CN113149926B - 一种3,5-二取代异恶唑衍生物的制备方法 - Google Patents
一种3,5-二取代异恶唑衍生物的制备方法 Download PDFInfo
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- -1 3, 5-disubstituted isoxazole Chemical class 0.000 title claims abstract description 35
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 48
- 238000006243 chemical reaction Methods 0.000 claims abstract description 33
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000012074 organic phase Substances 0.000 claims abstract description 19
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 15
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- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 61
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 3
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- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
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- 229910015900 BF3 Inorganic materials 0.000 claims description 2
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 5
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 1
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims 1
- ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 claims 1
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- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 26
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- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
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- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- DDTNTMAGRKDQGV-UHFFFAOYSA-N 2,2-dimethyl-1-(5-phenyl-1,2-oxazol-3-yl)propan-1-one Chemical compound O1N=C(C(=O)C(C)(C)C)C=C1C1=CC=CC=C1 DDTNTMAGRKDQGV-UHFFFAOYSA-N 0.000 description 1
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical group [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 239000005794 Hymexazol Substances 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 240000000111 Saccharum officinarum Species 0.000 description 1
- 235000007201 Saccharum officinarum Nutrition 0.000 description 1
- HTNUQGIVNNBJAP-UHFFFAOYSA-N [5-(4-methylphenyl)-1,2-oxazol-3-yl]-phenylmethanone Chemical compound Cc1ccc(cc1)-c1cc(no1)C(=O)c1ccccc1 HTNUQGIVNNBJAP-UHFFFAOYSA-N 0.000 description 1
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- DAMJCWMGELCIMI-UHFFFAOYSA-N benzyl n-(2-oxopyrrolidin-3-yl)carbamate Chemical compound C=1C=CC=CC=1COC(=O)NC1CCNC1=O DAMJCWMGELCIMI-UHFFFAOYSA-N 0.000 description 1
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- KIEDNEWSYUYDSN-UHFFFAOYSA-N clomazone Chemical compound O=C1C(C)(C)CON1CC1=CC=CC=C1Cl KIEDNEWSYUYDSN-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
