CN101125869A

CN101125869A - Modified producing method for trichlorosaccharose

Info

Publication number: CN101125869A
Application number: CNA2006101096878A
Authority: CN
Inventors: 林洪; 周若愚; 杨顺
Original assignee: QINGYUAN TIANJI GUTANG CO Ltd
Current assignee: QINGYUAN TIANJI GUTANG CO Ltd
Priority date: 2006-08-17
Filing date: 2006-08-17
Publication date: 2008-02-20

Abstract

An improved production method of sucralose is characterized by comprising the steps: (1) methoxy on benzene ring is used for replacing the three ortho-hydroxide radical of 6, 1' and 6' in trityl chloride etherified sucrose molecules and acylation reaction is carried out to prepare 6, 1', 6'-trimethoxy benzyl-penta acetic sucrose through etherealization and fine purification; (2) etherealization and acyl removal reactions are carried out to the 6, 1', 6'-trimethoxy benzyl-penta acetic sucrose in water-bearing weak acid at the same time, product 6-PAS generated from the reaction is refined and enters into the next chlorination reaction step; (3) 4, 1', 6'- trichloro-4, 1', 6'-trideoxidation galacto-sucrose (namely the sucralose) is prepared through the chlorination and acyl reaction of the 6-PAS. The invention combines the advantages of a full protective line and a single protective line, spurns the defects of the existing production methods and changes the original 'five steps' of the full protective line into 'four steps', thereby promoting the recovery rate of the full protective line greatly with less reaction steps and consumption, thus resulting in a more economic and environment protective production technology compared with the traditional production technologies of the full protective line or the single protective line.

Description

Improved production method of sucralose

Technical field

The present invention relates to a kind of production method of 4,1 ', 6 '-three chloro-, 4,1 ', 6 '-three deoxidation sucralose.

Background technology

(being Sucralose, Sucralose) is a kind of novel intense sweetener, and its feature is: the sugariness height is 600 times of sucrose sweetness to 4,1 ', 6 '-three chloro-, 4,1 ', 6 '-three deoxidation sucralose; Sweet taste is pure, mouthfeel and sucrose basically identical; Stable performance is difficult for being destroyed by severe environment such as soda acid, high temperature; Application surface is extensive, almost can be used for all food; Safe to use in food as sweeting agent; Heat is low, and no grinding tooth is suitable for diabetics and odontopathy patients.

Have 8 hydroxyls in the molecular structure of sucrose, optionally using 4,1 ', 6 ' hydroxyl in the chlorine atom substituting saccharose molecule is the ultimate principle of making Sucralose.If at first in the sucrose molecules except 4,1 ', 6 all outer other hydroxyls of hydroxyl carry out the acidylate protection, again with chlorinating agent to 4,1 ', 6 ' hydroxyl carries out chlorine and replaces, and sloughs the acidylate blocking group at last and obtains Sucralose, this is the full guard route (reactional equation is seen figure) of so-called preparation Sucralose, for example the method addressed of United States Patent (USP) 4362869 and English Patent 2182039; If at first only the most active 6 hydroxyls in the sucrose molecules are carried out the acidylate protection; again with chlorinating agent to activity take second place 4; 1 '; 6 ' hydroxyl carries out chlorine and replaces; slough the acidylate blocking group at last and obtain Sucralose; this is single protection route of so-called preparation Sucralose, for example United States Patent (USP) 4380476,4889928 and 4980463 and the method addressed of European patent 0515145.

In the above-mentioned full guard route before the acidylate protective reaction earlier with in triphenylmethyl chloride (as shown in Figure 1) the selective etherification sucrose molecules 6; 1 '; 6 ' three uncle position hydroxyls; carry out acidylate again, take off etherificate base and acyl migration (4 acyl migration to 6); have only 4 in the sucrose molecules thereby make; 1 ', 6 ' hydroxyl is free, can be by chloro.The density height though the full guard route responds; need not to consume a large amount of high boiling points, easily decompose, be difficult to recovered solvent; the advantage that three waste discharge is few, but reactions steps is more, when particularly the etherificate base is trityl; need under strong acid, long-time reaction could remove more fully; glycan molecule also is easier to hydrolysis simultaneously, thereby causes yield on the low side, and intermediates are difficult to purifying; cost is higher, has influenced its advantage performance.On the other hand, the relative merits of above-mentioned single protection route are just opposite with the relative merits of full guard route.This route is brief than the full guard route, but has lost the advantage of full guard route.Reaction density is low, needs to consume a large amount of high boiling points, easily decompose, be difficult to recovered solvent, and three waste discharge is many, and reaction conditions is wayward, and shortcomings such as yield, quality instability have also influenced its advantage performance.

Summary of the invention

The objective of the invention is to deficiency, provide a kind of and improved, thereby overcome existing full guard and the insufficient novel production method of sucralose of guarantee exchanging visit method at traditional full guard route at the prior art existence.。

Technical scheme of the present invention is: a kind of improved production method of sucralose, it is characterized in that, and may further comprise the steps:

(1) gets product 6,1 ', 6 '-three mono methoxy phenmethyl-pentaacetic acid sucrose with 6,1 ', 6 ' three uncle position hydroxyls in the triphenylmethyl chloride etherificate sucrose molecules that the methoxyl group replacement is arranged on the phenyl ring through acylation reaction and after making with extra care;

(2) 6,1 ', 6 '-three mono methoxies phenmethyl-pentaacetic acid sucrose takes off etherificate base and acyl migration reaction simultaneously in moisture weak acid, and reaction product 6-PAS enters follow-up chlorination step again after refining;

(3) 6-PAS obtains 4 through chloro and deacylated tRNA radical reaction, 1 ', 6 '-three chloro-, 4,1 ', 6 '-three deoxidation sucralose (being Sucralose); The reaction formula of reaction process is as follows:

Preferably, the triphenylmethyl chloride that has pair methoxyl group to replace on the described phenyl ring is single to the methoxyl group triphenylmethyl chloride.

Preferably; there is pair condition of the triphenylmethyl chloride etherificate sucrose of methoxyl group replacement to be on the phenyl ring: to make solvent with dimethyl formamide; N-methylmorpholine is as acid absorber; temperature of reaction is 30～70 ℃; reaction times is 6～10 hours, and reaction is carried out acylation reaction again after neutralization and steaming desolventize.

Preferably, in the step 2, moisture weak acid is that content is 60～95% the formic acid aqueous solution or aqueous acetic acid or the propionic acid aqueous solution or the phenylformic acid aqueous solution or the Succinic Acid aqueous solution.

Preferably, the time of taking off etherificate base and acyl migration successive reaction is 1～5 hour, and the successive reaction temperature is 0～50 ℃.Take off etherificate base and acyl migration successive reaction in 80% acetic acid, 5～15 ℃ of temperature continue 1.5～2 hours.

Beneficial effect of the present invention is: the advantage of full guard and single protection route is combined; abandoned simultaneously the deficiency that exists in the existing production method again; " five-step approach " with original full guard route; become " four step rule "; the full guard route rate of recovery is improved greatly, and reactions steps and consumption reduce.More traditional full guard or single protection route production technique are had the economy and the feature of environmental protection more.

Embodiment

First specific embodiment of the present invention; a kind of with single primary hydroxyl and acetylize to methoxyl group triphenylmethyl chloride etherificate sucrose; in 1000 milliliters there-necked flask; add 40 gram cane sugar powder (0.116mol) and 180 milliliters of dimethyl formamides successively; be warming up to 45 ℃ sucrose is dissolved fully, add 48 gram N-methylmorpholines (0.572mol).Add 130 gram mono methoxy triphenylmethyl chlorides (0.404mol) in 3 hours, isothermal reaction 8 hours.

Add 34.4 gram sodium bicarbonate (0.41mol) neutralizations.Steam under the reaction mixture vacuum and remove N-methylmorpholine, water and dimethyl formamide.After residuum is dissolved in 80ml diacetyl oxide (0.82mol), add 13 gram potassium acetates, carry out acetylization reaction as catalyzer (0.132mol).After the cooling, reaction mixture is poured in the frozen water a little, need do not stopped therebetween to stir.Filtering-depositing also washes with water, the solid that obtains is dried to constant weight in 50 ℃ under vacuum, add acetone-methyl alcohol (1: 9), place under 0 ℃, after filtration, processing such as washing, drying, recrystallization, obtain white crystal product 6,1 ', 6 '-three is single to mehtoxybenzyl-pentaacetic acid sucrose ester, shown in figure F.Yield is 66.1%

2. take off etherificate base and ethanoyl transport reaction

Single mehtoxybenzyl-pentaacetic acid sucrose ester (0.039mol) is dissolved in 600 ml concns is in 80% the acetic acid aqueous solution with 50 gram products 6,1 ', 6 '-three, is cooled to 10 ℃ ± 2 ℃ afterreactions 2 hours.Reclaim under reduced pressure acetate.Adding the methyl alcohol stirring separates out single to methoxyl group trityl alcohol solids.After the filtration, methanol solution is through concentrating, and the ether recrystallization washs drying and obtains solid product, and 2,3,6,3 ', 4 '-pentaacetic acid sucrose ester (6-PAS).Yield 62.8%.

So far merge above-mentionedly, the total recovery from sucrose to 6-PAS is 41.5%.

Claims

1. an improved production method of sucralose is characterized in that, may further comprise the steps:

(3) 6-PAS obtains 4 through chloro and deacylated tRNA radical reaction, and 1 ', 6 '-three chloro-, 4,1 ', 6 '-three deoxidation sucralose (being Sucralose): the reaction formula of reaction process is as follows:

2. improved production method of sucralose as claimed in claim 1 is characterized in that: the triphenylmethyl chloride that has pair methoxyl group to replace on the described phenyl ring is single to methoxyl group triphenylmethyl chloride or biconjugate methoxyl group triphenylmethyl chloride or three pairs of methoxyl group triphenylmethyl chlorides.

3. improved production method of sucralose as claimed in claim 1; it is characterized in that: have pair condition of the triphenylmethyl chloride etherificate sucrose of methoxyl group replacement to be on the phenyl ring: to make solvent with dimethyl formamide; N-methylmorpholine is as acid absorber; temperature of reaction is 30～70 ℃; reaction times is 6～10 hours, and reaction is carried out acylation reaction again after neutralization and steaming desolventize.

4. improved production method of sucralose as claimed in claim 1, it is characterized in that: in the step 2, moisture weak acid is that content is 60～95% the formic acid aqueous solution or aqueous acetic acid or the propionic acid aqueous solution or the phenylformic acid aqueous solution or the Succinic Acid aqueous solution.

5. improved production method of sucralose as claimed in claim 1 is characterized in that: the time of taking off etherificate base and acyl migration successive reaction is 1～5 hour.

6. improved production method of sucralose as claimed in claim 1 is characterized in that: take off the etherificate base and acyl migration successive reaction temperature is 0～50 ℃.

7. as any described improved production method of sucralose of claim 4 or 5 or 6, it is characterized in that: take off etherificate base and acyl migration successive reaction in 80% acetic acid, 5～15 ℃ of temperature continue 1.5～2 hours.