Title of Invention

"A PROCESS FOR THE PREPARATION OF POLYGLYCOLIC ACID FROM GLYCOLIC ACID ISOLATED FROM TECHNICAL GRADE GLYCOLIC ACID "

Abstract This invention relates to a process for the preparation of polyglycolic acid from glycolic acid isolated from technical grade glycolic acid by azeotropic distillation characterized by two stage melt polymerization of glycolic acid, said first stage comprising in melting glycolic acid to above its melting point and carrying out condensation reaction in presence of a metal catalyst such as Sb203 and dry nitrogen and removing water continuously thereon, said second stage is carried out under vacuum of 0.1 to 0.001 mbar for a period of 4 to 8 hours.
Full Text FIELD OF INVENTION
This invention relates to a process for the preparation of extra pure glycolic acid to prepare polyglycolic acid polymer for the development of suture materials.
The process for preparing glycolic acid comprises heating 70% aqueous solution of hydroxy acetic acid at 60-160°C specifically 80-120°C more specifically 90-110°C for 8-10 hours in presence of a aromatic solvent like benzene, toluene and/or like solvents to distill off water azeotropically.
The white crude solid (60% yield) so collected is dissolved in solvents like ethyl acetate, isopropanol. methylene chloride and recrystallised.
The snow white lustrous crystal of glycolic acid collected with a yield of 50-60% and purity of BACKGROUND OF THE INVENTION
Pure glycolic acid, a simple hydroxvl carboxylic acid (hydroxy acetic acid), is a low mole weight compound but has dual functionality of an alcohol and an acid. It is highly soluble in water, alcohols, acetone, acetates solvents; slightly soluble in ethyl ether; sparingly soluble in hydrocarbon solvents. Commercially, it is available in crystal form as well as in aqueous solutions of various concentrations, usually 70% or less.
Pure glycolic acid is a colourless, crystalline substance which start polymerization with the loss of water at or above 50°C. Activating both the hydroxyl and carboxylic acid group, glycolic acid has the property to form metal complexes and can be used in cleaning applications and hard water dissolution. Glycolic acid is a useful intermediate in organic synthesis including oxidation/reduction, esterification and formation of oligomers as well as long chain polymerization. Glycolic acid is naturally found in sugar beets, cane sugar, and unripe grapes. It is known that it diminishes the lines on the skin and makes skins look young. Synthetic glycolic acid and its derivatives are used in cosmetics. The}' are also used in emulsion polymers, as solvent and ink and paint additive to improve flow properties and impart gloss. Glycolic acid 70% high purity cosmetic grade is used in several cosmetic applications as the active ingredient. Major applications are skin peeling preparations (AI-IA effect), clinical preparations for the treatment of scars due to acne, as a skin cleansing agent and in preparations for the treatment of irregular skin pigmentation. Together with other active ingredients Glycolic acid 70% is also used in corticosteroid-containing creams and preparations used to treat skin cancer.
OBJECT OF PRESENT INVENTION
An object of the present invention is to propose a process for isolation of pure glycolic acid from the technical grade 70% glycolic acid solution.
.Another object of the present invention is to propose a process for isolation of pure glycolic acid from the technical grade 70% glycolic acid solution, which has a yield of 50
to 60%. Still another object of the present invention is to propose a process for isolation of pure glycolic acid from the technical grade 70% glycolic acid solution, which has a purity of 98%.
A further object of this invention is to propose a process for the preparation of polyglycolic acid from said glycolic acid.
A still further object of the present invention is to propose a process for isolation of pure glycolic acid from the technical grade 70% glycolic acid solution.
STATEMENT OF INVENTION
According to this invention there is provided a process for the preparation of polyglycolic acid from glycolic acid isolated from technical grade glycolic acid by azeotropic distillation characterized by two stage melt polymerization of glycolic acid, said first stage comprising in melting glycolic acid to above its melting point and carrying out condensation reaction in presence of a metal catalyst such as Sb2O3 and dry nitrogen and removing water continuously thereon, said second stage is carried out under vacuum of 0.1 to 0.001 mbar for a period of 4 to 8 hours.
This invention relates to process for consistently preparing the high purity glycolic acid, which can be used, for synthesis of polyglycolic acid for use in bio absorbable fiber and molded articles. More particularly, the glycolic acid is prepared by azeotropic distillation of water from technical grade 70% glycolic acid solution using various solvents like benzene, nitrobenzene, chlorobenzene, xylene, toluene etc. the azeotropic distillation is carried out at 60 to 160°C under the dry nitrogen flow with vigorous stirring for about 8-10 hrs. The estimated amount of water is collected as per the batch size. Higher viscous mass is separated from the immiscible solvent physically and the viscous mass is subjected for crystallization from various solvents like methanol, isopropanol, n-propanol, n-butanol, iso-amyl alcohol, n-pentanol, hexanol, ethylene glycol, acetic anhydride, ethyl acetate, butyl acetate, amyl acetate etc at above critical concentration. After keeping 12-50 hrs. under deep freeze condition, the crystals are washed with solvent. The crystals are periodically washed for about 2 to 6 times with the dry solvent and dried under vacuum in rotary evaporator from 25 to 75°C with 50-60% yield. The dried glycolic acid crystals arc analyzed using high performance liquid chromatography, hereafter called HPLC. for its purity 98% along with standard commercially available 99% glycolic acid as reference and melting point is in the range of 75 to 80°C.
The synthesis of polyglycolic acid by melt polycondensation reaction is carried out on melting the glycolic acid (98%) at 80-210°C i.e. above melting point and carrying out the condensation reaction in presence of metal catalyst like Sb20.i and dry nitrogen for about 2-6 hrs by removing the water continuously. The second stage of reaction is carried out for about 4 to 8 hrs under the vacuum of 0.1 to 0.001 mbar. Polymer is removed after melt condensation reaction and powdered using motor and pestle. The powder of particle size between 5 mm to 1mm is subjected for powder polymerization under vacuum of 0.1 to 0.001 mbar for about 10 to 24 hrs.
The intrinsic viscosity measurement of polymer is determined using the solvent mixture of phenol and trichlorophenol (60:40).
A I'bbelohdc suspended level viscometer is used to study the viscometric studies of polymer solution of 0.5% concentration. The thermal studies showed the melting transition temperature of the polymer is 225-228°C.

