CN117069556A - Preparation method and application of alkylaryl ketone compound - Google Patents

Preparation method and application of alkylaryl ketone compound Download PDF

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CN117069556A
CN117069556A CN202210502077.3A CN202210502077A CN117069556A CN 117069556 A CN117069556 A CN 117069556A CN 202210502077 A CN202210502077 A CN 202210502077A CN 117069556 A CN117069556 A CN 117069556A
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alkyl
halogen
compound
oxygen
mixture
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陈邦池
孙殷卫
王忠元
苏叶华
钟毅
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Heli Technology Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B41/00—Formation or introduction of functional groups containing oxygen
    • C07B41/06—Formation or introduction of functional groups containing oxygen of carbonyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06—Preparation of nitro compounds
    • C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
    • 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

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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

The invention provides a preparation method and application of an alkylaryl ketone compound. The method takes 2-alkylaryl acetonitrile compounds as raw materials to prepare alkylaryl ketone compounds through oxidation reaction under the action of transition metal catalysts. Compared with the prior art, the method provided by the invention does not need special low-temperature and expensive alkali reagents, has high reaction yield and short reaction time, can reduce the consumption of alkali, can obtain the product with higher yield even in the presence of alkali, and has fewer three wastes.

Description

Preparation method and application of alkylaryl ketone compound
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a preparation method and application of an alkylaryl ketone compound.
Background
Alkylaryl ketones are an important class of organic compounds which are key intermediates for the preparation of many important agricultural fungicides, for example 1- (4-chlorophenyl) -2-cyclopropyl-1-propanone is an important intermediate for the triazole fungicide cyproconazole (CN 103044230) and 4- (4-chlorophenoxy) -2-trifluoromethyl acetophenone is an important intermediate for the preparation of the fungicide triflumizole (CN 105152899). The simple and efficient preparation of the alkylaryl ketone compound has important significance.
The conventional method for preparing alkylaryl ketones is an F-C acylation reaction, but this reaction is often limited by the positioning effect of the substituents and does not produce all types of products, especially substrates for ortho and/or para electron withdrawing substituents, which often do not produce the desired product. Meanwhile, a large amount of metal catalyst (aluminum trichloride) is required to be used, and a large amount of wastewater and solid waste are generated.
Patent (CN 107709284, etc.) discloses a method for preparing corresponding aryl alkyl ketone by using halogenated benzene as substrate, first preparing grignard reagent and then reacting with acyl halide or anhydride, as shown in reaction formula 1, the method has high yield, but the grignard reaction requires harsh conditions such as no water, no oxygen, etc., and the grignard reaction can generate a large amount of metal waste salt, which is unfavorable for industrial production. Meanwhile, the Grignard reagent has compatibility requirement on the reactive group, and the compound with the nitro group, the ester group and other groups connected on the aromatic ring cannot be prepared by the method.
Another method for preparing alkylaryl ketone compounds is reported by Watt et al (J.org.chem.1983, 48, 4087-4096). The method takes alkylaryl acetonitrile compounds as raw materials, and prepares alkylaryl ketone compounds through oxygen oxidation under the action of alkali, as shown in a reaction formula 2. The method has low yield (36-60%).
In the process of developing a method for efficiently preparing alkylaryl ketones, the inventor surprisingly finds that 2-alkylaryl acetonitrile compounds can be reacted in one step to obtain target compounds with high yield under the action of transition metal catalysts, oxidants and alkali, thereby avoiding the defects of the prior art scheme.
Disclosure of Invention
The present invention relates to a novel process for the preparation of alkylaryl ketone compounds I. The novel process for preparing compound I comprises: optionally, in the presence of alkali, mixing the compound II, an oxidant and a catalyst, and reacting to obtain a compound I, wherein the reaction formula is as follows:
wherein R is 1 Is a carbon group; preferably C1-C10 alkyl, C6-C12 aryl or heteroaryl containing 1 or 2 atoms selected from nitrogen, oxygen and sulfur; any hydrogen atom on carbon atoms of the alkyl, aryl and heteroaryl groups can be substituted by halogen; further preferred are C1-C4 alkyl, C1-C4 halogen substituted alkyl.
