CN105131042A - 含杂芳基的螯合型氮杂环卡宾钯化合物及其制备方法 - Google Patents
含杂芳基的螯合型氮杂环卡宾钯化合物及其制备方法 Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims description 5
- 150000002941 palladium compounds Chemical class 0.000 claims abstract description 49
- 238000006243 chemical reaction Methods 0.000 claims abstract description 47
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 42
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 13
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 7
- 238000000034 method Methods 0.000 claims abstract description 7
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- 238000010189 synthetic method Methods 0.000 claims abstract description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 52
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 51
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 39
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 34
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
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- 229920002223 polystyrene Polymers 0.000 claims description 9
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 8
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- 238000001914 filtration Methods 0.000 claims description 6
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical class Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 6
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- VPSSPAXIFBTOHY-LURJTMIESA-N (2s)-2-amino-4-methylpentan-1-ol Chemical compound CC(C)C[C@H](N)CO VPSSPAXIFBTOHY-LURJTMIESA-N 0.000 claims description 4
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- ZNZYKNKBJPZETN-WELNAUFTSA-N Dialdehyde 11678 Chemical compound N1C2=CC=CC=C2C2=C1[C@H](C[C@H](/C(=C/O)C(=O)OC)[C@@H](C=C)C=O)NCC2 ZNZYKNKBJPZETN-WELNAUFTSA-N 0.000 claims description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 3
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- 239000011591 potassium Substances 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
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- 238000009833 condensation Methods 0.000 claims description 2
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- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 2
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- ADLVDYMTBOSDFE-UHFFFAOYSA-N 5-chloro-6-nitroisoindole-1,3-dione Chemical compound C1=C(Cl)C([N+](=O)[O-])=CC2=C1C(=O)NC2=O ADLVDYMTBOSDFE-UHFFFAOYSA-N 0.000 abstract 1
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- 125000001246 bromo group Chemical group Br* 0.000 description 2
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Classifications
-
- 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
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
