阅读说明：本技术 一种三酮类化合物的合成方法 (Synthetic method of triketone compound ) 是由 关爱莹 芦志成 刘鹏飞 李慧超 杨萌 叶艳明 刘长令 于 2021-06-16 设计创作，主要内容包括：本发明属于有机合成领域,本发明提供了一种三酮类化合物的合成方法,由烯醇酯于溶剂中,在氰酸盐或硫氰酸盐的存在下,发生反应并进行重排,获得目标物三酮类化合物。本发明提供的制备方法可以广泛的用于三酮类化合物及其过程中间体的合成,制备工艺简单,反应时间短,收率高、副产低、生产成本低。(The invention belongs to the field of organic synthesis, and provides a synthesis method of a triketone compound. The preparation method provided by the invention can be widely used for synthesizing triketone compounds and process intermediates thereof, and has the advantages of simple preparation process, short reaction time, high yield, low byproduct and low production cost.)

1. A synthetic method of triketone compounds is characterized in that enol ester reacts in a solvent in the presence of cyanate or thiocyanate and is rearranged to obtain target triketone compounds.

2. The synthesis method according to claim 1, wherein the enol ester shown in the formula II is reacted and rearranged in a solvent in the presence of a solvent containing cyanide or thiocyanate, so as to obtain the triketone compound shown in the formula I; wherein, the structural formulas of the compounds of the formula I and the formula II are as follows,

wherein the content of the first and second substances,

R₁、R₂are respectively selected from C₁-C₄Alkyl radical, C₁-C₄Alkoxy, or R₁、R₂The carbon atoms connected with the carbon atoms form five, six and seven-membered rings containing carbon or oxygen, and the structures are shown as follows:

Y、Y₁、Y₂、Y₃、Y₄、Y₅、Y₆、Y₇、Y₈same or different from O, S or

Q is selected from one of the groups shown below:

3. a synthesis process according to claim 1 or 2, characterized in that the molar ratio of cyanate or thiocyanate to enol ester is between 1.0 and 2.0.

4. The synthesis method according to claim 1 or 2, characterized in that the solvent is a polar organic solvent or a non-polar organic solvent.

5. The synthesis method according to claim 1 or 2, wherein the cyanate or thiocyanate is one or more of Sodium cyanate (Sodium cyanate), potassium cyanate, ammonium cyanate, calcium cyanate, cesium cyanate, magnesium cyanate, ferrous cyanate, iron cyanate, nickel cyanate, copper cyanate, Sodium thiocyanate, potassium thiocyanate or ammonium thiocyanate.

6. The synthesis method according to claim 2, wherein the rearrangement reaction is carried out at a temperature of 20 to 80 ℃ for 0.5 to 5 hours.

7. The synthesis method according to claim 2, wherein when the rearrangement reaction is carried out in a part of organic solvent, a phase transfer catalyst can be added to accelerate the reaction; wherein the addition amount of the phase transfer catalyst is 1-30% (mass fraction) of the mass of the enol ester.

Technical Field

The invention belongs to the field of organic synthesis, and particularly relates to a synthetic method of a triketone compound (a dicarboximide compound).

Background

Up to now, the method commonly used for preparing such dicarboximide compounds is by the reaction of benzoyl isocyanate and enol. Arbuzov, B.A. et al (BA Arbuzov, Zobova N, Dautova L A. ChemInformim Abstract: Reaction of Acyl (Aroyl) Isocyanates with Dimedone [ J ]. Chemischer informationsenst, 1982,13(20):115-116) reacted benzoylisocyanate with 3-hydroxy-5, 5-dimethylcyclohexanone at 60-70 ℃ to give the triketone compound in 51% yield with 25% by-product.

The above known methods have disadvantages in that the reaction is liable to produce by-products, or the reaction time is long, the conversion is low, resulting in a low yield; or unsafe reagents are used, and the discharge amount of three wastes is large, thereby causing environmental pollution.

Disclosure of Invention

The invention aims to provide a synthetic method for generating triketone herbicides (dicarboximide compounds) by enol ester reaction rearrangement, which has the advantages of simple synthetic process, high conversion rate and high yield.

In order to achieve the purpose, the invention adopts the technical scheme that:

a process for synthesizing triketone herbicide includes such steps as reaction of enol ester in solvent in the presence of cyanate or thiocyanate, and rearrangement to obtain triketone compound.

