CN103613551A - Synthesis method for substituted triazole compound - Google Patents
Synthesis method for substituted triazole compound Download PDFInfo
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- CN103613551A CN103613551A CN201310624234.9A CN201310624234A CN103613551A CN 103613551 A CN103613551 A CN 103613551A CN 201310624234 A CN201310624234 A CN 201310624234A CN 103613551 A CN103613551 A CN 103613551A
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- trifluoromethanesulfonic acid
- trifluoromethanesulfonate
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- QKCCIXXLTSPBQB-YIZGBOEJSA-N C/C=C\C=C(/C)\[n]1nncc1-c1ccccc1 Chemical compound C/C=C\C=C(/C)\[n]1nncc1-c1ccccc1 QKCCIXXLTSPBQB-YIZGBOEJSA-N 0.000 description 1
- FWITZOTYMRKHGW-UHFFFAOYSA-N c1c(-c2cc(cccc3)c3cc2)[n](-c2ccccc2)nn1 Chemical compound c1c(-c2cc(cccc3)c3cc2)[n](-c2ccccc2)nn1 FWITZOTYMRKHGW-UHFFFAOYSA-N 0.000 description 1
Classifications
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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
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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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
Abstract
The invention discloses a synthesis method for a substituted triazole compound. The method mainly comprises the following steps: under the existence of a rare earth metal catalyst, performing backflow reaction to nitroolefin and organic azido in an organic solvent at 80-110DEG C, to obtain a target crude product, wherein the rare earth metal catalyst is cerium trifluoromethanesulfonate, samarium trifluoromethanesulfonate, europium trifluoromethanesulfonate, ytterbium trifluoromethanesulfonate, praseodymium trifluoromethanesulfonate, lanthanum trifluoromethanesulfonate, neodymium trifluoromethanesulfonate, erbium trifluoromethanesulfonate or dysprosium trifluoromethanesulfonate. According to the synthesis method, 1,5-disubstituted-1,2,3-triazole compound can be efficiently selectively synthesized by taking nitroolefin and organic azido as active ingredients under the action of a rare earth metal catalyst. The method is easily available for active ingredients, and simple to operate, and the productivity can achieve more than 70%.
Description
Technical field
The present invention relates to the synthetic method of triazole compounds, be specifically related to the synthetic method of 1,5-, bis-replacement-1,2,3-triazoles.
Background technology
1,2,3-triazole is the important nitrogen-containing heterocycle compound of a class, its azoles ring has aromaticity and abundant electronics, can and there is multiple non-covalent bonding force and organism endoenzyme and the acceptor interactions such as hydrophobic interaction, pi-pi accumulation and electrostatic interaction by forming hydrogen bond, with metallic ion coordination, make triazole class compounds show antimycotic, antibacterium, tuberculosis, anticancer, antiviral, relieving inflammation and relaxing pain and the multiple biological activity such as anticonvulsion.Triazole class compounds is widely used in clinical as medicine, and triazole class compounds also has potential application widely at aspects such as agricultural chemicals, material, artificial receptors, Supramolecular Recognition and human simulations.Sangshetti etc. have reported 1,2, the effect of 3-triazole compounds anti-candida albicans and Aspergillus flavus is better than miconazole, the energy for growth that suppresses Fusarium oxysporum and black-koji mould (the < < Bioorg.Med.Chem.Lett. > > that can match in excellence or beauty with miconazole, 2009,13,3564).Zhou Chenghe study group is by 1,2,3-triazole ring is introduced sulfanilamide (SN), find that its external 7 kinds of bacteriums such as methicillin resistant staphylococcus aureus to streptococcus aureus, intestinal bacteria, Bacillus subtilus, Pseudomonas aeruginosa, salmonella typhi, Shigella dysenteriae and resistance show obvious restraining effect (< < Eur.J.Med.Chem. > >, 2010,45,4631).Shao Q.Yao study group has reported 1,2,3-triazole class compounds has extraordinary inhibition Mycobacterium tuberculosis Protein Tyrosine Phosphatases B(MptpB) ability and high selectivity, to suppress at present the strongest molecule of MptpB ability, be expected to become new anti-tuberculosis drugs (< < Org.Lett. > >, 2009,11,5102).Kamal etc. have reported 1,2,3-triazole compounds has the anticancer effect of wide spectrum to Human Breast Cancer, ovarian cancer, colorectal carcinoma, lung cancer, prostate cancer and cervical cancer cell, be expected to become new generation anti-cancer medicament (< < Bioorg.Med.Chem.Lett. > >, 2008,18,1468).Bai Xue, Zhou Chenghe etc. have summarized 1,2,3-triazole class compounds also has potential application widely (< < chemical research and application > > at aspects such as agricultural chemicals, material, artificial receptors, Supramolecular Recognition and human simulations, 2007,19,721).
