CN103182277B - Microfluidic channel reactor and the application in synthesis of sucrose-6-palmitate thereof - Google Patents
Microfluidic channel reactor and the application in synthesis of sucrose-6-palmitate thereof Download PDFInfo
- Publication number
- CN103182277B CN103182277B CN201110457554.0A CN201110457554A CN103182277B CN 103182277 B CN103182277 B CN 103182277B CN 201110457554 A CN201110457554 A CN 201110457554A CN 103182277 B CN103182277 B CN 103182277B
- Authority
- CN
- China
- Prior art keywords
- reaction
- sucrose
- palmitate
- channel
- syringe
- 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.)
- Active
Links
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 16
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 15
- 238000006243 chemical reaction Methods 0.000 claims abstract description 94
- 229930006000 Sucrose Natural products 0.000 claims abstract description 41
- 239000005720 sucrose Substances 0.000 claims abstract description 39
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 37
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims abstract description 32
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000000376 reactant Substances 0.000 claims abstract description 20
- 230000035484 reaction time Effects 0.000 claims abstract description 19
- 238000005917 acylation reaction Methods 0.000 claims abstract description 17
- UJRIYYLGNDXVTA-UHFFFAOYSA-N ethenyl hexadecanoate Chemical compound CCCCCCCCCCCCCCCC(=O)OC=C UJRIYYLGNDXVTA-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000002994 raw material Substances 0.000 claims abstract description 10
- 108010048733 Lipozyme Proteins 0.000 claims abstract description 8
- FCCDDURTIIUXBY-UHFFFAOYSA-N lipoamide Chemical compound NC(=O)CCCCC1CCSS1 FCCDDURTIIUXBY-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000012046 mixed solvent Substances 0.000 claims abstract description 8
- 238000012805 post-processing Methods 0.000 claims abstract description 5
- 239000003054 catalyst Substances 0.000 claims abstract description 3
- 229960004793 sucrose Drugs 0.000 claims description 40
- 239000000047 product Substances 0.000 claims description 14
- 239000006227 byproduct Substances 0.000 claims description 3
- 235000013681 dietary sucrose Nutrition 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 19
- -1 Sucrose fatty ester Chemical class 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 108090001060 Lipase Proteins 0.000 description 5
- 239000004367 Lipase Substances 0.000 description 5
- 102000004882 Lipase Human genes 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 235000019421 lipase Nutrition 0.000 description 5
- 230000002194 synthesizing effect Effects 0.000 description 5
- 230000003197 catalytic effect Effects 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 208000012839 conversion disease Diseases 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 238000004945 emulsification Methods 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 231100000614 poison Toxicity 0.000 description 3
- 230000007096 poisonous effect Effects 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 240000006439 Aspergillus oryzae Species 0.000 description 2
- 235000002247 Aspergillus oryzae Nutrition 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000009736 wetting Methods 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000223258 Thermomyces lanuginosus Species 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000012459 cleaning agent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 239000004088 foaming agent Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000002932 luster Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- 230000000050 nutritive effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical class CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 150000003445 sucroses Chemical class 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000009941 weaving Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
Abstract
The invention discloses a kind of method of lipase-catalyzed online synthesis of sucrose-6-palmitate, described method is: with mol ratio be 1: 3 ~ 8 sucrose and vinyl palmitate for raw material, with 0.5 ~ 0.8g Lipozyme TLIM for catalyst, with the mixed solvent of tert-pentyl alcohol and DMSO for reaction dissolvent, Lipozyme TLIM is uniformly filled in the reaction channel of microfluidic channel reactor, the reaction channel internal diameter of described microfluidic channel reactor is 0.8 ~ 2.4mm, and passage length is 0.5 ~ 1.0m; Under syringe pump promotes, raw material and reaction dissolvent are passed in reaction channel continuously and carry out acylation reaction; controlling acylation reaction temperature is 40 ~ 55 DEG C; the acylation reaction time is 20 ~ 40min, collects reactant liquor online, and reactant liquor obtains sucrose-6-palmitate through conventional post processing.The present invention has the advantage of reaction time short, high selectivity and high yield.