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- 125000000623 heterocyclic group Chemical group 0.000 description 1
- KGVPNLBXJKTABS-UHFFFAOYSA-N hymexazol Chemical compound CC1=CC(O)=NO1 KGVPNLBXJKTABS-UHFFFAOYSA-N 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- MSUDZPQDTNCHCN-UHFFFAOYSA-N methyl 3-benzoyl-1,2-oxazole-5-carboxylate Chemical compound O1C(C(=O)OC)=CC(C(=O)C=2C=CC=CC=2)=N1 MSUDZPQDTNCHCN-UHFFFAOYSA-N 0.000 description 1
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- CQEDKUUQCWMLEO-UHFFFAOYSA-N phenyl-(5-propyl-1,2-oxazol-3-yl)methanone Chemical compound O1C(CCC)=CC(C(=O)C=2C=CC=CC=2)=N1 CQEDKUUQCWMLEO-UHFFFAOYSA-N 0.000 description 1
- QUHRTCFSVITPGZ-UHFFFAOYSA-N phenyl-(5-trimethylsilyl-1,2-oxazol-3-yl)methanone Chemical compound O1C([Si](C)(C)C)=CC(C(=O)C=2C=CC=CC=2)=N1 QUHRTCFSVITPGZ-UHFFFAOYSA-N 0.000 description 1
- 230000008635 plant growth Effects 0.000 description 1
- 244000000003 plant pathogen Species 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 238000003786 synthesis reaction Methods 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D261/18—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/0825—Preparations of compounds not comprising Si-Si or Si-cyano linkages
- C07F7/083—Syntheses without formation of a Si-C bond
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
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- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
本发明公开了一种3，5‑二取代异恶唑衍生物的制备方法，包括如下步骤：(1)向反应容器中加入炔类化合物、硫叶立德、亚硝酸叔丁酯、添加剂和有机溶剂，于60‑100℃反应12‑24h；(2)将步骤(1)所得的物料经乙酸乙酯稀释后，再经水洗，分离得有机相；(3)将步骤(2)所得的有机相经干燥、过滤、浓缩和柱层析色谱或薄层色谱，得到所述3，5‑二取代异恶唑衍生物。本发明所用原料易得，收率高，反应条件温和，反应时间短，底物范围广，反应专一性强，后处理简便且绿色。
Description
技术领域
本发明属于有机合成技术领域，具体涉及一种3,5-二取代异恶唑衍生物的制备方法。
背景技术
3,5-二取代异恶唑衍生物是一种重要的有机化合物，由于其具有一定的生物活性，广泛应用于医药、农药等诸多领域，并且还可以用于合成药物中间体。例如，蝇蕈醇(Muscimol)，具有一定的药物活性，在脑神经细胞中有一定的活性，可用于精神治疗；除草剂异恶隆，可以除去甘蔗地中的杂草；杀菌剂恶霉灵可以对一些植物病菌所引发的疾病进行一定的预防作用，促进植物的生长。因此有效的、对环境友好的合成3,5-二取代异恶唑衍生物的方法已成为有机化学领域中的一个新挑战。
发明内容
本发明的目的在于克服现有技术缺陷，提供一种3,5-二取代异恶唑衍生物的制备方法。
本发明的技术方案如下：
一种3,5-二取代异恶唑衍生物的制备方法，包括如下步骤：
(1)向反应容器中加入炔类化合物、硫叶立德、亚硝酸叔丁酯、添加剂和有机溶剂，于60-100℃反应12-24h；
(2)将步骤(1)所得的物料经乙酸乙酯稀释后，再经水洗，分离得有机相；
(3)将步骤(2)所得的有机相经干燥、过滤、浓缩和柱层析色谱或薄层色谱，得到所述3,5-二取代异恶唑衍生物；
上述炔类化合物的结构式为
其中的R为烷基、烷基硅、酯基、苯环基或取代苯环基，且取代苯基中的取代基为烷基、烷氧基、三氟甲基或卤素；
上述硫叶立德的结构式为
其中R为烷基、酯基、苯环基、取代苯环基或杂环基，且取代苯基中的取代基为烷基、烷氧基、三氟甲基或卤素；
上述添加剂为三氟化硼二乙醚、三氟甲磺酸、三氟乙酸、氯化铁、氯化锌或三氯化锑；
上述有机溶剂为二甲基亚砜、N,N－二甲基甲酰胺、N-甲基-2-吡咯烷酮、1,2-二氯乙烷、甲苯、1,4-二氧六环、四氢呋喃、六氟异丙醇、甲基叔丁基醚或乙腈。
在本发明的一个优选实施方案中，所述炔类化合物为三甲基乙炔基硅、4-甲苯基乙炔、1-乙炔基-3-氟苯、环己乙炔、1-戊炔、丙烯酸甲酯或苯乙炔。
