Preparation method of mannitol carbonate sulfate

Abstract

The invention provides a preparation method of mannitol carbonic acid sulfate, belongs to the field of organic synthesis, and can solve the problems of more side reactions, difficulty in purification and inhibition of positive reaction in the reaction process in the existing preparation method of mannitol carbonic acid sulfate. According to the scheme, the method comprises the following steps: dropwise adding a thionyl chloride-ethylene glycol dimethyl ether solution into a D-mannitol-ethylene glycol dimethyl ether solution, and fully reacting to obtain bisulfite mannitol; the preparation method comprises the following steps: dissolving bisulfite mannitol in a dimethyl carbonate solvent, adding 1, 1 '-carbonyldiimidazole at intervals for multiple times, and fully reacting to obtain mannitol carbonylsulfite; the preparation method comprises the following steps: dissolving mannitol carbonate sulfite in a dimethyl carbonate solvent, adding a ruthenium trichloride aqueous solution, dropwise adding a sodium hypochlorite solution into a reaction system, and fully reacting to obtain mannitol carbonate sulfate. The preparation method disclosed by the invention is simple in steps, simple and convenient to operate, capable of improving the yield and reducing the production cost, and suitable for the requirements of large-scale production.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, and particularly relates to a method for preparing mannitol sulfate carbonate. Background Technology

[0002] Mannitol sulfate carbonate is a novel sulfate material, but due to its relatively large molecular weight, it exhibits numerous side reactions, making purification difficult and potentially inhibiting the forward reaction. Currently available mannitol sulfate carbonate additives have complex preparation processes, posing challenges to production efficiency and cost control. Chinese invention patent (CN120441561A) discloses a method for preparing mannitol sulfate carbonate, specifically involving the cyclic carbonate reaction of mannitol and dimethyl carbonate under alkaline catalysis. This reaction preferentially occurs at the cis-adjacent primary hydroxyl groups. Since mannitol has multiple hydroxyl groups, this reaction may generate complex mixtures including monocyclic and bicyclic carbonates, leading to decreased yield and difficulties in separation and purification. The ring strain and molecular configuration of cyclic carbonates may result in significant steric hindrance for the remaining hydroxyl groups, especially secondary hydroxyl groups, hindering their reaction with thionyl chloride. Even if the reaction occurs, steric hindrance may lead to incomplete sulfonation or poor regioselectivity, preventing the acquisition of a single, pure target intermediate. Therefore, a novel method for preparing mannitol sulfate carbonate is needed. Summary of the Invention

[0003] This invention addresses the numerous side reactions and difficulties in purification associated with the aforementioned methods for preparing mannitol sulfate carbonate, as well as the potential for inhibiting the forward reaction during the reaction process. It proposes a new method for preparing mannitol sulfate carbonate that is simple in steps and easy to operate. This method not only helps improve yield and reduce production costs but also meets the needs of large-scale production and yields high-purity products.

[0004] To achieve the above objectives, the technical solution adopted by the present invention is as follows: a method for preparing mannitol sulfate carbonate, comprising the following steps: S1, dissolving D-mannitol in ethylene glycol dimethyl ether solvent to obtain a first solution, dissolving thionyl chloride in ethylene glycol dimethyl ether solvent to obtain a second solution, adding the second solution dropwise to the first solution, heating and reacting completely to obtain a first compound, wherein the molar ratio of D-mannitol to thionyl chloride is 1:1-3, and the mass ratio of D-mannitol to ethylene glycol dimethyl ether solvent in the first solution is 1:10; S2, dissolving the first compound in dimethyl carbonate solvent to obtain a third compound. In the first solution, 1,1'-carbonyldiimidazole is added to the third solution in multiple portions at intervals. After heating and reacting completely, a second compound is obtained, wherein the molar ratio of the first compound to 1,1'-carbonyldiimidazole is 1:0.7-1.5; S3, the second compound is dissolved in dimethyl carbonate solvent to obtain a fourth solution. A ruthenium trichloride aqueous solution is added to the fourth solution, followed by the dropwise addition of sodium hypochlorite solution. After heating and reacting completely, mannitol carbonate sulfate is obtained, wherein the mass ratio of the second compound to ruthenium trichloride is 1:0.0005-0.01, and the molar ratio of the second compound to sodium hypochlorite is 1:4-8.

[0005] In one embodiment, in step S1, the reaction is carried out under inert gas protection. The temperature of the reaction system is controlled to rise from room temperature to 50°C, and then the second solution is added dropwise. After the addition is completed, the temperature is maintained and the reaction is allowed to stand for 3-10 hours.

[0006] In one embodiment, step S1 further includes: after the reaction is completed, filtering and rotary evaporating the reaction system to obtain a crude product; adding dimethyl carbonate to the crude product, adding water after the crude product dissolves, stirring thoroughly and allowing it to stand for phase separation, extracting and separating the phases, removing the aqueous phase, taking the upper organic phase, repeating the operation 2-3 times; removing water from the organic phase, filtering and rotary evaporating to obtain the first compound.

[0007] In one embodiment, in step S1, the molar ratio of D-mannitol to thionyl chloride is 1:2.2.

[0008] In one embodiment, in step S2, after the temperature of the reaction system is raised from room temperature to 50°C, 1,1'-carbonyldiimidazole is added to the third solution in 3-5 portions at intervals. After all the solution is added, the temperature is raised to 70°C and the reaction is allowed to stand for 3 hours.

[0009] In one embodiment, in step S2, the molar ratio of mannitol disulfite to 1,1'-carbonyldiimidazole is 1:1.

[0010] In one embodiment, in step S3, after controlling the temperature of the reaction system to 25°C, sodium hypochlorite solution is added dropwise, and after the addition is completed, the temperature is maintained and the reaction is allowed to stand for 3-6 hours.

[0011] In one embodiment, step S3 further includes: after the reaction is completed, the reaction system is allowed to stand and separate into layers, and the aqueous phase is removed by extraction and phase separation, and the upper organic phase is taken; water is added to the organic phase, and after thorough stirring, the system is allowed to stand and separate into layers, and the aqueous phase is removed by extraction and phase separation, and the upper organic phase is taken. This operation is repeated 2-3 times; the organic phase is dehydrated, filtered, and rotary evaporated to obtain mannitol sulfate carbonate.

[0012] In one embodiment, in step S3, the mass ratio of the second compound to ruthenium trichloride is 1:0.01, and the molar ratio of the second compound to sodium hypochlorite is 1:6.

