CN109988064A - A kind of pseudo ionone selectivity cyclisation method - Google Patents
A kind of pseudo ionone selectivity cyclisation method Download PDFInfo
- Publication number
- CN109988064A CN109988064A CN201910349736.2A CN201910349736A CN109988064A CN 109988064 A CN109988064 A CN 109988064A CN 201910349736 A CN201910349736 A CN 201910349736A CN 109988064 A CN109988064 A CN 109988064A
- Authority
- CN
- China
- Prior art keywords
- petroleum ether
- added
- parts
- weight
- pseudo ionone
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
-
- 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
- C07B2200/09—Geometrical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention provides a kind of pseudo ionone selectivity cyclisation methods, it is characterized in that, its raw material includes: 20~35 parts by weight of the concentrated sulfuric acid, 15~25 parts by weight of phosphorus pentoxide, 10~15 parts by weight of petroleum ether, 5~8 parts by weight of methanol, 25~40 parts by weight of pseudo ionone.A certain proportion of concentrated sulfuric acid and phosphorus pentoxide mixture is added as cyclizing agent in the present invention in false-irisone of rectifying, and petroleum ether, methanol is added as solvent, low temperature is uniform, obviously increase the alpha, beta-lonone during cyclization selectively, content reaches 97% or more, reduces separating difficulty.
Description
Technical field
The invention belongs to chemical field, it is related to increasing the selectivity of main reaction during the preparation process, especially purity is wanted
Very high pharmaceutical intermediate is sought, as alpha, beta-lonone increases the technology of main reaction selectivity.
Background technique
Have the method for false-irisone cyclization during cyclization at present following several:
1.98% concentrated sulfuric acid (density 1.84g/mL), temperature cannot be below -20 DEG C (with petroleum ether mixtures), otherwise dense
Sulfuric acid can solidify, and the selectivity of alpha, beta-lonone is no more than 85% in cyclization, and very big difficulty is brought to subsequent separating-purifying.
2.85% concentrated phosphoric acid (density 1.84), temperature cannot be below -10 DEG C (with petroleum ether mixtures), otherwise concentrated phosphoric acid
It can solidify, the selectivity of alpha, beta-lonone is no more than 55% in cyclization, and very big difficulty is brought to subsequent separating-purifying, can only
Do fragrance use.
As the medicine intermediate for preparing vitamin A, the purity of alpha, beta-lonone must reach 94%, in production synthesis
Alpha, beta-lonone selectivity is higher, and separating-purifying is easier, and yield is also higher, the every raising one percentage point of selectivity in synthesis,
Last yield at least improves five percentage points (in 90~99% ranges).Otherwise it can only scrap or the fragrance much lower as price
Raw material will cause very big loss.
Summary of the invention
The object of the present invention is to provide a kind of pseudo ionone selectivity cyclisation methods, to improve the production of alpha, beta-lonone
Rate.
In order to achieve the above object, the present invention provides a kind of pseudo ionone selectivity cyclisation method, feature exists
In raw material includes:
Preferably, the raw material of the pseudo ionone selectivity cyclisation method further includes dry ice, by warm in reaction kettle
Degree, is just suitably added higher than -30 DEG C.
Preferably, the boiling point of the petroleum ether is at 30-60 DEG C.The petroleum ether contains various pentanes, hexane etc..
Preferably, the concentration of the concentrated sulfuric acid is 96%-98%.
Preferably, the specific steps of the pseudo ionone selectivity cyclisation method include:
Step 1: 15~25 parts by weight phosphorus pentoxides being dissolved in into 20~35 parts by weight concentrated sulfuric acids and are stirred, by the mixing
Object is pumped into reaction kettle, and the petroleum ether that 5~8 parts by weight Methanol and 8~10 parts by weight are added is cooled to -30~-35 DEG C under stiring；
Step 2: petroleum ether is added in 25~40 parts by weight pseudo ionones and obtains mixture, the petroleum ether with
The sum of dosage of petroleum ether in step 1 is 10~15 parts by weight, and resulting mixture is added drop-wise in reaction kettle；
Step 3: continue stirring after being added dropwise 5~15 minutes, is gradually heated to -5~-15 DEG C, it then will reaction gained
Mixture be put into -8 DEG C added with petroleum ether~-12 DEG C ice water and stir extraction, the volume ratio of petroleum ether and ice water be 1:5~
15, gained organic phase is boiled off solvent petroleum ether, obtains alpha, beta-lonone by liquid separation.
