丙酮氰醇为氰源的卤代烃的氰基取代反应研究

doi:10.6023/cjoc20210203

摘要/Abstract

氰基取代反应是有机合成中引入氰基官能团的重要方法. 以丙酮氰醇为氰化试剂, 以脂肪族卤代烷R—X (X=Cl, Br, I)为底物, 通过亲核取代反应合成一系列氰基化合物. 研究结果表明, 在50 ℃下四氢呋喃(THF)与1,3-二甲基咪唑啉酮(DMI)(体积比为3:1)组成的混合物为反应溶剂, LiOH?H₂O为碱, 丙酮氰醇与相应的卤代烷反应可以得到氰化产物, 产率达到70%~99%. 该反应使用廉价低毒的丙酮氰醇替代剧毒的氰化钠或其他价格昂贵、使用条件苛刻的氰化试剂, 且不需要贵金属作催化剂, 反应条件温和, 适用范围广泛, 具有较大的应用价值.

关键词: 卤代烷, 丙酮氰醇, 氰基取代反应, 氰化产物

The cyano substitution reaction is an important method for introducing cyano functional groups in organic synthesis. In this paper, a series of cyano compounds were synthesized by nucleophilic substitution reaction using acetone cyanohydrin as cyanation reagent and aliphatic haloalkanes R—X (X=Cl, Br, I) as substrates. The results show that the cyanation product can be obtained by reacting the acetone cyanohydrin with the corresponding halogenated alkanes at 50 ℃, and the yield can reach 70%~99%. The reaction solvent is the mixture of tetrahydrofuran (THF) and 1,3-dime- thylimidazolinone (DMI) (volume ratio of 3:1), and the base is LiOH?H₂O. This reaction uses cheap and low toxicity acetone cyanohydrin instead of highly toxic sodium cyanide or other expensive cyanide reagents requiring harsh conditions and it also does not require precious metals as catalysts. The reaction conditions is mild so that it has extensive application and great value of practical application.

Key words: haloalkane, acetone cyanohydrin, cyanide substitution, cyanide

引用此文

郭芳, 由君, 武文菊, 喻艳超, 井彬, 刘波. 丙酮氰醇为氰源的卤代烃的氰基取代反应研究[J]. 有机化学, 2021, 41(5): 1968-1973.

Fang Guo, Jun You, Wenju Wu, Yanchao Yu, Bin Jing, Bo Liu. Study on the Cyanide Substitution Reaction of Acetone Cannolhydrin as Cyanogen Source[J]. Chinese Journal of Organic Chemistry, 2021, 41(5): 1968-1973.

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Entry	Base	Amount of base/equiv.	Time/h	Yield/%
1	咪唑	1.5	24	Trace
2	N-丁基咪唑	1.5	24	Trace
3	无水哌嗪	1.5	10	20
4	三乙胺	1.5	10	23
5	吡啶	1.5	10	40
6	叔丁醇钾	1.5	10	25
7	DMAP	1.5	10	53
8	NaOH	1.5	10	62
9	LiOH?H₂O	1.1	6	85
10	LiOH?H₂O	1.2	5	89
11	LiOH?H₂O	1.3	4	92
12	LiOH?H₂O	1.5	3	98
13	LiOH?H₂O	1.8	3	95
14	LiOH	1.5	3	98
15	CH₃COONa	1.5	10	Trace
16	Na₂CO₃	1.5	10	Trace
17	K₂CO₃	1.5	10	Trace
18	NaHCO₃	1.5	10	Trace
19^b	NaOH	1.5	10	60
20^b	CH₃COONa	1.5	10	Trace
21^b	Na₂CO₃	1.5	10	Trace

Entry	Base	Amount of base/equiv.	Time/h	Yield/%
1	咪唑	1.5	24	Trace
2	N-丁基咪唑	1.5	24	Trace
3	无水哌嗪	1.5	10	20
4	三乙胺	1.5	10	23
5	吡啶	1.5	10	40
6	叔丁醇钾	1.5	10	25
7	DMAP	1.5	10	53
8	NaOH	1.5	10	62
9	LiOH?H₂O	1.1	6	85
10	LiOH?H₂O	1.2	5	89
11	LiOH?H₂O	1.3	4	92
12	LiOH?H₂O	1.5	3	98
13	LiOH?H₂O	1.8	3	95
14	LiOH	1.5	3	98
15	CH₃COONa	1.5	10	Trace
16	Na₂CO₃	1.5	10	Trace
17	K₂CO₃	1.5	10	Trace
18	NaHCO₃	1.5	10	Trace
19^b	NaOH	1.5	10	60
20^b	CH₃COONa	1.5	10	Trace
21^b	Na₂CO₃	1.5	10	Trace

