Regiospecific Aminobromination of β-Nitrostyrene Derivatives with Acrylamide and N-Bromobutanimide†

doi:10.7503/cjcu20150883

Abstract

Abstract:

A new protocol for the high regioselective aminobromination of β-nitrostyrene derivatives with acrylamide and N-Bromobutanimide(NBS) as nitrogen/bromine sources was developed. β-Nitrostyrene derivatives reacted with acrylamide and NBS promoted by CH₃CH₂ONa at room temperature(without the protection of an inert gaseous atmosphere) in CH₂Cl₂, offered vicinal haloamine products in good yields(up to 83%). For the β-methyl-β-nitrostyrene, the good yields(up to 98%) were also achieved in CH₃OH promoted by Na₂CO₃. Although the strong electron-donating substituents(e.g., OCH₃) on the 4-position of benzene ring could deactivated the reaction activity of β-nitrostyrenederi-vetives, the vicinal haloamines were also afforded as the sole addition product. Whereas strong electron-withdrawing substituents(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 25 examples of β-nitrostyrenes were investigated and the structure of all products were confirmed by the corresponding nuclear magnetic resonance(NMR) spectra and high resolution mass spectrometer(HRMS). A possible mechanism involving a nucleophilic conjugate addition was proposed.

Key words: Aminobromination, β, -Nitrostyrene, Regiospecific, Acrylamide, N-Bromobutanimide

CLC Number:

O626.3

TrendMD:

DU Manfei, HOU Dan, HUI Wenping, CHEN Zhanguo. Regiospecific Aminobromination of β-Nitrostyrene Derivatives with Acrylamide and N-Bromobutanimide^†[J]. Chem. J. Chinese Universities, 2016, 37(5): 902.

Figures/Tables 10

References 37

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Compd.	m.p.(Ref.)/℃	Compd.	m.p.(Ref.)/℃
1a	57.1—58.5(58^[18])	14a	65.7—66.8(65—66^[28])
2a	100.1—102.1(102—102.5^[19])	15a	54.0—54.4(55^[29])
3a	84.4—86.0(85.5—87.5^[20])	16a	47.6—49(48^[30])
4a	143.6—144.2	17a	71.5—72.0
5a	133.6—135.1(133.5—134.5^[21])	18a	87.0—87.4(87—88^[31])
6a	98—99(98—99^[22])	19a	94.0—94.8(95^[32])
7a	101—103(101—102.5^[23])	20a	96.4—97.3(96—97^[22])
8a	114.3—115.4(113—114^[24])	21a	64.0—65.1(66^[33])
9a	149.3—150.6(151—153^[25])	22a	86—89(86—87^[34])
10a	56.2—57.8	23a	92.6—93.8(93—95^[33])
11a	123.1—124.3(124.5—126^[20])	24a	113.8—114.1(114—115^[35])
12a	105.4—105.8(106—107^[26])	25a	73.5—74.8(74^[36])
13a	120—122(121—122^[27])

Compd.	m.p.(Ref.)/℃	Compd.	m.p.(Ref.)/℃
1a	57.1—58.5(58^[18])	14a	65.7—66.8(65—66^[28])
2a	100.1—102.1(102—102.5^[19])	15a	54.0—54.4(55^[29])
3a	84.4—86.0(85.5—87.5^[20])	16a	47.6—49(48^[30])
4a	143.6—144.2	17a	71.5—72.0
5a	133.6—135.1(133.5—134.5^[21])	18a	87.0—87.4(87—88^[31])
6a	98—99(98—99^[22])	19a	94.0—94.8(95^[32])
7a	101—103(101—102.5^[23])	20a	96.4—97.3(96—97^[22])
8a	114.3—115.4(113—114^[24])	21a	64.0—65.1(66^[33])
9a	149.3—150.6(151—153^[25])	22a	86—89(86—87^[34])
10a	56.2—57.8	23a	92.6—93.8(93—95^[33])
11a	123.1—124.3(124.5—126^[20])	24a	113.8—114.1(114—115^[35])
12a	105.4—105.8(106—107^[26])	25a	73.5—74.8(74^[36])
13a	120—122(121—122^[27])

