DE2345775C3 - Enamine sulfoxides and process for their preparation - Google Patents

Description

R ¹ CN (II)

wherein R ^{1 has} the same meaning as above, with a sulfoxide of the formula

R ² SiLH ₁ SR ²

! i ο

(111)

wherein the two groups R ^{: have} the same definitions as given above, are reacted in the presence of a metallizing agent and the resulting reaction mixture is treated with a protic material.

The subject of the development are Fnaminsulloxide according to the following general formula (1)

NII ₁

C C

SOR ²

SR ²

worm R 'is an alkyl group having 1 to 3 carbon atoms, a phenyl. Benzyl-, Phenälhyl-, ToIyI-. Halophyl-. Methoxyphenyl group. an alkyl group with 1 to 3 carbon atoms substituted with dimethoxy or di.ilhoxy groups, a monomethoxymethyl or a benzyloxymelhyl group or a dimethoxyphenyl group and the two groups R ² independently of one another are alkyl groups with 1 to 3 carbon atoms. Phenyl, ToIyI and Halophenyigigruppen mean.

The amino sulfoxides of the above formula (I) are very valuable because they are easily converted into various useful ones Connections can be transferred. For example, from the Fnaminosulfoxden various Keto acid derivatives and acylamino acid esters are synthesized, and the compounds so synthesized can be converted further into the corresponding amino acids. The synthesis of these compounds rinsing from the amino sulfoxides is described in detail.

In the above formula 1, R 'preferably denotes Methyl. Ethyl. i-propyl. Dimethoxypropyl. Benzyl. Phenyllithyl. Phenyl. Chlorophenyl. ToIyI. Meihoxyphenyl and or dimethoxyphenyl.

In the above formula I, R ^{2 is} preferably methyl. Ethyl. i-propyl. ToIyI. Chlorophenyl or and

Phenyl.
Typical Fnaminosulfoxydc of the formula I are

following:

l-methylsulfine \ il-methylthio-2-aminopropene.
i-methylsulfinyl-l-methyhhio-2-amino-

3-methyl-1-buien.
l-methylsulnnyl-l-methylthio-2-amino-

2-phenyUithyIen.
l-methylsulfinyl-I-methylthio-2-amino-

3-phenylpropene,
l-methylthio-l- (p-tolylsulunyl) -2-amino-

2-phcnylethylene,
l- (p-chlorophenyl) -sulunyl-l- (p-chlorophenyl | -

thio-2-amino-5,5-dimethoxy-1-pentene.
l-isopropylsulfinyl-l-isopropylithio-2-amino-

5.5-dimethoxy-1-pentene.
l-methylsulfinyl-l-methylthio-2-amino-

5,5-dimethoxy-1 -penlen,
l-methylsulfinyl-l-methylthio-2-amino-

2- (m-tolyl) ethylene,
l-methylsulfinyl-l- (p-tolylthio) -2-amino-

2-phenylene.
1 -Methylsulfinyl-1 -methylthio-2-amino-

4-phenyl-l-butene,
l-methylsulfinyl-l-methylthio-2-amino-

2- (p-methoxyphenyl) ethylene.
l-methylsulfinyl-l-methylthio-2-amino-

2- (p-phenyl) ethylene.

The invention also relates to a process for the preparation of enaminosulfoxides Formula 1. The inventive method is characterized in that a nitrile of the following Formula (II)

R ¹ CN

(ID

wherein R ^{1 has} the meaning given above, with a sulfoxide of the formula (III)

R ² SCIUSR ² (111)

I! '
ο

wherein R ^{2 has} the meaning given above, is reacted in the presence of a metallizing agent or a metalizing agent and the resulting reaction mixture is treated with a specific material.

The nitriles of formula II used as starting materials are connections that are easily accessible. The sulfoxides of the formula HI can easily by oxidation of formaldehyde mercaptals or by converting a. <-! lalogen sulfoxyds with a thiol (cf. US Patent 37 42 066, German Ofl'enlegungsschrift 2130 923) will.

The "Metalalion" is known as a process at which a metal atom is bound to a carbon atom of an Omani molecule. and the me-

• Illierunnmitte! is the reagent that is used in the »Me- • il-ition« "" is used. The use of the Mei'iilieruntismitlels in the method according to the invention causes the replacement of a hydrogen atom in the Methylenu group, which is between the sulfoxide group and the sulfide group in the compound of Formula III is available. by an alkali metal. Suitable metalating agents include, for example, alkali metal hydrides such as sodium hydride and potassium hydride and Omani alkali metal compounds such as Meihvllithfum, Butyllithium, phenyllithium, lithium diisopropylamide and lithium cyclohexylisopropylamide. Of the metalating agents mentioned above, sodium hydride is the cheapest and readily available Grouting, and therefore it is most preferred. Satisfactory results are obtained when around equivalent amount of the metallizing agent. based on that used as starting material Sulfoxide, can be used.

The reaction of the compound of the formula II with that of the formula III in the presence of a Metallierunusmittcls is preferably carried out in an organic solvent. The solvent that should be inert or, in other words, aprolic during the implementation. Examples of such Solvents include tetrahydrofuran. Dioxane. 1'-dimethoxyethane, ether, benzene, toluene, dimethylformamide or and hexamethylphosphoric triamide.

The reaction temperature is not critical, usually Temperatures in the range from 0 to 100 C are selected. At temperatures below 0 C. the reaction rate is slow, and at temperatures above 100 ° C., side reactions can occur.

The reaction time is variable and depends on the type of starting materials and the type of metallizing agent and the reaction temperature used. usually it is in the range from 1 to 50 hours.

After completion of the above reaction, the reaction mixture is coated with a protic material treated, and the F.naminosulfoxyd of the formula 1 according to the invention is obtained in free form. The protic material is with the alkali metal ion, which is from the metallization or metallization

, medium stems, connected, being a hydrogen ion is released and the free enaminosulfoxide is formed. Examples of such protic materials include water, alcohols such as methanol and ethanol, organic carboxylic acids such as acetic acid.

ι aqueous solutions of inorganic acids such as hydrochloric acid and sulfuric acid and aqueous Solutions of ammonium chloride. Of the protic materials mentioned earlier, water is am Easiest available and for the desired purpose

s sufficient. The protic material is sufficient to use in an amount equivalent to that of the plating agent, but the use an excess of protic material gives no adverse effects.

ο The enaminosulfoxide of formula 1 is accordingly the reaction mechanism shown in the following equations:

CH ₁

SOR ²

SR-

Metallizing agent CH

R ¹ CN

C C

NH

R ¹

SOR-

SR ² SOR ²

SR ² NH

R ¹

H, N

C · - C

SOR ²

SR ²

SOR ²

SR ²

SOR ²

SR ²

Examples of the above enamino sulfoxides and processes for their preparation are in the following Examples 1 to 24 are given.

