3-(3,4-亚甲基二氧苯基)-5-苯基异噁唑啉的合成

摘要以3,4-亚甲基二氧苯甲醛为起始原料,经缩合、氯化和1,3-偶极环加成三步反应合成3-(3,4-亚甲基二氧苯基)-5-苯基异噁唑啉(3),其中第一、二步反应分别得到相应的肟(1)和氯代肟(2),第三步经氯代肟与三乙胺反应生成的腈氧化合物再与苯乙烯发生1,3-偶极环加成生成异噁唑啉。研究了三乙胺的用量和反应温度对反应的影响,在较好条件下,以氯代肟为基准,第三步1,3-偶极环加成得3-(3,4-亚甲基二氧苯基)-5-苯基异噁唑啉(3)的收率为92%。

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关键词： 1,3-偶极环加成; 肟; 氯代肟; 3-(3,4-亚甲基二氧苯基)-5-苯基异噁唑啉

Abstract： In order to synthesize 3-(3,4-methylenedioxyphenyl)-5-phenyl-2-isoxazoline (3), a three-step synthetic procedure was developed, which involved condensation, chlorination and 1,3-dipolar cycloaddition. In the first two steps, the oxime (1) and hydroximoyl chloride (2) were synthesized from heliotropin. In the presence of triethylamine (Et₃N), a series of hydroximoyl chloride was transformed into nitrile oxide, followed by reacting with styrene via 1,3-dipolar cycloaddition to afford (3). Dosage of Et₃N and temperature of reaction were optimized. Under the optimized conditions, the yield of (3) is 92%.

Keywords： 1,3-dipolar cycloaddition; oxime; hydroximoyl chloride; 3-(3,4-methylenedioxyphenyl)-5-pheny;l-2-isoxazoline

Received 2013-04-01;

Corresponding Authors: 唐向阳,电话:(022)27404615,E-mail:txy@tju.edu.cn。 Email: txy@tju.edu.cn

About author: 龚(1989-),女,硕士研究生,现从事有机合成方面的研究。

引用本文:

龚, 唐向阳, 齐欣, 闫春丽.3-(3,4-亚甲基二氧苯基)-5-苯基异噁唑啉的合成[J]. 化学工业与工程, 2015,32(1): 17-20

Gong Yan, Tang Xiangyang, Qi Xin, Yan Chunli.Synthesis of 3-(3,4-Methylenedioxyphenyl)-5-Phenyl-2-Isoxazoline[J]. Chemcial Industry and Engineering, 2015,32(1): 17-20

[1]	Talley J J, Brown D L, Carter J S, et al. 4-[5-Methyl-3-phenylisoxazol-4-yl]-benzenesulfonamide, Valdecoxib: A potent and selective inhibitor of COX-2 [J].Journal of Medicinal Chemistry.2000, 43:775-777
[2]	Wityak J, Sielecki T M, Pinto D J, et al. Discovery of potent isoxazoline glycoprotein IIb/IIIa receptor antagonists[J].Journal of Medicinal Chemistry.1997, 40:50-60
[3]	Simoni D, Roberti M, Invidiata F P, et al. Heterocycle-Containing retinoids. Discovery of a novel isoxazole arotinoid possessing potent apoptotic activity in multidrug and drug-induced apoptosis-resistant cells [J]. Journal of Medicinal Chemistry, 2001, 44: 2 308-2 318
[4]	James E J, John R S, Jui S H, et al. Alkylation of benzohydroxamic acid[J].Journal of Organic Chemistry.1971, 36(2):284-288
[5]	Cheng C, Li Z, Shu J, et al. Synthesis of isoxazolidines by 1,3-dipolar cycloaddition and their bioactivity[J].Frontiers of Chemistry in China.2006, 1:427-433
[6]	Tian L, Xu G, Liu L, et al. 1,3-Dipolar cycloaddition reactions of nitrile oxides to prop-1-ene-1,3-sultone[J].Journal of Hetero cyclic Chemistry.2003, 40:1-
[7]	Ye Y, Zheng Y, Xu G, et al. Reaction of nitrile oxides with vinylphosphonate: A facile, regioselective approach to 5-phosphonyl-4,5-dihydroisoxazoles[J].Heteroatom Chemistry.2003, 14:254-257
[8]	Liu K C, Shelton B R, Howe R K A. Particularly convenient preparation of benzohydroximinoyl chlorides (nitrile oxide precursors) [J]. Journal of Organic Chemistry, 1980, 45: 3 916-3 918
[9]	Howe R K, Schleppnik F M. Nitrile oxide cycloaddition routes to 2-(isoxazolyl)-benzoates and 2-(1,2,4-oxadiazol-3-yl)benzoates[J].Journal of Heterocyclic Chemistry.1982, 19:721-726
[10]	Kaffy J, Monneret C, Mailliet P, et al. 1,3-Dipolar cycloaddition route to novel isoxazole-type derivatives related to combretastatin A-4 [J]. Tetrahedron Letters, 2004, 45: 3 359-3 362
[11]	Auricchio S, Ricca A, Battista G R, et al. New aspects of nitrile oxides chemistry [J].Tetrahedron Letters.1993, 34:4363-4364