Compd.	Appearance	Yield^*(%)	m.p./℃	HRMS(calcd.), m/z[M+Na]⁺
1b	White solid	83	109.1—112.0	398.8948(398.8956)
2b	White solid	50	151.5—154.5	412.9104(412.9112)
3b	White solid	53	152.0—153.4	428.9033(428.9062)
4b	Faint yellow solid	43	142.4—144.8	458.9156(458.9167)
5b	Yellow solid	52	145.1—147.3	458.9140(458.9167)
6b	Faint yellow solid	50	167.0—168.7	536.8280(536.8272)
7b	White solid	48	153.7—156.3	416.8851(416.8862)
8b	White solid	56	162.3—164.5	432.8554(432.8586)
9b	White solid	56	142.2—148.7	476.8056(476.8061)
10b	White solid	57	141.2—143.0	466.8175(466.8176)
11b	White solid	81	138.9—140.8	443.8801(443.8807)
12b	Faint yellow solid	73	118.4—120.6	443.8802(443.8807)
13b	Faint yellow solid	58	169.4—171.5	448.9109(448.9112)
14b	White solid	93	144.8—148.5	335.0001(335.0007)
15b	White solid	44	153.0—154.2	349.0156(349.0164)
16b	White solid	51	128.9—129.6	365.0081(365.0113)
17b	White solid	44	109.8—112.0	395.0209(395.0219)
18b	White solid	19	173.5—175.1	395.0209(395.0219)
19b	White solid	16	149.7—152.0	425.0287(425.0324)
20b	White solid	45	177.4—179.5	472.9286(472.9324)
21b	White solid	52	139.9—141.9	352.9884(352.9913)
22b	White solid	54	156.1—160.5	368.9588(368.9618)
23b	White solid	55	146.2—149.6	412.9086(412.9112)
24b	Faint yellow solid	97	176.1—178.1	379.9825(379.9858)
25b	Orange red solid	60	150.9—152.7	379.9827(379.9858)

Compd.	Appearance	Yield^*(%)	m.p./℃	HRMS(calcd.), m/z[M+Na]⁺
1b	White solid	83	109.1—112.0	398.8948(398.8956)
2b	White solid	50	151.5—154.5	412.9104(412.9112)
3b	White solid	53	152.0—153.4	428.9033(428.9062)
4b	Faint yellow solid	43	142.4—144.8	458.9156(458.9167)
5b	Yellow solid	52	145.1—147.3	458.9140(458.9167)
6b	Faint yellow solid	50	167.0—168.7	536.8280(536.8272)
7b	White solid	48	153.7—156.3	416.8851(416.8862)
8b	White solid	56	162.3—164.5	432.8554(432.8586)
9b	White solid	56	142.2—148.7	476.8056(476.8061)
10b	White solid	57	141.2—143.0	466.8175(466.8176)
11b	White solid	81	138.9—140.8	443.8801(443.8807)
12b	Faint yellow solid	73	118.4—120.6	443.8802(443.8807)
13b	Faint yellow solid	58	169.4—171.5	448.9109(448.9112)
14b	White solid	93	144.8—148.5	335.0001(335.0007)
15b	White solid	44	153.0—154.2	349.0156(349.0164)
16b	White solid	51	128.9—129.6	365.0081(365.0113)
17b	White solid	44	109.8—112.0	395.0209(395.0219)
18b	White solid	19	173.5—175.1	395.0209(395.0219)
19b	White solid	16	149.7—152.0	425.0287(425.0324)
20b	White solid	45	177.4—179.5	472.9286(472.9324)
21b	White solid	52	139.9—141.9	352.9884(352.9913)
22b	White solid	54	156.1—160.5	368.9588(368.9618)
23b	White solid	55	146.2—149.6	412.9086(412.9112)
24b	Faint yellow solid	97	176.1—178.1	379.9825(379.9858)
25b	Orange red solid	60	150.9—152.7	379.9827(379.9858)