Processes are described below with which the enaminosulfoxides are converted into the corresponding i-keto acid derivatives. << - Acylamino-i / - [alkyl- (or aryU-thioJ-carboxylic acid thiol ester. Acylamino acid esters, fi-thioamino acid derivatives and amino acid derivatives, the specified order being used. In the following fractions, R ¹ and R ² that appear in the chemical formulas have the same definition as given before.

Production of n-keto acid derivatives

If the new enaminosulfoxide ¹ - 'of the formula 1 is acid hydrolyzed, the corresponding K-keto acid derivatives are easily formed. The implementation can be represented by the following equation:

I ₁ N

R ¹

C C

(D

SOR ²

SR ²

O O

I! ^! i

R ¹ C ■■ (■ SR ²

(IV)

(i-Acid derivatives of the formula IV are a group new connections.

The acids that can be used for acidic hydrolysis include mineral acids, organic ones Acids and Lewis acids. Hydrochloric acid and sulfuric acid can be used as mineral acids, as organic acids p-toluenesulfonic acid and acetic acid

and preferably use copper (II) chloride and tin (IV) chloride as Lewis acids. If the acid acts as a catalyst in the hydrolysis, the use of catalytic amounts is sufficient in the case of the mineral acid! and organic acids. ^

The reaction is preferably carried out in a solvent which does not take part in the reaction like water. Tetrahydiofuran or methylene chloride.

The reaction temperature is not critical. The um- ,,, Settlement proceeds smoothly at room temperature, and no special heating or cooling is required, and the desired products are obtained in high yield.

If the above reaction is carried out in the presence of an alcohol (R ³ OH), the α-keto acid derivatives of the formula V are obtained according to the following equations:

Η, Ν SOR ²

C C

R ¹ SR ²

(I)

OO
R ¹ - CC OR ³

(V)

The group R ³ in the formula R ³ OH denotes an alkyl group, preferably an alkyl group having 1 to 4 carbon atoms. It is believed that. Due to the presence of such an alcohol, the K-octo acid derivative of the formula IV. which is formed during the acid hydrolysis of the enaminosulfoxide of the formula 1, reacts further with the alcohol and is converted into a compound of the above formula V.

The .i-keto acid derivatives of the formulas IV and V are valuable as starting materials for various amino acids or heterocyclic compounds. Are these u-octoacid derivatives of the transamination reaction or subjected to fermentation, so can optically active amino acids getting produced. The amino acid can also be prepared by first adding the «i-keto acid derivative converted into oxime derivatives and then reduced this. Are α-keloic acid derivatives implemented, for example with o-Pheiiyicndiamine. so one can obtain heterocyclic compounds.

For the production of u-keto acids various Process proposed, however, the use of a nitrile as a starting material is at all not known. Advantages that are achieved industrially with the new process are remarkable, there the nitriles are readily available cheaply.

Examples of n-ketosliur derivatives of the formula IV and V and processes for their preparation are described in Application Examples 1 and 2 below specified.

Production of

((-Acylamino-!. <- alkyl (or aryl) -thio | -
carboxylic acid thiolesern

If the F.naminosulfoxides of the formula I are reacted with an Acylieriingsmiltel, the en tsn rechen de η α-Ac vlamino-f. (- alkyl! or aryl 1-

₄₀ lhio] -c;: carbonic acid lhiok-ster of the formula V! formed according to the following equation:

NH (OR ⁴

SOR ²

R ⁴ CO '

C C

IV ■ - ('C

R ¹ SR ²

(1)

SR ² SR ²

(Vl)

In the above equation, R ⁴ CO 'denotes the acyl group of the acylating agent. and R ⁴ denotes an alk \ l or aryl group. Acylic agents. which are generally used conveniently in acylation procedures are well known. As typical examples, acid anhydrides such as acetic anhydride or propionic anhydride and acid chlorides such as benzoyl chloride or acetyl chloride can be mentioned.

If appropriate, the reaction is carried out in the presence of a solvent as the reaction medium. If a solid compound is used as the acylic agent, the reaction medium is preferably a solvent in which see the acylic agent solves, used. When a basic compound is present in the reaction system, so one observes. that the compound acts as an acid acceptor and that the reaction is smoother. the However, the presence of such a basic compound is not essential. Examples of suitable basic Compounds include pyridine and acetates or Hydroxides of the alkali metals.

The reaction temperature is not critical. In general, there is special heating or cooling not required, and the implementation can be done at Room temperature. However, if the reaction is very exothermic, depending on the Ar "of the starting material, cooling is preferred.

The thiolesters of the formula VI are new. They have valuable uses as materials for amino acids. The corresponding amino acids can easily be prepared by taking the thiolesians a desulfurization treatment (== desulfurization treatment) subject.

Manufacture of Acvlamino Acid Esters

Acylamino acid esters can be prepared by adding the thiol esters of the formula VI to a reducing Desulfurization enclosure in the presence of an alcohol and an activated transition metal catalyst subject. The mechanism for the formation of the acylamino acid esters of Formula VH can be represented by the following equation:

NIICOR ⁴

NIlCOR ⁴

R ⁵ OM

R ¹ CC

SR-

(VII

(Viii

In the above equation: R ^{5 means} OII

a

Alcohol. And R ⁵ means an alkyl group. preferred

: a lower alkyl group of 1 to 4 carbon atoms.

The activated transition metal catalyst can be Raney nickel or cobalt and Urushibara nickel use what is familiar to those skilled in the art. For example, Raney nickel (W II) is preferred is used because it is easy to manufacture and store. The production of Raney-Nickcl (W 11) will in Org. Synth. Coll. Vol. Ul, 181 (1955).

The above reaction can be carried out in the presence of a stoichiometric amount or a larger amount of an alcohol at a temperature in the range from 0 C to the boiling point of the alcohol. the However, reaction generally proceeds smoothly at room temperature without any particular heating or cooling is required. When the reduction-desulfurization reaction in the absence of the alcohol, but in the presence of a deactivated transition metal (for example deactivated Nickel) takes place, the acylamino acid esters of the formula VIU according to the following equation will be obtained:

NHCOR ⁴

I °

R'-C-C

SR ² SR ²

(Vl)

NHCOR ⁴

R ¹ -C - C

SR ²

(VIII)

The deactivated nickel required for the above procedure suitable is. can be made by taking the activity of Raney nickel or Urushibara nickel reduced. Procedures to reduce activity, are well known per se. For example, the activated nickel can be treated in ethanol, by adding a small amount of hydrochloric acid or chloroform, or it can be dissolved in acetone Heated to reflux. Processes for the production of such deactivated nickel are for example in Chem. Reviews, Vol. 62, 347 (1962).

The reaction is preferably carried out in the presence of a suitable medium. As a medium can one uses organic solvents which are inert in the reaction, such as acetone, alcohol or ether. Although the temperature is not a critical factor in the reaction. is usually beneficial Room temperature used.

The acylamino acid esters of the formulas VIl and VIII can easily be converted into the corresponding amino acids be converted by hydrolysis.

An example of acylamino acid esters and processes for their preparation is given in the application example 3 given.

Manufacture of amino acids
or their esters

If you put the thiolsler of the formula VI. in which R ¹ denotes an unsubstituted or substituted alkyl group, with water or an alcohol of the formula R "OH, in which R ^h denotes a hydrogen atom or an alkyl group, preferably a lower alkyl group having 1 to 4 carbon atoms, in the presence of a base, so the acylamino acid of the formula IX or an ester thereof is formed according to the following equation:

NHCOR ⁴
O

R'-C-C

SR ² SR ²

(VI)

NHCOR ⁴

R "OH

R ¹ - CC

SR ² OR ⁶

(IX)

Suitable bases in the above reaction scheme are ammonia, organic amines such as diethylamine and triethylamine and inorganic bases such as potassium carbonate and alkali hydroxide. If you use an inorganic base, a salt of the desired compound is formed and hence the reaction system becomes preferably neutralized after the reaction. Since the base acts as a catalyst, it is sufficient to use these in catalytic amounts, while the inorganic bases are preferred in the Excess can be used.

It is sufficient to use a stoichiometric amount of water or alcohol. If you use however, an excess, the water and the alcohol can act simultaneously as reactants and serve as the reaction medium. If desired, organic solvents that are opposite to the Reaction are inert, such as chloroform or tetrahydrofuran used simultaneously as the reaction medium will. The temperature is not critical at the time of the reaction and room temperature can be used use. The system can be heated to increase the rate of reaction. It it is usually recommended that the reaction be carried out under reflux of the reaction medium used will.

When the acyl amino acid of the formula IX or an ester thereof, a reducing desulfurization treatment is subjected in the presence of a reducing desulfurizing agent, the Amino acid derivatives of the formula X formed according to the following equation:

NHCOR ⁴

NHCOR ⁴

R ¹ -C -C

R ¹ -C C

SR ² OR "

(IX)

I \

H OR '

(X)

The reducing desulfurizing agent used in the above reaction may be any be of those commonly used in reducing desulfurization treatments. Be Games of this include the aforementioned transition metal catalysts such as Raney nickel and Un shibara nickcl. Thiolate anions such as methyl mercaptk anion and thiophenolate anion, esters of phosphorous Acid and the anion of phosphorous acid.

The reaction is preferably carried out in a solution medium. Examples of suitable solutions medium include water. Acetone, methylene chloride, alcohol and ether. The implementation proceeds b Room temperature, however, it is recommended: warm to the reaction rate? U c high.

709 649/2

If the thiolesters of the formula VI, in which R ^{1 is} an unsubstituted or substituted phenyl group, are reacted with water or an alcohol of the aforementioned formula R ⁶ OH in the presence of a base, the amino acid derivatives of the formula X are formed directly according to the following equation:

NHCOR ⁴

NHCOR ⁴

[
I.
'[
j /
C.
\ O R ⁶ OH R ¹ - -C 'C (X) O SR ² ^ SR ² H OR " (Vl

Preferred bases for the above reaction include inorganic bases such as alkali hydroxides and alkali carbonates and organic bases such as trialkylamine, pyridine, triethylenediamine and tetraalkylammonium hydroxide.

Of the above-mentioned bases, inorganic bases and tetraalkylammonium hydroxide give desired products in salt form, and therefore they are preferably used in an amount larger than the equivalent amount. If the product obtained is in the form of the salt, it can be neutralized with an acid after the reaction, whereby the desired free acid is obtained. If less than the equivalent amount of an organic base is used, in the case of α-amino acid derivatives of the formula VI. where R ² denotes a methyl or ethyl group, κ-thioamino acid derivatives can be used

of formula IX are formed as by-products. To prevent this from happening, at least 5 moles of organic base moles of the starting thiol ester of the formula VI are used. If you use less than 5 moles of organic base, however, the desired amino acid derivatives of the formula X formed selectively when the reaction is carried out in the concomitant presence of a reducing desulfurizing agent such as the aforementioned thiol compounds, for example thiolphenol and alkyl mercaptan, or a window of phosphorous acid.

If an excessive amount of water or alcohol is used as a reactant, so do so this also acts as a reaction medium. If desired, you can connect to the Reaction is inert, such as using chloroform or tetrahydrofuran as the reaction medium.

The reaction proceeds smoothly at room temperature, but the reaction rate can run through Heating can be increased. In general, it is preferred to run the reaction at reflux temperature to perform the reaction medium.

The compounds of formulas IX and X can easily be broken down into the corresponding amino acids Hydrolysis are transferred.

Examples of compounds of the formulas IX and X and processes for their preparation are given in Application Examples 4 and i given below.

The advantageous commercial usability of the compounds according to the invention goes for example from the following Reaction Schemes I and II

Reaction scheme! Amino acid synthesis

reduction

RCN

RCHO

Strecker- NII, reaction |
► RCHCN

NH ₂ SOCH ₃
RC = C

SCH.,
(1-namine sulfoxide)

i! Acvlierunti

hydrolysis

tr
NHAc

R C- C

SCH,

SCH,

NH,

j "

R- CHCO ₂ H (racemic mixture)
Protecting group of the NH _: group

N HAc

-CIICO, !! (racemic mixture)
Splitting up

I ii-Ac_ \ lamino-f.i-alkylthiol-carboxylic acid ester]

method according to the invention known procedure

NH ₂

R ClK. OH
I amino acid ι

D- or 1 -I

'—CN

11 1 12

Reaction scheme 11 Synthesis of D-phenylglycine (starting material for synthetic cephalosporin)

NH ₂ -CHO r -► <f V-CHCN

(Example A-5 71.4%)

') 34-36 "/.

NH, SOCH ₃

SCH ₃

(Example C-IO 88%
NHAc

I ο

(Example E-20 91% NH ₂
<f VC-COOH

ι
i

¹ NHAc

. ι

f "Vc-COOH
H

* NH,
^; VC-COCH

(D-phenylglycine)

■ method according to the invention, total yield 71.4 χ SS> 91 = 57 "o

known process *) yield 34 - 36%
(cf. J. Am. Chem. Soc. 42, 2264-2265 [1920]) (racemic mixture)

(racemic mixture)

SCH ₃

SCH ₃

example 1

1.20 g of methyl methylthiomethyl sulfoxide are in 10 ml of tetrahydrofuran (THFi dissolved. 250 mg of sodium hydride are added to this with ice cooling. The system is then stirred for 30 minutes at room temperature. Then 1.25 ml of isobutyronium are added admitted. Then stir 1? Hours at room temperature, 50 ml of methylene chloride lies and Add 1 ml of water and stir for a further 30 minutes at room temperature. After drying over Glauber's salt the reaction mixture is concentrated under reduced pressure, giving a light yellow, crystalline Product received. Recrystallization (washing) of the product with carbon tetrachloride and cyclohexane gives 682 mg of 1-methylsulfinyl-1-methylthio-2-amino-3-methyl-1-butene as a light yellow solid.

