阅读说明：本技术 一种1，4-二甲基戊胺盐酸盐的制备方法 (Preparation method of 1, 4-dimethyl pentylamine hydrochloride ) 是由 唐保清 付志雄 于 2021-08-12 设计创作，主要内容包括：本发明公开一种1,4-二甲基戊胺盐酸盐的制备方法,涉及有机合成制备化学领域。本发明公开的1,4-二甲基戊胺盐酸盐的制备方法为：以5-甲基-2-己酮为原料,边搅拌边加入还原剂甲酸和甲酸铵或甲酰胺混合,升温至110～115℃反应3小时,再升温至130～135℃反应3小时,最后升温至150～160℃保温3小时,冷却,静置分层,洗涤,干燥,抽滤,得到1,4-二甲基甲酰戊胺；再将1,4-二甲基甲酰戊胺加入质量浓度为36％盐酸中,搅拌下升温回流反应,减压蒸馏,静置分层,收集下层料抽滤,经结晶干燥后,即得。本发明提供的1,4-二甲基戊胺盐酸盐的制备方法简单,原料易得,过程易控制,成本低,具有收率高、生产清洁、环保等特点,适合大批量生产。(The invention discloses a preparation method of 1, 4-dimethyl pentylamine hydrochloride, and relates to the field of organic synthesis preparation chemistry. The invention discloses a preparation method of 1, 4-dimethyl pentylamine hydrochloride, which comprises the following steps: taking 5-methyl-2-hexanone as a raw material, adding a reducing agent formic acid and ammonium formate or formamide while stirring, heating to 110-115 ℃ for reaction for 3 hours, heating to 130-135 ℃ for reaction for 3 hours, finally heating to 150-160 ℃ for heat preservation for 3 hours, cooling, standing for layering, washing, drying, and performing suction filtration to obtain 1, 4-dimethylformamidopentyl amine; and adding 1, 4-dimethylformamyl pentylamine into hydrochloric acid with the mass concentration of 36%, heating for reflux reaction under stirring, distilling under reduced pressure, standing for layering, collecting lower-layer materials, performing suction filtration, crystallizing and drying to obtain the compound. The preparation method of the 1, 4-dimethyl pentylamine hydrochloride provided by the invention is simple, the raw materials are easy to obtain, the process is easy to control, the cost is low, and the method has the characteristics of high yield, clean production, environmental protection and the like, and is suitable for mass production.)

1. A preparation method of 1, 4-dimethyl pentylamine hydrochloride is characterized by comprising the following steps:

(1) amidation: taking 5-methyl-2-hexanone as a raw material, adding a reducing agent formic acid and ammonium formate while stirring, mixing, heating, and carrying out amidation reaction to obtain 1, 4-dimethylformamyl amine;

(2) hydrolysis to form salt: hydrolyzing the 1, 4-dimethylformamyl-pentylamine in hydrochloric acid to form salt, and preparing the 1, 4-dimethylpentylamine hydrochloride.

2. A preparation method of 1, 4-dimethyl pentylamine hydrochloride is characterized by comprising the following steps:

(1) amidation: taking 5-methyl-2-hexanone as a raw material, adding reducing agents formic acid and formamide while stirring, mixing, heating, and carrying out amidation reaction to obtain 1, 4-dimethylformamyl amine;

(2) hydrolysis to form salt: hydrolyzing the 1, 4-dimethylformamyl-pentylamine in hydrochloric acid to form salt, and preparing the 1, 4-dimethylpentylamine hydrochloride.

3. The method for producing 1, 4-dimethylpentylamine hydrochloride according to claim 1 or 2, wherein the molar ratio of 5-methyl-2-hexanone to formic acid is 1:1 to 1.5.

4. The method of claim 1, 4-dimethylpentylamine hydrochloride production, wherein the molar ratio of 5-methyl-2-hexanone to ammonium formate is 1: 1.2-1.6.

