CN112225701A - 一种n-乙烯基唑类化合物的合成方法 - Google Patents
一种n-乙烯基唑类化合物的合成方法 Download PDFInfo
- Publication number
- CN112225701A CN112225701A CN202011276916.1A CN202011276916A CN112225701A CN 112225701 A CN112225701 A CN 112225701A CN 202011276916 A CN202011276916 A CN 202011276916A CN 112225701 A CN112225701 A CN 112225701A
- Authority
- CN
- China
- Prior art keywords
- azole compound
- vinyl
- synthesizing
- inorganic base
- compound according
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- -1 N-vinyl azole compound Chemical class 0.000 title claims abstract description 35
- 238000001308 synthesis method Methods 0.000 title claims abstract description 7
- 238000000034 method Methods 0.000 claims abstract description 18
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims abstract description 12
- 150000007529 inorganic bases Chemical class 0.000 claims abstract description 12
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 12
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims abstract description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 42
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 42
- 239000003960 organic solvent Substances 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 17
- 235000017281 sodium acetate Nutrition 0.000 claims description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- CTXUTPWZJZHRJC-UHFFFAOYSA-N 1-ethenylpyrrole Chemical class C=CN1C=CC=C1 CTXUTPWZJZHRJC-UHFFFAOYSA-N 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical group ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 150000003851 azoles Chemical class 0.000 claims description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- 239000007789 gas Substances 0.000 claims description 3
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 2
- 239000005695 Ammonium acetate Substances 0.000 claims description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical group [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 235000019257 ammonium acetate Nutrition 0.000 claims description 2
- 229940043376 ammonium acetate Drugs 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 2
- 238000004440 column chromatography Methods 0.000 claims description 2
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 claims description 2
- 229910052808 lithium carbonate Inorganic materials 0.000 claims description 2
- 125000005429 oxyalkyl group Chemical group 0.000 claims description 2
