Title of Invention

IMPROVED PROCESS FOR NITRATION OF PHENOL AND SUBSTITUTED PHENOLS USING PHASE TRANSFER CATALYST UNDER SONICATION

Abstract

The present invention relates to an improved process in which phenols and substituted phenols are selectively nitrated in high yield along with rate enhancement to o-nitro phenol using dilute nitric acid(4-12wt%)/tetra alkyl ammonium halide(TAAH)under sonication.The selectivity can be reversed to p-nitro phenol by using NaBr as a catalyst instead of TAAH under sonication.The reaction takes place at ambient conditions under sonication with a significant enhancement in reaction rate.

Full Text

FORM 2 THE PATENTS ACT, 1970 (39 OF 1970) COMPLETE SPECIFICATION 1. "IMPROVED PROCESS FOR NITRATION OF PHENOL AND SUBSTITUTED PHENOLS USING PHASE TRANSFER CATALYST UNDER SONICATION" 2. (a) Bhanage Bhalchandra Mahadeo (b) Department of Chemistry, Institute of Chemical Technology, University of Mumbai, Nathalal Parekh Marg., Matunga. Mumbai 400019, Maharashtra, India. (c) INDIAN. 2 Field Of The Invention: The present invention relates to an improved process for the selective nitration of phenols under sonication. The process is applicable for the nitration of wide range of phenols consisting of one or more functional groups of the type hydroxy, chloro, methoxy, methyl etc.. Specifically the invention relates to a process for the nitration of phenols using dilute nitric acid (4-12 wt%) / tetra alkyl ammonium halide under sonication. The improved process results in significant enhancement in the rate with high ortho selectivity under sonication. The selectivity can be reversed to para nitro phenol by using NaBr as a catalyst instead of TAAH under sonication. The reaction system comprises of two phases viz- the Organic phase and the Aqueous phase. The organic phase consists of a substrate and the aqueous phase consists of reactant such as nitric acid. Phase Transfer Catalyst such as Tetra alkyl Ammonium halide (TAAH), which generates HBr and this, facilitates the generation of nitronium ion required for nitration. The cavitation plays an important role for solublization of reactant in such a biphasic reactive system. Background Of The Invention: The nitrated products have wide range of industrial applications in fine chemicals dyes and pharmaceuticals. And this invention relates to a significant improvement in the catalytic process with high ortho selectivity under sonication. This is illustrated by a variety of substrates with different functional groups. The selectivity can also be reversed to para nitro phenol using NaBr as a catalyst instead of TAAH under sonication. Nitration of the aromatic compounds is one of the most widely studied reaction and finds extensive applications in the synthesis of variety of fine chemicals and pharmaceuticals "Nitration Methods and Mechanisms" by G. A. Olah (1989) published by VCH publications. Typical nitration procedure is not ecofriendly, as it requires use of mixed acids such as concentrated nitric acid and sulfuric acid. This leads to generate excessive acid waste. Additionally selectivity is also not very high and typical o/p ratio is in the range of 1.4 -1.5 "A Text book of practical organic chemistry" 4th ed. A. Vogel (1978) published by Longman, London. Several other 2 3 nitrating agents such as concentrated nitric acid, acid anhydrides/triflates, metal nitrates, nitrogen oxides have been reported. Regioselective nitrations using solid acid catalysts are also reported by several investigators. Use of ionic liquids, surfactants and microwave has also been demonstrated. In many cases applications are limited due to sophisticated techniques, expensive reagents, lower reaction rates and requirement of concentrated acids which leads to waste disposal problems "A. V. Joshi in Org. Proc. Res. Dev. 2003, 7, 95" In recent years the use of ultrasound in organic transformations is well known as it can enhance the rates and yield/selectivity of the reactions "Synthetic Organic Sonochemistry" by J. L. Luche in 1998 published by plenum press, New York This can also facilitate reactions at ambient conditions which otherwise requires drastic conditions such as temperature, pressure or concentrations. The ultrasound promoted nitration of phenol in expensive media such as ionic liquid has been reported by R. Rajgopalan in Ultrasonic Sonochemistry 2003, 10, 41. The reactions are feasible only with the activated phenol and are not applicable to deactivated phenols. Also nitration of phenol using ZnC2, which involves the use of, concentrated HNO3 under sonication, has been reported by Ahmed Kamal in Ultrasonic Sonochemistry 2004, 11, 455. Both of these reports give regioselectivity towards para isomer. There are few patents reported in the literature for nitration of phenols such as US Patent no PL367032 which involves the use of isopropyl nitrate, PTC and sulphuric acid; JP Patent no 5032589 which involves nitration 2,6 dichloro phenol using 10 - 70 % nitric acid; US Patent no 3694513 relates to a method for nitrating alkyl phenols with nitric acid in presence of tertiary alcohol, a secondary alkyl nitrate, an aldehyde or a ketone. There is lacking therefore in the prior art, a safe, economical and scaleable that may be used for the high yielding and regioselective ortho directed nitration of phenolic compounds especially where the formation of mixture of isomeric nitro products and / or formation of oxidized by products is possible. It is an object of the invention to provide a useful, high yielding and generally applicable method for the regioselective ortho-directed nitration of phenolic compounds. A further object of the invention is to provide