CN105254560B - A kind of preparation method of deccox - Google Patents
A kind of preparation method of deccox Download PDFInfo
- Publication number
- CN105254560B CN105254560B CN201510762509.4A CN201510762509A CN105254560B CN 105254560 B CN105254560 B CN 105254560B CN 201510762509 A CN201510762509 A CN 201510762509A CN 105254560 B CN105254560 B CN 105254560B
- Authority
- CN
- China
- Prior art keywords
- parts
- sodium
- deccox
- stream
- methanol
- 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.)
- Expired - Fee Related
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
- C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of preparation method of deccox, using industrialized 2-ethoxy-phenol as starting material, by diazonium coupling, sodium hydrosulfite reduction, condensation, etherificate, superpower solid acid SO4 2‑/Fe2O3The preferable product of quality is obtained with niter cake cyclization, this product synthetic route moiety intermediate is not required to purify, and solvent for use is single, reduce the post processing of intermediate and the use of organic solvent, reduce cost, entire process route is short, very high temperature or deep-etching liquid acid are not needed to, it is low for equipment requirements, it is easy to operate, it is with short production cycle, the three wastes of generation are few, product yield is high, high-quality, is suitble to industrialized production.
Description
Technical field
The present invention relates to a kind of preparation processes of poultry medicine, and in particular to a kind of preparation method of deccox.
Background technology
Deccox is to be researched and developed by the May ＆ Baker Ltd. (GB) Dageham, Essex RMIO 7XS, England of Britain the 1960s, it has wide spectrum coccidiostat activity,
Global-worm illness caused by murder by poisoning, tender, huge, heap-type and E.brunetti available for chicken etc., before having a vast market
Scape.Deccox plays an important role in the DNA building-up processes of coccidia, mainly prevents its numerous by interfering DNA synthesis
It grows, deccox toxicity is low, and tolerance is good, absorbs soon, effective concentration can be reached in the short time, and be metabolized in animal body
Soon, residual quantity is low, is widely used in countries such as America and Europes.
Ring-closure reaction can carry out under the action of high boiling solvent or cyclization reagent in deccox synthesis technology.CN
102816117th, CN102766094 obtains target product using high temperature (250 DEG C or more) cyclization, but because of reaction temperature height, right
Equipment requirement is high, and portion of product is carbonized, it is difficult to purify, yield is low.And it is unable to one-step synthesis during with phosphorus oxychloride cyclization
To target product, heat gathers in last handling process, is susceptible to material spray, there are larger security risks.Patent CN
101012195 use polyphosphoric acids cyclization, have corrosivity, and need that reaction is quenched in higher temperature, and heat release is violent, generation
Phosphate be difficult to detach with product, post processing is difficult.
Invention content
To solve the above problems, the present invention provides a kind of preparation method of deccox, with industrialized o-hydroxy
Ether is starting material, and using water, methanol, DMF as solvent, the organic solvent rate of recovery is high, and the generation three wastes are few, by diazotising idol
It closes, sodium hydrosulfite reduction, condensation, be etherified, superpower solid acid SO4 2-/Fe2O3High-quality product is obtained with niter cake cyclization, is dropped
Low cost.