Further, in a solvent, in the presence of a solvent containing a cyanide salt or a thiocyanate, reacting and rearranging the enol ester shown in the formula II with the cyanate salt or the thiocyanate salt in the solvent to obtain the triketone compound shown in the formula I; wherein, the structural formulas of the compounds of the formula I and the formula II are as follows,

wherein the content of the first and second substances,

R₁、R₂are respectively selected from C₁-C₄Alkyl radical, C₁-C₄Alkoxy, or R₁、R₂Connected theretoThe carbon atoms form five, six and seven-membered rings containing carbon or oxygen, and the structures are shown as follows:

Y、Y₁、Y₂、Y₃、Y₄、Y₅、Y₆、Y₇、Y₈same or different from O, S or

Q is selected from one of the groups shown below:

the molar ratio of the cyanate or thiocyanate to the enol ester of the formula II is 1.0-2.0; preferably 1.1 to 1.5;

the solvent is a polar organic solvent or a non-polar organic solvent;

further, the enol ester represented by the formula II, the dissolved cyanate or thiocyanate, and the solvent used in the reaction and rearrangement may be the same or different polar organic solvents or non-polar organic solvents

The polar organic solvent is acetonitrile, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, hexamethylphosphoric triamide (HMPA), tetrahydrofuran, methyl isobutyl ketone, ethyl acetate and 1, 3-dimethyl-2-imidazolidinone.

The non-polar organic solvent is: toluene, xylene, chlorobenzene, dichloromethane, dichloroethane, chloroform, carbon tetrachloride.

The cyanate or thiocyanate is one or more of Sodium cyanate (Sodium cyanate), potassium cyanate, ammonium cyanate, calcium cyanate, cesium cyanate, magnesium cyanate, ferrous cyanate, ferric cyanate, nickel cyanate, copper cyanate, Sodium thiocyanate, potassium thiocyanate or ammonium thiocyanate.

The rearrangement reaction is carried out at the temperature of 20-80 ℃ for 0.5-5 hours; preferably at 20-60 ℃ and the reaction time is 1-2.5 hours.

The conversion speed and the reaction time of the rearrangement reaction are related to the temperature, the temperature is low, the reaction time is long, the temperature is high, and the reaction time is short, but the method is usually 1-2 hours.

When the rearrangement reaction is carried out in a nonpolar organic solvent, a phase transfer catalyst can be added to accelerate the reaction; wherein the addition amount of the phase transfer catalyst is 1-30% (mass fraction) of the mass of the enol ester.

The phase transfer catalyst may be selected from one or two of the phase transfer catalysts conventional in the art, such as PEG-200, PEG-400, PEG-600, 18 crown-6, 15 crown-5, cyclodextrin, benzyltriethylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium hydrogen sulfate, tetramethylammonium bromide, tributylmethylammonium chloride, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride, tetradecyltrimethylammonium chloride, pyridine, tributylamine, methyltriphenylphosphonium bromide, tetrabutylphosphonium bromide, 1, 8-diazabicycloundecen-7-ene (DBU), or triethylenediamine.

The content of the product in the preparation process is determined by adopting an external standard method through high performance liquid chromatography.

In addition, the enol ester starting material (compound of formula II) used in the present invention, as well as the cyanate, thiocyanate and/or phase transfer catalyst, can be obtained commercially or prepared according to the prior art.

The invention has the advantages that:

the method uses a single reagent of cyanate or thiocyanate to complete the rearrangement reaction from enol ester to triketone target compounds in an organic solvent in a short time, thereby avoiding the problems of complicated operation, byproduct generation, long reaction time, low conversion rate and low yield caused by adding too many reagents into a reaction system; meanwhile, unsafe reagents are avoided, so that the discharge amount of three wastes is reduced, and the environment is protected; cheap and easily obtained cyanate or thiocyanate is used, so that the process is further simplified, and the production cost is effectively reduced; the reaction system of the invention is not easy to produce by-products, the conversion rate is high, and the method is easy for industrialized production.

Some of the compounds of the present invention can be illustrated by the specific compounds listed in Table 1, but are not intended to limit the present invention.

TABLE 1

Detailed Description

The following specific examples are intended to further illustrate the invention, but the invention is by no means limited to these examples; and the percentages referred to in the following examples are all mass percentages, such as content, purity, etc.

The starting materials (compounds of formula II) used according to the invention, as well as the cyanates, thiocyanates and/or phase transfer catalysts, can be obtained commercially or prepared according to the state of the art.

