CN105801361B - A kind of two replace the synthetic method of dulcitol - Google Patents
A kind of two replace the synthetic method of dulcitol Download PDFInfo
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Abstract
The present invention relates to the synthetic methods that one kind two replaces dulcitol.Provided by the invention two replace dulcitol, i.e. mitolactol synthetic method, and the average yield of gained mitolactol is 50% or more, and for average purity 80% or more, effect is substantially better than the prior art.
Description
Technical field
The present invention relates to chemical drugs fields, and in particular to one kind two replaces the synthetic method of dulcitol.
Background technique
Two replace dulcitol, i.e. mitolactol, also known as dibromo galactitol, are the isomers of dibromannitol, although
It is typically considered alkylating agent, but its effect cannot be explained with alkanisation theory completely, DNA synthesis is inhibited to synthesize compared with RNA
Inhibit strong, it is cell cycle nonspecific agent (CCNSA) that its main metabolites in vivo, which is di-epoxide,.The LD50 of rat
Are as follows: 470mg/kg is injected intraperitoneally in oral 1400mg/kg.Effect is similar to dibromannitol, is converted in vivo with diethyl ring
After the dianhydrogalactitol of oxide structure, alkanisation is played.
Synthesis about mitolactol, it has been disclosed that following preparation method:
" synthesis of anticancer agent Dibromoducitol " " Jiangxi Medical College's journal " second phase in 1984 it is disclosed the preparation method comprises the following steps:
It is under normal pressure 90 DEG C (± 1 DEG C) suitable heating time from melampyrin synthesis Dibromoducitol optimum temperature is 9 hours；Hydrobromic acid
Concentration should be not less than 69-70%, and otherwise yield substantially reduces；Recrystallization solution boiling point cannot be too high, and heating time cannot be too long,
Otherwise yield can all be significantly reduced.The recrystallization mitolactol highest yield for using this method to obtain be 40% (with mole
Meter).
" stability of Dibromoducitol indicates high pressure liquid chromatography in aqueous solution " " external medicine synthetic drug Biochemical Drugs
Preparation fascicle " the 4th phase of volume 10 in 1989, it also refers to the preparation method of mitolactol: galactitol 400mg being placed in cold
Freeze glass reaction kettle and be dissolved in dense HBr 1.2ml, the closed container, is heated 12 hours in 70 water-baths, mixed liquor is poured into
In 3g ice, DBD is crystallized immediately, and after ice all dissolution, filtration, filter residue is dissolved in hot methanol, is recrystallized." this method gained two
The yield of bromine dulcitol does not disclose, and dense HBr refers to the acetum of HBr.
Since dissolubility is all very poor in most solvent for dulcitol, the narrow range for making bromating agent can be selected, to anti-
Condition is answered to require harsh, and method made above is suitable only for laboratory lab scale, because experimental raw is all made of analysis rank, sample
All conditions can disregard cost and accomplish most preferably when trial-production, when mass production, in order to reduce production cost, generally use industry
Grade raw material, condition can not have that yield is low, purity is low such as the mitolactol that laboratory lab scale obtains, and uncomfortable
It is combined to for industry more than feather weight.
Mitolactol technology is prepared by existing, in addition to hydrobromic acid, if usage amount is mostly winged euonymus using remaining bromating agent
10 times or more of alcohol weight could react completely, cause waste of solvent and environmental pollution.When selection hydrobromic acid is bromating agent, if
Obtain the higher mitolactol of purity, must also select the solvent of high-purity, as concentration be 69% hydrobromic acid solution with
On, the mitolactol of 70% or so purity could be obtained, if use low concentration hydrobromic acid solution yield usually 10% with
Under.The maximum concentration hydrobromic acid being commercially available in the market is 62%, is more than this concentration, it is necessary to which oneself is prepared, complex process, behaviour
Make process danger close, and different is surely successfully prepared.
Summary of the invention
The object of the present invention is to provide the synthetic methods that one kind two replaces dulcitol.