Preferably, during the dropwise addition of the step 2, control temperature is no more than -30 DEG C.
Preferably, in the step 2, if temperature is more than -30 DEG C during being added dropwise, stopping being added dropwise and be added dry ice makes
It cools to -30 DEG C or less.
Preferably, the ice water in the step 3 contains 30%~50% sulfuric acid.
Preferably, the ice water in the step 3 is using liquid separation in step 3 in the preparation method of last consignment of alpha, beta-lonone
Resulting water phase, containing 30%~50% sulfuric acid, to reduce discharge of wastewater and energy conservation.
The concentrated sulfuric acid and phosphorus pentoxide mixture can efficiently slough a molecular water in pseudo ionone in the present invention, make point
Subring is closed, and cyclization is very high at alpha, beta-lonone probability when low temperature, and the addition of methanol can reduce the freezing point of concentrated sulfuric acid mixture, make
Keep liquid to come into full contact with and react with pseudo ionone at low temperature, the addition of dry ice can guarantee reaction process (instead
Answer very exothermic) maintain low temperature not to be mixed into impurity (dry ice heat is volatilized completely).
Compared with prior art, the beneficial effects of the present invention are:
A certain proportion of concentrated sulfuric acid and phosphorus pentoxide mixture is added in false-irisone of rectifying in the present invention
As cyclizing agent, and petroleum ether, methanol is added as solvent, low temperature is uniform, makes the alpha, beta-lonone during cyclization
Selectivity obviously increases, and content reaches 97% or more, reduces separating difficulty.
Specific embodiment
Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate the present invention
Rather than it limits the scope of the invention.In addition, it should also be understood that, after reading the content taught by the present invention, those skilled in the art
Member can make various changes or modifications the present invention, and such equivalent forms equally fall within the application the appended claims and limited
Range.
Used each raw material is commercial product in following embodiment.
Embodiment 1
A kind of pseudo ionone selectivity cyclisation method, raw material include: the concentrated sulfuric acid (98%, density 1.84g/mL),
Phosphorus pentoxide, petroleum ether (boiling point is at 30-60 DEG C), methanol, pseudo ionone, specific dosage such as table 1.
The specific steps of the pseudo ionone selectivity cyclisation method are as follows:
Step 1: 15Kg phosphorus pentoxide being dissolved in into the 22Kg concentrated sulfuric acid and is stirred, which is pumped into reaction kettle, is added
The petroleum ether for entering 8Kg methanol and 8Kg is cooled to -30~-35 DEG C under stiring, and speed of agitator is 200-250 revs/min；
Step 2: petroleum ether is added in 40Kg pseudo ionone and obtains mixture, in the petroleum ether and step 1
The sum of the dosage of petroleum ether be 15Kg, resulting mixture is added drop-wise in reaction kettle；Ramp case is paid attention to, as temperature is super
- 30 DEG C are crossed, then stopping being added dropwise and be added dry ice makes its cooling；
Step 3: continuing stirring 10 minutes after being added dropwise, be gradually heated to -10 DEG C, then will react resulting mixture
1000L is put into added with -10 DEG C of ice water of petroleum ether (using liquid separation institute in step 3 in the preparation method of last consignment of alpha, beta-lonone
Water phase, the sulfuric acid containing 30%~50%) in stirring extraction, the volume ratio of petroleum ether and ice water is 1:10, liquid separation, by gained
Organic phase boils off solvent petroleum ether, obtains alpha, beta-lonone.Chromatogram display content reaches 98.1% (deducting solvent petroleum ether).
Embodiment 2
A kind of pseudo ionone selectivity cyclisation method, raw material include: the concentrated sulfuric acid (98%, density 1.84g/mL),
Phosphorus pentoxide, petroleum ether (boiling point is at 30-60 DEG C), methanol, pseudo ionone, specific dosage such as table 1.
