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Synthesis of N-Diethoxyphosphinyl-1,2,3,4-Tetrahydroisoquinolines
Synthesis of N-Diethoxyphosphinyl-1,2,3,4-Tetrahydroisoquinolines
Journal of the Korean Chemical Society. 2004. Oct, 48(5): 542-548
Copyright © 2004, The Korean Chemical Society
  • Received : August 10, 2004
  • Published : October 20, 2004
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성일 안
동걸 이
정미 오
선희 김
한식 윤
채호 이

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실 험
시약은 Aldrich제를 정제하지 않고 사용하였고, 용매는 Aldrich 및 덕산시약 EP급을 사용하였으며 필요에 따라 알려진 방법으로 정제하여 사용하였다. 합성된 물질의 확인을 위한 IR 스펙트럼은 JASCO FT/IR-5300 spectrophotometer, 그리고 1 H 및 13 C NMR 스펙트럼은 JEOL FT/NMR spectrophotometer(500 MHz)를 사용하였으며 내부표준물질은 tetramethylsilane(TMS)을 사용하였다. 질량분석 스펙트럼은 원광대학교의 Quatro AC 분광기를 사용하여 얻었다.
- Diethoxyphosphinyl-1,2,3,4-tetrahydroisoquinolines 6의 일반적인 합성법
화합물 2 (1.0 mmol), aldehyde 3 또는 acetal 4 (1.0 mmol), 그리고 CH 3 SO 3 H(0.3 mL)을 녹인 dichloromethane(10 ml) 용액을 24 h동안 실온에서 교반한다. 반응용액을 물(50 mL×3)로 씻고, 무수 MgSO 4 로 건조시키고, 그리고 감압하에서 농축시킨다. 나머지를 flash column chromatography (chloroform: Ethylacetate=1:8)로 정제하면 THIQ 6 이 얻어진다.
2-Diethoxyphosphinyl-6-methoxy-1,2,3,4-tetrahydro-isoquinoline (6a). 수득률: 75% (0.22 g); IR (KBr) 1257, 1030 cm −1 ; 1 H NMR (CDCl 3 ) δ 1.24 (t, J =7.1 Hz, 6H), 2.76 (t, J =5.7 Hz, 2H), 3.36 (td, J =5.7 Hz, 3 J H,P =9.2 Hz, 2H), 3.72 (s, 3H), 3.93 (qdd, 3 J H,P =6.7 Hz, J =6.7 and 10.2 Hz, 2H), 4.01 (qdd, 3 J H,P =6.7 Hz, J =6.7 and 10.2 Hz, 2H), 4.19 (d, 3 J H,P =5.9 Hz, 2H), 6.59 (d, J =2.4 Hz, 1H), 6.69 (dd, J =8.6 and 2.4 Hz, 1H), 6.91 (d, J =8.6 Hz, 1H); 13 C NMR (CDCl 3 ) δ 16.1, 16.2, 29.3 (d, 3 J C,P =15.2 Hz), 42.1 (d, 2 J C,P =11.4 Hz), 45.7 (d, 2 J C,P =15.2 Hz), 5.51, 55.2, 62.2, 62.3, 112.4, 113.8, 125.8 (d, 3 J C,P =26.7 Hz), 127.0, 135.3, 158.0 ppm; LR FBA MS: calcd for [M-1] + 300.1, found 299.5
2-Diethoxyphosphinyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (6b). 7 수득률: 80% (0.26 g); mp 68-70 ℃; IR (KBr) 1248, 1020 cm −1 ; 1 H NMR (CDCl 3 ) δ 1.27 (t, J =7.1 Hz, 6H), 2.74 (t, J =5.7 Hz, 2H), 3.40 (td, J =5.7 Hz, 4 J H,P =9.0 Hz, 2H), 3.80 (s, 3H), 3.82 (s, 3H), 3.96 (qdd, 3 J H,P =7.1 Hz, J =7.1 and 10.2 Hz, 2H), 4.04 (qdd, 3 J H,P =7.1 Hz, J =7.1 and 10.2 Hz, 2H), 4.21 13 C (d, 3 J H,P =5.9 Hz, 2H), 6.51 (s, 1H), 6.58 (s, 1H); NMR (CDCl 3 ) δ 16.2, 16.3, 28.5 (d, 3 J C,P =15.2 Hz), 42.3 (d, 2 J C,P =11.4 Hz), 45.9 (d, 2 J C,P =15.3 Hz), 55.9, 56.0, 62.2, 62.3, 108.9, 111.9, 125.6 (d, 3 J C,P =26.7 Hz), 126.0, 147.5, 147.6 ppm; LR FBA MS: calcd for [M-1] + 330.1, found 330.6.