Of the present invention a kind of two replace the synthetic method of dulcitol to include bromination step, it is characterised in that: described
Bromination process reaction process carries out under elevated pressure, and the pressure of pressurization is not less than 0.5Mpa at the end of reaction.
Preferably: described being pressurised into is passed through the pressurization of gas gradient type；
Preferably: the gas is to be not involved in react and will not cause reaction dysgenic gas；
The preparation method of mitolactol of the present invention, which is characterized in that the bromination process includes the following steps:
It takes dulcitol to set in reaction kettle, hydrobromic acid solution is added, heating reaction 5-18 hours, heating temperature is 40-70 DEG C, small in 5-18
When reaction time in, pressure is started to step up by 0Mpa, until finally reach 3.0Mpa, is stirred continuously during reaction, instead
It should terminate up to mitolactol solution.
Preferably: the temperature when reaction is 50-60 DEG C；
Preferably: the temperature when reaction is 55 DEG C；
Preferably: the hydrobromic acid solution concentration is 30-62%；
Preferably: the hydrobromic acid solution concentration is 45-55%；
Preferably: the hydrobromic acid solution concentration is 50%；
Preferably: the amount of the hydrobromic acid solution is 2-15 times of dulcitol weight.
Of the present invention a kind of two replace the synthetic method of dulcitol, it is characterised in that include the following steps:
1) it takes dulcitol to set in reaction kettle, 2-15 times of dulcitol weight is added, the hydrobromic acid solution that concentration is 30-62%,
Heating reaction 5-18 hour, heating temperature be 40-70 DEG C, in 5-18 hours reaction time, pressure by 0Mpa gradually
Increase, until finally reaching 3.0Mpa, be stirred continuously during reaction, reaction terminates up to mitolactol solution.
2) mitolactol solution stands 12 hours or more at room temperature, and filtering obtains mitolactol coarse crystallization；
3) mitolactol coarse crystallization recrystallizing methanol is to get mitolactol.
Existing literature document announcement can prepare the mitolactol of 70% or more yield in a short time, and propose using more
The hydrobromic acid of high concentration is reacted (62% or more), and the prior art requires hydrobromic acid concentration 69% or more, to skilled behaviour
Make personnel, a small amount of mitolactol could be obtained, only when hydrobromic acid concentration is 80% or more, 30% or so could be obtained
Yield.Actually these technical solutions are not suitable for large-scale production, reason are as follows:
1, currently without the high concentration of hydrogen bromic acid of commercialization, large-scale production maximum concentration is 62%, is transported, is stored,
To often concentration has been reduced to 60% in actual use.The maximum concentration hydrobromic acid being commercially available currently on the market is 62%, is surpassed
Cross this concentration, it is necessary to oneself is prepared, complex process, operating process danger close, and it is different be surely successfully prepared, and be not suitable for public affairs
Industry more than jin grade is combined to.Therefore unrealistic using the large-scale production of high concentration hydrobromic acid solution.
2, material quality reacts excessively violent without guarantee, and under conditions of high concentration, and not only production environment is dangerous, and
Include excessive impurity in mitolactol crystallization and can not purify.
Since the reaction that dulcitol and hydrobromic acid reaction generate mitolactol is reversible reaction, when reaction just starts, by
Bromine content is high in reaction mass, overreact, terbromide easily generated, tetrabromo compound；With the progress of reaction, raw material
Concentration reduces, and the generation of mitolactol is increasingly difficult to, and can generate monobromo compound because when substitution reaction adds bromine insufficient；
Factors above is the main reason for causing mitolactol yield too low.
After the present invention have passed through a large amount of experimental study and grope, find in mitolactol preparation process, pressure is one
A very crucial factor enables to dulcitol bromination reaction to have higher dibromo by controlling the pressure of reaction process
Selectivity, overcomes the problems, such as that dulcitol bromination reaction side reaction is too many, can be obviously improved mitolactol yield, and final
The higher crystallization of purity can be obtained.
The present invention passes through pressure influence reaction process in bromination process, not strong to hydrobromic acid solution concentration selectivity, it is not necessary to
It is required that using the hydrobromic acid solution of high concentration, hydrobromic acid solution concentration can make reaction smoothly and good between 20-80%
Ground carries out, and the yield of mitolactol and purity can be made to be significantly improved.
