CN113307790B - A kind of preparation method of 1,2,4-triazole compound substituted by 3-quinolinyl-5-trifluoromethyl - Google Patents
A kind of preparation method of 1,2,4-triazole compound substituted by 3-quinolinyl-5-trifluoromethyl Download PDFInfo
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- -1 1,2,4-triazole compound Chemical group 0.000 title claims abstract description 37
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- SMUQFGGVLNAIOZ-UHFFFAOYSA-N quinaldine Chemical compound C1=CC=CC2=NC(C)=CC=C21 SMUQFGGVLNAIOZ-UHFFFAOYSA-N 0.000 claims abstract description 30
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims abstract description 11
- 239000003960 organic solvent Substances 0.000 claims abstract description 10
- ASMQGLCHMVWBQR-UHFFFAOYSA-N Diphenyl phosphate Chemical compound C=1C=CC=CC=1OP(=O)(O)OC1=CC=CC=C1 ASMQGLCHMVWBQR-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 12
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 239000007800 oxidant agent Substances 0.000 claims description 5
- 230000001590 oxidative effect Effects 0.000 claims description 5
- 239000000654 additive Substances 0.000 claims description 4
- 230000000996 additive effect Effects 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N tertiry butyl alcohol Natural products CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- QJQYPZZUKLQGGT-UHFFFAOYSA-N methyl hypobromite Chemical compound COBr QJQYPZZUKLQGGT-UHFFFAOYSA-N 0.000 claims description 2
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 24
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 abstract description 9
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical class C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 abstract description 6
- 239000003054 catalyst Substances 0.000 abstract description 3
- 239000007858 starting material Substances 0.000 abstract description 3
- 239000000758 substrate Substances 0.000 abstract description 3
- 229910001385 heavy metal Inorganic materials 0.000 abstract description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract 1
- HZVGIXIRNANSHU-UHFFFAOYSA-N naphthalene-1,2,3,4-tetrone Chemical compound C1=CC=C2C(=O)C(=O)C(=O)C(=O)C2=C1 HZVGIXIRNANSHU-UHFFFAOYSA-N 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 30
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- 238000005481 NMR spectroscopy Methods 0.000 description 10
- 239000002994 raw material Substances 0.000 description 7
- 238000004293 19F NMR spectroscopy Methods 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 150000004982 aromatic amines Chemical class 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 125000005493 quinolyl group Chemical group 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000000010 aprotic solvent Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 150000003852 triazoles Chemical class 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- PAVUDWZMNZHJLH-UHFFFAOYSA-N 1-(4-methoxyphenyl)-3-methyl-6-pyridin-4-yl-4-(trifluoromethyl)pyrazolo[3,4-b]pyridine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(C=3C=CN=CC=3)=CC(C(F)(F)F)=C2C(C)=N1 PAVUDWZMNZHJLH-UHFFFAOYSA-N 0.000 description 1
- UQVWFPMMIDUJMN-UHFFFAOYSA-N 3-methyl-1-phenyl-6-pyridin-4-yl-4-(trifluoromethyl)pyrazolo[3,4-b]pyridine Chemical compound C12=NC(C=3C=CN=CC=3)=CC(C(F)(F)F)=C2C(C)=NN1C1=CC=CC=C1 UQVWFPMMIDUJMN-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 238000005899 aromatization reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- ASMQGLCHMVWBQR-UHFFFAOYSA-M diphenyl phosphate Chemical compound C=1C=CC=CC=1OP(=O)([O-])OC1=CC=CC=C1 ASMQGLCHMVWBQR-UHFFFAOYSA-M 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000007336 electrophilic substitution reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000007243 oxidative cyclization reaction Methods 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了一种3‑喹啉基‑5‑三氟甲基取代的1,2,4‑三氮唑化合物的制备方法，包括如下步骤：将四丁基碘化铵、过氧化叔丁醇水溶液、二苯基磷酸、三氟乙基亚胺酰肼以及2‑甲基喹啉加入到有机溶剂中，加热至80～100℃反应8～14小时反应完全后，后处理得到所述的3‑喹啉基‑5‑三氟甲基取代的1,2,4‑三氮唑化合物。该制备方法操作简单，起始原料廉价易得，且反应无需在无水无氧条件下操作，也无需用到重金属作为催化剂，还可以通过底物设计合成出不同位置多样化取代的同时带喹啉基和三氟甲基的1,2,4‑三氮唑化合物，便于操作的同时拓宽了此方法的应用性。The invention discloses a preparation method of a 3-quinolinyl-5-trifluoromethyl substituted 1,2,4-triazole compound, comprising the following steps: tetrabutylammonium iodide, tert-butyl peroxide Aqueous alcohol solution, diphenylphosphoric acid, trifluoroethylimide hydrazide and 2-methylquinoline are added to the organic solvent, heated to 80～100°C and reacted for 8～14 hours. 3-quinolinyl-5-trifluoromethyl substituted 1,2,4-triazole compounds. The preparation method is simple to operate, the starting materials are cheap and easy to obtain, and the reaction does not need to be operated under anhydrous and oxygen-free conditions, nor does it need to use heavy metals as catalysts, and can also be synthesized through the design of substrates. The 1,2,4-triazole compounds of oxoline and trifluoromethyl are convenient for operation and broaden the applicability of this method.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a preparation method of a 3-quinolyl-5-trifluoromethyl substituted 1,2, 4-triazole compound.
