CN102295573A - Chemical synthetic method of oleoylethanolamide - Google Patents
Chemical synthetic method of oleoylethanolamide Download PDFInfo
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- CN102295573A CN102295573A CN2011101957577A CN201110195757A CN102295573A CN 102295573 A CN102295573 A CN 102295573A CN 2011101957577 A CN2011101957577 A CN 2011101957577A CN 201110195757 A CN201110195757 A CN 201110195757A CN 102295573 A CN102295573 A CN 102295573A
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Abstract
A chemical synthetic method of oleoylethanolamide relates to oleoylethanolamide. A chemical synthetic method of oleoylethanolamide is provided which is not only cheap and simple, but also is applicable to industrial production. The method comprises the following steps: allowing oleic acid and reactants to react by an acylation reaction in the presence of a catalyst to obtain an acylation product; concentrating the acylation product, allowing the product to react with ethanolamine by an aminolysis reaction in the presence of an organic base to obtain a product after the aminolysis reaction; performing filtering, pickling, and alkali washing of the product after the aminolysis reaction, performing concentration to obtain a crude product; washing and centrifuging the crude product by a low-polarity alkane to obtain oleoylethanolamide.
Description
Technical field
The present invention relates to a kind of Oleoyl monoethanolamide (OEA), especially relate to a kind of chemical synthesis process of Oleoyl monoethanolamide.
Background technology
Oleoyl monoethanolamide, chemistry N-(2-hydroxyethyl)-(Z) by name-9-octadecylene acid amides, English N-Oleoylethanolamine by name is called for short OEA.OEA is a kind of human body endogenous material, can regulate the health lipid metabolism, blood fat reducing function is arranged, this chemical substance can also activate in the intestines neural, send the signal of " full tripe " to brain, reduce the Mammals food intake and then reduce body weight, so OEA become the potential drug raw material or the foodstuff additive of novel reducing blood-fat and fat-reducing, its chemical structural formula is as follows:
Edward T etc. (Edward T, John T.J.Am.Chem.Soc.1949 71:2215) have reported with oleic acid to be raw material, and with thanomin direct reaction generation at high temperature OEA, its synthetic route is as follows:
Spain patent ES2337226 discloses the method for a kind of synthetic OEA, earlier oleic acid and thionyl chloride is carried out acylation reaction under the room temperature, obtains with thanomin it being carried out aminolysis again behind the oleoyl chloride, makes OEA.Its synthetic route is as follows:
Because the reactive behavior of acyl chlorides is very high, therefore, this method improves the productive rate of OEA greatly, but the later stage purifying uses column chromatography, is not suitable for a large amount of suitability for industrialized production.In addition, also have document (Cl é mentine Thabuis, Delphine Tissot-Favre, Jean-Baptiste Bezelgues, Journal of Chromatography A, 2008,1202:216) report directly reacts with triolein and thanomin, under 170 ℃ high temperature, the amido of thanomin carries out aminolysis to the ester group of olein, gets crude product OEA, after the washing of normal hexane and aqueous sodium persulfate solution, can purer OEA, its synthetic route is as follows:
But this method temperature is higher, and side reaction easily takes place, and raw material is rare, and price is more many than oleic acid costliness.
Summary of the invention
The objective of the invention is to all be not suitable for mass-produced shortcoming, provide a kind of not only cheap, easy, and can be applicable to the chemical synthesis process of the Oleoyl monoethanolamide of suitability for industrialized production at the means of purification of present OEA.
Technical scheme of the present invention be with oleic acid and chloride reagent under catalyst action; under normal temperature or low temperature, carry out acylation reaction; the product of chloride without separate directly and thanomin in the presence of acid binding agent; carry out aminolysis reaction; reacted product removes by filter the acid binding agent ammonium salt of generation, after the pickling alkali cleaning, concentrate yellow crude product; wash centrifugal several times with a small amount of low polarity alkane, can get white pure product OEA.Synthetic route of the present invention is as follows:
The present invention includes following steps:
1) oleic acid and reactant are carried out acylation reaction in the presence of catalyzer, get acylate;
In step 1), the mol ratio of described oleic acid and reactant can be 1: (2～6); Described reactant can be selected from chloride reagent, and described chloride reagent can be selected from a kind of in oxalyl chloride, phosphorus oxychloride, phosphorus pentachloride, the thionyl chloride etc.; Described catalyzer can be selected from N, dinethylformamide (DMF) etc.; The time of described acylation reaction can be 3～20h.