2-Diethoxyphosphinyl-1-cyanomethyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (6c). 수득률: 64%(0.23 g): mp 102-104 ℃; IR (KBr) 1228, 1024 cm −1 ; 1 H NMR (CDCl 3 ) δ 1.28 (t, J =7.1 Hz, 3H), 12.9 (t, J =7.1 Hz, 3H), 2.59~2.64 (m, 1H), 2.85 (d, J =6.3 Hz, 2H), 2.88 (ddd, J =16.6, 11.3, and 5.8 Hz, 1H), 3.29 (dddd, 3 J H,P =13.9 Hz, J =13.9, 11.3, and 3.9 Hz, 1H), 3.60 (dddd, J =13.9, 8.0, and 5.8 Hz, 3 J H,P =1.9 Hz 1H), 3.85 (s, 6H), 3.98 (qdd, 3 J H,P =7.6 Hz, J =7.6 and 10.2 Hz, 1H), 4.04 (qdd, 3 J H,P =7.6 Hz, J =7.6 and 10.2 Hz, 2H), 4.10 (qdd, 3 J H,P =7.6 Hz, J =7.6 and 10.2 Hz, 1H), 4.91 (td, J =6.3 Hz, 3 J H,P =8.6 Hz, 1H), 6.59 (s, 1H), 6.65 (s, 1H) ppm; 13 C NMR (CDCl 3 ) δ 16.1 (d, 3 J C,P =30.5 Hz), 16.2 (d, 3 J C,P =34.3 Hz), 26.0, 27.7, 37.7, 50.9 (d, 2 J C,P =22.9 Hz), 55.3, 56.1, 62.7 (d, 2 J C,P =22.9 Hz), 62.8 (d, 2 J C,P =22.9 Hz), 109.6, 111.9, 118.0, 125.9 (d, 3 J C,P =19.1 Hz), 126.2, 147.7, 148.6 ppm; LR FBA MS: calcd for [M-1] + 369.1, found 369.7
2-Diethoxyphosphinyl-1-phenyl-6-methoxy-1,2,3,4-tetrahydroisoquinoline (6d). 수득률: 50%(0.18 g): mp 70-72 ℃; IR (KBr) 1249, 1016 cm −1 ; 1 H NMR (CDCl 3 ) δ 1.15 (td, J =7.1 Hz, 4 J H,P =0.9 Hz, 3H), 1.25 (td, J =7.1 Hz, 4 J H,P =0.9 Hz, 3H), 2.65-2.69 (m, 1H), 3.00 (ddd, J = 12.1, 12.7, and 6.3 Hz, 1H), 3.07 (dddd, 3 J H,P =13.3 Hz, J =12.9, 12.7, and 3.8 Hz, 1H), 3.42 (ddd, J =12.9, 6.2, and 6.3 Hz, 1H), 3.70 (qdd, 3 J H,P =7.3 Hz, J =7.3 and 10.0 Hz, 1H), 3.79 (s, 1H), 3.86 (qdd, 3 J H,P =7.3 Hz, J =7.3 and 10.0 Hz, 1H), 3.92 (qdd, 3 J H,P =7.3 Hz, J =7.3 and 10.0 Hz, 1H), 4.00 (qdd, 3 J H,P =7.3 Hz, J =7.3 and 10.0 Hz, 1H), 5.82 (d, 3 J H,P =8.2 Hz, 1H) 6.66-6.71 (m, 2H), 6.86-6.88 (m, 1H), 7.18-7.28 (m, 5H) ppm; 13 C NMR (CDCl 3 ) δ 16.0 (d, 3 J C,P =30.5 Hz), 16.2 (d, 3 J C,P =30.5 Hz), 28.7, 36.8, 55.2, 57.3 (d, 2 J C,P =19.1 Hz), 61.9 (d, 2 J C,P =22.9 Hz), 62.2 (d, 2 J C,P =22.9 Hz), 112.4, 113.5, 127.2, 127.8, 128.0, 129.0, 129.6, 135.9, 143.6, 158.2 ppm; LR FBA MS: calcd for [M-1] + 376.1, found 376.4.