R 2 、R 3 、R 4 、R 5 、R 6 Independently of one another, hydrogen, C1-C10 alkyl, C6-C12 aryl or heteroaryl containing 1 or 2 atoms selected from nitrogen, oxygen, sulfur, halogen, nitro, cyano, C1-C6 alkanoyl, C1-C6 alkyloxy, C6-C12 aryloxy, -COOR 7 Any hydrogen atom on the carbon atom of the alkyl, aryl or heteroaryl group may be substituted with halogen;
alternatively, R 2 、R 3 、R 4 、R 5 、R 6 Any two adjacent substituents together form a C1-C10 cyclic substituent, carbon atoms in the substituent can be substituted by 1 or 2 nitrogen, oxygen and sulfur atoms, and any hydrogen atom on the carbon atoms on the cyclic substituent can be substituted by halogen;
and R is 2 、R 4 、R 6 At least 1 of them is haloalkyl, nitro, cyano, halogen, C1-C6 alkanoyl, -COOR 7 。
R 2 、R 4 Independently of one another, C1-C4 haloalkyl, nitro, cyano, C2-C4 alkanoyl, halogen, -COOR 7 ；
R 3 、R 5 、R 6 Independently of one another, hydrogen, C1-C4-alkyl;
R 1 is methyl, R 2 Is trifluoromethyl, R 3 、R 5 、R 6 Independently of each other, hydrogen; r is R 4 Is nitro;
R 7 is a carbon group; preferably C1-C10 alkyl, C6-C12 aryl or heteroaryl containing 1 or 2 atoms selected from nitrogen, oxygen and sulfur, any hydrogen atom of the carbon atoms of the alkyl, aryl and heteroaryl being substituted by halogen; further preferred are C1-C4 alkyl, C1-C2 haloalkyl.
The alkali is carbonate, bicarbonate, phosphate, C1-C6 alkyl carboxylate, formate, hydroxide, alkoxide, hydride, carbonate, bicarbonate, phosphate, C1-C6 alkyl carboxylate, formate, hydroxide, alkoxide, hydride of alkali metal, alkali metal alkyl, alkali metal amide, organic amine compound, and mixture of two or more thereof,
preferably alkali metal carbonates, phosphates, hydroxides, organic tertiary amine compounds (including substituted or unsubstituted pyridine compounds), and mixtures of two or more thereof,
further preferred are potassium carbonate, potassium hydroxide, sodium carbonate, sodium hydroxide, tertiary alkyl amine compounds (including tertiary cyclic alkyl amines), and mixtures of two or more thereof; the alkyl is a C1-C12 alkyl, preferably a C1-C6 alkyl.
The oxidant is oxygen, air, ozone, peroxidation compound, hypohalite, halate, perhalate, or their mixture,
the peroxidic compounds include metal peroxides, hydrogen peroxide, peroxo acid salts and organic peroxides, such as hydrogen peroxide, sodium peroxide, potassium peroxide, calcium peroxide, magnesium peroxide, zinc peroxide, potassium peroxymonosulfate, strontium peroxide, etc.;
hypohalites include calcium hypochlorite, lithium hypochlorite, sodium hypochlorite, potassium hypochlorite, and the like;
the halogenate salt comprises sodium chlorate, sodium bromate, potassium iodate and the like;
the perhalate comprises ammonium perchlorate, potassium perchlorate, sodium perchlorate, perchloric acid and the like;
the oxidant is preferably oxygen or air.
The catalyst is a group VIII, group IB or group IIB transition element or cations thereof and a mixture of two or more of the group VIII transition element, the group VIII transition element comprises iron, cobalt, nickel, ruthenium, rhodium, palladium, osmium, iridium and platinum, the group IB transition element comprises copper, silver and gold, the group IIB transition element comprises zinc, cadmium and mercury, preferably the group VIII or group IB transition element or cations thereof and the mixture of two or more of the group VIII or group IB transition element and the cations thereof, and further preferably metallic copper, metallic iron, metallic copper cations, metallic iron cations and the mixture of two or more of the group VIII, group IB transition element comprises zinc, cadmium and mercury. Particularly preferred are metallic copper, positive monovalent copper ions, positive divalent copper ions, and mixtures of two or more thereof. The corresponding salts of the metal cations include halides, halates, sulphates, bisulphates, nitrates, C1-C10 carboxylates, carbonates, phosphates, monohydrogenphosphates, dihydrogenphosphates, pyrophosphates, sulfonates of carbon groups, fluoroborates, hydroxides, oxides of the corresponding metals.