Background
The 1,2, 4-triazole compound is an extremely important five-membered nitrogen-containing heterocyclic ring and widely exists in a plurality of bioactive molecular frameworks (chem. Rev.2010,110, 1809). Many drug intermediates and functional material molecules contain 1,2, 4-triazole structures. The 1,2, 4-triazole molecule can also be used as a ligand to coordinate with a transition metal, and is often used in organic light emitting diodes (coord. chem. rev.,2003,241,119). Particularly, when other heterocyclic molecules are connected in the triazole molecule, the triazole is expected to be used as a bidentate ligand for various cross-coupling reactions.
At present, few synthesis methods for preparing quinolyl substituted 1,2, 4-triazole are reported in documents, and the traditional synthesis method adopts quinoline-2-formic acid as a raw material and can obtain the quinolyl substituted 1,2, 4-triazole with 17% of total yield after five-step reaction under severe reaction conditions. This method is not suitable for large scale synthetic applications due to some significant disadvantages.
Based on the method, the cheap and easily-obtained 2-methylquinoline and trifluoroethylimine hydrazide are used as starting materials, tetrabutylammonium iodide and tert-butyl peroxide are used for promoting oxidative cyclization reaction, and the method for simply and efficiently synthesizing the 3-quinolyl-5-trifluoromethyl substituted 1,2, 4-triazole is developed.
Disclosure of Invention
The invention provides a preparation method of a 3-quinolyl-5-trifluoromethyl substituted 1,2, 4-triazole compound, which has simple steps, cheap and easily obtained starting raw materials, does not need water and oxygen-free conditions, avoids the participation of toxic heavy metal catalysts and is convenient to operate and apply; the reaction can be easily expanded to gram-scale reaction, and the possibility is provided for future large-scale production and application.
A preparation method of 3-quinolyl-5-trifluoromethyl substituted 1,2, 4-triazole compound comprises the following steps: adding tetrabutylammonium iodide, tert-butyl peroxide aqueous solution, diphenyl phosphoric acid, trifluoroethylimine hydrazide and 2-methylquinoline into an organic solvent, heating to 80-100 ℃, reacting for 8-14 hours, and performing post-treatment to obtain the 3-quinolyl-5-trifluoromethyl substituted 1,2, 4-triazole compound;
the structure of the trifluoroethylimine hydrazide is shown as a formula (II):
the structure of the 2-methylquinoline is shown as the formula (III):
the structure of the 3-quinolyl-5-trifluoromethyl substituted 1,2, 4-triazole compound is shown as the formula (I):
in formulae (I) to (III), R1Is a substituted or unsubstituted aryl group;
R2is H, C1～C4Alkyl radical, C1～C4Alkoxy, halogen or nitro;
at R1Wherein the substituents on the aryl group are selected from C1～C4Alkyl radical, C1～C4Alkoxy, halogen or trifluoromethyl.
The molar ratio of tetrabutylammonium iodide to tert-butyl peroxide aqueous solution to diphenyl phosphoric acid is 1.0-1.5: 4: 2;
R1the substitution position of the upper aryl group can be ortho-position, para-position or meta-position.
