三组分反应合成5-(4-甲基苯基)-3-三氟甲基-1H-吡唑的综合实验设计

doi:10.3866/PKU.DXHX202209026

Abstract

Abstract:

Through scientific research back-feeding teaching, the two concepts of "multicomponent reaction" and "fluorinated organic compound" were integrated into undergraduate experiment teaching, and 5-(4-methylphenyl)-3-trifluoromethyl-1H-pyrazole was synthesized by the three-component reaction. This reaction features mild experimental conditions, simple operations, high yield, good reproducibility, and high safety. This comprehensive experiment integrates science and education and combines theory with practice, thus helping students to understand the new concept of step-economic synthesis and to establish the concept of green chemistry. This is a new subject suitable to introduce into the current organic experiment teaching course.

Key words: Organic fluorine chemistry, Multi-component reaction, 3-Trifluoromethyl-1H-pyrazole, Fluorinated building block

Rongbin Peng, Shang Zhou, Ziyang Wang, Dongen Lin, Chuanle Zhu. Comprehensive Experimental Design of Three Component Reaction for the Synthesis of 5-(4-Methylphenyl)-3-Trifluoromethyl-1H-Pyrazole[J].University Chemistry, 2023, 38(8): 248-258.

Figures/Tables 14

References 11

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编号	试剂名称	纯度	厂家
1	对甲基苯甲醛	98%	安耐吉化学
2	对甲苯磺酰肼	97%	安耐吉化学
3	2-溴代-3, 3, 3-三氟丙烯	98%	上氟科技有限公司
4	1, 8-二氮杂双环[5.4.0]十一碳-7-烯(DBU)	98%	安耐吉化学
5	无水乙醇	分析纯	同源化工有限公司
6	乙酸乙酯	分析纯	同源化工有限公司
7	石油醚	分析纯	同源化工有限公司
8	石英砂	99%	同源化工有限公司
9	氯化钠	分析纯	同源化工有限公司
10	硅胶	200–300目	青岛海洋化工厂
11	氘代DMSO	99.8%	安耐吉化学

编号	仪器	型号	厂家
1	电子分析天平	DH-JCS	帝衡精密电子天平
2	旋转蒸发仪	YRE-5299	巩义予华旋转蒸发仪
3	加热搅拌器	98-Ⅲ-B	黄骅菲斯福实验仪器有限公司
4	层析柱	C184462C	北京欣维尔公司
5	核磁共振波谱仪	400 MHz	布鲁克
6	圆底烧瓶	25 mL、100 mL	北京欣维尔公司
7	回流冷凝管	C621200	北京欣维尔公司
8	分液漏斗	125 mL	北京欣维尔公司
9	熔点仪	WRS-1B	申光数字熔点仪


编号	碱的种类	碱的用量/mmol	反应温度/℃	反应时长/h	溶剂的量/mL	收率/% ^a
1	DBU	1.50	60	3	1.5	70
2	t-BuOLi	1.50	60	3	1.5	0
3	Cs₂CO₃	1.50	60	3	1.5	11
4	K₂CO₃	1.50	60	3	1.5	12
5	MeONa	1.50	60	3	1.5	14
6	Li₂CO₃	1.50	60	3	1.5	0
7	t-BuOK	1.50	60	3	1.5	0
8	DABCO	1.50	60	3	1.5	0
9	Et₃N	1.50	60	3	1.5	9
10	DBU	1.50	45	3	1.5	40
11	DBU	1.50	70	3	1.5	74
12	DBU	1.50	80	3	1.5	78
13	DBU	1.50	80	1	1.5	37
14	DBU	1.50	80	2	1.5	78
15	DBU	1.00	80	2	1.5	77
16	DBU	1.25	80	2	1.5	77
17	DBU	1.75	80	2	1.5	80
18	DBU	2.00	80	2	1.5	82
19	DBU	1.50	80	2	0.5	80
20	DBU	1.50	80	2	1.0	85
21	DBU	1.50	80	2	2.0	79
22	DBU	1.50	80	2	3.0	80

样品名称	熔点/℃
重结晶所得产品	156–161
柱层析所得产品	163–165

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Comprehensive Experimental Design of Three Component Reaction for the Synthesis of 5-(4-Methylphenyl)-3-Trifluoromethyl-1H-Pyrazole

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