FORM 2
THE PATENT ACT 1970
&
The Patents Rules, 2003
/ COMPLETE SPECIFICATION (See section 10 and rule 13)
1. TITLE OF THE INVENTION:
'A Process of preparing 2, 5 Diphenyloxazole and 2,5 Diphenyloxazole obtained thereof.'
2. APPLICANT(S)
(a) NAME: SUDARSHAN CHEMICAL INDUSTRIES LTD.
(b) NATIONALITY: Indian Company registered under the provisions
of the Companies Act, 1956
(c) ADDRESS: 162, Wellesley road,
PUNE-411001, Maharashtra State, India
3. PREAMBLE TO THE DESCRIPTION

PROVISIONAL COMPLETE
The following specification invention describes The following specification
the invention. particularly describes the invention
and the manner in which it is to be performed
.

4. DESCRIPTION (Description starts from page 2)
5. CLAIMS: Given on a separate sheet
6. DATE AND SIGNATURE: Given at the end of last page of specification.
7. ABSTRACT OF THE INVENTION: Given on a separate sheet
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TECHNICAL FIELD:
The present invention relates to a process for the preparation of 2, 5-Diphenyloxazole (DPO) suitable for scintillation application. More particularly, the present invention relates to a process for the preparation of 2, 5-Diphenyloxazole comprising a three step process: (i) Chlorination of Hippuric acid with phosphorus penta chloride, (ii) Fried Craft acylation of benzene with resulting hippuryl chloride and (iii) Cyclization of N-phenacylbenzamide with concentrated sulphuric acid.
The expression DPO used in the specification means the compound of the present invention.
The main object of the present invention is to provide an improved process for the preparation of 2, 5-Diphenyloxazole.
Another object of the present invention is to make 2, 5-Diphenyloxazole suitable for commercial production using less expensive and less hazardous raw materials.
Still further object of the present invention is to make scintillation grade 2, 5-Diphenyloxazole with high yield and purity.
BACKGROUND AND PRIOR ART:
2, 5-Diphenyloxazole is a valuable compound used for scintillation application. It is common scintillator and laser dye. It has been reported that linked benzene ring, rather than large aromatic systems, generally makes superior scintillators. DPO is the most commonly used primary scintillator. It is also used as corrosion inhibitor.
In the prior art, 2, 5-Diphenyloxazole have been prepared by several known methods. One such method is described by Izvest. Akad.Nauk USSR otdel Khim. Nauk, 385
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(1957) which involves reaction of phenacyl bromide with urotropine in chloroform. The resultant quaternary salt is treated with concentrated hydrochloric acid in ethanol to form corresponding amine salt which is further reacted with benzoyl chloride in presence of sodium acetate in acetic acid followed by cyclohydration of N-phenacyl benzamide in cone, sulphric acid to afford final product. The product thus obtained is chromatographed to give pure product in very low overall yield.
The preparation of DPO is disclosed in USSR Pat No. 157686(1963), wherein, title product is obtained from its hydrobromide salt by reacting phenylbromoacetaldehyde with benzamide in aqueous methanol.
Another method is disclosed in J. Indian Chem. Soc, 49(3), 279-81(1972), in which, benzoylammomethylphenylketone is prepared by addition of aluminum chloride to hippuryl chloride and benzene at 0-10°C followed by cyclohydrated in cone, sulphuric acid or phosphorus oxychloride to afford crude product which was purified by column chromatography over alumina to obtain desired product with low overall yield.
A process for preparation of DPO is described in J. Heterocycl. Chem., 35(6), 1533(1998) which involves one step wherein, trifluromethanesulphonic acid is added to a solution of iodobenzene acetate in acetonitril followed by acetophenone is added and refluxed to get product in good yield.
Ger. DD 301191 A7 1992, described process for preparation by reacting benzamide with PhCHBrCHBrOAc.
Still another approach is disclosed in Pol. PL 97580(1978), wherein, DPO is prepared in 86-97% yield by the reaction of 2,5-diphenyl-4-oxazolidinone with phosphorus oxychloride, followed by heating of the resulting DPO Hydrochloride with alcohol and treatment with water.
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There are various disadvantages associated with the foregoing methods. However, it has now been found that the process reported in Journal of Indian Chem. Soc, 49(3), 279-81(1972) can be further improved replacing acetyl choride which is being used in chlorination step in large excess by chloroform with catalyst and alteration of purification techniques in subsequents steps to make process for commercial production of scintillation grade DPO.
DEFICIENCIES OF PRIOR ART:
1. The prior art processes either utilize relatively expensive starting materials or provide low yields.
2. The process for DPO either involves rigorous purification steps or non conventional purification techniques to get scintillation grade product.
3. Use of acetyl chloride as solvent which cannot be recovered and also its disposal involves considerable problems.
DESCRIPTION OF THE PRESENT INVENTION:
Detailed descriptions of the preferred embodiment are provided herein; however, it is to be understood that the present invention may be embodied in various forms. Therefore, specific details disclosed herein are not to be interpreted as limiting, but rather as a basis for the claims and as a representative basis for teaching one skilled in the art to employ the present invention in virtually any appropriately detailed system, structure or matter.
The present invention relates to a process for the prepararion of pure 2, 5-Diphenyloxazole (DPO) of formula (I) in relatively high yields and purity. More particularly, the present invention relates to a process for the preparation of pure high quality 2, 5-Diphenyloxazole (DPO) suitable for scintillation application. The present invention also discloses a process for the preparation of 2, 5-Diphenyloxazole (DPO) of formula (I) comprising of:
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(a) Chlorinating Hippuric acid of formula (II) with phosphorus pentachloride using N, N'-Dimethylformamide as catalyst in chloroform at 10-40°C to obtain hippuryl chloride (HC) of formula (III),
(b) reacting hippuryl chloride with benzene in presence of aluminum chloride at 10-80° to obtain N-phenacylbenzamide of formula (IV),
and (c) cyclizating N-phenacylbenzamide with concentrated sulphuric acid at 10-3 5 °C to obtain 2, 5-Diphenyloxazole (DPO) of formula (I).

EXAMPLE:
(a) Preparation of Hippurylchloride (HC)
In a four- necked round-bottomed flask equipped with overhead stirrer, thermo well, reflux condenser, nitrogen purger and guard tube were placed Hippuric acid( 0.273 moles) and N,N-dimethyl formamide ( 1 to5 mole%) diluted with 1ml to 3ml chloroform per 1 milimole of Hippuric acid and cooled reaction mixture under stirring to 20°C. In to the reaction mixture, phosphorus pentachloride (1 to 1.2 mole equivalent) was added during 0.5 to 2 hour at 10-40°C. The reaction was maintained at 30-45° C for about 2-10 hours. The progress of the reaction was monitored by HPLC. After completion, reaction mixture was cooled to 20-40 deg C, filtered through suction, washed with chloroform and dried under reduced pressure at 40°C. The crude product weighed 40 - 43g (72-78%), which was analyzed by High performance liquid chromatography (HPLC) for its purity.
(b) Preparation of N-phenacylbenzamide (NPB)
In a four- necked round-bottomed flask equipped with overhead stirrer, thermo well, reflux condenser, nitrogen purger and guard tube were placed Hippuryl chloride (0«213 moles) and Benzene (6 to 10 mole equivalent). The reaction mixture was cooled to 10°C under nitrogen atmosphere. In to the reaction mixture, aluminum chloride (3 to 3.5 mole equivalent) was added during 0.5 to 2 hour at 10-40°C. The reaction was maintained for 1-5 hours at 20-40°C and/or until the evolution of hydrochloric acid gas is ceased and raised temperature up to 80°C. The reaction was maintained at same temperature for about 4-10 hours. The progress of the reaction was monitored by HPLC. After completion, reaction mixture was cooled to 20-30 deg C and poured in 500ml chilled water. The resultant solid was filtered, washed with water and suck dried under reduced pressure. The crude product weighed 32 to 37gm was dissolved in 5 volume per 1 gm crude product of toluene at 60-80°C, cooled to 20°, filtered and dried to give off white crystalline product in 64-75% yield(30-35gm) which was analyzed by High performance liquid chromatography (HPLC) for its purity.
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(c) Preparation of 2, 5-Diphenyloxazole (DPO)
In a four- necked round-bottomed flask equipped with overhead stirrer, thermo well, reflux condenser, nitrogen purger and guard tube were placed N-phenacylbenzamide (0.139 moles) and concentrated sulphuric acid (1.8-3.0 moles). The reaction was maintained for 2-8 hours at 10-40°C. The progress of the reaction was monitored by HPLC. After completion, reaction mixture was poured in 500ml to 1000ml chilled water maintaining temperature 10-15°C. The resultant solid was filtered, washed with water till neutral pH and dried under reduced pressure. The crude product weighed 24gm was dissolved in 3-5 volume per gm crude product of toluene at 40°C, 3gm activated carbon was added and stirred for 0.5 hour. The activated carbon was filtered out, toluene evaporated under reduced pressure and 5-8 volume petroleum ether (60-80°C) per gm of crude product was added with 3 gm fresh activated carbon. The mixture was heated to 40°C, stirred for 0.5 hours and carbon was removed by filtration. The clear colorless filtrate obtained was cooled to 20°C to afford final product. It was then filtered and dried under reduced pressure at 45 °C till constant weight. Yield 20-22 g (71-78%) m.p. 72degree. C. It was analyzed by High performance liquid chromatography (HPLC) for its purity. The product obtained was characterized by elementary analysis, IR and NMR in comparison with reference standard sample obtained from Aldrich, US.
The embodiments of the invention as described above and the method disclosed of the present invention will suggest further modification and alterations to those skilled in the art. Such further modifications and alterations may be made without departing from the spirit and scope of the invention which is defined by the scope of the following claims.
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WE CLAIM:
1. A process of preparing 2,5-Diphenyloxazole(DPO) of formula(I) as shown below comprising of: (a) Chlorinating Hippuric acid of formula(II) with phosphorus pentachloride using N,N'-Dimethylformamide as catalyst in chloroform at 10-40°C to obtain hippuryl chloride(HC) of formula (III);
(b) reacting hippuryl chloride with benzene in presence of aluminum chloride at 10-80° to obtain N-phenacylbenzamide of formula (IV);
(c) cyclizing N-phenacylbenzamide with concentrated sulphuric acid at 10-40°C to obtain 2, 5-Diphenyloxazole (DPO) of formula (I).

2. A process of preparing 2, 5-Diphenyloxazole (DPO) of formula (I) as claimed in claim 1, wherein N, N'-dimethyl formamide is used in 1 to 5 mole % as catalyst.
3. A process as claimed in claim 1, wherein the phosphorus pentachloride is used in 1 to 1.2 mole equivalent as chlorinating agent.
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4. A process as claimed in claim 1, wherein benzene is used in 6 to 10 mole equivalent.
5. A process as claimed in claim 1, wherein aluminum chloride is used in 3 to 3.5 mole equivalents.
6. A process as claimed in claim 1, wherein sulphuric acid is used in 12 to 22 mole equivalent as cyclohydrating agent.
7. A process as claimed in claim 1, wherein all reactions performed is at atmospheric pressure.
8. A process of as claimed in claim 1 substantially as herein described with reference to the example and accompanying specification.
9. 2, 5-Diphenyloxazole (DPO) prepared by the process as claimed in claims 1 to 8 above.

(CHETAN V.GUNDECHA) AGENT FOR THE APPLICANT.
Dated this 28th day of May, 2007.
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Abstract
This invention relates to a process of preparing 2,5-Diphenyloxazole(DPO) of formula(I) as shown below comprising: (a) Chlorinating Hippuric acid of formula(II) with phosphorus pentachloride using N,N'-Dimethylformamide as catalyst in chloroform at 10-40°C to obtain hippuryl chloride(HC) of formula (III).
(b) Reacting hippuryl chloride with benzene in presence of aluminum chloride at 10-80°
to obtain N-phenacylbenzamide of formula (IV).
(c) Cyclizing N-phenacylbenzamide with concentrated sulphuric acid at 10-40°C to
obtain 2, 5-Diphenyloxazole (DPO) of formula (I).