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Facile Synthesis of Benzocyclohepta[1,2‐ c ]pyrazoles Starting from Morita–Baylis–Hillman Adducts Via an Intramolecular Friedel‐Crafts Alkenylation
Author(s) -
Yu Jin,
Lee Sangku,
Moon Hye Ran,
Kim Jae Nyoung
Publication year - 2015
Publication title -
bulletin of the korean chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.237
H-Index - 59
ISSN - 1229-5949
DOI - 10.1002/bkcs.10337
Subject(s) - intramolecular force , friedel–crafts reaction , adduct , chemistry , morita therapy , stereochemistry , organic chemistry , combinatorial chemistry , medicinal chemistry , mathematics , catalysis , pure mathematics
Recently, we reported the synthesis of 1H-benzo[g]indazoles via a sequential propargyl-allenyl isomerization and 6πelectrocyclization protocol of the pyrazole 2a, as shown in Scheme 1. We also observed that an intramolecular Friedel-Crafts (IMFC) alkenylation of the pyrazole 2a could produce benzocyclohepta[1,2-c]pyrazole 3a in the presence of H2SO4 via the vinyl cation intermediate I. 1 The pyrazole 2a, bearing an arylpropargyl moiety at position 4, was prepared from Morita–Baylis–Hillman (MBH) adduct by sequential bromination, introduction of arylpropargyl moiety to formα,β-enone1a, and a one-pot synthesis of pyrazole2a by the reaction of 1a and phenylhydrazine. Various benzocyclohepta[1,2-c]pyrazole derivatives have been known as canabinoid-1 (CB1) antagonists, and most of the syntheses of these compounds used benzosuberones (benzocycloheptanones) as starting materials. To the best of our knowledge, the construction of seven-membered ring of benzocyclohepta[1,2-c]pyrazole by IMFC approach has not been reported. Thus, we decided to examine the synthesis of benzocyclohepta[1,2-c]pyrazoles from 4-phenylpropargyl-5-arylpyrazoles by IMFC approach under various conditions. Initially, we examined the feasibility for the synthesis of 3a from 2a under various conditions as summarized in Table 1. The use of p-TsOH, FeCl3, 6d,g,7c InCl3, 7a or InBr3 7a