CN113372262A - Preparation method of trans-3, 5-dimethylpiperidine - Google Patents
Preparation method of trans-3, 5-dimethylpiperidine Download PDFInfo
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- CN113372262A CN113372262A CN202110638206.7A CN202110638206A CN113372262A CN 113372262 A CN113372262 A CN 113372262A CN 202110638206 A CN202110638206 A CN 202110638206A CN 113372262 A CN113372262 A CN 113372262A
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- dimethylpyridine
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- IDWRJRPUIXRFRX-BQBZGAKWSA-N (3s,5s)-3,5-dimethylpiperidine Chemical compound C[C@@H]1CNC[C@@H](C)C1 IDWRJRPUIXRFRX-BQBZGAKWSA-N 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- 238000006243 chemical reaction Methods 0.000 claims abstract description 74
- HWWYDZCSSYKIAD-UHFFFAOYSA-N 3,5-dimethylpyridine Chemical compound CC1=CN=CC(C)=C1 HWWYDZCSSYKIAD-UHFFFAOYSA-N 0.000 claims abstract description 56
- IDWRJRPUIXRFRX-UHFFFAOYSA-N 3,5-dimethylpiperidine Chemical compound CC1CNCC(C)C1 IDWRJRPUIXRFRX-UHFFFAOYSA-N 0.000 claims abstract description 55
- 239000003054 catalyst Substances 0.000 claims abstract description 35
- 239000002131 composite material Substances 0.000 claims abstract description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000008367 deionised water Substances 0.000 claims abstract description 14
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 13
- 239000001257 hydrogen Substances 0.000 claims abstract description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000012043 crude product Substances 0.000 claims abstract description 12
- 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
- 229910052751 metal Inorganic materials 0.000 claims description 22
- 239000002184 metal Substances 0.000 claims description 22
- NCPHGZWGGANCAY-UHFFFAOYSA-N methane;ruthenium Chemical compound C.[Ru] NCPHGZWGGANCAY-UHFFFAOYSA-N 0.000 claims description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 20
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 16
- 230000035484 reaction time Effects 0.000 claims description 11
- 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 10
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims description 5
- 239000004246 zinc acetate Substances 0.000 claims description 5
- 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 3
- 230000000694 effects Effects 0.000 abstract description 12
- 239000000047 product Substances 0.000 abstract description 5
- 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 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 3
- 238000004817 gas chromatography Methods 0.000 description 18
- 238000005984 hydrogenation reaction Methods 0.000 description 18
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- IDWRJRPUIXRFRX-KNVOCYPGSA-N (3r,5s)-3,5-dimethylpiperidine Chemical compound C[C@H]1CNC[C@@H](C)C1 IDWRJRPUIXRFRX-KNVOCYPGSA-N 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 229910052755 nonmetal Inorganic materials 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- UTVVREMVDJTZAC-UHFFFAOYSA-N furan-2-amine Chemical compound NC1=CC=CO1 UTVVREMVDJTZAC-UHFFFAOYSA-N 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- JTSDBFGMPLKDCD-XVFHVFLVSA-N tilmicosin Chemical compound O([C@@H]1[C@@H](C)[C@H](O)CC(=O)O[C@@H]([C@H](/C=C(\C)/C=C/C(=O)[C@H](C)C[C@@H]1CCN1C[C@H](C)C[C@H](C)C1)CO[C@H]1[C@@H]([C@H](OC)[C@H](O)[C@@H](C)O1)OC)CC)[C@@H]1O[C@H](C)[C@@H](O)[C@H](N(C)C)[C@H]1O JTSDBFGMPLKDCD-XVFHVFLVSA-N 0.000 description 2
- 229960000223 tilmicosin Drugs 0.000 description 2
- IECMOFZIMWVOAS-UHFFFAOYSA-N 4,4-dimethylpiperidine Chemical compound CC1(C)CCNCC1 IECMOFZIMWVOAS-UHFFFAOYSA-N 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- FHRUYXZYSXCYDM-UHFFFAOYSA-N [C].[Rh].[Ru].[Ni] Chemical compound [C].[Rh].[Ru].[Ni] FHRUYXZYSXCYDM-UHFFFAOYSA-N 0.000 description 1
