有机化学 ›› 2021, Vol. 41 ›› Issue (5): 1968-1973.DOI: 10.6023/cjoc20210203 上一篇 下一篇
研究论文
郭芳1, 由君1,*(), 武文菊1, 喻艳超1,*(), 井彬1, 刘波1
收稿日期:
2021-02-19
修回日期:
2021-03-23
发布日期:
2021-04-16
通讯作者:
由君, 喻艳超
基金资助:
Fang Guo1, Jun You1,*(), Wenju Wu1, Yanchao Yu1,*(), Bin Jing1, Bo Liu1
Received:
2021-02-19
Revised:
2021-03-23
Published:
2021-04-16
Contact:
Jun You, Yanchao Yu
About author:
Supported by:
文章分享
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.
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.
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 |
19b | NaOH | 1.5 | 10 | 60 |
20b | CH3COONa | 1.5 | 10 | Trace |
21b | 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 |
19b | NaOH | 1.5 | 10 | 60 |
20b | CH3COONa | 1.5 | 10 | Trace |
21b | Na2CO3 | 1.5 | 10 | Trace |
Entry | Solvent | Time/h | Yield/% | |
---|---|---|---|---|
1 | DMI | 3 | 97 | |
2 | NMP | 3 | 95 | |
3 | HMPA | 3 | 96 | |
4 | DMF | 10 | 50 | |
5 | Acetone | 24 | Trace | |
6 | CH3CN | 24 | Trace | |
7 | THF | 10 | 13 | |
8 | DMI/Acetone (V:V=1:1) | 10 | 64 | |
9 | DMI/CH3CN (V:V=1:1) | 10 | 67 | |
10 | DMI/THF (V:V=1:1) | 3 | 98 | |
11 | DMI/THF (V:V=1:3) | 3 | 98 | |
12 | DMI/THF (V:V=1:5) | 6 | 93 |
Entry | Solvent | Time/h | Yield/% | |
---|---|---|---|---|
1 | DMI | 3 | 97 | |
2 | NMP | 3 | 95 | |
3 | HMPA | 3 | 96 | |
4 | DMF | 10 | 50 | |
5 | Acetone | 24 | Trace | |
6 | CH3CN | 24 | Trace | |
7 | THF | 10 | 13 | |
8 | DMI/Acetone (V:V=1:1) | 10 | 64 | |
9 | DMI/CH3CN (V:V=1:1) | 10 | 67 | |
10 | DMI/THF (V:V=1:1) | 3 | 98 | |
11 | DMI/THF (V:V=1:3) | 3 | 98 | |
12 | DMI/THF (V:V=1:5) | 6 | 93 |
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 |
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