CN104926628B - 一种苯偶酰类衍生物的合成方法 - Google Patents
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- WURBFLDFSFBTLW-UHFFFAOYSA-N benzil Chemical class C=1C=CC=CC=1C(=O)C(=O)C1=CC=CC=C1 WURBFLDFSFBTLW-UHFFFAOYSA-N 0.000 title claims abstract description 25
- 238000010189 synthetic method Methods 0.000 title claims abstract description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 69
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 25
- 239000012363 selectfluor Substances 0.000 claims abstract description 24
- 238000006243 chemical reaction Methods 0.000 claims abstract description 20
- 239000004593 Epoxy Substances 0.000 claims abstract description 19
- 239000000376 reactant Substances 0.000 claims abstract description 19
- 230000001590 oxidative effect Effects 0.000 claims abstract description 16
- 239000007800 oxidant agent Substances 0.000 claims abstract description 12
- 239000012046 mixed solvent Substances 0.000 claims abstract description 10
- 150000007529 inorganic bases Chemical class 0.000 claims abstract description 9
- 238000003756 stirring Methods 0.000 claims abstract description 7
- 238000012805 post-processing Methods 0.000 claims abstract description 5
- 150000001788 chalcone derivatives Chemical class 0.000 claims abstract 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 45
- 239000002904 solvent Substances 0.000 claims description 40
- 239000003480 eluent Substances 0.000 claims description 39
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 30
- 239000000463 material Substances 0.000 claims description 30
- 238000004440 column chromatography Methods 0.000 claims description 19
- 238000000034 method Methods 0.000 claims description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 15
- 230000006837 decompression Effects 0.000 claims description 15
- 239000000741 silica gel Substances 0.000 claims description 15
- 229910002027 silica gel Inorganic materials 0.000 claims description 15
- 238000000926 separation method Methods 0.000 claims description 14
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- -1 methoxyl group Chemical group 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 239000003208 petroleum Substances 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
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- GUUNMTFSWQFNCZ-UHFFFAOYSA-I C(C=1C(C(=O)[O-])=CC=CC1)(=O)O.[K+].[C+4].C(C=1C(C(=O)[O-])=CC=CC1)(=O)O.C(C=1C(C(=O)[O-])=CC=CC1)(=O)O.C(C=1C(C(=O)[O-])=CC=CC1)(=O)O.C(C=1C(C(=O)[O-])=CC=CC1)(=O)O Chemical group C(C=1C(C(=O)[O-])=CC=CC1)(=O)O.[K+].[C+4].C(C=1C(C(=O)[O-])=CC=CC1)(=O)O.C(C=1C(C(=O)[O-])=CC=CC1)(=O)O.C(C=1C(C(=O)[O-])=CC=CC1)(=O)O.C(C=1C(C(=O)[O-])=CC=CC1)(=O)O GUUNMTFSWQFNCZ-UHFFFAOYSA-I 0.000 claims 1
- 150000002118 epoxides Chemical class 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 5
- 229910052760 oxygen Inorganic materials 0.000 abstract description 5
- 239000001301 oxygen Substances 0.000 abstract description 5
- 239000007858 starting material Substances 0.000 abstract description 3
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- 125000000524 functional group Chemical group 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 12
- 239000003054 catalyst Substances 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- 125000005594 diketone group Chemical group 0.000 description 10
- 238000013019 agitation Methods 0.000 description 9
- 150000002576 ketones Chemical class 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- DQFBYFPFKXHELB-UHFFFAOYSA-N Chalcone Natural products C=1C=CC=CC=1C(=O)C=CC1=CC=CC=C1 DQFBYFPFKXHELB-UHFFFAOYSA-N 0.000 description 7
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- 235000005513 chalcones Nutrition 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 239000002994 raw material Substances 0.000 description 5
- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical compound C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- ISAOCJYIOMOJEB-UHFFFAOYSA-N benzoin Chemical compound C=1C=CC=CC=1C(O)C(=O)C1=CC=CC=C1 ISAOCJYIOMOJEB-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- 229910052707 ruthenium Inorganic materials 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 2
