, thiadiazole ring). Example XCVI. Preparation of 3-[(5-methyl-1,3,4-thiadiazolyl-2)thiomethyl]-7-[5-carbomethoxy-5-(2,4-dichlorobenzamidovaleramido]-cefemo-3-carboxylic acid- 4 in 1,2-dichloroethane. 0.3 g (0.5 mmol) 7-[5-carbometcksy-5- (2,4- dichlorobenzamido/valeramido]-cephalosporanic acid and 0.1 g (0.75 mmol) 5-methyl-1,3,4-thiadiazolothiol-2 is reacted in 1,2-dichloroethane at reflux for 16.5 hours to give 3-[(5-methyl-1,3,4- thiadiazolyl-2)thiomethyl]-7-[5-carbometcksy-5-(2,4-dichlorobenzamido/valeramido]-cefemo-3-carboxylic acid-4. Example XCVII. Preparation of the lithium salt of 3-[(1-methyl - 1H- tetrazolyl-5(thiomethyl]-7-[2-(1H-tetrazolyl-1)acetamido]-cefemo-3-carboxylic acid-4 in acetonitrile. 1.91 g (5 millimoles) of 7-[2 acid -(1H - tetrazolUo-1) acetamido]-cephalosporan acid and 0.7 g (6 millimoles) of 1-methyl-1H- tetrazolothiol-5 in 50 ml of acetonitrile are heated at reflux temperature for 24 hours and cooled to room temperature The solvent is removed in a rotary evaporator to approximately 10 ml. 40 ml of ethanol are added and then 0.3 g of lithium hydroxide in 10 ml of methanol. The product, the lithium salt of 3-[(1-methyl-1H-tetrazolyl 5) thiomethyl [-7- [2- (1H-tetrazolyl-1)acetamido]-cephem-3-carboxylic acid, crystallizes. After the reaction, the mixture is stirred for 45 minutes at room temperature, the product is filtered off, washed with ethanol and dried under reduced pressure at 40°C. 1.60 g (72%) of the product are obtained, the identity of which is confirmed by CMR spectrum analysis. Example XCVIII. Preparation of 3-[(5-methyl-1,3,4-thiadiazolyl-2)lyomethyl]-7-(2-formyloxy-2-phenylacetamido)-cefemo-3-carboxylic acid-4 in 1,1-dichloroethane . 4.6 g (8.8 mmol) 7-(2-formyloxy-2-phenyl-acetamido)-cephalosporanic acid and 1.52 g (11.5 mmol) 5-methyl-1,3,4-thiadiazolothiol-2 in 50 ml of 1,2-dichloroethane, heated at reflux for 12 hours and cooled to room temperature. The product is 3-[(5-methyl-1,3,4-thiadiazoliIo-2)thiometyIo]-7-(2-formyloxy-2-phenylacetamido)-cefemo-3-carboxylic acid-4 and is precipitated in the form of a thick paste . The mixture is diluted with an additional 50 ml of 1,2-dichloroethane and stirred for 4 hours at room temperature. The product is filtered off, washed with 1,2-dichloroethane until the filtrate becomes clear and dried under reduced pressure at a temperature of 40-45°C. 2.8 g (63%) of product are obtained, the identity of which is confirmed by CMR spectrum analysis. Example XCIX. Preparation of 3-[(4,5-dihydro-6-hydroxy-4-methyl-5-keto-1,2,4-triazinyl-3)thiomethyl[-7-[2-(1H-tetrazolyl-1) )acetamido]-cefemo-3-carboxylic acid-4 in acetonitrile. 8.9 g (23.2 mmol) 7-[2-(1H-tetrazolyl-1)a-cetamido]-cephalosporanic acid and 4.1 g (25.8 mmol) 4,5-dihydro-6- hydroxy - 4-methyl-5-keto-1,2,4-42 triazinethiol-3 in 200 ml of acetonitrile, heated at reflux for 23 hours and then cooled to room temperature. During the reduction process, the product crystallizes and is filtered off, washed with 50 ml of acetonitrile and dried under reduced pressure at a temperature of 40-50°C. 9.70 g (86.6%) of 3-[(4,5- dihydro-6- hydroxy -4-methyl -5- keto-1,2,4-triazinyl-3)thiomethyl] -7- acid are obtained [2-(1H-tetrazolyl-1)acetamido]-cefemo-3-carboxylic acid-4, the identity of which is confirmed by CMR spectrum analysis. Example C—CXLIV. The method according to the invention involves the following reactions: the sodium salt of 7-(2-sulfo-2-phenylacetamido)-cephalosporanic acid is reacted with 1-methyl-1H-tetra-zolothiol-5 and the sodium salt of 3-[(l - methyl-1H-tetrazolyl-5)thiomethyl]-7-(2-sulfo-2-phenyl-acetamido)-cephemo-3-carboxylic acid-4, 7-[2-(4- pyridylthio)acetamido]-cephalosporanic acid undergoes reaction with 1-methyl-1H-tetrazolylthiol-5 20 to obtain 3-[(1-methyl-1H-tstrazolyl-5)thiomethyl [-7-[2-(4-pyridylthio)acetamido [-cefemo -3-carboxylic-4, 7-[5-carbo-n-butoxy-5-(2,4-dichlorobenzamido)valeramido]-cephalcsporanic acid is reacted with 5-methyl-1,3.4-thiadiazolothiolein -2 and obtains the acid 3-[(5- methyl - l3»^thia*a^iyló-2)thiomethyl] -7-15- car- bo -n- butoxy -5-)(2,4-dichlorobenzamido)valeramido] -cephemo-3-carboxylic acid-4, 7-[5-carbo-n-butoxy-5-(2,4-dichlorobenzamido)valeramido]-cephalosporan acid is reacted with 1-methyl-1H-tetrazolothiol-5 and 3- [(1-methyl -1H- tetrazolyl -5)thiomethyl] -7- [5-carbo-n- butoxy -5- (2,4-dichlorobeDzamido)valeramidc] -cefemo -3- carboxylic acid is obtained -4.35 