CN105801351A - Application of cation exchange resin to improvement of yield in bromination reaction of hexanehexol - Google Patents
Application of cation exchange resin to improvement of yield in bromination reaction of hexanehexol Download PDFInfo
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Abstract
The invention relates to an application of cation exchange resin to a bromination reaction of hexanehexol. Yield of dibromohexanehexol is substantially increased in the preparation processes of dibromohexanehexol from hexanehexol by using the cation exchange resin, and the effects are obviously better than the effects in the prior art.
Description
Technical field
The present invention relates to chemical drugs field, be specifically related to cation exchange resin in the purposes promoting hexanhexol bromination reaction yield.
Background technology
The compositions that hexanhexol is made up of fatty acid ester and the many alcohol of no esterification of hexitan (sorbitan), wherein no esterification many alcohol content is 0.05-6.59%.Common hexanhexol has mannitol, dulcitol, sorbitol etc. several.
During according to published technical method large-scale production dibromo hexitol, the dibromo hexitol crystallization purity of gained is not high, yield is unstable.In order to improve the yield of large-scale production, it is necessary to saving improvement of production process on the basis of cost.
Cation exchange resin, a kind of chemical substance, mainly for the manufacture of the purification of refined sugar and senior table syrup.
Containing a kind of (or several) chemical active radical in ion exchange resin, namely it is exchange functional group, some cation (such as h or na) or anion (such as oh-or cl-) can be dissociated out in aqueous, other cationes simultaneously originally having in adsorbent solution or anion.Namely the ion in resin is intercoursed with the ion in solution, thus by the ion isolation in solution out.
Ion exchange (ionexchangeprocess) is the ion in liquid phase and a kind of reversible chemical reaction carried out between solid phase intermediate ion, when comparatively ion exchange solid is liked for some ion in liquid phase, solid absorption will be ion exchanged, for maintaining the electric neutrality of aqueous solution, so ion exchange solid must disengage in equivalent ionic back dissolving liquid.
Cation exchange resin is typically used in the following aspects: 1, dehydration of alcohols synthesis ether；2, the etherification reaction of alcohol and alkene；3, esterification；4, alkylated reaction；5, isomerization and substituent group transfer reaction；6, acylation reaction；7, polyreaction；8, acetal, ketal reaction；9, ring-opening reaction and ring closure reaction；10, rearrangement reaction；11, substitution reaction.
The current application there are no cation exchange resin in hexanhexol bromination process.
Summary of the invention
It is an object of the invention to provide cation exchange resin and promote the purposes of hexanhexol bromination reaction yield.
Preferably, described cationic resin is gel-type, macroporous type, strong acid, faintly acid, polystyrene, acrylic acid series positive resin, strongly acidic styrene type cation exchange resin, macropore styrene ion exchange resin, weakly acidic cationic exchange resin of acrylic series, macropore strong acid cation exchanger resin.
Preferably, the 0.1-10% that described cation exchange resin makes consumption be hexanhexol weight.
Preferably, described cation exchange resin acid treatment adds in reaction solution when being 2-4 to pH.
Preferably, described hexanhexol is mannitol, dulcitol, sorbitol.
Preferably, described cation exchange resin using method is:
First hexanhexol being put into reaction vessel, then with mixing hydrobromic acid solution, cation exchange resin is together added reaction vessel, heating is also constantly reacted, and making hexanhexol bromination is dibromo hexanhexol；
Or hexanhexol is put into reaction vessel, add mixing hydrobromic acid solution reaction to after crystallization occurs, add cation exchange resin, organic acid or hydrogen bromide organic acid soln, keep heating and be stirred continuously, continue reaction 2～24 hours, letting cool to room temperature, stand more than 5 hours, making hexanhexol bromination is dibromo hexanhexol；
Described mixing hydrobromic acid solution is hydrobromic acid aqueous solution and organic acid mixed liquor, or the mixed liquor of hydrobromic acid aqueous solution and hydrogen bromide organic acid soln；.
Preferably, described hexanhexol bromination reaction comprises the steps:
A hexanhexol is put in reaction vessel by (), add mixing hydrobromic acid solution and cation exchange resin；Described mixing hydrobromic acid solution is hydrobromic acid aqueous solution and organic acid mixed liquor, or the mixed liquor of hydrobromic acid aqueous solution and hydrogen bromide organic acid soln；
B () heats to 30～70 DEG C, continuously stirred, makes hexanhexol dissolve, and continues heating and stirs to crystallization occur；
C () adds organic acid or hydrogen bromide organic acid soln, keep the temperature of step b) and be stirred continuously, and continues reaction 2～24 hours, lets cool to room temperature, stand more than 5 hours；
D () is filtered and is cleaned, dry, obtains dibromo hexanhexol coarse crystallization.
