Diastereoselective synthesis of new Thiazolyl-Indazole derivatives from R-carvone: A combined experimental and theoretical study

• DOI: 10.1016/j.tet.2020.131830
• Publication Date: 2020-12-03T02:01:02Z
• Authors: A. N’Ait Ousidi; M.Y. Ait Itto; A. Auhmani; M. Loubidi; A. Riahi; J.-C. Daran; M. Esseffar; Carol A. Parish
• Keywords: [CHIM.ORGA]Chemical Sciences/Organic chemistry; [CHIM]Chemical Sciences; 540; 01 natural sciences; 0104 chemical sciences

Abstract The reaction of (R)-carvone and (R)-pulegone thiosemicarbazones with phenacyl bromide yields two new thiazoles: (R)-2-(2-(5-isopropyl-2-methylcyclohex-2-enylidene) hydrazinyl)-4-phenylthiazole, I and (3aR,6R)-3,3,6-trimethyl-2-(4-phenylthiazol-2-yl)-3,3a,4,5,6,7-hexahydro-2H-indazol-3a-ol, II, respectively. While HRMS and NMR spectroscopic data confirm the expected structure of I, they show that the product from (R)-pulegone undergoes rearrangement and oxidation to give II. The orientation of the OH group in II produces two possible diastereoisomers; (3aR,6R) and (3aS,6R). X-Ray analysis was used to assign the (3aR,6R) configuration to II. Energetic analysis with the M052-X functional with 6-31+G(d,p) basis set showed that the (3aR,6R) is more stable than the (3aS,6R) diatereoisomer by approximately 4.5 kcal/mol. The dimerization of the (3aR,6R) isomer of II was studied computationally via two types of hydrogen bonding interactions: (OH⋯O), as the conventional hydrogen bonding, and the interaction of the OH group with the aromatic ring (OH⋯Ar). We find that these two modes of polymerization are approximately isoenergetic.