7-{2-[2-(p-nitrobenzyloxycarbonylamino)thiasclyl-4]-2-(methoxyimino)acetamido}-cephalosporanic acid is reacted with 1-methyl-1H-tetrazolothiol-5 and o- holds 3-[(1-methyl -1H-tetrazolyl-5)ticmethyl]-7-{2-[2-(p-nitrobenzyloxycarbonylamino)thiazolyl-4]-2-(methoxyimino)acetamido}- acid cefemo-3-xylic acid-4, 7-{2-[2-(p-nitrobenzyloxycarbonylamino)thiazo-HIo-4]acetamido}cephalosporanic acid is reacted with 1-methyl-1H-tretrazolothiol-5 and the acid is obtained 3-[(l-methyl-1H-tetrazolyl-5)thiomethyl[-7-{2-[2-(p-nitrobenzyloxycarbonylcamino)thiazolylc-4]acelamidol-ce-femo-3-carboxylic acid 7-[ (2,2,2 - trichlorcetoxy)carbonylamino]-ce- 50 phalosporanic acid is reacted with 6-hydroxypyridazinethiol-3 to obtain 3-[(6-hydroxypyridazinyl-3)thiomyl] -7- [( 2,2,2-trichloroethoxy)carbomythylamino]-cefemo-3-carboxylic acid-4, 7-[2-(tieryl-2)acetamido]-cephalosporan acid reacts with 6-hydroxypyridazinethiol-3 and 3-[(6-hydroxypyridazinyl-3)ticmethyl]-7-[2-(thienyl-2)acetamido]-cefemo-3-carbcylic acid-4 acid is obtained, 7-[(2,2,2 -trichloroethylcarbonylamino]-cephalosporanic acid is reacted with tetrazolo[1,5-b]pyridazinethiol-6 to obtain 3-(tetrazolo[1,5-b]pyridazinyl-6)thiomethyl acid - 7-[(2,2,2-trichloro-ethoxy)carbomylaminc]-cefemo-3-carbylmethyl acid 7-[2-(thienyl-2 (acetamido]-cephalcsporate is reacted with tetrazole [1, 5-b]pyridazinethiol-6es and the acid 3-[(tetrazolo]1,5-b[pyridazinyl-6)122 152 43 thiomethyl[-7-[2-(thienyl-2 (acetamido]-cefemo -3) is obtained -carboxylic-4, 7-[(2,2,2-trichloroethoxy)carbonylamino]-cephalosporanic acid is reacted with the sodium salt of 1-(sulfomethyl)-IH-tetrazolothiol-5 and the sodium salt is obtained 5 3-{[1-(sulfomethyl)-1H-tetrazolyl-5]thiomethyl}-7-[(2,2,2-trichloroethoxy)carbonlamino[-cefemo-3-carboxylic acid-4, 7-[2- (thienyl-2)acetamido]-cephalosporanic acid is reacted with the sodium salt of 1-(sulfomethylHH-tetrazolyl-5) to obtain the sodium salt of 3-{[1-sulfomethyl)-IH-tetrazolyl-5 ] thiomethyl}-7-[2-(thienyl-2)acetamido]-cefemo-3-carboxylic acid-4, 7-I(2f2,2-trichloroethoxy)carbonylamino]-cephalosporanic acid is reacted with 1- [2-(dimethylamino)ethyl]-1H-tetrazolothiol-5 and 3-{[ (1-(2-dimethylamino)ethyl)-1H-tetrazolyl-5 [thio¬methyl}-7-[ (2,2,2-trixMoroethoxy)carbonylcamino]-cefemo-2-carboxylic-4, 7-[2-(thienyl-2)acetamido[-cephalosporanic acid reacts with l-[2-( dimethylamino)ethyl]- -IH-tetrazolylthiol-5 and 3-{[1-(2-dimethylamino(ethyl)-IH-tetrazolyl-5]thiomethyl}-7-[2-(thienyl- -2)acetamido]-cefemo -3-carboxylic-4, 7-[2-(thienyl -2)acetamido]-cephalosporanic acid 25 is reacted with p-methoxybenzenethiol to obtain 3-[(p-methoxyphenayl)thiomethyl acid ]-7-[2-(thienyl-2 acetamido]-cefemo-3-carboxylic-4, 7-[2-(thienyl-2)acetamido]-cephalosporanic acid is reacted with p-chlorobenzenethiol to obtain 3 acid - [(p-chlorofaiyio)thiomethyl]-7-[2-(thienyl-2)acetamido]-cephemo-3-carboxylic-4, 7-[2-(thienyl-2(acetamido]-cephalesporanic acid is reacted with o-toluenethiol and obtain 3-[(o-tolyl)thiomethyl)-7-[2-(thienyl-2)acetamido]-cefemo-3-carboxylic acid-4, 7-[2-(lH -tetrazolyl-1)acetamido]-cephalosporan acid is reacted with 1,3,4-t? adiazolothiol-2 and 3-[(1,3,4-thiadiazolyl-2)thiomethyl]-7- [2-(1H-tetrazolyl-1)acetamido]-cefemo-3-carboxylic acid-4 is obtained, 40 acid 7 -phthalimide-ephaphosporanic acid is reacted with 5-methyl-1,3,4-thiadiazolothiol-2 to obtain 3-[(5-methyl-1,3,4-tadiazolyl-2)thiomethyl]-7-phthalimido- cefemo-3-carboxylic acid-4, 7-(2-hydroxy-3-phenylacetamido)-cephalospora-45 acid is reacted with 5-methyl-1,3,4-thiidiaz3-yl-2 and obtains 3-[( 5-methyl 1,3,4-thiadiazolyl-2)thiomethyl]-7-(2-hydroxy-2-phenylacetamido)-cefemo-3-carboxylic acid-4, 7-(2-acetoxy-2-phenylacetamido)-cephalcspora - 50 new is reacted with 5-methyl*1,3,4*thiidiazolothiol--2 to obtain 3-[(5-methyl-1,2,4-thiadiazolyl-2) thiomethyl]-7-(2) acid -acetoxy-2-phenylacetamido)-cefemo-3-carboxylic acid-4, 7-[2-(trifluoromethylthio)acetamido]-cephalosporic acid is reacted with 1-methyl-1H-tetrazol-thiol-5 and obtains 3-[(1-mctyl-1H-tetrazolyl-5)thiomethyl]-7-[2-(trifluoronethylthio)acetamido]-ce¬ 3-carboxylic acid-4 acid, 7-{2- [2 -(p-nitrobenzyloxycarbonylamino)thia- 60 zoliio-4]-2- (methoxyimino)acetamido}- cephalosporan is reacted with 4,5-dihydro-6-hydroxy-4-methyl-5-keto- 1,2 ,4-triazinethiol-3 and 3* acid is obtained [(4,5-dihydro -6- hydroxy -4- methyl -5-keto-1,2,4- triazinyl-3)thiomethyl] -7- {2- [2-(p-nitrobenzyloxycarbonylamino)thiazolyl-4]-2-(methoxyimino)acetamido}-ce-femo-3-carboxylic acid-4, 7-{2-[2-(p-nitrobenzyloxycarbonylamino)thia - zolyl-4]acetamido}-cephalosporanic acid is reacted with 1-[2-(dimethylamino)ethyl]-IH- tetrazolothiol-5 to obtain 3-{[l-(2-)dimethylamino(ethyl)- 1H- tetrazolyl-5]thiomethyl}-7-{2-[2-(p-nontrobenzyloxycarbonylamino)thiazolyl-4]acetamido}-cefemo-3-carboxylic acid-4, 7-{2-[o-(III) -n.-butoxycarbonylaminomethyl)phenyl]acetamido{- cephalosporanic acid is reacted with tetrazolo[1,5-b]pyridazinethiol-6 to obtain 3-[(tetrazolo]1,5-b[pyridazinyl-6)thiomethyl] acid - 7-{2-[o-III-rz,- butoxycarbonylaminomethyl)phenyl[acetamido}-cephemo-3-carboxylic-4, 7-(2-formyloxy-2-phenylacetamido)-cephalosporic acid is reacted with sodium salt 1-(sulfomethyl)-1K-tetrazolothiol-5, and 3-{[1-(sulfomethyl)-1H-tetrazoiyl-5[thiomethyl]}-7-(2-formyloxy-2-phenylacetamido)- cefemp -3-carboxylic acid-4, 7-(2-hydroxy-2-phenylacetamido)-cephalosporanic acid is reacted with sodium salt of 1-(sulfomethyl)-1H-tetrazolothiol-5 and 3-{[1-(sulfomethyl)- 1H-tetrazolyl-5]thiomethyl}-7-(2-hydroxy-2-phenyl-acetamido)-cephemo-3-carboxylic-4, 7-[2-(thienyl-2)acetamido]-cephalosporanic acid is reacted with oxazolethiolcm-2 and 3-[(oxazolyl-2)thiomethyl]-7-[2-(thienyl-2)acetamido]-cefemo-3-carboxylic acid-4 acid is obtained, 7-(2-formyloxy-2-phenylacetamido) )-cephalosporic acid is reacted with 1-(carbexymethyl)-IH-tetrazolylthiol-5 to obtain 3-{[1-(carboxymethyl)-IH-tetrazolyl-5]thiomethyl}-7-( 2-formyloxy-2-phenylacetamclo)-cephemo-3-carboxylic acid-4, 7-[2-(trifluoromethylthio)acetamido]-cephalosporanic acid is reacted with 1-methyl-1H-tetrazolothiol to obtain 3-[acid (1-methyl-1H-tetrazoyl-5)thiomethyl]-7-[2-(trifluoromethylthio)acetamido]-cefemo-3-carboxylic acid-4. 7-[2-(cyanomethylthio)acetamido]-cephalosporanic acid is reacted with 1-methyl-IH-tetrazolothiol-5 to obtain 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl] acid -7- [2-(cyanomethylthio)acetamido]-cefemo ^-carboxylic acid-, 7-methoxy -7- [2- (cyanomethylthio)acetamido]-cephalosporanic acid is reacted with 1-methyl -1H-tetrazolothiol- 5 and obtains 3-[(1-methyl-1H-tetrazolyl-5)thiomethyl]-7-methoxy-7-[2-(cyanomethylthio)acetamido]-cefemo-3-carboxylic-4 acid 7- [2- ( o-benzoylaminomethylphenyl)acetamido]-cephalosporanic acid is reacted with 1-(carboxymethyl)-1H-tetrazolylthiol-5 to obtain 3-[(1-carboxymethyl-1H-tetrazolyl-5)thiomethio]-7- [2 -(o-benzoyl-aminomethylphenyl)acetamido]-cefemo-3-carboxylic-4, 7-(2-ureido-2-thienylacetamido)-cephalosporanic acid is reacted with 1-methyl-1H-tetrazolothiol-5 and obtains 3- [(1-methyl -IH- tetrazolyl-5)thio- methyl] -7-(2-ureido -2- thienylacetamido)-cefemo -3- carboxylic acid-4, 7- [2-(2- aminothiazolyl-4)-cephalosporacetamide is reacted with 1-[2-(dimethylamino)ethyl]-1H-tetrazolothiol-5 to obtain 3-{ [1-(2-dimethylaminoethyl) - IH-tetrazolyl-5]thiomethyl}-7-[2-(2-aminotiazolyl-4)acetamido]-cephalosporanic acid, 7-(5-benzoylamino-5-carboxyvaleramido)-ce-122 152 45 phalosporanic acid is reacted with 4 ,5-dihydro-6-hydroxy-4-methyl-5-keto-1,2,4-triazinethiol-3 and [(4,5-dihydro-6-hydroxy-4-methyl- 5-keto-1,2,4-triazinyl-3)thiometyIo]-7-5-benzoyl- amino -5-carboxyvaleramido)-cefemo -3- carboxylic acid-, 7- (5-benzoylamino -5- carboxyvaleramido)- cephalosporanic acid is reacted with 1-methyl- 1H- 1,2,3- triazolothiocm-5 to obtain 3-[(1-methyl -1H- 1,2,3-triazolyl-5)u'omethyl] acid -7-(5-benzoylamino -5-carboxylamido)-cephemo-3-carboxylic-4, 7- (5- benzotlamino -5- carboxyvaleramido)-cephalosporanic acid is reacted with 1-(carboxymethyl)- lH -tetrazolothiol-5 and obtain 3-[(1-carboxymethyl-1H-tetrazolyl-5)thiomethyl]-7-(5-benzoylcamino-5-carboxyvaleramido)-cefemo-3-carboxylic acid-4, acid 7-(5-benzylamino-5-carboxyvaleramido)-cephalosporanic acid is reacted with 5-methyl-1,3,4-oxadiazolothi-2 to obtain 3-[(5-methyl-1,3, 4- bksadiazollo-2)tiomttlcl -7-(5-benzoylamino -5-carboxyvaleramidbcefemb *3-carboxylic acid-4, 7-(5-benzoflamino *5* carboxyvaleramido)-ce- phalosporan acid is reacted with 1-benzyl -1H-tetrazolothiol-5 And you get 3^[(£berizoiib -1H- tetrazolyl-5)ticmethyl] -7- (5-benzoylamino -5-carbclreywalefaniido)-cephalosp©ranic acid, °5 7- (5-benzofloamino-5-carboxyvaleramidb)-cephalosporanic acid is reacted with thiourea to obtain 3-amidinothiomethyl-7-(5-benzoylamino-5-carboxyvaleramido-cephcmo-3-carboxylic acid-4, 7-methoxy acid -7- (5-benzoylamino -5-carboxyvaleramido)-cephalosporants are reacted with 1-methyl-1H-tetrazolothio-5 to obtain 3-[(1-methyl-1H-tetrazolium-5)thiomethyl] acid - 7- methoxy -7-(5- benzoyl-amino -5-carboxyvaleramido)-ceremo -3- carboxylic-4, 7-methoxy -7- (5- benzoylamino -5-carboxyvaleramido)-cephalosporanic acid is reacted with 5-methyl-1,3,4-thiadiazolothiol-2 and 3-[(5-methyl-1,3,4-thiadiazolyl-2)thiomethyl-7-methoxy-7-(5-ben¬) acid is obtained zoylamino-5-carboxyvaleramido)-cefemo-3-carboxylic-4, 7-methoxy-7-(5-benzoylamino-5-carboxyvaleramido)-cephalcsporanic acid is reacted with 4,5-dihydrogen-6 - hydrcksy -4- methyl -5- keto -1,2,4- triazine-thiol-3 and 3- [(4,5-dihydro -6- hy¬hydroxy -4- methyl -5-keto- 1,2,4-triazinyl-3)trcmetyIc] -7- methoxy -7-(5-benzoylamino -5-carboxyvaleramido) - cefemo -3-carboxylic acid-4, 7-methoxy -7- (5-benzoylamino -5) - carboxyvaleramido)-cephalosporanic acid is reacted with thiourea to obtain 3-amidinothiomethyl-7-methoxy-7-(5-benzoylamino-5-carboxyvaleramido)-cephemc-3-carboxylic acid-4, acid 7 -(5-butoxycarbcnylcsmino -5-kaibcksywaIeramido) -3- carbamyloxymethylcephemo -3- carbcsyl-4 is reacted with thiourea to obtain 3-amidinothiomethyl -7-(5-butoxycarbonylamino -5-carboxyvaleramido)-cefemo acid -3-carboxylic acid-4, 7- (5-butoxycarbonylamino -5-carboxyvaleramido) -3-carbamyloxymethylcefemo -3- carboxylic acid is reacted with 1-methyl -1H-tetrazolothiol-5 and the acid is obtained 3- [(1-methyl -1H- tetrazolyl -5)ticmethylol -7-(5-butoxycarbonylamino -5- carbcyvaleramido)-cefemo -3-carboxylic acid-4, 7-(5-butoxycarbonylamino -5- carboxyvaleramido) -3-carbamyloxymethylcefemo-3-carboxylic acid-4 is reacted with 5-methyl-1,3,4-thiadiazolyl-2 to obtain 3-[(5-methyl-1,3,4-thiadiazolyl) acid «2) thiomethyl]-7-(5- butoxycarbonylamino-5-carboxy- valeramidocephem-3-carboxylic acid-4, 5 reaction with 1-(carboxymethyl)-1H- tetrazolothiol-5 to obtain 3- [(1-carboxymethyl -1H- tetrazolyl-5)thiomethyl] -7- (5-butoxycarbonylamino~5-10 carboxyvaleramido)- cephemo-3-carboxylic acid-4. Patent claims 1. Method for preparing derivatives of 3-(thiomethyl)cephalosporins of the general formula 1, in which R is a group of formula 2, in which each R4 is independently a hydrogen atom, an alkyl group with 1-4 carbon atoms, a group nyl alkyl with 2-3 carbon atoms, cyclohexyl or phenyl or R13 represents a group of the formula 3, an alkyl group with 1-4 carbon atoms, a group of the formula 4 or a group of the formula 5, in which each R5 is independently an alkyl group with 1-4 carbon atoms, an alkoxy group with 1-4 carbon atoms, a halogen atom, a hydroxyl, nitro, cyano, tethanesulfonamide or trifluoromethyl group, 25 fcu group of formula 14, optionally substituted, a tetra- or teto-terminal tiefero-aromatic ring containing a total of 1-4 heteroatoms in combinations of 1 nitrogen atom and O or 1 oxygen or sulfur atom, 2 nitrogen atoms and 1 oxygen or sulfur atom, 3 nitrogen atoms and 0 or 1 oxygen atom or 4 nitrogen atoms, with all remaining ring atoms being carbon atoms, or R < denotes a moiety forming together with the moiety of formula 14 a 2-benzoxazolyl, 2-benzimidazolyl, 2-benzothiazolyl radical or a radical of formula 15, Rl denotes a hydrogen atom or a methoxy group, and R* denotes a phthalmido, succinimide group, a group of the formula 6, in which L is a hydrogen atom or a nitroso group, or R2 is a group of the formula R3—.C(=*0)-^NH—, in which R3 is a hydrogen atom, an alkyl group with 1-6 carbon atoms, a group -CH2-chloroalkyl group with 1-3 carbon atoms in the alkyl part, -CH2-fluoroalkyl group with 1-3 carbon atoms in the alkyl part, cyanoalkyl group with 1-4 carbon atoms, hydroxyalkyl group with 1-4 a-45 carbon atoms, p-nitrobenzyloxy, tert-butoxy, 2,2,2-trichloroethoxyIcwa or R3 denotes a 4-keto-4-carboxybutyl group, 3-carboxypropyl pyl group, a group of formula 7, in which a and a1 are the same or different and denote a hydrogen atom, an alkyl group with 1-4 carbon atoms, an alkoxy group with 1-4 carbon atoms, a halogen atom or a hydroxyl group, Z denotes oxygen or sulfur and m denotes the number 0 or 1, or R3 denotes a group with the formula P -CH(Q)-^, in which P is a 2-thienyl, 3-thienyl or phenyl group of the formula 8, in which a and a1 have the same meanings, and Q is a hydroxyl, formyl-xyl, acetoxy, carboxyl group of the formula —C(—0)~- O—A2, in which A2 is a diphenylmethyl, p-nitrobenzyl, benzyl, 2,2,2-trichloroethylamine, tert-butyl or p-methoxybenzyl group or Q is a sulfone group, acylamino group with the formula —NH—C(=0) ~T, in which T is a group with the formula —NH—C(=* N)—NH2, N(R?)