- 244000028419 Styrax benzoin Species 0.000 description 2
- 235000000126 Styrax benzoin Nutrition 0.000 description 2
- 235000008411 Sumatra benzointree Nutrition 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 229960002130 benzoin Drugs 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 235000019382 gum benzoic Nutrition 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000344 soap Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- OXYYWXZNYBDKGC-UHFFFAOYSA-N C=C(C(c1ccccc1)=O)c(cc1)ccc1Br Chemical compound C=C(C(c1ccccc1)=O)c(cc1)ccc1Br OXYYWXZNYBDKGC-UHFFFAOYSA-N 0.000 description 1
- 238000007445 Chromatographic isolation Methods 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
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- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical class OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- HBGGXOJOCNVPFY-UHFFFAOYSA-N diisononyl phthalate Chemical compound CC(C)CCCCCCOC(=O)C1=CC=CC=C1C(=O)OCCCCCCC(C)C HBGGXOJOCNVPFY-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000012760 heat stabilizer Substances 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- AJAZMOFONMJGNP-WMZOPIPTSA-N n-[(2s)-4-methyl-1-oxo-1-[[(2s)-3-oxo-4-(pyridin-2-ylsulfonylamino)butan-2-yl]amino]pentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound O=C([C@H](C)NC(=O)[C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)CNS(=O)(=O)C1=CC=CC=N1 AJAZMOFONMJGNP-WMZOPIPTSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 1
- 150000003252 quinoxalines Chemical class 0.000 description 1
- 229910052761 rare earth metal Inorganic materials 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- XMVJITFPVVRMHC-UHFFFAOYSA-N roxarsone Chemical group OC1=CC=C([As](O)(O)=O)C=C1[N+]([O-])=O XMVJITFPVVRMHC-UHFFFAOYSA-N 0.000 description 1
- 230000001235 sensitizing effect Effects 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 150000001608 tolans Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/56—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds
- C07C45/57—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom
- C07C45/58—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom in three-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B41/00—Formation or introduction of functional groups containing oxygen
- C07B41/06—Formation or introduction of functional groups containing oxygen of carbonyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明公开了一种苯偶酰类衍生物的合成方法:式I所示的环氧查尔酮类化合物、Selectfluor氧化剂和无机碱加入乙腈和水的混合溶剂中,60‑100℃下搅拌反应4‑8小时,反应结束所得反应液后处理制备得到式II所示的苯偶酰类衍生物。本发明的合成方法具有原料廉价易得、无过渡金属催化,氧源易得且环境友好,反应条件温和,高效合成目标底物且官能团普适性好、操作简便等优点。
Description
(一)技术领域
本发明属于有机化合物合成技术领域,具体涉及一种苯偶酰类衍生物的合成方法。
(二)背景技术
苯偶酰及其衍生物是一类特殊且应用极其广泛的有机化合物。它是一种重要的有机化工原料,用于光敏剂、固化剂、杀虫剂、药品及各类功能材料的合成;也可以用于辅助热稳定剂,从而克服原有金属皂类稳定剂在耐候性上严重不足的缺陷,因而能大大扩展金属皂类稳定剂的应用范围;它们同时可以与多种稳定剂通过组分与组分之间的协同作用,有效改善塑料制品的热稳定性能等性质,一般也适用于制作食品包装用的印刷油墨等;其与稀土离子的配合物作为催化剂能够解决传统的催化剂在合成高分子量聚乙烯时长链支化的问题。还可以用来合成咪唑类,苯并吡嗪类等具有抗肿瘤活性的药物中间体。此外,苯偶酰配体还是齐聚反应的常用催化剂。
合成苯偶酰及其衍生物的相关文献报道很多,大体上可以分为三大类,第一种是由苯偶姻氧化合成苯偶酰,这是苯偶酰最常用的合成路线。第二种是由二苯基乙炔为原料,氧化合成苯偶酰,工艺较为通用,但收率一般不高。第三种是由二苯基乙烯、芳酯等其他物质为底物合成苯偶酰,目前此类研究还不够深入。总体上说,几大路线制备苯偶酰及其衍生物仍存在着一些不足之处,主要包括四个方面:(1)普遍使用一些较为昂贵的、有污染的过渡金属催化剂,如钯催化剂(参见Gao,A.等人.Tetrahedron,2012,68,4950;Chandrasekhar,S.等人.Tetrahedron Lett.,2010,51,3623;Muzart,J.J.Mol.Catal.A-Chem.,2011,338,7;Mori,S.等人.Adv.Synth.Catal.2010,352,1630)、钌催化剂(Tummatorn,J.等人.Tetrahedron,2007,63,11878;Ren,W.等人.Adv.Synth.Catal.,2010,352,1424;Che,C.-M.等人.J.Am.Chem.Soc.,2000,122,11380;Wing-Chi Chong.J.Chem.Soc.,Chem.Commun.,1994(9),1063、金催化剂(Xu,C.-F.等人.Org.Lett.,2011,13,1556)、铬催化剂(Chaudhuri,M K.等人.Synth.Commun.2004,34(22):4077-4087)等。(2)反应的原料不易得且代价高,反应条件苛刻,步骤繁琐,通常需使用高温(参见Gao,A.等人.Tetrahedron,2012,68,4950;Mori,S.等人.Adv.Synth.Catal.2010,352,1630;Sawama,Y.等人.Eur.J.Org.Chem.,2011,3361;L.Ruan,M.等人,Org.Lett.,2014,16,733-735)。(3)采用的氧源比较昂贵,且污染严重(参见Xu,C.-F.等人.Org.Lett.,2011,13,1556;Sawama,Y.等人.Eur.J.Org.Chem.,2011,3361;Kinio Nakagawa等人.J.Org.Chem.1962,27,1597-1601)。(4)反应收率普遍不高,(参见Soul Wolfe等人J.Am.Chem.SOC.1983;105(26):7755;Wing-Chi Chong等人.J.Chem.Soc.,Chem.Commun.1994(9),1063.)