a method, which avoids the disadvantage of the prior art. 3 4 Summary Of The Invention: The main objective of the present invention is to provide an improved process for the nitration of phenols under sonication, to obtain higher rates of reaction. Another objective of the present invention is to provide a process for the nitration of phenols using dilute nitric acid as the nitrating agent. Yet another objective of the present invention is to provide process for the nitration of phenols in biphasic media and using Phase Transfer Catalyst and substrates containing functional groups like hydroxy, chloro, methoxy, methyl etc.. Still another objective of the present invention is to provide a process for the nitration of phenols and substituted phenols with high ortho selectivity under sonication using TAAH. The selectivity can be reversed to para nitro phenol by using NaBr as a catalyst instead of TAAH under sonication. The improved process in the present invention has the following advantages over the processes described in the prior art: Significant enhancement in the rate of the reaction under ultrasonic condition. High selectivity towards ortho position in case of substituted as well as unsubstituted substrates using TAAH under sonication The selectivity can be reversed to the para position using NaBr as a catalyst. Typical nitration procedure is not ecofriendly, as it requires use of mixed acids such as concentrated nitric acid and sulfuric acid. This leads to generate excessive acid waste. The improved process involves the use of dilute nitric acid as the nitrating agent thus minimizing the handling and disposal problems. This invention shows a significant enhancement in the reaction rate under sonication. Where as the same reaction at room temperature requires longer time. This process can also be applied to deactivated substrates under milder conditions. According to present invention, it becomes possible to carry out nitration reaction at a low cost without necessity to invest a large some of money in plant and equipment. Reaction occurs at ambient temperatures. 4 5 Detailed Description of the invention: The present invention is concerned with the modification of the conventional nitration reactions. The reaction system comprises of two phases viz- the Organic phase and the Aqueous phase. The organic phase consist of a substrate and the aqueous phase consist of reactant such as nitric acid. Phase Transfer Catalyst such as Tetra alkyl Ammonium halide (TAAH), which generates HBr and this, facilitates the generation of nitronium ion required for nitration. The cavitation plays an important role for solublization of reactant in such a biphasic reactive system. Examples of substrates that can be used as a starting material consists of phenol and substituted phenols such as o-cresol, m-cresol, p-cresol, o-chloro phenol, m-chloro phenol, p-chloro phenol, o-nitro phenol, p-nitro phenol etc. Example of solvents immiscible in water which may be used in this invention include ethylene dichloride, methylene dichloride, diethyl ether, chloroform, carbon tetrachloride etc. Example of Phase Transfer Catalyst which may be used in this process include Tetrabutyl Ammonium Bromide, Cetyl Trimethyl Ammonium Bromide, Sodium Bromide, Tetraethyl Ammonium Bromide, Tetrabutyl Ammonium Chloride etc.. No process in hitherto known for the nitration of phenol under sonication in which there is a dramatic increase in the rate of a biphasic catalytic reaction system. The process of the invention is described in detail in the examples given below that are presented by the way of illustration only and should not be confined to limit the scope of the invention. Example 1 In a typical reaction phenol (10 mmol), tetra alkyl ammonium bromide(TAAB) (5 mol% of substrate), nitric acid (70 wt %, 20 mmol) water to makeup nitric acid concentration of 6 wt% and ethylene dichloride 20ml was sonicated at room temperature (25 °C) in an ultrasonic cleaning bath. The ultrasonic bath used for reactions had a frequency of 33 kHz and electric power rating of 100 W. The reaction was carried out in a round bottom flask of 100 ml capacity equipped with a mechanical agitator and the flask was suspended at the area of maximum cavitation, which was checked using ultrasonic probe. The progress of the reaction 5 6 was monitored using GC. After the completion of reaction, the organic layer was separated from aqueous layer. It was then washed with 3 x 25ml water, separated and finally dried over magnesium sulphate. The anhydrous ethylene dichloride layer thus obtained was subjected to GC analysis. The analysis of the reaction showed 94% conversion and 74% selectivity towards ortho nitro phenol in 40 min under sonication. In comparison the reaction carried out under silent conditions (other charge is same as above) took 6 h for completion. Conversion of this reaction was found to be 90% and selectivity of 59% towards ortho nitro phenol. Example 2 The charge similar to that given in example 1 was taken except that ortho cresol was used instead of phenol. The reaction was completed in 40 min.. Conversion of this reaction was found to 100% and selectivity towards ortho nitro o-cresol was 61% under sonication. In comparison the reaction carried out under silent conditions (other charge is same as above) took 12 h for completion. Conversion of this reaction was found to be 100% and selectivity of 53% towards ortho nitro phenol. Example 3 The charge similar to that given in example 1 was taken except that meta cresol was used instead of phenol. The reaction was completed in 40 min.. Conversion of this reaction was found to 90% and selectivity towards ortho nitro m-cresol was 45% under sonication. In comparison the reaction carried out under silent conditions (other charge is same as above) took 12 h for completion. Conversion of this reaction was found to be 75% and selectivity of 44% towards ortho nitro m-cresol. Example 4 The charge similar to that given in example 1 was taken except that para cresol was used instead of phenol. The reaction was completed in 40 min.. Conversion of this reaction was found to 100% and selectivity towards ortho nitro p-cresol was 96% under sonication. In comparison the reaction carried out under silent conditions (other charge is same as above) took 12 h for completion. Conversion of this reaction was found to be 100% and selectivity of 90% towards ortho nitro p-cresol. 