阅读说明：本技术 一种2-甲氧基乙胺的制备方法 (Preparation method of 2-methoxy ethylamine ) 是由 瞿军 吴宏祥 掌鹏程 沈润溥 于 2020-12-14 设计创作，主要内容包括：本发明涉及有机合成化工技术领域内的一种2-甲氧基乙胺的制备方法,其以N,N’-双(2-甲氧基乙基)硫脲为起始原料,溶于溶剂中,在氧化剂的参与下,经氧化反应制备2-甲氧基乙胺。本发明提供的路线步骤简短,条件温和,产品收率高,为2-甲氧基乙胺的制备提供了一种通用的新方法。(The invention relates to a preparation method of 2-methoxy ethylamine in the technical field of organic synthesis chemical industry, which takes N, N' -bis (2-methoxy ethyl) thiourea as a starting material, dissolves in a solvent, and prepares the 2-methoxy ethylamine through oxidation reaction in the presence of an oxidant. The method provided by the invention has the advantages of short steps, mild conditions and high product yield, and provides a universal new method for preparing 2-methoxy ethylamine.)

1. A preparation method of 2-methoxy ethylamine is characterized by comprising the following steps: dissolving N, N' -bis (2-methoxyethyl) thiourea as a starting material in a solvent, and preparing 2-methoxyethylamine through an oxidation reaction in the presence of an oxidant, wherein the reaction formula is as follows:

2. the method for preparing 2-methoxyethylamine according to claim 1, wherein: the oxidant selected in the reaction is one of tert-butyl peroxide, hydrogen peroxide, potassium persulfate and sodium persulfate.

3. The method for preparing 2-methoxyethylamine according to claim 2, wherein: the oxidant is potassium persulfate, and the molar ratio of the potassium persulfate to the N, N' -bis (2-methoxyethyl) thiourea is (1-4): 1.

4. the preparation method of 2-methoxyethylamine according to claim 3, wherein the molar ratio of the potassium persulfate to the N, N' -bis (2-methoxyethyl) thiourea is 3: 1.

5. a process for the preparation of a 2-methoxyethylamine according to any one of claims 1 to 4, wherein the solvent is selected from the group consisting of ethanol, acetonitrile, dichloromethane, water, acetonitrile/water.

6. The method for preparing 2-methoxyethylamine according to claim 5, wherein the solvent is a mixture of acetonitrile and water, and the volume ratio of acetonitrile to water is 1: (2.8-3.2).

7. The preparation method of 2-methoxyethylamine according to claim 6, wherein the volume ratio of acetonitrile to water is 1:3.

8. the process for preparing 2-methoxyethylamine according to any one of claims 1, 2, 3, 4, 6 and 7, wherein the reaction temperature is 60 ℃ to 90 ℃ and the reaction time is 5 to 7 hours.

9. The method of claim 8, wherein the reaction temperature is 80 ℃ and the reaction time is 6 hours.

Technical Field

The invention belongs to the technical field of organic synthesis chemical industry, and particularly relates to a novel synthesis method of 2-methoxyethylamine.

Background

2-methoxy ethylamine (formula I) is an important chemical raw material, has good nucleophilic property and active chemical property, and is widely used in the industries of chemical pharmacy, high molecular materials, flame retardants, metal ligands, fine chemicals and the like. For example, 2-methoxyethylamine can be used for synthesizing a tankyrase inhibitor (formula III) with anticancer activity, preparing a metal ligand (formula IV) with good catalytic action, synthesizing a functional material intermediate (formula VI) with good flame retardant action and the like.

At present, the preparation methods of 2-methoxyethylamine reported in the literature mainly include the following methods:

(1) in 1951, James et al used the alkaline hydrolysis of Gabriel intermediate (2-methoxy-1-phthalimide) to prepare 2-methoxyethylamine. The method has low atom economy, is easy to generate a large amount of waste residues and has great influence on the environment. Several years later, Harder et al developed the use of boron trifluoride to catalyze the reaction of cycloaminoethane with methanol to produce 2-methoxyethylamine. Compared with the James method, the method is simple to operate, has small influence on the environment, and is difficult to obtain and store raw materials. At present, the method for industrially producing the 2-methoxy ethylamine is mainly prepared by dehydrating ethylene glycol monomethyl ether and ammonia at high temperature under the catalysis of nickel or alumina, but has low reaction yield of only 6 to 17 percent and higher requirement on reaction equipment.

(2) David Milstein et al, in toluene solution, using ruthenium (Ru) metal ligand to catalytically oxidize 2-methoxyethanol to form 2-methoxyacetaldehyde and form imine intermediate with ammonia, followed by ligand insertion and ligand exchange reaction to prepare 2-methoxyethylamine; the reaction is simple to operate and has high yield of 94%, but expensive metal Ru is needed to prepare the ligand, the cost is high, and the industrial production is not easy to realize.

(3) In patent CN 103936599a, ethanolamine and benzaldehyde are used as reaction raw materials, and are heated and refluxed in toluene to generate aldimine intermediate, which is then methylated under alkaline condition, deprotected and alkalinized, and then rectified to obtain pure 2-methoxyethylamine, wherein the reaction formula is as follows:

the reaction yield is high and is 84%, but the reaction route is complicated, sodium hydroxide is needed, and the reaction equipment is corroded to a certain extent.

Disclosure of Invention

In order to overcome the defects of the method, the invention provides the preparation method of the 2-methoxy ethylamine, so that the reaction step is short, the condition is mild, the cost is low, and the yield can reach more than 80%.

Therefore, the technical scheme provided by the invention is as follows: a preparation method of 2-methoxyethylamine uses N, N' -bis (2-methoxyethyl) thiourea (formula II) as a starting material, is dissolved in a solvent, and is subjected to oxidation reaction in the presence of an oxidant to prepare the 2-methoxyethylamine, wherein the reaction formula is as follows:

the selected oxidants in the reaction are tert-butyl peroxide, hydrogen peroxide and potassium persulfate (K)₂S₂O₈) Sodium persulfate (Na)₂S₂O₈) One kind of (1).

The oxidant is preferably potassium persulfate, and the dosage molar ratio of the potassium persulfate to the N, N' -bis (2-methoxyethyl) thiourea is (1-4): 1. the optimal dosage is that the molar ratio of the potassium persulfate to the N, N' -bis (2-methoxyethyl) thiourea is 3: 1.

the solvent is selected from one of ethanol, acetonitrile, dichloromethane, water and acetonitrile/water. Preferably, the solvent is a mixed solution of acetonitrile and water, and the volume ratio of acetonitrile to water is 1: (2.8-3.2), the volume ratio of acetonitrile to water is optimally 1:3.

the reaction temperature is 60-90 deg.c, preferably 80 deg.c, and the reaction time is 5-7 hr.

Compared with the prior art, the invention has the following beneficial effects:

(1) the invention provides a new route for synthesizing 2-methoxy ethylamine, which takes N, N' -bis (2-methoxy ethyl) thiourea as a raw material to prepare the 2-methoxy ethylamine through oxidation reaction.

(2) The preparation method is simple in preparation route, and the reaction solvent meets the requirement of green chemistry.

(3) The route provided by the invention has the advantages of mild reaction conditions, simple operation and good popularization and application values.

Drawings

FIG. 1 is a nuclear magnetic hydrogen spectrum of a target compound;

FIG. 2 shows nuclear magnetic carbon spectra of the target compound.

Detailed Description

The present invention will be further described with reference to the following embodiments.

Analytical instrumentation and equipment used in the examples: nuclear magnetic resonance apparatus (AVANCE DMXIII 400M, Bruker).

Example 1: preparation of 2-methoxyethylamine

N, N' -bis (2-methoxyethyl) thiourea (19.2g, 0.1mol), 40ml acetonitrile, 120ml water, potassium persulfate (81g,0.3mol) were sequentially added to a 250ml round-bottom flask, and heated under reflux at 80 ℃ for 6 hours (GC tracing the progress of the reaction); the reaction formula is as follows:

after the reaction is finished, evaporating acetonitrile; cooling to room temperature, adding 100ml purified water, extracting with dichloromethane (40ml × 3), separating layers, drying the organic phase with anhydrous sodium sulfate, and concentrating to obtain crude product; the pure product 12.525g was obtained by distillation purification (87-90 ℃ fraction collected) with a yield of 83.5%.

Nuclear magnetic hydrogen spectrum and nuclear magnetic carbon of productThe spectral data are as follows:¹H NMR(400MHz,CDCl₃)δ3.38(t,J＝5.2Hz,2H)，3.34(s,3H),2.82(t, J＝5.2Hz,2H),1.56(s,2H).

