Application of gel type cation exchange resin to improvement of yield in bromination reaction of dulcitol

Abstract

The invention relates to an application of gel type cation exchange resin to a bromination reaction of dulcitol. The yield of dibromoducitol is substantially increased by 50% or above by using the resin in the preparation process of dibromoducitol, and the effects are obviously better than the effects in the prior art.

Description

technical field

[0001] The invention relates to the field of chemical medicines, in particular to the use of a gel-type cation exchange resin in improving the yield of dulcitol bromination reaction. Background technique

[0002] Dibromodulcitol, also known as dibromogalactitol, is an isomer of dibromomannitol, and its structure is as follows:

[0003]

[0004] Dibromodulcitol itself has pharmacological activity and is also the precursor of many compounds.

[0005] About the synthesis of dibromodunglitol, following preparation method has been disclosed:

[0006] The preparation method disclosed in the second phase of "Journal of Jiangxi Medical College" in 1984 in "The Synthesis of Anticancer Agent Dibromoguardol" is: under normal pressure, the optimum temperature for synthesizing dibromoguardol is 90 ℃ ( ±1°C) The suitable heating time is 9 hours; the concentration of hydrobromic acid should not be lower than 69-70%, otherwise the yield will be greatly reduced; the boil...

Examples

Embodiment 1

[0042] (a) 10kg of dulcitol is dropped into the reactor, and 100g of gel-type cationic resin AmberliteIR-120 that is treated with an acid until the pH is 4 is added, and 70% hydrobromic acid aqueous solution is added simultaneously: acetic acid=1:3 (weight ratio) The mixed solution, the addition is 2 times of dulcitol weight;

[0043] (b) heating in a water bath to 65°C and stirring continuously to dissolve dulcitol, and then continue heating and stirring until crystallization occurs;

[0044] (c) Add formic acid containing 0.1% hydrogen bromide 5 times the weight of dulcitol, keep stirring at 65° C., continue to react for 15 hours, let cool to room temperature, and let stand for 5 hours;

[0045] (d) Dilute the reaction solution with 1 times the amount of water, filter, wash the filter cake with water until neutral, drain it, add 0.5 times the volume percentage of ethanol with a concentration of 60%, soak it for 0.1 hour, drain it, and reduce the pressure at 25°C to -0.01 Dr...

Embodiment 2

[0048] (a) 10kg dulcitol is dropped into the reactor, add 30% hydrobromic acid aqueous solution: the mixed solution of acetic acid=1:2 (weight ratio), add-on is 5 times of dulcitol weight;

[0049](b) heating in a water bath to 50°C and stirring continuously to dissolve dulcitol, and then continue heating and stirring until crystallization occurs;

[0050] (c) Add 500 g of gel-type cationic resin Amberjet 1200Na that is treated with an acid until the pH value is 2, and simultaneously add formic acid that is 3 times the weight of dulcitol, keep stirring at 50° C., continue to react for 20 hours, let cool to room temperature, and set for 8 hours;

[0051] (d) Dilute the reaction solution with 2 times the amount of water, filter, wash the filter cake with water until neutral, drain it, add 1 times the volume percentage concentration of 50% ethanol to soak for 0.2 hours, drain it, and reduce the pressure to -0.02 at 30 ° C. Dry at MPa to obtain crude crystals of dibromodulcitol; ...

Embodiment 3

[0054] (a) 10kg of dulcitol is dropped into the reactor, add 10g of gel type cationic resin AmberliteIR-120 that is treated to pH 3 with acid, add 40% hydrobromic acid aqueous solution simultaneously: acetic acid=1:0.01 (weight ratio ) mixed solution, the addition amount is 1 time of dulcitol weight;

[0055] (b) heating in a water bath to 70°C and stirring continuously to dissolve dulcitol, and then continue heating and stirring until crystallization occurs;

[0056] (c) Add acetic acid with 1 times the weight of dulcitol, keep stirring at 70°C, continue to react for 2 hours, let cool to room temperature, and let stand for 9 hours;

[0057] (d) Dilute the reaction solution with 3 times the amount of water, filter, wash the filter cake with water until neutral, drain it, add 5 times the volume percentage concentration of 65% ethanol to soak for 0.5 hours, drain it, and reduce the pressure at 50 ° C to -0.05 Dry at MPa to obtain crude crystals of dibromodulcitol; add methanol ...

technical field

[0001] The invention relates to the field of chemical medicines, in particular to the use of a gel-type cation exchange resin in improving the yield of dulcitol bromination reaction. Background technique

[0002] Dibromodulcitol, also known as dibromogalactitol, is an isomer of dibromomannitol, and its structure is as follows:

[0003]

[0004] Dibromodulcitol itself has pharmacological activity and is also the precursor of many compounds.

