The new title compound, chiral 2-(3-methyl-2,3-dihydrobenzo[b][1,4]oxazin-4-yl)- 2-oxoethyl acetate, has been synthesized via reduction, cyclization and acylation reaction. The structure of the product has been confirmed by IR, 1H NMR, 13C NMR, LC-MS (ESI) and single-crystal X-ray diffraction. (R)-2-(3-methyl-2,3-dihydrobenzo[b][1,4]oxazin-4-yl)-2-oxoethyl acetate crystallizes in monoclinic, space group P21/c with a = 11.867(2), b = 8.4087(2), c = 14.325(6) Å, β = 117.59(2)º, Z = 4, V = 1266.9(6) Å3, Dc = 1.307 g/cm3, F(000) = 528, µ(MoKα) = 0.097 mm-1, R = 0.0453 and wR = 0.1237; (S)-2-(3-methyl-2,3-dihydrobenzo[b][1,4]oxazin-4-yl)-2-oxoethyl acetate belongs to the triclinic system, space group P with a = 8.2647(17), b = 8.7034(17), c = 9.5479(19) Å, α = 105.33(3), β = 100.95(3), γ = 105.14(3)º, Z = 2, V = 614.1(2) Å3, Dc = 1.348 g/cm3, F(000) = 264, µ(MoKα) = 0.10 mm-1, R = 0.0613 and wR = 0.1037. Both of the molecules prefer to form crystal packing through C–H•••O hydrogen bonds.
The new title compound, chiral 2-(3-methyl-2,3-dihydrobenzo[b][1,4]oxazin-4-yl)- 2-oxoethyl acetate, has been synthesized via reduction, cyclization and acylation reaction. The structure of the product has been confirmed by IR, 1H NMR, 13C NMR, LC-MS (ESI) and single-crystal X-ray diffraction. (R)-2-(3-methyl-2,3-dihydrobenzo[b][1,4]oxazin-4-yl)-2-oxoethyl acetate crystallizes in monoclinic, space group P21/c with a = 11.867(2), b = 8.4087(2), c = 14.325(6) Å, β = 117.59(2)º, Z = 4, V = 1266.9(6) Å3, Dc = 1.307 g/cm3, F(000) = 528, µ(MoKα) = 0.097 mm-1, R = 0.0453 and wR = 0.1237; (S)-2-(3-methyl-2,3-dihydrobenzo[b][1,4]oxazin-4-yl)-2-oxoethyl acetate belongs to the triclinic system, space group P with a = 8.2647(17), b = 8.7034(17), c = 9.5479(19) Å, α = 105.33(3), β = 100.95(3), γ = 105.14(3)º, Z = 2, V = 614.1(2) Å3, Dc = 1.348 g/cm3, F(000) = 264, µ(MoKα) = 0.10 mm-1, R = 0.0613 and wR = 0.1037. Both of the molecules prefer to form crystal packing through C–H•••O hydrogen bonds.
This work was supported by the National Natural Science Foundation of China (No. 31572042), Natural Science Foundation of Heilongjiang Province (B201303), and the Research Science Foundation in Technology Innovation of Harbin (No. 2015RAYXJ010)
REFERENCES
(1)Matsumoto, Y.; Tsuzuki, R.; Matsuhisa, A.; Masuda, N.; Yamagiwa, Y.; Yanagisawa, I.; Shibanuma, T.; Nohira, H. Novel potassium channel activators. II. Synthesis and pharmacological evaluation of 3,4-dihydro-2H-1,4-benzoxazine derivatives: modification of the aromatic part. Chem. Pharm. Bull 1999, 47, 971979.
(2) Largeron, M.; Lockart, B.; Pfeiffer, B.; Fleury, M. B. Synthesis and in vitro evaluation of new 8-amino-1,4-benzoxazine derivatives as neuroprotective antioxidants. J. Med. Chem. 1999, 42, 50435052.
(3) Sakami, S.; Kawai, K.; Maeda, M.; Aoki, T.; Fuji, H.; Ohno, H.; Ito, T.; Saitoh, A.; Nakao, K.; Izumimoto, N.; Matsuura, H.; Endo, T.; Ueno, S.; Natsume, K.; Nagase, H. Design and synthesis of a metabolically stable and potent antitussive agent, a novel delta opioid receptor antagonist, TRK-851. Bioorg. Med. Chem. 2008, 16, 79567967.
(4) Prasad, A. K.; Mukherjee, C.; Sharma, D.; Rastogi, S.; Mangalam, A.; Jha, A.; Olsen, C. E.; Patkar, S. A.; Parmar, V. S. Synthesis and lipase-catalyzed resolution studies on novel (±)-2-(2-acetoxyethyl)-4-arylmethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylates. J. Mol. Catal. B-Enzym. 2006, 40, 101110.
(5) Mayer, S.; Arrault, A.; Guillaumet, G.; Mérour, J. Y. Attempted synthesis of ethyl 3,4-dihydro-2H-1,4-benzoxazine-3-carboxylate and 3-acetate derivatives. J. Heterocycl. Chem. 2001, 38, 221225.
(6) Ismailov, V. M.; Mamedov, I. A.; Yusubov, N. N. Condensation of aniline and o-hydroxyaniline with 1,2-dibromoethane. Russ. J. Org Chem. 2004, 40, 284285.
(7) Wolfe, J. F.; Arnold, F. E. Rigid-rod polymers synthesis: synthesis and thermal properties of para-aromatic polymers with 2,6-benzobisoxazole units in the main chain. Macromolecules 1981, 14, 909915.
(8) Yoo, E. S.; Grvrin, A. J.; Farris, R. J.; Coughlin, E. B. Synthesis and characterization of the polyhydroxyamide/ polymethoxyamide family of polymers. High Perform. Polym. 2003, 15, 519535.
(9) Rowe, L; Kells, J. J.; Penner, D. Efficacy and mode of action of CGA-154281, a protectant for corn (zea-mays) from metolachlor injury. Weed Sci. 1991, 39, 7882.
(10) Zhou, Y. G.; Yang, P. Y.; Han, X. W. Synthesis and highly enantioselective hydrogenation of exocyclic enamides: (Z)-3-arylidene-4-acetyl-3,4- dihydro-2H-1,4-benzoxazines. J. Org. Chem. 2005, 70, 16791683.
(11) Gao, S.; Fu, Y.; Zhao, L. X.; Xing, Z. Y.; Ye, F. Synthesis and crystal structure of novel chiral N-dichloroacetyl-2-substitutes-5-methyl-1,3- oxazolidines. Heterocycles 2012, 85, 903910.
(12) Ye, F.; Yang, L.; Li, H. T.; Fu, Y.; Xu, W. J. A convenient synthesis of novel N-dichloroacetyl-1,3-oxazolidine. J. Heterocyclic. Chem. 2010, 47, 229232.
(13) Fu, Y.; Yang L.; Ye, F.; Gao, S. One-pot microwave-assisted synthesis of novel substituted N-dichloroacetyl-4,5-dimethyl-1,3-oxazolidines. J. Heterocycl. Chem. 2012, 49, 12351238.
(14) Bunce, R. A.; Herron, D. M.; Hale, L. Y. Dihydrobenzoxazines and tetrahydroquinoxalines by a tandem reduction-reductive amination reaction. J. Heterocycl. Chem. 2003, 40, 10311039.
(15) Kawase, M.; Kikugawa, Y. Intramolecular cyclization of alkylhydroxylamines in acid. Chem. Pharm. Bull. 1981, 29, 16151623.
(16) Parai, M. K.; Panda, G. A convenient synthesis of chiral amino acid derived 3,4-dihydro-2H-benzo[b][1,4]thiazines and antibiotic levofloxacin. Tetra. Lett. 2009, 50, 47034705.
(17) Gao, K.; Yu, C. B.; Wang, D. S.; Zhou, Y. G. Iridium-catalyzed asymmetric hydrogenation of 3-substituted 2H-1,4-benzoxazines. Adv. Synth. Catal. 2012, 354, 483488.
(18) Baraldi, P. G.; Saponaro, G.; Moorman, A. R.; Romagnoli, R.; Preti, D.; Baraldi, S.; Ruggiero, E.; Varani, E. K.; Targa, M. ; Vincenzi, F.; Borea, P. A.; Tabrizi, M. A. 7-Oxo-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamides as selective CB2 cannabinoid receptor ligands: structural investigations around a novel class of full agonists. J. Med. Chem. 2012, 55, 66086623.
(19) Fu, Y.; Qu, L. H.; Zhang, S. S.; Ye, F.; Zhao, L. X.; Gao, S.; Xing, Z. Y. Simple and efficient synthesis of novel N-dichloroacetyl-3,4-dihydro- 2H-1,4-benzoxazines. Heterocycl. Commun. 2012, 18, 143146.
(20) Fu, Y.; Wang, J.; Zhao, Q. S.; Wang, X. M.; Xing, Z. Y.; Ye, F. Synthesis, crystal structure and biological activity of N-dichloroacetyl-3,4-dihydro-3- methyl-2H-1,4-benzoxazines. Indian J. Heterocycl. Chem. 2014, 24, 4146.
(21) Sheldrick, G. M. SHELXS-97, Program for X-ray Crystal Structure Solution. University of Göttingen, Germany 1997.
(22) Sheldrick, G. M. SHELXL-97, Program for X-ray Crystal Structure Solution. University of Göttingen, Germany 1997.
2016, Vol. 35 
