CN113307790B - Preparation method of 3-quinolyl-5-trifluoromethyl substituted 1,2, 4-triazole compound - Google Patents
Preparation method of 3-quinolyl-5-trifluoromethyl substituted 1,2, 4-triazole compound Download PDFInfo
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Abstract
The invention discloses a preparation method of a 3-quinolyl-5-trifluoromethyl substituted 1,2, 4-triazole compound, which 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 preparation method is simple to operate, the initial raw materials are cheap and easy to obtain, the reaction does not need to be operated under the anhydrous and oxygen-free conditions, heavy metal is not needed to be used as a catalyst, and the 1,2, 4-triazole compound which is variously substituted at different positions and simultaneously has quinolyl and trifluoromethyl can be synthesized through substrate design, so that the method is convenient to operate and widens the applicability.
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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| CN113880781B (en) * | 2021-09-24 | 2023-08-18 | 浙江理工大学 | Method for synthesizing 3-trifluoromethyl substituted 1,2, 4-triazole compound by taking glucose as carbon source |
| CN114195726B (en) * | 2021-12-06 | 2023-08-18 | 浙江理工大学 | Preparation method of 1,2, 4-triazole substituted arylamine compound |
| CN114920707B (en) * | 2022-06-09 | 2023-04-11 | 浙江理工大学 | Preparation method of 3-trifluoromethyl substituted 1,2,4-triazole compound |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006123242A1 (en) * | 2005-05-18 | 2006-11-23 | Pfizer Limited | 1, 2, 4 -triazole derivatives as vasopressin antagonists |
| CN105646382A (en) * | 2016-01-28 | 2016-06-08 | 浙江理工大学 | Preparation method of 1,3,5-trisubstituted 1,2,4-triazole compound |
| CN110467579A (en) * | 2019-07-30 | 2019-11-19 | 浙江理工大学 | A kind of preparation method for the 1,2,4- 3-triazole compounds that 5- trifluoromethyl replaces |
| CN111423381A (en) * | 2020-01-17 | 2020-07-17 | 浙江理工大学 | Preparation method of 2-trifluoromethyl substituted imidazole compound |
| CN111675662A (en) * | 2020-06-17 | 2020-09-18 | 浙江理工大学 | Preparation method of 2-trifluoromethyl substituted quinazolinone compound |
| CN111978265A (en) * | 2020-09-08 | 2020-11-24 | 浙江理工大学 | Preparation method of 5-trifluoromethyl substituted 1,2, 4-triazole derivative |
| CN112125856A (en) * | 2020-09-08 | 2020-12-25 | 浙江理工大学 | Preparation method of 2-trifluoromethyl substituted quinazolinone derivative |
-
2021
- 2021-05-24 CN CN202110563437.6A patent/CN113307790B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006123242A1 (en) * | 2005-05-18 | 2006-11-23 | Pfizer Limited | 1, 2, 4 -triazole derivatives as vasopressin antagonists |
| CN105646382A (en) * | 2016-01-28 | 2016-06-08 | 浙江理工大学 | Preparation method of 1,3,5-trisubstituted 1,2,4-triazole compound |
| CN110467579A (en) * | 2019-07-30 | 2019-11-19 | 浙江理工大学 | A kind of preparation method for the 1,2,4- 3-triazole compounds that 5- trifluoromethyl replaces |
| CN111423381A (en) * | 2020-01-17 | 2020-07-17 | 浙江理工大学 | Preparation method of 2-trifluoromethyl substituted imidazole compound |
| CN111675662A (en) * | 2020-06-17 | 2020-09-18 | 浙江理工大学 | Preparation method of 2-trifluoromethyl substituted quinazolinone compound |
| CN111978265A (en) * | 2020-09-08 | 2020-11-24 | 浙江理工大学 | Preparation method of 5-trifluoromethyl substituted 1,2, 4-triazole derivative |
| CN112125856A (en) * | 2020-09-08 | 2020-12-25 | 浙江理工大学 | Preparation method of 2-trifluoromethyl substituted quinazolinone derivative |
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