Technical grade 70% glycolic acid is subjected to azeotropic distillation to remove the water along with organic solvents like benzene, nitrobenzene, chlorobenzenc. xylene, toluene etc. under the low stream of nitrogen and vigorous stirring at 60-160°C. More particularly the water along with organic solvents like benzene and toluene is removed by azeotropic distillation carried out at 80-100°C under nitrogen and vigorous stirring for about 4-10 hrs. more particularly within 6-8 hrs. The viscous mass is separated from the immiscible solvent physically using separating funnel and the viscous mass is subjected to crystallization from various solvents like methanol, isopropanol. n-propanol. n-butanol. iso-amyl alcohol, n-pentanol. hexanol. ethylene glycol, acetic anhydride, ethyl acetate, butyl acetate, amyl acetate etc. at above critical concentration, more particularly in the dry ethyl acetate for crystallization. After keeping 12-50 hrs. specifically 48 hrs. under deep freeze condition, the crystals are washed with solvent like acetic anhydride, ethyl acetate, butyl acetate, amyl acetate, here particularly with ethyl acetate. The crystals are periodically washed for about 2 to 6 times with the dry solvent and dried under vacuum in rotary evaporator from 25 to 75°C with 50-60% yield. The dried glycolic acid crystals are analyzed using high performance liquid chromatography, hereafter called IIPLC for its purity 98%) along with standard commercially available 99% glycolic acid as reference and melting point was in the range of 75 to 80°C.
The melt polycondensation reaction can be carried out by melting the 98% glycolic acid at 80-210°C and carrying out the condensation reaction in presence of metal catalyst and dry nitrogen for about 2-6 hrs. More specifically the glycolic acid is melted at 140-200°C under nitrogen steam in presence of metal catalysts like Sb203. In this phase polymerization is carried out by removing the water continuously.
The polymerization under nitrogen is carried out for about 2-6 firs, more specifically for 2-4 hrs. depending on catalyst dose range of 0.001% to 0.1% more particularly between 0.005%) to 0.05%. The second stage of reaction was carried out for about 4 to 8 hrs under the vacuum of 0.1 to 0.001 mbar. Polymer is removed after melt condensation reaction and powdered using motor and pestle. The powder of particle size between 5 mm to 1 mm more particularly between 1 mm to 0.50mm is subjected for powder polymerization under vacuum of 0.1 to 0.001 mbar for about 10 to 24 hrs.
Solution viscosity measurement is carried out to study the degree of polymerization attended. The molecular weight of the high molecular weight polymer is directly proportional to the intrinsic viscosity. The intrinsic viscosity measurement of polymer is determined using the solvent mixture of phenol and trichlorophenol (60:40).
An ubbelohde viscometer is used to find out the viscosity of polymer solution of 0.5% concentration. The thermal studies showed the melting transition temperature of the polymer was 225-228°C.
Invention is illustrated by following examples, which are not to be construed as limiting the invention.
WORKING EXAMPLE
500 gin of glycolic acid solution (70%o) is taken along with 260 grams of toluene in three necked flask equipped with mechanical stirrer, nitrogen inlet and azeotropic distillation condenser. The flask is immersed in the oil batch after attaining the temperature 100-120°C of oil bath and water is removed under stream of dry nitrogen with constant stirring using mechanical stirring along with toluene. The desired amount of water is collected over a period of 7 hrs and hence distillation is stopped.
The high viscous mass thus obtained is separated from toluene using separating funnel. The separated high viscous mass is dissolved in dry ethyl acetate above its critical concentration and kept at -10°C for crystallization for about 48 hrs. The crystals are washed with dry ethyl acetate 4 to 5 times and dried in the rotary evaporator at 50°C under vacuum, yield being 60%. HPLC analysis shows that the glycolic acid obtained with an assay content 98% and crystalline melting point 77°C.
A single neck 250 ml flask is used as a reaction vessel. 75 gm of glycolic acid and 0.0045 gm. of antimony trioxide is charged into the flask under nitrogen atmosphere. The flask is immersed in an oil bath after attaining the temperature 198-200°C of the oil bath and water is removed under stream of dry nitrogen with constant stirring using a.magnetic bar.
After about 2 hrs the water of reaction ceases distilling and the pressure is gradually reduced over a period of 30-40 min to a range of 1 mbar to 0.001 mbar and temperature is raised to 220°C over the period of 10 min. and held for 7 hrs. During reaction solid dimer distills out and reaction mass becomes very high viscous and solidification of the reaction mass is avoided by increasing the temperature from 220°C to 238°C periodically as and when there is a sign of solidification.
The polymer is broken and ground to sufficient fineness to pass a 20 mesh screen. The powder is then transferred to the flask and heated at 200°C under vacuum of 0.001 mbar for about 18 hrs. The polymer having intrinsic viscosity of 0.67 dl/gm with 63% yield was obtained. The polymer is having melting point between 225-228°C.













WE CLAIM:
1. A process for the preparation of polyglycolic acid from glycolic acid isolated from technical grade glycolic acid by azeotropic distillation characterized by two stage melt polymerization of glycolic acid, said first stage comprising in melting glycolic acid to above its melting point and carrying out condensation reaction in presence of a metal catalyst such as Sb2O3 and dry nitrogen and removing water continuously thereon, said second stage is carried out under vacuum of 0.1 to 0.001 mbar for a period of 4 to 8 hours.
2. A process as claimed in claim 1 wherein the polymer after melt condensation is powdered and subjected to powder polymerization under vaccum of 0.1 to 0.001 mbar for about 10 to 24 hours.
3. A process as claimed in claim 1 wherein the said glycolic acid is prepared by the step of azeotropic distillation of water in the presence of an aromatic solvent such as benzene, nitrobenzene, xylene and toluene at 60 to 160°C under dry nitrogen flow and vigorous stirring for 8 to 10 hours.
4. A process as claimed in claim 1 and 3 wherein the higher viscous mass obtained from azeotropic distillation is separated from the immiscible solvent and subjected to crystallization from solvents suchas methanol, isopropanol, n-propanol, n-butanol.
5. A process as claimed in claim 1 and 4, wherein the crystals are kept under deep freeze conditions for 12-50 hours, washed and then dried.
6. A process for the preparation of polyglycolic acid substantially as herein described and illustrated in the examples.

Documents:

1534-del-2005-Abstract-(08-04-2010).pdf

1534-DEL-2005-Abstract-(17-08-2010).pdf

1534-DEL-2005-Abstract-(18-08-2010).pdf

1534-del-2005-abstract.pdf

1534-del-2005-Claims-(08-04-2010).pdf

1534-DEL-2005-Claims-(17-08-2010).pdf

1534-DEL-2005-Claims-(18-08-2010).pdf

1534-del-2005-claims.pdf

1534-DEL-2005-Correspondence-Others-(06-05-2010).pdf

1534-del-2005-Correspondence-Others-(08-04-2010).pdf

1534-DEL-2005-Correspondence-Others-(16-04-2010).pdf

1534-del-2005-correspondence-others.pdf

1534-del-2005-correspondence-po.pdf

1534-del-2005-Description (Complete)-(08-04-2010).pdf

1534-DEL-2005-Description (Complete)-(17-08-2010).pdf

1534-DEL-2005-Description (Complete)-(18-08-2010).pdf

1534-del-2005-description (complete).pdf

1534-del-2005-Form-1-(08-04-2010).pdf

1534-del-2005-form-1.pdf

1534-del-2005-form-18.pdf

1534-del-2005-Form-2-(08-04-2010).pdf

1534-del-2005-form-2.pdf

1534-del-2005-Form-3-(08-04-2010).pdf

1534-DEL-2005-GPA-(16-04-2010).pdf


Patent Number 243757
Indian Patent Application Number 1534/DEL/2005
PG Journal Number 45/2010
Publication Date 05-Nov-2010
Grant Date 03-Nov-2010
Date of Filing 14-Jun-2005
Name of Patentee SHRIRAM INSTITUTE FOR INDUSTRIAL RESEARCH
Applicant Address 19 UNIVERSITY ROAD, DELHI-110007, INDIA
Inventors:
# Inventor's Name Inventor's Address
1 RAKESH KUMAR KHANDAL 19 UNIVERSITY ROAD, DELHI-110007, INDIA.
2 AMMANAMANCHI RADHAKRISHNA 19 UNIVERSITY ROAD, DELHI-110007, INDIA
3 S. BERA 19 UNIVERSITY ROAD, DELHI-110007, INDIA
4 JADHAV PARASHURAM 19 UNIVERSITY ROAD, DELHI-110007, INDIA
PCT International Classification Number C08G 63/06
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 NA