β-硝基苯乙烯衍生物与二溴海因高度区域选择性氨溴加成反应

doi:10.7503/cjcu20141110

摘要/Abstract

摘要：

以β-硝基苯乙烯衍生物为底物, 二溴海因为氮源/卤素源, 乙腈作溶剂, 建立了碳碳双键上高度区域选择性氨溴加成反应新体系. β-硝基苯乙烯衍生物与二溴海因在室温无水碳酸钠催化下反应, 可高收率获得邻位氨溴加成产物, 最高收率达97%; β-甲基-β-硝基苯乙烯衍生物在氢氧化钾催化下回流反应, 也可高收率得到邻位氨溴加成产物, 最高收率达95%. 实验结果表明, 对于硝基苯乙烯衍生物, 当苯环4-位具有强供电子基团如CH₃O时, 可以得到单一的α-氨基-β-溴加成产物, 但其收率相对较低; 当硝基苯乙烯衍生物的苯环4-位有强吸电子基团如NO₂时, 反应收率则很高. 这一实验结果证明β-硝基苯乙烯衍生物(缺电子烯烃)与二溴海因的氨溴加成反应具有亲核加成的特征. 本文共考察了20种不同结构的β-硝基苯乙烯衍生物的氨溴加成反应情况, 其产物结构经核磁共振波谱及质谱分析确证, 并提出了可能的反应机理.

关键词: 氨溴加成反应, β-硝基苯乙烯, 高度区域选择性, 二溴海因

Abstract:

A new protocol for the high regioselective aminobromination of β-nitrostyrene derivatives with 1,3-dibromo-5,5-dimethyl hydantoin(DBDMH) as nitrogen/bromine sources was developed. Two kinds of β-nitrostyrene derivatives got different reaction results under different reaction conditions. For the β-nitrostyrene derivatives, this protocol offered vicinal haloamine products in good to excellent yields(up to 97%) at room temperature in CH₃CN catalyzed by Na₂CO₃. For the β-methyl-β-nitrostyrene, the good to excellent yields(up to 95%)were also achieved refluxed in CH₃CN catalyzed by KOH. The strong electron-donating substituents(e.g., CH₃O) on the 4-position of benzene ring could deactivated the reaction activity of β-nitrostyrenederi-vetives with DBDMH. However, the vicinal haloamines were also afforded as the sole addition product. Whereas strong electron-withdrawing substituent(e.g., NO₂) could activated reaction activity remarkably and the vicinal haloamines were afforded as the sole addition product, too. The result revealed that the addition reaction has a nucleophilic addition feature. The aminobromination of 20 examples of β-nitrostyrenes were investigated in this work and the structure of all products were confirmed by the corresponding ¹H NMR, ¹³C NMR spectra and HRMS(ESI). A possible mechanism involving a nucleophilic conjugate addition was proposed.

Key words: Aminobromination, β-Nitrostyrene, High regioselective, 1,3-Dibromo-5, 5-dimethyl hydantoin

中图分类号:

O626.3

TrendMD:

刘亚丽, 刘德娥, 杜曼飞, 曹晨茜, 陈战国. β-硝基苯乙烯衍生物与二溴海因高度区域选择性氨溴加成反应. 高等学校化学学报, 2015, 36(6): 1117.

LIU Yali, LIU De’e, DU Manfei, CAO Chenxi, CHEN Zhanguo. High Regioselective Aminobromination of β-Nitrostyrene Derivatives with 1,3-Dibromo-5,5-dimethyl Hydantoin^†. Chem. J. Chinese Universities, 2015, 36(6): 1117.

图/表 8

参考文献 37

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Compd.	m.p.(ref.)/℃	Compd.	m.p.(ref.)/℃
1a	55.1—56.3(55—56^[21])	11a	145—146(128—131^[31])
2a	100.1—102.1(102—102.5^[22])	12a	61.5—61.7(60—61 ^[32])
3a	84.4—86.0(85.5—87.5^[23])	13a	54.0—54.4(55^[33])
4a	120.2—120.6(125.5—126.5^[24])	14a	42.0—42.3(43—44.5^[34])
5a	98—99(98—99^[25])	15a	96.4—97.3(96—97^[25])
6a	98.6—99.1(101—102.5^[26])	16a	64.0—65.1(66^[35])
7a	108.5—110.4(112—113^[27])	17a	88.6—89.9(86—87^[36])
8a	149.3—150.6(151—153^[28])	18a	89.3—91.3(93—95^[35])
9a	201.2—203.1(203—204^[29])	19a	113.8—114.1(114—115^[37])
10a	123.1—124.3(124.5—126^[30])	20a	56.1—56.3(55—55.5^[35])

