Patent GB-849166-A (GB)
Title: Process for the manufacture of carboxylic acid aryl esters
IPC: C07C69/76
Filed: 1957-01-25
Abstract: Process for the manufacture of carboxylic acid aryl esters, comprises reacting a carboxylic acid in the presence of an organic base with a sulphurous acid ester which contains as alcohol component at least one aryl radical.  The process is especially applicable to the esterification of amino-carboxylic acids wherein the amino-group is preferably substituted, e.g., by acyl, aryl or alkyl radicals.  The sulphite ester may be symmetrical or unsymmetrical and the aryl radical thereof preferably contains an electron-attracting substituent, i.e., a substituent which in aromatic rings is meta-directing or a halogen atom.  In an example: a solution of hippuric acid in pyridine is mixed with bis-p-nitrophenyl sulphite, the crystalline product filtered off and washed with ice water and cold alcohol to give hippuric acid p-nitrophenyl ester and the p-nitrophenyl esters of the following acids are similarly prepared:-N-carbobenzyloxy-glycine, or-L-leucine or-L-valine or-S-benzyl-cysteine, salicylic acid, (N-carbobenzyloxy-glycyl)-glycine, (N-carbobenzyloxy-L leucyl) D-phenylalanine and trityl-L-valyl-Nd -tosyl-L-ornithyl-L-leucyl - D p  - phenylalanyl - L - prolyl L valyl - Nd  - tosyl - L - ornithyl- L-leucyl-D-phenylalanyl-L-proline.  In further examples the following components are reacted:-N-carbobenzyloxy-glycine and bis-(o or p-carbomethoxyphenyl)-sulphite or ethyl p-nitrophenyl sulphite or phenyl p-nitrophenyl sulphite or diphenyl sulphite or bis-(p-dimethylaminophenyl) sulphite or bis-(p-methanesulphonylphenyl) sulphite or bis-(p-cyanophenyl) sulphite; succinic acid or N-triphenyl-methyl-glycine and di-/-naphthyl sulphite; phenylacetic acid or N-carbobenzyloxy-glycine and di-2-naphthyl sulphite; benzoic acid and bis-(2 : 6-dimethoxyphenyl) sulphite; p-bromobenzoic acid or nicotinic acid or N-phthalyl-glycine and diphenyl sulphite; hippuric acid and bis-(p-dimethyl-aminophenyl) sulphite.  Bis-p-nitrophenyl sulphite is prepared by treating a solution of p-nitrophenol in ether with thionyl chloride, adding dropwise a solution of triethylamine or pyridine in ether, filtering off the crystalline ester, washing with water, alcohol and ether and recrystallising from acetone and ether. Bis-(o-or p-carbomethoxy-or 2 : 6-dimethoxy-or p-dimethylamino-or p-methanesulphonyl-or p-cyanophenyl)-sulphite is similarly prepared using the appropriate phenol.  Ethyl and phenyl p-nitrophenyl sulphites are prepared by reacting p-nitrophenol with the ethyl or phenyl ester of chlorosulphinic acid in ether solution adding triethylamine-ether solution dropwise, then petroleum ether and filtering off the crystallised ester.  Trityl-L-valyl-Nd -tosyl-L-ornithyl-L-leucyl - D-phenylalanyl-L-prolyl-L-valyl-Nd -tosyl-L-ornithyl-L -leucyl-D-phenylalanyl-L-proline is prepared by treating L-valyl-Nd -tosyl-L-ornithyl-L-leucyl-D-phenylalanyl-L -proline methyl ester (compound A) with triphenyl-chloromethane to give the trityl derivative, hydrolysing this to the acid, which is condensed with compound A in the presence of N-cyclohexyl-N1- [b -morpholino-(4)-ethyl]-carbodiimide, to give the methyl ester of the decapeptide, which is finally hydrolysed.  Specifications 803,464 and 836,725 are referred to.