METHOXYCARBOSTYRILSThe central nervous sytein activity occasionally displayed by carbostyrils (1) led us t o prepare several methoxy-substituted 2-hydroxyquinolines (cf. I) and a number of 2-quinolyl esters (Table I) for pharmacological evaluation. In general, the quinoline derivatives were based on structural features2 of thc hypotensive and sedative Raz~wolJia alkaloids reserpine and resinnamine (2). Certain other 2-quinolyl esters (Table I), ethers, and 2-chloroquinolii~es were synthesized for comparison purposes.Initially, it was considered necessary t o prepare 6-methoxy-(Ia), 7-methox!--(Ib), and 6,7-dimcthoxy-carbostyril (Ic). Of these, only 7-methoxycarbostyril was previously undescribed and synthesis was accomplished by the follo.iving reaction scheme (I1 -+ I).3Chromyl chloride oxidation of 2-nitr0-4-i11ethoxytoluene ( 5 ) gave 2-nitro-4-~nethoxy-benzaldehyde (11) as described by Boon (6). Condensation of benzaldehyde I1 with malonic acid led t o 2-nitro-4-n1ethoxycii1na1nic acid (111). Ferrous sulphate reduction of nitrobenzene I11 afforded 2-amino-4-inethoxycinilainic acid (IV), which cyclized t o 7-inethoxycarbostyril (Ib) in hot 2-propanol -llydrochloric acid solution. P h o s p l~o r~~s oxychloride readily converted carbostyril Ib t o 2-chloro-7-methoxyquinolii~e (Id).Preparation of 2-chlorocluinoline Id illustrates the general reaction sequence employed for synthesis of 6,7-dimethox~~carbostyril (7) from 6-nitroveratraldehyde and subsequent conversion t o 2-cl~loro-6,7-di1netl1oxyquinoline (Ie). D i m e t l~y l f o r m a~~~i d e was found a superior solvent for effecting facile transforillation of chloroquinoline Ie to 2,6,7-triinethoxyquinoline (If)
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