Compd.	¹H NMR(CDCl₃), δ	¹³C NMR(CDCl₃), δ
1b	7.46(dd, J=7.4, 2.1 Hz, 2H, ArH), 7.42—7.3(m, 3H, ArH), 6.71(d, J=9.9 Hz, 1H, NH), 6.45—6.40(m, 1H, CH), 6.40—6.33(m, 1H, CH), 6.20(dd, J=16.9, 10.2 Hz, 1H, CH), 5.77(dd, J=10.2, 1.2 Hz, 1H, CH)	164.2, 133.2, 129.8, 129.6, 129.1, 129.0, 128.7, 93.06, 62.78
2b	7.38(d, J=8.2 Hz, 2H, ArH), 7.18(d, J =8.0 Hz, 2H, ArH), 7.01(d, J=10.1 Hz, 1H, NH), 6.42(d, J=10.1 Hz, 1H, CH), 6.39(dd, J=17.0, 1.1 Hz, 1H, CH), 6.26(dd, J=17.0, 10.3 Hz, 1H, CH), 5.77(dd, J=10.3, 1.0 Hz, 1H, CH), 2.36(s, 3H, CH₃)	164.5, 139.9, 130.3, 129.7, 129.4, 129.0, 128.9, 93.56, 62.69, 21.20
3b	7.32(d, J=8.8 Hz, 2H, ArH), 7.15(d, J=10.1 Hz, 1H, NH), 6.78(d, J=8.8 Hz, 2H, ArH), 6.33(d, J=10.1 Hz, 1H, CH), 6.28(d, J=17.0 Hz, 1H, CH), 6.18(dd, J=17.0, 10.2 Hz, 1H, CH), 5.65(d, J=11.4 Hz, 1H, CH), 3.70(s, 3H, OCH₃)	164.6, 160.5, 130.5, 129.7, 128.9, 125.2, 114.0, 93.97, 62.51, 55.31
4b	7.02(dd, J=8.4, 2.1 Hz, 1H, ArH), 6.93(d, J=2.1 Hz, 1H, ArH), 6.83(d, J=8.4 Hz, 1H, ArH), 6.70(d, J=9.6 Hz, 1H, NH), 6.38(d, J=17.0 Hz, 1H, CH), 6.34(d, J=10.0 Hz, 1H, CH), 6.21(dd, J=16.9, 10.3 Hz, 1H, CH), 5.78(d, J=10.4 Hz, 1H, CH), 3.87(s, 6H, 2OCH₃)	164.3, 150.2, 148.9, 129.6, 129.0, 125.4, 121.5, 112.5, 111.0, 93.46, 62.74, 56.11, 55.90
5b	7.01(dd, J=8.4, 2.1 Hz, 1H, ArH), 6.93(d, J=2.1 Hz, 1H, ArH), 6.84(d, J=8.4 Hz, 1H, CH), 6.63(d, J=9.9 Hz, 1H, NH), 6.39(d, J=17.0 Hz, 1H, ArH), 6.33(d, J=10.0 Hz, 1H, CH), 6.21(dd, J=16.9, 10.3 Hz, 1H, CH), 5.78(d, J=10.3 Hz, 1H, CH), 3.88(s, 3H, OCH₃), 3.87(s, 3H, OCH₃)	164.2, 150.2, 148.9, 129.6, 129.0, 125.4, 121.4, 112.5, 111.0, 93.41, 62.73, 56.12, 55.91
6b	7.08(s, 1H, ArH), 7.01(s, 1H, ArH), 6.98(d, J=9.6 Hz, 1H, CH), 6.75(d, J=9.5 Hz, 1H, NH), 6.36(d, J=16.9 Hz, 1H, CH), 6.14(dd, J=16.9, 10.3 Hz, 1H, CH), 5.74(d, J=10.4 Hz, 1H, CH), 3.88(s, 3H, OCH₃), 3.85(s, 3H, OCH₃)	164.0, 150.5, 148.7, 129.2, 125.6, 117.7, 116.0, 110.5, 92.43, 61.13, 56.31, 56.20
