Patent GB-836725-A (GB)
Title: Manufacture of condensation products of aminocarboxylic esters
IPC: C07C317/22
Filed: 1956-10-26
Abstract: Polyamides which may be linear or cyclic and simple cyclic amides are made from salts of aminocarboxylic acid ester having a free amino group which is separated from the ester carbonyl group by at least two carbon atoms and which contain in the alcohol or phenol component of the ester group a meta-directing substituent or a halogen atom, by condensing the ester on itself by treatment with a basic agent. Meta-directing substituents specified are cyano, free or esterified carboxyl, carbamyl, quaternary amino, nitro, sulpho, acyl, ammonium, aldehydo.  Alkaline agents used may be alkali hydroxides or carbonates or tertiary amines. Solvents such as dimethyl formamide, acetonitrile, dioxane, and tetrahydrofurane may be employed.  In examples: (1) triglycine cyanomethyl ester hydrochloride is treated with triethylamine in dimethyl formamide to give a (polytriglycine) cyanomethyl ester or with pyridine to give cyclohexaglycyl; (2) pyridine is added to a solution in dimethyl formamide of L - valyl - N - d  - tosyl - L - ornithyl - L - leucyl - D - phenylalanyl - L - prolyl - L - valyl - N - d  - tosyl - L - ornithyl - L - leucyl - D - phenylalanyl - L - proline p - nitrophenyl ester to convert it to its cyclo compound, which is treated with sodium in liquid ammonia to remove the tosyl groups and give the antibiotic Gramicidin S; (3) pyridine is added to solutions in dimethyl formamide of the cyanomethyl ester, the p-nitrophenyl ester, or the p-methanesulphonylphenyl ester of glycyl DL-phenylalanylglycine to give the cyclo body; (4) pyridine or triethylamine is similarly added to glycyl-glycyl - DL - phenylalanine - p - methanesulphonylphenyl ester to give the cyclo body; (5) pyridine is similarly added to e -amino-n-caproic acid-p-methanesulphonyl-phenyl ester hydrochloride to give e -n-caprolactam.  Trityl - L - valyl - N - tosyl - L - ornithyl - L - leucyl - D - phenylalanyl - L - proline methyl ester is made by reaction of triphenyl-chlormethane with the corresponding peptide.  It is hydrolysed to the free acid which is condensed with the untritylated methyl ester in presence of cyclohexyl - (morpholino - ethyl) - carbodiimide to give trityl - L - valyl - N - tosyl - L - ornithyl - L - leucyl - D - phenylalanyl - L - prolyl - L - valyl - N - tosyl - L - ornithyl - L - leucyl - D - phenylalanyl - L - proline methyl ester which is hydrolysed and the free acid converted to the p-nitrophenyl ester by reaction with di-p-nitrophenyl sulphite which is detritylated in trifluoroacetic acid to give the trifluoroacetic acid salt of the p-nitrophenyl ester.  Glycyl - DL - phenylalanylglycine p - nitrophenyl ester is obtained from the corresponding N-carbobenzoxy compound by treatment with a mixture of acetic and hydrobromic acids.  Glycyl - DL - phenylalanylglycine p - methanesulphophenyl ester is obtained by catalytic hydrogenation of the corresponding N-carbobenzoxy compound.  e  - Amino - n - caproic acid p - methanesulphonyl-phenyl ester hydrochloride is obtained by hydrogenation of the corresponding N-carbobenzoxy compound, which is obtained from carbobenzoxy-aminocaproic acid and di-(p-methanesulphonylphenyl)-sulphite.