The molar ratio of compound II to base is 1:0.001 to 2, preferably 1:0.01 to 0.3, more preferably 1:0.05 to 0.1.
The mol ratio of the catalyst to the compound II is 0.005-2.5: 1, preferably 0.008 to 1.0:1, more preferably 0.01 to 0.1:1.
the reaction may be carried out in the presence of a solvent. The solvent is nitrile, ester, haloalkane, ether, aromatic hydrocarbon, tertiary amine, amide, sulfone and sulfoxide, water, alcohol, ketone compound or mixture of the above substances, preferably amide, sulfone and sulfoxide compound, water or mixture of the above substances. Further preferred are N, N-dimethylformamide, N-methylpyrrolidone, N-dimethylacetamide, dimethylsulfoxide, water and mixtures of the foregoing.
The reaction may also be carried out in the absence of a solvent.
The temperature of the reaction is-20 to 150 degrees celsius, preferably 20 to 100 degrees celsius, and more preferably 50 to 80 degrees celsius.
The terms "comprising," "including," and "having," as used herein, are inclusive and mean a non-exclusive inclusion. For example: a process or method that comprises a series of elements is not necessarily limited to only those elements, but may include other elements not expressly listed.
Unless expressly stated to the contrary, "or" means an inclusive "or" rather than an exclusive "or". For example: the condition a or B represents the following possibilities: a is true (or present) and B is false (or absent), a is false (or absent) and B is true (or present), and both a and B are true (or present).
A carbon-based group refers to a positive monovalent group comprising a carbon atom through which the carbon-based group is attached to the remainder of the chemical structure. The carbon-based groups may include any of saturated, unsaturated (including aryl), chain, cyclic (including polycyclic), and heteroatom moieties. Although the carbon-based groups are not particularly limited in size, in the context of the present invention they typically comprise 1 to 16 carbon atoms and 0 to 3 heteroatoms. Important carbon-based groups are selected from C1-C6 alkyl, C1-C4 haloalkyl and phenyl optionally substituted with 1 to 3 substituents selected from C1-C3 alkyl, halo and nitro.
In the description herein, alkyl groups may be straight or branched. The term "halogen", whether alone or in compound words such as "haloalkyl", includes fluorine, chlorine, bromine or iodine. Furthermore, when used in compound words such as "haloalkyl", the alkyl groups may be partially or fully substituted with halogen atoms which may be the same or different. Examples of "haloalkyl" include F 3 C、ClCH 2 、CF 3 CH 2 And CF (compact F) 3 CCl 2 。
The invention also relates to application of the method in preparing triazole bactericides, wherein the triazole bactericides comprise but are not limited to penconazole, ipFenitrofluoroazole, epoxiconazole, flutriafol, cyproconazole, furfurazoles, difenoconazole, propiconazole, epoxiconazole and hexaconazole.
Compared with the existing method for preparing the alkylaryl ketone compound, the catalytic oxidation method provided by the invention uses a catalytic amount of metal catalyst, avoids the harsh reaction conditions required by the prior art scheme, does not need special low temperature (-78 ℃), and has high reaction yield.
Further, when the molar ratio of compound II to base is 1: when the amount of the three wastes is 0.01 to 0.1, the raw materials used in the technical scheme provided by the invention are less, the amount of the three wastes is less, and the comprehensive cost is lower.
Detailed Description
The following examples further illustrate some of the features of the present invention, but the scope and content of the invention is not limited by the examples.
