Preparation of Spiro[Benzopyran-Isoxazoles] from the Condensation–Cyclization of Oxime 1,4-Dianions with Select Coumarins

• Published in: Journal of chemical crystallography 2014-08, Vol.44 (8), p.401-406
• Main Authors: Metz, Clyde R., Radke, Jennifer L., Shuler, William G., Celli, Marco Gattoni, McMillen, Colin D., Pennington, William T., Beam, Charles F.
• Format: Article
• Language: English
• Subjects: Chemistry; Chemistry and Materials Science; Crystallography and Scattering Methods; Inorganic Chemistry; Organometallic Chemistry; Original Paper; Physical Chemistry
• ISSN: 1074-1542; 1572-8854
• DOI: 10.1007/s10870-014-0529-z

A representative spiro[benzopyran-isoxazole], 3′-(3,4-dimethoxyphenyl)- N,N -diethyl-4-methyl-4′ H -spiro[2 H -1-benzopyran-2,5′-isoxazol]-7-amine 3a , was submitted for single crystal X-ray analysis. It has been prepared by the condensation–cyclization of dilithiated C(α), O -3′,4′-dimethoxyacetophenone oxime with a substituted coumarin, 7-(diethylamino)-4-methyl-2 H -1-benzopyran-2-one. This results from the 1,2-carbonyl addition, Claisen type, of the dilithiated oxime with this coumarin ester carbonyl to afford C -acylated intermediates that were not isolated, but were acid cyclized to the spiro[benzopyran-isoxazoles], a new spiro heterocyclic system. There was no evidence for Michael-type 1,4-addition found during this initial investigation. An indication that the experimental multiple anion procedure is general, has been the preparation of two additional spiro(benzopyran-isoxazoles) 3b and 3c . Crystals of C 24 H 28 N 2 O 4 3a are triclinic, p 1 ¯ , a  = 9.161(2) Å, b  = 9.716(2) Å, c  = 12.869(3) Å, α = 75.84(3)°, β = 81.03(3)°, γ = 73.96(3)°, Z  = 2, V  = 1062.5(4) Å 3 , R 1  = 0.0539 and wR 2  = 0.1366 for reflections with I  > 2σ( I ). Graphical Abstract X-ray crystal analysis confirmed the structure of 3′-(3,4-dimethoxyphenyl)- N , N -diethyl-4-methyl-4′ H -spiro(2 H -1-benzopyran-2,5′-isoxazol)-7-amine prepared by the condensation–cyclization of dilithiated C(α), O -3′,4′-dimethoxyacetophenone oxime with a substituted coumarin, 7-(diethylamino)-4-methyl-2 H -1-benzopyran-2-one.