Three-Component Reaction of Isothiocyanates, Amines, and Sulfonium Salts Leading to S-Alkyl Isothioureas

doi:10.6023/cjoc202412015

Abstract

The base-promoted three-component reaction of isothiocyanates, amines, and sulfonium salts has been developed for the construction of S-alkyl substituted isothioureas. This method uses ^tBuONa as promoter to accomplish ring-opening reaction of aryl, alkenyl and alkynyl sulfonium salts, affording a green and efficient approach to access S-alkyl substituted isothioureas. The present protocol could be efficiently scaled up to gram quantities, which has advantages of mild condition, simple operation, and non-transition metal pollution.

Key words: isothiocyanate, amine, sulfonium salt, multi-component reaction, S-alkyl isothiourea

Cite this article

Zheng Wang, Min Yue, Zongcheng Wang. Three-Component Reaction of Isothiocyanates, Amines, and Sulfonium Salts Leading to S-Alkyl Isothioureas[J]. Chinese Journal of Organic Chemistry, 2025, 45(10): 3892-3902.

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Entry	Additive	Solvent	Yield^b/%
1	—	CH₃CN	21
2	K₂CO₃ (1 equiv.)	CH₃CN	45
3	Cs₂CO₃ (1 equiv.)	CH₃CN	53
4	Na₂CO₃ (1 equiv.)	CH₃CN	64
5	K₃PO₄ (1 equiv.)	CH₃CN	62
6	^tBuONa (1 equiv.)	CH₃CN	91
7	DABCO (1 equiv.)	CH₃CN	86
8	DBU (1 equiv.)	CH₃CN	84
9	^tBuONa (0.2 equiv.)	CH₃CN	54
10	^tBuONa (0.5 equiv.)	CH₃CN	72
11	^tBuONa (2 equiv.)	CH₃CN	91
12	^tBuONa (1 equiv.)	EtOH	61
13	^tBuONa (1 equiv.)	DMF	56
14	^tBuONa (1 equiv.)	CH₂Cl₂	73
15	^tBuONa (1 equiv.)	THF	56
16	^tBuONa (1 equiv.)	1,4-Dioxane	54
17	^tBuONa (1 equiv.)	EtOAc	60
18	^tBuONa (1 equiv.)	DMSO	42
19	^tBuONa (1 equiv.)	H₂O	0
20	I₂ (10 mol%)/^tBuONa (1 equiv.)	CH₃CN	89
21	CuI (10 mol%)/^tBuONa (1 equiv.)	CH₃CN	83
22	AgNO₃ (10 mol%)/^tBuONa (1 equiv.)	CH₃CN	90

Entry	Additive	Solvent	Yield^b/%
1	—	CH₃CN	21
2	K₂CO₃ (1 equiv.)	CH₃CN	45
3	Cs₂CO₃ (1 equiv.)	CH₃CN	53
4	Na₂CO₃ (1 equiv.)	CH₃CN	64
5	K₃PO₄ (1 equiv.)	CH₃CN	62
6	^tBuONa (1 equiv.)	CH₃CN	91
7	DABCO (1 equiv.)	CH₃CN	86
8	DBU (1 equiv.)	CH₃CN	84
9	^tBuONa (0.2 equiv.)	CH₃CN	54
10	^tBuONa (0.5 equiv.)	CH₃CN	72
11	^tBuONa (2 equiv.)	CH₃CN	91
12	^tBuONa (1 equiv.)	EtOH	61
13	^tBuONa (1 equiv.)	DMF	56
14	^tBuONa (1 equiv.)	CH₂Cl₂	73
15	^tBuONa (1 equiv.)	THF	56
16	^tBuONa (1 equiv.)	1,4-Dioxane	54
17	^tBuONa (1 equiv.)	EtOAc	60
18	^tBuONa (1 equiv.)	DMSO	42
19	^tBuONa (1 equiv.)	H₂O	0
20	I₂ (10 mol%)/^tBuONa (1 equiv.)	CH₃CN	89
21	CuI (10 mol%)/^tBuONa (1 equiv.)	CH₃CN	83
22	AgNO₃ (10 mol%)/^tBuONa (1 equiv.)	CH₃CN	90

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