CN112441997B - 一种合成α-(2-四氢呋喃基)-苯乙酮类化合物的方法 - Google Patents
一种合成α-(2-四氢呋喃基)-苯乙酮类化合物的方法 Download PDFInfo
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- -1 alpha- (2-tetrahydrofuryl) -acetophenone compound Chemical class 0.000 title claims abstract description 17
- 238000000034 method Methods 0.000 title claims abstract description 16
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 47
- 238000006243 chemical reaction Methods 0.000 claims abstract description 43
- 239000002904 solvent Substances 0.000 claims abstract description 39
- 239000003504 photosensitizing agent Substances 0.000 claims abstract description 24
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000000758 substrate Substances 0.000 claims abstract description 12
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- 239000003446 ligand Substances 0.000 claims abstract description 10
- FWCSGYRIUWCYDP-UHFFFAOYSA-N 2-(oxolan-2-yl)-1-phenylethanone Chemical class C=1C=CC=CC=1C(=O)CC1CCCO1 FWCSGYRIUWCYDP-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000000203 mixture Substances 0.000 claims abstract description 5
- 238000005286 illumination Methods 0.000 claims abstract description 3
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- 238000002156 mixing Methods 0.000 claims abstract description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 32
- 238000004440 column chromatography Methods 0.000 claims description 32
- 239000003480 eluent Substances 0.000 claims description 18
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 17
- TXNLQUKVUJITMX-UHFFFAOYSA-N 4-tert-butyl-2-(4-tert-butylpyridin-2-yl)pyridine Chemical compound CC(C)(C)C1=CC=NC(C=2N=CC=C(C=2)C(C)(C)C)=C1 TXNLQUKVUJITMX-UHFFFAOYSA-N 0.000 claims description 16
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- 229910002027 silica gel Inorganic materials 0.000 claims description 16
- 239000012295 chemical reaction liquid Substances 0.000 claims description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 6
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 claims description 4
- 238000001704 evaporation Methods 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
- 239000000126 substance Substances 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
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- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 238000005265 energy consumption Methods 0.000 abstract description 3
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
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- YKTNISGZEGZHIS-UHFFFAOYSA-N 2-$l^{1}-oxidanyloxy-2-methylpropane Chemical group CC(C)(C)O[O] YKTNISGZEGZHIS-UHFFFAOYSA-N 0.000 description 2
