CN113666837A - Preparation method of 1, 4-dimethyl pentylamine hydrochloride - Google Patents
Preparation method of 1, 4-dimethyl pentylamine hydrochloride Download PDFInfo
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- KXVIYAHOUAMVJX-UHFFFAOYSA-N 1-(3,4,5-trifluorophenyl)ethanone Chemical compound CC(=O)C1=CC(F)=C(F)C(F)=C1 KXVIYAHOUAMVJX-UHFFFAOYSA-N 0.000 title claims abstract description 37
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- 238000003756 stirring Methods 0.000 claims abstract description 46
- FFWSICBKRCICMR-UHFFFAOYSA-N 5-methyl-2-hexanone Chemical compound CC(C)CCC(C)=O FFWSICBKRCICMR-UHFFFAOYSA-N 0.000 claims abstract description 44
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 43
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims abstract description 36
- 238000006243 chemical reaction Methods 0.000 claims abstract description 35
- 238000010438 heat treatment Methods 0.000 claims abstract description 34
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims abstract description 24
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims abstract description 18
- 235000019253 formic acid Nutrition 0.000 claims abstract description 18
- 239000002994 raw material Substances 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 13
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000004519 manufacturing process Methods 0.000 claims abstract description 10
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 8
- 229940100684 pentylamine Drugs 0.000 claims abstract description 6
- 238000004321 preservation Methods 0.000 claims abstract description 5
- -1 1, 4-dimethylformamidopentyl amine Chemical class 0.000 claims abstract description 3
- 150000003839 salts Chemical class 0.000 claims description 19
- 238000007112 amidation reaction Methods 0.000 claims description 14
- 230000007062 hydrolysis Effects 0.000 claims description 14
- 238000006460 hydrolysis reaction Methods 0.000 claims description 14
- 150000001412 amines Chemical class 0.000 claims description 11
- 230000009435 amidation Effects 0.000 claims description 7
- 230000003301 hydrolyzing effect Effects 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 238000000967 suction filtration Methods 0.000 abstract description 19
- 238000001035 drying Methods 0.000 abstract description 13
- 239000000463 material Substances 0.000 abstract description 10
- 238000005406 washing Methods 0.000 abstract description 10
- 238000001816 cooling Methods 0.000 abstract description 9
- DPBLXKKOBLCELK-UHFFFAOYSA-N pentan-1-amine Chemical compound CCCCCN DPBLXKKOBLCELK-UHFFFAOYSA-N 0.000 abstract description 4
- 238000010992 reflux Methods 0.000 abstract description 4
- 150000001875 compounds Chemical class 0.000 abstract description 2
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 239000000706 filtrate Substances 0.000 description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 239000000843 powder Substances 0.000 description 9
- 238000001914 filtration Methods 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 230000010933 acylation Effects 0.000 description 7
- 238000005917 acylation reaction Methods 0.000 description 7
- 239000003208 petroleum Substances 0.000 description 7
- 239000008213 purified water Substances 0.000 description 7
- 238000001291 vacuum drying Methods 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- ZKKBPHUAHARETG-UHFFFAOYSA-N 4-methylhexan-2-amine;hydrochloride Chemical compound Cl.CCC(C)CC(C)N ZKKBPHUAHARETG-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- BYGQBDHUGHBGMD-UHFFFAOYSA-N 2-methylbutanal Chemical compound CCC(C)C=O BYGQBDHUGHBGMD-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 208000020832 chronic kidney disease Diseases 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 239000001893 (2R)-2-methylbutanal Substances 0.000 description 1
- XUPXMIAWKPTZLZ-UHFFFAOYSA-N 4-methylhexan-2-one Chemical compound CCC(C)CC(C)=O XUPXMIAWKPTZLZ-UHFFFAOYSA-N 0.000 description 1
- IZCBXLKODYZSDJ-UHFFFAOYSA-N 5-methylhexan-2-amine Chemical compound CC(C)CCC(C)N IZCBXLKODYZSDJ-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000009713 electroplating Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 235000020905 low-protein-diet Nutrition 0.000 description 1
- 230000001071 malnutrition Effects 0.000 description 1
- 235000000824 malnutrition Nutrition 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- MCSAJNNLRCFZED-UHFFFAOYSA-N nitroethane Chemical compound CC[N+]([O-])=O MCSAJNNLRCFZED-UHFFFAOYSA-N 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/08—Preparation of carboxylic acid amides from amides by reaction at nitrogen atoms of carboxamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/62—Preparation of compounds containing amino groups bound to a carbon skeleton by cleaving carbon-to-nitrogen, sulfur-to-nitrogen, or phosphorus-to-nitrogen bonds, e.g. hydrolysis of amides, N-dealkylation of amines or quaternary ammonium compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/10—Preparation of carboxylic acid amides from compounds not provided for in groups C07C231/02 - C07C231/08
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- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
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.
Description
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.
Claims (8)
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.
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