Synthesis Method of β-Aminophosphonate Derivatives†

doi:10.7503/cjcu20141126

Abstract

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

CLC Number:

O621.3

TrendMD:

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

Figures/Tables 6

References 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

Entry	Catalyst^a	Base^b	Solvent^c	Temperature/℃	Time/h	Yield^e(%)
1		K₂CO₃	Methanol	r.t.	15	60
2		K₂CO₃	Toluene/Methanol^d	r.t.	24	28
3		K₂CO₃	Toluene	r.t.	24	Trace
4	TBAI	Saturated K₂CO₃	Toluene	r.t.	48	16
5	TBAI	LiOH	Toluene	r.t.	24	62
6	TBAI	LiOH	Toluene	-20	24	85
7	TBAI	LiOH	Toluene	-40	25	93
8	TBAI	NaOH	Toluene	-40	20	85
9	TBAI	KOH	Toluene	-40	8	71
10	TBAB	LiOH	Toluene	-40	24	80
11	TMBAC	LiOH	Toluene	-40	24	55
12	18-Crown-6	LiOH	Toluene	-40	24	85
13	TBAI	LiOH	1,3-Xylene	-40	24	90
14	TBAI	LiOH	MTBE	-40	24	88
15	TBAI	LiOH	Ethylbenzene	-40	24	66
16	TBAI	LiOH	Isopropylbenzene	-40	24	50
17	TBAI	LiOH	Mesitylene	-40	24	Trace