5. The method for producing 1, 4-dimethylpentylamine hydrochloride according to claim 2, wherein the molar ratio of 5-methyl-2-hexanone to formamide is 1:1.2 to 1.6.

6. The method for preparing 1, 4-dimethylpentylamine hydrochloride according to claim 1 or 2, characterized in that the mass ratio of 1, 4-dimethylformylpentylamine to hydrochloric acid is 1: 2-4.

7. The method for preparing 1, 4-dimethylpentylamine hydrochloride according to claim 1 or 2, characterized in that the amidation reaction is carried out by: heating to 110-115 ℃ for reaction for 3 hours, heating to 130-135 ℃ for reaction for 3 hours, and finally heating to 150-160 ℃ for heat preservation for 3 hours.

8. The method according to claim 6, wherein the hydrochloric acid is used at a concentration of 36% by mass.

Technical Field

The invention belongs to the field of organic synthesis preparation chemistry, and particularly relates to a preparation method of 1, 4-dimethyl pentylamine hydrochloride.

Background

The 1, 4-dimethyl pentylamine hydrochloride is in the form of salt formed by hydrolyzing 1, 4-dimethyl pentylamine with hydrochloric acid, is white powder in appearance, has special odor, and is mainly used as a solvent and a catalyst for alkylation esterification and polymerization reaction. The product is mainly used in the fields of medicines and nutritional health products, is matched with low-protein diet, is used as a core medicament for preventing and treating damage caused by protein metabolic disorder caused by chronic renal insufficiency, chronic renal insufficiency and consumable malnutrition, is also used in the electroplating industry, and has very wide market prospect.

The literature methods for synthesizing 1, 4-dimethylpentylamine hydrochloride are few, and the existing synthesis method of 1, 4-dimethylpentylamine hydrochloride has the disadvantages of complex process, troublesome operation, high cost, low yield and product content less than 98 percent and cannot meet the application requirements. The invention discloses a preparation method of 1, 3-dimethylpentylamine hydrochloride, which is disclosed by CN201310437841.4, and the method is characterized in that 2-methyl butyraldehyde and nitroethane are taken as initial raw materials, in a toluene solvent, an acetic acid/ethylenediamine composite catalyst is used for carrying out catalytic condensation and dehydration to obtain a nitroolefin compound, potassium borohydride or sodium borohydride is used for reduction, palladium carbon reduction is carried out, and hydrochloric acid acidification is carried out to obtain the 1, 3-dimethylpentylamine hydrochloride. The preparation process is complex, raw material components are multiple, operation steps are multiple and troublesome, the reaction is firstly reduced by potassium borohydride or sodium borohydride and then reduced by palladium-carbon catalytic hydrogen, the hydrogenation process is involved, and the safety production is not facilitated.

The invention patent CN201010227035.0 discloses a method for synthesizing 1, 3-dimethylpentylamine hydrochloride, and the applicant adopts the reaction conditions to verify that 5-methyl-2-hexanone is used instead of 4-methyl-2-hexanone for amidation and hydrolysis to form salt, so as to obtain 1, 4-dimethylpentylamine hydrochloride, which has low yield and 98.2% of product content and cannot meet the requirements of downstream users (see comparative example 1 in the specific embodiment).

Disclosure of Invention

The invention mainly aims to provide the preparation method of the 1, 4-dimethylpentylamine hydrochloride, which has low cost, high purity and high yield, and the method has the advantages of simple and easily obtained raw materials, easy operation and suitability for mass production.

In order to realize the purpose of the invention, the invention provides a preparation method of 1, 4-dimethyl pentylamine hydrochloride, which specifically comprises the following steps:

(1) amidation: taking 5-methyl-2-hexanone as a raw material, adding a reducing agent formic acid and ammonium formate while stirring, mixing, heating, and carrying out amidation reaction to obtain 1, 4-dimethylformamyl amine;

(2) hydrolysis to form salt: hydrolyzing the 1, 4-dimethylformamyl-pentylamine in hydrochloric acid to form salt, and preparing the 1, 4-dimethylpentylamine hydrochloride.