- UAZIFGMQOVIVAH-UHFFFAOYSA-N 3-(4-bromophenyl)but-3-en-2-one Chemical compound CC(=O)C(=C)C1=CC=C(Br)C=C1 UAZIFGMQOVIVAH-UHFFFAOYSA-N 0.000 description 2
- RWQPCBHCESZZQG-UHFFFAOYSA-N 3-(4-methylphenyl)but-3-en-2-one Chemical compound CC(=O)C(=C)C1=CC=C(C)C=C1 RWQPCBHCESZZQG-UHFFFAOYSA-N 0.000 description 2
- RKOGZIGMKDJBMZ-UHFFFAOYSA-N 3-[4-(trifluoromethyl)phenyl]but-3-en-2-one Chemical compound FC(C1=CC=C(C=C1)C(=C)C(C)=O)(F)F RKOGZIGMKDJBMZ-UHFFFAOYSA-N 0.000 description 2
- FEZMTSUOSTXNBJ-UHFFFAOYSA-N 3-phenylbut-3-en-2-one Chemical compound CC(=O)C(=C)C1=CC=CC=C1 FEZMTSUOSTXNBJ-UHFFFAOYSA-N 0.000 description 2
- DQTUSXPBSMCBRY-UHFFFAOYSA-N CC(=O)c1c(C=C)ccc2ccccc12 Chemical group CC(=O)c1c(C=C)ccc2ccccc12 DQTUSXPBSMCBRY-UHFFFAOYSA-N 0.000 description 2
- XGOVQUPGPCBOPH-UHFFFAOYSA-N CC(C(C(C=CC=C1)=C1C1=CC=CC=C1)=C)=O Chemical compound CC(C(C(C=CC=C1)=C1C1=CC=CC=C1)=C)=O XGOVQUPGPCBOPH-UHFFFAOYSA-N 0.000 description 2
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- 150000008062 acetophenones Chemical class 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
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- 239000007800 oxidant agent Substances 0.000 description 2
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- URLVCROWVOSNPT-PSYGJSNASA-N (2s)-4-[(13r)-13-hydroxy-13-[(2s,5r)-5-[(2r,5s)-5-[(1s)-1-hydroxyundecyl]oxolan-2-yl]oxolan-2-yl]tridecyl]-2-methyl-2h-furan-5-one Chemical compound O1[C@H]([C@@H](O)CCCCCCCCCC)CC[C@@H]1[C@@H]1O[C@H]([C@H](O)CCCCCCCCCCCCC=2C(O[C@@H](C)C=2)=O)CC1 URLVCROWVOSNPT-PSYGJSNASA-N 0.000 description 1
- XMCRWEBERCXJCH-UHFFFAOYSA-N 1-(2,4-dichlorophenyl)ethanone Chemical compound CC(=O)C1=CC=C(Cl)C=C1Cl XMCRWEBERCXJCH-UHFFFAOYSA-N 0.000 description 1
- PZBPKYOVPCNPJY-UHFFFAOYSA-N 1-[2-(allyloxy)-2-(2,4-dichlorophenyl)ethyl]imidazole Chemical compound ClC1=CC(Cl)=CC=C1C(OCC=C)CN1C=NC=C1 PZBPKYOVPCNPJY-UHFFFAOYSA-N 0.000 description 1
- JNXLXKUWOOQOJH-UHFFFAOYSA-N 3-(4-methoxyphenyl)but-3-en-2-one Chemical compound COC1=CC=C(C(=C)C(C)=O)C=C1 JNXLXKUWOOQOJH-UHFFFAOYSA-N 0.000 description 1
- JFFQOKQBOFHZKF-UHFFFAOYSA-N 4,4-ditert-butyl-2-pyridin-2-yl-3h-pyridine Chemical compound C1=CC(C(C)(C)C)(C(C)(C)C)CC(C=2N=CC=CC=2)=N1 JFFQOKQBOFHZKF-UHFFFAOYSA-N 0.000 description 1
- 239000005795 Imazalil Substances 0.000 description 1
- URLVCROWVOSNPT-NLQNCNHRSA-N Membranacin Natural products O=C1C(CCCCCCCCCCCC[C@@H](O)[C@H]2O[C@H]([C@@H]3O[C@@H]([C@@H](O)CCCCCCCCCC)CC3)CC2)=C[C@@H](C)O1 URLVCROWVOSNPT-NLQNCNHRSA-N 0.000 description 1
- 239000005822 Propiconazole Substances 0.000 description 1
- WAZHZNCAXROREF-UHFFFAOYSA-N amphidinolide X Natural products O1C(=O)C=CC(C)CC(=O)OC(CC(C)=O)C(C)C=C(C)CCC2OC(CCC)(C)CC21 WAZHZNCAXROREF-UHFFFAOYSA-N 0.000 description 1
