CN113264867A - Preparation method of cis-2, 6-dimethylpiperidine - Google Patents
Preparation method of cis-2, 6-dimethylpiperidine Download PDFInfo
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- CN113264867A CN113264867A CN202110637143.3A CN202110637143A CN113264867A CN 113264867 A CN113264867 A CN 113264867A CN 202110637143 A CN202110637143 A CN 202110637143A CN 113264867 A CN113264867 A CN 113264867A
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- dimethylpiperidine
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- acetate
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- SDGKUVSVPIIUCF-KNVOCYPGSA-N (2r,6s)-2,6-dimethylpiperidine Chemical compound C[C@H]1CCC[C@@H](C)N1 SDGKUVSVPIIUCF-KNVOCYPGSA-N 0.000 title claims abstract description 42
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- 238000006243 chemical reaction Methods 0.000 claims abstract description 68
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 claims abstract description 66
- SDGKUVSVPIIUCF-UHFFFAOYSA-N 2,6-dimethylpiperidine Chemical compound CC1CCCC(C)N1 SDGKUVSVPIIUCF-UHFFFAOYSA-N 0.000 claims abstract description 45
- 239000003054 catalyst Substances 0.000 claims abstract description 29
- 239000002131 composite material Substances 0.000 claims abstract description 22
- 238000000034 method Methods 0.000 claims abstract description 15
- 239000012153 distilled water Substances 0.000 claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000001816 cooling Methods 0.000 claims abstract description 11
- 239000011541 reaction mixture Substances 0.000 claims abstract description 11
- 238000000967 suction filtration Methods 0.000 claims abstract description 11
- 239000006228 supernatant Substances 0.000 claims abstract description 11
- 239000012043 crude product Substances 0.000 claims abstract description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 26
- 229910052751 metal Inorganic materials 0.000 claims description 21
- 239000002184 metal Substances 0.000 claims description 21
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 13
- PVFSDGKDKFSOTB-UHFFFAOYSA-K iron(3+);triacetate Chemical compound [Fe+3].CC([O-])=O.CC([O-])=O.CC([O-])=O PVFSDGKDKFSOTB-UHFFFAOYSA-K 0.000 claims description 12
- 230000035484 reaction time Effects 0.000 claims description 10
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims description 4
- UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 claims description 4
- 239000011654 magnesium acetate Substances 0.000 claims description 4
- 229940069446 magnesium acetate Drugs 0.000 claims description 4
- 235000011285 magnesium acetate Nutrition 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000004246 zinc acetate Substances 0.000 claims description 4
- 229910052759 nickel Inorganic materials 0.000 claims description 3
- 150000003053 piperidines Chemical class 0.000 abstract description 2
- 238000004817 gas chromatography Methods 0.000 description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 15
- 238000005984 hydrogenation reaction Methods 0.000 description 13
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 10
- 229910052739 hydrogen Inorganic materials 0.000 description 10
- 239000001257 hydrogen Substances 0.000 description 10
- 230000003197 catalytic effect Effects 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 4
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 229960003530 donepezil Drugs 0.000 description 2
- 229910000510 noble metal Inorganic materials 0.000 description 2
- 229910052755 nonmetal Inorganic materials 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- SDGKUVSVPIIUCF-RNFRBKRXSA-N (2r,6r)-2,6-dimethylpiperidine Chemical compound C[C@@H]1CCC[C@@H](C)N1 SDGKUVSVPIIUCF-RNFRBKRXSA-N 0.000 description 1
- 241000711573 Coronaviridae Species 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical class [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000007036 catalytic synthesis reaction Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910044991 metal oxide Inorganic materials 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- NCPHGZWGGANCAY-UHFFFAOYSA-N methane;ruthenium Chemical compound C.[Ru] NCPHGZWGGANCAY-UHFFFAOYSA-N 0.000 description 1
- 239000011943 nanocatalyst Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/02—Preparation by ring-closure or hydrogenation
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
- B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
- B01J23/40—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals of the platinum group metals
- B01J23/44—Palladium
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
- B01J23/70—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of the iron group metals or copper
- B01J23/74—Iron group metals
- B01J23/755—Nickel
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/04—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing carboxylic acids or their salts
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J35/00—Catalysts, in general, characterised by their form or physical properties
- B01J35/19—Catalysts containing parts with different compositions
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/12—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with only hydrogen atoms attached to the ring nitrogen atom
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/60—Reduction reactions, e.g. hydrogenation
- B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
- B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
- B01J2231/646—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of aromatic or heteroaromatic rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
The invention discloses a preparation method of cis-2, 6-dimethylpiperidine, belonging to the technical field of preparation of piperidine compounds. The method comprises the following steps: A. under the protection of nitrogen, adding 2, 6-dimethylpyridine, distilled water and a composite catalyst into a high-pressure reaction kettle for reaction, and performing suction filtration after the reaction to obtain a crude product of 2, 6-dimethylpiperidine; B. and D, cooling the crude 2, 6-dimethylpiperidine obtained in the step A to room temperature, taking out the reaction mixture, standing, and taking the supernatant to obtain the high-purity cis-2, 6-dimethylpiperidine. The cis-2, 6-dimethylpiperidine content of the invention is about 15 percent, and is qualified when the content is more than 10 percent; the catalyst is easy to prepare, has low cost and can be repeatedly used.
Description
Technical Field
The invention belongs to the technical field of preparation of piperidine compounds, and particularly relates to a preparation method of cis-2, 6-dimethylpiperidine.
Background
the catalytic hydrogenation of pyridines can be roughly divided into four methods in terms of the handling of the catalytic process: 1. a method for direct catalytic hydrogenation by utilizing supported nano noble metal; 2. firstly, a salifying reaction is used and then catalytic hydrogenation is carried out; 3. methods using indirect salt formation; 4. a method of increasing the reactivity by benzylating the nitrogen atom.
Through search, Xuehang, etc. [ Xuehang, Linqi, Linchaofen, etc.. Supported nanometer noble metal catalyst catalyzes the hydrogenation of pyridine and its derivative, the catalytic report 2006,27(10):921 926.]The prepared high-dispersion nano catalyst Ru/C has high catalytic activity on the hydrogenation reaction of pyridine and derivatives thereof, the complete hydrogenation of the pyridine can be realized after 1h of reaction at 100 ℃ and 3MPa, and TOF reaches 406h-1The selectivity to piperidine was 100%. Studies on pyridine catalytic synthesis process [ Chenshenozong, Guo Yuliang, Yejiao, etc. ]]Chemical reaction engineering and processes 2000,4(16): 405-.]Raney nickel catalyst modified with Ni (NO)3)2And M (NO)3)3A novel catalyst for NHD-99 was prepared as a precursor, supported on a metal oxide, and used for the study of catalytic hydrogenation of pyridine. Elati et al [ R.Chandrashikar, navenkumar Kolla, et al.New Synthesis of Donepezil Through Palladium-catalysis Hydrogenation apparatus [ J.].Synthetic Communications,2006,36(2):169–174.]In the synthesis of donepezil, 5% Pd/C catalyst with substrate ratio of 25% and 1.2eq acetic acid in methanol at 60-65 deg.c and 4.0kg/cm are used2The reaction was carried out for 7h, and the product was worked up to 90.0% yield. The catalyst has limited catalytic efficiency, and the selectivity is not high when the catalyst is applied to the synthesis and preparation of cis-2, 6-dimethylpiperidine.
The production process of 2, 6-dimethylpiperidine has fewer published documents, so that the development of an environment-friendly, efficient and economic preparation method of cis-2, 6-dimethylpiperidine is significant in combination with the increase of the market demand at present.