The invention also provides a preparation method of the 1, 4-dimethyl pentylamine hydrochloride, which comprises the following steps:

(1) amidation: taking 5-methyl-2-hexanone as a raw material, adding reducing agents formic acid and formamide while stirring, mixing, heating, and carrying out amidation reaction to obtain 1, 4-dimethylformamyl amine;

(2) hydrolysis to form salt: hydrolyzing the 1, 4-dimethylformamyl-pentylamine in hydrochloric acid to form salt, and preparing the 1, 4-dimethylpentylamine hydrochloride.

Further, the molar ratio of the 5-methyl-2-hexanone to the formic acid is 1: 1-1.5.

Further, the molar ratio of the 5-methyl-2-hexanone to the ammonium formate is 1: 1.2-1.6.

Further, the molar ratio of the 5-methyl-2-hexanone to the formamide is 1: 1.2-1.6.

Further, the mass ratio of the 1, 4-dimethylformamidinate to the hydrochloric acid is 1: 2-4.

Further, the amidation reaction process is as follows: heating to 110-115 ℃ for reaction for 3 hours, heating to 130-135 ℃ for reaction for 3 hours, and finally heating to 150-160 ℃ for heat preservation for 3 hours.

Further, the mass concentration of the hydrochloric acid is 36%.

The invention achieves the following beneficial effects:

1. the product obtained by the invention is white powder, has no pungent smell, has a melting point of 125-127 ℃, and has a product content of more than 99.2%.

2. The invention adopts 5-methyl-2-hexanone as raw material, formic acid as reducing agent, and formamide or ammonium formate through amidation reaction, and then through hydrochloric acid hydrolysis salifying two-step synthesis method to obtain, the preparation method is simple, the raw material is easy to obtain, the process is easy to control, the cost is low, has the characteristics of high yield, clean production, environmental protection and the like, and is suitable for mass production.

Drawings

FIG. 1 is a schematic diagram of the reaction process for preparing 1, 4-dimethylpentylamine hydrochloride from formic acid and ammonium formate according to the present invention;

FIG. 2 is a schematic diagram of the reaction process of the present invention for preparing 1, 4-dimethylpentylamine hydrochloride from formic acid and formamide.

Detailed Description

The technical solutions in the embodiments of the present invention are clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

A preparation method of 1, 4-dimethyl pentylamine hydrochloride, the reaction process of which is shown in figure 1, comprises the following steps:

(1) amidation: taking 5-methyl-2-hexanone as a raw material, adding a reducing agent formic acid and ammonium formate while stirring, mixing, heating to 110-115 ℃ for reaction for 3 hours, heating to 130-135 ℃ for reaction for 3 hours, finally heating to 150-160 ℃ for heat preservation for 3 hours, cooling, standing for layering, washing, drying, and performing suction filtration to obtain the 1, 4-dimethylformamidopentyl amine.

(2) Hydrolysis to form salt: adding the 1, 4-dimethylformamido into hydrochloric acid with the mass concentration of 36%, heating and refluxing under stirring for reaction, carrying out reduced pressure distillation, standing for layering, collecting lower-layer materials, carrying out suction filtration, and carrying out crystallization and drying to obtain the 1, 4-dimethylvaleramine hydrochloride.

A preparation method of 1, 4-dimethyl pentylamine hydrochloride, the reaction process of which is shown in figure 2, comprises the following steps:

(1) amidation: taking 5-methyl-2-hexanone as a raw material, adding a reducing agent formic acid and formamide while stirring, heating to 110-115 ℃ for reaction for 3 hours, heating to 130-135 ℃ for reaction for 3 hours, finally heating to 150-160 ℃ for heat preservation for 3 hours, cooling, standing for layering, washing, drying, and performing suction filtration to obtain the 1, 4-dimethylformamido.

