Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
  • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
  • C07D493/04—Ortho-condensed systems

Definitions

• the present invention relates to a method for manufacturing crystals of 1, 4: 3,6-dianhydrohexitols, by manufacturing a solution of an internal dehydration product of at least one hexitol, distillation of said solution, crystallization, and characterized in that the mother liquors of crystallization undergo an evapocrystallization step.
• evapocrystallization is an economical and efficient substitute for the succession of steps consisting of at least one concentration, then at least one step of purification by distillation, chromatography, or crystallization.
• hexitols C 6 hydrogenated sugars
• sorbitol C 6 hydrogenated sugars
• mannitol C 6 hydrogenated sugars
• iditols C 6 hydrogenated sugars
• dianhydrohexitols includes isosorbide (1,4: 3,6-dianhydro sorbitol), isomannide (1,4: 3,6 dianhydro-mannitol), isoidide (1, 4: 3,6-dianhydro-iditol) of the following formulas, as well as the mixtures of these products:
• This dehydration step is always followed industrially by a purification step, in particular by distillation.
• This method is now well known to those skilled in the art, and in particular described in WO 00/14081, US 4,408,061 and EP 0 323 994.
• the plaintiff company has itself widely reported and exemplified, particularly in the patent application EP 1 446 373.
• the isosorbide distillate thus obtained is then crystallized. To do this, it is generally dissolved in a solvent, such as 2-propanol (or isopropanol), at a temperature of about 60 ° C, so as to obtain a solution of about 75% of material. dried. This solution is then cooled slowly, in a time ranging from 2 to 10 hours, to a temperature of 10 ° C.
• a solvent such as 2-propanol (or isopropanol)
• a recrystallized isosorbide primer is added when the temperature is close to 40 ° C in order to initiate the crystallization.
• the crystals are then wrung out in a wringer and washed with a little 2-propanol. After drying under vacuum, said crystals are optionally redissolved in water so as to obtain an aqueous solution of isosorbide which can be subjected to further treatments of discoloration and / or demineralization.
• the spinning stage leads to the formation of 2 streams: the main stream, which consists of a stream of isosorbide crystals (whose dry weight content of isosorbide is of the order of 98% of its total weight) and a secondary stream still called "mother liquors" whose isosorbide richness is much lower (its dry weight content of isosorbide is close to 30% of its total weight).
• Document KR 2014-0059906 which describes a process consisting in dehydrating sorbitol, distilling the obtained isosorbide and then crystallizing the distillate in acetone, is known in this regard.
• the mother liquors are then concentrated to dryness in an evaporator, and undergo crystallization after redissolution in acetone, before being reintroduced at the initial stage of crystallization of the distillate.
• the final isosorbide purity is then 99.7%, the crystallization yield 91.9% and the overall yield of the process is 68.7% according to Example 1 of this patent application.
• Document KR 2014-0059904 describes an identical process up to the stage of treatment of mother liquors. These are concentrated to dryness by evaporation and then distilled before being reintroduced at the initial stage of crystallization of the distillate. The final purity of isosorbide is then 99.8%, the crystallization yield 92.1% and the overall yield of the process is 71.0% according to Example 1 of this patent application.
• Document KR 2014-0080748 reproduces the upstream part of the process described above. In this case, the mother liquors are concentrated to dryness still by evaporation, redissolved in water and then purified by simulated mobile bed chromatography (SMB), before undergoing a new concentration step.
• SMB simulated mobile bed chromatography
• This method of manufacturing 1,4: 3,6-dianhydrohexitol crystals comprises the steps of: a) providing a solution of an internal dehydration product of a hexitol,
• evaporation-crystallization is used to denote the combination of the steps of: concentration by evaporation under vacuum so as to form a concentrated and supersaturated solution which begins to crystallize, seeding of the medium which consists of the supersaturated solution, crystallization under partial vacuum of to continue the process of crystallization.