The mother liquor is passed through a chromatography column (silica gel, methylene chloride, ethyl acetate and methanol), 672 my of a mixture of methylmethylthiomethylsulfoxide and I-methylsulfinyl-1-methylthio- 2- amino-3-diethyl-1-butene being obtained as a pale yellow oil. This consists of a mixture of 575 mg of methylmethylthiomethylsulfoxide and 97 mg of l-methylsullinyl-l-meihylthio-2-iini-Γιο-3-nicthyi-l-butene, as the NMR dialysis shows. The latter compound was isolated in 41.7% yield and the conversion was effected; S0.2 "n. Fine sample for analysis was obtained by recrystallizing the product from chloroform-n-hexane.

1 -methylsulfinyl-1 -methylthio ^ -amino-S-methyl-1-butene: mp 145 to 147 ⁰ C (dec.), Colorless crystals..

IR (KBr): 3410, 3250, 3170, 3010, 1620, 1528. KX) O cm " ¹ .

NMR (CDCI ₃ ):. 1.14 D (3H, J = 7 Hz). 1.25 D (3H. J = 7Hz). 3.67 Septctt (IH, J = 7 FIz) 5.33 broad (2H).

Analysis for C ₇ H ₁₅ ONS ₂ :

Calculated ... C 43.49. H 7.82. S 33.17%,: found. . . C 43.26. H 7.54. S 33.38%.

Example 2

1.7Sg methylmethylthiomethylsulfoxide are i: Dissolved 20 ml of THF, to this is added 375 mg of sodium hydride while cooling with ice. and then rühi one 30 minutes at room temperature. Then 1.6 ml isobutyronitrile are used! admitted, and ma stir for 6 hours at room temperature and for 6 hours at S () C. Then add a further 70 ml of methylene chloride and 2 ml of Wa: > he added, and then I hour at room temperature stirred. The reaction mixture we dried over Glauber's salt and diminished hot! Pressure concentrated, with an iiclber solid zi

fl

remains. The solid is washed with carbon tetrachloride-n-hexane. 1.525 g of 1-methylsulfinyll-methylthio-2-amino-3-methyl-1-butene are obtained as a light yellow solid. The washing solutions are concentrated under reduced pressure and chromatographed on a column (Silikagel®, methylene chloride, ethyl acetate and methanol), whereby one 117 mg of methylmethylthiomethylsulfoxide and 480 mg of 1-methylsulfinyl-1-methylthio ^ -amino - ^ - methyl-1-butene receives. The isolated yield is 72.3%. and the conversion is 77.5%.

Example 3

1.31 g of methyl methylthiomethyl sulfoxide are dissolved in 10 ml of THF. The solution will be under Ice cooling 7 ml of n-butyllithium solution (15% strength hexane) was added. The mixture is then stirred for 30 minutes and add 2.0 ml of isobutyronitrile. The mixture is then stirred for 1.5 hours at room temperature, and 50 ml of methylene chloride are added and 3 ml of water and stir for 30 minutes at room temperature, and finally 17 ml of water are added. The reaction mixture is extracted with methylene chloride (3 × 50 ml) with Dried Glauber's salt and concentrated under reduced pressure. The concentrate is subjected to column chromatography (Silikagel ®, methylene chloride, ethyl acetate and methanol), giving 231 mg Methylmethylthiomethylsulfoxide and 343 mg of 1-methylsulfinyl-1 -methylthio ^ -amino-S-methyl-1-butene receives. The yield is 16.9%. and the conversion is 20.4%.

Example 4

4.38 g of methylmethylthiomethylsulfoxide are dissolved in 45 ml of THF, and 900 ml are added to the solution Sodium hydride with ice cooling, and then the system is stirred at room temperature for 1 hour. To Addition of 4 ml of benzonitrile and subsequent stirring for 42.5 hours at room temperature the whole system solidifies. 100 ml of methylene chloride and 3 ml of water are then added, and then stirred for 30 minutes and dried with Glauber's salt. The pale yellow solid that you can find in the following Concentrate obtained under reduced pressure, washed with 100 ml of carbon tetrachloride, 5.158 g of 1-methylsulfinyl-1-methylthio-2-amino-2-phenylethylene are obtained as a light yellow solid. The washing solutions are concentrated under reduced pressure and subjected to column chromatography (SiIi- 5s kagel *. Ethyl acetate and methanol), wherein 1.106 g of a light yellow, oily compound are obtained. According to the NMR analysis, the oily exists Substance from 972 mg of methylmethylthiomethylsulfoxide and 134 mg of 1-methylsulfinyl-1-methylthio- < > o 2-amino-2-phenylethylc; n. The bulge on the latter Connection is 66.0%. and the conversion is 84.8%.

The one -methylsulfinyl-1-amino -methylthioO ^ -phenyläthylcn is purified by recrystallization from <, _s Methylcnchlor-carbon tetrachloride.

1-methylsulfinyl-1-methylthio-2-amino-2-phenyl-ethylene: m.p. 162 to 163 C (dec.). light yellow crystals: IR (KBr): 3360, 3260, 3130, 1617, 1514, 995 cm " ¹ NMR (CDCI ₃ ;: Λ 2.38 S (3 H, 2.57 S (3H), 5.42 slurry (2H) 7.38 S (5H).

Analysis for C ₁₀ H ₁₃ NOS ₂ :

Calculated ... C 52.83, H 5.76, S 28.21%;
Found ... C 52.57, H 5.62, S 28.38%.

Example 5

1.830 g of methylmethylthiomethylsulfoxide are dissolved in 20 ml of THF, and 415 ml are added to the solution Sodium hydride with ice cooling, and then stirred for 90 minutes at room temperature. Subsequently 1.520 g of benzonitrile are added. The system is left at room temperature for 1.5 hours and stirred for 16 hours at 50 ° C., and then 2 ml of water and 70 ml of methylene chloride are added unc stirs for 1 hour at room temperature. The reaction mixture is dried over Glauber's salt and filtered. The filtrate is concentrated under reduced pressure and the resulting yellow solid is crystallized from ethylene chloride carbon tetrachloride and a small amount of cyclohexane. Man receives 2.391 g of l-methylsulfmyl-l-methylthio-2-amino-2-phenylethylene. The yield is 71.4%.

