CN101698658A - Method for preparing wormer sec-Butyl 2-(2-hydroxyethyl)piperidine-1-carboxylate - Google Patents
Method for preparing wormer sec-Butyl 2-(2-hydroxyethyl)piperidine-1-carboxylate Download PDFInfo
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Abstract
The invention discloses a method for preparing a wormer sec-Butyl 2-(2-hydroxyethyl)piperidine-1-carboxylate, which comprises the following three steps: firstly, taking 2-methylpyridine as a starting material to undergo a condensation reaction with paraformaldehyde to produce 2-hydroxyethyl pyridine in the presence of a catalyst sodium carbonate or potassium carbonate; secondly, dissolving the 2-hydroxyethyl pyridine into a solvent and adding a high-efficient hydrogenation catalyst for reaction with hydrogen for a certain time at a certain temperature and under a certain pressure to produce 2-hydroxyethyl piperidine; and finally, placing the 2-hydroxyethyl piperidine and aqueous slkali into a reaction bulb, controlling the reaction temperature, dropwise adding sec-butyl chloroformate dropwise under the condition of no solvent, and after reacting for certain time, performing acid cleaning, water rinsing and drying to directly produce a finished product of the sec-Butyl 2-(2-hydroxyethyl)piperidine-1-carboxylate. The method is low in production cost, moderate in reaction conditions, less in side reaction, high in yield, good in product quality, simple and convenient in process and easy in operation.
Description
Technical field
The present invention relates to a kind of wormer preparation method, be meant a kind of preparation method of wormer sec-Butyl 2-(2-hydroxyethyl) piperidine-1-carboxylate especially.
Background technology
Ai Karuiding claims hydroxyl piperazine ester again, and hydroxyethyl piperidine carboxylic acid isobutyl ester, chemical name are 1-(1-sec-butyl carboxylate)-2-(2-hydroxyethyl) piperidines (CAS NO 87818-31-3), is a kind of wormer of safe, effective, environmental protection.It is direct kill insects not, and is and can effectively drives insect under the situation of harmless user's health by the volatilization of smell, allows the user avoid the hardship of mosquito bite, and can replace the Metadelphene that the smell is awful, viscosity is big.Ai Karuiding has been proved to be effective wormer composition, is playing an important role aspect prevention and control malaria, singapore hemorrhagic fever hemorrhagic fever, yellow jack, west Nile virus, lime borreliosis (Lyme disease), the contour mortality vector borne diseases of forest encephalitis.Special needs to be pointed out is that Ai Karuiding has obtained The World Health Organization (WHO) and has been recommended as the diseases such as malaria that can effectively prevent by the mosquito bite propagation.Ai Karuiding has some advantages that other wormers do not have: widely applicable, and all effective to mosquito, louse, sand fly and horse botfly etc.; Very gentle to skin, there is not glutinous soapy feeling, nonirritant, no anaphylaxis is difficult for by skin absorption, and safety has no side effect; 2 years old and above children all can use safely; To plastics, synthetic materials, plastic paint, lock packing, fiber and tamanori not damaged; Conceived and can use lactation, 2 years old and above children also all can use safely.
Ai Karuiding is developed in 20 worlds by Bayer (Bayer) company the earliest the end of the nineties; entered American market in 2005; product is also rare, has obtained state's approvals and approval such as Environmental Protection Agency and Sweden, Norway, Denmark at present, has vast potential for future development.About the preparation method of Ai Karuiding, more existing both at home and abroad documents and patent report.U.S. Pat 4900834 (1988) application documents disclose the synthetic method of series compounds such as Ai Karuiding the earliest, wherein Ai Karuiding is that employing 2-hydroxyethyl piperidine is a starting raw material, through obtaining crude product, obtain finished product through high vacuum rectification again with the sec-butyl chloroformate condensation.China's patent (publication number 101323588A) also discloses a kind of preparation method of Ai Karuiding, be to be starting raw material with 2-hydroxyethyl pyridine, after High Temperature High Pressure hydrogenation, obtain the 2-hydroxyethyl piperidine, obtain crude product with the sec-butyl chloroformate condensation again, obtain finished product through high vacuum rectification again.
