| dc.description.abstract | The thesis, dealing with two topics in two parts, is entitled "Facile Routes to Substituted Di- and Triformylbenzenes (Part I). Synthesis of Pterosin M and Onitin (Part II)". The first part, consisting of five chapters, deals with the Vilsmeier reaction on alkyl-, methoxy-, and carboxy-1,4-cyclohexadienes, 2,4-hexadienoic acids, and cyclohexenones. In each of these chapters, the work done is prefaced by a short account of Vilsmeier reactions known in literature on the relevant or related systems. The second part of the thesis, consisting of one chapter in two sections, describes the synthesis of a C??-monoterpenic acid which serves as a synthon for quassin, and two naturally occurring sesquiterpenoids, pterosin M and onitin, besides a new phenolic analogue of pterosin E.
Chapter 1 deals with the formation of the di- and triformylbenzenes 1–6 obtained on the Vilsmeier reaction of alkyl-substituted 1,4-cyclohexadienes, easily obtainable from suitably substituted aromatic substrates by Birch reduction.
Chapter 2 describes the Vilsmeier reaction on substituted 1-methoxy-1,4-cyclohexadienes, obtained by Birch reduction of the corresponding anisoles, to give di- and triformylbenzenes. The Vilsmeier reaction on the 1-methoxy-1,4-cyclohexadienes derived from o-cresol methyl ether and hydroquinone dimethyl ether afforded aldehydes 11 and 22 and the benzyl chloride 13, indicating some variation in the course of the reaction.
Chapter 3 relates the results of Vilsmeier reaction on substituted 1-carboxy-2,5-cyclohexadienes, obtained by Birch reduction of the corresponding benzoic acids, leading to the di- and triformylbenzenes 14–18. However, 1-carboxy-2,4,6-trimethyl-2,5-cyclohexadiene (19) (1,4-dihydromesitoic acid) gave only the acid chloride and no formylated product. As a direct route for the preparation of polyformylbenzenes, the present methodology appears to be exceptionally convenient.
In Chapter 4 is described a simple benzoannulation of substituted 2,4-hexadienoic acids under Vilsmeier reaction conditions to give 8, 14, 16, and 21–23, the structures of the products obtained depending on the starting dienoic acids.
Chapter 5 is divided into two sections. Section A deals with the polyformylchlorobenzenes 1, 8, and 24, obtained from the Vilsmeier reaction on substituted cyclohexenones. In Section B is described the synthesis of 5-chloro-2,2,4,6-tetramethylindane (29), a potential intermediate for the synthesis of a sesquiterpenic natural product. The known indanone 25, prepared from 2-methylanisole, was converted to the indane 26 by alkylation followed by Wolff-Kishner reduction. Birch reduction of 26 and hydrolysis of the resulting enol ether gave the enone 27. Vilsmeier reaction on the enone gave the chloroformylindane 28 which on reduction furnished 29, a substrate intended for the placement of a two-carbon chain at the halogen-carrying carbon through metallation.
Chapter 6 is also divided into two sections. Section A describes the synthesis of phenolic acids 31 and 32 of biogenetic interest and also synthons for quassin. The 6-position of 2,4-dimethylphenol was protected with t-butyl group to effect chloromethylation at 3-position. Halogen exchange reaction with cyanide gave the benzyl cyanide 30. Acidic hydrolysis of 30 gave the phenolic acid 31. Trans-alkylation of 30 with benzene in the presence of aluminium chloride, followed by basic hydrolysis, also gave the phenolic acid 31. Iodoxybenzene oxidation of the phenolic acid furnished the p-benzoquinone 32. Reductive acetylation of 32 followed by hydrolysis of the resulting diacetate gave 33.
In Section B, the first total syntheses of two naturally occurring sesquiterpenoids, pterosin M (47) (isolated from Onychium japonicum) and onitin (48) (isolated from Onychium auratum) are described. Formylation of the methoxy ester (obtained from 31) with hexamine in trifluoroacetic acid gave the aldehyde 34. On Wittig-Horner reaction with methyl 2-diethylphosphonopropionate, the aldehydo ester 34 gave the diester 36 which was hydrolysed to 37 and reduced to the dihydrodicarboxylic acid 38. Cyclodehydration of 38 to 39 followed by demethylation afforded the indanone carboxylic acid 40, a new phenolic analogue of the naturally occurring pterosin E (41).
Since elaboration of 40 to pterosin M (47) along expected lines could not be completed for paucity of material, a modified approach was adopted. The methoxy ether 42, prepared from the ester 34 by LAH reduction and methylation, was formylated with hexamine in trifluoroacetic acid to give the aldehydo ether 43. The sequence of reactions carried out on the aldehydo ester was repeated on the aldehydo ether 43 till in the end pterosin M (47) was obtained (43 ? 44 ? 45 ? 46 ? 47). Alkylation of the indanone 40 with methyl iodide followed by demethylation afforded onitin (48). | |
