Synthesis method of deet

Abstract

The invention relates to the technical field of chemical synthesis, in particular to a deet synthesis method which comprises the following steps: in an oxygen or air or inert atmosphere, taking 2-methyl furan and N, N-diethyl-2-acrylamide as raw materials, and performing cyclization-aromatization reaction under the catalysis of an acid catalyst to obtain deet. According to the method, 2-methyl furan and N, N-diethyl-2-acrylamide are used as raw materials, deet can be prepared in one step, the operation method is simple, the synthesis steps and time are greatly shortened, the biomass-based methyl furan raw material is used in the reaction, the great potential of replacing a traditional petroleum-based route is achieved, and the method is suitable for industrial production. The technical defects existing in a deet preparation method in the prior art are overcome.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of chemical synthesis, in particular to a synthesis method of diethyltoluamide. BACKGROUND

[0002] Diethyltoluamide (DEET, diethyltoluamide) is a widely used insecticide. Its chemical name is N, N-diethyl-m-toluamide, and its structural formula is , which is a widely used insecticide. Spraying it on the skin or clothes can avoid insect bites. Its boiling point is 297.5℃, and its density is 0.998g / cm 3 .

[0003] Existing patents and documents report that benzene ring structure is used as raw material to obtain diethyltoluamide product through multi-step or multi-component reaction. The current reaction process design includes: directly using carboxylic acid or carboxylic acid methyl ester to construct amide bond with amine; or using metal lithium reagent to condense with acyl chloride to produce one molecule of hydrochloric acid byproduct, but whether the preparation of lithium reagent or acyl chloride is very dangerous, and the reaction condition is harsh; or using a three-component tandem reaction, the operation is complicated; or using toxic reagents such as carbon monoxide, the operation is dangerous. The synthesis route is as follows:

[0004] In addition, these routes all use petroleum-based raw materials, the steps are complicated, there are many byproducts, and the operation is dangerous. SUMMARY

[0005] Based on the deficiencies of the prior art, the present application provides a synthesis method of diethyltoluamide. The present application uses 2-methylfuran and N, N-diethyl-2-propenamide as raw materials, and performs cyclization-aromatization reaction under the catalysis of an acid catalyst to obtain diethyltoluamide. The present application provides a new method for preparing diethyltoluamide in one step, which greatly shortens the synthesis steps and time, saves cost, improves production efficiency, and overcomes the technical defects of the existing diethyltoluamide preparation method.

[0006] Based on the above technical purposes, the present application adopts the following technical scheme: The present application protects a synthesis method of diethyltoluamide, which comprises the following steps: Under air or oxygen or inert atmosphere, 2-methylfuran , N, N-diethyl-2-propenamide , an acid catalyst and a solvent are mixed to perform cyclization-aromatization reaction to obtain diethyltoluamide.

[0007] Further, the solvent includes, but is not limited to, one or more of acetone, water, deuterium water, ethanol, methanol, isopropanol, n-hexane, n-pentane, cyclopentane, dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, methyl tert-butyl ether, diethyl ether, benzene, deuterated benzene, toluene, deuterated toluene, p-xylene, o-xylene, m-xylene, ethylbenzene, chlorobenzene, dichloromethane, deuterated dichloromethane, chloroform, deuterated chloroform, tetrahydrofuran, 1,4-dioxane. Preferably, p-xylene.

[0008] Further, the acid catalyst is selected from one or more of solid acid, heterogeneous acid catalyst, acidic metal salt, triflic acid, hydrochloric acid; wherein the solid acid is selected from silicotungstic acid, phosphotungstic acid or phosphomolybdic acid, the heterogeneous acid catalyst is selected from H-Y, MCM-22, MCM-41, ZCM-5 type molecular sieve, MIL-100-Fe, Cu-BTC, HUS-6-Hf or UiO-66, the acidic metal salt is selected from scandium triflate, hafnium triflate, gallium triflate, copper triflate, silver triflate, iron triflate, cerium triflate or hydrated iridium chloride. Preferably, hafnium triflate.

[0009] Further, the molar ratio of 2-methylfuran to N,N-diethyl-2-propenamide is 0.5-3:1.

[0010] Further, the molar ratio of 2-methylfuran to the acid catalyst is 1:0.01-0.1. Preferably, 1:0.05.

[0011] Further, the molar ratio of 2-methylfuran to the acid catalyst is 1:0.0025-1:0.05. In some specific implementations, the molar ratio of 2-methylfuran to the acid catalyst is 1:0.005-1:0.05. Preferably, 1:0.025.

