CN110003274A - 膦酰化二氢异喹啉酮类化合物及其制备方法 - Google Patents
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- -1 dihydro-isoquinoline ketone compounds Chemical class 0.000 title claims abstract description 45
- 238000005954 phosphonylation reaction Methods 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 238000006243 chemical reaction Methods 0.000 claims abstract description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229930015698 phenylpropene Natural products 0.000 claims abstract description 15
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims abstract description 12
- AUONHKJOIZSQGR-UHFFFAOYSA-N oxophosphane Chemical compound P=O AUONHKJOIZSQGR-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000002904 solvent Substances 0.000 claims abstract description 10
- 238000013019 agitation Methods 0.000 claims abstract description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- NHOWDZOIZKMVAI-UHFFFAOYSA-N (2-chlorophenyl)(4-chlorophenyl)pyrimidin-5-ylmethanol Chemical compound C=1N=CN=CC=1C(C=1C(=CC=CC=1)Cl)(O)C1=CC=C(Cl)C=C1 NHOWDZOIZKMVAI-UHFFFAOYSA-N 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 claims description 6
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 claims description 6
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 5
- 239000011630 iodine Substances 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 claims description 4
- 229910001958 silver carbonate Inorganic materials 0.000 claims description 4
- 229910001961 silver nitrate Inorganic materials 0.000 claims description 4
- 229910001923 silver oxide Inorganic materials 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- MDDUHVRJJAFRAU-YZNNVMRBSA-N tert-butyl-[(1r,3s,5z)-3-[tert-butyl(dimethyl)silyl]oxy-5-(2-diphenylphosphorylethylidene)-4-methylidenecyclohexyl]oxy-dimethylsilane Chemical compound C1[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)C(=C)\C1=C/CP(=O)(C=1C=CC=CC=1)C1=CC=CC=C1 MDDUHVRJJAFRAU-YZNNVMRBSA-N 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 8
- 238000004440 column chromatography Methods 0.000 abstract description 6
- 238000000926 separation method Methods 0.000 abstract description 6
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 abstract description 3
- 229910052709 silver Inorganic materials 0.000 abstract description 3