Preferably, described hexanhexol bromination reaction comprises the steps:
A hexanhexol is put in reaction vessel by (), add mixing hydrobromic acid solution；Described mixing hydrobromic acid solution is hydrobromic acid aqueous solution and organic acid mixed liquor, or the mixed liquor of hydrobromic acid aqueous solution and hydrogen bromide organic acid soln；
B () heats and is stirred continuously, make hexanhexol dissolve, and continues heating and stirs to crystallization occur；
C () adds cation exchange resin, organic acid or hydrogen bromide organic acid soln, keep heating and be stirred continuously, and continues reaction 2～24 hours, lets cool to room temperature, stand more than 5 hours；
D () is filtered and is cleaned, dry, obtains dibromo hexanhexol coarse crystallization.
Preferably, in described step (a), hexanhexol is 1:1-20 with the mass ratio mixing hydrobromic acid solution.
Preferably, in described step (a), the concentration of hydrobromic acid aqueous solution is 20-80%.
Preferably, the mixed liquor of hydrobromic acid aqueous solution and organic acid or hydrogen bromide organic acid soln in described step (a), mass ratio is 1:0.001～2.
Preferably, described organic acid is formic acid, acetic acid, propanoic acid or butanoic acid；Described hydrogen bromide organic acid soln is containing the formic acid solution that bromination hydrogen concentration is 0.01%～33%, acetic acid solution, propionic acid solution or butanoic acid solution.
Preferably, in described step (c), the continuation response time is 16～22 hours.
Preferably, described step (b) heating-up temperature is to 30～45 DEG C.
Described gel type resin includes but not limited to several as follows: AmberliteIR120Na, Amberjet1200Na
Described macroporous ion-exchange resin includes but not limited to several as follows: D001, D002, D751, D113
Described strong acid type resin includes but not limited to several as follows: 732,734,7120Na, Dowex50W-X8,
Described weak-type resin includes but not limited to several as follows: D113, HD-2, D851,724
Described styrene type resin includes but not limited to several as follows: 732, D751,7120Na, 001 × 3
Described acrylic type resin includes but not limited to several as follows: D113, D155, D110, D112
It is reversible reaction owing to hexanhexol generates the reaction of dibromo hexanhexol, when reaction just starts, owing in reaction mass, bromine content is high, overresponse, easily generate terbromide, tetrabormated compound, many bromines substituent and other product；Along with the carrying out of reaction, material concentration reduces, and the generation of dibromo hexanhexol is increasingly difficult to, and because adding bromine deficiency during substitution reaction, can generate monobromo compound；Factors above is the main cause causing dibromo hexanhexol yield too low.
For making technique simplify, and obtaining the dibromo hexanhexol of high yield, the present inventor finds a kind of simple, safe solution, by adding cation exchange resin in course of reaction, makes the yield of dibromo hexanhexol be greatly improved.By resin absorption on surface after the heated dissolving of hexanhexol, in being stirred continuously process, bromide ion exchanges with cation generation ion, enter the active center of resin, now, the hexanhexol being adsorbed on resin surface reacts with the bromide ion entering resin activity center, thus generating dibromo hexanhexol.Carrier function is played in cation exchange in course of reaction, improves the selectivity that dibromo hexanhexol generates, therefore improve yield after adding resin cation exchange.To different types of hexitol, yield impact is different, wherein, the impact of dulcitol is obvious.Use different bromating agent, variable concentrations, different temperatures reaction condition under, add resin reaction gained mitolactol compared with not adding resin gained mitolactol, yield improves more than 50%.
Cation exchange resin provided by the invention promotes the purposes of hexanhexol bromination reaction yield and has the advantage that
1, dibromo hexanhexol yield is compared with technique under the same terms not adding cation exchange resin, and yield significantly improves.
2, use different bromating agent, variable concentrations, different temperatures reaction condition under, add cation exchange resin reaction gained mitolactol compared with not adding resin gained mitolactol, yield improves more than 50%.
3, cation exchange resin is readily available, and reduces to obtain high yield, uses hazardous agents to the injury of operator ' s health and to reduce environmental pollution.
4, using low concentration reagent reacting at a lower temperature, product dibromo hexanhexol all can obtain comparatively ideal yield and purity.The reaction condition of low-temperature and low-concentration is easily controllable, low for equipment requirements.
Detailed description of the invention
Further illustrate the present invention by the examples below.It should be understood that embodiments of the invention are an illustration for the present invention rather than limitation of the present invention.The simple modifications that the present invention is carried out by the essence according to the present invention broadly falls into the scope of protection of present invention.Except as otherwise noted, the percent of the amount of alcohol in the present invention is percentage by volume, and v/v represents the volume ratio of solution.
