阅读说明：本技术 一种乙酰胺化合物的制备方法 (Preparation method of acetamide compound ) 是由 祁昕欣 包志鹏 缪仁冠 吴小锋 于 2021-01-19 设计创作，主要内容包括：本发明公开了一种乙酰胺化合物的制备方法,包括如下步骤：将四羰基二氯化二铑,1,3-双(二苯基膦)丙烷,羰基钨、磷酸钠、碘化钠、水、硝基化合物以及碳酸二甲酯于120℃进行反应24小时,反应完全后,后处理得到所述的乙酰胺化合物。该制备方法以碳酸二甲酯既作为C1来源又作为绿色溶剂,操作简单,反应起始原料廉价易得,底物官能团容忍范围广,反应效率高。可根据实际需要合成多种乙酰胺化合物,便于操作的同时拓宽了此方法的实用性。(The invention discloses a preparation method of an acetamide compound, which comprises the following steps: the method comprises the following steps of reacting tetracarbonyl dirhodium dichloride, 1, 3-bis (diphenylphosphino) propane, tungsten carbonyl, sodium phosphate, sodium iodide, water, a nitro compound and dimethyl carbonate at 120 ℃ for 24 hours, and carrying out post-treatment after the reaction is completed to obtain the acetamide compound. The preparation method uses dimethyl carbonate as a C1 source and a green solvent, has simple operation, cheap and easily obtained reaction starting materials, wide tolerance range of substrate functional groups and high reaction efficiency. Can synthesize a plurality of acetamide compounds according to actual needs, is convenient to operate and widens the practicability of the method.)

1. a method for preparing an acetamide compound, comprising the steps of: reacting a rhodium catalyst, a ligand, tungsten carbonyl, alkali, sodium iodide, water, a nitro compound and dimethyl carbonate at 110-130 ℃ for 20-28 hours, and after the reaction is completed, performing post-treatment to obtain the acetamide compound;

the structure of the nitro compound is shown as the formula (II):

RNO₂ (II)；

the structure of the dimethyl carbonate is shown as a formula (III):

the structure of the acetamide compound is shown as the formula (I):

in the formulas (I) to (III), R is C₃-C₆Alkyl, substituted or unsubstituted aryl, heteroaryl;

the substituent on the aryl is C₁～C₂Alkoxy, trifluoromethyl, halogen, methyl, thiomethyl, or acetyl.

2. The method for producing an acetamide compound of claim 1 wherein R is t-butyl, cyclohexyl, substituted or unsubstituted phenyl, heteroaryl, naphthyl;

and the substituent on the phenyl is methoxy, ethoxy, trifluoromethyl, F, Cl, Br, methyl, thiomethyl or acetyl.

3. The method for producing an acetamide compound according to claim 1 wherein, on a molar basis, the nitro compound: tungsten carbonyl: rhodium catalyst: ligand: alkali: sodium iodide: water is 1: 1.5-2: 0.01-0.05: 0.03-0.2: 1-2: 0-0.5: 1-2.

4. The method for producing an acetamide compound of claim 1 wherein the reaction uses dimethyl carbonate as a solvent.

5. The method of claim 1, wherein the rhodium catalyst is rhodium tetracarbonyl dichloride.

6. The method for producing an acetamide compound of claim 1 where the ligand is 1, 3-bis (diphenylphosphino) propane.

7. The method of claim 1, wherein the base is sodium phosphate.

8. The method for preparing an acetamide compound of claim 1, wherein the acetamide compound is one of the compounds of formula (I-1) to formula (I-5):

Technical Field

The invention belongs to the field of organic synthesis, and particularly relates to a preparation method of an acetamide compound.

Background

Dimethyl carbonate is a low-toxicity and biodegradable compound, can be obtained by converting carbon dioxide in the atmosphere, is often used as a green solvent in organic synthesis (chem. Rev.2010,110,4554-4581), and has a very wide development prospect. Meanwhile, dimethyl carbonate is used as an important organic synthesis intermediate and has wide application in industry and fine chemistry. Under different reaction conditions, dimethyl carbonate can be used as a methoxycarbonylation reagent and also can be used as a methylation reagent to react with various nucleophiles (Green chem.2018,20, 28-85). Conventional methylating agents such as diazomethane, dimethyl sulfate, methyl iodide and the like mostly have the defects of explosiveness, toxicity/corrosiveness, high price and the like. In addition, in these methylation reactions, a stoichiometric amount of base is usually required, resulting in the generation of useless inorganic salts that require disposal. Because the dimethyl carbonate is non-toxic and environment-friendly, the dimethyl carbonate can be used as a safe and environment-friendly methyl substitute, no unnecessary inorganic salt is generated in the reaction, and the methanol and the carbon dioxide released after the reaction can be recycled and reused for synthesizing the dimethyl carbonate. Therefore, the excellent environmental protection characteristic and the diversified reactivity of the dimethyl carbonate make the dimethyl carbonate as an ideal synthetic reagent and also have a development prospect as a reaction medium, and further development is needed.

