基于乙酸为溶剂和催化剂的芳乙酮Mannich反应

doi:10.7503/cjcu20131050

摘要/Abstract

摘要：

采用乙酸作溶剂和催化剂, 将芳乙酮与甲醛和二级胺进行Mannich反应及热解反应, 并未得到预期的Mannich碱或α,β-不饱和酮(2), 而是以较高产率(65%~73%)生成了乙酸(2-芳甲酰基)烯丙酯(3a~3o). 通过核磁共振波谱、高分辨质谱和红外光谱表征了化合物3a~3o的结构, 研究了此“异常”反应的发生条件, 并提出了可能的反应机理. 结果表明, 芳乙酮的特殊结构及反应中过量的乙酸是产生化合物3a~3o的决定因素.

关键词: Mannich反应, α, β, -不饱和酮, 乙酸(2-芳甲酰基)烯丙酯, 乙酸

Abstract:

Mannich reaction is one of the most important methods for preparation of β-amino ketones and aldehydes and α,β-unsaturated carbonyl compounds, as well as one of the most important basic reaction types in organic chemistry and it is widely applied as a key step in the synthesis of numerous pharmaceuticals and natural products. However, during the synthesis of 1-aryl acrylic ketone 2 by the Mannich reaction of aromatic ketones, formaldehyde and secondary amine using acetic acid as solvent and catalyst, the Mannich base and expected α,β-unsaturated ketones 2 were not obtained and another kind of compounds 3, 2-aryl formyl allyl acetate were obtained in moderate to good yields(65%—73%). The structure of compounds 3 was confirmed by ¹H NMR, ¹³C NMR, HRMS and IR spectra. The reasons of producing compounds 3 were studied and the results suggested that the special structure of aromatic ketones and excess acetic acid in reaction are responsible for the exceptional Mannich reaction. In addition, the reaction mechanism was postulated.

Key words: Mannich reaction, α, β, -Unsaturated ketone, 2-Aryl formyl allyl acetate, Acetic acid

中图分类号:

O626

TrendMD:

卜辉娟, 张静, 穆博帅, 李媛. 基于乙酸为溶剂和催化剂的芳乙酮Mannich反应. 高等学校化学学报, 2014, 35(9): 1912.

BU Huijuan, ZHANG Jing, MU Boshuai, LI Yuan. Mannich Reaction of Aromatic Ketones Based on Acetic Acid as Solvent and Catalyst^†. Chem. J. Chinese Universities, 2014, 35(9): 1912.

图/表 7

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Ketone	n(Ketone 1)∶n(HCHO)	Amine	n(Ketone 1)∶n(Amine)	Time/h	Product	Yield^b(%)
1a	1∶1.2	Et₂NH	1∶1.0	2	3a	30
1a	1∶1.2	Et₂NH	1∶1.0	4	3a	31
1a	1∶1.5	Et₂NH	1∶1.0	5	3a	43
1a	1∶3.0	Et₂NH	1∶2.0	3	3a	69
1a	1∶6.0	Et₂NH	1∶0.5	4	3a	67
1a	1∶3.0	Morpholine	1∶2.0	4	3a	38
1a	1∶3.0	(i-Pr)₂NH	1∶1.0	4	3a	45
1b	1∶1.3	Et₂NH	1∶1.0	5	3b	35
1b	1∶1.5	Et₂NH	1∶1.5	5	3b	40
1b	1∶3.0	Et₂NH	1∶2.0	3	3b	72

Ketone	n(Ketone 1)∶n(HCHO)	Amine	n(Ketone 1)∶n(Amine)	Time/h	Product	Yield^b(%)
1a	1∶1.2	Et₂NH	1∶1.0	2	3a	30
1a	1∶1.2	Et₂NH	1∶1.0	4	3a	31
1a	1∶1.5	Et₂NH	1∶1.0	5	3a	43
1a	1∶3.0	Et₂NH	1∶2.0	3	3a	69
1a	1∶6.0	Et₂NH	1∶0.5	4	3a	67
1a	1∶3.0	Morpholine	1∶2.0	4	3a	38
1a	1∶3.0	(i-Pr)₂NH	1∶1.0	4	3a	45
1b	1∶1.3	Et₂NH	1∶1.0	5	3b	35
1b	1∶1.5	Et₂NH	1∶1.5	5	3b	40
1b	1∶3.0	Et₂NH	1∶2.0	3	3b	72

Ketone	Solvent	Amine	Catalyst	Time/h	Product	Yield^b(%)
1a	HOAc	Et₂NH	HOAc	3	3a	69
1a	EtOH	Et₂NH	HOAc^c	5
1a	TFA	Et₂NH	TFA	15
1a	THF	Et₂NH	HOAc^c	12
1b	HOAc	Et₂NH	HOAc	3	3b	72
1b	EtOH	Et₂NH	HOAc^c	12
1b	TFA	Et₂NH	TFA	15
1b	THF	(i-Pr)₂NH	TFA^d	12
1b	THF	Et₂NH	HOAc^c	10

Ketone	Solvent	Amine	Catalyst	Time/h	Product	Yield^b(%)
1a	HOAc	Et₂NH	HOAc	3	3a	69
1a	EtOH	Et₂NH	HOAc^c	5
1a	TFA	Et₂NH	TFA	15
1a	THF	Et₂NH	HOAc^c	12
1b	HOAc	Et₂NH	HOAc	3	3b	72
1b	EtOH	Et₂NH	HOAc^c	12
1b	TFA	Et₂NH	TFA	15
1b	THF	(i-Pr)₂NH	TFA^d	12
1b	THF	Et₂NH	HOAc^c	10

Entry	Ar	Product	Yield^b(%)	Entry	Ar	Product	Yield^b(%)
1	C₆H₅	3a	69	9	3-F-C₆H₄	3i	71
2	4-F-C₆H₄	3b	72	10	2,4-F₂-C₆H₃	3j	70
3	4-Cl-C₆H₄	3c	70	11	3,4-F₂-C₆H₃	3k	65
4	4-Br-C₆H₄	3d	73	12	3-Cl-C₆H₄	3l	68
5	4-CH₃-C₆H₄	3e	68	13	3-NO₂-C₆H₄	3m	73
6	4-OCH₃-C₆H₄	3f	68	14	2-Naphthyl	3n	69
7	4-NO₂-C₆H₄	3g	72	15	4-C₆H₅C₆H₄	3o	71
8	2-F-C₆H₄	3h	72