- 235000011056 potassium acetate Nutrition 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 235000011181 potassium carbonates Nutrition 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
- 230000001681 protective effect Effects 0.000 claims description 2
- 238000001953 recrystallisation Methods 0.000 claims description 2
- 239000001632 sodium acetate Substances 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 235000017550 sodium carbonate Nutrition 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 125000005000 thioaryl group Chemical group 0.000 claims description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
- 229910052786 argon Inorganic materials 0.000 claims 1
- 239000001307 helium Substances 0.000 claims 1
- 229910052734 helium Inorganic materials 0.000 claims 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 claims 1
- 229910052754 neon Inorganic materials 0.000 claims 1
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 claims 1
- 229910052757 nitrogen Inorganic materials 0.000 claims 1
- 238000000746 purification Methods 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 3
- 239000000463 material Substances 0.000 abstract description 3
- 239000004065 semiconductor Substances 0.000 abstract description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 52
- 239000007788 liquid Substances 0.000 description 25
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 24
- 239000000758 substrate Substances 0.000 description 21
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 13
- 238000005160 1H NMR spectroscopy Methods 0.000 description 13
- BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 description 13
- 238000012512 characterization method Methods 0.000 description 13
- 239000012043 crude product Substances 0.000 description 13
- 238000010898 silica gel chromatography Methods 0.000 description 13
- 229940087562 sodium acetate trihydrate Drugs 0.000 description 13
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical class C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 3
- 150000003536 tetrazoles Chemical class 0.000 description 3
- PQAMFDRRWURCFQ-UHFFFAOYSA-N 2-ethyl-1h-imidazole Chemical compound CCC1=NC=CN1 PQAMFDRRWURCFQ-UHFFFAOYSA-N 0.000 description 2
- JXHKUYQCEJILEI-UHFFFAOYSA-N 3,5-diphenyl-1h-pyrazole Chemical compound C=1C(C=2C=CC=CC=2)=NNC=1C1=CC=CC=C1 JXHKUYQCEJILEI-UHFFFAOYSA-N 0.000 description 2
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 2
