CN109354678A - The preparation method of cetomacrogol 1000 - Google Patents
The preparation method of cetomacrogol 1000 Download PDFInfo
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- CN109354678A CN109354678A CN201811102733.0A CN201811102733A CN109354678A CN 109354678 A CN109354678 A CN 109354678A CN 201811102733 A CN201811102733 A CN 201811102733A CN 109354678 A CN109354678 A CN 109354678A
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- cetomacrogol
- preparation
- polyethylene glycol
- added dropwise
- bromohexadecane
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/338—Polymers modified by chemical after-treatment with inorganic and organic compounds
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/337—Polymers modified by chemical after-treatment with organic compounds containing other elements
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- Inorganic Chemistry (AREA)
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Abstract
The present invention provides a kind of preparation methods of cetomacrogol 1000, which comprises the following steps: (1) is dissolved in polyethylene glycol in dry organic solvent, under nitrogen protection, is added with stirring metallic sodium, heating reflux reaction；(2) cooling, bromohexadecane is added dropwise, heating reflux reaction obtains cetomacrogol 1000.Under conditions of this method is only heated to reflux under normal pressure; cetomacrogol can be prepared; preparation method is without high-tension apparatus, easy to operate and safe; avoid inflammable and explosive, the carcinogenic and harsh traffic condition disadvantage of ethylene oxide; with raw material simply easily acquisition, simple process, highly-safe, equipment input cost is low; there is no territory restriction, is applicable to a wide range of and large-scale production.
Description
Technical field
The present invention relates to the field of chemical synthesis, and in particular to a kind of preparation method of cetomacrogol 1000.
Background technique
Cetomacrogol 1000 (Cetomacrogol-1000) also known as cetomacrogol 1000 or cetanol polyoxyethylene ether, whale
Ceryl alcohol polyethers -20 are usually used in the emulsifier of emulsion, creme, the solubilizer of volatile oil.No. CAS is 9004-95-9, cetomacrogol
Structural formula such as formula (I).
Cetomacrogol 1000 is mainly made by hexadecanol or octadecyl alcolol with reacting ethylene oxide at present, the presently commercially available native horse in west
Brother 1000 is all made of industrial classical way: using hexadecanol potassium and ethylene oxide under -6 catalytic action of 18- crown ether, high temperature and pressure
It is reacted under (140 DEG C, 70psi), obtains cetomacrogol 1000 using purification process, synthetic route is as follows:
Above-mentioned technique is all made of in domestic most enterprise, but since in the classical process of above-mentioned industry, ethylene oxide is
Gas, it is inflammable and explosive, belong to a kind of carcinogenic substance, and high-tension apparatus is needed in synthesis technology, it needs to consider Explosion-Proof, pacifies
Full property is very low.In addition, the storage of ethylene oxide and traffic condition are harsh, therefore there is strong region.If without petrochemical industry
Chain realizes that the industrial mass production of cetomacrogol 1000 is more difficult.
Therefore, it is necessary to find a kind of synthesis under normal pressure, it is highly-safe, a wide range of, large-scale production west can be suitable for
The preparation method of native horse brother.
Summary of the invention
For above-mentioned+problem, the purpose of the present invention is to provide reaction under a kind of normal pressure, it is highly-safe, be suitble to it is a wide range of
And the preparation method of the cetomacrogol 1000 of large-scale production.
To achieve the above object, the present invention provides the following technical scheme that
A kind of preparation method of cetomacrogol 1000, comprising the following steps:
(1) polyethylene glycol is dissolved in dry non-alcohols organic solvent, under nitrogen protection, is added with stirring metal
Sodium, heating reflux reaction；
(2) bromohexadecane, heating reflux reaction is added dropwise；
In wherein some embodiments, the organic solvent is tetrahydrofuran.
In wherein some embodiments, heating reflux reaction described in step (1) and/or step (2), temperature be 68~
72 DEG C, when reaction a length of 18~22h.
In wherein some embodiments, molecular weight polyethylene glycol described in step (1) is 800~1000.
In wherein some embodiments, polyethylene glycol described in step (1) is polyethylene glycol-800.
In wherein some embodiments, the molar ratio of polyethylene glycol described in step (1) and the metallic sodium be (0.9~
1.1): 1, the tetrahydrofuran of the drying and the polyethylene glycol dosage mole, volume ratio (mol/L) be (0.09~
0.11):1。
Mole of polyethylene glycol in the bromohexadecane being added dropwise in step (2) in wherein some embodiments and step (1)
Than for (0.9~1.1): 1；And/or
The dropwise addition bromohexadecane are as follows: in the system obtained to step (1) reaction, bromo 16 is added dropwise at room temperature
Alkane.
In wherein some embodiments, above-mentioned preparation method further includes purification step: the west soil that step (2) is prepared
Horse brother 1000 is dissolved in ethyl acetate, and normal heptane is added dropwise, is stirred overnight at room temperature, and after solid is precipitated, filters, is dry, to obtain the final product.
In wherein some embodiments, the volume ratio of the ethyl acetate and the normal heptane is 1:(9~11).
In wherein some embodiments, the drying are as follows: vacuum drying.
Based on the above-mentioned technical proposal, the invention has the following advantages:
The present invention passes through a large amount of creative works of inventor, obtains the side that cetomacrogol is prepared under the completely new normal pressure of one kind
Method, by selecting polyethylene glycol, metallic sodium and bromohexadecane only to exist as reaction raw materials using tetrahydrofuran as solvent
Under conditions of being heated to reflux under normal pressure, cetomacrogol 1000 can be prepared, preparation method is without high-tension apparatus, operation letter
Just and it is safe, inflammable and explosive, the carcinogenic and harsh traffic condition disadvantage of ethylene oxide is avoided, there is raw material simply easily to obtain
Take, simple process, highly-safe, equipment input cost is low, without territory restriction, be applicable to a wide range of and large-scale production.
Detailed description of the invention
FIG. 1 to FIG. 4 is the relative molecular weight map for the cetomacrogol 1000 that embodiment 1 is prepared；
Fig. 5 is the infared spectrum for the cetomacrogol 1000 that embodiment 1 is prepared；
Fig. 6~9 are the relative molecular weight map for the cetomacrogol 1000 that embodiment 3 is prepared；
Figure 10 is the infared spectrum for the cetomacrogol 1000 that embodiment 3 is prepared.
Specific embodiment
To facilitate the understanding of the present invention, it below with reference to embodiment to invention is more fully described, is given below
Presently preferred embodiments of the present invention.But the invention can be realized in many different forms, however it is not limited to described herein
Embodiment.Purpose of providing these embodiments is makes the disclosure of the present invention more thorough and comprehensive.Embodiment
The middle all kinds of raw materials used are unless otherwise indicated commercial product.
Unless otherwise defined, all technical and scientific terms used herein and belong to technical field of the invention
The normally understood meaning of technical staff is identical.Used term is intended merely to describe specific reality in the description of the invention
Apply the purpose of example, it is not intended that in the limitation present invention.Term as used herein "and/or" includes one or more relevant institutes
Any and all combinations of list of items.
The preparation method of 1 cetomacrogol 1000 of embodiment
(1) polyethylene glycol-800 (157.50g, 191.61mmol, 1eq) is dissolved in dry tetrahydrofuran (2L), leads to nitrogen
The lower metallic sodium (4.85g, 210.77mmol, 1.1eq) for being added and being cut into small pieces, heating reflux reaction 20h is stirred at room temperature in protection.
(2) reaction solution is cooled to room temperature, and is added dropwise bromohexadecane (64.36g, 210.77mmol, 1.1eq), is added dropwise,
Heating reflux reaction 20h.
(3) reaction solution is cooled to room temperature, and filtering, filtrate is concentrated to dryness, and obtains 1000 crude product of cetomacrogol.
(4) 1000 crude product of cetomacrogol is dissolved in ethyl acetate (100mL), is added dropwise normal heptane (1000mL), room temperature is stirred
It mixes overnight, after solid is precipitated, filters, vacuum drying obtains cetomacrogol 1000 (122.00g), the yield of cetomacrogol 1000
It is 55%.
Wherein, the heating temperature of heating reflux reaction reaches the reflowable temperature of solvent depending on the boiling point of solvent.
Use tetrahydrofuran for solvent in the present embodiment, being heated to reflux temperature setting is 70 DEG C.
The preparation method of 2 cetomacrogol 1000 of embodiment
(1) polyethylene glycol-800 (157.50g, 191.61mmol, 1eq) is dissolved in dry methylene chloride in (2L), leads to nitrogen
The lower metallic sodium (4.85g, 210.77mmol, 1.1eq) for being added and being cut into small pieces is stirred at room temperature in gas shielded, and 45 DEG C are heated to reflux instead
Answer 20h.
