CN107337638A - A kind of high-efficiency synthesis method of pyridine carboxylic acid based food additive - Google Patents

A kind of high-efficiency synthesis method of pyridine carboxylic acid based food additive Download PDF

Info

Publication number
CN107337638A
CN107337638A CN201710689680.6A CN201710689680A CN107337638A CN 107337638 A CN107337638 A CN 107337638A CN 201710689680 A CN201710689680 A CN 201710689680A CN 107337638 A CN107337638 A CN 107337638A
Authority
CN
China
Prior art keywords
reaction
carboxylic acid
food additive
pyridine carboxylic
based food
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.)
Pending
Application number
CN201710689680.6A
Other languages
Chinese (zh)
Inventor
侯茜茜
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Mao Along
Original Assignee
侯茜茜
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by 侯茜茜 filed Critical 侯茜茜
Priority to CN201710689680.6A priority Critical patent/CN107337638A/en
Publication of CN107337638A publication Critical patent/CN107337638A/en
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C07D213/80—Acids; Esters in position 3
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/015—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/03—Organic compounds
    • A23L29/045—Organic compounds containing nitrogen as heteroatom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C07D213/803—Processes of preparation
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Nutrition Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Inorganic Chemistry (AREA)
  • Pyridine Compounds (AREA)

Abstract

The invention discloses a kind of high-efficiency synthesis method of pyridine carboxylic acid based food additive, belong to food additives synthesis technical field.A kind of chromium picolinate based food additive, there is following structure：

Description

A kind of high-efficiency synthesis method of pyridine carboxylic acid based food additive
Technical field
The invention belongs to food additives synthesis technical field, and in particular to a kind of height of pyridine carboxylic acid based food additive Imitate synthetic method.
Background technology
Chromium is well known as a kind of necessary micronutrient of people and mammal, and trivalent chromium passes through glucose Tolerance factor (GTF) acts synergistically and the effect of the sensitiveness of enhancing insulin influences lipid, carbohydrate, protein and nucleic acid Metabolism.Currently, trivalent Chroma-Pak has been widely used in the health products, medicine and video of people.From in the 1990s, trivalent Effect of the chromium in Animal nutrition is increasingly paid attention to and paid close attention to.As nourishing additive agent, chromium picolinate has obtained extensively Application.Chromium picolinate is pyridine carboxylic acid and Cr3+Complex compound, cell membrane can be passed through and directly act on cell tissue, Can strengthen insulin active, improve human body glycometabolism, be it is a kind of it is being allowed by the Ministry of Public Health, can be added in health food Functional component.In recent years, propolis is because it has antibacterial, anti-inflammatory, antipruritic, anti-oxidant, immune, the hypoglycemic, reducing blood lipid of enhancing, anti-swells The multiple functions such as knurl, there are extensive medical treatment, health-care effect to human body, it has also become emerging health products enjoy high praise, in the market Occur needing that there is the bee glue soft capsule class health food for adjusting blood glucose function, in which part bee glue soft capsule class health products Chromium picolinate is with the addition of, as nutritious supplementary pharmaceutical.In addition, lot of experiments proves that chromium has the work for promoting growth of animals or poultry really With, for example, chromium trichloride can stimulate feeding low-protein diet rat growth performance.To produce ox mend chromium, can increase feed intake and The output of milk, while also improve butterfat, lactose and newborn total solid.The milk cow addition chromium in 50 days or so postpartum can be significantly reduced Material milk ratio.The chromic salts of doses is added in aquatic animal feed can promote the growth of juvenile fish, increase fish body body weight and carry High feed efficiency etc..Nicotinate chromium is added in pig feed is fattened two months, compared with control group, adding weight is respectively increased 11.7%th, 11.1% and 12.5%, feed-weight ratio has been respectively increased 5.5%, 5.6% and 4.2%.We pass through new side in laboratory Method has synthesized a kind of new pyridine acid chromium class food additives, and the additive has that synthetic method is simple, bioconcentration it is low and The advantages that under getting fat effect.
The content of the invention
Present invention solves the technical problem that there is provided it is a kind of operation is simple, raw material is cheap and easy to get, reaction efficiency compared with A kind of high-efficiency synthesis method of high and reproducible pyridine carboxylic acid based food additive.
The present invention is to solve above-mentioned technical problem to adopt the following technical scheme that, a kind of height of pyridine carboxylic acid based food additive Imitate synthetic method, it is characterised in that concretely comprise the following steps：
A, cyanoacetic acid and the diethylamine reaction under trimethyl orthoformate effect obtains 3- (diethylamino) acrylonitrile；
B, trifluoromethyl ethanone and the Ethyl formate reaction under pyridine effect obtains 4- ethyoxyl -1,1,1- trifluoro butyl- 3- Alkene -2- ketone；
C, with 4- ethyoxyl -1,1,1- trifluoro butyl- 3- alkene -2- ketone substitution reaction life occurs for 3- (diethylamino) acrylonitrile Into 2-((diethylamino) methylene) the fluoro- 5- oxos hex- 3- alkene nitriles of-6,6,6- three；
D, 2-((diethylamino) methylene) the fluoro- 5- oxos hex- 3- alkene nitrile self-condensation cyclization of-6,6,6- three obtain 6- (trifluoromethyl) nicotinic acid nitrile；
E, 6- (trifluoromethyl) nicotinic acid nitrile is oxidized generation 6- (trifluoromethyl) pyridine carboxylic acid；
F, 6- (trifluoromethyl) pyridine carboxylic acids react with chromium trichloride in ultrasound reactor obtains
Further limit, step A detailed process is：Cyanoacetic acid is added in reaction bulb, diethylamine is added dropwise under water-bath, Control temperature to be no more than 60 DEG C during dropwise addition, 70 DEG C are warming up to after completion of dropwise addition, then trimethyl orthoformate is added dropwise, control temperature No more than 80 DEG C, after completion of dropwise addition, heating reflux reaction, 85 DEG C of reflux temperature, revolving removes raw material after terminating overnight, adds dichloromethane Alkane is extracted, and organic phase is washed with saturated sodium bicarbonate solution, until aqueous phase PH=8, is washed 2 times, organic phase is dried, and revolving is except molten Agent.Vacuum distillation takes more than 100 DEG C of cut to obtain 3- (diethylamino) acrylonitrile.
Further limit, step B detailed process is：Trifluoromethyl ethanone, pyridine and first are sequentially added in reaction bulb Acetoacetic ester, rear temperature rising reflux stirring reaction is added, reaction terminates rear reaction system and is washed with water, 10% salt pickling, unsaturated carbonate hydrogen Sodium solution is washed, and is dried, and is filtered, is obtained crude product, recrystallize to obtain 4- ethyoxyls -1,1,1- trifluoro butyl- 3- alkene -2- ketone.
Further limit, step C detailed process is：Sequentially added in reaction bulb 3- (diethylamino) acrylonitrile, 4- ethyoxyls -1,1,1- trifluoros butyl- 3- alkene -2- ketone and toluene；Heating reflux reaction adds n-hexane while hot after for a period of time, analysis Go out solid.1h is stirred under ice bath, filters, dry to obtain 2-((diethylamino) methylene)-6,6,6- tri- fluoro- 5- oxos hex- 3- Alkene nitrile.
Further limit, step D detailed process is：2-((diethylamino) methylene is sequentially added in reaction bulb Base) the fluoro- 5- oxos hex- 3- alkene nitriles of -6,6,6- three and DMF stirring reactions.Ammonium acetate is rapidly added, at room temperature stirring reaction mistake Night.Add water in reaction system, extracted with toluene, merge organic phase, twice, saturated common salt is washed once for washing, and drying is organic Phase, revolving obtain bronzing liquid 6- (trifluoromethyl) nicotinic acid nitrile.
Further limit, step E detailed process is：Water, sulfuric acid and glacial acetic acid are added in reaction bulb, is slowly added to 6- (trifluoromethyl) nicotinic acid nitrile；Flow back reaction overnight, and reaction adds ice cube after terminating, and uses cryosel water cooling, precipitation white solid, mistake Filtrate is extracted with ethyl acetate after filter, merges organic phase, twice, organic phase dries revolving for washing, and pickling decolourizes to obtain rice white Solid 6- (trifluoromethyl) pyridine carboxylic acid.
Further limit, step F detailed process is：Nitrogen is passed through into the ultrasonic response container for being provided with agitating device Gas, the dichloromethane solution dissolved with 6- (trifluoromethyl) pyridine carboxylic acid is then added, it is anti-to ultrasonic wave in 25 DEG C after adding ammoniacal liquor The methanol solution being added dropwise in container dissolved with chromium trichloride is answered, agitating device and ultrasonic generator are opened during dropwise addition, is surpassed The setpoint frequency of sound wave generating device is 80KHz, and it is clear state to drip rear solution, stops stirring, keeps ultrasonic wave Device works on, and is cooled to 0 DEG C of standing reaction solution, opens the steam vent on ultrasonic response container, keep the nitrogen being passed through Discharged from steam vent, nitrogen is discharged ultrasonic response container with reaction dissolvent, there is a clear crystal precipitation, crystallization is complete after 5h Entirely, reaction solution is filtered, filter cake is washed repeatedly to wash away unnecessary chromium chloride with methanol, and filter cake obtains after drying at room temperature
Further limit, step F gained compound is specifically act as：It is right Store pig plays good growth；With very low bioconcentration.
Embodiment
The above of the present invention is described in further details by the following examples, but this should not be interpreted as to this The scope for inventing above-mentioned theme is only limitted to following embodiment, and all technologies realized based on the above of the present invention belong to this hair Bright scope.
Embodiment 1
Cyanoacetic acid 625g (7.3mol) is added in 10L there-necked flask, be added dropwise under water-bath diethylamine 736mL (662g, 11mol), temperature is controlled to be no more than 60 DEG C during dropwise addition, 1h completion of dropwise addition.70 DEG C are warming up to after being added dropwise, primitive nail is added dropwise Sour trimethyl 1170mL, control temperature are no more than 80 DEG C, 2h completion of dropwise addition.After completion of dropwise addition, heating reflux reaction, reflux temperature 85 DEG C, reaction overnight.Revolving removes raw material, and added methylene chloride extraction, and organic phase is washed with saturated sodium bicarbonate solution, until aqueous phase PH=8, wash 2 times, organic phase is dried, and revolving removes solvent.Vacuum distillation takes more than 100 DEG C of cut, obtains 3- (diethyl aminos Base) acrylonitrile 860g, yield 95.5%.
Embodiment 2
Trifluoromethyl ethanone 112g (1.0mol), pyridine 250g, Ethyl formate are sequentially added in 10L there-necked flask 500mL, reaction are warming up to backflow, and stirring reaction 20h, TLC monitoring raw material reaction is complete, and reaction system is washed with water, 10% hydrochloric acid Wash, saturated sodium bicarbonate solution is washed, and is dried, and is filtered, is obtained crude product, recrystallize to obtain sterling 4- ethyoxyls -1,1,1- trifluoro butyl- 3- Alkene -2- ketone 155g, yield 92.2%.
