Patent GB-1274521-A (GB)
Title: Dithiocarbazinic ester derivatives
IPC: A61K31/435
Filed: 1969-06-19
Abstract: 1,274,521. Compounds containing hydrazono and dithiocarboxylic ester groups. EGYESULT GYOGYSZER ES TAPSZERGYAR. 19 June, 1969 [24 July, 1968], No. 31122/69. Heading C2C. Novel compounds I (including salts and hydrates thereof) wherein R<SP>1</SP> is H, straight or branched chain alkyl, alkenyl, aralkyl or aralkenyl (the aryl moiety embraces heteroaryl) which may be substituted by alkoxy, carboalkoxy, CO 2 H, amino, alkylamino, dialkylamino or trialkylammonium, or R<SP>1</SP> is phenyl, pyridyl, indolyl, quinolyl, thienyl or furyl which may be mono- or poly-substituted with halogen, alkyl, alkoxy, acyl, OH, SO 3 H, carboalkoxy or CO 2 H, R<SP>2</SP> is H, straight or branched chain alkyl or aralkyl which may be substituted as stated for R<SP>1</SP>, CO 2 H or R<SP>1</SP> and R<SP>2</SP> comprise together with the attached carbon a mono- or poly-cyclic radical having at least one of the ring carbons substituted by = O or = NÀNHCSSR<SP>3</SP>, and R<SP>3</SP> is straight or branched chain alkyl, alkenyl or aralkyl which may be mono- or poly-substituted by halogen and straight or branched alkyl, are obtained by reacting: (a) R<SP>1</SP>COR<SP>2</SP> (may be formed in situ) with NH 2 ÀNHÀCSSR<SP>3</SP>; (b) R<SP>1</SP>COR<SP>2</SP> with NH 2 NHÀCSSZ (one or both of the reactants may be formed in situ; Z is alkali or alkaline earth metal, ammonium or hydrazinium cation) and the intermediate compound so obtained is subsequently converted into 1 by standard methods; (c) R<SP>1</SP>R<SP>2</SP>C: NNH 2  with sodium, potassium, sodium amide or sodium hydride to afford R<SP>1</SP>R<SP>2</SP>ÀC: NNHZ 1  (Z 1  is sodium or potassium) which is in turn treated with carbon disulphide to give (converted to I by standard methods); (d) R<SP>1</SP>R<SP>2</SP>C = NNHZ 1  with ClCSSR<SP>3</SP>; (e) R<SP>1</SP>R<SP>2</SP>C = NNHZ 1  with thiophosgene to afford R<SP>1</SP>R<SP>2</SP>C: NNHCSCl which, in turn, is reacted with R<SP>3</SP>SZ to afford I; or (f) R<SP>1</SP>R<SP>2</SP>C: NNH 2  with R<SP>4</SP>SCSSR<SP>4</SP> at below 150 C. (R<SP>4</SP> is alkyl or aralkyl). The invention also encompasses exemplified novel compounds of the structure I but which are not covered by the preceding definitions of R 1  and R 2 . They are made from the following oxo-compounds (R 3  is given in parenthesis): chloral (Me, benzyl or p-chlorobenzyl), acetylacetone (Me), acetobutyrolactone (Me), pnitrobenzaldehyde (Me), piperonal (Me), pnitroacetophenone (Me or Et), p-nitro-α- acetamido - acetophenone (Me), 2 - hydroxy- 1 - naphthaldehyde (Me), 2 - methoxy - 3,4- methylenedioxy - 6 - vinyl - benzaldehyde (Me), α - formyl- or α - methoxymethylene - 3,4 - dimethoxyphenyl - acetonitrile (Me), DL - pnitro - α - acetamido - # hydroxy - propiophenone (Me and benzyl), 2-benzoylpyridine (Me), 2 - acetyl - 1 - naphthol (Me), 1- and 2- acetyl - naphthalenes (Me), 2,3 - dichloro - 4- butyryl - phenoxyacetic acid (Me), benzoylacetone (Me), benzophenone (Me), m-nitrobenzaldehyde (p - chlorobenzyl, 2,3 - dichloro- 4 - (2<SP>1 </SP>- methylenebutyryl) phenoxyacetic acid (Me), benzil (Me), benzoin (Me), #-piperidinopropiophenone (Me), 2-oxo-9,10-dimethoxy-, 2 - oxo - 3 - ethyl - 9,10 dimethoxy and 2-oxo - 4,4 - dimethyl - 9,10 - dimethoxy - 1,2,3,4,6,7- hexahydro - 11b - benzo[a]quinolizines (Me), dibenzal - acetone (Me), α - formyl - 3,4 - dimethoxy - phenyl - acetonitrile (p - chlorobenzyl), dibenzoylmethane (Me) and dibenzalacetone (p-chlorobenzyl). Dithiocarbazinic esters, NH 2 NHÀCSSR<SP>3</SP>, are obtained by reacting hydrazine hydrate with carbon disulphide in the presence of potassium hydroxide, ammonia or excess hydrazine hydrate and converting the dithiocarbazinic acid salt so obtained into the ester utilizing standard methods. Methyl - p - nitrophenyl - ketazin is obtained by the interaction of p-nitroacetophenone and NH 2 NHCSSEt. Pharmaceutical preparations, in particular, showing anthelmintic and tuberculostatic effects contain I as active ingredient; administration is, e.g. topically, orally and parenterally.