• this process for the manufacture of 1,4: 3,6-dianhydrohexitol crystals comprises the steps of: providing a solution of an internal dehydration product of at least one hexitol distilling the solution resulting from step a) to obtain a solution of at least 1, 4: 3,6-dianhydrohexitol
• the 1,4-3,6-dianhydrohexitol crystals from step c) are filtered off, which leads to a crystal-rich stream (1) and a mother liquor stream (1a) and is characterized in that all or part of the mother liquor stream (1a) undergoes a step of evapocrystallization e) in the presence of solvent, which leads to the formation of a solvent stream (2) and to the formation of a rich crystal stream of 1,4: 3,6-dianhydrohexitols (2a). More specifically, the crystallization according to step c) leads to a rich crystal stream of 1,4: 3,6-dianhydrohexitols.
• step d These crystals are dewatered in step d), which makes it possible to release on the one hand a main flow (1) rich in crystals of 1, 4: 3,6-dianhydrohexitols and on the other hand a stream of water (1a).
• the crystals of the main stream (1) are recovered and constitute the final recoverable product resulting from the process according to the present invention.
• the process according to the invention is characterized in that the flow of mother liquors (1a) resulting from the spinning step d) is completely subjected to an evapocrystallization step e).
• the process according to the invention is characterized in that the flow of mother liquors (1a) resulting from the dewatering stage d) undergoes partly a step of evapocrystallization e), preferably of 50% to 99.9% by weight of said stream undergoing the evapocrystallization step, from 0.1% to 50% by weight of said stream being reintroduced into the distillate at the stage of crystallization stage c).
• the evapocrystallization step e) carried out in an evapocrystallizer and in the presence of a solvent, preferably a linear or branched aliphatic alcohol, allows the distillation of said solvent and thus the formation of a solvent stream (2), as well as the formation a flow rich in crystals of 1, 4: 3,6-dianhydrohexitols (2a) after reaching a dry matter corresponding to a degree of supersaturation in 1, 4: 3,6-dianhydrohexitols sufficient to cause crystallization.
• This degree of supersaturation is generally achieved from a solids content of 75%.
• the solvent is chosen from a C 1 -C 4 linear or branched aliphatic alcohol, preferably from methanol, ethanol, propylene glycol and isopropanol, with isopropanol being the most preferred solvent.
• the supersaturation at 1, 4: 3,6-dianhydrohexitol of a solution of 1,4: 3,6-dianhydrohexitol at a given temperature is defined as the ratio of the weight of 1,4: 3,6-dianhydrohexitol on the solvent mass of the solution, reduced to the mass of 1,4: 3,6-dianhydrohexitol on the solvent mass of the saturated solution in pure form.
• a degree of supersaturation of 1 corresponds to a saturated solution of 1, 4: 3,6-dianhydrohexitol.
• a degree of supersaturation of less than 1 corresponds to a solution for which crystallization is not possible.
• the method according to the invention may also comprise an additional step, the said step consisting in that the crystals of the crystal-rich stream of 1,4: 3,6-dianhydrohexitols (2a) resulting from the evapocrystallization step e ), are dewatered in a step f) which leads to the formation on the one hand of a main flow (3) rich in crystals of 1, 4: 3,6-dianhydrohexitols and on the other hand to the formation of a flow of mother liquors (3 bis).
• this main stream (3) is reintroduced into the distillate in step c).
• the crystals are recovered in the main stream (3) and constitute the final recoverable product resulting from the process according to the present invention, in the same way as the crystals recovered at the main stream (1).
• the entire process that is the subject of the present invention can be carried out continuously.
• step a) consists of preparing a solution of an internal dehydration product of a hexitol.
• This solution has a mass concentration of 1, 4: 3,6-dianhydrohexitols between 65% and 80%, preferably between 70% and 75%.
• This solution is preferably obtained by removing water from an initial aqueous solution containing at least one hexitol.
• the removal of water is carried out by any means well known to those skilled in the art, in particular by heating, in particular by vacuum distillation.
• the initial aqueous solution is for example a product marketed by the applicant under the name NEOSORB.
• the solution containing at least one hexitol is also characterized in that the hexitol is chosen from sorbitol, mannitol and iditol and their mixtures, and is preferably sorbitol.
• Patent 4,861,513 discloses a sorbitol dehydration reaction conducted in the simultaneous presence of inert gas (nitrogen) and a reducing agent (sodium hypophosphite) for the preparation of particular polyol blends which are low in content. (10 to 26%) dianhydrosorbitol.
• inert gas nitrogen
• sodium hypophosphite sodium hypophosphite
• GB 613,444 already mentioned describes the obtaining, by dehydration in water / solvent medium, an isosorbide composition which is then subjected to a distillation treatment and then recrystallization in an alcohol / ether mixture.
• the conditions for carrying out this dehydration step are as follows: the solution containing the hexitol obtained after removal of the water from the initial solution is introduced into a reactor.
• the dehydration catalyst is introduced into the reactor.
• This catalyst can be of any type, as long as it allows the dehydration of hexitol in the next step.
• This catalyst may be a heterogeneous catalyst or a homogeneous catalyst. It may be an acid catalyst, in particular a strong acid, or ion exchange resins, in particular cationic acid exchange resins or acidic zeolite catalysts.
• the acidic catalyst may especially be sulfuric acid, hydrochloric acid, para toluenesulphonic acid, phosphoric acid, or methanesulphonic acid. Sulfuric acid is a particularly preferred catalyst for the manufacture of the composition according to the invention.
• the acidic cationic exchange resin may be a sulfonated polystyrene resin such as the BioRad AG50W-X12 resin.
• the acidic zeolite may be a zeolite beta.
• the dehydration catalyst is introduced in quantities enabling the dehydration step to be carried out.
• sulfuric acid it is preferred to use amounts of less than 2% by weight relative to the total weight of hexitol, preferably less than 1.5%, most preferably less than 1.2%. .
• the dehydration step may be carried out under vacuum, under an inert gas stream, for example nitrogen, or under pressure in an autoclave, these three methods making it possible to facilitate the removal of the water and thus to displace the water. balance of the reaction.
• To carry out the dehydration step it is necessary to supply heat to the reactor. This amount of heat required depends mainly on the nature and amount of catalyst used and, to a lesser extent, pressure conditions in the reactor during the dehydration stage.
• the temperature inside the reactor and under which the dehydration reaction is carried out can range from 1 to 400 ° C depending on the catalyst used.
• the temperature remains below 300 ° C.
• a catalyst neutralization step is preferably carried out.
• Step b) consists in distilling the solution resulting from step a).
• This distillation is carried out according to any technique accessible to those skilled in the art.
• This step can be carried out in any type of distiller for isolating the dianhydrohexitols.
• This step is carried out under conditions of vacuum, temperature and duration for isolating the dianhydrohexitols from the rest of the constituents of the composition.
• the distillation can be carried out until the dianhydrohexitol no longer distills at 50 mbar and at a temperature of 250 ° C. or at 5 mbar and at a temperature of 200 ° C.
• 1,4: 3,6-dianhydrohexitol is isosorbide (1,4: 3,6-dianhydro-sorbitol), isomannide (1,4: 3,6 dianhydro-mannitol), isoidide (1, 4: 3,6-dianhydro-iditol) or mixtures thereof and is preferably isosorbide.
• Step c) crystallizes the product from step b).
• This step is not limiting and can be carried out according to all the methods known to those skilled in the art.
• the distillate resulting from stage b) is dissolved in a solvent of the linear or branched aliphatic alcohol type, preferably a linear or branched C 1 -C 4 aliphatic alcohol, very preferably methanol, ethanol or propylene. glycol and isopropanol, with isopropanol being the most preferred solvent. Its dry matter is then between 50% and 80% of its total weight, and is preferably about 70%.
• This solution is then cooled slowly, in a time ranging from 2 to 10 hours, and preferably close to 5 hours, to a temperature between 5 ° C and 25 ° C, preferably between 10 ° C and 20 ° C.
• a primer of recrystallized 1,4-3,6-dianhydrohexitol is added when the temperature is close to 40 ° C in order to initiate the crystallization.
• the crystals are then wrung out in a wringer and washed with a little isopropanol (or 2-propanol).
• the wringing of the crystals makes it possible to release on the one hand a main stream (1) rich in crystals of 1, 4: 3,6-dianhydrohexitols and a mother liquor stream (1a).
• Their mass contents respective dry matter concentrations are between 95% and 99% on the one hand and between 30% and 35% on the other hand, and their richness in 1, 4: 3,6-dianhydrohexitols (or contents in dry weight in 1, 4: 3,6-dianhydrohexitols) are between 94.9% and 98.9% on the one hand and 27% and 32% on the other hand.
• An evapocrystallization step is then carried out on the mother liquors (1a). This takes place by evaporation in an evapocristallizer, by supplying saturated steam through a heat exchanger placed either in said evapocristallizer, or in a recirculation loop. This creates a degree of supersaturation sufficient to cause crystallization.
• isopropanol which corresponds to the preferred variant of the invention, makes it possible to implement quite "mild” conditions in terms of temperature and pressure.
• Isopropanol has the advantage of being used in conditions of near-ambient temperatures and low vacuum.
• the supersaturated solution is then seeded by introducing at least one crystalline seed.
• Said seed consists of a primer of 1,4: 3,6-dianhydrohexitol and may be in dispersed form, in a linear or branched aliphatic alcohol, preferably a linear or branched C 1 -C 4 aliphatic alcohol, very preferably selected from methanol, ethanol, propylene glycol and isopropanol, with isopropanol being the most preferred solvent.
• the crystallization continues under partial vacuum kept constant. The evaporation is carried out in such a way that a strong and well-controlled stirring of the supersaturated solution is obtained in the evapocristallizer.
• the solvent which evaporates from said solution will indeed create a pumping phenomenon which strongly agitates the solution. This phenomenon makes it possible to agitate the solution with a much greater amplitude than that which would be generated by mechanical agitation.
• the evaporated solvent is then either removed from the evapocristallizer or condensed therein.
• the dry matter of the solution at the inlet of the evapocristallizer is also adjusted so as to obtain the amount of saturated vapor necessary and sufficient for pumping.
• the evapocrystallization leads to a stream of solvent (2), preferably an isopropanol stream, and a rich crystal stream of 1,4: 3,6-dianhydrohexitols (2a).
• the dry matter mass content of the crystal-rich stream of 1, 4: 3,6-dianhydrohexitols (2 bis) is between 75% and 90%, and the richness in 1, 4: 3,6-dianhydrohexitols (or dry weight content in 1, 4: 3,6-dianhydrohexitols) is between 67.5% and 82.5% .
• Crystals of the crystal-rich stream of 1, 4: 3,6-dianhydrohexitols (2a) from the evapocrystallization step can then be dewatered (step f).
• This step f) makes it possible to release a main stream (3) rich in crystals of 1, 4: 3,6-dianhydrohexitols and a flow of mother liquors (3 bis).
• the dry matter mass contents of these two streams are respectively between 95% and 99% on the one hand and between 60% and 82% on the other hand, and their richness in 1, 4: 3,6-dianhydrohexitols (or contents in dry weight in 1, 4: 3,6-dianhydrohexitols) are between 94.5% and 98.8% on the one hand and 48% and 68% on the other hand.
• the isosorbide composition thus neutralized is then distilled under vacuum (pressure less than 50 mbar). 3900 g of isosorbide crude distillate of purity 98.0% are obtained as measured by gas phase chromatography (GPC).
• the crude isosorbide distillate is then dissolved in isopropanol (or 2-propanol) at a temperature of 60 ° C., so as to obtain a 70% solids (DM) solution.
• This solution is transferred to an agitated 8-liter crystallizer equipped with a water-filled double jacket, and is then slowly cooled over a period of 5 hours to a temperature of 20 ° C.
• the supersaturation of the solution is 1.23 and a recrystallized isosorbide primer is added to cause crystallization.
• the crystals are separated from the suspension obtained in a wringer and washed with 2-propanol. After drying under vacuum, a main stream (1) containing 3125 g of dry isosorbide crystals of purity equal to 99.9%, measured by GPC, is obtained.
• the crystallization isosorbide yield is 81.7%.
• the flow of mother liquors (1a) (mass 2380 g) has a solids content of 32.5%, has an isosorbide purity of 90.4%, measured as GPC with respect to the dry matter, and a supersaturation of 0.27.
