Synthesis and Properties of 1,3-Disubstituted Ureas Containing (Adamantan-1-yl)(phenyl)methyl Fragment Based on One-Pot Direct Adamantane Moiety Inclusion
Vladimir D’yachenko,
Dmitry Danilov,
Yaroslav Kuznetsov,
Semyon Moiseev,
Vladimir Mokhov,
Vladimir Burmistrov,
Gennady Butov
Affiliations
Vladimir D’yachenko
Department of Technology of Organic and Petrochemical Synthesis, Volgograd State Technical University (VSTU), 28 Lenin Avenue, Volgograd 400005, Russia
Dmitry Danilov
Department of Technology of Organic and Petrochemical Synthesis, Volgograd State Technical University (VSTU), 28 Lenin Avenue, Volgograd 400005, Russia
Yaroslav Kuznetsov
Department of Technology of Organic and Petrochemical Synthesis, Volgograd State Technical University (VSTU), 28 Lenin Avenue, Volgograd 400005, Russia
Semyon Moiseev
Volzhsky Polytechnic Institute (Branch), Volgograd State Technical University (VSTU), 42a Engels Street, Volzhsky 404121, Russia
Vladimir Mokhov
Department of Technology of Organic and Petrochemical Synthesis, Volgograd State Technical University (VSTU), 28 Lenin Avenue, Volgograd 400005, Russia
Vladimir Burmistrov
Department of Technology of Organic and Petrochemical Synthesis, Volgograd State Technical University (VSTU), 28 Lenin Avenue, Volgograd 400005, Russia
Gennady Butov
Department of Technology of Organic and Petrochemical Synthesis, Volgograd State Technical University (VSTU), 28 Lenin Avenue, Volgograd 400005, Russia
A one-stage method for the preparation of 1-[isocyanato(phenyl)methyl]adamantane containing a phenylmethylene fragment located between the adamantane fragment and the isocyanate group, and 1-[isocyanato(phenyl)methyl]-3,5-dimethyladamantane with additional methyl groups at the nodal positions of adamantane, with a yield of 95% and 89%, respectively, is described. The method includes the direct inclusion of an adamantane moiety through the reaction of phenylacetic acid ethyl ester with 1,3-dehydroadamantane or 3,5-dimethyl-1,3-dehydroadamantane followed by the hydrolysis of the obtained esters. The reaction of 1-[isocyanato(phenyl)methyl]adamantane with fluorine(chlorine)-containing anilines gave a series of 1,3-disubstituted ureas with 25–85% yield. 1-[Isocyanato(phenyl)methyl]-3,5-dimethyladamantane was involved in the reactions with fluorine(chlorine)-containing anilines and trans-4-amino-(cyclohexyloxy)benzoic acid to obtain another series of ureas with a yield of 29–74%. The resulting 1,3-disubstituted ureas are promising inhibitors of the human soluble epoxide hydrolase (hsEH).
