investigation of vilsmeier- haack reaction on homoallyic

Abstract

The thesis entitled "Investigation of Vilsmeier-Haack Reaction on Homoallylic, Allylic and Benzylic Alcohols" consists of seven chapters. Chapter 1 contains an account of the investigation of Vilsmeier reaction on the homoallylic alcohols (1) obtained from the aryl ketones (Ar-COCH?R) by Grignard reaction. The procedure afforded a wide variety of symmetrical and unsymmetrical biaryls or biphenyls (2). In a few cases, monoformyl compounds (3) in minor amounts were also detected. The carbinols (4) under similar reaction conditions gave the benzoannulated products (5) and (6). Chapter 2 describes the results of investigation of Vilsmeier reaction on the allyl alcohols (7) prepared by Grignard reaction with vinylmagnesium bromide on the aryl ketones (ArCOCHCH?R). This study led to the synthesis of various mono- and dicarboxaldehydes (8). The aldehydes so obtained were subjected to oxidation and reduction reactions to throw light on their structural pattern, the end reduction products being various di-, tri-, and tetramethylbiphenyls. In Chapter 3 is described a simple benzoannulation procedure involving the synthesis of five 1,1':2',1"-terphenyl-4'-carboxaldehydes (11) from the homoallyl alcohols (9) by Vilsmeier reaction. The homoallyl alcohols (9) were readily obtained by Grignard reaction with allylmagnesium bromide on desoxybenzoins. Chapter 4 is concerned with the Vilsmeier reaction on alicyclic alcohols (12), obtained by Grignard reaction with allylmagnesium bromide on the corresponding monocyclic ketones, to give the bicyclic mono- (13) and dicarboxaldehydes (14). A single-step synthesis of a biologically interesting natural product (13; n=2), isolated from a plant drug used in Chinese medicine, was achieved from the carbinol (12, n=2). Dehydrogenation of the dicarboxaldehyde (14, n=3) with DDQ gave the known naphthalene-1,3-dicarboxaldehyde (15). Vilsmeier reaction on the acyclic allyl (16) and homoallyl alcohols (17) gave uvitaldehyde (18) (5-methylisophthalaldehyde), used as a starting material in the synthesis of a naturally occurring alkaloid. In Chapter 5 is narrated an efficient synthesis of some 5-aryl-2(E),4(E)-pentadienals (20) and 7-aryl-2(E),4(E),6(E)-heptatrienals (22). Vilsmeier reaction on the unsaturated secondary alcohols (19) and (21) furnished the di- (20) and trienals (22) in excellent yields. Intermediates for polyenal natural products of fungal origin and analogues of the plant hormone abscisic acid have been synthesized by this route. Extension of this technique for the synthesis of vitamin A via the intermediate (23) obtained by the Vilsmeier reaction route is under exploration. Chapter 6 describes the synthesis of two polycyclic aromatic hydrocarbons (PAH) (29), useful in the study of carcinogenesis. Vilsmeier reaction on the tetralol (24) and on 4-methyl-1-tetralone gave the dihydronaphthaldehydes (25), which on DDQ dehydrogenation afforded the naphthalene-2-carboxaldehydes (26). Grignard reaction with benzylmagnesium bromide on the aldehydes (26) furnished the secondary alcohols (27). Compounds (28) and (29) were converted to 29 by chemical and photolytic methods. Oxidation of 29 (R=CH?) with BTAP (benzyltriethylammonium permanganate) followed by esterification gave the diester (30). Chapter 7 deals with the Vilsmeier reaction on the benzylic alcohols (31) derived from the Reformatsky reaction on the corresponding tetralones. The reaction led to heterocyclic annulation to give compounds (32). A minor variation in the work-up of the Vilsmeier reaction on 29 (R=CH?) gave the expected unsaturated aldehyde (33) which on condensation with diethyl malonate furnished the triester (34), the cyclization of which gave the difunctional dihydrophenanthrene (35).