- 239000004332 silver Substances 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 39
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 20
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 13
- 238000005160 1H NMR spectroscopy Methods 0.000 description 13
- 238000004679 31P NMR spectroscopy Methods 0.000 description 13
- 238000010998 test method Methods 0.000 description 8
- 239000012467 final product Substances 0.000 description 6
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 5
- 230000007935 neutral effect Effects 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 4
- SCHRRICRQNJJKN-UHFFFAOYSA-N P.[O] Chemical compound P.[O] SCHRRICRQNJJKN-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 235000010290 biphenyl Nutrition 0.000 description 3
- 239000004305 biphenyl Substances 0.000 description 3
- 125000006267 biphenyl group Chemical group 0.000 description 3
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 3
- 229930013930 alkaloid Natural products 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N iso-quinoline Natural products C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- YMIKANRMRRBHTB-UHFFFAOYSA-N 1-(trifluoromethyl)isoquinoline Chemical class C1=CC=C2C(C(F)(F)F)=NC=CC2=C1 YMIKANRMRRBHTB-UHFFFAOYSA-N 0.000 description 1
- HVAPLSNCVYXFDQ-UHFFFAOYSA-N 3,3-dimethyl-1-(trifluoromethyl)-1$l^{3},2-benziodoxole Chemical compound C1=CC=C2C(C)(C)OI(C(F)(F)F)C2=C1 HVAPLSNCVYXFDQ-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 1
- XCQQWDCKLLORFE-UHFFFAOYSA-N [O].C1(=CC=CC=C1)PC1=CC=CC=C1 Chemical compound [O].C1(=CC=CC=C1)PC1=CC=CC=C1 XCQQWDCKLLORFE-UHFFFAOYSA-N 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- ZHIPXAFNKGZMSC-UHFFFAOYSA-N bis(4-methylphenyl)-oxophosphanium Chemical group C1=CC(C)=CC=C1[P+](=O)C1=CC=C(C)C=C1 ZHIPXAFNKGZMSC-UHFFFAOYSA-N 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical group CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 description 1
- CZHYKKAKFWLGJO-UHFFFAOYSA-N dimethyl phosphite Chemical group COP([O-])OC CZHYKKAKFWLGJO-UHFFFAOYSA-N 0.000 description 1
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- MPQXHAGKBWFSNV-UHFFFAOYSA-N oxidophosphanium Chemical class [PH3]=O MPQXHAGKBWFSNV-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000006277 sulfonation reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/62—Isoquinoline or hydrogenated isoquinoline ring systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
