CN105130916B - 一种高效制备nh-1,2,3三唑化合物的方法 - Google Patents
一种高效制备nh-1,2,3三唑化合物的方法 Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 25
- -1 alkyne compound Chemical class 0.000 claims abstract description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 8
- 239000007800 oxidant agent Substances 0.000 claims abstract description 7
- 230000001590 oxidative effect Effects 0.000 claims abstract description 5
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims description 38
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N sodium azide Substances [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 13
- 239000002904 solvent Substances 0.000 claims description 13
- 239000012044 organic layer Substances 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- SYOANZBNGDEJFH-UHFFFAOYSA-N 2,5-dihydro-1h-triazole Chemical class C1NNN=C1 SYOANZBNGDEJFH-UHFFFAOYSA-N 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 11
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
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- 238000001514 detection method Methods 0.000 claims description 4
- 229910052710 silicon Inorganic materials 0.000 claims description 4
- 239000010703 silicon Substances 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 238000006467 substitution reaction Methods 0.000 claims description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 2
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims description 2
- 238000000605 extraction Methods 0.000 claims description 2
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical group C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims description 2
- 150000003003 phosphines Chemical class 0.000 claims description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 150000001345 alkine derivatives Chemical class 0.000 abstract description 13
- 238000003786 synthesis reaction Methods 0.000 abstract description 10
- 230000015572 biosynthetic process Effects 0.000 abstract description 8
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 abstract description 6
- 229910000667 (NH4)2Ce(NO3)6 Inorganic materials 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 abstract description 3
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- 230000007935 neutral effect Effects 0.000 abstract 1
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- 239000007832 Na2SO4 Substances 0.000 description 11
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- 229910052938 sodium sulfate Inorganic materials 0.000 description 11
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- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 7
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
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- 150000001540 azides Chemical class 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
