Studies in sesquiterpenes

Abstract

Sesquiterpenes of the Azulene Type It has long been known that some plants yield blue-coloured essential oils. The blue colour of chamomile oil was first observed in the fifteenth century. In 1923, Ruzicka, Pontalti and Balas found that, in general, the development of a blue colour in some essential oils may be induced by dehydrogenation. Sherndal was the first to isolate the substance responsible for the blue colour and found it to be a compound for which he retained the name azulene, first given by Piesse. The more important azulenes are:

Guaiazulene, present in geranium oil, and obtained by sulphur dehydrogenation of sesquiterpene or sesquiterpene alcohol fractions of the oil from guaiacum wood, Callistus, patchouli, gurjun balsam, and Eucalyptus globulus.

Chamazulene, isolated from chamomile and yarrow oils.

Lactarazulene, recently obtained from the fungus Lactarius deliciosus L.

Vetivazulene, obtained by dehydrogenation of vetivert oil.

Elemazulene, formerly considered a new azulene obtained by selenium dehydrogenation of elemol, but now shown to be identical with vetivazulene.

The Sherndal method for isolating azulenes using phosphoric acid has been widely used. Azulenes are characterised as addition compounds with polynitro compounds like T.N.T. Pure azulene is best obtained by passing a solution of the T.N.B. complex down a column of alumina.

Structure of Azulene The physical constants of the octa? and deca?hydro derivatives are very similar for the different azulenes. It is evident from the molecular refraction values that in all cases we are dealing with bicyclic structures. There was the possibility that the differences between individual azulenes merely consisted in the distribution of the double bonds. However, octahydro? and decahydro?guaiazulene as well as decahydro?chamazulene regenerate the original guaiazulene and chamazulene upon dehydrogenation. The five double bonds must be confined to twelve of the fifteen carbon atoms since Ruzicka and co-workers found isobutyric acid among the oxidation products. In an effort to correctly distribute the five double bonds over the molecule, several formulae were proposed. The most probable were those containing a fulvene ring system, accounting for the light extinction in the orange region of the visible spectrum. Investigations on a natural precursor of the azulenes, the sesquiterpene alcohol guaiol, by Semmler and Mayer, showed that it contains a bicyclic structure with one double bond and a tertiary hydroxyl group. Upon oxidation with permanganate or ozone, a crystalline compound was obtained which was thought to be a trihydroxy derivative. After dehydrogenation, a compound of formula C??H??O? was isolated. Since further oxidation experiments on guaiol did not prove promising, Pfau and Plattner turned their attention to the conversion of guaiol to naphthalene derivatives. Dehydrogenation with sulphur or heating with formic acid was unsuccessful, but treatment with phosphorus and hydriodic acid resulted in the production of 1,4?dimethyl?6?isopropylnaphthalene. In a similar way, vetivone furnished 1,5?dimethyl?7?isopropylnaphthalene. The oxidation of both guaiol and vetivone followed by ring closure and catalytic dehydrogenation yielded phenols. Since one ring carbon atom was lost during the opening and closing of the ring, it was concluded that the starting materials contained a seven?membered ring system. The phenol obtained from vetivone was shown by synthesis to be identical with 2?isopropyl?4,7?dimethylindan?1?ol. The isomerisation of azulene to a naphthalene derivative was then formulated as a retro?pinacol rearrangement, as indicated in the skeletal formulas (I) and (II) for guaiol.