CN110759955A - 一种含二茂铁基噻二唑或噁二唑基Mannich碱的制备方法 - Google Patents
一种含二茂铁基噻二唑或噁二唑基Mannich碱的制备方法 Download PDFInfo
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- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 125000001715 oxadiazolyl group Chemical group 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 title abstract description 12
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims abstract description 52
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 45
- -1 acetyl ferrocene Chemical compound 0.000 claims abstract description 38
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 35
- 239000002608 ionic liquid Substances 0.000 claims abstract description 31
- 238000006243 chemical reaction Methods 0.000 claims abstract description 21
- 239000002904 solvent Substances 0.000 claims abstract description 21
- 239000012043 crude product Substances 0.000 claims abstract description 20
- 238000001704 evaporation Methods 0.000 claims abstract description 20
- 239000000706 filtrate Substances 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 12
- 238000010992 reflux Methods 0.000 claims abstract description 12
- 239000012065 filter cake Substances 0.000 claims abstract description 10
- 238000010438 heat treatment Methods 0.000 claims abstract description 10
- 238000003756 stirring Methods 0.000 claims abstract description 10
- 238000000967 suction filtration Methods 0.000 claims abstract description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 3
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000006304 2-iodophenyl group Chemical group [H]C1=C([H])C(I)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 3
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 230000008020 evaporation Effects 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000001209 o-nitrophenyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])[N+]([O-])=O 0.000 claims description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000003208 petroleum Substances 0.000 claims description 2
- SPKJCVZOZISLEI-UHFFFAOYSA-N cyclopenta-1,3-diene;1-cyclopenta-1,3-dien-1-ylethanone;iron(2+) Chemical compound [Fe+2].C=1C=C[CH-]C=1.CC(=O)C1=CC=C[CH-]1 SPKJCVZOZISLEI-UHFFFAOYSA-N 0.000 claims 3
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 2
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims 2
- UGUHFDPGDQDVGX-UHFFFAOYSA-N 1,2,3-thiadiazole Chemical group C1=CSN=N1 UGUHFDPGDQDVGX-UHFFFAOYSA-N 0.000 claims 1
- 238000006555 catalytic reaction Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 230000035484 reaction time Effects 0.000 claims 1
