Eiichi Masumoto

A CONVENIENT APPROACH TO THE SYNTHESIS OF FURO- AND THIENO-[3,2-c]PYRIDINE DERIVATIVES

The title compounds were prepared from 4,5-dihydro-3-furan- and -3-thiophene-carbonitriles having an active methylene group at C-2 position 1, 2, 7, and 8 as key starting materials. Compounds 1 and 2 condensed with N,N-dimethylformamide dimethyl acetal to give the corresponding enamines 3 and 4. This condensation was followed by exchange reaction of amines and subsequent intramolecular cyclization reaction in the presence of ammonium acetate to lead the corresponding furo- and thieno-[3,2-c]pyridines 5 and 6. On the other hand, the reactions of compounds 7 and 8 with amines such as aqueous ammonium hydroxide and benzylamine afforded the intermediate acetamide derivatives A, without isolation of them, which underwent intramolecular cyclization reaction in the presence of sodium methoxide to yield the corresponding furo- and thieno-[3,2-c]pyridin-6(2H)-ones 9-12.

A simple approach to the synthesis of furofurans and furopyrroles using 3-phenacylated tetrahydro-2-imino-3-furancarbonitriles

A new and easy synthetic route to furo[2,3-b]furans 7a-d and furo[2,3-b]pyrroles 8a-d has been achieved by the C-phenacylation/cyclization reactions of 2-amino-4,5-dihydro-3-furancarbonitrile (5). Thermal treatment of the key intermediate 3-phenacylated tetrahydro-2-imino-3-furancarbonitriles 6a-d, which were prepared from compound 5 and phenacyl bromides, e.g. phenacyl bromide, 4-chlorophenacyl bromide, 4-methylphenacyl bromide and 4-methoxyphenacyl bromide, with acetic anhydride caused intramolecular cyclization to yield the corresponding furo[2,3-b]furans 7a-d. On the other hand, methanolic sodium methoxide-assisted cyclocondensation of compounds 6a-d gave the corresponding furo[2,3-b]pyrroles 8a-d.

Synthesis of fused thiopyranthione and thiophene derivatives from 4,5-dihydro-3-thiophene(and -3-furan)-carbonitriles having an active methylene group at C-2 position

A versatile strategy is described for the synthesis of new fused thiopyranthione and thiophene derivatives. The reaction of heterocyclic α,β-unsaturated nitriles 3a-c, 4a-d, 5a-c, and 6a-d, which were prepared from tetrahydro-2-oxo-3-thiophene- and -3-furan-carbonitriles 1a-c and/or 2a-d and alkylidene phosphoranes such as (triphenylphosphoranylidene)acetonitrile and methyl (triphenylphosphoranylidene)acetate through Wittig reaction, with carbon disulfide in the presence of sodium hydride in THF gave the corresponding 6-thioxothieno[3,2-c]thiopyran and 6-thioxothiopyrano[4,3-b]furan derivatives 7a-c, 8a-d, 9a-c, and 10a-d. On the other hand, treatment of compounds 3a-c, 5a-c, and 6a-d with sulfur powder in the presence of triethylamine in methanol caused Gewald reaction to provide the corresponding thieno[3,4-b]thiophene and - furan derivatives 11a-c,12a-c, and 13a-d.

SYNTHESIS OF DIHYDROINDOLES AND TETRAHYDROQUINOLINES BY THE INTRAMOLECULAR DIELS-ALDER REACTION OF N-ALKENYLATED 2-ACYLAMINO-3-FURANCARBONITRILES

An approach to dihydroindoles and tetrahydroquinolines from N-alkenylated 2-acylamino-3-furancarbonitriles via a [4 + 2] cycloaddition reaction is described. Thermal treatment of N-alkenylated 2-acylamino-3-furancarbonitriles 5a-d, 6a-d, 9a-d, and 10a-d, which were prepared from 2-acylamino-3-furancarbonitriles 3a-d and/or 4a-d and 4-bromo-1-butene and/or 5-bromo-1-pentene, caused an intramolecular Diels-Alder reaction to give the corresponding dihydroindole and tetrahydroquinoline derivatives 7a-d, 8a-d, 11a-d, and 12a-d. This method has the advantage of easier work-up procedure.