[0013] Compared with existing technologies, the advantages and positive effects of this invention are as follows: The preparation method of this invention is simple and easy to operate, which not only helps to improve yield and reduce production costs, but also meets the needs of large-scale production and obtains high-purity products. Mannitol and thionyl chloride undergo a condensation reaction. Since the hydroxyl groups at both ends of mannitol are primary hydroxyl groups, chloride ions attack carbon atoms from the back side. The reaction rate is highly dependent on steric hindrance; the primary carbon has the least steric hindrance and therefore the highest reactivity, which can improve reaction efficiency and increase yield. Attached Figure Description

[0014] Figure 1 The liquid chromatogram of mannitol sulfate prepared in Example 1 of this invention; Figure 2 The infrared spectrum of mannitol sulfate prepared in Example 1 of this invention; Figure 3 The carbon NMR spectrum of mannitol sulfate prepared in Example 1 of this invention; Figure 4 The image shows the 1H NMR spectrum of mannitol sulfate carbonate prepared in Example 1 of this invention. Detailed Implementation

[0015] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0016] This invention provides a method for preparing mannitol sulfate carbonate. First, mannitol disulfite is synthesized; second, mannitol sulfate carbonate is synthesized; and finally, mannitol sulfate carbonate is synthesized and purified to obtain the target product. Firstly, the synthesis of mannitol disulfite involves a condensation reaction of D-mannitol with thionyl chloride in a low dielectric constant, weakly polar organic system. This process is not a one-step direct substitution but is accomplished through a key cyclic chlorosulfonate intermediate. The reaction begins with the highly reactive primary hydroxyl group at the C1 position of D-mannitol preferentially attacking the sulfur atom of SOCl2, forming an alkoxychlorosulfonate intermediate and releasing HCl. The secondary hydroxyl group at the C2 position adjacent to C1 acts as an intramolecular nucleophile, attacking not the carbon atom but the chlorine atom bonded to sulfur in the intermediate, leading to the release of HCl. - It departs and forms a five-membered ring structure composed of O(C2)-S(reagent)-O(C1)-C1-C2 atoms; the outer chloride ion (Cl... - The cyclization process attacks the C1 carbon atom on the ring from the back, causing the ring to break and allowing the C1 hydroxyl group to be replaced by a chlorine atom. At the same time, the C2 hydroxyl group is regenerated and SO2 is released. Due to the high symmetry of the D-mannitol molecule, the same cyclization process will occur simultaneously at the other end (C5, C6).

[0017] When synthesizing mannitol sulfite, the condensation product reacts with N,N'-carbonyldiimidazole (CDI). First, a nucleophilic substitution reaction occurs with one of the secondary hydroxyl groups at the 3 or 4 position. The hydroxyl oxygen atom attacks the carbonyl carbon of CDI, replacing one molecule of imidazole and forming a key imidazole carbamate intermediate. The adjacent secondary hydroxyl group acts as an intramolecular nucleophile, attacking the highly reactive carbonyl carbon atom on the intermediate. This intramolecular nucleophilic addition-elimination reaction leads to the departure of a second molecule of imidazole, ultimately forming a five-membered cyclic carbonate with the carbon atoms at the 3 and 4 positions bridged by an -O-(C=O)-O- structure.

[0018] During the synthesis of mannitol sulfate carbonate, the cyclized ester product reacts with sodium hypochlorite. The sulfur atom, due to its +4 oxidation state and lone pair of electrons, exhibits strong nucleophilicity, actively attacking the partially positively charged chlorine atom (Cl) in the sodium hypochlorite molecule. + This nucleophilic attack causes heterolytic cleavage of the O-Cl bond of the hypochlorite ion, generating a highly reactive chlorosulfonate transition state and releasing chloride ions (Cl). - One oxygen atom in sodium hypochlorite is formally inserted into the bonding system between the sulfur atom and its original oxygen atom. Through electron recombination, the valence state of the sulfur atom is increased from +4 to +6, completing the oxidation process.

[0019] During purification, the reaction system is first filtered, and dimethyl carbonate is added to dissolve the crude product. After dissolution, water is added to fully disperse it. After standing, extraction and phase separation are performed to remove the aqueous phase. The organic phase is dehydrated by adding anhydrous magnesium sulfate and stirring for 1 hour. After the process is completed, it is filtered and then rotary evaporated to obtain the target product.

[0020] Furthermore, this invention uses solvents with low dielectric constants, such as dimethyl carbonate (DMC) and dimethyl ethylene glycol (DME), which is beneficial for obtaining high-purity products. A low dielectric constant means low polarity, resulting in low solubility of the product in the solvent system, which is more conducive to purification. Generally, the dielectric constant is a physical quantity that measures the ability of a dielectric to store charge under the influence of an electric field. Polar molecules undergo orientation polarization in an electric field, making it easier to store charge and resulting in a higher dielectric constant. Non-polar or weakly polar molecules have a low degree of polarization in an electric field, a weak ability to store charge, and therefore a low dielectric constant.

[0021] The method for preparing mannitol sulfate carbonate according to embodiments of the present invention includes three steps: synthesizing disulfite mannitol, synthesizing mannitol sulfate carbonate, and synthesizing mannitol sulfate carbonate. The step of synthesizing disulfite mannitol includes: adding D-mannitol and ethylene glycol dimethyl ether to a reaction vessel, dissolving D-mannitol in ethylene glycol dimethyl ether to obtain a first solution; dissolving thionyl chloride in ethylene glycol dimethyl ether solvent to obtain a second solution; and adding the second solution dropwise to the first solution, allowing the reaction to proceed fully to obtain disulfite mannitol. This step is a condensation reaction. During the dropwise addition, the temperature of the reaction system needs to be controlled: after the temperature of the reaction system is raised from room temperature to 50°C, the second solution is added dropwise. The dropwise addition rate should be kept slow, and it generally takes 3 hours to complete the addition. After the dropwise addition is completed, the temperature should be maintained and the reaction should be allowed to stand for 3-10 hours, preferably 6 hours, to allow D-mannitol and thionyl chloride to fully undergo the condensation reaction. During the reaction, nitrogen gas is introduced to remove the hydrogen chloride generated by the reaction, reduce the acidity of the reaction system, promote the forward reaction, increase the reaction rate, and improve the product yield.

[0022] In one embodiment of the present invention, the molar ratio of D-mannitol to thionyl chloride is 1:1-3, preferably 1:2.2; the mass ratio of D-mannitol to ethylene glycol dimethyl ether in the first solution is 1:10; and the mass ratio of thionyl chloride to ethylene glycol dimethyl ether solvent in the second solution is 1:1.2.

