Nucleophilic substitution of the nitro group in 4-nitro-3-pyridinecarboxanilide 1-oxide (IIa) afforded 4-hydroxy- (IIb), 4-chloro- (IIc), 4-methoxy- (IId), 4-ethoxy- (IIe), and 4-dimethylamino-3-pyridinecarboxanilide (IIf). The 1H and 13C NMR chemical shifts of the pyridine moiety were correlated with the Hammett constants of the substituent in position 4, with the exception of compound IIb. The reason of this phenomenon is discussed.
Nucleophilic Substitution in a Series of 4-Nitronicotinic Acid 1-Oxide Derivatives.-Nucleophilic substitution of the nitro group in 4-nitronicotinic acid N-oxide (I) or its anilide (IV) affords the 4-hydroxy (III), 4-chloro ( V), 4-methoxy (VIIa), 4-ethoxy (VIIb) and 4-dimethylamino (IX) derivative. -(POHL, R.; PRUTIANOV, V.; SMRCKOVA-VOLTROVA, S.; Collect.
Compounds 2-and 4-aminonicotinamide were quaternized with eight 4-substituted 1-bromomethylbenzenes to form 1-(4-substituted benzyl)-3-carbamoyl-1,2(1,4)-dihydropyridin-2(4)-iminium bromides. The optimal reaction conditions were found and the resulting iminium salts were characterized by 1 H and 13 C NMR spectra. No transmission of electronic effect of the substituent at the benzene ring on the spectral properties of dihydropyridine moiety was observed. The possible reason is discussed.In our previous communication 1 we have found 13 C NMR spectroscopy as a suitable tool for the proof of the structure of aminopyridine quaternary salts. We concluded that salts derived from 2-and 4-aminopyridine occur exclusively in the iminium form with dihydropyridine structure. This fact may be important from the biological point of view: dihydropyridiniminium structure behaves rather as an 1,4-dihydropyridine derivative than as a pyridinium quaternary salt and the hydride-donor properties are lost. This fact can be a reason of both the CNS activity of the alkaloid clitidin 2 and the powerful competitive inhibition of NAD by aminonicotinamide, which is by NADase catalyzed base-exchange reaction transformed into a coenzyme analog 3 . The chance to be therapeutically useful let us to the synthesis of 2-and 4-aminonicotinamides substituted in the position 1 with modified benzyl group. These compounds are interesting also from the chemical point of view, regarding the study on the substituent effects.The starting 2-aminonicotinamide was prepared from nicotinamide by oxidation to its N-oxide, chlorination with a mixture of phosphorus pentachloride and phosphorus oxychloride to 2-chloronicotinonitrile, reaction with alcoholic ammonia at 180 °C and hydrolysis according to the described procedure 4 . 4-Aminonicotinamide was obtained from the 3-methylpyridine-1-oxide by its nitration 5 , oxidation 6 to 4-nitronicotinic acid 1-oxide, catalytic hydrogenation 7 to 4-aminonicotinic acid and amide preparation via the anhydride intermediate 8 . The 1-substituted 2-and 4-aminonicotinamides I and II were prepared by reaction of the base with the corresponding 4-substituted 1-bromomethylbenzene in dimethylformamide or acetonitrile.Quaternized 2-and 4-Aminonicotinamides
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