—C(=0)—R», ~N (R*)—C)—CH= =CHR9or T denotes a group of the formula 9, 10, 11 or 12, in which R7 denotes a hydrogen atom or an alkyl group with 1-3 carbon atoms, R8 denotes a phenyl group, chlorine-122 152 47 Cofelliowa, Furyl, methylaminic, dual-methylaminate, ethillaminal, two-ethyllamine, methylethylaminate, propyllaminic, dual-cropylamine, twoisopropyl-amino, phenylamine or two-asyllamic, r* R10 denotes a hydrogen atom, an alkyl group with 1-3 carbon atoms or a methylsulfonyl group, R" denotes an ethylene, trimethylene or vinylene group and p denotes the number 2 or 3, or R3 denotes a group of the formula 13 or a group of the formula 13 , in which the OH group is replaced by the group —OCHj or the group —OC (=0)CH3, wherein P' in formula 13 has the meaning given above for P or represents a 2-furyl group, or R3 represents a group of the formula V—S( 0)n—CH2—, where V is a group of the formula —CFs or —CH2—X, where X is a hydrogen atom, a methyl group, a —CF3, CN or —Nj group and n is the number 0, 1 or 2, or R3 is a group of the formula Y—CH2, in which Y is a 2-thienyl, 3-thienyl, 2-furyl, 2-oxazolyl, 2-thiazolyl, 1-tetrazolyl, 1-benzotriazolyl, 2-oxazolyl- thio, 2-thiazolylthio, 1,2,3-triazolyl-5-thio, 1,3,4-triazolyl-2-thio, 1,3,4-thiadiazolyl-2-thio, 5-methyl-1,3, 4-thiadiazolyl-2-thio, 1,2,4-thiadiazolyl-5-thio, 3-methyl-1,2,4-thiadiazolyl- 5-thio, 1,2,5-thiadiazolyl-3-thio, 1, 3,4-Oxadiazolyl-2-thio, 5-methylIo-1,3,4-oxadiazolyl-2-thio, 1-methyl-tetrazolyl-5-thio, pyridiothio, 4-cyano-1,2,3-triazolyl- 1 or 3-cyano-1,2,4-triazolyl-1, according to which the compound of formula 16, in which R1 and R2 have the above-mentioned meanings and R means alkyl group with 1-3 carbon atoms, cycloalkyl group with 4-5 carbon atoms ,amine, mono- or di(alkyl)amine with 1-3 carbon atoms in the alkyl radical - the group of formula 17, 18 or 19 is reacted in the presence of an organic solvent with a sulfur nucleophilic compound of the formula R"-S-R14 , wherein R13 has the meaning given above and R" represents a hydrogen atom, or if R13 represents a methyleneamino group, and only then, R" together with R13 forms a thiourea, except that the reaction is carried out under anhydrous conditions. 2. The method according to claim 2, characterized in that the reaction is carried out at a temperature of 50-140°C. 3. The method according to claim 2, characterized in that the reaction is carried out at a temperature of 70-120°C. 4. The method according to claim 2. 1 or 2 or 3, characterized in that the solvent used is a hydrocarbon, an alcohol, an amide, a ketone, a carboxylic acid, a carboxylic acid ester, a halogenated hydrocarbon, a nitro compound, a nitrile or a ticether. 5. The method according to claim 4, characterized in that the solvent is acstonitrile, 1,2-dichloroethane, methylene chloride, propionitrile, nitromethane, nitroethane, acetic acid, isopropyl acetate, butyl acetate, methyl isobutyl ketone, fluorobenzene, methyl ethyl ketone, 1,1, 2-trichloroethane, chloroform, benzene, carbon tetrachloride, isopropanol, nitrobenzene, propylene carbonate, ethylene carbonate, 2-nitropropene, or n-butyl formate. 6. The method according to claim 1, characterized in that 7-[2-(1H-tetrazolyl-1)-acetamido]-cephalosporanic acid is reacted with 5-methyl-1,3,4-thiadiazolothiol-2 to obtain acid 3 - [(5-methyl-1,3,4-thiadiazolyl-2)-thiomethyl]-7-[2-(1H-tetrazolyl-1)acetamido]-cefemo-carboxylic acid. 48 7. The method according to claim 48. 1, characterized in that 7-(2-formyloxy-2-phenylacetamido)-cephalosporanic acid is reacted with 1-methyl-1H-tetrazolyl-5 to obtain 3-[(1-methyl -1H-tetrazolyl - 5)-thiomethyl]-7- » (2-formyloxy -2-phenylacetamido)-cefemo -3- carboxy- |Owy-4. 8. The method according to claim 1, characterized in that 7-[2-1H-tetrazolyl-1)acetamido]-cephalosporanic acid is reacted with 1,3,4-thiadiazolothiol-2 to obtain 3-[(1,3,4 -thiadiazolyl-2)thiomethyl]-7-[2-(1-tetrazolyl-1)acetamido]-cefemo-3-carboxylic acid-4. 9. The method according to claim 1, characterized in that 7-(2-hydroxy-2-phenylacetamido)-cephalosporanic acid is reacted with 1-methyl -1H-tetrazolothiol-5 to obtain 3-[(1-methyl -1H -tetrazolyl-5)-thiomethyl]-7-(2-hydroxy-2-phenylacetamido)-cefemo-3-carboxyl-4. 