[0023] The reaction formula for synthesizing disulfite mannitol is shown below:

[0024] In the synthesis of disulfite mannitol in this invention, the purity of the obtained product is typically below 90%, thus requiring further purification to remove impurities. The main product of the condensation reaction is disulfite mannitol. If the reaction temperature is too high or the thionyl chloride ratio is too high, trisubstituted trisulfite mannitol will form; conversely, if the thionyl chloride ratio is insufficient, monosubstituted trisulfite mannitol will form. Therefore, this invention strictly controls the feeding ratio of D-mannitol to thionyl chloride and the reaction temperature. Compared to the trisulfite mannitol byproduct, the trisulfite mannitol byproduct has stronger water solubility. When byproducts are difficult to completely avoid, this invention avoids the formation of hydrophobic trisulfite mannitol by adjusting the reaction conditions (including appropriately reducing the thionyl chloride ratio and strictly controlling the temperature), followed by purification after the reaction. To address the water-soluble impurities in mannitol disulfite, dimethyl carbonate (DMC) and water can be used for extraction and separation. During the extraction process, the product enters the aqueous phase while remaining in the organic phase. The specific steps are as follows: First, filter and rotary evaporate the reaction system after the reaction is complete, controlling the rotary evaporation temperature to be below 55°C to obtain a crude product. Dissolve the crude product in dimethyl carbonate, then add water, stir thoroughly to disperse it, allow it to stand and separate into layers, and then extract and separate the phases. Remove the aqueous phase and take the upper organic phase. To fully remove water-soluble impurities, repeat the aqueous phase extraction operation three times. Add anhydrous magnesium sulfate to the organic phase to remove water, then filter and rotary evaporate, controlling the rotary evaporation temperature to be below 55°C to obtain the target product, mannitol disulfite.

[0025] The synthesis of mannitol sulfite carbonate involves the following steps: dissolving mannitol disulfite in dimethyl carbonate to obtain a third solution; adding 1,1'-carbonyldiimidazole to the third solution in 4-5 portions at intervals, with each addition 1 hour apart; and allowing the reaction to proceed fully to obtain mannitol sulfite carbonate. This step is a cyclization esterification reaction, and the reaction system temperature needs to be controlled during the addition: the reaction system temperature is initially raised from room temperature to 50°C, and then 1,1'-carbonyldiimidazole is added to the third solution in 3-5 portions at intervals. After all the 1,1'-carbonyldiimidazole has been added, the temperature is raised to 70°C and maintained for 3 hours to allow the mannitol disulfite and 1,1'-carbonyldiimidazole to undergo a complete cyclization esterification reaction.

[0026] In one embodiment of the present invention, the molar ratio of mannitol disulfite to 1,1'-carbonyldiimidazole is 1:0.7-1.5, preferably 1:1; the mass ratio of mannitol disulfite to dimethyl carbonate solvent in the third solution is 1:40.

[0027] The reaction formula for synthesizing mannitol sulfite is shown below:

[0028] The steps for synthesizing mannitol sulfate carbonate include: dissolving mannitol sulfite carbonate in dimethyl carbonate to obtain a fourth solution; adding ruthenium trichloride aqueous solution to the fourth solution; and then adding sodium hypochlorite dropwise to the reaction system. After the reaction is complete, mannitol sulfate carbonate is obtained. This step is an oxidation reaction, and the temperature of the reaction system needs to be controlled during the dropwise addition: after controlling the temperature of the reaction system to 25°C, the sodium hypochlorite solution is added dropwise. After the dropwise addition is completed, the temperature is maintained and the reaction is allowed to stand for 3-6 hours, preferably 3 hours, to allow the mannitol sulfite carbonate and sodium hypochlorite to undergo a complete oxidation reaction.

[0029] In one embodiment of the present invention, the molar ratio of mannitol carbonate to sodium hypochlorite is 1:4-8, the mass ratio of mannitol carbonate to ruthenium trichloride catalyst is 1:0.0005-0.01, and the mass ratio of mannitol carbonate to dimethyl carbonate solvent in the fourth solution is 1:7.

[0030] In a preferred embodiment of the present invention, the molar ratio of mannitol sulfite carbonate to sodium hypochlorite is 1:6, and the mass ratio of mannitol sulfite carbonate to ruthenium trichloride catalyst is 1:0.01.

[0031] The reaction formula for synthesizing mannitol sulfate is shown below:

[0032] In the synthesis of mannitol sulfate carbonate in this invention, the oxidation reaction requires ruthenium trichloride as a catalyst. During this process, ruthenium is oxidized from a +3 oxidation state to a +7 oxidation state (as RuO4). - It exists in a catalytic oxidation form, but at the same time, it will give the reaction solution a yellow-green color. The amount of catalyst has a significant impact on the reaction: if the amount is too small, the oxidation effect is insufficient; if the amount of oxidant is increased, too much aqueous phase will be introduced, leading to easy hydrolysis of the final product. Increasing the amount of catalyst, RuO4 - The +7 valence ruthenium is difficult to reduce back to +3 valence, causing the organic phase of the reaction to be yellowish-green (normally it should be colorless and transparent), and the resulting product is a gray solid (normally it should be a white powder). The decolorization of the ruthenium trichloride catalyst is mainly due to: first, high-valence ruthenium is unstable in solution, slowly decomposing to form green +6 valence ruthenium (RuO4). 2- Dimethyl carbonate, a solvent, has reducing properties and can reduce high-valence ruthenium to mixed-valence ruthenium compounds (such as Ru). 3+ / Ru 4+ The oxides of Ru cause the solution to turn red or brown; secondly, under alkaline conditions, Ru... 3+ / Ru 4+ It can produce bluish-black hydrated ruthenium dioxide (RuO2·xH2O), and if it forms a hydroxyl complex (such as [Ru(OH)6)... 3-If the solution is yellowish-green, it may turn red. Letting the solution stand overnight will cause the yellowish-green liquid to gradually turn red or black; decolorization can be achieved by adding reducing agents such as dimethyl carbonate, oxalic acid, or ascorbic acid. It should be noted that heating the solution may produce ruthenium tetroxide (RuO4), a highly volatile, toxic, and explosive compound. After decolorization, filtration and washing with water are performed, followed by extraction and phase separation to allow the ruthenium compound to enter the aqueous phase, obtaining a colorless lower organic phase. After dehydration and rotary evaporation, a white powder product is obtained. Dehydration is achieved by adding anhydrous magnesium sulfate, with the rotary evaporation temperature controlled below 55°C.

[0033] To provide a clearer and more detailed description of the preparation method of mannitol sulfate carbonate provided in the embodiments of the present invention, specific embodiments will be described below.

