Patent GB-1103137-A (GB)
Title: 1,2,3,4-tetrahydrophenazine-5,10-dioxides, and derivatives thereof useful in veterinary applications
IPC: A23K1/18
Filed: 1966-04-15
Abstract: Novel compounds of the formulae <FORM:1103137/C2/1> <FORM:1103137/C2/2> <FORM:1103137/C2/3> (wherein R1 is lower alkoxy, SH, lower alkyl mercapto, CN, CO2H, carbo (lower) alkoxy, benzoyloxy, p-toluenesulphonyloxy or lower alkanoyloxy; R2 is H, OH, Cl, Br, lower alkoxy, SH, lower alkyl mercapto, CN, CO2H, carbo (lower) alkoxy, benzoyloxy or p-toluene-sulphonyloxy; and R3 has the values of R2 and can additionally be lower alkanoyloxy; the word "lower" referring to groups of 1 to 6 carbon atoms) and salts thereof, and the known 1 - hydroxy -, 1,4 - dihydroxy -, 1,4 - di (lower alkanoyloxy) - and 1,4 - dibromo - 1,2,3,4-tetrahydrophenazine - 5,10 - dioxides are prepared by oxidizing 1,2,3,4-tetrahydrophenazine to the corresponding mono- or di-oxide, acylating to give the 1-acyloxy- or 1,4-diacyloxy-1,2,3,4-tetrahydrophenazine, oxidizing to give the dioxides of these compounds, and hydrolysing to give the required 1-hydroxy- or 1,4-dihydroxy compounds, which may be re-acylated, or reacted with halogenating agents to give the 1-halo or 1,4-dihalo compounds, which by metathesis can be converted to the 1- and 1,4-cyano, mercapto, alkylmercapto and alkoxy compounds (the last two can also be obtained by alkylation of the ols and mercaptans), or by reaction with acid tertiary amine salts are converted to aryloxy compounds.  The monohydroxy compounds on oxidation give the monoketones and on dehydration give the mono-unsaturated compounds (dihydrophenazines).  The carbalkoxy compounds are prepared by condensation of the appropriate 1,2-cyclohexane dione mono- or di-carbalkoxy compounds with o-phenylenediamine, and subsequent oxidation of the 1- or 1,4-dicarbalkoxy-1,2,3,4-tetrahydrophenazines formed, and on hydrolysis give the carboxy compounds (which may also be prepared by hydrolysis of the cyano compounds), which may be re-esterified. The monocarbalkoxy compounds may be halogenated to give the 1 - halo - 4 - carbalkoxy compounds which may be hydrolysed to the free acids.  The isomeric 1,4 - dihydroxy - tetrahydrophenazinedioxides may be separated by standard procedures, or, preferably, by dissolving the isomeric mixture in dimethylsulphoxide when one isomer is precipitated as a complex, filtered off and recovered by crystallization.  The compounds of Formula (III) from addition compounds with nucleophilic reagents.ALSO:Chronic respiratory diseases of poultry are controlled by oral or parenteral administration thereto of the novel compounds of the formul  <FORM:1103137/A5-A6/1> <FORM:1103137/A5-A6/2> <FORM:1103137/A5-A6/3> (wherein R1 is lower alkoxy, SH, lower alkylmercapto, CN, CO2H, carbo (lower) alkoxy, benzoyloxy, p toluenesulphonyloxy, or lower alkanoyloxy; R2 is H, OH, Cl, Br, lower alkoxy, SH, lower alkylmercapto, CN, CO2H, carbo (lower) alkoxy, benzoyloxy or p-toluenesulphonyloxy; and R3 has the values of R2 and can additionally be lower alkanoyloxy; the word "lower" referring to groups of 1 to 6 carbon atoms) or of the known 1-hydroxy-, 1,4-dihydroxy-, 1,4-di-loweralkanoyloxy- and 1,4 - dibromo - 1,2,3,4 - tetrahydrophenazine-5, 10-dioxides, and salts thereof.  These compounds may also be used to promote growth and improve feed efficiency of animals, and for this purpose they may be administered in a nutritionally balanced feed.