单质碘/氢硅烷体系作用下由α-酮酰胺合成α-羟基酰胺的反应

doi:10.6023/cjoc202502026

摘要/Abstract

单质碘和氢硅烷都是易储存和易取用的物质, 由它们参与的反应具有操作简单的特点. 将单质碘/氢硅烷体系用于α-羟基酰胺的合成反应. 采用的原料为α-酮酰胺, 氢硅烷为二甲基一氯硅烷, 溶剂为乙酸乙酯, 在室温下40 min内反应就能实现合成. 该合成方法操作简单, 反应速率快, 具有较广的底物适用范围和良好的官能团耐受性. 共得到22个α-羟基酰胺产物, 并以N-(对甲苯基)-2-苯基-2-羰基乙酰胺为原料进行了克级规模放大实验.

关键词: 单质碘, 氢硅烷, 二甲基一氯硅烷, α-羟基酰胺

Both molecular iodine and hydrosilane are compounds that are easy to store and access, and the reactions involving them have the characteristic of simple operation. In this work, diiodine/hydrosilane system is used for the synthesis of α-hydroxyamides. α-Ketoamides are used as the raw materials with chlorodimethylsilane serving as the hydrosilane, and the solvent is ethyl acetate. The synthesis can be achieved within 40 min at room temperature. This synthesis method is easy to operate, and has a short reaction time, a wide range of substrate scope and good functional group tolerance. A total of 22 α-hydroxyamide products were obtained, and a gram-scale experiment was conducted using 2-oxo-2-phenyl-N-(p-tolyl)aceta- mide as the starting material.

Key words: molecular iodine, hydrosilane, chlorodimethylsilane, α-hydroxyamides

引用此文

冯思燕, 王卓, 蒋金. 单质碘/氢硅烷体系作用下由α-酮酰胺合成α-羟基酰胺的反应[J]. 有机化学, 2025, 45(12): 4417-4424.

Siyan Feng, Zhuo Wang, Jin Jiang. Reaction of Synthesizing α-Hydroxyamides from α-Ketoamides by Using Diiodine/Hydrosilane System[J]. Chinese Journal of Organic Chemistry, 2025, 45(12): 4417-4424.

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图/表 7

图1. 几种含α-羟基酰胺结构的生物活性化合物

Figure 1. Several bioactive compounds of α-hydroxy amides

图式1. 无过渡金属下氢硅烷用于还原α-酮酰胺制备α-羟基酰胺的反应

Scheme 1. Reductions of α-ketonamides to α-hydroxyamides using hydrosilanes without transition metals

Entry	Hydrosilane	Solvent	Yield^b/%
1	Et₃SiH	DCM	71
2	Et₃SiH	EtOAc	72
3	Et₃SiH	MeCN	Trace
4	Et₃SiH	CHCl₃	22
5	Et₃SiH	THF	71
6	Et₃SiH	Toluene	10
7	Et₃SiH	1,4-Dioxane	16
8	Et₃SiH	CH₃NO₂	58
9	Et₃SiH	C₆H₅NO₂	20
10	Et₃SiH	DMF	0
11	Et₃SiH	EtOH	0
12	Et₃SiH	H₂O	0
13	PMHS	EtOAc	78
14	TMDS	EtOAc	81
15	Ph₃SiH	EtOAc	17
16	Ph₂SiH₂	EtOAc	69
17	(EtO)₃SiH	EtOAc	Trace
18	DMCS	EtOAc	98
19^c	DMCS	EtOAc	85

表1. 反应条件优化a

Table 1. Optimization of reaction conditions

Entry	Yield^b/%	Entry	Yield^b/%
1	98	12	53
2	98	13	65
3	60	14	74
4	73	15	75
5	97	16	71
6	58	17	71
7	82	18	67
8	67	19	85
9	89	20	66
10	72	21	52
11	85	22	53

表2. 反应底物拓展a

Table 2. Reaction substrate expansion

图式2. 2b的大规模制备

Scheme 2. Large-scale preparation of 2b

图式3. 控制实验

Scheme 3. Control experiments

图式4. 可能的反应机理

Scheme 4. Possible reaction mechanism

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