The traditional synthetic method of 1,2,3-triazoles compound is by alkynes and organic nitrine Dipolar Cycloaddition, be Huisgen condensation, still, due to high activation energy (ca.24-26kcal/mol), this class cycloaddition reaction is conventionally very slow, and often obtains isomer mixture.Cycloaddition reaction (CuAAC) by the alkynes under Cu (I)-catalysis and organic nitrine can only obtain Isosorbide-5-Nitrae-bis-replacement-1,2,3-triazoles; Although the catalyzed cycloaddition (RuAAC) of [Cp*Ru (II)] can synthesize 1,5-, bis-replacements-1,2,3-triazoles simple and effective, expensive catalyzer has limited its application.Therefore, for selectively synthesizing 1,5-, bis-replacement-1,2,3-triazoles compounds, not yet there is at present gratifying catalyst system.
Summary of the invention
The technical problem to be solved in the present invention is to provide a kind of synthetic method of substituted triazole compounds.It is raw material that the method be take nitro alkene and organic nitrine, efficiently and has optionally synthesized 1,5-, bis-replacement-1,2,3-triazoles compounds under the effect of rare-earth metal catalyst.
The present invention relates to the synthetic method as shown in the formula compound shown in (I), mainly comprise the following steps: under rare-earth metal catalyst existence condition, by compound shown in compound shown in formula II and formula III in organic solvent, 80～110 ℃ of back flow reaction, make target compound crude product;
Wherein,
Described R
1for
or
Described R
2for
or
Described rare-earth metal catalyst is trifluoromethanesulfonic acid cerium, trifluoromethanesulfonic acid samarium, trifluoromethanesulfonic acid europium, Ytterbiumtriflate, trifluoromethanesulfonic acid praseodymium, trifluoromethanesulfonic acid lanthanum, trifluoromethanesulfonic acid neodymium, trifluoromethanesulfonic acid erbium or trifluoromethanesulfonic acid dysprosium;
Described organic solvent is toluene and/or chlorobenzene.
In above-mentioned synthetic method,
Shown in described formula II, shown in compound and formula III, the mol ratio of compound is stoichiometric ratio, is generally the mol ratio of 1:1.
The consumption of described rare-earth metal catalyst is 1～10mol% of compound amount shown in compound shown in formula II or formula III, preferably 5～10mol%.
Described organic solvent preferably adopts toluene and chlorobenzene with the combination of the volume ratio of 1:1.The consumption of described organic solvent can be determined as required, conventionally can dissolve the amount of the raw material of participating in reaction, particularly, shown in the formula II of 1mmol, the rare-earth metal catalyst of compound shown in the formula III of compound and 1mmol and phase application quantity, dissolves with the organic solvent of 2～10mL conventionally.
In above-mentioned synthetic method, whether back flow reaction can adopt thin-layer chromatography (TLC) to follow the tracks of is completely detected, and under the reaction conditions of above-mentioned restriction, reaction is to completely approximately needing the time of 8～48h.In order to reduce reaction to the complete required time, reaction is preferably carried out at 100～110 ℃, and now reaction is to the time is about 8～12h completely.
Above-mentioned synthetic method is synthetic, and what obtain is the crude product of formula (I) compound, can adopt the purification process of existing routine to carry out purifying with the purity of raising formula (I) compound to it.Conventionally adopt silica gel column chromatography to carry out purifying, specifically by the target compound crude product making through silica gel column chromatography, the eluent wash-out that the ethyl acetate that to use by volume ratio be 1:5～50 and sherwood oil form, elutriant removes solvent under reduced pressure, obtains the target compound after purifying.The ethyl acetate of described composition eluent and the volume ratio of sherwood oil are preferably 1:5～20.