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- JUINSXZKUKVTMD-UHFFFAOYSA-N hydrogen azide Chemical compound N=[N+]=[N-] JUINSXZKUKVTMD-UHFFFAOYSA-N 0.000 description 2
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- 239000011734 sodium Substances 0.000 description 2
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- DUAJIKVIRGATIW-UHFFFAOYSA-N trinitrogen(.) Chemical compound [N]=[N+]=[N-] DUAJIKVIRGATIW-UHFFFAOYSA-N 0.000 description 2
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- UAPNUNDZDVNTDQ-UHFFFAOYSA-N 4,5-diphenyl-1,2,3-triazole Chemical class C1=CC=CC=C1C1=NNN=C1C1=CC=CC=C1 UAPNUNDZDVNTDQ-UHFFFAOYSA-N 0.000 description 1
- VPCXIEUEKVLHAK-UHFFFAOYSA-N 4-(4-methylphenyl)-5-phenyl-2h-triazole Chemical class C1=CC(C)=CC=C1C1=NNN=C1C1=CC=CC=C1 VPCXIEUEKVLHAK-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- BOGNPBISACKTBA-UHFFFAOYSA-N 4-methyl-5-phenyl-2h-triazole Chemical class N1=NNC(C=2C=CC=CC=2)=C1C BOGNPBISACKTBA-UHFFFAOYSA-N 0.000 description 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Divinylene sulfide Natural products C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
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- TZRXHJWUDPFEEY-UHFFFAOYSA-N Pentaerythritol Tetranitrate Chemical compound [O-][N+](=O)OCC(CO[N+]([O-])=O)(CO[N+]([O-])=O)CO[N+]([O-])=O TZRXHJWUDPFEEY-UHFFFAOYSA-N 0.000 description 1
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- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
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- 230000001766 physiological effect Effects 0.000 description 1
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- 238000001308 synthesis method Methods 0.000 description 1
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- 229930192474 thiophene Natural products 0.000 description 1
- 150000003852 triazoles Chemical group 0.000 description 1
- XJUQFUWWPCIZRB-UHFFFAOYSA-N trimethyl(2-thiophen-3-ylethynyl)silane Chemical compound C[Si](C)(C)C#CC=1C=CSC=1 XJUQFUWWPCIZRB-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- 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
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
- C07D249/06—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
- C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
- C07F7/0814—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring said ring is substituted at a C ring atom by Si
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Abstract
本发明公开了一种高效制备NH‑1,2,3三唑化合物的方法,使用炔烃化合物在氧化剂的氧化下以NaN3或TMSN3为氮源,所述氧化剂为Ph(OAc)2、KMnO4、MnO2、PhI(CF3CO2)2、Mn(OAc)3、PhIO、(NH4)2Ce(NO3)6中的一种,在室温下反应得到NH‑1,2,3三唑衍生物,本发明实现了从简单炔烃合成NH‑1,2,3‑三唑,尤其是电中性或者是富电子的炔烃,从而使NH‑1,2,3‑三唑化合物的合成更直接简洁,更好地实现其潜在应用价值。
Description
技术领域
本发明涉及有机化学领域,尤其涉及一种高效制备NH-1,2,3三唑化合物的方法。
背景技术
