Basicities of thienopyridines

Miller

2001

Thieno[2,3‐b]pyridine (1) was warmed at 45 ± 7° with diazotized 4‐nitroaniline (2) (molar ratio 1:2 = 3.6:1) in buffered (sodium acetate‐acetic acid) aqueous solution until gas evolution ceased. The reaction mixture was separated into these fractions: (a) water‐soluble (discarded), (b) acetone‐soluble (tars), (c) ether‐soluble, and (d) ether‐ and chloroform‐soluble, but acetone‐insoluble (rust‐colored solids, Y, 12% yield as 4‐nitrophenyl‐1 isomers, 3). Fractional evaporative distillations of (b) and (c) gave recovered 1 (69%) and yellow‐red sublimates (Z, 20% yield as 3). Y and Z were handled separately for isolation and identification of isomers [2]. Three general methods for predicting the isomeric ratios of 3 which one should obtain are presented, viz. (1) an amalgamation of reported free‐radical phenylation results for quinoline and benzo[b]thiophene, (2) calculations of Frontier Radical Densities for positions 2‐6 only, and (3) Molecular Orbital calculations for electron densities and superdelocalizabilities for free‐radical attack at positions 1‐7, as modified by a proposed rearrangement of the attacking group from the heteroatomic N and S positions to adjacent alpha positions.

Section: General Experimental Proceduresmentioning

confidence: 99%

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

Miller

2001

Chemistry of thienopyridines. XVIII. Lithiation as a route to 2‐ and 3‐substituted thieno[2,3‐b]pyridines

Merrill

1974

Treatment of thieno[2,3‐b]pyridine (1a) with n‐butyllithium in hexane‐tetramethylethylene‐diamine at −70° plus subsequent addition of dimethylformamide produced 2‐formyl‐Ia (66%). Halogen‐metal exchange between 3‐bromothieno[2,3‐b]pyridine and n‐butyllithium was effected in ether at −70. Further reaction of the 3‐lithio‐Ia intermediate with a variety of carbonyl compounds gave 3‐substituted thieno[2,3‐b]pyridines bearing formyl (77%), acetyl, benzoyl, chloroacetyl, ethoxycarbonyl, N‐phenylcarbamyl, and diphenyl hydroxymethyl groups. Common characteristics of these derivatives in pmr and mass spectra are noted.

Chemistry of thienopyridines. XX. The relation of dipole moment to molecular structure

Jacquot

1975