Description:FIELD OF THE INVENTION

[0001] The present invention relates to a process of synthesis of propyl phosphonic anhydride, and more particularly, the present invention relates to an optimized, novel and scalable process of synthesis of propyl phosphonic anhydride.

BACKGROUND OF THE INVENTION

[0002] The compound 4-propyl phosphonic anhydride (T3P) 06 is a key regent for peptide synthesis. For example, 4-propyl phosphonic anhydride is very authentic reagent for peptide synthesis1-propylphosphoric cyclic anhydride is an important condensation reagent, and is gradually applied to dehydration and coupling reaction of acid and amine in a polypeptide synthesis process in organic synthesis due to high activity.

[0003] The n-propyl phosphonic cyclic anhydride is a colorless or light-yellow viscous liquid and is an important condensation reagent. This is also used as a coupling agent which is mainly used for amide or ester condensation reaction. The propyl phosphonic anhydride has high activity as compared with the conventional condensation reagent. Further, the propyl phosphonic anhydride has the advantages of high reaction yield, low toxicity, convenience in post-treatment and the like. The application is more and more extensive, and the DCC, DIC and EDC (what is DCC, DIC and EDC) are gradually replaced.

[0004] Recently, n-propyl phosphoric cyclic anhydride has found its use in lithium battery electrolyte, so that the SEI film-forming performance of the lithium battery electrode is improved. Though the n-propyl phosphoric cyclic anhydride has a dehydration effect and but can be effectively prolong the cycle service life of the lithium battery.

[0005] One prior art patent CN200480019925.5 discloses a method for distilling a product by dissolving a raw material of phosphoric acid in acetic anhydride and performing a reflux reaction for 2 hours, then distilling off acetic acid and acetic anhydride under reduced pressure, and then raising the external temperature and raising the vacuum. However, high purity of the propane phosphoric acid used in this process is not readily available, thereby limiting its commercial production.

[0006] Another Chinese Patent CN201310387005 discloses that dimethyl propyl phosphate is added into an ionic liquid solvent by controlling the temperature to be 0-80 ℃, acetic anhydride is added within 1-3 hours at the same process temperature after dripping, then the reaction liquid is obtained by heating reflux reaction for 1-8 hours, and the ionic liquid solvent is distilled under normal pressure to remove low-boiling components and then is distilled under reduced pressure to obtain the 1-propyl phosphoric cyclic anhydride. However, this method uses acetic anhydride as a raw material to perform the reaction, the reaction time is long, and the use of ionic liquid increases the cost.

[0007] Accordingly, there exists a need to provide a process of synthesis propyl phosphonic anhydride, which overcomes abovementioned drawbacks.

OBJECT OF THE INVENTION

[0008] An object of the present invention is to provide an improved process of synthesis of 1-propyl phosphonic anhydride.

[0009] Another object of the present invention is to provide improved process for synthesis of 1-propyl phosphonic anhydride by using free radicals’ catalyst and without solvent, which is green chemistry approach and having conversion more than 90%.

[00010] Yet another object of the present invention is to provides hydrolysis only with water without need of acidic condition for hydrolysis, hence, to provide simple efficient method for hydrolysis.

[00011] One more object of the present invention is to provide chlorination by using Oxalyl chloride, TMS Cl without adding extra solvent and extra reagent, hence to provide scalable, economical and efficient process.

SUMMARY OF THE INVENTION

[00012] Accordingly, the present invention provides a process of synthesis 1-propyl phosphonic anhydride. The process comprises adding any one of azaisobutyronitrile (AIBN), and peroxide catalyst to diethyl phosphate in 1:1 ratio to form a first reaction mass, purging propylene gas for 3 to 4 hrs. through the first reaction mass to obtain diethyl propyl phosphate.

[00013] The process further comprises adding any one of hydrochloric acid and water in diethyl propyl phosphate in a ratio of 5:1 to form a second reaction mass, heating the second reaction mass at 110 to 120°C for 24 hrs and adding toluene in a ratio of 1:1 to obtain propyl phosphonic acid.

[00014] The process furthermore comprises adding chloride compound to propyl phosphonic acid to form a third reaction mass, heating the third reaction mass at 110-120°C for 24 to 28 hrs to yield 1-propylphosphonic dichloride.

[00015] The process moreover comprises adding hydrochloric acid to 1-propylphosphonic dichloride in ratio of 1:10 to form fourth reaction mass and heating at 110-120°C; and purging nitrogen gas through the fourth reaction mass for 9 to 10 hrs to obtain 1-propyl phosphonic anhydride.

