1,5,2,4-Dioxadithiane, 2,2,4,4-tetraoxide

White crystalline solid

At room temperature, 48 g (0.5 mol) of methanesulfonic acid was added to the four-necked flask equipped with thermometer, condenser, stirrer and dropping funnel, and stirred. 48.5 g (0.5 mol) of sulfamic acid was added dropwise, and the internal temperature was controlled to 25 ° C - 35 ° C during the dropwise addition. The dropping time was controlled at 3-4h. After completion of the dropwise addition, the temperature was raised to 150 ° C, and refluxed for 3h. After completion of the reaction, the viscous liquid was obtained. The nuclear magnetic analysis showed that was methylene disulfonic acid. The system was cooled to room temperature, 300g of acetic anhydride was added, and stirred for 0.5 h till clear solution was obtained. 16.5g (0.55mol) of formaldehyde and 123.6 g (0.9 mol) of phosphorus trichloride were added to a three-neck bottle, stirred such that the resulting product was uniformly dispersed, and heated to 120 ° C for 5 h. After completion of the reaction, the product was obtained as a brown liquid. The reaction solution was poured into 100g of ice water (water temperature 0-5 ° C), stirred for 0.5h, suction-filtered and dried at 50 ° C under reduced pressure to obtain fine white product 83.4g. The yield was 88.72percent.Pre-toluene with calcium chloride removed 24 hours, water content of less than 1ppm;To the esterification reactor equipped with a condensate trap, methylene disulfonic acid was added, Paraformaldehyde, toluene, heating to 120 ° C, With water organic solvent to maintain the distillation cycle, The water carried by the waterborne organic solvent is separated by a water separator during the distillation and recycle cycle.The molar ratio of methylene disulfonic acid to waterborne organic solvent was 1: 1.5, The molar ratio of methylene disulfonic acid to polyoxymethylene was 1: 1.1; after 2 hours of esterification reaction, the reaction was stopped and cooled to room temperature;The reaction material was filtered to remove the insoluble matter, and the filtrate was distilled off at -0.095 MPa to remove the solvent until no solvent was introduced. Ethanol was then added to the distillation kettle and allowed to stand for half an hour for half an hour.Filtration to obtain white crystals, the white crystals in acetonitrile in the recrystallization, the molar ratio of material to acetonitrile 1: 3, Methyl methanesulfonate was obtained in a yield of 81.2percent.In a 100 ml four-necked flask used in the first batch (withdrawing the reaction mixture of the first batch and not being washed and dried)5.0 g (28.4 mmol) of methanedisulfonic acid and 4.0 g (28.4 mmol) of diphosphorous pentoxide were added, and 0.85 g (28.4 mmol) of paraformaldehyde was added with stirring. After completion of the addition, the mixture was stirred at 120 ° C. for 1 hour and then cooled to 80 ° C. 0.5 g of water was slowly added to the reaction mixture, stirred for 10 minutes, and then taken out in a 100 ml eggplant flask at 65 ° C. The reaction mixture taken out to the recovery flask was cooled to room temperature, and 35 g of water was added. After stirring for 30 minutes, insoluble matter was separated by filtration to obtain white crystals. The obtained crystals were dried at 40 ° C. and 10 mmHg for 6 hours to obtain 2.5 g (yield 47percent) of the objective methylene methane disulfonate.176 g of methanesulfonic acid and 30 g of paraformaldehyde were charged into a 1 L reaction flask and mechanically stirred for 15 minutes. Then no water120 g of magnesium sulfate was added to the above system, The temperature was raised to 100 ° C and reacted at 100 ° C for 5 hours. After the end of the reaction, the system was cooled and the solid was extracted with 200 mL of X3 times methylene chloride. The insoluble material was removed by filtration and the filtrate was spin-dried to give methyl methanesulfonate productIn a 200 ml four-necked flask equipped with a stirrer, a condenser, and a thermometer, were placed 8.8 g (0.05 