CN102584771A - Aminomethylation method for tocopherol concentrated solution - Google Patents
Aminomethylation method for tocopherol concentrated solution Download PDFInfo
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- CN102584771A CN102584771A CN2012100007957A CN201210000795A CN102584771A CN 102584771 A CN102584771 A CN 102584771A CN 2012100007957 A CN2012100007957 A CN 2012100007957A CN 201210000795 A CN201210000795 A CN 201210000795A CN 102584771 A CN102584771 A CN 102584771A
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Abstract
The invention discloses an aminomethylation method for a tocopherol concentrated solution, which belongs to the field of fine organic synthesis. The tocopherol concentrated solution is a product prepared by distilling and purifying a plant oil deodorized distillate, and contains high-content mixed tocopherols (alpha, beta, gamma and delta-tocopherols). The beta, gamma and the delta-tocopherols are called non-alpha-tocopherol. A Mannic reaction is a condensation process of three components, i.e., a Mannich alkali serving as a product is prepared by condensing amine, aldehyde and non-alpha-tocopherol containing active hydrogen. In the invention, a high-yield Mannich alkali, i.e., non-alpha-tocopherol is generated by adopting a 'one-pot method', adding an amine reagent, an aldehyde reagent and the tocopherol concentrated solution into a reaction system and undergoing an aminomethylation reaction in the presence of an organic solvent. Due to the adoption of the method, the convention rate of the non-alpha-tocopherol can be over 99 percent in the absence of a catalyst, and the yield of the non-alpha-tocopherol generated in the reaction is over 98 percent.
Description
Technical field
The aminomethyl method of a kind of Viteolin liquid concentrator of the present invention, this preparation method reach the purpose that improves target product yield, belong to the Minute Organic Synthesis field.
Background technology
Vitamin E has another name called Viteolin, and two kinds of synthetic and natural article are arranged.Natural VE is the mixtinite of four kinds of Viteolins and four kinds of Viteolin trienols, has opticity; Synthetic typically refers to the DL-alpha-tocopherol, is the racemic modification that is made up of various optical isomers.Because no matter natural VE all is superior to synthetic in biological activity and security, therefore in medicine, food, makeup and fodder additives, people trend towards using natural VE.Therefore present invention focuses on to study the development and use of natural VE.The Viteolin liquid concentrator is the plant oil deodorizing distillate product that purifying obtains after esterification and many-level molecule rectifying, contains other impurity such as mixed tocopherol and 50% glyceryl ester about 50%, sterol ester.Wherein mixed tocopherol comprises alpha-tocopherol, 5,8-dimethyl tocol, Gamma-Tocopherol and Delta-Tocopherol, and back three is called non-alpha-tocopherol.Because non-alpha-tocopherol has lower biological activity (each homologue biological activity of vitamin E is seen table 1); Therefore research emphasis of the present invention is the non-alpha-tocopherol alkali midbody that non-alpha-tocopherol is generated high yield through Mannich reaction; Thereby, finally obtain the alpha-tocopherol of high yield for next step non-alpha-tocopherol alkali midbody hydrogenating reduction is that highly active alpha-tocopherol is created good condition.
Each homologue biological activity of table 1 vitamin E
| Title | Biological activity (IU/mg) |
| The D-alpha-tocopherol | 1.49 |
| The D-5,8-dimethyl tocol | 0.75 |
| The D-Gamma-Tocopherol | 0.15 |
| The D-Delta-Tocopherol | 0.05 |
| DL-α-Vitamin E-acetate | 1 |
| The DL-alpha-tocopherol | 1.1 |
Annotate: the definition of biological activity iu (IU): the biological activity of 1mg synthesising complex E acetic ester (DL-α-Vitamin E-acetate) is an iu (IU).
At present, it is the production technology employing two-step approach of alpha-tocopherol that the non-alpha-tocopherol in the mixed tocopherol is made the transition: chloromethylation-reduction method, formylation-reduction method, methylolation-reduction method, amine-methylated-reduction method etc., and its main relative merits are as shown in table 2:
The relative merits of several kinds of different transformation process of the non-alpha-tocopherol of table 2
To sum up consider, be fit to adopt amine-methylated-reduction method, can play the purpose that Viteolin is purified, structure makes the transition simultaneously for the low Viteolin liquid concentrator of content.But, therefore be to hinder the bottleneck of producing progress at present because this complex technical process, yield are lower.
Summary of the invention
Technical problem to be solved by this invention is: seek a kind of reaction system of Mannich efficiently, easy realization of industrial production and non-alpha-tocopherol transformation efficiency and all higher preparation method of non-alpha-tocopherol alkali yield.