The present invention also provides the preferred preparation methods of mitolactol, and give detailed process and technological parameter, lead to
This preferred process control is crossed, so that cooperating the bromating agent and reaction temperature of debita spissitudo during bromination reaction, by difference
The response situation of period, steps up reaction pressure, and control pressure in a certain range, can make dulcitol in bromination process
Selectively being brominated agent replaces two primary hydroxyls to generate mitolactol, can further reduce the generation of by-product,
To preferably improve the yield and purity of industrialization dibromo hexitol.
A kind of synthetic method of two substitutions dulcitol provided by the invention has the advantage that
1, mitolactol purity is high: the obtained mitolactol product purity of the prior art 70% hereinafter, using
The mitolactol that the present invention is prepared, purity reach 80% or more.
2, high income when using the present invention applied to industrialization production mitolactol: the prior art is appropriate only for laboratory
Lab scale, be mass produced mitolactol yield below 40% (in mol), present invention process safe and reasonable, obtained two
Bromine dulcitol average yield is 50% or more.
3, when using low concentration hydrobromic acid solution equally available high yield and high-purity mitolactol, it is low dense
The hydrobromic acid solution of degree is easy to get, and is reduced in mass production to the injury of operator's health and reduced environmental pollution.
Specific embodiment
The present invention is further illustrated below by embodiment.It should be understood that the embodiment of the present invention is for illustrating
The present invention is rather than limiting the invention.The simple modifications that essence according to the present invention carries out the present invention belong to the present invention
Claimed range.Unless otherwise indicated, the percentage of the amount of alcohol in the present invention is percentage by volume, and v/v indicates solution
Volume ratio.
Embodiment 1:
It takes 10kg dulcitol to set in reaction kettle, 15 times of dulcitol weight is added, the hydrobromic acid solution that concentration is 50%, water-bath
55 DEG C are heated to, keep the temperature and is constantly stirred to react 12 hours, nitrogen pressurization is passed through during reaction, with reaction time pressure range
Are as follows: 0-1 hours, pressure gradually added to 0.1MPa by 0MPa；1-5 hours, pressure gradually added to 0.4MPa by 0.1MPa；5-9 is small
When, pressure gradually adds to 0.6MPa by 0.4MPa；9-12 hours, pressure gradually added to 0.8MPa by 0.6MPa；Reaction terminates
Mitolactol solution；Mitolactol solution stands 24 hours at room temperature, and filtering obtains mitolactol coarse crystallization；Dibromo is defended
Lance alcohol coarse crystallization adds the methanol of 100 times of coarse crystallization weight, recrystallizes at 2 DEG C, obtains mitolactol.
Experimental result: mitolactol average yield 59%, average purity 89%.
Embodiment 2:
It takes 10kg dulcitol to set in reaction kettle, 2 times of dulcitol weight is added, the hydrobromic acid solution that concentration is 30%, water-bath
70 DEG C are heated to, keep the temperature and is constantly stirred to react 5 hours, argon pressurization is passed through during reaction, with reaction time pressure range are as follows:
0-2 hours, pressure gradually added to 0.2MPa by 0MPa；2-5 hours, pressure gradually added to 0.5MPa by 0.2MPa；Reaction terminates
Obtain mitolactol solution；Mitolactol solution stands 12 hours at room temperature, and filtering obtains mitolactol coarse crystallization；Dibromo
Dulcitol coarse crystallization adds the methanol of 80 times of coarse crystallization weight, recrystallizes at 6 DEG C, obtains mitolactol.
Experimental result: mitolactol average yield 51%, average purity 81%.