- QYVRLHRCJOZEPM-UHFFFAOYSA-N [Rh].[Ni].[Ru] Chemical compound [Rh].[Ni].[Ru] QYVRLHRCJOZEPM-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- UBADKKCCQHYPIX-UHFFFAOYSA-N aluminum oxygen(2-) ruthenium(3+) Chemical compound [O-2].[Al+3].[Ru+3].[O-2].[O-2] UBADKKCCQHYPIX-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 239000012535 impurity 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
- 244000144972 livestock Species 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Images
Classifications
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/09—Geometrical isomers
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
The invention discloses a preparation method of trans-3, 5-dimethylpiperidine, belonging to the technical field of chemical products. The method comprises the following steps: A. under the condition of hydrogen protection, adding 3, 5-dimethylpyridine, deionized 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 3, 5-dimethylpiperidine; B. and D, cooling the crude 3, 5-dimethylpiperidine obtained in the step A to room temperature, taking out the reaction mixture, standing, and taking the supernatant to obtain the 3, 5-dimethylpiperidine. The reaction condition is mild and easy to control, the reaction effect is good, and the trans-form content can reach 20-35%.
Description
Technical Field
The invention belongs to the technical field of chemical products, and particularly relates to a preparation method of trans-3, 5-dimethylpiperidine.
Background
3, 5-dimethylpiperidine is a main intermediate of the common drug Tilmicosin, Tilmicosin is a special antibiotic for livestock and poultry, and the dosage is large; it is also a main intermediate of the environment-friendly new material automobile exhaust adsorbent. The 3, 5-dimethylpiperidine has cis-trans isomers, and the main synthesis mode is that a kettle type hydrogenation process is mainly adopted, and 3, 5-dimethylpiperidine is prepared by hydrogenation of 3, 5-dimethylpyridine by adopting a hydrogenation catalyst. In addition, the method of furan amine is also available, wherein the production cost of furan amine method is high, so the industrial production is generally carried out by hydrogenation.
In order to solve the above problems, there have been searched, for example, patent application nos.: 200610088375.3, filing date: in 2006, 7, 14, the invention and creation name is: a method for preparing cis-trans mixed isomer 3, 5-dimethylpiperidine, namely a method for preparing 3, 5-dimethylpiperidine mixture with cis form of 85% +/-3 and trans form of 15% +/-3 by adopting novel nickel ruthenium rhodium carbon composite catalyst one-step hydrogenation reaction from 3, 5-dimethylpyridine, which adopts tetrahydrofuran as an organic solvent and predetermined temperature and pressure, and uses a nickel ruthenium rhodium catalyst adsorbed on active carbon in the reaction process. As in patent application No.: 201710077728.8, filing date: in 2017, 2, 13 months, the name of invention creation is: a preparation method of high-purity cis-3, 5-dimethylpiperidine comprises the steps of taking 3, 5-dimethylpyridine as a raw material, adding potassium carbonate, neutral alumina and ruthenium carbon into a high-pressure reaction kettle to perform catalytic hydrogenation reaction to obtain a crude product of the 3, 5-dimethylpiperidine, and separating out and purifying to obtain the high-purity cis-3, 5-dimethylpiperidine, wherein the purity of a cis gas chromatography is more than 99.5%. As in patent application No.: 201810676458.7, filing date: in 2018, 6 and 27 months, the invention and creation name is: a method for synthesizing dimethylpiperidine comprises the steps of adding 3, 5-dimethylpyridine into an autoclave, adding methanol, ethanol or tetrahydrofuran organic solvent and Pd/C catalyst, heating to 90-160 ℃, and pressurizing to 3kg/cm2～10kg/cm2And introducing hydrogen for reduction to obtain the catalyst.