In addition, transition metal catalyzed carbonylation reactions have dramatically progressed over the past few decades and have been widely used in the production of carbonyl-containing compounds. The most representative example is the synthesis of acetic acid (Monsanto process). HI is often used as a cocatalyst during the reaction, with severe corrosive effects on the equipment. Recently, Han and coworkers developed LiI and LiBF₄Promoted RhCl₃A novel route to aryl acetates by catalyzed carbonylation of aryl methyl ethers. Therefore, the development of new methods for constructing carbonyl-containing compounds is urgent and attracts a great deal of attention from a great number of organic synthetic chemists.

Based on this, we developed a rhodium-catalyzed aminocarbonylation reaction to an acetamide compound. To our knowledge, this is the first aminocarbonylation reaction using dimethyl carbonate as both a source of C1 and a green solvent, with a cheap and readily available nitro compound as a nitrogen substitute. Dimethyl carbonate is used in rhodium-catalyzed amino carbonylation reaction, a new and sustainable approach is developed for the construction of acetamide compounds, and positive influence is generated on the future synthesis of carbonyl-containing compounds.

Disclosure of Invention

The invention provides a preparation method of an acetamide compound, which has simple steps, cheap and easily-obtained reaction raw materials, compatibility with various functional groups and good reaction applicability, and provides a new direction for the synthesis of an acetamide compound by taking dimethyl carbonate as a C1 source and a green solvent.

A method for preparing an acetamide compound, comprising the steps of: reacting a rhodium catalyst, 1, 3-bis (diphenylphosphino) propane, tungsten carbonyl, sodium phosphate, sodium iodide, water, a nitro compound and dimethyl carbonate at 110-130 ℃ for 20-28 hours, and performing post-treatment after complete reaction to obtain the acetamide compound;

the structure of the nitro compound is shown as the formula (II):

RNO₂ (II)；

the structure of the dimethyl carbonate is shown as a formula (III):

the structure of the acetamide compound is shown as the formula (I):

in the formulae (I) to (III), R is C₃-C₆Alkyl, substituted or unsubstituted aryl, heteroaryl, naphthyl;

the substituent on the aryl is C₁～C₂Alkoxy, trifluoromethyl, halogen, methyl, thiomethyl, or acetyl.

The molar ratio of the rhodium catalyst, the 1, 3-bis (diphenylphosphino) propane, the sodium phosphate, the sodium iodide and the water is 0.02:0.06:1.5:0.3: 2;

the substitution position on the aryl group of R may be ortho, para or meta.

The reaction formula is as follows:

in the present invention, the optional post-processing procedure includes: filtering, mixing the sample with silica gel, and finally purifying by column chromatography to obtain the corresponding acetamide compound, wherein the column chromatography purification is a technical means commonly used in the field.

Preferably, R is tert-butyl, cyclohexyl, substituted or unsubstituted phenyl, heteroaryl, naphthyl; the substituent on the aryl is methoxy, ethoxy, trifluoromethyl, F, Cl, Br, methyl, thiomethyl or acetyl, in this case, the nitro compound is easily obtained, and the reaction yield is high.

The nitro compound and dimethyl carbonate used for the preparation of the acetamide compound are relatively inexpensive and widely occur in nature, and preferably, the nitro compound: the catalyst is 1: 0.01-0.05; as a further preference, the nitro compound: catalyst 1: 0.02.

Preferably, the reaction time is 24 hours, and if the reaction time is too long, the reaction cost is increased, and conversely, it is difficult to ensure the completion of the reaction.

The dosage of the dimethyl carbonate can be used for better dissolving the raw materials, and the dosage of the dimethyl carbonate used by 0.5mmol of nitro compound is about 1-3 mL.

Preferably, the rhodium catalyst is rhodium dicarbonyl dichloride, among the rhodium catalysts, rhodium tetracarbonyl dichloride is relatively cheap, and the reaction efficiency is high when rhodium tetracarbonyl dichloride is used as the catalyst.

