CN101704779B - Preparation method for feed additive dihydropyridine - Google Patents
Preparation method for feed additive dihydropyridine Download PDFInfo
- Publication number
- CN101704779B CN101704779B CN 200910272640 CN200910272640A CN101704779B CN 101704779 B CN101704779 B CN 101704779B CN 200910272640 CN200910272640 CN 200910272640 CN 200910272640 A CN200910272640 A CN 200910272640A CN 101704779 B CN101704779 B CN 101704779B
- Authority
- CN
- China
- Prior art keywords
- dihydropyridine
- liquid
- feed additive
- mole
- ethanol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 0 C[*+]C1=C(C)NC(C)=C(*)C1 Chemical compound C[*+]C1=C(C)NC(C)=C(*)C1 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Fodder In General (AREA)
Abstract
The invention discloses a preparation method for feed additive dihydropyridine. The method comprises the following steps of: a, putting ethyl acetoacetate and formaldehyde of 40 percent into a reaction kettle provided with a reflux condenser; stirring, mixing and dissolving the materials at a normal temperature, and adding ethanol to perform reaction to obtain a solution A; b, putting the ethyl acetoacetate and ammonia water into the reaction kettle provided with the reflux condenser, and adding the ethanol to perform reaction to obtain a solution B; and c, putting the solution A and the solution B into the reaction kettle provided with the reflux condenser, adding sodium hydroxide, and carrying out reacting, cooling, crystallizing, filtering and drying to obtain the dihydropyridine. The obtained dihydropyridine is applied to livestock and poultry feeds, can improve the fecundation (fertilization) rate, the hatchability, the laying rate, the milk yield and the daily gain of livestock and poultry and the feed returns, and can reduce the feeding cost. The dihydropyridine is a multifunctional feed additive with small usage and high efficiency and has a wide application prospect.
Description
Technical field
The present invention relates to pharmaceutical chemistry technical field, more specifically relate to a kind of preparation method for feed additive dihydropyridine.Dihydropyridine is a kind of Multifunction fodder additives, usually as the control health medicine of cardiovascular disorder, has treatment fatty liver, toxic hepatitis, the anti-ageing effect of waiting for a long time medically.Can also be as greasy antioxidant.
Background technology
The preparation method of pyridine ring system is the Han Qi synthesis method, is by two molecule beta-hydroxy acid esters, a part aldehyde and the preparation of a part ammonia generation condensation.Reaction process is that a part beta-hydroxy acid esters and a part aldehyde generate α-acyl group olefin(e) acid ester, and another molecule beta-hydroxy acid esters and ammonia generate beta-amino olefin(e) acid ester:
Beautifully adorned ell reaction takes place in these two compounds again, forms closed hoop then in alkaline alcohol solution.The method that prepare at present dihydropyridine has multiple, and for example a kind of is to be raw material with ammoniacal liquor, formaldehyde, methyl aceto acetate, and ethanol is solvent, reacts and separates out crystallization after cooling off in 2-3 hour, uses washing with alcohol, and yield is 50%.Though this method reaction conditions gentleness, yield is lower.Another kind method is to be raw material with formaldehyde, methyl aceto acetate, and diethylamine is a catalyzer, and water is solvent, reacts 40-45 hour, and classification oil reservoir after drying adds ethanol again, feeds ammonia, places 40 hours, obtains product, yield 84% behind the recovery ethanol.Though this method yield height, reaction time is long, aftertreatment complexity, expense height.The third is to be raw material with urotropine, methyl aceto acetate and amine acetate, water, and Virahol is a media, reacts 1-2 hour, obtains product, yield 80-83% after steaming solvent.This method reaction times is short, the yield height, but to steam isopropanol solvent, power consumption cost height.We adopt makes two kinds of single components respectively, and closed loop generates dihydropyridine in the alcoholic solution of alkalescence, and the reaction times is short.Yield is at 80-83%, and cost is lower.
Summary of the invention
The objective of the invention is to be to provide a kind of preparation method of multifunctional feed additive dihydropyridine.Adopt present method to prepare dihydropyridine, the reaction times is short, yield is high, cost is low.Dihydropyridine abroad has been widely used in producing as a kind of green feed additive.A large amount of evidences, dihydropyridine can improve the livestock and poultry reproductive performances such as (essence) rate, hatching rate, laying rate, milk yield of being impregnated of livestock and poultry, also can improve production performances such as the day weight gain and the price of deed.Be that a kind of consumption is few, the multifunctional feed additive of high efficiency, application prospect is very wide.
In order to realize above-mentioned purpose, the present invention adopts following technical measures:
The chemical name of dihydropyridine is 2,6-dimethyl-3, and 5-diethyl-ester group-1, the 4-dihydropyridine, molecular formula is C
13H
19NO
4, structural formula is
Dihydropyridine can significantly improve Triiodothyronine in the serum (T3) level, and can raise serum follitropin (FSH) and lutropin (LH), promotes the g and D of ovarian follicle indirectly.In addition, dihydropyridine can also improve cAMP content in hypothalamus, the adenohypophysis, thereby promotes synthesizing of body internal protein to promote growing of livestock and poultry.
Dihydropyridine has the effect of promotes growth, reduction feed intake preferably to pig, every interpolation every day 25mg in swine rations, 50mg, the dihydropyridine of 100mg, day weight gain improves 4.0% than control group respectively, 6.6% and 8.8%, feed intake reduces by 5.8%, 6.2% and 8.8% than control group respectively.
A kind of preparation method for feed additive dihydropyridine the steps include:
1. the formaldehyde of the weight percent 40% of 1 mole of methyl aceto acetate and 1-3 mole is put in the reactor that reflux exchanger is housed, under 25-35 ℃ of temperature, mix, the ethanol that adds weight ratio 1-3 percentage concentration 95% doubly, controlled temperature 60-80 ℃, reacted 1-2 hour, and obtained A liquid.
2. 1 mole of methyl aceto acetate and 2-4 mole bicarbonate of ammonia being packed into has in the reactor of reflux exchanger, adds 1-3 times of percentage concentration of weight ratio and be 95% ethanol, and 60～80 ℃ of controlled temperature reacted 1～2 hour, obtained B liquid.
3. A liquid and B liquid are put in the reactor that reflux exchanger is housed, added 50-80 gram sodium hydroxide, control reaction temperature 60-80 ℃, to react 1-2 hour, crystallization is separated out in cooling, filters, and filter cake obtained dihydropyridine in 3 hours 80 ℃ of dryings.
The present invention compared with prior art has the following advantages and effect:
Reaction times is short, yield is high, cost is low.Dihydropyridine abroad has been widely used in producing as a kind of green feed additive.A large amount of evidences, dihydropyridine can improve the livestock and poultry reproductive performances such as (essence) rate, hatching rate, laying rate, milk yield of being impregnated of livestock and poultry, also can improve production performances such as the day weight gain and the price of deed.Be that a kind of consumption is few, the multifunctional feed additive of high efficiency, application prospect is very wide.Functional feed additive dihydropyridine more than the present invention, 0.01% dihydropyridine is added in evidence in finishing pigs diets, can improve average daily gain 5.6% than control group, and feedstuff-meat ratio reduces by 3.5%.In the milking sow daily ration, add 0.01% dihydropyridine, from farrowing sow just before giving birth before 15-20 days to the wean of piglet 21 ages in days, can improve weight gain of piglets 6.6%.Dihydropyridine can also improve the reproductive performance of sow.In agent of feed for pregnancy sow, add 0.01% dihydropyridine, can increase the young number 1-2 head of living, improve nascent litter weight 12%.
Embodiment
The present invention is described further in conjunction with following example.
Example 1:
A kind of preparation method for feed additive dihydropyridine the steps include:
One, the weight percent concentration with 1 mole of methyl aceto acetate and 1 mole is 40% formaldehyde, input is equipped with in the reactor of reflux condensing tube, 25 or 28 or 30 or 32 or 34 or 35 ℃ of following stirring and dissolving, percentage concentration 95% ethanol that adds 1 times of weight ratio, 60 ℃ of controlled temperature, reacted 1 hour, and obtained A liquid.
Two, the bicarbonate of ammonia input with 1 mole of methyl aceto acetate and 2 moles is equipped with in the reactor of reflux condensing tube, adds per-cent 95% ethanol of 1 times of weight ratio, and 60 ℃ of controlled temperature reacted 1 hour, obtained B liquid.
Three, A liquid and B liquid are put in the reactor that reflux condensing tube is housed, added 50 gram sodium hydroxide, 60 ℃ of control reaction temperature were reacted 1 hour, and crystallization is separated out in cooling, filters, and filter cake obtained dihydropyridine in 3 hours 80 ℃ of dryings.