(2) reaction solution is cooled to room temperature, and is added dropwise bromohexadecane (64.36g, 210.77mmol, 1.1eq), is added dropwise,
45 DEG C of heating reflux reaction 20h.
(3) reaction solution is cooled to room temperature, and filtering, filtrate is concentrated to dryness, and obtains 1000 crude product of cetomacrogol.
(4) 1000 crude product of cetomacrogol is dissolved in ethyl acetate (100mL), is added dropwise normal heptane (1000mL), room temperature is stirred
It mixes overnight, after solid is precipitated, filters, vacuum drying obtains cetomacrogol 1000 (110.28g), yield 49.7%.
In the present embodiment, the solvent used is different from tetrahydrofuran described in embodiment for methylene chloride, therefore according to two
The boiling point of chloromethanes, setting heating reflux reaction temperature are 45 degrees Celsius.The yield for finally obtaining cetomacrogol 1000 is relatively implemented
Example 1 is slightly lower, and possible cause is the reaction dissolvent difference used, and reaction rate and yield are affected.
The route of Examples 1 to 2 reaction is as follows:
The preparation method of 3 cetomacrogol 1000 of embodiment
(1) cetomacrogol 1000 (190g, 190mmol, 1eq) is dissolved in dry tetrahydrofuran (2L), leads to nitrogen protection,
The lower metallic sodium (4.85g, 210.77mmol, 1.1eq) for being added and being cut into small pieces, 70 DEG C of heating reflux reaction 20h are stirred at room temperature.
(2) reaction solution is cooled to room temperature, and is added dropwise bromohexadecane (64.36g, 210.77mmol, 1.1eq), is added dropwise,
70 DEG C of heating reflux reaction 20h.
(3) reaction solution is cooled to room temperature, and filtering, filtrate is concentrated to dryness, and obtains 1000 crude product of cetomacrogol.
(4) 1000 crude product of cetomacrogol is dissolved in ethyl acetate (100mL), is added dropwise normal heptane (1000mL), room temperature is stirred
It mixes overnight, after solid is precipitated, filters, vacuum drying obtains cetomacrogol 1000 (145.17g), yield 57%.
In the present embodiment, the reaction raw materials polyethylene glycol used is cetomacrogol 1000, and solvent is tetrahydrofuran, according to four
The temperature of the boiling point setting heating reflux reaction of hydrogen furans is 70 degrees Celsius, finally obtains yield and the implementation of cetomacrogol 1000
Example 1 is suitable.
The route that embodiment 3 is reacted is as follows:
The characterization of 4 cetomacrogol 1000 of embodiment
By conventional mass spectrometry method, the cetomacrogol 1000 that embodiment 1 is prepared is characterized, embodiment is obtained
The relative molecular weight spectrogram of cetomacrogol 1000 described in 1, as shown in figures 1-4, it is known that the relative molecular weight of cetomacrogol is
1092.69。
To the cetomacrogol 1000 that embodiment 1 is prepared, IR Characterization is carried out, result is as shown in Figure 5.Analysis can
, the information at each infrared peak is as shown in table 1.
The 1000 infared spectrum information table of cetomacrogol that 1 embodiment 1 of table is prepared
By conventional mass spectrometry method, the cetomacrogol 1000 that embodiment 3 is prepared is characterized, embodiment is obtained
The relative molecular weight spectrogram of cetomacrogol 1000 described in 3, as shown in Fig. 6~9, it is known that the relative molecular weight of cetomacrogol is
1406.04.Its relative molecular weight is bigger than normal.
To the cetomacrogol 1000 that embodiment 3 is prepared, IR Characterization is carried out, the results are shown in Figure 10.Analysis can
, the information at each infrared peak is as shown in table 2.
The 1000 infared spectrum information table of cetomacrogol that 2 embodiment 3 of table is prepared
As it can be seen that the cetomacrogol that embodiment 1-3 is prepared is referring to Japanese " pharmaceuticals additive specification 2003 " Chinese and Western soil
After 1000 quality standard of horse brother identification detection project detects, we are believed that implementing the product that 1-3 is obtained is cetomacrogol
1000。
Attached: it is specifically interior to identify detection for 1000 quality standard of cetomacrogol in Japanese " pharmaceuticals additive specification 2003 "
Hold:
[identification] (1) takes this product about 0.5g, adds water 10ml heating to make to dissolve, adds ammonium thiocyanate-cobalt nitrate (II) test solution
5mL, shaking add chloroform 5mL, and oscillation is placed after shaking up, the aobvious blue of chloroform layer.
(2) this product is taken, after heating melting, with embrane method sample preparation, according to infrared spectrophotometer (Chinese Pharmacopoeia version general rule in 2015
0402) it measures, in 2920cm-1、1468cm-1、1346cm-1And 1113cm-1There is characteristic absorption at wave number.
Each technical characteristic of embodiment described above can be combined arbitrarily, for simplicity of description, not to following reality
It applies all possible combination of each technical characteristic in example to be all described, as long as however, the combination of these technical characteristics is not deposited
In contradiction, all should be considered as described in this specification.
The embodiments described above only express several embodiments of the present invention, and the description thereof is more specific and detailed, but simultaneously
Limitations on the scope of the patent of the present invention therefore cannot be interpreted as.It should be pointed out that for those of ordinary skill in the art
For, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to guarantor of the invention
Protect range.Therefore, the scope of protection of the patent of the invention shall be subject to the appended claims.
Claims (10)
1. a kind of preparation method of cetomacrogol 1000, which comprises the following steps:
(1) polyethylene glycol is dissolved in dry non-alcohols organic solvent, under nitrogen protection, is added with stirring metallic sodium, adds
Hot back flow reaction；
(2) bromohexadecane is added dropwise, heating reflux reaction obtains cetomacrogol 1000.
2. preparation method according to claim 1, which is characterized in that the non-alcohols organic solvent is tetrahydrofuran.
3. preparation method according to claim 2, which is characterized in that heating described in step (1) and/or step (2)
Back flow reaction, temperature are 68~72 DEG C, when reaction a length of 18~22h.
4. preparation method according to claim 2, which is characterized in that molecular weight polyethylene glycol described in step (1) is
800~1000.
5. the preparation method according to claim 4, which is characterized in that polyethylene glycol described in step (1) is poly- second two
Alcohol 800.
6. described in any item preparation methods according to claim 1~5, which is characterized in that polyethylene glycol described in step (1) with
The molar ratio of the metallic sodium is (0.9~1.1): 1, the tetrahydrofuran of the drying and the polyethylene glycol dosage mole,
Volume ratio (mol/L) is (0.09~0.11): 1.
7. preparation method according to claim 1, which is characterized in that the bromohexadecane and step being added dropwise in step (2)
(1) molar ratio of polyethylene glycol is (0.9~1.1) in: 1；And/or
The dropwise addition bromohexadecane are as follows: in the system obtained to step (1) reaction, bromohexadecane is added dropwise at room temperature.
8. described in any item preparation methods according to claim 1~7, which is characterized in that further include purification step: by step
(2) cetomacrogol 1000 being prepared is dissolved in ethyl acetate, and normal heptane is added dropwise, is stirred overnight at room temperature, after solid is precipitated, mistake
It filters, is dry, to obtain the final product.
9. preparation method according to claim 8, which is characterized in that the volume ratio of the ethyl acetate and the normal heptane
For 1:(9~11).
10. preparation method according to claim 8, which is characterized in that the drying are as follows: vacuum drying.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102178240A (en) * | 2011-04-20 | 2011-09-14 | 华宝食用香精香料（上海）有限公司 | Method for preparing microemulsion of walnut oil |
| CN102178231A (en) * | 2011-04-20 | 2011-09-14 | 华宝食用香精香料（上海）有限公司 | Preparation method of fish oil microemulsion |
| US20140323588A1 (en) * | 2013-04-29 | 2014-10-30 | Helene Bertrand | Topical Formulation for Pain Relief |
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2018
- 2018-09-20 CN CN201811102733.0A patent/CN109354678A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102178240A (en) * | 2011-04-20 | 2011-09-14 | 华宝食用香精香料（上海）有限公司 | Method for preparing microemulsion of walnut oil |
| CN102178231A (en) * | 2011-04-20 | 2011-09-14 | 华宝食用香精香料（上海）有限公司 | Preparation method of fish oil microemulsion |
| US20140323588A1 (en) * | 2013-04-29 | 2014-10-30 | Helene Bertrand | Topical Formulation for Pain Relief |
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| SUJAN MAJUMDER, ET AL: "Eco-friendly PEG-based controlled release nano-formulations of Mancozeb: Synthesis and bioefficacy evaluation against phytopathogenic fungi Alternaria solani and Sclerotium rolfsii", 《JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH, PART B》 * |
| SUJAN MAJUMDER, ET AL: "Synthesis and characterization of functionalized amphiphilic polymers for utilization as surfactants", 《JOURNAL OF MACROMOLECULAR SCIENCE, PART A》 * |
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