在本发明的一个优选实施方案中，所述硫叶立德为2-(二甲基(氧代)-λ6-亚磺酰基)-1-苯基乙-1-酮、2-(二甲基(氧代)-λ6-亚磺酰基)-1-(2-(三氟甲基)苯基)乙-1-酮、2-(二甲基(氧代)-λ6-亚磺酰基)-1-(3-甲氧基苯基)乙-1-酮、2-(二甲基(氧代)-λ6-亚磺酰基)-1-(4-苯氧基苯基)乙-1-酮、2-(二甲基(氧代)-λ6-亚磺酰基)-1-(2,4-二甲基苯基)乙-1-酮、2-(二甲基(氧代)-λ6-亚磺酰基)-1-(噻吩-2-基)乙-1-酮、2-(二甲基(氧代)-λ6-亚磺酰基亚丙基)乙酸丙酯或1-(二甲基(氧代)-λ6-亚磺酰基)-3,3-二甲基丁烷-2-酮。
在本发明的一个优选实施方案中，所述添加剂为三氟化硼二乙醚。
在本发明的一个优选实施方案中，所述有机溶剂为1,2-二氯乙烷。
在本发明的一个优选实施方案中，所述炔类化合物为三甲基乙炔基硅、4-甲苯基乙炔、1-乙炔基-3-氟苯、环己乙炔、1-戊炔、丙烯酸甲酯或苯乙炔，所述硫叶立德为2-(二甲基(氧代)-λ6-亚磺酰基)-1-苯基乙-1-酮、2-(二甲基(氧代)-λ6-亚磺酰基)-1-(2-(三氟甲基)苯基)乙-1-酮、2-(二甲基(氧代)-λ6-亚磺酰基)-1-(3-甲氧基苯基)乙-1-酮、2-(二甲基(氧代)-λ6-亚磺酰基)-1-(4-苯氧基苯基)乙-1-酮、2-(二甲基(氧代)-λ6-亚磺酰基)-1-(2,4-二甲基苯基)乙-1-酮、2-(二甲基(氧代)-λ6-亚磺酰基)-1-(噻吩-2-基)乙-1-酮、2-(二甲基(氧代)-λ6-亚磺酰基亚丙基)乙酸丙酯或1-(二甲基(氧代)-λ6-亚磺酰基)-3,3-二甲基丁烷-2-酮，所述添加剂为三氟化硼二乙醚，所述有机溶剂为1,2-二氯乙烷。
进一步优选的，所述炔类化合物为三甲基乙炔基硅、4-甲苯基乙炔、1-乙炔基-3-氟苯、环己乙炔、1-戊炔或丙烯酸甲酯，所述硫叶立德为2-(二甲基(氧代)-λ6-亚磺酰基)-1-苯基乙-1-酮，所述添加剂为三氟化硼二乙醚，所述有机溶剂为1,2-二氯乙烷。
进一步优选的，所述炔类化合物为苯乙炔，所述硫叶立德为2-(二甲基(氧代)-λ6-亚磺酰基)-1-(2-(三氟甲基)苯基)乙-1-酮、2-(二甲基(氧代)-λ6-亚磺酰基)-1-(3-甲氧基苯基)乙-1-酮、2-(二甲基(氧代)-λ6-亚磺酰基)-1-(4-苯氧基苯基)乙-1-酮、2-(二甲基(氧代)-λ6-亚磺酰基)-1-(2,4-二甲基苯基)乙-1-酮、2-(二甲基(氧代)-λ6-亚磺酰基)-1-(噻吩-2-基)乙-1-酮、2-(二甲基(氧代)-λ6-亚磺酰基亚丙基)乙酸丙酯或1-(二甲基(氧代)-λ6-亚磺酰基)-3,3-二甲基丁烷-2-酮，所述添加剂为三氟化硼二乙醚，所述有机溶剂为1,2-二氯乙烷。
在本发明的一个优选实施方案中，所述炔类化合物、硫叶立德、亚硝酸叔丁酯、添加剂和有机溶剂的比例为0.1-0.3mmol:0.3-0.5mmol:0.3-0.5mmol:0.04-0.06mmol:0.8-1.2mL。
进一步优选的，所述炔类化合物、硫叶立德、亚硝酸叔丁酯、添加剂和有机溶剂的比例为0.2mmol:0.4mmol:0.4mmol:0.05mmol:1mL。
本发明的有益效果是：
1、本发明所制得的3,5-二取代异恶唑衍生物具有良好的区域选择性。
2、本发明所用原料易得，收率高，反应条件温和，反应时间短，底物范围广，反应专一性强，后处理简便且绿色。
具体实施方式
以下通过具体实施方式对本发明的技术方案进行进一步的说明和描述。
实施例1
苯基(5-(三甲基甲硅烷基)异恶唑-3-基)甲酮的制备
将三甲基乙炔基硅0.2mmol、2-(二甲基(氧代)-λ6-亚磺酰基)-1-苯基乙-1-酮0.4mmol、亚硝酸叔丁酯0.4mmol、三氟化硼二乙醚(BF3 46.5％)0.05mmol和1,2-二氯乙烷1mL加入到15mL的反应管中，置于80℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，薄层色谱纯化得到40.9mg的目标产物，收率为83％。本实施例制得的目标产物的核磁和高分辨质谱表征如下：1H NMR(500MHz,Chloroform-d)δ8.31(dd,J＝8.4,1.4Hz,2H),7.66–7.62(m,1H),7.52(t,J＝7.8Hz,2H),6.97(s,1H),0.41(s,9H)；13C NMR(126MHz,Chloroform-d)δ186.3,179.2,160.2,136.1,133.9,130.6,128.5,113.4,-2.0；HRMS(ESI-TOF)m/z:calcd for C13H16NO2Si+:246.0945(M+H)+,found:246.0946.
实施例2
苯基(5-(对甲苯基)异恶唑-3-基)甲酮的制备
将4-甲苯基乙炔0.2mmol、2-(二甲基(氧代)-λ6-亚磺酰基)-1-苯基乙-1-酮0.4mmol、亚硝酸叔丁酯0.4mmol、三氟化硼二乙醚(BF3 46.5％)0.05mmol和1,2-二氯乙烷1mL加入到15mL的反应管中，置于80℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，薄层色谱纯化得到32.5mg的目标产物，收率为62％。本实施例制得的目标产物的核磁和高分辨质谱表征如下：1H NMR(500MHz,Chloroform-d)δ8.34(dd,J＝8.4,1.4Hz,2H),7.73(d,J＝8.2Hz,2H),7.65(t,J＝7.4Hz,1H),7.53(t,J＝7.8Hz,2H),7.30(d,J＝7.9Hz,2H),6.99(s,1H),2.42(s,3H)；13C NMR(126MHz,Chloroform-d)δ185.9,170.9,162.3,141.1,135.8,134.0,130.6,129.8,128.5,125.9,124.0,99.6,21.5；HRMS(ESI-TOF)m/z:calcd for C17H14NO2 +:264.1019(M+H)+,found:264.1022.