- 239000003054 catalyst Substances 0.000 abstract description 6
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 abstract description 3
- 150000001299 aldehydes Chemical class 0.000 abstract description 3
- 150000002576 ketones Chemical class 0.000 description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 14
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- 238000012544 monitoring process Methods 0.000 description 7
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 6
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical class [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 238000001157 Fourier transform infrared spectrum Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 2
- RREANTFLPGEWEN-MBLPBCRHSA-N 7-[4-[[(3z)-3-[4-amino-5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidin-2-yl]imino-5-fluoro-2-oxoindol-1-yl]methyl]piperazin-1-yl]-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(\N=C/3C4=CC(F)=CC=C4N(CN4CCN(CC4)C=4C(=CC=5C(=O)C(C(O)=O)=CN(C=5C=4)C4CC4)F)C\3=O)=NC=2)N)=C1 RREANTFLPGEWEN-MBLPBCRHSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 238000006683 Mannich reaction Methods 0.000 description 2
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- DTOUTQSJZYYJEO-UHFFFAOYSA-N 1,3-benzothiazole;sulfuric acid Chemical compound OS(O)(=O)=O.C1=CC=C2SC=NC2=C1 DTOUTQSJZYYJEO-UHFFFAOYSA-N 0.000 description 1
- JCLFHZLOKITRCE-UHFFFAOYSA-N 4-pentoxyphenol Chemical compound CCCCCOC1=CC=C(O)C=C1 JCLFHZLOKITRCE-UHFFFAOYSA-N 0.000 description 1
- OAVULPOOAHQYDZ-UHFFFAOYSA-N 5-(4-chlorophenyl)-1,3,4-thiadiazol-2-amine Chemical compound S1C(N)=NN=C1C1=CC=C(Cl)C=C1 OAVULPOOAHQYDZ-UHFFFAOYSA-N 0.000 description 1
- OPZGULFMUGGIAS-UHFFFAOYSA-N 5-(4-fluorophenyl)-1,3,4-oxadiazol-2-amine Chemical compound O1C(N)=NN=C1C1=CC=C(F)C=C1 OPZGULFMUGGIAS-UHFFFAOYSA-N 0.000 description 1
- AXAUHVYAAUVJQR-UHFFFAOYSA-N 5-(4-methylphenyl)-1,3,4-oxadiazol-2-amine Chemical compound C1=CC(C)=CC=C1C1=NN=C(N)O1 AXAUHVYAAUVJQR-UHFFFAOYSA-N 0.000 description 1
- XAPNDVNSXWXPJS-UHFFFAOYSA-N 5-(4-nitrophenyl)-1,3,4-thiadiazol-2-amine Chemical compound S1C(N)=NN=C1C1=CC=C([N+]([O-])=O)C=C1 XAPNDVNSXWXPJS-UHFFFAOYSA-N 0.000 description 1
- CQSFYCBGVMWPCM-UHFFFAOYSA-N 5-phenyl-1,3,4-oxadiazol-2-amine Chemical compound O1C(N)=NN=C1C1=CC=CC=C1 CQSFYCBGVMWPCM-UHFFFAOYSA-N 0.000 description 1
- UHZHEOAEJRHUBW-UHFFFAOYSA-N 5-phenyl-1,3,4-thiadiazol-2-amine Chemical compound S1C(N)=NN=C1C1=CC=CC=C1 UHZHEOAEJRHUBW-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 229940124350 antibacterial drug Drugs 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229940072185 drug for treatment of tuberculosis Drugs 0.000 description 1
- 230000005518 electrochemistry Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- CMGNFILMNHGISN-UHFFFAOYSA-N oxadiazole;thiadiazole Chemical compound C1=CON=N1.C1=CSN=N1 CMGNFILMNHGISN-UHFFFAOYSA-N 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
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- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F17/00—Metallocenes
- C07F17/02—Metallocenes of metals of Groups 8, 9 or 10 of the Periodic Table
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0277—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides comprising ionic liquids, as components in catalyst systems or catalysts per se, the ionic liquid compounds being used in the molten state at the respective reaction temperature
- B01J31/0278—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides comprising ionic liquids, as components in catalyst systems or catalysts per se, the ionic liquid compounds being used in the molten state at the respective reaction temperature containing nitrogen as cationic centre
- B01J31/0281—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides comprising ionic liquids, as components in catalyst systems or catalysts per se, the ionic liquid compounds being used in the molten state at the respective reaction temperature containing nitrogen as cationic centre the nitrogen being a ring member
- B01J31/0284—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides comprising ionic liquids, as components in catalyst systems or catalysts per se, the ionic liquid compounds being used in the molten state at the respective reaction temperature containing nitrogen as cationic centre the nitrogen being a ring member of an aromatic ring, e.g. pyridinium
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Abstract
一种含二茂铁基噻二唑或噁二唑基Mannich碱的制备方法：向干燥的三口烧瓶中依次加入Amol 2‑氨基5‑取代‑1，3，4‑噻（噁）二唑、Bmol醛，无水乙醇，搅拌均匀；加入Cmol苯并噻唑离子液体，然后搅拌下慢慢滴加Dmol乙酰基二茂铁的无水乙醇溶液，滴完加热回流反应至结束。减压蒸除溶剂，剩余物中加入乙酸乙酯，抽滤，滤液蒸干即得粗品，粗品经无水乙醇重结晶得含二茂铁基噻二唑或噁二唑基Mannich碱。滤饼即苯并噻唑离子液体，可回收重复使用。其中，A:B:C:D＝1：（5~10）：（0.5~1.5）:1。本发明方法绿色环保，操作简便，后处理简单，产率高，效率高，催化剂可回收利用多次，反应成本低。
Description
技术领域
本发明属于化学合成技术领域，特别涉及一种含二茂铁基噻二唑或噁二唑基Mannich碱的制备方法
背景技术
Mannich反应是合成C-N键和C-C键的有效途径。Mannich反应可将芳环、杂环、不饱和基团等引入到Mannich碱中，极大的拓宽了Mannich碱的应用。例如抗菌药，抗结核药，抗惊厥药，抗增殖药等医药领域，聚氨酯材料、耐蚀剂等材料领域，调节细胞免疫等生物领域都涉及到Mannich碱。二茂铁的衍生物中引入噻(噁)二唑合成的Mannich碱有很好的应用前景。因为二茂铁类衍生物因其特殊的空间结构，可用做催化剂，并在医学领域以及通信、电化学等材料领域应用价值甚高。现有含二茂铁基噻二唑或噁二唑基Mannich碱的制备的方法一般是用浓盐酸、三氯化铝、醋酸等催化合成，以上工艺存在催化剂污染环境、催化效率低、不易回收利用、成本高等缺点。