(2) Hydrolysis to form salt: adding the 1, 4-dimethylformamyl pentylamine into hydrochloric acid with the mass concentration of 36 percent, heating and refluxing for reaction under stirring, and reducing

Distilling under pressure, standing for layering, collecting the lower layer material, performing suction filtration, and crystallizing and drying to obtain the 1, 4-dimethyl pentylamine hydrochloride.

The following will describe the method for producing 1, 4-dimethylpentylamine hydrochloride according to the present invention with reference to specific examples.

Example 1:

the preparation method of the 1, 4-dimethyl pentylamine hydrochloride comprises the following steps:

(1) amine acylation: a500 mL four-necked flask was charged with 11.4g (0.1mol) of 5-methyl-2-hexanone, and 4.6g (0.1mol) of formic acid and 7.6g (0.12mol) of ammonium formate were added thereto with stirring. Heating to 110 deg.C for 3 hr, heating to 130 deg.C for 3 hr, and holding at 155 deg.C for 3 hr. After cooling to about 40 ℃, 40g of water is added. Stirring for 30 minutes, standing for layering, washing an oil layer with saturated saline three times, adding anhydrous sodium sulfate, drying overnight, and performing suction filtration to obtain 11.6g of 1, 4-dimethylformamido oil, wherein the yield is 89.9 percent and the oil is directly used for the next reaction.

(2) Hydrolysis to form salt: a500 mL four-necked flask was charged with 11.6g (0.09mol) of the 1, 4-dimethylformamylamine reacted in the above step and 29g of 36% hydrochloric acid. The reaction was refluxed for 10 hours while stirring. Vacuum distilling to dry, adding 30g purified water, stirring for 20 min, standing and demixing. Collecting the lower material water layer, adding 0.3g of activated carbon, stirring for 30 minutes, and performing suction filtration. The filtrate is decompressed and steamed to remove water until the filtrate is dry; adding 25g of petroleum ether for recrystallization, filtering to obtain a wet product, and performing vacuum drying at 75 ℃ to obtain 12.2g of white powder, wherein the yield is 89.7 percent and the purity is 99.2 percent.

Example 2

The preparation method of the 1, 4-dimethyl pentylamine hydrochloride comprises the following steps:

(1) amine acylation: a500 mL four-necked flask was charged with 11.4g (0.1mol) of 5-methyl-2-hexanone, and 6.0g (0.13mol) of formic acid and 8.8g (0.14mol) of ammonium formate were added thereto with stirring. Heating to 115 deg.C for 3 hr, heating to 135 deg.C for 3 hr, and holding at 160 deg.C for 3 hr. After cooling to about 40 ℃, 40g of water is added. Stirring for 30 minutes, standing for layering, washing an oil layer with saturated saline three times, adding anhydrous sodium sulfate, drying overnight, and performing suction filtration to obtain 11.3g of 1, 4-dimethylformamido oil, wherein the yield is 87.6 percent and the oil is directly used for the next reaction.

(2) Hydrolysis to form salt: a500 mL four-necked flask was charged with 11.3g (0.088mol) of the 1, 4-dimethylformamylamine reacted in the above step and 33g of 36% hydrochloric acid. The reaction was refluxed for 10 hours while stirring. Vacuum distilling to dry, adding 35g purified water, stirring for 20 min, standing and demixing. Collecting the lower material water layer, adding 0.3g of activated carbon, stirring for 30 minutes, and performing suction filtration. The filtrate is decompressed and steamed to remove water until the filtrate is dry; adding 25g of petroleum ether for recrystallization, filtering to obtain a wet product, and performing vacuum drying at 75 ℃ to obtain 12g of white powder, wherein the yield is 90.4 percent and the purity is 99.4 percent.

Example 3

The preparation method of the 1, 4-dimethyl pentylamine hydrochloride comprises the following steps:

(1) amine acylation: a500 mL four-necked flask was charged with 11.4g (0.1mol) of 5-methyl-2-hexanone, and 6.9g (0.15mol) of formic acid and 10.1g (0.16mol) of ammonium formate were added thereto with stirring. Heating to 115 deg.C for 3 hr, heating to 135 deg.C for 3 hr, and holding at 160 deg.C for 3 hr. After cooling to about 40 ℃, 40g of water is added. Stirring for 30 minutes, standing for layering, washing an oil layer with saturated saline three times, adding anhydrous sodium sulfate, drying overnight, and performing suction filtration to obtain 11.6g of 1, 4-dimethylformamido oil, wherein the yield is 89.7 percent and the oil is directly used for the next reaction.

(2) Hydrolysis to form salt: a500 mL four-necked flask was charged with 11.3g (0.088mol) of the 1, 4-dimethylformamylamine reacted in the above step and 33g of 36% hydrochloric acid. The reaction was refluxed for 10 hours while stirring. Vacuum distilling to dry, adding 35g purified water, stirring for 20 min, standing and demixing. Collecting the lower material water layer, adding 0.3g of activated carbon, stirring for 30 minutes, and performing suction filtration. The filtrate is decompressed and steamed to remove water until the filtrate is dry; adding 25g of petroleum ether for recrystallization, filtering to obtain a wet product, and performing vacuum drying at 75 ℃ to obtain 12.1g of white powder, wherein the yield is 90.4% and the purity is 99.2%.

Example 4

The preparation method of the 1, 4-dimethyl pentylamine hydrochloride comprises the following steps:

(1) amine acylation: a500 mL four-necked flask was charged with 11.4g (0.1mol) of 5-methyl-2-hexanone, and 4.6g (0.1mol) of formic acid and 5.4g (0.12mol) of formamide were added thereto with stirring. Heating to 110 deg.C for 3 hr, heating to 130 deg.C for 3 hr, and holding at 155 deg.C for 3 hr. After cooling to about 40 ℃, 40g of water is added. Stirring for 30 minutes, standing for layering, washing an oil layer with saturated saline three times, adding anhydrous sodium sulfate, drying overnight, and performing suction filtration to obtain 11.7g of 1, 4-dimethylformamido oil, wherein the yield is 90.7 percent and the oil is directly used for the next reaction.

(2) Hydrolysis to form salt: into a 500mL four-necked flask were charged 11.7g (0.091mol) of the 1, 4-dimethylformamylamine reacted in the above step and 32g of 36% hydrochloric acid. The reaction was refluxed for 10 hours while stirring. Vacuum distilling to dry, adding 35g purified water, stirring for 20 min, standing and demixing. Collecting the lower material water layer, adding 0.3g of activated carbon, stirring for 30 minutes, and performing suction filtration. The filtrate is decompressed and steamed to remove water until the filtrate is dry; adding 25g of petroleum ether for recrystallization, filtering to obtain a wet product, and performing vacuum drying at 75 ℃ to obtain 12.4g of white powder, wherein the yield is 90.2 percent and the purity is 99.5 percent.

Example 5

The preparation method of the 1, 4-dimethyl pentylamine hydrochloride comprises the following steps:

(1) amine acylation: a500 mL four-necked flask was charged with 11.4g (0.1mol) of 5-methyl-2-hexanone, and 6.4g (0.14mol) of formic acid and 6.3 g (0.14mol) of formamide were added thereto with stirring. Heating to 115 deg.C for 3 hr, heating to 135 deg.C for 3 hr, and holding at 150 deg.C for 3 hr. After cooling to about 40 ℃, 40g of water is added. Stirring for 30 minutes, standing for layering, washing an oil layer with saturated saline three times, adding anhydrous sodium sulfate, drying overnight, and performing suction filtration to obtain 11.6g of 1, 4-dimethylformamido oil, wherein the yield is 89.9 percent and the oil is directly used for the next reaction.

