4- Carbamoyl-3- quinolines

The synthetic interest in direct substitution of protonated heteroaromatic bases by carbamoyl and a-amidoalkyl radicals arises because the reaction is applicable to a variety of heteroaromatic bases having highly reactive nucleophilic positions and because a variety of amides can be used. The selectivity of attack is complete at the a- and y-positions of the heterocyclic system owing to the nucleophilic character of both carbamoyl and a-amidoalkyl radicals, The results with formamide are shown in Table VI. Quinoline with dimethylformamide gave a variety... 

Attack by alkoxycarbonyl radicals, which are isoelectronic with but less nucleophilic than carbamoyl radicals, has been less well studied than acylation and amidation. An example is provided by the reaction of quinoline with ethyl pyruvate, hydrogen peroxide and an iron(II) salt (Scheme 213) (73TL645). 

Acyl radicals obtained by the oxidation of aldehydes or the oxidative decarboxylation of a-keto acids react selectively at the a- or y-position of the protonated heterocyclic nitrogen. Pyridines, quinolines, pyrazines and quinoxalines all react as expected yields are typically 40 to 70%. Similarly, pyridines can be carbamoylated in acid media at C-2 (Scheme 38). 

After studying various nitrogen-containing compounds, we found that the zinc alkoxide of 2-methyl-l-(3-quinolyl)propan-l-ol 5 (Fig. 1) catalyzes the enantioselective formation of itself with the same configuration in the reaction between quinoline-3-carbaldehyde and z-P Zn to produce the product 5 in high ee (up to 94% ee) [58]. In addition, the 5-carbamoyl-3-pyridyl alkanol 6 (Fig. 1) can act as an efficient autocatalyst to catalyze its own production in a highly enantioselective manner (up to 86% ee) [59]. 

Oxazolo[4,5-/2]quinolin-2(3//)-ones could be acylated effectively at the N-3 position with reagents such as AcCl, ethyl chloroformate, trans-cinna.moy chloride, and dimethyl carbamoyl chloride... 

Judging from the number of papers published over the last 20 years, the chemistry of 2,6-naphthyridines attracted much less attention than the 1,5-, 1,6- or 1,7-naphthyridines. Of the synthetic procedures developed over this period, noteworthy is oxidative cyclization of 4-carbamoyl-3-(2-hydroxyethyl)quinolines 121a-c under the action of Cr03 in glacial AcOH giving rise to benzo[c][2,6]naphthyridines 122a-c. The latter were used in the synthesis of 2,6-naphthyridines 123-125 (1985S541). 

Diethyl cyanophosphonate converts quinoline and isoqninoline iV-oxides into the 1- and 2-cyano-heterocycles in high yields in a process which must have 0-phosphorylation as a first step, and in which the elimination of diethylphosphate may proceed via a cyclic transition state trimethylsilyl cyanide and diazabicyclonndecene effect the same transformation. A chloroformate and an alcohol convert the iV-oxides into ethers, as illustrated below for isoquinoline iV-oxide, a chloroformate and a Grignard reagent prodnce 2-snbstitnted quinolines, and a chloroformate then an isonitrile produce 2-carbamoyl-... 

Other 1,2-diazines synthesized included 4-amino-3-cinnolinecarboxylic acids <97PHA91 >, I -aryl-6-chloro-l,4-dihydro-4-oxothieno[2,3-c]pyridazine-3-carboxylic acids <97JPR284>, 2H-benzo[2,3-g]pyridazino[4,5-<7,e]quinolin-3-ones <97M681>, 3-chloro-4-carbamoyl-5-aryl-6-methylpyridazine N-oxides <97F67>, 2-aroyl-6-(hetero substituted)-3(2//)-pyridazinones <97HCM267>, and 5-(4-hydroxycinnolin-3-yl)tetrazoles 2-methyl-5-(4-acetoxycinnolin-3-yl)-... 

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