1-Formyl-7-isopropyl-4-methylazulene (4) has been synthesized by DDQ oxidation method of 1-methyl group of guaiazulene (1). The overall synthetic procedures from 1 to 4 were completed within 2 h, and almost quantitative yield was achieved. The compound (4) was inaccessible so far, because of a poor yield of 4 in its total synthesis (<5%, overall), as well as in its preparation by non-selective oxidation of 1 (<1%).

Azulene analogs of biological active amines were synthesized. Reaction of azulene or guaiazulene with 1-butanoylaziridine or with 1-butanoyl-2-methylaziridine in the presence of Lewis acid catalyst formed the corresponding N-butanoyl-1-(1-azulenyl)-, N-butanoyl-2-(1-azulenyl)-, and N-butanoyl-2-(1-guaiazulenyl) derivatives of ethanamine, or 1-propanamine, or of 2-propanamine, respectively (5–9). Reaction of guaiazulene with 2-methyl-, or 1,1-dimethylaziridinium, or with 1,1,2,2-tetramethylaziridinium ions gave the corresponding 1-(1-guaiazulenyl)- and 2-(1-guaiazulenyl) derivatives of ethanamine, or 1-propanamine, or of 2-propanamine. 2-(1-Azulenyl)- and 2-(4,6,8-trimethyl-1-azulenyl) derivatives of ethanamine were also obtained by the action of 1,1-diethylaziridinium ion on azulene or on 4,6,8-trimethylazulene. Compounds 5, 6, and 9 were active in vitro in the inhibition of prostaglandin 15-hydroxydehydrogenase and of cyclic AMP-phosphodiesterase.

The title compound has been prepared from 2,6-dimethyl-3,5-nonamethylenepyrylium perchlorate and from 1,2,6-trimethyl-3,5-nonamethylenepyridinium iodide in low yield by reaction with sodium cyclopentadienide. The UV, visible and PMR spectra of the title compound are correlated with the structure.

2-(4-Azulenyl)ethanamine derivatives, nonbenzenoid analogs of the biologically active amine, were synthesized by the action of methyleneammonium salts on sodium 4-methylazulenide, sodium 4,6,8-trimethylazulenide, and sodium guaiazulenide. These compounds, as well as their hydrochlorides, were characterized by UV, IR, 1H NMR, 13C NMR, and MS data. The reaction of sodium guaiazulenide and N-ethylidenemethylamine also yielded the corresponding 2-(4-azulenyl)ethanamine derivatives, but the low yield of the product showed that the electrophilicity of azomethine carbon atom to 4-methylene carbanion was insufficient. The enzyme activity for some of those products was investigated. Negligible effect was found on prostaglandin 15-hydroxydehydrogenase, and considerable inhibition to cyclic AMP-phosphodiesterase, in vitro.

When 3-acetylguaiazulene was heated with sulfur at 200°C, three new azulenoids were obtained, in addition to the S-guaiazulene formed by the loss of the acetyl group; the structures were established as 2-acetylguaiazulene, 6-acetyl-, and 7-acetyl-3,5,8-trimethylazuleno [6,5-b] thiophenes. From the experimental results it became obvious that a sulfur atom linked one methyl carbon atom of the isopropyl group with the C6-azulene-ring carbon atom in 3-acetylguaiazulene, resulting in the formation of a thiophene ring, and also that the loss and the migration of the acetyl group took place in 3-acetylguaiazulene as well. The acetyl migration in this compound was ascertained to be a simple thermal reaction and to occur in one direction, from C3 to C2.