Synthetic investigations on Azulenes

Abstract

At present a variety of methods for the synthesis of azulenes are available. These can be divided under three main heads: I. Methods involving a change in ring size II. Methods by which a 7-membered ring is built on a cyclopentane system III. Methods wherein a 5-membered ring is fused onto a cycloheptane system

(a) Rearrangement of decalins system to bicyclo[5.3.0]decane system This method is based on the work of Huckel and Schmitz-Spahn, who transformed ?,?-octalin (XII) into cyclopentanocycloheptanone (XIII) by ozonolysis of the octalin followed by a base-catalyzed intramolecular aldol condensation of the resulting cyclodecane-1,6-dione. Previously, Pfau and Plattner utilized the intermediate (XIII) for the synthesis of 4-substituted azulenes. Later, the same group prepared azulene (XIV) from the same starting material. Improved procedures for the preparation of XII, XIII, XIV have been published. The conversion of octalin (XII) to the ketone (XIII) in three steps in an overall yield of 62% has been described.

(b) Ring enlargement of aromatic nucleus in an indane by ethyl diazoacetate This, the most widely employed but rather unusual method, is based on the ring enlargement of aromatic nucleus in an indane by ethyl diazoacetate. The reaction was first discovered by Buchner and applied to azulene synthesis by Plattner. This is illustrated below in the simple case of indane. It is apparent from the above scheme that in the case of substituted indanes, ambiguities as to the final structure of the azulene can arise; this has been well-documented by Gordon D. Approximately fifty azulenes have been synthesized by this reaction; these include mono-, di-, tri-, and tetrasubstituted alkyl azulenes, benzoazulenes, and polymethylene azulenes. A useful variation of the method is the conversion of the carbethoxy group of the addition product (XVI) to the corresponding alcohol by reduction. These procedures have been utilized for the synthesis of isopropyl azulenes and methyl azulenes. The intermediate carboxylic esters (XVI) have been utilized for the synthesis of azulene carboxylic acids. An apparatus useful for the decarboxylative-dehydrogenation of the acids derived from the intermediates (XVI) has been described.

(c) Ring enlargement of the benzene nucleus in an indane by diazomethane This method is based on the work of Doering. Photochemical decomposition of a solution of diazomethane in indane led to the production of a precursor suitable for dehydrogenation to azulene.

(d) Indane ring expansion Arnold was the first to apply the diazomethane ring expansion method for the synthesis of azulenes. In an attempt to prepare 6-methyl azulene, Arnold treated ?-amino-methyl hydrinindane (XVII) with nitrous acid to obtain a mixture of alcohols, from which an azulene was prepared, which later was shown by Plattner, Heilbronner, and Fürst to consist of a mixture of 6-methyl (XVIII) and 4-methyl azulenes (XIX) in the ratio 3:1. Plattner, Fürst, and Lütauer also investigated this method with similar results; these authors prepared (XVII) by a different procedure.

(e) Diazomethane ring expansion of a cyclopentanone-cyclohexanone This procedure, which was first utilized by Coats and Cook in the azulene field for the preparation of vetic azulene (IV), is based on the diazomethane ring expansion method of Doering. However, the yields were very poor. The method has also been utilized for the preparation of 5-methyl azulene (XVIII) and 1-benzazulene.

(f) Trans-annular ring closure in cyclodecane systems Prelog and Schenker have found that when cyclononene (XX) or cyclodecene or cyclododecanol was passed over a palladium catalyst, azulene was obtained and naphthalene was formed as a by-product.

(g) Starting with cyclopentanone carboxylic ester Cyclopentanone carboxylic ester (XXI) is condensed with a suitable bromo-ester to give the required side chain with the carboxyl group at the end; another chain is built up at the site of the carbonyl, and the resulting dicarboxylic acid ultimately obtained is converted into a suberone from which the azulene is prepared. Cerny and Fajkos and Plattner and Lütauer independently synthesized 6-methyl azulene (XIX) by this method.

(h) Arndt-Eistert synthesis The cyclopentane-1,5-diacetic acid (XXIII) synthesis is due to Linstead and Wood; improved procedure for its preparation has been published. The method has been used for the synthesis of 5-acetyl azulene, 4,6-dimethyl azulene, azulene, and 1,7-dimethyl azulene. This method has been recently developed by Czechoslovakian workers and has been successfully employed by them for the synthesis of 5-isopropyl azulene and 1,6-isopropyl azulene.

(i) Plattner synthesis Plattner has described a novel synthesis of azulene in which a tetrahydrofuranic ring is opened up to yield a 1,4-dinitrano fatty acid ester (XXVII), which through Perkin synthesis yielded the suitably constituted cyclopentane dicarboxylic acid (XXIX), from which the required azulene molecule could be elaborated. The method is described below for the synthesis of azulene itself. Azulene, 1-methyl-, 6-methyl-, 6,7-dimethyl-, 5-methyl-isopropyl-, 1,6-dimethyl-, and 1,6,7-trimethyl azulenes have been prepared by this procedure. This is a unique synthesis as it does not involve the step of dehydrogenation in the last phase of the synthesis. The method is based on the surmise that azulene can be regarded as inner given of cyclo-aldehyde (XXX), which implies that azulene.