For example, U.S. Pat. No. 4, 4138399A discloses a process for preparing cis 3, 5-dimethylpiperidine from 3, 5-dimethylpyridine by a one-step hydrogenation reaction under hydrogen pressure in the presence of 5% rhodium on carbon as a catalyst and ethanol as a solvent at room temperature in 1000 Psi. Chinese patent publication No. CN1636979A discloses a method for separating cis-3, 5-dimethylpiperidine from a geometric isomer of cis-3, 5-dimethylpyridine. Wherein the method is that 3, 5-dimethyl pyridine is reacted in water as solvent and 5 percent ruthenium alumina as catalyst at the temperature of 180 ℃ and the reaction pressure of 3-10kg/cm at 250 DEG C 25% ruthenium aluminum oxide 0.5-2.0%, water 10-60%, catalyst repeated use 10-20 times.
With the increase of the market demand of trans-3, 5-dimethylpiperidine and the addition of the trans-content of the product synthesized usually only 13-16%, the development of an environment-friendly, efficient and economic preparation method of trans-3, 5-dimethylpiperidine is of great significance.
Disclosure of Invention
1. Technical problem to be solved by the invention
Aiming at the problem of low proportion of trans-3, 5-dimethylpiperidine in the existing preparation of 3, 5-dimethylpiperidine, the invention provides a preparation method of trans-3, 5-dimethylpiperidine, which can improve the proportion of trans-3, 5-dimethylpiperidine.
2. Technical scheme
In order to achieve the purpose, the technical scheme provided by the invention is as follows:
the preparation method of the trans-3, 5-dimethylpiperidine comprises the following steps:
A. under the condition of hydrogen protection, adding 3, 5-dimethylpyridine, deionized 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 3, 5-dimethylpiperidine;
B. and D, cooling the crude 3, 5-dimethylpiperidine obtained in the step A to room temperature, taking out the reaction mixture, standing, and taking the supernatant to obtain the 3, 5-dimethylpiperidine. The step is to separate the catalyst and 3, 5-dimethyl piperidine, to settle the catalyst in the standing stage, and to clean the separated catalyst for reuse.
In one possible embodiment of the invention, the mass of the added composite catalyst is 5-10% of the mass of the 3, 5-dimethylpyridine.
In a possible embodiment of the invention, the mass of the deionized water added is 40-60% of the mass of the 3, 5-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 140-160 ℃, and the reaction time is5-8 h. Compared with the preparation method of trans-3, 5-dimethylpiperidine in the prior art, the reaction temperature of the invention is improved.
In one possible embodiment of the present invention, the composite catalyst is: the mixture of ruthenium carbon, nickel powder and metal acetate, wherein the mass ratio of the ruthenium carbon to the nickel powder to the metal acetate is 1: (0.05-0.1): (0.05-0.08). As can be known from the background art, cis-trans isomers can be generated in the preparation process of 3, 5-dimethylpiperidine, so that cis-3, 5-dimethylpiperidine and trans-3, 5-dimethylpiperidine can be obtained by controlling the reaction process. According to the invention, the density of electron clouds on the pyridine ring is greatly reduced through the metal acetate, the hydrogenation activity of one pyridine ring is improved, so that the hydrogenation has diastereoselectivity, in addition, acetate ions in the metal acetate do not influence the electronic state of the catalyst for selective hydrogenation of 3, 5-dimethylpyridine, and non-metal elements are not introduced.
