One-Pot Two-Step Strategy for Efficient Synthesis of 3-Aryl-4-(arylthio)-1H-pyrazol-5-amines Derivatives

doi:10.6023/cjoc202107045

Abstract

One-pot two-step reaction of 3-oxo-3-arylpropanenitriles, methyl hydrazinecarboxylate (or hydrazine hydrate), and arylsulfonyl hydrazides has been established, and a series of 3-aryl-4-(arylthio)-1H-pyrazol-5-amines were constructed by sequential cyclization, sulfenylation, and removal of COOMe group under the action of I₂ and N-iodo-succininide (NIS), respectively. The method represents good atomic economy, mild reaction conditions, broad substrate scope, and gram-scale synthesis. Moreover, the further transformations of 3-aryl-4-(arylthio)-1H-pyrazol-5-amine products were also investigated.

Key words: one-pot two-step, 1H-pyrazol-5-amine, cyclization, sulfenylation

Cite this article

Yijiao Feng, Jing He, Yueting Wei, Ting Tang, Chuntian Li, Ping Liu. One-Pot Two-Step Strategy for Efficient Synthesis of 3-Aryl-4-(arylthio)-1H-pyrazol-5-amines Derivatives[J]. Chinese Journal of Organic Chemistry, 2022, 42(1): 226-234.

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Fig. & Tab. 8

Scheme 1. Multicomponent reactions of β-ketonitriles with hydrazides

Entry	Catalyst (mol%)	Solvent/mL	Yield^b/%
1	—	EtOH	Trace
2	NIS (50)	EtOH	84
3	NIS (20)	EtOH	85
4	NIS (10)	EtOH	86
5	NIS (5)	EtOH	67
6	I₂ (10)	EtOH	97
7	I₂ (5)	EtOH	92
8	TBAI (10)	EtOH	Trace
9	I₂ (10)	1,4-Dixoane	57
10	I₂ (10)	DCE	64
11	I₂ (10)	DMSO	45
12	I₂ (10)	DMF	34
13	I₂ (10)	THF	56
14^c	I₂ (10)	EtOH	85

Table 1. Optimization of cyclization reactiona

Entry	[I] source (mol%)	T/℃	Yield^b/%
1	—	80	19
2	I₂(50)	80	78
3	KI (50)	80	54
4	NH₄I (50)	80	46
5	TBAI (50)	80	38
6	NIS (50)	80	88
7	NIS (30)	80	82
8	NIS (70)	80	87
9	NIS (50)	60	30
10	NIS (50)	100	75
11^c	NIS (50)	80	94
12^d	NIS (50)	80	70

Table 2. Optimization of sulfonation reactiona

Table 3. One-pot two-step reaction of 3-oxo-3-arylpropaneni- trile, NH2NHCOOMe and ArSO2NHNH2a

Table 4. One-pot two-step reaction of 3-oxo-3-arylpropaneni- trile, NH2NH2•H2O and ArSO2NHNH2a

Scheme 2. Gram-scale synthesis and transformations of 5a Reaction conditions: (i) 1a (6 mmol), 2a (9 mmol), EtOH (5 mL), I2 (10 mol%), room temperature, 16 h; (ii) 4a (2.5 equiv.), NIS (50 mol%), 80 ℃, 20 h; (iii) 5a (0.2 mmol), m-CPBA (0.6 mmol), CHCl3 (2 mL), 65 ℃, 18 h; (iv) 5a (0.2 mmol), (E)-chalcone (0.4 mmol), KOH (0.4 mmol), DMF (1 mL), 110 ℃, 20 min; (v) 5a (0.2 mmol), PhCHO (0.3 mmol), Et3N (0.4 mmol), DTBP (0.6 mmol), NH4I (0.2 mmol), toluene (2 mL), 130 ℃, 12 h.

Scheme 3. Control experiments

Scheme 4. Proposed reaction mechanism

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一锅两步策略高效合成3-芳基-4-(芳硫基)-1H-吡唑-5-胺衍生物