All there is deficiency in existing these synthetic methods, are mainly reflected in:
1), the market price height of starting raw material 2-hydroxyethyl piperidine or 2-hydroxyethyl pyridine, cause the product cost height;
2), used a large amount of organic solvents when 2-hydroxyethyl piperidine and sec-butyl chloroformate condensation, not only can damage, also strengthen production cost human body;
3), need high vacuum high temperature and add the antioxidant condition to get off to distill acquisition Ai Karuiding finished product, energy consumption height.
Summary of the invention
The object of the present invention is to provide that a kind of starting raw material cost is low, side reaction is few, technology is simply to realize the low and preparation method of the wormer sec-Butyl 2-(2-hydroxyethyl) piperidine-1-carboxylate that yield is high of production cost.
For achieving the above object, technical scheme of the present invention is:
A kind of preparation method of wormer sec-Butyl 2-(2-hydroxyethyl) piperidine-1-carboxylate, it comprises the steps:
1) preparation of 2-hydroxyethyl pyridine
2-picoline, Paraformaldehyde 96 and catalyzer are joined in the reaction flask, the heated and stirred reaction, 130～150 ℃/10～20mmHg cut is collected in underpressure distillation, gets product 2-hydroxyethyl pyridine;
2) preparation of 2-hydroxyethyl piperidine
2-hydroxyethyl pyridine is dissolved in the solvent, adds catalyzer, feed the hydrogen reacting by heating, gas chromatographic analysis shows the 1% o'clock stopped reaction of 2-hydroxyethyl pyridine content less than total amount, reacting liquid filtering is removed catalyzer, and distillating recovering solvent, residuum are the 2-hydroxyethyl piperidine;
3) preparation of Ai Karuiding
The 2-hydroxyethyl piperidine is placed reaction flask, adding concentration is 20% alkaline solution, mixed solution stirs, and drips sec-butyl chloroformate in mixed solution, continues to stir 2h after adding to the reaction end, branch vibration layer, organic phase concentration is 10% acid solution washing three times, wash twice again after, use anhydrous sodium sulfate drying, remove by filter siccative, get product Ai Karuiding finished product.
In the described step 1), 2-picoline and Paraformaldehyde 96 are 1 by mass ratio: (0.2～0.4); And the amount that adds catalyzer is 2%～5% of 2-picoline by mass percentage; Temperature of reaction is 60～100 ℃; The stirring reaction time is 15～20h.
Described catalyzer is yellow soda ash or salt of wormwood.
Described step 2) in, 2-hydroxyethyl pyridine and solvent are 1 by mass ratio: (2～5); And the add-on of catalyzer is 1%～5% of 2-hydroxyethyl pyridine by mass percentage; The pressure of described feeding hydrogen is 2～4Mpa; The temperature of reaction is 60～80 ℃; The time of reaction is 4～8h.
Described solvent is a kind of in toluene, ethyl acetate, tetrahydrofuran (THF) or the ethanol.
Described catalyzer is Raney's nickel (SC-4100) or 10% palladium carbon.
In the described step 3), 2-hydroxyethyl piperidine and alkali and sec-butyl chloroformate are 1 in molar ratio: (1.5～2.0): (0.95～1.0); The time of described dropping sec-butyl chloroformate is 60～100min, and the temperature that continues stirring reaction is 30～50 ℃.
Described alkali is a kind of in yellow soda ash, sodium hydroxide or the sodium bicarbonate.
Described acid solution is a kind of in hydrochloric acid soln, sulphuric acid soln or the acetic acid solution, and consumption is 3 times of 2-hydroxyethyl piperidine quality.
After adopting such scheme, because the preparation method of wormer sec-Butyl 2-(2-hydroxyethyl) piperidine-1-carboxylate of the present invention is to be starting raw material with low-cost 2-picoline, in the presence of catalyzer carbonic acid sodium or salt of wormwood, obtain the critical materials 2-hydroxyethyl pyridine that Ai Karuiding prepares with the Paraformaldehyde 96 condensation reaction, catalytic hydrogenation obtains the 2-hydroxyethyl piperidine again; Adopt at last under condition of no solvent and in the 2-hydroxyethyl piperidine, drip sec-butyl chloroformate, thereby significantly reduced the generation of by product, need not underpressure distillation and just can obtain the Ai Karuiding finished product of content more than 98%.
Therefore the present invention compares with existing Ai Karuiding preparation method, has following outstanding advantage:
1), the present invention is the critical materials 2-hydroxyethyl pyridine that starting raw material obtains Ai Karuiding preparation with low-cost 2-picoline, greatly reduces production cost.