- WAZHZNCAXROREF-NQASNHIQSA-N amphidinolide x Chemical compound O1C(=O)\C=C\C(C)CC(=O)OC(CC(C)=O)C(C)\C=C(C)\CCC2OC(CCC)(C)CC21 WAZHZNCAXROREF-NQASNHIQSA-N 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
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- 239000003124 biologic agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(I) oxide Inorganic materials [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 1
- 229940112669 cuprous oxide Drugs 0.000 description 1
- KRFJLUBVMFXRPN-UHFFFAOYSA-N cuprous oxide Chemical compound [O-2].[Cu+].[Cu+] KRFJLUBVMFXRPN-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- URLVCROWVOSNPT-QTTMQESMSA-N desacetyluvaricin Natural products O=C1C(CCCCCCCCCCCC[C@@H](O)[C@H]2O[C@@H]([C@@H]3O[C@@H]([C@@H](O)CCCCCCCCCC)CC3)CC2)=C[C@H](C)O1 URLVCROWVOSNPT-QTTMQESMSA-N 0.000 description 1
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- 229960002125 enilconazole Drugs 0.000 description 1
- DWRKFAJEBUWTQM-UHFFFAOYSA-N etaconazole Chemical compound O1C(CC)COC1(C=1C(=CC(Cl)=CC=1)Cl)CN1N=CN=C1 DWRKFAJEBUWTQM-UHFFFAOYSA-N 0.000 description 1
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- 239000013384 organic framework Substances 0.000 description 1
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- STJLVHWMYQXCPB-UHFFFAOYSA-N propiconazole Chemical compound O1C(CCC)COC1(C=1C(=CC(Cl)=CC=1)Cl)CN1N=CN=C1 STJLVHWMYQXCPB-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/12—Radicals substituted by oxygen atoms
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- Organic Chemistry (AREA)
Abstract
一种合成α‑(2‑四氢呋喃基)‑苯乙酮类化合物的方法,所述方法为:将底物(I)、光敏剂、催化剂、配体、溶剂四氢呋喃混合,在蓝色LED光照、温度30~70℃、惰性气体保护的条件下反应20~36h,之后经后处理,得到α‑(2‑四氢呋喃基)‑苯乙酮类化合物(II);本发明安全环保,不产生废气,操作危险性低;底物适应性好,各种取代基都可以实现双官能化;反应条件温和;同时,该反应具有一定的创新性,原子经济性高,采用光催化的方式来替代传统加热的模式,减少了能耗,更加符合现代绿色化学的理念;
Description
(一)技术领域
本发明涉及一种合成α-(2-四氢呋喃基)-苯乙酮类化合物的方法。
(二)背景技术
苯乙酮类化合物及其衍生物是一类含酮羰基苯环类化合物,具有低毒性,它能够表现出很好的化学活性,因此苯乙酮在有机合成中成为很重要的合成原料。同时,通过对苯乙酮类化合物不同位置进行修饰从而得到一系列衍生物,其中一些衍生物能够表现出良好的生物活性,及杀虫性,杀菌性以及除草性。例如以2,4-二氯苯乙酮为原料开发的杀菌剂丙环唑和乙环唑到如今的抑霉唑,都是以苯乙酮类化合物为基础原料开发的生物药剂,可见苯乙酮类化合物及其衍生物在农药医药方面发挥着巨大作用。
同时,氧杂环烷类骨架是非常重要的有机骨架结构,它们广泛存在于天然产物和生物活性化合物中,也因此而受到研究者的极大关注。而含有四氢呋喃环结构的化合物也广泛存在于各类天然产物中,被广泛利用于医药方面,如具有抗癌作用的AmphidinolideX、Membranacin,因此开发和研究一系列具有四氢呋喃环类化合物及其衍生物是非常有必要的。
目前关于合成α-2-四氢呋喃苯乙酮类化合物的方法还非常的少,2010年KangHyun Park等人(Bull.Korean Chem.Soc.2010,31,12)报道一种合成α-2-四氢呋喃苯乙酮类化合物的方法,他们采用苯乙烯类化合物为底物,氧化亚铜为催化剂,过氧叔丁醇为氧化剂,四氢呋喃为溶剂,在3个大气压的空气压力下,130℃温度下以高收率合成了目标产物α-2-四氢呋喃苯乙酮类化合物。这种方法虽然能实现放大量的反应,但是反应温度过高,能耗过大,过氧叔丁醇属于过氧化物,在高温条件下不稳定,容易发生爆炸,同时反应需要高压条件下进行,增加反应的危险性。而本发明所报道的是一种在光催化条件下,以α-乙酰基-苯乙烯类化合物为底物,Ni(dme)Br2为催化剂,4,4-二叔丁基-2,2-联吡啶为配体(L),[Cu]为光敏剂,四氢呋喃为溶剂,在15w蓝光照射下,50℃温度下反应,以高收率得到目标产物。该方法不需要在高温条件下进行,同时不需要额外加入氧化剂,反应条件温和,符合绿色化学的核心发展理念。
(三)发明内容
针对现有技术的不足,本发明提供了一种通用、简便、高效的合成α-(2-四氢呋喃基)-苯乙酮类化合物的方法。
本发明的技术方案如下:
一种合成α-(2-四氢呋喃基)-苯乙酮类化合物的方法,所述方法为:
将底物(I)、光敏剂、催化剂、配体、溶剂四氢呋喃混合,在蓝色LED(15w)光照、温度30~70℃(优选50℃)、惰性气体保护的条件下反应20~36h(优选24h),之后经后处理,得到α-(2-四氢呋喃基)-苯乙酮类化合物(II);
所述底物(I)、光敏剂、催化剂、配体的物质的量之比为1:0.01~0.1:0.05~0.15:0.1~0.2,优选1:0.05:0.1:0.15;
所述溶剂四氢呋喃的体积用量以底物(I)的物质的量计为10~20mL/mmol;
所述光敏剂为式(III)、式(IV)所示化合物中的一种或两种以任意比例的混合物;
所述催化剂为Ni(dme)Br2、Ni(dme)Cl2中的一种或两种以任意比例的混合物;
所述配体为4,4’-二叔丁基-2,2’-联吡啶(L1)或2,2’-联吡啶(L2);
所述后处理的方法为:反应结束后,反应液中加入柱层析硅胶(100~200目),减压蒸除溶剂,进行柱色谱分离,以石油醚与乙酸乙酯体积比3:1的混合液作为洗脱剂洗脱,收集含目标产物的洗脱液,蒸除溶剂并干燥,得到α-(2-四氢呋喃基)-苯乙酮类化合物(II);
反应式如下:
式(I)或式(II)中,
R为氢、甲基、甲氧基、溴、三氟甲基或苯基,或者R与所在苯环构成2-萘环;
所述光敏剂的结构式如下:
所述配体的结构式如下:
具体的,优选本发明所述α-(2-四氢呋喃基)-苯乙酮类化合物(II)为下列化合物之一:
与现有技术相比,本发明的有益效果是:
(1)安全环保,不产生废气,操作危险性低;
(2)底物适应性好,各种取代基都可以实现双官能化;
(3)反应条件温和;
(4)同时,该反应具有一定的创新性,原子经济性高,采用光催化的方式来替代传统加热的模式,减少了能耗,更加符合现代绿色化学的理念。
(四)具体实施方式
下面结合具体实施例对本发明作进一步详细说明,但本发明的保护范围不限于此:
实施例1
将α-乙酰基苯乙烯(0.3mmol,0.0438g)、光敏剂(III)(0.015mmol,0.0168g)、Ni(dme)Br2(0.03mmol,0.0092g)和4,4’-二叔丁基-2,2’-联吡啶(0.045mmol,0.0121g)加入到15mL封管反应管中,再加入3mL四氢呋喃作溶剂。接着,在15w Blue LED照射下,50℃条件,氮气环境下反应24h,反应结束后,在反应液中加入两药匙(0.5g)柱层析硅胶(100-200目),并通过减压蒸馏除去溶剂,再通过柱色谱分离得到如结构式所示的产物纯品(以石油醚/乙酸乙酯=3:1作为洗脱剂)。该物质为白色固体,产率73%。
表征数据:1H NMR(500MHz,CDCl3)δ7.97(m,2H),7.56(m,1H),7.46(m,2H),4.41(dddd,J=7.0,6.5,6.5,6.0Hz,1H),3.89(ddd,J=8.5,7.0,6.5Hz,1H),3.75(m,1H),3.40(dd,J1=16.0,J2=6.0Hz,1H),3.06(dd,J=16.0,6.5Hz,1H),2.20(m,1H),1.93(m,2H),1.57(m,1H).13C NMR(125MHz,CDCl3)δ198.4,137.1,133.1,128.6,128.2,75.4,67.8,44.7,31.6,25.6.
实施例2
将α-乙酰基-4甲基-苯乙烯(0.3mmol,0.0480g)、光敏剂(IV)(0.015mmol,0.0172g)、Ni(dme)Br2(0.03mmol,0.0092g)和4,4’-二叔丁基-2,2’-联吡啶(0.045mmol,0.0121g)加入到15mL封管反应管中,再加入3mL四氢呋喃作溶剂。接着,在15w Blue LED照射下,50℃条件,氮气环境下反应24h,反应结束后,在反应液中加入两药匙柱层析硅胶(100-200目),并通过减压蒸馏除去溶剂,再通过柱色谱分离得到如结构式所示的产物纯品(以石油醚/乙酸乙酯=3:1作为洗脱剂)。该物质为白色固体,产率65%。
表征数据:1H NMR(500MHz,CDCl3)δ7.86(d,J=8.0Hz,2H),7.25(d,J=8.0Hz,2H),4.39(dddd,J=7.0,6.5,6.5,6.0Hz,1H),3.89(m,1H),3.75(m,1H),3.37(dd,J1=16.0Hz,J2=5.0Hz,1H),3.03(dd,J1=16.0Hz,J2=7.0Hz,1H),2.41(s,3H),2.19(m,1H),1.92(m,2H),1.56(m,1H).13C NMR(125MHz,CDCl3)δ198.0,143.9,134.7,129.2,128.3,75.5,67.8,44.6,31.6,25.7,21.6.
实施例3
将α-乙酰基-4-甲氧基-苯乙烯(0.3mmol,0.0528g)、光敏剂(III)(0.003mmol,0.0034g)、Ni(dme)Br2(0.03mmol,0.0092g)和4,4’-二叔丁基-2,2’-联吡啶(0.045mmol,0.0121g)加入到15mL封管反应管中,再加入3mL四氢呋喃作溶剂。接着,在15w Blue LED照射下,50℃条件,氮气环境下反应24h,反应结束后,在反应液中加入两药匙柱层析硅胶(100-200目),并通过减压蒸馏除去溶剂,再通过柱色谱分离得到如结构式所示的产物纯品(以石油醚/乙酸乙酯=3:1作为洗脱剂)。该物质为白色固体,产率54%。
表征数据:1H NMR(500MHz,CDCl3)δ7.95(m,2H),6.93(m,2H),4.38(dddd,J=7.0,6.5,6.5,6.0Hz,1H),3.89(m,1H),3.86(s,3H),3.74(m,1H),3.35(dd,J1=16.0Hz,J2=6.0Hz,1H),3.00(dd,J1=16.0,J2=7.0Hz,1H),2.18(m,1H),1.92(m,2H),1.56(m,1H).13CNMR(125MHz,CDCl3)δ196.9,163.5,130.5,130.3,113.7,75.6,67.8,55.4,44.3,31.6,25.6.