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- Catalysts (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明属于有机化合物合成领域,公开了含杂芳基的螯合型氮杂环卡宾钯化合物及其合成、固载方法。该化合物具有如下结构通式:
Description
技术领域
本发明属于有机化合物合成领域,涉及含杂芳基的螯合型氮杂环卡宾钯化合物及其合成固载方法。
技术背景
氮杂环卡宾(NHC)具有较强的σ-配位能力,与过渡金属形成的化合物含稳定的金属-卡宾键,通常情况下对空气、水分及热均较为稳定,因此,氮杂环卡宾配体已经成为有机金属化学和均相催化领域非常重要的配体之一[参考文献1-4Hopkinson,M.N.;Richter,C.;Schedler,M.;Glorius,F.Nature.2014,510,485.Crabtree,R.H.Coord.Chem.Rev.2013,257,755.Nelson,D.J.;Nolan,S.P.Chem.Soc.Rev.2013,42,6723.Scott,N.M.;Nolan,S.P.Eur.J.Inorg.Chem.2005,1815.]。在金属有机催化中,氮杂环卡宾钯化合物催化的碳-碳、碳-杂键偶联反应由于具有反应活性高、选择性强及反应条件温和等特点,目前已在精细化工、药物合成、医药生产和电子工业等领域得到了广泛的应用[参考文献5-7Liu,L.F.;Dong,Y.;Tang,N.N.GreenChem.2014,16,2185.Han,F.S.Chem.Soc.Rev.2013,42,5270.Molnar,A.Chem.Rev.2011,111,2251.]。当N-取代基连有具有配位能力的杂原子的基团时,此杂原子和氮杂环卡宾中的卡宾碳与同一金属中心配位,形成螯合型氮杂环卡宾金属化合物(如结构式1)。螯合型氮杂环卡宾钯化合物由于结构稳定、催化性能优异,在Heck反应、Suzuki反应、Sonogashira反应等C-C成键以及Buchwald-Hartwig氨化反应中,都有良好的催化效果。但这类催化剂中的咪唑环上没有可进一步反应的活性基团,难以固载化,只能作为均相催化剂使用[参考文献8-11Krishnan,D.;Wu,M.;Chiang,M.;Li,Y.;Leung,P.-H.;Pullarkat,S.A.Organometallics2013,32,2389.Hahn,F.E.;Jahnke,M.C.;Pape,T.Organometallics2006,25,5927.Lee,H.M.;Chiu,P.L.;Zeng,J.Y.Inorg.Chim.Acta.2004,357,4313.Tsoureas,N.;Danopoulos,A.A.;Tulloch,A.A.;Light,M.E.Organometallics2003,22,4750.]。均相催化剂不易分离回收、使用成本高且污染产物,在很大程度上阻碍了氮杂环卡宾钯化合物在催化领域的进一步应用。
发明内容
本发明的目的在于提供固载型含杂芳基的螯合型氮杂环卡宾钯化合物;另一目的在于提供简单易行、收率高、固载型含杂芳基的螯合型氮杂环卡宾钯化合物的制备方法。
为实现本发明目的,本发明所述含杂芳基的螯合型氮杂环卡宾钯化合物具有以下通式:
优选结构如下化合物:
上述化合物合成路线如下:
氮杂环卡宾钯化合物的固载化如下:
本发明所述的固载型含杂芳基的螯合型氮杂环卡宾钯化合物的合成方法,通过如下步骤实现:
(1)L-氨基醇、甲醛、乙二醛或苯偶酰,在氯化铵或醋酸铵/L-脯氨酸存在下,在甲醇中加热,一步缩合关环得到N-取代基上含有羟基的咪唑衍生物;L-氨基醇与乙二醛或苯偶酰优选等摩尔比。
(2)N-取代基上含有羟基的咪唑衍生物与六元环杂芳烃卤代物,在甲苯或乙腈中加热回流,得到杂芳基、羟基双取代的咪唑鎓盐;N-取代基上含有羟基的咪唑衍生物与六元环杂芳烃卤代物摩尔比优选1:1~1:100。
(3)在有机溶剂中,杂芳基、羟基双取代的咪唑鎓盐与氯化钯或醋酸钯/碱性物质条件下,20~100℃温度反应,反应结束后,减压除去溶剂,过柱分离得到螯合型氮杂环卡宾钯化合物。咪唑鎓盐与氯化钯或醋酸钯优选1:1摩尔比。
(4)螯合型氮杂环卡宾钯化合物分别与氯甲基化聚苯乙烯交联微球(CCPS)在有机溶剂中、20~100℃搅拌反应,过滤,得到固载的氮杂环卡宾钯化合物催化剂。
步骤(1)所述的L-氨基醇为L-亮氨醇或L-苯丙氨醇;所述的六元环杂芳烃卤代物优选2-氯嘧啶、2-溴吡啶或2-溴甲基吡啶。
步骤(3)所述的有机溶剂为甲醇、四氢呋喃、二氯甲烷、甲苯、1,4-二氧六环、乙腈、二甲基甲酰胺、二甲基乙酰胺、N-甲基吡咯烷酮、乙二醇二甲醚、二甲基亚砜。
步骤(3)所述的碱性物质为醋酸钠、醋酸钾、叔丁醇钠、叔丁醇钾、叔戊醇钠、叔戊醇钾。
步骤(4)所述的有机溶剂为甲醇、四氢呋喃、甲苯、1,4-二氧六环、乙腈、乙二醇二甲醚。
本发明合成的固载型氮杂环卡宾钯化合物具有独特的结构特点,对苯并噁唑衍生物的C-H活化反应表现出高效的催化性能。2-芳基取代苯并噁唑衍生物具有重要的生物和物理特性,常见于药物分子及天然产物中,也是许多新型功能材料的重要结构单元。钯催化苯并噁唑衍生物经C-H活化、与卤代芳烃偶联,是合成2-芳基苯并噁唑衍生物的一种重要方法。本发明为苯并噁唑衍生物的C-H活化反应提供了一类新型的固载型金属催化剂,用于催化反应时,催化剂用量少、可重复使用,反应溶剂无需处理,使用廉价易得的碱,催化产率高,操作简单,易于分离。
催化苯并噁唑衍生物的C-H活化反应采用以下步骤:将本发明固载型氮杂环卡宾钯化合物催化剂、碱、苯并噁唑衍生物、卤代芳烃加到有机溶剂中,于80~130℃反应8~24小时后,降至室温,过滤分离催化剂,减压除去溶剂,柱色谱分离得到纯品。
本发明创新点及优点在于:本发明以多官能团化合物氨基醇为初始原料,通过关环、缩合反应,得到N-取代基上含有羟基的咪唑衍生物,再与杂芳烃卤代物经离子化反应,得到杂芳基、羟基双取代的咪唑鎓盐,进一步通过金属化反应得到NHC-N螯合型钯化合物。利用NHC-N螯合型钯化合物中具有反应活性的游离羟基与氯甲基化聚苯乙烯交联微球(CCPS)反应,得到CCPS固载的NHC-N螯合型钯化合物催化剂。此固载型催化剂合成方法简单易行,收率高,其不仅具有均相氮杂环卡宾钯催化剂的活性,而且在催化C-H活化反应中,反应产率高、易于分离、可反复使用,大大降低了其使用成本,在催化领域具有较好的应用前景。