2-Diethoxyphosphinyl-1-phenyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (6e). 수득률: 56%(0.23 g): mp 88-90 ℃; IR (KBr) 1230, 1026 cm −1 ; 1 H NMR (CDCl 3 ) δ 1.16 (t, J =7.1 Hz, 3H), 1.27 (t, J =6.9 Hz, 3H), 2.60-2.63 (m, 1H), 2.93-3.07 (m, 2H), 3.39 (ddd, J =13.3, 5.9, and 5.9 Hz, 1H), 3.72 (s, 3H), 3.86 (s,3H), 3.96-4.04 (m, 4H), 5.81 (d, 3 J H,P =8.2 Hz, 1H), 6.41 (s, 1H), 6.65 (s, 1H), 7.24~7.27 (m, 6H) ppm; 13 C NMR (CDCl 3 ) δ 16.0 (d, 3 J C,P =30.5 Hz), 16.2 (d, 3 J C,P =30.5 Hz), 27.8, 36.8, 55.8, 55.9, 57.4 (d, 2 J C,P =19.0 Hz), 61.9 (d, 2 J C,P =22.9 Hz), 62.2 (d, 2 J C,P =22.8 Hz), 111.0, 111.4, 126.8, 127.3, 128.0, 129.1, 143.3, 147.3, 148.0 ppm; LR FBA MS: calcd for [M-1] + 406.1, found 406.4
2-Diethoxyphosphinyl-1-[3-methoxy-4-hydroxyphenyl]-6-methoxy-1,2,3,4-tetrahydroisoquinoline (6f); 수득률 : 53%(0.22 g): mp 67-69 ℃; IR (KBr) 1246, 1032 cm −1 ; 1 H NMR (CDCl 3 ) δ 1.16 (t, J =7.1 Hz, 3H), 1.26 (t, J =7.1 Hz, 3H), 2.64-2.69 (m, 1H), 2.98 (ddd, J =14.2, 13.6, and 6.5 Hz, 1H), 3.05 (dddd, 3 J H,P =13.0 Hz, J =13.3, 13.6, and 3.0 Hz, 1H), 3.39 (ddd, J =13.3, 6.7, and 6.5 Hz, 1H), 3.72 (qdd, 3 J H,P =6.9 Hz, J =6.9 and 10.0 Hz, 1H), 3.79 (s, 3H), 3.83 (s, 3H), 3.89 (qdd, 3 J H,P =6.9 Hz, J =6.9 and 10.0 Hz, 1H), 3.92 (qdd, 3 J H,P =6.9 Hz, J =6.9 and 10.0 Hz, 1H), 4.01 (qdd, 3 J H,P =6.9 Hz, J =6.9 and 10.0 Hz, 1H), 3.69~4.04 (m, 4H), 5.77 (d, 3 J H,P =8.2 Hz, 1H), 6.48 (dd, J =8.2 and 1.9 Hz, 1H), 6.68-6.70 (m, 2H), 6.75 (d, J =8.2 Hz, 1H), 6.88 (d, J =8.2 Hz, 1H), 6.99 (d, J =1.9 Hz, 1H) ppm; 13 C NMR (CDCl 3 ) δ 16.1 (d, 3 J C,P =26.7 Hz), 16.2 (d, 3 J C,P =26.7 Hz), 28.7, 36.6, 55.2, 55.9, 57.0, 61.8 (d, 2 J C,P =19.1 Hz), 62.3 (d, 2 J C,P =19.1 Hz), 111.8, 112.3, 113.4, 113.5, 121.9, 128.1, 129.6, 135.9, 144.8, 146.3, 158.2 ppm; LR FBA MS: calcd for [M-1] 420.1, found 420.7.
