CN111848518B - 一种螺[茚-2,4’-吡唑]类化合物的制备方法 - Google Patents
一种螺[茚-2,4’-吡唑]类化合物的制备方法 Download PDFInfo
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- -1 spiro[indene-2,4'-pyrazole] compound Chemical class 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 22
- AOTDLIZVUODSDT-UHFFFAOYSA-N spiro[indene-2,4'-pyrazole] Chemical class N=1N=CC2(C=1)C=C1C=CC=CC1=C2 AOTDLIZVUODSDT-UHFFFAOYSA-N 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 13
- 150000001875 compounds Chemical class 0.000 claims abstract description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 12
- 239000003960 organic solvent Substances 0.000 claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims description 23
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- VKOCOPDOMDBRPG-UHFFFAOYSA-N 1-phenyl-2-(2-phenylethenyl)hydrazine Chemical compound C1(=CC=CC=C1)NNC=CC1=CC=CC=C1 VKOCOPDOMDBRPG-UHFFFAOYSA-N 0.000 claims description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 239000007800 oxidant agent Substances 0.000 claims description 10
- RVWUHFFPEOKYLB-UHFFFAOYSA-N 2,2,6,6-tetramethyl-1-oxidopiperidin-1-ium Chemical group CC1(C)CCCC(C)(C)[NH+]1[O-] RVWUHFFPEOKYLB-UHFFFAOYSA-N 0.000 claims description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- 230000001590 oxidative effect Effects 0.000 claims description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- 239000000376 reactant Substances 0.000 claims description 3
- 230000035484 reaction time Effects 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 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 abstract description 5
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- 229910052723 transition metal Inorganic materials 0.000 abstract description 5
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- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 2
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- 150000002391 heterocyclic compounds Chemical class 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 150000003219 pyrazolines Chemical class 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 1
- IXUDYDXBFVCVRY-UHFFFAOYSA-N 1-[2-(2-chlorophenyl)ethenyl]-2-phenylhydrazine Chemical compound C1(=CC=CC=C1)NNC=CC1=C(C=CC=C1)Cl IXUDYDXBFVCVRY-UHFFFAOYSA-N 0.000 description 1