- XHLKOHSAWQPOFO-UHFFFAOYSA-N 5-phenyl-1h-imidazole Chemical compound N1C=NC=C1C1=CC=CC=C1 XHLKOHSAWQPOFO-UHFFFAOYSA-N 0.000 description 2
- MARUHZGHZWCEQU-UHFFFAOYSA-N 5-phenyl-2h-tetrazole Chemical compound C1=CC=CC=C1C1=NNN=N1 MARUHZGHZWCEQU-UHFFFAOYSA-N 0.000 description 2
- ULKLGIFJWFIQFF-UHFFFAOYSA-N 5K8XI641G3 Chemical compound CCC1=NC=C(C)N1 ULKLGIFJWFIQFF-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- 238000006886 vinylation reaction Methods 0.000 description 2
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
- SEULWJSKCVACTH-UHFFFAOYSA-N 1-phenylimidazole Chemical compound C1=NC=CN1C1=CC=CC=C1 SEULWJSKCVACTH-UHFFFAOYSA-N 0.000 description 1
- ZCUJYXPAKHMBAZ-UHFFFAOYSA-N 2-phenyl-1h-imidazole Chemical compound C1=CNC(C=2C=CC=CC=2)=N1 ZCUJYXPAKHMBAZ-UHFFFAOYSA-N 0.000 description 1
- NIAXWFTYAJQENP-UHFFFAOYSA-N 3-ethenyl-2h-1,3-oxazole Chemical class C=CN1COC=C1 NIAXWFTYAJQENP-UHFFFAOYSA-N 0.000 description 1
- 238000006130 Horner-Wadsworth-Emmons olefination reaction Methods 0.000 description 1
- 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 1
- 238000003527 Peterson olefination reaction Methods 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- YFXCNIVBAVFOBX-UHFFFAOYSA-N ethenylboronic acid Chemical compound OB(O)C=C YFXCNIVBAVFOBX-UHFFFAOYSA-N 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明提供了一条低成本的由唑类化合物和炔丙基叔硫盐化合物在常用无机碱的促进下合成N‑乙烯基唑类化合物的新方法。本发明所合成的N‑乙烯基唑类化合物是医药、半导体和光敏材料的重要的结构单元，所以本发明所提供的合成方法有很重要的商业价值。
Description
技术领域
本发明属于药物化学和绿色化学化工技术领域，具体涉及一种由唑类化合物和炔丙基叔硫盐化合物合成N-乙烯基唑类化合物的新方法。
背景技术
N-乙烯基唑是有机合成中重要的结构单元，也是许多药物的重要结构单元。例如，N-乙烯基唑已被证明是合成聚N-乙烯基唑的重要单体，聚N-乙烯基唑被广泛应用于半导体和光敏材料。聚N-乙烯基唑也具有抗真菌活性。传统上其制备方法包括直接向炔烃中添加唑类化合物；唑类化合物与1,2-二溴乙烷烷基化，然后脱除溴化氢；其他制备N-乙烯基唑的方法包括Wittig-Horner，Horner-Wadsworth-Emmons和Peterson烯烃化反应。这些已知的合成方法的区域选择性和底物的通用性都有局限。此外，有些过程需要苛刻的反应条件。另外过渡金属（如钯催化剂）催化的N-乙烯基化是一种有吸引力的方法，但是昂贵的钯催化剂的使用限制了这些方法在工业应用中的吸引力。另外铜催化的乙烯基硼酸的N-乙烯基化反应条件比较温和可以在室温下进行，但需要当量的铜盐作为试剂。
发明内容
本发明提供了一条低成本的由唑类化合物和炔丙基叔硫盐化合物在常用无机碱的促
进下合成N-乙烯基唑类化合物的新方法。
本发明所合成的N-乙烯基唑类化合物是医药、半导体和光敏材料的重要的结构单元，所以本发明所提供的合成方法有很重要的商业价值。
本发明所述的合成N-乙烯基唑类化合物的新方法中底物B中X为Cl、Br或I。
本发明所述的合成N-乙烯基唑类化合物的新方法中底物A的适用范围包括取代的二唑、三唑和四唑；底物A和对应产物的结构通式如下：
其中R1、R2、R3、R4、R5、R6、R7、R8为H、烷基、芳香基、氧烷基、硫烷基、氧芳香基、硫芳香基。
本发明开发的合成N-乙烯基唑类化合物的新方法的具体操作的特征如下：在保护气保护下向含有唑类化合物、炔丙基叔硫盐化合物和第一种无机碱（如醋酸钠、醋酸钾、醋酸铵、碳酸钾、碳酸钠、碳酸氢钾、碳酸氢钠、碳酸铯、碳酸锂）的反应器中加入有机溶剂（如氯仿、1,2-二氯乙烷、四氢呋喃、乙腈、二甲基亚砜、N,N-二甲基甲酰胺），在15-25度反应直到唑类化合物完全消耗完，然后加入第二种无机碱（如氢氧化钠、氢氧化钾、氢氧化锂），然后反应在15-25度继续搅拌过夜，减压条件下除去有机溶剂，柱层析或重结晶纯化得到纯的N-乙烯基唑类化合物。
如上所述的合成方法中唑类化合物和炔丙基叔硫盐化合物的分子当量比例范围为1/1~1/3，唑类化合物和第一种无机碱的分子当量比例范围为1/1~1/3，唑类化合物和第二种无机碱的分子当量比例范围为1/1~1/3。