Compd.	m.p.(ref.)/℃	Compd.	m.p.(ref.)/℃
1a	55.1—56.3(55—56^[21])	11a	145—146(128—131^[31])
2a	100.1—102.1(102—102.5^[22])	12a	61.5—61.7(60—61 ^[32])
3a	84.4—86.0(85.5—87.5^[23])	13a	54.0—54.4(55^[33])
4a	120.2—120.6(125.5—126.5^[24])	14a	42.0—42.3(43—44.5^[34])
5a	98—99(98—99^[25])	15a	96.4—97.3(96—97^[25])
6a	98.6—99.1(101—102.5^[26])	16a	64.0—65.1(66^[35])
7a	108.5—110.4(112—113^[27])	17a	88.6—89.9(86—87^[36])
8a	149.3—150.6(151—153^[28])	18a	89.3—91.3(93—95^[35])
9a	201.2—203.1(203—204^[29])	19a	113.8—114.1(114—115^[37])
10a	123.1—124.3(124.5—126^[30])	20a	56.1—56.3(55—55.5^[35])

Compd.	Appearance	Yield^*(%)	m. p./℃	HRMS [M+Na]⁺(calcd.), m/z
1b	White solid	94	167—169	457.9151(457.9150)
2b	White solid	89	147—149	471.9295(471.9307)
3b	White solid	85	142—144	487.9246(487.9256)
4b	White solid	45	169—171	547.9466(547.9467)
5b	Pale yellow solid	65	200—202	595.8471(595.8466)
6b	Pale yellow solid	95	166.8—169.0	475.9046(475.9056)
7b	White solid	95	180—182	491.8763(491.8760)
8b	White solid	94	155—157	535.8259(535.8255)
9b	White solid	97	185—187	502.8991(502.9001)
10b	White solid	96	164—165	502.8988(502.9001)
11b	White solid	90	164—165	507.9308(507.9307)
12b	White solid	90	164.4—166.7	392.0214(392.0222)
13b	White solid	78	166.1—168.1	406.0374(406.0378)
14b	White solid	76	168.7—170.4	422.0327(422.0328)
15b	Yellow solid	84	156.1—157.5	531.9513(531.9518)
16b	Pale yellow solid	95	164.8—165.7	410.0123(410.0128)
17b	Yellow solid	94	199.5—201.4	425.9826(425.9832)
18b	White solid	94	177.1—178.9	471.9302(471.9307)
19b	White solid	95	148.6—149.9	437.0077(437.0073)
20b	White solid	93	175.5—176.3	437.0067(437.0073)

Compd.	Appearance	Yield^*(%)	m. p./℃	HRMS [M+Na]⁺(calcd.), m/z
1b	White solid	94	167—169	457.9151(457.9150)
2b	White solid	89	147—149	471.9295(471.9307)
3b	White solid	85	142—144	487.9246(487.9256)
4b	White solid	45	169—171	547.9466(547.9467)
5b	Pale yellow solid	65	200—202	595.8471(595.8466)
6b	Pale yellow solid	95	166.8—169.0	475.9046(475.9056)
7b	White solid	95	180—182	491.8763(491.8760)
8b	White solid	94	155—157	535.8259(535.8255)
9b	White solid	97	185—187	502.8991(502.9001)
10b	White solid	96	164—165	502.8988(502.9001)
11b	White solid	90	164—165	507.9308(507.9307)
12b	White solid	90	164.4—166.7	392.0214(392.0222)
13b	White solid	78	166.1—168.1	406.0374(406.0378)
14b	White solid	76	168.7—170.4	422.0327(422.0328)
15b	Yellow solid	84	156.1—157.5	531.9513(531.9518)
16b	Pale yellow solid	95	164.8—165.7	410.0123(410.0128)
17b	Yellow solid	94	199.5—201.4	425.9826(425.9832)
18b	White solid	94	177.1—178.9	471.9302(471.9307)
19b	White solid	95	148.6—149.9	437.0077(437.0073)
20b	White solid	93	175.5—176.3	437.0067(437.0073)

Compd.	¹H NMR(300 MHz, CDCl₃), δ	¹³C NMR(75 MHz, CDCl₃), δ
1b	7.74(dd, J=7.7, 1.5 Hz, 2H, ArH), 7.45—7.33(m, 3H, ArH), 6.80(s, 1H, NH), 6.46(s, 1H ,CH), 1.49(s, 3H ,CH₃), 1.43(s, 3H, CH₃)	176.12, 154.95, 131.95, 130.55, 129.97, 128.60, 89.90, 66.11, 58.56, 25.19, 24.88
2b	7.62(d, J=8.2 Hz, 2H, ArH), 7.17(d, J=8.1 Hz, 2H, ArH), 6.94(s, 1H , NH), 6.42(s, 1H, CH), 2.34(s, 3H, ArCH₃), 1.48(s, 3H , CH₃), 1.42(s, 3H, CH₃)	176.15, 155.01, 140.06, 130.45, 129.24, 128.87, 90.18, 65.96, 58.48, 25.11, 24.79, 21.20
3b	7.70(d, J=8.9 Hz, 2H, ArH), 6.88(d, J=8.9 Hz, 2H , ArH), 6.60(s, 1H, NH), 6.42(s, 1H, CH), 3.81(s, 3H, OCH₃), 1.49(s, 3H, CH₃), 1.43(s, 3H, CH₃)	176.07, 160.67, 154.90, 132.30, 123.62, 113.84, 90.55, 65.86, 58.47, 55.26, 25.20, 24.89
4b	7.07(s, 2H, ArH), 6.50(s, 1H, NH), 6.41(s, 1H, CH), 3.86(d, J=7.2 Hz, 9H, 3OCH₃), 1.45(s, 3H, CH₃)	176.14, 154.72, 152.89, 139.31, 126.70, 108.54, 90.31, 66.42, 60.84, 58.43, 56.35, 25.24, 24.94
5b	8.06(s, 1H, ArH), 7.04(s, 1H, NH), 6.76(s, 1H, NH), 6.74(s, 1H, CH), 3.91(s, 3H, OCH₃), 3.88(s, 3H, OCH₃), 1.47(s, 3H, CH₃), 1.39(s, 3H, CH₃)	175.98, 154.58, 150.33, 147.37, 122.62,116.50, 115.21, 114.83, 90.34, 63.98, 58.43, 56.09, 56.08, 25.16, 24.84
6b	7.79(d, J=3.7 Hz, 2H, ArH), 7.07(d, J=17.3 Hz, 2H ,ArH), 6.45(s, 1H, NH), 6.31(s, 1H, CH), 1.49(s, 3H, CH₃), 1.42(s, 3H, CH₃)	176.07, 154.87, 131.95, 130.56, 129.95, 128.58, 89.89, 66.12, 58.53, 25.20, 24.90
7b	7.72(d, J=8.4 Hz, 2H, ArH), 7.36(d, J=8.5 Hz, 2H, ArH), 6.52(s, 1H, NH), 6.41(s, 1H, CH), 1.46(d, J=22.2 Hz, 6H, 2CH₃)	175.93, 154.58, 136.28, 132.13, 130.28, 128.83, 89.45, 65.52, 58.61, 25.20, 24.92
8b	7.65(d, J=8.5 Hz, 2H, ArH), 7.52(d, J=8.5 Hz, 2H, ArH), 6.68(s, 1H, NH), 6.39(s, 1H, CH), 1.49(s, 3H, CH₃), 1.43(s, 3H, CH₃)	175.96, 154.69, 132.34, 131.81, 130.83, 124.62, 89.33, 65.60, 58.63, 25.17, 24.89
9b	8.25(d, J=8.9 Hz, 2H, ArH), 7.98(d, J=8.8 Hz, 2H, ArH), 6.51(s, 1H, NH), 5.94(s, 1H, CH), 1.51(s, 3H, CH₃), 1.45(s, 3H, CH₃)	175.70, 153.89, 148.63, 138.55, 131.81, 123.60 88.24, 65.14, 58.77, 25.24, 25.02
10b	8.75(d, J=1.5 Hz, 1H , ArH), 8.30(d, J=9.6 Hz, 1H, ArH), 8.14(d, J=7.9 Hz, 1H, ArH), 7.62(t, J=8.1 Hz, 1H, ArH), 6.69(s, 1H, NH), 6.50(s, 1H, CH), 1.52(s, 3H, CH₃), 1.47(s, 3H, CH₃)	175.96, 154.36, 148.03, 136.72, 133.66, 129.60, 126.00, 124.89, 88.53, 65.19, 58.87, 25.12, 24.92
11b	8.55(d, J=7.5 Hz, 1H, ArH), 7.99(d, J=8.6 Hz, 1H, ArH), 7.89(dd, J=14.0, 8.1 Hz, 2H, ArH), 7.53(dd, J=22.9, 15.0, 7.4 Hz, 3H, ArH), 7.22(s, 1H, NH), 6.17(s, 1H,CH), 1.42(s, 3H, CH₃), 1.27(s, 3H, CH₃)	175.84, 154.48, 133.87, 131.42, 130.59, 129.53, 128.57, 127.57, 126.50, 125.94, 124.43, 121.60, 89.73, 60.01, 58.47, 25.20, 24.79
12b	7.77(dd, J=7.3, 2.1 Hz, 2H, ArH), 7.45—7.34(m, 3H, ArH), 6.69(s, 1H, NH), 6.20(s, 1H, CH), 2.59(s, 3H, CH₃), 1.39(d, J=3.5 Hz, 6H, 2×CH₃)	176.99, 155.15, 132.96, 130.74, 129.54, 128.68, 95.75, 63.97, 58.35, 29.12, 24.93, 24.72
13b	7.65(d, J=8.2 Hz, 2H, ArH), 7.20(d, J=8.0 Hz, 2H, ArH), 6.51(s, 1H, NH), 6.17(s, 1H, CH), 2.59(s, 3H, CH₃), 2.37(ArCH₃), 1.38(d, J=6.2 Hz, 6H, 2×CH₃)	176.84, 139.39, 130.54, 129.96, 129.16, 96.02, 63.77, 58.31, 29.11, 24.98, 24.80
14b	7.71(d, J=8.8 Hz, 2H, ArH), 6.91(d, J=8.9 Hz, 2H, ArH), 6.48(s, 1H, NH), 6.15(s, 1H, CH), 3.82(s, 3H, OCH₃), 2.58(s,3H, CH₃), 1.38(d, J=4.5 Hz, 6H, 2×CH₃)	176.87, 160.38, 155.06, 132.31, 124.80, 113.98, 96.33, 63.55, 58.32, 55.29, 29.04, 24.90
15b	7.91(s, 1H, ArH), 7.06(s, 1H, ArH), 6.76(s, 1H, NH), 6.65(s, 1H, CH), 3.88(s, 3H, OCH₃), 3.87(s, 3H, OCH₃), 2.57(s, 3H, CH₃), 1.44(s, 3H, CH₃), 1.39(s, 2×CH₃)	176.87, 155.10, 150.08, 147.91, 123.87, 116.58, 115.49, 114.50, 97.83, 61.54, 58.45, 56.06, 31.20, 24.97
16b	7.67(d, J=8.5 Hz, 2H, ArH), 7.54(d, J=8.3 Hz, 2H, ArH), 6.51(s, 1H, NH), 6.16(s, 1H, CH), 2.57(s, 3H, CH₃), 1.39(d, J=6.4 Hz, 6H, 2×CH₃)	176.80, 154.84, 132.51, 132.30, 131.95, 124.15, 95.43, 63.37, 58.44, 29.10, 24.98, 24.83
17b	7.73(d, J=8.5 Hz, 2H, ArH), 7.38(d, J=8.5 Hz, 2H, ArH), 6.53—6.43(m, 1H, NH), 6.17(s, 1H, CH), 2.57(s, 3H, CH₃), 1.39(d, J=4.1 Hz, 6H, 2×CH₃)	176.79, 154.84, 135.85, 132.24, 131.37, 128.95, 95.53, 63.29, 58.43, 29.10, 24.89
18b	7.67(d, J=7.1 Hz, 2H, ArH), 7.54(d, J=5.5 Hz, 2H, ArH), 6.63(d, J=19.0 Hz, 1H, NH), 6.16(s, 1H, CH), 2.58(s, 3H, CH₃), 1.40(d, J=2.8 Hz, 6H, 2×CH₃)	176.83, 154.86, 132.49, 132.29, 131.94, 124.14, 95.45, 63.37, 58.43, 29.11, 24.96, 24.80
19b	8.26(d, J=8.8 Hz, 2H, ArH), 8.01(d, J=8.8 Hz, 2H, ArH), 6.51(s, 1H, NH), 6.30(s, 1H, CH), 2.59(s, 3H, CH₃), 1.42(d, J=7.1 Hz, 6H, 2×CH₃)	176.73, 154.57, 148.50, 139.71, 131.95,131.36, 128.87, 123.79, 94.87, 62.98, 58.62, 29.33, 24.98, 24.85
20b	8.74(s, 1H, ArH), 8.30(d, J=8.3 Hz, 1H, ArH), 8.17(d, J=7.8 Hz, 1H, ArH), 7.65(t, J=8.0 Hz, 1H, ArH), 6.85(s, 1H, NH), 6.31(s,1H, CH), 2.60(s, 3H, CH₃), 1.44(s, 6H, 2×CH₃)	176.82, 154.81, 148.20, 136.88, 134.72, 129.87, 125.89, 124.58, 95.18, 62.94, 58.71, 29.22, 25.08, 24.86