2), the catalyst efficiency height that uses in the preparation process of 2-hydroxyethyl piperidine, reaction pressure and temperature all can reduce greatly, have reduced the potential safety hazard of producing.
3), adopt and under condition of no solvent, to react, and sec-butyl chloroformate adds with the dropping form, reduced the generation of by product, need not underpressure distillation and just can directly obtain the Ai Karuiding finished product of content more than 98%.
4), the reaction conditions gentleness, by product is few, technology is simple, easy to operate, easily realize industrialized production.
Embodiment
§ embodiment 1
1) preparation of 2-hydroxyethyl pyridine
100g 2-picoline, 20g Paraformaldehyde 96 and 2g yellow soda ash are joined in the reaction flask, at 100 ℃ of following stirring reaction 15h.130～150 ℃/10～20mmHg cut is collected in the reaction solution underpressure distillation, gets product 2-hydroxyethyl pyridine, 115.6g, chromatogram content 98.9%.
2) preparation of 2-hydroxyethyl piperidine
50g 2-hydroxyethyl pyridine, 250g toluene and 2.5g Raney's nickel (SC-4100) are put in the high-pressure hydrogenation still, used nitrogen replacement three times, use twice of hydrogen exchange again.Stir down and slowly be warming up to 60 ℃, and keep hydrogen pressure 4Mpa, reaction 6h, gas chromatographic analysis shows the 1% o'clock stopped reaction of 2-hydroxyethyl pyridine content less than total amount.Reacting liquid filtering is removed catalyzer, and toluene is reclaimed in distillation, and residuum is the 2-hydroxyethyl piperidine, 50.6g, chromatogram content 99.2%.
3) preparation of Ai Karuiding
With 40g (99.2%, 0.307mol) the 2-hydroxyethyl piperidine places reaction flask, adding 325g concentration is 20% yellow soda ash (0.614mol) aqueous solution, mixed solution stirs, controlled temperature is 30 ℃, drip in the mixed solution simultaneously 42.2g (99%, 0.307mol) sec-butyl chloroformate, the dropping time is controlled at 60～100min, adds the back and continues to stir 2h end reaction.Branch vibration layer, organic phase concentration are 10% sulfuric acid scrubbing three times, each 120g, and then remove waste water with dividing after the 120g clear water washed twice, the organic phase anhydrous sodium sulfate drying removes by filter siccative, get product Ai Karuiding finished product, 61.2g, chromatogram content 98.3%.
§ embodiment 2
1) preparation of 2-hydroxyethyl pyridine
100g 2-picoline, 30g Paraformaldehyde 96 and 5g yellow soda ash are joined in the reaction flask, at 60 ℃ of following stirring reaction 20h.130～150 ℃/10～20mmHg cut is collected in the reaction solution underpressure distillation, gets product 2-hydroxyethyl pyridine, 116.5g, chromatogram content 98.7%.
2) preparation of 2-hydroxyethyl piperidine
50g 2-hydroxyethyl pyridine, 100g ethyl acetate and 0.5g Raney's nickel (SC-4100) are put in the high-pressure hydrogenation still, used nitrogen replacement three times, use twice of hydrogen exchange again.Stir down and slowly be warming up to 80 ℃, and keep hydrogen pressure 3Mpa, reaction 8h, gas chromatographic analysis shows the 1% o'clock stopped reaction of 2-hydroxyethyl pyridine content less than total amount.Reacting liquid filtering is removed catalyzer, and ethyl acetate is reclaimed in distillation, and residuum is the 2-hydroxyethyl piperidine, 50.5g, chromatogram content 99.3%.
3) preparation of Ai Karuiding
With 40g (99.3%, 0.308mol) the 2-hydroxyethyl piperidine places reaction flask, adding 245g concentration is 20% yellow soda ash (0.462mol) aqueous solution, mixed solution stirs, controlled temperature is 50 ℃, drip in the mixed solution simultaneously 40.2g (99%, 0.293mol) sec-butyl chloroformate, the dropping time is controlled at 60～100min, adds the back and continues to stir 2h end reaction.Branch vibration layer, organic phase concentration are 10% sulfuric acid scrubbing three times, each 120g, and then remove waste water with dividing after the 120g clear water washed twice, the organic phase anhydrous sodium sulfate drying removes by filter siccative, get product Ai Karuiding finished product, 60.4g, chromatogram content 98.4%.
