CN108821990A - A kind of preparation method of 5- amino -2,4,6- triiodo isophthaloyl chlorine - Google Patents
A kind of preparation method of 5- amino -2,4,6- triiodo isophthaloyl chlorine Download PDFInfo
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- CN108821990A CN108821990A CN201810986679.4A CN201810986679A CN108821990A CN 108821990 A CN108821990 A CN 108821990A CN 201810986679 A CN201810986679 A CN 201810986679A CN 108821990 A CN108821990 A CN 108821990A
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- amino
- isophthaloyl chlorine
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- triiodo isophthaloyl
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
Abstract
The invention discloses a kind of 5- amino -2,4, the preparation methods of 6- triiodo isophthaloyl chlorine, this method by being added quantitative 5- amino -2,4,6- tri- iodo- 1 in a kettle, 3- phthalic acid, hydrochloric acid and triphenylphosphine, after being heated to reaction temperature, it is passed through the oxygen of metering methane gas, nitrogen load, stirs lower reaction to terminating, collect reactant, it is post-treated to obtain 5- amino -2,4,6- triiodo isophthaloyl chlorine.The present invention uses one pot reaction technology, and product 5- amino -2,4 is made, and 6- triiodo isophthaloyl chlorine operates very simple.Raw material is cheap and easy to get, at low cost, can be recycled；Meanwhile the present invention synthesis after product post-processing it is simple, products obtained therefrom Chun Du≤99%.The present invention is a kind of clearer production technology of suitable enterprise scale production.
Description
Technical field
The present invention relates to a kind of 5- amino -2,4, the preparation method of 6- triiodo isophthaloyl chlorine belongs to chemical synthesising technology neck
Domain.
Background technique
Acyl chlorides is a kind of important carboxylic acid derivates, organic synthesis, in terms of suffer from important answer
With hydrolysis, alcoholysis, ammonia can occur（Amine）Solution is reacted with organometallic reagent, a variety of reactions such as reduction reaction, α hydrohalogenation.
5- amino -2,4,6- triiodo isophthaloyl chlorine are a kind of important fine chemical products, are the important of synthesis iodo X- line contrast agent
Intermediate.Over the past two years, with the raising of medical imaging diagnosis technical level, China's contrast agent huge market demand in recent years,
Have a good market prospects, and the radiography equipment technology of domestic large and medium-sized hospital is constantly reinforced, contrast agent from kind research and develop to
The market share has rapid growth, and average amplification has been more than 30%.The update of this kind of drugs has been driven simultaneously,
The market demand and production of this kind of intermediate are pushed.But it with environmental protection, the growth requirement of safety and sustainable development, opens
Hair ring protects free of contamination green synthesis method, and the cost for reducing product has significant economic and social benefit.
Currently, the method for preparing acyl chlorides mainly has thionyl chloride method, phosphorus trichloride method, phosphorus pentachloride method and phosgenation etc..
Thionyl chloride method prepares acyl chloride reaction mild condition, can react under room temperature or slightly heat condition.Product in addition to acyl chlorides other
It is gas, being not required to purification can apply, and purity is good, and yield is high.But when the acid chloride product boiling point of generation and thionyl chloride
When boiling point is close, then difficulty is separated, in addition thionyl chloride method dosage is big, high production cost, and equipment seriously corroded.Phosphorus trichloride
When method prepares acyl chlorides, suitable for preparing low boiling point acyl chlorides, because the phosphorous acid generated in reaction is not volatile, acyl can be conveniently steamed
Chlorine.
Phosphorus pentachloride method is suitable for preparing higher boiling acyl chlorides, is convenient to a POCl3It steams and separates.Phosgenation is mainly
Triphosgene, since triphosgene fusing point is high, volatility is low, hypotoxicity, industrially only it when the processing of general toxicity substance.It
Synthesis and to participate in condition required for chemical reaction very mild, and selectivity is strong, and high income is safe and convenient to use, and
Easily transport storage, medicine, pesticide, organic chemical industry and high molecular material etc. may replace phosgene or surpalite participates in related chemistry
The synthesis of product.In addition, oxalyl chloride is also a kind of more active acylating reagent, it can be used for acids, the acylation of amine substance,
To prepare Multiple Pesticides, fungicide, medical antitumor agent, X-ray contrast medium etc..Oxalyl chloride is generally used as acylating reagent
DMF makees catalyst.Carbon tetrachloride method generally requires to be made into acyl chlorides, traditional side in the reaction in relation to saccharide compound
Often yield is very low for method.And good yield can be obtained by preparing acyl chlorides with carbon tetrachloride and triphenylphosphine system.In recent years,
About the report for using hexachloroacetone as acylating agent and preparing acyl chlorides.But just for certain specific reactions, purposes is not
It is very universal.
Summary of the invention
The technical problem to be solved by the invention is to provide a kind of 5- amino -2,4, the preparation sides of 6- triiodo isophthaloyl chlorine
Method, this method is raw materials used at low cost, and synthesis post-processing is simple, products obtained therefrom purity is high.