本发明探索用苯并噻唑离子液体催化合成含二茂铁基噻二唑或噁二唑基Mannich碱，其特点是可回收利用、绿色环保、降低了成本。
发明内容
本发明的目的是提供一种含二茂铁基噻二唑或噁二唑基Mannich碱的制备方法，该方法绿色环保，操作简便，后处理简单，产率高，效率高，催化剂可回收利用多次，反应成本低。
为了实现上述目的，本发明采用如下技术方案：
一种含二茂铁基噻二唑或噁二唑基Mannich碱，其特征在于，其结构通式如式(1)所示：
其中，R1和R2为H、烷基、苯基、对氟苯基、邻氯苯基、对氯苯基、2,4-二氯苯基、邻溴苯基、间溴苯基、对溴苯基、邻碘苯基、2,4-二溴苯基、邻硝基苯基、间硝基苯基、对硝基苯基、3,5-二硝基苯基、邻甲基苯基、间甲基苯基、对甲基苯基、邻甲氧基苯基、间甲氧基苯基、对甲氧基苯基、呋喃基、噻吩基、3-吡啶基和4-吡啶基中同一种或者不同种取代基。
苯并噻唑离子液体，其特征在于，其结构通式如式(2)所示：
所述的一种含二茂铁基噻二唑或噁二唑基Mannich碱的制备方法，其特征在于，包括以下步骤：
向干燥的三口烧瓶中加入2-氨基5-取代-1，3，4-噻(噁)二唑(Amol)和醛(Bmol)，无水乙醇作为溶剂，搅拌均匀；加入苯并噻唑离子液体(Cmol)，然后慢慢滴加乙酰基二茂铁(Dmol)无水乙醇溶液，滴完加热回流至反应结束(TLC监测)，减压蒸除溶剂，剩余物中加入乙酸乙酯，抽滤，滤液蒸干即得粗品，粗品经无水乙醇重结晶得含二茂铁基噻二唑或噁二唑基Mannich碱。滤饼即苯并噻唑离子液体，可回收重复使用。其中，A:B:C:D＝1：(5～10)：(0.5～1.5):1。
所述步骤中，乙酰基二茂铁与苯并噻唑离子液体的摩尔比为1：(0.5～1.5)。
所述步骤中，反应的温度无水乙醇回流温度80℃，反应完全的时间为2.5～4h。
所述步骤中，乙酰基二茂铁无水乙醇溶液的浓度为0.03～0.06g/mL。
所述步骤中，反应过程用TLC板进行监测，当乙酰基二茂铁的原料点消失时表示反应完全，TLC板的展开剂是体积比为1:1的乙酸乙酯和石油醚的混合液。
所述步骤中，减压蒸除溶剂，剩余物中加入乙酸乙酯，抽滤，滤液减压蒸除乙酸乙酯后再经无水乙醇重结晶得含二茂铁基噻二唑或噁二唑基Mannich碱。
与现有技术相比，本发明具有以下优点：
本发明方法绿色环保，操作简便，后处理简单，产率高，效率高，催化剂可回收利用多次，反应成本低。
附图说明
图1为1-(5’-苯基-1’,3’,4’-噁二唑-2’-氨基)-乙基-二茂铁基酮FT-IR谱图；
图2为1-(5’-苯基-1’,3’,4’-噁二唑-2’-氨基)-乙基-二茂铁基酮1H NMR谱图；
图3为1-(5’-苯基-1’,3’,4’-噁二唑-2’-氨基)-乙基-二茂铁基酮13C NMR谱图；
图4为1-(5’-对甲氧基苯基-1’,3’,4’-噁二唑-2’-氨基)-乙基-二茂铁基酮FT-IR谱图；
图5为1-(5’-对甲氧基苯基-1’,3’,4’-噁二唑-2’-氨基)-乙基-二茂铁基酮1HNMR谱图；
图6为1-(5’-对甲氧基苯基-1’,3’,4’-噁二唑-2’-氨基)-乙基-二茂铁基酮13CNMR谱；
图7为1-(5’-对氟苯基-1’,3’,4’-噁二唑-2’-氨基)-乙基-二茂铁基酮FT-IR谱图；
图8为1-(5’-对氟苯基-1’,3’,4’-噁二唑-2’-氨基)-乙基-二茂铁基酮1H NMR谱图；
图9为1-(5’-对氟苯基-1’,3’,4’-噁二唑-2’-氨基)-乙基-二茂铁基酮13C NMR谱图；
图10为本发明所用离子液体的循环实用性。
具体实施方式
本发明是以乙酰基二茂铁、醛与2-氨基5-取代-1，3，4-噻(噁)二唑为原料，无水乙醇为溶剂，以苯并噻唑离子液体为催化剂，加热回流，制备一系列含二茂铁基噻二唑或噁二唑基Mannich碱，其反应方程式如式(3)所示：
其中，R1和R2为H、烷基、苯基、对氟苯基、邻氯苯基、对氯苯基、2,4-二氯苯基、邻溴苯基、间溴苯基、对溴苯基、邻碘苯基、2,4-二溴苯基、邻硝基苯基、间硝基苯基、对硝基苯基、3,5-二硝基苯基、邻甲基苯基、间甲基苯基、对甲基苯基、邻甲氧基苯基、间甲氧基苯基、对甲氧基苯基、呋喃基、噻吩基、3-吡啶基和4-吡啶基中同一种或者不同种取代基。
下面结合本发明的具体实例对本发明作进一步详细说明，但本发明的实施方式不限于此。
实施例1 1-(5’-苯基-1’,3’,4’-噻二唑-2’-氨基)-乙基-二茂铁基酮的制备
向干燥的三口烧瓶中加入2-氨基5-苯基-1，3，4-噻二唑(1mol)、37％甲醛(5mol)溶液，无水乙醇作为溶剂，搅拌均匀；加入苯并噻唑离子液体(1.2mol)，然后慢慢滴加乙酰基二茂铁(1mol)无水乙醇溶液，滴完加热回流至反应结束(TLC监测)，减压蒸除溶剂，剩余物中加入乙酸乙酯，抽滤，滤饼即苯并噻唑离子液体，可回收重复使用；滤液滤液蒸干即得粗品，粗品经无水乙醇重结晶得1-(5’-苯基-1’,3’,4’-噻二唑-2’-氨基)-乙基-二茂铁基酮，m.p.196-198℃，产率：91.8％。
IR(KBr)v:3324(νPh-H),2914(ν饱和C-H),1730(νC＝O),1611(νC＝C),1365(νC-N),806(γ1,4-Ph-H).
1HNMR(DMSO,400MHz)δ:7.70-7.88(m,4H,Ar-H),4.06(s,4H,Fc-H),3.88(s,5H,Fc-H),1.72(m,2H,-CH2-N),2.11(m,2H,-CH2-).
13C NMR(CDCl3,100MHz)δ:211.10,171.98，164.41,129.04,128.43,128.00,127.5,79.48,69.24,45.80,40.13.
实施例2 1-(5’-对氯苯基-1’,3’,4’-噻二唑-2’-氨基)-乙基-二茂铁基酮的制备
向干燥的三口烧瓶中加入2-氨基5-对氯苯基-1，3，4-噻二唑(1mol)和37％甲醛(5mol)溶液，无水乙醇作为溶剂，搅拌均匀；加入苯并噻唑离子液体(1.2mol)，然后慢慢滴加乙酰基二茂铁(1mol)无水乙醇溶液，滴完加热回流至反应结束(TLC监测)，减压蒸除溶剂，剩余物中加入乙酸乙酯，抽滤，滤饼即苯并噻唑离子液体，可回收重复使用；滤液蒸干即得粗品，粗品经无水乙醇重结晶得1-(5’-对氯苯基-1’,3’,4’-噻二唑-2’-氨基)-乙基-二茂铁基酮，m.p.170-172℃，产率：90.8％。
IR(KBr)v:3310(νPh-H),2999(ν饱和C-H),1708(νC＝O),1600(νC＝C),1320(νC-N),774(γ1,4-Ph-H).
1HNMR(DMSO,400MHz)δ:6.15-6.32(m,4H,Ar-H),4.47-4.68(s,4H,Fc-H),4.20(s,5H,Fc-H),1.77-1.81(m,2H,-CH2-N),1.92-2.05(m,2H,-CH2-).
13C NMR(CDCl3,100MHz)δ:210.84,171.76,164.70,133.54,133.32,129.27,128.66,79.48,68.97,46.03,40.70.
实施例3 1-(5’-对硝基苯基-1’,3’,4’-噻二唑-2’-氨基)-乙基-二茂铁基酮的制备
向干燥的三口烧瓶中加入2-氨基5-对硝基苯基-1，3，4-噻二唑(1mol)和37％甲醛(5mol)溶液，无水乙醇作为溶剂，搅拌均匀；加入苯并噻唑离子液体(1.2mol)，然后慢慢滴加乙酰基二茂铁(1mol)无水乙醇溶液，滴完加热回流至反应结束(TLC监测)，减压蒸除溶剂，剩余物中加入乙酸乙酯，抽滤，滤饼即苯并噻唑离子液体，可回收重复使用；滤液蒸干即得粗品，粗品经无水乙醇重结晶得1-(5’-对硝基苯基-1’,3’,4’-噻二唑-2’-氨基)-乙基-二茂铁基酮。m.p.199-201℃，产率：92.3％。
IR(KBr)v:3288(νPh-H),2994(ν饱和C-H),1759(νC＝O),1600(νC＝C),1233(νC-N),802(γ1,4-Ph-H).
1HNMR(DMSO,400MHz)δ:6.23-6.55(m,4H,Ar-H),4.81-4.97(s,5H,Fc-H),5.05-5.31(s,4H,Fc-H),2.21-2.33(m,2H,-CH2-N),2.50-2.78(m,2H,-CH2-).
13C NMR(CDCl3,100MHz)δ:211.47,172.21,164.7,143.27,141.98,128.88,128.81,128.43,79.48,69.42,46.70,46.03.
实施例4 1-(5’-苯基-1’,3’,4’-噁二唑-2’-氨基)-乙基-二茂铁基酮的制备
向干燥的三口烧瓶中加入2-氨基5-苯基-1，3，4-噁二唑(1mol)和37％甲醛(5mol)溶液，无水乙醇作为溶剂，搅拌均匀；加入苯并噻唑离子液体(1.2mol)，然后慢慢滴加乙酰基二茂铁(1mol)无水乙醇溶液，滴完加热回流至反应结束(TLC监测)，减压蒸除溶剂，剩余物中加入乙酸乙酯，抽滤，滤饼即苯并噻唑离子液体，可回收重复使用；滤液滤液蒸干即得粗品，粗品经无水乙醇重结晶得1-(5’-苯基-1’,3’,4’-噁二唑-2’-氨基)-乙基-二茂铁基酮，产率：92.6％。
IR(KBr)v:3067(νPh-H),2978(ν饱和C-H),1710(νC＝O),1564,1461(νC＝C),1054(νC-O-C),1096,1013(-Fc),763,690(γ单取代Ph-H).
