CN113683595B - Preparation method of simple sulfur-promoted 5-trifluoromethyl-substituted 1,2, 4-triazole compound - Google Patents
Preparation method of simple sulfur-promoted 5-trifluoromethyl-substituted 1,2, 4-triazole compound Download PDFInfo
- Publication number
- CN113683595B CN113683595B CN202111124490.2A CN202111124490A CN113683595B CN 113683595 B CN113683595 B CN 113683595B CN 202111124490 A CN202111124490 A CN 202111124490A CN 113683595 B CN113683595 B CN 113683595B
- Authority
- CN
- China
- Prior art keywords
- trifluoromethyl
- substituted
- triazole compound
- heterocyclyl
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- -1 5-trifluoromethyl-substituted 1,2, 4-triazole compound Chemical class 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 28
- 238000006243 chemical reaction Methods 0.000 claims abstract description 21
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 12
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 5
- 238000010438 heat treatment Methods 0.000 claims abstract description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 230000001590 oxidative effect Effects 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- 239000007800 oxidant agent Substances 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 6
- 239000002994 raw material Substances 0.000 abstract description 6
- 239000000758 substrate Substances 0.000 abstract description 4
- 150000002978 peroxides Chemical class 0.000 abstract description 3
- 239000002360 explosive Substances 0.000 abstract description 2
- 229910001385 heavy metal Inorganic materials 0.000 abstract description 2
- 238000006467 substitution reaction Methods 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 35
- 238000001514 detection method Methods 0.000 description 5
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical class C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 4
- 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
- 238000003786 synthesis reaction Methods 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 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
- 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
- 150000000178 1,2,4-triazoles Chemical class 0.000 description 1
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- WZFUQSJFWNHZHM-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 WZFUQSJFWNHZHM-UHFFFAOYSA-N 0.000 description 1
- CONKBQPVFMXDOV-QHCPKHFHSA-N 6-[(5S)-5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-2-oxo-1,3-oxazolidin-3-yl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C[C@H]1CN(C(O1)=O)C1=CC2=C(NC(O2)=O)C=C1 CONKBQPVFMXDOV-QHCPKHFHSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 238000005899 aromatization reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000002532 enzyme inhibitor Substances 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
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000011877 intramolecular nucleophilic addition Methods 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- MFFMDFFZMYYVKS-SECBINFHSA-N sitagliptin Chemical compound C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F MFFMDFFZMYYVKS-SECBINFHSA-N 0.000 description 1
- 229960004034 sitagliptin Drugs 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000001308 synthesis method 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
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a preparation method of a 3-heterocyclyl-5-trifluoromethyl substituted 1,2, 4-triazole compound, which comprises the following steps: heating elemental sulfur, dimethyl sulfoxide, trifluoro ethylimine hydrazide and methyl nitrogen heterocycle to 100-120 ℃ for reaction for 12-20 hours, and then carrying out post treatment to obtain the 3-heterocyclyl-5-trifluoromethyl substituted 1,2, 4-triazole compound. The preparation method is simple to operate, the initial raw materials and elemental sulfur are convenient and easy to obtain, the reaction does not need to operate under the anhydrous and anaerobic condition, heavy metals and explosive peroxides are not needed, and the 1,2, 4-triazole compound with heterocyclic groups and trifluoromethyl groups at the 3-position or the 4-position substitution can be synthesized through substrate design, so that the operation is convenient, and the applicability of the method is widened.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a preparation method of a simple sulfur-promoted 5-trifluoromethyl-substituted 1,2, 4-triazole compound.
Background
1,2, 4-triazole compounds have many important biological activities such as antihypertensive, antifungal, antibacterial, etc., which are widely present in many pharmaceutical intermediates and functional material molecules (chem. Rev. 2010,110,1809). Wherein the heterocyclic substituted 1,2, 4-triazole can be used for the coordination of bidentate ligands to transition metals and thus in the synthesis of luminescent materials (Polyhedron 2004,23,2141). Whereas trifluoromethyl substituted 1,2, 4-triazoles are the core backbone of many drug molecules and biological inhibitors, such as sitagliptin and CYP enzyme inhibitors, etc. (org.process res.dev.2005,9,634).
The prior art reports that the synthesis method for preparing the heterocyclic group and the trifluoromethyl and simultaneously replacing 1,2, 4-triazole is not more, but the prior art reports that the method of combining an iodo-compound and tert-butyl peroxide oxidizes the heterocyclic methyl, but the method involves the use of peroxide with potential explosiveness, and meanwhile, the substrate range of the methyl nitrogen heterocycle is not wide enough, and the method is not suitable for large-scale synthesis application due to obvious defects.
Based on the method, a method for simply and efficiently synthesizing 3-heterocyclyl-5-trifluoromethyl substituted 1,2, 4-triazole by using cheap and easily available methyl nitrogen heterocycle and trifluoro ethylimine hydrazide as starting materials and adopting common simple substance sulfur and dimethyl sulfoxide to promote oxidation cyclization reaction is developed.
Disclosure of Invention
The invention provides a preparation method of a 3-heterocyclyl-5-trifluoromethyl substituted 1,2, 4-triazole compound, which has the advantages of simple operation steps, low-cost and easily obtained initial raw materials and accelerator elemental sulfur, no need of anhydrous and anaerobic conditions, avoidance of toxic heavy metal catalysts and participation of explosive peroxides, and convenience for mass operation and application; the reaction can be easily extended to gram-scale reactions, which provides the potential for future scale-up applications.
A method for preparing a 3-heterocyclyl-5-trifluoromethyl substituted 1,2, 4-triazole compound, comprising the steps of: adding elemental sulfur, dimethyl sulfoxide, trifluoro ethylimine hydrazide and methyl nitrogen heterocycle into an organic solvent, heating to 100-120 ℃ to react for 12-20 hours, and after the reaction is completed, carrying out post treatment to obtain the 3-heterocyclyl-5-trifluoromethyl substituted 1,2, 4-triazole compound;
the structure of the trifluoro ethylimine hydrazide is shown as a formula (II):
the structure of the methyl nitrogen heterocycle is shown as a formula (III):
the structure of the 3-heterocyclyl-5-trifluoromethyl substituted 1,2, 4-triazole compound is shown as a formula (I):
in the formulae (I) to (III), R 1 Is a substituted or unsubstituted aryl group;
R 2 h, C of a shape of H, C 1 ~C 4 Alkyl, C 1 ~C 4 Alkoxy or halogen;
at R 1 Wherein the substituents on the aryl groups are selected from C 1 ~C 4 Alkyl, C 1 ~C 4 Alkoxy, C 1 ~C 4 Alkylthio or halogen.
The molar ratio of the elemental sulfur to the dimethyl sulfoxide is 4:25;
R 1 the substituted position of the upper aryl group may be ortho, para or meta.
The reaction scheme is exemplified as follows:
in the reaction, the isomerization of methyl nitrogen heterocycle is carried out firstly, the heterocyclic thioaldehyde is generated by oxidation reaction under the action of sulfur, the hydrogen sulfide is removed by condensation reaction of the heterocyclic thioaldehyde and trifluoro ethylimine hydrazide to obtain a hydrazone intermediate, then the cyclization process is realized by intramolecular nucleophilic addition reaction, and finally the oxidative aromatization is realized under the synergistic promotion effect of sulfur and dimethyl sulfoxide to obtain the final 3-heterocyclyl-5-trifluoromethyl substituted 1,2, 4-triazole compound.
In the invention, the optional post-treatment process comprises: filtering, mixing with silica gel, and purifying by column chromatography to obtain corresponding 3-heterocyclyl-5-trifluoromethyl substituted 1,2, 4-triazole compound, wherein column chromatography purification is a common technical means in the field.
Preferably, R 1 For a substituted or unsubstituted phenyl group, the substituent on the phenyl group is selected from methyl, methoxy, methylthio or bromo, and in this case, the aromatic amine and the trifluoroethyl imine hydrazide are easily available, and the yield of the reaction is high.
Preferably, R 2 Is H, methyl, methoxy, cl or Br, at which time the methylazacycle is readily available and the yield of the reaction is high.
Preferably, elemental sulfur is used as the promoter, and the yield of the reaction is high.
Preferably, dimethyl sulfoxide is used as the oxidant, which is very cheap and has high reaction yield.
The aromatic amine and trifluoroacetic acid used to prepare the trifluoroethyl imine hydrazide are relatively inexpensive and widely available in nature, and are used in excess relative to the para-methyl nitrogen heterocycle, preferably in molar amounts: methyl nitrogen heterocycle: elemental sulfur: dimethyl sulfoxide=1-2:1:3-5:20-30; as a further preference, the trifluoroethyl imine hydrazide is used in molar terms: methyl nitrogen heterocycle: elemental sulfur: dimethyl sulfoxide=1.5:1:4:25.
In the invention, no special organic solvent is needed, wherein 25 equivalent dimethyl sulfoxide part acts as a solvent, and most of methyl nitrogen heterocycle is liquid, so that various raw materials can be converted into products with higher conversion rate under high-concentration reaction conditions.
Preferably, the promoter is elemental sulfur, and the reaction efficiency is high when the elemental sulfur is used as a catalyst.
As a further preferred aspect, the 3-heterocyclyl-5-trifluoromethyl-substituted 1,2, 4-triazole compound is one of the compounds represented by the formula (I-1) -formula (I-5):
in the preparation method, the aromatic amine, the methyl nitrogen heterocycle, the elemental sulfur and the dimethyl sulfoxide are generally commercially available products and can be conveniently obtained from the market, and the trifluoro ethylimine hydrazide can be obtained from trifluoro ethylimine chloride and hydrazine hydrate in almost quantitative yield; the trifluoro ethylimide acyl chloride can be obtained by the rapid synthesis of 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 simple and convenient in post-treatment; the reaction initial raw material and the accelerator elemental sulfur are cheap and easy to obtain, the reaction substrate has strong designability and wide substrate functional group range, the 1,2, 4-triazole compound with heterocyclic groups and trifluoromethyl groups which are different substituted at the 3,4 positions can be designed and synthesized according to actual needs, and the practicability is strong.
Detailed Description
The invention is further described below in connection with specific embodiments.
Examples 1 to 15
Adding elemental sulfur, dimethyl sulfoxide, trifluoro ethylimine hydrazide (II) and methyl nitrogen heterocycle (III) into a 35mL Schlenk tube according to the raw material ratio of the table 1, uniformly mixing and stirring, reacting according to the reaction conditions of the table 2, filtering after the reaction is finished, mixing a sample with silica gel, and purifying by column chromatography to obtain the corresponding 3-heterocyclyl-5-trifluoromethyl substituted 1,2, 4-triazole compound (I), wherein the reaction process is shown as the following formula:
TABLE 1 amounts of raw materials to be added in 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, SMe is methylthio, T-Bu is T-butyl, and DMSO is dimethyl sulfoxide.
Structure confirmation data for the compounds prepared in examples 1 to 5:
nuclear magnetic resonance of 3-heterocyclyl-5-trifluoromethyl-substituted 1,2, 4-triazole Compound (I-1) obtained in example 1 1 H NMR、 13 C NMR 19 F NMR) detection data were:
1 H NMR(400MHz,CDCl 3 )δ8.60(d,J=5.3Hz,2H),7.42–7.34(m,4H), 7.23(d,J=8.1Hz,2H),2.50(s,3H).
13 C NMR(101MHz,CDCl 3 )δ154.3,150.3,146.6(q,J(C-F)=39.2Hz), 141.8,132.9,130.9,129.7,126.9,122.0,117.9(q,J(C-F)=271.5Hz),21.4.
19 F NMR(377MHz,CDCl 3 )δ-61.1.
HRMS(ESI):[M+H] + calcd.for C15H12F3N4 + 305.1009,found 305.1007.
m.p=166-167℃.
nuclear magnetic resonance of 3-heterocyclyl-5-trifluoromethyl-substituted 1,2, 4-triazole Compound (I-2) obtained in example 2 1 H NMR、 13 C NMR 19 F NMR) detection data were:
1 H NMR(400MHz,CDCl 3 )δ8.63(d,J=6.0Hz,2H),7.38–7.27(m,6H).
13 C NMR(101MHz,CDCl 3 )δ165.0,162.5,154.3,150.5,146.6(q,J(C-F)= 39.3Hz),132.6,129.3(d,J(C-F)=9.1Hz),128.3(d,J(C-F)=3.2Hz),122.0,117.9(q,J(C-F)=271.7Hz),177.7(d,J(C-F)=23.4Hz).
19 F NMR(377MHz,CDCl 3 )δ-61.01(s),-106.9–-107.1(m).
HRMS(ESI):[M+H] + calcd.for C14H9F4N4 + 309.0758,found 309.0759.
m.p=177-179℃.
nuclear magnetic resonance of 3-heterocyclyl-5-trifluoromethyl-substituted 1,2, 4-triazole Compound (I-3) obtained in example 3 1 H NMR、 13 C NMR 19 F NMR) detection data were:
1 H NMR(400MHz,CDCl 3 )δ8.57(d,J=6.1Hz,2H),7.35–7.30(m,2H), 7.22(d,J=8.9Hz,2H),7.05–6.98(m,2H),3.88(s,3H).
13 C NMR(101MHz,CDCl 3 )δ161.4,154.4,150.3,146.7(q,J(C-F)=38.9 Hz),133.0,128.4,124.6,122.0,118.0(q,J(C-F)=271.6Hz),115.4,55.7.
19 F NMR(377MHz,CDCl 3 )δ-61.2.
HRMS(ESI):[M+H] + calcd.for C15H12F3N4O + 321.0958,found 321.0958. m.p=159-161℃.
nuclear magnetic resonance of 3-heterocyclyl-5-trifluoromethyl-substituted 1,2, 4-triazole Compound (I-4) obtained in example 4 1 H NMR、 13 C NMR 19 F NMR) detection data were:
1 H NMR(400MHz,CDCl 3 )δ8.29(d,J=8.4Hz,1H),8.21(d,J=8.5Hz, 1H),7.78(d,J=7.9Hz,1H),7.61(t,J=7.4Hz,1H),7.51(t,J=9.7Hz,2H), 7.30(d,J=7.9Hz,2H),6.99(d,J=7.8Hz,2H),3.89(s,3H).
13 C NMR(101MHz,CDCl 3 )δ160.6,155.3,147.1,146.9(q,J(C-F)=38.5 Hz),145.5,136.9,130.0,129.9,128.9,127.9,127.6,126.8,120.8,118.2(q, J(C-F)=271.4Hz),114.1,55.7.
19 F NMR(377MHz,CDCl 3 )δ-61.1.
m.p=139-141℃.
nuclear magnetic resonance of 3-heterocyclyl-5-trifluoromethyl-substituted 1,2, 4-triazole Compound (I-5) obtained in example 5 1 H NMR、 13 C NMR 19 F NMR) detection data were:
1 H NMR(400 MHz,CDCl 3 )δ8.22(d,J=8.6 Hz,1H),8.11(d,J=8.6 Hz, 1H),7.54(s,1H),7.42(q,J=8.7 Hz,2H),7.29(d,J=8.5 Hz,2H),6.98(d,J=8.6 Hz,2H),3.89(s,3H),2.49(s,3H).
13 C NMR(101 MHz,CDCl 3 )δ160.6,155.5,146.7(q,J(C-F)=38.5 Hz), 145.7,144.5,138.1,136.1,132.3,129.5,128.9,127.9,126.8,126.4,120.8,118.2(q,J(C-F)=271.4 Hz),114.0,55.6,21.7.
19 F NMR(377 MHz,CDCl 3 )δ-61.1.
m.p=148-150℃。
Claims (4)
1. a method for preparing a simple sulfur-promoted 5-trifluoromethyl-substituted 1,2, 4-triazole compound, which is characterized by comprising the following steps: adding elemental sulfur, an oxidant, trifluoro ethylimine hydrazide and methyl nitrogen heterocycle into an organic solvent, heating to 100-120 ℃ for reaction for 12-20 hours, and performing post-treatment to obtain the 3-heterocyclyl-5-trifluoromethyl substituted 1,2, 4-triazole compound;
the structure of the trifluoro ethylimine hydrazide is shown as a formula (II):
the structure of the methyl nitrogen heterocycle is shown as a formula (III):
the structure of the 3-heterocyclyl-5-trifluoromethyl substituted 1,2, 4-triazole compound is shown as a formula (I):
in the formulae (I) to (III), R 2 H, C of a shape of H, C 1 ~C 4 Alkyl, C 1 ~C 4 Alkoxy or halogen;
the oxidant is dimethyl sulfoxide;
R 1 is a substituted or unsubstituted phenyl group;
the substituent on the phenyl group is selected from methyl, methoxy, methylthio, bromo or trifluoromethyl.
2. The process for the preparation of a 3-heterocyclyl-5-trifluoromethyl-substituted 1,2, 4-triazole compound according to claim 1, wherein R 2 Is H, methyl, methoxy, F or Br.
3. The method for producing a 3-heterocyclyl-5-trifluoromethyl-substituted 1,2, 4-triazole compound according to claim 1, wherein the trifluoroethyl imine hydrazide is represented by mole: methyl nitrogen heterocycle: elemental sulfur: dimethyl sulfoxide=1-2:1:3-5:20-30.
4. The method for producing a 3-heterocyclyl-5-trifluoromethyl-substituted 1,2, 4-triazole compound according to claim 1, wherein the 3-heterocyclyl-5-trifluoromethyl-substituted 1,2, 4-triazole compound is one of the compounds represented by the formula (I-1) -formula (I-5):
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111124490.2A CN113683595B (en) | 2021-09-24 | 2021-09-24 | Preparation method of simple sulfur-promoted 5-trifluoromethyl-substituted 1,2, 4-triazole compound |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111124490.2A CN113683595B (en) | 2021-09-24 | 2021-09-24 | Preparation method of simple sulfur-promoted 5-trifluoromethyl-substituted 1,2, 4-triazole compound |
Publications (2)
Publication Number | Publication Date |
---|---|
CN113683595A CN113683595A (en) | 2021-11-23 |
CN113683595B true CN113683595B (en) | 2023-11-28 |
Family
ID=78587183
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202111124490.2A Active CN113683595B (en) | 2021-09-24 | 2021-09-24 | Preparation method of simple sulfur-promoted 5-trifluoromethyl-substituted 1,2, 4-triazole compound |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN113683595B (en) |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 |
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 |
CN113105402A (en) * | 2021-03-19 | 2021-07-13 | 浙江理工大学 | Preparation method of 3,4, 5-trisubstituted 1,2, 4-triazole compound |
CN113307790A (en) * | 2021-05-24 | 2021-08-27 | 杭州职业技术学院 | Preparation method of 3-quinolyl-5-trifluoromethyl substituted 1,2, 4-triazole compound |
-
2021
- 2021-09-24 CN CN202111124490.2A patent/CN113683595B/en active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 |
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 |