Compared with prior art, it is raw material that nitro alkene (compound shown in formula II) and organic nitrine (compound shown in formula III) are take in the present invention, efficiently and has optionally synthesized 1,5-bis-and replace-1 under the effect of rare-earth metal catalyst, 2,3-triazole compounds; The method raw material is easy to get, simple to operate, and productive rate can reach more than 70%.
Embodiment
With specific embodiment, the invention will be further described below, but the present invention is not limited to these embodiment.
Embodiment 1:1-benzyl-5-phenyl-1H-1,2,3-triazole synthetic
In 25mL round-bottomed flask, add 1mmol, beta-nitrostyrene, 1mmol benzyl azide, 0.05mmol trifluoromethanesulfonic acid cerium and 2mL toluene, under 110 ℃ of conditions, back flow reaction is to complete (TLC follows the tracks of detection, about 10h), stopped reaction, question response liquid cool to room temperature, filters removal of solvent under reduced pressure, on resistates, (eluent is ethyl acetate/petroleum ether=1:20 to quick purification by silica gel column chromatography, volume ratio), obtain pale yellow oily liquid body 1a, productive rate 85%.
To gained pale yellow oily liquid body, 1a analyzes, and its spectral characteristic is as follows:
1H?NMR(400MHz,CDCl
3):δ7.74(s,1H),7.47-7.34(m,3H),7.27(m,5H),7.11-7.03(m,2H),5.55(s,2H)ppm；
13C?NMR(100MHz,CDCl
3)δ138.15,135.49,133.27,129.50,128.94,128.88,128.81,128.14,127.14,126.89,51.80ppm；
HRMS(m/z)(ESI):calcd?for?C
15H
14N
3236.2838[M+H
+]found?236.1185.
Therefore can determine that gained pale yellow oily liquid body 1a is 1-benzyl-5-phenyl-1H-1,2,3-triazole, its structural formula is shown below:
Embodiment 2:1-benzyl-5-(4-tolyl)-1H-1,2,3-triazole synthetic
In 25mL round-bottomed flask, add 1mmol4-methyl-beta-nitrostyrene, 1mmol benzyl azide, 0.08mmol trifluoromethanesulfonic acid samarium and 5mL toluene, under 100 ℃ of conditions, back flow reaction is to (TLC follows the tracks of detection completely, about 12h), stopped reaction, question response liquid cool to room temperature, filter, removal of solvent under reduced pressure, quick purification by silica gel column chromatography (eluent is ethyl acetate/petroleum ether=1:10, volume ratio) on resistates, obtain yellow oily liquid 1b, productive rate 80%.
To gained yellow oily liquid, 1b analyzes, and its spectral characteristic is as follows:
1H?NMR(400MHz,CDCl
3):δ7.71(s,1H),7.29(m,3H),7.22(d,J=8.0Hz,2H),7.14(d,J=8.1Hz,2H),7.12-7.02(m,2H),5.53(s,2H),2.39(s,3H)ppm；
13C?NMR(100MHz,CDCl
3):δ139.62,138.22,135.65,133.11,129.63,128.79,128.75,128.08,127.13,123.91,77.37,77.05,76.73,51.70,21.28ppm.
HRMS(m/z)(APCI):calcd?for?C
16H
16N
3250.3104[M+H
+]found?250.1328.
Therefore can determine that gained yellow oily liquid 1b is 1-benzyl-5-(4-tolyl)-1H-1,2,3-triazole, its structural formula is shown below:
Embodiment 3:1-benzyl-5-[4-(benzyloxy)-3-p-methoxy-phenyl]-1H-1,2,3-triazole synthetic
In 25mL round-bottomed flask, add the trans-3-benzyloxy-4-of 1mmol methoxyl group-beta-nitrostyrene, 1mmol benzyl azide, 0.01mmol trifluoromethanesulfonic acid europium and 2mL toluene, under 80 ℃ of conditions, back flow reaction is to (TLC follows the tracks of detection completely, about 48h), stopped reaction, question response liquid cool to room temperature, filter, removal of solvent under reduced pressure, on resistates, (eluent is ethyl acetate/petroleum ether=1:25 to quick purification by silica gel column chromatography, volume ratio), obtain yellow oily liquid 1c, productive rate 71%.
To gained yellow oily liquid, 1c analyzes, and its spectral characteristic is as follows:
Yellow oily;
1h NMR (400MHz, CDCl
3): δ 7.69 (s, 1H), 7.53-7.18 (m, 8H), 7.16-7.01 (m, 2H), 6.90 (d, J=8.3Hz, 1H), 6.76 (dd, J=8.2,2.0Hz, 1H), 6.62 (d, J=1.9Hz, 1H), 5.52 (s, 2H), 5.18 (s, 2H), 3.65 (s, 3H) ppm;
13C?NMR(100MHz,CDCl
3):δ149.66,149.06,138.10,136.52,135.92,133.10,128.89,128.65,128.11,128.07,127.26,126.93,121.60,119.55,113.78,112.26,70.91,55.81,51.72ppm；
HRMS(m/z)(ESI):calcd?for?C
23H
22N
3O
2372.4317[M+H
+]found?372.1688.
Therefore can determine that gained yellow oily liquid 1c is 1-benzyl-5-[3-(benzyloxy)-4-p-methoxy-phenyl]-1H-1,2,3-triazole, its structural formula is shown below:
Embodiment 4:1-benzyl-5-(2-chloro-phenyl-)-1H-1,2,3-triazole synthetic
In 25mL round-bottomed flask, add 1mmol 2-chloronitrobenzene ethene, 1mmol benzyl azide, 0.1mmol Ytterbiumtriflate and 2mL toluene, under 110 ℃ of conditions, back flow reaction is to (TLC follows the tracks of detection completely, about 10h), stopped reaction, question response liquid cool to room temperature, filter, removal of solvent under reduced pressure, quick purification by silica gel column chromatography (eluent is ethyl acetate/petroleum ether=1:50, volume ratio) on resistates, obtain red oily liquids 1d, productive rate 89%.
To gained, red oily liquids 1d analyzes, and its spectral characteristic is as follows:
1H?NMR(400MHz,CDCl
3):δ7.71(s,1H),7.49(dd,J=8.1,1.0Hz,1H),7.40(m,1H),7.28-7.16(m,4H),7.01(dd,J=7.6,1.6Hz,1H),6.95(dd,J=7.5,1.7Hz,2H),5.44(s,2H)ppm；
13C?NMR(100MHz,CDCl
3)δ134.83,134.75,134.42,134.28,132.00,131.20,129.96,128.61,128.21,127.70,126.90,126.37,52.49ppm；
HRMS(m/z)(ESI):calcd?for?C
15H
13ClN
3270.7288[M+H
+]found?270.0781.
Therefore can determine that the red oily liquids 1d of gained is 1-benzyl-5-(2-chloro-phenyl-)-1H-1,2,3-triazole, its structural formula is shown below:
Embodiment 5:1-benzyl-5-(4-bromophenyl)-1H-1,2,3-triazole synthetic
In 25mL round-bottomed flask, add the bromo-beta-nitrostyrene of the trans-3-of 1mmol, 1mmol benzyl azide, 0.03mmol trifluoromethanesulfonic acid cerium and 3mL toluene, under 90 ℃ of conditions, back flow reaction is to (TLC follows the tracks of detection completely, about 20h), stopped reaction, question response liquid cool to room temperature, filter, removal of solvent under reduced pressure, quick purification by silica gel column chromatography (eluent is ethyl acetate/petroleum ether=1:15, volume ratio) on resistates, obtain red oily liquids 1e, productive rate 90%.
To gained, red oily liquids 1e analyzes, and its spectral characteristic is as follows:
1H?NMR(400MHz,CDCl
3):δ7.70(s,1H),7.67(dd,J=7.8,1.4Hz,1H),7.35-7.24(m,2H),7.24-7.15(m,3H),7.02-6.91(m,3H),5.43(s,2H)ppm；
13C?NMR(100MHz,CDCl
3):δ136.37,134.69,134.25,133.12,132.11,131.34,128.61,128.43,128.23,127.79,127.44,124.30,52.52ppm；
HRMS(m/z)(ESI):calcd?for?C
15H
13N
3Br?314.1799[M+H
+]found?314.0275.
Therefore can determine that the red oily liquids 1e of gained is 1-benzyl-5-(4-bromophenyl)-1H-1,2,3-triazole, its structural formula is shown below:
Embodiment 6:1-benzyl-5-(2-naphthyl)-1H-1,2,3-triazole synthetic
In 25mL round-bottomed flask, add 1mmol 2-[(E)-2-nitroethylene base] naphthalene, 1mmol benzyl azide, 0.06mmol trifluoromethanesulfonic acid praseodymium and 2mL toluene, under 95 ℃ of conditions, back flow reaction is to (TLC follows the tracks of detection completely, about 15h), stopped reaction, question response liquid cool to room temperature, filter, removal of solvent under reduced pressure, quick purification by silica gel column chromatography (eluent is ethyl acetate/petroleum ether=1:5, volume ratio) on resistates, obtain yellow oily liquid 1f, productive rate 82%.
To gained yellow oily liquid, 1f analyzes, and its spectral characteristic is as follows:
1H?NMR(400MHz,CDCl
3):δ7.71(s,1H),7.49(dd,J=8.1,1.0Hz,1H),7.40(td,J=7.8,1.6Hz,1H),7.28-7.16(m,4H),7.01(dd,J=7.6,1.6Hz,1H),6.95(dd,J=7.5,1.7Hz,2H),5.44(s,2H)ppm；
13C?NMR(100MHz,CDCl
3):δ138.24,135.64,133.52,133.29,132.92,128.89,128.84,128.63,128.24,128.19,127.84,127.29,127.24,127.03,125.88,124.12,52.00ppm；
HRMS(m/z)(APCI):calcd?for?C
19H
16N
3286.3425[M+H
+]found?286.1331.
Therefore can determine that gained yellow oily liquid 1f is 1-benzyl-5-(2-naphthyl)-1H-1,2,3-triazole, its structural formula is shown below:
Embodiment 7:1-benzyl-5-(2-furyl)-1H-1,2,3-triazole synthetic
In 25mL round-bottomed flask, add 1mmol 2-[(E)-2-nitroethylene base] furans, 1mmol benzyl azide, 0.02mmol trifluoromethanesulfonic acid samarium and 2mL toluene, under 110 ℃ of conditions, back flow reaction is to (TLC follows the tracks of detection completely, about 10h), stopped reaction, question response liquid cool to room temperature, filter, removal of solvent under reduced pressure, quick purification by silica gel column chromatography (eluent is ethyl acetate/petroleum ether=1:20, volume ratio) on resistates, obtain brown oily liquids 1g, productive rate 84%.
To gained, brown oily liquids 1g analyzes, and its spectral characteristic is as follows:
1H?NMR(400MHz,CDCl
3):δ7.88(s,1H),7.52(dd,J=1.7,0.6Hz,1H),7.35-7.21(m,3H),7.21-7.09(m,2H),6.47(ddd,J=5.3,3.5,1.2Hz,2H),5.76(s,2H)ppm；
13C?NMR(100MHz,CDCl
3):δ143.61,141.33,135.13,132.35,129.05,128.86,128.20,127.05,111.79,110.37,52.79ppm；
HRMS(m/z)(APCI):calcd?for?C
13H
12N
3O?226.2459[M+H
+]found?226.0967.
Therefore can determine that the brown oily liquids 1g of gained is 1-benzyl-5-(2-furyl)-1H-1,2,3-triazole, its structural formula is shown below:
Embodiment 8:1-benzyl-5-(2-thienyl)-1H-1,2,3-triazole synthetic
In 25mL round-bottomed flask, add 1mmol 2-[(E)-2-nitroethylene base] thiophene, 1mmol benzyl azide, 0.1mmol trifluoromethanesulfonic acid europium and 8mL toluene, under 110 ℃ of conditions, back flow reaction is to (TLC follows the tracks of detection completely, about 10h), stopped reaction, question response liquid cool to room temperature, filter, removal of solvent under reduced pressure, quick purification by silica gel column chromatography (eluent is ethyl acetate/petroleum ether=1:30, volume ratio) on resistates, obtain brown oily liquids 1h, productive rate 86%.
To gained, brown oily liquids 1h analyzes, and its spectral characteristic is as follows:
1H?NMR(400MHz,CDCl
3)δ7.81(s,1H),7.44(dd,J=5.1,1.2Hz,1H),7.34-7.26(m,3H),7.13-7.05(m,3H),7.02(dd,J=3.6,1.2Hz,1H),5.66(s,2H)ppm；
13C?NMR(100MHz,CDCl
3)δ135.26,133.88,131.78,128.91,128.47,128.21,128.06,127.95,126.93,126.57,51.99ppm；
HRMS(m/z)(APCI):calcd?for?C
13H
12N
3S?242.3115[M+H
+]found?242.0739.
Therefore can determine that the brown oily liquids 1h of gained is 1-benzyl-5-(2-thienyl)-1H-1,2,3-triazole, its structural formula is shown below:
Embodiment 9:1-benzyl-5-(4-nitrophenyl)-1H-1,2,3-triazole synthetic
In 25mL round-bottomed flask, add 1mmol1-nitro-4-[(E)-2-nitroethylene base] benzene, 1mmol benzyl azide, 0.5mmol trifluoromethanesulfonic acid lanthanum and 2mL toluene, under 110 ℃ of conditions, back flow reaction is to (TLC follows the tracks of detection completely, about 10h), stopped reaction, question response liquid cool to room temperature, filter, removal of solvent under reduced pressure, on resistates, (eluent is ethyl acetate/petroleum ether=1:15 to quick purification by silica gel column chromatography, volume ratio), obtain reddish-brown oily liquids 1i, productive rate 88%.
To gained reddish-brown oily liquids, 1i analyzes, and its spectral characteristic is as follows:
1H?NMR(400MHz,CDCl
3):δ8.30-8.23(m,2H),7.85(s,1H),7.46-7.43(m,2H),7.32-7.29(m,3H),7.09-6.99(m,2H),5.61(s,2H)ppm
13C?NMR(100MHz,CDCl
3):δ148.25,134.83,134.08,131.10,129.73,129.10,128.58,127.57,126.94,124.14,52.37ppm；
HRMS(m/z)(ESI):calcd?for?C
15H
13N
4O
2281.2814[M+H
+]found?281.1018.
Therefore can determine that gained reddish-brown oily liquids 1i is 1-benzyl-5-(4-nitrophenyl)-1H-1,2,3-triazole, its structural formula is shown below:
Embodiment 10:1-benzyl-5-(2-nitrophenyl)-1H-1,2,3-triazole synthetic
In 25mL round-bottomed flask, add 1mmol1-nitro-2-[(E)-2-nitroethylene base] benzene, 1mmol benzyl azide, 0.1mmol trifluoromethanesulfonic acid dysprosium and 2mL toluene, under 110 ℃ of conditions, back flow reaction is to (TLC follows the tracks of detection completely, about 10h), stopped reaction, question response liquid cool to room temperature, filter, removal of solvent under reduced pressure, on resistates, (eluent is ethyl acetate/petroleum ether=1:8 to quick purification by silica gel column chromatography, volume ratio), obtain reddish-brown oily liquids 1j, productive rate 80%.
To gained reddish-brown oily liquids, 1j analyzes, and its spectral characteristic is as follows:
1H?NMR(400MHz,CDCl
3):δ8.29(dd,J=8.1,0.9Hz,1H),7.78(td,J=7.9,1.5Hz,1H),7.67-7.60(m,2H),7.25-7.16(m,5H),7.02(dd,J=7.6,1.3Hz,1H),5.41(s,2H)ppm;
13C?NMR(100MHz,CDCl
3):δ148.45,134.21,133.17,132.27,131.11,129.21,129.05,128.72,128.43,127.76,124.94,122.13,52.82ppm;HRMS(m/z)(APCI):calcd?for?C
15H
13N
4O
2281.2814[M+H
+]found?281.1019.
Therefore can determine that gained reddish-brown oily liquids 1j is 1-benzyl-5-(2-nitrophenyl)-1H-1,2,3-triazole, its structural formula is shown below:
Embodiment 11:1,5-phenylbenzene-1H-1,2,3-triazole synthetic
In 25mL round-bottomed flask, add 1mmol beta-nitrostyrene, 1mmol aziminobenzene, 0.5mmol trifluoromethanesulfonic acid neodymium and 2mL toluene, under 110 ℃ of conditions, back flow reaction is to (TLC follows the tracks of detection completely, about 10h), stopped reaction, question response liquid cool to room temperature, filter, removal of solvent under reduced pressure, quick purification by silica gel column chromatography (eluent is ethyl acetate/petroleum ether=1:5, volume ratio) on resistates, obtain colourless oil liquid 1k, productive rate 65%.