The specific steps of the pseudo ionone selectivity cyclisation method are as follows:
Step 1: 25Kg phosphorus pentoxide being dissolved in into the 25g concentrated sulfuric acid and is stirred, which is pumped into reaction kettle, is added
The petroleum ether of 7Kg methanol and 10Kg are cooled to -30~-35 DEG C under stiring, and speed of agitator is 200-250 revs/min；
Step 2: petroleum ether is added in 28Kg pseudo ionone and obtains mixture, in the petroleum ether and step 1
The sum of the dosage of petroleum ether be 15Kg, resulting mixture is added drop-wise in reaction kettle；Ramp case is paid attention to, as temperature is super
- 30 DEG C are crossed, then stopping being added dropwise and be added dry ice makes its cooling；
Step 3: continuing stirring after being added dropwise 10 minutes and be warming up to -10 DEG C, then will react resulting mixture and put
Enter 1000L added with -10 DEG C of ice water of petroleum ether (using obtained by liquid separation in step 3 in the preparation method of last consignment of alpha, beta-lonone
Water phase, the sulfuric acid containing 30%~50%) in stirring extraction, the volume ratio of petroleum ether and ice water is 1:10, and liquid separation has gained
Machine mutually boils off solvent petroleum ether, obtains alpha, beta-lonone.Chromatogram display content reaches 98.3% (deducting solvent petroleum ether).
Embodiment 3
A kind of pseudo ionone selectivity cyclisation method, raw material include: the concentrated sulfuric acid (98%, density 1.84g/mL),
Phosphorus pentoxide, petroleum ether (boiling point is at 30-60 DEG C), methanol, pseudo ionone, specific dosage such as table 1.
The specific steps of the pseudo ionone selectivity cyclisation method are as follows:
Step 1: 20Kg phosphorus pentoxide being dissolved in into the 30Kg concentrated sulfuric acid and is stirred, which is pumped into reaction kettle, is added
The petroleum ether for entering 6Kg methanol and 8g is cooled to -30~-35 DEG C under stiring, and speed of agitator is 200-250 revs/min；
Step 2: petroleum ether is added in 31Kg pseudo ionone and obtains mixture, in the petroleum ether and step 1
The sum of the dosage of petroleum ether be 13Kg, resulting mixture is added drop-wise in reaction kettle；Ramp case is paid attention to, as temperature is super
- 30 DEG C are crossed, then stopping being added dropwise and be added dry ice makes its cooling；
Step 3: continuing stirring after being added dropwise 10 minutes and be warming up to -10 DEG C, then will react resulting mixture and put
Enter 1000L added with stirring extraction, the volume of petroleum ether and ice water in -10 DEG C of ice water (sulfuric acid containing 30%~50%) of petroleum ether
Than for 1:10, gained organic phase is boiled off solvent petroleum ether, obtains alpha, beta-lonone by liquid separation.Chromatogram display content reaches
99.5% (deducting solvent petroleum ether).
Embodiment 4
A kind of pseudo ionone selectivity cyclisation method, raw material include: the concentrated sulfuric acid (98%, density 1.84g/mL),
Phosphorus pentoxide, petroleum ether (boiling point is at 30-60 DEG C), methanol, pseudo ionone, specific dosage such as table 1.
The specific steps of the pseudo ionone selectivity cyclisation method are as follows:
Step 1: 25Kg phosphorus pentoxide being dissolved in into the 35Kg concentrated sulfuric acid and is stirred, which is pumped into reaction kettle, is added
The petroleum ether for entering 6Kg methanol and 7Kg is cooled to -30~-35 DEG C under stiring, and speed of agitator is 200-250 revs/min；
Step 2: petroleum ether is added in 25Kg pseudo ionone and obtains mixture, in the petroleum ether and step 1
The sum of the dosage of petroleum ether be 10Kg, resulting mixture is added drop-wise in reaction kettle；Ramp case is paid attention to, as temperature is super
- 30 DEG C are crossed, then stopping being added dropwise and be added dry ice makes its cooling；
Step 3: continuing stirring after being added dropwise 10 minutes and be warming up to -10 DEG C, then will react resulting mixture and put
Enter 1000L added with stirring extraction, the volume of petroleum ether and ice water in -10 DEG C of ice water (sulfuric acid containing 30%~50%) of petroleum ether
Than for 1:10, gained organic phase is boiled off solvent petroleum ether, obtains alpha, beta-lonone by liquid separation.Chromatogram display content reaches
99.7% (deducting solvent petroleum ether).