7b	7.48(dd, J=8.7, 5.1 Hz, 2H, ArH), 7.06(t, J=8.6 Hz, 2H, ArH), 6.99(d, J=9.9 Hz, 1H, NH), 6.42(d, J=9.6 Hz, 1H, CH), 6.35(d, J=1.2 Hz, 1H, CH), 6.22(dd, J=16.9, 10.1 Hz, 1H, CH), 5.77(dd, J=10.1, 1.2 Hz, 1H, CH)	165.0, 164.5, 161.7, 131.2, 131.0, 129.4, 129.3, 129.2, 129.1, 115.9, 115.7, 93.04, 62.23
8b	7.42(d, J=8.6 Hz, 2H, ArH), 7.34(d, J=8.6 Hz, 2H, ArH), 6.94(d, J=9.9 Hz, 1H, NH), 6.42(s, 1H, CH), 6.40—6.33(m, 1H, CH), 6.21(dd, J=16.9, 10.1 Hz, 1H, CH), 5.78(dd, J=10.1, 1.2 Hz, 1H, CH)	164.4, 136.0, 131.8, 130.5, 129.4, 129.3, 129.0, 92.64, 62.28
9b	7.50(d, J=8.6 Hz, 2H, ArH), 7.35(d, J=8.5 Hz, 2H, ArH), 6.93(d, J=9.9 Hz, 1H, NH), 6.40(s, 1H, CH), 6.38—6.32(m, 1H, CH), 6.20(dd, J=16.9, 10.1 Hz, 1H, CH), 5.77(dd, J=10.1, 1.2 Hz, 1H, CH)	164.4, 132.3, 131.9, 130.8, 129.4, 129.3, 124.3, 92.49, 62.36
10b	7.62(d, J=2.1 Hz, 1H, ArH), 7.47(d, J=8.4 Hz, 1H, ArH), 7.35(dd, J=8.4, 2.2 Hz, 1H, ArH), 6.95(d, J=9.8 Hz, 1H, NH), 6.41(d, J=8.8 Hz, 1H, CH), 6.39(s, 1H, CH), 6.24(dd, J=16.9, 10.3 Hz, 1H, CH), 5.82(d, J=10.4 Hz, 1H, CH)	164.4, 134.4, 133.5, 133.0, 131.0, 130.6, 129.7, 129.2, 128.6, 91.92, 61.92
11b	8.24(d, J=8.8 Hz, 2H, ArH), 7.72(d, J=8.8 Hz, 2H, ArH), 6.88(d, J=9.7 Hz, 1H, NH), 6.52(d, J=9.8 Hz, 1H, CH), 6.40(dd, J=16.9, 1.2 Hz, 1H, CH), 6.22(dd, J=16.9, 10.2 Hz, 1H, CH), 5.82(dd, J=10.2, 1.1 Hz, 1H, CH)	164.4, 148.5, 140.3, 130.4, 129.9, 129.0, 123.7, 91.25, 62.25
12b	7.43—7.35(m, 2H, ArH), 7.32—7.29(m, 2H, ArH), 6.73(d, J=10.0 Hz, 1H, NH), 6.34(d, J=10.1 Hz, 1H, CH), 6.30(dd, J=16.9, 0.9 Hz, 1H, CH), 6.14(dd, J=17.0, 10.3 Hz, 1H, CH), 5.69(d, J=10.4 Hz, 1H, CH)	164.3, 133.3, 129.8, 129.6, 129.1, 129.0, 128.7, 93.12, 62.82
13b	7.97(s, 1H, ArH), 7.86(t, J=7.9 Hz, 3H, ArH), 7.62—7.52(m, 3H, ArH), 6.89(d, J=9.8 Hz, 1H, NH), 6.61(d, J=10.0 Hz, 1H, CH), 6.41(d, J=16.9 Hz, 1H, CH), 6.26(dd, J=16.9, 10.3 Hz, 1H, CH), 5.80(d, J=10.3 Hz, 1H, CH)	164.3, 133.6, 132.7, 130.5, 129.6, 129.5, 129.1, 128.6, 128.4, 127.7, 127.3, 126.8, 125.4, 93.04, 63.01