CN113105402A (en) * | 2021-03-19 | 2021-07-13 | 浙江理工大学 | Preparation method of 3,4, 5-trisubstituted 1,2, 4-triazole compound |
CN113307790A (en) * | 2021-05-24 | 2021-08-27 | 杭州职业技术学院 | Preparation method of 3-quinolyl-5-trifluoromethyl substituted 1,2, 4-triazole compound |
Non-Patent Citations (2)
Title |
---|
synthesis of 3,4,5-triamino-4H-1,2,4-triazole (guanazine) and its 4-arylideneamino derivatives;HAKAN EMILSSON;J.HETEROCYCLIC CHEM.;第26卷;1077-1081 * |
Synthesis of novel 1,3-thiazole-, 1,2,4-triazole- thione and triazepine derivatives;Wahid Mohamed Basyouni* and Khairy Abdel-Hamid Mohsen El-Bayouki;JOURNAL OF CHEMICAL RESEARCH;第2005卷;356-360 * |
Also Published As
Publication number | Publication date |
---|---|
CN113683595A (en) | 2021-11-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN113105402B (en) | Preparation method of 3,4, 5-trisubstituted 1,2, 4-triazole compound | |
CN111675662B (en) | Preparation method of 2-trifluoromethyl substituted quinazolinone compound | |
CN111978265B (en) | Preparation method of 5-trifluoromethyl substituted 1,2, 4-triazole derivative | |
CN110467579B (en) | Preparation method of 5-trifluoromethyl substituted 1,2, 4-triazole compound | |
CN113307790B (en) | Preparation method of 3-quinolyl-5-trifluoromethyl substituted 1,2, 4-triazole compound | |
CN113121462B (en) | Preparation method of 5-trifluoromethyl substituted 1,2,3-triazole compound | |
CN111423381B (en) | Preparation method of 2-trifluoromethyl substituted imidazole compound | |
CN113307778A (en) | Preparation method of 3-trifluoromethyl substituted 1,2, 4-triazole compound | |
CN112125856A (en) | Preparation method of 2-trifluoromethyl substituted quinazolinone derivative | |
CN112480015B (en) | Method for synthesizing 2-trifluoromethyl substituted quinazolinone by multi-component one-pot method | |
CN113735778A (en) | Preparation method of 5-trifluoromethyl substituted imidazole compound | |
CN113880781B (en) | Method for synthesizing 3-trifluoromethyl substituted 1,2, 4-triazole compound by taking glucose as carbon source | |
CN113683595B (en) | Preparation method of simple sulfur-promoted 5-trifluoromethyl-substituted 1,2, 4-triazole compound | |
CN109879792B (en) | Polysubstituted isoindole compound and preparation method thereof | |
CN115286578B (en) | Preparation method of trifluoromethyl-containing pyrazole compound | |
CN115197180A (en) | Synthesis method of visible light promoted 3-selenofuran compound | |
CN109232564B (en) | Method for synthesizing 3-sulfenyl substituted imidazo [1,2-a ] pyridine compound by molecular iodine promoted one-pot method | |
CN109988114B (en) | Preparation method of polysubstituted 4, 5-dihydropyrazole compound | |
CN115215810B (en) | Preparation method of heating-promoted 5-trifluoromethyl-substituted 1,2, 4-triazole compound | |
CN114195726B (en) | Preparation method of 1,2, 4-triazole substituted arylamine compound | |
CN114920707B (en) | Preparation method of 3-trifluoromethyl substituted 1,2,4-triazole compound | |
CN110590636A (en) | 4-sulfonyl pyrrolidone compound and synthesis method thereof | |
CN115353482B (en) | Preparation method of trifluoromethyl and selenium substituted azaspiro [4,5] -tetraenone compound | |
CN115466171B (en) | Preparation method of 2, 3-dihydro-1H-cyclopenteno [ a ] naphthalene derivative | |
CN115385895A (en) | Preparation method of 2-trifluoromethyl substituted indole compound |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
OL01 | Intention to license declared | ||
OL01 | Intention to license declared |