Technical scheme of the present invention: a kind of amine-methylated method of Viteolin liquid concentrator, its method steps and processing condition are:
(1) Mannich reaction of Viteolin liquid concentrator: (mol ratio of pure amount) ︰ amine Shi Ji ︰ aldehyde reagent=1:2 ~ 4:2 ~ 4 drops into reaction kettle, adds total volume of material 0.5-2.0 organic solvent doubly then according to the Viteolin liquid concentrator; Be warming up to 60-90 ℃ under the normal pressure, stirring and refluxing reaction 2.5-4.5h in the reaction kettle;
With the 5,8-dimethyl tocol is example, and its chemical equation is:
(2) layering, precipitation: feed liquid standing demix behind the Mannich reaction, upper strata are organic phase, and lower floor is a water, and excessive amine reagent and aldehyde reagent are soluble in water, therefore divide to fall with water layer; Change the organic phase that obtains over to the precipitation still, be warming up to 80-150 ℃, decompression steams solvent, gets the Mannich alkali of the high non-alpha-tocopherol of content and the mixture of glyceryl ester behind the precipitation;
With 5,8-dimethyl tocol alkali is example, and structure is following:
Said amine reagent is secondary amine, comprises in dimethylamine agueous solution, diethylamine aqueous solution, diethylolamine, the hexahydropyridine any;
Said aldehyde reagent is any in formalin, acetaldehyde solution, the Paraformaldehyde 96;
Said organic solvent is any in benzene, toluene, hexanaphthene, ETHYLE ACETATE, normal hexane, the sherwood oil.
Beneficial effect of the present invention: compared with prior art, its technique effect and advantage are:
1, choose suitable organic solvent and participate in the Mannich reaction system, impel whole reaction system in organic solvent, to carry out, and selected solvent boiling point is low is easy to remove, can not cause non-alpha-tocopherol Yin Gaowen and lose.
2, the non-alpha-tocopherol transformation efficiencys such as 5,8-dimethyl tocol, Gamma-Tocopherol and Delta-Tocopherol in the Viteolin liquid concentrator are up to more than 99%; The Mannich alkali yield of the non-alpha-tocopherol that reaction generates is up to more than 98%; Its Mannich reaction reaction temperature in the presence of organic solvent is stable with, product.
3, this Technology does not receive what influence of mixed tocopherol content in the Viteolin liquid concentrator; Do not receive what the influence of foreign matter contents such as other glyceryl ester, sterol ester; Do not receive what the influence of non-alpha-tocopherol content proportions such as 5,8-dimethyl tocol, Gamma-Tocopherol and Delta-Tocopherol, therefore for structure transition of industriallization alpha-tocopherol with stable production technology is provided.
Description of drawings
The performance liquid chromatography spectrogram of Fig. 1 Viteolin liquid concentrator, t=11.683min: Delta-Tocopherol; T=13.855min: beta, gamma-Viteolin; T=16.217min: alpha-tocopherol.
The performance liquid chromatography spectrogram of Fig. 2 embodiment 1 amine-methylated product, t=16.221min: alpha-tocopherol; T=17.586min: Delta-Tocopherol alkali; T=25.108min: beta, gamma-Viteolin alkali.
The performance liquid chromatography spectrogram of Fig. 3 embodiment 2 amine-methylated products, t=16.167min: alpha-tocopherol; T=17.626min: Delta-Tocopherol alkali; T=25.323min: beta, gamma-Viteolin alkali.
The performance liquid chromatography spectrogram of Fig. 4 embodiment 3 amine-methylated products, t=16.213min: alpha-tocopherol; T=19.655min: Delta-Tocopherol alkali; T=28.323min: beta, gamma-Viteolin alkali.
Embodiment
The present invention will obtain explanation through the following example.
Embodiment 1
All appts equipment all is laboratory scale, mixed tocopherol content 36.30% in the raw material Viteolin liquid concentrator, and wherein alpha-tocopherol accounts for 8.09%, and beta, gamma-Viteolin accounts for 63.03%, and Delta-Tocopherol accounts for 28.88%.
Get 75g Viteolin liquid concentrator (the about 0.06mol of non-alpha-tocopherol) in reactor drum; Add 21.6g (about 0.19mol) dimethylamine agueous solution (40%), then add the 106mL toluene solvant, open stirring behind the nitrogen purging three times; Temperature control is below 35 ℃; In the 20min 16.5g (about 0.20mol) formalin (37%) is slowly dripped the adding reactor drum, be warming up to 90 ℃ then, stopped reaction behind the condensing reflux reaction 2.5h; Feed liquid moves into skimmer, the impurity of lower floor's water and interlayer is drained after leaving standstill 0.5h, changes mother liquor over to the precipitation device; Be warming up to 120 ℃ at last toluene is steamed, stopped reaction when waiting not have distillate, the cooling sampling is weighed, and product is the mixture of impurity such as non-alpha-tocopherol alkali and glyceryl ester.
Getting 2-3 drips behind the precipitation weighing products and is mixed with the 25mL diluting soln with ethanol; Pass through hplc rp-hplc; With methyl alcohol: triethylamine=99:1 is moving phase, records 292nm place spectrogram, and the RPLC spectrogram of Viteolin liquid concentrator is as shown in Figure 1.The amine-methylated product of this example is as shown in Figure 2.
Material is formed before and after table 1 reaction
Embodiment 2
Get 75g Viteolin liquid concentrator (the about 0.06mol of non-alpha-tocopherol) in reactor drum; Add 21.6g (about 0.19mol) dimethylamine agueous solution (40%), then add the 106ml cyclohexane solvent, open stirring behind the nitrogen purging three times; Temperature control is below 35 ℃; In the 20min 16.5g (about 0.20mol) formalin (37%) is slowly dripped the adding reactor drum, be warming up to 80 ℃ then, stopped reaction behind the condensing reflux reaction 2.5h; Feed liquid moves into skimmer, the impurity of lower floor's water and interlayer is drained after leaving standstill 0.5h, changes mother liquor over to the precipitation device; Be warming up to 90 ℃ at last hexanaphthene is steamed, stopped reaction when waiting not have distillate, the cooling sampling is weighed, and product is the mixture of impurity such as non-alpha-tocopherol alkali and glyceryl ester.
Getting 2-3 and drip behind the precipitation weighing products and be mixed with the 25mL diluting soln with ethanol, through hplc rp-hplc, is moving phase with methyl alcohol: triethylamine=99:1, records 292nm place spectrogram, and the amine-methylated product of this example is as shown in Figure 3.
Material is formed before and after table 2 reaction
Embodiment 3
Get 75g Viteolin liquid concentrator (the about 0.06mol of non-alpha-tocopherol) in reactor drum; Add 36.5g (about 0.20mol) diethylamine aqueous solution (40%), then add the 110ml cyclohexane solvent, open stirring behind the nitrogen purging three times; Temperature control is below 35 ℃; In the 20min 16.5g (about 0.20mol) formalin (37%) is slowly dripped the adding reactor drum, be warming up to 85 ℃ then, stopped reaction behind the condensing reflux reaction 4.5h; Feed liquid moves into skimmer, the impurity of lower floor's water and interlayer is drained after leaving standstill 0.5h, changes mother liquor over to the precipitation device; Be warming up to 90 ℃ at last hexanaphthene is steamed, stopped reaction when waiting not have distillate, the cooling sampling is weighed, and product is the mixture of impurity such as non-alpha-tocopherol alkali and glyceryl ester.
Getting 2-3 and drip behind the precipitation weighing products and be mixed with the 25mL diluting soln with ethanol, through hplc rp-hplc, is moving phase with methyl alcohol: triethylamine=99:1, records 292nm place spectrogram, and the amine-methylated product of this example is as shown in Figure 4.
Material is formed before and after table 3 reaction
Claims (1)
1. the amine-methylated method of a Viteolin liquid concentrator is characterized in that step and processing condition are:
(1) Mannich reaction of Viteolin liquid concentrator: drop into reaction kettle according to the dense mol ratio that contracts liquid ︰ amine examination agent ︰ aldehyde reagent=1:2 ~ 4:2 ~ 4 of the scalar Viteolin of folding, add total volume of material 0.5-2.0 organic solvent doubly then; Be warming up to 60-90 ℃ under the normal pressure, stirring and refluxing reaction 2.5-4.5h in the reaction kettle;
(2) layering, precipitation: feed liquid standing demix behind the Mannich reaction, upper strata are organic phase, and lower floor is a water, and excessive amine reagent and aldehyde reagent are soluble in water, therefore divide to fall with water layer; Change the organic phase that obtains over to the precipitation still, be warming up to 80-150 ℃, decompression steams solvent, gets the Mannich alkali of the high non-alpha-tocopherol of content and the mixture of glyceryl ester behind the precipitation;
Said amine reagent is secondary amine, comprises in dimethylamine agueous solution, diethylamine aqueous solution, diethylolamine, the hexahydropyridine any;
Said aldehyde reagent is any in formalin, acetaldehyde solution, the Paraformaldehyde 96;
Said organic solvent is any in benzene, toluene, hexanaphthene, ETHYLE ACETATE, normal hexane, the sherwood oil.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5932748A (en) * | 1997-06-06 | 1999-08-03 | Roche Vitamins Inc. | Process for permethylating non-α-tocopherols to produce α-tocopherol |
| CN1401645A (en) * | 2002-09-19 | 2003-03-12 | 浙江大学 | Process for preparing high-purity alpha type natural vitamin E from high content mixed tocopherol |
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- 2012-01-04 CN CN2012100007957A patent/CN102584771A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5932748A (en) * | 1997-06-06 | 1999-08-03 | Roche Vitamins Inc. | Process for permethylating non-α-tocopherols to produce α-tocopherol |
| CN1401645A (en) * | 2002-09-19 | 2003-03-12 | 浙江大学 | Process for preparing high-purity alpha type natural vitamin E from high content mixed tocopherol |
Non-Patent Citations (2)
| Title |
|---|
| 《中国优秀硕士学位论文全文数据库工程科技Ⅰ辑》 20080411 吴春燕 "alpha-生育酚和alpha-生育酚醋酸酯的制备" B016-131 1 , 第04期 * |
| 吴春燕: ""α-生育酚和α-生育酚醋酸酯的制备"", 《中国优秀硕士学位论文全文数据库工程科技Ⅰ辑》 * |
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Application publication date: 20120718 |