대한화학회지 (Journal of the Korean Chemical Society)

  • 제48권5호
  • /
  • Pages.542-548
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  • 2004
  • /
  • 1017-2548(pISSN)
  • /
  • 2234-8530(eISSN)
대한화학회 (Korean Chemical Society)
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Synthesis of N-Diethoxyphosphinyl-1,2,3,4-tetrahydroisoquinoline 유도체의 합성

Synthesis of N-Diethoxyphosphinyl-1,2,3,4-Tetrahydroisoquinolines

  • 안성일 (원광대학교 자연과학부, 기초자연과학연구소) ;
  • 이동걸 (원광대학교 자연과학부, 기초자연과학연구소) ;
  • 오정미 (원광대학교 자연과학부, 기초자연과학연구소) ;
  • 김선희 (원광대학교 자연과학부, 기초자연과학연구소) ;
  • 윤한식 (원광보건대학 방사선과) ;
  • 이채호 (원광대학교 자연과학부, 기초자연과학연구소)
  • Al, Sung-Il (Department of Chemistry and Institute of Basic Natural Science, Wonkwang University) ;
  • Lee, Dong-Geol (Department of Chemistry and Institute of Basic Natural Science, Wonkwang University) ;
  • Oh, Jung-Mi (Department of Chemistry and Institute of Basic Natural Science, Wonkwang University) ;
  • Kim, Sun-Hee (Department of Chemistry and Institute of Basic Natural Science, Wonkwang University) ;
  • Yoon, Han-Sik (School of Medical Radiation, Wonkwang Helth Science College) ;
  • Lee, Chai-Ho (Department of Chemistry and Institute of Basic Natural Science, Wonkwang University)
  • 발행 : 2004.10.20
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초록

키워드

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 1H 및 13C 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 CH3SO3H(0.3 mL)을 녹인 dichloromethane(10 ml) 용액을 24 h동안 실온에서 교반한다. 반응용액을 물(50 mL×3)로 씻고, 무수 MgSO4로 건조시키고, 그리고 감압하에서 농축시킨다. 나머지를 flash column chromatography (chloroform: Ethylacetate=1:8)로 정제하면 THIQ 6이 얻어진다.

2-Diethoxyphosphinyl-6-methoxy-1,2,3,4-tetrahydro-isoquinoline (6a). 수득률: 75% (0.22 g); IR (KBr) 1257, 1030 cm−1; 1H NMR (CDCl3) δ 1.24 (t, J=7.1 Hz, 6H), 2.76 (t, J=5.7 Hz, 2H), 3.36 (td, J=5.7 Hz, 3JH,P=9.2 Hz, 2H), 3.72 (s, 3H), 3.93 (qdd, 3JH,P=6.7 Hz, J=6.7 and 10.2 Hz, 2H), 4.01 (qdd, 3JH,P=6.7 Hz, J=6.7 and 10.2 Hz, 2H), 4.19 (d, 3JH,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); 13C NMR (CDCl3) δ 16.1, 16.2, 29.3 (d, 3JC,P =15.2 Hz), 42.1 (d, 2JC,P=11.4 Hz), 45.7 (d, 2JC,P=15.2 Hz), 5.51, 55.2, 62.2, 62.3, 112.4, 113.8, 125.8 (d, 3JC,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; 1H NMR (CDCl3) δ 1.27 (t, J=7.1 Hz, 6H), 2.74 (t, J=5.7 Hz, 2H), 3.40 (td, J=5.7 Hz, 4JH,P=9.0 Hz, 2H), 3.80 (s, 3H), 3.82 (s, 3H), 3.96 (qdd, 3JH,P=7.1 Hz, J=7.1 and 10.2 Hz, 2H), 4.04 (qdd, 3JH,P=7.1 Hz, J=7.1 and 10.2 Hz, 2H), 4.21 13C (d, 3JH,P=5.9 Hz, 2H), 6.51 (s, 1H), 6.58 (s, 1H); NMR (CDCl3) δ 16.2, 16.3, 28.5 (d, 3JC,P=15.2 Hz), 42.3 (d, 2JC,P=11.4 Hz), 45.9 (d, 2JC,P=15.3 Hz), 55.9, 56.0, 62.2, 62.3, 108.9, 111.9, 125.6 (d, 3JC,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; 1H NMR (CDCl3) 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, 3JH,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, 3JH,P=1.9 Hz 1H), 3.85 (s, 6H), 3.98 (qdd, 3JH,P=7.6 Hz, J=7.6 and 10.2 Hz, 1H), 4.04 (qdd, 3JH,P=7.6 Hz, J=7.6 and 10.2 Hz, 2H), 4.10 (qdd, 3JH,P=7.6 Hz, J=7.6 and 10.2 Hz, 1H), 4.91 (td, J=6.3 Hz, 3JH,P=8.6 Hz, 1H), 6.59 (s, 1H), 6.65 (s, 1H) ppm; 13C NMR (CDCl3) δ 16.1 (d, 3JC,P=30.5 Hz), 16.2 (d, 3JC,P=34.3 Hz), 26.0, 27.7, 37.7, 50.9 (d, 2JC,P=22.9 Hz), 55.3, 56.1, 62.7 (d, 2JC,P=22.9 Hz), 62.8 (d, 2JC,P=22.9 Hz), 109.6, 111.9, 118.0, 125.9 (d, 3JC,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; 1H NMR (CDCl3) δ 1.15 (td, J=7.1 Hz, 4JH,P=0.9 Hz, 3H), 1.25 (td, J=7.1 Hz, 4JH,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, 3JH,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, 3JH,P=7.3 Hz, J=7.3 and 10.0 Hz, 1H), 3.79 (s, 1H), 3.86 (qdd, 3JH,P=7.3 Hz, J=7.3 and 10.0 Hz, 1H), 3.92 (qdd, 3JH,P=7.3 Hz, J=7.3 and 10.0 Hz, 1H), 4.00 (qdd, 3JH,P=7.3 Hz, J=7.3 and 10.0 Hz, 1H), 5.82 (d, 3JH,P=8.2 Hz, 1H) 6.66-6.71 (m, 2H), 6.86-6.88 (m, 1H), 7.18-7.28 (m, 5H) ppm; 13C NMR (CDCl3) δ 16.0 (d, 3JC,P=30.5 Hz), 16.2 (d, 3JC,P=30.5 Hz), 28.7, 36.8, 55.2, 57.3 (d, 2JC,P=19.1 Hz), 61.9 (d, 2JC,P=22.9 Hz), 62.2 (d, 2JC,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; 1H NMR (CDCl3) 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, 3JH,P=8.2 Hz, 1H), 6.41 (s, 1H), 6.65 (s, 1H), 7.24~7.27 (m, 6H) ppm; 13C NMR (CDCl3) δ 16.0 (d, 3JC,P=30.5 Hz), 16.2 (d, 3JC,P=30.5 Hz), 27.8, 36.8, 55.8, 55.9, 57.4 (d, 2JC,P=19.0 Hz), 61.9 (d, 2JC,P=22.9 Hz), 62.2 (d, 2JC,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; 1H NMR (CDCl3) 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, 3JH,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, 3JH,P=6.9 Hz, J=6.9 and 10.0 Hz, 1H), 3.79 (s, 3H), 3.83 (s, 3H), 3.89 (qdd, 3JH,P=6.9 Hz, J=6.9 and 10.0 Hz, 1H), 3.92 (qdd, 3JH,P=6.9 Hz, J=6.9 and 10.0 Hz, 1H), 4.01 (qdd, 3JH,P=6.9 Hz, J=6.9 and 10.0 Hz, 1H), 3.69~4.04 (m, 4H), 5.77 (d, 3JH,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; 13C NMR (CDCl3) δ 16.1 (d, 3JC,P=26.7 Hz), 16.2 (d, 3JC,P=26.7 Hz), 28.7, 36.6, 55.2, 55.9, 57.0, 61.8 (d, 2JC,P=19.1 Hz), 62.3 (d, 2JC,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; 1H NMR (CDCl3) δ 1.17 (td, J=6.9 Hz, 4JH,P =0.9 Hz, 3H), 1.26 (td, J=6.9 Hz, 4JH,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, 3JH,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, 3JH,P=7.0 Hz, J=7.0 and 10.1 Hz, 1H), 5.60 (bs, 1H), 5.76 (d, 3JH,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; 13C NMR (CDCl3) δ 16.1 (d, 3JC,P=30.5 Hz), 16.3 (d, 3JC,P=30.5 Hz), 27.9, 36.7, 55.8, 55.9, 56.0, 57.2 (d, 2JC,P=19.1 Hz), 61.8 (d, 2JC,P=19.1 Hz), 62.3 (d, 2JC,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; 1H NMR (CDCl3) 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, 3JH,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, 3JH,P=7.1 Hz, J=7.1 and 10.1 Hz, 1H), 3.92 (qdd, 3JH,P=7.1 Hz, J=7.1 and 10.1 Hz, 1H), 4.00 (qdd, 3JH,P=7.1 Hz, J=7.1 and 10.1 Hz, 1H), 4.04 (qdd, 3JH,P=7.1 Hz, J=7.1 and 10.1 Hz, 1H), 5.74 (d, 3JH,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; 13C NMR (CDCl3) δ 16.0 (d, 3JC,P=30.5 Hz), 16.1 (d, 3JC,P=30.5 Hz), 28.7, 37.9, 51.9 (d, 2JC,P=22.9 Hz), 55.2, 62.1 (d, 2JC,P=19.0 Hz), 62.3 (d, 2JC,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; 1H NMR (CDCl3) δ 1.19 (td, J=7.1 Hz, 4JH,P=0.9 Hz, 3H), 1.27 (td, J=7.1 Hz, 4JH,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, 3JH,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, 3JH,P=6.8 Hz, J=6.8 and 10.1 Hz, 1H), 3.99 (qdd, 3JH,P=6.8 Hz, J=6.8 and 10.1 Hz, 1H), 4.03 (qdd, 3JH,P=6.8 Hz, J=6.8 and 10.1 Hz, 1H), 5.71 (d, 3JH,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; 13C NMR (CDCl3) δ 16.1 (d, 3JC,P=30.5 Hz), 16.2 (d, 3JC,P=30.5 Hz), 27.9, 37.9 (d, 2JC,P=7.6 Hz), 52.0 (d, 2JC,P=22.9 Hz), 55.8, 56.0, 62.1 (d, 2JC,P=19.0 Hz), 62.3 (d, 2JC,P=19.0 Hz), 108.9, 109.9, 110.7, 111.5, 125.5 (d, 3JC,P=15.2 Hz), 126.6, 142.2, 147.2, 148.2, 155.8 (d, 3JC,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; 1H NMR (CDCl3) 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, 3JH,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, 3JH,P=6.8 Hz, J=6.8 and 10.0 Hz, 1H), 3.91 (qdd, 3JH,P=6.8 Hz, J=6.8 and 10.0 Hz, 1H), 3.98 (qdd, 3JH,P=6.8 Hz, J=6.8 and 10.0 Hz, 1H), 4.03 (qdd, 3JH,P=6.8 Hz, J=6.8 and 10.0 Hz, 1H), 5.98 (d, 3JH,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; 13C NMR (CDCl3) δ 16.1(d, 3JC,P=30.5 Hz), 16.2 (d, 3JC,P=30.5 Hz), 28.6, 37.3, 53.4 (d, 2JC,P=22.9 Hz), 55.2, 62.1 (d, 2JC,P=22.8 Hz), 62.4 (d, 2JC,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; 1H NMR (CDCl3) 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, 3JH,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, 3JH,P=7.2 Hz, J=7.2 and 10.2 Hz, 1H), 3.87 (s, 3H), 3.92 (qdd, 3JH,P=7.2 Hz, J=7.2 and 10.2 Hz, 1H), 4.01 (qdd, 3JH,P=7.2 Hz, J=7.2 and 10.2 Hz, 1H), 4.02 (qdd, 3JH,P=7.2 Hz, J=7.2 and 10.2 Hz, 1H), 5.95 (d, 3JH,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; 13C NMR (CDCl3) δ 16.0 (d, 3JC,P=26.7 Hz), 16.1 (d, 3JC,P=22.9 Hz), 27.7, 37.3, 53.5 (d, 2JC,P=26.7 Hz), 55.8, 56.0, 62.1 (d, 2JC,P=22.9 Hz), 62.4 (d, 2JC,P=22.9 Hz), 111.0, 111.4, 125.3, 126.2, 126.3, 127.0, 127.5 (d, 3JC,P=15.2 Hz), 147.2, 147.7 (d, 3JC,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; 1H NMR (CDCl3) 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, 3JH,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, 3JH,P=7.1, J=7.1 and 10.2 Hz, 1H), 3.72 (qdd, 3JH,P=7.1, J=7.1 and 10.2 Hz, 1H), 3.83 (s, 3H), 3.90 (qdd, 3JH,P=7.1, J=7.1 and 10.2 Hz, 1H), 4.77 (ddd, J=7.8 and 7.8 Hz, 3JH,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; 13C NMR (CDCl3) δ 16.1 (d, 3JC,P=30.5 Hz), 16.2 (d, 3JC,P=30.5 Hz), 27.7, 37.3, 43.5 (d, 2JC,P=11.4 Hz),, 55.6, 55.8, 61.8 (d, 2JC,P =22.9 Hz), 62.1 (d, 2JC,P=22.9 Hz), 110.3, 111.5, 125.4, 126.3, 128.3, 129.1 (d, 3JC,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 6l의 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 Table 2와 같다.

Table 1.aMelting points are uncorrected. bIsolated yields

Table 2.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 2는 이미 잘 알려진 방법에 따라, 2-arylethylamines 1과 diethyl chlorophospate/triethylamine의 반응으로 제조하였다.11 출발물질 2와 aldehyde 3(또는 4)의 반응은 dichloromethane에서 methanesulfonic acid를 촉매로 사용하였고, 실온에서 24시간의 반응으로 적당한 수득율로 THIQ 6이 생성되었으며, 반응은 iminium ion 5에 의하여 분자내 고리화 반응이 진행되는 것으로 예측된다.

THIQ 6의 수득율, 녹는점, 그리고 반응조건은 Table 1과 같다.

THIQ 6의 구조는 IR 흡수스펙트럼, NMR 스펙트럼 및 질량 분광스펙트럼, 그리고 6l의 X-선 구조결정 연구로 확인하였다. IR 스펙트럼에서 P=O기는 1226-126 cm−1에서 특정적 흡수띠가 나타났다.12 Aldehyde 3 또는 acetal 4에 의하여 주어진 THIQ 6의 methine 기의 양성자는 1H NMR 스펙트럼에서 δ 4.19-5.98 에서, 그리고 13C NMR 스펙트럼에서 탄소는 δ 45.7-57.4 ppm에서 나타났다. THIQ 6의 고리의 두 methylene 기의 양성자는 1H 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 13C NMR 스펙트럼에서 δ 36.3-42.3 과 27.4-29.3 ppm에서 각각 나타났다. 6의 대표적 화합물 6l의 X선 결정학 구조 연구에 의한 업체구조는 Fig. 1과 같으며 선별된 결합길이와 결합각은 Table 3에 나타내었다. 6I의 입체구조에서 두 개의 tetrahydroisoquinoline 고리의 평면에 대하여 고리와부의 벤질기는 서로 거의 수직을 이루어 입체장애를 최소화하고 있음을 보여준다.

Table 3.Selected bond lengths [Å] and angles [deg] for 6l

Fig. 1.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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피인용 문헌

  1. Synthesis, characterization and structure–activity relationship of novel N-phosphorylated E,E-3,5-bis(thienylidene)piperid-4-ones vol.45, pp.3, 2010, https://doi.org/10.1016/j.ejmech.2009.11.041
  2. 2‐(Het)aryl‐ N ‐phosphorylpyrrolidines via Cyclization of Phosphorus Acid Amides: A Regioselective Approach vol.5, pp.39, 2004, https://doi.org/10.1002/slct.202003353