DETAILED DESCRIPTION OF THE INVENTION

[00016] The foregoing objects of the present invention are accomplished and the problems and shortcomings associated with the prior art, techniques and approaches are overcome by the present invention as described below in the preferred embodiments.

[00017] The present invention provides a process of synthesis of -propyl phosphonic anhydride by using free radicals’ catalyst and without acidic environment for hydrolysis. The process carries out hydrolysis only with water without need of acidic condition for hydrolysis, hence, provides simple efficient method for hydrolysis.

[00018] In one aspect, the present invention provides a process of synthesis 1-propyl phosphonic anhydride.

[00019] The process at first step comprises adding any one of azaisobutyronitrile (AIBN), and peroxide catalyst to diethyl phosphate in 1:1 ratio to form a first reaction mass.

Diethyl Phosphate Diethyl Propyl Phosphate

[00020] The diethyl phosphate is heated at 120 to 125°C before mixing with azaisobutyronitrile (AIBN), and peroxide catalyst.

[00021] In an embodiment, peroxide catalyst includes but not limited to dibenzoyl peroxide, azaisobutyronitrile t-butyl peroxide, azaisobutyronitrile hydrogen peroxide.

[00022] The process at second step comprises purging propylene gas for 3 to 4 hrs. through the first reaction mass to obtain diethyl propyl phosphate.

[00023] The process at third step comprises adding any one of hydrochloric acid and water in diethyl propyl phosphate in a ratio of 5:1 to form a second reaction mass.

Diethyl Propyl Phosphate Propyl phosphonic Acid

[00024] The process at fourth step comprises heating the second reaction mass at 110 to 120°C for 24 hrs and adding toluene in a ratio of 1:1 to obtain propyl phosphonic acid.

[00025] The process at fifth step comprises adding chloride compound to propyl phosphonic acid to form a third reaction mass.

Propyl phosphonic Acid 1-Propylphosphonic dichloride

[00026] In an embodiment, the chloride includes but not limited to oxalyl chloride, thionyl chloride, trimethyl silyl chloride

[00027] The process at sixth step comprises heating the third reaction mass at 110-120°C for 24 to 28 hrs to yield 1-propylphosphonic dichloride.

[00028] The process at seventh step comprises adding hydrochloric acid to 1-propylphosphonic dichloride in ratio of 1:10 to form fourth reaction mass and heating at 110-120°C.

1-Propylphosphonic dichloride 1-Propanephosphonic acid cyclic anhydride

[00029] The process finally comprises purging nitrogen gas through the fourth reaction mass for 9 to 10 hrs to obtain -propyl phosphonic anhydride.

Example 1- Preparation of diethyl propyl phosphate
Diethyl Phosphate (1.0 kg) is charged in to RBF and heated to 120 to 125°C. To this Azaisobutyronitrile (AIBN)/Dibenzoyl Peroxide (0.1kg) is added and Propylene gas is purged for 3 to 4 hrs. After 4 hrs, the reaction mass is analyzed by gas chromatography which as purity of 90% yield 95%

Example 2- Preparation of diethyl propyl phosphate
Diethyl Phosphate (1.0 kg) is charged in to RBF and heated it to 120 to 125°C. To this Azaisobutyronitrile t-butyl peroxide (0.1kg) is added and Propylene gas is purged for 3 to 4 hrs. After 4 hrs, the reaction mass is analyzed by gas chromatography which as purity of 90% yield 95%

Example 3- Preparation of diethyl propyl phosphate

Diethyl Phosphate (1.0 kg) is charged in to RBF and heated it to 120 to 125°C. To this Azaisobutyronitrile Hydrogen peroxide (50%) (0.1kg) is added and Propylene gas is purged for 3 to 4 hrs. After 4 hrs, the reaction mass is analyzed by gas chromatography which as purity of 90% yield 95%

Example 4- Propyl phosphonic Acid
To a stirred solution of Hydrochloric acid (5.0 kg), Diethyl propyl Phosphate is added and the reaction mass is heated for 110 to 110°C for 24 hrs. After completion of reaction, water is distilled atmospherically and toluene (1.0 kg) is added and distilled. After complete distillation, high vacuum is applied for 3 to 4 hrs to unload the yellow Oil. Purity analyses by GC 95% and Yield 93%

Example 5- Propyl phosphonic Acid
To a stirred solution of water, Diethyl propyl Phosphate is added and the reaction mass is heated for 110 to 110°C for 24 hrs. After completion of reaction, water is distilled atmospherically and toluene (1.0 kg) is added and distilled. After complete distillation, high vacuum is applied for 3 to 4 hrs to unload the yellow Oil. Purity analyses by GC 95% and Yield 93%

Example 6 – 1-Propylphosphonic dichloride
To a solution of Propyl phosphonic Acid 1.0 kg, Oxalyl Chloride 5.0 kg is added and the reaction mass is heated for 110-120°C for 24 to 28 hrs. After completion of reaction, the oxalyl chloride is distilled atmospherically and degassed for 6 to 8 hrs at 55 to 60°C. After complete degassing, the reaction mass is cooled to 25 to 30°C and unloaded to obtain yellow oil having GC yield 90 % to 98%.

Example 7 – 1-Propylphosphonic dichloride
To a solution of Propyl phosphonic Acid 1.0 kg, Thionyl Chloride 4.0 is added and the reaction mass is heated for 110-120°C for 24 to 28 hrs. After completion of reaction, the thionyl chloride is distilled atmospherically and degassed for 6 to 8 hrs at 55 to 60°C. After complete degassing, the reaction mass is cooled to 25 to 30°C and unloaded to obtain yellow oil having GC yield 90 % to 98%.

Example 8 – 1-Propylphosphonic dichloride
To a solution of Propyl phosphonic Acid 1.0 kg, Trimethyl Silyl Chloride 4,5 kg is added and the reaction mass is heated for 110-120°C for 24 to 28 hrs. After completion of reaction, the Trimethyl Silyl Chloride is distilled atmospherically and degassed for 6 to 8 hrs at 55 to 60°C. After complete degassing, the reaction mass is cooled to 25 to 30°C and unloaded to obtain yellow oil having GC yield 90 % to 98%.

Example 9 -1-Propanephosphonic acid cyclic anhydride
To a solution of 1-Propylphosphonic dichloride, 1N HCl (100 gm) is added and the mixture is heated to 110 to 110°C. Thereafter, Nitrogen gas is purged for 9 to 10 hrs and then degassed for 9 to 10 hrs. After complete degassing, the final product is unloaded and kept under U/N2 atm.\

ADVANTAGES OF THE INVENTION
[00030] The process of the present invention is improved process for synthesis of 1-propyl phosphonic anhydride by using free radicals’ catalyst and without solvent, which is green chemistry approach and having conversion more than 90%.
[00031] The process of the present invention provides hydrolysis only with water and does not require acidic condition for hydrolysis, hence, it is simple efficient method for hydrolysis.
[00032] The process of the present invention provides chlorination by using Oxalyl chloride, TMS Cl without adding extra solvent and extra reagent, hence the process is scalable, economical and efficient process.

[00033] The foregoing descriptions of specific embodiments of the present invention have been presented for purposes of illustration and description. They are not intended to be exhaustive or to limit the present invention to the precise forms disclosed, and obviously many modifications and variations are possible in light of the above teaching. The embodiments were chosen and described in order to best explain the principles of the present invention and its practical application, and to thereby enable others skilled in the art to best utilize the present invention and various embodiments with various modifications as are suited to the particular use contemplated. It is understood that various omissions and substitutions of equivalents are contemplated as circumstances may suggest or render expedient, but such omissions and substitutions are intended to cover the application or implementation without departing from the spirit or scope of the claims of the present invention.

, Claims:
1. A process of synthesis 1-propyl phosphonic anhydride, the process comprising:
adding any one of azaisobutyronitrile (AIBN), and peroxide catalyst to diethyl phosphate in 1:1 ratio to form a first reaction mass;
purging propylene gas for 3 to 4 hrs. through the first reaction mass to obtain diethyl propyl phosphate;
adding any one of hydrochloric acid and water in diethyl propyl phosphate in a ratio of 5:1 to form a second reaction mass,
heating the second reaction mass at 110 to 120°C for 24 hrs and adding toluene in a ratio of 1:1 to obtain propyl phosphonic acid;
adding chloride compound to propyl phosphonic acid to form a third reaction mass;
heating the third reaction mass at 110-120°C for 24 to 28 hrs to yield 1-propylphosphonic dichloride;
adding hydrochloric acid to 1-propylphosphonic dichloride in ratio of 1:10 to form fourth reaction mass and heating at 110-120°C; and
purging nitrogen gas through the fourth reaction mass for 9 to 10 hrs to obtain 1-propyl phosphonic anhydride.

2. The process as claimed in claim 1, wherein peroxide catalyst includes any one of dibenzoyl peroxide, azaisobutyronitrile t-butyl peroxide, azaisobutyronitrile hydrogen peroxide.

3. The process as claimed in claim 1, wherein chloride includes any one of oxalyl chloride, thionyl chloride, trimethyl silyl chloride

4. The process as claimed in claim 1, wherein the diethyl phosphate is heated at to 120 to 125°C before mixing with azaisobutyronitrile (AIBN), and peroxide catalyst