NH-1,2,3-三唑化合物是一类具有极其重要生理活性的五元三氮芳香杂环化合物,应用价值非常广泛。它不但有良好的药理活性,而且是非常有价值的药物中间体和有机合成中间体,已被广泛应用于医药、生物化学、光学材料、材料化学和以及新兴的化学生物学等领域当中。自从被发现以来,其在医药领域的研究显得尤为活跃,以这一来,化学家们对这类化合物的药物活性、合成路线等方面都做了大量的研究并取的了惊人的进展。例如在医药方面,NH-1,2,3-三唑化合物普遍存在于药物分子中,并发现具有潜在的生物活性,例如IDO抑制剂,抗菌,抗过敏,抗肿瘤,抗癌活性等。
目前尚未出现从天然产物中提取NH-1,2,3-三唑化合物的报道,其来源基本上源于有机合成,并且其在有机合成化学和药物化学的重要的应用价值,因此对NH-1,2,3-三唑化合物的应用及其合成方法的研究一直都是化学家们致力研究的热点,并且做出了一些杰出的工作。
近十年来,NH-1,2,3-三唑的合成研究取得了许多突破与进展,其合成策略主要分为两步法与一步法。两步合成法是首先第一步通过有机叠氮化物与炔的点击化学(AAC)来构建三唑骨架结构,然后将N-取代基去除,从而得到NH-1,2,3-三唑。但是这种策略从原子经济性和合成步骤经济性上来讲是没有优势的,因为要先合成有机叠氮化物然后再把产物中的N-取代基去除。相比这种两步法之外,相对比较经济的一步法也得到了发展。最早的一步法合成NH-1,2,3-三唑是通过叠氮酸与炔烃的1,3-偶极环加成来实现的,但是该方法不但要用剧毒且易挥发的叠氮酸为原料,而且需要在高温下才能进行,因此限制了该方法的应用。最近化学家们发展了更温和的一步法,如美国西弗吉尼亚大学的Shi课题组发展了叠氮化钠与硝基烯烃来制备NH-1,2,3-三唑的例子;我国兰州大学Chen课题组开发了叠氮化钠与缺电子炔烃反应来制备NH-1,2,3-三唑。这两种方法很具有吸引力,因为他们通过简单易得的叠氮化钠通过一步反应就实现了NH-1,2,3-三唑的合成,而且反应条件相对比较温和。虽然如此,他们的方法也存在一些局限性,因为他们的策略是通过叠氮负离子对缺电子烯烃或者炔烃进行亲核进攻来实现的,只对带有强吸电子基团的烯烃和炔烃有效。所以对于电中性或者是富电子的炔烃来讲,目前还没有合适的方法来制备NH-1,2,3-三唑,尤其是4,5-二取代-NH-1,2,3-三唑的合成,目前对有机合成仍然具有很大的挑战性。面对目前这种现状,我们开发了一种比较通用的方法,来实现从简单炔烃合成NH-1,2,3-三唑,尤其是电中性或者是富电子的炔烃,从而使NH-1,2,3-三唑化合物的合成更直接简洁,更好地实现其潜在应用价值。
发明内容
本发明的目的在于提供一种高效制备NH-1,2,3三唑化合物的方法,相比现有的制备方法,本发明让电中性或者是富电子的炔烃能很好地参与反应。
本发明是用炔烃化合物1在Ph(OAc)2氧化以NaN3为氮源,在PhI(OAc)2的作用下,叠氮化钠释放叠氮自由基,炔烃化合物1与叠氮自由基反应,原位形成的乙烯自由基与叠氮官能团进行分子内关环转化成一个新的氮中心自由基,从而进一步通过氢原子转移,得到最终的NH-1,2,3-三唑化合物,其机理如下。
本发明是这样实现的,使用炔烃化合物在氧化剂的氧化下以NaN3或TMSN3为氮源,所述氧化剂为Ph(OAc)2、KMnO4、MnO2、PhI(CF3CO2)2、Mn(OAc)3、PhIO、(NH4)2Ce(NO3)6中的一种,在室温下反应得到NH-1,2,3三唑衍生物,其反应式为(1),
其中:式中1表示炔烃化合物,式中2表示NH-1,2,3三唑化合物。
上述制备方法的具体步骤为:(1)在干净的反应管中加入0.2mmol炔烃化合物和3mL MeCN,再加入19.5mg、0.3mmol NaN3和64.4mg,0.2mmol PhI(OAc)2,在经过N2的氛围下抽排3次后,在室温下反应8小时,TLC点板检测;(2)反应结束后,反应液通过3-5次萃取,有机层浓缩并经过柱层析得到纯的NH-1,2,3三唑衍生物2。
上述制备方法中,炔烃化合物和NaN3摩尔比为0.5—1:1—1.5。
上述制备方法中,所用氧化剂为0.5—2当量的Ph(OAc)2、KMnO4、MnO2、PhI(CF3CO2)2、Mn(OAc)3、PhIO、(NH4)2Ce(NO3)6中的一种。
上述制备方法中,所用的溶剂为乙腈、四氢呋喃、丙酮、甲苯、二氯甲烷中的一种。
上述制备方法中,反应体系中需要氮气进行保护。
上述制备方法中,反应时间为5—40小时。
上述制备方法中,其中R1为三取代硅基或二取代膦或噻吩环或者吡啶环或者苯环或者苯环上含有给电子基团,如-Me、-OMe或者吸电子基团,如-Br;R2为三取代硅基或二取代膦或H或者环丙烷环或者菲环或者三甲基硅基或者给电子基团,如-OH、-SBu、-PPh2、-NR2,脂肪烃,如-Me、-nBu或者噻吩环或者噻吩环上含有-CHO基或者苯基或者苯基上含有给电子基团-Me、-OMe或者吸电子基团,如-Br、-F、-NO2、-CN、-Ac、-COOMe。
本发明的技术效果是:本发明实现了从简单炔烃合成NH-1,2,3-三唑,尤其是电中性或者是富电子的炔烃,从而使NH-1,2,3-三唑化合物的合成更直接简洁,更好地实现其潜在应用价值。
具体实施方式
下面结合实施例1—11来详细说明本发明所具有的有益效果,旨在帮助阅读者更好地理解本发明的实质,但不能对本发明的实施和保护范围构成任何限定。
实例1,
在干净的25mL Schlenk管中加入1,2-二苯基乙炔(0.20mmol),NaN3(0.3mmol),PhI(OAc)2(0.2mmol),加入3mLCH3CN作溶剂,在室温反应8小时,TLC点板检测,反应结束后将反应液加入适量的水,通过乙酸乙酯(3×10mL)萃取,合并有机相并用无水Na2SO4干燥,有机层再经过浓缩并柱层析得到纯的4,5-二苯基-2H-1,2,3-三唑,淡黄色固体,收率95%。
1H NMR(400MHz,CDCl3)δ7.64-7.48(m,4H),7.40-7.27(m,6H).
13C NMR(100MHz,CDCl3)δ142.1,129.9,128.6,128.5,128.2ppm.
HRMS(ESI)calcd for C14H12N3(M+H)+:222.1031,found 222.1028.
实例2,
在干净的25mL Schlenk管中加入1-甲基-4-(苯基乙炔基)苯(0.20mmol),NaN3(0.3mmol),PhI(OAc)2(0.2mmol),加入3mLCH3CN作溶剂,在室温反应8小时,TLC点板检测,反应结束后将反应液加入适量的水,通过乙酸乙酯(3×10mL)萃取,合并有机相并用无水Na2SO4干燥,有机层再经过浓缩并柱层析得到纯的4-苯基-5-(对甲苯基)-2H-1,2,3-三唑,淡黄色固体,收率92%。
1H NMR(400MHz,CDCl3)δ7.71–7.52(m,2H),7.44(d,J=8.0Hz,2H),7.41–7.31(m,3H),7.18(d,J=7.8Hz,2H),2.38(s,3H).
13C NMR(100MHz,CDCl3)δ142.1,141.9,138.5,130.2,129.3,128.6,128.4,128.2,128.1,126.9,21.3ppm.
HRMS(ESI)calcd for C15H14N3(M+H)+:236.1188,found 236.1182.
实例3,
在干净的25mL Schlenk管中加入1-甲氧基-4-(苯基乙炔基)苯(0.20mmol),NaN3(0.3mmol),PhI(OAc)2(0.2mmol),加入3mLCH3CN作溶剂,在室温反应8小时,TLC点板检测,反应结束后将反应液加入适量的水,通过乙酸乙酯(3×10mL)萃取,合并有机相并用无水Na2SO4干燥,有机层再经过浓缩并柱层析得到纯的4-(4-甲氧基苯基)-5-苯基-2H-1,2,3-三唑,淡黄色固体,收率79%。
1H NMR(400MHz,CDCl3)δ7.60-7.53(m,2H),7.47(d,J=8.6Hz,2H),7.40-7.31(m,3H),6.89(d,J=8.7Hz,2H),3.83(s,3H).
13C NMR(100MHz,CDCl3)δ159.8,142.1,141.8,130.3,129.5,128.6,128.4,128.1,122.2,114.1,55.2ppm.
HRMS(ESI)calcd for C15H14N3O(M+H)+:252.1137,found 252.1130.
实例4,
在干净的25mL Schlenk管中加入1,2-二-对甲苯基乙炔(0.20mmol),NaN3(0.3mmol),PhI(OAc)2(0.2mmol),加入3mLCH3CN作溶剂,在室温反应8小时,TLC点板检测,反应结束后将反应液加入适量的水,通过乙酸乙酯(3×10mL)萃取,合并有机相并用无水Na2SO4干燥,有机层再经过浓缩并柱层析得到纯的4,5-二-对甲苯基-2H-1,2,3-三唑,淡黄色固体,收率93%。
1H NMR(400MHz,CDCl3)δ7.44(d,J=8.2Hz,4H),7.14(d,J=8.0Hz,4H),2.37(s,6H).
13C NMR(100MHz,CDCl3)δ141.8,138.3,129.3,128.1,127.1,21.3ppm.
HRMS(ESI)calcd for C16H16N3(M+H)+:250.1344,found 250.1346.
实例5,
在干净的25mL Schlenk管中加入甲基4-(苯基乙炔基)苯甲酸甲酯(0.20mmol),NaN3(0.3mmol),PhI(OAc)2(0.2mmol),加入3mLCH3CN作溶剂,在室温反应8小时,TLC点板检测,反应结束后将反应液加入适量的水,通过乙酸乙酯(3×10mL)萃取,合并有机相并用无水Na2SO4干燥,有机层再经过浓缩并柱层析得到纯的4-(5-苯基-2H-1,2,3-三唑-4-基)苯甲酸甲酯,黄色固体,收率92%。
1H NMR(400MHz,CDCl3)δ12.32(s,1H),8.04(d,J=8.5Hz,2H),7.67(d,J=8.5Hz,2H),7.55-7.50(m,2H),7.43-7.37(m,3H),3.94(s,3H).
13C NMR(100MHz,CDCl3)δ166.9,142.5,141.9,134.8,129.9,129.8,129.4,129.0,128.8,128.3,128.0,52.3ppm.
HRMS(ESI)calcd for C16H14N3O2(M+H)+:280.1086,found 280.107.
实例6,
在干净的25mL Schlenk管中加入1-(4-(苯基乙炔基)苯基)乙酮(0.20mmol),NaN3(0.3mmol),PhI(OAc)2(0.2mmol),加入3mLCH3CN作溶剂,在室温反应8小时,TLC点板检测,反应结束后将反应液加入适量的水,通过乙酸乙酯(3×10mL)萃取,合并有机相并用无水Na2SO4干燥,有机层再经过浓缩并柱层析得到纯的1-(4-(5-苯基-2H-1,2,3-三唑-4-基)苯基)乙酮,黄色固体,收率74%。
1H NMR(400MHz,CDCl3)δ7.91(d,J=8.5Hz,2H),7.66(d,J=8.4Hz,2H),7.52–7.47(m,2H),7.39–7.32(m,3H),2.60(s,3H).