Embodiment 3
3- (diethylamino) acrylonitrile 244g, 4- ethyoxyl -1,1,1- trifluoros are sequentially added in 10L there-necked flask Butyl- 3- alkene -2- ketone 370g and toluene 1800mL.Heating reflux reaction 48h, n-hexane 3900mL is added while hot, separate out solid.Ice The lower stirring 1h of bath, filters, dries to obtain 2-((diethylamino) methylene)-6,6,6- tri- fluoro- 5- oxos hex- 3- alkene nitrile 1410g, Yield is 100%.
Embodiment 4
Product 2-((diethylamino) methylene)-6,6,6- three that 1.2.3 is sequentially added in 10L there-necked flask is fluoro- 5- oxo hex- 3- alkene nitriles 1410g, DMF 1800mL stirring reactions.Ammonium acetate 1185g is rapidly added, at room temperature stirring reaction Overnight.Add water 10L in reaction system, extracted with toluene, merge organic phase, twice, saturated common salt is washed once for washing, is dried Organic phase, revolving obtain bronzing liquid 6- (trifluoromethyl) nicotinic acid nitrile 870g, yield 88%.
Embodiment 5
Water 1420g, sulfuric acid 2440g, glacial acetic acid 150mL are added in 10L there-necked flask, is slowly added to 6- (trifluoromethyl) Nicotinic acid nitrile 870g (5mol).Flow back reaction overnight.Cooling, add ice cube, and use cryosel water cooling, precipitation white solid.Filtering, filter Liquid is extracted with ethyl acetate, and merges organic phase, twice, organic phase dries revolving for washing, and pickling decolourizes to obtain beige solid 5- (trifluoromethyl) pyridine carboxylic acid 930g, yield 97.3%.
Embodiment 6
Nitrogen is passed through into the ultrasonic response container for being provided with agitating device, is then added dissolved with 6- (trifluoromethyl) pyrrole Pyridine formic acid 190g (1mol) dichloromethane 800mL solution, after adding the ammoniacal liquor that concentration is 25%, in 25 DEG C to ultrasonic response The methanol solution 500mL dissolved with chromium trichloride 133g (0.5mol) is added dropwise in container, agitating device is opened during dropwise addition and is surpassed Sound wave generating device, the setpoint frequency of ultrasonic generator is 80KHz, and it is clear state to drip rear solution, stops stirring, Keep ultrasonic generator to work on, be cooled to 0 DEG C of standing reaction solution, open the steam vent on ultrasonic response container, The nitrogen for keeping being passed through is discharged from steam vent, nitrogen is discharged ultrasonic response container with reaction dissolvent, there is clear crystal analysis Go out, crystallization is complete after 5h, filters reaction solution, and filter cake is washed repeatedly to wash away unnecessary chromium chloride with methanol, and filter cake is at room temperature Obtained after drying81g, yield 93%.
Embodiment 7
DLY ternary fattening pig 60 is selected in experiment, control group and test group is assigned randomly to according to body weight, in every group If 3 repetitions, 10 test pigs are each repeated.Test pig point circle raising, free choice feeding and drinking-water, pig house keep hygienically clean and Air circulation, periodically sterilization.Control group fed basal diet, test group added on the basis of basal diet 300 μ g/kg (with Chromium meter) chromium picolinate.The common 67d of test period, wherein preliminary trial period 7d, it is positive to try phase 60d.
Two groups of basal diet formula is consistent, and experiment daily ration is prepared with reference to U.S. NRC (1998 editions) fattening pig nutritional need.
Daily gain and feed intake：In on-test with the end of, respectively in breakfast 8:00 empty stomach is weighed to each group pig, Every group of feed consumption rate is counted, calculates the daily gain of each group pig, feed intake and feedstuff-meat ratio.
Data analysis：Data analysis is carried out using SPSS12.0 statistical analysis softwares, makees Multiple range test with duncan's method, is tried Data are tested to represent with mean+SD.
Influence of the target compound of table 1 to growing and fattening daily gain in pigs, feed intake and feedstuff-meat ratio
Embodiment 8
To rat feed high chromium daily ration (5000ng/g, withForm) 3 weeks, greatly In mouse kidney, liver, heart, leg gastrocnemius the accumulation of chromium be respectively 211,29,16,11ng/g, these accumulations are less than body Outer experiment can produce the concentration of mutation effect.
Embodiment above describes the general principle of the present invention, main features and advantages, the technical staff of the industry should Understand, the present invention is not limited to the above embodiments, the original for simply illustrating the present invention described in above-described embodiment and specification Reason, under the scope for not departing from the principle of the invention, various changes and modifications of the present invention are possible, and these changes and improvements are each fallen within In the scope of protection of the invention.

Claims (8)

1. a kind of high-efficiency synthesis method of pyridine carboxylic acid based food additive, it is characterised in that concretely comprise the following steps：
A, cyanoacetic acid and the diethylamine reaction under trimethyl orthoformate effect obtains 3- (diethylamino) acrylonitrile；
B, trifluoromethyl ethanone and the Ethyl formate reaction under pyridine effect obtains 4- ethyoxyl -1,1,1- trifluoro butyl- 3- alkene -2- Ketone；
C, 3- (diethylamino) acrylonitrile and 4- ethyoxyl-1,1,1- trifluoro butyl- 3- alkene-2- ketone occur substitution reaction generation 2- The fluoro- 5- oxos hex- 3- alkene nitriles of ((diethylamino) methylene) -6,6,6- three；
D, 2-((diethylamino) methylene) the fluoro- 5- oxos hex- 3- alkene nitrile self-condensation cyclization of-6,6,6- three obtain 6- (three Methyl fluoride) nicotinic acid nitrile；
E, 6- (trifluoromethyl) nicotinic acid nitrile is oxidized generation 6- (trifluoromethyl) pyridine carboxylic acid；
F, 6- (trifluoromethyl) pyridine carboxylic acids react with chromium trichloride in ultrasound reactor obtains
A kind of 2. high-efficiency synthesis method of pyridine carboxylic acid based food additive according to claim 1, it is characterised in that step Suddenly A detailed process is：Cyanoacetic acid is added in reaction bulb, diethylamine is added dropwise under water-bath, temperature is controlled not during dropwise addition More than 60 DEG C, 70 DEG C are warming up to after completion of dropwise addition, then trimethyl orthoformate is added dropwise, control temperature is no more than 80 DEG C, completion of dropwise addition Afterwards, heating reflux reaction, 85 DEG C of reflux temperature, revolving removes raw material after reaction terminates, and add methylene chloride extraction, organic phase saturation Sodium bicarbonate solution is washed, until aqueous phase PH=8, is washed 2 times, organic phase is dried, and revolving removes solvent, and vacuum distillation takes 100 DEG C Cut above obtains 3- (diethylamino) acrylonitrile.
A kind of 3. high-efficiency synthesis method of pyridine carboxylic acid based food additive according to claim 1, it is characterised in that step Suddenly B detailed process is：Trifluoromethyl ethanone, pyridine and Ethyl formate are sequentially added in reaction bulb, adds rear temperature rising reflux Stirring reaction, reaction terminate rear reaction system and are washed with water, and 10% salt pickling, saturated sodium bicarbonate solution is washed, and dry, and filter, obtain Crude product, recrystallize to obtain 4- ethyoxyls -1,1,1- trifluoro butyl- 3- alkene -2- ketone.
A kind of 4. high-efficiency synthesis method of pyridine carboxylic acid based food additive according to claim 1, it is characterised in that step Suddenly C detailed process is：3- (diethylamino) acrylonitrile, 4- ethyoxyl -1,1,1- trifluoro butyl- are sequentially added in reaction bulb 3- alkene -2- ketone and toluene, heating reflux reaction add n-hexane while hot after for a period of time, separate out solid, stir 1h under ice bath, take out Filter, dry to obtain 2-((diethylamino) methylene) the fluoro- 5- oxos hex- 3- alkene nitriles of-6,6,6- three.
A kind of 5. high-efficiency synthesis method of pyridine carboxylic acid based food additive according to claim 1, it is characterised in that step Suddenly D detailed process is：The fluoro- 5- oxos hex- of 2-((diethylamino) methylene)-6,6,6- three is sequentially added in reaction bulb 3- alkene nitrile and DMF stirring reactions, then add ammonium acetate, and stirring reaction is stayed overnight at room temperature, and reaction adds water after terminating, and uses toluene Extraction, merge organic phase, twice, saturated common salt is washed once for washing, dries organic phase, and revolving obtains bronzing liquid 6- (three Methyl fluoride) nicotinic acid nitrile.
A kind of 6. high-efficiency synthesis method of pyridine carboxylic acid based food additive according to claim 1, it is characterised in that step Suddenly E detailed process is：Water, sulfuric acid and glacial acetic acid are added in reaction bulb, 6- (trifluoromethyl) nicotinic acid nitrile is slowly added to, flowed back Night reacts；Reaction adds ice cube after terminating, and uses cryosel water cooling, precipitation white solid；Filtrate is extracted with ethyl acetate after filtering Take, merge organic phase, twice, organic phase dries revolving for washing, and pickling decolourizes to obtain beige solid 6- (trifluoromethyl) pyridine Formic acid.
A kind of 7. high-efficiency synthesis method of pyridine carboxylic acid based food additive according to claim 1, it is characterised in that step Suddenly F detailed process is：Nitrogen is passed through into the ultrasonic response container for being provided with agitating device, is then added dissolved with 6- (three Methyl fluoride) pyridine carboxylic acid dichloromethane solution, add ammoniacal liquor after, in 25 DEG C into ultrasonic response container be added dropwise dissolved with trichlorine Change the methanol solution of chromium, agitating device and ultrasonic generator, the setting frequency of ultrasonic generator are opened during dropwise addition Rate is 80KHz, and it is clear state to drip rear solution, stops stirring, keeps ultrasonic generator to work on, is cooled to 0 DEG C reaction solution is stood, open the steam vent on ultrasonic response container, keep the nitrogen that is passed through to be discharged from steam vent, make nitrogen companion Ultrasonic response container is discharged with reaction dissolvent, there is a clear crystal precipitation, crystallization is complete after 5h, filters reaction solution, filter cake first Alcohol is washed repeatedly to wash away unnecessary chromium chloride, and filter cake obtains after drying at room temperature
A kind of 8. application of chromium picolinate based food additive in food additives are prepared as claimed in claim 1.
CN201710689680.6A 2017-08-14 2017-08-14 A kind of high-efficiency synthesis method of pyridine carboxylic acid based food additive Pending CN107337638A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201710689680.6A CN107337638A (en) 2017-08-14 2017-08-14 A kind of high-efficiency synthesis method of pyridine carboxylic acid based food additive

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201710689680.6A CN107337638A (en) 2017-08-14 2017-08-14 A kind of high-efficiency synthesis method of pyridine carboxylic acid based food additive

Publications (1)

Publication Number Publication Date
CN107337638A true CN107337638A (en) 2017-11-10

Family

ID=60217802

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201710689680.6A Pending CN107337638A (en) 2017-08-14 2017-08-14 A kind of high-efficiency synthesis method of pyridine carboxylic acid based food additive

Country Status (1)

Country Link
CN (1) CN107337638A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109160897A (en) * 2018-10-16 2019-01-08 河南师范大学 A kind of synthetic method of 6- trifluoromethyl nicotinic acid

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101318929A (en) * 2008-07-04 2008-12-10 温州大学 Synthesis process for chromium picolinate
CN101535262A (en) * 2006-11-08 2009-09-16 陶氏益农公司 Heteroaryl (substituted) alkyl n-substituted sulfoximines as insecticides
CN101679446A (en) * 2007-05-17 2010-03-24 霍夫曼-拉罗奇有限公司 3,3-spiroindolinone derivatives
WO2015097122A1 (en) * 2013-12-23 2015-07-02 Norgine B.V. Benzene sulfonamides as ccr9 inhibitors

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101535262A (en) * 2006-11-08 2009-09-16 陶氏益农公司 Heteroaryl (substituted) alkyl n-substituted sulfoximines as insecticides
CN101679446A (en) * 2007-05-17 2010-03-24 霍夫曼-拉罗奇有限公司 3,3-spiroindolinone derivatives
CN101318929A (en) * 2008-07-04 2008-12-10 温州大学 Synthesis process for chromium picolinate
WO2015097122A1 (en) * 2013-12-23 2015-07-02 Norgine B.V. Benzene sulfonamides as ccr9 inhibitors

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109160897A (en) * 2018-10-16 2019-01-08 河南师范大学 A kind of synthetic method of 6- trifluoromethyl nicotinic acid

Similar Documents

Publication Publication Date Title
CN101032274B (en) Method of taking full use of egg white of salted duck eggs
CN106386692A (en) Method for breeding purebred Nubian goats
CN105394350A (en) Freshwater crayfish feed for improving meat quality and preparation method thereof
CN106212381A (en) The method that a kind of calf acidifying milk groupuscule health is raised
CN101786961B (en) Chromium threonine, preparation method and application thereof
CN106071420A (en) The preparation method of a kind of trace element chelated peptide and Litopenaeus vannamei breeding feed
CN107337638A (en) A kind of high-efficiency synthesis method of pyridine carboxylic acid based food additive
CN107333975B (en) A kind of novel processing step of chromium picolinate based food additive
CN107095006A (en) A kind of fattening feed fattened for high-density breeding adult sheep
WO2020093187A1 (en) Application of aspartic acid derivative in preparing animal feed additive
CN105210993A (en) A kind of breeding method of Moringa broiler chicken
CN104041676B (en) A kind of zeolite butanoic acid powder and its preparation method and application
CN101704779B (en) Preparation method for feed additive dihydropyridine
CN104860841B (en) 4-chlorocinnamaldehyde aminobutyric acid Schiff base, 4-chlorocinnamaldehyde aminobutyric acid Schiff base salt, and preparation method thereof
CN108094753A (en) A kind of button crab high calcium fermented feed
CN102028101A (en) Feed sweetener for livestock and poultry and preparation method thereof
CN101585796A (en) Preparation method of piglet intestinal canal nutrition controlling substance-alpha-pyrrole formic acid
CN105585477A (en) A synthetic method of sodium diacetate
CN204237778U (en) A kind of new device producing L-Trp with enzyme process binding film technology
CN111132962A (en) Tryptophan derivative and application thereof
CN104186974A (en) Animal feed additive
CN107880272B (en) β -polymalic acid chitosan oligosaccharide compound salt and preparation method and application thereof
CN1408708A (en) Process for synthesizing 2-pyridine chromium formate of fodder additive
CN105212224A (en) A kind of nutritious spirulina dry powder and containing the easily fresh preparation method of algae albumin
CN203393070U (en) Novel glycine production device

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
TA01 Transfer of patent application right

Effective date of registration: 20180920

Address after: 453007 46 East Jianhe Road, Xinxiang, Henan

Applicant after: Mao Along

Address before: 453007 46 East Jianhe Road, Xinxiang, Henan

Applicant before: Hou Qianqian

TA01 Transfer of patent application right
RJ01 Rejection of invention patent application after publication

Application publication date: 20171110

RJ01 Rejection of invention patent application after publication