除以上期刊文献报道之外,申请号为200910183716.9的中国发明专利申请文件中公开了一种以昂贵钌基催化剂催化的内炔的氧化反应,成本较大;申请号为201010018142.2和200810021756.9的中国发明专利申请文献公开了较为温和的氧化合成苯偶酰反应,但仍分别使用较为昂贵的钌或钯催化剂。鉴于以上存在的问题,发展一种廉价原料、无过渡金属催化的、低廉的氧化剂氧化的、反应条件温和的且收率较高的合成苯偶酰及其衍生物的方法仍是迫在眉睫。
(三)发明内容
发明目的:针对现有技术中存在的不足,本发明旨在提供一种制备苯偶酰及其衍生物的方法,克服现有技术的缺点,以廉价易得的环氧查尔酮为原料替代复杂昂贵不易制备的苯偶姻、二苯乙炔等、以无过渡金属催化替代昂贵的贵金属、以方便易得且环境友好的水和价格适中的氧化剂Selectfluor替代昂贵的氧源、并实现在温和高效的条件下进行反应。
为了达到上述发明目的,本发明采用的技术方案是:
一种苯偶酰类衍生物的合成方法,所述方法为,式I所示的环氧查尔酮类化合物、Selectfluor氧化剂和无机碱加入乙腈和水的混合溶剂中,60~100℃下搅拌反应4-8小时,反应结束所得反应液后处理制备得到式II所示的苯偶酰类衍生物;
式I或式II中,两个苯环上全部为H或各自独立的被单取代基R1、R2取代,所述取代基R1、R2各自独立为甲基、乙基、甲氧基、乙氧基、氟、氯、溴或硝基,优选为甲基、氟、氯、溴或硝基。
更进一步,取代基R1、R2各自独立优选为2-甲基、3-甲基、4-甲基、2-氯、4-氯、4-溴、4-氟或3-硝基。
所述无机碱为碳酸氢钾、碳酸氢钠、碳酸钾或碳酸钠,优选碳酸氢钾;
所述Selectfluor氧化剂为1-氯甲基-4-氟-1,4-二氮杂双环[2.2.2]辛烷二(四氟硼酸)盐,
所述无机碱的物质的量用量为式I所示的环氧查尔酮类化合物的物质的量的25%~200%,优选25%-100%,最优选50%。
所述Selectfluor氧化剂的物质的量用量为式I所示的环氧查尔酮类化合物的物质的量的1~3倍,优选为2倍。
所述乙腈和水的混合溶剂中,乙腈、水的体积比为5~500:1,优选5~200:1,最优选为100:1。
所述乙腈和水的混合溶剂的体积用量通常以式I所示的环氧查尔酮类化合物的物质的量计为5~50mL/mmol,优选为10~20mL/mmol。
本发明所述反应的温度优选80℃。
本发明所述反应的时间优选为4~8小时,更优选4~6小时,最优选6小时。
本发明所述反应液后处理方法为:反应结束后,反应液中加入柱层析硅胶,减压蒸馏除去溶剂,剩余混合物装柱,经柱层析分离,以石油醚、乙酸乙酯体积比为10:1的混合溶剂作为洗脱剂,收集含有产物的洗脱液,洗脱液蒸除溶剂得到式II所示的苯偶酰类衍生物。
本发明使用的原料环氧查尔酮类化合物,本领域技术人员可以根据现有文献公开的方法自行制备,例如文献[Ceylan,Mustafa.Gezegen,Hayreddin.Turk.J.Chem.2008,32(1),55-61.;Jin,H.;Zhao,H.Y.;Zhao,F.H.;Li,S.H.;Liu,W.;Zhou,G.P.;Tao,K.;Hou,T.P.Ultrason.Sonochem.2009,16(3),304.]等。
本发明原料廉价易得,无过渡金属催化剂,氧化剂价格适中,且无需额外配体辅助,反应条件温和,高效率合成苯偶酰类产物。