具体实施方式
以下结合实例,对本发明进行进一步描述,但本发明的保护范围并不仅限于此:
实施例1
(1)在250mL三口烧瓶中,将L-亮氨醇(60mmol,7.03g)和氯化铵(60mmol,3.21g)用120mL甲醇溶解,冰水浴冷却下,用恒压漏斗依次滴加质量百分比36%的甲醛溶液(60mmol,4.6mL)和质量百分比40%的乙二醛溶液(60mmol,7.6mL)。滴加完毕后,升温至60℃反应5h,将反应液旋干得红褐色粘稠液体。将上述红褐色粘稠液体溶于150mLNaOH溶液(2M),用二氯甲烷萃取(20mL×3),合并有机相,用无水Na2SO4干燥、过滤,减压除去溶剂,柱层析分离纯化得(S)-2-(1-咪唑基)-4-甲基戊醇纯品(7.57g,产率75%)。
(2)在50mL圆底烧瓶中加入(S)-2-(1-咪唑基)-4-甲基戊醇(5.0mmol,0.84g)、2-溴吡啶(3mL)和2mL甲苯,加热至110℃反应72h后,冷却至室温,将反应液滴入30mL乙醚中,将沉淀析出的深黄色粘稠固体收集,柱层析分离纯化得N-(1-羟基-4-甲基-2-戊基)-N’-(2-吡啶基)-咪唑溴鎓盐纯品(1.42g,产率87%)。1HNMR(400MHz,DMSO):δ10.25(s,1H,CHinimidazole),8.68-8.66(m,1H,CHinpyridine),8.62(t,J=1.8Hz,1H,CHinimidazole),8.26-8.22(m,1H,CHinpyridine),8.21(t,J=1.8Hz,1H,CHinimidazole),8.11(d,J=8.3Hz,1H,CHinpyridine),7.68-7.65(m,1H,CHinpyridine),5.26(s,1H,CH2OH),4.64-4.60(m,1H,NCH),3.77-3.70(m,2H,CH2OH),1.97-1.91(m,1H,CH2CH(CH3)2),1.70-1.63(m,1H,CH2CH(CH3)2),1.45-1.38(m,1H,CH2CH(CH3)2),0.93(d,3H,J=6.5Hz,CH2CH(CH3)2),0.89(d,1H,J=6.6Hz,CH2CH(CH3)2)ppm.13CNMR(100MHz,DMSO):δ149.7,146.9,141.0,135.2,125.7,122.8,120.1,114.8,63.5,62.3,38.6,24.4,23.2,22.0ppm.ESI-MS,m/z:246.08[M-Br]+.
(3)在50mL圆底烧瓶中加入N-(1-羟基-4-甲基-2-戊基)-N’-(2-吡啶基)-咪唑溴鎓盐(1.0mmol,0.33g)、醋酸钯(1.0mmol,0.22g)和10mL二氯甲烷,室温搅拌12h。反应结束后,减压除去二氯甲烷,残余物柱层析分离纯化(梯度洗脱,展开剂:二氯甲烷/丙酮=15:1~4:1,v/v),得螯合型氮杂环卡宾钯化合物NHC-Pd(I)(0.20g,产率39%)。黄色固体,1HNMR(400MHz,DMSO):δ9.44(s,1H,CHinpyridine),8.46(d,1H,J=2.2Hz,CHinimidazole),8.40-8.36(m,1H,CHinpyridine),8.18(d,1H,J=8.2Hz,CHinpyridine),7.78(d,1H,J=2.3Hz,CHinimidazole),7.62(t,1H,J=7.0Hz,CHinpyridine),6.25(s,1H,NCH),5.01(t,1H,J=5.3Hz,CH2OH),3.70-3.60(m,2H,CH2OH),1.90-1.82(m,1H,CH2CH(CH3)2),1.64-1.57(m,1H,CH2CH(CH3)2),1.41-1.35(m,1H,CH2CH(CH3)2),0.95(d,3H,J=6.5Hz,CH2CH(CH3)2),0.89(d,3H,J=6.5Hz,CH2CH(CH3)2)ppm.13CNMR(100MHz,DMSO):δ151.8,150.8,143.4,123.6,122.6,117.5,112.9,64.2,59.3,30.1,24.7,23.4,22.8ppm.AnalCacldforC14H19Br2N3OPd(511.55):C,32.87;H,3.74;N,8.21.Found:C,32.68;H,3.56;N,8.42.
(4)将螯合型氮杂环卡宾钯化合物NHC-Pd(I)(0.5mmol,0.26g)和氯甲基化聚苯乙烯交联微球(CCPS)(1.0g)在乙腈中80℃搅拌6小时,过滤,得到固载的氮杂环卡宾钯化合物催化剂CCPS-NHC-Pd(I)1.25g。
实施例2
步骤(1)同实施例1
(2)在50mL圆底烧瓶中加入(S)-2-(1-咪唑基)-4-甲基戊醇(5.0mmol,0.84g)、2-氯嘧啶(6mmol,0.69g)和15mL甲苯,加热至110℃反应72h后,冷至室温,将体系中生成粘稠黄色固体收集,柱层析分离纯化得N-(1-羟基-4-甲基-2-戊基)-N’-(2-嘧啶基)-咪唑氯鎓盐纯品(1.12g,产率79%)。1HNMR(400MHz,DMSO):δ10.34(s,1H,CHinimidazole),9.08(d,J=4.9Hz,2H,CHinpyrimidine),8.55(t,J=1.8Hz,1H,CHinimidazole),8.22(t,J=1.7Hz,1H,CHinimidazole),7.79(t,J=4.9Hz,1H,CHinpyrimidine),5.47(t,J=5.4Hz,1H,CH2OH),4.75-4.71(m,1H,NCH),3.68-3.77(m,2H,CH2OH),1.99-1.92(m,1H,CH2CH(CH3)2),1.67-1.60(m,1H,CH2CH(CH3)2),1.43-1.36(m,1H,CH2CH(CH3)2),0.93(d,J=6.5Hz,3H,CH2CH(CH3)2),0.88(d,J=6.6Hz,3H,CH2CH(CH3)2))ppm.13CNMR(100MHz,DMSO):δ160.5,152.7,136.3,122.9,122.8,119.9,63.4,62.4,38.5,24.4,23.2,22.0ppm.ESIMS,m/z:247.08[M-Cl]+.
(3)在50mL圆底烧瓶中加入N-(1-羟基-4-甲基-2-戊基)-N’-(2-嘧啶基)-咪唑氯鎓盐(1.0mmol,0.28g)、醋酸钯(1.0mmol,0.22g)和10mL二氯甲烷,室温搅拌12h。反应结束后,减压除去二氯甲烷,残余物柱层析分离纯化(梯度洗脱,展开剂:二氯甲烷/丙酮=15:1~4:1,v/v),得螯合型氮杂环卡宾钯化合物NHC-Pd(II)(0.18g,产率42%)。黄色固体,1HNMR(400MHz,DMSO):δ9.44(s,1H,CHinpyrimidine),9.07(s,1H,CHinpyrimidine),8.14(d,1H,J=2.3Hz,CHinimidazole),7.75(d,1H,J=2.4Hz,CHinimidazole),7.72(t,1H,J=5.3Hz,CHinpyrimidine),6.11-6.07(m,1H,NCH),5.02(t,1H,J=5.0Hz,CH2OH),3.65(t,2H,J=4.6Hz,CH2OH),1.89-1.82(m,1H,CH2CH(CH3)2),1.62-1.55(m,1H,CH2CH(CH3)2),1.39-1.34(m,1H,CH2CH(CH3)2),0.96(d,3H,J=6.5Hz,CH2CH(CH3)2).0.88(d,3H,J=6.6Hz,CH2CH(CH3)2)ppm.13CNMR(100MHz,DMSO):δ161.8,158.6,156.9,151.9,122.5,120.4,117.6,64.1,58.8,24.7,23.5,22.7ppm.AnalCacldforC13H18Cl2N4OPd(423.63):C,36.86;H,4.28;N,13.23.Found:C,36.69;H,4.03;N,13.45.
(4)将螯合型氮杂环卡宾钯化合物NHC-Pd(II)(0.5mmol,0.21g)和氯甲基化聚苯乙烯交联微球(CCPS)(1.0g)在乙腈中60℃搅拌8小时,过滤,得到固载的氮杂环卡宾钯化合物催化剂CCPS-NHC-Pd(II)1.20g。
实施例3
(1)在250mL三口烧瓶中,将L-苯丙氨醇(60mmol,9.07g)和氯化铵(60mmol,3.21g)用120mL甲醇溶解,冰浴冷却下,用恒压漏斗依次滴加质量百分比36%的甲醛溶液(60mmol,4.6mL)和质量百分比40%的乙二醛溶液(60mmol,7.6mL)。滴加完毕后,升温至60℃反应5h,将反应液旋干得红褐色粘稠液体。将上述黄色油状黏稠物溶于150mLNaOH溶液(2M),用二氯甲烷萃取(20mL×3),合并有机相,用无水Na2SO4干燥、过滤,减压除去溶剂,柱层析分离纯化得(S)-2-(1-咪唑基)-3-苯丙氨醇纯品(9.71g,产率80%)。
(2)在50mL圆底烧瓶中加入(S)-2-(1-咪唑基)-3-苯丙氨醇(5.0mmol,1.01g)、2-溴吡啶(3mL)和2mL甲苯,加热至110℃反应72h后,冷至室温,将反应液滴入30mL乙醚中,将沉淀析出的深黄色粘稠固体收集,柱层析分离纯化得N-(1-羟基-3-苯基-2-丙基)-N’-(2-吡啶基)-咪唑溴鎓盐纯品(1.35g,产率75%)。m.p.148-150℃.1HNMR(400MHz,DMSO):δ10.17(s,1H,CHinimidazole),8.65(d,1H,J=4.8Hz,CHinpyridine),8.54(t,1H,J=1.7Hz,CHinimidazole),8.24-8.20(m,1H,CHinpyridine),8.18(t,J=1.7Hz,1H,CHinimidazole)8.06(d,1H,J=8.2Hz,CHinpyridine),7.66-7.63(m,1H,CHinpyridine),7.30-7.20(m,5H,PhH),5.36(t,1H,J=5.6Hz,CH2OH),4.90-4.87(m,1H,NCH),3.86-3.82(m,2H,CH2OH),3.32-3.26(m,2H,PhCH2)ppm.13CNMR(100MHz,DMSO):δ149.7,146.7,141.1,136.9,135.0,129.4,129.1,127.3,125.8,123.2,119.7,114.7ppm.ESIMS,m/z:280.08[M-Br]+.
(3)在50mL圆底烧瓶中加入N-(1-羟基-3-苯基-2-丙基)-N’-(2-吡啶基)-咪唑溴鎓盐(1.0mmol,0.36g)、氯化钯(1.0mmol,0.18g)、叔戊醇钾(1.3mmol,0.15g)和10mL二氯甲烷,45℃搅拌12h。反应结束后,减压除去二氯甲烷,残余物柱层析分离纯化(梯度洗脱,展开剂:二氯甲烷/丙酮=15:1~4:1,v/v),得螯合型氮杂环卡宾钯化合物NHC-Pd(III)(0.24g,产率44%)。黄色固体,1HNMR(400MHz,DMSO):δ9.36(s,1H,CHinpyridine),8.42(d,1H,J=1.6Hz,CHinimidazole),8.37(t,1H,J=8.2Hz,CHinpyridine),8.13(d,1H,J=8.2Hz,CHinpyridine),7.91(d,1H,J=2.0Hz,CHinimidazole),7.61(t,1H,J=6.6Hz,CHinpyridine),7.34-7.26(m,4H,PhH),7.18(t,1H,J=7.3Hz,PhH),6.55(s,1H,NCH),5.12(s,1H,CH2OH),3.75-3.65(m,2H,C6H5CH2),3.20(d,2H,J=7.9Hz,CH2OH)ppm.13CNMR(100MHz,DMSO):δ151.7,143.4,137.4,129.6,128.8,127.0,123.7,122.7,117.4,112.8,68.9,63.0,56.3,36.7ppm.AnalCacldforC17H17Br2N3OPd(545.56):C,37.43;H,3.14;N,7.70.Found:C,37.28;H,2.97;N,7.89.
(4)将螯合型氮杂环卡宾钯化合物NHC-Pd(III)(0.5mmol,0.27g)和氯甲基化聚苯乙烯交联微球(CCPS)(1.0g)在乙腈中80℃搅拌7小时,过滤,得到固载的氮杂环卡宾钯化合物催化剂CCPS-NHC-Pd(III)1.26g。
实施例4
步骤(1)同实施例3
(2)在50mL圆底烧瓶中加入(S)-2-(1-咪唑基)-3-苯丙氨醇(5.0mmol,1.01g)、2-氯嘧啶(6mmol,0.69g)和15mL甲苯,加热至110℃反应72h后,冷至室温,将体系中生成粘稠黄色固体收集,柱层析分离纯化得N-(1-羟基-3-苯基-2-丙基)-N’-(2-嘧啶基)-咪唑氯鎓盐纯品(1.42g,产率90%)。1HNMR(400MHz,DMSO):δ10.27(s,1H,CHinimidazole),9.05(d,2H,J=4.9Hz,CHinpyrimidine),8.49(t,1H,J=1.7Hz,CHinimidazole),8.29(t,1H,J=1.6Hz,CHinimidazole),7.78(t,1H,J=4.9Hz,CHinpyrimidine),7.28(d,4H,J=4.4Hz,PhH),7.20-7.17(m,1H,PhH),5.68(t,1H,J=5.4Hz,CH2OH),5.10-5.03(m,1H,NCH),3.91-3.80(m,2H,CH2OH),3.41-3.32(m,2H,PhCH2)ppm.13CNMR(100MHz,DMSO):δ160.5,152.5,136.9,136.1,129.4,129.0,127.3,123.3,122.9,119.6,65.0,62.5,36.0ppm.ESIMS,m/z:281.08[M-Cl]+.
(3)在50mL圆底烧瓶中加入N-(1-羟基-3-苯基-2-丙基)-N’-(2-嘧啶基)-咪唑氯鎓盐(1.0mmol,0.32g)、醋酸钯(1.0mmol,0.22g)和15mL乙腈,80℃搅拌12h。反应结束后,减压除去乙腈,残余物柱层析分离纯化(梯度洗脱,展开剂:二氯甲烷/丙酮=15:1~4:1,v/v),得螯合型氮杂环卡宾钯化合物NHC-Pd(IV)(0.18g,产率39%)。黄色固体,1HNMR(400MHz,DMSO):δ9.42(s,1H,CHinpyrimidine),9.06(s,1H,CHinpyrimidine),8.12(d,1H,J=2.3Hz,CHinimidazole),7.88(d,1H,J=2.4Hz,CHinimidazole),7.71(t,1H,J=5.8Hz,CHinpyrimidine),7.34-7.26(m,4H,PhH),7.19(t,J=7.1Hz,1H,PhH),6.45-6.35(m,1H,NCH),5.14(t,1H,J=5.0Hz,CH2OH),3.78-3.72(m,1H,CH2OH),3.69-3.64(m,1H,CH2OH),3.20(d,2H,J=8.0Hz,C6H5CH2)ppm.13CNMR(100MHz,DMSO):δ161.7,158.6,156.7,152.0,137.46,129.6,128.8,127.0,122.7,120.5,117.4,62.6,60.6,36.7ppm.AnalCacldforC16H16Cl2N4OPd(457.65):C,41.99;H,3.52;N,12.24.Found:C,41.78;H,3.30;N,12.41.
(4)将螯合型氮杂环卡宾钯化合物NHC-Pd(IV)(0.5mmol,0.23g)和氯甲基化聚苯乙烯交联微球(CCPS)(1.0g)在乙腈中80℃搅拌6小时,过滤,得到固载的NHC钯化合物催化剂CCPS-NHC-Pd(IV)1.21g。
实施例5
(1)在250mL三口烧瓶中,将L-亮氨醇(60mmol,7.03g)、苯偶酰(60mmol,12.6g)、醋酸铵(60mmol,4.62g)、质量百分比36%的甲醛溶液(60mmol,4.6mL)和L-脯氨酸(9mmol,1.04g)溶于150mL甲醇中,升温至60℃反应12h,将反应液旋干得红褐色粘稠液体。将上述黄色油状黏稠物溶于乙酸乙酯与水混合液中(v/v,1:1),分液,水相再用乙酸乙酯萃取(20mL×3),合并有机相,用无水Na2SO4干燥、过滤,减压除去溶剂,柱层析分离纯化得(S)-2-(4,5-二苯基-咪唑基)-4-甲基戊醇纯品(13.46g,产率70%)。白色晶体,1HNMR(400MHz,CDCl3):δ7.67(s,1H,Imidazole-H),7.28-7.20(m,6H,PhH),7.13(t,J=7.7Hz,2H,PhH),6.67(bs,2H,PhH),3.77-3.70(m,3H,NCH&CH2OH),1.93-1.86(m,1H,CH2CH(CH3)2),1.45-1.39(m,1H,CH2CH(CH3)2)),1.32-1.27(m,1H,CH(CH3)2),0.76(d,J=6.6Hz,3H,CH(CH3)2),0.54(d,J=6.5Hz,3H,CH(CH3)2).13CNMR(100MHz,CDCl3):δ136.3,134.4,134.2,131.5,130.0,129.0,128.5,128.3,128.1,127.0,126.2,65.4,55.8,40.7,24.2,23.1,21.4.
(2)在50mLSchleck瓶中加入(S)-2-(4,5-二苯基-咪唑基)-4-甲基戊醇(10.0mmol,3.20g)、2-溴甲基吡啶(5mmol,0.86g)和10mL甲苯,氮气保护下加热至110℃反应72h后,减压除去溶剂。将残余粘稠固体柱层析分离纯化得1-(1-羟基-4-甲基-2-戊基)-4,5-二苯基-3-(2-吡啶甲基)-咪唑溴鎓盐纯品(1.95g,产率79%)。黄色粘稠液体,1HNMR(400MHz,DMSO):δ9.93(s,1H,Imidazole-H),8.50(d,J=4.7Hz,1H,PyH),7.76-7.72(m,1H,ArH),7.46(s,5H,ArH),7.38-7.16(m,7H,ArH),5.61-5.50(m,3H,PyCH2,CH2OH),4.22-4.19(m,1H,NCH),3.78(bs,2H,CH2OH),1.90-1.83(m,1H,CH2CH(CH3)2),1.68-1.61(m,1H,CH2CH(CH3)2),1.44(t,J=6.9Hz,1H,CH2CH(CH3)2),0.79(d,J=6.6Hz,3H,CH2CH(CH3)2),0.63(d,J=6.5Hz,3H,CH2CH(CH3)2).13CNMR(100MHz,DMSO):δ153.6,150.0,137.6,136.8,132.7,131.8,131.6,131.1,130.7,130.4,129.4,129.1,125.6,125.5,123.9,122.6,63.4,59.0,52.1,24.3,23.0,22.0.
(3)在50mL圆底烧瓶中加入1-(1-羟基-4-甲基-2-戊基)-4,5-二苯基-3-(2-吡啶甲基)-咪唑溴鎓盐(1.0mmol,0.49g)、氯化钯(1.0mmol,0.18g)、醋酸钠(1.30mmol,0.11g)和10mL乙腈,加热至85℃下反应24h。反应结束后,减压除去乙腈,残余物柱层析分离纯化(梯度洗脱,展开剂:二氯甲烷/丙酮=30:1~4:1,v/v),得螯合型氮杂环卡宾钯化合物NHC-Pd(V)(0.20g,产率39%)。黄色固体,1HNMR(400MHz,CDCl3):δ9.46(d,J=5.2Hz,1H,PyH),7.98-7.94(m,1H,ArH),7.50-7.13(m,12H,ArH),5.96(s,1H,CH2OH),5.92(d,J=14.8Hz,1H,PyCH2),5.12(d,J=14.9Hz,1H,PyCH2),3.70-3.65(m,1H,NCH),3.58-3.40(m,2H,CH2OH),1.35-1.12(m,6H,CH2CH(CH3)2),0.73(d,J=6.5Hz,3H,CH(CH3)2).13CNMR(100MHz,CDCl3):δ156.7,156.4,153.1,139.8,131.7,130.4,130.0,129.8,129.1,128.3,127.9,126.2,125.2,123.9,63.6,62.8,53.4,39.0,24.9,23.1,22.3.AnalCacldforC27H29Br2N3OPd(677.77):C,47.85;H,4.31;N,6.20.Found:C,47.69;H,4.18;N,6.35.
(4)将螯合型氮杂环卡宾钯化合物NHC-Pd(V)(0.5mmol,0.34g)和氯甲基化聚苯乙烯交联微球(CCPS)(1.0g)在甲苯中110℃搅拌10小时,过滤,得到固载的氮杂环卡宾钯化合物催化剂CCPS-NHC-Pd(V)1.32g。
实施例6
(1)在250mL三口烧瓶中,将L-苯丙氨醇(60mmol,9.07g)、苯偶酰(60mmol,12.6g)、醋酸铵(60mmol,4.62g)、质量百分比36%的甲醛溶液(60mmol,4.6mL)和L-脯氨酸(9mmol,1.04g)溶于150mL甲醇中,升温至60℃反应12h,将反应液旋干得红褐色粘稠液体。将上述黄色油状黏稠物溶于乙酸乙酯与水混合液中(v/v,1:1),分液,水相再用乙酸乙酯萃取(20mL×3),合并有机相,用无水Na2SO4干燥、过滤,减压除去溶剂,柱层析分离纯化得(S)-2-(4,5-二苯基-咪唑基)-苯丙氨醇纯品(15.52g,产率73%)。白色晶体,1HNMR(400MHz,DMSO):δ8.12(s,1H,Imidazole-H),7.45-7.36(m,3H,PhH),7.28-7.26(m,2H,PhH),7.20-7.18(m,3H,PhH),7.12(t,J=7.5Hz,2H,PhH),7.06-7.03(m,1H,PhH),6.90-6.82(m,4H,PhH),5.21(t,J=5.3Hz,1H,CH2OH),3.87-3.83(m,1H,NCH),3.76-3.70(m,1H,CH2OH),3.67-3.63(m,1H,CH2OH),3.06-3.03(m,2H,PhCH2).13CNMR(100MHz,DMSO):δ138.3,135.9,135.6,135.4,131.5,131.1,129.5,129.4,129.2,129.1,128.7,128.4,126.8,126.1,126.0,63.9,59.1,38.2.
(2)在50mLSchleck瓶中加入(S)-2-(4,5-二苯基-咪唑基)-苯丙氨醇(10.0mmol,3.54g)、2-溴甲基吡啶(5mmol,0.86g)和10mL乙腈,氮气保护下加热至80℃反应72h后,减压除去溶剂。将残余粘稠固体柱层析分离纯化得1-(1-羟基-3-苯基-2-丙基)-4,5-二苯基-3-(2-吡啶甲基)-咪唑溴鎓盐纯品(1.89g,产率72%)。白色晶体,1HNMR(400MHz,DMSO):δ10.31(s,1H,Imidazole-H),8.61(d,J=4.3Hz,1H,PyH),7.77-7.73(m,1H,ArH),7.38-7.21(m,10H,ArH),7.14-7.04(m,5H,ArH),6.74(d,J=6.9Hz,2H,ArH),5.71(d,J=16.1Hz,1H,PyCH2),5.62(t,J=5.6Hz,1H,CH2OH),5.48(d,J=16.1Hz,1H,PyCH2),4.28-4.22(m,NCH),4.03-3.97(m,1H,CH2OH),3.91-3.86(m,1H,CH2OH),3.24-3.14(m,2H,PhCH2).13CNMR(100MHz,DMSO):δ153.6,150.0,137.6,136.9,136.8,133.1,131.4,131.2,130.9,130.5,130.4,129.6,129.1,129.0,128.9,127.4,125.3,125.2,124.0,122.7,63.0,52.1,37.9.
(3)在50mL圆底烧瓶中加入1-(1-羟基-3-苯基-2-丙基)-4,5-二苯基-3-(2-吡啶甲基)-咪唑溴鎓盐(1.0mmol,0.53g)、氯化钯(1.0mmol,0.18g)、醋酸钠(1.30mmol,0.11g)和10mL乙腈,加热至85℃下反应24h。反应结束后,减压除去乙腈,残余物柱层析分离纯化(梯度洗脱,展开剂:二氯甲烷/丙酮=30:1~4:1,v/v),得螯合型氮杂环卡宾钯化合物NHC-Pd(VI)(0.31g,产率44%)。黄色粉末,1HNMR(400MHz,CDCl3):δ8.97(d,J=4.9Hz,1H,PyH),7.90(t,1H,J=7.4Hz,ArH),7.48-7.26(m,10H,ArH),7.09-6.90(m,7H,ArH),6.13(s,1H,CH2OH),5.62(d,J=14.8Hz,1H,PyCH2),4.93(d,J=14.9Hz,1H,PyCH2),3.83(t,J=8Hz,1H,NCH),3.68-3.57(m,2H,CH2OH),2.78(d,J=13.0Hz,1H,PhCH2),2.59(t,J=12.9Hz,1H,PhCH2).13CNMR(100MHz,CDCl3):δ157.4,156.4,151.8,139.4,136.9,131.9,130.4,130.1,129.9,129.2,128.6,128.5,128.2,127.9,127.0,126.2,124.7,123.2,66.8,63.2,53.0,36.9.AnalCacldforC27H29Br2N3OPd(711.78):C,50.62;H,3.82;N,5.90.Found:C,50.51;H,3.71;N,5.98.
(4)将螯合型氮杂环卡宾钯化合物NHC-Pd(VI)(0.5mmol,0.36g)和氯甲基化聚苯乙烯交联微球(CCPS)(1.0g)在甲苯中110℃搅拌12小时,过滤,得到固载的NHC钯化合物催化剂CCPS-NHC-Pd(VI)1.34g。
应用例
应用本发明化合物催化C-H活化反应实例:
将苯并噁唑衍生物(1.0mmol)、卤代芳烃(0.5mmol)、碱(2.5mmol)、本发明固载的氮杂环卡宾钯化合物催化剂(56~64mg)加入到有机溶剂中,于80~130℃反应8~24小时后,降至室温,减压除去溶剂,柱色谱分离得到纯品。
部分催化反应结果如下表:
a:反应温度:100℃;时间:12h;溶剂:DMF。
将本发明固载的氮杂环卡宾钯合物催化苯并噁唑衍生物的C-H活化,考察了其使用次数。以本发明优选化合物催化苯并噁唑与溴苯的反应进行实验,重复使用六次后,反应产率均仍在90%以上。
以上数据显示了所合成的固载型氮杂环卡宾钯合物对苯并噁唑衍生物的C-H活化反应具有很好的催化效果。而苯并噁唑衍生物C-H活化反应在有机合成、药物研发以及功能性材料开发等领域具有重要的地位,因此本发明合成的固载型氮杂环卡宾钯合物具有很好的应用前景。
Claims (5)
1.含杂芳基的螯合型氮杂环卡宾钯化合物,其特征在于,具有以下通式:
I。
2.如权利要求1所述的含杂芳基的螯合型氮杂环卡宾钯化合物,其特征在于,优选结构如下化合物:
。
3.如权利要求1或2所述的含杂芳基的螯合型氮杂环卡宾钯化合物固载体,其特征在于,通过如下方法制备而成:在有机溶剂中,20~100℃温度下,将螯合型氮杂环卡宾钯化合物通式I或NHC-Pd(I)、NHC-Pd(II)、NHC-Pd(III)、NHC-Pd(IV)、NHC-Pd(V)、NHC-Pd(VI)分别与氯甲基化聚苯乙烯交联微球搅拌反应,经过滤,得到固载的氮杂环卡宾钯化合物催化剂;所述的有机溶剂为甲醇、四氢呋喃、甲苯、1,4-二氧六环、乙腈或乙二醇二甲醚。
4.制备权利要求1所述的含杂芳基的螯合型氮杂环卡宾钯化合物的方法,其特征在于,通过如下合成方法实现:
(1)L-氨基醇、甲醛、乙二醛或苯偶酰,在氯化铵或醋酸铵/L-脯氨酸存在下,在甲醇中加热,一步缩合关环得到N-取代基上含有羟基的咪唑衍生物;
(2)N-取代基上含有羟基的咪唑衍生物与六元环杂芳烃卤代物,在甲苯或乙腈中加热回流,得到杂芳基、羟基双取代的咪唑鎓盐;
(3)在有机溶剂中,杂芳基、羟基双取代的咪唑鎓盐与氯化钯或醋酸钯/碱性物质条件下,20~100℃温度反应,反应结束后,减压除去溶剂,过柱分离得到螯合型氮杂环卡宾钯化合物;
步骤(1)所述的L-氨基醇为L-亮氨醇或L-苯丙氨醇;
步骤(2)所述的六元环杂芳烃卤代物为:;
步骤(3)所述的有机溶剂为甲醇、四氢呋喃、二氯甲烷、甲苯、1,4-二氧六环、乙腈、二甲基甲酰胺、二甲基乙酰胺、N-甲基吡咯烷酮、乙二醇二甲醚或二甲基亚砜;
步骤(3)所述的碱性物质选醋酸钠、醋酸钾、叔丁醇钠、叔丁醇钾、叔戊醇钠或叔戊醇钾。
5.如权利要求4所述的制备含杂芳基的螯合型氮杂环卡宾钯化合物的方法,其特征在于,所述的六元环杂芳烃卤代物选2-氯嘧啶、2-溴吡啶或2-溴甲基吡啶。
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