Patent GB-1101820-A (GB)
Title: Novel polymethylene quinoxaline dioxides
IPC: A23K20/195
Filed: 1965-11-24
Abstract: Novel quinoxaline dioxides of formula <FORM:1101820/C2/1> wherein R1 is hydroxy, lower alkoxy, mercapto, lower alkylmercapto, lower alkanoyloxy, cyano, carboxy, carbo (lower) alkoxy, chloro or bromo; R2 is hydrogen or R1; Z is methylene or trimethylene; and n is 0 or 2, and wherein said lower alkyl, lower alkoxy and lower alkanoyl groups contain 1 to 4 carbons, and the pharmaceutically acceptable acid and base salts are prepared by  (a) Oxidizing a quinoxaline compound of the formula <FORM:1101820/C2/2> wherein Z is as above, and R1 is the same as R2 and R2 is as defined above but is not mercapto or lower alkylmercapto.  (b) And, when required, doing the following:  (1) Hydrolysing to convert R1 and/or R2 from carbo (lower) alkoxy or cyano to carboxy or R1 and/or R2 from lower alkanoyloxy to hydroxy.  (2) Esterifying to convert R1 and/or R2 from carboxy to carbo (lower) alkoxy.  (3) Brominating or chlorinating to convert R1 and/or R2 from a hydrogen atom into a bromine or chlorine atom.  (4) Treating with a lower alkylating or lower alkanoylating agent to convert R1 and/or R2 from hydroxy into a lower alkoxy or lower alkanoyloxy group or from mercapto to lower alkyl mercapto. (5) Treating with hydrogen sulphide, a lower alkyl mercaptan, a metallic cyanide salt, or with a tertiary amine salt of a lower alkanoic acid to convert R1 and/or R2 from bromine or chlorine to a mercapto, lower alkyl mercapto, cyano, or lower alkanoyloxy group. (6) Converting R1 and/or R2 from a hydroxy group to a bromine or chlorine atom.  (7) When R1 and/or R2 are hydroxy groups, treating with a dehydrating agent to introduce conjugated unsaturation.  (8) Oxidizing to convert R1 and/or R2 from hydroxy (and when neither is mercapto or lower alkyl mercapto) to oxo.  (9) Forming the acid salt or the base salt (when R1 and/or R2 is carboxy).  2,3 - Dihydro - 1H - cyclopenta[b]quinoxaline-4 - oxide and 7,8,9,10 - tetrahydro - 6H - cyclohepta[b]quinoxaline -5-oxide are prepared by m-chloroperbenzoic acid oxidation of the corresponding quinoxalines (Examples 2 and 33). 2,3 - Dihydro - 1H - cyclopenta[b]quinoxaline and various 1-carbalkoxy and 1,3-dicarbalkoxy derivatives thereof, and 7,8,9,10-tetrahydro-6H-cyclohepta[b] quinoxaline and various 6-carbalkoxy and 6,10-dicarbalkoxy derivatives thereof are prepared by condensing o-phenylenediamine with appropriate 1,2-cyclopentanediones or 1,2-cycloheptanediones (Examples 1, 14, 25, 32, 41, 50 and 60).  2,3 - Dihydro - 1H - cyclopenta[b]quinoxaline-4,9 - dioxide and 7,8,9,10 - tetrahydro - 6H - cyclohepta[b]quinoxalin - 5,11 - dioxide are prepared by m-chloroperbenzoic acid oxidation of corresponding quinoxalines (Examples 3 and 34).  Various 1,3 - dicarbalkoxy - 2,3 - dihydro - 1H - cyclopenta[b] quinoxaline - 4 - oxides and 6,10-dicarbalkoxy - 7,8,9,10 - tetrahydro - 6H - cyclohepta[b]quinoxaline-5-oxides are prepared by m-chloroperbenzoic acid oxidation of corresponding quinoxalines (Examples 15 and 51).  Various 1-alkanoyloxy- and 1,3-dialkanoyloxy-2,3 - dihydro - 1H - cyclopenta[b]quinoxalines and 6-alkanoyloxy- and 6,10-dialkanoyloxy-7,8, 9,10 - tetrahydro - 6H - cyclohepta[b]quinoxalines are prepared by reacting alkanoic acid anhydrides with 2,3-dihydro-1H-cyclopenta[b]quinoxaline - 4 - oxide or -4,9 - dioxide or 7,8, 9,10 - tetrahydro - 6H - cyclohepta[b]quinoxaline - 5 - oxide or -5,11 - dioxide (Examples 4, 9, 35, 38 and 45).  The above novel quinoxaline dioxides are used for treatment of urinary tract and systemic infections and against air sacculitis in poultry They may be administered orally or parenterally as capsules, tablets, lozenges, troches, liquid mixtures and solutions or in food or drinking water.