(2) Hydrolysis to form salt: a500 mL four-necked flask was charged with 11.6g (0.09mol) of the 1, 4-dimethylformamylamine obtained in the above reaction and 30g of 36% hydrochloric acid. The reaction was refluxed for 10 hours while stirring. Vacuum distilling to dry, adding 35g purified water, stirring for 20 min, standing and demixing. Collecting the lower material water layer, adding 0.3g of activated carbon, stirring for 30 minutes, and performing suction filtration. The filtrate is decompressed and steamed to remove water until the filtrate is dry; adding 25g of petroleum ether for recrystallization, filtering to obtain a wet product, and performing vacuum drying at 75 ℃ to obtain 12.4g of white powder, wherein the yield is 91 percent, and the purity is 99.4 percent.

Example 6

The preparation method of the 1, 4-dimethyl pentylamine hydrochloride comprises the following steps:

(1) amine acylation: a500 mL four-necked flask was charged with 11.4g (0.1mol) of 5-methyl-2-hexanone, and 6.9g (0.15mol) of formic acid and 7.2g (0.16mol) of formamide were added thereto with stirring. Heating to 110 deg.C for 3 hr, heating to 130 deg.C for 3 hr, and holding at 155 deg.C for 3 hr. After cooling to about 40 ℃, 40g of water is added. Stirring for 30 minutes, standing for layering, washing an oil layer with saturated saline three times, adding anhydrous sodium sulfate, drying overnight, and performing suction filtration to obtain 11.6g of 1, 4-dimethylformamido oil, wherein the yield is 90.2 percent and the oil is directly used for the next reaction.

(2) Hydrolysis to form salt: into a 500mL four-necked flask were charged 11.7g (0.091mol) of the 1, 4-dimethylformamylamine reacted in the above step and 32g of 36% hydrochloric acid. The reaction was refluxed for 10 hours while stirring. Vacuum distilling to dry, adding 35g purified water, stirring for 20 min, standing and demixing. Collecting the lower material water layer, adding 0.3g of activated carbon, stirring for 30 minutes, and performing suction filtration. The filtrate is decompressed and steamed to remove water until the filtrate is dry; adding 25g of petroleum ether for recrystallization, filtering to obtain a wet product, and performing vacuum drying at 75 ℃ to obtain 12.4g of white powder, wherein the yield is 90.2 percent and the purity is 99.3 percent.

Comparative example 1

The preparation method of 1, 4-dimethylpentylamine hydrochloride in this comparative example was:

(1) amine acylation: a500 mL four-necked flask was charged with 10.8g (0.24mol) of formamide and 11.4g (0.1mol) of 5-methyl-2-hexanone, and 10.8g (0.17mol) of ammonium formate was added thereto with stirring. The temperature is raised to 130 ℃ for reaction for 12 hours, and GC is sampled until the raw materials disappear. Cooled to 40 ℃ and 30g of water are added. Stirring for 30 minutes, standing for layering, washing an oil layer with saturated saline for three times, adding anhydrous magnesium sulfate, drying, stirring overnight, and performing suction filtration to obtain 10.2g of 1, 4-dimethylformamido oil, wherein the yield is 79.1 percent and the oil is directly used for the next reaction.

(2) Hydrolysis to form salt: a500 mL four-necked flask was charged with 10.2g (0.079mol) of the 1, 4-dimethylformamidinereacted in the above step and 24.5g of 36% hydrochloric acid. The reaction was heated to reflux with stirring for 12 hours. Vacuum distilling to dry, adding 30g purified water, stirring for 20 min, standing and demixing. Collecting the lower layer material water layer, adding 0.3g of active carbon, stirring for 30 minutes and filtering. The filtrate is decompressed and steamed to remove water until the filtrate is dry; adding 20g of petroleum ether, recrystallizing, filtering to obtain a wet product, and vacuum drying at 80 ℃ for 16 hours to obtain 9.58g of white powder with the yield of 80%. The purity is 98.2%.

The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention are included in the scope of the present invention.