较为具体的,推荐本发明所述方法按以下步骤进行:式I所示的环氧查尔酮类化合物、碳酸氢钾和Selectfluor氧化剂加入乙腈和水体积比为100:1的混合溶剂中,80℃下搅拌反应4~8小时,反应结束后,反应液中加入柱层析硅胶,减压蒸馏除去溶剂,剩余混合物装柱,经柱层析分离,以石油醚、乙酸乙酯体积比为10:1的混合溶剂作为洗脱剂,收集含有产物的洗脱液,洗脱液蒸除溶剂得到式II所示的苯偶酰类衍生物;所述碳酸氢钾的物质的量用量为式I所示的环氧查尔酮类化合物的物质的量的50%,所述Selectfluor氧化剂的物质的量用量为式I所示的环氧查尔酮类化合物的物质的量的2倍。
本发明通过环氧查尔酮在无机碱的作用下,以Selectfluor为氧源,通过环氧查尔酮的开环氧化断裂重组制得苯偶酰及其衍生物,有益效果在于:与现有苯偶酰及其衍生物的制备方法相比,原料廉价易得,无需催化剂,成本大大降低,且无污染;所使用的氧源为水和Selectfluor;反应条件温和,节约能源消耗;此外,还具有产率高,底物普适性强,操作简便等特点。
(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44.8mg(0.2mmol)环氧查尔酮、141.7mg(0.4mmol)Selectfluor、10.0mg(0.1mmol)碳酸氢钾加入到10mL圆底烧瓶中,再加入2mL乙腈/水(V:V=100:1)作溶剂。接着,于80℃下磁力搅拌6h。然后,在反应液中加入1g柱层析硅胶(100-200目),并通过减压蒸馏除去溶剂,剩余物装柱,通过柱色谱分离,以石油醚/乙酸乙酯(V:V=10:1)作为洗脱剂,收集含有产物的洗脱液,洗脱液蒸除溶剂得到产物纯品1,2-二苯基乙二酮。该物质为淡黄色油状液体,产率83%。
表征数据:1H NMR(CDCl3,500MHz):δ7.99(dd,J1=7.4Hz,J2=1.4Hz,4H),7.68(dd,J1=7.5Hz,J2=1.0Hz,2H),7.53(t,J=7.9,4H);13C NMR(CDCl3,125MHz):δ194.6,134.9,133.1,129.9,129.0;m/z(%)=210(20)[M+],105(100),77(56),51(40).
实施例2
将47.6mg(0.2mmol 1-苯基-3-(3-甲基苯基)-2-环氧乙烷基甲酮)、70.8mg(0.2mmol)Selectfluor、10.0mg(0.1mmol)碳酸氢钾加入到10mL圆底烧瓶中,再加入2mL乙腈/水(V:V=50:1)作溶剂。接着,于100℃条件下磁力搅拌8h。然后,在反应液中加入1g柱层析硅胶(100-200目),并通过减压蒸馏除去溶剂,剩余物装柱,通过柱色谱分离,以石油醚/乙酸乙酯(V:V=10:1)作为洗脱剂,收集含有产物的洗脱液,洗脱液蒸除溶剂得到产物纯品1-苯基-2-(3-甲基苯基)乙二酮。该物质为淡黄色油状液体,产率63%。
表征数据:1H NMR(CDCl3,500MHz):δ=7.98(d,J=7.5Hz,2H),7.89(d,J=8.0Hz,2H),7.67(t,J=7.5Hz,1H),7.52(t,J=7.5Hz,2H),7.32(d,J=8.0Hz,2H),2.45(s,3H);MS(EI,70eV):m/z(%)=224(3)[M+],119(100).