Abstract
本发明公开了一种膦酰化二氢异喹啉酮类化合物及其制备方法，在银促进下以N‑烯丙基苯甲酰胺和氧化膦为原料一锅法制备出多种膦酰化的二氢异喹啉酮类化合物，以乙腈为溶剂，温度控制在80‑100 ℃，在搅拌条件下反应4‑12 h后，经过柱层析分离到产物膦酰化二氢异喹啉酮类化合物。本发明提供了一种新颖有效的策略来合成膦酰化二氢异喹啉酮类化合物，该方法所涉及的操作简便安全、具有反应条件温和、原子经济性好的优点。
Description
技术领域
本发明涉及化学合成领域，具体涉及一种膦酰化二氢异喹啉酮类化合物的制备方法。
背景技术
二氢异喹啉酮类生物碱作为一类特殊的生物碱，广泛存在于复杂的天然产物、生物分子和药物中，具有抗癌、抗恶心、抗炎等潜在应用。近年来，N-烯丙基苯甲酰胺的自由基串联环化反应已成为一种高效、有吸引力的方法，用于合成二氢异喹啉酮类化合物，具有操作简单，成本低等优势。目前文献报道了铜催化以Togni试剂为自由基前体和N-烯丙基苯甲酰胺的环化来合成三氟甲基异喹啉酮（Adv. Synth. Catal. 2016, 358, 746）；通过磺酰自由基引发的环化形成磺化二氢异喹啉酮（Chem. Commun. 2016, 52, 11559）；以芳香醛为自由基前体来合成酰化的二氢异喹啉酮衍生物(J. Org. Chem. 2018, 83, 9718)。尽管二氢异喹啉酮的合成已取得重大进展，但对于膦酰化二氢异喹啉酮类化合物的合成并无现成方法。本发明中所公布的在银促进下以N-烯丙基苯甲酰胺和氧化膦为原料合成膦酰化二氢异喹啉酮类化合物的方法暂时没有相关文献及专利报道。
发明内容
本发明提出了一种膦酰化二氢异喹啉酮类化合物的制备方法，提供了一种新的、有效的策略合成膦酰化二氢异喹啉酮类化合物。该合成方法反应条件温和，操作简便，在银盐存在下通过N-烯丙基苯甲酰胺和氧化膦的反应，一锅法制备出多种膦酰化的二氢异喹啉酮。
实现本发明的技术方案是：膦酰化二氢异喹啉酮类化合物，结构式如下：
其中，R1为氢、甲基、甲氧基、氯、溴、碘；R2为甲基、乙基、异丙基；R3为苯基、对甲基苯基、对氯苯基、甲氧基、乙氧基。
所述的膦酰化二氢异喹啉酮类化合物的制备方法，步骤如下：将N-烯丙基苯甲酰胺、氧化膦和溶剂加入反应瓶中，随后向其中加入银盐，在搅拌条件下反应，得到膦酰化二氢异喹啉酮类化合物。
所述N-烯丙基苯甲酰胺的结构式如下：
其中R1为氢、甲基、甲氧基、氯、溴、碘；R2为甲基、乙基、异丙基。
所述氧化膦的结构式如下：
其中R3为苯基、对甲基苯基、对氯苯基、甲氧基、乙氧基。
所述溶剂为乙腈或二甲基亚砜的任意一种；银盐为硝酸银、碳酸银和氧化银中的任意一种。
所述N-烯丙基苯甲酰胺、氧化膦、银盐的摩尔比为1：（2-3）：（2-3）。
所述的反应温度为80-100 ℃，反应时间为4-12 h。
本发明所述制备方法的反应通式如下：
本发明的有益效果是：本发明提供了一种新颖有效的策略来合成膦酰化二氢异喹啉酮类化合物，该方法所涉及的操作简便安全、具有反应条件温和、原子经济性好的优点。
具体实施方式
下面将结合本发明实施例，对本发明的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有付出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
实施例1
膦酰化二氢异喹啉酮类化合物的制备方法，步骤如下：
在25 mL圆底烧瓶中加入N-甲基-N-（2-甲基烯丙基）苯甲酰胺0.5 mmol，二苯基膦氧1.0 mmol，溶剂乙腈3.0 ml，硝酸银1.0 mmol于空气中搅拌，控制反应温度为80 ℃，反应8小时后，中性氧化铝柱层析分离得到最终产物，以N-甲基-N-（2-甲基烯丙基）苯甲酰胺摩尔量为100%计，终产物的产率为74%。
具体结果如下：
1H NMR (400 MHz, Chloroform-d) δ 8.02 (dd, J = 7.7, 1.2 Hz, 1H), 7.69 -7.63 (m, 4H), 7.48 - 7.39 (m, 6H), 7.35 - 7.31 (m, 1H), 7.29 - 7.24 (m, 2H),3.80 (d, J = 12.7 Hz, 1H), 3.50 (d, J = 12.7 Hz, 1H), 3.01 (s, 3H), 2.74 -2.67 (m, 1H), 2.58 - 2.52 (m, 1H), 1.59 (s, 3H); 13C NMR (101 MHz, Chloroform-d) δ 164.6, 145.3 (d, J = 10.4 Hz), 134.8 (d, J = 98.7 Hz), 133.4 (d, J =98.1 Hz), 132.1, 131.7 (d, J = 2.7 Hz), 131.4 (d, J = 2.8 Hz), 130.5 (d, J =9.1 Hz), 130.2 (d, J = 9.2 Hz), 128.8 (d, J = 11.5 Hz), 128.59 (d, J = 11.5Hz), 128.58, 127.8, 127.3, 123.9, 58.1 (d, J = 5.1 Hz), 37.9 (d, J = 67.6Hz), 37.4 (d, J = 3.5 Hz), 34.9, 23.2 (d, J = 2.0 Hz); 31P NMR (162 MHz,Chloroform-d) δ 27.48; HRMS Calcd for C24H24NO2P [M + H]+: 390.1617, found:390.1612。
实施例2
膦酰化二氢异喹啉酮类化合物的制备方法，步骤如下：
在25 mL圆底烧瓶中加入N,2-二甲基-N-（2-甲基烯丙基）苯甲酰胺0.5 mmol，二苯基膦氧1.0 mmol，溶剂二甲基亚砜3.0 ml，硝酸银1.5 mmol于空气中搅拌，控制反应温度为90℃，反应12小时后,中性氧化铝柱层析分离得到最终产物。
具体结果如下：
1H NMR (400 MHz, Chloroform-d) δ 7.68 - 7.62 (m, 4H), 7.48 - 7.36 (m,6H), 7.18 - 7.10 (m, 2H), 7.00 (d, J = 7.2 Hz, 1H), 3.75 (d, J = 12.8 Hz,1H), 3.47 (d, J = 12.8 Hz, 1H), 3.08 (s, 3H), 2.68 – 2.51 (m, 5H), 1.53 (s,3H); 13C NMR (101 MHz, Chloroform-d) δ 165.1, 146.3 (d, J = 10.1 Hz), 141.0,135.1 (d, J = 98.7 Hz), 133.2 (d, J = 97.9 Hz), 131.6 (d, J = 2.7 Hz), 131.3(d, J = 2.2 Hz), 131.0, 130.5 (d, J = 9.1 Hz), 130.1 (d, J = 9.2 Hz), 128.7(d, J = 11.6 Hz), 128.4 (d, J = 11.7 Hz), 126.5, 121.9, 57.9 (d, J = 5.1 Hz),38.0 (d, J = 3.5 Hz), 37.2 (d, J = 67.9 Hz), 35.1, 23.4 (d, J = 1.9 Hz),22.7; 31P NMR (162 MHz, Chloroform-d) δ 27.58; HRMS Calcd for C25H26NO2P [M +H]+: 404.1774, found: 404.1771。
实施例3
膦酰化二氢异喹啉酮类化合物的制备方法，步骤如下：
在25 mL圆底烧瓶中加入4-氯-N-甲基-N-（2-甲基烯丙基）苯甲酰胺0.5 mmol，二苯基膦氧1.0 mmol，溶剂二甲基亚砜3.0 ml，碳酸银1.0 mmol于空气中搅拌，控制反应温度为80℃，反应12小时后,中性氧化铝柱层析分离得到最终产物。
具体结果如下：
1H NMR (400 MHz, Chloroform-d) δ 7.92 (d, J = 8.3 Hz, 1H), 7.69 - 7.64(m, 4H), 7.51 - 7.39 (m, 6H), 7.25 (d, J = 2.0 Hz, 1H), 7.16 (dd, J = 8.3,2.0 Hz, 1H), 3.78 (d, J = 12.0 Hz, 1H),, 3.51 (d, J = 12.8 Hz, 1H), 3.04 (s,3H), 2.68 - 254 (m, 2H), 1.59 (s, 3H); 13C NMR (101 MHz, Chloroform-d) δ163.8, 146.6 (d, J = 9.7 Hz), 138.3, 134.7 (d, J = 99.1 Hz), 132.9 (d, J =98.1 Hz), 131.8 (d, J = 2.8 Hz), 131.5 (d, J = 2.8 Hz), 130.5, 130.3 (d, J =9.7 Hz), 130.1 (d, J = 9.3 Hz), 128.8 (d, J = 11.7 Hz), 128.6 (d, J = 11.8Hz), 127.7, 126.4, 124.6, 58.4 (d, J = 5.8 Hz), 37.7 (d, J = 68.7 Hz), 37.6(d, J = 3.4 Hz), 34.9, 23.0 (d, J = 2.1 Hz); 31P NMR (162 MHz, Chloroform-d) δ27.16; HRMS Calcd for C24H24NO2P [M + H]+: 424.1228, found: 424.1224。
实施例4
膦酰化二氢异喹啉酮类化合物的制备方法，步骤如下：
在25 mL圆底烧瓶中加入4-溴-N-甲基-N-（2-甲基烯丙基）苯甲酰胺0.5 mmol，二苯基膦氧1.0 mmol，溶剂二甲基亚砜3.0 ml，碳酸银1.5 mmol于空气中搅拌，控制反应温度为90℃，反应4小时后,中性氧化铝柱层析分离得到最终产物。
具体结果如下：
