Patent GB-1243209-A (GB)
Title: Ketene derivatives and their preparation
IPC: C07D499/00
Filed: 1968-07-08
Abstract: 1,243,209. Ketene derivatives. PFIZER Inc. 8 July, 1968 [5 Jan., 1968], No. 2285/69. Divided out of 1,243,207. Heading C2C. Novel compounds I in which R 1  is thienyl, furyl, pyridyl, phenyl which may be substituted by, C 1-4  alkyl, chloro, bromo, C 1-4  alkoxy, di(C 1 _ 4 )alkylamino, or trifluoromethyl; X<SP>1</SP> is X, -OR 2  or -SR 7 ; X is halo; R 2  is phenyl, optionally substituted by at least one of Cl, Br, F, C 1-4  alkyl. C 1-4  alkoxy, C 1-4  alkanoyl, C 2-5  carbalkoxy, nitro, or di(C 1-4 ) alkylamino; furyl; quinolyl; methyl-substituted quinolyl; phenazinyl; 9,10-anthraquinonyl; phenanthrenequinonyl; anthracenyl; phenanthryl; 1,3 - benzodioxolyl; 3- (2 - methyl - 4 pyronyl); 3 (4 - pyronyl)-; (N - methyl) - pyridyl; radicals of Formula III and IV respectively  in which Y 2  is and Z<SP>1</SP> is C 1-4  alkylene or substituted derivatives of IV ih which the substituent is CH 3 , Br, or Cl; benzyl optionally substituted by Cl, Br, F, C 1-4  alkyl, C 1-4  alkoxy; C 1-4  alkanoyl, C 2-5  carbalkoxy, nitro di(C 1- 4 )alkylamino; phthalimido -  methyl; trityl; benzhydryl; cHolesteryl;. C 2-8  alkenyl; C 2-8  alkvnyl; C 3-7  cycloalkyl; C 1-4  alkyl substituted C 3-7  cycloalkyl; {'2,2-di-(C 1-4   alkyl) - ],3 - dioxolon - 4 -- yl} - methyl; bicycle [4.4.0] - decyl; thujyl; fenehyl; isofenchyl; 7 - adamahtanyl; (2 - pyrrolidino) methyl; (4 - imidazolyl)methyl; 1 - indanylmethyl; 2- indanylmethyl; furylmethyl; pyridylmethyl; ac-indanyl optionally substituted by methyl, Cl or Br; ac-tetrahydronaphthyl optionally substituted by methyl, Cl or Br; alkyl; or substituted C 1-4  alkyl in which, the substituent is at least one of Cl, Br, F; N0 2 , C 2-5  carbalkoxy, C 1-4  alkanoyl, C 1-4  alkoxy, cyano, C 1-4  alkylmercapto) C 1-4  alkylsulfinyl, C 1-4  alkylsulfonyl or - (C 1-3 -alkylene)-Y 1  wherein. -NK 5 B 6  is C 1-4 -alkanoylamino, di(C 1-4 )alkylamino in which the alkyl groups may be similar or different), or N(C 1-4  alkyl)anilino; and Y 1  is azetidino, aziridinb, pyrrolidino, morpholino, thiamorpholino, N - (C 1-4  alkyl) - piperazino, pyrrolo, imidazolo, 2 - imidazolino, 2,5 - dimethylpyrrolidino, 1,4,5,6 - tetrahydro pyrimidino, 4 - methyl - piperidino or 2,6  -  dimethyl-piperidino'; and R 7  is phenyl, mono, di- or tri-substituted phenyl wherein the substituent(s) is (are) selected from chloro, bromo, fluoro, C 1-4  alkyl, C 1-4  alkoxy, or trifluoromethyl, with the proviso that only one of the positions ortho to the thio group of the phenyl moiety may be substituted are prepared by reacting a malonic acid derivative or a functional derivative thereof with a halogenating agent to give I where X<SP>1</SP> is halo and where necessary reacting said compound with X<SP>1</SP>H to give I in which X1 is-OR 2  or--SB 7 . Intermediates isolated are dibehzyl phenylmalonate prepared from phenyl-chlorbcarbonylketene and benzyl alcohol; benzyl phenyl-N- benzyl malonamate prepared from phenylchlorocarbohyl ketene, benzyl alcohol and benzylamine and compounds of formula R 1 CH(COOH) 2  prepared by reaction of R 1 CH 2 COOEt with diethylcarbonate, followed by hydrolysis of the resulting ester.