2-Diethoxyphosphinyl-1-[3-methoxy-4-hydroxyphenyl]-6,7-methoxy-1,2,3,4-tetrahydroisoquinoline (6g); 수득 률: 56%(0.25 g): mp 118-120 ℃; IR (KBr) 1228, 1032 cm −1 ; 1 H NMR (CDCl 3 ) δ 1.17 (td, J =6.9 Hz, 4 J H,P =0.9 Hz, 3H), 1.26 (td, J =6.9 Hz, 4 J H,P =0.9 Hz, 3H), 2.58~2.62 (m, 1H), 2.93 (ddd, J =15.8, 15.0, and 6.4 Hz, 1H), 3.03 (dddd, 3 J H,P =14.2 Hz, J =13.9, 15.0, and 4.1 Hz, 1H), 3.37 (ddd, J =13.9, 6.4, and 6.7 Hz, 1H), 3.73 (s, 3H), 3.69-3.77 (m, 1H) 3.83 (s, 3H), 3.89 (s, 3H), 3.85-3.95 (m, 2H), 4.01 (qdd, 3 J H,P =7.0 Hz, J =7.0 and 10.1 Hz, 1H), 5.60 (bs, 1H), 5.76 (d, 3 J H,P =8.2 Hz, 1H), 6.43 (s, 1H), 6.52 (dd, J =8.0 and 1.8 Hz, 1H), 6.63 (s, 1H), 6.76 (d, J =8.0 Hz, 1H), 7.00 (d, J =1.8 Hz, 1H) ppm; 13 C NMR (CDCl 3 ) δ 16.1 (d, 3 J C,P =30.5 Hz), 16.3 (d, 3 J C,P =30.5 Hz), 27.9, 36.7, 55.8, 55.9, 56.0, 57.2 (d, 2 J C,P =19.1 Hz), 61.8 (d, 2 J C,P =19.1 Hz), 62.3 (d, 2 J C,P =22.9 Hz), 111.0, 111.3, 111.8, 113.4, 122.0, 126.7, 127.4, 135.5, 144.9, 146.3, 147.2, 147.9 ppm; LR FBA MS: calcd for [M-1] 450.1, found 450.7.
2-Diethoxyphosphinyl-1-[2-furyl]-6-methoxy-1,2,3,4-tetrahydroisoquinoline (6h); 수득률: (0.19 g): mp 90-91 ℃; IR (KBr) 1251, 1022 cm −1 ; 1 H NMR (CDCl 3 ) δ 1.20 (t, J =7.1 Hz, 3H), 1.27 (t, J =7.1 Hz, 3H), 2.63-2.67 (m, 1H), 2.97 (ddd, J =16.7, 12.2, and 6.4 Hz, 1H), 3.19 (dddd, 3 J H,P =12.9 Hz, J =13.3, 12.2, and 4.0 Hz, 1H), 3.53 (ddd, J =13.3, 7.1, and 6.4 Hz, 1H), 3.78 (s, 3H), 3.86 (qdd, 3 J H,P =7.1 Hz, J =7.1 and 10.1 Hz, 1H), 3.92 (qdd, 3 J H,P =7.1 Hz, J =7.1 and 10.1 Hz, 1H), 4.00 (qdd, 3 J H,P =7.1 Hz, J =7.1 and 10.1 Hz, 1H), 4.04 (qdd, 3 J H,P =7.1 Hz, J =7.1 and 10.1 Hz, 1H), 5.74 (d, 3 J H,P =8.2 Hz, 1H), 5.92 (d, J =3.0 Hz, 1H), 6.24 (dd, J =3.0 and 1.8 Hz, 1H), 6.66 (d, J =2.5 Hz, 1H), 6.71 (dd, J =8.2 and 2.5 Hz, 1H), 7.00 (d, J =8.2 Hz, 1H), 7.34 (d, J =1.8 Hz, 1H) ppm; 13 C NMR (CDCl 3 ) δ 16.0 (d, 3 J C,P =30.5 Hz), 16.1 (d, 3 J C,P =30.5 Hz), 28.7, 37.9, 51.9 (d, 2 J C,P =22.9 Hz), 55.2, 62.1 (d, 2 J C,P =19.0 Hz), 62.3 (d, 2 J C,P =19.0 Hz), 108.8, 109.9, 112.4, 113.6, 125.9, 129.2, 135.8, 142.2, 156.0, 158.4 ppm; LR FBA MS: calcd for [M-1] + 366.1, found 366.5.