实施例4
将α-乙酰基-4-溴苯乙烯(0.3mmol,0.0672g)、光敏剂(III)(0.03mmol,0.0335g)、Ni(dme)Br2(0.03mmol,0.0092g)和4,4’-二叔丁基-2,2’-联吡啶(0.045mmol,0.0121g)加入到15mL封管反应管中,再加入3mL四氢呋喃作溶剂。接着,在15w Blue LED照射下,50℃条件,氮气环境下反应24h,反应结束后,在反应液中加入两药匙柱层析硅胶(100-200目),并通过减压蒸馏除去溶剂,再通过柱色谱分离得到如结构式所示的产物纯品(以石油醚/乙酸乙酯=3:1作为洗脱剂)。该物质为白色固体,产率70%。
表征数据:1H NMR(500MHz,CDCl3)δ7.83(m,2H),7.60(m,2H),4.38(dddd,J=7.0,6.5,6.5,6.0Hz,1H),3.88(ddd,J=8.0,7.0,6.5Hz,1H),3.75(ddd,J=8.0,7.5,7.0,Hz1H),3.33(dd,J1=16.0,J2=6.0Hz,1H),3.02(dd,J1=16.0Hz,J2=6.5Hz,1H),2.19(m,1H),1.93(m,2H),1.56(m,1H).13C NMR(125MHz,CDCl3)δ197.4,135.8,131.9,129.8,128.3,75.3,67.9,44.6,31.6,25.6.
实施例5
将α-乙酰基-4-三氟甲基苯乙烯(0.3mmol,0.0642g)、光敏剂(III)(0.015mmol,0.0168g)、Ni(dme)Cl2(0.03mmol,0.00657g)和4,4’-二叔丁基-2,2’-联吡啶(0.045mmol,0.0121g)加入到15mL封管反应管中,再加入3mL四氢呋喃作溶剂。接着,在15w Blue LED照射下,50℃条件,氮气环境下反应24h,反应结束后,在反应液中加入两药匙柱层析硅胶(100-200目),并通过减压蒸馏除去溶剂,再通过柱色谱分离得到如结构式所示的产物纯品(以石油醚/乙酸乙酯=3:1作为洗脱剂)。该物质为白色固体,产率68%。
表征数据:1H NMR(500MHz,CDCl3)δ8.07(d,J=8.0Hz,2H),7.73(d,J=8.0Hz,2H),4.40(dddd,J=7.0,6.5,6.5,6.0Hz,1H),3.89(ddd,J=8.5,7.0,6.5Hz,1H),3.76(m,1H),3.39(dd,J1=16.0Hz,J2=6.5Hz,1H),3.08(dd,J=16.0,6.0Hz,1H),2.21(m,1H),1.94(m,2H),1.58(m,1H).13C NMR(125MHz,CDCl3)δ197.5,139.7,134.4(q,J=32.7Hz),128.5,125.6(q,J=3.8Hz),123.6(q,J=272.6Hz),75.2,67.9,44.9,31.6,25.6.
实施例6
1-([1,1'-biphenyl]-2-yl)-2-(tetrahydrofuran-2-yl)ethan-1-one
将α-乙酰基-2-苯基苯乙烯(0.3mmol,0.0666g)、光敏剂(III)(0.015mmol,0.0168g)、Ni(dme)Br2(0.015mmol,0.0046g)和4,4’-二叔丁基-2,2’-联吡啶(0.045mmol,0.0121g)加入到15mL封管反应管中,再加入3mL四氢呋喃作溶剂。接着,在15w Blue LED照射下,50℃条件,氮气环境下反应24h,反应结束后,在反应液中加入两药匙柱层析硅胶(100-200目),并通过减压蒸馏除去溶剂,再通过柱色谱分离得到如结构式所示的产物纯品(以石油醚/乙酸乙酯=3:1作为洗脱剂)。该物质为白色固体,产率57%。
表征数据:1H NMR(500MHz,CDCl3)δ7.53-7.50(m,2H),7.45-7.38(m,5H),7.36-7.35(m,2H),4.13-4.08(m,1H),3.72-3.67(m,1H),3.64-3.60(m,1H),2.63(dd,J1=16.5Hz,J2=7Hz,1H),2.37(dd,J1=16Hz,J2=6.5Hz,1H),1.97-1.91(m,1H),1.82-1.69(m,2H),1.29-1.22(m,2H).13C NMR(125MHz,CDCl3)δ205.7,141.0,140.5,140.1,130.6 130.2,129.0,128.,127.9,127.8,127.5,75.3,67.6,48.7,31.2,25.4.