- JHHNVOAIEORAAD-UHFFFAOYSA-N 1-phenyl-2-[2-(4-propan-2-ylphenyl)ethenyl]hydrazine Chemical compound C1(=CC=CC=C1)NNC=CC1=CC=C(C=C1)C(C)C JHHNVOAIEORAAD-UHFFFAOYSA-N 0.000 description 1
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000006179 2-methyl benzyl group Chemical group [H]C1=C([H])C(=C(C([H])=C1[H])C([H])([H])*)C([H])([H])[H] 0.000 description 1
- 125000006180 3-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000002528 4-isopropyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000003352 4-tert-butyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])*)C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- HOONQMAPLUALQI-UHFFFAOYSA-N 5-benzoyl-9-(4-methylphenyl)-6-phenyl-8,9,10,11-tetrahydro-6h-benzo[b][1,4]benzodiazepin-7-one Chemical compound C1=CC(C)=CC=C1C1CC(NC=2C(=CC=CC=2)N(C2C=3C=CC=CC=3)C(=O)C=3C=CC=CC=3)=C2C(=O)C1 HOONQMAPLUALQI-UHFFFAOYSA-N 0.000 description 1
- XTHZURCYOBLMRE-UHFFFAOYSA-N 5-benzyl-2-phenyl-3-(4-propan-2-ylphenyl)spiro[3H-pyrazole-4,2'-indene]-1',3'-dione Chemical compound CC(C)C1=CC=C(C=C1)C2C3(C(=NN2C4=CC=CC=C4)CC5=CC=CC=C5)C(=O)C6=CC=CC=C6C3=O XTHZURCYOBLMRE-UHFFFAOYSA-N 0.000 description 1
- LGARJDMJPUIIIK-UHFFFAOYSA-N 5-benzyl-3-(4-tert-butylphenyl)-2-phenylspiro[3H-pyrazole-4,2'-indene]-1',3'-dione Chemical compound C(C1=CC=CC=C1)C1=NN(C(C12C(C1=CC=CC=C1C2=O)=O)C2=CC=C(C=C2)C(C)(C)C)C2=CC=CC=C2 LGARJDMJPUIIIK-UHFFFAOYSA-N 0.000 description 1
- KDEXJZXCXHVCJU-UHFFFAOYSA-N C(C1=CC=CC=C1)C1=NN(C(C12N=C1C=CC=CC1=C2)C=2C=C(C=CC2)C)C2=CC=CC=C2 Chemical compound C(C1=CC=CC=C1)C1=NN(C(C12N=C1C=CC=CC1=C2)C=2C=C(C=CC2)C)C2=CC=CC=C2 KDEXJZXCXHVCJU-UHFFFAOYSA-N 0.000 description 1
- 102000009132 CB1 Cannabinoid Receptor Human genes 0.000 description 1
- 108010073366 CB1 Cannabinoid Receptor Proteins 0.000 description 1
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
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- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 1
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- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
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- RPMXALUWKZHYOV-UHFFFAOYSA-N nitroethene Chemical group [O-][N+](=O)C=C RPMXALUWKZHYOV-UHFFFAOYSA-N 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
本发明公开了一种螺[茚‑2,4’‑吡唑]类化合物的制备方法,在氧化剂存在的条件下,1‑苯基‑2‑(2‑苯基乙烯基)肼与式Ⅱ所示化合物(2‑取代苄基‑1,3‑茚二酮),在有机溶剂中进行反应,一步反应得到式III所示的螺[茚‑2,4’‑吡唑]类化合物。此发明的目标物分子是重要的五元氮杂环化合物,广泛存在于许多天然化合物和药物分子的结构中。此发明的所用原料易得,不需要使用过渡金属催化剂,操作简便,同时具有一定的立体选择性,为合成螺[茚‑2,4’‑吡唑]类化合物提供了一种高效且经济适用的方法。
Description
技术领域
本发明属于有机合成技术领域,具体涉及一种螺[茚-2,4’-吡唑]类化合物的制备方法。
背景技术
含氮杂环化合物及其衍生物具有广泛的生物活性,在医药、农药和生命科学等各个领域中都占有极其重要的地位,这些化合物的 合成一直是有机合成领域的研究热点。吡唑啉是一种重要的五元氮杂环化合物,具有一系列显著的生物活性。吡唑啉衍生物也具有很强的生物活性,包括抑制一氧化氮合酶(NOS)以及大麻素CB1受体的拮抗作用(E.,Budzisz;P.,Paneth;I., Geromino;T.,M.,Rozalski;U.,Krajewska;P.,Pipiak;M.B.,Ponczek; M.,B.,Kupcewicz.Journal of Molecular Structure,2017,1137, 267-276)。螺吡唑啉杂环化合物在医药领域的应用广泛,也是众多天然产物的核心化学结构。(A.,Rezvanian;M.,Babashah.J.Heterocyclic Chem.,2019, 56,1362-1368.)。
现有文献报道的关于吡唑啉类衍生物的合成方法很多,比如2003年,MohamedRammah课题组利用二芳基腈亚胺2与2-芳基甲基-1,3-茚二酮的环加成反应生成螺吡唑啉类化合物(S.,Boudrigaa;M.,Askria;R.,Gharbib; M.,Rammaha;K.,Ciamala.J.Chem.Research.2003,4,204-207.)。2009年, Gábor Tóth课题组以(E,E)-肉桂基对苯乙酮与重氮甲烷为反应物,4℃下反应48小时得到3-苯基4-苯乙烯基2-吡唑啉类化合物(A.,Levai;A.,Simon;A., Jenei;G.,Kalman;J.,Jeko;G.,Toth.ARKIVOC,2009,xii,161-172.)。2018年,Lyudmila A.Kayukova等人发现在H2O和DMF-H2O中,1,2,4-噁二唑被转化为螺吡唑啉(L.A.,Kayukova1,A.B.,Uzakova1;A.V.,Vologzhanina;K., Akatan;E.Shaymardan;S.K.,Kabdrakhmanova.Chemistry of Heterocyclic Compounds,2018,54,643–649)。2019年,Atieh Rezvanian和Maedeh Babashah研究了靛红与丙二腈和1,1-二肼基-2-
硝基乙烯(由水合肼和硝基乙烯酮二硫缩醛原位制备)的多组分反应,以乙醇为溶剂,室温下合成了螺吡唑啉类化合物(A.,Rezvanian;M., Babashah.J.HeterocyclicChem.,2019,56,1362-1368.)。但这些方法在不同程度上存在一些问题,包括所用原料昂贵或需要预先制备,反应条件苛刻,使用毒性溶剂,需要过渡金属催化剂,反应时间较长,产率较低,底物拓展范围小等,并且不能用于合成螺[茚-2,4’-吡唑]类化合物。因此,发展高效、经济、绿色化且底物拓展范围大的螺-茚吡唑类化合物的合成方法意义重大。
发明内容
目的:为解决现有技术的不足,本发明提供一种螺[茚-2,4’-吡唑]类化合物的制备方法,底物拓展范围大、原料易得、操作简单、无需过渡金属催化剂、一步合成。
技术方案:为解决上述技术问题,本发明采用的技术方案为:
一种螺[茚-2,4’-吡唑]类化合物的制备方法,包括:在氧化剂存在的条件下,式Ⅰ所示的1-苯基-2-(2-苯基乙烯基)肼、式Ⅱ所示化合物,在有机溶剂中进行反应,得到式III所示的螺[茚-2,4’-吡唑]类化合物;
其中,R代表邻甲基苯基、邻氯苯基、间甲基苯基、对异丙基苯基、对叔丁基苯基、对甲氧基苯基中的任意一种。
在一些实施例中,所述的螺[茚-2,4’-吡唑]类化合物的制备方法,式Ⅰ所示的1-苯基-2-(2-苯基乙烯基)肼、式Ⅱ所示化合物的投料摩尔比为1: (0.5~1.5)。
在一些实施例中,所述的螺[茚-2,4’-吡唑]类化合物的制备方法,所述氧化剂的加入量为式Ⅱ所示化合物摩尔量的1~3倍。
进一步的,在一些实施例中,所述氧化剂为TEMPO(2,2,6,6-四甲基哌啶氧化物)、过硫酸钾、DDQ(二氯二氰基苯醌)或乙酸铜中的一种或几种。更为优选的,所述氧化剂采用TEMPO(2,2,6,6-四甲基哌啶氧化物)。
在一些实施例中,有机溶剂的加入量为1mmol 1-苯基-2-(2-苯基乙烯基)肼反应物使用1.5~3mL有机溶剂。更为优选的,1mmol 1-苯基-2-(2-苯基乙烯基)肼反应物使用2mL有机溶剂。
在一些实施例中,反应的有机溶剂是乙腈、异丙醇、甲苯或二甲基甲酰胺中的一种或几种。更为优选的,有机溶剂采用乙腈。
在一些实施例中,所述的螺[茚-2,4’-吡唑]类化合物的制备方法,反应的投料顺序依次为氧化剂、式Ⅱ所示化合物、式Ⅰ所示的1-苯基-2-(2-苯基乙烯基)肼,用氮气进行保护后,最后加入有机溶剂进行反应。
在一些实施例中,所述的螺[茚-2,4’-吡唑]类化合物的制备方法,反应的气氛条件是氮气保护下进行反应。反应的温度是70℃~100℃,反应的时间是24h~72h。更为优选的,80℃下反应48小时。
有益效果:本发明提供的一种螺[茚-2,4’-吡唑]类化合物的制备方法,以易得的1-苯基-2-(2-苯基乙烯基)肼与2-取代苄基-1,3-茚二酮为原料,在无过渡金属催化剂存在下,在氧化剂存在的条件下,通过一步反应得到螺[茚 -2,4’-吡唑]类化合物。该合成方法高效、操作简单、收率高且环境友好。
具体实施方式
下面结合实施例对本发明作进一步描述。以下实施例只是用于更加清楚地说明本发明的性能,而不能仅局限于下面的实施例。
实施例1
以制备结构式如下的3’-苄基-1’-苯基-5’-(邻甲苯基)-1’,5’-二氢化螺[吲哚-2,4’-吡唑]-1,3-二酮为例,其制备方法如下:
在10mL Schlenk瓶中加入1.5mmol TEMPO(2,2,6,6-四甲基哌啶氧化物),0.5mmol2-(2-甲基苄基)-1H-茚-1,3(2H)-二酮,1mmol 1-苯基-2-(2- 苯基乙烯基)肼,用氮气保护后,加入2mL乙腈作为溶剂,80℃下搅拌反应48h,薄层色谱跟踪检测反应进程,反应结束后将溶剂蒸发浓缩,利用硅胶柱进行柱层析提纯处理即可得到油状液体,再用乙醇重结晶,得到固体产物3’-苄基-1’-苯基-5’-(邻甲苯基)-1’,5’-二氢化螺旋[吲哚-2,4’-吡唑]-1,3-二酮,其分离收率为85%,结构表征数据如下:
1H NMR(400MHz,CDCl3)δ:7.73-7.67(m,3H,ArH),7.55-7.51(m,2H, ArH),7.18-7.13(m,3H,ArH),7.10-7.06(m,1H,ArH),7.03-6.99(m,1H,ArH), 6.96-6.94(m,2H,ArH),6.92-6.89(m,3H,ArH),6.85-6.81(m,3H,ArH),5.75 (s,1H,CH),3.72(d,J=16.0Hz,1H,CH),3.49(d,J=16.4Hz,1H,CH),1.84 (s,3H,CH3);13C NMR(100MHz,CDCl3)δ:197.7,194.2,144.9,144.7,141.7, 136.1,135.7,134.4,133.9,132.5,130.4,129.9,129.4,128.8,128.1,128.0, 127.0,126.4,123.3,123.2,120.1,114.6,74.1,70.4,35.6,19.5;IR(KBr)υ: 3032,1743,1706,1596,1495,1343,1255,1125,1098,1069,886,759cm-1; MS(m/z):HRMS(ESI-TOF)Calcd.for C31H24N2O2([M+Na]+):479.1730, Found:479.1736.
实施例2
以制备结构式如下的3'-苄基-1'-苯基-5'-(间甲苯基)-1',5'-二氢螺[吲哚 -2,4'-吡唑]-1,3-二酮为例,其制备方法如下:
在10mL Schlenk瓶中加入1.5mmol TEMPO(2,2,6,6-四甲基哌啶氧化物),0.5mmol2-(3-甲基苄基)-1H-茚-1,3(2H)-二酮,1mmol 1-苯基-2-(2- 苯基乙烯基)肼,用氮气保护后,加入3mL甲苯作为溶剂,100℃下搅拌反应48h,薄层色谱跟踪检测反应进程,反应结束后将溶剂蒸发浓缩,利用硅胶柱进行柱层析提纯处理即可得到油状液体,再用乙醇重结晶,得到固体产物3'-苄基-1'-苯基-5'-(间甲苯基)-1',5'-二氢螺旋[吲哚-2,4'-吡唑]-1,3-二酮,其分离收率为70%,结构表征数据如下:
1H NMR(400MHz,CDCl3)δ:7.78-7.70(m,2H,ArH),7.68-7.64(m,1H, ArH),7.47(d,J=7.6Hz,1H,ArH),7.20-7.16(m,2H,ArH),7.03-6.98(m,4H, ArH),6.95-6.93(m,2H,ArH),6.92-6.89(m,2H,ArH),6.87-6.85(m,2H,ArH), 6.83-6.81(m,2H,ArH),5.52(s,1H,CH),3.67(d,J=15.6Hz,1H,CH),3.57 (d,J=16.0Hz,1H,CH),2.14(s,3H,CH3);13C NMR(101MHz,CDCl3)δ: 197.5,194.4,146.1,145.6,142.2,142.1,138.2,136.0,135.6,134.4,134.3, 130.1,129.90,129.2,129.0,128.7,128.4,128.2,128.1,127.7,127.1,125.4,124.2,123.3,123.3,120.5,115.5,75.0,74.4,35.7,21.3;IR(KBr)υ:3030,1745, 1706,1595,1496,1325,1262,1182,1118,1029,891,777,746cm-1;MS(m/z): HRMS(ESI-TOF)Calcd.for C31H24N2O2([M+Na]+):479.1730,Found: 479.1737.