2-Diethoxyphosphinyl-1-[2-furyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (6i). 수득률: 59%(0.23 g): IR (KBr) 1248, 1024 cm −1 ; 1 H NMR (CDCl 3 ) δ 1.19 (td, J =7.1 Hz, 4 J H,P =0.9 Hz, 3H), 1.27 (td, J =7.1 Hz, 4 J H,P =0.9 Hz, 3H), 2.56-2.60 (m, 1H), 2.91 (ddd, J =16.7, 12.3, and 6.3 Hz, 1H), 3.16 (dddd, 3 J H,P =13.0 Hz, J =13.4, 12.3, and 4.1 Hz, 1H), 3.51 (ddd, J =13.4, 6.9, and 6.3 Hz, 1H), 3.76 (s, 3H), 3.85 (s, 3H), 3.82-3.88 (m, 1H), 3.92 (qdd, 3 J H,P =6.8 Hz, J =6.8 and 10.1 Hz, 1H), 3.99 (qdd, 3 J H,P =6.8 Hz, J =6.8 and 10.1 Hz, 1H), 4.03 (qdd, 3 J H,P =6.8 Hz, J =6.8 and 10.1 Hz, 1H), 5.71 (d, 3 J H,P =7.3 Hz, 1H), 5.93 (dd, J =3.2 and 0.9 Hz, 1H), 6.24 (dd, J =3.2 and 1.8 Hz, 1H), 6.54 (s, 1H), 6.60 (s, 1H), 7.34 (dd, J =1.8 and 0.9 Hz, 1H) ppm; 13 C NMR (CDCl 3 ) δ 16.1 (d, 3 J C,P =30.5 Hz), 16.2 (d, 3 J C,P =30.5 Hz), 27.9, 37.9 (d, 2 J C,P =7.6 Hz), 52.0 (d, 2 J C,P =22.9 Hz), 55.8, 56.0, 62.1 (d, 2 J C,P =19.0 Hz), 62.3 (d, 2 J C,P =19.0 Hz), 108.9, 109.9, 110.7, 111.5, 125.5 (d, 3 J C,P =15.2 Hz), 126.6, 142.2, 147.2, 148.2, 155.8 (d, 3 J C,P =11.4 Hz) ppm; LR FBA MS: calcd for [M-1] + 396.1, found 396.7.
2-Diethoxyphosphinyl-1-[2-thiophenyl]-6-methoxy-1,2,3,4-tetrahydroisoquinoline (6j). 수득률: 54%(0.20 g): mp 92-94 ℃; IR (KBr) 1247, 1020 cm −1 ; 1 H NMR (CDCl 3 ) δ 1.19 (t, J =7.1 Hz, 3H), 1.27 (t, J =7.1 Hz, 3H), 2.63-2.67 (m, 1H), 2.98 (ddd, J =17.0, 12.6, and 6.4 Hz, 1H), 3.21 (dddd, 3 J H,P =13.5 Hz, J =13.8, 12.6, and 4.1 Hz, 1H), 3.51 (ddd, J =13.8, 7.1, and 6.4 Hz, 1H), 3.79 (s, 3H), 3.83 (qdd, 3 J H,P =6.8 Hz, J =6.8 and 10.0 Hz, 1H), 3.91 (qdd, 3 J H,P =6.8 Hz, J =6.8 and 10.0 Hz, 1H), 3.98 (qdd, 3 J H,P =6.8 Hz, J =6.8 and 10.0 Hz, 1H), 4.03 (qdd, 3 J H,P =6.8 Hz, J =6.8 and 10.0 Hz, 1H), 5.98 (d, 3 J H,P =8.2 Hz, 1H), 6.67 (d, J =2.6 Hz, 1H), 6.71 (dd, J =8.3 and 2.6 Hz, 1H), 6.77 (dd, J =3.6 and 1.1 Hz, 1H), 6.87 (dd, J =5.1 and 3.6 Hz, 1H), 7.02 (d, J =8.3 Hz, 1H), 7.20 (dd, J =5.1 and 1.1 Hz, 1H) ppm; 13 C NMR (CDCl 3 ) δ 16.1(d, 3 J C,P =30.5 Hz), 16.2 (d, 3 J C,P =30.5 Hz), 28.6, 37.3, 53.4 (d, 2 J C,P =22.9 Hz), 55.2, 62.1 (d, 2 J C,P =22.8 Hz), 62.4 (d, 2 J C,P =22.8 Hz), 112.3, 113.6, 125.3, 126.2, 126.9, 127.9, 129.5, 135.4, 148.1, 158.4 ppm; LR FBA MS: calcd for [M-1] + 382.1, found 382.4.