具体实施方式
下面结合具体的实施例对本发明作进一步说明，但本发明不限于这些实施例。
实施例1
在氮气保护下向含有咪唑（0.2mmol, 1.0equiv）、底物B(73mg, 0.4mmol, 2.0equiv)和三水合醋酸钠(42mg, 0.3mmol, 1.5equiv)的反应器中加入干燥的1,2-二氯乙烷（2mL,c = 0.1M），之后在20度反应直到咪唑完全消耗完，然后加入氢氧化钾（22mg, 0.4mmol,2.0equiv），然后反应在20度继续搅拌12小时。在减压条件下除去有机溶剂，所得粗产物经硅胶柱层析纯化得到纯的无色油状液体产物P-1(23 mg, 产率69%)；
表征：无色油状液体IR νmax (neat)/cm-1: 2992, 2854, 1684, 1302, 1223, 854; 1HNMR (600 MHz, CDCl3): δ 7.63 (s, 1H), 7.04 (s, 2H), 5.09 (s, 1H), 4.84 (s,1H),2.73 (t, J = 7.2 Hz, 2H), 2.55 (t, J = 7.2 Hz, 2H), 2.05 (s, 3H); 13C NMR(150 MHz, CDCl3): δ 141.0, 135.2, 130.0, 117.0, 104.6, 34.0, 31.4, 15.6. HRMS(ESI, m/z): calcd for C8H13N2S+, [M + H]+, 169.0794, found 169.0790。
实施例2
在氮气保护下向含有咪唑（0.2mmol, 1.0equiv）、底物B(73mg, 0.4mmol, 2.0equiv)和三水合醋酸钠(42mg, 0.3mmol, 1.5equiv)的反应器中加入干燥的乙腈（2mL, c =0.1M），之后在20度反应直到咪唑完全消耗完，然后加入氢氧化钾（22mg, 0.4mmol,2.0equiv），然后反应在20度继续搅拌12小时。在减压条件下除去有机溶剂，所得粗产物经硅胶柱层析纯化得到纯的无色油状液体产物P-1(25 mg, 产率74%)；
表征：无色油状液体IR νmax (neat)/cm-1: 2992, 2854, 1684, 1302, 1223, 854; 1HNMR (600 MHz, CDCl3): δ 7.63 (s, 1H), 7.04 (s, 2H), 5.09 (s, 1H), 4.84 (s,1H),2.73 (t, J = 7.2 Hz, 2H), 2.55 (t, J = 7.2 Hz, 2H), 2.05 (s, 3H); 13C NMR(150 MHz, CDCl3): δ 141.0, 135.2, 130.0, 117.0, 104.6, 34.0, 31.4, 15.6. HRMS(ESI, m/z): calcd for C8H13N2S+, [M + H]+, 169.0794, found 169.0790。
实施例3
在氮气保护下向含有咪唑（0.2mmol, 1.0equiv）、底物B(73mg, 0.4mmol, 2.0equiv)和三水合醋酸钠(42mg, 0.3mmol, 1.5equiv)的反应器中加入干燥的乙腈（2mL, c =0.1M），之后在20度反应直到咪唑完全消耗完，然后加入氢氧化钠（16mg, 0.4mmol,2.0equiv），然后反应在20度继续搅拌12小时。在减压条件下除去有机溶剂，所得粗产物经硅胶柱层析纯化得到纯的无色油状液体产物P-1(22 mg, 产率65%)；
表征：无色油状液体IR νmax (neat)/cm-1: 2992, 2854, 1684, 1302, 1223, 854; 1HNMR (600 MHz, CDCl3): δ 7.63 (s, 1H), 7.04 (s, 2H), 5.09 (s, 1H), 4.84 (s,1H),2.73 (t, J = 7.2 Hz, 2H), 2.55 (t, J = 7.2 Hz, 2H), 2.05 (s, 3H); 13C NMR(150 MHz, CDCl3): δ 141.0, 135.2, 130.0, 117.0, 104.6, 34.0, 31.4, 15.6. HRMS(ESI, m/z): calcd for C8H13N2S+, [M + H]+, 169.0794, found 169.0790。
实施例4
在氮气保护下向含有咪唑（0.2mmol, 1.0equiv）、底物B(73mg, 0.4mmol, 2.0equiv)和三水合醋酸钠(54mg, 0.4mmol, 2.0equiv)的反应器中加入干燥的乙腈（2mL, c =0.1M），之后在20度反应直到咪唑完全消耗完，然后加入氢氧化钾（22mg, 0.4mmol,2.0equiv），然后反应在20度继续搅拌12小时。在减压条件下除去有机溶剂，所得粗产物经硅胶柱层析纯化得到纯的无色油状液体产物P-1(26 mg, 产率77%)；
表征：无色油状液体IR νmax (neat)/cm-1: 2992, 2854, 1684, 1302, 1223, 854; 1HNMR (600 MHz, CDCl3): δ 7.63 (s, 1H), 7.04 (s, 2H), 5.09 (s, 1H), 4.84 (s,1H),2.73 (t, J = 7.2 Hz, 2H), 2.55 (t, J = 7.2 Hz, 2H), 2.05 (s, 3H); 13C NMR(150 MHz, CDCl3): δ 141.0, 135.2, 130.0, 117.0, 104.6, 34.0, 31.4, 15.6. HRMS(ESI, m/z): calcd for C8H13N2S+, [M + H]+, 169.0794, found 169.0790。