Disclosure of Invention
1. Technical problem to be solved by the invention
Aiming at the problem of low cis-2, 6-dimethylpiperidine content obtained by the existing preparation method, the invention provides a preparation method of cis-2, 6-dimethylpiperidine, which can improve the cis-2, 6-dimethylpiperidine content.
2. Technical scheme
In order to achieve the purpose, the technical scheme provided by the invention is as follows:
the preparation method of the cis-2, 6-dimethylpiperidine comprises the following steps:
A. under the condition of hydrogen protection, adding 2, 6-dimethylpyridine, distilled water and a composite catalyst into a high-pressure reaction kettle for reaction, and performing suction filtration after the reaction to obtain a crude product of 2, 6-dimethylpiperidine;
B. cooling the crude 2, 6-dimethylpiperidine obtained in the step A to room temperature, taking out a reaction mixture, standing, and taking a supernatant to obtain cis-2, 6-dimethylpiperidine;
the composite catalyst is as follows: the palladium-carbon-nickel powder-metal acetate composite material comprises a mixture of palladium-carbon, nickel powder and metal acetate, wherein the mass ratio of the palladium-carbon to the nickel powder to the metal acetate is 1: (0.05-0.1): (0.05-0.08).
In one possible embodiment of the invention, the mass of the added composite catalyst is 5-10% of the mass of the 2, 6-dimethylpyridine.
In one possible embodiment of the invention, the mass of the distilled water added is 40-60% of the mass of the 2, 6-lutidine.
In one possible embodiment of the invention, the reaction pressure of the high-pressure reaction kettle is 30-40 kg/cm2The reaction temperature is 120-150 ℃, and the reaction time is 5-8 h.
In one possible embodiment of the present invention, the metal acetate includes one or a mixture of iron acetate, zinc acetate and magnesium acetate.
In one possible embodiment of the present invention, the nickel powder is preferably electrolytic nickel powder, which has high activity and can form a catalytic layer on the surface of palladium carbon after being mixed with metal acetate, so as to enlarge the catalytic area of palladium carbon.
3. Advantageous effects
Compared with the prior art, the technical scheme provided by the invention comprises the following steps:
(1) according to the preparation method of cis-2, 6-dimethylpiperidine, the composite catalyst of palladium carbon, nickel powder and metal acetate is adopted, the palladium carbon and the nickel have catalytic action on the hydrogenation of pyridine rings, and hydrogen is enriched on the surface of the catalyst in the reaction process, wherein the palladium carbon can improve the content of the cis-2, 6-dimethylpiperidine; in addition, the nickel powder, palladium carbon and metal acetate act together to reduce the density of electron cloud on the pyridine ring and improve the hydrogenation activity of the pyridine ring, so that the hydrogenation has diastereoselectivity, the yield of cis-2, 6-dimethylpiperidine is relatively improved, and the cis-2, 6-dimethylpiperidine can reach about 15 percent; in addition, acetate ions in the metal acetate do not influence the electronic state of the catalyst for selective hydrogenation of 2, 6-dimethylpyridine, and a non-metal element is not introduced;
(2) according to the preparation method of cis-2, 6-dimethylpiperidine, the composite catalyst composed of palladium-carbon, nickel powder and metal acetate is used, and the composite catalyst is easy to prepare, low in cost and reusable;
(3) the preparation method of cis-2, 6-dimethylpiperidine uses distilled water as a solvent, and is environment-friendly and safe;
(4) the preparation method of cis-2, 6-dimethylpiperidine has orderly connected process steps and is convenient for industrial mass production.
Drawings
FIG. 1 is a chromatogram of example 5 of the present invention.
Detailed Description
For a further understanding of the invention, reference should be made to the following detailed description taken in conjunction with the accompanying drawings and examples.
Example 1
The preparation method of cis-2, 6-dimethylpiperidine according to this embodiment includes the following steps:
A. under the condition of hydrogen protection, 100g of 2, 6-lutidine, 40g of distilled water and 5g of composite catalyst (the mass ratio of palladium-carbon to nickel powder to metallic iron acetate is 1: 0.05: 0.05) are added into a high-pressure reaction kettle for reaction, and the reaction pressure for reaction is 30kg/cm2The reaction temperature is 120 ℃, the reaction time is 5 hours, and the crude 2, 6-dimethylpiperidine is obtained by suction filtration after the reaction is finished;
B. and D, cooling the crude 2, 6-dimethylpiperidine obtained in the step A to room temperature, taking out the reaction mixture, standing, and taking the supernatant to obtain the 2, 6-dimethylpiperidine.
Since the boiling points of the product 2, 6-dimethylpiperidine and the starting material 2, 6-dimethylpyridine are not high, a relatively simple and rapid gas chromatography method was employed in this example, as shown in FIG. 1, the analysis was performed on a GC-9790 gas chromatograph, the type of capillary column was SE-30, the column length was 30m, the inner diameter was 0.25mm, the liquid film thickness was 0.25pum, and the injection port and detector temperatures were 250 ℃.
The peak positions of the starting 2, 6-lutidine and the product 2, 6-dimethylpiperidine by chromatography were determined to be consistent with the standards provided by this company.
The cis content of the 2, 6-dimethylpiperidine mixture was measured to be 15.4% by Gas Chromatography (GC).
Comparative examples 1 to 1
On the basis of example 1, the composite catalyst does not contain iron acetate, and the preparation method of the cis-2, 6-dimethylpiperidine of the comparative example comprises the following steps:
A. under the condition of hydrogen protection, 100g of 2, 6-lutidine, 40g of distilled water and 5g of composite catalyst (the mass ratio of palladium-carbon to nickel powder is 1: 0.05) are added into a high-pressure reaction kettle for reaction, and the reaction pressure for reaction is 30kg/cm2The reaction temperature is 120 ℃, the reaction time is 5 hours, and the crude 2, 6-dimethylpiperidine is obtained by suction filtration after the reaction is finished;
B. and D, cooling the crude 2, 6-dimethylpiperidine obtained in the step A to room temperature, taking out the reaction mixture, standing, and taking the supernatant to obtain the 2, 6-dimethylpiperidine.
The cis content of the 2, 6-dimethylpiperidine mixture was measured to be 11.3% by Gas Chromatography (GC).
Comparative examples 1 to 2
On the basis of example 1, no palladium carbon is added into the composite catalyst, and the preparation method of the cis-2, 6-dimethylpiperidine of the comparative example comprises the following steps:
A. under the condition of hydrogen protection, 100g of 2, 6-lutidine, 40g of distilled water and 5g of composite catalyst (the mass ratio of nickel powder to metal iron acetate is 1: 1) are added into a high-pressure reaction kettle for reaction, and the reaction pressure for reaction is 30kg/cm2The reaction temperature is 120 ℃, the reaction time is 5 hours, and the crude 2, 6-dimethylpiperidine is obtained by suction filtration after the reaction is finished;
B. and D, cooling the crude 2, 6-dimethylpiperidine obtained in the step A to room temperature, taking out the reaction mixture, standing, and taking the supernatant to obtain the 2, 6-dimethylpiperidine.
The cis content of the 2, 6-dimethylpiperidine mixture was determined to be 10.5% by Gas Chromatography (GC).
Comparative examples 1 to 3
On the basis of the example 1, the ruthenium-carbon + nickel powder is not added into the composite catalyst, and the preparation method of the cis-2, 6-dimethylpiperidine of the comparative example comprises the following steps:
A. under the condition of hydrogen protection, 100g of 2, 6-lutidine, 40g of distilled water and 5g of metallic iron acetate are added into a high-pressure reaction kettle for reaction, and the reaction pressure for the reaction is 30kg/cm2The reaction temperature is 120 ℃, the reaction time is 5h, and the reaction is carried outAfter the reaction is finished, performing suction filtration to obtain a crude product of 2, 6-dimethylpiperidine;
B. and D, cooling the crude 2, 6-dimethylpiperidine obtained in the step A to room temperature, taking out the reaction mixture, standing, and taking the supernatant to obtain the 2, 6-dimethylpiperidine.
The cis content of the 2, 6-dimethylpiperidine mixture was determined to be 10.2% by Gas Chromatography (GC).
The 2, 6-dimethyl pyridine is hydrogenated to obtain a mixture of 2, 6-dimethyl piperidine isomers, wherein the cis-form and the trans-form account for 5-6 percent: 94-95%, the cis-2, 6-dimethylpiperidine ratio generally obtained by the presently disclosed process is 5-6%, and the greatest problem with the hydrogenation of 2, 6-dimethylpyridine to 2, 6-dimethylpiperidine is the hydrogenation selectivity.
Comparing example 1 with comparative examples 1-1, 1-2 and 1-3, it can be seen that palladium-carbon, nickel powder and metallic iron acetate are all conventional substances, but the combination of the three can play an unexpected role, especially the metallic iron acetate (other metallic acetates such as metallic zinc acetate and magnesium acetate can achieve the effect of the present invention). The inventors consider that possible reasons are: the mixture of nickel powder and metal acetate can not only form a catalytic layer on the surface of palladium-carbon, enlarge the catalytic area of the palladium-carbon and improve the content of cis-2, 6-dimethylpiperidine; the activity of metal acetate can be improved, so that the electron cloud density on a pyridine ring is reduced, the hydrogenation activity of the pyridine ring is improved, the hydrogenation has diastereoselectivity, the yield of cis-2, 6-dimethylpiperidine is relatively improved, and the proportion of cis-2, 6-dimethylpiperidine can reach about 15%; in addition, acetate ions in the metal acetate do not influence the electronic state of the catalyst for selective hydrogenation of 2, 6-dimethylpyridine, and a non-metal element is not introduced.
Example 2
The preparation method of cis-2, 6-dimethylpiperidine according to this embodiment includes the following steps:
A. under the condition of hydrogen protection, 100g of 2, 6-lutidine, 50g of distilled water and 6g of composite catalyst (substances of palladium carbon, nickel powder and metallic iron acetate)The quantity ratio is 1: 0.05: 0.08) into a high-pressure reaction kettle for reaction, wherein the reaction pressure for the reaction is 40kg/cm2The reaction temperature is 150 ℃, the reaction time is 6 hours, and the crude 2, 6-dimethylpiperidine is obtained by suction filtration after the reaction is finished;
B. and D, cooling the crude 2, 6-dimethylpiperidine obtained in the step A to room temperature, taking out the reaction mixture, standing, and taking the supernatant to obtain the 2, 6-dimethylpiperidine.
The cis content of the 2, 6-dimethylpiperidine mixture was determined to be 14.9% by Gas Chromatography (GC).
Example 3
The preparation method of cis-2, 6-dimethylpiperidine according to this embodiment includes the following steps:
A. under the condition of hydrogen protection, 100g of 2, 6-lutidine, 60g of distilled water and 8g of composite catalyst (the mass ratio of palladium-carbon to nickel powder to metallic iron acetate is 1: 0.1: 0.05) are added into a high-pressure reaction kettle for reaction, and the reaction pressure for reaction is 35kg/cm2The reaction temperature is 140 ℃, the reaction time is 8 hours, and the crude 2, 6-dimethylpiperidine is obtained by suction filtration after the reaction is finished;
B. and D, cooling the crude 2, 6-dimethylpiperidine obtained in the step A to room temperature, taking out the reaction mixture, standing, and taking the supernatant to obtain the 2, 6-dimethylpiperidine.
The cis content of the 2, 6-dimethylpiperidine mixture was measured to be 15.3% by Gas Chromatography (GC).
Example 4
The preparation method of cis-2, 6-dimethylpiperidine according to this embodiment includes the following steps:
A. under the condition of hydrogen protection, 100g of 2, 6-lutidine, 60g of distilled water and 10g of composite catalyst (the mass ratio of palladium carbon, nickel powder, metal iron acetate and metal zinc acetate is 1: 0.05: 0.08) are added into a high-pressure reaction kettle for reaction, and the reaction pressure for reaction is 40kg/cm2The reaction temperature is 140 ℃, the reaction time is 6 hours, and the crude 2, 6-dimethylpiperidine is obtained by suction filtration after the reaction is finished;
B. and D, cooling the crude 2, 6-dimethylpiperidine obtained in the step A to room temperature, taking out the reaction mixture, standing, and taking the supernatant to obtain the 2, 6-dimethylpiperidine.
The cis content of the 2, 6-dimethylpiperidine mixture was determined to be 15.1% by Gas Chromatography (GC).
Example 5
The preparation method of cis-2, 6-dimethylpiperidine according to this embodiment includes the following steps:
A. under the condition of hydrogen protection, 100g of 2, 6-lutidine, 60g of distilled water and 8g of composite catalyst (the mass ratio of palladium carbon, nickel powder, metal iron acetate and metal magnesium acetate is 1: 0.08: 0.08) are added into a high-pressure reaction kettle for reaction, and the reaction pressure for reaction is 40kg/cm2The reaction temperature is 130 ℃, the reaction time is 8 hours, and the crude 2, 6-dimethylpiperidine is obtained by suction filtration after the reaction is finished;
B. and D, cooling the crude 2, 6-dimethylpiperidine obtained in the step A to room temperature, taking out the reaction mixture, standing, and taking the supernatant to obtain the 2, 6-dimethylpiperidine.
The cis content of the 2, 6-dimethylpiperidine mixture was measured by Gas Chromatography (GC) to be 15.8%, as shown in FIG. 1.
The present invention and its embodiments have been described above schematically, without limitation, and what is shown in the drawings is only one of the embodiments of the present invention, and the actual structure is not limited thereto. Therefore, if the person skilled in the art receives the teaching, without departing from the spirit of the invention, the person skilled in the art shall not inventively design the similar structural modes and embodiments to the technical solution, but shall fall within the scope of the invention.
Claims (6)
1. A preparation method of cis-2, 6-dimethylpiperidine is characterized by comprising the following steps:
A. under the protection of nitrogen, adding 2, 6-dimethylpyridine, distilled water and a composite catalyst into a high-pressure reaction container for reaction, and performing suction filtration after the reaction to obtain a crude product of 2, 6-dimethylpiperidine;
B. cooling the crude 2, 6-dimethylpiperidine obtained in the step A to room temperature, taking out a reaction mixture, standing, and taking a supernatant to obtain cis-2, 6-dimethylpiperidine;
the composite catalyst is as follows: the palladium-carbon-nickel powder-metal acetate composite material comprises a mixture of palladium-carbon, nickel powder and metal acetate, wherein the mass ratio of the palladium-carbon to the nickel powder to the metal acetate is 1: (0.05-0.1): (0.05-0.08).
2. The method for producing cis-2, 6-dimethylpiperidine according to claim 1, wherein the mass of the composite catalyst added is 5 to 10% of the mass of 2, 6-dimethylpyridine.
3. The method for producing cis-2, 6-dimethylpiperidine according to claim 2, wherein the distilled water is added in an amount of 50 to 60% by mass based on the mass of 2, 6-dimethylpyridine.
4. The method for preparing cis-2, 6-dimethylpiperidine according to claim 3, wherein the reaction pressure in the autoclave is 30 to 40kg/cm2The reaction temperature is 120-150 ℃, and the reaction time is 5-8 h.
5. The method according to claim 4, wherein the metal acetate comprises one or more selected from the group consisting of iron acetate, zinc acetate, and magnesium acetate.
6. The method according to claim 5, wherein the nickel powder is electrolytic nickel powder.
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