β-氨基膦酸酯衍生物的合成方法

doi:10.7503/cjcu20141126

摘要/Abstract

摘要：

以四丁基碘化铵(TBAI)为相转移催化剂, 催化(1-重氮基-2-氧代丙基)膦酸二甲酯(Ohira-Bestmann试剂)与芳香醛衍生的α-氨基砜的Mannich反应. 通过对反应条件进行筛选, 确定了-40 ℃下, 以甲苯为反应溶剂和质量分数为10%的LiOH溶液为碱的最佳反应条件. 通过底物的扩展, 合成了一系列β-氨基膦酸酯衍生物, 收率为52%~93%, 所得产物结构经核磁共振谱(NMR)和质谱(MS)表征. 通过Ohira-Bestmann试剂与α-氨基砜的Mannich反应, 提供了一条有效制备β-氨基膦酸酯衍生物的方法.

关键词: β-氨基膦酸酯衍生物, Mannich反应, α-氨基砜, 相转移催化

Abstract:

The Mannich reaction of Ohira-Bestmann reagent and α-amino sulfone was preliminary studied with tetrabutyl ammonium iodide(TBAI) as a phase transfer catalyst. Under the optimal reaction conditions, the Mannich reaction between Ohira-Bestmann reagent and a series α-amino sulfone derived from substituted aromatic aldehyde can be smoothly achieved. Moderate to good yields(52%—93%) were obtained and the structure of β-aminophosphonate derivatives 5a—5k were confirmed by ¹H NMR, ¹³C NMR and MS. By the Mannich reaction of Ohira-Bestmann reagent and α-amino sulfone, an effective method for the preparation of β-amino phosphonate derivatives was developed.

Key words: β-Aminophosphonate derivative, Mannich reaction, α-Amino sulfone, Phase-transfer catalysis

中图分类号:

O621.3

TrendMD:

熊珍, 季四平, 钏永明, 蒋琳, 袁明龙. β-氨基膦酸酯衍生物的合成方法. 高等学校化学学报, 2015, 36(6): 1112.

XIONG Zhen, JI Siping, CHUAN Yongming, JIANG Lin, YUAN Minglong. Synthesis Method of β-Aminophosphonate Derivatives^†. Chem. J. Chinese Universities, 2015, 36(6): 1112.

图/表 6

参考文献 27

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Compd.	Apperance	Yield^*(%)	LC-MS ([M+Na]⁺), m/z	Elemental analysis(%, calcd.)
Compd.	Apperance	Yield^*(%)	LC-MS ([M+Na]⁺), m/z	C	H	N
1a	Yellow oil	80	215.09(215.02)
1b	Yellow oil	75	243.08(243.05)
5a	Pale yellow oil	93	408.09(408.13)
5b	Pale yellow oil	90	408.07	50.01(49.87)	6.42(6.28)	11.13(10.90)
5c	Pale yellow oil	91	408.10	49.95(49.87)	6.39(6.28)	11.10(10.90)
5d	Pale yellow oil	85	378.15(378.12)
5e	Pale yellow oil	88	392.09(192.13)
5f	Pale yellow oil	83	422.14	47.85(48.12)	5.27(5.55)	10.24(10.52)
5g	Pale yellow oil	70	396.17(396.11)
5h	Pale yellow oil	65	412.20(412.08)
5i	Pale yellow oil	52	428.04	55.07(56.29)	5.78(5.97)	10.51(10.37)
5j	Pale yellow oil	70	384.15	43.08(43.21)	5.29(5.58)	11.47(11.63)
5k	Pale yellow oil	92	436.10	52.11(52.30)	6.92(6.83)	9.95(10.16)

Compd.	Apperance	Yield^*(%)	LC-MS ([M+Na]⁺), m/z	Elemental analysis(%, calcd.)
Compd.	Apperance	Yield^*(%)	LC-MS ([M+Na]⁺), m/z	C	H	N
1a	Yellow oil	80	215.09(215.02)
1b	Yellow oil	75	243.08(243.05)
5a	Pale yellow oil	93	408.09(408.13)
5b	Pale yellow oil	90	408.07	50.01(49.87)	6.42(6.28)	11.13(10.90)
5c	Pale yellow oil	91	408.10	49.95(49.87)	6.39(6.28)	11.10(10.90)
5d	Pale yellow oil	85	378.15(378.12)
5e	Pale yellow oil	88	392.09(192.13)
5f	Pale yellow oil	83	422.14	47.85(48.12)	5.27(5.55)	10.24(10.52)
5g	Pale yellow oil	70	396.17(396.11)
5h	Pale yellow oil	65	412.20(412.08)
5i	Pale yellow oil	52	428.04	55.07(56.29)	5.78(5.97)	10.51(10.37)
5j	Pale yellow oil	70	384.15	43.08(43.21)	5.29(5.58)	11.47(11.63)
5k	Pale yellow oil	92	436.10	52.11(52.30)	6.92(6.83)	9.95(10.16)