Description
(1) technical field
The present invention relates to a kind of microfluidic channel reactor and the application in synthesis of sucrose-6-palmitate thereof.
(2) background technology
Micro-fluidic (Microfluidics) manipulates to receive to rise to technology and the science that skin rises volume fluid in micron scale construction, is the new cross discipline emerged rapidly nearly ten years.Current, the development of micro-fluidic has surmounted the original object being mainly analytical chemistry service greatly, and is becoming the important technological platform of whole chemistry subject, life science, instrumental science and even information science new round innovation research.
Delivered after a first section synthesizes the document of compound in micro-fluidic chip microreactor from Harrison seminar in 1997, micro-fluidic chip reactor has been successfully used to multiple organic synthesis, and illustrates application prospect widely.Along with the development of microring array, micro-reacting tcchnology in micro-fluidic chip, carry out synthetic reaction in the chips and become one of the study hotspot in micro-fluidic chip field.
Compare with conventional chemical reactor, micro passage reaction not only has makes the diffusion length between reactant greatly shorten, and mass transfer velocity is fast; The easy control of reaction conditions such as reactant ratio, temperature, reaction time and flow velocity, side reaction is less; Need reactant consumption very micro-, not only can reduce the consumption of costliness, poisonous, adverse reaction thing, the environmental contaminants produced in course of reaction are also few, are the technology of a kind of environmental friendliness, study on the synthesis novel substance.
Sucrose fatty ester, as a kind of sucrose derivative, is a kind of safe, nontoxic, free from extraneous odour of function admirable, pollution-free, polyol-based non-ionic surfactant to human body non-stimulated, good stability, fully biodegradable without any side effects.It can reduce the surface tension of water effectively, in wetting power, dispersion force, solubilising, foaming power, emulsifying ability, detergency etc., have excellent performance.Meanwhile, also there is killing pests and suppressing bacteria performance.Therefore, its strong adaptability, applied range.The fields such as food industry, daily-use chemical industry, medical industry, weaving, agriculture and animal husbandry are widely used in, in particular as the emulsifying agent in food industry, dispersant, foaming agent, wetting agent and cleaning agent at present; Cosmetics in daily-use chemical industry, washing agent etc.
Sucrose ester is generally white powder, bulk or waxy solid, sometimes also exists with colourless or micro-yellow, viscous or resin-like liquid form, nontoxic, not chafe and mucous membrane.Eat in human body, hydrolyzable is edible fat acid and sucrose, has nutritive value, participates in the metabolism of human body, have emulsification, dispersion, wetting, bubble, viscosity regulates, prevents aging and prevent the performances such as partial crystallization, be soluble in the organic solvents such as ethanol, propyl alcohol, chloroform, propane diols, without sharp melting point, more than 50 DEG C, namely start fusing, disperse or dissolve in warm water, solubility in cold water is less, stable under weak acid and weak base, is easily hydrolyzed under strong acid and strong base.
So far the synthesis of sucrose ester has solvent method, mini-emulsion process, water-soluble fluorine, enzyme process and solventless method etc.But existing method also exists defect more or less.
Mini-emulsion process and water-soluble fluorine all need a large amount of soaps to make emulsifying agent, product purification difficulty, and color and luster is comparatively dark, and the shortcoming that water-soluble fluorine also has productive rate low.Although the solventless method reaction time is short, do not use any solvent, meet the demand for development of Green Chemistry, due to the low conversion rate of the fatty acid ester of solventless method synthesis, the monoester content of sucrose ester is low, and product cost is high, limits their application.Solvent method due to solvent DMSO, DMF etc. inflammable, poisonous, purifying products is more difficult, therefore should not be applied to the production of food grade sucrose ester.Therefore the synthetic method developing efficient sucrose ester has very important practical significance.
At present, there is more Chinese scholars to be studied the Enzyme catalyzed synthesis of sucrose ester in organic media, successively report the esterification of lipase-catalyzed multiple disaccharides in tert-butyl alcohol system and the tert-butyl alcohol and DMSO mixed solvent system (4: 1).Compared with traditional solvent method, mixed solvent system adopts nontoxic or that toxicity is less tert-pentyl alcohol as reaction medium, greatly reduces the use of toxic solvent, is applicable to develop the various sucrose ester product with using value.But the method often needs the longer reaction time (24h), and the conversion ratio of reaction is not with selective high, and later separation is difficult.Therefore we have studied the method for synthesizing sucrose-6-palmitate by using lipase through catalytic selectivity in microfluidic channel reactor.
(3) summary of the invention
First technical problem that the present invention will solve is to provide a kind of microfluidic channel reactor, and this reactor is used for synthesizing sucrose-6-palmitate by using lipase through catalytic selectivity, has reaction time short, selective height and the high advantage of productive rate.
Microfluidic channel reactor of the present invention, comprise syringe pump, syringe, reaction channel and product collector, described syringe is installed in syringe pump, is connected with reaction channel entrance by an interface, and described product collector is exported with reaction channel by an interface and is connected; Described reaction channel internal diameter is 0.8 ~ 2.4mm, and reaction channel length is 0.5 ~ 1.0m.
Further, described syringe number can be one or more, depending on concrete reaction requirement.Such as, when use two syringes, can adopt T-shaped or Y type interface that different reactants is introduced from two entrances, conflux and enter public reaction channel, increased with collision probability by reactant molecule contact in microchannel, make two strands of reactant liquor streams mix in public reaction channel and react.
Further, described microfluidic channel reactor also comprises insulating box, and described reaction channel is placed in insulating box, effectively can control reaction temperature with this.Described insulating box can require to select voluntarily according to reaction temperature, such as constant temperature water box etc.
The present invention does not limit for the material of reaction channel, and recommendation is green, the material of environmental protection, such as silicone tube; Shape for reaction channel is preferably shaped form, can ensure at the uniform velocity stable the passing through of reactant liquor.
Second technical problem that the present invention will solve is to provide a kind of new technology utilizing described microfluidic channel reactor synthesizing sucrose-6-palmitate by using lipase through catalytic selectivity, has reaction time short, selective height and the high advantage of productive rate.
For solving the problems of the technologies described above, the present invention adopts following technical scheme:
The application of microfluidic channel reactor of the present invention in synthesis of sucrose-6-palmitate, described application comprises: with mol ratio be 1: 3 ~ 8 sucrose and vinyl palmitate for raw material, with 0.5 ~ 0.8g Lipozyme TLIM for catalyst, with the mixed solvent of tert-pentyl alcohol and methyl-sulfoxide (DMSO) for reaction dissolvent, raw material and reaction dissolvent are placed in syringe, Lipozyme TLIM is uniformly filled in reaction channel; Under the promotion of syringe pump, make raw material and reaction dissolvent pass into continuously in reaction channel carry out acylation reaction; controlling acylation reaction temperature is 40 ~ 55 DEG C; the acylation reaction time is 20 ~ 40min; collect reactant liquor online by product collector, reactant liquor obtains sucrose-6-palmitate through conventional post processing.
The present invention, can first with the mixed solvent of tert-pentyl alcohol and DMSO, (tert-pentyl alcohol: DMSO=4: 1) dissolving saccharose, as long as its consumption ensures that sucrose can fully dissolve, and be loaded in syringe for subsequent use in implementation process; Only dissolve vinyl palmitate with nontoxic tert-pentyl alcohol, be loaded in another syringe for subsequent use; Then under syringe pump (such as PHD2000 syringe pump) promotes, raw material and reaction dissolvent are passed in reaction channel to react.Therefore, in the present invention, in reaction dissolvent, tert-pentyl alcohol and DMSO volume ratio are greater than 4: 1, react compared to the shaking table of routine, can be down to minimum by the use amount of poisonous DMSO.
In the present invention, the commodity that described Lipozyme TLIM uses letter (novozymes) company of Novi to produce, its be a kind ofly to be prepared by microorganism, 1,3 position-specific, food-grade lipase (EC3.1.1.3) preparation on particle silica gel.It obtains from Thermomyces lanuginosus, produce through submerged fermentation with a kind of gene-modified aspergillus oryzae (Aspergillus oryzae) microorganism.
Further, the mol ratio of described sucrose and vinyl palmitate is preferably 1: 5 ~ 6, most preferably is 1: 5.
Further, described acylation reaction temperature is preferably 50 ~ 55 DEG C, most preferably is 52 DEG C.
Further, the described acylation reaction time is preferably 25 ~ 30min, most preferably is 30min.
Product of the present invention can be collected online, and gained reactant liquor can obtain sucrose-6-palmitate by conventional post-processing approach.Described conventional post-processing approach can be: the decompression distillation of gained reactant liquor is except desolventizing, with 200-300 order silica gel wet method dress post, elution reagent is chloroform: methyl alcohol=10: 1, wet method upper prop after sample dissolves with a small amount of elution reagent, collect eluent, TLC follows the tracks of wash-out process simultaneously, and the eluent containing single product obtained is merged evaporate to dryness, the monoesters crystal of white can be obtained, be sucrose-6-palmitate.
In the present invention, although there is the hydroxyl of 8 similar nature in sucrose, but synthesizing sucrose-6-palmitate by using lipase through catalytic selectivity has higher conversion ratio and selective in micro-fluidic micro passage reaction, the conversion ratio of diester is very low, almost do not have, the content of the monoesters obtained by column chromatography for separation can reach 98%.The structure warp of product
1h NMR confirms.This shows that the enzymatic selectivity synthesis of sucrose-6-palmitate in micro-fluidic micro passage reaction has good reaction conversion ratio and selective, can realize high monoesters rate.
Compared with prior art, beneficial effect of the present invention is: this invention exploits a kind of new microfluidic channel reactor, selectively synthesizing sucrose-6-palmitate, not only shortens the reaction time widely in the reactor, and has high conversion ratio and reaction selectivity; Reduce the use amount of DMSO simultaneously, there is environment-friendly advantage.
(4) accompanying drawing explanation
Fig. 1 is the structural representation of the microfluidic channel reactor that the embodiment of the present invention adopts.
(5) detailed description of the invention
With specific embodiment, protection scope of the present invention is described further below, but protection scope of the present invention is not limited thereto:
The structural reference Fig. 1 of the microfluidic channel reactor that the embodiment of the present invention uses, comprise a syringe pump (not shown), two syringes 1 and 2, reaction channel 3, constant temperature water box (5, only show its floor map) and product collector 4; Two syringes 1 and 2 are installed in syringe pump, be connected with reaction channel 3 entrance by a Y type interface, described reaction channel 3 is placed in constant temperature water box 5, reaction temperature is controlled by constant temperature water box 5, the internal diameter 2.4mm of described reaction channel 3, the long 1m of reaction channel, described reaction channel 3 is exported and is connected with product collector 4 by an interface.
Embodiment 1: the synthesis of sucrose-6-palmitate
With reference to figure 1, sucrose (0.4mmol) is dissolved in 10mL tert-pentyl alcohol: in the mixed solvent of DMSO=4: 1 (v/v), vinyl palmitate (2.0mmol) is dissolved in 10mL tert-pentyl alcohol, is then loaded in 10mL syringe for subsequent use respectively.0.70g Lipozyme TLIM is uniformly filled in the reaction channel of microfluidic channel reactor, and under PHD2000 syringe pump promotes, two-way reactant liquor is respectively with totally 10.4 μ Lmin
-1flow velocity under to be entered in reaction channel by " Y " joint and carry out acylation reaction; reaction channel temperature is controlled at 52 DEG C by constant temperature water box; reactant liquor is continuous-flow reaction 30min in reaction channel, and collect reactant liquor online by product collector, decompression distillation is except desolventizing; with 200-300 order silica gel wet method dress post; elution reagent is chloroform: methyl alcohol=10: 1, post height 35cm, column diameter 4.5cm; wet method upper prop after sample dissolves with a small amount of elution reagent, flow velocity 2mLmin collected by eluent
-1tLC follows the tracks of wash-out process simultaneously, the eluent containing single product obtained is merged evaporate to dryness, the monoesters crystal of white can be obtained, obtain sucrose-6-palmitate, it is 94% that HPLC detects Sucrose conversion, and selective (the sucrose ester total content of sucrose-6-palmitate content/synthesis) of sucrose-6-palmitate is 98%.
