FORM 2
THE PATENTS ACT, 1970 (39 OF 1970)
COMPLETE SPECIFICATION
[SECTION 10; RULE 13]
"PROCESS OF MANUFACTURING PARA ETHOXY ETHYL
t BENZOATE"
GUJRAT ORGANICS LIMITED, AN INDIAN COMPANY INCORPORATED UNDER THE COMPANIES ACT, 1956 HAVING ITS OFFICE AT PLOT NO. 127/1, GIDC ESTATE, ANKLESHWAR 393 002, DIST.BHARUCH, GUJARAT STATE, INDIA.
THE FOLLOWING SPECIFICATION PARTICULARLY DESCRIBES THE NATURE OF THIS INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED: -


Original
259/MUM/2003

The present invention relates to a process of manufacturing Para Ethoxy Ethyl Benzoate (PEEB).
The prior art (Theodor Curtious J. Prakt. Chim. (1930)) discloses a method of preparing Para Ethoxy Ethyl Benzoate, wherein Para Ethoxy Ethyl Benzoate is prepared in two steps; firstly etherification of Potassium salt of Para Hydroxy Benzoic Acid by heating the Potassium salt of Para Hydroxy Benzoic Acid and Ethyl Iodide to yield Para Ethoxy Benzoic Acid. The second step involves esterification of the said Para Ethoxy Benzoic Acid with Ethyl Alcohol in the presence of concentrated Sulphuric Acid to produce Para Ethoxy Ethyl Benzoate. The esterification is accompanied by a side reaction of Ethyl Alcohol and Sulphuric Acid, resulting into an undesired Diethyl Sulphate formation.
Patent No. JP 01,294,654 also provides with a one-pot reaction to prepare Para Ethoxy Ethyl Benzoate, wherein etherification of phenolic OH and esterification of carboxylic group are achieved in one pot. Anhydrous reaction mixture containing Para Hydroxy Benzoic Acid, Sodium Carbonate, and Tetrabutyl Ammonium Bromide in solvent xylene was treated drop wise with diethyl sulphate at 80°C and stirred for 60 minutes at 120°C to give Para Ethoxy Ethyl Benzoate. The residual diethyl
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sulphate content is high (> 2000 ppm). The residual diethyl sulphate content of typical commercial PEEB sample is desired from 5 to 10 ppm.
Para Ethoxy Ethyl Benzoate is used along with Ziegler Nata catalyst in the polymerization of propylene to polypropylene. Diethyl sulphate, an impurity in Para Ethoxy Ethyl Benzoate is carried over to polypropylene. The presence of Diethyl sulphate in polypropylene is objectionable, more so when it is used for food packaging. Para Ethoxy Ethyl Benzoate free of diethyl sulphate or low diethyl sulphate content is the desired catalyst for the manufacture of polypropylene. Purification of Para Ethoxy Ethyl Benzoate is needed to free it from the undesired by product, viz diethyl sulphate.
The present invention obviates these drawbacks by manufacturing Para Ethoxy Ethyl Benzoate with a very low residual diethyl sulphate content (< 5 ppm).
The present invention relates to a process of preparing Para Ethoxy Ethyl Benzoate comprising of i) reacting Para Hydroxy Benzoic Acid with diethyl sulphate, Sodium Carbonate and a phase transfer catalyst in
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the presence of an aromatic organic solvent and ii) reacting the resultant product with an aliphatic acid or a phenol.
The present invention discloses a one-pot synthesis of Para Ethoxy Ethyl Benzoate. Etherification and esterification of Para-Hydroxy Benzoic Acid is achieved when Para Hydroxy Benzoic Acid is treated with di ethyl sulphate in the presence of Sodium Carbonate, Benzyl chloride and Tri ethyl amine in an aromatic organic solvent like xylene under anhydrous reaction condition. Para Hydroxy Benzoic Acid or Sodium Para Hydroxy Benzoate are not soluble in xylene. Solubility in xylene is essential for total reaction with diethyl sulphate, which is soluble in xylene. This is achieved by generating in situ phase transfer catalyst, preferably a quaternary ammonium salt like Tri ethyl benzyl ammomum chloride (Formed from adding benzyl chloride and tri ethyl amine), Benzyl tributyl ammonium bromide, Benzyl tributyl ammonium chloride, Benzyl trimethyl ammomum iodide, Benzyl trimethyl ammonium chloride, Benzyl triethyl ammonium bromide, Methyl tributyl ammomum chloride, Phenyl trimethyl ammonium chloride, Phenyl trimethyl ammonium iodide, Tetrabutyl ammomum chloride, Tetrabutyl ammomum fluoride and Tetrabutyl ammonium hydrogen sulphate, etc.
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The reaction is monitored on Thin Layer Chromatography (TLC). After the disappearance of Para Hydroxy Benzoic Acid and intermediate Para Ethoxy Benzoic Acid in the reaction mixture, the unreacted diethyl sulphate present in the reaction mixture is quenched by the addition of aliphatic acids like acetic acid/ propionic acid / formic acid or a mixture of any of the aforesaid aliphatic acids or a phenol like o-cresol or salicylic acid or a mixture of any of the said phenols. Quenching of diethyl sulphate with acids and/or phenols results into corresponding ethyl esters or ethyl ethers respectively. These products have different boiling points in comparison with PEEB and therefore can be easily separated from PEEB.


The present invention is now illustrated with the help of the following examples. The examples are only illustrative and in no way limit the scope of the invention.
EXAMPLE-1
Charge Para Hydroxy Benzoic Acid (400 gm) in solvent xylene 2500 ml. Charge Sodium Carbonate (500 gm), Diethyl sulphate (644 ml or 758 gm), Benzyl Chloride (8 gm) and triethyl amine (4 ml). Heat the contents at 135°C -140°C and niaihtain for 18 hours. Progress of the reaction is monitored over TLC. Cool the contents to 100°C. Add Acetic Acid 100 ml. Raise the temperature again to about 135°C -140°C and maintain for 4.0 hours. Cool the contents to 30°C. Add water (2000 ml) and separate the aqueous layer from the organic layer. Wash the organic layer with water and distill it to collect the solvent by distillation at 100°C -150°C. Then collect the main fraction by distillation under vacuum (Temp 130°C) pressure 1 mm/Hg.
Distilled PEEB = 413 gms % Yield = 80% (Theory)
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HPLC purity = 99.5% Diethyl Sulphate Content = < 5 ppm
EXAMPLE -2
Charge Para Hydroxy Benzoic Acid (400 gm) in solvent xylene (2500 ml). Charge Sodium Carbonate (500 gm), Diethyl Sulphate, (644 ml or 758 gms), Benzyl Chloride (8 gm) and triethyl amine (4 ml). Heat the contents at 135°C -140°C for 18 hours. Progress of the reaction is monitored over TLC. Cool the contents to 100°C. Add Formic acid (100 ml). Raise the temperature again to about 135°C -140°C and maintain for 4.0 hours. Cool the contents to 30°C and add water (2000 ml). Separate the aqueous layer 'from orgamc layer and wash the organic layer for distillation to collect the solvent by distillation at 110°C -150°C, Then collect the main fraction by distillation under vacuum (Temp 130°C/1 mm/Hg).
Distilled PEEB = 414 gms. % Yield = 80% (Theory)
HPLC purity = 99.4% Diethyl sulphate content < 5 ppm
EXAMPLE -3
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Charge Para Hydroxy Benzoic acid (400 gm) in solvent xylene (2500 ml). Charge Sodium Carbonate (500 gms), Diethyl sulphate (644 ml or 758 gms), Benzyl Chloride (8 gm) and triethyl amine (4 ml). Heat the contents at 135°C -140°C for 18 hours. Progress of the reaction is monitored over TLC. Cool the contents to 100°C. Add Propionic Acid (100 ml). Raise the temperature again to 135°C -140°C and maintain for 4.0 hours. Cool the contents to 30°C and add water (2000 ml). Separate the aqueous layer from organic layer. Wash the organic layers for distillation to collect the solvent by distillation at 100°C -150°C. Then collect the main fraction by distillation under vacuum (130°C/1 mm/Hg).