In order to solve the above technical problems, 5- amino -2,4 of the present invention, the preparation method of 6- triiodo isophthaloyl chlorine, passes through
Quantitative 5- amino -2,4 is added in a kettle, iodo- 1, the 3- phthalic acid of 6- tri-, hydrochloric acid and triphenylphosphine are heated to reaction temperature
After degree, it is passed through the oxygen of metering methane gas, nitrogen load, stirs lower reaction to terminating, collects reactant, post-treated 5- ammonia
Base -2,4,6- triiodo isophthaloyl chlorine, industry byproduct can be used in hydrochloric acid, methane gas and triphenylphosphine used.
Further, the reaction temperature is 30~100 DEG C.
Further, the reaction time of the reaction is 1~10 hour.
Further, the mole dosage of the 5- amino -2,4, iodo- 1, the 3- phthalic acid of 6- tri- and triphenylphosphine is than 1：2
~5.
Further, the hydrogen chloride in the hydrochloric acid and 5- amino -2,4, the mole dosage of iodo- 1, the 3- phthalic acid of 6- tri-
Than being 5~10：1, hydrochloric acid mass concentration used uses normal concentration.
Further, the methane gas, oxygen and 5- amino -2,4, iodo- 1, the 3- phthalic acid mole dosage ratio of 6- tri- are 3
~6：3~6：1.
Further, the weight consumption of the nitrogen and oxygen ratio is 1~3：1.
The present invention uses one pot reaction technology, uses hydrochloric acid, methane gas and triphenylphosphine negative in nitrogen for primary raw material
Under the oxygen effect of load, with 5- amino -2,4, product 5- amino -2,4,6- triiodo is made in the reaction of iodo- 1, the 3- phthalic acid of 6- tri-
Isophthaloyl chlorine operates very simple.Wherein, hydrochloric acid, methane gas and triphenylphosphine can be used what chemical and medicine industry company obtained itself
Byproduct, it is cheap and easy to get, it is at low cost, it can be recycled；Meanwhile the present invention synthesis after product post-processing it is simple, products obtained therefrom
Chun Du≤99%.The present invention is a kind of clearer production technology of suitable enterprise scale production.
Specific embodiment
The present invention is described further combined with specific embodiments below, but protection scope of the present invention is not limited in
This.The synthesis of 1 5- amino -2,4,6- triiodo isophthaloyl chlorine of embodiment
Three 558.8 grams of iodo- 1,3- phthalic acid of 5- amino -2,4,6- is added in 5000 mL three-necked flasks（1 mole）, triphen
524 grams of base phosphine（2 moles）, 365 grams of containing hydrogen chloride（10 moles）Hydrochloric acid, be heated to 100 DEG C, measured by gas flowmeter logical
Enter 96 grams of reaction kettle methane gas（6 moles）, 192 grams of oxygen（6 moles）, 576 grams of nitrogen.It is stirred to react 10 hours, collects anti-
Object is answered, it is cooling, it filters, is refined with 1000 milliliters of toluene and 577.8 grams of product, yield 97%, Chan product Chun Du≤99% is made.
The synthesis of 2 5- amino -2,4,6- triiodo isophthaloyl chlorine of embodiment
Three 558.8 grams of iodo- 1,3- phthalic acid of 5- amino -2,4,6- is added in 5000 mL three-necked flasks（1 mole）, triphen
524 grams of base phosphine（2 moles）, 182.5 grams of containing hydrogen chloride（5 moles）Hydrochloric acid, be heated to 60 DEG C, measured by gas flowmeter logical
Enter 96 grams of reaction kettle methane gas（6 moles）, 128 grams of oxygen（4 moles）, 256 grams of nitrogen.It is stirred to react 1 hour, collects reaction
Object, it is cooling, it filters, is refined with 1000 milliliters of toluene and 577.8 grams of product, yield 97%, Chan product Chun Du≤99% is made.
The synthesis of 3 5- amino -2,4,6- triiodo isophthaloyl chlorine of embodiment
Three 558.8 grams of iodo- 1,3- phthalic acid of 5- amino -2,4,6- is added in 5000 mL three-necked flasks（1 mole）, triphen
786 grams of base phosphine（3 moles）, 255.5 grams of containing hydrogen chloride（7 moles）Hydrochloric acid, be heated to 50 DEG C, measured by gas flowmeter logical
Enter 64 grams of reaction kettle methane gas（4 moles）, 160 grams of oxygen（5 moles）, 320 grams of nitrogen.It is stirred to react 3 hours, collects reaction
Object, it is cooling, it filters, is refined with 1000 milliliters of toluene and 565.9 grams of product, yield 95%, Chan product Chun Du≤99% is made.
The synthesis of 4 5- amino -2,4,6- triiodo isophthaloyl chlorine of embodiment
Three 558.8 grams of iodo- 1,3- phthalic acid of 5- amino -2,4,6- is added in 5000 mL three-necked flasks（1 mole）, triphen
786 grams of base phosphine（3 moles）, 255.5 grams of containing hydrogen chloride（7 moles）Hydrochloric acid, be heated to 50 DEG C, measured by gas flowmeter logical
Enter 64 grams of reaction kettle methane gas（4 moles）, 160 grams of oxygen（5 moles）, 320 grams of nitrogen.It is stirred to react 3 hours, collects reaction
Object, it is cooling, it filters, is refined with 1000 milliliters of toluene and 565.9 grams of product, yield 95%, Chan product Chun Du≤99% is made.