Embodiment 3:
It takes 10kg dulcitol to set in reaction kettle, 6 times of dulcitol weight is added, the hydrobromic acid solution that concentration is 62%, water-bath
40 DEG C are heated to, keep the temperature and is constantly stirred to react 8 hours, helium pressurization is passed through during reaction, with reaction time pressure range are as follows:
0-1 hours, pressure gradually added to 0.1MPa by 0MPa；1-4 hours, pressure gradually added to 0.5MPa by 0.1MPa；4-8 hours,
Pressure gradually adds to 1.0MPa by 0.5MPa；Reaction terminates to obtain mitolactol solution；Mitolactol solution is stood at room temperature
30 hours, filtering obtained mitolactol coarse crystallization；Mitolactol coarse crystallization adds the methanol of 70 times of coarse crystallization weight, at 8 DEG C
Recrystallization, obtains mitolactol.
Experimental result: mitolactol average yield 53%, average purity 85%.
Embodiment 4:
It takes 10kg dulcitol to set in reaction kettle, 8 times of dulcitol weight is added, the hydrobromic acid solution that concentration is 45%, water-bath
60 DEG C are heated to, keep the temperature and is constantly stirred to react 10 hours, carbon dioxide pressurization is passed through during reaction, with reaction time pressurization model
It encloses are as follows: 0-1 hours, pressure gradually added to 0.8MPa by 0MPa；1-5 hours, pressure gradually added to 1.6MPa by 0.8MPa；5-10
Hour, pressure gradually adds to 2.5MPa by 1.6MPa；Reaction terminates to obtain mitolactol solution；Mitolactol solution is at room temperature
48 hours are stood, filtering obtains mitolactol coarse crystallization；Mitolactol coarse crystallization adds the methanol of 60 times of coarse crystallization weight, 4
It is recrystallized at DEG C, obtains mitolactol.
Experimental result: mitolactol average yield 58%, average purity 88%.
Embodiment 5:
It takes 10kg dulcitol to set in reaction kettle, 7 times of dulcitol weight is added, the hydrobromic acid solution that concentration is 55%, water-bath
50 DEG C are heated to, keep the temperature and is constantly stirred to react 15 hours, carbon dioxide pressurization is passed through during reaction, with reaction time pressurization model
It encloses are as follows: 0-1 hours, pressure gradually added to 0.1MPa by 0MPa；1-5 hours, pressure gradually added to 0.3MPa by 0.1MPa；6-10
Hour, pressure gradually adds to 0.6MPa by 0.3MPa；10-15 hours, pressure gradually added to 0.9MPa by 0.6MPa；Reaction terminates
Obtain mitolactol solution；Mitolactol solution stands 18 hours at room temperature, and filtering obtains mitolactol coarse crystallization；Dibromo
Dulcitol coarse crystallization adds the methanol of 50 times of coarse crystallization weight, recrystallizes at 3 DEG C, obtains mitolactol.
Experimental result: mitolactol average yield 54%, average purity 83%.
Embodiment 6:
It takes 8kg dulcitol to set in reaction kettle, 10 times of dulcitol weight is added, the hydrobromic acid solution that concentration is 50%, water-bath
55 DEG C are heated to, keep the temperature and is constantly stirred to react 18 hours, nitrogen pressurization is passed through during reaction, with reaction time pressure range
Are as follows: 0-1 hours, pressure gradually added to 0.5MPa by 0MPa；1-6 hours, pressure gradually added to 1.0MPa by 0.5MPa；6-12 is small
When, pressure gradually adds to 2.0MPa by 1.0MPa；12-18 hours, pressure gradually added to 3.0MPa by 2.0MPa；Reaction terminates
Mitolactol solution；Mitolactol solution stands 20 hours at room temperature, and filtering obtains mitolactol coarse crystallization；Dibromo is defended
Lance alcohol coarse crystallization adds the methanol of 100 times of coarse crystallization weight, recrystallizes at 7 DEG C, obtains mitolactol.
Experimental result: mitolactol average yield 57%, average purity 87%.
Comparative example 1: the embodiment of the present invention 1, no pressure are referred to
It takes 10kg dulcitol to set in reaction kettle, 15 times of dulcitol weight is added, the hydrobromic acid solution that concentration is 50%, water-bath
55 DEG C are heated to, keep the temperature and is constantly stirred to react 12 hours, reaction terminates to obtain mitolactol solution；Mitolactol solution room
Temperature is lower to stand 24 hours, and filtering obtains mitolactol coarse crystallization；Mitolactol coarse crystallization adds the first of 100 times of coarse crystallization weight
Alcohol recrystallizes at 2 DEG C, obtains mitolactol.Experimental result: mitolactol average yield 38%, average purity 67%.
Comparative example 2: the embodiment of the present invention 2, no pressure are referred to
It takes 10kg dulcitol to set in reaction kettle, 2 times of dulcitol weight is added, the hydrobromic acid solution that concentration is 30%, water-bath
70 DEG C are heated to, keep the temperature and is constantly stirred to react 5 hours, reaction terminates to obtain mitolactol solution；Mitolactol solution room
Temperature is lower to stand 12 hours, and filtering obtains mitolactol coarse crystallization；Mitolactol coarse crystallization adds the first of 80 times of coarse crystallization weight
Alcohol recrystallizes at 6 DEG C, obtains mitolactol.
Experimental result: mitolactol average yield 35%, average purity 65%.
Comparative example 3: the embodiment of the present invention 3, no pressure are referred to
It takes 10kg dulcitol to set in reaction kettle, 6 times of dulcitol weight is added, the hydrobromic acid solution that concentration is 62%, water-bath
40 DEG C are heated to, keep the temperature and is constantly stirred to react 8 hours, reaction terminates to obtain mitolactol solution；Mitolactol solution room
Temperature is lower to stand 30 hours, and filtering obtains mitolactol coarse crystallization；Mitolactol coarse crystallization adds the first of 70 times of coarse crystallization weight
Alcohol recrystallizes at 8 DEG C, obtains mitolactol.
Experimental result: mitolactol average yield 36%, average purity 64%.
Comparative example 4: the embodiment of the present invention 4, no pressure are referred to
It takes 10kg dulcitol to set in reaction kettle, 8 times of dulcitol weight is added, the hydrobromic acid solution that concentration is 45%, water-bath
60 DEG C are heated to, keep the temperature and is constantly stirred to react 10 hours；Reaction terminates to obtain mitolactol solution；Mitolactol solution room
Temperature is lower to stand 48 hours, and filtering obtains mitolactol coarse crystallization；Mitolactol coarse crystallization adds the first of 60 times of coarse crystallization weight
Alcohol recrystallizes at 4 DEG C, obtains mitolactol.
Experimental result: mitolactol average yield 33%, average purity 63%.
Comparative example 5: the embodiment of the present invention 5, no pressure are referred to
It takes 10kg dulcitol to set in reaction kettle, 7 times of dulcitol weight is added, the hydrobromic acid solution that concentration is 55%, water-bath
50 DEG C are heated to, keep the temperature and is constantly stirred to react 15 hours；Reaction terminates to obtain mitolactol solution；Mitolactol solution room
Temperature is lower to stand 18 hours, and filtering obtains mitolactol coarse crystallization；Mitolactol coarse crystallization adds the first of 50 times of coarse crystallization weight
Alcohol recrystallizes at 3 DEG C, obtains mitolactol.
Experimental result: mitolactol average yield 32%, average purity 59%.
Process ration experiment:
Experimental method: disclosed reaction pressure, reaction temperature and hydrobromic acid solution concentration according to the present invention prepare embodiment
1-6 sample；On the basis of the preparation method for wanting embodiment 1-5, the reaction condition of pressurization is subtracted, prepares comparative example 1-5 sample respectively
Product.It the results are shown in Table 1.
Yield calculation method:
Method for detecting purity: method for detecting purity: shining high effective liquid chromatography for measuring, by external standard method with calculated by peak area,
To obtain the final product.Reference substance is laboratory self-control, purity 98.57%.
Table 1: mitolactol yield and purity
Table 1 is as the result is shown: comparative example 1-5 respectively corresponds the operating procedure of embodiment 1-5, only subtracts compressive reaction item
Part, the yield of mitolactol have a significant difference with purity compared with pressurization, average yield the 56-68% of embodiment it
Between, average purity is between the 70-80% of embodiment.