[0012] Further, the temperature of the cyclization-aromatization reaction is 0-250°C, preferably 120-220°C, more preferably 180-210°C; the reaction time is 1-36h, preferably 5-30h, more preferably 6-24h. In some specific implementations, the reaction is preferably carried out in an oil bath.

[0013] After the reaction is completed, the reaction medium (i.e. the solvent) is removed, and the obtained residue is eluted by silica gel column chromatography to obtain the diethyltoluamide.

[0014] Compared with the prior art, the present application has the following advantages: 1. The present application takes 2-methylfuran and N,N-diethyl-2-propenamide as raw materials, and performs cyclization-aromatization reaction under the catalysis of an acid catalyst to obtain diethyltoluamide, and the reaction principle is that 2-methylfuran first performs Diels-Alder reaction with N,N-diethyl-2-propenamide under the catalysis of an acid to obtain an intermediate product N,N-diethyl-4-methyl-7-oxabicyclo[2.2.1]hept-5-ene-2-carboxamide, then the oxygen-carbon bond of N,N-diethyl-4-methyl-7-oxabicyclo[2.2.1]hept-5-ene-2-carboxamide is broken, and a dehydration step is performed under the catalysis of an acid to obtain the target product diethyltoluamide.

[0015] 0. The present application provides a brand-new preparation method of diethyltoluamide, in which no lithium metal or acyl chloride is used as a raw material, and the problem of dangerous raw materials is overcome; in addition, the reaction can be performed in air or oxygen or an inert atmosphere, and the technical defect of harsh reaction conditions in the preparation of diethyltoluamide using lithium metal or acyl chloride as a raw material is overcome.

[0016] 1. Diethyltoluamide is prepared in one step, the synthesis steps and time are greatly shortened, and the defect of complicated operation of a three-component serial reaction is overcome.

[0017] 2. The present application takes 2-methylfuran and N,N-diethyl-2-propenamide as raw materials, and solves the safety problem caused by the use of toxic carbon monoxide reagent as a raw material in the prior art.

[0018] 3. The reaction raw materials for preparing diethyltoluamide are simple and easy to obtain, the feeding mode is simple, the obtained diethyltoluamide has high purity, and biomass-based methylfuran is used as a raw material in the reaction, which has great potential to replace traditional petroleum-based routes; the results show that the present application is not only superior to the existing preparation method of diethyltoluamide, but also has a wide application prospect. BRIEF DESCRIPTION OF DRAWINGS

[0019] Figure 1 The hydrogen spectrum of diethyltoluamide provided for Example 1 of the present application.

[0020] Figure 2 The carbon spectrum of diethyltoluamide provided for Example 1 of the present application. DETAILED DESCRIPTION

[0021] It should be understood that the expression “one or more of…” individually includes each of the objects described after the expression, as well as various different combinations of two or more of the described objects, unless otherwise understood from the context and usage. The expression “and / or” combined with three or more described objects should be understood to have the same meaning, unless otherwise understood from the context.

[0022] The terms “including,” “having,” or “containing,” including the use of their grammatical synonyms, should generally be understood as open-ended and non-restrictive, for example, not excluding other unstated elements or steps, unless otherwise specifically stated or understood from the context.

[0023] It should be understood that the order of the steps or the order in which certain actions are performed is not important as long as the invention remains operational. Furthermore, two or more steps or actions can be performed simultaneously.

[0024] The use of any and all instances or exemplary language such as “e.g.” or “including” in this document is merely intended to better illustrate the invention and is not intended to limit the scope of the invention unless the claims are made. No language in this specification should be construed as indicating that any unclaimed element is essential to the practice of the invention.

[0025] Furthermore, the numerical ranges and parameters used to define the present invention are approximate values, and the relevant values ​​in the specific embodiments have been presented as precisely as possible. However, any value inevitably contains standard deviations due to individual test methods. Therefore, unless explicitly stated otherwise, it should be understood that all ranges, quantities, values, and percentages used in this disclosure are modified with the word "approximately". Here, "approximately" generally means that the actual value is within plus or minus 10%, 5%, 1%, or 0.5% of a specific value or range.

[0026] This invention provides a method for synthesizing DEET, comprising the following steps: 2-Methylfuran in air, oxygen, or an inert atmosphere N,N-Diethyl-2-acrylamide Acid catalyst and solvent are mixed to carry out a cyclization-aromatization reaction to obtain DEET.

