CN103483212B - Synthesis method for O-tert-Butyl-L-threonine tert-butyl ester acetate salt - Google Patents
Synthesis method for O-tert-Butyl-L-threonine tert-butyl ester acetate salt Download PDFInfo
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- 238000001308 synthesis method Methods 0.000 title abstract 4
- -1 O-tert-Butyl-L-threonine tert-butyl ester acetate salt Chemical class 0.000 title abstract 3
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims abstract description 59
- 238000006243 chemical reaction Methods 0.000 claims abstract description 53
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 46
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical compound CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 claims abstract description 42
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims abstract description 31
- 239000004473 Threonine Substances 0.000 claims abstract description 29
- 229960002898 threonine Drugs 0.000 claims abstract description 29
- 239000007787 solid Substances 0.000 claims abstract description 27
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims abstract description 25
- 229960000583 acetic acid Drugs 0.000 claims abstract description 23
- 239000012362 glacial acetic acid Substances 0.000 claims abstract description 23
- 239000003054 catalyst Substances 0.000 claims abstract description 21
- 239000002994 raw material Substances 0.000 claims abstract description 16
- 239000000047 product Substances 0.000 claims abstract description 15
- 238000001816 cooling Methods 0.000 claims abstract description 9
- 238000002425 crystallisation Methods 0.000 claims abstract description 9
- 239000012071 phase Substances 0.000 claims abstract description 8
- 238000007670 refining Methods 0.000 claims abstract description 7
- 239000007791 liquid phase Substances 0.000 claims abstract description 6
- 239000012265 solid product Substances 0.000 claims abstract description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 27
- 239000012043 crude product Substances 0.000 claims description 22
- 238000004821 distillation Methods 0.000 claims description 22
- 238000010189 synthetic method Methods 0.000 claims description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 14
- 238000009423 ventilation Methods 0.000 claims description 14
- 238000001914 filtration Methods 0.000 claims description 12
- 238000002156 mixing Methods 0.000 claims description 10
- 239000000243 solution Substances 0.000 claims description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- 238000003786 synthesis reaction Methods 0.000 claims description 8
- 239000008367 deionised water Substances 0.000 claims description 7
- 229910021641 deionized water Inorganic materials 0.000 claims description 7
- 238000000605 extraction Methods 0.000 claims description 7
- 239000011259 mixed solution Substances 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 7
- 229910010413 TiO 2 Inorganic materials 0.000 claims description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 230000008929 regeneration Effects 0.000 claims description 6
- 238000011069 regeneration method Methods 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 4
- 239000011973 solid acid Substances 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 3
- 238000009835 boiling Methods 0.000 claims description 3
- 229910052761 rare earth metal Inorganic materials 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- 238000001291 vacuum drying Methods 0.000 claims description 3
- LJOODBDWMQKMFB-UHFFFAOYSA-N cyclohexyl-acetic acid Natural products OC(=O)CC1CCCCC1 LJOODBDWMQKMFB-UHFFFAOYSA-N 0.000 claims description 2
- 239000012153 distilled water Substances 0.000 claims description 2
- 230000003068 static effect Effects 0.000 claims description 2
- 239000000203 mixture Substances 0.000 abstract description 7
- 238000007086 side reaction Methods 0.000 abstract description 6
- 230000008901 benefit Effects 0.000 abstract description 4
- 239000003930 superacid Substances 0.000 abstract description 4
- 238000005292 vacuum distillation Methods 0.000 abstract description 4
- 238000005265 energy consumption Methods 0.000 abstract description 3
- 239000002131 composite material Substances 0.000 abstract description 2
- 230000008025 crystallization Effects 0.000 abstract 1
- 230000003247 decreasing effect Effects 0.000 abstract 1
- 239000002904 solvent Substances 0.000 abstract 1
- 238000000034 method Methods 0.000 description 16
- 239000007788 liquid Substances 0.000 description 12
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- 239000000284 extract Substances 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 239000003513 alkali Substances 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
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- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000005530 etching Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 229910044991 metal oxide Inorganic materials 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000011949 solid catalyst Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- BFKJFAAPBSQJPD-UHFFFAOYSA-N tetrafluoroethene Chemical group FC(F)=C(F)F BFKJFAAPBSQJPD-UHFFFAOYSA-N 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses a synthesis method for O-tert-Butyl-L-threonine tert-butyl ester acetate salt. The synthesis method is characterized by taking 1,4-dioxane, L-threonine and isobutene as raw materials, and taking a series solid superacid composite system based on SO4<2-> as a catalyst, as well as being performed in a room-temperature phase. The synthesis method has the advantages of being moderate in reaction conditions, easy to control, few in side reactions, high in product purity; refining for the product is performed by normal-pressure and reduced-pressure vacuum distillation, thus simplifying operation and greatly decreasing energy consumption. The solid product can be obtained by directly using liquid-phase O-tert-Butyl-L-threonine tert-butyl ester acetate salt as the raw material, further dripping the mixture of glacial acetic acid and cyclohexane, and performing cooling crystallization. The operation is simple, convenient and efficient, and the use of an organic volatile solvent is avoided.