实施例3
将47.6mg(0.2mmol)(2-甲基苯基)-3-苯基-2-环氧乙烷基甲酮、212.5mg(0.6mmol)Selectfluor、10.0mg(0.1mmol)碳酸氢钾加入到10mL圆底烧瓶中,再加入2mL乙腈/水(V:V=100:1)作溶剂。接着,于60℃下磁力搅拌8h。然后,在反应液中加入1g柱层析硅胶(100-200目),并通过减压蒸馏除去溶剂,剩余物装柱,通过柱色谱分离,以石油醚/乙酸乙酯(V:V=10:1)作为洗脱剂,收集含有产物的洗脱液,洗脱液蒸除溶剂得到产物纯品1-苯基-2-(2-甲基苯基)乙二酮。该物质为淡黄色固体,产率55%。
表征数据:1H NMR(CDCl3,500MHz):δ=8.0(d,J=7.0Hz,2H),7.68(t,J=7.5Hz,2H),7.55-7.29(m,5H),2.73(s,3H);MS(EI,70eV):m/z(%)=224(3)[M+],119(100).
实施例4
将47.6mg(0.2mmol)(4-甲基苯基)-3-苯基-2-环氧乙烷基甲酮、141.7mg(0.4mmol)Selectfluor、8.4mg(0.1mmol)碳酸氢钠加入到10mL圆底烧瓶中,再加入2mL乙腈/水(V:V=500:1)作溶剂。接着,于80℃下磁力搅拌8h。然后,在反应液中加入1g柱层析硅胶(100-200目),并通过减压蒸馏除去溶剂,剩余物装柱,通过柱色谱分离,以石油醚/乙酸乙酯(V:V=10:1)作为洗脱剂,收集含有产物的洗脱液,洗脱液蒸除溶剂得到产物纯品1-苯基-2-(4-甲基苯基)乙二酮。该物质为淡黄色固体,产率75%。
表征数据:1H NMR(CDCl3,500MHz):δ=7.98(d,J=7.0Hz,2H),7.88(d,J=8.0Hz,2H),7.66(t,J=7.5Hz,1H),7.52(t,J=7.5Hz,2H),7.32(d,J=8.0Hz,2H),2.45(s,3H);MS(EI,70eV):m/z(%)=224(3)[M+],119(100).
实施例5
将48.4mg(0.2mmol)(4-氟苯基)-3-苯基-2-环氧乙烷基甲酮、141.7mg(0.4mmol)Selectfluor、6.9mg(0.05mmol)碳酸钾加入到10mL圆底烧瓶中,再加入2mL乙腈/水(V:V=500:1)作溶剂。接着,于80℃下磁力搅拌6h。然后,在反应液中加入1g柱层析硅胶(100-200目),并通过减压蒸馏除去溶剂,剩余物装柱,通过柱色谱分离,以石油醚/乙酸乙酯(V:V=10:1)作为洗脱剂,收集含有产物的洗脱液,洗脱液蒸除溶剂得到产物纯品1-苯基-2-(4-氟苯基)乙二酮。该物质为淡黄色固体,产率77%。
表征数据:1H NMR(CDCl3,500MHz):δ=8.04(dd,J1=9.0Hz,J1=0.5Hz,,2H),7.99(d,J=7.5Hz,2H),7.69(t,J=7.5Hz,1H),7.54(t,J=8.0Hz,2H),7.21(t,J=8.5Hz,2H);MS(EI,70eV):m/z(%)=228(3)[M+],105(100).
实施例6
将51.7mg(0.2mmol)1-苯基-3-(4-氯苯基)-2-环氧乙烷基甲酮、141.7mg(0.4mmol)Selectfluor、21.2mg(0.2mmol)碳酸钠加入到10mL圆底烧瓶中,再加入2mL乙腈/水(V:V=5:1)作溶剂。接着,于90℃下磁力搅拌6h。然后,在反应液中加入1g柱层析硅胶(100-200目),并通过减压蒸馏除去溶剂,剩余物装柱,通过柱色谱分离,以石油醚/乙酸乙酯(V:V=10:1)作为洗脱剂,收集含有产物的洗脱液,洗脱液蒸除溶剂得到产物纯品1-苯基-2-(4-氯苯基)乙二酮。该物质为淡黄色固体,产率80%。
表征数据:1H NMR(CDCl3,500MHz):δ=7.98(d,J=7.0Hz,2H),7.94(d,J=8.5Hz,2H),7.69(t,J=7.5Hz,1H),7.56-7.50(m,4H);MS(EI,70eV):m/z(%)=244(2)[M+],105(100).