Distilled PEEB = 413 gms. * % tield = 80% (Theory)
HPLC purity = 99.6% Diethyl sulphate content < 5 ppm.
EXAMPLE -4
Charge Para Hydroxy Benzoic acid (400 gm) in solvent xylene (2500 ml). Charge Sodium Carbonate (500 gms), Diethyl Sulphate (644 ml or 758 gms), Benzyl tributyl ammonium bromide (12 gms). Heat the contents at about 135°C -140°C for 18 hours. Progress of the reaction
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is monitored over TLC. Cool the contents to 100°C. Add Propionic Acid (100 ml). Raise the temperature again to 135°C -140°C and maintain for 4.0 hours. Cool the contents to 30°C and add water (2000 ml). Separate the aqueous layer from organic layer. Wash the organic layers for distillation to collect the solvent by distillation at 100°C -150°C. Then collect the main fraction by distillation under vacuum (130°C/1 mm/Hg).
Distilled PEEB = 413 gms. % Yield = 80% (Theory)
HPLC purity = 99.6% Diethyl sulphate content < 5 ppm.
EXAMPLE -5
Charge Para Hydroxy Benzoic acid (400 gm) in solvent xylene (2500 ml). Charge Sodium Carbonate (500 gms), Diethyl sulphate (644 ml or 758 gms) and Benzyl tributyl ammonium chloride (12 gms). Heat the contents at 135°C -140°C for 18 hours. Progress of the reaction is monitored over TLC. Cool the contents to 100°C. Add Propionic Acid (100 ml). Raise the temperature again to about 135°C -140°C and maintain for 4.0 hours. Cool the contents to 30°C and add water (2000 ml). Separate the aqueous layer from organic layer. Wash the organic
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layers for distillation to collect the solvent at 100°C -150°C. Then collect the main fraction by distillation under vacuum (130°C/1 mm/Hg).
Distilled PEEB = 413 gms. % Yield = 80% (Theory)
HPLC purity = 99.6% Diethyl sulphate content < 5 ppm.
EXAMPLE -6
Charge Para Hydroxy Benzoic Acid (400 gm) in solvent xylene (2500 ml). Charge Sodium Carbonate (500 gms) diethyl sulfate (644 ml or 758 gms) and benzyl trimethyl ammonium chloride (12 gms). Heat the contents at 135°C -140°C for 18 hours. Progress of the reaction is monitored over TLC. Cool the contents to 100°C. Add Propionic Acid (100 ml). Raise the temperature again to 135°C -140°C and maintain for 4.0 hours. Cool the contents to 30°C and add water (2000 ml). Separate the aqueous layer from organic layer. Wash the organic layers for distillation to collect the solvent by distillation at 100-150°C. Then collect the main fraction by distillation under vacuum (130°C/1 mm/Hg).
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Distilled PEEB = 413 gms. % Yield = 80% (Theory)
HPLC purity = 99.6% Diethyl sulphate content < 5 ppm.
EXAMPLE -7
Charge Para Hydroxy Benzoic Acid (400 gm) in solvent xylene (2500 ml). Charge Sodium Carbonate (500 gms), Diethyl Sulphate (644 ml or 758 gms) and Benzyl trimethyl ammonium iodide (12 gms). Heat the contents at 135°C -140°C for 18 hours. Progress of the reaction is monitored over TLC. Cool the contents to 100°C. Add Propionic Acid (100 ml). Raise the temperature again to 135°C -140°C and maintain for 4.0 hours. Cool the contents to 30°C and add water (2000 ml). Separate the aqueous layer from organic layer. Wash the organic layers for distillation to collect the solvent by distillation at 100-150°C. Then collect the main fraction by distillation under vacuum (130°C/1 mm/Hg).
Distilled PEEB = 413 gms. % Yield = 80% (Theory)
HPLC purity = 99.6% Diethyl sulphate content < 5 ppm.
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EXAMPLE -8
Charge Para Hydroxy Benzoic acid (400 gm) in solvent xylene (2500 ml). Charge Sodium Carbonate (500 gms), Diethyl Sulphate (644 ml or 758 gms) and Benzyl triethyl ammonium bromide (12 gms). Heat the contents at 135°C -140°C for 18 hours. Progress of the reaction is monitored over TLC. Cool the contents to 100°C Add Propionic Acid (100 ml). Raise the temperature again to 135°C -140°C and maintain for 4.0 hours. Cool the contents to 30°C and add water (2000 ml). Separate the aqueous layer from Organic layer. Wash the organic layers for distillation to collect the solvent by distillation at 100-150°C. Then collect the main fraction by distillation under vacuum (130T/1 mm/Hg).
Distilled PEEB = 413 gms. % Yield = 80% (Theory)
HPLC purity = 99.6% Diethyl sulphate content < 5 ppm.
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EXAMPLE -9
Charge Para Hydroxy Benzoic Acid (400 gm) in solvent xylene (2500 ml). Charge Sodium Carbonate (500 gms), Diethyl Sulphate (644 ml or 758 gms) and Methyl tributyl ammonium chloride (12 gms). Heat the contents at 135-140°C for 18 hours. Progress of the reaction is monitored over TLC. Cool the contents to 100°C. Add Propionic Acid (100 ml). Raise the temperature again to 135°C -140°C and maintain for 4.0 hours. Cool the contents to 30°C and add water (2000 ml). Separate the aqueous layer from organic layer. Wash the organic layers for distillation to collect the solvent by distillation at 100-150°C. Then collect the main fraction by distillation under vacuum (130°C/1 mm/Hg).
Distilled PEEB - 413 gms. % Yield - 80% (Theory)
HPLC purity = 99.6% Diethyl sulphate content < 5 ppm.
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EXAMPLE -10
Charge Para Hydroxy Benzoic Acid (400 gm) in solvent xylene (2500 ml). Charge Sodium Carbonate (500 gms), Diethyl Sulphate (644 ml or 758 gms) and Phenyl Trimethyl ammonium chloride (12 gms). Heat the contents at 135-140°C for 18 hours. Progress of the reaction is monitored over TLC. Cool the contents to 100°C. Add Propionic Acid (100 ml). Raise the temperature again to 135°C -140°C and maintain for 4.0 hours. Cool the contents to 30°C and add water (2000 ml). Separate the aqueous layer from organic layer. Wash the organic layers for distillation to collect the solvent by distillation at 100°C -150°C. Then collect the main fraction by distillation under vacuum (130°C/1 mm/Hg).
Distilled PEEB = 413 gms. % Yield = 80% (Theory)
HPLC purity = 99.6% Diethyl sulphate content < 5 ppm.
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EXAMPLE -11
Charge Para Hydroxy Benzoic Acid (400 gm) in solvent xylene (2500 ml). Charge Sodium Carbonate (500 gms), Diethyl Sulphate (644 ml or 758 gms) and Phenyl trimethyl ammonium iodide (12 gms). Heat the contents at 135-140°C for 18 hours. Progress of the reaction is monitored over TLC. Cool the contents to 100°C. Add Propionic Acid (100 ml). Raise the temperature again to 135°C -140°C and maintain for 4.0 hours. Cool the contents to 30°C and add water (2000 ml). Separate the aqueous layer from organic layer. Wash the organic layers for distillation to collect the solvent by distillation at 100°C -150°C. Then collect the main fraction by distillation under vacuum (130°C/1 mm/Hg).
Distilled PEEB = 413 gms. % Yield = 80% (Theory)
HPLC purity = 99.6% Diethyl sulphate content < 5 ppm.