6 7 Example 5 The charge similar to that given in example 1 was taken except that p-chloro phenol was used instead of phenol. The reaction was completed in 45 min.. Conversion of this reaction was found to 100% and selectivity towards ortho nitro p-chloro phenol was 94% under sonication. In comparison the reaction carried out under silent conditions (other charge is same as above) took 14 h for completion. Conversion of this reaction was found to be 100% and selectivity of 90% towards ortho nitro p-chloro phenol. Example 6 The charge similar to that given in example 1 was taken except that o-chloro phenol was used instead of phenol. The reaction was completed in 45 min.. Conversion of this reaction was found to 100% and selectivity towards ortho nitro o-chloro phenol was 64% under sonication. In comparison the reaction carried out under silent conditions (other charge is same as above) took 14 h for completion. Conversion of this reaction was found to be 100% and selectivity of 52% towards ortho nitro o-chloro phenol. Example 7 The charge similar to that given in example 1 was taken except that 20 mole% of TAAB with respect to substrate was taken instead of 5 mole%. The reaction was completed in 20 min.. Conversion of this reaction was found to 94% and selectivity towards ortho nitro phenol was 83% under sonication. Example 8 The charge similar to that given in example 1 was taken except that NaBr was used as a catalyst instead of TAAB and 20-mole% of NaBr was taken with respect to the substrate. The reaction was completed in 1 h. Conversion of this reaction was found to 72% and selectivity towards p-nitro phenol was 73% under sonication. It is evident from these examples that ultrasound promotes a selective nitration towards ortho and para position depending on the catalysts along with a significant enhancement in the rate of the reaction. 7 8 I claim: 1. An improved process for selective nitration of phenols and substituted phenols under sonication having frequency range between 20 kHz to 100 kHz using phase transfer catalyst comprising of two phases viz- the Organic phase and the Aqueous phase. a) The organic phase consist of phenol/substituted phenol in a solvent being immiscible in water in the molar ratio of nitric acid/phenol ranging from 40 to l0 mmol. b) The aqueous phase consist of reactant such as dilute nitric acid (4-12 wt %). 2. A process as claimed in claim 1 for selective nitration of phenol to o-nitrophenol using Phase transfer catalyst such as tetra alkyl ammonium halides (2-20 mole % with respect to substrate) under sonication. one can also reverse the selectivity to p-nitrophenol using NaBr as a catalyst under sonication. 3. A process as claimed in claim 1 where in the catalysts that may be used include Tetrabutyl Ammonium Bromide, Cetyl Trimethyl Ammonium Bromide, Sodium Bromide, Tetraethyl Ammonium Bromide, Tetrabutyl Ammonium Chloride etc. 4. A process as claimed in claim 1 where in the starting material consists of phenol and substituted phenols such as o-cresol, w-cresol, p-cresol, o-chloro phenol, m-chloro phenol, /?-chloro phenol, o-nitro phenol, ^-nitro phenol etc. 5. A process where in the solvent immiscible in water used in the process are ethylene dichloride, chloroform, carbon tetrachloride, diethyl ether, methylene dichloride etc. 5. A process where in nitration of phenols can be significantly enhanced with respect to the reaction rate under sonication. 6. A process for nitration of phenols in the temperature range of 20-60°c with ultrasound as the promoter. 7. A process wherein the ultrasound bath, which was used for the process, had a frequency of 33 kHz and electric power of 100 W. 1 Abstract: The present invention relates to an improved process in which phenols and substituted phenols are selectively nitrated in high yield along with rate enhancement to o-nitro phenol using dilute nitric acid (4-12 wt%) / tetra alkyl ammonium halide (TAAH) under sonication. The selectivity can be reversed to p-nitro phenol by using NaBr as a catalyst instead of TAAH under sonication. The reaction takes place at ambient conditions under sonication with a significant enhancement in reaction rate. 1

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848-mum-2005-abstract.doc

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848-mum-2005-cancelled pages(3-1-2008).pdf

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848-mum-2005-claims(granted)-(23-6-2010).pdf

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848-mum-2005-correspondence(3-1-2008).pdf

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848-mum-2005-description(granted)-(23-6-2010).pdf

848-mum-2005-form 18(9-2-2007).pdf

848-mum-2005-form 2(granted)-(23-6-2010).pdf

848-mum-2005-form 2(title page)-(granted)-(23-6-2010).pdf

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848-mum-2005-form-2.doc

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