mole) of methanedisulfonic acid and 7.1 g (0.05 mole) of phosphorus pentoxide. To the mixture, 1.6 g (0.05 mole) of 92percent paraformaldehyde was added while stirring at room temperature. After completion of the addition, the mixture was heated to 120°C and stirred for one hour. The mixture was then cooled to room temperature and 100 g of methylene chloride was added thereto. After stirring for one hour, insoluble matter was filtered off. The resulting filtrate was concentrated to obtain crystals, and the resulting crystals were dried at 40°C and 10 mmHg for 6 hours, giving 4.7 g of light brown crystals of methylene methanedisulfonate represented by General Formula (2) wherein RComparative Synthesis of methylene methanedisulfonate using acetonitrile as a reaction solvent; To a silver methanedisulfonate (2.0 g, 5.1 mmol) in acetonitrile (5 mL), diiodomethane (1.4 g, 5.1 mmol) was added dropwise, and the mixture was reacted at reflux for 4 hours. The reaction mixture was then cooled, and the desired product was extracted with adding ethyl acetate. The extract was concentrated under reduced pressure, to give crude product of methylene methanedisulfonate. Determination by internal reference method using 176 g of methanesulfonic acid and 30 g of paraformaldehyde were charged into a 1 L reaction flask and mechanically stirred for 15 minutes. Then no water120 g of magnesium sulfate was added to the above system, The temperature was raised to 100 ° C and reacted at 100 ° C for 5 hours. After the end of the reaction, the system was cooled and the solid was extracted with 200 mL of X3 times methylene chloride. The insoluble material was removed by filtration and the filtrate was spin-dried to give methyl methanesulfonate productAt room temperature, 48 g (0.5 mol) of methanesulfonic acid was added to the four-necked flask equipped with thermometer, condenser, stirrer and dropping funnel, and stirred. 48.5 g (0.5 mol) of sulfamic acid was added dropwise, and the internal temperature was controlled to 25 ° C - 35 ° C during the dropwise addition. The dropping time was controlled at 3-4h. After completion of the dropwise addition, the temperature was raised to 150 ° C, and refluxed for 3h. After completion of the reaction, the viscous liquid was obtained. The nuclear magnetic analysis showed that was methylene disulfonic acid. The system was cooled to room temperature, 300g of acetic anhydride was added, and stirred for 0.5 h till clear solution was obtained. 16.5g (0.55mol) of formaldehyde and 123.6 g (0.9 mol) of phosphorus trichloride were added to a three-neck bottle, stirred such that the resulting product was uniformly dispersed, and heated to 120 ° C for 5 h. After completion of the reaction, the product was obtained as a brown liquid. The reaction solution was poured into 100g of ice water (water temperature 0-5 ° C), stirred for 0.5h, suction-filtered and dried at 50 ° C under reduced pressure to obtain fine white product 83.4g. The yield was 88.72percent.Pre-toluene with calcium chloride removed 24 hours, water content of less than 1ppm;To the esterification reactor equipped with a condensate trap, methylene disulfonic acid was added, Paraformaldehyde, toluene, heating to 120 ° C, With water organic solvent to maintain the distillation cycle, The water carried by the waterborne organic solvent is separated by a water separator during the distillation and recycle cycle.The molar ratio of methylene disulfonic acid to waterborne organic solvent was 1: 1.5, The molar ratio of methylene disulfonic acid to polyoxymethylene was 1: 1.1; after 2 hours of esterification reaction, the reaction was stopped and cooled to room temperature;The reaction material was filtered to remove the insoluble matter, and the filtrate was distilled off at -0.095 MPa to remove the solvent until no solvent was introduced. Ethanol was then added to the distillation kettle and allowed to stand for half an hour for half an hour.Filtration to obtain white crystals, the white crystals in acetonitrile in the recrystallization, the