2) with after the acylate concentration, in the presence of organic bases and thanomin carry out aminolysis reaction, the product behind the aminolysis reaction;
In step 2) in, the mol ratio of described acylate and thanomin can be 1: (1～4); Add acid binding agent during described aminolysis reaction, described acid binding agent can be selected from triethylamine class aliphatic amide, N, a kind of in accelerine, the pyridine etc.; The temperature of described aminolysis reaction can be-20～20 ℃, and the time of aminolysis reaction can be 3～20h; Described organic bases can be selected from triethylamine class aliphatic amide, N, a kind of in accelerine, the pyridine etc.
3) with the product behind the aminolysis reaction after filtration, after the pickling, alkali cleaning, concentrate crude product;
In step 3), the used acid of described pickling can be mineral acid, and described mineral acid can be selected from the hydrochloric acid soln of 1～2M, can be washed till pH=1～2 during pickling; The used alkali of described alkali cleaning can be mineral alkali, and a kind of in the optional self-saturation yellow soda ash of described mineral alkali, saturated potassium carbonate, saturated sodium bicarbonate, the saturated potassium hydrogen carbonate solution etc. can be washed till pH=5～7 during alkali cleaning.
4) crude product is washed with low polarity alkane, centrifugal, get Oleoyl monoethanolamide.
In step 4), described low polarity alkane can be selected from C
5～C
8Alkane etc., described low polarity alkane can be selected from a kind of in sherwood oil, normal hexane, Skellysolve A, octane, normal heptane, the hexanaphthene etc.; Described washing is preferably washed 2 times at least.
Compare with existing OEA synthetic method, the invention has the advantages that:
1) use active higher oxalyl chloride, phosphorus oxychloride, phosphorus pentachloride etc. as chloride reagent, shortened the time of producing acylate, and product need not separate, be directly used in the next step, reduced acylate separate with shifted in hydrolysis.
2) purge process in later stage is directly removed impurity with solvent wash, without column chromatography, promptly removes inorganic salt with the pickling alkali cleaning; Remove raw material and organism by product with low polar alkane washing.Wherein used organic solvent can reclaim, and recycles, and reduces cost, and reduces environmental pollution.
3) the present invention adopts centrifugal method to substitute filter method commonly used and removes impurity, makes technological operation easy, has improved efficient.It is high-volume synthetic to the most important thing is that above method of purification is applicable to, is suitable for suitability for industrialized production.
Description of drawings
Fig. 1 is the GC-MS total ion current figure (purity 87.5%) of 5 μ g/L OEA solution.In Fig. 1, X-coordinate is time t/min, and ordinate zou is Abundance.
Fig. 2 is the 400M nuclear magnetic spectrum of 20mg/ml OEA solution.In Fig. 2, X-coordinate is chemical shift/ppm.
Embodiment
Embodiment 1
The 30mL oxalyl chloride that normal temperature will be dissolved in the 50mL methylene dichloride down dropwise is added in the 40mL oleic acid that is dissolved in the 50mL methylene dichloride, adds 2mLDMF, stirring at room 4h.The oleoyl chloride that makes dropwise is added in the mixed solution of 12mL thanomin and 30mL triethylamine at normal temperatures, stirring at room 4h.Remove by filter insolubles, reaction solution, is collected organic phase and is washed with saturated sodium bicarbonate solution to acid with the 2mol/LHCl washing, concentrates and obtains thick product.Add the normal hexane agitator treating, centrifugal, get white solid OEA.
The 30mL oxalyl chloride that normal temperature will be dissolved in the 50mL methylene dichloride down dropwise is added in the 40mL oleic acid that is dissolved in the 50mL methylene dichloride, adds 2mLDMF, stirring at room 4h.The oleoyl chloride that makes dropwise is added in the mixed solution of 12mL thanomin and 30mL triethylamine at normal temperatures, stirring at room 4h.Remove by filter insolubles, reaction solution, is collected organic phase and is washed with saturated sodium bicarbonate solution to acid with the 2mol/LHCl washing, concentrates and obtains thick product.Add the petroleum ether and stirring washing, centrifugal, get white solid OEA.
Embodiment 3
The 30mL oxalyl chloride that normal temperature will be dissolved in the 50mL methylene dichloride down dropwise is added in the 40mL oleic acid that is dissolved in the 50mL methylene dichloride, adds 2mLDMF, stirring at room 4h.The oleoyl chloride that makes dropwise is added in the mixed solution of 12mL thanomin and 30mL triethylamine at normal temperatures, stirring at room 4h.Remove by filter insolubles, reaction solution, is collected organic phase and is washed with saturated sodium carbonate solution to acid with the 2mol/LHCl washing, concentrates and obtains thick product.Add the Skellysolve A agitator treating, centrifugal, get white solid OEA.