Nuclear-magnetism characterization result is as follows:
1h-NMR (DMSO-d6, δ, ppm): sucrose-6-palmitate: 5.18-5.14 (m, 3H, 2 β-OH of sucrose, 3 α-OH of sucrose and 4 β-OH of sucrose), 5.03 (d, 1H, J=5.5Hz, 3 ' β-OH of sucrose), 4.90 (s, 1H, 4 ' α-OH of sucrose), 4.83-4.80 (t, 1H, J=6.5Hz, 5 ' β-OH of sucrose), 4.58 (d, 1H, J=8.0Hz, 1 ' β-OH of sucrose), 4.41-4.39 (t, 1H, J=5.0Hz, H α-6 α of sucrose), 4.24 (d, 1H, J=10.5Hz, the H of sucrose
b-6 α), 4.04-3.99 (m, 1H, the H-5 β of sucrose), 3.92-3.86 (m, 2H, the H-5 ' α of sucrose and H
α-1 ' α), 3.73 (d, 1H, J=6.0Hz, the H of sucrose
b-1 ' α), 3.60-3.47 (m, 4H, the H-3 ' α of sucrose, H-4 ' β, H
a-6 ' β and H
b-6 ' β), 3.35 (m, 1H, the H-3 β of sucrose), 3.22-3.19 (m, 1H, the H-2 β of sucrose), 3.09-3.04 (m, 1H, the H-4 β of sucrose), 2.31-2.29 (m, 2H, a-CH
2), 1.52-1.50 (t, 2H, J=7.0Hz, β-CH
2), 1.25 (m, 24H, n-CH
2), 0.86 (t, 3H, J=7.0Hz, CH
3).
Embodiment 2-5
Change the temperature of microfluidic channel reactor, other are with embodiment 1, and reaction result is as shown in table 1:
Table 1: temperature is on the impact of reaction
| Entry | Flow velocity [μ Lmin -1] | Reaction time [min] | Reaction temperature [DEG C] | Conversion ratio [%] | Selective [%] |
| 1 | 10.4 | 30 | 40 | 35 | 100 |
| 2 | 10.4 | 30 | 45 | 65 | 95 |
| 3 | 10.4 | 30 | 50 | 88 | 96 |
| 4 | 10.4 | 30 | 52 | 94 | 98 |
| 5 | 10.4 | 30 | 55 | 90 | 98 |
The result of table 1 shows, when flow velocity is 10.4 μ Lmin
-1reaction time is when being 30min, react the rising with temperature, conversion ratio also obviously raises, when reaction temperature reaches 52 DEG C, and the conversion ratio of reaction and selective all the bests, if now continue to heat up, the reduction of enzymatic activity will be caused, thus result in the conversion ratio of reaction and selectively to decrease, so the optimal reaction temperature of synthesis of sucrose-6-palmitate is 52 DEG C in micro-fluidic micro passage reaction.
Embodiment 6-10
Changing vinyl palmitate and the substrate ratio of sucrose in micro-fluidic micro passage reaction is 3: 1 (embodiments 6), 4: 1 (embodiments 7), 6: 1 (embodiments 8), 7: 1 (embodiments 9), 8: 1 (embodiments 10), other are with embodiment 1, and result is as shown in table 2.
Table 2: the impact that sucrose and the comparison of vinyl palmitate substrate are reacted
| Embodiment | Vinyl palmitate: sucrose | Conversion ratio [%] | Selective [%] |
| 6 | 3∶1 | 78 | 99 |
| 7 | 4∶1 | 80 | 98 |
| 1 | 5∶1 | 94 | 98 |
| 8 | 6∶1 | 92 | 98 |
| 9 | 7∶1 | 91 | 95 |
| 10 | 8∶1 | 90 | 93 |
The result of table 2 shows, along with the increase of reactant vinyl palmitate, the conversion ratio of reaction also along with increase, when substrate ratio is 5: 1, the conversion ratio of reaction and selective optimum.If now continue the consumption increasing reactant vinyl palmitate, will cause the conversion ratio that reacts and/or selectively greatly to reduce, thus, the best substrate ratio of reaction is 5: 1.
Embodiment 11-15
Changing the reaction time in micro-fluidic micro passage reaction is 15min (embodiment 11), 20min (embodiment 12), 25min (embodiment 13), 35min (embodiment 14), 40min (embodiment 15), other are with embodiment 1, and result is as shown in table 3.
Table 3: the reaction time is on reaction conversion ratio and optionally affect
| Embodiment | Reaction time [mm] | Conversion ratio [%] | Selective [%] |
| 11 | 15 | 50 | 100 |
| 12 | 20 | 78 | 99 |
| 13 | 25 | 85 | 99 |
| 1 | 30 | 94 | 98 |
| 14 | 35 | 88 | 93 |
| 15 | 40 | 80 | 87 |
The result of table 3 shows, along with the increase in reaction time, the conversion ratio of reaction and selectively also to increase gradually, when 30min is carried out in reaction, the conversion ratio of reaction and selective optimum, if now continue to extend the reaction time, will cause reaction conversion ratio and optionally reduce, thus, in micro-fluidic micro passage reaction, the Best Times of synthesis of sucrose-6-palmitate is 30min.
Claims (5)
1. the application of microfluidic channel reactor in synthesis of sucrose-6-palmitate, it is characterized in that described microfluidic channel reactor comprises syringe pump, syringe, reaction channel and product collector, described syringe is installed in syringe pump, be connected with reaction channel entrance by an interface, described product collector is exported with reaction channel by an interface and is connected, described reaction channel internal diameter is 0.8 ~ 2.4mm, and reaction channel length is 0.5 ~ 1.0m; Described microfluidic channel reactor also comprises insulating box, and described reaction channel is placed in insulating box;
Described application comprises: take mol ratio as sucrose and the vinyl palmitate of 1:3 ~ 8 be raw material, with 0.5 ~ 0.8g Lipozyme TLIM for catalyst, with the mixed solvent of tert-pentyl alcohol and DMSO for reaction dissolvent, raw material and reaction dissolvent are placed in syringe, Lipozyme TLIM is uniformly filled in the reaction channel of microfluidic channel reactor, under the promotion of syringe pump, make raw material and reaction dissolvent pass into continuously in reaction channel carry out acylation reaction, controlling acylation reaction temperature is 40 ~ 55 DEG C, the acylation reaction time is 20 ~ 40min, reactant liquor is collected online by product collector, reactant liquor obtains sucrose-6-palmitate through conventional post processing.
2. apply as claimed in claim 1, it is characterized in that: described syringe number is one or more.
3. apply as claimed in claim 1, it is characterized in that: described application comprises the following steps: to be first the tert-pentyl alcohol of 4:1 and the mixed solvent dissolving saccharose of DMSO by volume ratio, is loaded in syringe for subsequent use; Dissolve vinyl palmitate with tert-pentyl alcohol, be loaded in another syringe for subsequent use; Then under syringe pump promotes, raw material and reaction dissolvent are passed in reaction channel and carry out acylation reaction.
4. the application as described in one of claims 1 to 3, is characterized in that: the mol ratio of described sucrose and vinyl palmitate is 1:5 ~ 6, and described acylation reaction temperature is 50 ~ 55 DEG C, and the described acylation reaction time is 25 ~ 30min.
5. the application as described in one of claims 1 to 3, is characterized in that: the mol ratio of described sucrose and vinyl palmitate is 1:5, and described acylation reaction temperature is 52 DEG C, and the described acylation reaction time is 30min.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110457554.0A CN103182277B (en) | 2011-12-31 | 2011-12-31 | Microfluidic channel reactor and the application in synthesis of sucrose-6-palmitate thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110457554.0A CN103182277B (en) | 2011-12-31 | 2011-12-31 | Microfluidic channel reactor and the application in synthesis of sucrose-6-palmitate thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103182277A CN103182277A (en) | 2013-07-03 |
| CN103182277B true CN103182277B (en) | 2015-08-26 |
Family
ID=48673872
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201110457554.0A Active CN103182277B (en) | 2011-12-31 | 2011-12-31 | Microfluidic channel reactor and the application in synthesis of sucrose-6-palmitate thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103182277B (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107988279A (en) * | 2017-12-21 | 2018-05-04 | 浙江工业大学 | A kind of method of lipase-catalyzed online synthesis 6- ((4- chlorobenzyls) sulfenyl) -6- oxo vinyl caproates |
| CN108060184A (en) * | 2017-12-21 | 2018-05-22 | 浙江工业大学 | A kind of method of lipase-catalyzed online synthesis S- thioacetic acid benzyl esters |
| CN108060185A (en) * | 2017-12-21 | 2018-05-22 | 浙江工业大学 | A kind of method of lipase-catalyzed online synthesis S- (4- methylbenzyls) thiacetate |
| CN107955823A (en) * | 2017-12-21 | 2018-04-24 | 浙江工业大学 | A kind of method of lipase-catalyzed online synthesis 6- ((4- methyl-benzyls) sulfenyl) -6- oxo vinyl caproates |
| CN108070625A (en) * | 2017-12-21 | 2018-05-25 | 浙江工业大学 | A kind of lipase-catalyzed online synthesis S-（4- methylbenzyls）The method of palmitic acid thioesters |
| CN108060183A (en) * | 2017-12-21 | 2018-05-22 | 浙江工业大学 | A kind of lipase-catalyzed online synthesis 6-（Benzylthio）The method of -6- oxo vinyl caproates |
| CN112299995B (en) * | 2020-11-08 | 2022-03-18 | 复旦大学 | Method for continuously preparing (R) -4-halo-3-hydroxy-butyric acid ester using micro-reaction system |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1687770A (en) * | 2005-04-21 | 2005-10-26 | 南京大学 | Microflow control chip integrated unit in integrated constant temperature system in high efficiency |
| CN101507909A (en) * | 2009-02-25 | 2009-08-19 | 中国科学院过程工程研究所 | Molecular engram microspheres preparation method using micro-fluidic reactor |
| CN102161683A (en) * | 2011-02-24 | 2011-08-24 | 浙江工业大学 | Method for synthesizing sucrose-6-palmitate by using lipase through catalytic selectivity |
| CN102284262A (en) * | 2011-06-14 | 2011-12-21 | 东南大学 | Microfluidic microsphere preparation device |
-
2011
- 2011-12-31 CN CN201110457554.0A patent/CN103182277B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1687770A (en) * | 2005-04-21 | 2005-10-26 | 南京大学 | Microflow control chip integrated unit in integrated constant temperature system in high efficiency |
| CN101507909A (en) * | 2009-02-25 | 2009-08-19 | 中国科学院过程工程研究所 | Molecular engram microspheres preparation method using micro-fluidic reactor |
