CN106588787B - A kind of application of the triazole of 1,2,3- containing sweet-smelling formacyl ligand - Google Patents

A kind of application of the triazole of 1,2,3- containing sweet-smelling formacyl ligand Download PDF

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CN106588787B
CN106588787B CN201610945800.XA CN201610945800A CN106588787B CN 106588787 B CN106588787 B CN 106588787B CN 201610945800 A CN201610945800 A CN 201610945800A CN 106588787 B CN106588787 B CN 106588787B
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triazole
ethyl acetate
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methylphenyl
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CN106588787A (en
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江玉波
赵粉
刘耀文
马欣园
杨睿
谢凯
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Kunming University of Science and Technology
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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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    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/22—Organic complexes
    • B01J31/2204—Organic complexes the ligands containing oxygen or sulfur as complexing atoms
    • B01J31/2208—Oxygen, e.g. acetylacetonates
    • B01J31/2217—At least one oxygen and one nitrogen atom present as complexing atoms in an at least bidentate or bridging ligand
    • 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
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
    • B01J2531/0238—Complexes comprising multidentate ligands, i.e. more than 2 ionic or coordinative bonds from the central metal to the ligand, the latter having at least two donor atoms, e.g. N, O, S, P
    • B01J2531/0241—Rigid ligands, e.g. extended sp2-carbon frameworks or geminal di- or trisubstitution

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Abstract

The present invention discloses one kind containing 1,2,3- triazole ligand of sweet-smelling formacyl and preparation method thereof, belongs to technical field of organic synthesis；Isosorbide-5-Nitrae-diaryl -1,2 of the present invention to be easy to get, 3- triazole and aryl formaldehyde are starting material, and under the catalysis of " palladium/phosphorus ligand " system, 1,2, the 3- triazole derivatives containing sweet-smelling formacyl are selectively synthesized by C-C coupling reaction；Synthesized 1,2, the 3- triazole derivatives containing sweet-smelling formacyl contain 1 simultaneously; 2,3- triazole rings and carbonyl functional group's structural unit, two functional groups are in ortho position; it can be used as ligand transition metal and be applied to catalysis reaction, also provide new method and fresh target for the synthesis of drug and modification.

Description

A kind of application of the triazole of 1,2,3- containing sweet-smelling formacyl ligand
Technical field
The present invention relates to a kind of applications of 1,2,3- triazole ligand Han sweet-smelling formacyl, belong to organic synthesis technology neck Domain.
Background technique
Triazole compound has been widely used in fields such as medicine, pesticide and materials, all the time by chemists Attention.Especially after the click-reaction of Sharpless discovery organic nitrine and end alkynes, 1,2,3- triazole compound Synthesis developed in recent years especially rapidly, and be widely used in antibacterial, sterilization, immune and treat tumour, arthritis, osteomalacia etc. Aspect (Kantheti S., Narayan R., Raju K.V.S.N.RSC Adv., 2015,5,3687；Schulze B., Schubert U.S.Chem.S℃. Rev.,2014,43,2522；Bromidge S.M.,Arban R.,Bertani B., Bison S., et al.Med.Chem., 2010,53,5827.), while being also applied to organic synthesis as ligand transition metal Field (Chen Y., Yan W., Akhmedov N., et al. Org.Lett., 2010,12 (2), pp 344-347；Yan W.,Ye X.,Akhmedov N.,et al.Org.Lett.,2012,14(9), 2358.)。
There are two main classes for the synthetic method of such compound: method is first is that occur cycloaddition by alkynes and azide compounds Reaction, the two selectively obtains Isosorbide-5-Nitrae-diaryl -1,2,3- triazole derivatives under cuprous catalysis, and urges in ruthenium or quaternary amine alkali Change it is lower then arrive 1,5- diaryl -1,2,3- triazole derivatives (Chen, Z., Yan, Q., Liu, Z., Zhang, Y.Chem.Eur.J.,2014,20, 17635；Bai,H.,Cai,Z.,Wang,S.,Ji S.Org.Lett.2015,17, 2898.Smith,C.,Greaney,M.Org.Lett. 2013,15,4826；Wang,Y.,Xie,Y.,Qu,H.,et al.J.Org.Chem.2014,79,4463.).Method is second is that directly modify 1,2,3- triazole derivatives, current master Concentrate on the ortho position functional group of the monosubstituted -1,2,3- triazole of 2- and 4- benzyl -1- aryl -1,2,3- triazole derivatives Change, including alkenyl, acyloxylation, alkoxylate etc. (Liu W., Li Y., Xu, B., Kuang, C.Org.Lett., 2013, 15,2342；Zhao S., Yu R., Chen W., Liu M., Wu H., Org.Lett., 2015,17,2828.), and Isosorbide-5-Nitrae-two The direct sweet-smelling formacylization of aryl 1,2,3- triazole is still not implemented.
Summary of the invention
The purpose of the present invention is to provide a kind of 1,2,3- Triazole ligand containing sweet-smelling formacyl, the structural formulas of ligand are as follows:
Wherein, R1Group is selected from H, CH3、OCH3,I,Cl,Br；R2Group is selected from H, CH3、CH(CH3)2、OCH3、Br、Cl、 NO2、SOCH3；R3Group is selected from H, CH3、OCH3。
Another object of the present invention is to provide the preparation methods of above-mentioned 1,2, the 3- Triazole ligand Han sweet-smelling formacyl, specifically The following steps are included:
(1) 1,4- diaryl -1,2,3- triazole, aryl formaldehyde, the molar ratio of catalyst, ligand, oxidant, solvent are pressed For 1:(1~3): (0.01~0.2): (0.01~0.4): (1~5): the ratio of (10~100) successively by diaryl -1 1,4-, 2,3- triazoles, aryl formaldehyde, catalyst, ligand, oxidant, solvent are added in reactor, react 5 at 70 DEG C -150 DEG C ~60 hours, generate mix products；
(2) mix products 2~5 times that step (1) obtains, combining extraction liquid are extracted with ethyl acetate, washing, subtracts drying It obtains crude product after pressure distillation, then column chromatography for separation is carried out to crude product with ethyl acetate/petroleum ether leacheate and is purified to obtain the final product The triazole ligand product of 1,2,3- containing sweet-smelling formacyl.
1,4- diaryl -1,2,3- triazole of the present invention be 1- p-methylphenyl -4- phenyl -1,2,3- triazole, Aminomethyl phenyl -4- phenyl -1,2,3- triazole, 1- o-methyl-phenyl -4- phenyl -1,2,3- triazole, 1- o-methyl-benzene between 1- Aminomethyl phenyl -1,2,3- triazole, 1- are to methoxy between base -4- o-methyl-phenyl -1,2,3- triazole, 1- o-methyl-phenyl -4- Base phenyl -4- phenyl -1,2,3- triazole, 1- p-methylphenyl -4- p-methoxyphenyl -1,2,3- triazole, 1- are to methoxy Bromine between base phenyl -4- p-methylphenyl -1,2,3- triazole, 1- neighbour iodophenyl -4- p-methylphenyl -1,2,3- triazole, 1- Phenyl -4- p-methylphenyl -1,2,3- triazole, 1- Chloro-O-Phenyl -4- p-methylphenyl -1,2,3- triazole, 1- neighbour's chlorobenzene One of base -4- phenyl -1,2,3- triazole.
Aryl formaldehyde of the present invention is benzaldehyde, o-tolualdehyde, tolyl aldehyde, p-tolyl aldehyde, right Propylbenzyl aldehyde, o-methoxybenzaldehyde, m-methoxybenzaldehyde, P-methoxybenzal-dehyde, 3-bromobenzaldehyde, to bromobenzene first Aldehyde, p-chlorobenzaldehyde, m chlorobenzaldehyde, o-chlorobenzaldehyde, m-nitrobenzaldehyde, to one of methanesulfinyl benzaldehyde.
Catalyst of the present invention is tris(dibenzylideneacetone) dipalladium (Pd2(dba)3), palladium acetate (Pd (OAc)2), four (triphenylphosphine) palladium (Pd (PPh3)4), palladium chloride (PdCl2One of).
Ligand of the present invention is 2- dicyclohexyl phosphine -2', 6'- dimethoxy-biphenyl (S-Phos), 2- dicyclohexyl phosphorus - 2,4,6- tri isopropyl biphenyl (X-Phos), triphenylphosphine (PPh3One of).
Oxidant of the present invention be tert-butyl peroxide alcohol (TBHP), the chloro- 5,6- dicyanoquinone (DDQ) of 2,3- bis-, Iodobenzene acetate [PhI (OAc)2], potassium peroxydisulfate (K2S2O8One of).
Solvent of the present invention is 1,2- dichloroethanes (DCE), dimethyl acetamide (DMA), dimethylformamide (DMF), one of acetonitrile (MeCN), dimethyl sulfoxide (DMSO).
The triazole derivatives of 1,2,3- containing sweet-smelling formacyl of the present invention contain 1,2,3- triazole ring and carbonyl function simultaneously Group's structural unit, two functional groups be in ortho position, can be used as ligand transition metal and are applied to catalysis and react, also for pharmaceutical synthesis with repair Decorations provide a kind of new method and fresh target.
The invention has the benefit that former for starting with the 1,4- diaryl -1,2,3- triazole and aryl formaldehyde being easy to get Material selectively obtains 1,2,3- tri- nitrogen containing sweet-smelling formacyl by C-C coupling reaction under the catalysis of " palladium/phosphorus ligand " system Zole derivatives, synthesized compound contain 1,2,3-triazoles ring and carbonyl functional group's structural unit simultaneously, and two functional groups are in Ortho position can be used as ligand transition metal and be applied to catalysis reaction, also provides new method and new mesh for the synthesis of drug and modification Mark.
Specific embodiment
Below with reference to embodiment, invention is further described in detail, but the scope of the present invention is not limited in described Hold.
Embodiment 1:1- (p-methylphenyl) -4- (2- benzoyloxy phenyl) -1, the synthesis of 2,3- triazoles (3a) specifically include Following steps:
(1) 1- p-methylphenyl -4- phenyl -1,2,3- triazole (1a), benzaldehyde (2a), three (dibenzalacetones) are pressed Two palladium (Pd2(dba)3), 2- dicyclohexyl phosphine -2', 6'- dimethoxy-biphenyl (S-Phos), tert-butyl peroxide alcohol (TBHP), The molar ratio of 1,2- dichloroethanes (DCE) is the ratio of 1:1:0.01:0.01:1:10, successively by 1mmol 1- to methylbenzene Base -4- phenyl -1,2,3- triazole, 1mmol benzaldehyde, 0.01mmol Pd2(dba)3、0.01mmol S-Phos、1mmol TBHP, 10mmol DCE are added in reactor, are reacted 10 hours at 70 DEG C.
(2) gained mix products are diluted with 40mL water, then with the mix products 2 of 100mmol ethyl acetate extraction step (1) Secondary, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then (is pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of ethyl acetate and petroleum ether 1:5 by volume are mixed to prepare) carry out column chromatography (400 mesh silica gel) purification Up to 224mg product 1- (p-methylphenyl) -4- (2- benzoyloxy phenyl) -1,2,3- triazole 3a, yield 66%, reactional equation Formula is as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3): δ=8.21-8.03 (m, 1H), 7.93 (s, 1H), 7.87-7.70 (m, 2H), 7.66-7.61 (m, 1H), 7.54-7.42 (m, 5H), 7.37 (t, J=7.7Hz, 2H),7.28 –7.25(m,2H),2.39(s,3H)；13C NMR(100MHz,CDCl3): δ=198.5,145.5,138.8, 137.9,136.9, 134.5,133.4,130.3,130.1,129.1,128.7,128.4,128.1,127.8,120.6, 120.4,21.0。
Embodiment 2:1- (p-methylphenyl) -4- [2- (2- toluyl) phenyl] -1, the synthesis of 2,3- triazoles (3b), Specifically includes the following steps:
(1) 1- p-methylphenyl -4- phenyl -1,2,3- triazole (1a), o-tolualdehyde (2b), three (two benzal are pressed Benzylacetone) two palladium (Pd2(dba)3), 2- dicyclohexyl phosphine -2', 6'- dimethoxy-biphenyl (S-Phos), tert-butyl peroxide alcohol (TBHP), the molar ratio of 1,2- dichloroethanes (DCE) is the ratio of 1:1.2:0.02:0.02:1.5:20, successively by 1mmol 1- p-methylphenyl -4- phenyl -1,2,3- triazole, 1.2mmol 2- tolyl aldehyde, 0.02mmol Pd2(dba)3、 0.02mmol S-Phos, 1.5 mmol TBHP, 20mmol DCE are added in reactor, are reacted 10 hours at 80 DEG C.
(2) gained mix products are diluted with 40mL water, then with the mix products 2 of 100mmol ethyl acetate extraction step (1) Secondary, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then (is pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of ethyl acetate and petroleum ether 1:6 by volume are mixed to prepare) carry out column chromatography (400 mesh silica gel) purification Up to 254mg product 1- (p-methylphenyl) -4- [2- (2- toluyl) phenyl] -1,2,3- triazole 3b, yield 72%, Reaction equation is as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows: 1H-NMR (400MHz, CDCl3): δ=8.00 (d, J=6.3Hz, 2H), 7.64-7.58 (m, 1H), 7.52 (d, J=8.4Hz, 2H), 7.46 (t, J=3.8Hz, 2H), 7.32-7.27 (m, 4H), 7.20 (d, J=7.7Hz, 1H), 7.09 (t, J=7.6Hz, 1H), 2.55 (s, 3H), 2.41 (s, 3H)；13C NMR(100MHz, CDCl3): δ=200.0,145.8,139.6,139.4,138.8,137.4,134.6,131.8,131.5,13 1.5,130.6, 130.1, 129.6,129.2,129.0,128.8,127.9,125.3,120.9,120.5,77.3,21.2,21.0。
Embodiment 3:1- (p-methylphenyl) -4- [2- (3- toluyl) phenyl] -1, the synthesis of 2,3- triazoles (3c), Specifically includes the following steps:
(1) 1- p-methylphenyl -4- phenyl -1,2,3- triazole (1a), tolyl aldehyde (2c), three (two benzal are pressed Benzylacetone) two palladium (Pd2(dba)3), 2- dicyclohexyl phosphine -2', 6'- dimethoxy-biphenyl (S-Phos), tert-butyl peroxide alcohol (TBHP), the molar ratio of 1,2- dichloroethanes (DCE) is the ratio of 1:1.6:0.05:0.05:2:30, successively by 1mmol 1- couple Aminomethyl phenyl -4- phenyl -1,2,3- triazole, 1.6mmol 3- tolyl aldehyde, 0.05mmol Pd2(dba)3、0.05mmol S-Phos, 2mmol TBHP, 30mmol DCE are added in reactor, are reacted 15 hours at 90 DEG C.
(2) gained mix products are diluted with 40mL water, then with the mix products 3 of 100mmol ethyl acetate extraction step (1) Secondary, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then (is pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of ethyl acetate and petroleum ether 1:8 by volume are mixed to prepare) carry out column chromatography (400 mesh silica gel) purification Up to 240mg product 1- (p-methylphenyl) -4- [2- (3- toluyl) phenyl] -1,2,3- triazole 3c, yield 68%, Reaction equation is as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3): δ=8.12 (d, J=7.8Hz, 1H), 7.93 (s, 1H), 7.67-7.60 (m, 2H), 7.56 (d, J=7.6Hz, 1H), 7.47-7.41 (m, 4H), 7.32 (d, J =7.5Hz, 1H), 7.28 (d, J=2.4Hz, 2H), 7.24 (d, J=7.8Hz, 1H), 2.40 (s, 3H), 2.33 (s, 3H)；13C NMR(100 MHz,CDCl3): δ=198.7,145.5,138.8,138.3,138.1,137.0,134.5,134.3,130.4, 130.2,130.1,129.1, 128.6,128.3,128.1,127.7,127.5,120.7,120.4,21.2,21.0。
The conjunction of embodiment 4:1- (p-methylphenyl) -4- [2- (4- diisopropylbenzoyl peroxide) phenyl] -1,2,3- triazole (3d) At, specifically includes the following steps:
(1) by 1- p-methylphenyl -4- phenyl -1,2,3- triazole (1a), cumaldehyde (2d), three (two Asias Benzylacetone) two palladium (Pd2(dba)3), 2- dicyclohexyl phosphine -2', 6'- dimethoxy-biphenyl (S-Phos), the chloro- 5,6- of 2,3- bis- Dicyanoquinone (DDQ), the ratio that the molar ratio of 1,2- dichloroethanes (DCE) is 1:1.8:0.08:0.15:2.5:40, successively By 1mmol 1- p-methylphenyl -4- phenyl -1,2,3- triazole, 1.8mmol 4- propylbenzyl aldehyde, 0.08mmol Pd2 (dba)3, 0.15mmol S-Phos, 2.5mmol DDQ, 40mmol DCE be added in reactor, it is small in 100 DEG C of reactions 20 When.
(2) gained mix products are diluted with 40mL water, then with the mix products 3 of 100mmol ethyl acetate extraction step (1) Secondary, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then (presses second with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of acetoacetic ester and petroleum ether 1:9 by volume are mixed to prepare) carry out column chromatography (400 mesh silica gel) purification i.e. 290mg product 1- (p-methylphenyl) -4- [2- (4- diisopropylbenzoyl peroxide) phenyl] -1,2,3- triazole 3d are obtained, yield is 76%, reaction equation is as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3): δ=8.13 (d, J=7.9Hz, 1H), 7.93 (s, 1H), 7.72 (d, J=8.3Hz, 2H), 7.65-7.60 (m, 1H), 7.50-7.39 (m, 4H), 7.28-7.21 (m, 4H), 2.91 (dt, J=13.8,6.9Hz, 1H), 2.39 (s, 3H), 1.21 (d, J=6.9Hz, 6H)；13C NMR (100MHz,CDCl3): δ=198.2,155.2,145.5,138.8,138.1,134.7,134.5,130.5,130.1, 130.1,129.0,128.5,128.0,127.7, 126.6,120.7,120.4,34.2,23.5,21.0。
Embodiment 5:1- (p-methylphenyl) -4- [2- (4- toluyl) phenyl] -1, the synthesis of 2,3- triazoles (3e), Specifically includes the following steps:
(1) 1- p-methylphenyl -4- phenyl -1,2,3- triazole (1a), p-tolyl aldehyde (2e), palladium acetate (Pd are pressed (OAc)2), 2- dicyclohexyl phosphine -2', 6'- dimethoxy-biphenyl (S-Phos), tert-butyl peroxide alcohol (TBHP), 1,2- bis- The molar ratio of chloroethanes (DCE) is the ratio of 1:1.8:0.1:0.18:3:50, successively by 1mmol 1- p-methylphenyl -4- benzene Base -1,2,3- triazole, 1.8mmol4- tolyl aldehyde, 0.1mmol Pd (OAc)2、0.18mmol S-Phos、3mmol TBHP, 10mmol DCE are added in reactor, are reacted 25 hours at 110 DEG C.
(2) gained mix products are diluted with 40mL water, then with the mix products 4 of 100mmol ethyl acetate extraction step (1) Secondary, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then (is pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of ethyl acetate and petroleum ether 1:10 by volume are mixed to prepare) carry out column chromatography (400 mesh silica gel) purification Up to 265mg product 1- (p-methylphenyl) -4- [2- (4- toluyl) phenyl] -1,2,3- triazole 3e, yield 75%, Reaction equation is as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3): δ=8.12 (d, J=7.8Hz, 1H), 7.93 (d, J=1.1Hz, 1H), 7.80-7.57 (m, 3H), 7.56-7.35 (m, 4H), 7.31-7.24 (m, 2H), 7.17 (d, J=7.7Hz, 2H), 2.39 (s, 3H), 2.35 (s, 3H)；13C NMR(100MHz,CDCl3): δ=198.3,145.5, 144.5,138.8, 138.1,134.5,134.4,130.3,130.1,130.1,129.2,129.0,128.5,127.9, 127.7,120.6,120.4,21.6, 21.0。
The conjunction of embodiment 6:1- (p-methylphenyl) -4- [2- (2- methoxybenzoyl) phenyl] -1,2,3- triazole (3f) At, specifically includes the following steps:
(1) 1- p-methylphenyl -4- phenyl -1,2,3- triazole (1a), o-methoxybenzaldehyde (2f), palladium acetate are pressed (Pd(OAc)2), 2- dicyclohexylphosphontetrafluoroborate -2,4,6- tri isopropyl biphenyl (X-Phos), iodobenzene acetate (PhI (OAc)2), 1,2- bis- The molar ratio of chloroethanes (DCE) is the ratio of 1:2.2:0.12:0.2:3.5:60, successively by 1mmol 1- p-methylphenyl -4- Phenyl -1,2,3- triazole, 2.2mmol o-methoxybenzaldehyde, 0.12mmol Pd (OAc), 0.2mmol X-Phos, 3.5mmol PhI(OAc)2, 60mmol DCE be added in reactor, 120 DEG C react 60 hours.
(2) gained mix products are diluted with 40mL water, then with the mix products 2 of 100mmol ethyl acetate extraction step (1) Secondary, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then (is pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of ethyl acetate and petroleum ether 1:12 by volume are mixed to prepare) carry out column chromatography (400 mesh silica gel) purification Up to 299mg product 1- (p-methylphenyl) -4- [2- (2- methoxybenzoyl) phenyl] -1,2,3- triazole 3f, yield is 81%, reaction equation is as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3): δ=8.28-7.96 (m, 2H), 7.67-7.34 (m, 7H), 7.31-7.25 (m, 2H), 6.91 (dd, J=9.5,5.5Hz, 1H), 6.88-6.57 (m, 1H), 3.63(s, 3H),2.41(s,3H)；13C NMR(100MHz,CDCl3): δ=197.7,158.8,145.6,140.1,138.7, 134.6,133.9, 131.5,130.4,130.0,129.3,128.8,128.3,128.1,127.7,121.3,120.4, 120.2,111.8,55.7,21.0。
The conjunction of embodiment 7:1- (p-methylphenyl) -4- [2- (3- methoxybenzoyl) phenyl] -1,2,3- triazole (3g) At, specifically includes the following steps:
(1) 1- p-methylphenyl -4- phenyl -1,2,3- triazole (1a), m-methoxybenzaldehyde (2g), palladium acetate are pressed (Pd(OAc)2), 2- dicyclohexylphosphontetrafluoroborate -2,4,6- tri isopropyl biphenyl (X-Phos), tert-butyl peroxide alcohol (TBHP), diformazan The molar ratio of yl acetamide (DMA) is the ratio of 1:2.4:0.15:0.1:4:70, successively by 1mmol 1- p-methylphenyl -4- Phenyl -1,2,3- triazole, 2.4mmol m-methoxybenzaldehyde, 0.15mmol Pd (OAc)2、0.1mmol X-Phos、 4mmol TBHP, 70mmol DMA are added in reactor, are reacted 35 hours at 130 DEG C.
(2) gained mix products are diluted with 40mL water, then with the mix products of 100mmol ethyl acetate extraction step (1) 4 times, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then (is pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of ethyl acetate and petroleum ether 1:8 by volume are mixed to prepare) carry out column chromatography (400 mesh silica gel) purification i.e. 288mg product 1- (p-methylphenyl) -4- [2- (3- methoxybenzoyl) phenyl] -1,2,3- triazole 3g, yield 78%, Reaction equation is as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3): δ=8.09 (d, J=7.8Hz, 1H), 7.94 (s, 1H), 7.63 (td, J=7.6,1.7Hz, 1H), 7.51-7.39 (m, 5H), 7.33-7.26 (m, 3H), 7.24 (d, J=7.6Hz, 1H), 7.08-7.03 (m, 1H), 3.80 (s, 3H), 2.40 (s, 3H)；13C NMR(100MHz,CDCl3):δ =198.2,159.7,145.6,138.8,138.3,138.0,134.5,130.3,130.1,12 9.4,129.0,128.7, 128.1,127.7, 123.3,120.6,120.4,120.1,113.7,55.4,21.0。
The conjunction of embodiment 8:1- (p-methylphenyl) -4- [2- (4- methoxybenzoyl) phenyl] -1,2,3- triazole (3h) At, specifically includes the following steps:
(1) 1- p-methylphenyl -4- phenyl -1,2,3- triazole (1a), P-methoxybenzal-dehyde (2h), palladium acetate are pressed (Pd(OAc)2), 2- dicyclohexylphosphontetrafluoroborate -2,4,6- tri isopropyl biphenyl (X-Phos), potassium peroxydisulfate (K2S2O8), dimethylacetamide The molar ratio of amine (DMA) is the ratio of 1:2.6:0.18:0.08:4.5:80, successively by 1mmol 1- p-methylphenyl -4- benzene Base -1,2,3- triazole, 2.6mmol P-methoxybenzal-dehyde, 0.18mmol Pd (OAc)2、0.08mmol X-Phos、 4.5mmol K2S2O8, 80mmol DMA be added in reactor, 140 DEG C react 40 hours.
(2) gained mix products are diluted with 40mL water, then with the mix products 5 of 100mmol ethyl acetate extraction step (1) Secondary, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then (is pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of ethyl acetate and petroleum ether 1:15 by volume are mixed to prepare) carry out column chromatography (400 mesh silica gel) purification Up to 262mg product 1- (p-methylphenyl) -4- [2- (4- methoxybenzoyl) phenyl] -1,2,3- triazole 3h, yield is 71%, reaction equation is as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3): δ=8.13 (d, J=7.8Hz, 1H), 7.93 (s, 1H), 7.76 (dd, J=9.3,2.3Hz, 2H), 7.61 (td, J=7.7,1.4Hz, 1H), 7.49-7.39 (m, 4H), 7.29-7.22 (m, 2H), 6.84 (d, J=8.9Hz, 2H), 3.81 (s, 3H), 2.39 (s, 3H)；13C NMR (100MHz,CDCl3): δ=197.3,163.9,145.5,138.8,138.2,134.5,132.5,130.1,130.0, 129.8,128.9,128.3,127.8,127.7, 120.6,120.4,113.7,55.4,21.0。
Embodiment 9:1- (p-methylphenyl) -4- [2- (3- Bromophenacyl) phenyl] -1, the synthesis of 2,3- triazoles (3i), tool Body the following steps are included:
(1) 1- p-methylphenyl -4- phenyl -1,2,3- triazole (1a), 3-bromobenzaldehyde (2i), four (triphenylphosphines) are pressed Palladium (Pd (PPh3)4), 2- dicyclohexylphosphontetrafluoroborate -2,4,6- tri isopropyl biphenyl (X-Phos), tert-butyl peroxide alcohol (TBHP), two The molar ratio of methylacetamide (DMA) is the ratio of 1:2.8:0.2:0.12:5:90, successively by 1mmol 1- p-methylphenyl- 4- phenyl -1,2,3- triazole, 2.8mmol 3-bromobenzaldehyde, 0.2mmol Pd (PPh3)4、0.12mmol X-Phos、5mmol TBHP, 90mmol DMA are added in reactor, are reacted 45 hours at 150 DEG C.