Example 1

Adding 2.34g (0.036mol) of sodium cyanate and 50mL of N, N-dimethylformamide into a reaction bottle, then dropwise adding 30mL of N, N-dimethylformamide solution of 9.81g (0.03mol) of enol ester II-1-1 into the reaction bottle, stirring at room temperature for 2 hours after the addition, monitoring the reaction completion by HPLC, pouring the reaction solution into ice water, adjusting the pH to about 1.5 by using dilute hydrochloric acid, filtering the solid, washing with water and drying in the air to obtain 8.40g of light yellow solid I-1-1 with the content of 97% (HPLC normalization). The yield thereof was found to be 75.6%. Melting point: 124 ℃ and 126 ℃.

Example 2

Adding 2.15g (0.033mol) of sodium cyanate and 50mL of dimethyl sulfoxide into a reaction bottle, then dropwise adding 10.20g (0.03mol) of 30mL of dimethyl sulfoxide solution of enol ester II-1-6, stirring at room temperature for reaction for 1 hour after the addition is finished, monitoring the reaction completion by HPLC, pouring the reaction liquid into ice water, adjusting the pH to about 1.5 by using dilute hydrochloric acid, filtering the solid, washing with water and drying in the air to obtain 10.49g of yellow solid I-1-6 with the content of 98% (HPLC normalization). The yield thereof was found to be 91.5%. Melting point: 212 ℃ and 214 ℃.

Example 3

Adding 10.73g (0.165mol) of sodium cyanate and 300mL of N, N-dimethylformamide into a reaction bottle, then adding 50.85g (0.15mol) of 100mL of N, N-dimethylformamide solution of enol ester II-1-6 dropwise, stirring at room temperature for 2 hours after the addition, monitoring the reaction completion by HPLC, pouring the reaction solution into ice water, adjusting the pH to about 1.5 by using dilute hydrochloric acid, filtering the solid, washing with water and drying in the air to obtain 52.20g of yellow solid I-1-6 with the content of 99% (HPLC normalization). The yield thereof was found to be 91.1%.

Example 4

Adding 10.73g (0.165mol) of sodium cyanate and 300mL of N, N-dimethylformamide into a reaction bottle, then dropwise adding 56.77g (0.15mol) of 100mL of N, N-dimethylformamide solution of enol ester II-2-10, stirring at room temperature for reaction for 1.5 hours after the addition is finished, monitoring the reaction completion by HPLC, pouring the reaction solution into ice water, adjusting the pH to about 1.5 by using dilute hydrochloric acid, filtering the solid, washing with water and drying in the air to obtain 55.89g of white solid I-2-10 with the content of 99% (HPLC normalization) and the yield of 88.5%. Melting point: 181 ℃ and 183 ℃.

Example 5

10.73g (0.165mol) of sodium cyanate and 300mL of N, N-dimethylformamide are added into a reaction bottle, then 66.0g (0.15mol) of 100mL of N, N-dimethylformamide solution of enol ester II-1-11 is dropwise added into the reaction bottle, after the addition is finished, the reaction is stirred at room temperature for 1.5 hours, HPLC monitors that the reaction is complete, the reaction solution is poured into ice water, diluted hydrochloric acid is used for adjusting the pH value to about 1.5, the solid is filtered, washed by water and dried in the air, 63.46g of yellow solid I-1-11 is obtained, the content is 98% (HPLC normalization), and the yield is 87.6%. Melting point: 145-147 ℃.

Example 6

Adding 14.58g (0.18mol) of potassium cyanate and 200mL of N-methylpyrrolidone into a reaction bottle, then dropwise adding 37.73g (0.15mol) of 80mL of N-methylpyrrolidone solution of enol ester II-3-2, stirring and reacting at room temperature for 1 hour after the addition is finished, monitoring the reaction completion by HPLC, pouring the reaction solution into ice water, adjusting the pH to about 1.5 by using dilute hydrochloric acid, filtering the solid, washing and drying in the air to obtain 37.11g of yellow solid I-3-2 with the content of 97% (HPLC normalization) and the yield of 84.02%. Melting point: 129-131 ℃.

In addition, the compound shown in the formula I with different substituents can be obtained by changing different substituents of raw materials in the reaction formula according to the description of the preparation process, and the application of the method of the invention is also shown.

Other compounds of the invention may be prepared by reference to the above examples.

The physical and nuclear magnetic data (1HNMR, 600MHz, internal standard TMS, ppm) of some compounds are as follows:

compound I-1-1: yellow solid, melting point 124-. Delta (CDCl3)12.49(s,1H, NH), 8.88-8.80 (m,1H, phenyl-3-H), 8.41-8.32 (m,1H, phenyl-6-H), 7.73-7.65 (m,1H, phenyl-5-H),3.18–3.16(s,3H,SO₂CH₃),2.50(s,3H,COCH₃),2.26(s,3H,CH₃)。

Compounds I-1-6: yellow solid, melting point 212-. δ (CDCl3)12.61(s,1H, NH),8.79(d, J ═ 1.7Hz,1H, phenyl-3-H),8.29(dd, J ═ 7.9,1.7Hz,1H, phenyl-6-H),7.63(d, J ═ 7.9Hz,1H, phenyl-5-H),3.17(s,3H, CH, H)₃),2.69(t,J＝6.4Hz,2H,Cyclohexyl-5,5-2H),2.61–2.53(m,2H,Cyclohexyl-3,3-2H),2.05–1.98(m,2H,Cyclohexyl-4,4-2H)。

Compounds I-1-10: white solid, melting point 246-248 ℃. δ (CDCl3)12.11(s,1H, NH),8.84(d, J ═ 1.7Hz,1H, phenyl-3-H),8.34(dd, J ═ 7.9,1.7Hz,1H, phenyl-6-H),8.04(dd, J ═ 8.0,1.6Hz,1H, phenyl-5-H),7.78(ddd, J ═ 8.7,7.3,1.6Hz,1H, phenyl-6-H),7.70(d, J ═ 7.9Hz, phenyl-5-H), 7.44-7.39 (m,2H, phenyl-7,8-2H),3.19(s,3H, CH-3H, and the like₃)。

Compounds I-1-11: yellow solid, melting point 145-147 ℃. δ (CDCl3)12.49(s,1H, NH),8.78(d, J ═ 2.0Hz,1H, phenyl-3-H),8.28(dd, J ═ 8.0,1.9Hz,1H, phenyl-6-H),7.63(t, J ═ 8.3Hz,1H, phenyl-5-H), 3.96-3.79 (m,2H, NCH)₂),3.21–3.13(s,3H,SO₂CH₃),2.74(t,2H,CH₂),1.55(s,9H,3CH₃)。

Compound I-2-6: yellow solid, melting point 139-141 ℃. δ (CDCl3)12.73(s,1H, NH),8.01(d, J ═ 1.9Hz,1H, phenyl-3-H),7.91(dd, J ═ 8.1,1.8Hz,1H, phenyl-6-H),7.65(d, J ═ 8.1Hz,1H, phenyl-5-H), 3.10-3.07 (s,3H, CH, H₃),2.73(t,J＝6.6Hz,2H,Cyclohexyl-5,5-2H),2.61–2.47(m,2H,Cyclohexyl-3,3-2H),2.03(dd,J＝8.5,5.1Hz,2H,Cyclohexyl-4,4-2H)。

Compounds I-2-10: white solid, melting point 181-. δ (CDCl3)12.23(s,1H, NH),8.09(dd, J ═ 8.0,1.6Hz,1H, phenyl-5-H),8.06(d, J ═ 1.7Hz,1H, phenyl-3-H),7.96(dd, J ═ 8.0,1.7Hz,1H, phenyl-6-H),7.79(dd, J ═ 8.7,7.3,1.6Hz,1H, phenyl-6-H),7.74(d, J ═ 8.0Hz,1H, phenyl-5-H), 7.46-7.42 (m,1H, phenyl-7-H),7.41(d, J ═ 8.5Hz,1H, phenyl-8-H),3.12 (CH, 3H, 1H, and 1H₃)。

Compound I-3-2: yellow solid, melting point 129-. Delta (CDCl3)12.74(s,1H, NH),8.52(dd,1H, pyridyl-6-H), 7.89-7.85 (m,1H, pyridyl-4-H), 7.44-7.35 (m,1H, pyridyl-5-H),2.74(t, J ═ 6.4Hz,2H, cyclohexoxyl-5, 5-2H), 2.62-2.53 (m,2H, cyclohexoxyl-3, 3-2H), 2.10-2.00 (m,2H, cyclohexoxyl-4, 4-2H).

Compound I-4-3: white solid, melting point 235-. δ (CDCl3)12.39(s,1H, NH),8.13(dd, J ═ 8.1,1.9Hz,1H, phenyl-5-H),8.02(s,1H, Pyrazolyl-5-H), 7.85-7.76 (m,1H, phenyl-6-H), 7.51-7.44 (m,1H, phenyl-7-H), 7.45-7.40 (m,1H, phenyl-8-H),7.04(t,1H, CHF)₂),4.05(s,3H,CH₃)。