Example 11 preparation of- (4-nitro-2-trifluoromethylphenyl) ethyl-1-one (comparative experiment)
To a 50mL reaction flask, 1.1g of potassium carbonate, 2.2g of water, 1g of 2- (4-nitro-2-trifluoromethylphenyl) propionitrile and 10mL of N, N-dimethylformamide were successively added. Oxygen replacement, placing the reaction bottle in an oil bath at 65 ℃ and reacting for 2 hours in an oxygen atmosphere. After completion of the reaction, the reaction mixture was cooled and added to 50mL of toluene. The obtained mixture was washed, concentrated and purified to obtain 0.4g of a product in 42% yield. 1 H NMR(CDCl 3 ,500MHz,TMS)：δ8.58(d,J＝1.5Hz,1H),8.48(dd,J 1 ＝8.5Hz,J 2 ＝1.5Hz,1H),7.66(d,J＝8.5Hz,1H),2.63(s,3H)。 13 C NMR(CDCl 3 ,125MHz)：δ199.8,148.2,145.7,128.5(q,J＝33Hz),128.4,126.9,122.3(q,J＝273Hz),122.3(q,J＝6Hz),30.5。
Example 2 screening of oxidation catalysts
To a 50mL reaction flask, 1.1g of potassium carbonate, 2.2g of water, 1g of 2- (4-nitro-2-trifluoromethylphenyl) propionitrile, 10mL of N, N-dimethylformamide and 0.05g of the catalyst listed in Table 1 were successively added. Oxygen replacement, placing the reaction bottle in 65 ℃ oil bath, and reacting for 2h under heat preservation. After completion of the reaction, the reaction mixture was cooled and added to 50mL of toluene. The obtained mixture is washed, concentrated and purified to obtain the product. Specific catalysts and reaction results are shown in table 1.
TABLE 1 oxidation catalyst forms
Sequence number Catalyst Weight of the product Reaction yield
1 Ferrous chloride 0.6g 63％
2 Ferric chloride 0.6g 63％
3 Cuprous chloride 0.9g 94％
4 Copper chloride 0.8g 84％
Example 3 1 preparation of- (4-nitro-2-trifluoromethylphenyl) ethyl-1-one
To a 50mL reaction flask, 0.1g of sodium hydroxide, 13mL of dimethyl sulfoxide, 5g of 2- (4-nitro-2-trifluoromethylphenyl) propionitrile and 0.25g of cuprous chloride were sequentially added. The reaction flask was placed in a 60 ℃ oil bath and air-blown for reaction for 24h. The reaction mixture was cooled and added to 100mL of toluene. The resulting mixture was washed, concentrated and purified to give 3.8g of a product in 79% yield.
Example 4 1 preparation of- (4-nitro-2-trifluoromethylphenyl) ethyl-1-one
To a 50mL reaction flask, 0.6g of sodium carbonate, 25mL of N, N-dimethylformamide, 10g of 2- (4-nitro-2-trifluoromethylphenyl) propionitrile and 0.4g of cuprous chloride were sequentially added. Oxygen replacement, placing the reaction bottle in an oil bath at 50 ℃, and carrying out heat preservation reaction for 4 hours. After completion of the reaction, the reaction mixture was cooled and added to 150mL of toluene. The obtained mixture was washed, concentrated and purified to obtain 9.1g of a product with a yield of 95%.
Example 51 preparation of- (4-nitro-2-trifluoromethylphenyl) ethyl-1-one
To a 50mL reaction flask, 10g of 2- (4-nitro-2-trifluoromethylphenyl) propionitrile, 0.2g of CuCl and 25mL of N, N-dimethylformamide were sequentially added. Oxygen replacement, placing the reaction flask in an oil bath at 65 ℃ and heating for reaction for 14h. The reaction mixture was cooled and added to 100mL of toluene. The obtained mixture was washed, concentrated and purified to obtain 7.6g of 2- (4-nitro-2-trifluoromethylphenyl) propionitrile as a product, with a yield of 80%.
Example 65 preparation of methyl-2, 4-dinitroacetophenone
To a 50mL reaction flask were successively added 0.5g of 2- (5-methyl-2, 4-dinitrophenyl) propionitrile, 2mL of N, N-dimethylformamide, 0.1g of sodium carbonate, 0.8g of water and 0.03g of cuprous chloride. Oxygen was replaced, the reaction mixture was warmed to 50℃and allowed to react for 4 hours. After the completion of the reaction, the reaction mixture was cooled and added to toluene (50 mL). The obtained mixture is washed, concentrated and purified to obtain 0.4g of 5-methyl-2, 4-dinitroacetophenone with the yield of 84 percent.
Example 7 4 preparation of acetyl-2-nitroacetophenone
To a 50mL reaction flask were successively added 3.5mL of N, N-dimethylformamide, 0.7g of 2- (4-acetyl-2-nitrophenyl) propionitrile, 0.1g of sodium carbonate and 10mg of cuprous chloride. Oxygen was replaced, the reaction mixture was warmed to 80℃and allowed to react for 2.5 hours. After the reaction, the reaction mixture was cooled and added to 50mL of toluene. The obtained mixture was washed, concentrated and purified to obtain 0.55g of 4-acetyl-2-nitroacetophenone with a yield of 83%. 1 H NMR(CDCl 3 ,500MHz,TMS)：δ8.63(s,1H),8.29(dd,J 1 ＝8.0Hz,J 2 ＝1.0Hz,1H),7.55(d,J＝8.0Hz,1H),2.70(s,3H),2.59(s,3H)。 13 C NMR(CDCl 3 ,125MHz)：δ199.0,194.8,145.8,141.3,138.7,133.5,127.8,124.1,30.1,26.7。
Example 8 2 preparation of acetyl-5-nitrobenzonitrile
To a 50mL reaction flask were successively added 7.5mL of N, N-dimethylformamide, 1.5g of 2- (1-cyanoethyl) -5-nitrobenzonitrile, 0.1g of potassium carbonate and 20mg of cuprous chloride. Oxygen was replaced, the reaction mixture was warmed to 60℃and allowed to react for 3 hours. After the reaction, the reaction mixture was cooled and added to 50mL of toluene. The obtained mixture was washed, concentrated and purified to obtain 1.2g of 2-acetyl-5-nitrobenzonitrile in 85% yield.
Example 92 preparation of ethyl-5-acetyl-nitrobenzoate
To a 50mL reaction flask were successively added 5mL of N, N-dimethylformamide, 1g of ethyl 2- (1-cyanoethyl) -5-nitrobenzoate, 0.1g of potassium carbonate and 50mg of cuprous chloride. Oxygen was replaced, the reaction mixture was warmed to 60℃and allowed to react for 2 hours. After the reaction, the reaction mixture was cooled and added to 50mL of toluene. The resulting mixture was washed, concentrated and purified to give 0.8g of ethyl 2-acetyl-5-nitrobenzoate in 84% yield. 1 H NMR(CDCl 3 ,500MHz,TMS)：δ8.29(d,J＝2.5Hz,1H),8.08(dd,J 1 ＝9.0Hz,J 2 ＝2.5Hz,1H),7.58(d,J＝9.0Hz,1H),4.50(q,J＝7.0Hz,2H),2.37(s,3H),1.47(t,J＝7.0Hz,3H)。 13 C NMR(CDCl 3 ,125MHz)：δ201.6,164.2,148.8,148.0,129.8,127.2,127.0,125.1,62.5,30.3,13.9。
Example 10 preparation of 4-acetyl-3-nitrobenzotrifluoride
To a 50mL reaction flask, 5mL of N, N-dimethylformamide, 1g of 4- (1-cyanoethyl) -3-nitrobenzotrifluoride, 0.1g of potassium carbonate and 50mg of cuprous chloride were successively added, and the reaction mixture was warmed to 60℃and reacted at a constant temperature for 2 hours by oxygen substitution. After the reaction, the reaction mixture was cooled and added to 50mL of toluene. The obtained mixture was washed, concentrated and purified to obtain 0.8g of 4-acetyl-3-nitrobenzotrifluoride in 84% yield. 1 H NMR(CDCl 3 ,500MHz,TMS)：δ8.38(s,1H),8.02(d,J＝8Hz,1H),7.63(d,J＝8Hz,1H),2.60(s,3H)。
EXAMPLE 11 preparation of 1- (4-nitro-2-trifluoromethylphenyl) -2-phenylethanone
To a 50mL reaction flask were successively added 7.5mL of N, N-dimethylformamide, 1.5g of 2- (4-nitro-2-trifluoromethylphenyl) -3-phenylpropionitrile, 0.2g of potassium carbonate, 2.6g of water and 70mg of cuprous chloride. Oxygen was replaced, the reaction mixture was warmed to 50℃and allowed to react for 4 hours. After the reaction, the reaction mixture was cooled and added to 50mL of toluene. The resulting mixture was washed, concentrated and purified to give 1.3g of 1- (4-nitro-2-trifluoromethylphenyl) -2-phenylethanone in 90% yield.
Example 12 preparation of 1- (4- (4-chlorophenoxy) -2-trifluoromethylphenyl) ethyl-1-one
To a 25mL reaction flask, 0.5g of 1- (4-nitro-2-trifluoromethylphenyl) ethyl-1-one, 0.3g of p-chlorophenol, 0.2g of potassium carbonate and 2.5mL of N, N-dimethylformamide were successively added. The reaction flask was placed in an oil bath at 125℃for 5h, and the reaction was complete. The reaction solution was cooled and added to 50mL of toluene. The resulting mixture was washed, concentrated and purified to give 0.57g of a product in 85% yield.
EXAMPLE 13 preparation of Fluconazole
To a 50mL three-port reaction flask was added 0.7g of water and 3.9g of dimethyl sulfate. The temperature was raised to 33 ℃. And 2.0g of dimethyl sulfide was added dropwise. Stirring was continued for 15 minutes after the completion of the dropwise addition. 6.3g of 1- (4- (4-chlorophenoxy) -2-trifluoromethylphenyl) ethyl-1-ketone prepared as in example 12 were added at 35 ℃. 4.5g potassium hydroxide (85% wt) was added with stirring at 35-45 ℃. Stirring was then continued for 2 hours at 38 ℃. The material was sampled and analyzed for disappearance. 30g of water were added at 60℃and the mixture was stirred for 20 minutes. The lower organic phase was separated and dissolved in 30g DMF. Dimethyl sulfide was removed by distillation to give a DMF solution of the product 2- [4- (4-chlorophenoxy) -2- (trifluoromethyl) phenyl ] -2-methyl oxirane, which contained 6.6g of the product in 99% yield by quantitative HPLC analysis.
The resulting mixture of 6.6g of 2- [4- (4-chlorophenoxy) -2- (trifluoromethyl) phenyl ] -2-methyl oxirane in 30g of DMF was heated to 60 ℃. 1.7g (99% by weight) of 1,2, 4-triazole and 0.3g of sodium hydroxide powder are then added in succession with stirring. The reaction mixture was heated to 125℃and then stirred at this temperature for 5 hours, the medium reaction being completed. Most of the DMF was distilled off under reduced pressure. To the concentrated reaction mixture was added 30g toluene and 20g water. The aqueous phase was then separated at 60 ℃. The toluene phase is again washed with 20g of water. The aqueous phase was separated and the toluene solution was concentrated under reduced pressure to a solution containing about 50% of the product. The temperature was raised to dissolve the solid (about 80 ℃) and slowly cooled to 0℃with stirring and stirred at that temperature for 30min. Suction filtration is carried out, a filter cake is washed twice by using 10g of toluene precooled to 0 ℃, and 6.6g of the triflumizole product is obtained after solid drying, and the yield is 84%.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and not for limiting the same; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some or all of the technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit of the invention.

