Patent GB-1030400-A (GB)
Title: Sulphur-containing derivatives of vitamin b and process for their preparation
IPC: C08G75/02
Filed: 1965-01-20
Abstract: Disulphides of formula <FORM:1030400/C6-C7/1> wherein R1 and R2 which are the same, are hydrogen atoms, acyl groups containing from 1 to 6 carbon atoms or together form a group of formula <FORM:1030400/C6-C7/2> where R3 and R4, which may be the same or different, are H or alkyl groups containing from 1 to 5 carbon atoms or together represent a lower alkylidene group and form, with the carbon atom to which they are attached, a carbocyclic ring containing 5 or 6 carbon atoms are produced by electrolytic oxidation on platinum electrodes of the corresponding mercapto compounds and subsequent treatment with dilute acid when R1 and R2 represent H atoms.ALSO:The invention comprises the preparation of <FORM:1030400/C2/1> by the oxidation of a mercapto compound of formula <FORM:1030400/C2/2> where R1 and R2 which are the same, are acyl groups containing from 1 to 6 carbon atoms or together form a group of formula <FORM:1030400/C2/3> where R3 and R4 which may be the same or different, are H or alkyl groups containing from 1 to 5 carbon atoms or together represent a lower alkylidene group and form, with the carbon atom to which they are attached, a carbocyclic ring containing five or six carbon atoms; or by the oxidation of the mercapto compound of the second formula above in the form of its metal salt in an alkaline solution to form a compound of the formula <FORM:1030400/C2/4> where R1 and R2 are the same as above and treating this compound with dilute acid.  The bis - [6 - methyl - pyridyl - (3) - methyl] disulphides of the fourth formula above are claimed per se and are also obtainable by the reaction of a compound of the formula <FORM:1030400/C2/5> where X is chlorine, bromine or iodine, with a water-soluble inorganic disulphide.  The mercapto compound of the second formula above can be produced in situ and used without being isolated by the reaction of a compound of the last formula above with thiourea or with alkali metal- or ammonium-xanthogenate, -dithiocarbamate, -thioacetate or -thiosulphate and the product oxidized to form a disulphide without isolating the intermediately formed mercapto compound.  3 - Chloromethyl - 5 - acetoxy - 4 - acetoxymethyl - 6 - methyl - pyridine hydrochloride is prepared by treating 5 - acetoxy - 4 - acetoxymethyl - 3 - hydroxymethyl - 6 - methyl - pyridine with thionyl chloride.  3 - Iso - thio - ureidomethyl - 6 - methyl - 5 - propionyloxy - 4 - propionyloxy - methyl - pyridine-hydrochloride is made by refluxing thiourea with 3 - chloromethyl - 5 - propionyloxy - 4 - propionyloxymethyl - 6 - methyl pyridine hydrochloride which is formed by chlorinating the corresponding hydroxymethyl compound. O,O1 - Isobutylidene - 5 - hydroxy - 4 - hydroxymethyl - 3 - isothioureidomethyl - 6 - methyl - pyridine-dihydrochloride is made by refluxing thiourea and O,O1 - isobutylidene - 3 - chloromethyl -5 - hydroxy - 4 - hydroxymethyl - 6 - methyl - pyridine hydrochloride which is prepared by chlorinating O,O1 - isobutylidene - 3,4 - dihydroxymethyl - 5 - hydroxy - 6 - methyl - pyridine - hydrochloride which is formed from pyridoxolhydrochloride, isobutyraldehyde and hydrochloric acid.  O,O1 - Cyclohexylidene - 5 - hydroxy - 4 - hydroxymethyl - 6 - methyl - 3 - thiocarbamyl -thiomethyl pyridine is prepared by reacting ammonium dithiocarbamate with O,O1-cyclohexylidene - 3 - chloromethyl - 5 - hydroxy - 4 - hydroxymethyl - 6 - methyl - pyridine - hydrochloride which has been formed by chlorinating O,O1 - cyclohexylidene - 5 - hydroxy - 3,4 - dihydroxymethyl - 6 - methyl - pyridine - hydrochloride formed from pyridoxol hydrochloride, cyclohexanone and concentrated sulphuric acid.  O,O1-Isopropylidene-5-hydroxy-4-hydroxymethyl - 3 - isothio - ureidomethyl - 6 - methyl - pyridine dihydrochloride is formed by treating O,O1 - isopropylidene - 3 - chloromethyl - 5 - hydroxy - 4 - hydroxymethyl - 6 - methyl pyridine hydrochloride with thiourea. O,O1-Isopropylidene-3-acetylthiomethyl-5-hydroxy -4-hydroxymethyl-6-methyl-pyridine hydrochloride is prepared by treating O,O1-isopropylidene -3-chloromethyl-5-hydroxy-4-hydroxymethyl - 6 - methyl pyridine hydrochloride with potassium thioacetate.  5 - Acetoxy - 4 - acetoxymethyl - 6 - methyl - pyridyl - (3) - methyl thiosulphate is prepared by reacting sodium thiosulphate with 5-acetoxy-4-acetoxymethyl -6-methyl pyridyl-(3)-methylbromide which is formed in admixture with the corresponding hydrochloride salt by acetylating the corresponding hydroxy compound.  Pharmaceutical compositions having application in the treatment of geriatric disorders contain as the active ingredient the compound of the first formula above.  The compositions may be in the form of tablets and pills for enteral application, ointments and creams, for topical application, and solutions, suspensions, emulsions and implants for parenteral application.