Entry	Substrate R—X	Time/h	Product (4)	Yield/%
1	PhCH₂Cl	3.5	PhCH₂CN (4a)	88
2	PhCH₂CH₂Cl	4.0	PhCH₂CH₂CN (4b)	85
3	ClCH₂CH₂CN	4.0	CNCH₂CH₂CN (4c)	78
4	ClCH₂CH₂Cl	4.5	CNCH₂CH₂CN (4c)	77
5	ClCH₂CH₂CH₂CH₂Cl	3.5	CNCH₂CH₂CH₂CH₂CN (4d)	79
6	ClCH₂CH₂COOCH₂CH₃	4.0	CNCH₂CH₂COOCH₂CH₃ (4e)	77
7	ClCH₂CH₂CH₂CH₃	7.0	CNCH₂CH₂CH₂CH₃ (4f)	71
8	Cl(CH₂)₇CH₃	6.5	CN(CH₂)₇CH₃ (4g)	72
9	Cl(CH₂)₁₁CH₃	5.5	CN(CH₂)₁₁CH₃ (4h)	72
10	Cl(CH₂)₁₃CH₃	5.0	CN(CH2)₁₃CH₃ (4i)	74
11	Cl(CH₂)₁₅CH₃	4.5	CN(CH₂)₁₅CH₃ (4j)	76
12	Cl(CH₂)₁₇CH₃	4.0	CN(CH₂)₁₇CH₃ (4k)	77
13	PhCH₂CH₂CH₂Br	3.0	PhCH₂CH₂CH₂CN (4l)	91
14	PhCHBrCH₃	4.0	PhCHCNCH₃(4m)	91
15	PhCHBrPh	5.0	PhCHCNPh (4n)	93
16	BrCH₂CH₂COOCH₃	4.0	CNCH₂CH₂COOCH₃(4o)	85
17	BrCH₂CH₂CH₂COOCH₃	3.5	CNCH₂CH₂CH₂COOCH₃ (4p)	89
18	Br(CH₂)₆COOCH₂CH₃	3.0	CN(CH₂)₆COOCH₂CH₃ (4q)	93
19	BrCH₂CH₂Br	4.0	CNCH₂CH₂CN (4c)	80
20	BrCH₂CH₂CH₂CH₂Br	3.0	CNCH₂CH₂CH₂CH₂CN (4d)	85
21	BrCH₂CH₂CH₂CH₃	6.0	CNCH₂CH₂CH₂CH₃ (4f)	75
22	Br(CH₂)₇CH₃	5.5	CN(CH₂)₇CH₃ (4g)	77
23	Br(CH₂)₁₁CH₃	4.5	CN(CH₂)₁₁CH₃ (4h)	79
24	Br(CH₂)₁₃CH₃	4.0	CN(CH₂)₁₃CH₃ (4i)	81
25	Br(CH₂)₁₅CH₃	3.5	CN(CH₂)₁₅CH₃ (4j)	83
26	Br(CH₂)₁₇CH₃	3.0	CN(CH₂)₁₇CH₃ (4k)	86
27	PhCH₂I	2.5	PhCH₂CN (4a)	99
28	PhCH₂CH₂CH₂I	2.5	PhCH₂CH₂CH₂CN (4l)	92
29	PhCHICH₃	3.0	PhCHCNCH₃ (4m)	93
30	ICH₂CH₂CH₂COOCH₃	3.0	CNCH₂CH₂CH₂COOCH₃ (4p)	90
31	ICH₂CH₂CH₂CH₃	5.0	CNCH₂CH₂CH₂CH₃ (4f)	80
32	I(CH₂)₇CH₃	4.5	CN(CH₂)₇CH₃ (4g)	83
33	I(CH₂)₁₁CH₃	4.0	CN(CH₂)₁₁CH₃(4h)	85
34	I(CH₂)₁₃CH₃	3.5	CN(CH₂)₁₃CH₃ (4i)	87
35	I(CH₂)₁₅CH₃	3.0	CN(CH₂)₁₅CH₃ (4j)	89
36	I(CH₂)₁₇CH₃	2.5	CN(CH₂)₁₇CH₃ (4k)	92

