CN109776436B - Preparation method of triazole compound - Google Patents
Preparation method of triazole compound Download PDFInfo
- Publication number
- CN109776436B CN109776436B CN201910195020.1A CN201910195020A CN109776436B CN 109776436 B CN109776436 B CN 109776436B CN 201910195020 A CN201910195020 A CN 201910195020A CN 109776436 B CN109776436 B CN 109776436B
- Authority
- CN
- China
- Prior art keywords
- formula
- compound shown
- compound
- independently
- solvent
- 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 triazole compound Chemical class 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 64
- 238000000034 method Methods 0.000 claims abstract description 15
- 238000006467 substitution reaction Methods 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims description 22
- 239000002904 solvent Substances 0.000 claims description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 11
- 229910052801 chlorine Inorganic materials 0.000 claims description 11
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 10
- 239000011230 binding agent Substances 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- 229910052731 fluorine Inorganic materials 0.000 claims description 9
- 229910052740 iodine Inorganic materials 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 8
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 7
- 239000003513 alkali Substances 0.000 claims description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
- 238000004321 preservation Methods 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 239000007789 gas Substances 0.000 claims description 5
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 claims description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 4
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 claims description 4
- 238000011534 incubation Methods 0.000 claims description 4
- 239000012074 organic phase Substances 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 235000011181 potassium carbonates Nutrition 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- LZDKZFUFMNSQCJ-UHFFFAOYSA-N 1,2-diethoxyethane Chemical compound CCOCCOCC LZDKZFUFMNSQCJ-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- MHABMANUFPZXEB-UHFFFAOYSA-N O-demethyl-aloesaponarin I Natural products O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=C(O)C(C(O)=O)=C2C MHABMANUFPZXEB-UHFFFAOYSA-N 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
- 235000011118 potassium hydroxide Nutrition 0.000 claims description 2
- 235000017550 sodium carbonate Nutrition 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical class CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical class COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims 1
- 230000007613 environmental effect Effects 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 239000000047 product Substances 0.000 description 7
- 230000000844 anti-bacterial effect Effects 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 238000004364 calculation method Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 3
- 239000003899 bactericide agent Substances 0.000 description 3
- 238000004817 gas chromatography Methods 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 244000241257 Cucumis melo Species 0.000 description 2
- 235000015510 Cucumis melo subsp melo Nutrition 0.000 description 2
- 241000221785 Erysiphales Species 0.000 description 2
- 240000007594 Oryza sativa Species 0.000 description 2
- 235000007164 Oryza sativa Nutrition 0.000 description 2
- 206010039509 Scab Diseases 0.000 description 2
- 241000209140 Triticum Species 0.000 description 2
- 235000021307 Triticum Nutrition 0.000 description 2
- 125000003368 amide group Chemical group 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 230000002888 effect on disease Effects 0.000 description 2
- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 2
- ANGDWNBGPBMQHW-UHFFFAOYSA-N methyl cyanoacetate Chemical compound COC(=O)CC#N ANGDWNBGPBMQHW-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 235000009566 rice Nutrition 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 235000013311 vegetables Nutrition 0.000 description 2
- ICPWFHKNYYRBSZ-UHFFFAOYSA-M 2-methoxypropanoate Chemical compound COC(C)C([O-])=O ICPWFHKNYYRBSZ-UHFFFAOYSA-M 0.000 description 1
- 241000223600 Alternaria Species 0.000 description 1
- 241000235349 Ascomycota Species 0.000 description 1
- 241001530056 Athelia rolfsii Species 0.000 description 1
- 241000221198 Basidiomycota Species 0.000 description 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
- 241000207199 Citrus Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 241000233679 Peronosporaceae Species 0.000 description 1
- 244000046052 Phaseolus vulgaris Species 0.000 description 1
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 1
- 241000918585 Pythium aphanidermatum Species 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- DUEPRVBVGDRKAG-UHFFFAOYSA-N carbofuran Chemical compound CNC(=O)OC1=CC=CC2=C1OC(C)(C)C2 DUEPRVBVGDRKAG-UHFFFAOYSA-N 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- 239000007799 cork Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- CKSRFHWWBKRUKA-UHFFFAOYSA-N ethyl 2-ethoxyacetate Chemical compound CCOCC(=O)OCC CKSRFHWWBKRUKA-UHFFFAOYSA-N 0.000 description 1
- JLEKJZUYWFJPMB-UHFFFAOYSA-N ethyl 2-methoxyacetate Chemical compound CCOC(=O)COC JLEKJZUYWFJPMB-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- PPFNAOBWGRMDLL-UHFFFAOYSA-N methyl 2-ethoxyacetate Chemical compound CCOCC(=O)OC PPFNAOBWGRMDLL-UHFFFAOYSA-N 0.000 description 1
- 235000012015 potatoes Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
Classifications
-
- 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
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
The invention discloses a preparation method of a triazole compound, which comprises the following synthetic route; the compound shown in formula III is used as a main raw material to carry out substitution reaction with the compound shown in formula IV under an alkaline condition, so as to synthesize the triazole compound shown in formula V. The method has the following advantages: simple operation, low cost, no pollution, high yield, environmental protection, and suitability for modern industrial production.