Embodiment 4
Under 0 ℃ the 50mL thionyl chloride is added drop-wise in the 40mL oleic acid, behind the stirring at room 1h, solvent-free 90 ℃ of backflow 4h, the cool to room temperature of being heated to, the hydrogen chloride gas and the unreacted thionyl chloride that use the alkali lye scrubbing bottle will react generation absorb, and vacuum concentration makes purer oleoyl chloride again.The oleoyl chloride that makes is dissolved in the 50mL methylene dichloride, dropwise is added in the mixed solution of 12mL thanomin and 30mL triethylamine stirring at room 4h under the normal temperature.Remove by filter insolubles, reaction solution, is collected organic phase and is washed with saturated sodium bicarbonate solution to acid with the 2mol/LHCl washing, concentrates and obtains thick product.Add the petroleum ether and stirring washing, centrifugal, get white solid OEA.
Embodiment 5
Under 0 ℃ the 50mL thionyl chloride is added drop-wise in the 40mL oleic acid, behind the stirring at room 1h, solvent-free 90 ℃ of backflow 4h, the cool to room temperature of being heated to, the hydrogen chloride gas and the unreacted thionyl chloride that use the alkali lye scrubbing bottle will react generation absorb, and vacuum concentration makes purer oleoyl chloride again.The oleoyl chloride that makes is dissolved in the 50mL methylene dichloride, dropwise is added in the mixed solution of 12mL thanomin and 30mL triethylamine stirring at room 4h under the normal temperature.Remove by filter insolubles, reaction solution, is collected organic phase and is washed with saturated sodium bicarbonate solution to acid with the 2mol/LHCl washing, concentrates and obtains thick product.Add the normal hexane agitator treating, centrifugal, get white solid OEA.
Embodiment 6
Under 0 ℃ the 50mL thionyl chloride is added drop-wise in the 40mL oleic acid, behind the stirring at room 1h, solvent-free 90 ℃ of backflow 4h, the cool to room temperature of being heated to, the hydrogen chloride gas and the unreacted thionyl chloride that use the alkali lye scrubbing bottle will react generation absorb, and vacuum concentration makes purer oleoyl chloride again.The oleoyl chloride that makes is dissolved in the 50mL methylene dichloride, dropwise is added in the mixed solution of 12mL thanomin and 30mL triethylamine stirring at room 4h under the normal temperature.Remove by filter insolubles, reaction solution, is collected organic phase and is washed with saturated sodium carbonate solution to acid with the 2mol/LHCl washing, concentrates and obtains thick product.Add the Skellysolve A agitator treating, centrifugal, get white solid OEA.
Fig. 1 is given the GC-MS total ion current figure (purity 87.5%) of 5 μ g/L OEA solution, and Fig. 2 provides the 400M nuclear magnetic spectrum of 20mg/ml OEA solution.
Claims (10)
1. the chemical synthesis process of Oleoyl monoethanolamide is characterized in that its synthetic route is as follows:
2. the chemical synthesis process of Oleoyl monoethanolamide as claimed in claim 1 is characterized in that may further comprise the steps:
1) oleic acid and reactant are carried out acylation reaction in the presence of catalyzer, get acylate;
2) with after the acylate concentration, in the presence of organic bases and thanomin carry out aminolysis reaction, the product behind the aminolysis reaction;
3) with the product behind the aminolysis reaction after filtration, after the pickling, alkali cleaning, concentrate crude product;
4) crude product is washed with low polarity alkane, centrifugal, get Oleoyl monoethanolamide.
3. the chemical synthesis process of Oleoyl monoethanolamide as claimed in claim 2 is characterized in that in step 1), and the mol ratio of described oleic acid and reactant is 1: 2～6.
4. the chemical synthesis process of Oleoyl monoethanolamide as claimed in claim 2 is characterized in that in step 1), and described reactant is selected from chloride reagent, and described chloride reagent is selected from a kind of in oxalyl chloride, phosphorus oxychloride, phosphorus pentachloride, the thionyl chloride; Described catalyzer is selected from N, dinethylformamide; The time of described acylation reaction is 3～20h.
5. the chemical synthesis process of Oleoyl monoethanolamide as claimed in claim 2 is characterized in that in step 2) in, the mol ratio of described acylate and thanomin is 1: 1～4.
