Patent GB-834553-A (GB)
Title: Derivatives of 2-mercaptopyridine 1-oxide and methods of preparing same
Inventor: BERNSTEIN JACK
IPC: C07D213/89
Filed: 1956-02-24
Abstract: The invention comprises bis-(pyridine-N-oxide) compounds of the general formula <FORM:0834553/IV (b)/1> wherein R1 and R2 represent hydrogen, halogen or alkyl or alkoxy groups having not more than 4 carbon atoms, the R's being symmetrically located as between the two pyridine nuclei and M represents <FORM:0834553/IV (b)/2> The compounds wherein M represents -S-may be prepared by reacting an ammonium, alkali metal or alkaline earth metal salt of a 2-mercapto-pyridine I-oxide of the general formula <FORM:0834553/IV (b)/3> with a 2-halo-pyridine I-oxide of the general formula <FORM:0834553/IV (b)/4> preferably in the form of its acid-addition salt, in a solvent for the reagents; numerous organic and inorganic acid addition salts are specified.  These monosulphides may also be prepared by reacting an excess of an appropriate 2-halo-pyridine I-oxide with an alkali metal sulphide, e.g. Na2S, in water.  The compounds in which M represents -S-S- may be prepared by reacting a 2-mercapto pyridine I-oxide as above defined, with an oxidizing agent of the peroxide type, such as H2O2 or other peroxide or peracid, using suitable proportions of reagents and reaction times.  The sulphoxides and sulphones defined above wherein the pyridine nuclei are joined together by one or two sulphyr atoms may be prepared by reacting the corresponding compounds wherein M represents -S- or -S-S- with an oxidizing agent of the peroxide type, particularly H2O2 in aqueous acid, in an amount and for a time sufficient to give the desired product.  The sulphones and sulphoxides wherein the pyridine nuclei are joined by two sulphur atoms may also be prepared in a single stage by reacting a 2-mercapto pyridine I-oxide as above defined with an oxidizing agent of the peroxide type in an amount and for a time sufficient to give the desired product.  Some of the dithio, thiosulphinyl and disulphinyl compounds have antimicro-organism activity.  In examples: (1) 2 : 21 - dithiodipyridine, 1,11 - dioxide, and (2) the corresponding 4-methyl, 6-methyl, 5-bromo and 3 - ethoxy - substituted dithiodipyridine dioxides are prepared by slowly adding aqueous H2O2 to an aqueous suspension of the appropriate 2-mercaptopyridine 1-oxide; (3) 2,21-dithiodipyridine 1,11-S-trioxide and the corresponding di-4-methyl pyridine compound are prepared from the appropriate dithiodipyridine 1,11-dioxides by treatment with aqueous H2O2 in acetic acid without heating; (4) 2,21-disulphinyl dipyridine 1,11-dioxide and the analogous di-6-methyl, 4:6-dimethyl, and 3-ethyl-6-methyl pyridine compounds are prepared from the corresponding dithio compounds by treatment as in (3) with a larger quantity of H2O2 at room temperature; 2,21-dithio dipyridine, 1,11-dioxide similarly treated but with a larger amount of H2O2 at 60-70 DEG  C. yields the sulphoxide-sulphonyl compound; (5) 2,21-thiodipyridine 1,11-dioxide is prepared by adding the solid Na salt of 2-mercapto-pyridine 1-oxide to a suspension of 2-bromo-pyridine 1-oxide in an alcoholic solution of sodium ethoxide and refluxing; (6) 2,21-sulphinyl dipyridine 1,11-pyridine is prepared from the corresponding monosulphide by the method of (3); (7) the method of (6) is modified by the use of more H2O2 and a longer reaction time giving 2,21-sulphonyl dipyridine, 1,11-dioxide; (8) 2,2-dithio-bis-(4,6-dimethyl pyridine) 1,11-dioxide and the analogous 3-ethyl-6-methyl compound are prepared by reacting 2-mercapto-4,6-dimethyl (or 3-ethyl-6-methyl) pyridine 1-oxide with aqueous H2O2.  Many other similar compounds are named.  The 2-mercapto pyridine oxides used in (8) above are prepared by converting the corresponding 2-amino alkyl substituted pyridines via the diazonium bromides to the 2-bromo compounds which are oxidized to the pyridine 1-oxides with per-acetic acid and the oxides in the form of their hydrochlorides, are refluxed with alcoholic thiourea and the product worked up to give the desired mercapto-pyridine 1-oxide. Alternatively, the bromo-pyridine hydrochloride is treated in aqueous NaOH with NaHS and the product converted into the desired mercapto 1-oxide by the method of U.S.A. Specification 2,686,786.