Patent GB-1210104-A (GB)
Title: Thiamine derivatives and production thereof
IPC: C07D415/00
Filed: 1968-03-04
Abstract: 1,210,104. Thiamine derivatives. TAKEDA YAKUHIN KOGYO K.K. 4 March, 1968 [3 March, 1967; 27 May, 1967], No. 10487/68. Heading C2V. The invention comprises thiamine derivatives of formula where R<SP>1</SP> is hydrogen or α-hydroxyethyl, n is an integer from 1 to 5, R<SP>2</SP> is hydrogen, an acyl residue of a carboxylic acid with up to 8 carbon atoms, an alkoxycarbonyl group having up to 4 carbon atoms or phosphono, n<SP>1</SP> is an integer from 1 to 3 and X is fluorine, chlorine, bromine or iodine. The derivatives may be in the form of pharmaceutically acceptable salts. The derivatives are obtained by reacting a compound of formula where R<SP>1</SP> and R<SP>2</SP> are as above under alkaline conditions with a compound of formula where A-S- is such that on reaction with a thiol group a disulphide linkage is formed with elimination of H-A, and X, n and n<SP>1</SP> are as above. In examples thiamine hydrochloride is reacted with sodium 2-fluorobenzylthiosulphate to obtain thiamine 2-fluorobenzyl disulphide, with 3-fluorobenzylthiosulphate to obtain thiamine 3-fluorobenzyl disulphide, with 2-chlorobenzylthiosulphate to obtain thiamine 2-chlorobenzyl disulphide, with S-2-chlorobenzylsulphenyl isothiourea to obtain thiamine 2-chlorobenzyl sulphide, with S-2-chlorobenzylsulphinyl- 2-chlorobenzylmercaptan to obtain thiamine 2- chlorobenzyl disulphide, with sodium 2-iodobenzylthiosulphate to obtain thiamine 2-iodobenzyl disulphide, with sodium 2,6-dichlorobenzylthiosulphate to obtain thiamine 2,6-dichlorobenzyl disulphide, with N - (S - 2,6 - dichlorobenzylsulphenyl - dithiocarboxy) - morpholine to obtain thiamine 2,6-diohlorobenzyl disulphide, with sodium 2 - bromo - 6 - chlorobenzylthiosulphate to obtain thiamine 2-bromo- 6 - chlorobenzyldisulphide, with N - (S - 4- chlorobenzylsulphenyldithiocarboxy) morpholine to obtain thiamine 4-chlorobenzyl disulphide, with sodium 4-fluorobenzylthiosulphate to obtain thiamine 4-fluorobenzyl disulphide, with S - 3 - chlorobenzylsulphenyl isothiourea hydrochloride to obtain thiamine 3-chlorobenzyl disulphide, with sodium 2 - (2 - fluorophenyl) ethylthiosulphate to obtain thiamine 2 - (2- fluorophenyl) - ethyl disulphide, with sodium 2 - (4 - fluorophenyl) - ethylthiosulphate to obtain thiamine 2-(4-fluorophenyl) ethyl disulphide with sodium 2-(2-chlorophenyl) ethylthiosulphate to obtain thiamine 2-(2-chlorophenyl) ethyl disulphide, with sodium 2-(4- chlorophenyl)-ethylthiosulphate to obtain thiamine 2 - (4 - chlorophenyl) - ethyl disulphide, with sodium 2 - (3 - chlorophenyl) - ethylthiosulphate to obtain thiamine 2-(3-chlorophenyl)- ethyl disulphide, and with sodium 2-(2,6-dichlorophenyl)-ethylthiosulphate to obtain thiamine 2-(2,6-dichlorophenyl)-ethyl disulphide; hydroxyethylthiamine hydrochloride is reacted with sodium 2,6-dichlorobenzylthiosulphate to obtain hydroxyethylthiamine 2,6-dichlorobenzyl disulphide; O-benzoylthiamine hydrobromide is reacted with 2,6-dichlorobenzylthiosulphate to obtain O-benzoylthiamine 2,6-dichlorobenzyl disulphide; thiamine O-monophosphate hydrochloride is reacted with S-2,6- dichlorobenzyl - sulphenyl isothiourea hydrochloride to obtain thiamine O-monophosphate 2,6-dichlorobenzyl disulphide, and with S-4- chlorobenzylsulphenyl isothiourea hydrochloride to obtain thiamine O-monophosphate 4-ehlorobenzyl disulphide. Pharmaceutical compositions comprise the thiamine derivatives described above together with the usual carriers.