• Step e) The flow of mother liquors (1a) is transferred to a 5-liter reactor equipped with a double jacket supplied with a thermostatic circulating bath of water, a stirring liquor, a thermometer, a distillation head provided with a valve associated with a refrigerant and with a distillation recipe for carrying out the evapocrystallization step.
• the solution is heated at 40 ° C under vacuum (pressure 100 mbar) to allow the distillation of isopropanol.
• the vacuum is then gradually increased which has the effect of gradually lowering the temperature during the distillation of isopropanol.
• the pressure is 60 mbar
• the dry matter is 85% and the supersaturation is 3.53.
• a recrystallized isosorbide primer is added to induce crystallization.
• the vacuum is gradually increased which has the effect of gradually lowering the temperature while maintaining a constant dry matter by total reflux of the isopropanol under boiling.
• the pressure reaches 30 mbar, the temperature is 20 ° C.
• the flow of distilled isopropanol (2) is 1470 g.
• the choice of isopropanol makes it possible to work in particularly "mild" conditions, as evidenced by the temperature at the end of the crystallization.
• the crystals are separated from the suspension obtained (2a) in a wringer and washed with 2-propanol. After drying under vacuum, a main stream (3) containing 390 g of isosorbide crystals with a purity of 99.7%, measured as GPC, is obtained.
• the isosorbide yield of the evapocrystallization is 55.5%.
• the streams (1) and (3) of crystals are combined and constitute a flow of 3515 g of isosorbide of purity equal to 99.87% measured by GPC.
• the overall yield of crystallization relative to the crude isosorbide distillate used is equal to 90.1% by mass.
• the flow of mother liquors (3 bis) is 510 g and has a solids content of 75.5% with a purity measured as GPC of 80.8% relative to the dry matter.
• This stream (3a) is then concentrated to dryness in order to recover the isopropanol, and then stored for reintegration during a next production in step a) of the process.
• Example 1 is repeated until step f).
• step d) of Example 1 After drying and drying the crystals as indicated in step d) of Example 1, 3442 g of dry crystals with a purity of 99.95%, measured by GPC with overall yield of crystallization relative to the crude isosorbide distillate employed of 88.3% by weight.
• the process according to the invention is applied in continuous mode operation.
• a crystallization is carried out according to Example 1.
• the crystallizer is fed at a rate of 1000 g / h by a mixture of isosorbide distillate and isopropanol dry matter equal to 70%.
• a stream of crystals is continuously extracted from the crystallizer at a rate equivalent to the feed rate of the isosorbide / isopropanol distillate mixture.
• This stream is separated continuously on a wringer into a flow (1) rich in crystals (about 550 g / h dried purity equal to 99.9%) and a flow (1a) of mother liquors.
• the flow (1a) of a flow rate of approximately 440 g / h is introduced continuously into an evapocristallizer and the vacuum and temperature conditions described in Example 1 are used to evaporate the isopropanol and increase the dry matter to cause crystallization of the crystals.
• This stream (2a) is separated continuously on a wringer in a flow (3) rich in crystals (about 70 g / h dried purity equal to 99.6%) and a flow (3 bis) bis waters -merous.
• the flows (1) and (3) of crystals are combined and constitute a flow of 620 g / h of isosorbide of purity equal to 99.87% measured by GPC.
• the overall yield of crystallization relative to the continuous feed flow of crude isosorbide distillate is 88.6% by mass.
• the flow of mother liquors (3 bis) of approximately 105 g / h is concentrated to dryness to recover the isopropanol, and then recycled in step b) of the process.
• Example 3 is repeated until the different feed and outlet flows of the two crystallizers are balanced.
• the flow of dewatered crystals (3) resulting from the evapocristallizer is then reintroduced continuously in the first crystallizer, thereby decreasing the isosorbide distillate feed rate in order to keep the level of the crystallizer constant.
• the crystal stream (1) from the first crystallizer equilibrates at a flow rate of 555 g / h of dewatered crystals and dried with a purity of 99.95% measured by GPC.
• the overall yield of crystallization relative to the continuous feed flow of crude isosorbide distillate is 88.1% by weight.
• this example demonstrates that the method according to the invention is perfectly suited to continuous operation, which is an advantage in terms of cost effectiveness of an industrial process.

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• 2016
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