Example 6

1,753 g of methylmethylthiomethylsulfoxide are dissolved in 20 ml of 1,2-dimethoxyethane, and 580 mg of potassium hydride are added to the solution while cooling with ice. The system is stirred for I ¹ Z ₂ hours at room temperature. Are then added 1.460 g of benzonitrile, and the mixture is stirred for 15 hours at room temperature and 1 hour at 50 ⁰ C. Then the reaction mixture is added to 70 ml of methylene chloride and 2 ml of water and stirred for 1 hour at room temperature. The mixture is dried over Glauber's salt and filtered. The filtrate is concentrated under reduced pressure and the resulting yellow solid! is crystallized from methylene chloride-carbon tetrachloride-Cyclohcxan, giving 2.208 g of 1-methylsulfinyl-1-methylthio-2-amino-2-phenylethylene. The yield is 69%.

Example 7

1.815 g of methylmethylthiomethylsulfoxide are ir Dissolve 20 ml of dimethylformamide, and to the solution are added 380 mg of sodium hydride with cooling Ice cream. The mixture is then stirred for 1.5 hours at room temperature. Then 1.515 g of Benzonilril are added given. The mixture is then stirred for 1.5 hours at room temperature and 10 hours at 50.degree 70 ml of methylene chloride and 2 ml of Was scr are then added and the mixture is stirred for 20 minutes at room temperature. After drying with Glauber's salt and filtering, the filtrate is reduced at reduced Focused pressure. The resulting product is made from methylene chloride-carbon tetrachloride-cyclohexane crystallized, giving 2.332 g of 1-methylsulfinyl-1-methylthio-2-amino-2-phenylethylene. The yield is 70%.

Example 8
991mg of n-butyllithium become 10 ml of a

I HF SOLUTION. the 1,539 1> Diicnnrnnvhimin pilth-ill

added to a THF solution of lithium diisopropylamide to manufacture. 10 ml of THF solution, the 1890 g of methylmethylthiomethylsulfoxide, are added to this solution contains, added dropwise. The mixture is then stirred for 1.5 hours at room temperature. After adding 1.570 g of benzonitrile and stirring for 1 hour at room temperature and for 18 hours at 50'C it is added to the mixture 70 ml of methylene chloride and 2 ml of water and stir for 1 hour at room temperature, and then it is dried with Glauber's salt and nitrated.

The solid obtained after concentrating the filtrate under reduced pressure becomes from methylene chloride-carbon tetrachloride-cyclohexane crystallized, 2.284 g of I-methysulfinyl-1 -methylthio-2-amino-2-phenylethylene is obtained. The yield is 66%.

Examples 9-11

Methylmtthylthiomethylsulfoxyd is dissolved in 20 ml of THF, and added to the solution Ice-cooling sodium hydride, and then stirred for 1.5 hours at room temperature. In addition System is given different amounts of nitrile and then stirred for 1.5 hours at room temperature and for 16 hours at 50 ° C. Then 70 ml of methylene and 2 ml of water are added, and the mixture is stirred for 1 hour at room temperature. The reaction mixture is poured over Glauber's salt dried and nitrided. The resulting product is made from methylene chloride-carbon tetrachloride-cyclohexane crystallized, whereby 1-methylsulfinyl-1-methy! thio-2-amino-2-arylethylene receives.

The reaction conditions and the results are shown in the table below.

example

Ar

Amount of amount of amount of

Compound-'nglA) Compound (B) NaH

(mg)

Amount of
received
Product (C)

(G)

yield

ArCN + CH ₃ SCH ₂ SCH,

(A)

(B)

NH ₂ SOCH ₃

/ X ₁

Ar 'SCH ₃

(C)

Cl ~ <
MeO

1470

1801

1860

1554

1623

1735

330

345

370

2058

2569

2075

68

75

80

The products obtained in Examples 9-11 have the following properties:

Example 9

l-methylsulfinyl-l-methylthio-2-amino-2- (m-tolyl) ethylene

Colorless crystals: m.p. 129 to 130 ° C.
IR (KBr): 3370, 3230, 3095, 1620, 1535, 1005 cm " ^1. NMR (CDCl,): Λ 2.38 S (3H). 2.41 S (3H). 2.58 S (3H), 5.40 broad (2H) 7.23 M (4H).

Analysis for H ₁₁ H ₁₅ NOS ₂ :

Calculated ... C 54.73. H 6.26. S 26.57 ",,:
found ... C 54.80. H 6.18. S 26.39%.

Example 10

l-methylsulfinyl-l-methylthio-2-amino-2- (p-chlorophenyl-ethylene

Pale yellow crystals: m.p. 150 to 150.5 C (dec. |. IR (KBr): 3360, 3230, 3080, 1620, 1530, 1000 cm '. NMR (CDCl ₃ ): Λ 2.38 S (3H). 2.56 S. (3H), broad 5.54 (2H), 7.32 S (4H).

Analysis for C _1n H ₁₂ NOS ₂ Cl:

Calculated
found

C 45.88, H 4.62, S 24.50%:
C 45.71, H 4.60, S 24.29%.

Example 11

i-methylsulnnyl-1-methylthio-2-amino-2- (p-methoxyphenyl) ethylene

Colorless crystals: m.p. 156.5 to 157.5 C (Zcrs.).

IR (KBr): 3385, 3230, 3030, 1625, 1605, 1500, 1260, 990, 840 cm ^-1 .

NMR (CD (I,): Λ 2.38 S (3H), 2.57 S (3H). 2.81 S (3H). 5.39 broad (2H). 6.87 D (2H. .1 = 9 H?), 7.2ND (2H. J = 9Hz).

Analysis for C _n H ₁₅ NO ₂ S ₂ :

Calculated ... C 51.33. 115.88. S 24.92%;
Findings ... C 51.39. H 5.92. S 24.88%.

Example! 2

2.90 g of methylmethylthiomethylsulfoxide are in Dissolve 25 ml of THF, and add to it while cooling with ice 650 mg of sodium hydride and stir for 1 hour at room temperature. Then become the system 1.8 ml of acetonitrile are added, and then the mixture is stirred at room temperature for 12 hours, at 50 C for 4.5 hours, and then 2 ml of water and 70 ml of methylene chloride are added, and then stir ι ο finally 2 hours at room temperature. The reaction mixture is dried with Glauber's salt, concentrated under reduced pressure, and the residue is subjected to column chromatography (Magnesium silica gel, which is commercially available under the name "Florisil" ", methylene chloride. Ethyl acetate and methanol), 341 mg of methylmethylthiomethylsulfoxide and 2,889 g l-methylsulfinyl-l-methylthio-2-aminopropene light yellow Crystals). The yield of the latter compound is 75.6% and the conversion is is 84.7%.

An analytical sample of 1-methylsulfmyl-l-methylthio-2-aminopropene was obtained by recrystallization from methylene chloride-carbon tetrachloride.

1 - methylsulfinyl - 1 - methylthio - 2 - aminopropene: M.p. 114.5 to 115.5 X.

IR (KBr): 3340, 3300 (sh). 3170, 1632, 1550, 1012, 1000 cm ' ¹ .

NMR (CDCl.,): Λ 2.28 S (6H), 2.66 S (3H). 5.60 broad (2H).

