Some Reactions of Ethyl 2-Pyridineacetate: 1,2-Dicarbethoxy-3-Oxo-Octahydropyrrocoline

Abstract

Ethyl a-acetosy-2-pyridineacetate ant1 ethyl a-bromo-2-pyridineacetate have been prepared, and the latter converted in three steps to 1,2-dicarbethoxy-3-0x0-octahydropyrrocoline. The main carbonyl hand of simple saturated five membered lactams in the infrared is observed to lie close t o 1700 cm-I.The methyleile group of ethyl 2-pyridineacetate is of comparable activity to that of ethyl acetoacetate. For example, a useful anion can be obtained by reaction with sodiuin or potassiuin (1, 4). Further parallel between the reactivities of the two compouilds has now been found in the ease of bromination and acetoxylation. Like acetoacetic ester (6), 2-pyridineacetic esters react rapidly with a molar equivaleilt of bromine a t 5OC. in carbon disulphide solution to give a-bromo esters, and react a t room temperature with lead tetraacetate in benzene to give the a-acetoxy compound. In contrast, the methylene group of malonic esters does not react a t a useful rate with lead tetraacetate in benzene until the solution is heated to around 100' (6).The synthesis of octahydropyrrocolines with reactive substituents has been achieved by Clemo and co-workers (2, 3, 4) and by Lions and Willison (10). The work of Diels and co-workers (5, and earlier papers) has led to pyrrocolines substituted with carboxyls, which presumably could be reduced to the corresponding octahydro derivatives. By reaction of ethyl a-bromo-2-pyridineacetate with the anion from ethyl malonate, reduction of the product, and cyclization, 1,2-dicarbethoxy-3-0x0-octah~~dropyrrocoline 111 has now been obtained. The malonic hydrogen and carboxyl groups in this compound are of potential value for building additional rings on the five membered ring.The reactions used in preparing and characterizing the various products are shown in the flowsheet. The mixture obtained when the bromo compound reacted with the ~nalonic anion contained some ethyl 1,1,2,2-ethanetetracarboxylate, probably arising from ethyl bromomalonate formed by bromine exchange. This could be partly removed by distillation under high vacuum, but the desired product I could not be distilled without considerable decomposition. By chron~atography on neutral alumina, however, I could be freed from the ethanetetracarboxylic ester, unchanged malonic ester, and colored impurities.I proved to be a very weak base (pKA around 2.4 in 50% aqueous methanol). A somewhat low basicity (PI< 3.6) has been observed for a,a-di-(2-pyridy1)-1 Alanuscript received M a y 7 , 1954.

Pyridine (Continued) the Properties of Functional Groups

“…The decarboxylation temperatures of solid pyridine-dicarboxylic acids depend roughly on their strengths as acidsthe stronger the acid the lower the temperature76, At 185°-190°, pyridine-2,3,4-tricarboxylic acid gives pyridine-3,4-dicarboxylic acid, which above Et ester (0-2) (b.p. 240-1 °) amide (107) chloride anhydride (124) anilide hydrazide nitrile (26) Derivatives ( m.p., oq picrate (100) hydrochloride ( 154) hydrochloride ( 131) picrate (223) hydroc4loride (220) Et ester (25) 83b Et ester (b.p. 159°/14 mm, m.p.…”