实施例7
将α-乙酰基-2-萘乙烯(0.3mmol,0.0588g)、光敏剂(III)(0.015mmol,0.0168g)、Ni(dme)Br2(0.045mmol,0.0138g)和4,4’-二叔丁基-2,2’-联吡啶(0.045mmol,0.0121g)加入到15mL封管反应管中,再加入3mL四氢呋喃作溶剂。接着,在15w Blue LED照射下,50℃条件,氮气环境下反应24h,反应结束后,在反应液中加入两药匙柱层析硅胶(100-200目),并通过减压蒸馏除去溶剂,再通过柱色谱分离得到如结构式所示的产物纯品(以石油醚/乙酸乙酯=3:1作为洗脱剂)。该物质为白色固体,产率71%。
表征数据:1H NMR(CDCl3)δ8.49(s,1H),8.04(d,J=9.0Hz,1H),7.97(d,J=8.0Hz,1H),7.90(d,J=9.0Hz,1H),7.88(d,J=8.5Hz,1H),7.60(dd,J1=8.0Hz,J2=7.0Hz,1H),7.56(dd,J1=8.5,J2=7.0Hz),4.47(dddd,J=7.0,6.5,6.5,6.0Hz,1H),3.92(m,1H),3.78(m,1H),3.54(dd,J1=16.0Hz,J2=6.0Hz,1H),3.19(dd,J1=16.0Hz,J2=6.5Hz,1H),2.23(m,1H),1.95(m,2H),1.63(m,1H).13C NMR(125MHz,CDCl3)δ198.3,135.6,134.5,132.5,130.0,129.6,128.5,128.4,127.8,126.7,123.9,75.6,67.9,44.8,31.7,25.7.
实施例8
将α-乙酰基苯乙烯(0.3mmol,0.0438g)、光敏剂(III)(0.015mmol,0.0168g)、Ni(dme)Br2(0.03mmol,0.0092g)和2,2’-联吡啶(0.045mmol,0.007g)加入到15mL封管反应管中,再加入3mL四氢呋喃作溶剂。接着,在15w Blue LED照射下,50℃条件,氮气环境下反应24h,反应结束后,在反应液中加入两药匙柱层析硅胶(100-200目),并通过减压蒸馏除去溶剂,再通过柱色谱分离得到如结构式所示的产物纯品(以石油醚/乙酸乙酯=3:1作为洗脱剂)。该物质为白色固体,产率51%。
表征数据:1H NMR(500MHz,CDCl3)δ7.97(m,2H),7.56(m,1H),7.46(m,2H),4.41(dddd,J=7.0,6.5,6.5,6.0Hz,1H),3.89(ddd,J=8.5,7.0,6.5Hz,1H),3.75(m,1H),3.40(dd,J1=16.0,J2=6.0Hz,1H),3.06(dd,J=16.0,6.5Hz,1H),2.20(m,1H),1.93(m,2H),1.57(m,1H).13C NMR(125MHz,CDCl3)δ198.4,137.1,133.1,128.6,128.2,75.4,67.8,44.7,31.6,25.6.
实施例9
将α-乙酰基-4-甲基苯乙烯(0.3mmol,0.0480g)、光敏剂(III)(0.015mmol,0.0168g)、Ni(dme)Br2(0.03mmol,0.0092g)和4,4’-二叔丁基-2,2’-联吡啶(0.03mmol,0.008g)加入到15mL封管反应管中,再加入3mL四氢呋喃作溶剂。接着,在15w Blue LED照射下,50℃条件,氮气环境下反应24h,反应结束后,在反应液中加入两药匙柱层析硅胶(100-200目),并通过减压蒸馏除去溶剂,再通过柱色谱分离得到如结构式所示的产物纯品(以石油醚/乙酸乙酯=3:1作为洗脱剂)。该物质为白色固体,产率68%。
表征数据:1H NMR(500MHz,CDCl3)δ7.86(d,J=8.0Hz,2H),7.25(d,J=8.0Hz,2H),4.39(dddd,J=7.0,6.5,6.5,6.0Hz,1H),3.89(m,1H),3.75(m,1H),3.37(dd,J1=16.0Hz,J2=5.0Hz,1H),3.03(dd,J1=16.0Hz,J2=7.0Hz,1H),2.41(s,3H),2.19(m,1H),1.92(m,2H),1.56(m,1H).13C NMR(125MHz,CDCl3)δ198.0,143.9,134.7,129.2,128.3,75.5,67.8,44.6,31.6,25.7,21.6.
实施例10
将α-乙酰基-4-甲氧基苯乙烯(0.3mmol,0.0528g)、光敏剂(III)(0.015mmol,0.0168g)、Ni(dme)Br2(0.03mmol,0.0092g)和4,4’-二叔丁基-2,2’-联吡啶(0.06mmol,0.0161g)加入到15mL封管反应管中,再加入3mL四氢呋喃作溶剂。接着,在15w Blue LED照射下,50℃条件,氮气环境下反应24h,反应结束后,在反应液中加入两药匙柱层析硅胶(100-200目),并通过减压蒸馏除去溶剂,再通过柱色谱分离得到如结构式所示的产物纯品(以石油醚/乙酸乙酯=3:1作为洗脱剂)。该物质为白色固体,产率69%。
表征数据:1H NMR(500MHz,CDCl3)δ7.86(d,J=8.0Hz,2H),7.25(d,J=8.0Hz,2H),4.39(dddd,J=7.0,6.5,6.5,6.0Hz,1H),3.89(m,1H),3.75(m,1H),3.37(dd,J1=16.0Hz,J2=5.0Hz,1H),3.03(dd,J1=16.0Hz,J2=7.0Hz,1H),2.41(s,3H),2.19(m,1H),1.92(m,2H),1.56(m,1H).13C NMR(125MHz,CDCl3)δ198.0,143.9,134.7,129.2,128.3,75.5,67.8,44.6,31.6,25.7,21.6.
实施例11
将α-乙酰基-4-溴苯乙烯(0.3mmol,0.0672g)、光敏剂(III)(0.015mmol,0.0168g)、Ni(dme)Br2(0.03mmol,0.0092g)和4,4’-二叔丁基-2,2’-联吡啶(0.045mmol,0.0121g)加入到15mL封管反应管中,再加入3mL四氢呋喃作溶剂。接着,在15w Blue LED照射下,30℃条件,氮气环境下反应24h,反应结束后,在反应液中加入两药匙柱层析硅胶(100-200目),并通过减压蒸馏除去溶剂,再通过柱色谱分离得到如结构式所示的产物纯品(以石油醚/乙酸乙酯=3:1作为洗脱剂)。该物质为白色固体,产率47%。
表征数据:1H NMR(500MHz,CDCl3)δ7.83(m,2H),7.60(m,2H),4.38(dddd,J=7.0,6.5,6.5,6.0Hz,1H),3.88(ddd,J=8.0,7.0,6.5Hz,1H),3.75(ddd,J=8.0,7.5,7.0,Hz1H),3.33(dd,J1=16.0,J2=6.0Hz,1H),3.02(dd,J1=16.0Hz,J2=6.5Hz,1H),2.19(m,1H),1.93(m,2H),1.56(m,1H).13C NMR(125MHz,CDCl3)δ197.4,135.8,131.9,129.8,128.3,75.3,67.9,44.6,31.6,25.6.
实施例12
将α-乙酰基-4-三氟甲基苯乙烯(0.3mmol,0.0642g)、光敏剂(III)(0.015mmol,0.0168g)、Ni(dme)Br2(0.03mmol,0.0092g)和4,4’-二叔丁基-2,2’-联吡啶(0.045mmol,0.0121g)加入到15mL封管反应管中,再加入3mL四氢呋喃作溶剂。接着,在15w Blue LED照射下,70℃条件,氮气环境下反应24h,反应结束后,在反应液中加入两药匙柱层析硅胶(100-200目),并通过减压蒸馏除去溶剂,再通过柱色谱分离得到如结构式所示的产物纯品(以石油醚/乙酸乙酯=3:1作为洗脱剂)。该物质为白色固体,产率63%。
表征数据:1H NMR(500MHz,CDCl3)δ8.07(d,J=8.0Hz,2H),7.73(d,J=8.0Hz,2H),4.40(dddd,J=7.0,6.5,6.5,6.0Hz,1H),3.89(ddd,J=8.5,7.0,6.5Hz,1H),3.76(m,1H),3.39(dd,J1=16.0Hz,J2=6.5Hz,1H),3.08(dd,J=16.0,6.0Hz,1H),2.21(m,1H),1.94(m,2H),1.58(m,1H).13C NMR(125MHz,CDCl3)δ197.5,139.7,134.4(q,J=32.7Hz),128.5,125.6(q,J=3.8Hz),123.6(q,J=272.6Hz),75.2,67.9,44.9,31.6,25.6.