The synthesis of 5 5- amino -2,4,6- triiodo isophthaloyl chlorine of embodiment
Three 558.8 grams of iodo- 1,3- phthalic acid of 5- amino -2,4,6- is added in 5000 mL three-necked flasks（1 mole）, triphen
524 grams of base phosphine（2 moles）, 219 grams of containing hydrogen chloride（6 moles）Hydrochloric acid, be heated to 80 DEG C, by gas flowmeter metering be passed through
64 grams of reaction kettle methane gas（4 moles）, 96 grams of oxygen（3 moles）, 288 grams of nitrogen.It is stirred to react 3 hours, collects reactant,
It is cooling, it filters, is refined with 1000 milliliters of toluene and 571.8 grams of product, yield 96%, Chan product Chun Du≤99% is made.
The synthesis of 6 5- amino -2,4,6- triiodo isophthaloyl chlorine of embodiment
Three 558.8 grams of iodo- 1,3- phthalic acid of 5- amino -2,4,6- is added in 5000 mL three-necked flasks（1 mole）, triphen
524 grams of base phosphine（4 moles）, 183 grams of containing hydrogen chloride（5 moles）Hydrochloric acid, be heated to 80 DEG C, by gas flowmeter metering be passed through
96 grams of reaction kettle methane gas（6 moles）, 128 grams of oxygen（4 moles）, 576 grams of nitrogen.It is stirred to react 5 hours, collects reaction
Object, it is cooling, it filters, is refined with 1000 milliliters of toluene and 577.8 grams of product, yield 97%, Chan product Chun Du≤99% is made.
Claims (7)
1. a kind of 5- amino -2,4, the preparation method of 6- triiodo isophthaloyl chlorine, it is characterised in that：This method is by a kettle
Quantitative 5- amino -2,4 is added, iodo- 1, the 3- phthalic acid of 6- tri-, hydrochloric acid and triphenylphosphine, after being heated to reaction temperature, it is fixed to be passed through
The oxygen for measuring methane gas, nitrogen load stirs lower reaction to terminating, and collects reactant, post-treated 5- amino -2,4,6- tri-
Iodine isophthaloyl chlorine.
2. 5- amino -2,4 according to claim 1, the preparation method of 6- triiodo isophthaloyl chlorine, it is characterised in that：It is described anti-
Answering temperature is 30~100 DEG C.
3. 5- amino -2,4 according to claim 1, the preparation method of 6- triiodo isophthaloyl chlorine, it is characterised in that：It is described anti-
The reaction time answered is 1~10 hour.
4. 5- amino -2,4 according to claim 1, the preparation method of 6- triiodo isophthaloyl chlorine, it is characterised in that：The 5-
The mole dosage of the iodo- 1,3- phthalic acid of amino -2,4,6- three and triphenylphosphine is than 1：2~5.
5. 5- amino -2,4 according to claim 1, the preparation method of 6- triiodo isophthaloyl chlorine, it is characterised in that：The salt
The mole dosage ratio of hydrogen chloride and the iodo- 1,3- phthalic acid of 5- amino -2,4,6- three in acid is 5~10：1.
6. 5- amino -2,4 according to claim 1, the preparation method of 6- triiodo isophthaloyl chlorine, it is characterised in that：The first
Alkane gas, oxygen and the iodo- 1,3- phthalic acid mole dosage ratio of 5- amino -2,4,6- three are 3~6：3~6：1.
7. 5- amino -2,4 according to claim 1, the preparation method of 6- triiodo isophthaloyl chlorine, it is characterised in that：The nitrogen
The weight consumption of gas and oxygen ratio is 1~3：1.
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|---|---|---|---|
| CN201810986679.4A CN108821990A (en) | 2018-08-28 | 2018-08-28 | A kind of preparation method of 5- amino -2,4,6- triiodo isophthaloyl chlorine |
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| CN201810986679.4A CN108821990A (en) | 2018-08-28 | 2018-08-28 | A kind of preparation method of 5- amino -2,4,6- triiodo isophthaloyl chlorine |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101379023A (en) * | 2006-02-15 | 2009-03-04 | 通用电气医疗集团股份有限公司 | Contrast agents |
| CN102887833A (en) * | 2011-07-21 | 2013-01-23 | 浙江司太立制药股份有限公司 | Iodine-containing dimer contrast medium |
-
2018
- 2018-08-28 CN CN201810986679.4A patent/CN108821990A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101379023A (en) * | 2006-02-15 | 2009-03-04 | 通用电气医疗集团股份有限公司 | Contrast agents |
| CN102887833A (en) * | 2011-07-21 | 2013-01-23 | 浙江司太立制药股份有限公司 | Iodine-containing dimer contrast medium |
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Application publication date: 20181116 |
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