Comparative example 1: a method of make pseudo ionone cyclization at alpha, beta-lonone, raw material such as the following table 1 is specific to walk
Suddenly are as follows:
The 55Kg concentrated sulfuric acid is pumped into reaction kettle, 10Kg petroleum ether is added and is cooled to -20 DEG C under high velocity agitation, speed of agitator
It is 200-250 revs/min；5Kg petroleum ether is added in 30Kg pseudo ionone, is slowly added drop-wise in reaction kettle, pays attention to heating
Situation, if temperature is more than -10 DEG C, then stopping being added dropwise and be added dry ice is added dropwise it again after cooling down.Continue to stir after being added dropwise
It mixes 10 minutes and is slightly warming up to -5 DEG C, then reaction mixture is put into and (is adopted added with 1000L added with -10 DEG C of ice water of petroleum ether
With the resulting water phase of liquid separation in step 3 in the preparation method of last consignment of alpha, beta-lonone) in stirring extraction, organic phase boils off solvent
Petroleum ether obtains the less high thick alpha, beta-lonone of selectivity.
- 1 alpha, beta-lonone meter purity of table (solution quality deducts when analysis)
Claims (7)
1. a kind of pseudo ionone selectivity cyclisation method, which is characterized in that its raw material includes:
2. pseudo ionone selectivity cyclisation method as described in claim 1, which is characterized in that the false violet
The raw material of ketone selectivity cyclisation method further includes dry ice.
3. pseudo ionone selectivity cyclisation method as described in claim 1, which is characterized in that the boiling of the petroleum ether
Point is at 30-60 DEG C.
4. pseudo ionone selectivity cyclisation method as described in claim 1, which is characterized in that the concentrated sulfuric acid it is dense
Degree is 96%-98%.
5. pseudo ionone selectivity cyclisation method as described in claim 1, which is characterized in that specific steps include:
Step 1: 15~25 parts by weight phosphorus pentoxides being dissolved in into 20~35 parts by weight concentrated sulfuric acids and are stirred, which is pumped
Enter reaction kettle, the petroleum ether that 5~8 parts by weight Methanol and 8-10 parts by weight are added is cooled to -30~-35 DEG C under stiring；
Step 2: petroleum ether is added in 25~40 parts by weight pseudo ionones and obtains mixture, the petroleum ether and step
The sum of dosage of petroleum ether in 1 is 10~15 parts by weight, and resulting mixture is added drop-wise in reaction kettle；
Step 3: continuing stirring after being added dropwise 5~15 minutes, be gradually heated to -5~-15 DEG C, then will react resulting mixed
Conjunction object, which is put into -8 DEG C added with petroleum ether~-12 DEG C ice water, stirs extraction, and the volume ratio of petroleum ether and ice water is 1:5~15,
Gained organic phase is boiled off solvent petroleum ether, obtains alpha, beta-lonone by liquid separation.
6. pseudo ionone selectivity cyclisation method as described in claim 1, which is characterized in that the drop of the step 2
During adding, control temperature is no more than -30 DEG C.