13C NMR(100MHz,CDCl3)δ198.3,142.1,141.4,136.4,135.1,129.3,128.9,128.8,128.7,128.3,128.0,26.5ppm.
HRMS(ESI)calcd for C16H14N3O(M+H)+:264.1137,found 264.1139.
实例7,
在干净的25mL Schlenk管中加入三甲基(噻吩-3-基乙炔基)硅烷(0.20mmol),NaN3(0.3mmol),PhI(OAc)2(0.2mmol),加入3mLCH3CN作溶剂,在室温反应8小时,TLC点板检测,反应结束后将反应液加入适量的水,通过乙酸乙酯(3×10mL)萃取,合并有机相并用无水Na2SO4干燥,有机层再经过浓缩并柱层析得到纯的4-(噻吩-3-基)-5-(三甲基甲硅烷基)-2H-1,2,3-三唑,黄色固体,收率60%。
1H NMR(400MHz,CDCl3)δ12.39(s,1H),8.57(d,J=3.5Hz,1H),8.23(d,J=7.9Hz,1H),7.76(dd,J=11.0,4.5Hz,1H),7.20(dd,J=6.8,5.1Hz,1H),0.43(s,9H).
13C NMR(100MHz,CDCl3)δ153.1,151.1,148.5,136.4,134.9,122.3,120.6,-1.2ppm.
HRMS(ESI)calcd for C10H15N4Si(M+H)+:219.1066,found 219.1065.
如上为实例7的单晶化学结构式
实例8,
在干净的25mL Schlenk管中加入(环丙基乙炔基)-苯(0.20mmol),NaN3(0.3mmol),PhI(OAc)2(0.2mmol),加入3mLCH3CN作溶剂,在室温反应8小时,TLC点板检测,反应结束后将反应液加入适量的水,通过乙酸乙酯(3×10mL)萃取,合并有机相并用无水Na2SO4干燥,有机层再经过浓缩并柱层析得到纯的4-环丙基-5-苯基-2H-1,2,3-三唑,淡黄色固体,收率90%。
1H NMR(400MHz,CDCl3)δ7.97-7.78(m,2H),7.54-7.33(m,3H),2.07-2.00(m,),1.13-0.92(m,4H).
13C NMR(100MHz,CDCl3)δ143.5,143.3,130.4,128.5,127.9,127.3,7.7,6.3ppm.
HRMS(ESI)calcd for C11H12N3(M+H)+:186.1031,found 186.1030.
实例9,
在干净的25mL Schlenk管中加入1-氟-4-(对-甲苯基乙炔基)苯(0.20mmol),NaN3(0.3mmol),PhI(OAc)2(0.2mmol),加入3mLCH3CN作溶剂,在室温反应8小时,TLC点板检测,反应结束后将反应液加入适量的水,通过乙酸乙酯(3×10mL)萃取,合并有机相并用无水Na2SO4干燥,有机层再经过浓缩并柱层析得到纯的4-(4-氟苯基)-5-(对甲苯基)-2H-1,2,3-三唑,白色固体,收率88%。
1H NMR(400MHz,CDCl3)δ7.48(s,4H),7.33(d,J=5.8Hz,3H),7.00(t,J=7.7Hz,2H).
13C NMR(101MHz,CDCl3)δ162.82(d,J=248.4Hz),141.7,141.4,130.1,123.0,129.5,128.7,128.1,126.0,115.7(d,J=21.7Hz)ppm.
HRMS(ESI)calcd for C14H11N3F(M+H)+:240.0937,found 240.0935.