实施例5
在氮气保护下向含有2-苯基咪唑（底物A-2）（0.2mmol, 1.0equiv）、底物B(73mg,0.4mmol, 2.0equiv)和三水合醋酸钠(54mg, 0.4mmol, 2.0equiv)的反应器中加入干燥的乙腈（2mL, c = 0.1M），之后在20度反应直到2-苯基咪唑完全消耗完，然后加入氢氧化钾（22mg, 0.4mmol, 2.0equiv），然后反应在20度继续搅拌12小时。在减压条件下除去有机溶剂，所得粗产物经硅胶柱层析纯化得到纯的无色油状液体产物P-2(37 mg, 产率76%)；
表征：无色油状液体IR νmax (neat)/cm-1: 3087, 3030, 2985, 2932, 1712, 1684,1412, 1368, 1163, 873, 728; 1H NMR (600 MHz, CDCl3): δ 7.66 (dd, J = 1.2, 1.8Hz, 2H), 7.32–7.29 (m, 3H), 7.06 (d, J = 1.2 Hz, 1H), 6.93 (d, J = 1.2 Hz,1H), 5.23 (d, J = 1.2 Hz, 1H), 5.16 (s, 1H), 2.39 (t, J = 7.2 Hz, 2H), 2.29(t, J = 7.2 Hz, 2H), 1.86 (dd, J =1.2, 1.8 Hz, 3H); 13C NMR (150 MHz, CDCl3):δ 145.5, 143.9, 130.9, 128.5, 128.4, 128.3, 127.7, 122.9, 34.8, 30.9, 15.2.HRMS (ESI, m/z): calcd for C14H17N2S+, [M + H]+, 245.1107, found 245.1102。
实施例6
在氮气保护下向含有2-乙基咪唑（底物A-3）（0.2mmol, 1.0equiv）、底物B(73mg,0.4mmol, 2.0equiv)和三水合醋酸钠(54mg, 0.4mmol, 2.0equiv)的反应器中加入干燥的乙腈（2mL, c = 0.1M），之后在20度反应直到2-乙基咪唑完全消耗完，然后加入氢氧化钾（22mg, 0.4mmol, 2.0equiv），然后反应在20度继续搅拌12小时。在减压条件下除去有机溶剂，所得粗产物经硅胶柱层析纯化得到纯的无色油状液体产物P-3(31mg, 产率79%)；
表征：无色油状液体IR νmax (neat)/cm-1: 2957, 2876, 1624, 1382, 1159, 983; 1HNMR (600 MHz, CDCl3): δ 6.91 (s, 1H), 6.78 (d, J = 0.6 Hz, 1H), 5.20 (s, 1H),5.04 (s, 1H), 2.65 (t, J = 7.2 Hz, 2H), 2.61 (d, J = 7.2 Hz, 2H), 2.42 (t, J = 7.2 Hz, 2H), 2.02 (s, 3H), 1.25(d, J = 7.2 Hz, 3H); 13C NMR (150 MHz,CDCl3): δ 149.1, 142.1, 127.5, 118.6, 113.2, 35.6, 31.0, 20.4, 15.4, 12.4.HRMS (ESI, m/z): calcd for C10H17N2S+, [M + H]+, 197.1107, found 197.1105。
实施例7
在氮气保护下向含有4-苯基咪唑（底物A-4）（0.2mmol, 1.0equiv）、底物B(73mg,0.4mmol, 2.0equiv)和三水合醋酸钠(54mg, 0.4mmol, 2.0equiv)的反应器中加入干燥的乙腈（2mL, c = 0.1M），之后在20度反应直到4-苯基咪唑完全消耗完，然后加入氢氧化钾（22mg, 0.4mmol, 2.0equiv），然后反应在20度继续搅拌12小时。在减压条件下除去有机溶剂，所得粗产物经硅胶柱层析纯化得到纯的无色油状液体产物P-4(29 mg, 产率60%)；
表征：无色油状液体IR νmax (neat)/cm-1: 3062, 2976, 2839, 1561, 1433, 1095;1H NMR (600 MHz, CDCl3): δ 7.71 (d, J = 7.8 Hz, 2H), 7.64 (s, 1H),7.30 (t, J =7.2 Hz, 3H), 7.17 (d, J = 7.2 Hz, 1H), 5.11 (s, 1H), 4.83 (s, 1H), 2.73 (t, J = 7.2 Hz, 2H) , 2.56 (t, J = 7.2 Hz, 2H), 2.03 (s, 3H); 13C NMR (150 MHz,CDCl3): δ 142.6, 140.9, 135.2, 133.5, 128.5, 127.0, 124.8, 112.5, 104.4,33.8, 31.3, 15.6. HRMS (ESI, m/z): calcd for C14H17N2S+, [M + H]+, 245.1107,found 245.1109。
实施例8
在氮气保护下向含有2-乙基-4-甲基咪唑（底物A-5）（0.2mmol, 1.0equiv）、底物B(73mg, 0.4mmol, 2.0equiv)和三水合醋酸钠(54mg, 0.4mmol, 2.0equiv)的反应器中加入干燥的乙腈（2mL, c = 0.1M），之后在20度反应直到2-乙基-4-甲基咪唑完全消耗完，然后加入氢氧化钾（22mg, 0.4mmol, 2.0equiv），然后反应在20度继续搅拌12小时。在减压条件下除去有机溶剂，所得粗产物经硅胶柱层析纯化得到纯的无色油状液体产物P-5 (30mg, 产率70%)；