(2) gained mix products are diluted with 40mL water, then with the mix products 2 of 100mmol ethyl acetate extraction step (1) Secondary, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then (is pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of ethyl acetate and petroleum ether 1:18 by volume are mixed to prepare) carry out column chromatography (400 mesh silica gel) purification Up to 255mg product 1- (p-methylphenyl) -4- [2- (3- Bromophenacyl) phenyl] -1,2,3- triazole 3i, yield 61%, instead Answer equation as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3): δ=8.16 (s, 1H), 8.04 (d, J =7.8Hz, 1H), 7.66 (td, J=7.7,1.3Hz, 1H), 7.60 (d, J=8.4Hz, 2H), 7.58-7.49 (m, 2H), 7.47 (t, J=7.5Hz, 1H), 7.40-7.36 (m, 1H), 7.30 (d, J=8.4Hz, 2H), 7.26-7.20 (m, 2H), 2.42 (s,3H)；13C NMR(100MHz,CDCl3): δ=197.2,145.5,139.6,138.8,137.5,134.6,133.8, 132.3,131.8,131.5, 130.3,130.2,130.1,130.0,128.12,127.1,121.3,121.0,120.5, 21.0。
Embodiment 10:1- (p-methylphenyl) -4- [2- (4- Bromophenacyl) phenyl] -1, the synthesis of 2,3- triazoles (3j), Specifically includes the following steps:
(1) 1- p-methylphenyl -4- phenyl -1,2,3- triazole (1a), p-bromobenzaldehyde (2j), four (triphenylphosphines) are pressed Palladium (Pd (PPh3)4), 2- dicyclohexylphosphontetrafluoroborate -2,4,6- tri isopropyl biphenyl (X-Phos), tert-butyl peroxide alcohol (TBHP), two The molar ratio of methylacetamide (DMA) is the ratio of 1:3:0.05:0.1:2:100, successively by 1mmol 1- p-methylphenyl- 4- phenyl -1,2,3- triazole, 3mmol 4- bromobenzaldehyde, 0.05mmol Pd (PPh3)4、0.1mmol X-Phos、2mmol TBHP, 100mmol DMA are added in reactor, are reacted 55 hours at 120 DEG C.
(2) gained mix products are diluted with 40mL water, then with the mix products of 100mmol ethyl acetate extraction step (1) 3 times, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then (is pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of ethyl acetate and petroleum ether 1:20 by volume are mixed to prepare) carry out column chromatography (400 mesh silica gel) purification Up to 226mg product 1- (p-methylphenyl) -4- [2- (4- Bromophenacyl) phenyl] -1,2,3- triazole 3j, yield 54%, instead Answer equation as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3): δ=8.03 (d, J=7.8Hz, 1H), 7.95 (s, 1H), 7.64 (d, J=8.5Hz, 3H), 7.61-7.32 (m, 6H), 7.28 (d, J=8.4Hz, 2H), 2.40 (s,3H)；13C NMR(100MHz,CDCl3): δ=197.3,145.5,138.9,137.5,135.8,134.4,131.7, 131.6,131.4, 130.5,130.1,129.1,128.7,128.6,128.0,127.9,120.4,21.0。
Embodiment 11:1- (p-methylphenyl) -4- [2- (4- chlorobenzoyl) phenyl] -1, the synthesis of 2,3- triazoles (3k), Specifically includes the following steps:
(1) 1- p-methylphenyl -4- phenyl -1,2,3- triazole (1a), p-chlorobenzaldehyde (2k), four (triphenylphosphines) are pressed Palladium (Pd (PPh3)4), 2- dicyclohexylphosphontetrafluoroborate -2,4,6- tri isopropyl biphenyl (X-Phos), tert-butyl peroxide alcohol (TBHP), two The molar ratio of methylacetamide (DMA) is the ratio of 1:1.5:0.01:0.01:1:40, successively by 1mmol 1- p-methylphenyl- 4- phenyl -1,2,3- triazole, 1.5mmol p-chlorobenzaldehyde, 0.01mmol Pd (PPh3)4、0.01mmol X-Phos、1mmol TBHP, 40mmol DMA are added in reactor, are reacted 5 hours at 90 DEG C.
(2) gained mix products are diluted with 40mL water, then with the mix products 2 of 100mmol ethyl acetate extraction step (1) Secondary, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then (is pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of ethyl acetate and petroleum ether 1:5 by volume are mixed to prepare) carry out column chromatography (400 mesh silica gel) purification Up to 232mg product 1- (p-methylphenyl) -4- [2- (4- chlorobenzoyl) phenyl] -1,2,3- triazole 3k, yield 62%, instead Answer equation as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3): δ=8.03 (d, J=7.8Hz, 1H), 7.95 (s, 1H), 7.80-7.68 (m, 2H), 7.65-7.60 (m, 1H), 7.54-7.46 (m, 3H), 7.42 (dd, J= 7.6,1.2 Hz, 1H), 7.39-7.30 (m, 2H), 7.27 (d, J=9.1Hz, 2H), 2.40 (s, 3H)；13C NMR(100MHz, CDCl3): δ=197.1,145.5,139.9,138.9,137.5,135.4,134.4,131.4,130.5,13 0.1,129.1, 128.8,128.6,128.5, 128.0,127.9,120.4,21.0。
Embodiment 12:1- (p-methylphenyl) -4- [2- (3- chlorobenzoyl) phenyl] -1, the synthesis of 2,3- triazoles (3l), Specifically includes the following steps:
(1) 1- p-methylphenyl -4- phenyl -1,2,3- triazole (1a), m chlorobenzaldehyde (2l), palladium chloride are pressed (PdCl2), triphenylphosphine (PPh3), tert-butyl peroxide alcohol (TBHP), dimethyl acetamide (DMA) molar ratio be 1:1.5: The ratio of 0.02:0.02:1.5:50, successively by 1mmol 1- p-methylphenyl -4- phenyl -1,2, between 3- triazole, 1.5mmol Chlorobenzaldehyde, 0.02mmol PdCl2、0.02mmol PPh3, 1.5mmol TBHP, 50mmol DMA be added in reactor, 100 DEG C are reacted 10 hours.
(2) gained mix products are diluted with 40mL water, then with the mix products 3 of 100mmol ethyl acetate extraction step (1) Secondary, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then (is pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of ethyl acetate and petroleum ether 1:4 by volume are mixed to prepare) carry out column chromatography (400 mesh silica gel) purification Up to 254mg product 1- (p-methylphenyl) -4- [2- (3- chlorobenzoyl) phenyl] -1,2,3- triazole 3l, yield 68%, instead Answer equation as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3): δ=8.03 (d, J=7.8Hz, 1H), 7.97 (s, 1H), 7.81 (dd, J=5.3,3.5Hz, 1H), 7.66-7.60 (m, 2H), 7.52-7.44 (m, 5H), 7.33–7.27(m, 3H),2.40(s,3H)；13C NMR(100MHz,CDCl3): δ=196.9,145.5,138.9,138.7, 137.3,134.7,134.5, 133.2,130.6,130.1,129.7,129.7,129.1,128.8,128.8,128.3, 128.2,127.9,120.4,21.0。
Embodiment 13:1- (p-methylphenyl) -4- [2- (2- chlorobenzoyl) phenyl] -1, the synthesis of 2,3- triazoles (3m), Specifically includes the following steps:
(1) 1- p-methylphenyl -4- phenyl -1,2,3- triazole (1a), o-chlorobenzaldehyde (2m), palladium chloride are pressed (PdCl2), triphenylphosphine (PPh3), tert-butyl peroxide alcohol (TBHP), dimethylformamide (DMF) molar ratio be 1:1.5: The ratio of 0.05:0.05:2:60, successively by 1mmol 1- p-methylphenyl -4- phenyl -1,2,3- triazole, 1.5mmol neighbour's chlorine Benzaldehyde, 0.05mmol PdCl2、0.05mmol PPh3, 2mmol TBHP, 60mmol DMF be added in reactor, 110 DEG C reaction 15 hours.
(2) gained mix products are diluted with 40mL water, then with the mix products of 100mmol ethyl acetate extraction step (1) 4 times, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then (is pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of ethyl acetate and petroleum ether 1:10 by volume are mixed to prepare) carry out column chromatography (400 mesh silica gel) purification Up to 236mg product 1- (p-methylphenyl) -4- [2- (2- chlorobenzoyl) phenyl] -1,2,3- triazole 3m, yield 63%, instead Answer equation as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3): δ=8.12 (s, 1H), 8.01 (d, J =7.8Hz, 1H), 7.65 (t, J=7.6Hz, 1H), 7.63-7.50 (m, 3H), 7.47 (t, J=7.5Hz, 1H), 7.40 (d, J =8.0 Hz, 1H), 7.35-7.26 (m, 4H), 7.25-7.15 (m, 1H), 2.42 (s, 3H)；13C NMR(100MHz,CDCl3): δ=196.7,145.5,138.8,138.0,137.8,134.5,132.7,132.3,131.6,13 1.4,130.6,130.2, 130.1,129.9, 129.7,128.1,126.6,121.2,120.4,21.0。
The conjunction of embodiment 14:1- (p-methylphenyl) -4- [2- (3- nitrobenzene formyl) phenyl] -1,2,3- triazole (3n) At, specifically includes the following steps:
(1) 1- p-methylphenyl -4- phenyl -1,2,3- triazole (1a), m-nitrobenzaldehyde (2n), palladium chloride are pressed (PdCl2), triphenylphosphine (PPh3), tert-butyl peroxide alcohol (TBHP), dimethylformamide (DMF) molar ratio be 1:1.5: The ratio of 0.08:0.15:2.5:70, successively by 1mmol 1- p-methylphenyl -4- phenyl -1,2, between 3- triazole, 1.5mmol Nitrobenzaldehyde, 0.08mmol PdCl2、0.15mmol PPh3, 2.5mmol TBHP, 70mmol DMF be added in reactor, It is reacted 20 hours at 120 DEG C.