Claims (10)

1. A process for the preparation of compound I, characterized in that: mixing the compound II, an oxidant and a catalyst, and reacting to obtain a compound I, wherein the reaction formula is as follows:
wherein R is 1 Is a carbon group;
R 2 、R 3 、R 4 、R 5 、R 6 independently of one another, hydrogen, C1-C10 alkyl, C6-C12 aryl or heteroaryl containing 1 or 2 atoms selected from nitrogen, oxygen, sulfur, halogen, nitro, cyano, C1-C6 alkanoyl, C1-C6 alkyloxy, C6-C12 aryloxy, -COOR 7 Any hydrogen atom on the carbon atom of the alkyl, aryl or heteroaryl group may be substituted with halogen; or R is 2 、R 3 、R 4 、R 5 、R 6 Any two adjacent substituents together form a C1-C10 cyclic substituent, carbon atoms in the substituent can be substituted by 1 or 2 nitrogen, oxygen and sulfur atoms, and any hydrogen atom on the carbon atoms on the cyclic substituent can be substituted by halogen;
and R is 2 、R 4 、R 6 At least 1 of them is haloalkyl, nitro, cyano, halogen, C1-C6 alkanoyl, -COOR 7 ；
R 7 Is a carbon group;
the catalyst is VIII or IB or IIB transition element or cation thereof, and two or more of them;
the oxidant is oxygen, air, ozone, peroxidation compound, hypohalite, halate, perhalate, or mixture of two or more thereof.
2. A method according to claim 1, characterized in that: the catalyst is a group VIII or group IB transition element or a cation thereof, and a mixture of two or more of the group VIII or group IB transition element and the cation thereof;
the oxidant is oxygen or air.
3. A method according to claim 2, characterized in that: the catalyst is metallic copper, metallic iron, metallic copper cations, metallic iron cations, and mixtures of two or more thereof.
4. A method according to claim 3, characterized in that: the catalyst is metal copper, positive monovalent copper ions, positive divalent copper ions or a mixture of two or more of the metal copper, the positive monovalent copper ions and the positive divalent copper ions.
5. The method according to any one of claims 1-4, wherein: the reaction is carried out in the presence of a base,
the alkali is carbonate, bicarbonate, phosphate, C1-C6 alkyl carboxylate, formate, hydroxide, alkoxide, hydride, carbonate, bicarbonate, phosphate, C1-C6 alkyl carboxylate, formate, hydroxide, alkoxide, hydride of alkali metal, alkali metal alkyl, alkali metal amide, organic amine compound, and mixture of two or more thereof;
the base is preferably an alkali metal carbonate, phosphate, hydroxide, organic tertiary amine compound, or a mixture of two or more thereof.
6. The method according to claim 5, wherein: the alkali is potassium carbonate, potassium hydroxide, sodium carbonate and sodium hydroxide, and the organic tertiary amine compound is an alkyl tertiary amine compound.
7. The method according to claim 1, characterized in that: r is R 1 Is C1-C10 alkyl, C6-C12 aryl or heteroaryl containing 1 or 2 atoms selected from nitrogen, oxygen and sulfur, any hydrogen atom on the carbon atoms of the alkyl, aryl and heteroaryl can be substituted by halogen;
R 2 、R 4 independently of one another, C1-C4 haloalkyl, nitro, cyano, C2-C4 alkanoyl, halogen, -COOR 7 ，R 7 Is C1-C10 alkyl, C6-C12 aryl or heteroaryl containing 1 or 2 atoms selected from nitrogen, oxygen and sulfur, any hydrogen atom on the carbon atoms of the alkyl, aryl and heteroaryl can be substituted by halogen;
R 3 、R 5 、R 6 independently of one another, hydrogen, C1-C4-alkyl.
8. The method according to claim 7, wherein: r is R 1 Alkyl substituted by C1-C4 alkyl, C1-C4 halogen; r is R 7 Is C1-C4 alkyl, C1-C2 haloalkyl.
9. The method according to claim 5, characterized in that: the molar ratio of compound II to base is 1:0.001 to 2, preferably 1:0.01 to 0.3, more preferably 1:0.05 to 0.1;
the mol ratio of the catalyst to the compound II is 0.005-2.5: preferably 0.01 to 0.1:1.
10. the use of the process according to claim 1 for the preparation of a triazole fungicide, preferably difenoconazole, ipfentridicazole, epoxiconazole, flutriafol, cyproconazole, furazoles, difenoconazole, propiconazole, epoxiconazole, hexaconazole.
CN202210502077.3A 2022-05-09 2022-05-09 Preparation method and application of alkylaryl ketone compound Pending CN117069556A (en)

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