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Access to Variously Substituted 5,6,7,8‐Tetrahydro‐3 H ‐quinazolin‐4‐ones via Diels–Alder Adducts of Phenyl Vinyl Sulfone to Cyclobutene‐Annelated Pyrimidinones
Author(s) -
Dalai Suryakanta,
Belov Vladimir N.,
Nizamov Shamil,
Rauch Karsten,
Finsinger Dirk,
de Meijere Armin
Publication year - 2006
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200600060
Subject(s) - chemistry , cyclobutene , regioselectivity , deprotonation , cycloaddition , medicinal chemistry , nucleophile , michael reaction , nucleophilic substitution , ring (chemistry) , organic chemistry , catalysis , ion
Under basic conditions (Et 3 N, dioxane), the aromatic amidines 4 and also S ‐methylisothiourea 4g cleanly undergo Michael addition to methyl 2‐chloro‐2‐cyclopropylideneacetate ( 5 ), followed by intramolecular nucleophilic substitution, cyclopropyl to cyclobutyl ring enlargement, deprotonation and cyclization with elimination of methanol to afford the cyclobutene‐annelated pyrimidinones 6 in 43–83 % yield (7 examples). Thermal cyclobutene‐ring opening of the latter at 175 °C followed by regioselective Diels–Alder cycloaddition with phenyl vinyl sulfone gives the 2‐aryl‐6‐(phenylsulfonyl)‐5,6,7,8‐tetrahydroquinazolinone derivatives 12 in 39–83 % yield (7 examples). Base‐induced elimination of benzenesulfinic acid and subsequent catalytic hydrogenation leads to the 2‐aryltetrahydroquinazolinone derivatives 14 in excellent yields (6 examples). Deprotonation at the sulfonyl‐substituted center, alkylation and subsequent elimination of benzenesulfinic acid followed by catalytic hydrogenation gives the 2,6‐disubstituted tetrahydroquinazolinones 17a ‐R. Nucleophilic substitution of the methylthio group in 12g by secondary amines yields the 2‐(dialkylamino)tetrahydroquinazolinones 14i – k .(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)