实施例3
以制备结构式如下的3’-苄基-5’-(2-氯苯基)-1’-苯基-1’,5’-二氢螺[茚 -2,4’-吡唑]-1,3-二酮为例,其制备方法如下:
在10mL Schlenk瓶中加入2mmol TEMPO(2,2,6,6-四甲基哌啶氧化物), 0.5mmol2-(2-氯苄基)-1H-茚-1,3(2H)-二酮,1mmol 1-苯基-2-(2-氯苯基乙烯基)肼,用氮气保护后,加入2mL异丙醇作为溶剂,90℃下搅拌反应48h,薄层色谱跟踪检测反应进程,反应结束后将溶剂蒸发浓缩,利用硅胶柱进行柱层析提纯处理即可得到油状液体,再用乙醇重结晶,得到固体产物3’- 苄基-5’-(2-氯苯基)-1’-苯基-1’,5’-二氢螺[茚-2,4’-吡唑]-1,3-二酮,其分离收率为65%,结构表征数据如下:
1H NMR(400MHz,CDCl3)δ:7.74-7.68(m,3H,ArH),7.59-7.54(m,2H, ArH),7.24-7.20(m,1H,ArH),7.22-7.17(m,3H,ArH),7.16-7.13(m,1H,ArH), 7.04-7.00(m,1H,ArH),6.96-6.90(m,4H,ArH),6.88-6.85(m,1H,ArH), 6.79-6.77(m,2H,ArH),5.90(s,1H,CH),3.71(d,J=16.0Hz,1H,CH),3.43 (d,J=16.0Hz,1H,CH);13C NMR(101MHz,CDCl3)δ:196.7,194.1,144.9, 144.4,141.8,141.5,135.8,135.7,134.3,132.7,131.8,130.6,129.8,129.4, 129.2,128.9,128.1,127.1,127.0,123.3,123.1,120.1,114.3,73.9,69.5,35.4;IR(KBr)υ:2933,2868,1710,1661,1598,1512,1490,1352,1294,1257,1216, 1172,1147,1110,1082,1030,981,944,830,755cm-1;MS(m/z):HRMS (ESI-TOF)Calcd.for C30H21ClN2O2([M+Na]+):499.1184,Found:499.1193.