6. the chemical synthesis process of Oleoyl monoethanolamide as claimed in claim 2 is characterized in that in step 2) in, adding acid binding agent during described aminolysis reaction, described acid binding agent is selected from triethylamine class aliphatic amide, N, a kind of in accelerine, the pyridine.
7. the chemical synthesis process of Oleoyl monoethanolamide as claimed in claim 2 is characterized in that in step 2) in, the temperature of described aminolysis reaction is-20～20 ℃, the time of aminolysis reaction is 3～20h.
8. the chemical synthesis process of Oleoyl monoethanolamide as claimed in claim 2 is characterized in that in step 2) in, described organic bases is selected from triethylamine class aliphatic amide, N, a kind of in accelerine, the pyridine.
9. the chemical synthesis process of Oleoyl monoethanolamide as claimed in claim 2 is characterized in that in step 3), and the used acid of described pickling is mineral acid, and described mineral acid is selected from the hydrochloric acid soln of 1～2M, is washed till pH=1～2 during pickling; The used alkali of described alkali cleaning is mineral alkali, and described mineral alkali is selected from a kind of in saturated sodium carbonate, saturated potassium carbonate, saturated sodium bicarbonate, the saturated potassium hydrogen carbonate solution, is washed till pH=5～7 during alkali cleaning.
10. the chemical synthesis process of Oleoyl monoethanolamide as claimed in claim 2 is characterized in that in step 4), and described low polarity alkane is selected from C
5～C
8Alkane, described low polarity alkane is selected from a kind of in sherwood oil, normal hexane, Skellysolve A, octane, normal heptane, the hexanaphthene.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103521125A (en) * | 2013-10-25 | 2014-01-22 | 陕西科技大学 | Method for preparing oleic acid Gemini surfactant |
| CN103833587A (en) * | 2014-03-26 | 2014-06-04 | 国家海洋局第三海洋研究所 | Method for preparing highly-unsaturated fatty acyl propanolamine through one-pot method |
| CN104758276A (en) * | 2015-03-12 | 2015-07-08 | 厦门大学 | Medicine for treating ischemic cerebral arterial thrombosis |
| CN107805210A (en) * | 2017-11-13 | 2018-03-16 | 盐城师范学院 | A kind of chemical synthesis process of Oleoyl monoethanolamide |
| CN112174848A (en) * | 2020-11-04 | 2021-01-05 | 吉林大学 | Oleoylethanolamide compound with antibacterial activity in parasitic loranthus, preparation method and application thereof |
| CN115477931A (en) * | 2022-09-19 | 2022-12-16 | 西南石油大学 | Extreme pressure lubricant for shale gas horizontal well and preparation method and application thereof |
-
2011
- 2011-07-12 CN CN2011101957577A patent/CN102295573A/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| 孙翠玲等: "油酰乙醇胺类似物的合成", 《厦门大学学报(自然科学版)》 * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103521125A (en) * | 2013-10-25 | 2014-01-22 | 陕西科技大学 | Method for preparing oleic acid Gemini surfactant |
| CN103521125B (en) * | 2013-10-25 | 2015-04-22 | 陕西科技大学 | Method for preparing oleic acid Gemini surfactant |
| CN103833587A (en) * | 2014-03-26 | 2014-06-04 | 国家海洋局第三海洋研究所 | Method for preparing highly-unsaturated fatty acyl propanolamine through one-pot method |
| CN103833587B (en) * | 2014-03-26 | 2016-04-13 | 国家海洋局第三海洋研究所 | One kettle way prepares the method for high unsaturated fatty acyl Propanolamine |
| CN104758276A (en) * | 2015-03-12 | 2015-07-08 | 厦门大学 | Medicine for treating ischemic cerebral arterial thrombosis |
| CN107805210A (en) * | 2017-11-13 | 2018-03-16 | 盐城师范学院 | A kind of chemical synthesis process of Oleoyl monoethanolamide |
| CN112174848A (en) * | 2020-11-04 | 2021-01-05 | 吉林大学 | Oleoylethanolamide compound with antibacterial activity in parasitic loranthus, preparation method and application thereof |
| CN112174848B (en) * | 2020-11-04 | 2021-11-12 | 吉林大学 | Oleoylethanolamide compound with antibacterial activity in parasitic loranthus, preparation method and application thereof |
| CN115477931A (en) * | 2022-09-19 | 2022-12-16 | 西南石油大学 | Extreme pressure lubricant for shale gas horizontal well and preparation method and application thereof |
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Application publication date: 20111228 |