Issue in Honor of Prof. Gurnos Jones ARKIVOC 2000 (iii) 240-251
The preparation of some heteroaromatic and aromatic aldehydes
Alan R. Katritzky,*a Hai-Ying He,a Qiuhe Long,a Xilin Cui,a Julian Levelb, and Allan L. Wilcoxb
a Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, PO Box 117200, Gainesville, FL 32611-7200, USA b Centaur Pharmaceuticals, Inc., 484 Oakmead Parkway, Sunnyvale, CA 94086, USA E-mail:
[email protected]
Dedicated to Gurnos Jones on the occasion of his 70th birthday (received 20 Dec 99; accepted 20 Aug 00; published on the web 28 Aug 00)
Abstract
Heteroaromatic a- and ß-carboxaldehydes were prepared by the formylation with DMF of alithio benzofuran, benzothiophene, N-methylbenzimidazole and 10-methylphenothiazine obtained by direct lithiation and ß-lithio compounds from lithium-bromine exchange. Dialkoxybenzaldehydes were prepared by the formylation of dialkoxybenzenes with hexamethylenetetramine (HMTA) or by the alkylation of dihydroxybenzaldehydes with alkyl bromides or iodides.
Keywords: Heteroaromatic aldehyde synthesis, dialkoxybenzaldehyde synthesis, lithio benzofuran, lithio benzothiophene, formylation, lithium-bromine exchange
Introduction
Heteroaromatic and aromatic aldehydes carrying additional substituents are important as versatile intermediates in the pharmaceutical industry and for organic synthesis in general. Ongoing studies on the synthesis of nitrones1 required the preparation of heteroaromatic aldehydes and dialkoxybenzaldehydes. As the published methods for preparing many of these compounds are frequently low yielding and/or not suitable for large-scale preparation,2 we now report the preparation of heteroaromatic aldehydes by the lithiation-formylation approach and of dialkoxybenzaldehydes by the formylation of dialkoxy-benzenes or by the alkylation of dihydroxybenzaldehydes.
ISSN 1424-6376 Page 240 ©ARKAT USA, Inc