实例10,
在干净的25mL Schlenk管中加入1-苯基-丙炔(0.20mmol),NaN3(0.3mmol),PhI(OAc)2(0.2mmol),加入3mLCH3CN作溶剂,在室温反应8小时,TLC点板检测,反应结束后将反应液加入适量的水,通过乙酸乙酯(3×10mL)萃取,合并有机相并用无水Na2SO4干燥,有机层再经过浓缩并柱层析得到纯的4-甲基-5-苯基-2H-1,2,3-三唑,淡黄色固体,收率63%。
1H NMR(400MHz,CDCl3)δ7.75-7.69(m,2H),7.50-7.44(m,2H),7.42-7.36(m,1H),2.55(s,3H).
13C NMR(100MHz,DMSO)δ142.8,139.0,130.9,128.2,127.1,126.3,10.95ppm.
HRMS(ESI)calcd for C9H10N3(M+H)+:160.0875,found 160.0877.
实例11,
在干净的25mL Schlenk管中加入2-(苯基乙炔基)噻吩(0.20mmol),NaN3(0.3mmol),PhI(OAc)2(0.2mmol),加入3mLCH3CN作溶剂,在室温反应8小时,TLC点板检测,反应结束后将反应液加入适量的水,通过乙酸乙酯(3×10mL)萃取,合并有机相并用无水Na2SO4干燥,有机层再经过浓缩并柱层析得到纯的4-苯基-5-噻吩-2H-1,2,3-三唑,淡黄色固体,收率76%。
1H NMR(400MHz,CDCl3)δ7.65-7.52(m,2H),7.40-7.38(m,3H),7.32-7.27(m,1H),7.23-7.16(m,1H),6.99(dd,J=4.9,3.7Hz,1H).
13C NMR(100MHz,CDCl3)δ141.6,137.9,131.5,129.3,128.9,128.6,128.5,127.4,126.5,126.2ppm.
HRMS(ESI)calcd for C12H10N3S(M+H)+:228.0595,found 228.0595.
以上所述的实施例仅仅是对本发明的优选实施方式进行描述,并非对本发明的范围进行限定,在不脱离本发明设计精神的前提下,本领域普通技术人员对本发明的技术方案作出的各种变形和改进,均应落入本发明权利要求书确定的保护范围内。
Claims (8)
1.一种高效制备NH-1,2,3三唑化合物的方法,其特征在于,使用炔烃化合物在氧化剂PhI(OAc)2的氧化下,以NaN3或TMSN3为氮源,在室温下反应得到NH-1,2,3三唑衍生物,其反应式为(1),
其中:式中1表示炔烃化合物,式中2表示NH-1,2,3三唑化合物;式中R1为三取代硅基、二取代膦、噻吩环、吡啶环、苯环、含有给电子基团的苯环或者含有吸电子基团的苯环;R2为三取代硅基、二取代膦、H、环丙烷环、菲环、脂肪烃、噻吩环、含有-CHO的噻吩环、苯基、含有给电子基团的苯基或者含有吸电子基团的苯基。
2.根据权利要求1所述的方法,其特征在于,具体步骤为:
(1)在干净的反应管中加入0.2mmol炔烃化合物和3mL MeCN,再加入19.5mg、0.3mmolNaN3和64.4mg、0.2mmol PhI(OAc)2,在经过N2的氛围下抽排3次后,在室温下反应8小时,TLC点板检测;
(2)反应结束后,反应液通过3~5次萃取,有机层浓缩并经过柱层析得到纯的NH-1,2,3三唑衍生物2。
3.根据权利要求1所述的方法,其特征在于,炔烃化合物和NaN3摩尔比为0.5~1:1~1.5。
4.根据权利要求1所述的方法,其特征在于,所用氧化剂为0.5~2当量的PhI(OAc)2。
5.根据权利要求1所述的方法,其特征在于,所用的溶剂为乙腈、四氢呋喃、丙酮、甲苯、二氯甲烷中的一种。
6.根据权利要求1所述的方法,其特征在于,反应体系中需要氮气进行保护。
7.根据权利要求1所述的方法,其特征在于,反应时间为5~40小时。
8.根据权利要求1所述的方法,其特征在于,式中R1为含有-Me或-OMe的苯环,或者R1为含有-Br的苯环;R2为-OH、-SBu、-PPh2或-NR2,或者R2为-Me或-nBu,或者R2为含有-Me或-OMe的苯基,或者R2为含有-Br、-F、-NO2、-CN、-Ac或-COOMe的苯基。
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