2- pyridine, oxidative cyclisation

In this particular instance the correct oxidation level automatically results from the condensation reaction, giving pyrrole 2.16 directly. In other cases cyclisation does not afford the correct oxidation level and an unsaturated system has to be oxidised to achieve aromaticity. For instance, 1,5-diketones 1.27 react with ammonia to give dihydropyridines 1.28 which can be oxidised to pyridines 1.29. 

Pyridine pesticides are usually synthesized by starting with pyridine or a picoline nucleus, which is then further treated by halogenation, ammoniation, oxidation, etc. Quite often however it is impossible to introduce the desired substituents into the adequate ring position, in which case the corresponding aliphatic compound is prepared and then cyclised. 

The initial compound (9) was prepared by stirring 1,3,5 trimethoxybenzene with 1 -methyl-4-piperidone in glacial acetic acid. The tram alcohol (10) was obtained by hydration of the double bond and the corresponding cis compound (11) then made via the ketone by oxidation then reduction. Treatment with acetic anhydride and an acid catalyst such as boron trifluoride etherate gave (12). Treatment of this compound at room temperature with ethyl benzoate in the presence of sodium metal produced the diketone (13) which was cyclised to (14) by the addition of mineral acid. Final demethoxylation of the chromone hydroxy groups with pyridine hydrochloride was carried out for several hours at 180°. 

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