(2) gained mix products are diluted with 40mL water, then with the mix products of 100mmol ethyl acetate extraction step (1) 2 times, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then (is pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of ethyl acetate and petroleum ether 1:8 by volume are mixed to prepare) carry out column chromatography (400 mesh silica gel) purification i.e. 277mg product 1- (p-methylphenyl) -4- [2- (3- nitrobenzene formyl) phenyl] -1,2,3- triazole 3m, yield 72%, instead Answer equation as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3): δ=8.59 (d, J=1.5Hz, 1H), 8.36-8.28 (m, 1H), 8.15-8.10 (m, 1H), 8.05 (s, 1H), 7.92 (d, J=7.8Hz, 1H), 7.67 (td, J =7.6,1.4Hz, 1H), 7.60-7.45 (m, 5H), 7.28 (d, J=8.4Hz, 2H), 2.40 (s, 3H)；13C NMR (100MHz, CDCl3): δ=195.7,148.2,145.7,139.3,138.8,136.8,135.4,134.4,131.1, 130.2,129.6,129.1, 128.9,128.5,128.3,127.2,124.4,120.3,120.0,21.0。
Embodiment 15:1- (p-methylphenyl) -4- [2- (4- methanesulfinyl benzoyl) phenyl] -1,2,3- triazole The synthesis of (3o), specifically includes the following steps:
(1) by 1- p-methylphenyl -4- phenyl -1,2,3- triazole (1a), to methanesulfinyl benzaldehyde (2o), chlorination Palladium (PdCl2), triphenylphosphine (PPh3), tert-butyl peroxide alcohol (TBHP), dimethylformamide (DMF) molar ratio be 1: The ratio of 1.5:0.1:0.18:3:80, successively by 1mmol 1- p-methylphenyl -4- phenyl -1,2,3- triazole, 1.5mmol To methanesulfinyl benzaldehyde, 0.1mmol PdCl2、0.18mmol PPh3, 3mmol TBHP, 80mmol DMF be added to reaction In device, reacted 25 hours at 130 DEG C.
(2) gained mix products are diluted with 40mL water, then with the mix products of 100mmol ethyl acetate extraction step (1) 2 times, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then (is pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of ethyl acetate and petroleum ether 1:2 by volume are mixed to prepare) carry out column chromatography (400 mesh silica gel) purification i.e. Obtain 261mg product 1- (p-methylphenyl) -4- [2- (4- methanesulfinyl benzoyl) phenyl] -1,2,3- triazole 3o, yield It is 65%, reaction equation is as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3): δ=8.02 (s, 1H), 8.01- 7.82 (m, 5H), 7.66 (td, J=7.6,1.4Hz, 1H), 7.54-7.45 (m, 4H), 7.28 (d, J=8.3Hz, 2H), 3.00 (s,3H), 2.40(s,3H)；13C NMR(100MHz,CDCl3): δ=196.6,145.6,143.9,141.5,139.1, 137.2,134.3, 130.9,130.6,130.2,129.0,128.9,128.4,128.2,127.4,120.3,120.0, 44.2,21.0。
Embodiment 16:1- (3- tolyl) -4- (2- benzoyloxy phenyl) -1, the synthesis of 2,3- triazoles (3p) are specific to wrap Include following steps:
(1) by aminomethyl phenyl -4- phenyl -1,2,3- triazole (1b), benzaldehyde (2a), palladium acetate (Pd between 1- (OAc)2), 2- dicyclohexylphosphontetrafluoroborate -2,4,6- tri isopropyl biphenyl (X-Phos), tert-butyl peroxide alcohol (TBHP), dimethyl The molar ratio of formamide (DMF) is the ratio of 1:1.5:0.1:0.18:3:80, successively by aminomethyl phenyl -4- benzene between 1mmol 1- Base -1,2,3- triazole, 1.5mmol benzaldehyde, 0.1mmol Pd (OAc)2、0.18mmol X-Phos、3mmol TBHP、 80mmol DMF is added in reactor, is reacted 5 hours at 90 DEG C.
(2) gained mix products are diluted with 40mL water, then with the mix products of 100mmol ethyl acetate extraction step (1) 3 times, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then (is pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of ethyl acetate and petroleum ether 1:4 by volume are mixed to prepare) carry out column chromatography (400 mesh silica gel) purification i.e. Obtain 190mg product 1- (3- tolyl) -4- (2- benzoyloxy phenyl) -1,2,3- triazole 3p, yield 56%, reaction equation It is as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3): δ=8.10 (d, J=7.8Hz, 1H), 7.93 (s, 1H), 7.79 (d, J=7.8Hz, 2H), 7.63 (t, J=7.5Hz, 1H), 7.54-7.41 (m, 5H), 7.37 (t, J=7.7 Hz, 2H), 7.29-7.25 (m, 2H), 2.39 (s, 3H)；13C NMR(100MHz,CDCl3): δ=198.5, 145.5,138.8, 137.9,136.9,134.5,133.4,133.0,132.2,130.3,130.1,129.8,129.1, 128.7,128.4,128.1,127.8, 120.7,120.4,120.4,21.0。
Embodiment 17:1- (2- tolyl) -4- (2- benzoyloxy phenyl) -1, the synthesis of 2,3- triazoles (3q) are specific to wrap Include following steps:
(1) 1- o-methyl-phenyl -4- phenyl -1,2,3- triazole (1c), benzaldehyde (2a), palladium acetate (Pd are pressed (OAc)2), 2- dicyclohexylphosphontetrafluoroborate -2,4,6- tri isopropyl biphenyl (X-Phos), tert-butyl peroxide alcohol (TBHP), dimethyl The molar ratio of formamide (DMF) is the ratio of 1:1.5:0.15:0.1:4:100, successively by 1mmol 1- o-methyl-phenyl -4- Phenyl -1,2,3- triazole, 1.5mmol benzaldehyde, 0.15mmol Pd (OAc)2、0.1mmol X-Phos、4mmol TBHP、 100mmol DMF is added in reactor, is reacted 10 hours at 100 DEG C.
(2) gained mix products are diluted with 40mL water, then with the mix products of 100mmol ethyl acetate extraction step (1) 2 times, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then (is pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of ethyl acetate and petroleum ether 1:5 by volume are mixed to prepare) carry out column chromatography (400 mesh silica gel) purification i.e. Obtain 207mg product 1- (2- tolyl) -4- (2- benzoyloxy phenyl) -1,2,3- triazole 3q, yield 61%, reaction equation It is as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3): δ=8.13 (d, J=7.8Hz, 1H), 7.77 (d, J=7.4Hz, 2H), 7.70-7.58 (m, 2H), 7.55-7.44 (m, 3H), 7.36 (dd, J=9.3, 6.0Hz, 3H), 7.31-7.26 (m, 2H), 7.16 (d, J=7.7Hz, 1H), 1.92 (s, 3H)；13C NMR(100MHz, CDCl3): δ=198.5,144.9,138.0,136.7,136.1,133.6,133.4,131.3,130.4,13 0.0,129.8, 128.9,128.6,128.4,128.1, 128.0,126.7,125.8,124.1,17.4。
Embodiment 18:1- (2- tolyl) -4- (2- methyl -5- benzoyloxy phenyl) -1, the synthesis of 2,3- triazoles (3r), Specifically includes the following steps:
(1) 1- o-methyl-phenyl -4- o-methyl-phenyl -1,2,3- triazole (1d), benzaldehyde (2a), palladium acetate (Pd are pressed (OAc)2), 2- dicyclohexylphosphontetrafluoroborate -2,4,6- tri isopropyl biphenyl (X-Phos), tert-butyl peroxide alcohol (TBHP), dimethyl The molar ratio of formamide (DMF) is the ratio of 1:1.5:0.18:0.08:2.5:60, successively by 1mmol 1- o-methyl-phenyl- 4- o-methyl-phenyl -1,2,3- triazole, 1.5mmol benzaldehyde, 0.18mmol Pd (OAc)2、0.08mmol X-Phos、 2.5mmol TBHP, 60mmol DMF are added in reactor, are reacted 15 hours at 110 DEG C.
(2) gained mix products are diluted with 40mL water, then with the mix products of 100mmol ethyl acetate extraction step (1) 4 times, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then (is pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of ethyl acetate and petroleum ether 1:6 by volume are mixed to prepare) carry out column chromatography (400 mesh silica gel) purification i.e. 244mg product 1- (2- tolyl) -4- (2- methyl -5- benzoyloxy phenyl) -1,2,3- triazole 3r, yield 66%, instead Answer equation as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3): δ=7.96 (s, 1H), 7.81- 7.73 (m, 2H), 7.66 (s, 1H), 7.51-7.47 (m, 1H), 7.37 (dd, J=12.6,7.8Hz, 4H), 7.33-7.25 (m, 3H), 7.15 (d, J=7.9Hz, 1H), 2.52 (s, 3H), 1.93 (s, 3H)；13C NMR(100MHz,CDCl3): δ=198.5, 145.0, 142.8,140.8,137.0,136.1,135.2,133.6,133.2,131.2,130.0,129.8,129.6, 128.7,128.5,128.4, 126.7,125.8,124.3,21.4,17.4。
Embodiment 19:1- (2- tolyl) -4- (5- methyl -2- benzoyloxy phenyl) -1, the synthesis of 2,3- triazoles (3s), Specifically includes the following steps:
(1) aminomethyl phenyl -1,2,3- triazole (1e), benzaldehyde (2a), palladium acetate (Pd between 1- o-methyl-phenyl -4- (OAc)2), 2- dicyclohexylphosphontetrafluoroborate -2,4,6- tri isopropyl biphenyl (X-Phos), tert-butyl peroxide alcohol (TBHP), acetonitrile (MeCN) molar ratio is the ratio of 1:1.5:0.2:0.12:3:70, successively by methylbenzene between 1mmol 1- o-methyl-phenyl -4- Base -1,2,3- triazole, 1.5mmol benzaldehyde, 0.02mmol Pd (OAc)2、0.12mmol X-Phos、3mmol TBHP、 70mmol MeCN is added in reactor, is reacted 20 hours at 120 DEG C.
(2) gained mix products are diluted with 40mL water, then with the mix products of 100mmol ethyl acetate extraction step (1) 2 times, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then (is pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of ethyl acetate and petroleum ether 1:7 by volume are mixed to prepare) carry out column chromatography (400 mesh silica gel) purification i.e. 194mg product 1- (2- tolyl) -4- (5- methyl -2- benzoyloxy phenyl) -1,2,3- triazole 3s, yield 55%, instead Answer equation as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3): δ=7.69 (d, J=7.6Hz, 2H), 7.57 (s, 1H), 7.54-7.42 (m, 3H), 7.44-7.21 (m, 6H), 7.15 (d, J=7.6Hz, 1H), 2.49 (s, 3H),1.91(s, 3H)；13C NMR(100MHz,CDCl3): δ=198.5,143.7,140.8,138.2,136.8,136.1, 133.7,133.0,132.2, 131.2,129.9,129.8,128.4,128.2,127.7,126.6,125.8,125.5, 125.3,20.6,17.4。
Embodiment 20:1- (4- anisyl) -4- (2- benzoyloxy phenyl) -1, the synthesis of 2,3- triazoles (3t), specifically The following steps are included:
(1) 1- p-methoxyphenyl -4- phenyl -1,2,3- triazole (1f), benzaldehyde (2a), palladium acetate (Pd (OAc)2), 2- dicyclohexylphosphontetrafluoroborate -2,4,6- tri isopropyl biphenyl (X-Phos), tert-butyl peroxide alcohol (TBHP), acetonitrile (MeCN) molar ratio is the ratio of 1:1.5:0.05:0.1:3.5:80, successively by 1mmol 1- p-methoxyphenyl -4- benzene Base -1,2,3- triazole, 1.5mmol benzaldehyde, 0.05mmol Pd (OAc)2、0.1mmol X-Phos、3.5mmol TBHP、 80mmol MeCN is added in reactor, is reacted 25 hours at 130 DEG C.
(2) gained mix products are diluted with 40mL water, then with the mix products of 100mmol ethyl acetate extraction step (1) 2 times, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then (is pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of ethyl acetate and petroleum ether 1:8 by volume are mixed to prepare) carry out column chromatography (400 mesh silica gel) purification i.e. Obtain 238mg product 1- (4- anisyl) -4- (2- benzoyloxy phenyl) -1,2,3- triazole 3t, yield 67%, reactional equation Formula is as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3): δ=8.10 (d, J=7.8Hz, 1H), 7.88 (s, 1H), 7.78 (t, J=8.9Hz, 2H), 7.66-7.59 (m, 1H), 7.56-7.41 (m, 5H), 7.40-7.31 (m, 2H), 6.97 (d, J=9.0Hz, 2H), 3.84 (s, 3H)；13C NMR(100MHz,CDCl3): δ=198.5,159.8, 145.5,137.9, 136.9,133.4,130.3,130.2,130.1,129.0,128.7,128.4,128.1,127.8, 122.2,120.9,114.6,55.5。
Embodiment 21:1- (4- aminomethyl phenyl) -4- (2- benzoyl -4- anisyl) -1,2,3- triazole (3u) Synthesis, specifically includes the following steps:
(1) 1- p-methylphenyl -4- p-methoxyphenyl -1,2,3- triazole (1g), benzaldehyde (2a), palladium acetate (Pd (OAc)2), 2- dicyclohexylphosphontetrafluoroborate -2,4,6- tri isopropyl biphenyl (X-Phos), tert-butyl peroxide alcohol (TBHP), acetonitrile (MeCN) molar ratio is the ratio of 1:1.5:0.01:0.1:4:40, successively by 1mmol 1- p-methylphenyl -4- to methoxyl group Phenyl -1,2,3- triazole, 1.5mmol benzaldehyde, 0.01mmol Pd (OAc)2、0.1mmol X-Phos、4mmol TBHP、 40mmol MeCN is added in reactor, is reacted 5 hours at 90 DEG C.
(2) gained mix products are diluted with 40mL water, then with the mix products of 100mmol ethyl acetate extraction step (1) 2 times, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then (is pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of ethyl acetate and petroleum ether 1:8 by volume are mixed to prepare) carry out column chromatography (400 mesh silica gel) purification i.e. 262mg product 1- (4- aminomethyl phenyl) -4- (2- benzoyl -4- anisyl) -1,2,3- triazole 3u are obtained, yield is 71%, reaction equation is as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3): δ=8.01 (d, J=8.7Hz, 1H), 7.80 (d, J=10.6Hz, 2H), 7.70-7.42 (m, 4H), 7.37 (t, J=7.6Hz, 2H), 7.25 (d, J= 7.7Hz, 2H), 7.16 (d, J=8.7Hz, 1H), 6.96 (d, J=1.4Hz, 1H), 3.87 (s, 3H), 2.39 (s, 3H)；13C NMR(100MHz, CDCl3): δ=198.2,159.1,145.4,139.2,138.7,136.7,134.5,133.5,130.5, 130.1,128.5,121.2, 120.4,119.9,116.2,113.1,55.5,29.6,21.0。
Embodiment 22:1- (4- methoxyphenyl) -4- (4- methyl -2- benzoyloxy phenyl) -1,2,3- triazole (3v) Synthesis, specifically includes the following steps:
(1) 1- p-methoxyphenyl -4- p-methylphenyl -1,2,3- triazole (1h), benzaldehyde (2a), palladium acetate (Pd (OAc)2), 2- dicyclohexylphosphontetrafluoroborate -2,4,6- tri isopropyl biphenyl (X-Phos), tert-butyl peroxide alcohol (TBHP), acetonitrile (MeCN) molar ratio is the ratio of 1:1.5:0.02:0.08:2.5:50, successively by -4- pairs of p-methoxyphenyl of 1mmol 1- Aminomethyl phenyl -1,2,3- triazole, 1.5mmol benzaldehyde, 0.02mmol Pd (OAc)2、0.08mmol X-Phos、 2.5mmol TBHP, 50mmol MeCN are added in reactor, are reacted 10 hours at 100 DEG C.
(2) gained mix products are diluted with 40mL water, then with the mix products of 100mmol ethyl acetate extraction step (1) 2 times, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then (is pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of ethyl acetate and petroleum ether 1:8 by volume are mixed to prepare) carry out column chromatography (400 mesh silica gel) purification i.e. 270mg product 1- (4- methoxyphenyl) -4- (4- methyl -2- benzoyloxy phenyl) -1,2,3- triazole 3v are obtained, yield is 73%, reaction equation is as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3): δ=7.98 (d, J=8.0Hz, 1H), 7.82 (s, 1H), 7.79 (d, J=7.7Hz, 2H), 7.56-7.42 (m, 4H), 7.37 (t, J=7.7Hz, 2H), 7.25 (s, 1H), 6.96 (d, J=8.9Hz, 2H), 3.84 (s, 3H), 2.44 (s, 3H)；13C NMR(100MHz,CDCl3): δ= 198.8,159.7, 145.5,137.9,137.0,133.4,131.1,130.3,130.1,128.9,128.5,128.4, 128.3,125.9,122.1,120.6, 114.6,55.5,21.1。
Embodiment 23:1- (2- iodophenyl) -4- (4- methyl -2- benzoyloxy phenyl) -1, the synthesis of 2,3- triazoles (3w), Specifically includes the following steps:
(1) 1- neighbour's iodophenyl -4- p-methylphenyl -1,2,3- triazole (1i), benzaldehyde (2a), palladium acetate (Pd (OAc)2), 2- dicyclohexylphosphontetrafluoroborate -2,4,6- tri isopropyl biphenyl (X-Phos), tert-butyl peroxide alcohol (TBHP), acetonitrile (MeCN) molar ratio is the ratio of 1:1.5:0.05:0.12:3:60, successively by 1mmol 1- neighbour iodophenyl -4- to methylbenzene Base -1,2,3- triazole, 1.5mmol benzaldehyde, 0.05mmol Pd (OAc)2、0.12mmol X-Phos、3mmol TBHP、 60mmol MeCN is added in reactor, is reacted 15 hours at 110 DEG C.
(2) gained mix products are diluted with 40mL water, then with the mix products of 100mmol ethyl acetate extraction step (1) 2 times, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then (is pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of ethyl acetate and petroleum ether 1:6 by volume are mixed to prepare) carry out column chromatography (400 mesh silica gel) purification i.e. 354mg product 1- (2- iodophenyl) -4- (4- methyl -2- benzoyloxy phenyl) -1,2,3- triazole 3w, yield 76%, instead Answer equation as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3): δ=7.91 (s, 1H), 7.68 (dd, J=7.1,1.3Hz, 3H), 7.66-7.57 (m, 4H), 7.44 (t, J=7.4Hz, 1H), 7.31 (t, J=7.7Hz, 2H), 7.19 (d, J=8.0Hz, 2H), 2.35 (s, 3H)；13C NMR(100MHz,CDCl3): δ=194.9,148.1,138.1, 136.1,135.0, 134.6,133.5,133.4,131.4,130.0,129.7,129.4,129.2,128.3,127.0, 125.7,124.7,120.5,21.2。
Embodiment 24:1- (3- bromophenyl) -4- (4- methyl -2- benzoyloxy phenyl) -1, the synthesis of 2,3- triazoles (3x), Specifically includes the following steps:
(1) 1- m-bromophenyl -4- p-methylphenyl -1,2,3- triazole (1j), benzaldehyde (2a), palladium acetate (Pd (OAc)2), 2- dicyclohexylphosphontetrafluoroborate -2,4,6- tri isopropyl biphenyl (X-Phos), tert-butyl peroxide alcohol (TBHP), diformazan it is sub- The molar ratio of sulfone (DMSO) is the ratio of 1:1.5:0.08:0.1:3.5:70, successively by 1mmol 1- m-bromophenyl -4- to first Base phenyl -1,2,3- triazole, 1.5mmol benzaldehyde, 0.08mmol Pd (OAc)2、0.1mmol X-Phos、3.5mmol TBHP, 70mmol DMSO are added in reactor, are reacted 20 hours at 120 DEG C.
(2) gained mix products are diluted with 40mL water, then with the mix products of 100mmol ethyl acetate extraction step (1) 2 times, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then (is pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of ethyl acetate and petroleum ether 1:5 by volume are mixed to prepare) carry out column chromatography (400 mesh silica gel) purification i.e. 289mg product 1- (3- bromophenyl) -4- (4- methyl -2- benzoyloxy phenyl) -1,2,3- triazole 3x, yield 69%, instead Answer equation as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3): δ=7.86 (s, 1H), 7.82 (s, 1H), 7.69 (d, J=7.7Hz, 2H), 7.59-7.52 (m, 2H), 7.50-7.42 (m, 3H), 7.39-7.27 (m, 4H), 2.44 (s,3H)；13C NMR(100MHz,CDCl3): δ=198.4,144.7,140.7,138.4,137.7,137.1,133.1, 132.3,131.6, 130.9,129.9,128.3,128.2,127.6,125.6,123.5,123.2,121.8,118.9, 20.7。
Embodiment 25:1- (2- chlorphenyl) -4- (4- methyl -2- benzoyloxy phenyl) -1, the synthesis of 2,3- triazoles (3y), Specifically includes the following steps:
(1) 1- Chloro-O-Phenyl -4- p-methylphenyl -1,2,3- triazole (1k), benzaldehyde (2a), palladium acetate (Pd (OAc)2), 2- dicyclohexylphosphontetrafluoroborate -2,4,6- tri isopropyl biphenyl (X-Phos), tert-butyl peroxide alcohol (TBHP), diformazan it is sub- The molar ratio of sulfone (DMSO) is the ratio of 1:1.5:0.1:0.05:4:80, successively by 1mmol 1- Chloro-O-Phenyl -4- to methyl Phenyl -1,2,3- triazole, 1.5mmol benzaldehyde, 0.1mmol Pd (OAc)2、0.05mmol X-Phos、4mmol TBHP、 80mmol DMSO is added in reactor, is reacted 25 hours at 130 DEG C.
(2) gained mix products are diluted with 40mL water, then with the mix products of 100mmol ethyl acetate extraction step (1) 2 times, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then with ethyl acetate/petroleum ether leacheate (mixed liquor being mixed to prepare in the ratio of ethyl acetate and petroleum ether 1:6 by volume) carries out column chromatography (400 mesh silica gel) and mentions Pure 265mg product 1- (2- chlorphenyl) -4- (4- methyl -2- benzoyloxy phenyl) -1,2,3- triazole 3y, yield to obtain the final product are 71%, reaction equation is as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3): δ=8.01 (d, J=8.0Hz, 1H), 7.85 (s, 1H), 7.78 (dd, J=6.1,2.4Hz, 2H), 7.54-7.43 (m, 4H), 7.40-7.31 (m, 4H), 7.27 (d, J=2.6 Hz, 1H), 2.45 (s, 3H)；13C NMR(100MHz,CDCl3): δ=198.7,144.9,138.2,138.1, 136.6,134.6, 133.4,131.1,130.6,130.5,130.1,128.8,128.7,128.5,128.4,127.7, 127.6,125.5,124.2,21.1。
Embodiment 26:1- (2- chlorphenyl) -4- (2- benzoyloxy phenyl) -1, the synthesis of 2,3- triazoles (3z) are specific to wrap Include following steps:
(1) 1- Chloro-O-Phenyl -4- phenyl -1,2,3- triazole (1l), benzaldehyde (2a), palladium acetate (Pd (OAc)2)、2- Dicyclohexylphosphontetrafluoroborate -2,4,6- tri isopropyl biphenyl (X-Phos), tert-butyl peroxide alcohol (TBHP), dimethyl sulfoxide (DMSO) Molar ratio is the ratio of 1:1.5:0.12:0.02:3.5:50, successively by 1mmol 1- Chloro-O-Phenyl -4- phenyl -1,2, tri- nitrogen of 3- Azoles, 1.5mmol benzaldehyde, 0.12mmol Pd (OAc)2、0.02mmol X-Phos、3.5mmol TBHP、50mmol DMSO It is added in reactor, is reacted 20 hours at 120 DEG C.
(2) gained mix products are diluted with 40mL water, then with the mix products of 100mmol ethyl acetate extraction step (1) 2 times, combining extraction liquid, vacuum distillation goes solvent to obtain crude product after washing is dry, then (is pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of ethyl acetate and petroleum ether 1:5 by volume are mixed to prepare) carry out column chromatography (400 mesh silica gel) purification i.e. Obtain 219mg product 1- (2- chlorphenyl) -4- (2- benzoyloxy phenyl) -1,2,3- triazole 3z, yield 61%, reaction equation It is as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3): δ=8.10 (d, J=7.8Hz, 1H), 7.98 (s, 1H), 7.82-7.71 (m, 2H), 7.64 (td, J=7.6,1.5Hz, 1H), 7.62-7.56 (m, 2H), 7.56-7.48 (m, 2H), 7.46 (dt, J=7.6,3.0Hz, 3H), 7.39 (t, J=7.7Hz, 2H)；13C NMR(100MHz, CDCl3): δ=198.4,145.9,137.9,136.9,135.2,134.5,133.5,130.4,130.1,12 9.8,129.2, 128.7,128.6,128.5,128.2, 127.9,127.7,121.6,120.5。
Embodiment 27: product 1- (p-methylphenyl) -4- (2- benzoyloxy phenyl) -1,2,3- triazoles (3a) are used as ligand, Applied to nitrine-alkynes cycloaddition reaction, specifically includes the following steps:
(1) by 1mmol o-tolyl nitrine (4a), 1.1mmol to methyl phenylacetylene (5a), 0.05mmol cuprous iodide, 0.1mmol product 1- (p-methylphenyl) -4- (2- benzoyloxy phenyl) -1,2,3- triazole (3a), 20mmol dimethyl sulfoxide add Enter into 25mL round-bottomed flask, at room temperature i.e. fully reacting in magnetic agitation 3 hours.
(2) gained mix products are diluted with 40mL water, then with the mix products 3 of 100mmol ethyl acetate extraction step (1) Secondary, extract liquor is successively washed with the saturated salt solution of the water of 10mL and 10mL again after merging, and then uses 2g anhydrous sodium sulfate It is dry, boil off solvent by Rotary Evaporators up to crude product, then with ethyl acetate/petroleum ether leacheate (by ethyl acetate and The mixed liquor that the ratio of petroleum ether 1:10 by volume is mixed to prepare) column chromatography (silica gel of 400 mesh) are carried out to gained crude product Separating-purifying is up to 229mg product 1- o-tolyl -4- p-methylphenyl -1,2,3- triazole (6a), yield 92%, reaction Equation is as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3) δ=7.92 (s, 1H), 7.81 (d, J =8.1 Hz, 2H), 7.45-7.39 (m, 2H), 7.39-7.33 (m, 2H), 7.27 (d, J=8.5Hz, 2H), 2.40 (s, 3H), 2.28(s, 3H)；13C-NMR(100MHz,CDCl3) δ=147.7,138.2,136.6,133.8,131.5,129.8,129.6, 127.5,126.8, 126.0,125.7,120.8,21.3,17.9。
Embodiment 28: product 1- (p-methylphenyl) -4- [2- (3- toluyl) phenyl] -1,2,3- triazole (3c) is made For ligand, applied to nitrine-alkynes cycloaddition reaction, specifically includes the following steps:
(1) by 1mmol o-tolyl nitrine (4a), 1.1mmol to chlorobenzene acetylene (5b), 0.05mmol cuprous iodide, 0.1mmol product 1- (p-methylphenyl) -4- [2- (3- toluyl) phenyl] -1,2,3- triazole (3c), 20mmol diformazan Base sulfoxide is added in 25mL round-bottomed flask, at room temperature i.e. fully reacting in magnetic agitation 3 hours.
(2) gained mix products are diluted with 40mL water, then with the mix products 3 of 100mmol ethyl acetate extraction step (1) Secondary, extract liquor is successively washed with the water of 10mL and 10mL saturated salt solution again after merging, then dry with 2g anhydrous sodium sulfate It is dry, solvent is boiled off up to crude product by Rotary Evaporators, then ethyl acetate and stone (are pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that the ratio of oily ether 1:10 by volume is mixed to prepare) column chromatography (silica gel of 400 mesh) point are carried out to gained crude product From purifying up to 256mg product 1- o-tolyl -4- rubigan -1,2,3- triazole (6b), yield 95%, reactional equation Formula is as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(400MHz,CDCl3) δ=7.95 (s, 1H), 7.88-7.86 (m,1H),7.86–7.84(m,1H),7.46–7.42(m,3H),7.42–7.34(m,3H),2.28(s,3H)；13C-NMR (100MHz,CDCl3) δ=146.6,136.4,134.1,133.8,131.6,130.0,129.2,128.9,127.1,12 6.9, 126.0, 121.2,17.9。
Embodiment 29: product 1- (3- bromophenyl) -4- (4- methyl -2- benzoyloxy phenyl) -1,2,3- triazole (3x) is made For ligand, applied to nitrine-alkynes cycloaddition reaction, specifically includes the following steps:
(1) by acetyl aziminobenzene (4b) between 1mmol, 1.1mmol phenylacetylene (5c), 0.05mmol cuprous iodide, 0.1mmol product 1- (3- bromophenyl) -4- (4- methyl -2- benzoyloxy phenyl) -1,2,3- triazole (3x), 20mmol dimethyl Sulfoxide is added in 25mL round-bottomed flask, at room temperature i.e. fully reacting in magnetic agitation 3 hours.
(2) gained mix products are diluted with 40mL water, then with 3 extractions of 100mmol ethyl acetate point, after extract liquor merges It is then dry with 2g anhydrous sodium sulfate again successively with the saturated common salt water washing of the water of 10mL and 10mL, pass through Rotary Evaporators Solvent is boiled off up to crude product, then ethyl acetate and petroleum ether 1:10 by volume (are pressed with ethyl acetate/petroleum ether leacheate The mixed liquor that is mixed to prepare of ratio) column chromatography (silica gel of 400 mesh) separating-purifying is carried out up to 221mg to gained crude product Acetyl phenyl -4- phenyl -1,2 between product 1-, 3- triazole 6c, yield 84%, reaction equation is as follows:
Product nuclear magnetic resoance spectrum characterize data is as follows:1H-NMR(300MHz,CDCl3) δ=8.38-8.32 (m, 1H), 8.30 (s, 1H), 8.15-8.06 (m, 1H), 8.05-8.00 (m, 1H), 7.95-7.88 (m, 2H), 7.68 (t, J=7.9Hz, 1H), 7.47 (dd, J=8.1,6.6Hz, 2H), 7.40 (d, J=7.3Hz, 1H), 2.70 (s, 3H).

Claims (4)

1. the triazole ligand of 1,2,3- containing sweet-smelling formacyl is applied to nitrine-alkynes cycloaddition reaction as ligand transition metal The general structure of purposes, ligand is as follows:
Wherein, R1Group is selected from H, CH3、OCH3,I,Cl,Br；
R2Group is selected from H, CH3、CH(CH3)2、OCH3、Br、Cl、NO2、SOCH3；
R3Group is selected from H, CH3、OCH3。
2. the triazole ligand of 1,2,3- containing sweet-smelling formacyl described in claim 1 as in ligand transition metal be applied to nitrine- The purposes of the cycloaddition reaction of alkynes, which is characterized in that specific step is as follows:
(1) 1mmol o-tolyl nitrine, 1.1mmol are contained into fragrant formyl to chlorobenzene acetylene, 0.05mmol cuprous iodide, 0.1mmol Base 1,2,3- triazole ligand, 20mmol dimethyl sulfoxide are added in reaction vessel, are within magnetic agitation 3 hours at room temperature Fully reacting；Wherein the triazole ligand of 1,2,3- containing sweet-smelling formacyl is 1- (p-methylphenyl) -4- [2- (3- toluyl) benzene Base] -1,2,3- triazole；
(2) the 40mL water of mix products obtained by step (1) is diluted, then is extracted mix products 3 times with 100mmol ethyl acetate, Extract liquor is successively washed with the saturated salt solution of the water of 10mL and 10mL again after merging, then dry with 2g anhydrous sodium sulfate It is dry, solvent is boiled off up to crude product by Rotary Evaporators, then is carried out with ethyl acetate/petroleum ether leacheate to gained crude product Column chromatography for separation purifies up to product 1- o-tolyl -4- rubigan -1,2,3- triazole；Wherein ethyl acetate and petroleum ether It is by volume 1:10.
3. the triazole ligand of 1,2,3- containing sweet-smelling formacyl described in claim 1 as in ligand transition metal be applied to nitrine- The purposes of the cycloaddition reaction of alkynes, which is characterized in that specific step is as follows:
(1) 1mmol o-tolyl nitrine, 1.1mmol are contained into fragrant first to methyl phenylacetylene, 0.05mmol cuprous iodide, 0.1mmol Acyl group 1,2,3- triazole ligand, 20mmol dimethyl sulfoxide are added in 25mL round-bottomed flask, at room temperature magnetic agitation 3 Hour is fully reacting；Wherein the triazole ligand of 1,2,3- containing sweet-smelling formacyl is 1- (p-methylphenyl) -4- (2- benzophenone Base) -1,2,3- triazole；
(2) the 40mL water of mix products obtained by step (1) is diluted, then is extracted mix products 3 times with 100mmol ethyl acetate, Extract liquor is successively washed with the saturated salt solution of the water of 10mL and 10mL again after merging, then dry with 2g anhydrous sodium sulfate It is dry, solvent is boiled off up to crude product by Rotary Evaporators, then is carried out with ethyl acetate/petroleum ether leacheate to gained crude product Column chromatography for separation purifies up to product 1- o-tolyl -4- p-methylphenyl -1,2,3- triazole；Wherein ethyl acetate and petroleum ether It is by volume 1:10.
4. the triazole ligand of 1,2,3- containing sweet-smelling formacyl described in claim 1 as in ligand transition metal be applied to nitrine- The purposes of the cycloaddition reaction of alkynes, which is characterized in that specific step is as follows:
(1) acetyl aziminobenzene, 1.1mmol phenylacetylene, 0.05mmol cuprous iodide, 0.1mmol between 1mmol are contained into sweet-smelling formacyl 1,2,3- triazole ligand, 20mmol dimethyl sulfoxide are added in 25mL round-bottomed flask, at room temperature magnetic agitation 3 hours That is fully reacting；Wherein the triazole ligand of 1,2,3- containing sweet-smelling formacyl is 1- (3- bromophenyl) -4- (4- methyl -2- benzoyl Phenyl) -1,2,3- triazole；
(2) the 40mL water of mix products obtained by step (1) is diluted, then is extracted mix products 3 times with 100mmol ethyl acetate, Extract liquor is successively washed with the saturated salt solution of the water of 10mL and 10mL again after merging, then dry with 2g anhydrous sodium sulfate It is dry, solvent is boiled off up to crude product by Rotary Evaporators, then is carried out with ethyl acetate/petroleum ether leacheate to gained crude product Column chromatography for separation purifies up to acetyl phenyl -4- phenyl -1,2,3- triazole between product 1-；Wherein ethyl acetate and petroleum ether are pressed Volume ratio is 1:10.
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104945339A (en) * 2015-06-11 2015-09-30 昆明理工大学 Preparation method for 1,4-disubstituted-1,2,3-triazole derivatives

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Palladium-Catalyzed Acylation of Arenes by 1,2,3-Triazole-Directed C-H Activation;Fen Zhao等;《European Journal of Organic Chemistry》;20161004;第2016卷(第36期);第5971页左栏第2段、第5972页表1、第5973页表2、第5974页表3、第5975-5978页 *
席夫碱的合成及其金属配合物的合成与表征;罗斌;《化学工程与装备》;20081031(第10期);第45-49页 *

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