Description
Technical Field
The invention relates to a preparation method of triazole compounds.
Background
The triazole compound has bactericidal bioactivity, high activity, unique action mechanism and environment friendship, and has specific effect on diseases difficult to control, such as rice blast, downy mildew, gray mold, damping off and the like. The bactericidal composition is mainly used for preventing and controlling banded sclerotial blight, rust disease, early blight, leaf spot disease, scab and powdery mildew on crops such as fruit trees, vegetables, wheat, potatoes, beans, melons and the like, has excellent control effects, has good protection and treatment effects on various fungal diseases such as vegetables, melons and fruits and the like, has the characteristic of long lasting period, and has no cross resistance with other bactericides. The bactericide has the characteristics of no environmental pollution, no agricultural product pollution and no natural enemy killing, and is an ideal bactericide for preventing and treating crop resistant diseases such as citrus scab, alternaria leaf spot and the like in various countries at present.
The triazole compound is a systemic triazole fungicide with protection and treatment effects, can be absorbed by roots, stems and leaves, can be quickly conducted upwards in plant bodies, and has a good control effect on diseases caused by ascomycetes, basidiomycetes and imperfect fungi, particularly wheat take-all, powdery mildew, rust disease, root rot, rice bakanae disease and sigatoka.
Disclosure of Invention
The invention provides an improved preparation method of a triazole compound, which adopts a formula III as a main raw material to carry out substitution reaction with a formula IV under an alkaline condition to synthesize the triazole compound shown in a formula V. The product has high yield, high purity, no pollution, environmental protection and suitability for modern industrial production.
The invention adopts the following technical scheme:
a preparation method of a triazole compound shown in the following formula V is provided, and the reaction route is as follows:
wherein:
R1selected from F, Cl, Br, I, Ra-S(＝O)-O-，RbSO3-，-N+≡N，-NRcRdReOR-ORf；Ra、RbEach independently selected from-CH3，-CF3，-CF2H or phenyl; ra、RbMay be the same or different; rc、Rd、ReEach independently selected from hydrogen and C1-C6Alkyl, acyl, ester, dialkyl or amide groups, RfIs selected from C1-C6An alkyl group;
R2is selected from-OH, -ORg，-NRhRior-SRj；RgIs selected from C1-C6An alkyl group; rh、RiEach independently selected from hydrogen and C1-C6Alkyl, acyl, ester, dialkyl or amide groups, RjSelected from hydrogen, alkyl, ester or phenyl;
R3selected from H, -CORk，-CN，-SO2Rl，-SORm，-PORnR°Rp-NO, or-NO2；Rk、Rl、RmEach independently selected from hydrogen and C1-C6Alkyl, phenyl or heteroaryl; rn、R°、RpEach independently selected from hydrogen and C1-C6Alkyl, acyl, ester or dialkyl;
R4、R5each independently selected from H, -COOH, -COORq，-CN，-OH，-SH，-SRs，-NH2，-N+≡N，-S-S-Rtor-CORu；Rq、Rs、RtEach independently selected from C1-C6An alkyl group; r4、R5The same or different;
R6、R7、R8、R9、R10each independently selected from H, Cl, Br, F, I, -NO2，-ORv，-NH2，-N+N, heterocyclic substituents or-NH2；RvIs selected from C1-C6Alkyl radical, C2-C6Alkenyl radical, C2-C6Alkynyl or unsaturated monocyclic hydrocarbyl, aromatic hydrocarbyl or aromatic hydrocarbyl substituents;
x is selected from H, Cl, Br, I, F, -ORw，-NRx，-SRy，-OCORzImidazolyl, an N-containing heterocycle, or a sulfur-containing heterocycle.
Further, said C of the present invention1-C6The alkyl group can be a straight chain alkyl group, a straight chain alkyl group or a cycloalkyl group; in particular, it may be chosen from methyl, ethyl, propyl, butyl, pentyl or hexyl.
In some embodiments of the invention, R1、R2Each independently selected from H, F, Cl, Br, I, -CN, -OCH3or-OCH2CH3；R3Selected from-OH and-OCH3or-OCH2CH3。
In some embodiments of the present invention, the compound represented by formula I is selected from methyl haloacetate, ethyl haloacetate, methyl 2-haloacetoacetate, ethyl 2-haloacetoacetate, dimethyl halomalonate, ethyl halomalonate, methyl cyanoacetate or ethyl cyanoacetate, methyl methoxyacetate, ethyl methoxyacetate, methyl ethoxyacetate, and ethyl ethoxyacetate.
In some embodiments of the invention, R4、R5Each independently selected from H, -COOH, -CN, -OH, -SH, -NH2or-N+≡N。
In some embodiments of the invention, R6、R7、R8、R9、R10Each independently selected from H, Cl, Br, F, I, -NO2，-NH2，-N+N, or-NH2(ii) a X is selected from H, Cl, Br, I or F.
In some embodiments of the invention, R1、X、R8、R10Each independently is Cl or F; r2is-ORg，RgIs selected from C1-C6An alkyl group; preferably, RgIs methyl, ethyl, propyl, butyl, pentyl or hexyl; r3、R4、R5、R6、R7、R9Each independently is H.
Further, the compound shown in the formula III is used as a main raw material to perform substitution reaction with the compound shown in the formula IV under the alkaline condition, so that the triazole compound shown in the formula V can be prepared. The alkali is preferably any one or a combination of several of sodium hydrogen, triethylamine, N-dimethylaniline, DBU, diisopropylethylamine, sodium methoxide, sodium ethoxide, potassium methoxide, sodium tert-butoxide and potassium tert-butoxide.
Specifically, the preparation method of the triazole compound shown in the formula V comprises the following steps:
1) preparation of a compound of formula III:
stirring and mixing the compound shown in the formula II, an acid-binding agent and a solvent at a certain temperature, slowly dropwise adding the compound shown in the formula I, carrying out heat preservation reaction, and recovering the solvent.
Preferably, the compound represented by the formula I is selected from any one of methyl haloacetate, ethyl haloacetate, methyl 2-haloacetoacetate, ethyl 2-haloacetoacetate, dimethyl halomalonate, ethyl halomalonate, methyl cyanoacetate, ethyl cyanoacetate and the like.
Preferably, the acid-binding agent is any one or a combination of more of potassium carbonate, potassium hydroxide, sodium carbonate, potassium bicarbonate, sodium bicarbonate, DBU (1, 8-diazabicycloundecen-7-ene), triethylamine, N-dimethylaniline and diisopropylethylamine, and preferably is potassium carbonate. Researches find that the reaction rate can be remarkably improved by using the acid-binding agent.
Preferably, the solvent is methanol, acetonitrile, toluene or DMF (N, N-dimethylformamide), more preferably acetonitrile. Research finds that the reaction selectivity can be remarkably improved by using the solvent.
Preferably, the stirring and mixing temperature is 0-30 ℃;
preferably, the temperature of the heat preservation reaction is 0-120 ℃, and more preferably 0-30 ℃; studies have found that by-product production can be significantly reduced at this preferred temperature.
Preferably, the incubation reaction time is 6 to 12 hours, more preferably 8 to 10 hours.
Preferably, the molar ratio of the compound shown in the formula II to the compound shown in the formula I to the acid binding agent is 1 (1.1-2): (1.1-2), more preferably 1 (1.1-1.5): (1.1-1.5);
2) preparation of a Compound of formula V:
stirring and mixing a compound shown as a formula III, alkali and a solvent at a certain temperature, slowly dropwise adding a compound shown as a formula IV dissolved in the solvent under the protection of nitrogen, carrying out heat preservation reaction, adding water, standing for layering, recovering an organic phase, and removing the solvent to obtain the compound shown as the formula III;
preferably, the solvent is any one or more of toluene, THF (tetrahydrofuran), methyltetrahydrofuran, benzene, DMF, DMAC, dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, cyclohexane and xylene. The research finds that the reaction yield can be obviously improved by selecting the solvents.
Preferably, the base is any one or a combination of several of sodium hydrogen, triethylamine, N-dimethylaniline, DBU, diisopropylethylamine, sodium methoxide, sodium ethoxide, potassium methoxide, sodium tert-butoxide and potassium tert-butoxide, and more preferably sodium hydrogen or triethylamine.
Preferably, the stirring and mixing temperature and the heat preservation reaction temperature are respectively-15 to 20 ℃, and more preferably 5 to 10 ℃;
preferably, the reaction time is 1-6h, more preferably 2-4 h;
preferably, the molar ratio of the compound shown in the formula III to the compound shown in the formula IV to the base is 1 (1.0-1.5) to (3-5), and more preferably 1 (1.1-1.2) to (2.5-3).
The invention has the following advantages:
1) the acid-binding agent, the alkali and the solvent are easy to recycle and reuse;
2) the method has the advantages of simple operation, low cost, high yield and low requirement on equipment;
3) no pollution, environmental protection, and suitability for modern industrial production.
Detailed Description
The following examples further illustrate the embodiments of the present invention in detail. The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention.
The following reagents were purchased from carbofuran technologies, Inc.
The overall yields in the following examples are obtained according to the following formula:
yield of the compound represented by formula III ═ (mass of the compound represented by formula III × content of the compound represented by formula III × 100%)/(molar mass of the structural compound represented by formula II × molar mass of the structural compound represented by formula III)
The yield of the compound of the formula v ═ (mass of the compound of the formula v × content of the compound of the formula v × 100%)/(molar mass of the structural compound of the formula iii × molar mass of the structural compound of the formula v)
The purity of the compound of formula III in the following examples was determined by gas chromatography; the purity of the structural compound of formula V was determined by liquid chromatography.
Example 1
Adding 1.0mol of a compound shown as the following formula II into a 500ml four-mouth bottle, adding 240ml of toluene, adding 1.1mol of an acid-binding agent sodium carbonate, stirring at the temperature of 90 ℃, slowly dropwise adding 1.1mol of a compound shown as the following formula I (a Sea reagent, 98%), keeping the temperature for reacting for 6 hours, detecting the content of the compound to be less than 1% by using a gas chromatographic analyzer, filtering the solid after the reaction is finished, and recovering the toluene solvent to obtain 119.5 of a compound shown as the following formula III. The yield is 80.4% by calculation; the purity of the pure product is 95.0 percent through detection.
The reaction route is as follows:
wherein R is1Is Cl; r2is-OCH3；R3、R4、R5Each independently is H.
Example 2
Adding 1.0mol (141.1g) of a compound shown in the following formula III into a 1000ml four-mouth bottle, adding 400g of THF solvent (98%), slowly adding 3.0mol of sodium hydrogen at 5 ℃, reacting for 2h, then adding 1.1mol of a compound shown in the following formula IV, continuing to react for 2h, detecting that the content of the compound is less than 1% by using a gas chromatography analyzer, adding 200g of water when the reaction is finished, stirring for 30min, standing for layering, desolventizing an organic phase at normal pressure, and recovering THF; 299.8g of a compound represented by the following formula V was obtained. The calculated yield is 94%; the purity of the pure product is 98.5 percent through detection.
The reaction route is as follows:
wherein R is2is-OCH3；R3、R4、R5、R6、R7、R9Each independently is H; x, R8、R10Each independently Cl.
In this example, the compound of formula III can be prepared as in example 1.
Example 3
Adding 1.0mol (141.1g) of a compound shown in the following formula III into a 1000ml four-neck bottle, adding 400g of a methyl tetrahydrofuran solvent (98%), slowly dropwise adding 3.0mol of sodium hydrogen at 5 ℃, reacting for 2h, adding 1.1mol of a compound shown in the following formula IV, continuing to react for 2h, measuring the content of the compound to be less than 1% by using a gas chromatography analyzer, adding 200g of water when the reaction is finished, stirring for 30min, standing for layering, desolventizing an organic phase at normal pressure, and recovering the methyl tetrahydrofuran; 254.8g of a compound represented by the following formula V was obtained. The yield is 88.8% by calculation; the purity of the pure product is 98.0 percent through detection.
The reaction route is as follows:
wherein R is2is-OCH3；R3、R4、R5、R6、R7、R9Each independently is H; x is Cl;
R8、R10each independently is F.
In this example, the compound of formula III can be prepared as in example 1.
Example 4
The only difference from example 2 was that sodium hydrogen was replaced with an equal amount of DBU to give 180.4g of the compound of formula V. The yield is 57.4 percent by calculation; the purity of the pure product is 98.0 percent through detection.
Example 5
The only difference from example 2 was that 3.0mol of sodium hydrogen was slowly added dropwise at 30 ℃ to obtain 240.5g of the compound represented by the formula V. The yield is 75.0 percent by calculation; the purity of the pure product is 98.0 percent through detection.
Example 6
Substantially as described in examples 1 and 2, R in the compound of formula I2Replacement by-ORgWherein R isgEthyl, propyl, butyl, pentyl or hexyl, respectively, to prepare the compound of formula V.
Example 7
Substantially as described in examples 1 and 3, R in the compound of formula I2Replacement by-ORgWherein R isgEthyl, propyl, butyl, pentyl or hexyl, respectively, to prepare the compound of formula V.
The preferred embodiments of the present invention have been described above in detail, but the present invention is not limited thereto. Within the scope of the technical idea of the invention, many simple modifications can be made to the technical solution of the invention, including combinations of various technical features in any other suitable manner and including the sequence of combinations, and these simple modifications and combinations should also be regarded as the disclosure of the invention, and all fall within the scope of the invention.
Claims (18)
1. The preparation method of the triazole compound shown in the formula V is characterized in that the reaction route is as follows,
wherein:
R1selected from Cl, Br, I;
R2is selected from-OH, -ORg，-SRj；RgIs selected from C1-C6An alkyl group; rjSelected from hydrogen, C1-C6An alkyl group;
R3is selected from H;
R4、R5each independently selected from H;
R6、R7、R8、R9、R10each independently selected from H, Cl, Br, F, I;
x is selected from Cl;
wherein, the compound of formula III and the compound of formula IV are subjected to substitution reaction under alkaline condition to synthesize the triazole compound shown in formula V; the alkali is sodium hydrogen; the reaction temperature is 5-10 ℃.
2. The method according to claim 1, wherein C is1-C6Alkyl is straight chain alkyl.
3. The method according to claim 1, wherein C is1-C6Alkyl radicalSelected from methyl, ethyl, propyl, butyl, pentyl or hexyl.
4. The method of claim 1, wherein R is1Selected from Cl, Br, I; r2Is selected from-OCH3、-OCH2CH3。
5. The preparation method according to claim 1, wherein the compound represented by formula I is selected from halogenated methyl acetate and halogenated ethyl acetate, and the halogen generation is Cl generation, Br generation or I generation.
6. The method of claim 1, wherein R is1Selected from Cl; r2Is selected from-OCH3；R3、R4、R5Each independently is H.
7. The method of claim 1, wherein R is6、R7、R8、R9、R10Each independently selected from H; x is Cl.
8. The method of claim 1, wherein R is1、X、R8、R10Each independently is Cl or F; r2is-ORg，RgIs selected from C1-C6An alkyl group; r3、R4、R5、R6、R7、R9Each independently is H.
9. The method of claim 8, wherein R isgIs methyl, ethyl, propyl, butyl, pentyl or hexyl.
10. The method of claim 1, wherein R is1Selected from Cl; r2Is selected from-OCH3；R3、R4、R5、R6、R7、R9Each independently is H; x, R8、R10Each independently Cl.
11. The method of claim 1, wherein R is1Selected from Cl; r2Is selected from-OCH3；R3、R4、R5、R6、R7、R9Each independently is H; x is Cl; r8、R10Each independently is F.
12. The method of any one of claims 1 to 11, comprising the steps of:
1) stirring and mixing the compound shown in the formula II, an acid-binding agent and a solvent at a certain temperature, slowly dropwise adding the compound shown in the formula I, carrying out heat preservation reaction, and recovering the solvent to obtain a compound shown in the formula III;
2) stirring and mixing the compound shown in the formula III, alkali and a solvent at a certain temperature, slowly dropwise adding the compound shown in the formula IV dissolved in the solvent under the protection of nitrogen, keeping the temperature for reaction, adding water for standing and layering, recovering an organic phase, and removing the solvent to obtain the compound shown in the formula V.
13. The preparation method of claim 12, wherein the acid-binding agent in step 1) is any one or a combination of potassium carbonate, potassium hydroxide, sodium carbonate, potassium bicarbonate, sodium bicarbonate, DBU, triethylamine, N-dimethylaniline and diisopropylethylamine; and/or the solvent is methanol, acetonitrile, toluene or DMF;
the solvent in the step 2) is any one or more of toluene, THF, methyltetrahydrofuran, benzene, DMF, DMAC, dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, cyclohexane and xylene.
14. The preparation method of claim 12, wherein the molar ratio of the compound of formula II, the compound of formula I and the acid-binding agent in step 1) is 1 (1.1-2): (1.1-2); and/or the presence of a gas in the gas,
the molar ratio of the compound shown in the formula III to the compound shown in the formula IV to the alkali in the step 2) is 1 (1.0-1.5) to 3-5.
15. The preparation method of claim 12, wherein the molar ratio of the compound of formula II, the compound of formula I and the acid-binding agent in step 1) is 1 (1.1-1.5) to (1.1-1.5); and/or the presence of a gas in the gas,
the molar ratio of the compound shown in the formula III to the compound shown in the formula IV to the alkali in the step 2) is 1 (1.1-1.2) to 2.5-3.
16. The method according to claim 12, wherein the incubation reaction temperature in step 1) is 0 to 120 ℃; and/or, the temperature of the heat preservation reaction in the step 2) is-15 to 20 ℃.
17. The method according to claim 12, wherein the incubation reaction temperature in step 1) is 0 to 30 ℃; and/or, the reaction temperature of the heat preservation in the step 2) is 5-10 ℃.
18. The method according to claim 12, wherein the incubation temperature in step 2) is 5 ℃.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910195020.1A CN109776436B (en) | 2019-03-14 | 2019-03-14 | Preparation method of triazole compound |
| PCT/CN2019/086613 WO2020181646A1 (en) | 2019-03-14 | 2019-05-13 | Method for preparing triazole compounds |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910195020.1A CN109776436B (en) | 2019-03-14 | 2019-03-14 | Preparation method of triazole compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109776436A CN109776436A (en) | 2019-05-21 |
| CN109776436B true CN109776436B (en) | 2020-12-18 |
Family
ID=66488654
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910195020.1A Active CN109776436B (en) | 2019-03-14 | 2019-03-14 | Preparation method of triazole compound |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN109776436B (en) |
| WO (1) | WO2020181646A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111978302B (en) * | 2019-05-24 | 2022-03-22 | 帕潘纳(北京)科技有限公司 | Triazole cyanide compound and preparation method thereof |
| CN112552248A (en) * | 2019-09-10 | 2021-03-26 | 帕潘纳(北京)科技有限公司 | Preparation method of imidazole and triazole compound intermediate |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0209738A1 (en) * | 1985-07-15 | 1987-01-28 | Chemie Linz Aktiengesellschaft | Benzoyl-triazolyl-acetic-acid or -thio-acetic-acid derivatives, their production and biocidal agents containing them |
| CN103958500A (en) * | 2011-10-10 | 2014-07-30 | 奥赖恩公司 | Protein kinase inhibitors |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU6016696A (en) * | 1996-06-14 | 1998-01-07 | Toyama Chemical Co. Ltd. | Process for producing 2-(1h-1,2,4-triazol-1-yl)acetophenones |
-
2019
- 2019-03-14 CN CN201910195020.1A patent/CN109776436B/en active Active
- 2019-05-13 WO PCT/CN2019/086613 patent/WO2020181646A1/en not_active Ceased
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0209738A1 (en) * | 1985-07-15 | 1987-01-28 | Chemie Linz Aktiengesellschaft | Benzoyl-triazolyl-acetic-acid or -thio-acetic-acid derivatives, their production and biocidal agents containing them |
| CN103958500A (en) * | 2011-10-10 | 2014-07-30 | 奥赖恩公司 | Protein kinase inhibitors |
Non-Patent Citations (2)
| Title |
|---|
| Antimycobacterial activities of novel 2-(sub)-3-fluoro/nitro-5, 12-dihydro-5-oxobenzothiazolo[3,2-a]quinoline-6-carboxylic acid;Murugesan Dinakaran等;《Bioorganic & Medicinal Chemistry》;20071109;第16卷(第6期);第3414页方案1 * |
| Synthesis of new 1,2,4-triazolylmethylthiadiazolylazetidines as antimicrobial, anticonvulsant and ntiinflammatory agents;S.K.Srivastava等;《Indian Journal of Chemistry》;20021130;第41B卷(第11期);第2358页方案I * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2020181646A1 (en) | 2020-09-17 |
| CN109776436A (en) | 2019-05-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101075383B1 (en) | Biphenyl derivatives and their use as fungicides | |
| JP4511191B2 (en) | O-cyclopropyl-carboxanilide and their use as fungicides | |
| US4810724A (en) | Fungicidal compositions | |
| EA023393B1 (en) | Azole derivatives, methods for producing the same, intermediates, agro-horticultural agents | |
| US20100305351A1 (en) | Chemical compounds | |
| CN108314656B (en) | Unsaturated hydrocarbon pyrimidine sulfide compound and preparation method and application thereof | |
| CN109776436B (en) | Preparation method of triazole compound | |
| MXPA05004463A (en) | Cyclopropyl-thienyl-carboxamide as fungicides. | |
| NZ197830A (en) | Arylamine derivatives and use as microbicides (particularly fungicides) | |
| US5128371A (en) | Acylated naphthlamines as plant fungicides | |
| US4287210A (en) | Microbicidal meta oxy- and thio-substituted phenylanilines | |
| WO1989011794A1 (en) | Plant growth inhibitor | |
| KR20060076308A (en) | Silicon Compounds With Microbial Activity | |
| CH629939A5 (en) | MICROBICIDAL AGENT. | |
| CN112552248A (en) | Preparation method of imidazole and triazole compound intermediate | |
| CN103524523B (en) | Trichodermin C8 oxime ether derivative and uses thereof | |
| JPS6344154B2 (en) | ||
| JPS629105B2 (en) | ||
| US4382954A (en) | Fungicidal N-1-substituted cyclopropyl-N-acyl-2,6-dialkylaniline | |
| CN103333135A (en) | Synthesis technology of benthiavalicarb isopropyl | |
| US4590198A (en) | Fungicidal isonicotinanllide retals, their compositions and method of using them | |
| GB2037746A (en) | Microbicidal anilides | |
| KR20060011988A (en) | 3-carbonylaminothiophene and its use as fungicides | |
| JPS6072870A (en) | Triazole ethanols | |
| JP2001501943A (en) | Fungicides containing hydroxymes and hydrazone groups |
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 | ||
| CB02 | Change of applicant information | ||
| CB02 | Change of applicant information |
Address after: 102206 6th floor, building 4, hospital 9, medical Road, Life Science Park, Changping District, Beijing Applicant after: Purpana (Beijing) Technologies Co.,Ltd. Address before: 102206, No. 9, building 4, 4 Life Garden Road, Changping District science and Technology Park, Beijing, 401 Applicant before: Purpana (Beijing) Technologies Co.,Ltd. |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Preparation of a triazole compound Effective date of registration: 20210702 Granted publication date: 20201218 Pledgee: Agricultural Development Bank of China Baiyin branch business department Pledgor: Purpana (Beijing) Technologies Co.,Ltd. Registration number: Y2021990000573 |