1HNMR(DMSO,400MHz)δ:7.94-7.87(m,2H,Ar-H),7.44(m,3H,Ar-H),5.63(s,2H,Fc-H),5.36(s,2H,Fc-H),4.06(s,5H,Fc-H),3.64(m,2H,-CH2-N),1.21(m,2H,-CH2-).
13C NMR(CDCl3,100MHz)δ:202.43,130.48,130.31,128.46,128.41,127.54,125.52,125.47,123.73,74.56,73.97,73.22,71.25,70.20,68.23,67.84,63.89,63.65,62.75,29.22,14.58.
实施例5 1-(5’-对甲氧基苯基-1’,3’,4’-噁二唑-2’-氨基)-乙基-二茂铁基酮的制备
向干燥的三口烧瓶中加入2-氨基5-对甲基苯基-1，3，4-噁二唑(1mol)和37％甲醛(5mol)溶液，无水乙醇作为溶剂，搅拌均匀；加入苯并噻唑离子液体(1.2mol)，然后慢慢滴加乙酰基二茂铁(1mol)无水乙醇溶液，滴完加热回流至反应结束(TLC监测)，减压蒸除溶剂，剩余物中加入乙酸乙酯，抽滤，滤饼即苯并噻唑离子液体，可回收重复使用；滤液滤液蒸干即得粗品，粗品经无水乙醇重结晶得1-(5’-对甲氧基苯基-1’,3’,4’-噁二唑-2’-氨基)-乙基-二茂铁基酮，产率：91.2％。
IR(KBr)v:3222(ν-NH-),3043(νPh-H),2969(ν饱和C-H),1714(νC＝O),1635(νC＝N),1397(δMe),1271(νC-N),1081,1007(-Fc),822(γ1,4-Ph-H).
1HNMR(DMSO,400MHz)δ:7.78-7.76(m,2H,Ar-H),7.23-7.21(m,2H,Ar-H),5.43(s,2H,Fc-H),5.16(s,2H,Fc-H),4.87(s,5H,Fc-H),3.63-3.61(m,2H,-CH2-N),2.37(s,3H,-CH3),1.21-1.18(m,2H,-CH2-).
13C NMR(CDCl3,100MHz)δ:205.35,161.66,151.02,141.54,129.91,129.79,129.66,129.33,126.10,78.10,77.21,76.43,75.28,75.12,73.97,68.45,64.32,63.89,63.65,29.88,21.76,15.21.
实施例6 1-(5’-对氟苯基-1’,3’,4’-噁二唑-2’-氨基)-乙基-二茂铁基酮的制备
向干燥的三口烧瓶中加入2-氨基5-对氟苯基-1，3，4-噁二唑(1mol)和37％甲醛(5mol)溶液，无水乙醇作为溶剂，搅拌均匀；加入苯并噻唑离子液体(1.2mol)，然后慢慢滴加乙酰基二茂铁(1mol)无水乙醇溶液，滴完加热回流至反应结束(TLC监测)，减压蒸除溶剂，剩余物中加入乙酸乙酯，抽滤，滤饼即苯并噻唑离子液体，可回收重复使用；滤液滤液蒸干即得粗品，粗品经无水乙醇重结晶得1-(5’-对氟苯基-1’,3’,4’-噁二唑-2’-氨基)-乙基-二茂铁基酮，m.p.148.1-151℃，产率：91.2％。
IR(KBr)v:3070(νPh-H),2970,2922,2853(ν饱和C-H),1709(νC＝O),1614,1561,1498,1461(νC＝C),1276(νC-N),1160(νC-O-C),1091,1013(-Fc),844(γ1,4-Ph-H).
1HNMR(DMSO,400MHz)δ:7.91-7.86(m,2H,Ar-H),7.12(d,2H,Ar-H),5.33(s,2H,Fc-H),5.05(s,2H,Fc-H),4.77(s,5H,Fc-H),3.63(m,2H,-CH2-N),1.20-1.18(m,2H,-CH2-).
13C NMR(CDCl3,100MHz)δ:201.35,164.89,162.54,158.36,150.47,127.59,119.76,115.73,115.52,78.12,76.44,75.78,72.14,71.84,68.45,65.41,65.11,63.83,63.68,29.15,14.43.
离子液体的重复使用性
以苯并噻唑硫酸氢盐离子液体催化合成1-(5’-苯基-1’,3’,4’-噁二唑-2’-氨基)-乙基-二茂铁基酮为例。研究了离子液体的重复使用性。如图10所示离子液体重复使用5次，催化活性略有降低。
Claims (9)
1.一种制备含二茂铁基噻二唑或噁二唑基Mannich碱的方法，其特征在于，包括以下步骤：
2-氨基5-取代-1，3，4-噻二唑或2-氨基5-取代-1，3，4-噁二唑与醛和乙酰基二茂铁在苯并噻唑离子液体催化下反应，得到含二茂铁基噻二唑基Mannich碱或含二茂铁基噁二唑基Mannich碱。
2.如权利要求1所述的方法，其特征在于，包括以下步骤：
向干燥的三口烧瓶中加入Amol 2-氨基5-取代-1，3，4-噻二唑或2-氨基5-取代-1，3，4-噁二唑、Bmol醛、无水乙醇，搅拌均匀；加入Cmol苯并噻唑离子液体，然后慢慢滴加Dmol乙酰基二茂铁的无水乙醇溶液，滴完加热回流反应至结束，减压蒸除溶剂；剩余物中加入乙酸乙酯，抽滤，滤液蒸干即得粗品，粗品经无水乙醇重结晶得含二茂铁基噻二唑基Mannich碱或含二茂铁基噁二唑基Mannich碱；滤饼即苯并噻唑离子液体，可回收重复使用；其中，A:B:C:D＝1：(5～10)：(0.5～1.5):1。
3.如权利要求1所述的方法，其特征在于，反应以无水乙醇为溶剂，反应的温度为无水乙醇的回流温度80℃，反应时间为2.5～4h。
4.如权利要求3所述的方法，其特征在于，乙酰基二茂铁在无水乙醇中的浓度为0.03～0.06g/mL。
5.如权利要求1所述的方法，其特征在于，反应过程用TLC板进行监测，当乙酰基二茂铁的原料点消失时表示反应完全，TLC板的展开剂是体积比为1:1的乙酸乙酯和石油醚的混合液。
6.如权利要求1所述的方法，其特征在于，反应结束后，减压蒸除溶剂，剩余物中加入乙酸乙酯，抽滤，滤液减压蒸干即得粗品，粗品经无水乙醇重结晶得含二茂铁基噻二唑基Mannich碱或含二茂铁基噁二唑基Mannich碱。
7.如权利要求1所述的方法，其特征在于，反应结束后，减压蒸除溶剂，剩余物中加入乙酸乙酯，抽滤，滤饼即苯并噻唑离子液体，可回收重复使用。
8.一种含二茂铁基噻二唑或噁二唑基Mannich碱，其特征在于，结构式为：
其中，R1和R2为H、烷基、苯基、对氟苯基、邻氯苯基、对氯苯基、2,4-二氯苯基、邻溴苯基、间溴苯基、对溴苯基、邻碘苯基、2,4-二溴苯基、邻硝基苯基、间硝基苯基、对硝基苯基、3,5-二硝基苯基、邻甲基苯基、间甲基苯基、对甲基苯基、邻甲氧基苯基、间氧基苯基、对甲氧基苯基、呋喃基、噻吩基、3-吡啶基和4-吡啶基中同一种或者不同种取代基。
9.一种苯并噻唑离子液体用于制备含二茂铁基噻二唑或噁二唑基Mannich碱的应用，其特征在于，苯并噻唑离子液体的结构式为：
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