Synthesis and characterization of (1 ' S)-3-(1 ',2 '-O-isopropylidenedioxyethyl)-5,5-dimethyl-4,5-dihydro-1,2-oxazole and its isoxazolidine-3-carbonitrile derivatives

摘要

In this study, a new chiral isoxazoline, namely, (1'S)-3- (1',2'-O-isopropylidenedioxyethyl)-5,5-dimethyl-4,5-dihydro-1,2-oxazole and (3RS,1'S)-3- (1 ',2'-O-isopropylidenedioxyethyl)-2,5,5-trimethyltetrahydro-1,2-oxazole-3-carbonitrile were successfully synthesized and characterized by FT-IR, 1(H) NMR, C-13 NMR, DEPT, H,H- and C,H-COSY, and HRMS. The preparation of (1'S)-3- (1',2'-O-isopropylidenedioxyethyl)-5,5-dimethyl-4,5-dihydro-1,2-oxazole was achieved by 1,3-dipolar cycloaddition reaction between the nitrile oxide, obtained in situ from 2,3-O-isopropylidenedioxyethyl-D-glycerohydroximoyl chloride, and isobutene in ether at 0 degrees C. The absolute configuration is determined and the chirality at the 1'-position (C6) is S. Derivative (3RS,1'S)-3- (1',2'-O-isopropylidenedioxyethyl)-2,5,5-trimethyltetrahydro-1,2-oxazole-3-carbonitrile was obtained by the reaction of (1'S)-3- (1',2'-O-isopropylidenedioxyethyl)-5,5-dimethyl-4,5-dihydro-1,2-oxazole with Meerwein's salt (Me3OBF4) followed by sodium cyanide in a stereoselective manner with the chirality at the 3 and 1'-positions (C1 and C8, respectively) being S. In an effort to complete the chemical structure description of the synthetized compounds, crystal structure determination of (1'S)-3- (1',2'-O-isopropylidenedioxyethyl)-5,5-dimethyl-4,5-dihydro-1,2-oxazole and the minor derivative (3R,1'S)-3- (1',2'-O-isopropylidenedioxyethyl)-2,5,5-trimethyltetrahydro-1,2-oxazole-3-carbonitrile was done. The molecular structure of both derivatives consists of two five-membered rings, isoxazole C1/C2/C3-N1/O1 and 4,4-dihydro-1,3-dioxolane C6/C7/C8-O2/O3 in the 1,2-oxazole derivative and isoxazolidine C1/C2/C3-N1/O1 and 1,3-dioxolane C8/C9/C10-O2/O3 in the carbonitrile derivative. The rings adopt envelope conformations with atoms Cl and C6 (in the 1,2-oxazole derivative) and Cl and C8 (in the carbonitrile derivative) at the flap. The crystal packing is stabilized by C-H center dot center dot center dot O (in the 1,2-oxazole derivative) and C-H center dot center dot center dot O/N (in the carbonitrile derivative) interactions to assemble supramolecular arrays of both crystals. Hirshfeld surface analysis revealed that H center dot center dot center dot H (71.1 and 75.8% in 1,2-oxazole derivative and the carbonitrile derivative, respectively) are the most significant interactions, along with additional N center dot center dot center dot H/H center dot center dot center dot N and O center dot center dot center dot H/H center dot center dot center dot O interactions. The energy framework calculations indicate that the both electrostatic and dispersion energy contribute significantly in stabilizing both structures. [GRAPHICS] .