实施例7
将60.8mg(0.2mmol)(4-溴苯基)-3-苯基-2-环氧乙烷基甲酮、70.8mg(0.2mmol)Selectfluor、10.0mg(0.1mmol)碳酸氢钾加入到10mL圆底烧瓶中,再加入2mL乙腈/水(V:V=100:1)作溶剂。接着,于80℃下磁力搅拌8h。然后,在反应液中加入1g柱层析硅胶(100-200目),并通过减压蒸馏除去溶剂,剩余物装柱,通过柱色谱分离,以石油醚/乙酸乙酯(V:V=10:1)作为洗脱剂,收集含有产物的洗脱液,洗脱液蒸除溶剂得到产物纯品1-苯基-2-(4-溴苯基)乙二酮。该物质为淡黄色固体,产率73%。
表征数据:1H NMR(CDCl3,500MHz):δ=7.98(d,J=8.0Hz,2H),7.86(d,J=8.5Hz,2H),7.69-7.67(m,3H),7.54(t,J=8.0Hz,2H);MS(EI,70eV):m/z(%)=288(1)[M+],105(100).
实施例8
将53.8mg(0.2mmol)(3-硝基苯基)-3-苯基-2-环氧乙烷基甲酮、212.5mg(0.6mmol)Selectfluor、10.6mg(0.1mmol)碳酸钠加入到10mL圆底烧瓶中,再加入2mL乙腈/水(V:V=100:1)作溶剂。接着,于90℃下磁力搅拌4h。然后,在反应液中加入1g柱层析硅胶(100-200目),并通过减压蒸馏除去溶剂,剩余物装柱,通过柱色谱分离,以石油醚/乙酸乙酯(V:V=10:1)作为洗脱剂,收集含有产物的洗脱液,洗脱液蒸除溶剂得到产物纯品1-苯基-2-(3-硝基苯基)乙二酮。该物质为淡黄色固体,产率80%。
表征数据:H NMR(CDCl3,400MHz):δ8.83(t,J=2.0Hz,1H),8.53-8.50(m,1H),8.34-8.31(m,1H),8.03-8.00(m,2H),7.77-7.70(m,2H),7.58-7.54(m,2H);MS(EI,70eV):m/z(%)=255(3)[M+],105(100).
实施例9
将54.5mg(0.2mmol)(4-甲基苯基)-3-(2-氯苯基)-2-环氧乙烷基甲酮、141.7mg(0.4mmol)Selectfluor、55.2mg(0.4mmol)碳酸钾加入到10mL圆底烧瓶中,再加入2mL乙腈/水(V:V=100:1)作溶剂。接着,于80℃下磁力搅拌6h。然后,在反应液中加入1g柱层析硅胶(100-200目),并通过减压蒸馏除去溶剂,剩余物装柱,通过柱色谱分离,以石油醚/乙酸乙酯(V:V=10:1)作为洗脱剂,收集含有产物的洗脱液,洗脱液蒸除溶剂得到产物纯品1-(2-氯苯基)2-(4-甲基苯基)乙二酮。该物质为黄色固体,产率77%。
表征数据:1H NMR(CDCl3,500MHz):δ=7.95(d,J=8.5Hz,2H),7.92(d,J=8.0Hz,1H),7.56(t,J=7.5Hz,1H),7.47-7.35(m,5H),2.48(s,3H);MS(EI,70eV):m/z(%)=258(2)[M+].
实施例10
将51.2mg(0.2mmol)(4-氟苯基)-3-(4-甲基苯基)-2-环氧乙烷基甲酮、141.7mg(0.4mmol)Selectfluor、10.0mg(0.1mmol)碳酸氢钾加入到10mL圆底烧瓶中,再加入2mL乙腈/水(V:V=100:1)作溶剂。接着,于80℃下磁力搅拌6h。然后,在反应液中加入1g柱层析硅胶(100-200目),并通过减压蒸馏除去溶剂,剩余物装柱,通过柱色谱分离,以石油醚/乙酸乙酯(V:V=10:1)作为洗脱剂,收集含有产物的洗脱液,洗脱液蒸除溶剂得到产物纯品1-(4-甲基苯基)2-(4-氟苯基)乙二酮。该物质为淡黄色固体,产率68%。
表征数据:1H NMR(CDCl3,400MHz):δ7.96-7.92(m,2H),7.79(d,J=10.0Hz,2H),7.24(d,J=10.0Hz,2H),7.12-7.08(m,2H),2.36(s,3H).MS(EI,70eV):m/z(%)=242(2)[M+],119(100);.
实施例11
将55.3mg(0.2mmol)(4-氟苯基)-3-(4-氯苯基)-2-环氧乙烷基甲酮、141.7mg(0.4mmol)Selectfluor、10.0mg(0.1mmol)碳酸氢钾加入到10mL圆底烧瓶中,再加入2mL乙腈/水(V:V=100:1)作溶剂。接着,于70℃下磁力搅拌6h。然后,在反应液中加入1g柱层析硅胶(100-200目),并通过减压蒸馏除去溶剂,剩余物装柱,通过柱色谱分离,以石油醚/乙酸乙酯(V:V=10:1)作为洗脱剂,收集含有产物的洗脱液,洗脱液蒸除溶剂得到产物纯品1-(4-氟苯基)-2-(4-氯苯基)乙二酮。该物质为淡黄色固体,产率73%。
表征数据:1H NMR(CDCl3,400MHz):δ8.04-7.99(m,2H),7.94-7.91(m,2H),7.51-7.48(m,2H),7.22-7.19(m,2H);MS(EI,70eV):m/z(%)=262(4)[M+],123(100).
Claims (9)
1.一种苯偶酰类衍生物的合成方法,其特征在于所述方法为,式I所示的环氧查尔酮类化合物、Selectfluor氧化剂和无机碱,加入乙腈和水的混合溶剂中,60~100℃下搅拌反应4-8小时,反应结束所得反应液后处理制备得到式II所示的苯偶酰类衍生物;所述无机碱为碳酸氢钾、碳酸氢钠、碳酸钾或碳酸钠;
式I或式II中,两个苯环上全部为H或各自独立的被单取代基R1、R2取代,所述取代基R1、R2各自独立为甲基、乙基、甲氧基、乙氧基、氟、氯、溴或硝基。
2.如权利要求1所述的方法,其特征在于式I或式II中,两个苯环上全部为H或各自独立的被单取代基R1、R2取代,所述取代基R1、R2各自独立为甲基、氟、氯、溴或硝基。
3.如权利要求1所述的方法,其特征在于所述Selectfluor氧化剂的物质的量用量为式I所示的环氧查尔酮类化合物的物质的量的1~3倍。
4.如权利要求1所述的方法,其特征在于所述乙腈和水的混合溶剂中,乙腈、水的体积比为5~500:1。
5.如权利要求1所述的方法,其特征在于所述无机碱的物质的量用量为式I所示的环氧查尔酮类化合物的物质的量的25%~200%。
6.如权利要求1所述的方法,其特征在于所述乙腈和水的混合溶剂中,乙腈、水的体积比为100:1。
7.如权利要求1所述的方法,其特征在于所述无机碱为碳酸氢钾。
8.如权利要求1所述的方法,其特征在于所述反应液后处理方法为:反应结束后,反应液中加入柱层析硅胶,减压蒸馏除去溶剂,剩余混合物装柱,经柱层析分离,以石油醚、乙酸乙酯体积比为10:1的混合溶剂作为洗脱剂,收集含有产物的洗脱液,洗脱液蒸除溶剂得到式II所示的苯偶酰类衍生物。
9.如权利要求1所述的方法,其特征在于所述方法按以下步骤进行:式I所示的环氧查尔酮类化合物、碳酸氢钾和Selectfluor氧化剂加入乙腈和水体积比为100:1的混合溶剂中,80℃下搅拌反应4~8小时,反应结束后,反应液中加入柱层析硅胶,减压蒸馏除去溶剂,剩余混合物装柱,经柱层析分离,以石油醚、乙酸乙酯体积比为10:1的混合溶剂作为洗脱剂,收集含有产物的洗脱液,洗脱液蒸除溶剂得到式II所示的苯偶酰类衍生物;所述碳酸氢钾的物质的量用量为式I所示的环氧查尔酮类化合物的物质的量的50%,所述Selectfluor氧化剂的物质的量用量为式I所示的环氧查尔酮类化合物的物质的量的2倍。
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