14b	7.34(dd, J=5.0, 1.8 Hz, 3H, ArH), 7.29—7.25(m, 2H, ArH), 6.37(dd, J=17.0, 0.9 Hz, 1H, CH), 6.24(dd, J=17.0, 10.3 Hz, 1H, CH), 5.83(d, J=9.7 Hz, 1H, CH), 5.76(dd, J=10.3, 0.9 Hz, 1H), 2.25(s, 3H, CH₃)	164.6, 134.1, 130.2, 129.4, 129.0, 128.2, 96.19, 60.63, 29.55
15b	7.14(s, 4H, ArH), 6.36(dd, J=17.0, 1.5 Hz, 1H, CH), 6.23(dd, J=17.0, 10.0 Hz, 1H, CH), 5.80(d, J=9.7 Hz, 1H, CH), 5.74(dd, J=10.0, 1.5 Hz, 1H, CH), 2.33(d, J=8.9 Hz, 3H, CH₃), 2.22(d, J=14.5 Hz, 3H, CH₃)	164.7, 139.3, 131.1, 130.2, 129.6, 129.3, 128.5, 128.1, 96.61, 60.37, 29.34, 21.09
16b	7.19(d, J=8.7 Hz, 2H, ArH), 6.84(d, J=8.8 Hz, 2H, ArH), 6.36(dd, J=17.0, 1.2 Hz, 1H, CH), 6.23(dd, J=17.0, 10.3 Hz, 1H, CH), 5.80(d, J=9.7 Hz, 1H, CH), 5.74(dd, J=10.3, 1.2 Hz, 1H, CH), 3.78(s, 3H, CH₃), 2.24(s, 3H, CH₃)	164.6, 160.2, 130.2, 129.8, 129.4, 128.1, 126.0, 114.4, 114.1, 96.7, 60.11, 55.29, 29.4
17b	7.74(d, J=9.4 Hz, 1H, NH), 6.88(d, J=8.0 Hz, 1H, ArH), 6.83(s, 1H, ArH), 6.76(d, J=8.2 Hz, 1H, ArH), 6.31(d, J=17.1 Hz, 1H, CH), 6.25(t, J=13.4 Hz, 1H, CH), 5.89(d, J=9.5 Hz, 1H, CH), 5.66(d, J=8.7 Hz, 1H, CH), 3.80(s, 3H, OCH₃), 3.77(s, 3H, OCH₃), 2.25(s, 3H, CH₃)	165.0, 149.7, 149.0, 130.1, 128.2, 126.5, 121.0, 111.8, 111.2, 96.9, 60.40, 55.98, 55.81, 28.87
18b	7.51(d, J=8.7 Hz, 1H, ArH), 6.72(dd, J=7.5, 5.8 Hz, 1H, ArH), 6.51(dd, J=5.8, 3.0 Hz, 1H, ArH), 6.45(d, J=2.6 Hz, 1H, CH), 6.38(dt, J=17.1, 3.7 Hz, 1H, CH), 6.26(t, J=6.5 Hz, 1H, CH), 5.75(dd, J=10.1, 1.4 Hz, 1H, CH), 3.86(s, 3H, OCH₃), 3.74(s, 3H, OCH₃), 2.27(s, 3H, CH₃)	164.5, 160.4, 157.2, 136.1, 129.9, 128.3, 105.8, 103.8, 100.2, 93.82, 59.33, 56.43, 55.58, 28.24
19b	6.46(s, 2H, ArH), 6.39(dd, J=17.0, 1.1 Hz, 1H, CH), 6.26(dd, J=17.0, 10.3 Hz, 1H, CH), 5.78(dd, J=10.3, 1.1 Hz, 1H, CH), 5.72(d, J=9.6 Hz, 1H, CH), 3.82(s, 9H, 3OCH₃), 2.25(s, 3H, CH₃)	164.6, 153.5, 138.9, 130.1, 129.4, 128.3, 105.4, 95.68, 60.93, 60.82, 56.28, 29.71
20b	7.04(t, J=17.9 Hz, 2H, ArH), 6.56(s, 1H, CH), 6.43—6.38(m, 1H, CH), 6.29—6.26(m, 1H, CH), 5.77(d, J=10.3 Hz, 1H, CH), 3.86(s, 3H, OCH₃), 3.78(s, 3H, OCH₃), 2.27(s, 3H, CH₃)	164.5, 150.1, 149.3, 129.9, 128.4, 125.8, 116.2, 116.0, 115.7, 109.6, 94.06, 60.40, 59.44, 21.04
21b	7.27(dd, J=6.0, 2.7 Hz, 2H, ArH), 7.02(t, J=8.6 Hz, 2H, ArH), 6.37(dd, J=17.0, 1.1 Hz, 1H, CH), 6.23(dd, J=17.0, 10.3 Hz, 1H, CH), 5.85(d, J=9.6 Hz, 1H, CH), 5.76(dd, J=10.3, 1.1 Hz, 1H, CH), 2.25(s, 3H, CH₃)	164.7, 163.9, 130.5, 130.1, 130.1, 129.9, 128.5, 116.1, 116.0, 96.41, 59.98, 29.41
22b	7.31(d, J=8.5 Hz, 2H, ArH), 7.22(d, J=8.5 Hz, 2H, ArH), 6.37(dd, J=17.0, 1.1 Hz, 1H, CH), 6.23(dd, J=17.0, 10.3 Hz, 1H, CH), 5.83(d, J=9.6 Hz, 1H, CH), 5.76(dd, J=10.3, 1.1 Hz, 1H, CH), 2.25(s, 3H, CH₃)	164.7, 135.5, 132.7, 130.0, 129.9, 129.6, 129.2, 128.9, 128.5, 96.17, 60.06, 29.39
23b	7.47(d, J=8.5 Hz, 2H, ArH), 7.16(d, J=8.5 Hz, 2H, ArH), 6.37(dd, J=17.0, 1.0 Hz, 1H, CH), 6.23(dd, J=17.0, 10.3 Hz, 1H, CH), 5.81(d, J=9.6 Hz, 1H, CH), 5.77(dd, J=10.3, 1.0 Hz, 1H, CH), 2.25(s, 3H, CH₃)	164.7, 133.2, 132.2, 131.9, 130.2, 129.9, 129.9, 128.5, 123.7, 96.03, 60.13, 29.44
24b	8.21(d, J=7.0 Hz, 3H, ArH, NH), 7.49(d, J=8.7 Hz, 2H, ArH), 6.39(d, J=16.3 Hz, 1H, CH), 6.2(dd, J=17.0, 10.3 Hz, 1H, CH), 5.92(d, J=9.3 Hz, 1H, CH), 5.82(d, J=10.4 Hz, 1H, CH), 2.30(s, 3H, CH₃)	171.6, 165.3, 148.2, 141.7, 130.0, 129.9, 129.5, 129.0, 123.7, 96.59, 59.95, 21.04
25b	7.99(dd, J=20.3, 8.1 Hz, 1H, ArH), 7.72(d, J=53.7 Hz, 1H, ArH), 7.63—7.50(m, 2H, ArH), 7.01(dd, J=31.6, 8.0 Hz, 1H, CH), 6.79—6.66(m, 1H, CH), 6.34(dd, J=27.1, 16.6 Hz, 1H, CH), 5.75(dd, J=17.5, 9.7 Hz, 1H, CH), 2.27(d, J=6.2 Hz, 3H, CH₃)	164.7, 149.9, 133.9, 133.4, 130.2, 129.6, 128.0, 125.6, 125.4, 102.3, 54.90, 29.98