Patent GB-1007590-A (GB)
Title: Lower alkyl esters of 6,7-di(lower)alkoxy-4-hydroxy-3-quinolinecarboxylic acid
IPC: A23K1/10
Filed: 1963-12-03
Abstract: The invention comprises quinolines of the general formula <FORM:1007590/C2/1> wherein R and R1 are C3-C4 alkyl or are ethyl when R2 is methyl and R2 is alkyl containing up to 4 carbon atoms and the preparation thereof either (a) by the action of heat on the required 3,4-dialkoxyanaline and diethyl ethoxy-methylene malonate or dimethyl methoxy-methylene malonate in a temperature regulating medium at 200 DEG  to 250 DEG  C., or (b) by ester interchanger or saponification, followed by re-esterification to replace one R2 group by another, in a compound of the above general formula, for example by reaction of a compound of the above general formula wherein R and R1 have the above meanings and R2 is a reactive ester group, e.g. an acid chloride, with an alcohol of formula R2OH. The Specification refers briefly to the following additional methods for the preparation of the above quinolines: (a) formylation of the required dialkoxyaniline and reaction of the resulting compound of the formula <FORM:1007590/C2/2> wherein R and R1 have the above significance, with a dialkyl malonate or malonamide; (b) a modification of the Camps quinoline synthesis by ring closure of a substituted dialkoxy aniline in accordance with the following equation <FORM:1007590/C2/3> wherein R, R1 and R2 have the above significance, R3 represents an alkoxycarbonylmethyl or formyl substituted alkoxycarbonylmethyl group and R4 represents hydrogen or a formyl group; (c) by the carboxylation and subsequent esterification of a compound of the formula <FORM:1007590/C2/4> wherein R and R1 have the above significance and X represents a group convertible to a carboxyl group, for example alkoxydicarbonyl (by decarbonylation), nitrile, alkoxycarbonyl, carbamyl, halocarbonyl (all by hydrolysis), alkyl, hydroxyalkyl, formyl, alkylcarbonyl (by oxidation) and halogen and hydrogen (by treatment with carbon dioxide in the presence of a catalyst such as lithium); (d) exchange of a functional group in a compound of the formula <FORM:1007590/C2/5> wherein R, R1 and R2 have the above significance and Y represents a group which can be converted to a hydroxy group such as amino, halogen, sulphonic acid, alkylmercapto and alkylsulphonyl; and (e) dehydrogenation of the corresponding partially hydrogenated quinolines. 3,4-Dialkoxy-anilines, in which the alkoxy groups contain 3 or 4 carbon atoms, are prepared by hydrogenating the corresponding dialkoxy-nitrobenzene in the presence of a hydrogenation catalyst. Quinoline carboxylic acid chlorides defined above are prepared by hydrolysing the quinoline esters of the first general formula above and treating the resulting qionoline carboxylic acids with thionyl chloride.  3,4 - Di - isopropoxy - 4 - nitro - benzene is prepared by alkylation of the catechol with isopropyl bromide in alkali, followed by nitration of the resulting o-di-isoproxybenzene with 1 : 1 nitric acid.  Therapeutic veterinary compositions containing a quinoline of the above general formula as the active ingredient and a suitable carrier.  The composition has anticoccidial properties on oral administration in animal foodstuffs or oral administration in animal foodstuffs or water.  The composition is preferably in the form of food concentrates or in the form of tablets, gelatin capsules or suspensions.