Patent GB-1164608-A (GB)
Title: Semicarbazone and Thiosemicarbazone Quaternary Salts
Inventor: BAMFORD DAVID GEORGE
IPC: C07D295/135
Filed: 1966-08-23
Abstract: 1,164,608. Semicarbazone and thiosemicarbazone quaternary salts. MAY & BAKER Ltd. 21 Aug., 1967 [23 Aug., 1966; 7 July, 1967], Nos. 37800/66 and 31375/67. Heading C2C. Novel compounds of formula (wherein R represents the group R 1 R 2 R 3 N+ in the 3- or 4-position of the benzene radical, in which R 1 , R 2  and R 3  each represents a C 1-4  alkyl group or R 1  and R 2  and the adjacent nitrogen atom represent a saturated monocyclic heterocyclic group optionally containing oxygen as a second hetero atom, R 4  represents hydrogen, a C 1-12  alkyl or alkenyl group, or a C 3-8  cycloalkyl group, A represents an oxygen or sulphur atom, R 5  and R 6  each represents hydrogen or a C 1-4  alkyl group, with the proviso that R 3 , R 5  and R 6  are not simultaneously hydrogen atoms, R, represents hydrogen, or R 7  and R 4  linked together represent a trimethylene chain, and X- represents a pharmaceutically acceptable anion) are prepared (a) by reacting a compound of Formula II with one of Formula III and (b) by quaternization of the grouping R 1 R 2 N- of a compound of formula with a compound of formula R 3 X 1  wherein X 1  is the acid residue of a reactive ester. Salts of Formula I with various anions X can be interconverted (a) by metathesis, e.g. by reaction with the silver salt of the appropriate acid, (b) by treating an aqueous solution thereof with a water-soluble salt (e.g. Na, NH 4 ) of embonic or amsonic acid, whereby the embonate or amsonate with the required cation is precipitated and treating the precipitate or a hot aqueous solution thereof with an acid having the required anion, whereby embonic or amsonic acid is precipitated, leaving the desired product in solution and (c) by ion exchange. Quaternized aldehydes and ketones of Formula II are prepared by (a) condensing disubstituted anilines of formula R 1 R 2 N.C 6 H 5  with acids of formula R 4 COOH to yield amino-aldehydes or -ketones of formula p-(R 1 R 2 N)-C 6 H 4 -COR 4  which are then quaternized with a compound of formula R 3 X 1  to yield compounds of Formula II wherein R is in the 4-position and R 7  is hydrogen, (b) alkylation of 6- or 7-amino-1-tetralone to yield 6- or 7-(R 1 R 2 N)-1-tetralone which is quaternized with a compound of formula R 3 X 1  to yield a compound of Formula II wherein R 4  and R 7  together represent a trimethylene chain and (c) quaternization of compounds of Formula IX with a compound of formula R 3 X 1 . Compounds of Formula IX are obtained by oxidation of the corresponding carbinols which, when R 4  is alkyl, alkenyl, or cycloalkyl and R 7  is hydrogen, are in turn obtained by reaction of the appropriate (R 1 R 2 N)-substituted benzaldehyde with a Grignard reagent of formula R 4 MgX 2  wherein R 4  is as just defined and X 2  is chlorine, bromine or iodine. Semicarbazones of Formula XI are obtained by reacting a compound of Formula IX with one of Formula III. Pharmaceutical compositions, suitable for parenteral administration, comprise at least one compound of Formula I with a pharmaceutical carrier. Pharmaceutically acceptable anions X include halide ions, ions of formula R 8 -SO 2 -O- wherein R 8  is alkyl, alkoxy, hydroxyalkyl, or mononuclear aryl, and ions derived from organic carboxylic acids (e.g. tartrate, citrate).