CN113402411A

CN113402411A - Oxidation reaction-based synthesis method of propyzamide

Info

Publication number: CN113402411A
Application number: CN202110278180.XA
Authority: CN
Inventors: 颜春云; 程彦霓; 其他发明人请求不公开姓名
Original assignee: Shenzhen Qianmo Tongchen Experiment Co ltd
Current assignee: Shenzhen Qianmo Tongchen Experiment Co ltd
Priority date: 2021-03-15
Filing date: 2021-03-15
Publication date: 2021-09-17
Anticipated expiration: 2041-03-15
Also published as: CN113402411B

Abstract

The invention discloses a novel method for synthesizing propyzamide, which is characterized in that cheap dichlorobenzoic acid is used as a raw material, complex, harsh and high-toxicity reaction is not carried out, and a high-activity, expensive and environmentally-harmful reagent is not used to obtain the propyzamide product. Compared with the existing synthesis method, the route in the invention avoids high-activity acyl chloride reagent and expensive and easily-degradable alkynyl amine substance, and the route is overall simple, economic, environment-friendly, safe and efficient, and has strong industrial application potential.

Description

Oxidation reaction-based synthesis method of propyzamide

Technical Field

The invention belongs to the field of organic chemical synthesis of pesticide molecules, and particularly relates to a method for preparing and industrializing propyzamide, a pesticide molecule, by using an independently designed and innovative synthesis method.

Background

Propyzamide (also known as propyzamide) belongs to amide herbicides. It is suitable for small-grain leguminous crops, peanuts, soybeans, potatoes, lettuce and certain orchard economic crops. At present, the herbicide for peanut fields is limited by the safety of crops, and only a single herbicide with limited fungicide spectrum is often selected, so that the production of weeds in peanut fields cannot be completely and effectively controlled. In addition, some herbicides are prone to residual toxicity to current season crops or succeeding crops due to factors such as high water solubility, long field duration, large dosage, uneven application and the like. Studies have found that propyzamide can avoid the problem. Meanwhile, synergistic compounding of the herbicide is a good measure for expanding the weed control spectrum and improving the control effect, and the propyzamide can be usually compounded with other herbicides such as glufosinate-ammonium, halosulfuron-methyl, oxyfluorfen and the like to achieve a better comprehensive effect. In conclusion, propyzamide is a herbicide with wide application and good effect, and the industrial synthesis thereof is an important research subject in the modern agricultural field.

Chemical structure of propyzamide

At present, the synthesis of propyzamide mainly adopts the following two modes:

in the first method, 3, 5-dichlorobenzonitrile is used as a raw material and reacts with 3-methyl-3-hydroxybutyne under the catalysis of Lewis acid (usually zinc dichloride) to generate the propyzamide product. The method has the defects that 3, 5-dichlorobenzonitrile has certain toxicity, and the reaction catalyst is heavy metal salts, so that the pollution is serious. The reaction type is rearrangement reaction, the yield is low, and the product purity is not high.

In the second method, 3, 5-dichlorobenzoyl chloride is used as a raw material, 3-methyl-3-aminobutyne is used as a nucleophile in the presence of alkali, and the condensation reaction is carried out on the raw material and the nucleophile to generate the propyzamide product.

The 3, 5-dichlorobenzoyl chloride used in the method is a high-activity acidic reagent, is easy to hydrolyze to generate acid mist, and is not safe in production and personnel safety. In addition, 3-methyl-3-aminobutyne is expensive, and the compound is unstable and is easy to oxidize or generate self-polymerization reaction to generate complex impurities, so that the quality of raw materials is reduced, and the reaction yield is influenced.

In conclusion, there is a need for improvement of the synthesis process of propyzamide.

Disclosure of Invention

Aiming at the defects of the prior art, the invention provides an independently designed and innovative synthesis method for solving the problems of high cost, high safety risk, high toxicity and the like in the synthesis of propyzamide. The synthesis method has the innovation point that a reverse synthesis analysis mode is adopted, cheap, safe and clean 3, 3-dichlorobenzoic acid is used as a raw material for reaction, and the use of a high-toxicity reagent is avoided.