To achieve the above object, the technical solution taken of the present invention is：
A kind of preparation method of deccox, includes the following steps：
S1,7.5 parts of aniline, 22 parts of water are put into reaction kettle, is cooled to 0 DEG C, is slowly stirred, stream plus 30~32% dense salt
21 parts of acid, stream add complete, and temperature is down to 0 DEG C, stream plus sodium nitrite solution, stream plus after, 1h is reacted in continuation at this temperature,
The diazonium salt solution of aniline is obtained, low temperature is spare；
S2, into reaction kettle add in 11.8 parts of 2-ethoxy-phenols, 170 parts of methanol, with sodium hydroxide solution adjust pH to
8.5, after 1h is stirred at room temperature, -5 DEG C are cooled to hereinafter, stream adds the diazonium salt solution of the aniline obtained by step S1, while uses hydroxide
Sodium solution adjust pH=7, stream add it is complete, adjust pH=7~8, be warming up to 8 DEG C, continue to be stirred to react 4h, depressurizing will be in system
Methanol steams recycling, obtains 3- ethyoxyl -4- hydroxyazo benzene distillation viscous fluids；
S3,3- ethyoxyl -4- hydroxyazo benzene distillation viscous fluids and 15.8 parts of sodium hydroxides, the 70 parts of water of gained are mixed
Afterwards, quick stirring is warming up to 85~90 DEG C, 38 parts of sodium hydrosulfite is added portionwise, insulation reaction 4-5h is cooled to room temperature, uses concentrated hydrochloric acid
PH to 5-7 is adjusted, stirs 1h, filtering, 50 DEG C are dried in vacuo 6h, after testing, yield 85%；
S4,10.5 parts of 3- ethyoxyl -4- hydroxyanilines, 11.6 parts of ethoxy Asia methylene malonic acid diethyls are added in a kettle
Ester, 45 parts of methanol are warming up to 90~100 DEG C, after reacting 4~5h, are cooled to 60 DEG C；
S5,11.3 parts of potassium carbonate, 15.7 parts of bromo-decane are added in, 6~8h of temperature rising reflux is filtered, and filter cake is washed with 10 parts of methanol
It washs, filtrate decompression distillation obtains dope；
S6, the dope of gained is added in 6 parts of DMF, stirring adds in 2 parts of superpower solid acid SO4 2-/Fe2O3, 0.02 part
Niter cake, is heated to 150 DEG C of reaction 4h, and filtering removal solid after concentrating filtrate, adds in 4 parts of water, 30% sodium hydroxide solution
PH=7~8 are adjusted, filters, obtains deccox crude product, obtain off-white color crystalline powder after refined, after testing, total recovery is
65%.
The sodium nitrite solution is made by 5.9 parts of sodium nitrites and 22 parts of water.
The sodium hydrosulfite is sodium dithionite.
Low temperature in step S1 is 0-10 degree
The invention has the advantages that：
The present invention uses superpower solid acid SO4 2-/Fe2O3The deccox obtained with niter cake progress ring-closure reaction, surpasses
Strong solid acids overcome the shortcomings that liquid acid, have easily detached with liquid-phase reaction system, not etching apparatus, post processing it is simple,
The features such as environmental pollution is small, high selectivity.Superpower solid acid SO4 2-/Fe2O3With niter cake as catalyst make cyclization yield compared with
Document report is high by 10~15%, and post-processes simple.Entire process route is short, does not need to very high temperature or deep-etching liquid acid, right
Equipment requirement is low, easy to operate, with short production cycle, and the three wastes of generation are few；Solvent is single and dosage is few, at low cost, product yield
Height, it is high-quality, it is suitble to industrialized production.
Description of the drawings
Fig. 1 is a kind of reaction principle figure of the preparation method of deccox of the embodiment of the present invention.
Specific embodiment
In order to which objects and advantages of the present invention are more clearly understood, the present invention is carried out with reference to embodiments further
It is described in detail.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, it is not used to limit this hair
It is bright.
As shown in Figure 1, an embodiment of the present invention provides a kind of preparation method of deccox, include the following steps：
S1, diazotising
7.5 parts of aniline, 22 parts of water are put into reaction kettle, 0 DEG C is cooled to, is slowly stirred, stream plus 30~32% concentrated hydrochloric acids
21 parts, stream adds complete, and temperature is down to 0 DEG C, stream plus sodium nitrite solution (5.9 parts, 22 parts of water), stream plus after, continue herein
At a temperature of react 1h, obtain the diazonium salt solution of aniline, low temperature is spare；
S2, coupling
11.8 parts of 2-ethoxy-phenols, 170 parts of methanol are added in into reaction kettle, pH to 8.5 is adjusted with sodium hydroxide solution,
After 1h is stirred at room temperature, -5 DEG C are cooled to hereinafter, stream adds the diazonium salt solution of the aniline obtained by step S1, while molten with sodium hydroxide
Liquid adjust pH=7, stream add it is complete, adjust pH=7~8, be warming up to 8 DEG C, continue to be stirred to react 4h, depressurize the methanol in system
Recycling is steamed, obtains 3- ethyoxyl -4- hydroxyazo benzene distillation viscous fluids；
S3, reduction
After the 3- ethyoxyl -4- hydroxyazo benzene distillation viscous fluids of gained are mixed with 15.8 parts of sodium hydroxides, 70 parts of water,
Quick stirring is warming up to 85~90 DEG C, 38 parts of sodium hydrosulfite is added portionwise, insulation reaction 4-5h is cooled to room temperature, with concentrated hydrochloric acid tune
PH to 5-7 is saved, stirs 1h, filtering, 50 DEG C are dried in vacuo 6h, after testing, yield 85%；
S4, condensation
10.5 parts of 3- ethyoxyl -4- hydroxyanilines of addition in a kettle, 11.6 parts of ethoxy methylenes fork diethyl malonates,
45 parts of methanol are warming up to 90~100 DEG C, after reacting 4~5h, are cooled to 60 DEG C；
S5, etherificate
11.3 parts of potassium carbonate, 15.7 parts of bromo-decane are added in, 6~8h of temperature rising reflux is filtered, and filter cake is washed with 10 parts of methanol,
Filtrate decompression is distilled, and obtains dope；
S6, cyclization
The dope of gained is added in 6 parts of DMF, stirring adds in 2 parts of superpower solid acid SO4 2-/Fe2O3, 0.02 part of sulfuric acid
Hydrogen sodium is heated to 150 DEG C of reaction 4h, and filtering removal solid after concentrating filtrate, adds in 4 parts of water, and 30% sodium hydroxide solution is adjusted
PH=7~8 filter, obtain deccox crude product, obtain off-white color crystalline powder after refined, after testing, total recovery is
65%.
