Patent GB-791190-A (GB)
Title: New heterocyclic compounds and processes for their preparation
IPC: C07D213/70
Filed: 1956-03-29
Abstract: The invention comprises the new compounds 1-, 3- and 4-azaphenthiazines of formula <FORM:0791190/IV (b)/1> in which the pyridyl nitrogen atom is in the 1, 3 or 4 position and which may be unsubstituted or C-substituted in either or both of the benzene and pyridine nuclei.  Typical substituents are halogen, alkyl groups and alkoxy groups.  The 1- and 3-azaphenthiazines may be prepared by heating a phenylthiapyridine of formula <FORM:0791190/IV (b)/2> in which <FORM:0791190/IV (b)/3> is a pyridyl group having the nitrogen atom in the a or b position, one of the groups X and Y is a halogen atom and the other a primary amine group, and in which the phenyl and pyridyl groups may contain one or more further substituents, in an anhydrous solvent in the presence of an alkaline condensation agent. Suitable condensation agents are, for example, potassium and sodium carbonates (preferably in the presence of a dehydrohalogenation catalyst such as copper powder) and caustic alkalis.  Preferred solvents are dimethyl aniline and N-substituted fatty acid amides containing not more than 3 carbon atoms, for example, dimethyl formamide and N-methylacetamide. The 4-azaphenthiazines may be obtained by adding the corresponding phenylthiopyridine to an alkaline medium.  In the examples: (a) 2,21 - bromophenyl - thio - 3 - aminopyridine is heated with dimethylformamide, potassium carbonate and copper powder to give 1-azaphenthiazine; (b) 4,21-bromophenylthio-3-aminopyridine is heated with dimethylformamide, potassium carbonate and copper powder to give 3-azaphenthiazine; (c) 4,21-bromo-41-chlorophenyl-thio-3-aminopyridine is heated with dimethyl formamide, potassium carbonate and copper powder to give 6-chloro-3-azaphenthiazine; (d) 3,21-nitrophenylthio-2-chloropyridine is heated with ethanol, stannous chloride and hydrochloric acid to give 3,21-aminophenyl thio-2-chloropyridine to which caustic soda is added to produce 4-azaphenthiazine; and (e) the process of (d) is carried out using 3,21 - nitro - 4 - chlorophenyl thio-2-chloropyridine as starting material to give 6-chloro-4-azaphenthiazine.  The 2,21-bromophenylthio-3-aminopyridine used as starting material in (a) is obtained by heating an alcoholic solution of 2-chloro-3-nitropyridine with a solution of 2-bromothiophenol in caustic soda to give 2,21-bromophenylthio-3-nitropyridine which is reduced with stannous chloride and hydrochloric acid to give the required compound.  The 4,21-bromophenylthio-3-aminopyridic used as starting material in (b) is obtained similarly using 3-nitro-4-chloropyridine as starting material.  The 4,21-bromo-41-chlorophenyl - 3 - aminopyridine used as starting material in (c) is obtained by treating 2 - bromo - 4 - chloroaniline hydrochloride with sodium nitrite solution, adding the diazo solution obtained to potassium xanthate solution, hydrolysing the xanthic ester formed with potassium hydroxide and acidifying to give 2-bromo-4-chlorothiophenol which is treated as above to give first 4,21-bromo-41-chlorphenylthio-3-nitropyridine and the the corresponding aminopyridine.  The 3,21-nitrophenylthio-2-chloropyridine used as starting material in (d) is obtained by treating 2-chloro-3-aminopyridine with sodium nitrite and hydrochloric acid, heating the diazo compound obtained with potassium xanthate, treating the resulting xanthic ester with potassium hydroxide to obtain 2-chloro-3-mercaptopyridine which is dissolved in caustic soda and heated with o-nitrochlorbenzene.  Th starting material used in (e) is obtained similarly to that of (d), using 2,5-dichloronitrobenzene instead of o-nitrochlorbenzene.