The synthesis method of propyzamide provided by the invention comprises the following steps: 3, 5-dichlorobenzoic acid is used as a raw material and is subjected to condensation reaction with 2-amino-2-methyl-1-propanol under the action of a coupling reagent, and a product is subjected to oxidation and alkynylation reaction to generate an propyzamide product. The reaction process is as follows:

according to one embodiment of the invention, the synthesis method comprises the steps of:

s1.3, 5-dichlorobenzoyl chloride and 2-amino-2-methyl 1-propanol are subjected to condensation reaction in an organic solvent under the action of a coupling reagent to generate 3, 5-dichloro-N- (1-hydroxy-2-methylpropane-2-yl) benzamide;

s2, carrying out oxidation reaction on the 3, 5-dichloro-N- (1-hydroxy-2-methylpropane-2-yl) benzamide obtained in the step S1 in an organic solvent by using an oxidant to generate 3, 5-dichloro-N- (2-methyl-1-oxopropane-2-yl) benzamide;

s3, performing an alkynylation reaction on the 3, 5-dichloro-N- (2-methyl-1-oxoprop-2-yl) benzamide obtained in the step S2 by using (1-diazo-2-oxopropyl) phosphonic acid dimethyl ester to generate 3, 5-dichloro-N- (2-methylbut-3-alkyne-2-yl) benzamide, namely the propyzamide product.

In step S1, a condensation reaction is performed in an organic solvent using a coupling reagent: the coupling reagent is N, N' -carbonyldiimidazole, dicyclohexylcarbodiimide, diisopropylcarbodiimide, 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and hydroxybenzotriazole; the organic solvent is at least one of dichloromethane, tetrahydrofuran, N-dimethylformamide, methanol, ethanol and isopropanol or a combination thereof, preferably, the coupling reagent is N, N' -carbonyldiimidazole, and the organic solvent is dichloromethane. In step S2, an oxidation reaction is performed in an organic solvent using an oxidizing agent: the oxidant is dess-martin reagent, pyridinium chlorochromate (PCC), Pyridinium Dichromate (PDC) or oxalyl chloride/dimethyl sulfoxide; the organic solvent is at least one of dichloromethane tetrahydrofuran, N-dimethylformamide, methanol, ethanol and isopropanol or a combination thereof, preferably, the oxidant is dess-martin reagent, and the organic solvent is dichloromethane.

Compared with the existing synthesis mode, the synthesis route provided by the invention has the following advantages:

1. the synthesis route provided by the invention does not relate to noble and heavy metal catalysts, and has low cost;

2. the synthetic route provided by the invention does not relate to high-toxicity substances, and is clean and green.

The synthetic route provided by the invention has relatively mild reaction conditions, solves a plurality of defects of the existing route, and has great commercial value and potential.

Drawings

FIG. 1 is a NMR spectrum of 3, 5-dichloro-N- (1-hydroxy-2-methylpropan-2-yl) benzamide;

FIG. 2 is a NMR spectrum of 3, 5-dichloro-N- (2-methyl-1-oxoprop-2-yl) benzamide;

FIG. 3 shows the NMR spectrum of 3, 5-dichloro-N- (2-methylbut-3-yn-2-yl) benzamide, propyzamide.

Example one

An original bottom flask is taken and internally provided with a stirrer. 3, 5-Dichlorobenzoic acid (2.00 g, 10.47 mmol) and dichloromethane (20 ml) were added thereto, followed by stirring, and N, N' -dicarbonylimidazole (1.87 g, 11.52 mmol) was added thereto, followed by stirring for 30 minutes, followed by reaction until the system was clear. 2-amino-2-methyl-1-propanol (1.03 g, 11.52 mmol) was added to the reaction system, and the reaction was carried out at ordinary temperature for 1 hour. After completion of the reaction, water (40 ml) and methylene chloride (20 ml) were added to the reaction system, and the organic phase (lower layer) was separated and the aqueous phase was extracted 3 times with methylene chloride (10 ml). And combining the organic phases, and concentrating to dryness to obtain a crude product of the 3, 5-dichloro-N- (1-hydroxy-2-methylpropane-2-yl) benzamide, wherein the crude product is a light yellow oily substance, the yield is 89%, and the content is 92% by nuclear magnetic spectrum calculation. The crude product was used directly in the next reaction.

Example two

An original bottom flask is taken and internally provided with a stirrer. 3, 5-dichloro-N- (1-hydroxy-2-methylpropan-2-yl) benzamide (2.05 g, 7.82 mmol) and dichloromethane (10 ml) were added thereto, and the mixture was stirred until the system was clear. To this was added dess-martin reagent (3.65 g, 8.60 mmol) and water (0.1 ml), and the reaction was carried out at ordinary temperature for 1 hour. After completion of the reaction, a saturated sodium hydrogencarbonate solution (5 ml) was added thereto and reacted for 5 minutes. The organic phase was separated, the aqueous phase was extracted 3 times with dichloromethane (5 ml), the organic phases were combined and washed with saturated sodium thiosulfate solution (5 ml) and concentrated to dryness. 3, 5-dichloro-N- (2-methyl-1-oxoprop-2-yl) benzamide was obtained as a white solid with a yield of 95% and a purity of 95% by NMR. The product was used directly in the next reaction.