The results showed that pressing response parameter provided by the invention, it may be significantly and prepare institute better than existing technical solution
Obtain the effect of mitolactol.
Although above having used general explanation, specific embodiment and test, the present invention is made to retouch in detail
It states, but on the basis of the present invention, it can be made some modifications or improvements, this is apparent to those skilled in the art
's.Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, belong to claimed
Range.
Claims (9)
1. a kind of synthetic method of mitolactol, including bromination step, it is characterised in that: the bromination process reaction process
Using hydrobromic acid solution as bromating agent, and carry out under elevated pressure；Described being pressurised into is passed through the pressurization of gas gradient type；The pressurization
Pressure is not less than 0.5Mpa at the end of reaction；The gas is to be not involved in react and will not cause adverse effect to reaction
Gas, the gas be nitrogen, argon gas, carbon dioxide or helium.
2. synthetic method as described in claim 1, which is characterized in that the bromination process includes the following steps:
It takes dulcitol to set in reaction kettle, hydrobromic acid solution is added, heating reaction 5-18 hours, heating temperature is 40-70 DEG C, in 5-
In 18 hours reaction time, pressure is started to step up by 0Mpa, until finally reaching 3.0Mpa, is constantly stirred during reaction
It mixes, reaction terminates up to mitolactol solution.
3. synthetic method as claimed in claim 2, which is characterized in that the temperature when reaction is 50-60 DEG C.
4. synthetic method as claimed in claim 2, which is characterized in that the temperature when reaction is 55 DEG C.
5. synthetic method as claimed in claim 2, which is characterized in that the hydrobromic acid solution concentration is 30-62%.
6. synthetic method as claimed in claim 2, which is characterized in that the hydrobromic acid solution concentration is 45-55%.
7. synthetic method as claimed in claim 2, which is characterized in that the hydrobromic acid solution concentration is 50%.
8. such as the described in any item synthetic methods of claim 5-7, which is characterized in that the weight of the hydrobromic acid solution is winged euonymus
2-15 times of alcohol weight.
9. the synthetic method of mitolactol as described in claim 1, it is characterised in that include the following steps:
1) it takes dulcitol to set in reaction kettle, 2-15 times of dulcitol weight is added, the hydrobromic acid solution that concentration is 30-62%, heating
Reaction 5-18 hours, heating temperature are 40-70 DEG C, and in 5-18 hours reaction time, pressure is started to step up by 0Mpa,
Until finally reaching 3.0Mpa, it is stirred continuously during reaction, reaction terminates up to mitolactol solution；
2) mitolactol solution stands 12 hours or more at room temperature, and filtering obtains mitolactol coarse crystallization；
3) mitolactol coarse crystallization recrystallizing methanol is to get mitolactol.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080107598A1 (en) * | 2006-10-05 | 2008-05-08 | Yang David J | Efficient Synthesis of Chelators for Nuclear Imaging and Radiotherapy: Compositions and Applications |
| CN103270035A (en) * | 2010-08-18 | 2013-08-28 | 德玛医药 | Method of synthesis of substituted hexitols such as dianhydrogalactitol |
| CN103923039A (en) * | 2014-01-30 | 2014-07-16 | 天津中津药业股份有限公司 | Method for preparing dianhydrogalactitol |
-
2014
- 2014-12-30 CN CN201410839603.0A patent/CN105801361B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080107598A1 (en) * | 2006-10-05 | 2008-05-08 | Yang David J | Efficient Synthesis of Chelators for Nuclear Imaging and Radiotherapy: Compositions and Applications |
| CN103270035A (en) * | 2010-08-18 | 2013-08-28 | 德玛医药 | Method of synthesis of substituted hexitols such as dianhydrogalactitol |
| CN103923039A (en) * | 2014-01-30 | 2014-07-16 | 天津中津药业股份有限公司 | Method for preparing dianhydrogalactitol |
Non-Patent Citations (1)
| Title |
|---|
| 抗癌剂二溴卫茅醇的合成;刘铭勋等;《江西医学院学报》;19841231(第2期);第8-9页 * |
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