For this specific implementation present invention compared with the technique of document report, ring-closure reaction is with superpower solid acid SO4 2-/Fe2O3
It is completed at a higher temperature with niter cake, post-reaction treatment is simple, is further refining to obtain qualified products.Entire technique
With good safety, controllability, target product yield is high, and high-quality, totle drilling cost is low, is suitble to industrialized production.
The above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, without departing from the principle of the present invention, several improvements and modifications can also be made, these improvements and modifications also should
It is considered as protection scope of the present invention.
Claims (2)
1. a kind of preparation method of deccox, which is characterized in that include the following steps：
S1,7.5 parts of aniline, 22 parts of water are put into reaction kettle, is cooled to 0 DEG C, is slowly stirred, stream plus 30~32% concentrated hydrochloric acids 21
Part, stream adds complete, and temperature is down to 0 DEG C, stream plus sodium nitrite solution, stream plus after, 1h is reacted in continuation at this temperature, obtains benzene
The diazonium salt solution of amine, low temperature are spare；
S2,11.8 parts of 2-ethoxy-phenols, 170 parts of methanol are added in into reaction kettle, pH to 8.5 are adjusted with sodium hydroxide solution,
After 1h is stirred at room temperature, -5 DEG C are cooled to hereinafter, stream adds the diazonium salt solution of the aniline obtained by step S1, while molten with sodium hydroxide
Liquid adjust pH=7, stream add it is complete, adjust pH=7~8, be warming up to 8 DEG C, continue to be stirred to react 4h, depressurize the methanol in system
Recycling is steamed, obtains 3- ethyoxyl -4- hydroxyazo benzene distillation viscous fluids；
S3, after 3- ethyoxyl -4- hydroxyazo benzene distillation viscous fluids and 15.8 parts of sodium hydroxides, the 70 parts of water of gained are mixed,
Quick stirring is warming up to 85~90 DEG C, 38 parts of sodium hydrosulfite is added portionwise, insulation reaction 4-5h is cooled to room temperature, with concentrated hydrochloric acid tune
PH to 5-7 is saved, stirs 1h, filtering, 50 DEG C are dried in vacuo 6h, after testing, yield 85%；
S4, in a kettle 10.5 parts of 3- ethyoxyl -4- hydroxyanilines of addition, 11.6 parts of ethoxy methylenes fork diethyl malonates,
45 parts of methanol are warming up to 90~100 DEG C, after reacting 4~5h, are cooled to 60 DEG C；
S5,11.3 parts of potassium carbonate, 15.7 parts of bromo-decane are added in, 6~8h of temperature rising reflux is filtered, and filter cake is washed with 10 parts of methanol, is filtered
Liquid is evaporated under reduced pressure, and obtains dope；
S6, the dope of gained is added in 6 parts of DMF, stirring adds in 2 parts of superpower solid acid SO4 2-/Fe2O3, 0.02 part of sulfuric acid
Hydrogen sodium is heated to 150 DEG C of reaction 4h, and filtering removal solid after concentrating filtrate, adds in 4 parts of water, and 30% sodium hydroxide solution is adjusted
PH=7~8 filter, obtain deccox crude product, obtain off-white color crystalline powder after refined, after testing, total recovery is
65%；
The sodium nitrite solution is made by 5.9 parts of sodium nitrites and 22 parts of water；
The sodium hydrosulfite is sodium dithionite.
2. the preparation method of a kind of deccox according to claim 1, which is characterized in that the low temperature in step S1 is 0-
10 degree.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510762509.4A CN105254560B (en) | 2015-11-04 | 2015-11-04 | A kind of preparation method of deccox |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510762509.4A CN105254560B (en) | 2015-11-04 | 2015-11-04 | A kind of preparation method of deccox |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105254560A CN105254560A (en) | 2016-01-20 |
| CN105254560B true CN105254560B (en) | 2018-06-22 |
Family
ID=55094554
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510762509.4A Expired - Fee Related CN105254560B (en) | 2015-11-04 | 2015-11-04 | A kind of preparation method of deccox |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105254560B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107382855B (en) * | 2017-06-28 | 2018-09-25 | 浙江荣耀生物科技股份有限公司 | A kind of synthetic method of deccox |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1469416A (en) * | 1973-07-03 | 1977-04-06 | Ciba Geigy Ag | Process for the preparation of quinoline derivatives |
| CN101012195A (en) * | 2007-02-15 | 2007-08-08 | 常熟市欧亚吉生物医药研究所 | Method of preparing 4-hydroxy-6-decyloxy-7-ethoxy-3-quinoline carboxylic acid ethyl ester |
| CN102816117A (en) * | 2012-09-04 | 2012-12-12 | 江苏昊华精细化工有限公司 | Synthesis method of decoquinate |
-
2015
- 2015-11-04 CN CN201510762509.4A patent/CN105254560B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1469416A (en) * | 1973-07-03 | 1977-04-06 | Ciba Geigy Ag | Process for the preparation of quinoline derivatives |
| CN101012195A (en) * | 2007-02-15 | 2007-08-08 | 常熟市欧亚吉生物医药研究所 | Method of preparing 4-hydroxy-6-decyloxy-7-ethoxy-3-quinoline carboxylic acid ethyl ester |
| CN102816117A (en) * | 2012-09-04 | 2012-12-12 | 江苏昊华精细化工有限公司 | Synthesis method of decoquinate |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105254560A (en) | 2016-01-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105367557A (en) | Method for preparing cycloxylidin | |
| WO2013007054A1 (en) | Method for preparation of ketoxime compound and method for preparation of alkoxy-amine hydrochloride | |
| CN104262200B (en) | One recycles waste water and prepares N, N ' production method of-dicyclohexylcarbodiimide | |
| CN102276483A (en) | Production method of oamino pheylmethyl ether | |
| CN104140420A (en) | Synthesis process of thiothiamine | |
| CN103588815A (en) | Preparation method of hexaphenoxy cyclotriphosphazene fire retardant | |
| CN105254560B (en) | A kind of preparation method of deccox | |
| CN103130657A (en) | Synthetic method of 2-chloro-4-aminophenol | |
| CN102311394B (en) | Preparation method for 5-ethyl-5-phenyl barbituric acid | |
| CN105175317B (en) | A kind of method for preparing picosulfate sodium | |
| CN102731357A (en) | Preparation method of high purity N,N'-dicyclohexylthiourea | |
| CN103880717B (en) | The preparation method of two (3-allyl group-4-hydroxy phenyl) sulfones and derivative thereof | |
| CN102702122B (en) | Method for preparing tetrazine by oxidizing dihydro tetrazine | |
| CN106810554A (en) | A kind of preparation method of Tadalafei compound | |
| CN103497157A (en) | 2-imidazolidone synthesis method | |
| CN106279005B (en) | A method of trichloro pyridyl sodium alcoholate is recycled from trichloro pyridyl sodium alcoholate production waste material | |
| CN105541729B (en) | The process for separation and purification of salt in 2,4,5- triamido -6- hydroxy pyrimidine sulfate production process | |
| CN108164423A (en) | A kind of preparation method of naftifine hydrochloride | |
| CN105753765A (en) | Preparation method of ziprasidone intermediate | |
| CN105175316B (en) | A kind of method for preparing laxative picosulfate sodium | |
| CN109384683B (en) | Preparation method of 2-amino-5-fluoroacetophenone | |
| CN106749098A (en) | A kind of friendly process for preparing dioxopromethazine hydrochloride as oxidant with oxygen | |
| CN107382855B (en) | A kind of synthetic method of deccox | |
| CN101774939A (en) | Trans-N-(4- hydroxyl-3-methoxybenzy)-8-methyl-5-nonenamide and preparation method thereof | |
| CN220656435U (en) | Device for recycling pyridine or pyridine derivative in hexachlorocyclo-triphosphazene synthetic waste residues |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20180622 Termination date: 20201104 |