1H NMR (400 MHz, Chloroform-d) δ 7.83 (d, J = 8.3 Hz, 1H), 7.68 - 7.63(m, 4H), 7.49 - 7.39 (m, 7H), 7.32 (dd, J = 8.3, 1.9 Hz, 1H), 3.76 (d, J =12.8 Hz, 1H), 3.51 (d, J = 12.8 Hz, 1H), 3.03 (s, 3H), 2.67 - 2.54 (m, 2H),1.58 (s, 3H); 13C NMR (101 MHz, Chloroform-d) δ 163.8, 146.7 (d, J = 9.7 Hz),134.7 (d, J = 99.0 Hz), 132.8 (d, J = 98.3 Hz), 131.8 (d, J = 2.7 Hz), 131.5(d, J = 2.8 Hz), 130.7, 130.4 (d, J = 8.9 Hz), 130.1 (d, J = 9.2 Hz), 128.8(d, J = 11.6 Hz), 128.6 (d, J = 11.8 Hz), 127.5, 127.0, 126.8, 58.4 (d, J =5.8 Hz), 37.7 (d, J = 67.7 Hz), 37.5 (d, J = 3.5 Hz), 34.9, 23.0 (d, J = 2.0Hz); 31P NMR (162 MHz, Chloroform-d) δ 27.22; HRMS Calcd for C24H23BrNO2P [M +H]+: 468.0723, found: 468.0723。
实施例5
膦酰化二氢异喹啉酮类化合物的制备方法，步骤如下：
在25 mL圆底烧瓶中加入4-碘-N-甲基-N-（2-甲基烯丙基）苯甲酰胺0.5 mmol，二苯基膦氧1.5 mmol，溶剂乙腈3.0 ml，氧化银1.0 mmol于空气中搅拌，控制反应温度为100 ℃，反应8小时后,中性氧化铝柱层析分离得到最终产物。
具体结果如下：
1H NMR (400 MHz, Chloroform-d) δ 7.68 - 7.61 (m, 6H), 7.55 (dd, J = 8.2,1.7 Hz, 1H), 7.50 - 7.39 (m, 6H), 3.73 (d, J = 12.8 Hz, 1H), 3.50 (dd, J =12.8, 1.6 Hz, 1H), 3.03 (s, 3H), 2.65 - 2.54 (m, 2H), 1.58 (s, 3H); 13C NMR(101 MHz, Chloroform-d) δ 164.0, 146.5 (d, J = 9.6 Hz), 136.7, 134.7 (d, J =99.0 Hz), 133.5, 132.8 (d, J = 98.2 Hz), 131.7 (d, J = 2.5 Hz), 131.5 (d, J =2.9 Hz), 130.4 (d, J = 9.1 Hz), 130.2, 130.1 (d, J = 9.2 Hz), 128.8 (d, J =11.9 Hz), 128.7 (d, J = 11.9 Hz), 127.4, 99.9, 58.5 (d, J = 5.9 Hz), 38.1,37.7 (d, J = 67.7 Hz), 37.4, 34.9, 23.0; 31P NMR (162 MHz, Chloroform-d) δ27.23; HRMS Calcd for C24H23INO2P [M + H]+: 516.0584, found: 516.0588。
实施例6
N-烯丙基苯甲酰胺为N,4-二甲基-N-（2-甲基烯丙基）苯甲酰胺，其他试验方法和条件同实施例1，具体结果如下：
1H NMR (400 MHz, Chloroform-d) δ 7.88 (d, J = 7.9 Hz, 1H), 7.67 - 7.60(m, 4H), 7.47 - 7.34 (m, 6H), 7.04 - 6.97 (m, 2H), 3.68 (d, J = 12.7 Hz, 1H),3.47 (d, J = 12.6 Hz, 1H), 2.99 (s, 3H), 2.67 - 2.55 (m, 2H), 2.25 (s, 3H),1.60 (s, 3H); 13C NMR (101 MHz, Chloroform-d) δ 164.8, 144.9 (d, J = 9.6 Hz),142.5, 134.9 (d, J = 98.7 Hz), 133.3 (d, J = 98.0 Hz), 131.6 (d, J = 2.8 Hz),131.3 (d, J = 2.9 Hz), 130.3 (d, J = 9.1 Hz), 130.1 (d, J = 9.2 Hz), 128.73(d, J = 11.7 Hz), 128.67, 128.5 (d, J = 11.7 Hz), 128.1, 125.2, 124.7, 58.7(d, J = 6.0 Hz), 37.9 (d, J = 68.1 Hz), 37.4 (d, J = 3.7 Hz), 34.8, 23.1,21.7; 31P NMR (162 MHz, Chloroform-d) δ 27.50; HRMS Calcd for C25H26NO2P [M +H]+:404.1774, found: 404.1767。
实施例7
N-烯丙基苯甲酰胺为4-甲氧基-N-甲基-N-（2-甲基烯丙基）苯甲酰胺，其他试验方法和条件同实施例1，具体结果如下：
1H NMR (400 MHz, Chloroform-d) δ 7.95 (d, J = 8.6 Hz, 1H), 7.67 - 7.59(m, 4H), 7.48 - 7.34 (m, 6H), 6.76 (d, J = 2.5 Hz, 1H), 6.67 (dd, J = 8.7,2.5 Hz, 1H), 3.77 (s, 3H), 3.66 (d, J = 12.7 Hz, 1H), 3.47 (d, J = 12.6 Hz,1H), 2.98 (s, 3H), 2.66 - 2.55 (m, 2H), 1.59 (s, 3H); 13C NMR (101 MHz,Chloroform-d) δ 164.6, 162.4, 147.0 (d, J = 9.6 Hz), 134.9 (d, J = 98.7 Hz),133.2 (d, J = 98.1 Hz), 131.6 (d, J = 2.8 Hz), 131.3 (d, J = 2.8 Hz), 130.8,130.3 (d, J = 9.1 Hz), 130.1 (d, J = 9.2 Hz), 128.7 (d, J = 11.7 Hz), 128.5(d, J = 11.7 Hz), 120.7, 112.1, 109.9, 58.7 (d, J = 6.1 Hz), 55.3, 37.8, (d,J = 68.7 Hz), 37.5 (d, J = 3.6 Hz), 34.7, 23.1 (d, J = 1.8 Hz); 31P NMR (162MHz, Chloroform-d) δ 27.46; HRMS Calcd for C25H26NO3P [M + H]+:420.1723, found:420.1718。
实施例8
氧化膦为二（对氯苯基）氧化膦，其他试验方法和条件同实施例1，具体结果如下：
1H NMR (400 MHz, Chloroform-d) δ 7.99 (dd, J = 7.2, 1.4 Hz, 1H), 7.56 -7.46 (m, 4H), 7.40 (dd, J = 8.5, 2.4 Hz, 2H), 7.33 (dd, J = 8.5, 2.4 Hz, 2H),7.28 - 7.23 (m, 3H), 3.66 (d, J = 12.7 Hz, 1H), 3.54 (dd, J = 12.8, 2.0 Hz,1H), 3.07 (s, 3H), 2.59 (d, J = 10.5 Hz, 2H), 1.62 (s, 3H); 13C NMR (101 MHz,Chloroform-d) δ 164.5, 144.2 (d, J = 9.0 Hz), 138.5 (d, J = 3.3 Hz), 138.2(d, J = 3.5 Hz), 133.0 (d, J = 100.3 Hz), 132.1, 131.8 (d, J = 10.0 Hz),131.4 (d, J = 10.1 Hz), 131.1 (d, J = 100.0 Hz), 129.2 (d, J = 12.2 Hz),129.0 (d, J = 12.3 Hz), 128.6, 127.9, 127.5, 124.2, 58.9 (d, J = 6.7 Hz),37.9 (d, J = 69.4 Hz), 37.4 (d, J = 3.6 Hz), 35.0, 23.2 (d, J = 2.1 Hz); 31PNMR (162 MHz, Chloroform-d) δ 26.64; HRMS Calcd for C24H22Cl2NO2P [M + H]+:458.0838, found: 458.0831。
实施例9
氧化膦为二对甲苯基氧化膦，其他试验方法和条件同实施例1，具体结果如下：
1H NMR (400 MHz, Chloroform-d) δ 8.04 (dd, J = 8.0, 1.5 Hz, 1H), 7.57 -7.51 (m, 4H), 7.36 - 7.32 (m, 1H), 7.29 - 7.25 (m, 2H), 7.24 - 7.20 (m, 4H),3.85 (d, J = 12.7 Hz, 1H), 3.49 (d, J = 12.7 Hz, 1H), 3.00 (s, 3H), 2.72 -2.65 (m, 1H), 2.50 - 2.44 (m, 1H), 2.37 (s, 3H), 2.35 (s, 3H), 1.56 (s, 3H);13C NMR (101 MHz, Chloroform-d) δ 164.6, 145.8 (d, J = 10.9 Hz), 142.1 (d, J =2.8 Hz), 141.8 (d, J = 2.8 Hz), 132.1, 130.5 (d, J = 9.4 Hz), 130.5 (d, J =101.0 Hz), 130.2 (d, J = 9.6 Hz), 131.7 (d, J = 102.0 Hz), 129.4 (d, J = 12.1Hz), 129.3, 128.6, 127.8, 127.1, 123.7, 57.9 (d, J = 4.4 Hz), 38.1 (d, J =67.4 Hz), 37.4 (d, J = 3.6 Hz), 34.8, 23.1 (d, J = 2.1 Hz), 21.5; 31P NMR (162MHz, Chloroform-d) δ 27.80; HRMS Calcd for C26H28NO2P [M + H]+: 418.1930,found: 418.1920。
实施例10
N-烯丙基苯甲酰胺为N-乙基-N-（2-甲基烯丙基）苯甲酰胺，其他试验方法和条件同实施例1，具体结果如下：
1H NMR (400 MHz, Chloroform-d) δ 8.04 (dd, J = 7.7, 1.4 Hz, 1H), 7.71 -7.62 (m, 4H), 7.49 - 7.39 (m, 6H), 7.35 - 7.31 (m, 1H), 7.27 - 7.23 (m, 2H),3.90 (d, J = 12.7 Hz, 1H), 3.82 - 3.73 (m, 1H), 3.53 (d, J = 12.7 Hz, 1H),3.43 - 3.35 (m, 1H), 2.75 - 2.67 (m, 1H), 2.59 - 2.53 (m, 1H), 1.57 (s, 3H),1.23 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, Chloroform-d) δ 163.8, 145.2 (d, J= 10.5 Hz), 135.1 (d, J = 99.0 Hz), 133.4 (d, J = 97.7 Hz), 132.0, 131.6 (d,J = 2.7 Hz), 131.4 (d, J = 2.9 Hz), 130.5 (d, J = 9.1 Hz), 130.0 (d, J = 9.2Hz), 128.7 (d, J = 12.5 Hz), 128.6 (d, J = 10.6 Hz), 128.2, 127.3, 123.8,55.6(d, J = 4.8 Hz), 42.1, 37.8, 37.42 (d, J = 67.7 Hz), 37.36 (d, J = 3.6Hz), 37.1, 23.1, 12.6; 31P NMR (162 MHz, Chloroform-d) δ 27.37; HRMS Calcd forC25H26NO2P [M + H]+: 404.1774, found: 404.1765。
实施例11
N-烯丙基苯甲酰胺为N-异丙基-N-（2-甲基烯丙基）苯甲酰胺，其他试验方法和条件同实施例1，具体结果如下：
1H NMR (400 MHz, Chloroform-d) δ 8.06 - 7.97 (m, 1H), 7.68 - 7.60 (m,4H), 7.46 - 7.36 (m, 6H), 7.30 - 7.24 (m, 2H), 7.22 - 7.18 (m, 1H), 5.14 –5.08 (m, 1H), 3.81 (d, J = 12.7 Hz, 1H), 3.31 (dd, J = 12.8, 1.6 Hz, 1H),2.69 - 2.57 (m, 2H), 1.59 (s, 3H), 1.28 (d, J = 6.8 Hz, 3H), 1.20 (d, J = 6.8Hz, 3H); 13C NMR (101 MHz, Chloroform-d) δ 163.5, 144.3 (d, J = 9.2 Hz), 135.4(d, J = 99.0 Hz), 133.3 (d, J = 97.9 Hz), 131.9, 131.5 (d, J = 2.8 Hz), 131.3(d, J = 2.9 Hz), 130.5 (d, J = 8.9 Hz), 129.9 (d, J = 9.1 Hz), 128.8, 128.7(d, J = 11.1 Hz), 128.54 (d, J = 12.1 Hz), 128.45, 127.3, 124.0, 50.4 (d, J =5.8 Hz), 43.9, 37.1, 37.0 (d, J = 3.5 Hz), 36.7 (d, J = 68.7 Hz), 36.4, 23.4,20.0, 19.3; 31P NMR (162 MHz, Chloroform-d) δ 27.10; HRMS Calcd for C25H26NO2P[M + H]+: 418.1930, found: 418.1922。
实施例12
氧化膦为亚磷酸二甲酯，其他试验方法和条件同实施例1，具体结果如下：
1H NMR (400 MHz, Chloroform-d) δ 8.11 (dd, J = 7.7, 1.4 Hz, 1H), 7.51 -7.47 (m, 1H), 7.39-7.34 (m, 2H), 3.70 - 3.52 (m, 8H), 3.20 (s, 3H), 2.22 -2.13 (m, 1H), 2.07 - 1.99 (m, 1H), 1.61 (s, 3H); 13C NMR (101 MHz, Chloroform-d) δ 164.5, 145.4 (d, J = 14.8 Hz), 132.1, 128.7, 128.0, 127.4, 123.7, 57.8(d, J = 5.8 Hz), 52.2 (dd, J = 6.8, 1.6 Hz), 35.5 (d, J = 2.2 Hz), 35.1,34.4, 33.1, 22.9 (d, J = 2.4 Hz); 31P NMR (162 MHz, Chloroform-d) δ 29.60;HRMS Calcd for C14H20NO4P [M + H]+: 298.1203, found: 298.1194。