Embodiment 1:
A 10kg dulcitol is put in reactor by (), add 100g acid treatment to the gel type resin AmberliteIR-120 that PH is 2, being simultaneously introduced 65% hydrobromic acid aqueous solution: the mixed liquor of acetic acid=1:1.5 (weight ratio), addition is 20 times of dulcitol weight；
B () heating in water bath is to 65 DEG C and be stirred continuously, and makes dulcitol dissolve, and then proceedes to heating and stirs until there is crystallization；
C () adds the formic acid of dulcitol weight 5 times, keep 65 DEG C and be stirred continuously, and continues reaction 2 hours, lets cool to room temperature, stand 5 hours；
D () reactant liquor adds 1 times amount water dilution, filter, and filter cake is washed with water to neutrality, drains, and adds the soak with ethanol 0.1 hour that 0.5 times of concentration of volume percent is 60%, drains, and 25 DEG C are decompressed to-0.01MPa and dry, obtain mitolactol coarse crystallization；Mitolactol coarse crystallization adds the methanol of 100 times of coarse crystallization weight, recrystallization at 4 DEG C, obtains mitolactol.
Experimental result: mitolactol average yield 46%, average purity is 80%.
Embodiment 2:
A 10kg sorbitol is put in reactor by (), add 80% hydrobromic acid aqueous solution: the mixed liquor of acetic acid=1:0.001 (weight ratio), and addition is 18 times of sorbitol weight；
B () heating in water bath is to 50 DEG C and be stirred continuously, and makes sorbitol dissolve, and then proceedes to heating and stirs until there is crystallization；
C () adds 600g acid treatment to the macroporous resin D001 that pH value is 2.3, be simultaneously introduced the acetic acid of sorbitol weight 3 times, keep 50 DEG C and be stirred continuously, and continues reaction 8 hours, lets cool to room temperature, stand 6 hours；
D () reactant liquor adds 2 times amount water dilutions, filter, and filter cake is washed with water to neutrality, drains, and adds the soak with ethanol 0.2 hour that 1 times of concentration of volume percent is 50%, drains, and 30 DEG C are decompressed to-0.02MPa and dry, and obtain dibromo sorbitol coarse crystallization；Dibromo sorbitol coarse crystallization adds the methanol of 70 times of coarse crystallization weight, recrystallization at 6 DEG C, obtains dibromo sorbitol.
Experimental result: dibromo sorbitol average yield 47%, average purity is 80%.
Embodiment 3:
A 10kg mannitol is put in reactor by (), add 10g acid treatment to the strong acid type resin 732 that PH is 2.5, be simultaneously introduced 70% hydrobromic acid aqueous solution: the mixed liquor of acetic acid=1:2 (weight ratio), and addition is 10 times of mannitol weight；
B () heating in water bath is to 70 DEG C and be stirred continuously, and makes mannitol dissolve, and then proceedes to heating and stirs until there is crystallization；
C () adds mannitol weight 1 again containing the acetic acid of 10% hydrogen bromide, keep 70 DEG C and be stirred continuously, and continues reaction 10 hours, lets cool to room temperature, stand 10 hours；
D () reactant liquor adds 3 times amount water dilutions, filter, and filter cake is washed with water to neutrality, drains, and adds the soak with ethanol 0.5 hour that 5 times of concentration of volume percent are 65%, drains, and 50 DEG C are decompressed to-0.05MPa and dry, obtain mitobronitol coarse crystallization；Mitobronitol coarse crystallization adds the methanol of 80 times of coarse crystallization weight, recrystallization at 2 DEG C, obtains mitobronitol.
Experimental result: mitobronitol average yield 50%, average purity is 86%.
Embodiment 4:
A 10kg mannitol is put in reactor by (), add 45% hydrobromic acid aqueous solution: the mixed liquor of acetic acid=1:0.1 (weight ratio), and addition is 1 times of mannitol weight；
B () heating in water bath is to 40 DEG C and be stirred continuously, and makes mannitol dissolve, and then proceedes to heating and stirs until there is crystallization；
C () adds 1000g acid treatment to the weak-type resin D113 that pH value is 4.0, be simultaneously introduced mannitol weight 0.01 again containing the formic acid of 33% hydrogen bromide, keep 40 DEG C and be stirred continuously, and continues reaction 16 hours, lets cool to room temperature, stand 8 hours；
D () reactant liquor adds 2 times amount water dilutions, filter, and filter cake is washed with water to neutrality, drains, and adds the soak with ethanol 1 hour that 100 times of concentration of volume percent are 70%, drains, and 65 DEG C are decompressed to-0.1MPa and dry, obtain mitobronitol coarse crystallization；Mitobronitol coarse crystallization adds the methanol of 150 times of coarse crystallization weight, recrystallization at 5 DEG C, obtains mitobronitol.
Experimental result: mitobronitol average yield 52%, average purity is 94%.
Embodiment 5:
A 10kg dulcitol is put in reactor by (), add 800g acid treatment to the styrene type resin D751 that PH is 3.0, being simultaneously introduced 35% hydrobromic acid aqueous solution: the mixed liquor of acetic acid=1:0.005 (weight ratio), addition is 12 times of dulcitol weight；
B () heating in water bath is to 30 DEG C and be stirred continuously, and makes dulcitol dissolve, and then proceedes to heating and stirs until there is crystallization；
C () adds the propanoic acid of dulcitol weight 0.1 times, keep 30 DEG C and be stirred continuously, and continues reaction 15 hours, lets cool to room temperature, stand 15 hours；
D () reactant liquor adds 1 times amount water dilution, filter, and filter cake is washed with water to neutrality, drains, and adds the soak with ethanol 2 hours that 50 times of concentration of volume percent are 55%, drains, and 40 DEG C are decompressed to-0.5MPa and dry, obtain mitolactol coarse crystallization；Mitolactol coarse crystallization adds the methanol of 90 times of coarse crystallization weight, recrystallization at 3 DEG C, obtains mitolactol.
Experimental result: mitolactol average yield 54%, average purity is 92%.
Embodiment 6:
A 10kg sorbitol is put in reactor by (), add 20% hydrobromic acid aqueous solution: the mixed liquor of acetic acid=1:0.5 (weight ratio), and addition is 8 times of sorbitol weight；
B () heating in water bath is to 60 DEG C and be stirred continuously, and makes sorbitol dissolve, and then proceedes to heating and stirs until there is crystallization；
C () adds 50g acid treatment is the acrylic type resin D852 of 3.2 to pH value, is simultaneously introduced sorbitol weight 0.5 again containing the propanoic acid of 0.1% hydrogen bromide, keeps 60 DEG C and be stirred continuously, and continues reaction 22 hours, lets cool to room temperature, stand 12 hours；
D () reactant liquor adds 3 times amount water dilutions, filter, and filter cake is washed with water to neutrality, drains, and adds the soak with ethanol 0.5 hour that 10 times of concentration of volume percent are 60%, drains, and 50 DEG C are decompressed to-0.03MPa and dry, and obtain dibromo sorbitol coarse crystallization；Dibromo sorbitol coarse crystallization adds the methanol of 100 times of coarse crystallization weight, recrystallization at 4 DEG C, obtains dibromo sorbitol.
Experimental result: dibromo sorbitol average yield 53%, average purity is 93%.
Embodiment 7:
A 10kg sorbitol is put in reactor by (), add 400g acid treatment to the strongly acidic styrene type cation exchange resin 001 × 10 that PH is 3.5, being simultaneously introduced 55% hydrobromic acid aqueous solution: the mixed liquor of acetic acid=1:0.01 (weight ratio), addition is 15 times of sorbitol weight；
B () heating in water bath is to 45 DEG C and be stirred continuously, and makes sorbitol dissolve, and then proceedes to heating and stirs until there is crystallization；
C () adds sorbitol weight 2 again containing the butanoic acid of 20% hydrogen bromide, keep 45 DEG C and be stirred continuously, and continues reaction 24 hours, lets cool to room temperature, stand 16 hours；
D () reactant liquor adds 2 times amount water dilutions, filter, and filter cake is washed with water to neutrality, drains, and adds the soak with ethanol 1 hour that 0.5 times of concentration of volume percent is 70%, drains, and 25 DEG C are decompressed to-0.1MPa and dry, and obtain dibromo sorbitol coarse crystallization；Dibromo sorbitol coarse crystallization adds the methanol of 90 times of coarse crystallization weight, recrystallization at 3 DEG C, obtains dibromo sorbitol.
Experimental result: dibromo sorbitol average yield 55%, average purity is 95%.
Embodiment 8:
A 10kg mannitol is put in reactor by (), add 30% hydrobromic acid aqueous solution: the mixed liquor of acetic acid=1:1 (weight ratio), and addition is 5 times of mannitol weight；
B () heating in water bath is to 35 DEG C and be stirred continuously, and makes mannitol dissolve, and then proceedes to heating and stirs until there is crystallization；
C () adds 200g acid treatment to the macropore styrene ion exchange resin D-61 that pH value is 3.7, be simultaneously introduced the butanoic acid of mannitol weight 1 times, keep 35 DEG C and be stirred continuously, and continues reaction 6 hours, lets cool to room temperature, stand 18 hours；
D () reactant liquor adds 5 times amount water dilutions, filter, and filter cake is washed with water to neutrality, drains, and adds the soak with ethanol 0.1 hour that 100 times of concentration of volume percent are 55%, drains, and 25 DEG C are decompressed to-1MPa and dry, obtain mitobronitol coarse crystallization；Mitobronitol coarse crystallization adds the methanol of 150 times of coarse crystallization weight, recrystallization at 5 DEG C, obtains mitobronitol.
Experimental result: mitobronitol average yield 53%, average purity is 92%.
Embodiment 9:
A 10kg dulcitol is put in reactor by (), add 300g acid treatment to the weakly acidic cationic exchange resin of acrylic series D151 that PH is 3.9, being simultaneously introduced 45% hydrobromic acid aqueous solution: the mixed liquor of acetic acid=1:1.8 (weight ratio), addition is 3 times of dulcitol weight；
B () heating in water bath is to 45 DEG C and be stirred continuously, and makes dulcitol dissolve, and then proceedes to heating and stirs until there is crystallization；
C () adds dulcitol weight 4 again containing the acetic acid of 1% hydrogen bromide, keep 45 DEG C and be stirred continuously, and continues reaction 16 hours, lets cool to room temperature, stand 20 hours；
D () reactant liquor adds 2 times amount water dilutions, filter, and filter cake is washed with water to neutrality, drains, and adds the soak with ethanol 1 hour that 0.5 times of concentration of volume percent is 70%, drains, and 25 DEG C are decompressed to-0.1MPa and dry, obtain mitolactol coarse crystallization；Mitolactol coarse crystallization adds the methanol of 90 times of coarse crystallization weight, recrystallization at 3 DEG C, obtains mitolactol.
Experimental result: mitolactol average yield 52%, average purity is 96%.
Embodiment 10:
A 10kg dulcitol is put in reactor by (), add 60% hydrobromic acid aqueous solution: the mixed liquor of acetic acid=1:0.8 (weight ratio), and addition is 16 times of dulcitol weight；
B () heating in water bath is to 55 DEG C and be stirred continuously, and makes dulcitol dissolve, and then proceedes to heating and stirs until there is crystallization；
C () adds 700g acid treatment to the macropore strong acid cation exchanger resin D-62 that pH value is 2.8, be simultaneously introduced the formic acid of dulcitol weight 0.5 times, keep 55 DEG C and be stirred continuously, and continues reaction 9 hours, lets cool to room temperature, stand 12 hours；
D () reactant liquor adds 5 times amount water dilutions, filter, and filter cake is washed with water to neutrality, drains, and adds the soak with ethanol 0.1 hour that 100 times of concentration of volume percent are 55%, drains, and 25 DEG C are decompressed to-1MPa and dry, obtain mitolactol coarse crystallization；Mitolactol coarse crystallization adds the methanol of 150 times of coarse crystallization weight, recrystallization at 5 DEG C, obtains mitolactol.
Experimental result: mitolactol average yield 54%, average purity is 92%.
Comparative example 1: with reference to the embodiment of the present invention 1, without resin, step C is without organic acid or hydrogen bromide organic acid soln
A 10kg dulcitol is put in reactor by (), add 65% hydrobromic acid aqueous solution: the mixed liquor of acetic acid=1:1.5 (weight ratio), and addition is 20 times of dulcitol weight；
B () heating in water bath is to 65 DEG C and be stirred continuously, and makes dulcitol dissolve, and then proceedes to heating and stirs until there is crystallization；
C () keeps 65 DEG C and is stirred continuously, continue reaction 5 hours, let cool to room temperature, stand 2 hours；
D () reactant liquor adds 1 times amount water dilution, filter, and filter cake is washed with water to neutrality, drains, and adds the soak with ethanol 0.1 hour that 0.5 times of concentration of volume percent is 60%, drains, and 25 DEG C are decompressed to-0.01MPa and dry, obtain mitolactol coarse crystallization；Mitolactol coarse crystallization adds the methanol of 100 times of coarse crystallization weight, recrystallization at 4 DEG C, obtains mitolactol.
Experimental result: mitolactol average yield 32%, average purity is 65%.
