BE561091A

BE561091A -

Info

Publication number: BE561091A
Authority: BE

Description

       

   <Desc/Clms Page number 1> 
 



   La présente invention est relative à une série de nouveaux dérivés d'hydrazinopyrimidine, qui possèdent une activité   tuberculostatique   ou fongicide. L'invention concerne plus particulièrement des produits de condensation d'hydrazinopyrimidines avec des dérivés carbonylés choisis parmi les aldéhydes et cétones aromatiques et hétérocycliques. 



   L'invention concerne également un procédé de préparation des nouveaux dérivés   d'hydrazinopyrimidines.   



   Les nouveaux dérivés   d'hydrazinopyrimidines   peuvent être représentés par les formules suivantes : 
 EMI1.1 
 dans laquelle R et   R@   représentent un atome d'hydrogène ou un radical mé-   thyle, R3 représente un atome d'hydrogène, ou un groupe hydroxy, alcoxy ou amino, X et Y représentent un atome d'hydrogène ou un radical méthyle, et   A est un noyau aromatique ou hétérocyclique, éventuellement substitué par des groupes nitro, amino, halogéno,hydroxy ou alcoxy. 



   Les nouveaux dérivés d'hydrazinipyrimidines suivant l'invention peuvent être préparés par la condensation d'une hydrazinopyrimidine avec l' aldéhyde ou la cétone aromatique ou hétérocyclique. 



   La synthèse des dérivés suivant l'invention peut être schématisée comme suit : 
 EMI1.2 
 

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 EMI2.1 
 
La condensation d'une hydrazinopyrimidine avec une aldéhyde ou une cétone aromatique ou hétérocyclique s'opère, de préférence, en milieu alcool-eau, contenant éventuellement un acide, tel que l'acide acétique ou l'acide   chlorhydrique.   



   La plupart des dérivés de formules I et II possèdent une activité tuberculostatique. Cette activité est la plus prononcée quand le substi-   tuant R3 est un groupe hydroxy ou amino et A est un noyau benzoique possédant un groupe hydroxy en position ortho. A titre d'indication, les con-   centrations de quelques dérivés qui inhibent le développement du Mycobac-   'terium tuberculosis, souche H37Rv dans le milieu de Dubos, sont mentionnées dans le tableau I suivant.   

 <Desc/Clms Page number 3> 

 



     TABLEAU   I.- 1) Dérivés de formule I.- 
 EMI3.1 
 Y X Rl R2 R3 Concentration inhibitrice m> miorogrammes/ millilitre.- \1==" H H CH3 H OH a 5 H <- CHg CEg OH \ CH3 CR.> OH w,, ¯ H H CH3 OH cr ,=#' H .z-->- H H OH3 H OH 5 N02 OH N0-.- H H CH3 H OH 10 rrz OH N .- H H CH3 H OH 10 OH H0-.- H H CH3 H OH 100 OH C1, ±Q- H H CH3 H OH OH N02 .- H H CH3 H OH 10 ., H 

 <Desc/Clms Page number 4> 

 
Tableau I   (Suite).-     1)   Dérivés de formule   1(suite).-   
 EMI4.1 
 A Y X Rl IL, R3 Concentra. 



  -tion inhi -bitrice en micro-* grammes/mill! -tritre '.- H CHg OH 100 É CRs OH' Ho, e¯-. 



  .!/ \ - Qg¯ ,à CH3 \.##.. 



  OH CH30-,- H H OH3 ' H OH 100 . ,#/' o OH bzz - \-- H H C H OH 10 /m/ l .J. 



  -¯.-OH H H CH3 H OH 5 ..¯..? #'\, H H CH3 H OH 20 ,.::::.N 7 .'.- C H CE;3' OH ' 10 N- H H . CH3 H OH 100 #-- ---¯, H H CH3 H OH 20 -/ 

 <Desc/Clms Page number 5> 

 
 EMI5.1 
 Tableau I suite .- 1)Dérivés de formule I(suite).- 
 EMI5.2 
 1 2 R3 Concentration inhibitrice en microgrammes/ millilitre =¯ ¯ H CR.3 CH3 H OH H / ..-.- v .. H CH3 CH3 H OH H " H CH3 CH3 H on 20 1'' H H S CH3 OH OH Cl -v\.¯ CH3 OH cH3 OH -<=,- OH3' H Î2 20 OH Cl @- H H CR.3 H NB 100 OH ;7-- \..- H H CH3 H NHg 12 '.=N/ Chez NHZ '=='" CH3 OCH3  ).

   J6  '6 ¯ ? ''" CH B CH H 0 - H H S S  CR.3 100 OH 

 <Desc/Clms Page number 6> 

 
Tableau   I(suite).-     l)Dérivés   de formule I (suite).- 
 EMI6.1 
 Y X RI R2 R3 Concentration inhibitrice en mi crogramraes/ millilitre.- 1 / \ - H H H H OCH3 10 DH *l H H H H 01!1H;

  ) 5 /""-- H H CH H 0 C2H5 10 q- 'OH ¯ H , H CH3 H 002H5 10 O- H H CH3 H 0 C3H7 100 OH Cl <- H H CH3 H OC3H, 100 OH - H H CH3 , H OC3H7 5 , r---/, ¯ H H I H H 20 OH 2)Dérivés de formule II.- 
 EMI6.2 
 H H "3 OH 0,5 OH ¯ CE/ H OH3 OH 0,5 OH 

 <Desc/Clms Page number 7> 

 
TABLEAU I (suite).- 2) Dérivés de formule II (suite). - 
 EMI7.1 
 Y X Ri R2 R3 Concentration inhibitrice en miorogrannnes/ millilitre.C1 H H CH3 OH 5 OH <##\ H H CI! 3 - N?32 2,5 OH - CI! 3 H CI!3 - Jffi2 10 oH ci .- H H CI!3 - NH2 12 OH <-> - H H CH3 rH2 5 
Certains composés dela même série possèdent un pouvoir fongistatique notable. Des test ont été exécutés en préparant une série de dilutions du produit dans du "nutrient agar" liquéfié. Celui-ci a été versé dans une boite de Pétri, et sur cet agar solidifié, on a ensemencé différentes moisissures.

   Après une incubation à une température de 37  pendant 3-6 jours, on a examiné s'il y a développement ou non. 



   Dans le tableau II suivant, les concentrations inhibitrices (en   microgrammes   par millimètre) de quelques composés sont indiquées. 

 <Desc/Clms Page number 8> 

 
TABLEAU II.Microorganismes 
 EMI8.1 
 
<tb> 
<tb> Composé <SEP> de <SEP> Candida <SEP> Cryptococ- <SEP> Trichophy <SEP> Sporatri- <SEP> Philiaphoformule <SEP> I <SEP> albicans <SEP> ous.sp.

   <SEP> ton <SEP> rubrum <SEP> chon <SEP> ra <SEP> pedrosii
<tb> Y <SEP> R1 <SEP> R3 <SEP> schenckii
<tb> CH3 <SEP> CH3 <SEP> OH <SEP> 20 <SEP> 40 <SEP> 20 <SEP> 20 <SEP> 30
<tb> H <SEP> CH3 <SEP> NH2 <SEP> - <SEP> - <SEP> 10
<tb> H <SEP> CH3 <SEP> OCH3 <SEP> 20 <SEP> 30 <SEP> 20 <SEP> 20 <SEP> 30
<tb> H <SEP> H <SEP> OCH3 <SEP> 10 <SEP> 20 <SEP> 10 <SEP> 20 <SEP> 15
<tb> OH3 <SEP> H <SEP> OCH3 <SEP> 10 <SEP> 10 <SEP> 5 <SEP> 10 <SEP> 10
<tb> Composés <SEP> de
<tb> formule <SEP> II
<tb> H <SEP> CH3 <SEP> OH <SEP> - <SEP> - <SEP> 10
<tb> CH3 <SEP> CH3 <SEP> OH <SEP> 30 <SEP> 50 <SEP> 30 <SEP> 30 <SEP> 30
<tb> 
 
Dans les composés de formule I et II mentionnés dans le tableau II :   A = #; X = R2 ou H   
Dans ce tableau II, le signe - indique qu'il n'y a pas d'inhibition décroissance. 



   Comme hydrazinopyrimidines utilisables dans le procédé suivant l'invention, on peut citer, à titre d'exemples, les suivantes :   2-hydrazino-4-méthyl-6hydroxypyrimidine;2-méthyl-hydrazino-4-méthyl-6-hy-   droxypyrimidine; 2-hydrazino-5-méthyl-6-hydroxypyrimidine; 2-hydrazino-4-méthyl-6-aminopyrimidine;   2-hydrazino-4-méthyl-6-méthoxypyrimidine;   2-hydrazino-6-méthoxypyrimidine; 2-hydrazino-4-méthyl-6-éthoxypyrimidine; 2-hydrazino- 4-méthyl-6-isopropoxypyrimidine; 2-hydrazino-4-méthylpyrimidine; 6-hydrazi-   no-4-méthylpyridimidine;   2-hydroxy-4-méthyl-6-hydrazinopyrimidine; 2-amino- 4-méthyl-6-hydrazinopyrimidine. 



   Comme aldéhydes aromatiques et hétérocycliques utilisables dans le procédé suivant l'invention, on peut citer, à titre d'exemples, les suivantes : aldéhyde salicylique, aldéhyde cuminique, aldéhyde 3-nitrosalicylique, aldéhyde 3-chlorosalicylique, aldéhyde   résorcylique,   ,aldéhyde 4-nitrosalicylique, aldéhyde 4-aminosalicylique, aldéhyde gentisique, aldéhyde 5-nitrosalicylique, aldéhyde 5-aminosalicylique, aldéhyde 5-chlorosalicylique, aldéhyde ' o-méthoxybenzoïque, aldéhyde   o-nitrobenzoique,   aldéhyde   o-aminobenzoiqve,   aldéhyde o-carboxybenzoïque, aldéhyde m-nitrobenzoique, aldéhyde m-hydroxybenzoïque, aldéhyde   p-hydroxybenzoique,   aldéhyde anisique, aldéhyde p-nitrobenzoique, al- déhyde   p-aminobenzoique;

     aldéhyde p-acétylaminobenzoique, aldéhyde p-dimé-   thylaminobenzoique,   aldéhyde p-chlorobenzoique, aldéhyde   2,4-dichlorobenzol-   que, aldéhyde   2,3-diméthoxybenzoique,     aldéhyde ss-hydroxy-[alpha]-naphtalénique,   al- 

 <Desc/Clms Page number 9> 

 
 EMI9.1 
 déhydea-hydroicy-p-naphtalénique, aldéhyde nicotinique, aldéhyde isonicotinique, aldéhyde picolinique, aldéhyde 6-méthylpicoliniquee aldéhyde 2- quinolénique, 6-hydroxy-4-pyrimidine aldéhyde,   2,6-dihydroxy-4-pyrimidine   aldéhyde, furfural aldéhyde 2-pyrrolique. 



   Comme cétones aromatiques et hétérocycliques utilisables dans le procédé suivant l'invention, on peut citer, à titre d'exemples, les suivantes :acétophénone, o-hydroxy-acétophénone, p-hydroxyacétophénone, pnitroacétophénone, 2-acétylpyridine, 3-acétylpyridine, isatine. 



   Les exemples suivants illustrent l'invention, mais il est bien entendu qu'ils ne doivent âs être considérés comme limitatifs. 



   EXEMPLE   1.-   
 EMI9.2 
 2-(salïcylidène-hdrazino)-°-méthyl-6-hydrox,ypyrl¯midine.- (Formule I : R1CH3 ' R=OH; R2=X=Y=H) 
1,4 g de 2-hydrazino-4-méthyl-6-hydroxypyrimidine sont dissous   dans 3 ml d'acide chlorhydrique 2N et 2 ml d'eau ; onajoute une solution   de 1,2 g d'aldéhyde salicylique dissoute dans 4 ml d'alcool éthylique et on chauffe au bain-marie pendant 1 1/2 heure. Le précipité qui se forme est essoré et recristallisé dans l'alcool méthylique et l'acide acétique. 



  On obtient des cristaux blancs qui fondent à 249,   2510C   (avec décomposition). 
 EMI9.3 
 Analyse : calculé pour C1GH12N°02,HC1: N=19,96%. Trouvé : N=19,88%. 



  EXEMPLE 2.- 2- salic lidène-h drazino-°-méth 1-6-h drox imidine.- 
Ce composé peut encore être préparé par le mode opératoire suivant :
4,2 g de   2-hydrazino-4-méthyl-6-hydroxypyrimidine   sont dissous dans 15 ml d'acide acétique et 10 ml d'eau. On ajoute 3,7 g d'aldéhyde salicylique dissoute dans 5 ml d'alcool éthylique et on chauffe au bain-marie pendant 1/2 heure. Le précipité qui se forme est essoré. On obtient 7,0 g d' un produit, qui fond à 244- 245 C. Par recristallisation dans l'acide acétique, le point de fusion monte à   249-251 C   (décomposition). 



   En utilisant le même mode opératoire et en remplaçant l'aldéhyde salicylique par les aldéhydes et cétones mentionnées ci-dessous, on obtient avec des rendements analogues, des produits de structure analogue : 

 <Desc/Clms Page number 10> 

 
 EMI10.1 
 
<tb> Aldéhyde <SEP> ou <SEP> cétone <SEP> Point <SEP> de <SEP> fusion <SEP> Solvant <SEP> de <SEP> recris- <SEP> 'Calculé <SEP> % <SEP> N' <SEP> Trio
<tb> ( C) <SEP> (avec <SEP> décom- <SEP> tallisation <SEP> Calculé' <SEP> Trouvé <SEP> 
<tb> position) <SEP> du <SEP> produit <SEP> de <SEP> condensation
<tb> aldéhyde <SEP> cuminique <SEP> 141-143 C <SEP> alcool <SEP> éthylique <SEP> 20,73 <SEP> 20,37
<tb> o-hydroxyacétophénone <SEP> 245-246 C <SEP> alcool <SEP> éthylique-pyridine <SEP> 21,69 <SEP> 21,66
<tb> aldéhyde <SEP> 3-nitrosalicylique <SEP> 243-244 C <SEP> acide <SEP> acétique <SEP> 24,21 <SEP> 24,

  08
<tb> aldéhyde <SEP> 3-chlorosalicylique <SEP> 241-243 C <SEP> acide <SEP> acétique <SEP> 20,10 <SEP> 19,92
<tb> aldéhyde <SEP> résorcylique <SEP> 276 c <SEP> acide <SEP> acétique-alcool <SEP> éthy- <SEP> 21,63 <SEP> 21,59
<tb> lique
<tb> aldéhyde <SEP> 4-nitrosalicylique <SEP> 306-307 C <SEP> acide <SEP> acétique-alcool <SEP> méthy- <SEP> 24,18 <SEP> 24,31
<tb> lique
<tb> aldéhyde <SEP> 4-aminosalicylique <SEP> 248-249 C <SEP> acide <SEP> acétique <SEP> 21,98(a) <SEP> 21,90
<tb> aldéhyde <SEP> gentisique <SEP> 277 C <SEP> acide <SEP> acétique <SEP> 21,53 <SEP> 20,61
<tb> aldéhyde <SEP> 5-nitrosalicylique <SEP> 285-286 C <SEP> acide <SEP> acétique <SEP> 24,21 <SEP> 24,57
<tb> aldéhyde <SEP> 5-aminosalicylique <SEP> 286 C <SEP> acide <SEP> acétique-eau <SEP> 21,08(b) <SEP> 21,

  26
<tb> aldéhyde <SEP> 5-chlorosalicylique <SEP> 251-252 C <SEP> acide <SEP> acétique <SEP> 20,10 <SEP> 20,24
<tb> aldéhyde <SEP> o-méthoxybenzoïque <SEP> 197-199 C <SEP> acide <SEP> acétique <SEP> 21,69 <SEP> 21,50
<tb> 
 

 <Desc/Clms Page number 11> 

 
 EMI11.1 
 
<tb> Aldéhyde <SEP> ou <SEP> cétone <SEP> Point <SEP> de <SEP> fusion <SEP> Solvant <SEP> de <SEP> recris- <SEP> % <SEP> N
<tb> ( C) <SEP> (avec <SEP> décom- <SEP> tallisation <SEP> Calculé <SEP> Trouvé
<tb> position) <SEP> du <SEP> produit <SEP> Calcule <SEP> Trouve
<tb> de <SEP> condensation
<tb> aldéhyde <SEP> o-nitrobenzoique <SEP> 209-210 C <SEP> alcool <SEP> éthylique-pyridine <SEP> 25,63 <SEP> 25,61
<tb> aldéhyde <SEP> o-aminobenzoïque <SEP> 222-224 C <SEP> pyridine <SEP> 28,79 <SEP> 28,72
<tb> aldéhyde <SEP> o-chlorobenzoique <SEP> 214-216 C <SEP> acide <SEP> acétique <SEP> 21,32 <SEP> 21,

  29
<tb> aldéhyde <SEP> o-carboxybenzoique. <SEP> 273-274 C <SEP> acide <SEP> acétique <SEP> 20,59 <SEP> 20,60
<tb> aldéhyde <SEP> m-nitrobenzoique <SEP> 274-276 C <SEP> acide <SEP> acétique <SEP> 2563 <SEP> 25p8O
<tb> aldéhyde <SEP> m-hydroxybenzoique <SEP> 244 C <SEP> acide <SEP> acétique <SEP> 22,94 <SEP> 23,02
<tb> aldéhyde <SEP> p-hdroxybenzoique <SEP> 267-269oc <SEP> acide <SEP> acétique <SEP> 22,94 <SEP> 22,85
<tb> p-hydroxyacétophénone <SEP> 254-256 C <SEP> acide <SEP> acétique-alcool <SEP> éthyli-21,69 <SEP> 21,72
<tb> que
<tb> aldéhyde <SEP> anisique <SEP> 217-218 C <SEP> alcool <SEP> éthylique <SEP> 21,69 <SEP> 21,62
<tb> aldéhyde <SEP> p-nitrobenzoique <SEP> 295-296 C <SEP> acide <SEP> acétique-alcool <SEP> mé- <SEP> 25,63 <SEP> 25,$3
<tb> thylique
<tb> p-nitroacétophénone <SEP> 269-270 C <SEP> pyridine <SEP> 24,98 <SEP> 24,

  12
<tb> aldéhyde <SEP> p-aminobenzoique <SEP> 241-243 C <SEP> pyridine <SEP> 28,79 <SEP> 27,98
<tb> 
 

 <Desc/Clms Page number 12> 

 
 EMI12.1 
 
<tb> Laldéhyde <SEP> ou <SEP> cétone <SEP> .Point <SEP> de <SEP> fusion <SEP> Solvant <SEP> de <SEP> recris- <SEP> % <SEP> N
<tb> ( C) <SEP> (avec <SEP> décom- <SEP> tallisation <SEP> Calculé <SEP> Trouvé
<tb> position) <SEP> du <SEP> produit <SEP> Calculé <SEP> Trouve
<tb> de <SEP> condensation
<tb> 
 
 EMI12.2 
 1 -¯¯¯#¯¯¯¯¯##-¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯ aldéhyde p-acétylaminobenzoique 301-05 C acide acétique 24,55 24,54 aldéhyde p-diméthylaminobenzolque 226-227 C dioxane 25,81 25,81 aldéhyde p-chlorobenzorque 265-267 C acide acétique 18,85 18,92 aldéhyde 2,3-diméthoxybenzoïque 235-237 C acide acétique 19,43 19,

  57 
 EMI12.3 
 
<tb> aldéhyde <SEP> / <SEP> -hydroxy- <SEP> c(-naphtalé- <SEP> 283 C <SEP> acide <SEP> acétique <SEP> 19,04 <SEP> 18,88
<tb> nique
<tb> 
 
 EMI12.4 
 aldéhyde o(-hydroxy .-aaphtalé- 276 C acide acétique 19,04 1g 75 
 EMI12.5 
 
<tb> . <SEP> nique <SEP> 
<tb> aldéhyde <SEP> isonicotinique <SEP> 290 C <SEP> acide <SEP> acétique <SEP> 30,55 <SEP> 30,42
<tb> aldéhyde <SEP> nicotihique <SEP> 285-287 C <SEP> acide <SEP> acétique-alcool <SEP> 26,6l(c) <SEP> 26,21
<tb> @ <SEP> méthylique
<tb> aldéhyde <SEP> picolinique <SEP> 256-257 C <SEP> pyridine <SEP> 30,55 <SEP> 31,94
<tb> 2-acétylpyridine <SEP> 154-155 C <SEP> alcool <SEP> éthylique <SEP> 28,79 <SEP> 28,60
<tb> 
 

 <Desc/Clms Page number 13> 

 
 EMI13.1 
 
<tb> aldéhyde <SEP> ou <SEP> cétone <SEP> Point <SEP> de <SEP> fusion <SEP> Solvant <SEP> de <SEP> recris- <SEP> % <SEP> N
<tb> ( C)

   <SEP> (avec <SEP> décom- <SEP> tallisation <SEP> Calculé <SEP> Trouvé
<tb> position) <SEP> du <SEP> produit <SEP> Calculé <SEP> Trouvé
<tb> @ <SEP> de <SEP> condensation
<tb> aldéhyde <SEP> 2-quinoléique <SEP> 265 <SEP> acide <SEP> acétique <SEP> 25,07 <SEP> 24,79
<tb> isatine <SEP> 314-316 C <SEP> acide <SEP> acétique <SEP> 26,01 <SEP> 26,05
<tb> furfural <SEP> 202-203&C <SEP> alcool <SEP> éthylique <SEP> 25,35 <SEP> 25,61
<tb> (a) <SEP> calculé <SEP> pour <SEP> C12H13N5O2.HOOC.CH3
<tb> (b) <SEP> calculé <SEP> pour <SEP> C12H13N3O2.2HCl
<tb> (c) <SEP> calculé <SEP> pour <SEP> C11H11N5O.CH3OH
<tb> 
 

 <Desc/Clms Page number 14> 

 EXEMPLE 3.- 
 EMI14.1 
 2- salic lidène-méthylhydrazino q.-méthyl6hydroxyp rimidine. 



  (Formule 1 : R 1=X=CH 3eR2=Y=He R3=OH) 
On dissout 2 g de 2-méthylhydrazino-4-méthyl-6-hydroxypyrimidine   dans 15 ml d'un mélange 1 :1 acideacétique-eau et on ajoute une solution   
 EMI14.2 
 de 1,6 g d'aldéhyde salicylique dans 5 ml d'alcool. On c'l3.huff'e ':tu bain-ma- rie pendant 1 1/2 heures. Le précipité qui se forme est essoté, lavé et séché. Le produit (3,2 g) est recristallisé dans l'acide acétique. On obtient des cristaux blancs qui fondent à 248-249 C (avec décomposition). 



  Analyse : calculé pour   0 EN 0 :  N=21,69%. trouvé :   N=21,60%  
On prépare de la même façon, avec des aldéhydes appropriées, les produits de condensation suivants : 
 EMI14.3 
 2(5'-chlorosalicylidène-méthylhydrazino)-4-méthyl-6-hydroxypyrimidine,P.F.   266-267 C;   
 EMI14.4 
 Analyse : Calculé pour C13H13Nq.02C1oH20 : N=18,03%; 
Trouvé :   N=18,21%.   



    2-(6'-méthylpicolinyl-méthylhydrazino)-4-méthyl-6-hydroxypyrimidine,   P.F. 



  276-278 C. 



  Analyse : Calculé pour C13H15N5O :   N=27,2%.   



   Trouvé :   N=27,55%     2-(pioolynyl-méthylhydrazino)-4-méthyl-6-hydroxypyrimidine.   P.F.245-247 C. 



  Analyse : Calculé pour   C12H13N50 :  N=28,79% 
Trouvé :   N=28,81%   
On a constaté qu'il est plus avantageux de purifier les produits mentionnés ci-avant par recristallisation dans la pyridine. 



   EXEMPLE 4.- 
 EMI14.5 
 2- salia lidène-h drazino - -méth 1-6-h drox iimidineo- 
Formule I : R1=Y=X=H,   R2=CH3,   R3=OH)
On dissout 0,7 g de   2-hydrazino-5-méthyl-6-hydroxypyrimidine   dans 8 ml d'un mélange 1:1 acide acétique-eau et on ajoute une solution de 0,6 g d'aldéhyde salicylique dans 2 ml d'alcool éthylique; on chauffe au bainmarie pendant   21/2   heures. Le précipité qui se forme est essoré, lavé et séché (1,15 g). Après recristallisation dans un mélange acide acétique-alcool éthylique, on obtient des cristaux blancs; P.F. 289-291 C (décomposition). 



  Analyse : calculé pour C12H12N4O2 :  N=22,94%.   trouvé : N=22,85%. 



   Par le même mode opératoire, on prépare les produits de condensation suivants : 
 EMI14.6 
 2-(5'-chlorosalicylidène hydrazino)-5méthyl6mhydroxypyrimidine; P.F. : 327 C; Analyse : Calculé : N=20,10%; 
Trouvé :   N=20,03%.   



    2-(pioolinyl-hydrazino)-5-méthyl-6-hydroxypyrimidine;   P.F. 255-256 C; Analyse : Calculé : N=30,55%; Trouvé :   N=30,54%.   

 <Desc/Clms Page number 15> 

 EXEMPLE 5.- 
 EMI15.1 
 2-(2'-hydnoxy-ce-méthylbenzylidène-hydrazino)-4-méthyl-5-aminopynidine.- (Formule I : R2=X=H; Y=R,=CH3; R3WNH 2) 
On dissout 1,6 g de   2-hydrazino-4-méthyl-6-aminopyrimidine   dans 10 ml d'un mélange acide acétique-eau 1 :1, et on ajoute une solution de 1,6 g   d'o-hydroxyacétophénone   dans 3 ml d'alcool éthylique; on chauffe au bain-marie pendant 4 1/2 heures. La solution est évaporée à sec et le résidu est traité avec de l'eau. Le produit est essoré, lavé et séché (1,6g). 



  Après recristallisation dans l'alcool éthylique, on obtient des cristaux blancs; P.F. : 257-259 C   (déc.)   Analyse : Calculé pour C13H15NSO : 
N= 27,10% 
Trouvé : N= 27,22%. 



   On prépare de la même façon les produits de condensation suivants :   2-(salicylidène-hydrazino)-4-méthyl-6-aminopyrimidine-,   P.F.   244-246 C.   Analyse : calculé N=28,79%; trouvé :   N=28,57%.   
 EMI15.2 
 



  2-(5'-ahlorosalicylidêne-hydrazino)-q.-méthyl-6-aminopyrimidine. P.F. 



  213-215 C. Analyse : Calculé : N=25,22%;
Trouvé :   N=24,64%.   



    2-(picolinyl-hydrazino)-4-méthyl-6-aminopyrimidine.   P.F. : 210-211 C. Analyse : calculé :  N=36,82%.   Trouvé :N= 36,16%. 



   EXEMPLE 6. - 
 EMI15.3 
 2- salic lidène-lz drazino -q.mé,h 1-6-mêthox rimidine.- (Formule I:   R2=Y=X=H;   R1=CH3;   R3OCH3).   



   1,55 g de 2-hydrazino-4-méthyl-6-méthoxypyrimidine sont dissous dans 15 ml d'un mélange 1:1 eau-acide acétique; on ajoute une solution de 1,25 g d'aldéhyde salicylique dans 5 ml d'alcool éthylique et on chauffe au bain-marie pendant 1 heure. Le précipité qui se forme est essoré, lavé et séché (2,15g). Après recristallisation dans l'alcool éthylique, on obtient 
 EMI15.4 
 un produit blanc.,P.F: oc. Analyse: calculé pour C13H14N402 'I=21,69 trouvé : N=21,59%. 



   La condensation de 2-hydrazino-4-méthyl-6-méthoxypyrimidine   avec   les aldéhydes ou cétones mentionnés ci-dessous a été effectuée par   le   même mode opératoire et avec les mêmes rendements. Pour les aldéhydes ou cétones, à noyau pyridinique, ou pyrimidinique, on n'a généralement pas ajouté de l'alcool au milieu de réaction. Pour les aldéhydes pyrimidiniques, on a employé 20 ml d'acide acétique et 10 ml d'eau pour solubiliser les réactifs.

   Les produits de réaction ont précipité généralement dans le milieu de réaction à chaud ou après refroidissement, mais dans certains cas, il a fallu concentrer la solution. 

 <Desc/Clms Page number 16> 

 
 EMI16.1 
 
<tb> aldéhyde <SEP> ou <SEP> cétone <SEP> Point <SEP> de <SEP> fusion <SEP> Solvant <SEP> de <SEP> recris- <SEP> % <SEP> N
<tb> ( C) <SEP> du <SEP> produit <SEP> de <SEP> tallisation <SEP> Calculé <SEP> Trouvé
<tb> condensation
<tb> aldéhyde <SEP> 5-chlorosalicylique <SEP> 199-200 C <SEP> alcool <SEP> éthylique <SEP> 19,14 <SEP> 19,00
<tb> .o-hydroxyacétophénone <SEP> 149-151 C <SEP> alcool <SEP> éthylique <SEP> 20,57 <SEP> 20,56
<tb> 
 
 EMI16.2 
 aldéhyde picolinique 174-175 C benzène 28p79 28t6g 
 EMI16.3 
 
<tb> aldéhyde <SEP> 6-méthylpicolinique <SEP> 126-128 C <SEP> alcool <SEP> éthylique <SEP> absolu <SEP> 27,22 <SEP> 26,

  94
<tb> 
 
 EMI16.4 
 aldéhyde nicotinique 205-207,0 alcool éthylique 28e79 28957 aldéhyde isonicotinique 160,1651c alcool éthylique-acétate 2$,79 27948 
 EMI16.5 
 
<tb> d'éthyle
<tb> 2-acétylpyridine <SEP> 162-164 C <SEP> acétate <SEP> d'éthyle <SEP> 27,22 <SEP> 27,08
<tb> 
 
 EMI16.6 
 3-acétylpyridine 153-1540e acétatedtéthylé-a7cool éthy- 27,22 26,99 
 EMI16.7 
 
<tb> lique
<tb> aldéhyde <SEP> 2-quinoléique <SEP> 200-202 C <SEP> acétate <SEP> d'éthyle <SEP> 23,88 <SEP> 23,57
<tb> 
 
 EMI16.8 
 6-hydroxy-.-pyrimidiâne aldéhyde 24600(dée.) alcool éthylique 32,29 31,96 2,6-.dihydroxy-4-pyrimidine aldéhyde 34000(déc.) pyridine 30,L,.2 30,14 

 <Desc/Clms Page number 17> 

 EXEMPLE 7.- 
 EMI17.1 
 2-(pi¯aoignyih>4nzzinç>=1=*+¯tàyi-6=mé<hoxypyràmoeàine-¯ 
On dissout 31 g de 2-hydrazino-4-méthyl-6-méthoxypyrimidine et 32,

  5 g d'aldéhyde picolinique dans 150 ml d'alcool absolu, et on chauffe au bain-marie pendant 5 heures- Après avoir refroidi, on essore les cristaux, et par concentration des eaux-mères, on obtient encore une deuxième et troisième fraction. On obtient ainsi 37 g de cristaux légèrement jaunâtres. 



  P.F.:   174-176 C.   



    EXEMPLE 8.-   
 EMI17.2 
 2- salic .idènétßdrz.io .: "-6-méthoxyimidine .- (Formule 1 : Y=X=R1=R2=R; R3=CH30). 



   On dissout 1 g de 2-hydrazino-6-méthoxypyrimidine dans 10 ml d'un mélange 1:1 acide acétique-eau et on ajoute une solution de 0,9 g d'aldéhyde salicylique dans 2 ml d'alcool éthylique, et on chauffe au bainmarie pendant 1 1/2 heures. Après refroidissement, on essore le précipité, qui est lavé et séché (1,45 g). Après recristallisation dans l'acide acé- 
 EMI17.3 
 tique, le point de fusion est 230-231- Ca Analyse Calculé pour C12H12N402: 
N=22,94%; Trouvé :   N=22,68%.   



   En suivant le même mode opératoire, on a condensé la 2-hydrazino- 6-méthoxypyrimidine avec des aldéhydes de cétones mentionnées ci-dessous. 



  Pour les réactions avec l'aldéhyde picolinique et la 2-acétylpyridine, on n'a pas ajouté d'acide acétique-eau, mais uniquement de l'alcool absolu et on a chauffé plus longtemps (3 à 5 heures). 

 <Desc/Clms Page number 18> 

 
 EMI18.1 
 
<tb> aldéhyde <SEP> ou <SEP> cétone <SEP> Point <SEP> de <SEP> fusion <SEP> Solvant <SEP> de <SEP> % <SEP> N
<tb> ( C) <SEP> du <SEP> produit <SEP> recristallisation <SEP> Calculé <SEP> Trouvé
<tb> de <SEP> condensation <SEP> Calcule <SEP> Trouvé
<tb> o-hydroxyacéto-phénone <SEP> 135-136 C <SEP> alcool <SEP> éthylique <SEP> 21,69 <SEP> 21,36
<tb> aldéhyde-5-chloro-salicylique <SEP> 260-261 C <SEP> acide <SEP> acétique <SEP> 20,10 <SEP> 19,66
<tb> 
 
 EMI18.2 
 2-pyrrolaldéhyde 2.5 c(déc.) eau 27261 27,40 
 EMI18.3 
 
<tb> aldéhyde <SEP> picolinique <SEP> 158-160 C <SEP> benzène <SEP> 30,55 <SEP> 29,

  95
<tb> 
 
 EMI18.4 
 2-acétyl-pyridine 13941410C alcool éthylique à 90% 28e79 28959 

 <Desc/Clms Page number 19> 

 EXEMPLE 9.- 
 EMI19.1 
 2- icola.n lhydrazino-Q.mméthylm6éthoxypyrïmidine,-   (Formule 1 :   Y=X=R2=H; R1=CH3; R3=OC2H5)
On dissout 1,7 g de 2-hydrazino-4-méthyl-6-éthoxypyrimidine et 1,15 g d'aldéhyde picolinique dans 10 ml d'alcool absolu, et on chauffe'au bainmarie pendant 3 heures. Cette solution est évaporée à sec, sous vide et le résidu est trituré dans de l'éther. On obtient ainsi 0,95 g de cristaux. 



  P.F.   161-163 C   (déco)o Le point de fusion ne change pas après recristallisation dans le benzène. 



  Analyse. Calculé pour C13H15N5O2 :   N=27,22%.   



   Trouvé   : N=26,99%.   



   On prépare de la même façon les produits de condensation suivants : 2-(salicylidène   hydrazino)-4-méthyl-6-éthoxypyrimidine;   P.F.:144-146 C. 



  Analyse : Calculé :  N=20,57%;   trouvé N=   20,49%.   
 EMI19.2 
 



  2-(cc-méthylpicolinyl-hydrazino)-q.-méthyl-6-éthoxypyrinidine; P.F..,   161-163 C.   Analyse: Calculé :   N=25,81%;   trouvé : N=25,60%. 



   EXEMPLE 10.- 
 EMI19.3 
 2- ( salicylidè¯ne-hrazino )-4-méthylp6 irooxypyrimidine . 



  (Formule I : X=Y=R =H, R1=CH , R =00 H iso). 



  On dissou 1,5 g de -hydaziffo-q.-méthyl-6-isopropoxypyrimidine dans 15 ml d'un mélange 1:1 acide acétique-eau, on ajoute une solution de 1,05 g d'aldéhyde salicylique dans 2 ml d'alcool et on chauffe au bain-marie pendant 1 1/2 heures. Cette solution est évaporée à sec sous vide, et le résidu est cristallisé dans un mélange eau-alcool. On obtient ainsi 1 g de cristaux. Après recristallisation dans un mélange eau-alcool, le point de fusion est 154-155 C. 



  Analyse : Calculé pour C15H18N4O2 :N=19,56%. 



   Trouvé : N=19,31%. 



   Par le même mode opératoire, on a préparé encore les produits de condensation suivants : 
 EMI19.4 
 2-(2'-hydroxy-o;-méthyl-benzylidène-hydrazino)-4-méthyl-6-isoiropoxy-pyrimidine; P.F. 165-167 C. Analyse : Calculé: N =18,65%; trouvé : N= 18,56%. 



  2-(51-ohloro-salicylidène-hydrazino)-4-méthyl-6-isopropoxypyrimidine; P.F. : 202-204 C; Analyse: calculé : N=17,46%; trouvé:N=17,74%. 



  2-(picolinyl-hydrazino)-q.méthyl-6-isopropoxypyrimidine; P.F, : 191-192 C; Analyse : calculé : N=25,81%; trouvé : N=25 ,'59%. 



  2-(cx-méthylpicolinyl-hydrazino)-4-méthyl-6-isopropoxypyrimidine; P.F. ;   142-144 C.   Analyse : calculé :   N=24,54%;   trouvé :   N=24,12%.  
EXEMPLE 11.- 
 EMI19.5 
 2-  -chlorosalic lidèneh drazino -q.-méth 1 rimidine,- (Formule I : X=Y=R 2=R3 =H; R1=CH3) On ajoute 1 g de 2-hydrazino; 4-méthylprrimidine . dans 10 ml d'un mélange 1:1 acide acétique-eau à une solution de 1,2 g d'àldéhyde 5chlorosalicylique dans 4 ml d'alcool éthylique, et chauffés au bain-marie   pendant 1 1/2 heures. Les cristaux qui se séparent après refroidissement, sont essorés, lavés et séchés (1,2 g). Après recristallisation dans l'alcool   éthylique, le point de fusion est 206-208 C. 

 <Desc/Clms Page number 20> 

 
 EMI20.1 
 Analyse Calculé pour C12H11N40Cl : N= 21532%. 



   Trouvé   : N=21,56%.   



   Par le même mode opératoire, on a préparé encore le produit de condensation suivant :   2-(salicylidène-hydrazino)-4-méthylpyrimidine.   P.F. 162-164 C. Analyse ; Calculé :   N=24,54%;   trouvé :   N=24,53%.   



     EXEMPLE   12.- 
 EMI20.2 
 lidène-h drazino - -méth 1 rimidine.- (Formule II :   R3=X=Y=H;   R1=CH3)
On dissout 2 g de   6-hydrazino-4-méthylpyrimidine   et 2 g d'aldéhyde salicylique dans 10 ml d'alcool absolu, et on chauffe au bain-marie pendant 1/4 heure . Le précipité qui se forme est essoré, lavé et recristallisé dans le dioxaneo P.F. :   251-252 Co   Analyse :Calculé pour C12H12N4O ; N=   24,55%  
Trouvé   : N=24,54%.   



   EXEMPLE 13.- 
 EMI20.3 
 6- 2 -hdro -cx-méth lbenz lidêne-h drazi,no -2-h dro -°-méth 1 rimidine.Formule II : R 1 =Y=CH 3; X=H; R3=OH) 
1,4 g de   2-hydroxy-4-méthyl-6-hydrazinopyrimidine   sont dissous dans 15 ml d'un mélange 1:1 d'acide acétique-eau; on ajoute une solution de 1,4 g   d'o-hydroxyacétophénone   dans 3 ml d'alcool éthylique et on chauffe au bainmarie pendant 1   1/2   heures. Le précipité qui se forme est essoré, lavé et séché. (2,2 g)o Par recristallisation dans l'acide acétique, on obtient des cristaux blancs. P.F.   283-285 C   (déc.). 
 EMI20.4 
 



  Analyse : Calculé pour C13H14N402 ' N=21,69; 
Trouvé : N=   21,44%.   



   En appliquant le même mode opératoire, on a encore préparé les produits de condensation suivants : 
 EMI20.5 
 6-(salicylidène-hydrazino)-2-hydroxy-°-méthylprimidine; P.F. 289 C. 



  Analyse : Calculé : N= 22,93%; trouvé : N=22,77%. 



  6-(5 -chlorosalicylidène-hydrazino)-2-hydroxy-°-méthylpyrimidine; P.F.; 310 C; Analyse : Calculé :   N=20,10%;   trouvé :   N=20,08%.   



    6-(picolinyl-hydrazino)-2-hydroxy-4-méthylpyrimidine;   P.F. : 273 C; Analyse : calculé :  N=30,55%;   trouvé :   N=30,80%.   
 EMI20.6 
 



  6-(a-méthylpicolinyl-hydrazino)-2-hydroxyq.méthy-lpyrimidine; P.F. 238-2400c; Analyse : calculé :   N=28,79%;   trouvé :   N=29,07%.  
EXEMPLE   15.-   
 EMI20.7 
 6- salic lidêne-hydrazino)-2-amino-°-mêthylprimidine.- (Formule II : X=Y=H; R1=CH3; R 3=NH 2 ) 
A une solution de 1,15 g de 2-amino-4-méthyl-6-hydrazino pyrimidi-   ne dans 10 ml d'un mélange 1 :1 acideacétique-eau, on ajoute une solution   de 1 g d'aldéhyde salicylique dans 2 ml d'alcool éthylique, et on chauffe au bain-marie pendant 1 1/2 heures. Le produit, qui se sépare en refroidissant, est essoré, lavé et séché (1,38 g). Après recristallisation dans l'alcool   éthylique, le point de fusion est de 209-211 . Analyse pour C12H13N5O : calculé N=28,79%; trouvé : N=28,7%.   



   On a préparé de la même façon, avec les aldéhydes ou cétones apprc - 

 <Desc/Clms Page number 21> 

 priées, les produits de  condensation,suivants :   
 EMI21.1 
 6-(2 -hydroxyma-méthylbenzylidéne-hydrazino-2-amino-4-méthylpyrimidine; P.P..214-2160C. Calculé : N=27,229 trouvé : N=26,96%. 



    6-(5'-chlorosalicylidène-hydrazino)-2-amino-4-méthylpyrimidine.   P.F.; 234-241 C; Calculé :   N=25,22%;   trouvé :   N=24,45%.   



    6-picolinyl-hydrazino)-2-amino-4-méthylpyrimidine;   P.F. :  236-238 C;   calculé : N=36,82%; trouvé :   N=36,94%.   



   L'invention concerne également des compositions thérapeutiques utilisables comme tuberculostatiques ou fongicides. Ces compositions peuvent se présenter sous forme d'onguents, de lotions ou de poudres.et contiennent, en plus des excipients connus, au moins un nouveau dérivé d'hydrazinopyrimidine suivant l'invention en quantité thérapeutiquement active. 



    REVENDICATIONS.-   1.- A titre de nouveaux composés   chimiques utisables   en thérapeutique, les produits de condensation   d'hydrazinopyrimidines   avec des dérivés carbonylés choisis parmi les aldéhydes et cétones aromatiques et   hétérocycli-   ques.



   <Desc / Clms Page number 1>
 



   The present invention relates to a series of novel hydrazinopyrimidine derivatives, which have tuberculostatic or fungicidal activity. The invention relates more particularly to condensation products of hydrazinopyrimidines with carbonyl derivatives chosen from aromatic and heterocyclic aldehydes and ketones.



   The invention also relates to a process for preparing the novel hydrazinopyrimidines derivatives.



   The new hydrazinopyrimidines derivatives can be represented by the following formulas:
 EMI1.1
 in which R and R @ represent a hydrogen atom or a methyl radical, R3 represents a hydrogen atom, or a hydroxy, alkoxy or amino group, X and Y represent a hydrogen atom or a methyl radical, and A is an aromatic or heterocyclic ring, optionally substituted by nitro, amino, halo, hydroxy or alkoxy groups.



   The novel hydrazinipyrimidine derivatives according to the invention can be prepared by the condensation of a hydrazinopyrimidine with the aromatic or heterocyclic aldehyde or ketone.



   The synthesis of the derivatives according to the invention can be schematized as follows:
 EMI1.2
 

 <Desc / Clms Page number 2>

 
 EMI2.1
 
The condensation of a hydrazinopyrimidine with an aldehyde or an aromatic or heterocyclic ketone is preferably carried out in an alcohol-water medium, optionally containing an acid, such as acetic acid or hydrochloric acid.



   Most of the derivatives of formulas I and II have tuberculostatic activity. This activity is most pronounced when the substituent R3 is a hydroxy or amino group and A is a benzo ring having a hydroxy group in the ortho position. By way of indication, the concentrations of some derivatives which inhibit the development of Mycobacterium tuberculosis, strain H37Rv in Dubos' medium, are given in Table I below.

 <Desc / Clms Page number 3>

 



     TABLE I.- 1) Derivatives of formula I.-
 EMI3.1
 YX Rl R2 R3 Inhibitory concentration m> miorograms / milliliter.- \ 1 == "HH CH3 H OH a 5 H <- CHg CEg OH \ CH3 CR.> OH w ,, ¯ HH CH3 OH cr, = # 'H. z -> - HH OH3 H OH 5 N02 OH N0 -.- HH CH3 H OH 10 rrz OH N .- HH CH3 H OH 10 OH H0 -.- HH CH3 H OH 100 OH C1, ± Q- HH CH3 H OH OH NO 2 .- HH CH3 H OH 10., H

 <Desc / Clms Page number 4>

 
Table I (Continued) .- 1) Derivatives of formula 1 (continued) .-
 EMI4.1
 A Y X Rl IL, R3 Concentra.



  -tion inhi -bitrice in micro- * grams / mill! -tritre '.- H CHg OH 100 É CRs OH' Ho, ē-.



  .! / \ - Qg¯, at CH3 \. ## ..



  OH CH30 -, - H H OH3 'H OH 100. , # / 'o OH bzz - \ - H H C H OH 10 / m / l .J.



  -¯.-OH H H CH3 H OH 5 ..¯ ..? # '\, H H CH3 H OH 20,. ::::. N 7 .'.- C H CE; 3' OH '10 N- H H. CH3 H OH 100 # - --- ¯, H H CH3 H OH 20 - /

 <Desc / Clms Page number 5>

 
 EMI5.1
 Table I continued .- 1) Derivatives of formula I (continued) .-
 EMI5.2
 1 2 R3 Inhibitory concentration in micrograms / milliliter = ¯ ¯ H CR.3 CH3 H OH H / ..-.- v .. H CH3 CH3 H OH H "H CH3 CH3 H on 20 1 '' HHS CH3 OH OH Cl -v \ .¯ CH3 OH cH3 OH - <=, - OH3 'H Î2 20 OH Cl @ - HH CR.3 H NB 100 OH; 7-- \ ..- HH CH3 H NHg 12'. = N / Chez NHZ '==' "CH3 OCH3).

   J6 '6 ¯? '' "CH B CH H 0 - H H S S CR.3 100 OH

 <Desc / Clms Page number 6>

 
Table I (continued) .- 1) Derivatives of formula I (continued) .-
 EMI6.1
 Y X RI R2 R3 Inhibitory concentration in micrograms / milliliter. - 1 / \ - H H H H OCH3 10 DH * 1 H H H H 01! 1H;

  ) 5 / "" - HH CH H 0 C2H5 10 q- 'OH ¯ H, H CH3 H 002H5 10 O- HH CH3 H 0 C3H7 100 OH Cl <- HH CH3 H OC3H, 100 OH - HH CH3, H OC3H7 5, r --- /, ¯ HHIHH 20 OH 2) Derivatives of formula II.-
 EMI6.2
 H H "3 OH 0.5 OH ¯ CE / H OH3 OH 0.5 OH

 <Desc / Clms Page number 7>

 
TABLE I (continued) .- 2) Derivatives of formula II (continued). -
 EMI7.1
 Y X Ri R2 R3 Inhibitory concentration in monograms / milliliter C1 H H CH3 OH 5 OH <## \ H H CI! 3 - N? 32 2.5 OH - CI! 3 H CI! 3 - Jffi2 10 oH ci .- H H CI! 3 - NH2 12 OH <-> - H H CH3 rH2 5
Certain compounds of the same series have a notable fungistatic power. Tests were performed by preparing a series of dilutions of the product in liquefied "nutrient agar". This was poured into a Petri dish, and on this solidified agar, various molds were seeded.

   After incubation at a temperature of 37 for 3-6 days, it was examined whether there was development or not.



   In the following Table II, the inhibitory concentrations (in micrograms per millimeter) of some compounds are indicated.

 <Desc / Clms Page number 8>

 
TABLE II Microorganisms
 EMI8.1
 
<tb>
<tb> Compound <SEP> of <SEP> Candida <SEP> Cryptococ- <SEP> Trichophy <SEP> Sporatri- <SEP> Philiaphoformule <SEP> I <SEP> albicans <SEP> ous.sp.

   <SEP> your <SEP> rubrum <SEP> chon <SEP> ra <SEP> pedrosii
<tb> Y <SEP> R1 <SEP> R3 <SEP> schenckii
<tb> CH3 <SEP> CH3 <SEP> OH <SEP> 20 <SEP> 40 <SEP> 20 <SEP> 20 <SEP> 30
<tb> H <SEP> CH3 <SEP> NH2 <SEP> - <SEP> - <SEP> 10
<tb> H <SEP> CH3 <SEP> OCH3 <SEP> 20 <SEP> 30 <SEP> 20 <SEP> 20 <SEP> 30
<tb> H <SEP> H <SEP> OCH3 <SEP> 10 <SEP> 20 <SEP> 10 <SEP> 20 <SEP> 15
<tb> OH3 <SEP> H <SEP> OCH3 <SEP> 10 <SEP> 10 <SEP> 5 <SEP> 10 <SEP> 10
<tb> Compounds <SEP> of
<tb> formula <SEP> II
<tb> H <SEP> CH3 <SEP> OH <SEP> - <SEP> - <SEP> 10
<tb> CH3 <SEP> CH3 <SEP> OH <SEP> 30 <SEP> 50 <SEP> 30 <SEP> 30 <SEP> 30
<tb>
 
In the compounds of formula I and II mentioned in Table II: A = #; X = R2 or H
In this Table II, the sign - indicates that there is no decrease inhibition.



   As hydrazinopyrimidines which can be used in the process according to the invention, mention may be made, by way of examples, of the following: 2-hydrazino-4-methyl-6hydroxypyrimidine; 2-methyl-hydrazino-4-methyl-6-hydroxypyrimidine; 2-hydrazino-5-methyl-6-hydroxypyrimidine; 2-hydrazino-4-methyl-6-aminopyrimidine; 2-hydrazino-4-methyl-6-methoxypyrimidine; 2-hydrazino-6-methoxypyrimidine; 2-hydrazino-4-methyl-6-ethoxypyrimidine; 2-hydrazino-4-methyl-6-isopropoxypyrimidine; 2-hydrazino-4-methylpyrimidine; 6-hydrazino-4-methylpyridimidine; 2-hydroxy-4-methyl-6-hydrazinopyrimidine; 2-amino-4-methyl-6-hydrazinopyrimidine.



   As aromatic and heterocyclic aldehydes which can be used in the process according to the invention, there may be mentioned, by way of examples, the following: salicylic aldehyde, cumin aldehyde, 3-nitrosalicylic aldehyde, 3-chlorosalicylic aldehyde, resorcylic aldehyde, 4- aldehyde nitrosalicyl, 4-aminosalicyl aldehyde, gentisic aldehyde, 5-nitrosalicyl aldehyde, 5-aminosalicyl aldehyde, 5-chlorosalicyl aldehyde, o-methoxybenzoic aldehyde, o-nitrobenzoic-aldehyde-nitrobenzoic-aldehyde-nitrobenzoic-aldehyde-aldehyde-nitrobenzoic acid-aldehyde-nitrobenzoic-aldehyde-nitrobenzoic-aldehyde-nitrobenzoic-aldehyde-nitrobenzoic-aldehyde-nitrobenzoic-aldehyde-nitrobenzoic-aldehyde-nitrobenzoic-aldehyde-nitrobenzoic-aldehyde , m-hydroxybenzoic aldehyde, p-hydroxybenzoic aldehyde, anisic aldehyde, p-nitrobenzoic aldehyde, p-aminobenzoic aldehyde;

     p-acetylaminobenzoic aldehyde, p-dimethylaminobenzoic aldehyde, p-chlorobenzoic aldehyde, 2,4-dichlorobenzole aldehyde, 2,3-dimethoxybenzoic aldehyde, ss-hydroxy- [alpha] -naphthalene aldehyde, al-

 <Desc / Clms Page number 9>

 
 EMI9.1
 dehydea-hydroicy-p-naphthalenic, nicotinic aldehyde, isonicotin aldehyde, picolinic aldehyde, 6-methylpicolinic aldehyde, 2- quinolenic aldehyde, 6-hydroxy-4-pyrimidine aldehyde, 2,6-dihydroxy-4-pyrimfuraldehyde, 2-4-pyrimidine aldehyde, pyrrolic.



   As aromatic and heterocyclic ketones which can be used in the process according to the invention, the following may be mentioned, by way of examples: acetophenone, o-hydroxy-acetophenone, p-hydroxyacetophenone, pnitroacetophenone, 2-acetylpyridine, 3-acetylpyridine, isatin .



   The following examples illustrate the invention, but it is understood that they should not be considered as limiting.



   EXAMPLE 1.-
 EMI9.2
 2- (salicylidene-hdrazino) - ° -methyl-6-hydrox, ypyrl¯midine.- (Formula I: R1CH3 'R = OH; R2 = X = Y = H)
1.4 g of 2-hydrazino-4-methyl-6-hydroxypyrimidine are dissolved in 3 ml of 2N hydrochloric acid and 2 ml of water; a solution of 1.2 g of salicylic aldehyde dissolved in 4 ml of ethyl alcohol is added and the mixture is heated in a water bath for 1 1/2 hours. The precipitate which forms is filtered off and recrystallized from methyl alcohol and acetic acid.



  White crystals are obtained which melt at 249, 2510C (with decomposition).
 EMI9.3
 Analysis: calculated for C1GH12N ° 02, HCl: N = 19.96%. Found: N = 19.88%.



  EXAMPLE 2.- 2- salic lidene-h drazino- ° -meth 1-6-h drox imidine.-
This compound can also be prepared by the following procedure:
4.2 g of 2-hydrazino-4-methyl-6-hydroxypyrimidine are dissolved in 15 ml of acetic acid and 10 ml of water. 3.7 g of salicylic aldehyde dissolved in 5 ml of ethyl alcohol are added and the mixture is heated in a water bath for 1/2 hour. The precipitate which forms is drained. 7.0 g of a product are obtained, which melts at 244-245 C. On recrystallization from acetic acid, the melting point rises to 249-251 C (decomposition).



   By using the same procedure and replacing the salicylic aldehyde with the aldehydes and ketones mentioned below, products of similar structure are obtained with similar yields:

 <Desc / Clms Page number 10>

 
 EMI10.1
 
<tb> Aldehyde <SEP> or <SEP> ketone <SEP> Melting point <SEP> <SEP> <SEP> Solvent <SEP> of <SEP> recris- <SEP> 'Calculated <SEP>% <SEP> N '<SEP> Trio
<tb> (C) <SEP> (with <SEP> decom- <SEP> metallization <SEP> Calculated '<SEP> Found <SEP>
<tb> position) <SEP> of <SEP> product <SEP> of <SEP> condensation
<tb> aldehyde <SEP> cuminic <SEP> 141-143 C <SEP> alcohol <SEP> ethyl <SEP> 20.73 <SEP> 20.37
<tb> o-hydroxyacetophenone <SEP> 245-246 C <SEP> alcohol <SEP> ethyl-pyridine <SEP> 21.69 <SEP> 21.66
<tb> aldehyde <SEP> 3-nitrosalicylic <SEP> 243-244 C <SEP> acetic <SEP> acid <SEP> 24,21 <SEP> 24,

  08
<tb> aldehyde <SEP> 3-chlorosalicylic <SEP> 241-243 C <SEP> acetic <SEP> acid <SEP> 20.10 <SEP> 19.92
<tb> aldehyde <SEP> resorcylic <SEP> 276 c <SEP> acid <SEP> acetic-alcohol <SEP> ethyl- <SEP> 21.63 <SEP> 21.59
<tb> lique
<tb> aldehyde <SEP> 4-nitrosalicylic <SEP> 306-307 C <SEP> acid <SEP> acetic-alcohol <SEP> methy- <SEP> 24.18 <SEP> 24.31
<tb> lique
<tb> aldehyde <SEP> 4-aminosalicylic <SEP> 248-249 C <SEP> acetic acid <SEP> <SEP> 21.98 (a) <SEP> 21.90
<tb> aldehyde <SEP> gentisic <SEP> 277 C <SEP> acid <SEP> acetic <SEP> 21.53 <SEP> 20.61
<tb> aldehyde <SEP> 5-nitrosalicylic <SEP> 285-286 C <SEP> acetic <SEP> acid <SEP> 24.21 <SEP> 24.57
<tb> aldehyde <SEP> 5-aminosalicylic <SEP> 286 C <SEP> acid <SEP> acetic-water <SEP> 21.08 (b) <SEP> 21,

  26
<tb> aldehyde <SEP> 5-chlorosalicylic <SEP> 251-252 C <SEP> acetic <SEP> acid <SEP> 20.10 <SEP> 20.24
<tb> aldehyde <SEP> o-methoxybenzoic acid <SEP> 197-199 C <SEP> acetic <SEP> acid <SEP> 21.69 <SEP> 21.50
<tb>
 

 <Desc / Clms Page number 11>

 
 EMI11.1
 
<tb> Aldehyde <SEP> or <SEP> ketone <SEP> Melting point <SEP> <SEP> <SEP> Solvent <SEP> of <SEP> recris- <SEP>% <SEP> N
<tb> (C) <SEP> (with <SEP> decom- <SEP> metallization <SEP> Calculated <SEP> Found
<tb> position) <SEP> of the <SEP> product <SEP> Calculate <SEP> Find
<tb> from <SEP> condensation
<tb> aldehyde <SEP> o-nitrobenzoic <SEP> 209-210 C <SEP> alcohol <SEP> ethyl-pyridine <SEP> 25.63 <SEP> 25.61
<tb> aldehyde <SEP> o-aminobenzoic acid <SEP> 222-224 C <SEP> pyridine <SEP> 28.79 <SEP> 28.72
<tb> aldehyde <SEP> o-chlorobenzoic <SEP> 214-216 C <SEP> acid <SEP> acetic <SEP> 21.32 <SEP> 21,

  29
<tb> o-carboxybenzoic aldehyde <SEP>. <SEP> 273-274 C <SEP> Acetic <SEP> acid <SEP> 20.59 <SEP> 20.60
<tb> aldehyde <SEP> m-nitrobenzoic <SEP> 274-276 C <SEP> acetic <SEP> acid <SEP> 2563 <SEP> 25p8O
<tb> aldehyde <SEP> m-hydroxybenzoic <SEP> 244 C <SEP> acid <SEP> acetic <SEP> 22.94 <SEP> 23.02
<tb> aldehyde <SEP> p-hdroxybenzoic <SEP> 267-269oc <SEP> acetic <SEP> acid <SEP> 22.94 <SEP> 22.85
<tb> p-hydroxyacetophenone <SEP> 254-256 C <SEP> acid <SEP> acetic-alcohol <SEP> ethyl-21.69 <SEP> 21.72
<tb> that
<tb> aldehyde <SEP> anisic <SEP> 217-218 C <SEP> alcohol <SEP> ethyl <SEP> 21.69 <SEP> 21.62
<tb> aldehyde <SEP> p-nitrobenzoic <SEP> 295-296 C <SEP> acid <SEP> acetic-alcohol <SEP> m- <SEP> 25.63 <SEP> 25, $ 3
<tb> thylic
<tb> p-nitroacetophenone <SEP> 269-270 C <SEP> pyridine <SEP> 24,98 <SEP> 24,

  12
<tb> aldehyde <SEP> p-aminobenzoic <SEP> 241-243 C <SEP> pyridine <SEP> 28.79 <SEP> 27.98
<tb>
 

 <Desc / Clms Page number 12>

 
 EMI12.1
 
<tb> Laldehyde <SEP> or <SEP> ketone <SEP>. Point <SEP> of <SEP> fusion <SEP> Solvent <SEP> of <SEP> recris- <SEP>% <SEP> N
<tb> (C) <SEP> (with <SEP> decom- <SEP> metallization <SEP> Calculated <SEP> Found
<tb> position) <SEP> of <SEP> product <SEP> Calculated <SEP> Find
<tb> from <SEP> condensation
<tb>
 
 EMI12.2
 1 -¯¯¯ # ¯¯¯¯¯ ## - ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯ p-acetylaminobenzoic aldehyde 301 -05 C acetic acid 24.55 24.54 p-dimethylaminobenzoic aldehyde 226-227 C dioxane 25.81 25.81 p-chlorobenzoic aldehyde 265-267 C acetic acid 18.85 18.92 2,3-dimethoxybenzoic aldehyde 235- 237 C acetic acid 19.43 19,

  57
 EMI12.3
 
<tb> aldehyde <SEP> / <SEP> -hydroxy- <SEP> c (-naphthal- <SEP> 283 C <SEP> <SEP> acetic acid <SEP> 19.04 <SEP> 18.88
<tb> picnic
<tb>
 
 EMI12.4
 aldehyde o (-hydroxy.-aaphtha- 276 C acetic acid 19.04 1g 75
 EMI12.5
 
<tb>. <SEP> pic <SEP>
<tb> aldehyde <SEP> isonicotinic <SEP> 290 C <SEP> acid <SEP> acetic <SEP> 30.55 <SEP> 30.42
<tb> aldehyde <SEP> nicotihique <SEP> 285-287 C <SEP> acid <SEP> acetic-alcohol <SEP> 26.6l (c) <SEP> 26.21
<tb> @ <SEP> methyl
<tb> aldehyde <SEP> picolinic <SEP> 256-257 C <SEP> pyridine <SEP> 30.55 <SEP> 31.94
<tb> 2-acetylpyridine <SEP> 154-155 C <SEP> ethyl <SEP> alcohol <SEP> 28.79 <SEP> 28.60
<tb>
 

 <Desc / Clms Page number 13>

 
 EMI13.1
 
<tb> aldehyde <SEP> or <SEP> ketone <SEP> Melting point <SEP> <SEP> <SEP> Solvent <SEP> of <SEP> recris- <SEP>% <SEP> N
<tb> (C)

   <SEP> (with <SEP> decom- <SEP> setup <SEP> Calculated <SEP> Found
<tb> position) <SEP> of <SEP> product <SEP> Calculated <SEP> Found
<tb> @ <SEP> of <SEP> condensation
<tb> aldehyde <SEP> 2-quinoleic <SEP> 265 <SEP> acid <SEP> acetic <SEP> 25.07 <SEP> 24.79
<tb> isatin <SEP> 314-316 C <SEP> acetic <SEP> acid <SEP> 26.01 <SEP> 26.05
<tb> furfural <SEP> 202-203 & C <SEP> ethyl <SEP> alcohol <SEP> 25.35 <SEP> 25.61
<tb> (a) <SEP> calculated <SEP> for <SEP> C12H13N5O2.HOOC.CH3
<tb> (b) <SEP> calculated <SEP> for <SEP> C12H13N3O2.2HCl
<tb> (c) <SEP> calculated <SEP> for <SEP> C11H11N5O.CH3OH
<tb>
 

 <Desc / Clms Page number 14>

 EXAMPLE 3.-
 EMI14.1
 2- salic lidene-methylhydrazino q.-methyl6hydroxyp rimidine.