[0034] Example 1 Raw material preparation: D-mannitol, commercially available industrial grade, 99% purity; thionyl chloride, commercially available product, Maclean, 99.5% purity; ethylene glycol dimethyl ether, commercially available product, 99% purity; 1,1'-carbonyldiimidazole, commercially available industrial grade, 99% purity; dimethyl carbonate, commercially available product, 99% purity; ruthenium trichloride, commercially available industrial grade, 99.99% purity; sodium hypochlorite, commercially available industrial grade, with an effective chlorine concentration of 6%-14%; all raw and auxiliary materials need to be dehydrated, with moisture content less than 100 ppm; The preparation method of mannitol sulfate carbonate in this embodiment includes the following steps: 1. Synthesis of disulfite mannitol: 1.1 Weigh 18.46 g of D-mannitol and 185.2 g of ethylene glycol dimethyl ether (EDGD) into a four-necked flask using an electronic balance; weigh 33.308 g of thionyl chloride and 40.65 g of EDGD into a constant pressure funnel. The molar ratio of D-mannitol to thionyl chloride is 1:2.8. 1.2 In an oil bath, add a magnetic stir bar. Connect one end of a four-necked flask to a thermometer sleeve, another end to a constant pressure dropping funnel, and a third end to a condenser for connecting to a high-low temperature circulating machine. Connect the other end to nitrogen. Turn on the high-low temperature circulating machine to cool down to 5°C. Raise the oil bath temperature to 50°C and begin adding a thionyl chloride-ethylene glycol dimethyl ether mixture. During the addition process, maintain the system temperature above 50°C for 3 hours. After the addition is complete, continue to maintain the temperature and allow the reaction to stand for 6 hours to allow D-mannitol and thionyl chloride to fully undergo the condensation reaction. 1.3 The solution after reaction was filtered using a sand core F4 vacuum filter device, and the filtrate was separated from the filter cake (D-mannitol); 1.4 The filtrate was transferred to a rotary evaporator flask for rotary evaporation, and the temperature of the rotary evaporation oil bath was controlled to be less than 55℃, to obtain 27.5g of crude disulfite mannitol; 1.5 Add 200g of dimethyl carbonate to the crude product to dissolve it. After dissolving, add 41g of water to disperse it fully. After standing, extract and separate the phases to remove the aqueous phase. Repeat the operation 3 times. Add anhydrous magnesium sulfate to the dehydrated organic phase, stir for 1 hour, filter, and then rotary evaporate the filtrate to obtain 26.4g of disulfite mannitol. 2. Synthesis of mannitol sulfite: 2.1 Weigh 201.3 g of dimethyl carbonate and 25.7 g of mannitol disulfite into a four-necked flask using an electronic balance. Weigh 15.618 g of 1,1'-carbonyldiimidazole. Calculate and weigh 1,1'-carbonyldiimidazole according to the molar ratio of mannitol disulfite to 1,1'-carbonyldiimidazole of 1:1. Divide the weighed 1,1'-carbonyldiimidazole into four equal portions. 2.2 In an oil bath, add a magnetic stir bar. Connect one end of a four-necked flask to a thermometer sleeve and the other end to a condenser tube for connecting to the high-low temperature circulating machine. Seal the remaining two ends tightly. Turn on the high-low temperature circulating machine to cool down to 5°C. Raise the oil bath temperature to 50°C and start adding 1,1'-carbonyldiimidazole in four batches, with an interval of 1 hour between each batch. After all the 1,1'-carbonyldiimidazole has been added, continue to maintain the temperature and let the reaction stand for 3 hours to allow the mannitol disulfite and 1,1'-carbonyldiimidazole to undergo a complete cyclization reaction. 2.3 The filtrate was separated from the filter cake (1,1'-carbonyldiimidazole) by using a sand core F4 vacuum filtration device; 2.4 The filtrate was transferred to a rotary evaporator flask for rotary evaporation. The temperature of the rotary evaporation oil bath was controlled to be less than 55°C to obtain 28.4 g of crude mannitol sulfite carbonate.

[0035] 3. Synthesis of mannitol sulfate: 3.1 Weigh 0.2 g of ruthenium trichloride and 19.8 g of pure water using an electronic balance to prepare a 1% ruthenium trichloride aqueous solution; weigh 137.625 g of sodium hypochlorite into a constant pressure funnel, and weigh 202.3 g of dimethyl carbonate into a four-necked flask, wherein the molar ratio of mannitol sulfite carbonate to sodium hypochlorite is 1:4, and the mass ratio of mannitol sulfite carbonate to ruthenium trichloride is 1:0.005; 3.2 Set the temperature of the high and low temperature cycle integrated machine to 5℃. Dissolve the intermediate mannitol sulfite carbonate in dimethyl carbonate in a 500mL glass jacketed reactor. Add 1% ruthenium trichloride aqueous solution at 5℃. Add sodium hypochlorite solution to the constant pressure dropping funnel and control the dropping rate to 1g / min. Keep the system at 5℃ for 3h. The color of the reaction solution is initially light yellow and transparent. After adding ruthenium trichloride aqueous solution, it turns black. After adding sodium hypochlorite solution, it turns yellow-green during the reaction. 3.3 Use a separatory funnel to separate the aqueous phase and the organic phase. After purifying the organic phase, continue to add water to disperse it. After standing, separate the phases and take the upper organic phase. Repeat the operation three times. 3.4 The filtrate after extraction was transferred to a rotary evaporator flask for rotary evaporation. The temperature of the rotary evaporation oil bath was controlled to be less than 55°C to obtain 30.6 g of mannitol carbonate sulfate.

[0036] Example 2 Raw material preparation: D-mannitol, commercially available industrial grade, 99% purity; thionyl chloride, commercially available product, Maclean, 99.5% purity; ethylene glycol dimethyl ether, commercially available product, 99% purity; 1,1'-carbonyldiimidazole, commercially available industrial grade, 99% purity; dimethyl carbonate, commercially available product, 99% purity; ruthenium trichloride, commercially available industrial grade, 99.99% purity; sodium hypochlorite, commercially available industrial grade, with an effective chlorine concentration of 6%-14%; all raw and auxiliary materials need to be dehydrated, with moisture content less than 100 ppm; The preparation method of mannitol sulfate carbonate in this embodiment includes the following steps: 1. Synthesis of disulfite mannitol: 1.1 Weigh 18.42 g of D-mannitol and 184.2 g of ethylene glycol dimethyl ether solvent into a four-necked flask using an electronic balance; weigh 27.3 g of thionyl chloride and 30.45 g of ethylene glycol dimethyl ether into a constant pressure funnel. The molar ratio of D-mannitol to thionyl chloride is 1:2.2. 1.2 In an oil bath, add a magnetic stir bar. Connect one end of a four-necked flask to a thermometer sleeve, another end to a constant pressure dropping funnel, and a third end to a condenser for connecting to a high-low temperature circulating machine. Connect the other end to nitrogen. Turn on the high-low temperature circulating machine to cool down to 5°C. Raise the oil bath temperature to 50°C and begin adding a thionyl chloride-ethylene glycol dimethyl ether mixture. During the addition process, maintain the system temperature above 50°C for 3 hours. After the addition is complete, continue to maintain the temperature and allow the reaction to stand for 6 hours to allow D-mannitol and thionyl chloride to fully undergo the condensation reaction. 1.3 The solution after reaction was filtered using a sand core F4 vacuum filter device, and the filtrate was separated from the filter cake (D-mannitol); 1.4 The filtrate was transferred to a rotary evaporator flask for rotary evaporation, and the temperature of the rotary evaporation oil bath was controlled to be less than 55℃, to obtain 29g of crude disulfite mannitol; 1.5 Add 200g of dimethyl carbonate to the crude product to dissolve it. After dissolving, add 40g of water to disperse it fully. After standing, extract and separate the phases to remove the aqueous phase. Repeat the operation 3 times. Add anhydrous magnesium sulfate to the dehydrated organic phase, stir for 1 hour, filter, and then rotary evaporate the filtrate to obtain 27.12g of disulfite mannitol. 2. Synthesis of mannitol sulfite: 2.1 Weigh 200.3 g of dimethyl carbonate solvent and 27.12 g of the above-mentioned disulfite mannitol into a four-necked flask using an electronic balance. Weigh 16.96 g of 1,1'-carbonyldiimidazole. Calculate and weigh 1,1'-carbonyldiimidazole according to the molar ratio of disulfite mannitol to 1,1'-carbonyldiimidazole of 1:1. Divide the weighed 1,1'-carbonyldiimidazole into four equal portions. 2.2 In an oil bath, add a magnetic stir bar. Connect one end of a four-necked flask to a thermometer sleeve and the other end to a condenser tube for connecting to the high-low temperature circulating machine. Seal the remaining two ends tightly. Turn on the high-low temperature circulating machine to cool down to 5°C. Raise the oil bath temperature to 50°C and start adding 1,1'-carbonyldiimidazole in four batches, with an interval of 1 hour between each batch. After the addition is complete, continue to maintain the temperature and let the reaction stand for 3 hours to allow the mannitol disulfite and 1,1'-carbonyldiimidazole to undergo a complete cyclization reaction. 2.3 The filtrate was separated from the filter cake (1,1'-carbonyldiimidazole) by using a sand core F4 vacuum filtration device; 2.4 The filtrate was transferred to a rotary evaporator flask for rotary evaporation. The temperature of the rotary evaporation oil bath was controlled to be less than 55℃ to obtain 29.4g of crude mannitol sulfite carbonate.

[0037] 3. Synthesis of mannitol sulfate: 3.1 Weigh 0.2 g of ruthenium trichloride and 19.8 g of pure water using an electronic balance to prepare a 1% ruthenium trichloride aqueous solution; weigh 201.7 g of sodium hypochlorite into a constant pressure funnel and 202.3 g of dimethyl carbonate into a four-necked flask, wherein the molar ratio of mannitol sulfite carbonate to sodium hypochlorite is 1:6 and the mass ratio of mannitol sulfite carbonate to ruthenium trichloride is 1:0.01; 3.2 Set the temperature of the high and low temperature cycle integrated machine to 5℃. Dissolve the intermediate mannitol sulfite carbonate in dimethyl carbonate in a 500mL glass jacketed reactor. Add 1% ruthenium trichloride aqueous solution at 5℃. Add sodium hypochlorite solution to the constant pressure dropping funnel and control the dropping rate to 1g / min. Keep the system at 5℃ for 3h. The color of the reaction solution is initially light yellow and transparent. After adding ruthenium trichloride aqueous solution, it turns black. After adding sodium hypochlorite solution, it turns yellow-green during the reaction. 3.3 Use a separatory funnel to separate the aqueous phase and the organic phase. After purifying the organic phase, continue to add water to disperse it. After standing, separate the phases and take the upper organic phase. Repeat the operation three times. 3.4 The filtrate after extraction was transferred to a rotary evaporator flask for rotary evaporation. The temperature of the rotary evaporation oil bath was controlled to be less than 55℃ to obtain 32.4g of mannitol carbonate sulfate.

[0038] Example 3 Raw material preparation: D-mannitol, commercially available industrial grade, 99% purity; thionyl chloride, commercially available product, Maclean, 99.5% purity; ethylene glycol dimethyl ether, commercially available product, 99% purity; 1,1'-carbonyldiimidazole, commercially available industrial grade, 99% purity; dimethyl carbonate, commercially available product, 99% purity; ruthenium trichloride, commercially available industrial grade, 99.99% purity; sodium hypochlorite, commercially available industrial grade, with an effective chlorine concentration of 6%-14%; all raw and auxiliary materials need to be dehydrated, with moisture content less than 100 ppm; The preparation method of mannitol sulfate carbonate in this embodiment includes the following steps: 1. Synthesis of disulfite mannitol: 1.1 Weigh 18.45 g of D-mannitol and 184.2 g of dimethyl ethylene glycol ether (DMGE) into a four-necked flask using an electronic balance; weigh 35.67 g of thionyl chloride and 42.83 g of DMGE into a constant pressure funnel. The molar ratio of D-mannitol to thionyl chloride is 1:3. 1.2 In an oil bath, add a magnetic stir bar. Connect one end of a four-necked flask to a thermometer sleeve, another end to a constant pressure dropping funnel, and a third end to a condenser for connecting to a high-low temperature circulating machine. Connect the other end to nitrogen. Turn on the high-low temperature circulating machine to cool down to 5°C. Raise the oil bath temperature to 50°C and begin adding a thionyl chloride-ethylene glycol dimethyl ether mixture. During the addition process, maintain the system temperature above 50°C for 3 hours. After the addition is complete, continue to maintain the temperature and allow the reaction to stand for 6 hours to allow D-mannitol and thionyl chloride to fully undergo the condensation reaction. 1.3 The solution after reaction was filtered using a sand core F4 vacuum filter device, and the filtrate was separated from the filter cake (D-mannitol); 1.4 The filtrate was transferred to a rotary evaporator flask for rotary evaporation, and the temperature of the rotary evaporation oil bath was controlled to be less than 55℃, to obtain 28.4g of crude disulfite mannitol; 1.5 Add 200g of dimethyl carbonate to the crude product to dissolve it. After dissolving, add 40g of water to disperse it fully. After standing, extract and separate the phases to remove the aqueous phase. Repeat the operation 3 times. Add anhydrous magnesium sulfate to the dehydrated organic phase, stir for 1 hour, filter, and then rotary evaporate the filtrate to obtain 25.8g of disulfite mannitol. 2. Synthesis of mannitol sulfite: 2.1 Weigh 205.6 g of dimethyl carbonate and 24.8 g of mannitol disulfite into a four-necked flask using an electronic balance. Weigh 22.05 g of 1,1'-carbonyldiimidazole. Calculate and weigh 1,1'-carbonyldiimidazole according to the molar ratio of mannitol disulfite to 1,1'-carbonyldiimidazole of 1:1.5. Divide the weighed 1,1'-carbonyldiimidazole into four equal portions. 2.2 In an oil bath, add a magnetic stir bar. Connect one end of a four-necked flask to a thermometer sleeve and the other end to a condenser tube for connecting to the high-low temperature circulating machine. Seal the remaining two ends tightly. Turn on the high-low temperature circulating machine to cool down to 5°C. Raise the oil bath temperature to 50°C and start adding 1,1'-carbonyldiimidazole in four batches, with an interval of 1 hour between each batch. After the addition is complete, continue to maintain the temperature and let the reaction stand for 3 hours to allow the mannitol disulfite and 1,1'-carbonyldiimidazole to undergo a complete cyclization reaction. 2.3 The filtrate was separated from the filter cake (1,1'-carbonyldiimidazole) by using a sand core F4 vacuum filtration device; 2.4 The filtrate was transferred to a rotary evaporator flask for rotary evaporation. The temperature of the rotary evaporation oil bath was controlled to be less than 55°C to obtain 27.1 g of mannitol sulfite carbonate.

[0039] 3. Synthesis of mannitol sulfate: 3.1 Weigh 0.2 g of ruthenium trichloride and 19.8 g of pure water using an electronic balance to prepare a 1% ruthenium trichloride aqueous solution; weigh 242.32 g of sodium hypochlorite into a constant pressure funnel and 206.2 g of dimethyl carbonate into a four-necked flask, wherein the molar ratio of mannitol sulfite carbonate to sodium hypochlorite is 1:8 and the mass ratio of mannitol sulfite carbonate to ruthenium trichloride is 1:0.005; 3.2 Set the temperature of the high and low temperature cycle integrated machine to 5℃. Dissolve the intermediate mannitol sulfite carbonate in dimethyl carbonate in a 500mL glass jacketed reactor. Add 1% ruthenium trichloride aqueous solution at 5℃. Add sodium hypochlorite solution to the constant pressure dropping funnel and control the dropping rate to 1g / min. Keep the system at 5℃ for 4 hours. The color of the reaction solution is initially light yellow and transparent. After adding ruthenium trichloride aqueous solution, it turns black. After adding sodium hypochlorite solution, it turns yellow-green during the reaction. 3.3 Use a separatory funnel to separate the aqueous phase and the organic phase. After purifying the organic phase, continue to add water to disperse it. After standing, separate the phases and take the upper organic phase. Repeat the operation three times. 3.4 The filtrate after extraction was transferred to a rotary evaporator flask for rotary evaporation. The temperature of the rotary evaporation oil bath was controlled to be less than 55℃ to obtain 29.12g of mannitol carbonate sulfate.

[0040] Example 4 Raw material preparation: D-mannitol, commercially available industrial grade, 99% purity; thionyl chloride, commercially available product, Maclean, 99.5% purity; ethylene glycol dimethyl ether, commercially available product, 99% purity; 1,1'-carbonyldiimidazole, commercially available industrial grade, 99% purity; dimethyl carbonate, commercially available product, 99% purity; ruthenium trichloride, commercially available industrial grade, 99.99% purity; sodium hypochlorite, commercially available industrial grade, with an effective chlorine concentration of 6%-14%; all raw and auxiliary materials need to be dehydrated, with moisture content less than 100 ppm; The preparation method of mannitol sulfate carbonate in this embodiment includes the following steps: 1. Synthesis of disulfite mannitol: 1.1 Weigh 18.42 g of D-mannitol and 184.2 g of ethylene glycol dimethyl ether solvent into a four-necked flask using an electronic balance; weigh 12.5 g of thionyl chloride and 14.6 g of ethylene glycol dimethyl ether into a constant pressure funnel. The molar ratio of D-mannitol to thionyl chloride is 1:1. 1.2 In an oil bath, add a magnetic stir bar. Connect one end of a four-necked flask to a thermometer sleeve, another end to a constant pressure dropping funnel, and a third end to a condenser for connecting to a high-low temperature circulating machine. Connect the other end to nitrogen. Turn on the high-low temperature circulating machine to cool down to 5°C. Raise the oil bath temperature to 50°C and begin adding a thionyl chloride-ethylene glycol dimethyl ether mixture. During the addition process, maintain the system temperature above 50°C for 3 hours. After the addition is complete, continue to maintain the temperature and allow the reaction to stand for 6 hours to allow D-mannitol and thionyl chloride to fully undergo the condensation reaction. 1.3 The solution after reaction was filtered using a sand core F4 vacuum filter device, and the filtrate was separated from the filter cake (D-mannitol); 1.4 The filtrate was transferred to a rotary evaporator flask for rotary evaporation, and the temperature of the rotary evaporation oil bath was controlled to be less than 55℃, to obtain 26.2g of crude disulfite mannitol; 1.5 Add 200g of dimethyl carbonate to the crude product to dissolve it. After dissolving, add 40g of water to disperse it fully. After standing, extract and separate the phases to remove the aqueous phase. Repeat the operation 3 times. Add anhydrous magnesium sulfate to the dehydrated organic phase, stir for 1 hour, filter, and then rotary evaporate the filtrate to obtain 26.1g of disulfite mannitol. 2. Synthesis of mannitol sulfite: 2.1 Weigh 205.6 g of dimethyl carbonate and 23.2 g of mannitol disulfite into a four-necked flask using an electronic balance. Weigh 10.5 g of 1,1'-carbonyldiimidazole. Calculate and weigh 1,1'-carbonyldiimidazole according to the molar ratio of mannitol disulfite to 1,1'-carbonyldiimidazole of 1:0.7. Divide the weighed 1,1'-carbonyldiimidazole into four equal portions. 2.2 In an oil bath, add a magnetic stir bar. Connect one end of a four-necked flask to a thermometer sleeve and the other end to a condenser tube for connecting to the high-low temperature circulating machine. Seal the remaining two ends tightly. Turn on the high-low temperature circulating machine to cool down to 5°C. Raise the oil bath temperature to 50°C and start adding 1,1'-carbonyldiimidazole in four batches, with an interval of 1 hour between each batch. After the addition is complete, continue to maintain the temperature and let the reaction stand for 3 hours to allow the mannitol disulfite and 1,1'-carbonyldiimidazole to undergo a complete cyclization reaction. 2.3 The filtrate was separated from the filter cake (1,1'-carbonyldiimidazole) by using a sand core F4 vacuum filtration device; 2.4 The filtrate was transferred to a rotary evaporator flask for rotary evaporation. The temperature of the rotary evaporation oil bath was controlled to be less than 55°C to obtain 28.4 g of crude mannitol sulfite carbonate.

[0041] 3. Synthesis of mannitol sulfate: 3.1 Weigh 0.2 g of ruthenium trichloride and 19.8 g of pure water using an electronic balance to prepare a 1% ruthenium trichloride aqueous solution; weigh 134.4 g of sodium hypochlorite into a constant pressure funnel and 206.2 g of dimethyl carbonate solvent into a four-necked flask, wherein the molar ratio of mannitol sulfite carbonate to sodium hypochlorite is 1:4 and the mass ratio of mannitol sulfite carbonate to ruthenium trichloride is 1:0.005; 3.2 Set the temperature of the high and low temperature cycle integrated machine to 5℃. Dissolve the intermediate mannitol sulfite carbonate in dimethyl carbonate in a 500mL glass jacketed reactor. Add 1% ruthenium trichloride aqueous solution at 5℃. Add sodium hypochlorite solution to the constant pressure dropping funnel and control the dropping rate to 1g / min. Keep the system at 5℃ for 4 hours. The color of the reaction solution is initially light yellow and transparent. After adding ruthenium trichloride aqueous solution, it turns black. After adding sodium hypochlorite solution, it turns yellow-green during the reaction. 3.3 Use a separatory funnel to separate the aqueous phase and the organic phase. After purifying the organic phase, continue to add water to disperse it. After standing, separate the phases and take the upper organic phase. Repeat the operation three times. 3.4 The filtrate after extraction was transferred to a rotary evaporator flask for rotary evaporation. The temperature of the rotary evaporation oil bath was controlled to be less than 55℃ to obtain 30.4g of crude mannitol carbonate sulfate.

[0042] Comparative Example 1 Raw material preparation: D-mannitol, commercially available industrial grade, 99% purity; thionyl chloride, commercially available product, Maclean, 99.5% purity; ethylene glycol dimethyl ether, commercially available product, 99% purity; 1,1'-carbonyldiimidazole, commercially available industrial grade, 99% purity; dimethyl carbonate, commercially available product, 99% purity; ruthenium trichloride, commercially available industrial grade, 99.99% purity; sodium hypochlorite, commercially available industrial grade, with an effective chlorine concentration of 6%-14%; all raw and auxiliary materials need to be dehydrated, with moisture content less than 100 ppm; The preparation method of this comparative mannitol sulfate carbonate includes the following steps: 1. Synthesis of disulfite mannitol: 1.1 Weigh 18.44 g of D-mannitol and 184.2 g of ethylene glycol dimethyl ether solvent into a four-necked flask using an electronic balance; weigh 59.48 g of thionyl chloride and 70.56 g of ethylene glycol dimethyl ether into a constant pressure funnel. The molar ratio of D-mannitol to thionyl chloride is 1:5. 1.2 In an oil bath, add a magnetic stir bar. Connect one end of a four-necked flask to a thermometer sleeve, another end to a constant pressure dropping funnel, and a third end to a condenser for connecting to a high-low temperature circulating machine. Connect the other end to nitrogen. Turn on the high-low temperature circulating machine to cool down to 5°C. Raise the oil bath temperature to 50°C and begin adding a thionyl chloride-ethylene glycol dimethyl ether mixture. During the addition process, maintain the system temperature above 50°C for 3 hours. After the addition is complete, continue to maintain the temperature and allow the reaction to stand for 5 hours to allow D-mannitol and thionyl chloride to fully undergo the condensation reaction. 1.3 The solution after reaction was filtered using a sand core F4 vacuum filter device, and the filtrate was separated from the filter cake (D-mannitol); 1.4 The filtrate was transferred to a rotary evaporator flask for rotary evaporation, and the temperature of the rotary evaporation oil bath was controlled to be less than 55℃, to obtain 24.8g of crude disulfite mannitol; 2. Synthesis of mannitol sulfite: 2.1 Weigh 200.89 g of dimethyl carbonate solvent and 24.8 g of crude mannitol disulfite using an electronic balance into a four-necked flask. Weigh 7.4 g of 1,1'-carbonyldiimidazole. Calculate and weigh 1,1'-carbonyldiimidazole according to the molar ratio of mannitol disulfite to 1,1'-carbonyldiimidazole of 1:0.5. 2.2 In an oil bath, add a magnetic stir bar. Connect one end of a four-necked flask to a thermometer sleeve and the other end to a condenser tube for connecting to the high-low temperature circulating machine. Seal the remaining two ends tightly. Turn on the high-low temperature circulating machine to cool down to 5°C. Raise the oil bath temperature to 50°C and start adding 1,1'-carbonyldiimidazole. Then continue to maintain the temperature and let the reaction stand for 3 hours to allow the mannitol disulfite and 1,1'-carbonyldiimidazole to undergo a complete cyclization reaction. 2.3 The filtrate was separated from the filter cake (1,1'-carbonyldiimidazole) by using a sand core F4 vacuum filtration device; 2.4 The filtrate was transferred to a rotary evaporator flask for rotary evaporation. The temperature of the rotary evaporation oil bath was controlled to be less than 55°C to obtain 26.4 g of crude mannitol sulfite carbonate.

[0043] 3. Synthesis of mannitol sulfate: 3.1 Weigh 0.2 g of ruthenium trichloride and 19.8 g of pure water using an electronic balance to prepare a 1% ruthenium trichloride aqueous solution; weigh 62.57 g of sodium hypochlorite into a constant pressure funnel, and weigh 201.24 g of dimethyl carbonate into a four-necked flask, wherein the molar ratio of mannitol sulfite carbonate to sodium hypochlorite is 1:2, and the mass ratio of mannitol sulfite carbonate to ruthenium trichloride is 1:0.01; 3.2 Set the temperature of the high and low temperature cycle integrated machine to 5℃. Dissolve the intermediate mannitol sulfite carbonate in dimethyl carbonate in a 500mL glass jacketed reactor. Add 1% ruthenium trichloride aqueous solution at 5℃. Add sodium hypochlorite solution to the constant pressure dropping funnel and control the dropping rate to 1g / min. Keep the system at 5℃ for 3h. The color of the reaction solution is initially light yellow and transparent. After adding ruthenium trichloride aqueous solution, it turns black. After adding sodium hypochlorite solution, it turns yellow-green during the reaction. 3.3 Use a separatory funnel to separate the aqueous phase and the organic phase. After purifying the organic phase, continue to add water to disperse it. After standing, separate the phases and take the upper organic phase. Repeat the operation three times. 3.4 The filtrate after extraction was transferred to a rotary evaporator flask for rotary evaporation. The temperature of the rotary evaporation oil bath was controlled to be less than 55℃ to obtain 28.4g of crude mannitol carbonate sulfate.

[0044] Performance testing The mannitol carbonate sulfate obtained in Examples 1-4 and Comparative Example 1 were analyzed by liquid chromatography using an Agilent 789oB. The results are shown in Table 1. The liquid chromatogram of Example 1 is shown below. Figure 1 As shown.

[0045] Table 1. Test results of mannitol sulfate obtained in Examples 1-2 and Comparative Example 1

[0046] As shown in Table 1, the mannitol sulfate content in the products prepared by the method of the present invention in Examples 1-4 can reach 97.59%, while the mannitol sulfate content in the product prepared in Comparative Example 1 is only 85.54%, indicating that the preparation method of the present invention can improve the yield of mannitol sulfate.

[0047] Mannitol sulfate ester liquid chromatography showed a peak value around 8.0 in an acetonitrile mobile phase at 60 °C. Figure 1 It can be seen that the mannitol carbonate sulfate prepared in the embodiments of the present invention has a peak value of 8.037 and the content can reach 99.78%, indicating that the target product mannitol carbonate sulfate was prepared in Example 1 of the present invention.

[0048] The mannitol sulfate obtained in Example 1 was analyzed by infrared spectroscopy using a Thermo Fisher Nicolet iS50. The infrared spectrum is shown below. Figure 2 As shown. By Figure 2 It can be seen that the most prominent feature in the spectrum is at approximately 1740 cm⁻¹. -1 The strong absorption peak at 1250 cm⁻¹ is attributed to the stretching vibration of the carbonyl group (C=O) in the carbonate group, directly confirming the existence of the carbonate structure; simultaneously, at 1250 cm⁻¹... -1 and 1050cm -1 The strong and broad absorption band appearing nearby is a characteristic vibrational peak of the sulfate ester group (S=O), confirming the formation of the sulfate ester moiety; at approximately 2900 cm⁻¹ -1 The absorption peaks at the point originate from the CH bonds of the mannitol skeleton; the common appearance of these characteristic peaks is highly consistent with the molecular structure of the target compound, further corroborating the chemical structure of the mannitol carbonate sulfate prepared in Example 1 of this invention.

[0049] The mannitol sulfate carbonate obtained in Example 1 was subjected to solid-state NMR analysis using Bruker AVANCE 400 and Bruker AVANCE 600 equipment. The carbon NMR spectra are shown below. Figure 3 As shown, the proton NMR spectrum is as follows: Figure 4 As shown. According to Figure 3 Nuclear magnetic resonance (NMR) spectral analysis fully confirmed that the compound is mannitol sulfate carbonate. Specific analysis is as follows: First, in the 13C NMR spectrum, a clear signal peak appeared in the chemical shift range of δ 150-160 ppm. This position is a typical peak region for the carbonyl carbon in the carbonate group (-O-CO-O-), and its presence acts like a "molecular fingerprint," directly proving the formation of the carbonate structure in the compound. Furthermore, multiple signals appearing in the δ 60-90 ppm range correspond to carbon atoms on the mannitol molecular skeleton. The overall distribution and quantity of these signals are consistent with the expected six-carbon sugar alcohol structure, and some signals shift to lower fields (i.e., in the direction of larger δ values), suggesting that the hydroxyl groups attached to the carbon atoms have been converted to sulfates (-O-SO3). - The substitution of electron-withdrawing groups, such as electron-withdrawing groups, alters the surrounding electronic environment. Secondly, Figure 4¹H NMR spectroscopy revealed that the hydrogen atom signals connecting oxygen atoms to the mannitol skeleton mainly appeared in a wide range of δ 3.5 ppm to 5.5 ppm. Particularly important were the signals observed at δ 4.8–5.5 ppm, which are usually attributed to the hydrogen atoms closest to the carbonate group (-CH₂-O-CO-). Due to the strong electron-withdrawing effect of the carbonate group, the signals of these hydrogen atoms shifted significantly to the lower field. The signals at δ 4.2–4.8 ppm may be related to hydrogen atoms at the sulfate substitution sites. The entire ¹H NMR spectrum exhibited a complex multipeak shape, which reflects the complex interactions between multiple hydrogen atoms in the mannitol molecule due to their different chemical environments (i.e., different degrees of substitution and positions).

[0050] In summary, the establishment of the characteristic peaks of carbonates in the carbon spectrum and the systematic shift of hydrogen atom signals in the proton spectrum due to esterification are consistent and mutually supportive, jointly confirming that the structure of this compound is mannitol carbonate sulfate.

[0051] The above-described embodiments are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Any modifications, alterations, evolutions, or improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope of the present invention.

Claims

1. A method for preparing mannitol sulfate carbonate, characterized in that, Includes the following steps: S1. Dissolve D-mannitol in ethylene glycol dimethyl ether solvent to obtain a first solution, dissolve thionyl chloride in ethylene glycol dimethyl ether solvent to obtain a second solution, add the second solution dropwise to the first solution, heat to react completely, and obtain the first compound. The molar ratio of D-mannitol to thionyl chloride is 1:1-3, and the mass ratio of D-mannitol to ethylene glycol dimethyl ether solvent in the first solution is 1:

10. S2. Dissolve the first compound in dimethyl carbonate solvent to obtain a third solution. Add 1,1'-carbonyldiimidazole to the third solution in 3-5 portions at intervals. After heating and reacting completely, obtain the second compound. The molar ratio of the first compound to 1,1'-carbonyldiimidazole is 1:0.7-1.

5. S3. Dissolve the second compound in dimethyl carbonate solvent to obtain a fourth solution. Add an aqueous solution of ruthenium trichloride catalyst to the fourth solution, and then add sodium hypochlorite solution dropwise. After heating and reacting completely, mannitol carbonate sulfate is obtained. The mass ratio of the second compound to ruthenium trichloride is 1:0.0005-0.01, and the molar ratio of the second compound to sodium hypochlorite is 1:4-8.

2. The method for preparing mannitol sulfate according to claim 1, characterized in that, In step S1, the reaction is carried out under inert gas protection. The temperature of the reaction system is controlled to rise from room temperature to 50°C, and then the second solution is added dropwise. After the addition is completed, the temperature is maintained and the reaction is allowed to stand for 3-10 hours.

3. The method for preparing mannitol sulfate according to claim 1, characterized in that, Step S1 also includes: After the reaction was completed, the reaction system was filtered and rotary evaporated to obtain the crude product; Add dimethyl carbonate to the crude product. After the crude product dissolves, add water, stir thoroughly, and let stand to separate the layers. Extract and separate the phases, remove the aqueous phase, and take the upper organic phase. Repeat the operation 2-3 times. The organic phase was dehydrated, filtered, and rotary evaporated to obtain the first compound.

4. The method for preparing mannitol sulfate according to claim 1, characterized in that, In step S1, the molar ratio of D-mannitol to thionyl chloride is 1:2.

2.

5. The method for preparing mannitol sulfate according to claim 1, characterized in that, In step S2, the temperature of the reaction system is raised from room temperature to 50°C. Then, 1,1'-carbonyldiimidazole is added to the third solution in 3-5 portions at intervals. After all the solution is added, the temperature is raised to 70°C and the reaction is allowed to stand for 3 hours.

6. The method for preparing mannitol sulfate according to claim 1, characterized in that, In step S2, the molar ratio of mannitol disulfite to 1,1'-carbonyldiimidazole is 1:

1.

7. The method for preparing mannitol sulfate according to claim 1, characterized in that, In step S3, after controlling the temperature of the reaction system to 25°C, sodium hypochlorite solution is added dropwise. After the addition is complete, the temperature is maintained and the reaction is allowed to stand for 3-6 hours.

8. The method for preparing mannitol sulfate according to claim 1, characterized in that, Step S3 also includes: after the reaction is completed, the reaction system is allowed to stand and separate into layers, and the aqueous phase is removed by extraction and phase separation, and the upper organic phase is taken. Add water to the organic phase, stir thoroughly, let stand to separate the layers, extract and separate the phases, remove the aqueous phase, take the upper organic phase, and repeat the operation 2-3 times. The organic phase was dehydrated, filtered, and rotary evaporated to obtain mannitol sulfate carbonate.

9. The method for preparing mannitol sulfate according to claim 1, characterized in that, In step S3, the mass ratio of the second compound to ruthenium trichloride is 1:0.01, and the molar ratio of the second compound to sodium hypochlorite is 1:6.

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