NEW RESULTS IN THE SYNTHESIS OF STYRYLAZULENE DERIVATIVES - APPLICATION OF THE ANIL-SYNTHESIS TO THE PREPARATION OF AZULENES SUBSTITUTED WITH STYRYL GROUPS AT THE 7-MEMBERED RING

The synthesis of 4,6,8-trimethyl-1-[(E)-4-R-styryl]azulenes 5 (R=H, MeO, Cl) has been performed by Wittig reaction of 4,6,8-trimethylazulene-1-carbaldehyde (1) and the corresponding 4-(R-benzyl)(triphenyl)phosphonium chlorides 4 in the presence of EtONa/EtOH in boiling toluene (see Table 1). In the same way, guaiazulene-3-carbaldehyde (2) as well as dihydrolactaroviolin (3) yielded with 4a the corresponding styrylazulenes 6 and 7, respectively (see Table 1). It has been found that 1 and 4b yield, in competition to the Wittig reaction, alkylation products, namely 8 and 9, respectively (cf. Scheme 1), The reaction of 4,6,8-trimethylazulene (10) with 4b in toluene showed that azulenes can, indeed, be easily alkylated with the phosphonium sale 4b. 4,6,8-Trimethylazulene-2-carbaldehyde (12) has been synthesized from the corresponding carboxylate 15 by a reduction (LiAIH(4)) and dehydrogenation (MnO2) sequence (see Scheme 2). The Swern oxidation of the intermediate 2-(hydroxymethyl)azulene 16 yielded only 1,3-dichloroazulene derivatives (cf. Scheme 2). The Wittig reaction of 12 with 4a and 4b in the presence of EtONa/EtOH in toluene yielded the expected 2-styryl derivatives 19a and 19b, respectively (see Scheme 3). Again, the yield of 19b was reduced by a competing alkylation reaction of 19b with 4b which led to the formation of the 1-benzylated product 20 (see Scheme 3). The 'anil synthesis' of guaiazulene (21) and the 4-R-benzanils 22 (R=H, MeO, Cl, Me(2)N) proceeded smoothyl under standard conditions (powered KOH in DMF) to yield the corresponding 4-[(E)-styryl]azulene derivatives 23 (see Table 4). In minor amounts, bis(azulen-4-yl) compounds of type 24 and 25 were also formed (see Table 4). The 'anil reaction' of 21 and 4-NO2C6H4CH=NC6H5 (22e) in DMF yielded no corresponding styrylazulene derivative 23e. Instead, (E)-1,2-bis(7-isopropyl-1-methylazulen-4-yl)ethene (27) was formed (see Scheme 4). The reaction of 4,6,8-trimethylazulene (10) and benzanil (22a) in the presence of KOH in DMF yielded the benzanil adducts 28 to 31 (cf. Scheme 5). Their direct base-catalyzed transformation into the corresponding styryl-substituted azulenes could not be realized (cf. Scheme 6). However, the transformation succeeded smoothly with KOH in boiling EtOH after N-methylation (cf. Scheme 6).