The reaction formula is exemplified as follows:
in the reaction, tetrabutylammonium iodide and tert-butyl peroxide are promoted to carry out oxidation reaction to convert 2-methylquinoline into 2-quinoline formaldehyde, the 2-quinoline formaldehyde and trifluoroethylimine hydrazide are subjected to condensation reaction to obtain a dehydrated hydrazone intermediate, and then oxidative iodination, intramolecular electrophilic substitution reaction and aromatization are carried out to form the final 3-quinolyl-5-trifluoromethyl substituted 1,2, 4-triazole compound. It is also possible for the reaction to proceed by a free radical process.
In the present invention, the optional post-processing procedure includes: filtering, mixing the sample with silica gel, and finally performing column chromatography purification to obtain the corresponding 3-quinolyl-5-trifluoromethyl substituted 1,2, 4-triazole compound, wherein the column chromatography purification is a technical means commonly used in the field.
Preferably, R1The substituted or unsubstituted phenyl is selected from methyl, methoxy, bromine or trifluoromethyl, and in this case, the aromatic amine and the trifluoroethylimine hydrazide are easily obtained and the reaction yield is high.
Preferably, R2Is H, methyl, methoxy, Cl, Br or nitro, in this case, the 2-methylquinoline is easily obtained, and the reaction yield is high.
Preferably, tetrabutylammonium iodide is used as the iodide, and the reaction yield is high.
Preferably, the oxidant is 70% tert-butyl alcohol peroxide water solution, and the peroxide oxidant is relatively cheap and has high reaction yield.
Preferably, the additive is selected from the group consisting of perdiphenylphosphoric acid, which is relatively inexpensive and has a high reaction yield.
The aromatic amine and trifluoroacetic acid used for preparing trifluoroethylimine hydrazide are relatively cheap and widely exist in nature, and are used in excess relative to the amount of the p-2-methylquinoline, and preferably, the trifluoroethylimine hydrazide is prepared by the following steps in terms of molar amount: 2-methylquinoline: tetrabutylammonium iodide: tert-butyl peroxide: 1-2: 1: 1-1.5: 3-5: 1-3 of diphenyl phosphoric acid; as a further preference, trifluoroethylimine hydrazide: 2-methylquinoline: tetrabutylammonium iodide: tert-butyl peroxide: diphenylphosphoric acid ═ 1.5:1:1.2:4: 2.
In the present invention, the organic solvent capable of sufficiently dissolving the raw material can cause the reaction, but the difference in reaction efficiency is large, and the aprotic solvent is preferably an aprotic solvent which can effectively promote the reaction; preferably, the organic solvent is DMF, DMSO or dioxane; as a further preference, the organic solvent is DMSO, in which case the starting materials can be converted into the product with a high degree of conversion.
The amount of the organic solvent can be used for better dissolving the raw materials, and the amount of the organic solvent used for 1mmol of 2-methylquinoline is about 5-10 mL.
Preferably, the iodide is tetrabutylammonium iodide, and the reaction efficiency is high when tetrabutylammonium iodide is used as a catalyst.
More preferably, the 3-quinolyl-5-trifluoromethyl substituted 1,2, 4-triazole compound is one of compounds shown in formula (I-1) and formula (I-5):
in the above preparation method, the aromatic amine, 2-methylquinoline, tetrabutylammonium iodide, tert-butyl peroxide aqueous solution and diphenyl phosphoric acid are generally commercially available products and can be conveniently obtained from the market, and the trifluoroethylimine hydrazide can be obtained from trifluoroethylimine acyl chloride and hydrazine hydrate in almost quantitative yield; the trifluoroethylimidoyl chloride can be quickly synthesized from corresponding aromatic amine, triphenylphosphine, carbon tetrachloride and trifluoroacetic acid.
Compared with the prior art, the invention has the beneficial effects that: the preparation method does not need anhydrous and anaerobic conditions, is easy to operate, and has simple and convenient post-treatment; the reaction starting raw materials are cheap and easy to obtain, the designability of a reaction substrate is strong, the tolerance range of a substrate functional group is wide, the 1,2, 4-triazole compound with quinolyl and trifluoromethyl, which are substituted at 3,5 positions differently, can be designed and synthesized according to actual needs, and the practicability is strong.
Detailed Description
The invention is further described with reference to specific examples.
Examples 1 to 15
Adding tetrabutylammonium iodide, tert-butyl peroxide aqueous solution, diphenyl phosphate, trifluoroethylimine hydrazide (II), 2-methylquinoline (III) and 2mL of organic solvent into a 35mL Schlenk tube according to the raw material ratio of Table 1, mixing and stirring uniformly, reacting according to the reaction conditions of Table 2, filtering after the reaction is finished, mixing silica gel, and purifying by column chromatography to obtain the corresponding 3-quinolyl-5-trifluoromethyl substituted 1,2, 4-triazole compound (I), wherein the reaction process is shown as the following formula:
TABLE 1 raw material addition amounts of examples 1 to 15
TABLE 2
In tables 1 and 2, T is the reaction temperature, T is the reaction time, Ph is phenyl, Me is methyl, OMe is methoxy, T-Bu is ethyl, DMSO is dimethyl sulfoxide.
Structure confirmation data of the compounds prepared in examples 1 to 5:
nuclear magnetic resonance of 3-quinolyl-5-trifluoromethyl-substituted 1,2, 4-triazole compound (I-1) prepared in example 1 (II-1)1H NMR、13C NMR and19f NMR) the data were:
1H NMR(400MHz,CDCl3)δ8.29(d,J＝8.6Hz,1H),8.22(d,J＝8.6Hz,1H),7.79(d,J＝7.5Hz,1H),7.65–7.58(m,1H),7.56–7.50(m,1H),7.46(d,J＝8.4Hz,1H),7.34–7.24(m,4H),2.48(s,3H).
13C NMR(101MHz,CDCl3)δ155.2,147.0,146.7(q,J(C-F)＝38.6Hz),145.4,140.2,136.8,131.6,130.0,129.7,129.5,127.9,127.6,127.4,120.8,118.2(q,J(C-F)＝271.5Hz),21.4,21.3.
19F NMR(377MHz,CDCl3)δ-60.92.
HRMS(ESI):[M+H]+calcd.for C19H13F3N4 355.1165,found 355.1172.m.p＝146-148℃.
nuclear magnetic resonance of 3-quinolyl-5-trifluoromethyl-substituted 1,2, 4-triazole compound (I-2) prepared in example 2 (II-2)1H NMR、13C NMR and19f NMR) the data were:
1H NMR(400MHz,CDCl3)δ8.36(d,J＝8.6Hz,1H),8.22(d,J＝8.6Hz,1H),7.79(d,J＝8.1Hz,1H),7.61(t,J＝7.6Hz,1H),7.53(t,J＝7.4Hz,1H),7.45–7.35(m,3H),7.22(t,J＝8.3Hz,2H).
13C NMR(101MHz,CDCl3)δ164.5,162.0,155.0,146.9,146.7(q,J(C-F)＝38.7Hz),145.2,137.0,130.4(d,J(C-F)＝3.2Hz),130.1,129.8,129.7,129.7,128.0,127.9,127.6,120.6,118.1(q,J(C-F)＝271.5Hz),116.1(d,J(C-F)＝23.3Hz).
19F NMR(377MHz,CDCl3)δ-60.93,-110.16～-110.23(m).
HRMS(ESI):[M+H]+calcd.for C18H10F4N4 359.0914,found 359.0924.m.p＝134-136℃.
nuclear magnetic resonance of 3-quinolyl-5-trifluoromethyl-substituted 1,2, 4-triazole compound (I-3) prepared in example 3 (II-3)1H NMR、13C NMR and19f NMR) the data were:
1H NMR(400MHz,CDCl3)δ8.41(d,J＝8.6Hz,1H),8.25(d,J＝8.6Hz,1H),7.85–7.78(m,3H),7.64–7.53(m,4H),7.26(d,J＝8.6Hz,1H).
13C NMR(101MHz,CDCl3)δ154.7,146.7,146.3(q,J(C-F)＝39.0Hz),144.9,137.8,137.1,132.3(q,J(C-F)＝33.1Hz),130.3,129.4,128.5,128.1,127.9,127.6,126.2,123.6(q,J(C-F)＝272.5Hz),120.4,118.0(q,J(C-F)＝271.6Hz).
19F NMR(377MHz,CDCl3)δ-60.78,-62.63.
HRMS(ESI):[M+H]+calcd.for C19H10F6N4 409.0882,found 409.0888.m.p＝192-194℃.
nuclear magnetic resonance of 3-quinolyl-5-trifluoromethyl-substituted 1,2, 4-triazole compound (I-4) prepared in example 4 (II-4)1H NMR、13C NMR and19f NMR) the data were:
1H NMR(400MHz,CDCl3)δ8.31(d,J＝8.6Hz,1H),8.11(d,J＝8.6Hz,1H),7.93(d,J＝2.1Hz,1H),7.68–7.63(m,1H),7.36–7.25(m,3H),6.99(d,J＝9.0Hz,2H),3.89(s,3H).
