Patent GB-790044-A (GB)
Title: Derivatives of 2-mercaptopyridine-1-oxide
IPC: C07D213/89
Filed: 1954-05-10
Abstract: The invention comprises substituted pyridine-N-oxide amine and quaternary salts of the general formula <FORM:0790044/IV (b)/1> wherein R represents hydrogen or a halogen or a lower alkyl or lower alkoxy group, R1 and R2 each represent hydrogen or a lower alkyl group or a halo-substituted or hydroxy-substituted derivative of such a group, R3 represents hydrogen or a lower alkyl or aralkyl group or halo-substituted or hydroxy-substituted derivative of such groups (except when R1 and R2 taken together with the nitrogen atom to which they are joined represent a piperidyl group and R3 represents a lower alkyl group or an aralkyl group or a halo-substituted or hydroxy-substituted derivative of such groups, and except when R1, R2 and R3 taken together with the nitrogen atom to which they are joined represent a pyridyl group), and R4 represents a higher alkyl, higher alkenyl, higher alkyl-aryloxy-lower alkoxy-lower-alkyl group, and the preparation of the above quaternary salts by reacting a nitrogen compound of the general formula <FORM:0790044/IV (b)/2> wherein R1, R2, R3 and R4 have the above significance but excluding hydrogen, with an alkali metal (including ammonium) or alkaline earth metal salt of a 2-mercaptopyridine-1-oxide of the general formula <FORM:0790044/IV (b)/3> wherein R has the above significance, the preparation of compounds of the general formula <FORM:0790044/IV (b)/4> wherein R, R3 and R4 have the above significance by reacting a nitrogen compound of the formula <FORM:0790044/IV (b)/5> with a 2-mercaptopyridine-1-oxide of the above general formula in a substantially aqueous medium, and the preparation of the above amine salts by reacting the required amine with a 2-mercaptopyridine-1-oxide of the above general formula in a substantially dry organic solvent.  By the expressions "lower alkyl" and "lower alkoxy" are meant radicals having from 1 to 7 carbon atoms and by the expressions "higher alkyl" and "higher alkenyl" are meant radicals having from 8 to 30 (or more) carbon atoms.  When using reactants of the general formula <FORM:0790044/IV (b)/6> it is preferable to choose the anion thereof, the cation of the 2-mercapto-pyridine-1-oxide reactant and a reaction solvent so that the by-product salt is insoluble in said solvent, e.g. the anion is a sulphate, the cation is an alkaline earth metal and the solvent is a substantially aqueous solution, or the anion is a halide, the cation is an alkali metal and the solvent is a substantially dry hydroxylated organic solvent such as alcohol, ethylene glycol or propylene glycol.  The salt of the 2-mercaptopyridine-1-oxide used in the above process may be a barium, calcium, sodium, potassium or ammonium salt of 2- mercaptopyridine-1-oxide or of 3-methoxy-, 3-ethoxy-, 3-ethyl-, 4-methyl-, 5-methyl-, 5-bromo-, 6-methyl- or 6-propyl-pyridine-1-oxide.  Suitable amines for the formation of amine addition salts are higher alkyl- and dialkyl-amines such as cetyl, dodecyl, octadecyl, octyl and myristyl amines, di-(lower alkyl)-(higher alkyl) amines such as dimethyl cetyl, diethyl dodecyl, dimethyl dodecyl, dimethyl octadecyl and di-isopropyl cetyl amines. The quaternary reactants of the general formula <FORM:0790044/IV (b)/7> include quaternary compounds in which the anion is a sulphate, nitrate, halide such as the bromide, chloride or iodide, cyanide, sec.-orthophosphate, salicylate, hydrocinnamate, a -amylcinnamate, acetate, benzoate, methosulphate, ethosulphate, oleate or laurate, and in which the cation is n-octyltrimethylammonium, dodecyltrimethylammonium, myristyltrimethylammonium, octadecyltrimethylammonium, octadecyl-b  - hydroxyethyldimethylammonium, cetyltrimethylammonium, cetyltriethylammonium, cetyldimethylethylammonium, n - butylcetyldimethylammonium, cetyl - 2,3 - dihydroxy - propyldimethylammonium cetyldiethyl - b  - hydroxyethylammonium, octadecenyldimethylethylammonium, cetyl - di - n - propyl - (b  - hydroxyethyl) - ammonium, cetylmethylpiperidinium, cetylethylpiperidinium, dodecylethylpiperidinium, dodecylpyridinium, cetylpyridinium, p - tert. - octylphenoxyethoxyethylpyridinium, octylpyridinium, o  - octadecenylpyridinium, a