[0005] About the synthesis of dibromodunglitol, following preparation method has been disclosed:

[0006] The preparation method disclosed in the second phase of "Journal of Jiangxi Medical College" in 1984 in "The Synthesis of Anticancer Agent Dibromoguardol" is: under normal pressure, the optimum temperature for synthesizing dibromoguardol is 90 ℃ ( ±1°C) The suitable heating time is 9 hours; the concentration of hydrobromic acid should not be lower than 69-70%, otherwise the yield will be greatly reduced; the boil...

Examples

Embodiment 1

[0042] (a) 10kg of dulcitol is dropped into the reactor, and 100g of gel-type cationic resin AmberliteIR-120 that is treated with an acid until the pH is 4 is added, and 70% hydrobromic acid aqueous solution is added simultaneously: acetic acid=1:3 (weight ratio) The mixed solution, the addition is 2 times of dulcitol weight;

[0043] (b) heating in a water bath to 65°C and stirring continuously to dissolve dulcitol, and then continue heating and stirring until crystallization occurs;

[0044] (c) Add formic acid containing 0.1% hydrogen bromide 5 times the weight of dulcitol, keep stirring at 65° C., continue to react for 15 hours, let cool to room temperature, and let stand for 5 hours;

[0045] (d) Dilute the reaction solution with 1 times the amount of water, filter, wash the filter cake with water until neutral, drain it, add 0.5 times the volume percentage of ethanol with a concentration of 60%, soak it for 0.1 hour, drain it, and reduce the pressure at 25°C to -0.01 Dr...

Embodiment 2

[0048] (a) 10kg dulcitol is dropped into the reactor, add 30% hydrobromic acid aqueous solution: the mixed solution of acetic acid=1:2 (weight ratio), add-on is 5 times of dulcitol weight;

[0049](b) heating in a water bath to 50°C and stirring continuously to dissolve dulcitol, and then continue heating and stirring until crystallization occurs;

[0050] (c) Add 500 g of gel-type cationic resin Amberjet 1200Na that is treated with an acid until the pH value is 2, and simultaneously add formic acid that is 3 times the weight of dulcitol, keep stirring at 50° C., continue to react for 20 hours, let cool to room temperature, and set for 8 hours;

[0051] (d) Dilute the reaction solution with 2 times the amount of water, filter, wash the filter cake with water until neutral, drain it, add 1 times the volume percentage concentration of 50% ethanol to soak for 0.2 hours, drain it, and reduce the pressure to -0.02 at 30 ° C. Dry at MPa to obtain crude crystals of dibromodulcitol; ...

Embodiment 3

[0054] (a) 10kg of dulcitol is dropped into the reactor, add 10g of gel type cationic resin AmberliteIR-120 that is treated to pH 3 with acid, add 40% hydrobromic acid aqueous solution simultaneously: acetic acid=1:0.01 (weight ratio ) mixed solution, the addition amount is 1 time of dulcitol weight;

[0055] (b) heating in a water bath to 70°C and stirring continuously to dissolve dulcitol, and then continue heating and stirring until crystallization occurs;

[0056] (c) Add acetic acid with 1 times the weight of dulcitol, keep stirring at 70°C, continue to react for 2 hours, let cool to room temperature, and let stand for 9 hours;

[0057] (d) Dilute the reaction solution with 3 times the amount of water, filter, wash the filter cake with water until neutral, drain it, add 5 times the volume percentage concentration of 65% ethanol to soak for 0.5 hours, drain it, and reduce the pressure at 50 ° C to -0.05 Dry at MPa to obtain crude crystals of dibromodulcitol; add methanol ...

Images