表征：无色油状液体IR νmax (neat)/cm-1: 2978, 2843, 1502, 1423, 1207, 1035;1H NMR (600 MHz, CDCl3): δ 6.48 (s, 1H), 5.14 (s, 1H), 4.99 (s, 1H), 2.62 (t,J = 7.2 Hz, 2H), 2.58 (t, J = 7.2 Hz, 2H), 2.42 (t, J = 7.2 Hz, 2H), 2.13 (s,3H), 2.02 (s, 3H), 1.24 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3): δ148.6, 142.3, 136.5, 114.9, 112.5, 35.7, 31.1, 20.5, 15.5, 13.5, 12.8. HRMS(ESI, m/z): calcd for C11H19N2S+, [M + H]+, 211.1263, found 211.1263。
实施例9
在氮气保护下向含有吡唑（0.2mmol, 1.0equiv）、底物B(73mg, 0.4mmol, 2.0equiv)和三水合醋酸钠(54mg, 0.4mmol, 2.0equiv)的反应器中加入干燥的乙腈（2mL, c =0.1M），之后在20度反应直到吡唑完全消耗完，然后加入氢氧化钾（22mg, 0.4mmol,2.0equiv），然后反应在20度继续搅拌12小时。在减压条件下除去有机溶剂，所得粗产物经硅胶柱层析纯化得到纯的无色油状液体产物P-6 (19 mg, 产率57%)；
表征：无色油状液体IR νmax (neat)/cm-1: 2926, 2852, 1472, 1261, 1028; 1H NMR(600 MHz, CDCl3): δ 7.64 (d, J = 1.2 Hz, 1H), 7.54 (s, 1H), 6.27 (s, 1H),5.19 (s, 1H), 4.72 (s, 1H), 2.91 (t, J = 7.8 Hz, 2H), 2.63 (t, J = 7.8 Hz,2H), 2.06 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 144.2, 140.4, 127.0, 106.8,100.9, 33.0, 32.0, 15.6. HRMS (ESI, m/z): calcd for C8H13N2S+, [M + H]+,169.0794, found 169.0796。
实施例10
在氮气保护下向含有3,5-二苯基吡唑（0.2mmol, 1.0equiv）、底物B(73mg, 0.4mmol,2.0equiv)和三水合醋酸钠(54mg, 0.4mmol, 2.0equiv)的反应器中加入干燥的乙腈（2mL,c = 0.1M），之后在20度反应直到3,5-二苯基吡唑完全消耗完，然后加入氢氧化钾（22mg,0.4mmol, 2.0equiv），然后反应在20度继续搅拌12小时。在减压条件下除去有机溶剂，所得粗产物经硅胶柱层析纯化得到纯的无色油状液体产物P-7 (43 mg, 67% yield)；
表征：无色油状液体IR νmax (neat)/cm-1: 3069, 3042, 2932, 2816, 1576, 1533,1429, 1377, 1236, 1089; 1H NMR (600 MHz, CDCl3): δ 7.79 (d, J = 7.8 Hz, 2H),7.43 (d, J = 7.2 Hz, 2H), 7.33 (t, J = 7.2 Hz, 4H), 7.30 (t, J = 7.2 Hz, 1H),7.24 (t, J = 7.2 Hz, 1H), 6.61 (s, 1H), 4.95 (s, 1H), 4.79 (s, 1H), 2.82 (t,J = 7.8 Hz, 2H), 2.62 (t, J = 7.8 Hz, 2H), 2.01 (s, 3H); 13C NMR (150 MHz,CDCl3): δ 151.1, 144.6, 144.1, 133.0, 131.0, 128.6, 128.6, 128.5, 128.4,128.0, 125.7, 110.6, 105.2, 34.5, 31.6, 15.4. HRMS (ESI, m/z): calcd forC20H21N2S+, [M + H]+, 321.1420, found 321.1421。
实施例11
在氮气保护下向含有1,2,4-三氮唑（0.2mmol, 1.0equiv）、底物B(73mg, 0.4mmol,2.0equiv)和三水合醋酸钠(54mg, 0.4mmol, 2.0equiv)的反应器中加入干燥的乙腈（2mL,c = 0.1M），之后在20度反应直到1,2,4-三氮唑完全消耗完，然后加入氢氧化钾（22mg,0.4mmol, 2.0equiv），然后反应在20度继续搅拌12小时。在减压条件下除去有机溶剂，所得粗产物经硅胶柱层析纯化得到纯的无色油状液体产物P-8 (22 mg, 65% yield)；
表征：无色油状液体IR νmax (neat)/cm-1: 2933, 2817, 1505, 1433, 1109, 966; 1HNMR (600 MHz, CDCl3): δ 8.35 (s, 1H), 8.00 (s, 1H), 5.45 (d, J = 1.2 Hz, 1H),5.02 (d, J = 0.6 Hz, 1H), 2.97–2.94 (m, 2H), 2.68 (t, J = 7.2 Hz, 2H), 2.13(s, 3H); 13C NMR (150 MHz, CDCl3): δ 152.1, 141.7, 141.2, 104.8, 32.8, 31.6,15.5. HRMS (ESI, m/z): calcd for C7H12N3S+, [M + H]+, 170.0746, found 170.0747。