Further preferably, the acetamide compound is one of compounds represented by the formulae (I-1) to (I-5):

the compounds represented by the formulae (I-1) to (I-5) are known compounds.

In the above preparation method, the nitro compound, dimethyl carbonate, tungsten carbonyl, dicarbonyl dihidromethyl, 1, 3-bis (diphenylphosphino) propane, sodium phosphate and sodium iodide are generally commercially available products and can be conveniently obtained from the market.

Compared with the prior art, the invention has the beneficial effects that: dimethyl carbonate is used as a C1 source and a green solvent, the preparation method is simple, the operation is easy, the post-treatment is simple and convenient, the reaction starting raw materials are cheap and easy to obtain, the tolerance range of substrate functional groups is wide, and the reaction efficiency is high. Can synthesize various acetamide compounds according to actual needs, and has strong practicability.

Detailed Description

The invention is further described with reference to specific examples.

Examples 1 to 15

Adding dicarbonyl dihidromethodium chloride, 1, 3-bis (diphenylphosphino) propane (DPPP), tungsten carbonyl, sodium phosphate, sodium iodide, water, nitro compound (II) and dimethyl carbonate (III) into a 15mL sealed tube according to the raw material ratio shown in Table 1, uniformly mixing and stirring, reacting according to the reaction conditions shown in Table 2, filtering after the reaction is finished, mixing silica gel, and purifying by column chromatography to obtain a corresponding acetamide compound (I), wherein the reaction process is shown as the following formula:

TABLE 1 raw material addition amounts of examples 1 to 15

TABLE 2

In tables 1 and 2, T is the reaction temperature, T is the reaction time, Et is ethyl, Ph is phenyl, CF₃Is trifluoromethyl, Me is methyl, SMe is methylthio, OMe is methoxy and t-Bu is tert-butyl.

Structure confirmation data of the compounds prepared in examples 1 to 5:

nuclear magnetic resonance of the acetamide Compound (I-1) prepared in example 1: (¹H NMR and¹³c NMR) the data were:

¹H NMR(400MHz,CDCl₃)δ7.96(s,1H),7.36(d,J＝8.9Hz,2H),6.79(d,J＝8.9Hz,2H),3.97(q,J＝7.0Hz,2H),2.09(s,3H),1.37(t,J＝7.0Hz,3H).

¹³C NMR(101MHz,CDCl₃)δ168.9,155.5,131.0,122.0,114.5,63.5,23.9,14.7.

nuclear magnetic resonance of acetamide Compound (I-2) obtained in example 2: (¹HNMR and¹³CNMR) detection data were:

¹H NMR(400MHz,CDCl₃)δ7.71(s,1H),7.63(d,J＝8.4Hz,2H),7.55(d,J＝8.6Hz,2H),2.20(s,3H).

¹³C NMR(101MHz,CDCl₃)δ168.8,140.9,126.2(d,J＝3.4Hz),125.9,124.1(q,J＝271.5Hz),119.4,24.6.

nuclear magnetic resonance of acetamide Compound (I-3) obtained in example 3: (¹H NMR and¹³c NMR) the data were:

¹H NMR(400MHz,CDCl₃)δ7.45(d,J＝8.7Hz,2H),7.34(s,1H),7.27(d,J＝7.8Hz,2H),2.17(s,3H).

¹³C NMR(101MHz,CDCl₃)δ168.3,136.4,129.3,129.0,121.1,24.6.

nuclear magnetic resonance of acetamide Compound (I-4) obtained in example 4: (¹H NMR and¹³c NMR) the data were:

¹H NMR(400MHz,CDCl₃)δ8.07(s,1H),7.15(s,1H),6.77(d,J＝7.5Hz,1H),6.68(d,J＝7.9 Hz,1H),5.90(s,2H),2.09(s,3H).

¹³C NMR(101MHz,CDCl₃)δ168.6,147.6,144.2,132.1,113.4,107.9,103.1,101.2,24.2.

nuclear magnetic resonance of acetamide Compound (I-5) obtained in example 5: (¹H NMR and¹³c NMR) the data were:

¹H NMR(400MHz,CDCl₃)δ5.49(s,1H),3.78–3.66(m,1H),1.93(s,3H),1.89(dd,J＝12.5,3.3Hz,2H),1.73–1.65(m,2H),1.63–1.56(m,1H),1.40–1.27(m,2H),1.20–1.03(m,3H).

¹³C NMR(101MHz,CDCl₃)δ169.2,48.2,33.1,25.5,24.9,23.5.