Description
Technical field
The invention belongs to technical field of organic chemistry, relate to based on solid super-strong acid series composite solid alkali systems for catalyzer, 1.4 dioxane, L-threonine, iso-butylene is starting raw material, adopt room temperature reaction, the solid phase O-tertiary butyl-L-Thr tert-butyl ester acetate is prepared in air distillation and azeotropic underpressure distillation.
Background technology
The O-tertiary butyl-L-Thr tert-butyl ester acetate is as the intermediate of important bio-pharmaceuticals.
The synthetic method of the O-tertiary butyl-L-Thr tert-butyl ester can be divided into single stage method and the large class of two step method two according to the difference of reaction raw materials:
Wherein single stage method is with the vitriol oil, 1.4 dioxane, L-threonine, and iso-butylene is starting raw material is raw material, the single step reaction synthesis O-tertiary butyl-L-Thr tert-butyl ester, and reaction formula is as follows:
Two step method is then with the trimethyl carbinol, and oxalic acid is starting raw material, is first obtained by reacting isobutene liquid, and isobutene liquid is obtained by reacting the O-tertiary butyl-L-Thr tert-butyl ester again with L-threonine, its reaction formula is as follows:
The method of single step reaction is with the vitriol oil, 1.4 dioxane, L-threonine, and iso-butylene is starting raw material is raw material, the single step reaction synthesis O-tertiary butyl-L-Thr tert-butyl ester; Two step reactions are first with the trimethyl carbinol, oxalic acid is starting raw material, first be obtained by reacting isobutene liquid, liquid iso-butylene is obtained by reacting the O-tertiary butyl-L-Thr tert-butyl ester again with L-threonine, due to after the isobutene liquid reaction that first generates in two steps reactions, L-threonine reaction generates crude product, therefore the by product existed in reaction is more, and reactions steps is loaded down with trivial details, strict to technologic requirement, therefore, single stage method is the current synthetic method generally adopted.From the method preparation adopting two step method reaction, the by product of reaction is many, poor stability.In single stage method, iso-butylene is constantly passed into the bottom of reaction solution, special reactor is utilized to react, this method is easy and simple to handle, be easy to control, by product is few, but iso-butylene boiling point low (-6 DEG C), requires at airtight pressure vessel: as the tetrafluoroethylene reactor of special function.One step forwarding method have reaction conditions gentleness, easy to operate, be easy to industrialized advantage.
In single stage method, the building-up reactions mechanism of the O-tertiary butyl-L-Thr tert-butyl ester is that hydroxyl in L-threonine 3 is replaced by the tertiary butyl and generates the O-tertiary butyl-L-threonine, then continues reaction and generates the O-tertiary butyl-L-Thr tert-butyl ester; Reaction process is as follows:
Simultaneous reactions is attended by following side reaction in addition and occurs:
1) product 1.4 dioxane and the vitriol oil mixing environment under, portion of product rests on the O-tertiary butyl-L-threonine;
2) the amino acid tert-butyl ester is easily decomposed by acid under certain environment,
In reaction process, the environment controlling reaction system is in suitable scope, and for reducing, side reaction occurs, raising product purity is most important.In addition, this reaction is thermopositive reaction, and the selection of temperature of reaction is most important to reducing side reaction with control.Solid super-strong acid is that super acids refers to the acid that strength of acid is also eager to excel than 100% sulfuric acid, its Hammett functional value
<-11.9 be ((100% sulfuric acid
value is-11.9).It mainly contains following three types: 1) liquid superacid, and liquid superacid exists catalyzer and product separation difficulty, to water and poor heat stability, etching apparatus, contaminate environment and regenerate the shortcomings such as difficult; 2) solid super-strong acid, it mainly comprises the oxide compound or mixed oxide etc. of non-transition element, and catalyzer is widely used in the catalyzed reaction of ionic mechanism, and kind is a lot; 3) carried oxide solid super-strong acid, SO
4 2/ MX OY type solid super-strong acid is a kind of solid acid of classics, and it is with some metal oxide (M
xo
y) be carrier, with SO
4 2for the solid catalyst of loaded article.Only need heat and just the removing of the water of surface adsorption can be got final product activity recovery.The SO of its surface adsorption
4 2-be combined very stable with carrier surface, even if washing also not easily removes.Can at high temperature use, its corrodibility is very little, the advantage that its tool strength of acid is adjustable, easy to prepare.
For the feature of this reaction system, development as catalyst system based on solid super-strong acid, not only effectively can promote steadily carrying out smoothly of reaction, reduce the generation of side reaction, and catalyzer itself also have inexpensive, be easy to get, be convenient to reclaim and the advantage that recycles.
Summary of the invention
The object of the invention is to based on solid super-strong acid as catalyst system, effectively promote steadily carrying out smoothly of reaction, reduce the generation of side reaction; Thus the synthetic method of a kind of O-tertiary butyl-L-Thr tert-butyl ester acetate is provided.
Technical scheme of the present invention:
A synthetic method for the O-tertiary butyl-L-Thr tert-butyl ester acetate, it with 1.4 dioxane, L-threonine and iso-butylene for raw material, based on SO
4 2serial solid super-strong acid compound system be catalyzer, carry out the synthetic method of the O-tertiary butyl-L-Thr tert-butyl ester acetate in the room temperature stage.
Follow these steps to carry out:
A, reaction mass 1.4 dioxane added in reactor after abundant stirring and dissolving, add catalyzer, wherein, catalyzer: the mass ratio=10-35:100 of 1.4 dioxane, then add L-threonine, wherein 1.4 dioxane: the mass ratio=10-25:1 of L-threonine;
Preferred: catalyst charge is catalyzer: the mass ratio=20-35:100 of 1.4 dioxane.
Described catalyzer is: CrSO
4/ ZrO
2series (pH value 8-9 of its aqueous solution of 10%), and SO
4 2/ MOO
3-TiO
2type; SO
4 2/ TiO
2/ La
3rare earth solid acid; SO
4 2/ ZrO
2one in/MCM-41 tetra-species complex system.
B, temperature of reaction kettle remain on 10 ~ 25 DEG C to start to pass into iso-butylene, wherein iso-butylene: the mass ratio=4-10:1 of L-threonine, temperature of reaction is kept to be 5-13 10 DEG C of-25 DEG C of pH value to system, after system becomes homogeneous phase, reactor is remained on room temperature, continue the pH value 7-9 of reaction to system, reaction terminates;
Preferred: 1.4 dioxane: L-threonine: iso-butylene mass ratio=10-20:1:4-7.
After c, reaction terminate, filtering separation obtains liquid phase crude product and catalyzer, and crude product proceeds to lower one-step refining, and catalyzer can be recycled 5-10 times, and 2-5 catalyzer are without the need to processing direct reuse, and when using for 6-10 times, catalyzer will carry out manipulation of regeneration.
Described synthetic method divides three steps to carry out, and first, reacts 3-7 hours being less than at 25 DEG C at 1.4 dioxane and L-threonine; Secondly, after the reaction of system terminates, under pressure is 0.05MPa, temperature passes into iso-butylene at 17 ~ 25 DEG C, ventilation continuously in first 12 hours, latter 48 hours, is interrupted ventilation, reacts within 60 hours and terminates, finally, after system is static, pH value is down to 7-8, and Filtration of catalyst obtains crude product.
The process for purification of d, described crude product is: extracted by crude product, crude product divides 3 times and adds, carry out water rinses, crude product in water washing process each time: mass ratio=1:5-10 of water, then utilize hexanaphthene to extract, then carry out air distillation and underpressure distillation two portions, air distillation temperature is at 80-100 DEG C, vacuum distillation temperature, at 45-85 DEG C, makes system remain system boiling state in vacuum distillation process.
First hexanaphthene and distilled water is utilized by thick product to carry out respectively centrifugal, after extraction, carry out atmospheric distillation and underpressure distillation two portions, underpressure distillation is that vacuum tightness is-0.075 to-0.09MPa, distillation temperature 45-80 DEG C, the obtained O-tertiary butyl-L-Thr tert-butyl ester after underpressure distillation.
The solid preparation method of e, the described O-tertiary butyl-L-Thr tert-butyl ester acetate: directly with the liquid phase O-tertiary butyl-L-Thr tert-butyl ester after refining for raw material, add and dripped by hexanaphthene and Glacial acetic acid mixing solutions, wherein mass ratio=1-the 5:1 of mixing solutions cyclohexane and Glacial acetic acid, the O-tertiary butyl-L-Thr tert-butyl ester: the mass ratio=5-10:1 of hexanaphthene and Glacial acetic acid mixed solution, crystallisation by cooling obtain water content mass percent lower than 5% solid product.
The regeneration of f, described catalyzer: catalyzer is washed successively, each deionized water consumption is catalyzer 2-8 times of volumes, after washing 1-5 times, use chloroform again, each chloroform: catalyst quality, than=2-4:1, washs 1-5 times, finally vacuum-drying 8-18 hours at 90-120 DEG C.
The present invention is based on SO
4 2serial solid super-strong acid compound system be catalyzer, reaction carries out the synthetic method of the O-tertiary butyl-L-Thr tert-butyl ester acetate in the room temperature stage respectively, and in synthetic method, the pH value of reaction system is easy to regulation and control, reaction conditions is gentle.Have employed underpressure distillation to crude product is refining, not only shorten the operating time, also facilitate actual behaviour's body.This synthetic method is had, and the reaction times is short, selectivity is high, productive rate is high, product purity is high, energy consumption is low, catalyzer can be recycled, without the need to using the feature of volatile organic solvent.
To refining employing normal pressure and the reduced vacuum distillation of product, not only simplify operation, also greatly reduce energy consumption.Can directly with the liquid phase O-tertiary butyl-L-threonine tert-butyl ester raw material, the mixture dripping glacial acetic acid and hexanaphthene through a step, the solid product obtained after crystallisation by cooling, simple to operation, convenient, efficient, and avoid use volatile organic solvent.
Embodiment
Below in conjunction with embodiment, the present invention is described in further detail; it is important to point out; following embodiment is only for the present invention is described further; limiting the scope of the invention can not be interpreted as; affiliated art skilled staff is according to foregoing invention content; some nonessential improvement are made to the present invention and adjustment is specifically implemented, still should belong to protection scope of the present invention.
embodiment 1
The solid O-tertiary butyl-L-Thr tert-butyl ester acetate synthesis:
In reaction flask, add 1.4 dioxane 1kg successively, add acidity of catalyst SO
4 20.29kg, constantly adds L-threonine 0.07kg, opens stirring after L-threonine dissolves completely, keeps the pH value of system 8.Maintain the temperature at 15 DEG C to start to pass into isobutene gas, ventilation continuously in first 12 hours, latter 48 hours, being interrupted ventilation (maintaining the temperature at 10 DEG C-25 DEG C) system becomes homogeneous phase and terminates, and the usage quantity of iso-butylene is 0.42kg.Filtration of catalyst obtains crude product, crude product adds hexanaphthene and extracts, then add deionized water (divide and add for the 4 times) extraction of 4 times of volumes, normal pressure and the underpressure distillation of carrying out thick product obtain the O-tertiary butyl-L-Thr tert-butyl ester liquid, then drip mixture (the wherein mixing solutions cyclohexane: the mass ratio=2.1:1 of Glacial acetic acid of glacial acetic acid and hexanaphthene; The O-tertiary butyl-L-Thr tert-butyl ester: the mass ratio=5.35:1 of hexanaphthene and Glacial acetic acid mixed solution), crystallisation by cooling obtains the solid O-tertiary butyl-L-Thr tert-butyl ester acetate 37.5g, purity 95.5.
embodiment 2
The solid O-tertiary butyl-L-Thr tert-butyl ester acetate synthesis:
In reaction flask, add 1.4 dioxane 1kg successively, add acidity of catalyst SO
4 2/ TiO
2/ La
3rare earth solid acid 0.28kg, constantly adds L-threonine 0.09kg, opens stirring after L-threonine dissolves completely, keeps the pH value of system 8.Maintain the temperature at 15 DEG C to start to pass into isobutene gas, ventilation continuously in first 12 hours, latter 48 hours, being interrupted ventilation (maintaining the temperature at 10 DEG C-25 DEG C) system becomes homogeneous phase and terminates, and the usage quantity of iso-butylene is 0.45kg.Filtration of catalyst obtains crude product, crude product adds hexanaphthene and extracts, then add deionized water (divide and add for the 6 times) extraction of 6 times of volumes, normal pressure and the underpressure distillation of carrying out thick product obtain the O-tertiary butyl-L-Thr tert-butyl ester liquid, then drip mixture (the wherein mixing solutions cyclohexane: the mass ratio=2.1:1 of Glacial acetic acid of glacial acetic acid and hexanaphthene; The O-tertiary butyl-L-Thr tert-butyl ester: the mass ratio=5.35:1 of hexanaphthene and Glacial acetic acid mixed solution), crystallisation by cooling obtains the solid O-tertiary butyl-L-Thr tert-butyl ester acetate 40.10g, purity 96.5.
embodiment 3
The solid O-tertiary butyl-L-Thr tert-butyl ester acetate synthesis:
In reaction flask, add 1.4 dioxane 1kg successively, add acidity of catalyst CrSO
4/ ZrO
2series 0.26kg, constantly adds L-threonine 0.09kg, opens stirring after L-threonine dissolves completely, keeps the pH value of system 8.Maintain the temperature at 15 DEG C to start to pass into isobutene gas, ventilation continuously in first 12 hours, latter 48 hours, being interrupted ventilation (maintaining the temperature at 10 DEG C-25 DEG C) system becomes homogeneous phase and terminates, and the usage quantity of iso-butylene is 0.45kg.Filtration of catalyst obtains crude product, crude product adds hexanaphthene and extracts, then add deionized water (divide and add for the 6 times) extraction of 6 times of volumes, normal pressure and the underpressure distillation of carrying out thick product obtain the O-tertiary butyl-L-Thr tert-butyl ester liquid, drip mixture (the wherein mixing solutions cyclohexane: the mass ratio=2.1:1 of Glacial acetic acid of glacial acetic acid and hexanaphthene again, the O-tertiary butyl-L-Thr tert-butyl ester: the mass ratio=5.35:1 of hexanaphthene and Glacial acetic acid mixed solution), crystallisation by cooling obtains the solid O-tertiary butyl-L-Thr tert-butyl ester acetate 41.5g, purity 97.8.
embodiment 4
The solid O-tertiary butyl-L-Thr tert-butyl ester acetate synthesis:
In reaction flask, add 1.4 dioxane 1kg successively, add acidity of catalyst SO
4 2/ MOO
3-TiO
2type 0.26kg, constantly adds L-threonine 0.09kg, opens stirring after L-threonine dissolves completely, keeps the pH value of system 8.Maintain the temperature at 15 DEG C to start to pass into isobutene gas, ventilation continuously in first 12 hours, latter 48 hours, being interrupted ventilation (maintaining the temperature at 10 DEG C-25 DEG C) system becomes homogeneous phase and terminates, and the usage quantity of iso-butylene is 0.45kg.Filtration of catalyst obtains crude product, crude product adds hexanaphthene and extracts, then add deionized water (divide and add for the 6 times) extraction of 6 times of volumes, normal pressure and the underpressure distillation of carrying out thick product obtain the O-tertiary butyl-L-Thr tert-butyl ester liquid, drip mixture (the wherein mixing solutions cyclohexane: the mass ratio=2.1:1 of Glacial acetic acid of glacial acetic acid and hexanaphthene again, the O-tertiary butyl-L-Thr tert-butyl ester: the mass ratio=5.35:1 of hexanaphthene and Glacial acetic acid mixed solution), crystallisation by cooling obtains the solid O-tertiary butyl-L-Thr tert-butyl ester acetate 41.8g, purity 97.6.
embodiment 5
The solid O-tertiary butyl-L-Thr tert-butyl ester acetate synthesis:
In reaction flask, add 1.4 dioxane 1kg successively, add acidity of catalyst SO
4 2/ ZrO
2/ MCM-41 type 0.26kg, constantly adds L-threonine 0.09kg, opens stirring after L-threonine dissolves completely, keeps the pH value of system 8.Maintain the temperature at 15 DEG C to start to pass into isobutene gas, ventilation continuously in first 12 hours, latter 48 hours, being interrupted ventilation (maintaining the temperature at 10 DEG C-25 DEG C) system becomes homogeneous phase and terminates, and the usage quantity of iso-butylene is 0.45kg.Filtration of catalyst obtains crude product, crude product adds hexanaphthene and extracts, then add deionized water (divide and add for the 6 times) extraction of 6 times of volumes, normal pressure and the underpressure distillation of carrying out thick product obtain the O-tertiary butyl-L-Thr tert-butyl ester liquid, then drip mixture (the wherein mixing solutions cyclohexane: the mass ratio=2.1:1 of Glacial acetic acid of glacial acetic acid and hexanaphthene; The O-tertiary butyl-L-Thr tert-butyl ester: the mass ratio=5.35:1 of hexanaphthene and Glacial acetic acid mixed solution), crystallisation by cooling obtains the solid O-tertiary butyl-L-Thr tert-butyl ester acetate 41.0g, purity 98.0.
embodiment 6
The first time of catalyzer recycles:
The catalyzer that filtration obtains is without the need to further process, and directly use, reaction conditions is with embodiment 1.Obtain solid contents: the solid O-tertiary butyl-L-Thr tert-butyl ester acetate 41.5g, purity 97.3.
embodiment 7
Recycle for the 5th time of catalyzer:
The catalyzer that filtration obtains is without the need to further process, and directly use, reaction conditions is with embodiment 1.Obtain solid contents: the solid O-tertiary butyl-L-Thr tert-butyl ester acetate 37.5g, purity 96.5.
embodiment 8
The regeneration of catalyzer:
Catalyst recirculation uses when the 6th and regenerates, and first joining 35 ml deionized waters, fully washing filtering the catalyzer that obtains, after repeating this operation 1-5 times.Catalyzer is joined in 40 ml anhydrous chloroforms again and fully washs, repeat this operation 1-5 times after, finally catalyzer vacuum-drying at 105 DEG C is completed regeneration in 8-18 hours.
Claims (6)
1. a synthetic method for the O-tertiary butyl-L-Thr tert-butyl ester acetate, it with Isosorbide-5-Nitrae dioxane, L-threonine and iso-butylene for raw material, based on SO
4 2serial solid super-strong acid compound system be catalyzer, carry out the synthetic method of the O-tertiary butyl-L-Thr tert-butyl ester acetate in the room temperature stage, it is characterized in that following these steps to carry out:
A, reaction mass Isosorbide-5-Nitrae dioxane added in reactor after abundant stirring and dissolving, add catalyzer, wherein, catalyzer: the mass ratio=10-35:100 of Isosorbide-5-Nitrae dioxane, then add L-threonine, wherein Isosorbide-5-Nitrae dioxane: the mass ratio=10-25:1 of L-threonine;
B, temperature of reaction kettle remain on 10-25 DEG C to start to pass into iso-butylene, wherein iso-butylene: the mass ratio=4-10:1 of L-threonine, temperature of reaction is kept to be 5-13 10 DEG C-25 DEG C pH value to system, after system becomes homogeneous phase, reactor is remained on room temperature, continue the pH value 7-9 of reaction to system, reaction terminates;
After c, reaction terminate, filtering separation obtains liquid phase crude product and catalyzer, and crude product proceeds to lower one-step refining, and catalyst recirculation uses 5-10 times, and 2-5 catalyzer are without the need to processing direct reuse, and when using for 6-10 times, catalyzer will carry out manipulation of regeneration;
D, first to utilize hexanaphthene and distilled water to carry out respectively thick product centrifugal, after extraction, carry out atmospheric distillation and underpressure distillation two portions, underpressure distillation is that vacuum tightness is-0.075 to-0.09MPa, distillation temperature 45-80 DEG C, system is made to remain boiling state during underpressure distillation, the obtained O-tertiary butyl-L-Thr tert-butyl ester after underpressure distillation;
e,directly with the liquid phase O-tertiary butyl-L-Thr tert-butyl ester after refining for raw material, add and dripped by hexanaphthene and Glacial acetic acid mixing solutions, wherein mass ratio=1-the 5:1 of mixing solutions cyclohexane and Glacial acetic acid, the O-tertiary butyl-L-Thr tert-butyl ester: the mass ratio=5-10:1 of hexanaphthene and Glacial acetic acid mixed solution, crystallisation by cooling obtain water content mass percent lower than 5% solid product.
2. the synthetic method of the O-tertiary butyl according to claim 1-L-Thr tert-butyl ester acetate, is characterized in that described catalyzer is: CrSO
4/ ZrO
2series, and SO
4 2/ MoO
3-TiO
2type; SO
4 2/ TiO
2/ La
3rare earth solid acid; SO
4 2/ ZrO
2one in/MCM-41 tetra-species complex system.
3. the synthetic method of the O-tertiary butyl according to claim 1-L-Thr tert-butyl ester acetate, is characterized in that catalyst charge is catalyzer: the mass ratio=20-35:100 of Isosorbide-5-Nitrae dioxane.
4. the synthetic method of the O-tertiary butyl according to claim 1-L-Thr tert-butyl ester acetate, is characterized in that synthesis is with Isosorbide-5-Nitrae dioxane, L-threonine, iso-butylene is starting raw material, Isosorbide-5-Nitrae dioxane: L-threonine: iso-butylene mass ratio=10-20:1:4-7.
5. the synthetic method of the O-tertiary butyl according to claim 1-L-Thr tert-butyl ester acetate, is characterized in that: first, and Isosorbide-5-Nitrae dioxane and L-threonine react 3-7 hours being less than at 25 DEG C; Secondly, after the reaction of system terminates, under pressure is 0.05MPa, temperature passes into iso-butylene at 17-25 DEG C, ventilation continuously in first 12 hours, latter 48 hours, is interrupted ventilation, reacts within 60 hours and terminates, finally, after system is static, pH value is down to 7-8, and Filtration of catalyst obtains crude product.
6. the synthetic method of the O-tertiary butyl according to claim 1-L-Thr tert-butyl ester acetate, it is characterized in that the regeneration to described catalyzer: washed successively by catalyzer, each deionized water consumption is catalyzer 2-8 times of volumes, after washing 1-5 times, use chloroform again, each chloroform: catalyst quality, than=2-4:1, washs 1-5 times, finally vacuum-drying 8-18 hours at 90-120 DEG C.
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