实施例4
以制备结构式如下的3'-苄基-5'-(4-异丙基苯基)-1'-苯基-1',5'-二氢化螺[茚-2,4'-吡唑]-1,3-二酮为例,其制备方法如下:
[在10mL Schlenk瓶中加入2mmol TEMPO(2,2,6,6-四甲基哌啶氧化物),0.5mmol2-(4-异丙基苄基)-1H-茚-1,3(2H)-二酮,1mmol 1-苯基-2-(4- 异丙基苯基乙烯基)肼,用氮气保护后,加入2mL乙腈作为溶剂,90℃下搅拌反应24h,薄层色谱跟踪检测反应进程,反应结束后将溶剂蒸发浓缩,利用硅胶柱进行柱层析提纯处理即可得到油状液体,再用乙醇重结晶,得到固体产物3'-苄基-5'-(4-异丙基苯基)-1'-苯基-1',5'-二氢化螺旋[茚-2,4'-吡唑]-1,3-二酮,其分离收率为50%,结构表征数据如下:
1H NMR(400MHz,CDCl3)δ:7.88-7.77(m,1H,ArH),7.74-7.70(m,1H, ArH),7.67-7.63(m,1H,ArH),7.45(d,J=7.6Hz,1H,ArH),7.20-7.16(m,2H, ArH),7.03-7.00(m,3H,ArH),6.98-6.97(m,3H,ArH),6.95-6.92(m,3H,ArH), 6.89-6.81(m,3H,ArH),5.54(s,1H,CH),3.66(d,J=16.0Hz,1H,CH),3.58 (d,J=15.6Hz,1H,CH),2.78-2.71(m,1H,CH),1.12-1.09(m,6H,CH3[2]);13C NMR(101MHz,CDCl3)δ:197.5,194.4,148.7,146.1,145.6,142.2,142.1, 135.9,135.5,134.4,131.6,129.9,128.7,128.1,127.0,126.5,123.2,120.5,115.5,75.1,74.3,35.7,33.6,23.8,23.6;IR(KBr)υ:3031,2963,1744,1707, 1594,1494,1457,1420,1323,1258,1185,1112,1025,897,844,790,754, 721cm-1;MS(m/z):HRMS(ESI-TOF)Calcd.for C33H28N2O2 ([M+Na]+):507.2043,Found:507.2048.
实施例5
以制备结构式如下的3'-苄基-5'-(4-叔丁基苯基)-1'-苯基-1',5'-二氢化螺[茚-2,4'-吡唑]-1,3-二酮为例,其制备方法如下:
在10mL Schlenk瓶中加入0.5mmol TEMPO(2,2,6,6-四甲基哌啶氧化物),0.5mmol2-(4-叔丁基苄基)-1H-茚-1,3(2H)-二酮,1mmol 1-苯基-2-(2- 苯基乙烯基)肼,用氮气保护后,加入2mL二甲基甲酰胺作为溶剂,80℃下搅拌反应48h,薄层色谱跟踪检测反应进程,反应结束后将溶剂蒸发浓缩,利用硅胶柱进行柱层析提纯处理即可得到油状液体,再用乙醇重结晶,得到固体产物3'-苄基-5'-(4-叔丁基苯基)-1'-苯基-1',5'-二氢化螺旋[茚-2,4'-吡唑]-1,3-二酮,其分离收率为55%,结构表征数据如下:
1H NMR(400MHz,CDCl3)δ:7.79-7.77(m,1H,ArH),7.74-7.70(m,1H, ArH),7.66-7.63(m,1H,ArH),7.45-7.43(m,1H,ArH),7.20-7.16(m,2H,ArH), 7.11(d,J=8.4Hz,2H,ArH),7.03-6.98(m,5H,ArH),6.95-6.92(m,2H,ArH), 6.89-6.82(m,3H,ArH),5.54(s,1H,CH),3.66(d,J=15.6Hz,1H,CH),3.59 (d,J=16.0Hz,1H,CH),1.17(s,9H,CH3[3]);13C NMR(101MHz,CDCl3)δ: 197.6,194.5,151.0,146.1,145.6,142.2,142.1,135.9,135.5,134.3,131.2, 129.9,128.7,128.1,127.0,126.8,125.4,123.2,120.5,115.6,75.1,74.3,74.2,35.7,34.42,31.2,31.1;IR(KBr)υ:3031,2957,1745,1707,1592,1496,1320, 1262,1186,1116,1026,897,789,754,718cm-1;MS(m/z):HRMS(ESI-TOF) Calcd.for C34H30N2O2([M+Na]+):521.2199,Found:521.2206.