EXAMPLE III

A round bottom flask is provided with a stirrer. To this was added 3, 5-dichloro-N- (2-methyl-1-oxoprop-2-yl) benzamide (2.59 g, 10.0 mmol), (1-diazo-2-oxopropyl) phosphonic acid dimethyl ester (1.92 g, 10.0 mmol), potassium carbonate (2.76 g, 20.0 mmol) and methanol (20 ml). After the mixture was allowed to react at room temperature for 4 hours, it was concentrated to 5 ml, ethyl acetate (50 ml) and water (20 ml) were added thereto, and the organic phase was separated and concentrated to dryness. Recrystallizing the obtained white solid in an ethyl acetate/petroleum ether system to obtain the pure propyzamide, wherein the pure propyzamide is white needle-shaped crystals, the yield is 88%, and the purity is 98% by nuclear magnetic spectrum calculation.

Claims

1. A method for synthesizing propyzamide is characterized in that: the method comprises the steps of taking 3, 5-dichlorobenzoic acid as a raw material, carrying out condensation reaction with 2-amino-2-methyl-1-propanol under the action of a coupling reagent, and carrying out oxidation and alkynylation reactions on a product to generate a propyzamide product, wherein key intermediates are 3, 5-dichloro-N- (1-hydroxy-2-methylpropane-2-yl) benzamide (formula II) and 3, 5-dichloro-N- (2-methyl-1-oxypropylene-2-yl) benzamide.

2. The method of claim 1, wherein the product is 3, 5-dichloro-N- (2-methylbut-3-yn-2-yl) benzamide, propyzamide; the synthesis method is characterized by comprising the following steps:

3, 5-dichlorobenzoyl chloride and 2-amino-2 methyl 1-propanol are subjected to condensation reaction in an organic solvent under the action of a coupling reagent to generate 3, 5-dichloro-N- (1-hydroxy-2-methylpropane-2-yl) benzamide;

carrying out oxidation reaction on the 3, 5-dichloro-N- (1-hydroxy-2-methylpropan-2-yl) benzamide obtained in the step S1 in an organic solvent by using an oxidant to generate 3, 5-dichloro-N- (2-methyl-1-oxoprop-2-yl) benzamide;

performing an alkynylation reaction on the 3, 5-dichloro-N- (2-methyl-1-oxoprop-2-yl) benzamide obtained in the step S2 by using (1-diazo-2-oxopropyl) phosphonic acid dimethyl ester to generate 3, 5-dichloro-N- (2-methylbut-3-yn-2-yl) benzamide, namely the propyzamide product, preferably, in the step S1, the coupling reagent is N, N' -carbonyldiimidazole, and the organic solvent is dichloromethane; in step S2, the oxidant is dess-martin reagent and the organic solvent is dichloromethane.

3. The compound 3, 5-dichloro-N- (1-hydroxy-2-methylpropan-2-yl) benzamide is shown as the following formula II,

。

4. use of a compound according to claim 3 for the synthesis of 3, 5-dichloro-N- (2-methyl-1-oxoprop-2-yl) benzamide.

5. The compound 3, 5-dichloro-N- (2-methyl-1-oxoprop-2-yl) benzamide is shown as the following formula III,

。

6. use of a compound according to claim 5 for the synthesis of 3, 5-dichloro-N- (2-methylbut-3-yn-2-yl) benzamide.

7. The synthesis method according to claim 2, wherein the condensation reaction is carried out in an organic solvent using a coupling reagent in step S1: the coupling reagent is N, N' -carbonyldiimidazole, dicyclohexylcarbodiimide, diisopropylcarbodiimide, 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and hydroxybenzotriazole; the organic solvent is at least one of dichloromethane, tetrahydrofuran, N-dimethylformamide, methanol, ethanol and isopropanol or the combination thereof,

preferably, the coupling reagent is N, N' -carbonyldiimidazole and the organic solvent is dichloromethane.

8. The synthesis method according to claim 2, wherein the oxidation reaction is carried out in an organic solvent using an oxidant in step S2: the oxidant is dess-martin reagent, pyridinium chlorochromate (PCC), Pyridinium Dichromate (PDC) or oxalyl chloride/dimethyl sulfoxide; the organic solvent is at least one or the combination of dichloromethane tetrahydrofuran, N-dimethylformamide, methanol, ethanol and isopropanol,

preferably, the oxidant is dess-martin reagent and the organic solvent is dichloromethane.