实施例12
在氮气保护下向含有四氮唑（0.2mmol, 1.0equiv）、底物B(73mg, 0.4mmol,2.0equiv)和三水合醋酸钠(54mg, 0.4mmol, 2.0equiv)的反应器中加入干燥的乙腈（2mL,c = 0.1M），之后在20度反应直到四氮唑完全消耗完，然后加入氢氧化钾（22mg, 0.4mmol,2.0equiv），然后反应在20度继续搅拌12小时。在减压条件下除去有机溶剂，所得粗产物经硅胶柱层析纯化得到纯的无色油状液体产物P-9 (8 mg, 23% yield)；
表征：无色油状液体IR νmax (neat)/cm-1: 2946, 2815, 1512, 1368, 1178, 973,;1H NMR (600 MHz, CDCl3): δ 8.76 (s, 1H), 5.53 (s, 1H), 5.20 (s, 1H), 2.98 (s,2H), 2.64 (d, J = 2.4 Hz, 2H), 2.05 (d, J = 2.4 Hz, 3H); 13C NMR (150 MHz,CDCl3): δ 140.5, 139.2, 108.6, 32.9, 31.1, 15.5. HRMS (ESI, m/z): calcd forC6H11N4S+, [M + H]+, 171.0699, found 171.0696。
实施例13
在氮气保护下向含有5-苯基四氮唑（0.2mmol, 1.0equiv）、底物B(73mg, 0.4mmol,2.0equiv)和三水合醋酸钠(54mg, 0.4mmol, 2.0equiv)的反应器中加入干燥的乙腈（2mL,c = 0.1M），之后在20度反应直到5-苯基四氮唑完全消耗完，然后加入氢氧化钾（22mg,0.4mmol, 2.0equiv），然后反应在20度继续搅拌12小时。在减压条件下除去有机溶剂，所得粗产物经硅胶柱层析纯化得到纯的无色油状液体产物P-10 (34 mg, 73% yield)；
表征：无色油状液体IR νmax (neat)/cm-1: 3033, 2966, 2847, 1556, 1384, 1163,966; 1H NMR (600 MHz, CDCl3): δ 8.12 (dd, J = 1.8, 7.2 Hz, 2H), 7.42 (d, J =7.2 Hz, 3H), 6.09 (d, J = 0.6 Hz, 1H), 5.17 (s, 1H), 3.12 (t, J = 7.2 Hz,2H), 2.78 (t, J = 7.2 Hz, 2H), 2.10 (s, 3H); 13C NMR (150 MHz, CDCl3): δ164.7, 141.4, 130.5, 128.9, 127.0, 107.4, 32.2, 31.9, 15.6. HRMS (ESI, m/z):calcd for C12H15N4S+, [M + H]+, 247.1012, found 247.1014。
Claims (8)
1.一种N-乙烯基唑类化合物的合成方法，其特征为在保护气的保护下向含有唑类化合物、炔丙基叔硫盐化合物和第一种无机碱的反应器中加入有机溶剂，在15-25度反应直到唑类化合物完全消耗完，然后加入第二种无机碱，然后反应在15-25度继续搅拌过夜，减压条件下除去有机溶剂，柱层析或重结晶纯化得到纯的N-乙烯基唑类化合物。
2.权利1所述的一种N-乙烯基唑类化合物的合成方法，其特征在于所述保护气为氮气、氦气、氖气或氩气。
3.权利1所述的一种N-乙烯基唑类化合物的合成方法，其特征在于所述唑类化合物有如下结构式：
其中R1、R2、R3、R4、R5、R6、R7、R8为H、烷基、芳香基、氧烷基、硫烷基、氧芳香基、硫芳香基。
4.权利1所述的一种N-乙烯基唑类化合物的合成方法，其特征在于所述炔丙基叔硫盐化合物有如下结构式：
其中X为Cl、Br或I。
5.权利1所述的一种N-乙烯基唑类化合物的合成方法，其特征在于所述第一种无机碱为醋酸钠、醋酸钾、醋酸铵、碳酸钾、碳酸钠、碳酸氢钾、碳酸氢钠、碳酸铯或碳酸锂。
6.权利1所述的一种N-乙烯基唑类化合物的合成方法，其特征在于所述有机溶剂为氯仿、1,2-二氯乙烷、四氢呋喃、乙腈、二甲基亚砜或N,N-二甲基甲酰胺。
7.权利1所述的一种N-乙烯基唑类化合物的合成方法，其特征在于所述第二种无机碱为氢氧化钠、氢氧化钾或氢氧化锂。
8.权利1所述的一种N-乙烯基唑类化合物的合成方法，其特征在于所述唑类化合物和炔丙基叔硫盐化合物的分子当量比例范围为1/1~1/3，唑类化合物和第一种无机碱的分子当量比例范围为1/1~1/3，唑类化合物和第二种无机碱的分子当量比例范围为1/1~1/3。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011276916.1A CN112225701A (zh) | 2020-11-16 | 2020-11-16 | 一种n-乙烯基唑类化合物的合成方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011276916.1A CN112225701A (zh) | 2020-11-16 | 2020-11-16 | 一种n-乙烯基唑类化合物的合成方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112225701A true CN112225701A (zh) | 2021-01-15 |