实施例3
(5-(3-氟苯基)异恶唑-3-基)(苯基)甲酮的制备
将1-乙炔基-3-氟苯0.2mmol、2-(二甲基(氧代)-λ6-亚磺酰基)-1-苯基乙-1-酮0.4mmol、亚硝酸叔丁酯0.4mmol、三氟化硼二乙醚(BF3 46.5％)0.05mmol和1,2-二氯乙烷1mL加入到15mL的反应管中，置于80℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，薄层色谱纯化得到36.6mg的目标产物，收率为68％。本实施例制得的目标产物的核磁和高分辨质谱表征如下：1H NMR(500MHz,Chloroform-d)δ8.37–8.31(m,2H),7.69–7.65(m,1H),7.63(dt,J＝7.8,1.3Hz,1H),7.54(t,J＝7.8Hz,3H),7.48(td,J＝8.1,5.6Hz,1H),7.19(tdd,J＝8.4,2.6,0.9Hz,1H),7.08(s,1H)；13C NMR(126MHz,Chloroform-d)δ185.5,169.4(d,J＝2.9Hz),162.9(d,J＝247.7Hz),162.4,135.6,134.1,130.9(d,J＝8.2Hz),130.7,128.6,128.5(d,J＝8.5Hz),121.7(d,J＝3.2Hz),117.7(d,J＝21.3Hz),113.0(d,J＝23.8Hz),101.1；HRMS(ESI-TOF)m/z:calcd for C16H11FNO2 +:268.0768(M+H)+,found:268.0770.
实施例4
(5-环己基异恶唑-3-基)(苯基)甲酮的制备
将环己乙炔0.2mmol、2-(二甲基(氧代)-λ6-亚磺酰基)-1-苯基乙-1-酮0.4mmol、亚硝酸叔丁酯0.4mmol、三氟化硼二乙醚(BF3 46.5％)0.05mmol和1,2-二氯乙烷1mL加入到15mL的反应管中，置于80℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，薄层色谱纯化得到35.5mg的目标产物，收率为70％。本实施例制得的目标产物的核磁和高分辨质谱表征如下：1H NMR(500MHz,Chloroform-d)δ8.32–8.26(m,2H),7.66–7.61(m,1H),7.51(t,J＝7.8Hz,2H),6.49(s,1H),2.87(tt,J＝11.3,3.7Hz,1H),2.11(dd,J＝12.8,3.6Hz,2H),1.85(dt,J＝12.9,3.6Hz,2H),1.79–1.70(m,1H),1.55–1.37(m,4H),1.30(ddt,J＝16.0,12.3,6.0Hz,1H)；13C NMR(126MHz,Chloroform-d)δ186.2,178.7,161.7,135.9,133.8,130.6,128.5,100.0,36.2,31.1,25.7,25.6；HRMS(ESI-TOF)m/z:calcd for C16H18NO2 +:256.1332(M+H)+,found:256.1333.
实施例5
苯基(5-丙基异恶唑-3-基)甲酮的制备
将1-戊炔0.2mmol、2-(二甲基(氧代)-λ6-亚磺酰基)-1-苯基乙-1-酮0.4mmol、亚硝酸叔丁酯0.4mmol、三氟化硼二乙醚(BF3 46.5％)0.05mmol和1,2-二氯乙烷1mL加入到15mL的反应管中，置于80℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，薄层色谱纯化得到26.4mg的目标产物，收率为61％。本实施例制得的目标产物的核磁和高分辨质谱表征如下：1H NMR(500MHz,Chloroform-d)δ8.30(d,J＝7.5Hz,2H),7.64(t,J＝7.3Hz,1H),7.52(t,J＝7.7Hz,2H),6.53(s,1H),2.83(t,J＝7.5Hz,2H),1.80(h,J＝7.4Hz,2H),1.04(t,J＝7.4Hz,3H)；13C NMR(126MHz,Chloroform-d)δ186.1,174.5,161.8,135.9,133.8,130.6,128.5,101.7,28.5,20.9,13.6；HRMS(ESI-TOF)m/z:calcd for C13H14NO2 +:216.1019(M+H)+,found:216.1016.
实施例6
3-苯甲酰基异恶唑-5-羧酸甲酯的制备
将丙烯酸甲酯0.2mmol、2-(二甲基(氧代)-λ6-亚磺酰基)-1-苯基乙-1-酮0.4mmol、亚硝酸叔丁酯0.4mmol、三氟化硼二乙醚(BF3 46.5％)0.05mmol和1,2-二氯乙烷1mL加入到15mL的反应管中，置于80℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，薄层色谱纯化得到40.4mg的目标产物，收率为87％。本实施例制得的目标产物的核磁和高分辨质谱表征如下：1H NMR(500MHz,Chloroform-d)δ8.31(dd,J＝8.4,1.4Hz,2H),7.72–7.64(m,1H),7.55(t,J＝7.9Hz,2H),7.44(s,1H),4.02(s,3H)；13C NMR(126MHz,Chloroform-d)δ184.4,162.1,160.7,156.6,135.1,134.4,130.7,128.7,110.2,53.1；HRMS(ESI-TOF)m/z:calcd for C12H10NO4 +:232.0604(M+H)+,found:232.0600.
实施例7
(5-苯基异恶唑-3-基)(2-(三氟甲基)苯基)甲酮的制备
将苯乙炔0.2mmol、2-(二甲基(氧代)-λ6-亚磺酰基)-1-(2-(三氟甲基)苯基)乙-1-酮0.4mmol、亚硝酸叔丁酯0.4mmol、三氟化硼二乙醚(BF3 46.5％)0.05mmol和1,2-二氯乙烷1mL加入到15mL的反应管中，置于80℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，薄层色谱纯化得到62.8mg的目标产物，收率为99％。本实施例制得的目标产物的核磁和高分辨质谱表征如下：1H NMR(500MHz,Chloroform-d)δ7.87–7.77(m,3H),7.73–7.64(m,3H),7.53–7.48(m,3H),7.09(s,1H)；13C NMR(126MHz,Chloroform-d)δ187.7,171.9,162.6,136.4,131.4,131.45,131.05,129.2,129.0,128.5(d,J＝32.5Hz),126.9(q,J＝4.6Hz),126.5,126.0,123.5(d,J＝273.8Hz),98.8；HRMS(ESI-TOF)m/z:calcd for C17H11F3NO2 +:318.0736(M+H)+,found:318.0733.
实施例8
(3-甲氧基苯基)(5-苯基异恶唑-3-基)甲酮的制备
将苯乙炔0.2mmol、2-(二甲基(氧代)-λ6-亚磺酰基)-1-(3-甲氧基苯基)乙-1-酮0.4mmol、亚硝酸叔丁酯0.4mmol、三氟化硼二乙醚(BF3 46.5％)0.05mmol和1,2-二氯乙烷1mL加入到15mL的反应管中，置于80℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，薄层色谱纯化得到42.7mg的目标产物，收率为76％。本实施例制得的目标产物的核磁和高分辨质谱表征如下：1H NMR(500MHz,Chloroform-d)δ7.99(ddd,J＝7.7,1.6,1.0Hz,1H),7.87–7.84(m,3H),7.53–7.49(m,3H),7.45(t,J＝7.9Hz,1H),7.21(ddd,J＝8.2,2.7,1.0Hz,1H),7.05(s,1H),3.90(s,3H)；13CNMR(126MHz,Chloroform-d)δ185.5,170.7,162.4,159.7,136.9,130.7,129.6,129.1,126.7,126.0,123.7,120.9,114.3,100.3,55.5；HRMS(ESI-TOF)m/z:calcd for C17H14NO3 +:280.0968(M+H)+,found:280.0969.
实施例9
(4-苯氧基苯基)(5-苯基异恶唑-3-基)甲酮的制备
将苯乙炔0.2mmol、2-(二甲基(氧代)-λ6-亚磺酰基)-1-(4-苯氧基苯基)乙-1-酮0.4mmol、亚硝酸叔丁酯0.4mmol、三氟化硼二乙醚(BF3 46.5％)0.05mmol和1,2-二氯乙烷1mL加入到15mL的反应管中，置于80℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，薄层色谱纯化得到53.1mg的目标产物，收率为78％。本实施例制得的目标产物的核磁和高分辨质谱表征如下：1H NMR(500MHz,Chloroform-d)δ8.40–8.36(m,2H),7.85(dd,J＝7.8,1.8Hz,2H),7.54–7.46(m,3H),7.45–7.38(m,2H),7.23(t,J＝7.5Hz,1H),7.11(dd,J＝7.6,1.3Hz,2H),7.08–7.05(m,2H),7.04(s,1H)；13C NMR(126MHz,Chloroform-d)δ184.1,170.6,163.0,162.5,155.1,133.2,130.7,130.2,130.1,129.1,126.7,125.9,124.8,120.4,117.2,100.3；HRMS(ESI-TOF)m/z:calcdfor C22H16NO3 +:342.1125(M+H)+,found:342.1128.
实施例10
(2,4-二甲基苯基)(5-苯基异恶唑-3-基)甲酮的制备
将苯乙炔0.2mmol、2-(二甲基(氧代)-λ6-亚磺酰基)-1-(2,4-二甲基苯基)乙-1-酮0.4mmol、亚硝酸叔丁酯0.4mmol、三氟化硼二乙醚(BF3 46.5％)0.05mmol和1,2-二氯乙烷1mL加入到15mL的反应管中，置于80℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，薄层色谱纯化得到39.5mg的目标产物，收率为71％。本实施例制得的目标产物的核磁和高分辨质谱表征如下：1H NMR(500MHz,Chloroform-d)δ7.84(dd,J＝7.6,2.1Hz,3H),7.53–7.47(m,3H),7.16–7.10(m,2H),7.01(s,1H),2.53(s,3H),2.39(s,3H)；13C NMR(126MHz,Chloroform-d)δ188.4,170.9,163.3,143.1,139.5,133.1,132.6,131.9,130.6,129.1,126.8,126.1,125.9,99.8,21.5,20.9；HRMS(ESI-TOF)m/z:calcd for C18H16NO2 +:278.1176(M+H)+,found:278.1177.
实施例11
(5-苯基异恶唑-3-基)(噻吩-2-基)甲酮的制备
将苯乙炔0.2mmol、2-(二甲基(氧代)-λ6-亚磺酰基)-1-(噻吩-2-基)乙-1-酮0.4mmol、亚硝酸叔丁酯0.4mmol、三氟化硼二乙醚(BF3 46.5％)0.05mmol和1,2-二氯乙烷1mL加入到15mL的反应管中，置于80℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，薄层色谱纯化得到35.2mg的目标产物，收率为69％。本实施例制得的目标产物的核磁和高分辨质谱表征如下：1H NMR(500MHz,Chloroform-d)δ8.51(dd,J＝3.9,1.2Hz,1H),7.85(dd,J＝7.8,1.8Hz,2H),7.82(dd,J＝4.9,1.2Hz,1H),7.54–7.48(m,3H),7.24(dd,J＝4.9,3.9Hz,1H),7.06(s,1H)；13C NMR(126MHz,Chloroform-d)δ177.1,170.9,162.2,141.6,136.7,136.1,130.7,129.1,128.6,126.6,126.0,99.7；HRMS(ESI-TOF)m/z:calcd for C14H10NO2S+:256.0427(M+H)+,found:256.0426.
实施例12
5-苯基异恶唑-3-羧酸丙酯的制备
将苯乙炔0.2mmol、2-(二甲基(氧代)-λ6-亚磺酰基亚丙基)乙酸丙酯0.4mmol、亚硝酸叔丁酯0.4mmol、三氟化硼二乙醚(BF3 46.5％)0.05mmol和1,2-二氯乙烷1mL加入到15mL的反应管中，置于80℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，薄层色谱纯化得到26.9mg的目标产物，收率为58％。本实施例制得的目标产物的核磁和高分辨质谱表征如下：1H NMR(500MHz,Chloroform-d)δ7.84–7.81(m,2H),7.53–7.48(m,3H),6.94(s,1H),4.38(t,J＝6.8Hz,2H),1.85(h,J＝7.3Hz,2H),1.05(t,J＝7.5Hz,3H)；13C NMR(126MHz,Chloroform-d)δ171.7,160.1,156.9,130.8,129.1,126.6,125.9,99.9,67.7,21.9,10.3；HRMS(ESI-TOF)m/z:calcd for C13H14NO3 +:232.0968(M+H)+,found:232.0970.
实施例13
2,2-二甲基-1-(5-苯基异恶唑-3-基)丙-1-酮的制备
将苯乙炔0.2mmol、1-(二甲基(氧代)-λ6-亚磺酰基)-3,3-二甲基丁烷-2-酮0.4mmol、亚硝酸叔丁酯0.4mmol、三氟化硼二乙醚(BF3 46.5％)0.05mmol和1,2-二氯乙烷1mL加入到15mL的反应管中，置于80℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，薄层色谱纯化得到33.4mg的目标产物，收率为73％。本实施例制得的目标产物的核磁和高分辨质谱表征如下：1H NMR(500MHz,Chloroform-d)δ7.80(dd,J＝7.8,1.8Hz,2H),7.53–7.44(m,3H),6.87(s,1H),1.44(s,9H)；13C NMR(126MHz,Chloroform-d)δ199.9,170.1,161.2,130.5,129.1,126.8,125.9,100.0,44.8,26.7；HRMS(ESI-TOF)m/z:calcd for C14H16NO2 +:230.1176(M+H)+,found:230.1172.
以上所述，仅为本发明的较佳实施例而已，故不能依此限定本发明实施的范围，即依本发明专利范围及说明书内容所作的等效变化与修饰，皆应仍属本发明涵盖的范围内。
Claims (6)
1.一种3,5-二取代异恶唑衍生物的制备方法，其特征在于：包括如下步骤：
（1）向反应容器中加入炔类化合物、硫叶立德、亚硝酸叔丁酯、添加剂和有机溶剂，于60-100℃反应12-24h；
（2）将步骤（1）所得的物料经乙酸乙酯稀释后，再经水洗，分离得有机相；
（3）将步骤（2）所得的有机相经干燥、过滤、浓缩和柱层析色谱或薄层色谱，得到所述3,5-二取代异恶唑衍生物；
上述炔类化合物为三甲基乙炔基硅、4-甲苯基乙炔、1-乙炔基-3-氟苯、环己乙炔、1-戊炔或苯乙炔；
上述硫叶立德为2-（二甲基（氧代）-λ6-亚磺酰基）-1-苯基乙-1-酮、2-（二甲基（氧代）-λ6-亚磺酰基）-1-（2-（三氟甲基）苯基）乙-1-酮、2-（二甲基（氧代）-λ6-亚磺酰基）-1-（3-甲氧基苯基）乙-1-酮、2-（二甲基（氧代）-λ6-亚磺酰基）-1-（4-苯氧基苯基）乙-1-酮、2-（二甲基（氧代）-λ6-亚磺酰基）-1-（2,4-二甲基苯基）乙-1-酮、2-（二甲基（氧代）-λ6-亚磺酰基）-1-（噻吩-2-基）乙-1-酮、2-（二甲基（氧代）-λ6-亚磺酰基亚丙基）乙酸丙酯或1-（二甲基（氧代）-λ6-亚磺酰基）-3,3-二甲基丁烷-2-酮；
上述添加剂为三氟化硼二乙醚；
上述有机溶剂为二甲基亚砜、N,N－二甲基甲酰胺、N-甲基-2-吡咯烷酮、1,2-二氯乙烷、甲苯、1,4-二氧六环、四氢呋喃、六氟异丙醇、甲基叔丁基醚或乙腈。
2.如权利要求1所述的制备方法，其特征在于：所述炔类化合物为三甲基乙炔基硅、4-甲苯基乙炔、1-乙炔基-3-氟苯、环己乙炔、1-戊炔或苯乙炔，所述硫叶立德为2-（二甲基（氧代）-λ6-亚磺酰基）-1-苯基乙-1-酮、2-（二甲基（氧代）-λ6-亚磺酰基）-1-（2-（三氟甲基）苯基）乙-1-酮、2-（二甲基（氧代）-λ6-亚磺酰基）-1-（3-甲氧基苯基）乙-1-酮、2-（二甲基（氧代）-λ6-亚磺酰基）-1-（4-苯氧基苯基）乙-1-酮、2-（二甲基（氧代）-λ6-亚磺酰基）-1-（2,4-二甲基苯基）乙-1-酮、2-（二甲基（氧代）-λ6-亚磺酰基）-1-（噻吩-2-基）乙-1-酮、2-（二甲基（氧代）-λ6-亚磺酰基亚丙基）乙酸丙酯或1-（二甲基（氧代）-λ6-亚磺酰基）-3,3-二甲基丁烷-2-酮，所述添加剂为三氟化硼二乙醚，所述有机溶剂为1,2-二氯乙烷。
3.如权利要求2所述的制备方法，其特征在于：所述炔类化合物为三甲基乙炔基硅、4-甲苯基乙炔、1-乙炔基-3-氟苯、环己乙炔或1-戊炔，所述硫叶立德为2-（二甲基（氧代）-λ6-亚磺酰基）-1-苯基乙-1-酮，所述添加剂为三氟化硼二乙醚，所述有机溶剂为1,2-二氯乙烷。
4.如权利要求2所述的制备方法，其特征在于：所述炔类化合物为苯乙炔，所述硫叶立德为2-（二甲基（氧代）-λ6-亚磺酰基）-1-（2-（三氟甲基）苯基）乙-1-酮、2-（二甲基（氧代）-λ6-亚磺酰基）-1-（3-甲氧基苯基）乙-1-酮、2-（二甲基（氧代）-λ6-亚磺酰基）-1-（4-苯氧基苯基）乙-1-酮、2-（二甲基（氧代）-λ6-亚磺酰基）-1-（2,4-二甲基苯基）乙-1-酮、2-（二甲基（氧代）-λ6-亚磺酰基）-1-（噻吩-2-基）乙-1-酮、2-（二甲基（氧代）-λ6-亚磺酰基亚丙基）乙酸丙酯或1-（二甲基（氧代）-λ6-亚磺酰基）-3,3-二甲基丁烷-2-酮，所述添加剂为三氟化硼二乙醚，所述有机溶剂为1,2-二氯乙烷。
5.如权利要求1至4中任一权利要求所述的制备方法，其特征在于：所述炔类化合物、硫叶立德、亚硝酸叔丁酯、添加剂和有机溶剂的比例为0.1-0.3mmol: 0.3-0.5mmol: 0.3-0.5mmol: 0.04-0.06 mmol: 0.8-1.2mL。
6. 如权利要求5所述的制备方法，其特征在于：所述炔类化合物、硫叶立德、亚硝酸叔丁酯、添加剂和有机溶剂的比例为0.2mmol: 0.4mmol: 0.4mmol: 0.05mmol: 1mL。
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5273989A (en) * | 1990-04-12 | 1993-12-28 | Hoechst Aktiengesellschaft | 3,5-disubstituted 2-isoxazolines and isoxazoles, agents containing them and their use |
| CN102584735A (zh) * | 2011-12-13 | 2012-07-18 | 大连理工大学 | 一种异噁唑类化合物的制备方法 |
| JP2014172851A (ja) * | 2013-03-07 | 2014-09-22 | Chiba Univ | ピラゾール誘導体の製造方法およびイソオキサゾール誘導体の製造方法 |
| CN105237491A (zh) * | 2015-09-17 | 2016-01-13 | 上海大学 | 异噁唑类化合物及其合成方法 |
| CN108069918A (zh) * | 2018-01-18 | 2018-05-25 | 江西师范大学 | 一锅法制备3-二氟甲基异噁唑化合物的方法 |
| CN108191785A (zh) * | 2018-02-01 | 2018-06-22 | 湖北科技学院 | 一种多取代4，5－二氢异噁唑类化合物及其合成方法 |
| WO2020070610A1 (en) * | 2018-10-01 | 2020-04-09 | Pi Industries Ltd. | Novel oxadiazoles |
-
2021
- 2021-04-30 CN CN202110487764.8A patent/CN113149926B/zh active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5273989A (en) * | 1990-04-12 | 1993-12-28 | Hoechst Aktiengesellschaft | 3,5-disubstituted 2-isoxazolines and isoxazoles, agents containing them and their use |
| CN102584735A (zh) * | 2011-12-13 | 2012-07-18 | 大连理工大学 | 一种异噁唑类化合物的制备方法 |
| JP2014172851A (ja) * | 2013-03-07 | 2014-09-22 | Chiba Univ | ピラゾール誘導体の製造方法およびイソオキサゾール誘導体の製造方法 |
| CN105237491A (zh) * | 2015-09-17 | 2016-01-13 | 上海大学 | 异噁唑类化合物及其合成方法 |
| CN108069918A (zh) * | 2018-01-18 | 2018-05-25 | 江西师范大学 | 一锅法制备3-二氟甲基异噁唑化合物的方法 |
| CN108191785A (zh) * | 2018-02-01 | 2018-06-22 | 湖北科技学院 | 一种多取代4，5－二氢异噁唑类化合物及其合成方法 |
| WO2020070610A1 (en) * | 2018-10-01 | 2020-04-09 | Pi Industries Ltd. | Novel oxadiazoles |
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