实施例13
1-([1,1'-biphenyl]-2-yl)-2-(tetrahydrofuran-2-yl)ethan-1-one
将α-乙酰基-2-苯基苯乙烯(0.3mmol,0.0666g)、光敏剂(III)(0.015mmol,0.0168g)、Ni(dme)Br2(0.03mmol,0.0092g)和4,4’-二叔丁基-2,2’-联吡啶(0.045mmol,0.0121g)加入到15mL封管反应管中,再加入3mL四氢呋喃作溶剂。接着,在15w Blue LED照射下,50℃条件,氮气环境下反应20h,反应结束后,在反应液中加入两药匙柱层析硅胶(100-200目),并通过减压蒸馏除去溶剂,再通过柱色谱分离得到如结构式所示的产物纯品(以石油醚/乙酸乙酯=3:1作为洗脱剂)。该物质为白色固体,产率68%。
表征数据:1H NMR(500MHz,CDCl3)δ7.53-7.50(m,2H),7.45-7.38(m,5H),7.36-7.35(m,2H),4.13-4.08(m,1H),3.72-3.67(m,1H),3.64-3.60(m,1H),2.63(dd,J1=16.5Hz,J2=7Hz,1H),2.37(dd,J1=16Hz,J2=6.5Hz,1H),1.97-1.91(m,1H),1.82-1.69(m,2H),1.29-1.22(m,2H).13C NMR(125MHz,CDCl3)δ205.7,141.0,140.5,140.1,130.6 130.2,129.0,128.,127.9,127.8,127.5,75.3,67.6,48.7,31.2,25.4.
实施例14
将α-乙酰基-2-萘乙烯(0.3mmol,0.0588g)、光敏剂(III)(0.015mmol,0.0168g)、Ni(dme)Br2(0.03mmol,0.0092g)和4,4’-二叔丁基-2,2’-联吡啶(0.045mmol,0.0121g)加入到15mL封管反应管中,再加入3mL四氢呋喃作溶剂。接着,在15w Blue LED照射下,50℃条件,氮气环境下反应36h,反应结束后,在反应液中加入两药匙柱层析硅胶(100-200目),并通过减压蒸馏除去溶剂,再通过柱色谱分离得到如结构式所示的产物纯品(以石油醚/乙酸乙酯=3:1作为洗脱剂)。该物质为白色固体,产率72%。
表征数据:1H NMR(CDCl3)δ8.49(s,1H),8.04(d,J=9.0Hz,1H),7.97(d,J=8.0Hz,1H),7.90(d,J=9.0Hz,1H),7.88(d,J=8.5Hz,1H),7.60(dd,J1=8.0Hz,J2=7.0Hz,1H),7.56(dd,J1=8.5,J2=7.0Hz),4.47(dddd,J=7.0,6.5,6.5,6.0Hz,1H),3.92(m,1H),3.78(m,1H),3.54(dd,J1=16.0Hz,J2=6.0Hz,1H),3.19(dd,J1=16.0Hz,J2=6.5Hz,1H),2.23(m,1H),1.95(m,2H),1.63(m,1H).13C NMR(125MHz,CDCl3)δ198.3,135.6,134.5,132.5,130.0,129.6,128.5,128.4,127.8,126.7,123.9,75.6,67.9,44.8,31.7,25.7。
Claims (4)
1.一种合成α-(2-四氢呋喃基)-苯乙酮类化合物的方法,其特征在于,所述方法为:
将底物(I)、光敏剂、催化剂、配体、溶剂四氢呋喃混合,在蓝色LED光照、温度30~70℃、惰性气体保护的条件下反应20~36h,之后经后处理,得到α-(2-四氢呋喃基)-苯乙酮类化合物(II);
所述底物(I)、光敏剂、催化剂、配体的物质的量之比为1:0.01~0.1:0.05~0.15:0.1~0.2;
所述光敏剂为式(III)、式(IV)所示化合物中的一种或两种以任意比例的混合物;
所述催化剂为Ni(dme)Br2、Ni(dme)Cl2中的一种或两种以任意比例的混合物;
所述配体为4,4’-二叔丁基-2,2’-联吡啶或2,2’-联吡啶;
反应式如下:
式(I)或式(II)中,
R为氢、甲基、甲氧基、溴、三氟甲基或苯基,或者R与所在苯环构成2-萘环。
2.如权利要求1所述合成α-(2-四氢呋喃基)-苯乙酮类化合物的方法,其特征在于,所述底物(I)、光敏剂、催化剂、配体的物质的量之比为1:0.05:0.1:0.15。
3.如权利要求1所述合成α-(2-四氢呋喃基)-苯乙酮类化合物的方法,其特征在于,所述溶剂四氢呋喃的体积用量以底物(I)的物质的量计为10~20mL/mmol。
4.如权利要求1所述合成α-(2-四氢呋喃基)-苯乙酮类化合物的方法,其特征在于,所述后处理的方法为:反应结束后,反应液中加入柱层析硅胶,减压蒸除溶剂,进行柱色谱分离,以石油醚与乙酸乙酯体积比3:1的混合液作为洗脱剂洗脱,收集含目标产物的洗脱液,蒸除溶剂并干燥,得到α-(2-四氢呋喃基)-苯乙酮类化合物(II)。
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