¹³C NMR(100MHz,CDCl₃)δ77.03,58.91,41.94.

the structural formula of the product is shown as the following formula I:

example 2: screening of oxidizing Agents

The experimental conditions and the charge amount in this example were the same as in example 1, and different oxidizing agents (3 times (molar ratio) of the raw material II) were selected for the experiment, and the specific conditions and charge amounts are shown in table 1:

TABLE 1

	Oxidizing agent	Yield of
			1	tert-Butanol peroxide	46.2％
2	Hydrogen peroxide solution	13.5％
			3	Potassium persulfate	83.5％
4	Sodium persulfate	78.3％

As can be seen from table 1, when hydrogen peroxide was selected as the oxidant, the reaction yield was the lowest, only 13.5%, when sodium persulfate was selected as the oxidant, the reaction yield was 78.3%, and when potassium persulfate was selected as the oxidant, the reaction yield was the highest, 83.5%; in summary, potassium persulfate is preferred as the reaction oxidant in the present invention.

Example 3: potassium persulfate (K)₂S₂O₈) Screening of dosage

The experimental conditions and the amount of the feed in this example were the same as in example 1, and different dosages of K were selected₂S₂O₈Experiments were performed as shown in table 2:

TABLE 2

	Dosage (mol)	Yield of
			1	0.1	58.5％
2	0.2	71.3％
			3	0.3	83.5％
4	0.4	84.0％

As can be seen from Table 2, when the amount of potassium persulfate was 0.1mol, the reaction yield was only 58.5%; when the amount is 0.3mol, the reaction yield is 83.5%, however, the reaction yield is not obviously improved by continuously increasing the amount of potassium persulfate; in conclusion, the invention selects 0.3mol of potassium persulfate to be optimal.

Example 4: screening of solvents

The experimental conditions and the charge amount of the present example were the same as those of example 1, and different reaction solvents were selected for the experiment, as shown in table 3:

TABLE 3

	Solvent(s)	Yield of
			1	Ethanol	68.0％
2	Acetonitrile	46.2％
			3	Methylene dichloride	23.5％
4	Acetonitrile/water	83.5％
			5	Water (W)	76.5％

As can be seen from table 3, the reaction yield was the lowest when dichloromethane was selected as the solvent and was only 23.5%, while the reaction yield was 76.5% when water was selected as the solvent, and the reaction yield was the highest when a mixed solvent of acetonitrile and water was selected and was 83.5%; in summary, in the present invention, a mixed solution of acetonitrile and water is preferred as the reaction solvent.

Example 5: proportional screening of mixed solvent

The experimental conditions and the charge amount in this example were the same as those in example 1, and the experiment was carried out by selecting different solvent mixing ratios, as shown in table 4:

TABLE 4

	Acetonitrile: water (W)	Yield of
			1	1:1	65.2％
2	1:2	73.7％
			3	1:2.5	76.8％
4	1:2.8	83.3％
			5	1:3	83.5％
6	1:3.2	83.5％
			7	1:4	83.6％
8	1:5	83.5％

As can be seen from table 4, when the mixing ratio of acetonitrile and water is 1:1, the reaction yield is the lowest, only 65.2%, and when the mixing ratio of acetonitrile and water is 1:2, the reaction yield is 73.7%, when the mixing ratio of acetonitrile and water is 1:2.8, the reaction yield is 83.3%, when the mixing ratio of acetonitrile and water is 1:3, 1:3.2, the reaction yield is the highest, 83.5%, however, when the amount of water is continuously increased, the reaction yield is not significantly improved; in summary, the invention selects the mixing ratio of acetonitrile and water as 1: (2.8-3.2), preferably 1:3.

Example 6: screening of reaction temperature

The experimental conditions and the charge amount in this example were the same as those in example 1, and different reaction temperatures were selected for the experiment, as shown in table 5:

TABLE 5

	Temperature of	Yield of
			1	60	55.3％
2	70	71.5％
			3	80	83.5％
4	90	81.0％

As can be seen from Table 5, the reaction yield was the lowest at 60 ℃ and was only 55.3%, the reaction yield increased significantly with the increase of the reaction temperature, and the reaction yield was the highest at 83.5% when the selection reaction temperature was 80 ℃, but the reaction yield decreased with the continued increase of the temperature; in summary, the reaction temperature is 80 ℃.

The present invention is not limited to the above-mentioned embodiments, and based on the technical solutions disclosed in the present invention, those skilled in the art can make some substitutions and modifications to some technical features without creative efforts according to the disclosed technical contents, and these substitutions and modifications are all within the protection scope of the present invention.