Entry	Substrate R—X	Time/h	Product (4)	Yield/%
1	PhCH₂Cl	3.5	PhCH₂CN (4a)	88
2	PhCH₂CH₂Cl	4.0	PhCH₂CH₂CN (4b)	85
3	ClCH₂CH₂CN	4.0	CNCH₂CH₂CN (4c)	78
4	ClCH₂CH₂Cl	4.5	CNCH₂CH₂CN (4c)	77
5	ClCH₂CH₂CH₂CH₂Cl	3.5	CNCH₂CH₂CH₂CH₂CN (4d)	79
6	ClCH₂CH₂COOCH₂CH₃	4.0	CNCH₂CH₂COOCH₂CH₃ (4e)	77
7	ClCH₂CH₂CH₂CH₃	7.0	CNCH₂CH₂CH₂CH₃ (4f)	71
8	Cl(CH₂)₇CH₃	6.5	CN(CH₂)₇CH₃ (4g)	72
9	Cl(CH₂)₁₁CH₃	5.5	CN(CH₂)₁₁CH₃ (4h)	72
10	Cl(CH₂)₁₃CH₃	5.0	CN(CH2)₁₃CH₃ (4i)	74
11	Cl(CH₂)₁₅CH₃	4.5	CN(CH₂)₁₅CH₃ (4j)	76
12	Cl(CH₂)₁₇CH₃	4.0	CN(CH₂)₁₇CH₃ (4k)	77
13	PhCH₂CH₂CH₂Br	3.0	PhCH₂CH₂CH₂CN (4l)	91
14	PhCHBrCH₃	4.0	PhCHCNCH₃(4m)	91
15	PhCHBrPh	5.0	PhCHCNPh (4n)	93
16	BrCH₂CH₂COOCH₃	4.0	CNCH₂CH₂COOCH₃(4o)	85
17	BrCH₂CH₂CH₂COOCH₃	3.5	CNCH₂CH₂CH₂COOCH₃ (4p)	89
18	Br(CH₂)₆COOCH₂CH₃	3.0	CN(CH₂)₆COOCH₂CH₃ (4q)	93
19	BrCH₂CH₂Br	4.0	CNCH₂CH₂CN (4c)	80
20	BrCH₂CH₂CH₂CH₂Br	3.0	CNCH₂CH₂CH₂CH₂CN (4d)	85
21	BrCH₂CH₂CH₂CH₃	6.0	CNCH₂CH₂CH₂CH₃ (4f)	75
22	Br(CH₂)₇CH₃	5.5	CN(CH₂)₇CH₃ (4g)	77
23	Br(CH₂)₁₁CH₃	4.5	CN(CH₂)₁₁CH₃ (4h)	79
24	Br(CH₂)₁₃CH₃	4.0	CN(CH₂)₁₃CH₃ (4i)	81
25	Br(CH₂)₁₅CH₃	3.5	CN(CH₂)₁₅CH₃ (4j)	83
26	Br(CH₂)₁₇CH₃	3.0	CN(CH₂)₁₇CH₃ (4k)	86
27	PhCH₂I	2.5	PhCH₂CN (4a)	99
28	PhCH₂CH₂CH₂I	2.5	PhCH₂CH₂CH₂CN (4l)	92
29	PhCHICH₃	3.0	PhCHCNCH₃ (4m)	93
30	ICH₂CH₂CH₂COOCH₃	3.0	CNCH₂CH₂CH₂COOCH₃ (4p)	90
31	ICH₂CH₂CH₂CH₃	5.0	CNCH₂CH₂CH₂CH₃ (4f)	80
32	I(CH₂)₇CH₃	4.5	CN(CH₂)₇CH₃ (4g)	83
33	I(CH₂)₁₁CH₃	4.0	CN(CH₂)₁₁CH₃(4h)	85
34	I(CH₂)₁₃CH₃	3.5	CN(CH₂)₁₃CH₃ (4i)	87
35	I(CH₂)₁₅CH₃	3.0	CN(CH₂)₁₅CH₃ (4j)	89
36	I(CH₂)₁₇CH₃	2.5	CN(CH₂)₁₇CH₃ (4k)	92