10. A method for preparing derivatives of 3-(thiomethyl-cephalosporins of the general formula 1, in which R" is a group of formula 2, in which each R4 is independently a hydrogen atom, an alkyl group with 1-4 carbon atoms, an alkenyl group with 2- 3 carbon atoms, a cyclohexyl or phenyl group or R13 represents a group of formula 3, an alkyl group of 1-4 carbon atoms, a group of formula 4 or a group of formula 5, wherein each R5 is independently an alkyl group of 1-4 carbon atoms , an alkoxy group with 1-H4 carbon atoms, a halogen atom, a hydroxyl, nitro, cyano, methanesulfonamide or trifluoromethyl group, q is 0, 1 or 2, and R6 is a moiety forming together with the moiety of formula 14 optionally substituted a five- or six-membered heteroaromatic ring containing a total of 1-4 heteroatoms in combinations of 1 nitrogen atom and 0 or 1 oxygen or sulfur atom, 2 nitrogen atoms and 1 oxygen or sulfur atom, 3 nitrogen atoms and 0 or 1 oxygen atom, or 4 α atoms - gold, where all the remaining atoms of the ring are carbon atoms or R6 is a group forming together with the group of formula 14 a 2-benzoxazolyl, 2-benzothiazolyl, 2-benzimidazolyl radical or a radical of formula 15, R1 is a hydrogen atom or a group methoxy, and R2 is a group of the formula R3—C(=0)——NH—, wherein R3 is a group of the formula P—CH(Q)— wherein and a1 are the same or different and denote a hydrogen atom, an alkyl group with 1-4 carbon atoms, an alkoxy group with 1-4 carbon atoms, a halogen atom or a hydroxyl group, and Q denotes a group of the formula Me—O—SO2—, in which Me is an alkali metal atom 50 or an acylamino group of the formula -NH-C(=0)-T, in which T is an amino group according to which the compound of formula 16, in which R1 and R2 have the meanings given above, and R is an alkyl group with 1-3 carbon atoms, an amine mono- or di(alkyl)amine with 1-3 carbon atoms in the alkyl radical or a group of the formula 17, 18 or 19, is reacted in the presence of an organic solvent with a nucleophilic sulfur compound of the formula R13 —S—R14, in which R1J has the above-mentioned meaning and R" is hydrogen 60 or if R13 is a methyleneamino group and only then, R14 together with R13 forms a thiourea, characterized in that the reaction is carried out under anhydrous conditions. 122 152 R1 COOH \^& pattern1 +\, q pattern 2 pattern 4 pattern 5 Oh-? ^ CHb tH3 W20r 7 formula6 ° s^. f(, o °1 JLf formula 8 V*0 tfi^A n D10 \ kl/~u formula 10 formula 9 plO122 152 (OH), O formula 11 1)I-0H P- C-C- II formula 13 W* ? -c oR1 k/S formula 12 formula 14 f-r5 ^Ny-CHjOCOR formula 15 COOH formula 16 -C"CHOOH -OCH OCH, ÓCH3 formula 17 -C-CH^yOSOsH OCH3 formula 19 OH OH formula 18122 152 ^CH3 - — S^k^CHs HS- formula 20 formula 21 0 (^-CH-C-NH -rf^ N—N formula 22 C00H U ^CH-C-NH-r^^ N-i^J OCHO 0^No. CH2_S^ N^ COOH X, formula 23 un3 r^=y formula 24 COOH122 152 l)Ms| -S.NH, COOH formula 27 CH2-CH2-N(CH3)2122 152 O {^CH2CNH-pTS 000.4 CH2COOH -i—(^ U—H -. My-cH2-sX^ formula 28 O OCI-fa NCCH^Cr^CNHffs^, N-N nM^CH2-S"VN &'y ^2 o-y. formula 29 o COOH CH3 NCCHSC^CNH-r^ S N-M COOH CH, formula 30122 152 _ O ( VcH-CNH^h rHf OH O' CH2-S^ tf**1 cksoh formula 31 COOH formula 32 o if^CH-CNH-rY^ *t~y ^ 0^CH2-SY c=0 ^ CH3 ^IH2 formula 33 H HO^iCH- pattern 3^ LDD Z-d 2, «. U68/I400y« 3, n. 85+20 copies Price PLN 100 PL PL PL PL PL

Claims (10)

1. Patent claims 1. Method for preparing derivatives of 3-(thiomethyl)cephalosporins of the general formula 1, in which R is a group of formula 2, in which each R4 is independently a hydrogen atom, an alkyl group with 1-4 carbon atoms , an alkyl group with 2-3 carbon atoms, cyclohexyl or phenyl or R13 represents a group of the formula 3, an alkyl group with 1-4 carbon atoms, a group of the formula 4 or a group of the formula 5, in which each R5 represents an independently group alkyl group with 1-4 carbon atoms, alkoxy group with 1-4 carbon atoms, halogen atom, hydroxyl group, nitro, cyano, tethanesulfonamide or trifluoromethyl group, 25 a means the number 0,1 or 2, and R" means a group forming connected with: fcu grouping of formula 14, optionally substituted, tetra- or teto-terminal ring of tiefero-aromatics containing a total of 1-4 heteroatoms in combinations of 1 nitrogen atom and O or 1 oxygen atom or sulfur sulfur atom, 2 nitrogen atoms and 1 oxygen or sulfur atom, 3 atoms nitrogen and 0 or 1 oxygen atom or 4 nitrogen atoms, all remaining atoms of the ring being carbon atoms, or R< is a moiety forming together with the moiety of formula 14 the radical 2-benzoxazolyl, 2-benzimidazolyl, 2 -benzothiazolyl or a radical of the formula 15, Rl is a hydrogen atom or a methoxy group, and R* is a phthalmido, succinimide group, a group of the formula 6, in which L is a hydrogen atom or a nitroso group or R2 is a group of the formula R3-.C( =*0)-^NH-, 40 in which R3 is a hydrogen atom, an alkyl group with 1-6 carbon atoms, a -CH3-chloroalkyl group with 1-3 carbon atoms in the alkyl part, a -CH2-fluoroalkyl group with 1-3 carbon atoms in the alkyl part, a cyanoalkyl group with 1-4 carbon atoms, a hydroxyalkyl group with 1-4 carbon atoms, p-nitrobenzyloxy, tert-butoxy, 2,2,2-trichloroethoxyhydroxy or R3 represents a group 4-keto-4-carboxybutyl, 3-carboxypropyl, a group of the formula 7, in which a and a1 are the same or different and denote a hydrogen atom, an alkyl group with 1-4 carbon atoms, an alkoxy group with 1-4 carbon atoms, a halogen atom or a hydroxyl group, Z stands for oxygen or sulfur and m stands for 0 or 1, or R3 stands for a group of the formula P-CH(Q)-^, in which P stands for a 2-thienyl, 3-thienyl or phenyl group of formula 8, in which a and a1 have the same meaning, and Q denotes a hydroxyl, formyloxy, acetoxy, carboxyl group with the formula —C(—0)~- O—A2, in which A2 denotes a diphenylmethyl, p-nitrobenzyl, benzyl group, 2,2,2-trichloroethylamine, tert-butyl or p-methoxybenzyl or Q is a sulfonic acid group, an acylamino group with the formula —NH—C(=0) ~T, in which T is a group with the formula —NH—C (=* N)—NH2, N(R?)—C(=0)—R», ~N(R*)—C)—CH= =CHR9or T denotes a group of the formula 9, 10, 11 or 12, in which R7 is a hydrogen atom or an alkyl group 65 with 1-3 carbon atoms, R8 is a phenyl group, chlorine-122 152 47 cophenyl, furyl, methylamino, dimethylamino, ethylamino, diethylamino, methylethylamino, propylamino, dipropylamino, diisopropylamino , phenylamino or diphenylamino, R* means a hydrogen atom, an alkyl group with 1-4 carbon atoms or a phenyl group, R10 means a hydrogen atom, an alkyl group with 1-3 carbon atoms or a methylsulfonyl group, R" means an ethylene group, trimethylene or vinylene and p is the number 2 or 3, or R3 is a group of the formula 13 or a group of the formula 13 in which the OH group is replaced by the —OCHj group or the —OC (=0)CH3 group, wherein P' in formula 13 has the meaning given above for P or represents a 2-furyl group, or R3 represents a group of the formula V—S(0)n—CH2—, in which V represents a group of the formula —CFs or —CH2—X, wherein means a hydrogen atom, a methyl group, a group -CF3, CN or -Nj and n means the number 0, 1 or 2, or R3 means a group with the formula Y-CH2, in which Y means a 2-thienyl, 3-thienyl group, 2 -furyl, 2-oxazolyl, 2-thiazolyl, 1-tetrazolyl, 1-benzotriazolyl, 2-oxazolylthio, 2-thiazolylthio, 1,2,3-triazolyl-5-thio, 1,3,4-triazolyl -2- thio, 1,3,4-thiadiazolyl-2-thio, 5-methyl-1,3,4-thiadiazolyl- 2-thio, 1,2,4-thiadiazolyl-5-thio, 3-methyl-1 ,2,4-thiadiazolyl-5-thio, 1,2,5-thiadiazolyl-3-thio, 1,3,4-oxadiazolyl-2-thio, 5-methylIo-1,3,4-oxadiazolyl-2-thio , 1-methyl-tetrazolyl-5-thio, pyridiothio, 4-cyano-1,2,3-triazolyl-1 or 3-cyano-1,2,4-triazolyl-1, according to which the compound of formula 16, in which R1 and R2 have the meanings given above and R stands for an alkyl group with 1-3 carbon atoms, a cycloalkyl group with 4-5 carbon atoms, an amino group, one or two (alkyl) amino groups with 1-3 carbon atoms in the alkyl radical - a group of formula 17 , 18 or 19 are reacted in the presence of an organic solvent with a sulfur nucleophilic compound of the formula R"—S—R14, in which R13 has the meaning given above and R" represents a hydrogen atom, or if R13 represents a methyleneamino group, and only then "R" together with R13 forms thiourea, except that the reaction is carried out under anhydrous conditions. 2. The method according to claim 2, characterized in that the reaction is carried out at a temperature of 50-140°C. 3. The method according to claim 2, characterized in that the reaction is carried out at a temperature of 70-120°C 4. The method according to claim 1 or 2 or 3, characterized in that the solvent used is a hydrocarbon, an alcohol, an amide, a ketone, a carboxylic acid, a carboxylic acid ester, a halogenated hydrocarbon, a nitro compound, a nitrile or a ticether. 5. The method according to claim 4, characterized in that the solvent used is acstonitrile, 1,2-dichloroethane, methylene chloride, propionitrile, nitromethane, nitroethane, acetic acid, isopropyl acetate, butyl acetate, methyl isobutyl ketone, fluorobenzene, methyl ethyl ketone, 1,1, 2-trichloroethane, chloroform, benzene, carbon tetrachloride, isopropanol, nitrobenzene, propylene carbonate, ethylene carbonate, 2-nitropropene, or n-butyl formate. 