molar ratio of material to acetonitrile 1: 3, Methyl methanesulfonate was obtained in a yield of 81.2percent.In a 100 ml four-necked flask used in the first batch (withdrawing the reaction mixture of the first batch and not being washed and dried)5.0 g (28.4 mmol) of methanedisulfonic acid and 4.0 g (28.4 mmol) of diphosphorous pentoxide were added, and 0.85 g (28.4 mmol) of paraformaldehyde was added with stirring. After completion of the addition, the mixture was stirred at 120 ° C. for 1 hour and then cooled to 80 ° C. 0.5 g of water was slowly added to the reaction mixture, stirred for 10 minutes, and then taken out in a 100 ml eggplant flask at 65 ° C. The reaction mixture taken out to the recovery flask was cooled to room temperature, and 35 g of water was added. After stirring for 30 minutes, insoluble matter was separated by filtration to obtain white crystals. The obtained crystals were dried at 40 ° C. and 10 mmHg for 6 hours to obtain 2.5 g (yield 47percent) of the objective methylene methane disulfonate.11.0 g (0.05 mol) of sodium salt of methanedisulfonic acid, 5.0 g (0.05 mol) of concentrated sulfuric acid, and 7.2 g (0.05 mol) of phosphorus pentoxide were placed in a four-necked flask equipped with a stirrer, a condenser, a thermometer, and a dropping funnel. 1.6 g (0.05 mol) of 92percent paraformaldehyde was added to the mixture while stirring at room temperature. After completion of the addition, the mixture was heated to 120° C. and stirred for one hour. The mixture was then cooled to room temperature and 200 g of methylene chloride was added thereto. After stirring for one hour, insoluble matter was filtered off. The filtrate was concentrated to obtain crystals, and the resulting crystals were dried at 40° C. and 10 mmHg for 6 hours, giving 3.8 g of light brown crystals of methylene methanedisulfonate represented by Formula (3) wherein R1 and R2 are hydrogen atoms, and n is 1. The yield of the resulting methylene methanedisulfonate was 40 mol percent relative to sodium salt of methanedisulfonic acid. [0057] The following analysis results confirmed that the resulting light brown crystals were methylene methanedisulfonate. [0058] 1H-NMR (400 MHz, CD3CN) delta (ppm): 5.32 (s, 2H), 6.00 (s, 2H).12.6 g (0.05 mol) of potassium salt of methanedisulfonic acid, 2.5 g (0.025 mol) of concentrated sulfuric acid, and 7.2 g (0.05 mol) of phosphorus pentoxide were placed in a four-necked flask equipped with a stirrer, a condenser, a thermometer, and a dropping funnel. 1.6 g (0.05 mol) of 92percent paraformaldehyde was added to the mixture while stirring at room temperature. After completion of the addition, the mixture was heated to 120° C. and stirred for one hour. The mixture was then cooled to room temperature and 200 g of methylene chloride was added thereto. After stirring for one hour, insoluble matter was filtered off. The filtrate was concentrated to obtain crystals, and the resulting crystals were dried at 40° C. and 10 mmHg for 6 hours, giving 4.8 g of light brown crystals of methylene methanedisulfonate represented by formula (3) wherein R1 and R2 are hydrogen atoms, and n is 1. The yield of the resulting methylene methanedisulfonate was 51 mol percent relative to potassium salt of methanedisulfonic acid. [0060] In the same manner as Example 1, the 1H-NMR analysis results confirmed that the resulting light brown crystals were methylene methanedisulfonate.Synthesis of methylene methanedisulfonate using isooctane as a reaction solvent To a silver methanedisulfonate (20.0 g, 51.3 mmol) in isooctane (50 mL), diiodomethane (13.7 g, 51.3 mmol) was added dropwise, and the mixture was reacted at reflux for 4 hours. The reaction mixture was then cooled, and the desired product was extracted with adding ethyl acetate. The extract was concentrated under reduced pressure, to give crude product of methylene methanedisulfonate. After the crude product was dissolved in ethyl acetate, the solution was treated with activated charcoal, then concentrated. n-Hexane was added thereto, and precipitation was filtered, to obtain the precipitation and dried under reduced pressure to give methylene methanedisulfonate (7.8 g, yield: 81percent) as white crystal. 