EXAMPLE - 12
Charge Para Hydroxy Benzoic Acid (400 gm) in solvent xylene (2500 ml). Charge Sodium Carbonate (500 gms), Diethyl Sulphate (644 ml
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or 758 gms), Tetra butyl ammonium chloride (12 gms) solid or solutions. Heat the contents at 135°C -140°C for 18 hours. Progress of the reaction is monitored over TLC. Cool the contents to 100°C. Add Propionic Acid (100 ml). Raise the temperature again to 135°C -140°C and maintain for 4.0 hours. Cool the contents to 30°C and add water (2000 ml). Separate the aqueous layer from organic layer. Wash the organic layers for distillation to collect the solvent by distillation at 100°C -150°C. Then collect the main fraction by distillation under vacuum (130°C/1 mm/Hg).
Distilled PEEB = 413 gms. % Yield - 80% (Theory)
HPLC purity = 99.6% Diethyl sulphate content < 5 ppm.
Advantages:
1. The present invention produces Para Ethoxy Ethyl Benzoate with a very low diethyl sulphate content (<5 ppm) and is useful for the manufacture of food grade polypropylene.
2. The present invention is also a more economical method of manufacturing Para Ethoxy Ethyl Benzoate.
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We Claim:
1. A process of preparing Para Ethoxy Ethyl Benzoate comprising of i) reacting Para Hydroxy Benzoic Acid with diethyl sulphate, Sodium Carbonate and a phase transfer catalyst in the presence of an aromatic organic solvent and ii) reacting the resultant product with an aliphatic acid or a phenol.
2. A process of preparing Para Ethoxy Ethyl Benzoate as claimed in Claim 1, wherein the reaction is carried out under anhydrous conditions.
3. A process of preparing Para Ethoxy Ethyl Benzoate as claimed in Claim 1, wherein the aromatic organic solvent is xylene.
4. A process of preparing Para Ethoxy Ethyl Benzoate as claimed in Claim 1, wherein the phase transfer catalyst is a quaternary ammonium salt.
5. A process of preparing Para Ethoxy Ethyl Benzoate as claimed in Claim 4, wherein the quaternary ammonium salt is either tri ethyl
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benzyl ammonium chloride, Benzyl tributyl ammonium bromide, Benzyl tributyl ammonium chloride, Benzyl trimethyl ammonium iodide, Benzyl trimethyl anunonium chloride, Benzyl triethyl ammonium bromide, Methyl tributyl ammonium chloride, Phenyl trimethyl ammonium chloride, Phenyl trimethyl ammonium iodide, Tetrabutyl ammonium chloride, Tetrabutyl ammonium fluoride or Tetrabutyl ammonium hydrogen sulphate or a mixture of any of them..
6. A process as claimed in Claim 5 wherein the quaternary ammonium salt is prepared in situ.
7. A process of preparing Para Ethoxy Ethyl Benzoate as claimed in Claim 1, wherein the alphatic acid is acetic acid or propionic acid or formic acid or a mixture of any of them.
8. A process of preparing Para Ethoxy Ethyl Benzoate as claimed in Claim 1, wherein the phenol is either o-cresol or salicylic acid or a mixture of them.
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9. A process of preparing Para Ethoxy Ethyl Benzoate as claimed in Claim 1, wherein the first step of reacting Para Hydroxy Benzoic Acid with Diethyl Sulphate, Sodium Carbonate and a phase transfer catalyst in the presence of an aromatic organic solvent is carried out at a temperature of 135°C-140°C for about 18 hours; the temperature is cooled to 100°C and then an aliphatic acid or a phenol is added.
10. A process as claimed in Claim 9, wherein the temperature of the resulting mixture is raised to 135°C-140°C and maintained for about 4 hours; the reacting mixture is thereafter cooled to about 30°C; water is added to separate the aqueous layer from the organic layer; the organic layer is distilled.
11. A process of preparing Para Ethoxy Ethyl Benzoate as herein described with reference to the examples (1-12) accompanying the specification.
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Dated this 10th day of March 2004.
Himanshu Wasudeo Kane Applicants' Patent Agent
To:
The Controller of Patents, The Patent Office, Mumbai400 013.
i-l/D/PATENT/GUJRAT ORGANICS - PARA ETHOXY ETHYL BENZOA1E I. CS