  (Formula 1: R 1 = X = CH 3eR2 = Y = He R3 = OH)
2 g of 2-methylhydrazino-4-methyl-6-hydroxypyrimidine are dissolved in 15 ml of a 1: 1 mixture of acetic acid-water and a solution is added.
 EMI14.2
 1.6 g of salicylic aldehyde in 5 ml of alcohol. We c'l3.huff'e ': you bathe for 1 1/2 hours. The precipitate which forms is drained, washed and dried. The product (3.2 g) is recrystallized from acetic acid. White crystals are obtained which melt at 248-249 C (with decomposition).



  Analysis: calculated for 0 EN 0: N = 21.69%. found: N = 21.60%
The following condensation products are prepared in the same way with suitable aldehydes:
 EMI14.3
 2 (5'-Chlorosalicylidene-methylhydrazino) -4-methyl-6-hydroxypyrimidine, P.F. 266-267 C;
 EMI14.4
 Analysis: Calculated for C13H13Nq.02C1oH2O: N = 18.03%;
Found: N = 18.21%.



    2- (6'-methylpicolinyl-methylhydrazino) -4-methyl-6-hydroxypyrimidine, P.F.



  276-278 C.



  Analysis: Calculated for C13H15N5O: N = 27.2%.



   Found: N = 27.55% 2- (pioolynyl-methylhydrazino) -4-methyl-6-hydroxypyrimidine. P.F. 245-247 C.



  Analysis: Calculated for C12H13N50: N = 28.79%
Found: N = 28.81%
It has been found that it is more advantageous to purify the products mentioned above by recrystallization from pyridine.



   EXAMPLE 4.-
 EMI14.5
 2- salia lidene-h drazino - -meth 1-6-h drox iimidineo-
Formula I: R1 = Y = X = H, R2 = CH3, R3 = OH)
0.7 g of 2-hydrazino-5-methyl-6-hydroxypyrimidine is dissolved in 8 ml of a 1: 1 mixture of acetic acid-water and a solution of 0.6 g of salicylic aldehyde in 2 ml of water is added. 'ethyl alcohol; it is heated in a water bath for 21/2 hours. The precipitate which forms is filtered off, washed and dried (1.15 g). After recrystallization from an acetic acid-ethyl alcohol mixture, white crystals are obtained; M.p. 289-291 C (decomposition).



  Analysis: Calculated for C12H12N4O2: N = 22.94%. found: N = 22.85%.



   By the same procedure, the following condensation products are prepared:
 EMI14.6
 2- (5'-chlorosalicylidene hydrazino) -5methyl6mhydroxypyrimidine; M.p .: 327 C; Analysis: Calculated: N = 20.10%;
Found: N = 20.03%.



    2- (pioolinyl-hydrazino) -5-methyl-6-hydroxypyrimidine; M.p. 255-256 C; Analysis: Calculated: N = 30.55%; Found: N = 30.54%.

 <Desc / Clms Page number 15>

 EXAMPLE 5.-
 EMI15.1
 2- (2'-Hydnoxy-ce-methylbenzylidene-hydrazino) -4-methyl-5-aminopynidine.- (Formula I: R2 = X = H; Y = R, = CH3; R3WNH 2)
1.6 g of 2-hydrazino-4-methyl-6-aminopyrimidine are dissolved in 10 ml of a 1: 1 acetic acid-water mixture, and a solution of 1.6 g of o-hydroxyacetophenone in 3 is added. ml of ethyl alcohol; it is heated in a water bath for 4 1/2 hours. The solution is evaporated to dryness and the residue is treated with water. The product is drained, washed and dried (1.6 g).



  After recrystallization from ethyl alcohol, white crystals are obtained; M.P .: 257-259 C (dec.) Analysis: Calculated for C13H15NSO:
N = 27.10%
Found: N = 27.22%.



   The following condensation products were prepared in the same way: 2- (salicylidene-hydrazino) -4-methyl-6-aminopyrimidine-, m.p. 244-246 C. Analysis: calculated N = 28.79%; found: N = 28.57%.
 EMI15.2
 



  2- (5'-ahlorosalicylidene-hydrazino) -q.-methyl-6-aminopyrimidine. P.F.



  213-215 C. Analysis: Calculated: N = 25.22%;
Found: N = 24.64%.



    2- (picolinyl-hydrazino) -4-methyl-6-aminopyrimidine. M.P .: 210-211 C. Analysis: Calculated: N = 36.82%. Found: N = 36.16%.



   EXAMPLE 6. -
 EMI15.3
 2- salic lidene-lz drazino -q.mé, h 1-6-methox rimidine.- (Formula I: R2 = Y = X = H; R1 = CH3; R3OCH3).



   1.55 g of 2-hydrazino-4-methyl-6-methoxypyrimidine are dissolved in 15 ml of a 1: 1 mixture of water-acetic acid; a solution of 1.25 g of salicylic aldehyde in 5 ml of ethyl alcohol is added and the mixture is heated in a water bath for 1 hour. The precipitate which forms is drained, washed and dried (2.15 g). After recrystallization from ethyl alcohol, one obtains
 EMI15.4
 a white product., P.F: oc. Analysis: Calculated for C13H14N4O2 'I = 21.69 Found: N = 21.59%.



   The condensation of 2-hydrazino-4-methyl-6-methoxypyrimidine with the aldehydes or ketones mentioned below was carried out by the same procedure and with the same yields. For aldehydes or ketones, with a pyridine ring, or pyrimidine, generally no alcohol has been added to the reaction medium. For the pyrimidine aldehydes, 20 ml of acetic acid and 10 ml of water were used to dissolve the reagents.

   The reaction products generally precipitated in the reaction medium when hot or after cooling, but in some cases the solution had to be concentrated.

 <Desc / Clms Page number 16>

 
 EMI16.1
 
<tb> aldehyde <SEP> or <SEP> ketone <SEP> Melting point <SEP> <SEP> <SEP> Solvent <SEP> of <SEP> recris- <SEP>% <SEP> N
<tb> (C) <SEP> of <SEP> product <SEP> of <SEP> tallization <SEP> Calculated <SEP> Found
<tb> condensation
<tb> aldehyde <SEP> 5-chlorosalicylic <SEP> 199-200 C <SEP> alcohol <SEP> ethyl <SEP> 19,14 <SEP> 19.00
<tb> .o-hydroxyacetophenone <SEP> 149-151 C <SEP> alcohol <SEP> ethyl <SEP> 20.57 <SEP> 20.56
<tb>
 
 EMI16.2
 picolinic aldehyde 174-175 C benzene 28p79 28t6g
 EMI16.3
 
<tb> aldehyde <SEP> 6-methylpicolinic <SEP> 126-128 C <SEP> alcohol <SEP> ethyl <SEP> absolute <SEP> 27,22 <SEP> 26,

  94
<tb>
 
 EMI16.4
 nicotinic aldehyde 205-207.0 ethyl alcohol 28e79 28957 isonicotin aldehyde 160.1651c ethyl alcohol acetate $ 2.79 27948
 EMI16.5
 
ethyl <tb>
<tb> 2-acetylpyridine <SEP> 162-164 C <SEP> ethyl acetate <SEP> <SEP> 27.22 <SEP> 27.08
<tb>
 
 EMI16.6
 3-acetylpyridine 153-1540e acetatedtethyl-a7coolethy- 27.22 26.99
 EMI16.7
 
<tb> lique
<tb> aldehyde <SEP> 2-quinoleic <SEP> 200-202 C <SEP> ethyl acetate <SEP> <SEP> 23.88 <SEP> 23.57
<tb>
 
 EMI16.8
 6-hydroxy -.- pyrimidane aldehyde 24600 (dee.) Ethyl alcohol 32.29 31.96 2,6-.dihydroxy-4-pyrimidine aldehyde 34000 (dec.) Pyridine 30, L, .2 30.14

 <Desc / Clms Page number 17>

 EXAMPLE 7.-
 EMI17.1
 2- (pīaoignyih> 4nzzinç> = 1 = * + ¯tàyi-6 = mé <hoxypyràmoeàine-¯
31 g of 2-hydrazino-4-methyl-6-methoxypyrimidine and 32 g are dissolved,

  5 g of picolinic aldehyde in 150 ml of absolute alcohol, and the mixture is heated in a water bath for 5 hours - After cooling, the crystals are filtered off, and by concentrating the mother liquors, a second and third fraction is still obtained. . 37 g of slightly yellowish crystals are thus obtained.



  P.F .: 174-176 C.



    EXAMPLE 8.-
 EMI17.2
 2-salic .idenetßdrz.io .: "-6-methoxyimidine .- (Formula 1: Y = X = R1 = R2 = R; R3 = CH30).



   1 g of 2-hydrazino-6-methoxypyrimidine is dissolved in 10 ml of a 1: 1 mixture of acetic acid-water and a solution of 0.9 g of salicylic aldehyde in 2 ml of ethyl alcohol is added, and one adds heat in a bain-marie for 1 1/2 hours. After cooling, the precipitate is filtered off, which is washed and dried (1.45 g). After recrystallization from ac-
 EMI17.3
 tick, the melting point is 230-231- Ca Analysis Calculated for C12H12N402:
N, 22.94%; Found: N = 22.68%.



   Following the same procedure, 2-hydrazino-6-methoxypyrimidine was condensed with aldehydes of ketones mentioned below.



  For reactions with picolinic aldehyde and 2-acetylpyridine, acetic acid-water was not added, but only absolute alcohol and heated for a longer period (3 to 5 hours).

 <Desc / Clms Page number 18>

 
 EMI18.1
 
<tb> aldehyde <SEP> or <SEP> ketone <SEP> Melting point <SEP> <SEP> <SEP> Solvent <SEP> of <SEP>% <SEP> N
<tb> (C) <SEP> from <SEP> product <SEP> recrystallization <SEP> Calculated <SEP> Found
<tb> of <SEP> condensation <SEP> Calculate <SEP> Found
<tb> o-hydroxyaceto-phenone <SEP> 135-136 C <SEP> alcohol <SEP> ethyl <SEP> 21.69 <SEP> 21.36
<tb> 5-chloro-salicylic-aldehyde <SEP> 260-261 C <SEP> acetic <SEP> acid <SEP> 20.10 <SEP> 19.66
<tb>
 
 EMI18.2
 2-pyrrolaldehyde 2.5 c (dec.) Water 27261 27.40
 EMI18.3
 
<tb> aldehyde <SEP> picolinic <SEP> 158-160 C <SEP> benzene <SEP> 30.55 <SEP> 29,

  95
<tb>
 
 EMI18.4
 2-acetyl-pyridine 13941410C 90% ethyl alcohol 28e79 28959

 <Desc / Clms Page number 19>

 EXAMPLE 9.-
 EMI19.1
 2- icola.n lhydrazino-Q.mmethylm6ethoxypyrimidine, - (Formula 1: Y = X = R2 = H; R1 = CH3; R3 = OC2H5)
1.7 g of 2-hydrazino-4-methyl-6-ethoxypyrimidine and 1.15 g of picolinic aldehyde are dissolved in 10 ml of absolute alcohol, and heated in a water bath for 3 hours. This solution is evaporated to dryness under vacuum and the residue is triturated in ether. 0.95 g of crystals are thus obtained.



  M.p. 161-163 C (deco) o The melting point does not change after recrystallization from benzene.



  Analysis. Calculated for C13H15N5O2: N = 27.22%.



   Found: N = 26.99%.



   The following condensation products are prepared in the same way: 2- (salicylidene hydrazino) -4-methyl-6-ethoxypyrimidine; M.P.:144-146 C.



  Analysis: Calculated: N = 20.57%; found N = 20.49%.
 EMI19.2
 



  2- (cc-methylpicolinyl-hydrazino) -q.-methyl-6-ethoxypyrinidine; M.p., 161-163 C. Analysis: Calculated: N = 25.81%; found: N = 25.60%.



   EXAMPLE 10.-
 EMI19.3
 2- (salicylidene-hrazino) -4-methylp6 irooxypyrimidine.



  (Formula I: X = Y = R = H, R1 = CH, R = 00 H iso).



  1.5 g of -hydaziffo-q.-methyl-6-isopropoxypyrimidine are dissolved in 15 ml of a 1: 1 mixture of acetic acid-water, a solution of 1.05 g of salicylic aldehyde in 2 ml of water is added. alcohol and heat in a water bath for 1 1/2 hours. This solution is evaporated to dryness under vacuum, and the residue is crystallized from a water-alcohol mixture. In this way 1 g of crystals is obtained. After recrystallization from a water-alcohol mixture, the melting point is 154-155 C.



  Analysis: Calculated for C15H18N4O2: N = 19.56%.



   Found: N = 19.31%.



   By the same procedure, the following condensation products were also prepared:
 EMI19.4
 2- (2'-hydroxy-o; -methyl-benzylidene-hydrazino) -4-methyl-6-isoiropoxy-pyrimidine; M.p. 165-167 C. Analysis: Calculated: N = 18.65%; found: N = 18.56%.



  2- (51-ohloro-salicylidene-hydrazino) -4-methyl-6-isopropoxypyrimidine; M.p .: 202-204 C; Analysis: Calculated: N = 17.46%; found: N = 17.74%.



  2- (picolinyl-hydrazino) -q.methyl-6-isopropoxypyrimidine; M.p .: 191-192 C; Analysis: Calculated: N = 25.81%; found: N = 25, '59%.



  2- (cx-methylpicolinyl-hydrazino) -4-methyl-6-isopropoxypyrimidine; P.F.; 142-144 C. Analysis: Calculated: N = 24.54%; found: N = 24.12%.
EXAMPLE 11.-
 EMI19.5
 2- -chlorosalic lideneh drazino -q.-meth 1 rimidine, - (Formula I: X = Y = R 2 = R3 = H; R1 = CH3) 1 g of 2-hydrazino is added; 4-methylprrimidine. in 10 ml of a 1: 1 mixture of acetic acid-water to a solution of 1.2 g of 5chlorosalicyl aldehyde in 4 ml of ethyl alcohol, and heated in a water bath for 1 1/2 hours. The crystals which separate after cooling are drained, washed and dried (1.2 g). After recrystallization from ethyl alcohol the melting point is 206-208 C.

 <Desc / Clms Page number 20>

 
 EMI20.1
 Analysis Calculated for C12H11N40Cl: N = 21532%.



   Found: N = 21.56%.



   By the same procedure, the following condensation product was further prepared: 2- (salicylidene-hydrazino) -4-methylpyrimidine. Mp 162-164 C. Analysis; Calculated: N = 24.54%; found: N = 24.53%.



     EXAMPLE 12.-
 EMI20.2
 lidene-h drazino - -meth 1 rimidine.- (Formula II: R3 = X = Y = H; R1 = CH3)
2 g of 6-hydrazino-4-methylpyrimidine and 2 g of salicylic aldehyde are dissolved in 10 ml of absolute alcohol, and the mixture is heated in a water bath for 1/4 hour. The precipitate which forms is filtered off, washed and recrystallized from dioxaneo M.P .: 251-252 Co Analysis: Calculated for C12H12N4O; N = 24.55%
Found: N = 24.54%.



   EXAMPLE 13.-
 EMI20.3
 6- 2 -hdro -cx-meth lbenz lidene-h drazi, no -2-h dro - ° -meth 1 rimidine.Formula II: R 1 = Y = CH 3; X = H; R3 = OH)
1.4 g of 2-hydroxy-4-methyl-6-hydrazinopyrimidine are dissolved in 15 ml of a 1: 1 mixture of acetic acid-water; a solution of 1.4 g of o-hydroxyacetophenone in 3 ml of ethyl alcohol is added and the mixture is heated in a water bath for 1 1/2 hours. The precipitate which forms is drained, washed and dried. (2.2 g) o By recrystallization from acetic acid, white crystals are obtained. M.p. 283-285 C (dec.).
 EMI20.4
 



  Analysis: Calculated for C13H14N4O2 'N = 21.69;
Found: N = 21.44%.



   By applying the same procedure, the following condensation products were further prepared:
 EMI20.5
 6- (salicylidene-hydrazino) -2-hydroxy- ° -methylprimidine; P.F. 289 C.



  Analysis: Calculated: N = 22.93%; found: N = 22.77%.



  6- (5 -chlorosalicylidene-hydrazino) -2-hydroxy- ° -methylpyrimidine; P.F .; 310 C; Analysis: Calculated: N = 20.10%; found: N = 20.08%.



    6- (picolinyl-hydrazino) -2-hydroxy-4-methylpyrimidine; M.p .: 273 C; Analysis: Calculated: N = 30.55%; found: N = 30.80%.
 EMI20.6
 



  6- (α-methylpicolinyl-hydrazino) -2-hydroxyq.methyl-lpyrimidine; M.p. 238-2400c; Analysis: Calculated: N = 28.79%; found: N = 29.07%.
EXAMPLE 15.-
 EMI20.7
 6- salic lidene-hydrazino) -2-amino- ° -methylprimidine.- (Formula II: X = Y = H; R1 = CH3; R 3 = NH 2)
To a solution of 1.15 g of 2-amino-4-methyl-6-hydrazino pyrimidine in 10 ml of a 1: 1 mixture of acetic acid-water is added a solution of 1 g of salicylic aldehyde in 2 ml of ethyl alcohol, and heated in a water bath for 1 1/2 hours. The product, which separates on cooling, is drained, washed and dried (1.38 g). After recrystallization from ethyl alcohol, the melting point is 209-211. Analysis for C12H13N5O: calculated N = 28.79%; found: N = 28.7%.



   We prepared in the same way, with the aldehydes or ketones apprc -

 <Desc / Clms Page number 21>

 required, the following condensation products:
 EMI21.1
 6- (2-Hydroxyma-methylbenzylidene-hydrazino-2-amino-4-methylpyrimidine; P.P..214-2160C. Calculated: N = 27.229 Found: N = 26.96%.



    6- (5'-Chlorosalicylidene-hydrazino) -2-amino-4-methylpyrimidine. P.F .; 234-241 C; Calculated: N = 25.22%; found: N = 24.45%.



    6-picolinyl-hydrazino) -2-amino-4-methylpyrimidine; M.p .: 236-238 C; calculated: N = 36.82%; found: N = 36.94%.



   The invention also relates to therapeutic compositions which can be used as tuberculostatics or fungicides. These compositions can be in the form of ointments, lotions or powders and contain, in addition to known excipients, at least one new hydrazinopyrimidine derivative according to the invention in a therapeutically active amount.



    CLAIMS 1.- As new chemical compounds which can be used in therapy, the condensation products of hydrazinopyrimidines with carbonyl derivatives chosen from aromatic and heterocyclic aldehydes and ketones.

Claims

2.- As novel chemical compounds according to claim 1, the compounds of formula: EMI21.2 in which R and R denote a hydrogen atom or a methyl radical, R denotes a hydrogen atom or a hydroxy, alkoxy or amino group, X and Y denote a hydrogen atom or a methyl radical and A denotes a ring aromatic or heterocyclic optionally substituted by nitro, amino, halo, hydroxy or alkoxy groups.

3.- As new chemical compounds according to claim 1, the compounds of formula: EMI21.3 in which R1 denotes a hydrogen atom or a methyl radical, R denotes a hydrogen atom or a hydroxy, alkoxy or amino group, Y denotes a hydrogen atom or a methyl radical and A denotes an aromatic or heterocyclic ring optionally substituted with nitro, amino, halo, hydroxy or alkoxy groups.

4.- New chemical compound according to claim 2, consisting of EMI21.4 2- (salicylidene-hydrazino- ° -methyl-6-hydroxypyrimidine.

5. - New chemical compound according to claim 2, consisting of 2- (cuminyl-hydrazino) -4-methyl-6-hydroxypyrimidine. <Desc / Clms Page number 22> 6.- New chemical compound according to claim 2, consisting EMI22.1 by 2- (3nitrosalicylidene-hydrazino) q.-methyl-6-hydroypyrimidine.

7. A new chemical compound according to claim 2, consisting of 2- (3-ohlorosalicylidene-hydrazino) -4-methyl-6-hydroxypyrimidine. 8. - New chemical compound according to claim 2, consisting of 2- (resorcylidene-hydrazino) -4-methyl-6-hydroxypyrimidine.

9. - New chemical compound according to claim 2, consisting of EMI22.2 2- (° -nitrosalicylidene-hydrazino) - ° -methyl-6hydroxypyrimidine.

10. A new chemical compound according to ± claim 2, consisting of 2- (4-aminosalicylidene-hydrazino) -4-methyl-6-hydroxypyrimidine.

11. A novel chemical compound according to claim 2, consisting of 2- (gentisylidene-hydrazino) -4-methyl-6-hydroxypyrimidine.

12. A novel chemical compound according to claim 2, consisting of 2- (5-nitrosalicylidene-hydrazino) -4-methyl-6-hydroxypyrimidine.

13.- New chemical compound according to claim 2, consisting of EMI22.3 2- (5-aminosalicylidene-hydrazino) -4-methyl-6-hydroxycyrimidine.

14.- New chemical compound according to claim 2, consisting of 2- (5-chlorosalicylidene-hydrazino) -Q.-methyl-6-hydrorpyrimidine.

15. A new chemical compound according to claim 2, consisting of 2- (o-nitro-benzylidene-hydrazino) -4-methyl-6-hydroxypyrimidine.

16. - New chemical compound according to claim 2, consisting of 2- (o-methoxybenzylidene-hydrazino) -4-methyl-6-hydroxypyrimidine.

17. - New chemical compound according to claim 2, consisting of EMI22.4 2- (o-aminobenzylidene-hydrazino) -4-methyl-6-hydroxyryrimidine. 18. A novel chemical compound according to claim 2, consisting of 2- (o-chlorobenzylidene-hydrazino) -4-methyl-6-hydroxypyrimidine.

19. New chemical compound according to claim 2, consisting of 2- (o-carboxybenzylidene-hydrazino) -4-methyl-6-hydroxypyrimidine.

20. New chemical compound according to claim 2, consisting of 2- (m-nitrobenzylidene-hydrazino) -4-methyl-6-hydroxypyrimidine.

21. - New chemical compound according to claim 2, consisting of EMI22.5 2 = (m-hydroybenzyidene-hydrazino) - ° -methyl-6-hydroxypyrimidine.

22. New chemical compound according to claim 2, consisting of 2- (p-hydroxybenzylidene-hydrazino) -4-methyl-6-hydroxypyrimidine.

23. New chemical compound according to claim 2, consisting of 2- (anisylidene-hydrazino) -4-methyl-6-hydroxypyrimidine.

24.- New chemical compound according to claim 2, consisting of EMI22.6 2- (p-nitrobenzylidene> hydrazino) = ° = methylm6-hydroxypyrimidine.

25. A novel chemical compound according to claim 2, consisting of 2- (p-aminobenzylidene-hydrazino) - ° -mëthyl6-hydroxypyr..midine.

26.- New chemical compound according to claim 2, consisting of 2- (p-acetylamino'benzylidene hydrazino) - ° -methyl-6hydrorpyrimidine.

27.- New chemical compound according to claim 2, consisting of 2- (p-dimethylaminobenzylidene-hydrazino) -q - methyl-6-hydroypyr.midine. 28. - New chemical compound according to claim 2, consisting of 2- (p-chlorobenzylidene-hydrazino) -4-methyl-6-hydroxypyrimidine. <Desc / Clms Page number 23> EMI23.1

2go A novel chemical compound according to claim 2, consisting of 2- (2'-4'-dichlorobenzylidene-hydnazino) -4-methyl-6-hydnoxypyrimidine.

30. New chemical compound according to claim 2, consisting of 2- (2 ', 3 "-dimethoxybenzylidene-hydrazino) -4-methyl-6-hydroxypyrimidine. EMI23.2

31. - New chemical compound according to claim 2, consisting EMI23.3 by 2- (3hydroxy-a-na, phtylidene-hyd.razino) mq.-methyl-6-hydroxypyr.midine. EMI23.4 32.- New chemical compound according to claim 2, consisting of EMI23.5 2- (cG-h.hydroxy 3mnaphthylidenehydrG zino) -q.methyl-6-hydroxypyrimidine. EMI23.6 33. - New chemical compound according to claim 2, consisting of EMI23.7 2- (isonioovinyl-hydrazino) 4-methyl-6-hydroxypyrimidine. EMI23.8

34. New chemical compound according to claim 2, consisting of 2- (nicotinyl-hydrazino) -4-methyl-6-hydroxypyrimidine.

35.- New chemical compound according to claim 2, consisting of EMI23.9 2- (picolinyl-hydrazino) -q.-methyl-6-hydroxypyr.m.dine. EMI23.10 36. - New chemical compound according to claim 2, consisting of EMI23.11 2- (quinolylhydrazino) -q.-methyl-6ihydroxypyrimidine. EMI23.12 37.- New chemical compound according to claim 2, consisting of EMI23.13 2- (furfuryl-hyàrazino) -4-methyl-6-hyàroxypyrimidine. EMI23.14 38. - New chemical compound according to claim 2, consisting of EMI23.15 2- (sallcylidenemethylhydrazino) - ° -methyl.6mhydroxypyrimidine. EMI23.16 39.- New chinic compound according to claim 2, consisting of EMI23.17 2- (5 -chlorosalicylidenemethylhydrazino) - ° -methyl-6-hydroxypyrimidine.

EMI23.18 40.- New chemical compound according to claim 2, consisting of EMI23.19 2 (picolinyl-methylhydrazino) -q.methyl-6hydroxypyrimidine. q.1.- New chemical compound according to claim 2, consisting of 2- (6mmethylpicolinylmmethylhydrazino) Q.-methylm6-hydroxypyrimidine.

42c A new chemical compound according to claim 2 consisting of 2- (salicylien-hyàrazino) -5-methyl-6-hyàroxypyrimaine. EMI23.20

43.- New chemical compound according to claim 2, consisting of EMI23.21 2- (5-chlorosalicylidene-hydrazino) -5-methyl-6-hydroxypyrimidine. EMI23.22 44. New chemical compound according to claim 2, consisting of 2- (picolinyl-hydrazino) -5-methyl-6-hydroxypyrimidine.

45.- New chemical compound according to claim 2, consisting of EMI23.23 2- (salicylidene-hydrazino) m4-methyl-6.minopyrimidïné.w, EMI23.24 46.- New chemical compound according to claim 2, consisting of EMI23.25 2- (5 '-ohlorosalicylidene-hydrazino) -4-methyl-6-Aminopyr imidine EMI23.26 47.- New chemical compound according to claim 2, consisting of EMI23.27 2- (picolinyl-hydrazino) -4-methyl-6 àinoPYimidiriê ;; o EMI23.28 48.- New chemical compound according to claim 2, consisting of EMI23.29 2- (salicylidene-hydrazino) -q.methylm6methoxypyrim.dine.

49.- New chemical compound, according to claim 2, consisting of 2- (5'-ohlonosalicylidene-hyàrazino) -4-methyl-6-methoxypyiimidine. EMI23.30

50.- New chemical compound according to claim 2, consisting of EMI23.31 2- (picolinyl-hydrazino) -q..methyl-6-methoxypyrimidinea EMI23.32 51. - New chemical compound according to claim 2, consisting of EMI23.33 2- (6'-methylpscolinylhydrazino) -4methyl-Emmethoxypyrimidine. <Desc / Clms Page number 24>

52. A novel chemical compound according to claim 2, consisting of 2- (nicotinyl-hydrazino) -4-methyl-6-methoxypyrimidine.

53. - A new chemical compound according to claim 2, consisting EMI24.1 by 2- (isonicotinyl-hydrazino) -4-methyl-6-ine-thoxypyrimidine.

54. New chemical compound according to claim 2, consisting of 2- (quinolyl-hydrazino) -4-methyl-6-methoxypyrimidine.

55.- New chemical compound according to claim 2, consisting EMI24.2 by 2- (6'-hydroxy- ° -pyrimidyl) -hydrazïn- ° -methyl-6-methoxypyrii = dine.

56.- New chemical compound according to resell 2, consisting EMI24.3 with 2- (2,6'dihydrox ° '-pyrimidyl) mhydrazin -4-methyl-6-methoxy-pyrimidine.

57.- New chemical compound according to claim 2, consisting of EMI24.4 2- (saloylidene-hydrazino) -6-methoxypyrimidine.

58.- New chemical compound according to claim 2, consisting of 2- (5'-chlorosalicylidene-hydiazino) -6-methoxypyiimidine, 59.- New chemical compound according to claim 2, consisting of 2- (21-pyrrolyl- hydrazino) -6-methoxypyiimidine.

60. A novel chemical compound according to claim 2, consisting of 2- (picolinyl-hydrazino) -6-methoxypyrimidine.

61. New chemical compound according to claim 2, consisting of 2- (picolin.yl-hydrazino) - ° -methyl-6 ', Ithoxypyrimidine.

62. A novel chemical compound according to claim 2, consisting of 2- (salicylidene-hydrazino) -4-methyl-6-ethoxypyrimidine.

63.- New chemical compound according to claim 2, consisting of 2- (a-methylpicolinyl-hydrazino) -4-methyl-6- ethoxypyrimidine.

64.- New chemical compound according to claim 2, consisting EMI24.5 by 2- (salicylidene-hydrazino) -4-methyl-6-isopropoxypyrimidine.

65. New chemical compound according to claim 2, consisting of 2- (5'-chlorosalicylidene-hyd: razino) - ° methyl-6isopropoxypyximidine. 66. New chemical compound according to claim 2, consisting of 2- (picolinyl-hydrazino) -4-methyl-6-isopropoxypyrimidine.

67. New chemical compound according to claim 2, consisting of 2- (a-methylpicolinyl-hydrazino) -4-methyl-6-isopropoxypyrimidine.

68. - New chemical compound according to claim 2, consisting EMI24.6 by 2- (5'-chlorosalicylidenehydrazino) - ° -methylpyr mdinē.

69. A novel chemical compound according to claim 2 consisting of - (salioylidene-hydrazino) -4-methoJPyrimidine.

70. A novel chemical compound according to claim 2, consisting of 2- (2'-hydroxy-a-methyl'benzylidene-hydrazino) - 4-methyl-6-hydroxypyri-midine.

71. - New chemical compound according to claim 2, consisting EMI24.7 by 2- (° '-hydroxy a-methyl'benzylidenemhydrazino) - ° -methyl-6-hydroxypyri- midine.

72. - New chemical compound according to claim 2, consisting EMI24.8 by 2- (4'-nitro-a-methylbenzylidene-hydrazino) -4-methyl-6-hydroxypyri-midine. <Desc / Clms Page number 25> 730- A new chemical compound according to claim 2, consisting EMI25.1 by 2- (cxmethylpicoinylhydrazino) tj.mmethyl6hydroxypyrimidine.

74. - New chemical compound according to claim 2, consisting of 2- (isatino-hydrazino) -4-methyl-6-hydroxypyrimidine.

75. A novel chemical compound according to claim 2, consisting of 2- (2'-hydroxy-a-methylbenzylidene-hydrazino) -4-methyl-6-aminopyri- midine.

76.- New chemical compound according to claim 2, consisting EMI25.2 by 2- (21-hydroxy-a-methylbenzylidene-hydrazino) -4-methyl-6-methoxypyri- midine.

77. New chemical compound according to claim 2, consisting EMI25.3 by 2- (r-methyl-picolinyl-hydrazino) - ° methyl-6-methoxypyrimidine, 780- New chemical compound according to claim 2, COLS hi killed by 2- (ccmëthylnicotinyl-hydrazino) ° methyl-6methoxypyrimidine, 79. - New chemical compound according to claim 2, consisting of 2- (2'-hydroxy-a-methylbenzylidene-hydrazino) -6-methoxy-pyrimidine.

80. A novel chemical compound according to claim 2, consisting of 2- (α-methylpicolinyl-hydrazino) -6-methoxypyrimidine.

81. - New chemical compound according to claim 3, consisting EMI25.4 by 6- (salicylidene-hydrazino) ° -methylpyrimidine.

82. New chemical compound according to claim 3, consisting of 6- (2 -hydroxy-cx-methyl.benzylidenehydrazino) -2-hydroxy- ° -methylpyri-midine.

83.- New chemical compound according to claim 3, consisting EMI25.5 by 6- (salicyliàene-hyàiazino) -2-hyànoxy-4-methylpyrimidine.

8q.o A novel chemical compound according to claim 3 consisting of 6- (5'-chlorosalicylidene-hydrazino) -2-hydroxy-4-methylpyrimidine.

85. A novel chemical compound according to claim 3, consisting of 6- (Picolinyl-hydrazino) -2-hydroxy-4-methylpyrimidine. z A novel chemical compound according to claim 3 consisting of 6- (x-methylpicolinyl-hydrazino) -2-hydroxy-4-methylpyrimidine.

87. New chemical compound according to claim 3, consisting of 6 (salicylidene-hydrazino-2-amino-q.mmethyl.pyrimidine.

88. New chemical compound according to claim 3, consisting of 6- (2 -hydroYycc-methylbnzylidene-hydrazino) -2-amino- ° -methylpyri-midine.

89.- New chemical compound according to claim 3, consisting EMI25.6 by 6- (5'-chlorosalicylidene-hydrazino) -2-amino-4-methylpyrimidine.

90. A novel chemical compound according to claim 3 consisting of 6- (picolinyl-hydrazino) -2-amino-4-methylpyrimidine.

91.- Compositions for therapeutic use, containing in admixture with an excipient or a vehicle at least one excipient or a vehicle at least one compound according to any one of the preceding claims.

92. - Process for the preparation of new chemical compounds according to either of claims 1 to 90, characterized in that a hydrazinopyrimidine condenses with a carbonyl compound selected from the group of aromatic and heterocyclic aldehydes and ketones. <Desc / Clms Page number 26>

930- The method of claim 92, characterized in that the condensation is carried out in the presence of an acid, such as acetic acid or hydrochloric acid.

94.- A method according to either of claims 92 and 93. characterized in that the condensation is carried out in an alcohol medium.

95.- Process according to either of claims 92 to 94, characterized in that a hydrazino-pyrimidine of formula is condensed: EMI26.1 wherein R1, R2, R and X have the meaning given in claim 2 with an aldehyde or ketone of the formula A-C = O, wherein A and Y have the meaning given in claim 2.

96. - Process according to one or the other of claims 92 to 94, characterized in that one condenses a hydrazino-pyrimidine of "ormule: EMI26.2 wherein R1 and R3 have the meaning given in claim 3 together with an aldehyde or ketone of the formula A-C = O wherein A and Y have the meaning given in claim 3.

97.- Process according to either of claims 92 to 96, characterized in that an aldehyde chosen from the group of the following aldehyde is used: salicylic aldehyde, cumin aldehyde, 3-nitro-salicylic aldehyde, 3-chlorosalicyl aldehyde, resorcylic aldehyde, 4-nitrosalicyl aldehyde, 4-aminosalicyl aldehyde, gentisic aldehyde, 5-nitrosalicyl aldehyde, 5-aminosalicyl aldehyde, 5-chlorosalicyl aldehyde, aldehyde 5-chlorosalicyldehyde-aldehyde-aldehyde-aldehyde-aldehyde-aldehyde-aldehyde-aldehyde-aldehyde-aldehyde-5-aldehyde-aldehyde-aldehyde-aldehyde-aldehyde-aldehyde-aldehyde-aldehyde-aldehyde o - nobenzoic acid, o-carboxybenzoic aldehyde, m-nitrobenzoic aldehyde, m-hydroxybenzoic aldehyde, p-hydroxybenzoic aldehyde,

enisaldehyde, p-nitrobenzoic aldehyde- p-aminobenzoic aldehyde, p-acetylaminobenzoic aldehyde, p-dimethylaminobenzoic aldehyde, p-chlorobenzoic aldehyde, 2,4-dichlorobenzoic aldehyde, 2,3-hydroxydehyde-s-aldehyde-dimethoxydehyde -naphthalene, [alpha] -hydroxy-ss-naphthalene, nicotinic aldehyde, isonicotin aldehyde, picolinic aldehyde, 6-methylpicolinic aldehyde, 2-quinolenic aldehyde, 6-hydroxy-4-pyrimidine aldehyde, 2,6-dihydroxy-2,6-dihyde 4-pyrimidine aldehyde .., furfural 2-pyrrolic aldehyde. <Desc / Clms Page number 27>

980- Process according to either of claims 92 to 96, characterized in that a ketone selected from the group of the following ketones is used: acetophenone, o-hydroxy-acetophenone, p-hydroxyacetophenone, p-nitroacetophenone , 2-acetylpyridine, 3-acetylpyridine, isatin.

99.- Dihydrazinopyrimidine derivatives obtained by the process according to one or the other of claims 92 to 980