Compd.	¹H NMR(300 MHz, CDCl₃), δ	¹³C NMR(75 MHz, CDCl₃), δ
5b	7.26(d, J=7.4 Hz, 2H), 6.92(t, J=7.4 Hz, 1H), 6.89(t, J=7.5 Hz, 1H), 5.97—5.94(m, 1H), 5.68—5.61(m, 1H), 3.85(s, 3H), 3.71(d, J=11.6 Hz, 3H), 3.68—3.50(m, 3H), 1.43(s, 9 H)	156.7, 154.6, 128.8, 127.8, 127.7, 120.5, 110.4, 81.2, 55.2, 53.0, 52.2, 28.3
5c	7.27(d, J=6.0 Hz, 1H), 7.27(d, J=7.6 Hz, 1H), 6.91(s, 1H), 6.81(d, J=7.8 Hz, 1H), 5.59—5.44(m, 2H), 3.80(s, 3H), 3.71(d, J=11.6 Hz, 3H), 3.64(d, J=11.5 Hz, 3H), 1.44(s, 9H)	159.8, 154.8, 141.1, 129.6, 118.6, 113.2, 112.1, 80.9, 55.2, 52.5, 51.2, 28.4
5f	6.87—6.83(m, 2H), 6.77(d, J=8.0 Hz, 1H), 5.95(s, 2H), 5.57—5.38(m, 2H), 3.73(d, J= 11.8 Hz, 3H), 3.67(d, J=11.9 Hz, 3H), 1.46(s, 9 H)	154.7, 147.8, 147.1, 133.6, 119.7, 108.1, 107.1, 101.1, 81.2, 52.1, 50.9, 28.4
5i	7.85—7.80(m, 4H), 7.48—7.45(m, 3H), 5.72—5.68(m, 2H), 3.75(d, J=12.1 Hz, 3H), 3.69(d, J=11.8 Hz, 3H), 1.45(s, 9H)	154.9, 136.9, 133.2. 132.9. 128.5, 128.0, 127.6, 126.2, 126.0, 125.0, 124.6, 81.5, 52.5, 50.8, 30.0, 28.3
5j	7.22(d, J=4.7 Hz, 1H), 7.03(t, J=3.3 Hz, 1H), 7.95(dd, J=4.8, 3.6 Hz, 1H), 5.75—5.62(m, 2H), 3.80(d, J=12.3 Hz, 3H), 3.72(d, J=12.1 Hz, 3H), 1.45(s, 9H)	154.6, 143.9, 126.8, 124.9, 124.7, 80.1, 53.0, 52.5, 47.0, 28.4
5k	7.37—7.19(m, 2H), 6.95—6.77(m, 2H), 5.48(dd, J=18.0, 8.5 Hz, 1H), 4.24—3.86(m, 4H), 3.80(d, J=8.0 Hz, 3H), 1.56—1.36(m, 9H), 1.35—1.12(m, 6H)	159.3, 154.7, 131.3, 129.0, 127.5, 114.1, 80.1, 62.7, 62.0, 55.3, 28.1, 16.1

Compd.	¹H NMR(300 MHz, CDCl₃), δ	¹³C NMR(75 MHz, CDCl₃), δ
5b	7.26(d, J=7.4 Hz, 2H), 6.92(t, J=7.4 Hz, 1H), 6.89(t, J=7.5 Hz, 1H), 5.97—5.94(m, 1H), 5.68—5.61(m, 1H), 3.85(s, 3H), 3.71(d, J=11.6 Hz, 3H), 3.68—3.50(m, 3H), 1.43(s, 9 H)	156.7, 154.6, 128.8, 127.8, 127.7, 120.5, 110.4, 81.2, 55.2, 53.0, 52.2, 28.3
5c	7.27(d, J=6.0 Hz, 1H), 7.27(d, J=7.6 Hz, 1H), 6.91(s, 1H), 6.81(d, J=7.8 Hz, 1H), 5.59—5.44(m, 2H), 3.80(s, 3H), 3.71(d, J=11.6 Hz, 3H), 3.64(d, J=11.5 Hz, 3H), 1.44(s, 9H)	159.8, 154.8, 141.1, 129.6, 118.6, 113.2, 112.1, 80.9, 55.2, 52.5, 51.2, 28.4
5f	6.87—6.83(m, 2H), 6.77(d, J=8.0 Hz, 1H), 5.95(s, 2H), 5.57—5.38(m, 2H), 3.73(d, J= 11.8 Hz, 3H), 3.67(d, J=11.9 Hz, 3H), 1.46(s, 9 H)	154.7, 147.8, 147.1, 133.6, 119.7, 108.1, 107.1, 101.1, 81.2, 52.1, 50.9, 28.4
5i	7.85—7.80(m, 4H), 7.48—7.45(m, 3H), 5.72—5.68(m, 2H), 3.75(d, J=12.1 Hz, 3H), 3.69(d, J=11.8 Hz, 3H), 1.45(s, 9H)	154.9, 136.9, 133.2. 132.9. 128.5, 128.0, 127.6, 126.2, 126.0, 125.0, 124.6, 81.5, 52.5, 50.8, 30.0, 28.3
5j	7.22(d, J=4.7 Hz, 1H), 7.03(t, J=3.3 Hz, 1H), 7.95(dd, J=4.8, 3.6 Hz, 1H), 5.75—5.62(m, 2H), 3.80(d, J=12.3 Hz, 3H), 3.72(d, J=12.1 Hz, 3H), 1.45(s, 9H)	154.6, 143.9, 126.8, 124.9, 124.7, 80.1, 53.0, 52.5, 47.0, 28.4
5k	7.37—7.19(m, 2H), 6.95—6.77(m, 2H), 5.48(dd, J=18.0, 8.5 Hz, 1H), 4.24—3.86(m, 4H), 3.80(d, J=8.0 Hz, 3H), 1.56—1.36(m, 9H), 1.35—1.12(m, 6H)	159.3, 154.7, 131.3, 129.0, 127.5, 114.1, 80.1, 62.7, 62.0, 55.3, 28.1, 16.1