The invention adopts the composite catalyst, the components comprise ruthenium carbon, nickel powder and metal acetate, and the composite effect of the ruthenium carbon, the nickel powder and the metal acetate is (1) to improve the dispersion condition of the catalyst components; (2) the mixture of nickel powder and metal acetate can not only form a catalytic layer on the surface of ruthenium carbon, enlarge the catalytic area of the ruthenium carbon and improve the content of trans-3, 5-dimethylpiperidine; (3) the activity of metal acetate is 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, and the yield of the trans-3, 5-dimethylpiperidine is relatively improved. In addition, the ratio of cis-trans isomers of 3, 5-dimethylpiperidine is related to reaction conditions such as temperature, pressure, and the ratio of cis-trans isomers is further controlled by controlling the reaction pressure, the reaction temperature and the reaction time.
In one possible embodiment of the present invention, the metal acetate includes one or a mixture of iron acetate, zinc acetate and magnesium acetate.
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 the trans-3, 5-dimethylpiperidine, provided by the invention, through the composite catalyst, the reaction condition is mild and easy to control, the reaction effect is good, and the trans-content can reach 20-35%, because the ruthenium carbon can improve the conversion of the trans-3, 5-dimethylpiperidine, the activity of the electrolytic nickel powder is higher, the electron cloud density on a pyridine ring can be greatly reduced under the combined action of the electrolytic nickel powder, the ruthenium carbon and the metal acetate, and the hydrogenation activity of one pyridine ring is improved, so that the hydrogenation has diastereoselectivity; in addition, acetate ions in the metal acetate do not influence the electronic state of the catalyst for selective hydrogenation of 3, 5-dimethylpyridine, and a non-metal element is not introduced;
(2) the preparation method of the trans-3, 5-dimethylpiperidine provided by the invention uses deionized water as a solvent, is environment-friendly and reduces the cost;
(3) the preparation method of the trans-3, 5-dimethylpiperidine provided by the invention has colorless and transparent color and less impurities;
(4) the preparation method of the trans-3, 5-dimethylpiperidine provided by the invention is convenient for industrial production;
(5) according to the preparation method of the trans-3, 5-dimethylpiperidine, the catalyst can be repeatedly used, and the loss is small.
Drawings
FIG. 1 is a chromatogram of example 1 of the present invention.
Detailed Description
For a further understanding of the contents of the present invention, reference will now be made in detail to the following examples.
Example 1
The preparation method of trans-3, 5-dimethylpiperidine of this example includes the following steps:
A. under the condition of hydrogen protection, 100g of 3, 5-lutidine, 40g of deionized water and 5g of composite catalyst (the mass ratio of ruthenium 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 140 ℃, the reaction time is 5 hours, and the crude product of the 3, 5-dimethylpiperidine is obtained by suction filtration after the reaction is finished;
B. and D, cooling the crude 3, 5-dimethylpiperidine obtained in the step A to room temperature, taking out the reaction mixture, standing, and taking the supernatant to obtain the 3, 5-dimethylpiperidine.
Since the boiling points of the product 3, 5-dimethylpiperidine and the starting material 3, 5-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 temperature was 250 ℃.
The peak positions of the starting 3, 5-lutidine and the product 3, 5-dimethylpiperidine by chromatography were determined to be consistent with the standards provided by this company.
The content of the trans isomer of the 3, 5-dimethylpiperidine mixture was determined to be 29.44% by Gas Chromatography (GC).
Comparative examples 1 to 1
On the basis of example 1, the composite catalyst is not added with iron acetate, and the preparation method of the trans-3, 5-dimethylpiperidine of the comparative example comprises the following steps:
A. under the protection of hydrogen, 100g of 3, 5-lutidine, 40g of deionized water and 5g of composite catalyst (the mass ratio of ruthenium to 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 140 ℃, the reaction time is 5 hours, and the crude product of the 3, 5-dimethylpiperidine is obtained by suction filtration after the reaction is finished;
B. and D, cooling the crude 3, 5-dimethylpiperidine obtained in the step A to room temperature, taking out the reaction mixture, standing, and taking the supernatant to obtain the 3, 5-dimethylpiperidine.
The content of the trans isomer of the 3, 5-dimethylpiperidine mixture was found to be 18.5% by Gas Chromatography (GC).
Comparative examples 1 to 2
On the basis of example 1, the composite catalyst does not contain ruthenium carbon, and the preparation method of trans-3, 5-dimethylpiperidine of the comparative example comprises the following steps:
A. under the condition of hydrogen protection, 100g of 3, 5-lutidine, 40g of deionized 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 reactorThe reaction is carried out in a kettle, and the reaction pressure for carrying out the reaction is 30kg/cm2The reaction temperature is 140 ℃, the reaction time is 5 hours, and the crude product of the 3, 5-dimethylpiperidine is obtained by suction filtration after the reaction is finished;
B. and D, cooling the crude 3, 5-dimethylpiperidine obtained in the step A to room temperature, taking out the reaction mixture, standing, and taking the supernatant to obtain the 3, 5-dimethylpiperidine.
The content of the trans isomer of the 3, 5-dimethylpiperidine mixture was determined to be 19.1% by Gas Chromatography (GC).
Comparative examples 1 to 3
On the basis of example 1, the ruthenium-carbon + nickel powder is not added into the composite catalyst, and the preparation method of the trans-3, 5-dimethylpiperidine of the comparative example comprises the following steps:
A. under the condition of hydrogen protection, 100g of 3, 5-lutidine, 40g of deionized 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 140 ℃, the reaction time is 5 hours, and the crude product of the 3, 5-dimethylpiperidine is obtained by suction filtration after the reaction is finished;
B. and D, cooling the crude 3, 5-dimethylpiperidine obtained in the step A to room temperature, taking out the reaction mixture, standing, and taking the supernatant to obtain the 3, 5-dimethylpiperidine.
The content of the trans isomer of the 3, 5-dimethylpiperidine mixture was determined to be 16.9% by Gas Chromatography (GC).
The 3, 5-dimethyl pyridine is hydrogenated to obtain a mixture of 3, 5-dimethyl piperidine isomers, wherein the cis-form and the trans-form are 85% + -3%: 15% + -3%, the currently disclosed process typically yields trans 3, 5-dimethylpiperidine in a ratio of 13-16%, with the greatest problem with 3, 5-dimethylpyridine being hydroprocessed to yield 3, 5-dimethylpiperidine being the hydrogenation selectivity.
Comparing example 1 with comparative examples 1-1, 1-2 and 1-3, it can be seen that ruthenium 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 ruthenium carbon, enlarge the catalytic area of the ruthenium carbon and improve the content of trans-3, 5-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 the trans-3, 5-dimethylpiperidine is relatively improved, and the content of the trans-3, 5-dimethylpiperidine can reach 20-35%; in addition, acetate ions in the metal acetate do not influence the electronic state of the catalyst for selective hydrogenation of 3, 5-dimethylpyridine, and a non-metal element is not introduced.
Example 2
The preparation method of trans-3, 5-dimethylpiperidine of this example includes the following steps:
A. under the condition of hydrogen protection, 100g of 3, 5-dimethylpyridine, 60g of deionized water and 8g of composite catalyst (the mass ratio of ruthenium carbon to nickel powder to metal zinc 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 150 ℃, the reaction time is 8 hours, and the crude product of the 3, 5-dimethylpiperidine is obtained by suction filtration after the reaction is finished;
B. and D, cooling the crude 3, 5-dimethylpiperidine obtained in the step A to room temperature, taking out the reaction mixture, standing, and taking the supernatant to obtain the 3, 5-dimethylpiperidine.
The content of the trans isomer of the 3, 5-dimethylpiperidine mixture was determined to be 34.9% by Gas Chromatography (GC).
Example 3
The preparation method of trans-3, 5-dimethylpiperidine of this example includes the following steps:
A. under the condition of hydrogen protection, 100g of 3, 5-dimethylpyridine, 50g of deionized water and 6g of composite catalyst (the mass ratio of the ruthenium carbon to the nickel powder to the metal magnesium acetate is 1: 0.1: 0.05) are added into a high-pressure reaction kettle for reaction, and the reaction pressure for the reaction is 35kg/cm2Reaction temperature of 160 ℃ and reaction time of 6 hoursAfter reaction, carrying out suction filtration to obtain a crude product of the 3, 5-dimethylpiperidine;
B. and D, cooling the crude 3, 5-dimethylpiperidine obtained in the step A to room temperature, taking out the reaction mixture, standing, and taking the supernatant to obtain the 3, 5-dimethylpiperidine.
The content of the trans isomer of the 3, 5-dimethylpiperidine mixture was determined to be 32.7% by Gas Chromatography (GC).
Example 4
The preparation method of trans-3, 5-dimethylpiperidine of this example includes the following steps:
A. under the condition of hydrogen protection, 100g of 3, 5-dimethylpyridine, 60g of deionized water and 10g of composite catalyst (the mass ratio of ruthenium carbon to nickel powder to metallic iron 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 145 ℃, the reaction time is 8 hours, and the crude product of the 3, 5-dimethylpiperidine is obtained by suction filtration after the reaction is finished;
B. and D, cooling the crude 3, 5-dimethylpiperidine obtained in the step A to room temperature, taking out the reaction mixture, standing, and taking the supernatant to obtain the 3, 5-dimethylpiperidine.
The content of the trans isomer of the 3, 5-dimethylpiperidine mixture was determined to be 24.8% by Gas Chromatography (GC).
Example 5
The preparation method of trans-3, 5-dimethylpiperidine of this example includes the following steps:
A. under the condition of hydrogen protection, 100g of 3, 5-dimethylpyridine, 50g of deionized water and 6g of composite catalyst (the mass ratio of ruthenium 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 155 ℃, the reaction time is 5 hours, and the crude product of the 3, 5-dimethylpiperidine is obtained by suction filtration after the reaction is finished;
B. and D, cooling the crude 3, 5-dimethylpiperidine obtained in the step A to room temperature, taking out the reaction mixture, standing, and taking the supernatant to obtain the 3, 5-dimethylpiperidine.
The content of the trans isomer of the 3, 5-dimethylpiperidine mixture was measured to be 27.3% by Gas Chromatography (GC).
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 trans-3, 5-dimethylpiperidine is characterized by comprising the following steps:
A. under the condition of hydrogen protection, adding 3, 5-dimethylpyridine, deionized 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 3, 5-dimethylpiperidine;
B. and D, cooling the crude 3, 5-dimethylpiperidine obtained in the step A to room temperature, taking out the reaction mixture, standing, and taking the supernatant to obtain the 3, 5-dimethylpiperidine.
2. A method for preparing trans-3, 5-dimethylpiperidine according to claim 1, wherein the mass of the composite catalyst added is 5 to 10% of the mass of the 3, 5-dimethylpyridine.
3. A process for preparing trans-3, 5-dimethylpiperidine according to claim 1, wherein deionized water is added in an amount of 40 to 60% by mass based on the mass of 3, 5-dimethylpyridine.
4. The method for preparing trans-3, 5-dimethylpiperidine according to claim 1, wherein the reaction pressure in the autoclave is 30 to 40kg/cm2The reaction temperature is 140-160 ℃, and the reaction time is 5-8 h.
5. The method for preparing trans-3, 5-dimethylpiperidine according to claim 1, wherein the composite catalyst is: the mixture of ruthenium carbon, nickel powder and metal acetate, wherein the mass ratio of the ruthenium carbon to the nickel powder to the metal acetate is 1: (0.05-0.1): (0.05-0.08).
6. The method for preparing trans 3, 5-dimethylpiperidine according to claim 1, wherein the metal acetate comprises a mixture of one or more of iron acetate, zinc acetate and magnesium acetate.
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