| CN102161683A (en) * | 2011-02-24 | 2011-08-24 | 浙江工业大学 | Method for synthesizing sucrose-6-palmitate by using lipase through catalytic selectivity |
| CN102284262A (en) * | 2011-06-14 | 2011-12-21 | 东南大学 | Microfluidic microsphere preparation device |
Non-Patent Citations (4)
| Title |
|---|
| Lipase‐catalyzed regioselective acylation of sucrose in two‐solvent mixtures;Manuel Ferrer等;《Biotechnology and Bioengineering》;19991005;第65卷(第1期);摘要、第11页第2栏倒数第2段-第12页第1栏第1段 * |
| 微通道反应器在合成反应中的应用;穆金霞等;《化学进展》;20080131;第20卷(第01期);第62页第1栏第2段，图1 * |
| 方肇伦等.微流控芯片在化学合成中的应用.《微流控分析芯片》.科学出版社,2003,338-339. * |
| 酶促反应合成蔗糖棕榈酸酯的研究;吴可克等;《中国油脂》;20040331;第29卷(第03期);第37页第2栏第1.3.1节 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103182277A (en) | 2013-07-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103184257B (en) | Method for on-line synthesizing sucrose-6-acetate catalyzed by lipase | |
| CN103184256B (en) | Method for on-line synthesizing saccharose-6-laurate by lipase catalysis | |
| CN103182277B (en) | Microfluidic channel reactor and the application in synthesis of sucrose-6-palmitate thereof | |
| CN103184249B (en) | Method for on-line synthesizing glucose-6-palmitate by lipase catalysis | |
| CN103184252B (en) | Method of using lipase to catalyze and synthesize glucose-6-laurate on line | |
| CN103184253B (en) | Method of using lipase to catalyze and synthesize mannose-6-laurate on line | |
| CN103667402B (en) | A kind of lipase-catalyzed online synthesis 6 " method of-O-lauroyl-naringin ester | |
| CN103184255B (en) | Method of using lipase to catalyze and synthesize galactose-6-acetate on line | |
| CN103184251B (en) | Method for on-line synthesizing glucose-6-acetate catalyzed by lipase | |
| CN103667396B (en) | A kind of lipase-catalyzed online synthesis 6 " method of-O-lauroyl-naringin dihydrochalcone ester | |
| CN105838600B (en) | A kind of method of 5 ' O palmityl uridines of lipase-catalyzed online synthesis | |
| CN107384991B (en) | Method for synthesizing 5' -O-ethylene adipamide uridine on line by lipase catalysis | |
| CN107475330A (en) | A kind of method of lipase-catalyzed online synthesis N (5 glucose ester valeryl) metoprolol | |
| CN102161683A (en) | Method for synthesizing sucrose-6-palmitate by using lipase through catalytic selectivity | |
| CN107384782A (en) | A kind of method of lipase-catalyzed online synthesis 5 '-O- ethene adipyls -5-FUD | |
| CN103667400B (en) | A kind of lipase-catalyzed online synthesis 6 " method of-O-palmityl-naringin ester | |
| CN107488691A (en) | A kind of method of lipase-catalyzed online synthesis N (5 lauroyl mannoses valeryl) metoprolol | |
| CN107488690A (en) | A kind of method of lipase-catalyzed online synthesis N (5 glucose ester valeryl) mexiletine | |
| CN103667393B (en) | A kind of lipase-catalyzed online synthesis 6 " method of-O-palmityl-neohesperidin dihydrochalcone ester | |
| CN107475329A (en) | A kind of method of lipase-catalyzed online synthesis N (5 sucrose ester valeryl) mexiletine | |
| CN103667394B (en) | A kind of lipase-catalyzed online synthesis 6 " method of-O-lauroyl-neohesperidin dihydrochalcone ester | |
| CN103184250B (en) | Method for on-line synthesizing mannose-6-acetate by lipase catalysis | |
| CN103667399B (en) | A kind of lipase-catalyzed online synthesis 6 " method of-O-palmityl-Neohesperidin ester | |
| CN103184254B (en) | Method of using lipase to catalyze and synthesize mannose-6-palmitate on line | |
| CN107418989A (en) | A kind of method of lipase-catalyzed online synthesis N (5 sucrose ester valeryl) metoprolol |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |