CN106883165A - A kind of preparation method of template intermediate - Google Patents
A kind of preparation method of template intermediate Download PDFInfo
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- CN106883165A CN106883165A CN201710001425.8A CN201710001425A CN106883165A CN 106883165 A CN106883165 A CN 106883165A CN 201710001425 A CN201710001425 A CN 201710001425A CN 106883165 A CN106883165 A CN 106883165A
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- template intermediate
- preparation
- ammonium salt
- organic solvent
- template
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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
- C07D211/04—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
- C07D211/14—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 hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
Abstract
The invention belongs to chemical industry synthesis field, more particularly to a kind of preparation method of template intermediate, comprise the following steps：A, in the autoclave of hydrogen shield gas pyridine derivate, catalyst, alkylating reagent, organic solvent is added to be reacted, suction filtration removes catalyst after reaction, takes off dry organic solvent, obtains template intermediate piperidine quarternary ammonium salt crude product；B, the template intermediate piperidine quarternary ammonium salt crude product that will be obtained in step A mix with organic solvent, and mashing stirring, suction filtration obtains template intermediate piperidine quarternary ammonium salt；The template intermediate piperidine quarternary ammonium salt that the present invention is prepared, its high income, up to more than 85%, low cost, one-step method is obtained yield, and reactions steps are simple, convenient post-treatment, are adapted to industrialized production.
Description
Technical field
The invention belongs to chemical industry synthesis field, more particularly to a kind of preparation method of template intermediate.
Background technology
Template intermediate piperidine quarternary ammonium salt is the important intermediate in chemical industry synthesis field, and conventional synthesis process is as follows
(being illustrated by taking piperidines quarternary ammonium salt as an example)：
Wherein X can for carbonic acid mono-methyl ion, methyl sulfate ion, carbonic acid mono ethyl ester ion or Ethyl Sulfate from
Son；The conventional synthesis process first step is, with pyridine derivate as raw material, corresponding piperidine derivative to be obtained through catalytic hydrogenation；
Second step with piperidine derivative as raw material, through alkyl base reagent (formic acid/formaldehyde, iodomethane, dimethyl carbonate, dimethyl sulfate
Ester, diethyl carbonate, dithyl sulfate etc.) tertiary amine is obtained；3rd step is obtained phase with tertiary amine as raw material through quaternary ammonium reagent
The template intermediate piperidine quarternary ammonium salt answered.
Above-mentioned preparation method is found through the present inventor's research, its reactions steps is cumbersome, yield is relatively low is difficult in adapt in industry
Metaplasia is produced.
The content of the invention
The technical problems to be solved by the invention are to provide a kind of reactions steps simply, and high income is adapted to industrialized production
Template intermediate piperidine quarternary ammonium salt preparation method.
The technical scheme that the present invention solves above-mentioned technical problem is as follows：A kind of template intermediate, it is characterised in that its knot
Structure formula is as follows：
R1It is methyl or ethyl；R2、R3、R4、R5、R6Respectively methyl, ethyl, isopropyl, tertiary fourth
Base, straight chain, side chain C1-C30One kind in alkyl or cycloalkyl；X is carbonic acid mono-methyl ion, methyl sulfate ion, carbonic acid list
One kind in ethyl ester ion or Ethyl Sulfate ion.
A kind of preparation method of template intermediate, comprises the following steps：
A, add in the autoclave of hydrogen shield gas pyridine derivate, catalyst, alkylating reagent, organic
Solvent is reacted, and suction filtration removes catalyst after reaction, takes off dry organic solvent, obtains template intermediate piperidine quarternary ammonium salt thick
Product；
B, the template intermediate piperidine quarternary ammonium salt crude product that will be obtained in step A mix with organic solvent, mashing stirring,
Suction filtration, obtains template intermediate piperidine quarternary ammonium salt.
On the basis of above-mentioned technical proposal, the present invention can also do following improvement.
Further, in step, the alkylating reagent is dimethyl carbonate, diethyl carbonate, dimethyl suflfate, sulphur
One or more in diethyl phthalate.
Further, in step, the pyridine derivate structural formula is as follows：
R2、R3、R4、R5、R6Respectively methyl, ethyl, isopropyl, the tert-butyl group, straight chain, side chain C1-C30
One kind in alkyl or cycloalkyl；Preferably 3,5- lutidines, 3,5- parvolines, 2,6- lutidines, 2,6-
Parvoline.
Further, in step, the catalyst is the one kind or several in palladium carbon, ruthenium carbon, activated carbon, palladium aluminum oxide, nickel
Kind.
Further, in step, the organic solvent be toluene, methyl alcohol, THF, acetonitrile, petroleum ether, n-hexane, DMF,
One or more in ethyl acetate.
Further, in step, the pyridine derivate, alkylating reagent and organic solvent mol ratio are 1：(2-12):
(1-30), the pyridine derivate is 1 with the catalyst quality ratio:(0.01-1.0).
Further, in step, the reaction temperature is 50-250 DEG C, and pressure is 0.10-1.20Mpa.
Further, in stepb, the organic solvent be toluene, methyl alcohol, THF, acetonitrile, petroleum ether, n-hexane, DMF,
One or more in dimethyl carbonate, ethyl acetate.
Further, in stepb, the organic solvent and the template intermediate piperidine quarternary ammonium salt crude product quality ratio
It is 1：(0.5-10).
The beneficial effects of the invention are as follows：Pyridine is hydrogenated to piperidines, piperidine methyl chemical conversion N- methyl piperidines, N- first by the present invention
Phenylpiperidines methyl chemical conversion salt three step synthesizes a step, directly synthesizes template intermediate piperidine quarternary ammonium salt by pyridine derivate,
Its high income, up to more than 85%, low cost, one-step method is obtained yield, and reactions steps are simple, convenient post-treatment, are adapted to industry
Metaplasia is produced.
Brief description of the drawings
Fig. 1 is the template intermediate nuclear-magnetism carbon spectrogram of the embodiment of the present invention 1；
Fig. 2 is the template intermediate nucleus magnetic hydrogen spectrum figure of the embodiment of the present invention 1.
Specific embodiment
Principle of the invention and feature are described below, example is served only for explaining the present invention, is not intended to limit
Determine the scope of the present invention.
Embodiment 1
A, by 214.3g (2.0mol) 3,5- lutidines, 540.0g (6.0mol) dimethyl carbonate, 64.0g
(2.0mol) methyl alcohol, 10.7g rutheniums carbon (effective content 5%) are added in the autoclave of 2L, close autoclave, and nitrogen is put
Change 6 times, hydrogen replace 6 times, pressurising be warming up to Hydrogen Vapor Pressure for 9.0MPa, temperature be 150 DEG C after, Hydrogen Vapor Pressure in course of reaction
Can be greatly reduced, heat-insulation pressure keeping reaction 10.0h, pressure release of lowering the temperature, suction filtration removes catalyst, deviates from methyl alcohol and dries to obtain faint yellow product
Product crude product 403.6g；
B, 2L there-necked flask are furnished with mechanical agitation, thermometer, drying tube, 403.6g crude products, the 200g that above-mentioned reaction is obtained
N-hexane, 200.0g ethyl acetate are added in 2L there-necked flasks, are warming up to 50 DEG C, are beaten 1.0h, are cooled to room temperature suction filtration, and 100g is just
Hexane and 100g ethyl acetate mixed solvent drip washing filter cakes, filter cake dry to obtain white powdery solids 381.9g, and yield is
87.8%, as template intermediate piperidine quarternary ammonium salt.
Nuclear-magnetism carbon composes (D2O, 100MHZ)：δ=160.295,67.630,56.437,48.109,38.096,25.849,
17.397。
Nucleus magnetic hydrogen spectrum (D2O, 400MHZ)：δ=3.196-3.206 (t, 1H), 3.165-3.174 (t, 1H), 2.903-
2.955 (d, 6H), 2.598-2.661 (t, 2H), 1.918-1.996 (m, 2H), 1.726-1.768 (m, 1H), 0.761-0.778
(d,6H),0.595-0.690(m,1H)
Embodiment 2
A, by 212.3g3,5- lutidines, 538.0g diethyl carbonates, 64.0g (2.0mol) methyl alcohol, 15.7g palladium carbons
Add in the autoclave of 2L, close autoclave, nitrogen displacement 6 times, hydrogen is replaced 6 times, and pressurising is warming up to hydrogen pressure
Power be 9.0MPa, temperature be 200 DEG C after, Hydrogen Vapor Pressure can be greatly reduced in course of reaction, heat-insulation pressure keeping reaction 10.0h, cooling
Pressure release, suction filtration removes catalyst, deviates from methyl alcohol and dries to obtain light yellow product crude product 386.4g；
B, 2L there-necked flask are furnished with mechanical agitation, thermometer, drying tube, 386.4g crude products, the 200g that above-mentioned reaction is obtained
N-hexane, 200.0g ethyl acetate are added in 2L there-necked flasks, are warming up to 50 DEG C, are beaten 1.0h, are cooled to room temperature suction filtration, and 100g is just
Hexane and 100g ethyl acetate mixed solvent drip washing filter cakes, filter cake dry to obtain white powdery solids 371.3g, and yield is
85.5%, as template intermediate piperidine quarternary ammonium salt.
Embodiment 3
A, by 212.4g3,5- lutidines, 540.0g (6.0mol) dimethyl carbonate, 64.0g (2.0mol) methyl alcohol,
11.2g rutheniums carbon (effective content 5%) are added in the autoclave of 2L, closing autoclave, nitrogen displacement 6 times, and hydrogen is put
Change 6 times, pressurising is warming up to Hydrogen Vapor Pressure for 9.0MPa, temperature for after 250 DEG C, Hydrogen Vapor Pressure can be greatly reduced in course of reaction,
Heat-insulation pressure keeping reacts 10.0h, and pressure release of lowering the temperature, suction filtration removes catalyst, deviates from methyl alcohol and dries to obtain light yellow product crude product
401.8g；
B, 2L there-necked flask are furnished with mechanical agitation, thermometer, drying tube, 401.8g crude products, the 200g that above-mentioned reaction is obtained
Acetonitrile, 200.0gDMF are added in 2L there-necked flasks, are warming up to 50 DEG C, are beaten 1.0h, are cooled to room temperature suction filtration, 100g acetonitriles with
100gDMF mixed solvent drip washing filter cakes, filter cake dries to obtain white powdery solids 391.3g, and yield is 90.16%, as template
Agent intermediate piperidine quarternary ammonium salt.
The foregoing is only presently preferred embodiments of the present invention, be not intended to limit the invention, it is all it is of the invention spirit and
Within principle, any modification, equivalent substitution and improvements made etc. should be included within the scope of the present invention.
Claims (10)
1. a kind of template intermediate, it is characterised in that its structural formula is as follows：
R1It is methyl or ethyl；R2、R3、R4、R5、R6Respectively methyl, ethyl, isopropyl, the tert-butyl group,
Straight chain, side chain C1-C30One kind in alkyl or cycloalkyl；X is carbonic acid mono-methyl ion, methyl sulfate ion, carbonic acid list second
One kind in ester ion or Ethyl Sulfate ion.
2. a kind of preparation method of template intermediate, it is characterised in that comprise the following steps：
A, addition pyridine derivate, catalyst, alkylating reagent, organic solvent in the autoclave of hydrogen shield gas
Reacted, suction filtration removes catalyst after reaction, taken off dry organic solvent, obtained template intermediate piperidine quarternary ammonium salt crude product；
B, the template intermediate piperidine quarternary ammonium salt crude product that will be obtained in step A mix with organic solvent, mashing stirring, take out
Filter, obtains template intermediate piperidine quarternary ammonium salt.
3. a kind of preparation method of template intermediate according to claim 2, it is characterised in that in step, the alkane
Base reagent is one or more in dimethyl carbonate, diethyl carbonate, dimethyl suflfate, dithyl sulfate.
4. a kind of preparation method of template intermediate according to claim 2, it is characterised in that in step, the pyrrole
Piperidine derivatives structural formula is as follows：
R2、R3、R4、R5、R6Respectively methyl, ethyl, isopropyl, the tert-butyl group, straight chain, side chain C1-C30Alkyl
Or the one kind in cycloalkyl.
5. a kind of preparation method of template intermediate according to claim 2, it is characterised in that in step, described to urge
Agent is one or more in palladium carbon, ruthenium carbon, activated carbon, palladium aluminum oxide, nickel.
6. a kind of preparation method of template intermediate according to claim 2, it is characterised in that in step, described to have
Machine solvent is one or more in toluene, methyl alcohol, THF, acetonitrile, petroleum ether, n-hexane, DMF, ethyl acetate.
7. a kind of preparation method of template intermediate according to claim 2, it is characterised in that in step, the pyrrole
Piperidine derivatives, alkylating reagent and organic solvent mol ratio are 1：(2-12):(1-30), the pyridine derivate and the catalysis
Agent mass ratio is 1:(0.01-1.0).
8. a kind of preparation method of template intermediate according to claim 2, it is characterised in that in step, described anti-
Answer temperature for 50-250 DEG C, pressure is 0.10-1.20Mpa.
9. a kind of preparation method of template intermediate according to claim 2, it is characterised in that in stepb, described to have
Machine solvent is the one kind or several in toluene, methyl alcohol, THF, acetonitrile, petroleum ether, n-hexane, DMF, dimethyl carbonate, ethyl acetate
Kind.
10. a kind of preparation method of template intermediate according to claim 2, it is characterised in that in stepb, described
Organic solvent is 1 with the template intermediate piperidine quarternary ammonium salt crude product quality ratio：(0.5-10).
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020002908A1 (en) | 2018-06-26 | 2020-01-02 | Johnson Matthey Public Limited Company | Hydrogenation process |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1087640A (en) * | 1992-05-29 | 1994-06-08 | 普罗格特甘布尔药品有限公司 | Novel phosphononosulfonatecompounds compounds, pharmaceutical composition, and the method for treatment abnormal calcium and phosphate metabolism |
| CN1241986A (en) * | 1996-12-31 | 2000-01-19 | 切夫里昂美国公司 | A process for preparing zeolites using substituted-piperidinium cations |
| CN101104146A (en) * | 2006-07-14 | 2008-01-16 | 常州艾坛化学有限公司 | Method for preparing cis-and-trans mixed isomers 3,5-dimethylpiperidine |
| CN105315195A (en) * | 2014-07-29 | 2016-02-10 | 孙红 | Template agent and preparation method therefor and application thereof |
| CN105314646A (en) * | 2014-07-29 | 2016-02-10 | 孙红 | AEI-type aluminosilicate molecular sieves, and preparation methods and applications thereof |
-
2017
- 2017-01-03 CN CN201710001425.8A patent/CN106883165B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1087640A (en) * | 1992-05-29 | 1994-06-08 | 普罗格特甘布尔药品有限公司 | Novel phosphononosulfonatecompounds compounds, pharmaceutical composition, and the method for treatment abnormal calcium and phosphate metabolism |
| CN1241986A (en) * | 1996-12-31 | 2000-01-19 | 切夫里昂美国公司 | A process for preparing zeolites using substituted-piperidinium cations |
| CN101104146A (en) * | 2006-07-14 | 2008-01-16 | 常州艾坛化学有限公司 | Method for preparing cis-and-trans mixed isomers 3,5-dimethylpiperidine |
| CN105315195A (en) * | 2014-07-29 | 2016-02-10 | 孙红 | Template agent and preparation method therefor and application thereof |
| CN105314646A (en) * | 2014-07-29 | 2016-02-10 | 孙红 | AEI-type aluminosilicate molecular sieves, and preparation methods and applications thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020002908A1 (en) | 2018-06-26 | 2020-01-02 | Johnson Matthey Public Limited Company | Hydrogenation process |
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Denomination of invention: A preparation method of template intermediate Effective date of registration: 20211202 Granted publication date: 20190326 Pledgee: Yantai Branch of China Merchants Bank Co.,Ltd. Pledgor: VALIANT Co.,Ltd. Registration number: Y2021980013807 |
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