实施例6
以制备结构式如下的3’-苄基-5’-(4-甲氧基苯基)-1’-苯基-1’,5’-二氢化螺[茚-2,4’-吡唑]-1,3-二酮为例,其制备方法如下:
在10mL Schlenk瓶中加入1.5mmol TEMPO(2,2,6,6-四甲基哌啶氧化物),0.5mmol2-(4-甲氧基苄基)-1H-茚-1,3(2H)-二酮,1mmol 1-苯基-2-(2- 苯基乙烯基)肼,用氮气保护后,加入2mL甲苯作为溶剂,80℃下搅拌反应48h,薄层色谱跟踪检测反应进程,反应结束后将溶剂蒸发浓缩,利用硅胶柱进行柱层析提纯处理即可得到油状液体,再用乙醇重结晶,得到固体产物3’-苄基-5’-(4-甲氧基苯基)-1’-苯基-1’,5’-二氢化螺旋[茚-2,4’-吡唑]-1,3- 二酮,其分离收率为65%,结构表征数据如下:
1H NMR(400MHz,CDCl3)δ:7.78-7.76(m,1H,ArH),7.74-7.70(m,1H, ArH),7.67-7.64(m,1H,ArH),7.48(d,J=7.6Hz,1H,ArH),7.19-7.15(m,2H, ArH),7.03-6.98(m,5H,ArH),6.95-6.91(m,2H,ArH),6.88-6.82(m,3H,ArH), 6.65(d,J=8.0Hz,2H,ArH),5.73(s,1H,CH),3.68(s,3H,OCH3),3.64-3.55 (m,2H,CH);13C NMR(101MHz,CDCl3)δ:197.6,194.6,159.3,146.1,145.5, 142.1,142.1,135.9,135.5,134.3,130.0,128.7,128.4,128.1,128.0,127.1, 126.3,123.3,123.2,120.5,115.5,113.9,75.0,74.0,55.0,35.7,31.4;IR(KBr)υ: 2974,1724,1604,1511,1492,1454,1364,1306,1249,1213,1179,1075,1027,948,875,832,815,769,744cm-1;MS(m/z):HRMS(ESI-TOF)Calcd.for C31H24N2O3([M+Na]+):495.1679,Found:495.1681.
由上述提供的实例表明,本发明提供了一种一步反应合成螺旋[茚-2,4’- 吡唑]类化合物的方法,该方法具有原料易得、无需过渡金属催化剂、操作简单、收率高及底物拓展范围大的优点。
以上已以较佳实施例公开了本发明,然其并非用以限制本发明,凡采用等同替换或者等效变换方式所获得的技术方案,均落在本发明的保护范围之内。
Claims (8)
2.根据权利要求1所述的螺[茚-2,4’-吡唑]类化合物的制备方法,其特征在于,式Ⅰ所示的1-苯基-2-(2-苯基乙烯基)肼、式Ⅱ所示化合物的投料摩尔比为1:(0.5~1.5)。
3.根据权利要求1所述的螺[茚-2,4’-吡唑]类化合物的制备方法,其特征在于,所述氧化剂的加入量为式Ⅱ所示化合物摩尔量的1~3倍。
4.根据权利要求1所述的螺[茚-2,4’-吡唑]类化合物的制备方法,其特征在于,反应的有机溶剂是乙腈、异丙醇、甲苯或二甲基甲酰胺中的一种或几种。
5.根据权利要求1所述的螺[茚-2,4’-吡唑]类化合物的制备方法,其特征在于,反应的投料顺序依次为氧化剂、式Ⅱ所示化合物、式Ⅰ所示的1-苯基-2-(2-苯基乙烯基)肼,用氮气进行保护后,最后加入有机溶剂进行反应。
6.根据权利要求1所述的螺[茚-2,4’-吡唑]类化合物的制备方法,其特征在于,反应的气氛条件是氮气保护下进行反应。
7.根据权利要求1所述的螺[茚-2,4’-吡唑]类化合物的制备方法,其特征在于,反应的温度是70℃~100℃,反应的时间是24h~72h。
8.根据权利要求1所述的螺[茚-2,4’-吡唑]类化合物的制备方法,其特征在于,有机溶剂的加入量为1mmol 1-苯基-2-(2-苯基乙烯基)肼反应物使用1.5~3mL有机溶剂。
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