7. pseudo ionone selectivity cyclisation method as described in claim 1, which is characterized in that in the step 2, if
Temperature is more than -30 DEG C during dropwise addition, then stopping being added dropwise and be added dry ice makes it cool to -30 DEG C or less.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910349736.2A CN109988064B (en) | 2019-04-28 | 2019-04-28 | Selective cyclization method of pseudo ionone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910349736.2A CN109988064B (en) | 2019-04-28 | 2019-04-28 | Selective cyclization method of pseudo ionone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109988064A true CN109988064A (en) | 2019-07-09 |
| CN109988064B CN109988064B (en) | 2021-11-19 |
Family
ID=67133088
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910349736.2A Expired - Fee Related CN109988064B (en) | 2019-04-28 | 2019-04-28 | Selective cyclization method of pseudo ionone |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109988064B (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4565894A (en) * | 1983-08-06 | 1986-01-21 | Basf Aktiengesellschaft | Preparation of ionones |
| CN1109462A (en) * | 1994-10-08 | 1995-10-04 | 中标标准技术研究所 | Synthesis for high purity beta ionone |
| CN1129209A (en) * | 1995-10-05 | 1996-08-21 | 复旦大学 | Process for production of beta-jonone |
| CN1508113A (en) * | 2002-12-19 | 2004-06-30 | 上海应用技术学院 | Industrial method for preparing beta-ionone |
| EP1921058A1 (en) * | 2006-11-10 | 2008-05-14 | DSMIP Assets B.V. | Process for the preparation of ionones and vitamin A, vitamin A derivatives, carotenes and carotenoids |
| CN101333154A (en) * | 2007-06-28 | 2008-12-31 | 拜耳技术工程（上海）有限公司 | Method for synthesizing beta-ionone |
-
2019
- 2019-04-28 CN CN201910349736.2A patent/CN109988064B/en not_active Expired - Fee Related
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4565894A (en) * | 1983-08-06 | 1986-01-21 | Basf Aktiengesellschaft | Preparation of ionones |
| CN1109462A (en) * | 1994-10-08 | 1995-10-04 | 中标标准技术研究所 | Synthesis for high purity beta ionone |
| CN1129209A (en) * | 1995-10-05 | 1996-08-21 | 复旦大学 | Process for production of beta-jonone |
| CN1508113A (en) * | 2002-12-19 | 2004-06-30 | 上海应用技术学院 | Industrial method for preparing beta-ionone |
| EP1921058A1 (en) * | 2006-11-10 | 2008-05-14 | DSMIP Assets B.V. | Process for the preparation of ionones and vitamin A, vitamin A derivatives, carotenes and carotenoids |
| CN101333154A (en) * | 2007-06-28 | 2008-12-31 | 拜耳技术工程（上海）有限公司 | Method for synthesizing beta-ionone |
Non-Patent Citations (1)
| Title |
|---|
| 王兰明: "β-紫罗兰的制备", 《中国医药工业杂志》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109988064B (en) | 2021-11-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107573500A (en) | A kind of preparation method of high-purity polyether-ether-ketone resin | |
| CN109876489A (en) | The method and eutectic solvent of eutectic solvent combination microwave abstracting plant sample | |
| CN106674244A (en) | Preparation method of cineole | |
| CN101263891B (en) | Method for making lutein extract microcapsule | |
| CN109988064A (en) | A kind of pseudo ionone selectivity cyclisation method | |
| CN112047825A (en) | Production process of dichloro pinacolone | |
| CN109970535A (en) | A kind of preparation method of alpha, beta-lonone | |
| CN106008187B (en) | A kind of preparation method of synthesis anthraquinone | |
| CN103922933A (en) | Preparation method of ethyl lactate | |
| CN104862157B (en) | It is a kind of can relieving alcoholism and protecting liver beer additive and preparation method thereof | |
| CN101194707A (en) | High purity stevioside glycoside refining process | |
| CN103695179A (en) | Production process method of cinnamon volatile oil | |
| CN105884822A (en) | Technology for preparing tributyl phosphate by means of synthesizing alkali alcoholate by aid of cryogenic process | |
| CN101292770B (en) | Solid lactic acid and preparation method thereof | |
| CN101805268B (en) | Method for preparing acetyl salicylamide | |
| CN112661649B (en) | 2,6-dinitro-4-tert-amylphenol and preparation method thereof | |
| CN104628670A (en) | 6-nitro-1,2-diazoxynaphthalene-4-sulfonic acid and preparation method thereof | |
| CN112500260B (en) | Preparation method of 2-fluoro-5-bromoiodobenzene | |
| CN110183359A (en) | A kind of preparation method of 2,2 '-dihydroxybiphenyls | |
| CN108586365A (en) | A kind of preparation method of high-purity 4- methyl benzotriazazoles | |
| CN115024478B (en) | Refining method of capsicum oleoresin | |
| CN109336810A (en) | A kind of preparation method of haloperidid class nitrogen oxides | |
| CN107892746A (en) | A kind of Industrialized synthesis method of coating level superfine powder polyaryl ether sulphone resin | |
| CN101514160B (en) | Method for preparing 2, 7-dibromo-4-nitrofluorenone | |
| CN111454138A (en) | Continuous preparation method of high-selectivity α -ionone |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20211119 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |