Development of potential manufacturing routes for substituted thiophenes – Preparation of halogenated 2-thiophenecarboxylic acid derivatives as building blocks for a new family of 2,6-dihaloaryl 1,2,4-triazole insecticides

• John W. Hull Jr.,
• Duane R. Romer,
• David E. Podhorez,
• Mezzie L. Ash and
• Christine H. Brady

Beilstein J. Org. Chem. 2007, 3, No. 23, doi:10.1186/1860-5397-3-23

• /debromination procedure developed for 3-methylthiophene gave 2,4-dibromo-3-methylthiophene. Carboxylic acid functionality was then introduced either by a Grignard metallation followed by carbonation with CO2, or by a palladium catalyzed carbonylation procedure under CO pressure. The vapor phase chlorination of

• position. Although 9 and 10 are co-products (Scheme 1), dibromide 8 is a low-melting solid that can be vacuum distilled to improve purity. Introduction of carboxyl functionality in 8 to give 19 was achieved either by metallation with MeMgBr [11] followed by treatment with CO2 gas, or by a palladium

• the preparation of 23 could also be carried out from 22 via metallation with n-butyllithium in an ether solvent with sub-zero cooling, followed by quenching of the 2-thienyllithium species with CO2. We have found that the choice of solvent for the metal-halogen exchange reaction is important. Diethyl