Competitive free radical 4‐nitrophenylation of pyridine and thiophene

Abstract

Competitive free radical 4‐nitrophenylation of pyridine and thiophene shows a relative reactivity of thiophene:pyridine of 1.3:1 as based on product isolation. A three‐center reaction is proposed to account for the predominance of alpha substitution in each system. Column chromatography and 1H nmr are used for separation and identification of products.

Free radical 4‐nitrophenylation of thieno[2,3‐b]pyridine. Part 1: General experimental procedure and prediction of isomeric ratios of products

“…Klemm and Dorsey studied competitive free radical 4-nitrophenylation of pyridine and thiophene under conditions somewhat more acidic than those used in the present study [9]. They found that thiophene is more reactive than pyridine (in a ratio of 1.3:1) and, in agreement with reports from other workers [10], that substitution alpha to the heteroatom predominates in both rings.…”

“…and Dorsey proposed that attack by an electron-seeking free radical (such as 4-nitrophenyl) will occur preferentially at the heteroatom (S or N), where electrons are readily available, but that a rearrangement of the free radical will occur to an alpha position via a three-center reaction mechanism [9,11]. Since the sulfur atom of thiophene should furnish an electron more readily than the nitrogen atom of pyridine one can rationalize the greater reactivity of thiophene.…”

Free‐radical 4‐nitrophenylation of thieno[2,3‐b]pyridine. Part 3: Consideration of mechanistic and selectivity factors involved in the substitution process

“…For use of 4-nitroaniline an isomeric selectivity of 24:1 was reported. This compares favorably with other data from the literature [25]. Extending these relationships to 4-nitrophenylation of 1, we expect that the reaction should be kinetically controlled and could well result in markedly different yields of the five possible isomers 3a-3e (as observed).…”

“…38 tron-attracting than 6, Porter has suggested that thiophene might even transfer an electron to a phenyldiazonium cation, with formation of nitrogen gas and a phenyl free radical [20]. Whatever the reaction mechanism might be, the diazonium intermediates from 2-nitro-, 4-nitro-, and 2,4-dinitroanilines all give preferential substitution into the alpha position of thiophene [23][24][25][26].…”

“…The free radicals 2-thieno[2,3-b]pyridyl and 4 then couple to form 3a. An analogous mechanism can be written for the predominant formation of the 2-isomer from thiophene and 2 [25,32]. Conceivably, this concept can be extended to Scheme 3, where a much less stringent geometric relationship would be required between the thiophene molecule and one heptafluoropropyl group of 6 in the encounter complex.…”