Analysis for C ₅ H ₁₁ NOS ₂ :

Calculated ... C 36.33. H 6.71. S 38.80%:
found ... C 36.56, H 6.51. S 38.80 "',,.

.15

Example 13

1.84 g of methyl methylthiomethyl sulfoxide are dissolved in 20 ml of THF. 800 mg of sodium hydride (as a 50% solution) are added with ice cooling and the mixture is stirred for 30 minutes at room temperature. To the system there is then added 1.8 ml of benzyl cyanide, and then the mixture is stirred for 14 hours at room temperature, 6 hours at 6O ⁰ C, adding 2 ml of water and 70 ml of methylene chloride and finally is stirred for 2 hours. The reaction mixture is dried with Glauber's salt, concentrated under reduced pressure, and the residue is subjected to column chromatography (silica gel / ethyl acetate-methylene chloride [1: 1 mixture], ethyl acetate and methanol), giving 998 mg of methylmethylthiomethylsulfoxide and 286 mg of I -Methylsulfinyl-l-methylthio ^ -amino-S-phenylpropene wins. The latter compound is purified by recrystallization from chloroform-carbon tetrachloride-n-hexane. The yield is 8.0%. and the conversion is 18.4%.

1 -Meihylsulfinyl-1-methylthio ^ -amino ^ -phenylpropcn: Mp. 135 to 136 ° C (decomp.) Pale yellow crystals, do

IR (KBr): 3380, 3240, 3160, 3100, 1620, 1536, 1010 cm " ¹ .

NMR (CnCK): 2.31 S (3H). 2.60 S (3H). 4.00 wide (2H). Broad 5.40 (2H-NH ₂ ).

Analysis for C ₁₁ H ₁₅ ONS ₂ : ^

Calculated ... C 54.73, H 6.26, S 26.57%;
found ... C 54.53. H 6.11. S 26.39%.

Example 14

1 316 11 methylthiomethyl-p-tolyl sulfoxide are used in 10 ml of THF are dissolved, and 175 mg of sodium hydride are added with ice-cooling and the mixture is stirred for 1 hour at room temperature. Then 0.9 ml of benzonitrile were added and the system was operated for 20 hours stirred at room temperature and for 4 hours at 60 C. After the further addition of 50 ml of methylene chloride and 1 ml of water, the reaction mixture is dried over Glauber's salt and reduced Focused pressure. The residue is washed with carbon tetrachloride and η-hexane, whereby one 2.017 si of a pale yellow solid obtained in hot Chloroform has been dissolved and the insoluble material is filtered off. The filtrate is at reduced Concentrated pressure, 1.569 g of 1-methylthiol (p-tolylsulfinyl) -2-amino-2-phenylethylene obtained as pale yellow crystals.

"The analytical sample is made by Umknstalhsation of the above product from methylene chloride-carbon tetrachloride-n-hexane receive.

1-methylthio-l- (p-tolylsulfinyl) -2-amino-2-phenvläthylen · mp. 145-146 ^C C (dec.) Of colorless crystals.

IR (KBr) - 3470, 3225, 3025, 1610, 1520, 1003 cm '.

NMR (CDCl ₃ ): Λ 2.02 S (3H), 2.38 S (3H). 5.38 broad (2H). 7.17 S (5H). 7.47 M (4H).

Example

l 15

3.00 g of p-chlorophenyl-p-chlorophenylthiomethylsulfoxide were dissolved in 40 ml of anhydrous THF. To this, 240 mg of sodium hydride are added while cooling with ice. The mixture is then stirred for 1 hour at 0 ° C. and for a further hour at room temperature. Then 1.29 ml of 4,4-dimethoxybutyiOnitrile are added dropwise. The mixture is then stirred for 18 hours at room temperature and then for a further 24 hours at 60 ° C. Then 80 ml of methylene chloride and 1 ml of water are added, and finally the mixture is stirred for 30 minutes at OC and 4 hours at room temperature. The reaction mixture is dried over Glauber's salt and filtered. After concentrating the filtrate, 3.530 g of a brown oil are obtained. which is purified by column chromatography (Florisil ^v . methylene chloride, ethylene acetate and methanol) to give 595 mg of! - (p-ChlorophenyD-sulfinyl-Mp-chlorophenyl) -thio-2-amino-5,5-dimethoxy-1-pentene . The yield is 14% and the conversion is 25%.

I - (p - chlorophenyl) - sulfinyl - 1 - (p - chlorophenyl} thio-2-amino-5,5-dimethoxy-1-pentene (recrystallized from carbon tetrachloride-cyclohexane): mp. 103 bis 104 C, colorless crystals.

IR (KBr): 1005, 3183, 3290, 3370 cm- ¹ .
NMR (CDCl3,): Λ 1.6 to 2.7 M (2H). 3.02 T (2H). I = 7 cP). 3.42 S (6H), 4.49 T (IH). J - 5 cP). Broad 5.61 (2Hl. 7.08 S (4H). 7.38 A ₂ B ₂₀ (4H).

Analysis for

Calculated
found

C 51.12. 114.74. S 14.37%:
C 51.19. H 4.69. S 14.41 ¹¹ O.

C i S μ i Ο i Iu

5.0 g of isopropylisopropylthiomethylsutoxide are used dissolved in 70 ml of anhydrous THF. 675 mg of sodium hydride are added with ice cooling and the mixture is stirred I hour at 0 C and another hour at room

_oeru tur. The reaction mixture is again placed in μ'- "water, and then 5.42 ml of dimethoxybutyronitrile are added dropwise, followed by 11.5 hours at room temperature and 50 hours at 50 ^° C. Then 50 ml of methylene chloride and 1 ml of water are added and the ^{mixture is stirred at 0 °} C. for 10 minutes and at room temperature for 1 hour. The reaction mixture is dried over Glauber's salt and filtered. The filtrate is concentrated under reduced pressure. The residue is subjected to column chromatography (silica gel *, methylene chloride, methyl acetate, 10% methanol-ethyl acetate and methanol). 1.66 g of 1-isopropyl-ifinyl -1-isopropylthio-2-amino-5,5-dimethoxyl ^U pentene are obtained as a light yellow, oily compound. The yield ^be ! ^r Rfrein) - ° 3150, 3175, 3275, 3420, 1007 cm " ¹ .

NMR (CDCl ₃ ): Λ 0.86 D (3 H, J = 7 Hz), 1.20 D "J = 7 Hz) '1.25 D (3H, J = 7 Hz), 1.38 D (3H, 1 -7 Hz) 1 54 to 2.18 M (2H), 2.36 to 2.93 M (2H), 2.98 to 3.72 M (2H), 3.33 S (6H), 4.35T ( IH) J = 5Hz),

5 * 50 wide (1H).