To gained colourless oil liquid, 1k analyzes, and its spectral characteristic is as follows:
1H?NMR(400MHz,CDCl
3):δ7.87(s,1H),7.49-7.19(m,10H)ppm;
13C?NMR(100MHz,CDCl
3)δ137.73,136.60,133.42,129.37,129.24,128.86,128.60,126.76,125.21ppm;
HRMS(m/z)(ESI):calcd?for?C
14H
12N
3222.2572[M+H
+]found?222.1018.
Therefore can determine that gained colourless oil liquid 1k is 1,5-phenylbenzene-1H-1,2,3-triazole, its structural formula is shown below:
Embodiment 12:5-(2-naphthyl)-1-phenyl-1H-1,2,3-triazole synthetic
In 25mL round-bottomed flask, add 1mmol 2-[(E)-2-nitroethylene base] naphthalene, 1mmol aziminobenzene, 0.4mmol trifluoromethanesulfonic acid erbium and 3mL toluene, under 110 ℃ of conditions, back flow reaction is to (TLC follows the tracks of detection completely, about 10h), stopped reaction, question response liquid cool to room temperature, filter, removal of solvent under reduced pressure, quick purification by silica gel column chromatography (eluent is ethyl acetate/petroleum ether=1:10, volume ratio) on resistates, obtain yellow oily liquid 1l, productive rate 65%.
To gained yellow oily liquid, 1l analyzes, and its spectral characteristic is as follows:
1H?NMR(400MHz,CDCl
3):δ7.97(s,1H),7.84-7.75(m,4H),7.56-7.48(m,2H),7.48-7.35(m,5H),7.22(dd,J=8.5,1.8Hz,1H)ppm;
13C?NMR(100MHz,CDCl
3):δ137.77,136.69,133.67,133.15,133.00,129.39,129.24,128.63,128.25,128.20,127.77,127.20,126.89,125.55,125.19,124.12ppm；
HRMS(m/z)(ESI):calcd?for?C
18H
14N
3272.3159[M+H
+]found?272.1184.
Therefore can determine that gained yellow oily liquid 1l is 5-(2-naphthyl)-1-phenyl-1H-1,2,3-triazole, its structural formula is shown below:
Claims (5)
1. a synthetic method as shown in the formula compound shown in (I), it is characterized in that: mainly comprise the following steps: under rare-earth metal catalyst existence condition, by compound shown in compound shown in formula II and formula III in organic solvent, 80～110 ℃ of back flow reaction, make target compound crude product;
Wherein,
Described R
1for
or
Described R
2for
or
Described rare-earth metal catalyst is trifluoromethanesulfonic acid cerium, trifluoromethanesulfonic acid samarium, trifluoromethanesulfonic acid europium, Ytterbiumtriflate, trifluoromethanesulfonic acid praseodymium, trifluoromethanesulfonic acid lanthanum, trifluoromethanesulfonic acid neodymium, trifluoromethanesulfonic acid erbium or trifluoromethanesulfonic acid dysprosium;
Described organic solvent is toluene and/or chlorobenzene.
2. method according to claim 1, is characterized in that: the consumption of described rare-earth metal catalyst is 1～10mol% of compound amount shown in formula III.
3. method according to claim 2, is characterized in that: the consumption of described rare-earth metal catalyst is 5～10mol% of compound amount shown in formula III.
4. according to the method described in any one in claim 1～3, it is characterized in that: also comprise purification step: specifically by the target compound crude product making through silica gel column chromatography, the eluent wash-out that the ethyl acetate that to use by volume ratio be 1:5～50 and sherwood oil form, elutriant removes solvent under reduced pressure, obtains the target compound after purifying.
5. method according to claim 4, is characterized in that: for the eluent of wash-out, the volume ratio of ethyl acetate and sherwood oil is 1:5～20.
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| CN104496966A (en) * | 2014-12-24 | 2015-04-08 | 广西师范大学 | Method for synthesizing quinoxaline-triazole compounds from o-phenylenediamine, phenylacetylene and nitrine |
| CN104829545A (en) * | 2015-04-02 | 2015-08-12 | 东南大学 | Method for forming 1,5-subsituted triazole ring through catalyzing click by rare earth |
| CN104892587A (en) * | 2015-05-04 | 2015-09-09 | 刘增峰 | Medicine intermediate triazole compound synthesis method |
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| CN105418638B (en) * | 2015-12-24 | 2018-01-19 | 广西师范大学 | With terminal alkyne, two bromoalkanes, CO2The method that thick triazole compound is synthesized with sodium azide |
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