2-Diethoxyphosphinyl-1-[2-thiophenyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (6k). 수득률: 58% (0.249 g); IR (KBr) 1228, 1030 cm −1 ; 1 H NMR (CDCl 3 ) δ 1.19 (t, J =6.9 Hz, 3H), 1.27 (t, J =7.1 Hz, 3H), 2.58-2.6의 (m, 1H), 2.94 (ddd, J =16.9, 12.6, and 6.5 Hz, 1H), 3.19~3.21 (dddd, 3 J H,P =13.6 Hz, J =13.9, 12.6, and 3.9 Hz, 1H), 3.49 (ddd, J =13.9, 7.1, and 6.5 Hz, 1H), 3.77 (s, 3H), 3.92 (qdd, 3 J H,P =7.2 Hz, J =7.2 and 10.2 Hz, 1H), 3.87 (s, 3H), 3.92 (qdd, 3 J H,P =7.2 Hz, J =7.2 and 10.2 Hz, 1H), 4.01 (qdd, 3 J H,P =7.2 Hz, J =7.2 and 10.2 Hz, 1H), 4.02 (qdd, 3 J H,P =7.2 Hz, J =7.2 and 10.2 Hz, 1H), 5.95 (d, 3 J H,P =8.2 Hz, 1H), 6.57 (s, 1H), 6.6의 (s, 1H), 6.79 (d, J =3.4 Hz, 1H) 6.88 (dd, J =5.0 and 3.4 Hz, 1H), 7.21 (d, J =5.0 Hz, 1H) ppm; 13 C NMR (CDCl 3 ) δ 16.0 (d, 3 J C,P =26.7 Hz), 16.1 (d, 3 J C,P =22.9 Hz), 27.7, 37.3, 53.5 (d, 2 J C,P =26.7 Hz), 55.8, 56.0, 62.1 (d, 2 J C,P =22.9 Hz), 62.4 (d, 2 J C,P =22.9 Hz), 111.0, 111.4, 125.3, 126.2, 126.3, 127.0, 127.5 (d, 3 J C,P =15.2 Hz), 147.2, 147.7 (d, 3 J C,P =15.3 Hz), 148.2 ppm; LR FBA MS: calcd for [M-1] + 412.1, found 412.6.
2-Diethoxyphosphinyl-1-benzyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (6l). 수득률: 6의%(0.25 g): mp 99-101 ℃; IR (KBr) 1244, 1028 cm −1 ; 1 H NMR (CDCl 3 ) δ 1.11 (t, J =7.1 Hz, 3H), 1.19 (t, J =7.1 Hz, 3H), 2.54-2.58 (m, 1H), 2.91 (ddd, J =16.7, 11.4, and 5.9 Hz, 1H), 3.01 (dd, J =7.8 and 13.5 Hz, 1H), 3.13 (dd, J =7.8 and 13.5 Hz, 1H), 3.28 (dddd, 3 J H,P =14.8 Hz, J =14.8, 11.4, and 4.1 Hz, 1H), 3.52-3.57 (m, 2H), 3.58 (s, 3H), 3.69 (qdd, 3 J H,P =7.1, J =7.1 and 10.2 Hz, 1H), 3.72 (qdd, 3 J H,P =7.1, J =7.1 and 10.2 Hz, 1H), 3.83 (s, 3H), 3.90 (qdd, 3 J H,P =7.1, J =7.1 and 10.2 Hz, 1H), 4.77 (ddd, J =7.8 and 7.8 Hz, 3 J H,P =7.9 Hz, 1H), 69.1 (s, 1H), 6.55 (s, 1H), 7.17 (s, 1H), 7.19 (s, 1H), 7.20 (s, 1H), 7.26 (s, 1H), 7.28 (s, 1H) ppm; 13 C NMR (CDCl 3 ) δ 16.1 (d, 3 J C,P =30.5 Hz), 16.2 (d, 3 J C,P =30.5 Hz), 27.7, 37.3, 43.5 (d, 2 J C,P =11.4 Hz),, 55.6, 55.8, 61.8 (d, 2 J C,P =22.9 Hz), 62.1 (d, 2 J C,P =22.9 Hz), 110.3, 111.5, 125.4, 126.3, 128.3, 129.1 (d, 3 J C,P =15.2 Hz), 130.0, 138.7, 146.5, 147.6 ppm; LR FBA MS: calcd for [M-1] + 420.1, found 420.7.
