CN108558673B - Method for producing 2- (1-cyclohexenyl) ethylamine - Google Patents
Method for producing 2- (1-cyclohexenyl) ethylamine Download PDFInfo
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- IUDMXOOVKMKODN-UHFFFAOYSA-N 2-(cyclohexen-1-yl)ethanamine Chemical compound NCCC1=CCCCC1 IUDMXOOVKMKODN-UHFFFAOYSA-N 0.000 title claims abstract description 32
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 64
- 239000001257 hydrogen Substances 0.000 claims abstract description 64
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 61
- 238000006243 chemical reaction Methods 0.000 claims abstract description 44
- OYEXEQFKIPJKJK-UHFFFAOYSA-N 2-(cyclohexen-1-yl)acetonitrile Chemical compound N#CCC1=CCCCC1 OYEXEQFKIPJKJK-UHFFFAOYSA-N 0.000 claims abstract description 28
- 239000003054 catalyst Substances 0.000 claims abstract description 26
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000002904 solvent Substances 0.000 claims abstract description 17
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- -1 nickel-aluminum-iron Chemical group 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 4
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 claims description 2
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 238000005984 hydrogenation reaction Methods 0.000 abstract description 13
- 238000000926 separation method Methods 0.000 abstract description 12
- 239000002994 raw material Substances 0.000 abstract description 10
- 238000001816 cooling Methods 0.000 abstract description 7
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 abstract description 5
- 229910000564 Raney nickel Inorganic materials 0.000 abstract description 4
- 238000009776 industrial production Methods 0.000 abstract description 4
- 238000007086 side reaction Methods 0.000 abstract description 4
- 230000009286 beneficial effect Effects 0.000 abstract description 3
- 230000009467 reduction Effects 0.000 abstract description 3
- 239000000047 product Substances 0.000 description 10
- HFACYWDPMNWMIW-UHFFFAOYSA-N 2-cyclohexylethanamine Chemical compound NCCC1CCCCC1 HFACYWDPMNWMIW-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- MXFPACNADGXIQY-UHFFFAOYSA-N 2-cyclohexylacetonitrile Chemical compound N#CCC1CCCCC1 MXFPACNADGXIQY-UHFFFAOYSA-N 0.000 description 7
- 239000000498 cooling water Substances 0.000 description 7
- 238000010438 heat treatment Methods 0.000 description 7
- 238000009835 boiling Methods 0.000 description 6
- 239000012295 chemical reaction liquid Substances 0.000 description 5
- 238000004817 gas chromatography Methods 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 238000005070 sampling Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- MKXZASYAUGDDCJ-SZMVWBNQSA-N LSM-2525 Chemical compound C1CCC[C@H]2[C@@]3([H])N(C)CC[C@]21C1=CC(OC)=CC=C1C3 MKXZASYAUGDDCJ-SZMVWBNQSA-N 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 229960001985 dextromethorphan Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 238000010907 mechanical stirring Methods 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000000607 poisoning effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 206010011224 Cough Diseases 0.000 description 1
- 208000005374 Poisoning Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- HOFDWPHQRUGAEI-UHFFFAOYSA-N acetonitrile;cyclohexene Chemical compound CC#N.C1CCC=CC1 HOFDWPHQRUGAEI-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000003434 antitussive agent Substances 0.000 description 1
- 229940124584 antitussives Drugs 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 238000005485 electric heating Methods 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 229910052735 hafnium Inorganic materials 0.000 description 1
- VBJZVLUMGGDVMO-UHFFFAOYSA-N hafnium atom Chemical compound [Hf] VBJZVLUMGGDVMO-UHFFFAOYSA-N 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 229910052758 niobium Inorganic materials 0.000 description 1
- 239000010955 niobium Substances 0.000 description 1
- GUCVJGMIXFAOAE-UHFFFAOYSA-N niobium atom Chemical compound [Nb] GUCVJGMIXFAOAE-UHFFFAOYSA-N 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- LEONUFNNVUYDNQ-UHFFFAOYSA-N vanadium atom Chemical compound [V] LEONUFNNVUYDNQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/44—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of carboxylic acids or esters thereof in presence of ammonia or amines, or by reduction of nitriles, carboxylic acid amides, imines or imino-ethers
- C07C209/48—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of carboxylic acids or esters thereof in presence of ammonia or amines, or by reduction of nitriles, carboxylic acid amides, imines or imino-ethers by reduction of nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a method for producing 2- (1-cyclohexenyl) ethylamine, which comprises the following steps: s1, reacting 1-cyclohexene acetonitrile, a solvent, a catalyst and liquid ammonia at 55-130 ℃ in the presence of hydrogen under the condition that the reaction pressure is controlled to be 1.5-5.5 MPa until the consumption of the hydrogen is 90-95% of the theoretical consumption; and S2, reducing the addition of hydrogen under the condition of unchanged temperature, reducing the reaction pressure to 1.0-3.0 MPa, continuing to react until the consumption of the hydrogen is 102-110% of the theoretical consumption, stopping adding the hydrogen, cooling to below 50 ℃, and finishing the reaction. The invention adopts a cheap Raney nickel catalyst to catalyze the hydrogenation of 1-cyclohexene acetonitrile to prepare 2- (1-cyclohexenyl) ethylamine. By controlling the precision of the hydrogenation process, the occurrence of double bond reduction side reaction is reduced, the utilization rate of raw materials is improved to the maximum extent, and finally the advanced technical indexes that the product purity is more than 99 percent and the separation yield is more than 80 percent are achieved, thereby being very beneficial to industrial production.
Description
Technical Field
The invention relates to a method for producing 2- (1-cyclohexenyl) ethylamine, belonging to the technical field of fine chemical engineering.
Background
2- (1-cyclohexenyl) ethylamine, english name: 2- (1-Cyclohexenyl) ethalamine, CASNO. 3399-73-3, which is a basic raw material of a cough-relieving medicine dextromethorphan. Dextromethorphan is collected and carried by multi-national pharmacopoeias, and no industrial production exists in China at present, and all raw material medicines depend on import. Therefore, the strain is a key development variety in the field in China.
The 2- (1-cyclohexenyl) ethylamine is industrially produced by catalytic hydrogenation of 1-cyclohexene acetonitrile. However, in the reaction, the double bond of the raw material 1-cyclohexene acetonitrile can also undergo hydrogenation reaction to generate byproducts such as 2-cyclohexylethylamine, 2-cyclohexylacetonitrile and the like, and the specific reaction equation is as follows:
after the hydrogenation is finished, the product is separated and purified by rectification. In the actual rectification separation process, the boiling point of 2-cyclohexylethylamine is lower than that of 2- (1-cyclohexenyl) ethylamine by about 10 ℃ under normal pressure, the 2-cyclohexylethylamine can be enriched in a front fraction in the rectification separation process in a full reflux mode and removed, the boiling points of 1-cyclohexeneacetonitrile and 2-cyclohexylacetonitrile (the boiling points are 215 ℃ and 760mmHg) are lower than that of 2- (1-cyclohexenyl) ethylamine by 10 ℃, if the 1-cyclohexeneacetonitrile and 2-cyclohexylacetonitrile are removed by rectification, the rectification efficiency can be greatly reduced, and meanwhile, a large amount of 2- (1-cyclohexenyl) ethylamine products can be lost. Therefore, how to reduce the generation of byproducts with double bonds hydrogenated in the hydrogenation reaction, especially 2-cyclohexylacetonitrile byproduct, is a core problem of the process for preparing 2- (1-cyclohexenyl) ethylamine.
In 2016, Chinese CN201610114613.7 proposed that vanadium, niobium, hafnium and other metals were used to prepare hydrogenation catalysts, and expensive noble metals were used for the preparation of the catalysts, and the preparation process required high temperature and high pressure, and the yield of the target product was only 71%.
In 2017, chinese patent CN201710285404.3 proposed that a sulfide (such as dimethyl sulfide) was used to treat Pd/C catalyst to reduce its reactivity, so as to reduce the side reaction of double bond reduction during hydrogenation. However, in this method, the main reaction rate of reducing cyano groups to amino groups is also decreased after the catalyst poisoning activity is decreased. In best example 1 of this patent, the feed conversion was 83.4%, the selectivity for 2- (1-cyclohexenyl) ethylamine was 86.7%, and the single pass reaction yield was only 72.3%, which was not significantly higher than that described in the suti ito pharmaceutical chemical company patent. In addition, the palladium-carbon catalyst subjected to sulfur poisoning treatment has high inactivation rate and can be repeatedly applied for a few times, and if the palladium-carbon catalyst needs to be frequently replaced, the method is not suitable for industrial production in cost.
At present, the antitussive drug dextromethorphan is a key development variety in China, and as the basic raw material 2- (1-cyclohexenyl) ethylamine of the drug, a simple and reliable manufacturing method with high yield and good product quality is urgently needed in industry and is suitable for large-scale production.
Disclosure of Invention
In view of the drawbacks of the prior art, it is an object of the present invention to provide a process for the production of 2- (1-cyclohexenyl) ethylamine.
The invention is realized by the following technical scheme:
the invention provides a method for producing 2- (1-cyclohexenyl) ethylamine, which comprises the following steps:
s1, reacting 1-cyclohexene acetonitrile, a solvent, a catalyst and liquid ammonia at 55-130 ℃ in the presence of hydrogen under the condition that the reaction pressure is controlled to be 1.5-5.5 MPa until the consumption of the hydrogen is 90-95% of the theoretical consumption;
and S2, reducing the addition of hydrogen under the condition of unchanged temperature, reducing the reaction pressure to 1.0-3.0 MPa, continuing to react until the consumption of the hydrogen is 102-110% of the theoretical consumption, stopping adding the hydrogen, cooling to below 50 ℃, and finishing the reaction.
Preferably, the weight ratio of the 1-cyclohexene acetonitrile to the solvent is 1 (1-10), preferably 1: (2-4).
Preferably, the solvent comprises one or more of methanol, ethanol, isopropanol, toluene, cyclohexanol and ethylene glycol monomethyl ether.
Preferably, the weight ratio of the catalyst to the 1-cyclohexene acetonitrile is (0.01-0.1): 1, and preferably (0.05-0.08): 1.
Preferably, the catalyst is a raney nickel catalyst.
Preferably, the raney nickel catalyst comprises a nickel-aluminum two-component catalyst, a nickel-aluminum-iron three-component catalyst or a nickel-aluminum-iron-cobalt four-component catalyst, and preferably a nickel-aluminum-iron three-component catalyst.
Preferably, the molar ratio of the liquid ammonia to the 1-cyclohexene acetonitrile is (0.1-1): 1, and preferably (0.3-0.6): 1.
Preferably, the reaction pressure in step S1 is 2.5 to 3.0MPa, and the reaction temperature is 100 to 105 ℃.
Preferably, the reaction pressure in step S2 is 1.5-2.0 MPa, and the reaction temperature is 95-100 ℃.
Compared with the prior art, the invention has the following beneficial effects:
1. sampling reaction liquid, and performing GC analysis, wherein the content of the 1-cyclohexene acetonitrile serving as a raw material is less than 1%, the content of the 2- (1-cyclohexenyl) ethylamine is 85-90%, and the content of the 2-cyclohexylethylamine serving as a side reaction product is 10-15%;
2. the invention adopts a cheap Raney nickel catalyst to catalyze the hydrogenation of 1-cyclohexene acetonitrile to prepare 2- (1-cyclohexenyl) ethylamine. By controlling the precision of the hydrogenation process, the occurrence of double bond reduction side reaction is reduced, the utilization rate of raw materials is improved to the maximum extent, and finally the advanced technical indexes that the product purity is more than 99 percent and the separation yield is more than 80 percent are achieved, thereby being very beneficial to industrial production.
Detailed Description
The present invention will be described in detail with reference to specific examples. The following examples will assist those skilled in the art in further understanding the invention, but are not intended to limit the invention in any way. It should be noted that variations and modifications can be made by persons skilled in the art without departing from the spirit of the invention. All falling within the scope of the present invention.
Example 1
The embodiment relates to a method for producing 2- (1-cyclohexenyl) ethylamine, which specifically comprises the following steps:
500Kg of raw material 1-cyclohexene acetonitrile, 1000Kg of solvent isopropanol and 33Kg of Ni/Al/Fe three-component catalyst are introduced into a 2000-liter high-pressure hydrogenation reaction kettle equipped with a steam heating jacket, an internal cooling coil, strong mechanical stirring and a hydrogen flow meter (capable of displaying the flow rate and the total flow rate of hydrogen), the gas in the kettle is replaced by nitrogen and hydrogen in sequence, and then 31Kg of liquid ammonia is pressed in. Pressurizing hydrogen to 2.5MPa, starting stirring, heating to above 80 deg.C, and consuming a large amount of hydrogen. Controlling the introduction amount of hydrogen and the flow rate of cooling water to keep the reaction temperature at 100-105 ℃ and the reaction pressure at 2.5-3.0 MPa. And simultaneously, the hydrogen flowmeter displays the consumption speed of the hydrogen and the total adding amount.
After the reaction is carried out for 1.5 hours, the total hydrogen consumption amount reaches 95% of the theoretical amount, the hydrogen consumption rate is slowed, the hydrogen adding rate is reduced, the reaction pressure is reduced to 1.7-1.8 MPa, and the temperature is reduced to 95-96 ℃ for continuous reaction. After 30 minutes, the hydrogen flowmeter shows that the hydrogen consumption reaches 108 percent of the theoretical amount, the hydrogen inlet valve is closed, the cooling water is opened to reduce the temperature to 45 ℃ after 30 minutes, and the reaction is finished.
Sampling and GC analysis, deducting the solvent, wherein the contents of 1-cyclohexene acetonitrile, 2- (1-cyclohexenyl) ethylamine, 2-cyclohexyl ethylamine, coupled high boiling point impurities and 2-cyclohexyl acetonitrile are respectively 0.53%, 85.5%, 8.9%, 4.7% and 0.10%. The reaction liquid is filtered to recover the catalyst, the filtrate is distilled under normal pressure to remove the solvent and ammonia, and the residual concentrate is subjected to reduced pressure rectification separation by a high-efficiency rectifying tower (the theoretical plate number is 60-80) to obtain 423Kg of 2- (1-cyclohexenyl) ethylamine product with the content of 99.3 percent and the separation yield of 81.9 percent (calculated by 1-cyclohexene acetonitrile).
Example 2
The embodiment relates to a method for producing 2- (1-cyclohexenyl) ethylamine, which specifically comprises the following steps:
500Kg of raw material 1-cyclohexene acetonitrile, 1000Kg of solvent methanol and 40Kg of Ni/Al/Fe three-component catalyst are introduced into a 2000-liter high-pressure hydrogenation reaction kettle equipped with a steam heating jacket, an internal cooling coil, strong mechanical stirring and a hydrogen flow meter (capable of displaying the flow rate and the total flow rate of hydrogen), the gas in the kettle is replaced by nitrogen and hydrogen in sequence, and then 31Kg of liquid ammonia is pressed in. Pressurizing hydrogen to 2.5MPa, starting stirring, heating to above 80 deg.C, and consuming a large amount of hydrogen. Controlling the introduction amount of hydrogen and the flow rate of cooling water, wherein the reaction temperature is kept between 100 and 105 ℃, and the reaction pressure is kept between 2.5 and 3.0 MPa. And simultaneously, the hydrogen flowmeter displays the consumption speed of the hydrogen and the total adding amount.
After the reaction is carried out for 1 hour and 15 minutes, the total hydrogen consumption reaches 95 percent of the theoretical amount, the hydrogen consumption rate is slowed, the hydrogen adding rate is reduced, the reaction pressure is reduced to 1.7-1.8 MPa, and the temperature is reduced to 95-96 ℃ for continuous reaction. After 20 minutes, the hydrogen flowmeter shows that the hydrogen consumption reaches 110% of the theoretical amount, the hydrogen inlet valve is closed, the cooling water is opened to reduce the temperature to 45 ℃ after 30 minutes, and the reaction is finished.
Sampling and GC analysis show that the solvent is subtracted, the contents of the 1-cyclohexene acetonitrile, the 2- (1-cyclohexenyl) ethylamine, the 2-cyclohexyl ethylamine and the coupled high-boiling-point impurities are respectively 0.26%, 81.8%, 12.7% and 4.9%, the contents are respectively 0.26%, 86.1% and 13.4%, and the 2-cyclohexyl acetonitrile cannot be detected. The reaction liquid is filtered to recover the catalyst, the filtrate is distilled under normal pressure to remove the solvent and ammonia, and the residual concentrate is subjected to reduced pressure rectification separation in a high-efficiency rectification tower (the theoretical plate number is 60-80) to obtain 398Kg of 2- (1-cyclohexenyl) ethylamine product with the content of 99.4 percent and the separation yield of 77.0 percent (calculated by 1-cyclohexene acetonitrile).
Example 3
The embodiment relates to a method for producing 2- (1-cyclohexenyl) ethylamine, which specifically comprises the following steps:
500Kg of raw material 1-cyclohexene acetonitrile, 1000Kg of solvent isopropanol and 33Kg of Ni/Al/Fe three-component catalyst are introduced into a 2000-liter high-pressure hydrogenation reaction kettle equipped with a steam heating jacket, an internal cooling coil, strong mechanical stirring and a hydrogen flow meter (capable of displaying the flow rate and the total flow rate of hydrogen), the gas in the kettle is replaced by nitrogen and hydrogen in sequence, and then 31Kg of liquid ammonia is pressed in. Pressurizing hydrogen to 2.5MPa, starting stirring, heating to above 80 deg.C, and consuming a large amount of hydrogen. Controlling the introduction amount of hydrogen and the flow rate of cooling water to keep the reaction temperature at 100-105 ℃ and the reaction pressure at 2.5-3.0 MPa. And simultaneously, the hydrogen flowmeter displays the consumption speed of the hydrogen and the total adding amount.
After the reaction is carried out for 1.5 hours, the total hydrogen consumption amount reaches 95% of the theoretical amount, the hydrogen consumption rate is slowed, the hydrogen adding rate is reduced, the reaction pressure is reduced to 1.7-1.8 MPa, and the temperature is reduced to 95-96 ℃ for continuous reaction. After 15 minutes, the hydrogen flowmeter shows that the hydrogen consumption reaches 100% of the theoretical amount, the hydrogen inlet valve is closed, the cooling water is opened to reduce the temperature to 45 ℃ after 30 minutes, and the reaction is finished.
Sampling and GC analysis, deducting the solvent, the contents of 1-cyclohexene acetonitrile, 2- (1-cyclohexenyl) ethylamine, 2-cyclohexyl ethylamine, coupled high boiling point impurities and 2-cyclohexyl acetonitrile are respectively 3.6%, 82.4%, 8.0%, 5.2% and 0.80%. The reaction liquid is filtered to recover the catalyst, the filtrate is distilled under normal pressure to remove the solvent and ammonia, and the residual concentrate is subjected to reduced pressure rectification separation in a high-efficiency rectification tower (the theoretical plate number is 60-80) to obtain 404Kg of 2- (1-cyclohexenyl) ethylamine product with the content of 97.8 percent and the separation yield of 78.3 percent (calculated by 1-cyclohexene acetonitrile).
Comparative example 1
The comparative example relates to a method for producing 2- (1-cyclohexenyl) ethylamine, which specifically comprises the following steps:
a2000 ml high-pressure hydrogenation kettle is cleaned and dried, and 1000g of methanol, 500g of 1-cyclohexene acetonitrile and 40g of Ni/Al/Fe three-component catalyst are sequentially added. And (3) sealing the reaction kettle, replacing ten times with nitrogen at 0-0.5 MPa, replacing ten times with hydrogen at 0-0.5 Map, releasing the pressure to 0.15MPa, and pressing 31.0g of liquid ammonia. Pressurizing hydrogen to 2.5MPa, and detecting the air tightness of the reaction kettle. Stirring is started, electric heating is started, when the temperature in the reaction kettle rises to 85 ℃, a large amount of hydrogen is consumed in the reaction, heating is closed, cooling water is introduced into a coil pipe to cool, the adding rate of hydrogen is adjusted, and the pressure and the temperature of the reaction hydrogen are controlled to be 2.5-3.0 MPa and 95-120 ℃. After 2.0 hours of reaction, the hydrogen absorption is slowed down, the hydrogen valve is closed, the temperature is reduced by cooling, and the temperature is reduced to 45 ℃ within 30 minutes, thus finishing the reaction. After cooling, the contents of the products 1-cyclohexene acetonitrile, 2- (1-cyclohexenyl) ethylamine, 2-cyclohexylethylamine and coupled high-boiling impurities are respectively 0.17%, 69.6%, 24.9% and 5.1% by GC analysis, and the 2-cyclohexene acetonitrile can not be detected. The reaction liquid is filtered to recover the catalyst, the filtrate is distilled under normal pressure to remove the solvent and ammonia, and the residual concentrate is subjected to reduced pressure rectification separation by a high-efficiency rectifying tower to obtain 310g of 2- (1-cyclohexenyl) ethylamine product with the content of 99.0 percent and the separation yield of 61.0 percent (calculated by 1-cyclohexene acetonitrile).
The foregoing description of specific embodiments of the present invention has been presented. It is to be understood that the present invention is not limited to the specific embodiments described above, and that various changes and modifications may be made by one skilled in the art within the scope of the appended claims without departing from the spirit of the invention.
Claims (2)
1. A method for producing 2- (1-cyclohexenyl) ethylamine, comprising the steps of:
s1, reacting 1-cyclohexene acetonitrile, a solvent, a catalyst and liquid ammonia at 100-105 ℃ in the presence of hydrogen under the condition that the reaction pressure is controlled to be 2.5-3.0 MPa until the consumption of the hydrogen is 90-95% of the theoretical consumption;
s2, reducing the addition of hydrogen under the condition of unchanged temperature, reducing the reaction pressure to 1.7-1.8 MPa, keeping the reaction temperature at 95-96 ℃, continuing to react until the consumption of the hydrogen is 102-110% of the theoretical consumption, stopping adding the hydrogen, reducing the temperature to below 50 ℃, and finishing the reaction;
the weight ratio of the 1-cyclohexene acetonitrile to the solvent is 1: 1-10; the weight ratio of the catalyst to the 1-cyclohexene acetonitrile is (0.01-0.1) to 1; the molar ratio of the liquid ammonia to the 1-cyclohexene acetonitrile is (0.1-1) to 1;
the catalyst is a nickel-aluminum-iron three-component catalyst.
2. A process for the production of 2- (1-cyclohexenyl) ethylamine as claimed in claim 1 wherein the solvent comprises one or more of methanol, ethanol, isopropanol, toluene, cyclohexanol, ethylene glycol monomethyl ether.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB685747A (en) * | 1949-10-14 | 1953-01-07 | Hoffmann La Roche | Cyclohexen-(1)-yl-ethylamine and process for the manufacture thereof |
| CN105669465A (en) * | 2016-03-01 | 2016-06-15 | 苏州艾缇克药物化学有限公司 | Preparing method of 1-cyclohexene ethylamine |
| CN107011178A (en) * | 2017-04-27 | 2017-08-04 | 江苏理工学院 | A kind of method that modified Pd/C catalysts selective hydrogenation prepares 1 cyclohexene ethamine |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB685747A (en) * | 1949-10-14 | 1953-01-07 | Hoffmann La Roche | Cyclohexen-(1)-yl-ethylamine and process for the manufacture thereof |
| CN105669465A (en) * | 2016-03-01 | 2016-06-15 | 苏州艾缇克药物化学有限公司 | Preparing method of 1-cyclohexene ethylamine |
| CN107011178A (en) * | 2017-04-27 | 2017-08-04 | 江苏理工学院 | A kind of method that modified Pd/C catalysts selective hydrogenation prepares 1 cyclohexene ethamine |
Non-Patent Citations (3)
| Title |
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| Chemoselective Hydrogenation of α,β-Unsaturated Nitriles;Pavel Kukula 等;《Advanced Synthesis & Catalysis》;20041026;第346卷(第12期);第1488页图1和第1492页图6 * |
| Structure-selectivity relationship in the chemoselective hydrogenation of unsaturated nitriles;Pavel Kukula 等;《Journal of Catalysis》;20050719;第234卷(第1期);第161-171页 * |
| 张春勇 等.骨架镍催化1-环己烯乙腈选择加氢制备1-环己烯乙胺反应动力学研究.《高校化学工程学报》.2012,第26卷(第2期),第360-363页. * |
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