亚硝酸异戊酯活化伯磺酰胺制备磺酰溴与磺酰氯

doi:10.6023/cjoc202310005

摘要/Abstract

磺酰溴与磺酰氯是一类十分重要的化合物, 是有机转换中常用的合成砌块. 以亚硝酸异戊酯(ⁱAmONO)为活化剂, 二溴海因(DBDMH)为溴源或三氯异氰尿酸(TCCA)为氯源, 实现了伯磺酰胺(包含药物分子)到磺酰溴或磺酰氯的合成转换. 该方法具有原料来源广泛、底物普适性好、收率优良以及条件温和等优点, 不仅能进行克级制备, 还能进行一系列后期官能团衍生, 具有良好的实用价值. 机理研究表明, N,N-二卤磺酰胺是该方法可能的中间体, 亚硝酸异戊酯在该转化过程中起到了至关重要的作用.

关键词: 伯磺酰胺, 亚硝酸异戊酯, 磺酰溴, 磺酰氯

Sulfonyl bromide and sulfonyl chloride are important compounds commonly used as building blocks in organic synthesis. This paper presents the successful synthesis of sulfonyl bromide or sulfonyl chloride from primary sulfonamide using isoamyl nitrite (ⁱAmONO) as an activator, dibromantine (DBDMH) as a bromine source, or trichloroisocyanuric acid (TCCA) as a chlorine source. The method offers several advantages such as wide range of raw materials, compatibility with various substrates, high yield, and mild reaction conditions. It is suitable for both gram-scale preparations and subsequent derivations, demonstrating practical value. Mechanistic studies suggest that N,N-dihalosulfonamide is a potential intermediate in this process and isoamyl nitrite plays a crucial role in the conversion process.

Key words: primary sulfonamide, isoamyl nitrite, sulfonyl bromide, sulfonyl chloride

引用此文

江港钟, 林嘉欣, 鲍晓光, 万小兵. 亚硝酸异戊酯活化伯磺酰胺制备磺酰溴与磺酰氯[J]. 有机化学, 2024, 44(2): 533-549.

Gangzhong Jiang, Jiaxing Lin, Xiaoguang Bao, Xiaobing Wan. Isoamyl Nitrite Activated Primary Sulfonamide to Sulfonyl Bromide and Sulfonyl Chloride[J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 533-549.

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参考文献 12

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Entry	Variation from the "standard conditions"	Yield^b/%
1	None	82
2	NBS instead of DBDMH	22
3	CBr₄ instead of DBDMH	N.d.
4	TBAB instead of DBDMH	N.d.
5	^tBuONO instead of ⁱAmONO	40
6	ⁿBuONO instead of ⁱAmONO	32
7	ⁱPrONO instead of ⁱAmONO	21
8	ⁱBuONO instead of ⁱAmONO	75
9	NaNO₂＋HCl instead of ⁱAmONO	50
10	CHCl₃ instead of DCM	58
11	DCE instead of DCM	35
12	DIOX instead of DCM	66
13	DMF instead of DCM	N.d.
14	MeOH instead of DCM	N.d.
15	O₂ instead of air	59
16	N₂ instead of air	42
17	No DBDMH^c	N.d.
18	No ⁱAmONO	N.d.

Entry	Variation from the "standard conditions"	Yield^b/%
1	None	82
2	NBS instead of DBDMH	22
3	CBr₄ instead of DBDMH	N.d.
4	TBAB instead of DBDMH	N.d.
5	^tBuONO instead of ⁱAmONO	40
6	ⁿBuONO instead of ⁱAmONO	32
7	ⁱPrONO instead of ⁱAmONO	21
8	ⁱBuONO instead of ⁱAmONO	75
9	NaNO₂＋HCl instead of ⁱAmONO	50
10	CHCl₃ instead of DCM	58
11	DCE instead of DCM	35
12	DIOX instead of DCM	66
13	DMF instead of DCM	N.d.
14	MeOH instead of DCM	N.d.
15	O₂ instead of air	59
16	N₂ instead of air	42
17	No DBDMH^c	N.d.
18	No ⁱAmONO	N.d.

Entry	Variation from the "standard conditions"	Yield^b/%
1	None	72
2	NCS instead of TCCA	48
3	DCDMH instead of TCCA	27
4	TCAB instead of TCCA	23
5	^tBuONO instead of ⁱAmONO	50
6	ⁿBuONO instead of ⁱAmONO	66
7	ⁱPrONO instead of ⁱAmONO	52
8	ⁱBuONO instead of ⁱAmONO	65
9	NaNO₂＋HCl instead of ⁱAmONO	Trace
10	DCM instead of CHCl₃	68
11	DCE instead of CHCl₃	63
12	MeCN instead of CHCl₃	65
13	EA instead of CHCl₃	Trace
14	MeOH instead of CHCl₃	N.d.
15	25 °C instead of 35 °C	65
16	3 h instead of 6 h	58
17	O₂ instead of air	63
18	N₂ instead of air	50
19	No TCCA	N.d.
20	No ⁱAmONO	N.d.

Entry	Variation from the "standard conditions"	Yield^b/%
1	None	72
2	NCS instead of TCCA	48
3	DCDMH instead of TCCA	27
4	TCAB instead of TCCA	23
5	^tBuONO instead of ⁱAmONO	50
6	ⁿBuONO instead of ⁱAmONO	66
7	ⁱPrONO instead of ⁱAmONO	52
8	ⁱBuONO instead of ⁱAmONO	65
9	NaNO₂＋HCl instead of ⁱAmONO	Trace
10	DCM instead of CHCl₃	68
11	DCE instead of CHCl₃	63
12	MeCN instead of CHCl₃	65
13	EA instead of CHCl₃	Trace
14	MeOH instead of CHCl₃	N.d.
15	25 °C instead of 35 °C	65
16	3 h instead of 6 h	58
17	O₂ instead of air	63
18	N₂ instead of air	50
19	No TCCA	N.d.
20	No ⁱAmONO	N.d.