6. The method according to claim 1, characterized in that 7-[2-(1H-tetrazolyl-1)-acetamido]-cephalosporanic acid is reacted with 5-methyl-1,3,4-thiadiazolyl-2-thiol to obtain acid 3 - [(5-methyl-1,3,4-thiadiazolyl-2)-thiomethyl]-7-[2-(1H-tetrazolyl-1)acetamido]-cefemo-carboxylic acid. 487. 7. The method according to claim 1, characterized in that 7-(2-formyloxy-2-phenylacetamido)-cephalosporanic acid is reacted with 1-methyl-1H-tetrazolyl-5 to obtain 3-[(1-methyl -1H-tetrazolyl - 5)-thiomethyl]-7- » (2-formyloxy -2-phenylacetamido)-cefemo -3- carboxy- |Owy-4. 8. The method according to claim 1, characterized in that 7-[2-1H-tetrazolyl-1)acetamido]-cephalosporanic acid is reacted with 1,3,4-thiadiazolothiol-2 to obtain 3-[(1,3,4) -thiadiazolyl-2)thiomethyl]-7-[2-(1-tetrazolyl-1)acetamido]-cefemo-3-carboxylic acid-4. 9. The method according to claim 1, characterized in that 7-(2-hydroxy-2-phenylacetamido)-cephalosporanic acid is reacted with 1-methyl -1H-tetrazolothiol-5 to obtain 3-[(1-methyl -1H -tetrazolyl-5)-thiomethyl]-7-(2-hydroxy-2-phenylacetamido)-cefemo-3-carboxyl-4. 10. A method for preparing derivatives of 3-(thiomethyl-cephalosporins of the general formula 1, in which R" is a group of formula 2, in which each R4 is independently a hydrogen atom, an alkyl group with 1-4 carbon atoms, an alkenyl group with 2- 3 carbon atoms, a cyclohexyl or phenyl group or R13 represents a group of formula 3, an alkyl group of 1-4 carbon atoms, a group of formula 4 or a group of formula 5, wherein each R5 is independently an alkyl group of 1-4 carbon atoms , an alkoxy group with 1-H4 carbon atoms, a halogen atom, a hydroxyl, nitro, cyano, methanesulfonamide or trifluoromethyl group, q is 0, 1 or 2, and R6 is a moiety forming together with the moiety of formula 14 optionally substituted a five- or six-membered heteroaromatic ring containing a total of 1-4 heteroatoms in combinations of 1 nitrogen atom and 0 or 1 oxygen or sulfur atom, 2 nitrogen atoms and 1 oxygen or sulfur atom, 3 nitrogen atoms and 0 or 1 oxygen atom, or 4 α atoms - gold, where all the remaining atoms of the ring are carbon atoms or R6 is a group forming together with the group of formula 14 a 2-benzoxazolyl, 2-benzothiazolyl, 2-benzimidazolyl radical or a radical of formula 15, R1 is a hydrogen atom or a group methoxy, and R2 is a group of the formula R3—C(=0)——NH—, wherein R3 is a group of the formula P—CH(Q)— wherein and a1 are the same or different and denote a hydrogen atom, an alkyl group with 1-4 carbon atoms, an alkoxy group with 1-4 carbon atoms, a halogen atom or a hydroxyl group, and Q denotes a group of the formula Me—O—SO2—, in which Me is an alkali metal atom 50 or an acylamino group of the formula -NH-C(=0)-T, in which T is an amino group according to which the compound of formula 16, in which R1 and R2 have the meanings given above, and R is an alkyl group with 1-3 carbon atoms, an amine mono- or di(alkyl)amine with 1-3 carbon atoms in the alkyl radical or a group of the formula 17, 18 or 19, is reacted in the presence of an organic solvent with a nucleophilic sulfur compound of the formula R13 —S—R14, in which R1J has the above-mentioned meaning and R" is hydrogen 60 or if R13 is a methyleneamino group and only then, R14 together with R13 forms a thiourea, characterized in that the reaction is carried out under anhydrous conditions. 122 152 R1 COOH \^& pattern1 +\, q pattern 2 pattern 4 pattern 5 Oh-? ^ CHb tH3 W20r 7 formula6 ° s^. f(, o °1 JLf formula 8 V*0 tfi^A n D10 \ kl/~u formula 10 formula 9 plO122 152 (OH), O formula 11 1)I-0H P- C-C- II formula 13 W* ? -c oR1 k/S formula 12 formula 14 f-r5 ^Ny-CHjOCOR formula 15 COOH formula 16 -C"CHOOH -OCH OCH, ÓCH3 formula 17 -C-CH^yOSOsH OCH3 formula 19 OH OH formula 18122 152 ^CH3 - — S^k^CHs HS- formula 20 formula 21 0 (^-CH-C-NH -rf^ N—N formula 22 C00H U ^CH-C-NH-r^^ N-i^J OCHO 0^No. CH2_S^ N^ COOH X, formula 23 un3 r^=y formula 24 COOH122 152 l)Ms| -S. NH, COOH formula 27 CH2-CH2-N(CH3)2122 152 O {^CH2CNH-pTS 000.4 CH2COOH -i—(^ U—H -. My-cH2-sX^ formula 28 O OCI-fa NCCH^Cr^CNHffs^, N-N nM^CH2-S"VN &'y ^2 o-y. formula 29 o COOH CH3 NCCHSC^CNH-r^ S N-M COOH CH, formula 30122 152 _ O ( VcH-CNH^h rHf OH O' CH2-S^ tf**1 cksoh formula 31 COOH formula 32 o if^CH-CNH-rY^ *t~y ^ 0^CH2-SY c=0 ^ CH3 ^IH2 formula 33 H HO^iCH- pattern 3^ LDD Z-d 2, «. U68/I400y« 3, n. 85+20 copies Price PLN 100 PL PL PL PL PL