Example 17

ι 370 "Methylmethylthiomethylsulfoxyd be dissolved in VMI anhydrous THF are added to 475 mn sodium hydride under ice-cooling and stirring hlißend 50 minutes at OC. Then you stir

4 / j UlU nuuiuiu.-j- -

then 50 minutes at OC. The mixture is then stirred for a further 50 minutes at room temperature. The system is cooled again with ice, 3 73 ml of 4 4-dimethoxybutyronitrile are added dropwise and the mixture is subsequently stirred for 18 hours and then for a further 23 hours, _{50 to} 55 ° C. The reaction liquid is again cooled with ice while 30 ml of methylene chloride and TmI water can be added. The mixture is then stirred for hours at room temperature. It is dried overnight with Glauber's salt, then the friction mixture is filtered and the solvent is evaporated under reduced pressure. The residue trium hydride with ice cooling and stirred for 1 hour at room temperature. Then become the solution

1 ml of benzonitrile are added, and the mixture is then stirred for 16.5 hours at room temperature and for 5 hours

at 60 ⁰ C. Then methylene chloride and

2 ml of water were added. After drying over Glauber's salt and filtering, the filtrate is at concentrated reduced pressure. The residue is washed with cyclohexane, 1.212 g

, o 1-methylsulfinyl-l- (p-tolylthio) -2-amino-2-phenyl -

ethylene receives; colorless crystals, m.p. 171-172L

HMKBr): 3400, 3240, 3105, 1620, 1517, 1493, 1008 cm "1., _L.

, s NMR (CDCl ₃ ): Λ 2.30 S (3H), 2.44 S (3 H), 5.40 broad "(2H), 7.17 A ₂ B ₂₀ (4H, J = 8 Hz) , 7.43 S (5H).

Example 19

995 mg of methylmethylthiomethylsulfoxide are dissolved in .ο 10 ml of THF, and 235 mg of sodium hydride are added to the solution while cooling with ice and then stirred for 10 minutes. After stirring for 30 minutes at room temperature, 1.4 ml of hydrocinnamonitrile are added to the system, and the mixture is stirred for 37.5 hours at room temperature and for 9 hours at 55 ° C. After the addition of 50 ml of methylene chloride and 2 ml of water, the system is 10 minutes stirred at room temperature, then dried over Glauber's salt and filtered. The filtrate is concentrated under reduced pressure. The residue is subjected to column chromatography (silica gel *, methylene chloride, ethyl acetate and methanol), 1.515 g of 1-methylsulfinyM-methylthio ^ -amino - ^ - phenyl-1-butene being separated off. The yield is / 4 / b; colorless crystals. Mp. 119 to 121 ⁰ C (from

CH ₂ Cl ₂ -CCl ₄

C ₆ H ₁₂ )

IR (KBr): 3300, 3125, 1638, 1544, 997 cm "NMR (CDCl ₃ ): Λ 2.20 S (3H), 2.27 S (3H), 2.87 M

invl-

457 mg of methylmyyy and 4,332 g of crystalline product are obtained. The crystals are dissolved in hot methylene chloride and the insoluble material is separated off by filtration. The filtrate is concentrated under reduced pressure, whereby 3.70 g of 1-methylsulfinyl-1-methylthio ? - imino-5,5-dimethoxy-l-pentene in light yellow crystalline form. The yield is 76.5%. and the conversion is 94.8%. _

1-methylsulfinyl -1-methylthio-2-amino-5,5-dimethoxy-1-pentene (recrystallized from carbon tetrachloride): m.p. 86 to 87 "C.

IR (KBr) - 1008, 1627, 3150, 3273, 3400 cm ".

NMR (CDCl ₃ ): There are two kinds of geometric isomers between E and Z.

/ N 29 S (3H), 2.65 S (3H), 3.37 S (6H), 1.65-3.15 M.

h74 40 T (1 H, J = 5.3 Hz). 5.53 broad (2H).

"•» 19 S (3H) 2.74 S (3H), 3.37 S (6H), 1.65-3.15 M ? 4.45 T (IH, J = 5.3 Hz), 5.90 wide (211).

Analysis for C ₀ H ₁₄ O ₃ S ₂ N:

Calculated. C 42.66. H 7.56. S 25.31%: found ... C 42.54. 117.61. S 25.15%.

Example 18

1.20 g of methyl p-tolylthiomethylsulfoxide are in

15 ml of THF dissolved, and 165 mg of Na-

and 2.77).

Analysis for C ₁₂ H ₁₇ NOS ₂ :

Calculated ... C 56.43, H 6.71, S 25.11%: found ... C 56.46, H 6.63, S 25.08%.

Example 20

5 ml of THF become 0.901 g (7.3 mmol) of methylmethylthiomethylsulfoxide given, and then 5.0 ml of n-hexane solution of n-butyllythium (1.3 mmol / ml) was added at -10 C with stirring for 30 minutes. 0.850 g (6.6 mmol) diethoxyacelonitrile are added at - IOC, and the mixture is then stirred for 2 hours. The temperature rises to OC, and then 20 ml of methylene chloride and 0.1 ml of water are added. The mixture is dried over Glauber's salt and concentrated under reduced pressure. The residue is purified by column chromatography separated (Florisil \ methylene chloride-ethyl acetate-methanol), whereby 0.86! g of 1-methylsulfinyl-1-methylthio-2-amino-3,3-diethoxypiOpen receives. Yield:

54.9%.

NMR (CDCi ₁ ): Λ 1.15 (i, 311, J = 6.8 Hz). !, 25, (t, 3H. J = 6.8 Hz). 2.27 (p. 3H), 2.58 (S, 3H). 3.60 (m. 4H).

IR (pure): 3420, 3305, 2950, 1600, 1545, 1105, 1056,

1025, 946, 691 cm ".

Example 21

0.895 g of 1-methylsulfinyl-1-methylthio-2-amino-3,3-dimethoxypropene are in the same manner as in Example 20 except that 0.666 g of dimethoxyacetonitrile can be used instead of 0.850 g of diethoxyacetonitrile.

Yield: 55%.

NMR (CDCl ₃ ): Λ 2.31 (S, 3H), 2.60 (S. 3H). 3.28 (S, 3H), 3.46 (S, 3H), 5.52 (S, IH), 5.49 (broad S, 2H).

Example 22

8 ml of THF become 1.07 g (8.6 mmol) of methylmethylthiomethyl sulfoxide added. Then 160 mg of sodium hydride and 0.861 g (6.7 mmol) are added Diethoxyacetonitrile is added and the mixture is stirred at room temperature for 18 hours (the progress of the reaction followed by thin-layer chromatography). Treating the mixture in the same way as in Example 20 described, 1.25 g of 1-methylsulfinyll-methylthio-2-amino-3,3-dimethoxypropene are obtained.

Yield: 74%.