Family
ID=74123736
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011276916.1A Pending CN112225701A (zh) | 2020-11-16 | 2020-11-16 | 一种n-乙烯基唑类化合物的合成方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112225701A (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115677568A (zh) * | 2022-10-27 | 2023-02-03 | 南京晓庄学院 | 一种对甲基苯酚一步法胺化的方法 |
-
2020
- 2020-11-16 CN CN202011276916.1A patent/CN112225701A/zh active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115677568A (zh) * | 2022-10-27 | 2023-02-03 | 南京晓庄学院 | 一种对甲基苯酚一步法胺化的方法 |
| CN115677568B (zh) * | 2022-10-27 | 2024-04-19 | 南京晓庄学院 | 一种对甲基苯酚一步法胺化的方法 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2230234B1 (en) | Process for the preparation of rufinamide | |
| EP1747190B1 (en) | Process for the preparation of valsartan and precursors thereof | |
| EP2819997B1 (en) | Process for the preparation of phenyl substituted 3 - difluoromethyl - 1 -methyl - 1h - pyrazole - 4 - carboxylic acid n-methoxy- [1 -methyl- 2 - phenylethyl]amides | |
| Shin et al. | An efficient Cu-catalyzed azide–alkyne cycloaddition (CuAAC) reaction in aqueous medium with a zwitterionic ligand, betaine | |
| CN112225701A (zh) | 一种n-乙烯基唑类化合物的合成方法 | |
| CN1154637C (zh) | 取代的吡唑类化合物的制备方法 | |
| US4960911A (en) | Process for the preparation of oxiranes | |
| US5146001A (en) | Preparation of benzyl ketones and an oxirane | |
| US4992565A (en) | Preparation of oxiranes | |
| US4632999A (en) | Process for the preparation of oxiranes | |
| RU2412940C2 (ru) | Способ получения лосартана | |
| CN112321518A (zh) | 一种n-乙烯基苯并唑类化合物的合成方法 | |
| Panigrahi et al. | N-Triflination of pyrazolones: a new method for N–S bond formation | |
| Ma et al. | Synthesis of 2-alkyl triazoles with solvothermal conditions | |
| CN109280022B (zh) | 一种(e)-1,2-二硒氰酸乙烯芳香酯化合物的合成方法 | |
| EP0415320A2 (en) | Selective production of threo-epoxy compounds | |
| KR19980066917A (ko) | 플루코나졸의 제조방법 | |
| CN114635145B (zh) | 一种酰亚胺衍生物的电化学制备方法 | |
| CN110372616B (zh) | 一种n1位取代的1,2,3-三唑类衍生物的合成方法 | |
| MX2012006388A (es) | Procedimiento para preparacion de un derivado combrestastatina. | |
| CN111606808A (zh) | 一种3’,4’,5’-三氟-2-硝基-1,1’-联苯的合成方法 | |
| CN115260103A (zh) | 一种4,5-二卤代-1-(二氟甲基)-1h-咪唑的制备方法 | |
| CN116905020A (zh) | 一种通过电化学的方式合成1，3-氟胺化产物的方法 | |
| US20230098262A1 (en) | Method for synthesizing beta-cyano ketone compound | |
| JPS5840939B2 (ja) | シクロヘキサンジオン誘導体の製造方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20210115 |