13C NMR(101MHz,CDCl3)δ160.6,154.9,147.0(q,J(C-F)＝38.7Hz),145.8,145.5,135.8,133.5,131.4,129.6,128.9,126.6,122.0,121.6,118.1(q,J(C-F)＝271.5Hz),114.0,55.6.
19F NMR(377MHz,CDCl3)δ-61.02.
HRMS(ESI):[M+H]+calcd.for C19H12BrF3N4O 449.0219,found449.0226.
m.p＝170-172℃
nuclear magnetic resonance of 3-quinolyl-5-trifluoromethyl-substituted 1,2, 4-triazole compound (I-5) prepared in example 5 (II-5)1H NMR、13C NMR and19f NMR) the data were:
1H NMR(400MHz,CDCl3)δ8.21(d,J＝8.6Hz,1H),8.10(d,J＝8.6Hz,1H),7.52(s,1H),7.45–7.37(m,2H),7.28(d,J＝8.9Hz,2H),6.97(d,J＝9.0Hz,2H),3.88(s,3H),2.48(s,3H).
13C NMR(101MHz,CDCl3)δ160.5,155.5,146.7(q,J(C-F)＝38.5Hz),145.7,144.5,138.1,136.1,132.3,129.5,128.9,127.9,126.7,126.3,120.8,118.2(q,J(C-F)＝271.4Hz),114.0,55.6,21.7.
19F NMR(377MHz,CDCl3)δ-61.00.
HRMS(ESI):[M+H]+calcd.for C20H15F3N4O 385.1271,found 385.1279.m.p＝148-150℃。
Claims (6)
1. a preparation method of 3-quinolyl-5-trifluoromethyl substituted 1,2, 4-triazole compound is characterized by comprising the following steps: adding iodide, an oxidant, an additive, trifluoroethylimine hydrazide and 2-methylquinoline into an organic solvent, heating to 80-100 ℃, reacting for 8-14 hours, and performing post-treatment to obtain the 3-quinolyl-5-trifluoromethyl substituted 1,2, 4-triazole compound;
the structure of the trifluoroethylimine hydrazide is shown as a formula (II):
the structure of the 2-methylquinoline is shown as the formula (III):
the structure of the 3-quinolyl-5-trifluoromethyl substituted 1,2, 4-triazole compound is shown as the formula (I):
in the formulae (I) to (III), R1Is a substituted or unsubstituted aryl group;
R2is H, C1~C4Alkyl radical, C1~C4Alkoxy, halogen or nitro;
at R1Wherein the substituents on the aryl group are selected from C1~C4Alkyl radical, C1~C4Alkoxy, halogen or trifluoromethyl;
the iodide is tetrabutylammonium iodide;
the oxidant is tert-butyl alcohol peroxide aqueous solution;
the additive is diphenyl phosphoric acid.
2. The method for preparing 3-quinolyl-5-trifluoromethyl-substituted 1,2, 4-triazole compound as claimed in claim 1, wherein R is1Is substituted or unsubstituted phenyl；
The substituent on the phenyl is selected from methyl, methoxy, bromine or trifluoromethyl.
3. The method for preparing 3-quinolyl-5-trifluoromethyl-substituted 1,2, 4-triazole compound as claimed in claim 1, wherein R is2Is H, methyl, methoxyl, Cl, Br or nitro.
4. The method for preparing 3-quinolyl-5-trifluoromethyl-substituted 1,2, 4-triazole compound according to claim 1, wherein the molar amount of trifluoroethylimine hydrazide is: 2-methylquinoline: iodide: oxidizing agent: the additive = 1-2: 1: 0.5-1.5: 3-5: 1-3.
5. The method for preparing 3-quinolyl-5-trifluoromethyl substituted 1,2, 4-triazole compound as claimed in claim 1, wherein the organic solvent is dimethyl sulfoxide.
6. The method for preparing 3-quinolyl-5-trifluoromethyl substituted 1,2, 4-triazole compound according to claim 1, wherein the 3-quinolyl-5-trifluoromethyl substituted 1,2, 4-triazole compound is one of compounds shown in formula (I-1) and formula (I-5):
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