Example 23

1.292 g of methylmethylthiomethyl sulfoxide are dissolved in 15 ml of THF and 8.0 ml of n-hexane solution of n-butyllithium (1.44 mmol / ml) are added dropwise at -17 ° C. The mixture is stirred for 30 minutes, and then 0, 94 g of methoxyacetonitrile was added dropwise at -17 ⁰ C was added the temperature rises from -.. 17 ° C at to room temperature The mixture is stirred 16.5 hours, and then 40 ml of methylene chloride and 6 drops (0.2 ml) of water was added the mixture. is dried with Glauber's salt and concentrated under reduced pressure. The residues are separated by column chromatography (silica gel, ^see methylene chloride, ethyl acetate, methanol). 995 mg of 1-methylsulfinyl-1-methylthio-2-amino-3-methoxypropene are obtained.

Yield: 49% (conversion yield 59.7%).

NMR (CDCl ₃ ): Λ 2.29 (S, 3H), 2.62 (S. 3H). 3.40 (S, 3H), 4.42 (i.e. 1 H. J = 13.8 cps). 4.53 (i.e. 1 H. J = 13.8 cps), 5.70 (broad S, IH).

IR (neat): 697, 1009, 1102, 1562, 1638, 3125, 3260, 3330 cm ^-1 .

Example 24

1.220 g of methyl methylthiomethyl sulfoxide are dissolved in 15 ml of tetrahydrofuran (THF), and 7.5 ml n-Hexane solution of n-butyllithium (1.44 mmol / ml) is added dropwise at -8 ° C. The mixture The mixture is stirred for 30 minutes, and 1.580 g of benzyloxyacetonitrile are added dropwise at -10.degree. The temperature rises from -10 ° C. to room temperature. The mixture is stirred for 21 hours. 40 ml of methyl chloride and 7 drops (0.3 ml) of water are added, it is dried with Glauber's salt and concentrated under reduced pressure. The arrears will by column chromatography (Florisil *, methyl chloride. Ethyl octal, methanol) separated, whereby one

1.584g of l-methylsulfinyl-l-methylthio ^ -amino ^ -benzyloxypropene receives.

Yield: 59.5%.

NMR (CDCl ₃ ): Λ 2.27 (S. 3H), 2.58 (S, 3H). 4.49 (S 2H). 4.43 (d. IH. J = 13 cps), 4.59 (d. IH J = 13 cps). 5.59 (broad S. IH), 8.28 (S, 5H).

Application examples
example 1

144 mg of l-methylsulnnyl-l-methylthio-2-amino-2-phenylethylene are dissolved in 5 ml of methylene chloride. 96 mg of copper (II) chloride are added and the mixture is stirred for 3 days at room temperature. The reaction mixture is filtered, the filtrate is concentrated under reduced pressure, and the residue is chromatographed through a column (silica gel * and benzene). 106 mg of phenylglyoxylic acid methanethiol ester are obtained in the form of yellow crystals. The yield is 92.8%.

Example 2

236 mg of l-methylsulfinyl-l-methylthio-2-amino-2-phenylethylene are dissolved in 10 ml of ethanol. 114 mg of copper (II) chloride (anhydride) are added and the reaction mixture is allowed to stand for 4 days at room temperature. The system is at reduced Pressure concentrated, then 30 ml of methylene chloride are added to the concentrate, and the insoluble Material is separated off by filtration. The filtrate is concentrated again under reduced pressure and separated by column chromatography (Florisil * and benzene). 135 mg of ethyl phenylglyoxy ester are obtained as a colorless liquid. The yield is 72.9%. The product was made with a standard sample identified by IR and NMR analyzes.

Example 3

1.8 ecm of Raney nickel were added to 10 ml of acetone (WIl) and heated to reflux for 5 minutes. The system was cooled to room temperature, and 250 mg methanethiol ester of "-acetylamino-" -methylthiophenylacetic acid were added. Subsequently was stirred for 4 hours at room temperature. The insoluble material was removed by filtration removed, and the filtrate was concentrated under reduced pressure and subjected to column chromatography (Silica gel and ethyl acetate). 157 mg of methanethiol ester of N-acetylphenylglycine were obtained as colorless crystals.

N-acetylphenylglycine methanethiol ester, m.p. 82 bis 84 "C.

IR (KBr): 3225, 1680, 1640, 1515 cm " ¹ .

NMR (CDCl ₃ ) Λ 1.98 S (3 H), 2.27 S (3 H), 5.72 D (IH. .1 = 7 H ?.). 7.37 S (5 H). 7.30 wide (1 H).

Analysis for C _n H ₁₃ NO ₂ S:

Calculated ... C 59.17, H 5.87, S 14.36%;
found ... C 59.23, H 5.64, S 13.95.

Example 4

194 mg of α-acetylamino-K-methylthiophenylacetic acid-methanethiol ester are in 5 ml of methanol

dissolved, 2 drops of triethylamine are added and the mixture is refluxed for 10.5 hours. The reaction mixture was concentrated under reduced pressure and the residue was purified by column chromatography (silica gel and methylene chloride). 158 mg of methyl-n-acelylamino-a-methylthyllhiophynyl acetal were thus obtained as colorless crystals, mp 166-167 ° C. The yield was 86%.
IR (KBr): 3200, 1737, 1650, 1530cm '.

NMR (CDCl ₃ ): Λ 2.06 (6H). 3.75 S (3H). 7.07 wide (IH). 7.17 to 7.74 M (5H).

Analysis for C ₁₂ H ₁₅ O ₃ SN:

Calculated ... C 56.89, H 5.97. S 12.66%:
found ... C 56.89. H 5.88. S 12.77%.

e ι s ρ ι el

368 mg of Ί-acetylamino-u-melhyllhiophenylacetic acid methanethiol ester and 355 mg of potassium carbonate are added to a methanol-water mixture (9: 1) and refluxed for 3 hours. the The reaction mixture is concentrated to approximately 1 ml under reduced pressure. The concentrate will diluted with 20 ml of water and extracted (methylene chloride 3 30 ml and ethyl acetate 3 χ 30 ml). the organic phases are collected, dried with Glauber's salt and concentrated under reduced pressure. The residue is crystallized from ether and n-Hxane, 241 mg n-Acctylaminophenylcssigsäure receives. The yield is 91%.

Claims (2)

Patent claims:
• namine sulfoxide of the formula NH ₂ SOR ² C 'C
R 'SR ² wherein R 'is an alkyl group having 1 to 3 carbon atoms, a phenyl. Benzyl, phenyl. ToIyI, halophenyl, meihoxyphenyl group. an alkyl group of 1 to 3 carbon atoms substituted with dimethoxy or diethoxy groups. a monomeihoxymethyl or a benzyloxymethyl group or a dimethoxyphenyl group and the two groups R ² independently of one another denote alkyl groups having 1 to 3 carbon atoms, phenyl, toly and halophenyl groups. 2. Process for the preparation of Fnaminsulfoxiden of the formula I. characterized, that one is a nitrile of the formula