Example 2:
A kind of preparation method for feed additive dihydropyridine the steps include:
One, the weight percent concentration 40% formaldehyde input with 1 mole of methyl aceto acetate and 1.5 moles is equipped with in the reactor of reflux condensing tube, 25 or 27 or 39 or 31 or 33 or 35 ℃ of following stirring and dissolving, percentage concentration 95% ethanol that adds 1.5 times of weight ratios, 65 ℃ of controlled temperature, reacted 1.5 hours, and obtained A liquid.
Two, the bicarbonate of ammonia input with 1 mole of methyl aceto acetate and 2.5 moles is equipped with in the reactor of reflux condensing tube, adds percentage concentration 95% ethanol of 1.5 times of weight ratios, and 65 ℃ of controlled temperature reacted 1.5 hours, obtained B liquid.
Three, A liquid and B liquid are put in the reactor that reflux condensing tube is housed, added 60 gram sodium hydroxide, 65 ℃ of control reaction temperature were reacted 1.5 hours, and crystallization is separated out in cooling, filters, and filter cake obtained dihydropyridine in 3 hours 80 ℃ of dryings.
Example 3:
A kind of preparation method for feed additive dihydropyridine the steps include:
One, the weight percent concentration 40% formaldehyde input with 1 mole of methyl aceto acetate and 2 moles is equipped with in the reactor of reflux condensing tube, 25 or 26 or 29 or 31 or 33 or 35 ℃ of following stirring and dissolving, percentage concentration 95% ethanol that adds 2 times of weight ratios, 70 ℃ of controlled temperature, reacted 1.5 hours, and obtained A liquid.
Two, the bicarbonate of ammonia input with 1 mole of methyl aceto acetate and 3 moles is equipped with in the reactor of reflux condensing tube, adds percentage concentration 95% ethanol of 2 times of weight ratios, and 70 ℃ of controlled temperature reacted 1.5 hours, obtained B liquid.
Three, A liquid and B liquid are put in the reactor that reflux condensing tube is housed, added 70 gram sodium hydroxide, 70 ℃ of control reaction temperature were reacted 2 hours, and crystallization is separated out in cooling, filters, and filter cake obtained dihydropyridine in 3 hours 80 ℃ of dryings.
Example 4:
A kind of preparation method for feed additive dihydropyridine the steps include:
One, the weight percent concentration 40% formaldehyde input with 1 mole of methyl aceto acetate and 3 moles is equipped with in the reactor of reflux condensing tube, 25 or 26 or 29 or 31 or 33 or 35 ℃ of following stirring and dissolving, percentage concentration 95% ethanol that adds 3 times of weight ratios, 80 ℃ of controlled temperature, reacted 2 hours, and obtained A liquid.
Two, the bicarbonate of ammonia input with 1 mole of methyl aceto acetate and 4 moles is equipped with in the reactor of reflux condensing tube, adds percentage concentration 95% ethanol of 3 times of weight ratios, and 80 ℃ of controlled temperature reacted 2 hours, obtained B liquid.
Three, A liquid and B liquid are put in the reactor that reflux condensing tube is housed, added 80 gram sodium hydroxide, 80 ℃ of control reaction temperature were reacted 2 hours, and crystallization is separated out in cooling, filters, and filter cake obtained dihydropyridine in 3 hours 80 ℃ of dryings.
Claims (1)
1. a preparation method for feed additive dihydropyridine the steps include:
1. the formaldehyde of the weight percent 40% of 1 mole of methyl aceto acetate and 1-3 mole is put in the reactor that reflux exchanger is housed, under 25-35 ℃ of temperature, mix, the ethanol that adds weight ratio 1-3 percentage concentration 95% doubly, controlled temperature 60-80 ℃, reacted 1-2 hour, and obtained A liquid;
2. 1 mole of methyl aceto acetate and 2-4 mole bicarbonate of ammonia being packed into has in the reactor of reflux exchanger, adds 1-3 times of percentage concentration of weight ratio and be 95% ethanol, and 60～80 ℃ of controlled temperature reacted 1～2 hour, obtained B liquid;
3. A liquid and B liquid are put in the reactor that reflux exchanger is housed, added 50-80 gram sodium hydroxide, control reaction temperature 60-80 ℃, to react 1-2 hour, crystallization is separated out in cooling, filters, and filter cake obtained dihydropyridine in 3 hours 80 ℃ of dryings, and its structural formula is as follows:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200910272640 CN101704779B (en) | 2009-11-03 | 2009-11-03 | Preparation method for feed additive dihydropyridine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200910272640 CN101704779B (en) | 2009-11-03 | 2009-11-03 | Preparation method for feed additive dihydropyridine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101704779A CN101704779A (en) | 2010-05-12 |
| CN101704779B true CN101704779B (en) | 2011-08-24 |
Family
ID=42375044
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200910272640 Active CN101704779B (en) | 2009-11-03 | 2009-11-03 | Preparation method for feed additive dihydropyridine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101704779B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101973929B (en) * | 2010-09-10 | 2012-07-18 | 济南青禾生物技术有限公司 | Synthesis method of 2,6-dimethyl-3,5-dicarbethoxy-1,4-dihydropyridine |
| CN103044315A (en) * | 2013-01-12 | 2013-04-17 | 石家庄学院 | Method for preparing 1,4-dihydropyridine by taking acidic ionic liquid as catalyst |
| CN107389843B (en) * | 2017-07-29 | 2020-03-31 | 黑龙江谱尼测试科技有限公司 | Method for detecting dihydropyridine in feed |
-
2009
- 2009-11-03 CN CN 200910272640 patent/CN101704779B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN101704779A (en) | 2010-05-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103694107B (en) | The preparation method of fodder additives beta-hydroxy-Beta-methyl Calcium Butyrate | |
| CN103980163B (en) | Method for continuously synthesizing N-carbamylglutamic acid by using micro-channel reactor | |
| CN101704779B (en) | Preparation method for feed additive dihydropyridine | |
| CN101402612A (en) | Synthesis of quinocetone | |
| CN111072508A (en) | Preparation method and application of zinc valine | |
| CN109651274A (en) | Thiocarbamide composite feed additive with urease inhibiting activity and preparation method thereof | |
| US8754256B2 (en) | Process for preparation of L-Arginine α-ketoglutarate 1:1 and 2:1 | |
| CN106431969A (en) | Method for preparing 2-methyl-4-formaldoxime methyl benzoate | |
| CN103880712A (en) | Diaminoguanidine derivatives and application thereof in preparation of growth promoter for animal feeds | |
| CN102093467A (en) | Dipeptide iron chelate for feed additives and preparation method thereof | |
| CN106188200B (en) | The preparation method of sucrose zinc complex | |
| CN102146052A (en) | Method for preparing tryptophan | |
| CN101845070B (en) | Synthesis method of antineoplastic medicine capecitabine | |
| CN102408384A (en) | Improved synthesis method of quinocetone | |
| CN104672155A (en) | Synthetic method of improved quinocetone | |
| CN101411404B (en) | Process for synthesizing novel high-efficient feeding promoting agent for fish and prawn | |
| CN101973929B (en) | Synthesis method of 2,6-dimethyl-3,5-dicarbethoxy-1,4-dihydropyridine | |
| CN103641756B (en) | The preparation method of high purity and high-bulk-density HMBC | |
| CN101255118A (en) | Method for preparing beet alkali hydrochlorate | |
| CN105693558B (en) | A kind of method that glycocyamine is continuously produced by microchannel reaction unit | |
| CN102146022A (en) | Method for preparing 3-chlorine-5-bromophenol | |
| CN104788392A (en) | Synthetic method for high-purity and high-yield quinocetone | |
| CN108017534A (en) | A kind of method for preparing sodium Diacetate | |
| CN103641757A (en) | Preparation method for calcium D,L-2-hydroxy-4-methylthiobutyrate | |
| CN105585477A (en) | A synthetic method of sodium diacetate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: HUNAN XINWUFENG CO., LTD. Free format text: FORMER OWNER: TROPICAL AGRICULTURAL ECOLOGICAL INST., CHINESE ACADEMY OF SCIENCES Effective date: 20131105 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 410125 CHANGSHA, HUNAN PROVINCE TO: 410005 CHANGSHA, HUNAN PROVINCE |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20131105 Address after: 19-20, No. 2, No. 410005, first West Road, Furong West Road, Furong district, Hunan, Changsha Patentee after: Hunan New Wellful Co., Ltd. Address before: 410125 Hunan province Changsha Furong district Mapoling two Yuanda Road No. 1071 Patentee before: Institute of Subtropical Agriculture, Chinese Academy of Sciences |