cetylpicolinium, benzyldimethyldodecylammonium, benzyldimethylpentadecylammonium, benzylcetyldimethylammonium, cetyl - o - chlorobenzyldimethylammonium, benzylcetyldiethylammonium, benzylcetylethylpropylammonium, dodecyldimethyl - 3,4 - dichlorobenzylammonium, benzyldimethyloleylammonium, (1 - phenyldodecyl) - dimethylcinnamylammonium, dimethylethyl - 9 - o  - octadecenylammonium, (p - tert. - octylphenoxyethoxyethyl) - trimethylammonium, (p - 2,2,4,4 - tetramethylbutylphenoxyethoxyethyl) - dimethylbenzylammonium, (p - tert. - octylphenoxyethoxyethyl) - dimethylbenzylammonium, (p - tert. - octylphenoxyethoxyethyl) - diethylbenzylammonium, and (p - tert. - octyl - o - cresoylethoxyethyl)-dimethylbenzylammonium.  The preferred compounds of the invention are aralkyl-di-(lower alkyl)-(higher alkyl)-ammonium salts of 2-mercaptopyridine-1-oxide and N-(higher alkyl)-N-(pyridyl) ammonium salts of 2-mercaptopyridine-1-oxide. In the examples the following compounds are prepared: the cetyltrimethylammonium, cetyltriethylammonium, cetyl - 2,3 - dihydroxypropyldimethylammonium, (p - tert. - octylphenoxyethoxyethyl)trimethylammonium, tetradecyltrimethylammonium, dodecylbenzyldimethylammonium, laurylpyridinium, cetylpyridinium, cetylamine, octylamine, cetyldimethylamine and lauryldiethylamine salts of 2-mercaptopyridine - 1 - oxide, the cetyltrimethylammonium salts of 3-ethoxy-2-mercaptopyridine-1-oxide and 5-bromo-2-mercaptopyridine-1-oxide, and the cetyltrimethylammonium salt of 2-mercapto-6-methylpyridine-1-oxide.ALSO:A plant protective or chenotherapeutic preparation having antibacterial and antifungal properties comprises an inert diluent and, as the active ingredient a 2-mercapto-pyridine-1-oxide amine addition or quaternary salt of the general formula <FORM:0790044/VI/1> wherein R represents hydrogen or a halogen or a lower alkyl or lower alkoxy group, R1 and R2 each represents hydrogen or a lower alkyl group or a halo substituted or hydroxy substituted derivative of such a group, R3 represents hydrogen or a lower alkyl or aralkyl group or a halosubstituted or hydroxy-substituted derivative of such groups (except when R1 and R2 taken together with the nitrogen atom to which they are joined represent a piperidyl group and R3 represents a lower alkyl or an aralkyl group or a halo-substituted or hydroxy-substituted derivative of such groups, and except when R1, R2 and R3 taken together with the nitrogen atom to which they are joined represent a pyridyl group), and wherein R4 represents a higher alkyl or higher alkenyl group or a higher-alkylaryloxy-lower-alkoxy-lower alkyl group.  By the expression "lower alkyl" and "lower alkoxy" are meant groups having from 1 to 7 carbon atoms, and by the expressions "higher alkyl" and "higher alkenyl" are meant groups having from 8 to 30 (or more) carbon atoms.  Typical amine and quaternary salts of the above general formula are the cetyltrimethylammonium, cetyltriethylammonium, cetyl - 2,3 - dihydroxypropyldimethylammonium, (p - tert. - octylphenoxy - ethoxyethyl)-trimethylammonium, tetradecyltrimethylammonium, dodecylbenzyldimethylammonium, laurylpyridinium, cetylpyridinium, cetylamine, octylamine, cetyldimethylamine, and lauryldiethylamine salts of 2-mercapto-pyridine-1-oxide, the cetyltrimethylammonium salts of 3-ethoxy-2-mercaptopyridine - 1 - oxide and 5 - bromo - 2 - mercaptopyridine-1-oxide, and the cetyltrimethylammonium salt of 2-mercapto-6-methylpyridine-1-oxide.  Examples are given of chemotherapeutic compositions as follows: (1) nose drop composition containing the cetyltrimethylammonium salt of 2-mercaptopyridine-1-oxide, phenylephrine hydrochloride and phosphate buffer; (2) a lubricating jelly containing the ammonium salt as at (1), carboxymethylcellulose and water; (3) an eardrop composition containing the ammonium salt as at (1), urea, b -diethylaminoethyl p-ethoxybenzoate and polyethyleneglycol; (4) a foot powder containing the ammonium salt as at (1) and starch; and (5) ointments containing the ammonium salt as at (1), white wax, white petroleum jelly and peanut or mineral oil, the ammonium salt as at (1), wetting agents known under the Registered Trade Mark "Span" and "Tween," an antioxidant and water, and the ammonium salt as at (1), cetyl alcohol, stearyl alcohol, beeswax white, petroleum white, glycerine, sodium lauryl sulphate, an antioxidant and water.