6l의 X선 결정학적 실험. X선 결정학적 연구에 적당한 6l 의 단결정은 methanol-chloroform 포화용액으로부터 느린 증발법으로 만들었으며, 적절한 단결정을 선택하여 무작위 배향의 유리봉에 부착하였다. 회절반점의 세기는 Enraf-Nonius CAD-4 회절기로 얻었으며, Mo-Karadiatio(λ=0.71073Å)을 사용하였다. 분자구조는 SHELX-86의 직접법으로 풀었으며, 9 자료의 정밀화에는 SHELX-97 최소자승법을 이용하여 해석하였다. 10 회절자료 수집 및 정밀화 단계에서 사용한 정보와 최종 단위 세포상수 값 등은 2 와 같다.
Reaction condition, mp, and yield of THIQs 6
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aMelting points are uncorrected. bIsolated yields
Crystal data and structure refinement for6l
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aR1 = Σ‖Fo|-|Fc‖ (based on reflections with Fo2>2σF2) bwR2 = [Σ[w(Fo2-Fc2)2]/Σ[w(Fo2)2]]1/2; w = 1/[σ2(Fo2)+(0.095P)2]; P = [max(Fo2, 0)+2Fc2]/3(also with Fo2>2σF2)
결과 및 고찰
N -diethoxyphosphinyl-2-arylethylamine 2 는 이미 잘 알려진 방법에 따라, 2-arylethylamines 1 과 diethyl chlorophospate/triethylamine의 반응으로 제조하였다. 11 출발물질 2 와 aldehyde 3 (또는 4 )의 반응은 dichloromethane에서 methanesulfonic acid를 촉매로 사용하였고, 실온에서 24시간의 반응으로 적당한 수득율로 THIQ 6 이 생성되었으며, 반응은 iminium ion 5 에 의하여 분자내 고리화 반응이 진행되는 것으로 예측된다.
THIQ 6 의 수득율, 녹는점, 그리고 반응조건은 1 과 같다.
THIQ 6 의 구조는 IR 흡수스펙트럼, NMR 스펙트럼 및 질량 분광스펙트럼, 그리고 6l 의 X-선 구조결정 연구로 확인하였다. IR 스펙트럼에서 P=O기는 1226-126 cm −1 에서 특정적 흡수띠가 나타났다. 12 Aldehyde 3 또는 acetal 4 에 의하여 주어진 THIQ 6 의 methine 기의 양성자는 1 H NMR 스펙트럼에서 δ 4.19-5.98 에서, 그리고 13 C NMR 스펙트럼에서 탄소는 δ 45.7-57.4 ppm에서 나타났다. THIQ 6 의 고리의 두 methylene 기의 양성자는 1 H NMR 스펙트럼에서 δ 3.01-3.32, 3.13-3.60 및 2.55-2.69, 2.91-3.007 ppm에서 다중선으로 각각 나타났으며, 두 methylene기의 탄소는 13 C NMR 스펙트럼에서 δ 36.3-42.3 과 27.4-29.3 ppm에서 각각 나타났다. 6 의 대표적 화합물 6l 의 X선 결정학 구조 연구에 의한 업체구조는 . 1 과 같으며 선별된 결합길이와 결합각은 3 에 나타내었다. 6I 의 입체구조에서 두 개의 tetrahydroisoquinoline 고리의 평면에 대하여 고리와부의 벤질기는 서로 거의 수직을 이루어 입체장애를 최소화하고 있음을 보여준다.
Selected bond lengths [Å] and angles [deg] for6l
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Selected bond lengths [Å] and angles [deg] for 6l
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ORTEP view of 6l, with atom labeling scheme.
결 론
N -diethoxyphosphinyl-(2-arylethyl)amine 과 aldehyde (또는 acetal)의 반응으로 N -diethoxyphosphinyl-1,2,3,4-tetrahydroisoquinoline의 일반적인 합성법을 개발하였으며, X-선 구조결정법으로 화학구조를 확인하였다.
본 연구는 2003 년도 원광대학교 교내연구비 지원에 의하여 수행되었으며, 이에 감사드립니다. 본 실험의 측정된 X-선 회절자료는 저자( chaiho@wonkwang.ac.kr ) 로부터 구할 수 있습니다.
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