[0027] This invention uses 2-methylfuran and N,N-diethyl-2-acrylamide as raw materials, and reacts them in air, oxygen or an inert atmosphere under the action of an acid catalyst to prepare DEET in one step, which greatly shortens the synthesis steps and time. The reaction raw materials are simple and readily available, the feeding method is simple, and the yield and purity are high.

[0028] The synthesis method of DEET provided by the present invention will be further described below with reference to the embodiments.

[0029] Example 1 A method for synthesizing diethyltoluamide, comprising the following steps: Under air atmosphere, 0.5 mL of p-xylene was added into a reaction vessel, then 0.05 mmol of hafnium triflate, 1.0 mmol of N,N-diethyl-2-propenamide and 2.0 mmol of 2-methylfuran were added into the reaction vessel in sequence, and the reaction was carried out at 210°C for 12 h; after the reaction was completed, the solvent was removed, the residue was subjected to silica gel column chromatography, then elution was carried out using DCM:MeOH=30:1 as an eluent, and the product was collected to obtain diethyltoluamide in the form of yellow oily liquid, 97 mg, purity 94%, yield 51%.

[0030] Example 2 A method for synthesizing diethyltoluamide, comprising the following steps: Under air atmosphere, 0.5 mL of toluene was added into a reaction vessel, then 0.05 mmol of hafnium triflate, 1.0 mmol of N,N-diethyl-2-propenamide and 1.0 mmol of 2-methylfuran were added into the reaction vessel in sequence, and the reaction was carried out at 210°C for 8 h; after the reaction was completed, the solvent was removed, the residue was subjected to silica gel column chromatography, then elution was carried out using DCM:MeOH=30:1 as an eluent, and the product was collected to obtain diethyltoluamide in the form of yellow oily liquid, 78 mg, purity 93%, yield 41%.

[0031] Example 3 A method for synthesizing diethyltoluamide, comprising the following steps: Under air atmosphere, 0.5 mL of toluene was added into a reaction vessel, then 0.05 mmol of hafnium triflate, 1.0 mmol of N,N-diethyl-2-propenamide and 1.0 mmol of 2-methylfuran were added into the reaction vessel in sequence, and the reaction was carried out at 210°C for 8 h; after the reaction was completed, the solvent was removed, the residue was subjected to silica gel column chromatography, then elution was carried out using DCM:MeOH=30:1 as an eluent, and the product was collected to obtain diethyltoluamide in the form of yellow oily liquid, 78 mg, purity 93%, yield 41%.

[0032] Example 4 A method for synthesizing diethyltoluamide, comprising the following steps: Under an argon atmosphere, 0.5 mL of toluene was added to the reaction vessel, followed by 0.05 mmol of hafnium trifluoromethanesulfonate, 1.0 mmol of N,N-diethyl-2-acrylamide, and 2.0 mmol of 2-methylfuran. The reaction was carried out at 210 °C for 12 h. After the reaction was completed, the solvent was removed, and the residue was subjected to silica gel column chromatography. The residue was then eluted with a DCM:MeOH ratio of 30:1, and the product was collected to give DEET, a yellow oily liquid, 72 mg, with a purity of 96% and a yield of 38%.

[0033] Example 5 A method for synthesizing DEET includes the following steps: Under air atmosphere, 0.5 mL of toluene was added to the reaction vessel, followed by 0.5 mmol of hafnium trifluoromethanesulfonate, 10 mmol of N,N-diethyl-2-acrylamide, and 20 mmol of 2-methylfuran. The reaction was carried out at 210 °C for 12 h. After the reaction was completed, the solvent was removed, and the residue was subjected to silica gel column chromatography. The product was then eluted with a DCM:MeOH ratio of 30:1, and the product was collected to give DEET, a yellow oily liquid, 874 mg, with a purity of 94% and a yield of 46%.

[0034] Example 6 A method for synthesizing DEET includes the following steps: Under air atmosphere, 0.5 mL of n-hexane was added to the reaction vessel, followed by 0.05 mmol of phosphomolybdic acid, 2.0 mmol of N,N-diethyl-2-acrylamide, and 2.0 mmol of 2-methylfuran. The reaction was carried out at 0 °C for 36 h. After the reaction was completed, the solvent was removed, and the residue was subjected to silica gel column chromatography. The product was then eluted with a DCM:MeOH ratio of 30:1, and the product was collected to give DEET, a yellow oily liquid, 130 mg, with a purity of 96% and a yield of 34%.

[0035] Example 7 A method for synthesizing DEET includes the following steps: Under air atmosphere, 0.5 mL of methyl tert-butyl ether was added to the reaction vessel, followed by the sequential addition of 3 mmol of MCM-22, 1.0 mmol of N,N-diethyl-2-acrylamide, and 3.0 mmol of 2-methylfuran. The reaction was carried out at 250 °C for 1 h. After the reaction was completed, the solvent was removed, and the residue was subjected to silica gel column chromatography. The residue was then eluted with a DCM:MeOH ratio of 30:1, and the product was collected to give DEET, a yellow oily liquid, 80 mg, with a purity of 97% and a yield of 42%.

[0036] The reaction processes of Examples 1 through 7 are all as follows: The product prepared in Example 1 was subjected to NMR analysis, and the results are shown in [reference needed]. Figure 1 and Figure 2 , Figure 1 This is the hydrogen spectrum of DEET provided in Example 1 of the present invention. Figure 2 The carbon spectrum of DEET provided in Example 1 of this invention is shown below. Its NMR data are as follows:

[0037] 1 ¹H NMR (600 MHz, Chloroform-d) δ 7.36–7.09 (m, 4H), 3.57 (q, 2H), 3.28 (q, 2H), 2.39 (s, 3H), 1.27 (t, 3H), 1.12 (t, 3H). (The singlets at 3.57 / 3.28 / 1.27 / 1.12 in the graph are due to the influence of amide bonds; the actual peaks are q and t.) 13 C NMR (151MHz, Chloroform-d) δ 171.5, 138.2, 137.3, 129.8, 128.2, 127.0, 123.2, 43.2, 39.2, 21.4, 14.2, 12.9.

[0038] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method of synthesizing diethyltoluamide, characterized by, Includes the following steps: DEET is obtained by cyclization-aromatization reaction of 2-methylfuran and N,N-diethyl-2-acrylamide as raw materials in air, oxygen or an inert atmosphere, under acid catalyst and solvent conditions.

2. The method for synthesizing DEET according to claim 1, characterized in that, The molar ratio of 2-methylfuran to N,N-diethyl-2-acrylamide is 0.5 to 3:

1.

3. The method for synthesizing DEET according to claim 1, characterized in that, The acid catalyst is selected from one or more of the following: solid acid, heterogeneous acid catalyst, acidic metal salt, trifluoromethanesulfonic acid, and hydrochloric acid.

4. The method for synthesizing DEET according to claim 3, characterized in that, The solid acid is selected from silicotungstic acid, phosphotungstic acid, or phosphomolybdic acid; the heterogeneous acid catalyst is selected from HY, MCM-22, MCM-41, ZCM-5 type molecular sieve, MIL-100-Fe, Cu-BTC, HUS-6-Hf, or UiO-66; and the acidic metal salt is selected from scandium trifluoromethanesulfonate, hafnium trifluoromethanesulfonate, gallium trifluoromethanesulfonate, copper trifluoromethanesulfonate, silver trifluoromethanesulfonate, iron trifluoromethanesulfonate, cerium trifluoromethanesulfonate, or hydrated iridium chloride.

5. The method for synthesizing DEET according to claim 1, characterized in that, The molar ratio of 2-methylfuran to the acid catalyst is 1:0.01~0.

1.

6. The method for synthesizing DEET according to claim 5, characterized in that, The molar ratio of 2-methylfuran to the acid catalyst is 1:0.0025 to 1:0.

05.

7. The method for synthesizing DEET according to claim 1, characterized in that, The conditions for the cyclization-aromatization reaction are: reaction at 0℃~250℃ for 1h~36h.

8. The method for synthesizing DEET according to claim 7, characterized in that, The conditions for the cyclization-aromatization reaction are: reaction at 120℃~220℃ for 5h~30h.

9. The method for synthesizing DEET according to claim 8, characterized in that, The conditions for the cyclization-aromatization reaction are: reaction at 180℃~210℃ for 6h~24h.

10. The method for synthesizing DEET according to claim 1, characterized in that, The solvent is selected from one or more of the following: acetone, water, deuterated water, ethanol, methanol, isopropanol, n-hexane, n-pentane, cyclopentane, dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, methyl tert-butyl ether, diethyl ether, benzene, deuterated benzene, toluene, deuterated toluene, p-xylene, o-xylene, m-xylene, ethylbenzene, chlorobenzene, dichloromethane, deuterated dichloromethane, chloroform, deuterated chloroform, tetrahydrofuran, and 1,4-dioxane.

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