Alkylpyridines acetic anhydride

The reactions shown in this section illustrate the versatility of Af-substituted pyridines in the synthesis of condensed heterocycles containing pyrrole. Some of the cyclizations proceed without the need for externally applied heat [2419, 2422,2830,2980a], and for most of the cyclizations, the conditions are relatively mild. The preformed ylide is used in some of the reactions while in others, it is generated in situ. It is even possible to react a 2-methylpyridine with an Af-alkyl-ating agent, such as bromoacetone, and then cyclize the intermediate iV-alkyl derivative by heating with sodium acetate-acetic anhydride or carbonate without isolating either the intermediate. /V-alkylpyridine or the ylide [2157, 2295, 2393, 3512]. 

A-Oxides of 2- and 4-alkylpyridines are functionalized in the side-chain by acylating agents (acid anhydrides, sulfonyl chloride, POCI3). For instance, 2- or 4-picoline-l-oxide with acetic anhydride yields a mixture of acetoxy compounds in which the methyl-substituted products, namely 2- and 4-acetoxymethylpyridine, dominate (87 and 90). Some nuclear-substituted products (88, 89, 91) are also formed ... 

A rearrangement of alkylpyridine-1-oxides that is related was also investigated. Ethyl 2-methylnicotinate-l-oxide (X-229) afforded an oil on treatment with acetic anhydride, which, after acid hydrolysis, yielded the... 

A soln. of 4(lH)-pyridone and 5-butylbarbituric acid in acetic anhydride heated 2 days at 90° 5 butyl-5-(4-pyridyl)barbituric acid (Y 75%) refluxed 2 days with 5 parts 15%-Na2C03-soln. -> 4-pentylpyridine (Y 80%). F. e. with 2-step degradation, also condensation with isopropylidene alkylmalonates and conversion into 2-(4-pyridyl)alkanoic acids and anilides in addition to 4-alkylpyridines, s. F. X. Smith and G. G. Evans, Tetrah. Let. 1972, 1237. 

If the 4-position is sterically hindered, the intermediate 4-acylpyridines can be isolated in good yield in place of the usually resulting 4-alkylpyridines.—E 3,5-Dimethylpyridine and acetic anhydride -> 3,5-dimethyl-4-acetylpyridine. Y 70%. J. P. Kutney and T. Tabata, Can. J. Chem. 41, 695 (1963). 

The use of zinc chloride and related substances, or acetic anhydride, is a common feature of many reactions of alkylpyridines. The first type of reagent probably exercises a generalized acid catalysis, augmenting the reactivity of alkyl groups by coordination with the nitrogen atom. Acetic anhydride... 

A unique method for preparing 4-alkylpyridines consists in treatment of pyridine with aliphatic anhydrides in the presence of zinc dust. The intermediate l,4-diacyl-l,4-dihydropyridines are not isolated but are further reduced to the 4-alkylpyridlnes by the action of zinc dust and acetic acid. The procedure is illustrated by the synthesis of 4-ethyl-pyridine (38% over-all). ... 

---