1H-NMR (CD3CN) delta: 5.30 (s, 2H), 5.97 (s, 2H); 13C-NMR (CD3CN) delta: 68.9, 91.8; Melting Point: 146°C.Synthesis of methylene methanedisulfonate using cyclohexane as a reaction solvent To a silver methanedisulfonate (2.0 g, 5.1 mmol) in cyclohexane (5 mL), diiodomethane (1.4 g, 5.1 mmol) was added dropwise, and the mixture was reacted at reflux for 4 hours. The reaction mixture was then cooled, and the desired product was extracted with adding ethyl acetate. The extract was concentrated under reduced pressure, to give crude product of methylene methanedisulfonate. Determination by internal reference method using 1H-NMR gave a reaction rate of 47percent. Synthesis of methylene methanedisulfonate using cyclohexane as a reaction solvent under a pressurized condition; After silver methanedisulfonate (2.0 g, 5.1 mmol) and cyclohexane (5 mL) were charged into a sealed tube, diiodomethane (1.4 g, 5.1 mmol) was added dropwise to the mixture, and the sealed tube was hermetically sealed. The reaction mixture was heated to 120°C, and reacted with stirring for 4 hours. The reaction mixture was then cooled, and the desired product was extracted with adding ethyl acetate. The extract was concentrated under reduced pressure, to give crude product of methylene methanedisulfonate. Determination by internal reference method using 1H-NMR gave a reaction rate of 89percent.Comparative Synthesis of methylene methanedisulfonate using acetonitrile as a reaction solvent; To a silver methanedisulfonate (2.0 g, 5.1 mmol) in acetonitrile (5 mL), diiodomethane (1.4 g, 5.1 mmol) was added dropwise, and the mixture was reacted at reflux for 4 hours. The reaction mixture was then cooled, and the desired product was extracted with adding ethyl acetate. The extract was concentrated under reduced pressure, to give crude product of methylene methanedisulfonate. Determination by internal reference method using 1H-NMR gave a reaction rate of 15percent.In a 200 ml four-necked flask equipped with a stirrer, a condenser, and a thermometer, were placed 8.8 g (0.05 mole) of methanedisulfonic acid and 7.1 g (0.05 mole) of phosphorus pentoxide. To the mixture, 1.6 g (0.05 mole) of 92percent paraformaldehyde was added while stirring at room temperature. After completion of the addition, the mixture was heated to 120°C and stirred for one hour. The mixture was then cooled to room temperature and 100 g of methylene chloride was added thereto. After stirring for one hour, insoluble matter was filtered off. The resulting filtrate was concentrated to obtain crystals, and the resulting crystals were dried at 40°C and 10 mmHg for 6 hours, giving 4.7 g of light brown crystals of methylene methanedisulfonate represented by General Formula (2) wherein R1 and R2 are hydrogen atoms, and n is 1. The yield of the resulting methylene methanedisulfonate was 50.0percent relative to methanedisulfonic acid. It was confirmed that the resulting light brown crystals were methylene methanedisulfonate by the following analysis results: 1H-NMR (400 MHz, CD3CN) delta (ppm): 5.33 (s, 2H), 6.00 (s, 2H).

1. The methylene disulfonate compound can be used as a pharmaceutical preparation for treating leukemia in animals. 2. The battery added with MMDS has good high temperature cycling performance. It is suitable for power batteries, especially power batteries with lithium manganese oxide as the positive electrode material. MMDS can prevent the Mn melted at high temperature from adsorbing on the surface of the negative electrode, suppress the rise of impedance, effectively improve the cycle characteristics, and greatly increase its cycle life.

Molecular Weight:188.18
XLogP3:-1
Hydrogen Bond Acceptor Count:6
Exact Mass:187.94493019
Monoisotopic Mass:187.94493019
Topological Polar Surface Area:104
Heavy Atom Count:10
Complexity:265
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes