利用Heck反应合成咖啡酸苯乙酯

doi:10.7503/cjcu20141076

摘要/Abstract

摘要：

以4-溴儿茶酚和丙烯酸苯乙酯为原料, 经过邻二酚羟基的保护、 Heck偶联和脱保护3步反应合成了咖啡酸苯乙酯. 其中, 以乙酰基保护的4-溴儿茶酚在优化的Heck反应条件下, 可获得40%收率的咖啡酸苯乙酯. 确定的最佳Heck反应条件为: 混合溶剂甲苯/二甲基甲酰胺的体积比为4∶1, 醋酸钯(0.05 mmol), 三苯基膦(0.15 mmol), 三乙胺(2 mmol), 反应温度90 ℃, 反应时间24 h. 该方法具有通用性好、原料易得和操作相对简单的优点.

关键词: 咖啡酸苯乙酯, 合成, Heck反应

Abstract:

Many caffeic acid ester compounds are known because of their various pharmacological activities, with great commercial values such as medicine, health-care products and functional foods, especially caffeic acid phenethyl esters. Existing synthetic methods for caffeic acid esters, such as “acyl halide”, the alkylation, catalytic esterification, condensation agent method, Wittig reaction and Knoevenagel condensation, present certain limitation for their wide use. This research aims to explore a synthetic method with versatile conditions for caffeic acid esters by Heck reaction using commercially available materials. A total of three steps were operated to synthesize caffeic acid phenethyl ester(CAPE) protecting reaction, Heck reaction and de-protecting reaction, with 4-bromocatechol and acrylic acid phenethyl alcohol ester as starting materials. CAPE was obtained in a moderate yield of 40% under the optimized conditions of Heck reaction, which were V(Toluene)∶V(DMF)=4∶1, Pd(OAc)₂(0.05 mmol), Ph₃P(0.15 mmol), NEt₃(2 mmol), reaction temperature of 90 ℃ and reaction time of 24 h. Compared with the exising synthestic methods, the new method of constructing caffeic acid ester by Heck reaction developed in this work had advantages of versatile conditions, commercially available materials and simple synthetic steps.

Key words: Caffeic acid phenethyl ester, Synthesis, Heck reaction

中图分类号:

O621.3

TrendMD:

杨凤志, 张曼, 谢谨, 谢东升, 傅磊. 利用Heck反应合成咖啡酸苯乙酯. 高等学校化学学报, 2015, 36(5): 914.

YANG Fengzhi, ZHANG Man, XIE Jin, XIE Dongsheng, FU Lei. Synthetic Method of Caffeic Acid Phenethyl Ester by Heck Reaction^†. Chem. J. Chinese Universities, 2015, 36(5): 914.

图/表 4

参考文献 25

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Protecting group	Protection yield(%)	Heck reaction yield^*(%)	De-protection yield(%)	Total yield(%)
—COOC(CH₃)₃	84	22	85	16
—COCH₃	96	26	94	23
—CH₃	100	82	≤20	≤16
—CH₂—	70	79	≤20	≤11

Protecting group	Protection yield(%)	Heck reaction yield^*(%)	De-protection yield(%)	Total yield(%)
—COOC(CH₃)₃	84	22	85	16
—COCH₃	96	26	94	23
—CH₃	100	82	≤20	≤16
—CH₂—	70	79	≤20	≤11

Entry	Solvent	Temperature/℃	Time/h	Conversion(%)	Yield(%)
Entry	Solvent	Temperature/℃	Time/h	Conversion(%)	CAPE	4-Br catechol	Others
1	DMF	100	3	100	26	58	16
2	1,4-Dioxane	Reflux	12	94	9	37	48
3	ACN	Reflux	12	87	12	45	30
4	Toluene	Reflux	24	30	18	Race	12
5	Xylene	Reflux	24	36	21	Race	15
6	V(Toluene)∶V(DMF)=4∶1	Reflux	24	92	39	41	12
7	V(Toluene)∶V(DMF)=4∶1	90	24	81	44	28	9
8	V(Toluene)∶V(DMF)=4∶1	70	24	24	6	14	4

Entry	Solvent	Temperature/℃	Time/h	Conversion(%)	Yield(%)
Entry	Solvent	Temperature/℃	Time/h	Conversion(%)	CAPE	4-Br catechol	Others
1	DMF	100	3	100	26	58	16
2	1,4-Dioxane	Reflux	12	94	9	37	48
3	ACN	Reflux	12	87	12	45	30
4	Toluene	Reflux	24	30	18	Race	12
5	Xylene	Reflux	24	36	21	Race	15
6	V(Toluene)∶V(DMF)=4∶1	Reflux	24	92	39	41	12
7	V(Toluene)∶V(DMF)=4∶1	90	24	81	44	28	9
8	V(Toluene)∶V(DMF)=4∶1	70	24	24	6	14	4

Entry	Product	Heck reaction yield(%)	De-protection yield(%)	Total yield(%)	m.p./℃(ref.)
1		44	94	40	128—130(126—128^[19])
	(5)
2		42	93	37	122—124(121—122^[25])
3		23	79	17	151—153(150—152^[19])
4		41	75	29	144—147(147—148^[19])
5		38	95	35	152—154(150—151^[19])
6		26	87	22	133—135(132—133^[19] )