§ embodiment 3
1) preparation of 2-hydroxyethyl pyridine
100g 2-picoline, 40g Paraformaldehyde 96 and 3g yellow soda ash are joined in the reaction flask, at 90 ℃ of following stirring reaction 16h.130～150 ℃/10～20mmHg cut is collected in the reaction solution underpressure distillation, gets product 2-hydroxyethyl pyridine, 115.3g, chromatogram content 98.8%.
2) preparation of 2-hydroxyethyl piperidine
50g 2-hydroxyethyl pyridine, 200g tetrahydrofuran (THF) and 2g Raney's nickel (SC-4100) are put in the high-pressure hydrogenation still, used nitrogen replacement three times, use twice of hydrogen exchange again.Stir down and slowly be warming up to 70 ℃, and keep hydrogen pressure 4Mpa, reaction 7h, gas chromatographic analysis shows the 1% o'clock stopped reaction of 2-hydroxyethyl pyridine content less than total amount.Reacting liquid filtering is removed catalyzer, and tetrahydrofuran (THF) is reclaimed in distillation, and residuum is the 2-hydroxyethyl piperidine, 50.3g, chromatogram content 99.1%.
3) preparation of Ai Karuiding
With 40g (99.1%, 0.307mol) the 2-hydroxyethyl piperidine places reaction flask, adding 277g concentration is 20% yellow soda ash (0.522mol) aqueous solution, mixed solution stirs, controlled temperature is 40 ℃, drip in the mixed solution simultaneously 40.9g (99%, 0.298mol) sec-butyl chloroformate, the dropping time is controlled at 60～100min, adds the back and continues to stir 2h end reaction.Branch vibration layer, organic phase concentration are 10% sulfuric acid scrubbing three times, each 120g, and then remove waste water with dividing after the 120g clear water washed twice, the organic phase anhydrous sodium sulfate drying removes by filter siccative, get product Ai Karuiding finished product, 60.7g, chromatogram content 98.4%.
§ embodiment 4
1) preparation of 2-hydroxyethyl pyridine
100g 2-picoline, 20g Paraformaldehyde 96 and 4g yellow soda ash are joined in the reaction flask, at 70 ℃ of following stirring reaction 18h.130～150 ℃/10～20mmHg cut is collected in the reaction solution underpressure distillation, gets product 2-hydroxyethyl pyridine, 113.8g, chromatogram content 99.2%.
2) preparation of 2-hydroxyethyl piperidine
50g 2-hydroxyethyl pyridine, 250g ethanol and 1g Raney's nickel (SC-4100) are put in the high-pressure hydrogenation still, used nitrogen replacement three times, use twice of hydrogen exchange again.Stir down and slowly be warming up to 80 ℃, and keep hydrogen pressure 2Mpa, reaction 5h, gas chromatographic analysis shows the 1% o'clock stopped reaction of 2-hydroxyethyl pyridine content less than total amount.Reacting liquid filtering is removed catalyzer, and ethanol is reclaimed in distillation, and residuum is the 2-hydroxyethyl piperidine, 49.8g, chromatogram content 99.2%.
3) preparation of Ai Karuiding
With 40g (99.2%, 0.307mol) the 2-hydroxyethyl piperidine places reaction flask, adding 92.2g concentration is 20% sodium hydroxide (0.461mol) aqueous solution, mixed solution stirs, controlled temperature is 40 ℃, drip in the mixed solution simultaneously 42.2g (99%, 0.307mol) sec-butyl chloroformate, the dropping time is controlled at 60～100min, adds the back and continues to stir 2h end reaction.Branch vibration layer, organic phase concentration are 10% salt acid elution three times, each 120g, and then remove waste water with dividing after the 120g clear water washed twice, the organic phase anhydrous sodium sulfate drying removes by filter siccative, get product Ai Karuiding finished product, 59.9g, chromatogram content 98.2%.
§ embodiment 5
1) preparation of 2-hydroxyethyl pyridine
100g 2-picoline, 30g Paraformaldehyde 96 and 3g salt of wormwood are joined in the reaction flask, at 80 ℃ of following stirring reaction 19h.130～150 ℃/10～20mmHg cut is collected in the reaction solution underpressure distillation, gets product 2-hydroxyethyl pyridine, 116.2g, chromatogram content 98.6%.
2) preparation of 2-hydroxyethyl piperidine
50g 2-hydroxyethyl pyridine, 100g ethanol and 1.5g Raney's nickel (SC-4100) are put in the high-pressure hydrogenation still, used nitrogen replacement three times, use twice of hydrogen exchange again.Stir down and slowly be warming up to 80 ℃, and keep hydrogen pressure 4Mpa, reaction 4h, gas chromatographic analysis shows the 1% o'clock stopped reaction of 2-hydroxyethyl pyridine content less than total amount.Reacting liquid filtering is removed catalyzer, and ethanol is reclaimed in distillation, and residuum is the 2-hydroxyethyl piperidine, 50.1g, chromatogram content 99.1%.
3) preparation of Ai Karuiding
With 40g (99.1%, 0.307mol) the 2-hydroxyethyl piperidine places reaction flask, adding 104.5g concentration is 20% sodium hydroxide (0.522mol) aqueous solution, mixed solution stirs, controlled temperature is 30 ℃, drip in the mixed solution simultaneously 41.3g (99%, 0.301mol) sec-butyl chloroformate, the dropping time is controlled at 60～100min, adds the back and continues to stir 2h end reaction.Branch vibration layer, organic phase concentration are 10% salt acid elution three times, each 120g, and then remove waste water with dividing after the 120g clear water washed twice, the organic phase anhydrous sodium sulfate drying removes by filter siccative, get product Ai Karuiding finished product, 58.6g, chromatogram content 98.4%.
§ embodiment 6
1) preparation of 2-hydroxyethyl pyridine
100g 2-picoline, 20g Paraformaldehyde 96 and 4g salt of wormwood are joined in the reaction flask, at 100 ℃ of following stirring reaction 15h.130～150 ℃/10～20mmHg cut is collected in the reaction solution underpressure distillation, gets product 2-hydroxyethyl pyridine, 114.6g, chromatogram content 99.1%.
2) preparation of 2-hydroxyethyl piperidine
50g 2-hydroxyethyl pyridine, 100g toluene and 1.5g Raney's nickel (SC-4100) are put in the high-pressure hydrogenation still, used nitrogen replacement three times, use twice of hydrogen exchange again.Stir down and slowly be warming up to 60 ℃, and keep hydrogen pressure 4Mpa, reaction 8h, gas chromatographic analysis shows the 1% o'clock stopped reaction of 2-hydroxyethyl pyridine content less than total amount.Reacting liquid filtering is removed catalyzer, and toluene is reclaimed in distillation, and residuum is the 2-hydroxyethyl piperidine, 50.4g, chromatogram content 99.2%.
3) preparation of Ai Karuiding
With 40g (99.2%, 0.307mol) the 2-hydroxyethyl piperidine places reaction flask, adding 122.8g concentration is 20% sodium hydroxide (0.614mol) aqueous solution, mixed solution stirs, controlled temperature is 50 ℃, drip in the mixed solution simultaneously 41.3g (99%, 0.301mol) sec-butyl chloroformate, the dropping time is controlled at 60～100min, adds the back and continues to stir 2h end reaction.Branch vibration layer, organic phase concentration are 10% salt acid elution three times, each 120g, and then remove waste water with dividing after the 120g clear water washed twice, the organic phase anhydrous sodium sulfate drying removes by filter siccative, get product Ai Karuiding finished product, 59.3g, chromatogram content 98.2%.
§ embodiment 7
1) preparation of 2-hydroxyethyl pyridine
100g 2-picoline, 40g Paraformaldehyde 96 and 5g salt of wormwood are joined in the reaction flask, at 60 ℃ of following stirring reaction 20h.130～150 ℃/10～20mmHg cut is collected in the reaction solution underpressure distillation, gets product 2-hydroxyethyl pyridine, 115.2g, chromatogram content 98.8%.
2) preparation of 2-hydroxyethyl piperidine
50g 2-hydroxyethyl pyridine, 150g toluene and 1.5g 10% palladium carbon are put in the high-pressure hydrogenation still, used nitrogen replacement three times, use twice of hydrogen exchange again.Stir down and slowly be warming up to 80 ℃, and keep hydrogen pressure 2Mpa, reaction 4h, gas chromatographic analysis shows the 1% o'clock stopped reaction of 2-hydroxyethyl pyridine content less than total amount.Reacting liquid filtering is removed catalyzer, and toluene is reclaimed in distillation, and residuum is the 2-hydroxyethyl piperidine, 49.2g, chromatogram content 99.1%.
3) preparation of Ai Karuiding
With 40g (99.1%, 0.307mol) the 2-hydroxyethyl piperidine places reaction flask, adding 257.8g concentration is 20% sodium bicarbonate (0.614mol) aqueous solution, mixed solution stirs, controlled temperature is 50 ℃, drip in the mixed solution simultaneously 40.1g (99%, 0.292mol) sec-butyl chloroformate, the dropping time is controlled at 60～100min, adds the back and continues to stir 2h end reaction.Branch vibration layer, organic phase concentration are 10% acetate washing three times, each 120g, and then remove waste water with dividing after the 120g clear water washed twice, the organic phase anhydrous sodium sulfate drying removes by filter siccative, get product Ai Karuiding finished product, 59.4g, chromatogram content 98.3%.
§ embodiment 8
1) preparation of 2-hydroxyethyl pyridine
100g 2-picoline, 20g Paraformaldehyde 96 and 2g salt of wormwood are joined in the reaction flask, at 90 ℃ of following stirring reaction 17h.130～150 ℃/10～20mmHg cut is collected in the reaction solution underpressure distillation, gets product 2-hydroxyethyl pyridine, 116.5g, chromatogram content 98.6%.
2) preparation of 2-hydroxyethyl piperidine
50g 2-hydroxyethyl pyridine, 250g ethyl acetate and 2.5g 10% palladium carbon are put in the high-pressure hydrogenation still, used nitrogen replacement three times, use twice of hydrogen exchange again.Stir down and slowly be warming up to 70 ℃, and keep hydrogen pressure 4Mpa, reaction 7h, gas chromatographic analysis shows the 1% o'clock stopped reaction of 2-hydroxyethyl pyridine content less than total amount.Reacting liquid filtering is removed catalyzer, and ethyl acetate is reclaimed in distillation, and residuum is the 2-hydroxyethyl piperidine, 48.6g, chromatogram content 99.2%.
3) preparation of Ai Karuiding
With 40g (99.2%, 0.307mol) the 2-hydroxyethyl piperidine places reaction flask, adding 193.4g concentration is 20% sodium bicarbonate (0.461mol) aqueous solution, mixed solution stirs, controlled temperature is 30 ℃, drip in the mixed solution simultaneously 42.2g (99%, 0.307mol) sec-butyl chloroformate, the dropping time is controlled at 60～100min, adds the back and continues to stir 2h end reaction.Branch vibration layer, organic phase concentration are 10% acetate washing three times, each 120g, and then remove waste water with dividing after the 120g clear water washed twice, the organic phase anhydrous sodium sulfate drying removes by filter siccative, get product Ai Karuiding finished product, 58.7g, chromatogram content 98.3%.
§ embodiment 9
1) preparation of 2-hydroxyethyl pyridine
100g 2-picoline, 30g Paraformaldehyde 96 and 5g yellow soda ash are joined in the reaction flask, at 70 ℃ of following stirring reaction 20h.130～150 ℃/10～20mmHg cut is collected in the reaction solution underpressure distillation, gets product 2-hydroxyethyl pyridine, 114.3g, chromatogram content 99%.
2) preparation of 2-hydroxyethyl piperidine
50g 2-hydroxyethyl pyridine, 100g tetrahydrofuran (THF) and 0.5g 10% palladium carbon are put in the high-pressure hydrogenation still, used nitrogen replacement three times, use twice of hydrogen exchange again.Stir down and slowly be warming up to 60 ℃, and keep hydrogen pressure 4Mpa, reaction 5h, gas chromatographic analysis shows the 1% o'clock stopped reaction of 2-hydroxyethyl pyridine content less than total amount.Reacting liquid filtering is removed catalyzer, and tetrahydrofuran (THF) is reclaimed in distillation, and residuum is the 2-hydroxyethyl piperidine, 47.9g, chromatogram content 99.3%.
3) preparation of Ai Karuiding
With 40g (99.3%, 0.308mol) the 2-hydroxyethyl piperidine places reaction flask, adding 220g concentration is 20% sodium bicarbonate (0.524mol) aqueous solution, mixed solution stirs, controlled temperature is 50 ℃, drip in the mixed solution simultaneously 41.1g (99%, 0.299mol) sec-butyl chloroformate, the dropping time is controlled at 60～100min, adds the back and continues to stir 2h end reaction.Branch vibration layer, organic phase concentration are 10% acetate washing three times, each 120g, and then remove waste water with dividing after the 120g clear water washed twice, the organic phase anhydrous sodium sulfate drying removes by filter siccative, get product Ai Karuiding finished product, 58.5g, chromatogram content 98.4%.
§ embodiment 10
1) preparation of 2-hydroxyethyl pyridine
100g 2-picoline, 40g Paraformaldehyde 96 and 2g yellow soda ash are joined in the reaction flask, at 100 ℃ of following stirring reaction 15h.130～150 ℃/10～20mmHg cut is collected in the reaction solution underpressure distillation, gets product 2-hydroxyethyl pyridine, 113.4g, chromatogram content 99.1%.
2) preparation of 2-hydroxyethyl piperidine
50g 2-hydroxyethyl pyridine, 200g toluene and 2.5g Raney's nickel (SC-4100) are put in the high-pressure hydrogenation still, used nitrogen replacement three times, use twice of hydrogen exchange again.Stir down and slowly be warming up to 60 ℃, and keep hydrogen pressure 4Mpa, reaction 6h, gas chromatographic analysis shows the 1% o'clock stopped reaction of 2-hydroxyethyl pyridine content less than total amount.Reacting liquid filtering is removed catalyzer, and toluene is reclaimed in distillation, and residuum is the 2-hydroxyethyl piperidine, 50.4g, chromatogram content 99.3%.
3) preparation of Ai Karuiding
With 40g (99.3%, 0.308mol) the 2-hydroxyethyl piperidine places reaction flask, adding 245g concentration is 20% yellow soda ash (0.461mol) aqueous solution, mixed solution stirs, controlled temperature is 40 ℃, drip in the mixed solution simultaneously 41.5g (99%, 0.302mol) sec-butyl chloroformate, the dropping time is controlled at 60～100min, adds the back and continues to stir 2h end reaction.Branch vibration layer, organic phase concentration are 10% sulfuric acid scrubbing three times, each 120g, and then remove waste water with dividing after the 120g clear water washed twice, the organic phase anhydrous sodium sulfate drying removes by filter siccative, get product Ai Karuiding finished product, 60.9g, chromatogram content 98.3%.
To sum up, adopt the inventive method to prepare wormer sec-Butyl 2-(2-hydroxyethyl) piperidine-1-carboxylate, it is low to have a production cost, the reaction condition gentleness, and side reaction is few, receipts rate height, good product quality, and technology is easy, the characteristics such as easy operating.
Claims (9)
1. the preparation method of a wormer sec-Butyl 2-(2-hydroxyethyl) piperidine-1-carboxylate, it comprises the steps:
1) preparation of 2-hydroxyethyl pyridine
2-picoline, Paraformaldehyde 96 and catalyzer are joined in the reaction flask, the heated and stirred reaction, 130～150 ℃/10～20mmHg cut is collected in underpressure distillation, gets product 2-hydroxyethyl pyridine;
2) preparation of 2-hydroxyethyl piperidine
2-hydroxyethyl pyridine is dissolved in the solvent, adds catalyzer, feed the hydrogen reacting by heating, gas chromatographic analysis shows the 1% o'clock stopped reaction of 2-hydroxyethyl pyridine content less than total amount, reacting liquid filtering is removed catalyzer, and distillating recovering solvent, residuum are the 2-hydroxyethyl piperidine;
3) preparation of Ai Karuiding
The 2-hydroxyethyl piperidine is placed reaction flask, adding concentration is 20% alkaline solution, mixed solution stirs, and drips sec-butyl chloroformate in mixed solution, continues to stir 2h after adding to the reaction end, branch vibration layer, organic phase concentration is 10% acid solution washing three times, wash twice again after, use anhydrous sodium sulfate drying, remove by filter siccative, get product Ai Karuiding finished product.
2. the preparation method of wormer sec-Butyl 2-(2-hydroxyethyl) piperidine-1-carboxylate as claimed in claim 1, it is characterized in that: in the described step 1), 2-picoline and Paraformaldehyde 96 are 1 by mass ratio: (0.2～0.4); And the amount that adds catalyzer is 2%～5% of 2-picoline by mass percentage; Temperature of reaction is 60～100 ℃; The stirring reaction time is 15～20h.
3. the preparation method of wormer sec-Butyl 2-(2-hydroxyethyl) piperidine-1-carboxylate as claimed in claim 1 or 2, it is characterized in that: described catalyzer is yellow soda ash or salt of wormwood.
4. the preparation method of wormer sec-Butyl 2-(2-hydroxyethyl) piperidine-1-carboxylate as claimed in claim 1, it is characterized in that: described step 2), 2-hydroxyethyl pyridine and solvent are 1 by mass ratio: (2～5); And the add-on of catalyzer is 1%～5% of 2-hydroxyethyl pyridine by mass percentage; The pressure of described feeding hydrogen is 2～4Mpa; The temperature of reaction is 60～80 ℃; The time of reaction is 4～8h.
5. as the preparation method of claim 1 or 4 described wormer sec-Butyl 2-(2-hydroxyethyl) piperidine-1-carboxylates, it is characterized in that: described solvent is a kind of in toluene, ethyl acetate, tetrahydrofuran (THF) or the ethanol.
6. as the preparation method of claim 1 or 4 described wormer sec-Butyl 2-(2-hydroxyethyl) piperidine-1-carboxylates, it is characterized in that: described catalyzer is Raney's nickel (SC-4100) or 10% palladium carbon.
7. the preparation method of wormer sec-Butyl 2-(2-hydroxyethyl) piperidine-1-carboxylate as claimed in claim 1, it is characterized in that: in the described step 3), 2-hydroxyethyl piperidine and alkali and sec-butyl chloroformate are 1 in molar ratio: (1.5～2.0): (0.95～1.0); The time of described dropping sec-butyl chloroformate is 60～100min, and the temperature that continues stirring reaction is 30～50 ℃.
8. as the preparation method of claim 1 or 7 described wormer sec-Butyl 2-(2-hydroxyethyl) piperidine-1-carboxylates, it is characterized in that: described alkali is a kind of in yellow soda ash, sodium hydroxide or the sodium bicarbonate.
9. as the preparation method of claim 1 or 7 described wormer sec-Butyl 2-(2-hydroxyethyl) piperidine-1-carboxylates, it is characterized in that: described acid solution is a kind of in hydrochloric acid soln, sulphuric acid soln or the acetic acid solution, and consumption is 3 times of 2-hydroxyethyl piperidine quality.
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| CN105237468A (en) * | 2015-10-08 | 2016-01-13 | 济南大学 | New method for synthesizing 2-hydroxyethylpyridine |
| CN106265097A (en) * | 2016-08-30 | 2017-01-04 | 杭州国光旅游用品有限公司 | A kind of mosquito-eliminating wet tissue and preparation method thereof |
| CN106580776A (en) * | 2016-12-11 | 2017-04-26 | 东莞小猕猴户外用品有限公司 | Preparation method of long-acting mosquito repellent liquid and long-acting mosquito repellent liquid |
| CN111270337A (en) * | 2020-04-13 | 2020-06-12 | 浙江正凯化纤有限公司 | Mosquito-repellent polyester fiber and preparation method thereof |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102167681A (en) * | 2010-12-30 | 2011-08-31 | 常州药物研究所 | Method for preparing insect repellant icaridin |
| CN102167681B (en) * | 2010-12-30 | 2012-10-24 | 常州药物研究所有限公司 | Method for preparing insect repellant icaridin |
| CN105237468A (en) * | 2015-10-08 | 2016-01-13 | 济南大学 | New method for synthesizing 2-hydroxyethylpyridine |
| CN106265097A (en) * | 2016-08-30 | 2017-01-04 | 杭州国光旅游用品有限公司 | A kind of mosquito-eliminating wet tissue and preparation method thereof |
| CN106580776A (en) * | 2016-12-11 | 2017-04-26 | 东莞小猕猴户外用品有限公司 | Preparation method of long-acting mosquito repellent liquid and long-acting mosquito repellent liquid |
| CN111270337A (en) * | 2020-04-13 | 2020-06-12 | 浙江正凯化纤有限公司 | Mosquito-repellent polyester fiber and preparation method thereof |
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| CN101698658B (en) | 2012-06-13 |
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