The autooxidation of methyl-and dimethyl-substituted N-, S-, and O-heterocyclic compound derivatives has been studied in 1,2-dimethoxyethane--t-BuOK in the presence of l8-crown-6. Monoand dicarboxylic acid derivatives of pyrazine, pyridine, pyrimidine, and thiophene have been synthesized.
Autooxidation of carbanions, prepared by action of strong bases on C--H acids under phase transfer catalysis conditions, offers a method for the preparation of a variety of oxygen-containing organic compounds [1,2]. For instance, pyridinedicarboxylic acids have been prepared via oxidation of picotines by oxygen in benzene--t-BuOK--PEG-6000 [3] and 1,2-dimethoxyethane--KOH--18-crown-6 [4, 5] phase transfer systems. We have also demonstrated recently that 2,5-dimethylpyrazine (I) is oxidized by oxygen in 1,2-dimethoxyethane--t-BuOK solvent system in the presence of 18-crown-6, to give pyrazine-2,5-dicarboxylic acid [6].
In the present paper we have explored the potential applications of this method for the preparation of a variety of hetarylcarboxylic acids; in particular, we have examined the autooxidation behavior of methyl-and dimethytsubstituted pyrazine, pyridine, pyrimidine, thiophene and furan derivatives. The pertinent reactions were studied under conditions developed previously for the preparation of the diacid product from compound I [6]: initial starting material concentration in 1,2-dimethoxyethane 0.5 mole/liter; mole ratio of methylheterocycle--t-BuOK--18-crown-6 equal to 1:2.5 (per one CH 3 group): 0.05; oxygen pressure 5 arm; temperature 60~ (Table 1). In the oxidation of monomethyl derivatives of mono-and diazines, namely methylpyrazine (II), 4-methylpyridine (III), and 4methylpyrimidine (IV), the corresponding hetarylcarboxylic acids were obtained in 64, 75, and 32% yields, respectively. The relatively low yield of 4-pyrimidinecarboxylic acid is probably due to partial destruction of the diazine ring upon treatment with base; this is characteristic of pyrimidine compounds [7]. The reactivity of methylpyrazine II is higher than that of dimethylpyrazine I, while picoline III is more reactive than methylpyrazine II.
In the case of the oxidation of 2,4-, 2,6-, 3,4-, 2,5-, and 3,5-1utidines (V-IX), the corresponding acid product was obtained in only one case, from 2,4-1utidine (V). Compound V, in analogy with the behavior of compound I [6], was converted to dicarboxylic acid (methyipyridinecarboxylic acid was not detected in the reaction mixture), indicating that a singular or identical mechanism is operating in the oxidation of compounds I and V (the proposed mechanism for this transformation under phase transfer catalysis conditions has been discussed in the previous paper [6] for the oxidation of compound I as an example). The reactivity of dimethylpyridine V is lower than that of dimethylpyrazine I, and considerably lower than that observed for methylpyridine III. Azinecarboxylic acid products are not formed in the oxidation of 2,6-dimethylpyridine or 2,6-dimethylpyrazine; these heterocycles undergo ring destruction under the reaction conditions, as evidenced by the observation of acetic acid among the reaction products (the latter was identified by GLC and chromatography-mass spectrometry). This bebavior can be explained on the basis of the instability of the intermediate carbanions generated in the reaction mixture; it is known from the literature [8] that carbanion instability represents an obstacle to the preparation of oxidation products from weak C--H acids via reaction with oxygen. Compounds VII-IX, which contain/3-CH 3 groups, are practically inert under phase transfer catalyzed-autooxidation conditions; it is not possible to prepare mono-or dicarboxyic acids from these substrates via this reaction pathway 2-Thiophenecarboxylic acid was obtained in 67% yield upon oxidation of 2-methylthiophene (XI); the corresponding acids were not formed, however, from 3-methyl-and 2,5-dimethylthiophenes (XII and XIII) under these reaction conditions. The reactivity of compound XI is substantially lower than for N-heterocyclic methyl derivatives II-IV. It was found that in all cases involving the formation hetarylcarboxylic acid conversion of the