Comparative example 2: with reference to the embodiment of the present invention 2, without resin, step C is without organic acid or hydrogen bromide organic acid soln
A 10kg sorbitol is put in reactor by (), add 80% hydrobromic acid aqueous solution: the mixed liquor of acetic acid=1:0.001 (weight ratio), and addition is 18 times of sorbitol weight；
B () heating in water bath is to 50 DEG C and be stirred continuously, and makes sorbitol dissolve, and then proceedes to heating and stirs until there is crystallization；
C () keeps 50 DEG C and is stirred continuously, continue reaction 8 hours, let cool to room temperature, stand 6 hours；
D () reactant liquor adds 2 times amount water dilutions, filter, and filter cake is washed with water to neutrality, drains, and adds the soak with ethanol 0.2 hour that 1 times of concentration of volume percent is 50%, drains, and 30 DEG C are decompressed to-0.02MPa and dry, and obtain dibromo sorbitol coarse crystallization；Dibromo sorbitol coarse crystallization adds the methanol of 70 times of coarse crystallization weight, recrystallization at 6 DEG C, obtains dibromo sorbitol.
Experimental result: dibromo sorbitol average yield 31%, average purity is 67%.
Comparative example 3: with reference to the embodiment of the present invention 3, without resin, step C is without organic acid or hydrogen bromide organic acid soln
A 10kg mannitol is put in reactor by (), add 70% hydrobromic acid aqueous solution: the mixed liquor of acetic acid=1:2 (weight ratio), and addition is 10 times of mannitol weight；
B () heating in water bath is to 70 DEG C and be stirred continuously, and makes mannitol dissolve, and then proceedes to heating and stirs until there is crystallization；
C () keeps 70 DEG C and is stirred continuously, continue reaction 10 hours, let cool to room temperature, stand 10 hours；
D () reactant liquor adds 3 times amount water dilutions, filter, and filter cake is washed with water to neutrality, drains, and adds the soak with ethanol 0.5 hour that 5 times of concentration of volume percent are 65%, drains, and 50 DEG C are decompressed to-0.05MPa and dry, obtain mitobronitol coarse crystallization；Mitobronitol coarse crystallization adds the methanol of 80 times of coarse crystallization weight, recrystallization at 2 DEG C, obtains mitobronitol.
Experimental result: mitobronitol average yield 30%, average purity is 63%.
Comparative example 4: with reference to the embodiment of the present invention 4, without resin
A 10kg mannitol is put in reactor by (), add 45% hydrobromic acid aqueous solution: the mixed liquor of acetic acid=1:0.1 (weight ratio), and addition is 1 times of mannitol weight；
B () heating in water bath is to 40 DEG C and be stirred continuously, and makes mannitol dissolve, and then proceedes to heating and stirs until there is crystallization；
C () adds mannitol weight 0.01 again containing the formic acid of 33% hydrogen bromide, keep 40 DEG C and be stirred continuously, and continues reaction 16 hours, lets cool to room temperature, stand 8 hours；
D () reactant liquor adds 2 times amount water dilutions, filter, and filter cake is washed with water to neutrality, drains, and adds the soak with ethanol 1 hour that 100 times of concentration of volume percent are 70%, drains, and 65 DEG C are decompressed to-0.1MPa and dry, obtain mitobronitol coarse crystallization；Mitobronitol coarse crystallization adds the methanol of 150 times of coarse crystallization weight, recrystallization at 5 DEG C, obtains mitobronitol.
Experimental result: mitobronitol average yield 39%, average purity is 71%.
Comparative example 5: with reference to the embodiment of the present invention 9, without resin
A 10kg dulcitol is put in reactor and adds 45% hydrobromic acid aqueous solution by (): the mixed liquor of acetic acid=1:1.8 (weight ratio), addition is 3 times of dulcitol weight；
B () heating in water bath is to 45 DEG C and be stirred continuously, and makes dulcitol dissolve, and then proceedes to heating and stirs until there is crystallization；
C () adds dulcitol weight 4 again containing the acetic acid of 1% hydrogen bromide, keep 45 DEG C and be stirred continuously, and continues reaction 16 hours, lets cool to room temperature, stand 20 hours；
D () reactant liquor adds 2 times amount water dilutions, filter, and filter cake is washed with water to neutrality, drains, and adds the soak with ethanol 1 hour that 0.5 times of concentration of volume percent is 70%, drains, and 25 DEG C are decompressed to-0.1MPa and dry, obtain mitolactol coarse crystallization；Mitolactol coarse crystallization adds the methanol of 90 times of coarse crystallization weight, recrystallization at 3 DEG C, obtains mitolactol.
Experimental result: mitolactol average yield 41%, average purity is 73%.
Comparative example 6: with reference to the embodiment of the present invention 6, without resin
A 10kg sorbitol is put in reactor by (), add 20% hydrobromic acid aqueous solution: the mixed liquor of acetic acid=1:0.5 (weight ratio), and addition is 8 times of sorbitol weight；
B () heating in water bath is to 60 DEG C and be stirred continuously, and makes sorbitol dissolve, and then proceedes to heating and stirs until there is crystallization；
C () adds sorbitol weight 0.5 again containing the propanoic acid of 0.1% hydrogen bromide, keep 60 DEG C and be stirred continuously, and continues reaction 22 hours, lets cool to room temperature, stand 12 hours；
D () reactant liquor adds 3 times amount water dilutions, filter, and filter cake is washed with water to neutrality, drains, and adds the soak with ethanol 0.5 hour that 10 times of concentration of volume percent are 60%, drains, and 50 DEG C are decompressed to-0.03MPa and dry, and obtain dibromo sorbitol coarse crystallization；Dibromo sorbitol coarse crystallization adds the methanol of 100 times of coarse crystallization weight, recrystallization at 4 DEG C, obtains dibromo sorbitol.
Experimental result: dibromo sorbitol average yield 41%, average purity is 70%.
Comparative example 7: with reference to the embodiment of the present invention 9, step C is without organic acid or hydrogen bromide organic acid soln
A 10kg dulcitol is put in reactor by (), add 300g acid treatment to the weakly acidic cationic exchange resin of acrylic series D151 that PH is 3.9, being simultaneously introduced 45% hydrobromic acid aqueous solution: the mixed liquor of acetic acid=1:1.8 (weight ratio), addition is 3 times of dulcitol weight；
B () heating in water bath is to 45 DEG C and be stirred continuously, and makes dulcitol dissolve, and then proceedes to heating and stirs until there is crystallization；
C () adds dulcitol weight 4 again containing the acetic acid of 1% hydrogen bromide, keep 45 DEG C and be stirred continuously, and continues reaction 16 hours, lets cool to room temperature, stand 20 hours；
D () reactant liquor adds 2 times amount water dilutions, filter, and filter cake is washed with water to neutrality, drains, and adds the soak with ethanol 1 hour that 0.5 times of concentration of volume percent is 70%, drains, and 25 DEG C are decompressed to-0.1MPa and dry, obtain mitolactol coarse crystallization；Mitolactol coarse crystallization adds the methanol of 90 times of coarse crystallization weight, recrystallization at 3 DEG C, obtains mitolactol.
Experimental result: mitolactol average yield 39%, average purity is 72%.
Comparative example 8: with reference to the embodiment of the present invention 9, step C organic acid or hydrogen bromide organic acid soln are added to step a
A 10kg dulcitol is put in reactor by (), add 300g acid treatment to the weakly acidic cationic exchange resin of acrylic series D151 that PH is 3.9, being simultaneously introduced 45% hydrobromic acid aqueous solution: the mixed liquor of acetic acid=1:1.8 (weight ratio), addition is 3 times of dulcitol weight；And dulcitol weight 4 is again containing the acetic acid of 1% hydrogen bromide；
B () heating in water bath is to 45 DEG C and be stirred continuously, and makes dulcitol dissolve, and then proceedes to heating and stirs until there is crystallization；
C () keeps 45 DEG C and is stirred continuously, continue reaction 16 hours, let cool to room temperature, stand 20 hours；
D () reactant liquor adds 2 times amount water dilutions, filter, and filter cake is washed with water to neutrality, drains, and adds the soak with ethanol 1 hour that 0.5 times of concentration of volume percent is 70%, drains, and 25 DEG C are decompressed to-0.1MPa and dry, obtain mitolactol coarse crystallization；Mitolactol coarse crystallization adds the methanol of 90 times of coarse crystallization weight, recrystallization at 3 DEG C, obtains mitolactol.
Experimental result: mitolactol average yield 41%, average purity is 73%.
Process ration is tested:
Experimental technique: according to reaction pressure disclosed by the invention, reaction temperature and hydrobromic acid solution concentration, prepares embodiment 1-10 sample；Want, on the preparation method basis of embodiment, to be individually subtracted committed step and prepare comparative example 1-8.Result is in Table 1.
Yield computational methods:
Table 1: hexanhexol bromination reaction experimental result
Table 1 result shows:
1, the operating procedure of comparative example 1,2,3 corresponding embodiment 1,2,3 respectively, deducts resin, and step C is without organic acid or hydrogen bromide organic acid soln condition, and the yield of its mitolactol has pole significant difference (P < 0.01) with purity compared with embodiment.
2, all comparative example groups are respectively compared with embodiment group, and yield and purity all have pole significance (P < 0.01).
Test result indicate that: by response parameter provided by the invention, it is possible to obtain being substantially better than existing technical scheme and prepare the effect of gained mitolactol.
Although, above use generality explanation, detailed description of the invention and test, the present invention is described in detail, but on basis of the present invention, it is possible to it is made some modifications or improvements, and this will be apparent to those skilled in the art.Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, belong to the scope of protection of present invention.
Claims (14)
1. cation exchange resin promotes the purposes of hexanhexol bromination reaction yield.
2. purposes as claimed in claim 1, it is characterised in that: described cationic resin is gel-type, macroporous type, strong acid, faintly acid, polystyrene, acrylic acid series positive resin, strongly acidic styrene type cation exchange resin, macropore styrene ion exchange resin, weakly acidic cationic exchange resin of acrylic series, macropore strong acid cation exchanger resin.
3. purposes as claimed in claim 1 or 2, it is characterised in that: the 0.1-10% that described cation exchange resin makes consumption be hexanhexol weight.
4. purposes as claimed in claim 1 or 2, it is characterised in that: described cation exchange resin acid treatment adds in reaction solution when being 2-4 to pH.
5. purposes as claimed in claim 1 or 2, it is characterised in that: described hexanhexol is mannitol, dulcitol, sorbitol.
6. purposes as claimed in claim 1, it is characterised in that described cation exchange resin using method is:
First hexanhexol being put into reaction vessel, then with mixing hydrobromic acid solution, cation exchange resin is together added reaction vessel, heating is also constantly reacted, and making hexanhexol bromination is dibromo hexanhexol；
Or hexanhexol is put into reaction vessel, add mixing hydrobromic acid solution reaction to after crystallization occurs, add cation exchange resin, organic acid or hydrogen bromide organic acid soln, keep heating and be stirred continuously, continue reaction 2～24 hours, letting cool to room temperature, stand more than 5 hours, making hexanhexol bromination is dibromo hexanhexol；
Described mixing hydrobromic acid solution is hydrobromic acid aqueous solution and organic acid mixed liquor, or the mixed liquor of hydrobromic acid aqueous solution and hydrogen bromide organic acid soln.
7. purposes as claimed in claim 6, it is characterised in that described hexanhexol bromination reaction comprises the steps:
A hexanhexol is put in reaction vessel by (), add mixing hydrobromic acid solution and cation exchange resin；Described mixing hydrobromic acid solution is hydrobromic acid aqueous solution and organic acid mixed liquor, or the mixed liquor of hydrobromic acid aqueous solution and hydrogen bromide organic acid soln；
B () heats to 30～70 DEG C, continuously stirred, makes hexanhexol dissolve, and continues heating and stirs to crystallization occur；
C () adds organic acid or hydrogen bromide organic acid soln, keep the temperature of step b) and be stirred continuously, and continues reaction 2～24 hours, lets cool to room temperature, stand more than 5 hours；
D () is filtered and is cleaned, dry, obtains dibromo hexanhexol coarse crystallization.
8. purposes as claimed in claim 6, it is characterised in that described hexanhexol bromination reaction comprises the steps:
A hexanhexol is put in reaction vessel by (), add mixing hydrobromic acid solution；Described mixing hydrobromic acid solution is hydrobromic acid aqueous solution and organic acid mixed liquor, or the mixed liquor of hydrobromic acid aqueous solution and hydrogen bromide organic acid soln；
B () heats and is stirred continuously, make hexanhexol dissolve, and continues heating and stirs to crystallization occur；
C () adds cation exchange resin, organic acid or hydrogen bromide organic acid soln, keep heating and be stirred continuously, and continues reaction 2～24 hours, lets cool to room temperature, stand more than 5 hours；
D () is filtered and is cleaned, dry, obtains dibromo hexanhexol coarse crystallization.
9. the purposes according to any one of claim 6-8, it is characterised in that in described step (a), hexanhexol is 1:1-20 with the mass ratio mixing hydrobromic acid solution.
10. the purposes according to any one of claim 6-8, it is characterised in that in described step (a), the concentration of hydrobromic acid aqueous solution is 20-80%.
11. according to the purposes described in any one of claim 6-8, it is characterised in that the mixed liquor of hydrobromic acid aqueous solution and organic acid or hydrogen bromide organic acid soln in described step (a), mass ratio is 1:0.001～2.
12. according to the purposes described in any one of claim 6-8, it is characterised in that described organic acid is formic acid, acetic acid, propanoic acid or butanoic acid；Described hydrogen bromide organic acid soln is containing the formic acid solution that bromination hydrogen concentration is 0.01%～33%, acetic acid solution, propionic acid solution or butanoic acid solution.
13. purposes according to claim 7, it is characterised in that described step (b) heating-up temperature is to 30～45 DEG C.
14. purposes according to claim 7, it is characterised in that in described step (c), the continuation response time is 16～22 hours.
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| 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 |
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| 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 |
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| ALAIN BOUILLAUD等: "Synthesis of Dibromohydrins from Glycerol by Using an Ion Exchange Resin as Catalyst", 《AUST. J. CHEM.》 * |
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Application publication date: 20160727 |