实施例13
氧化膦为亚磷酸二乙酯，其他试验方法和条件同实施例1，具体结果如下：
1H NMR (400 MHz, Chloroform-d) δ 8.11 (dd, J = 8.2, 1.5 Hz, 1H), 7.50 -7.46 (m, 1H), 7.38 - 7.34 (m, 2H), 4.06 - 3.94 (m, 4H), 3.73 (d, J = 12.7 Hz,1H), 3.53 (d, J = 12.6 Hz, 1H), 3.20 (s, 3H), 2.21 - 1.98 (m, 2H), 1.61 (s,3H), 1.28 (t, J = 7.1 Hz, 3H), 1.24 (t, J = 7.1 Hz, 4H); 13C NMR (101 MHz,Chloroform-d) δ 164.5, 145.6 (d, J = 14.9 Hz), 132.0, 128.6, 128.0, 127.3,123.7, 61.6 (d, J = 5.7 Hz), 61.5, (d, J = 6.1 Hz), 57.7 (d, J = 5.7 Hz),35.6 (d, J = 2.3 Hz), 35.2 (d, J = 36.4 Hz), 23.0 (d, J = 2.4 Hz), 16.43 (d,J = 6.3 Hz), 16.35 (d, J = 6.3 Hz); 31P NMR (162 MHz, Chloroform-d) δ 27.01;HRMS Calcd for C16H24NO4P [M + H]+: 326.1516, found: 326.1502。
以上所述仅为本发明的较佳实施例而已，并不用以限制本发明，凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。
Claims (8)
1.膦酰化二氢异喹啉酮类化合物，其特征在于结构式如下：
其中，R1为氢、甲基、甲氧基、氯、溴、碘；R2为甲基、乙基、异丙基；R3为苯基、对甲基苯基、对氯苯基、甲氧基、乙氧基。
2.膦酰化二氢异喹啉酮类化合物的制备方法，其特征在于步骤如下：将N-烯丙基苯甲酰胺、氧化膦和溶剂加入反应瓶中，随后向其中加入银盐，在搅拌条件下反应，得到膦酰化二氢异喹啉酮类化合物。
3.根据权利要求2所述的膦酰化二氢异喹啉酮类化合物的制备方法，其特征在于所述N-烯丙基苯甲酰胺的结构式如下：
其中R1为氢、甲基、甲氧基、氯、溴、碘；R2为甲基、乙基、异丙基。
4.根据权利要求2所述的膦酰化二氢异喹啉酮类化合物的制备方法，其特征在于所述氧化膦的结构式如下：
其中R3苯基、对甲基苯基、对氯苯基、甲氧基、乙氧基。
5.根据权利要求2所述的膦酰化二氢异喹啉酮类化合物的制备方法，其特征在于：所述溶剂为乙腈或二甲基亚砜中的任意一种；银盐为硝酸银、碳酸银和氧化银中的任意一种。
6.根据权利要求2所述的膦酰化二氢异喹啉酮类化合物的制备方法，其特征在于：所述N-烯丙基苯甲酰胺、氧化膦、银盐的摩尔比为1：（2-3）：（2-3）。
7.根据权利要求2所述的膦酰化二氢异喹啉酮类化合物的制备方法，其特征在于：所述的反应温度为80-100 ℃，反应时间为4-12 h。
8.根据权利要求2-7任一项所述的膦酰化二氢异喹啉酮类化合物的制备方法，其特征在于所述膦酰化二氢异喹啉酮类化合物的结构式如下：
其中，R1为氢、甲基、甲氧基、氯、溴、碘；R2为甲基、乙基、异丙基；R3为苯基、对甲基苯基、对氯苯基、甲氧基、乙氧基。
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| CN110041367A (zh) * | 2019-05-28 | 2019-07-23 | 郑州大学 | 光催化合成膦酰化二氢异喹啉酮类化合物 |
| CN110845411A (zh) * | 2019-11-07 | 2020-02-28 | 江苏理工学院 | 一种多氯甲基取代二氢异喹啉酮化合物的合成方法 |
| CN110903319A (zh) * | 2019-11-12 | 2020-03-24 | 信阳农林学院 | 2-膦酰基硫代黄酮类化合物的制备方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110041367A (zh) * | 2019-05-28 | 2019-07-23 | 郑州大学 | 光催化合成膦酰化二氢异喹啉酮类化合物 |
| CN110845411A (zh) * | 2019-11-07 | 2020-02-28 | 江苏理工学院 | 一种多氯甲基取代二氢异喹啉酮化合物的合成方法 |
| CN110845411B (zh) * | 2019-11-07 | 2021-09-24 | 江苏理工学院 | 一种多氯甲基取代二氢异喹啉酮化合物的合成方法 |
| CN110903319A (zh) * | 2019-11-12 | 2020-03-24 | 信阳农林学院 | 2-膦酰基硫代黄酮类化合物的制备方法 |
| CN110903319B (zh) * | 2019-11-12 | 2022-06-14 | 信阳农林学院 | 2-膦酰基硫代黄酮类化合物的制备方法 |
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