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New Results in the Synthesis of Styrylazulene Derivatives: Application of the ‘Anil synthesis’ to the preparation of azulenes substituted with styryl groups at the seven‐membered ring
Author(s) -
Briquet Anne Andrée Sophie,
Hansen HansJürgen
Publication year - 1994
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19940770722
Subject(s) - chemistry , wittig reaction , toluene , alkylation , phosphonium salt , medicinal chemistry , dehydrogenation , azulene , phosphonium , yield (engineering) , swern oxidation , organic chemistry , salt (chemistry) , catalysis , materials science , metallurgy , dimethyl sulfoxide
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 salt 4b . 4,6,8‐Trimethylazulene‐2‐carbaldehyde ( 12 ) has been synthesized from the corresponding carboxylate 15 by a reduction (LiAlH 4 ) and dehydrogenation (MnO 2 ) 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‐NO 2 C 6 H 4 CH=NC 6 H 5 ( 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 ).