TECHNICAL FIELD
The present disclosure relates to an improved process for the preparation of N, N-Diethyl Phenyl Acetamide (DEPA).
BACKGROUND
N, N- Diethyl Phenyl Acetamide, commonly known as DEPA is used as a safe and effective multi insect repellant. As compared to other insect repellants it is more effective against blood sucking organisms, mosquitoes, flies and leeches etc. There are various types of mosquito repellants available in market in the form of mosquito coils, mats, and electric vaporizer etc.
DEPA is a clear to light yellow oily liquid having a pleasant odor. It is insoluble in water, stable in air, and boils at 288°C-290°C, without any decomposition. Its specific gravity at 20°C is 1.00-1.01 g / cm3. DEPA has an excellent solubility in alcohols at all temperatures.
Some processes for the preparation of DEPA are known in the art, one of them is disclosed in Indian patent no. 166260 which involves the reaction of dialkylamine with arylacetic acid in the presence of inorganic acid as catalyst along with an organic acid anhydride to give dialkyl aryl acetamides.
The main drawback of this process is that this reaction has to be carried out at higher temperatures upto 800°C and higher pressures up to 1000 psi. Another drawback of this process is that the yield is poor and the process is expensive.
Another process is described in Indian patent no. 169195 where the reaction of arylacetic acid with dialkylamine is carried out in presence of an inorganic acid and in absence of any organic acid catalyst. The reaction can be carried out at atmospheric pressure as well as at high pressure.
This process suffers from several disadvantages that are as follows:
1. The maintenance of a high temperature for the reaction to proceed in the
forward direction requires high and continuous heating of the apparatus.
2. The removal of water formed during the course of the reaction has to be
carried out at high temperature, hence it poses a fire hazard and requires
special fire safety measures.
3. The instantaneous reaction involved in the process is exothermic and
results in formation of a thick slurry of solids that hinder the stirring of the
reaction.
4. Energy is required to maintain the reflux conditions in all the steps which
make the process energy consuming and expensive.
5. The quantity of environmentally hazardous effluent from complete process
is very high.
6. It is applicable to laboratory scale but not suitable for upscaling the
process.
Another process known in the art for the preparation of DEPA which is only of academic interest is the conversion of thioamides in to amides by trimethyl oxoniumfluoroborates. This method is not commercially viable for various reasons. It involves the use of an inorganic acid acid like phosphorous acid in the first step to carry the reaction in the forward direction at atmospheric pressure. And also some times the reaction is not completed and leaving high amount of unreacted phenyl acetic acid. The second step of the reaction is temperature sensitive and requires more stringent conditions. The whole process requires extra precautions for the removal of water formed during the reaction and the reaction should be carried out at controlled temperature. Lastly, it is not suitable for upscaling the process as the overall yield of the reaction is very low.
Thus there is a need for a suitable process that overcomes the disadvantages of the above processes.
SUMMARY
The present disclosure relates to the improved process for the preparation of N,N-Diethyl Phenyl Acetamide (DEPA), comprising the steps of refluxing phenylacetic acid and thionylchloride to obtain phenylacetylchloride; stirring phenyl acetylchloride dissolved in dry ether along with diethyl amine; extracting the obtained crude product with dichloromethane, evaporating and distilling under vacuum to obtain the pure product. The process is environment friendly, time efficient and low-cost.
BRIEF DESCRIPTION OF DRAWINGS
Figure 1 shows the gas chromatogram that confirmed the complete consumption of
phenyl acetic acid in the process / conversion of phenyl acetic acid into phenyl
acetylchloride.
Figure 2 shows the spectrum obtained by gas chromatography-mass spectroscopy
(GC-MS) that confirms the complete consumption of phenyl acetic acid in the
process/ conversion of phenyl acetic acid into phenyl acetyl chloride.
Figure 3 shows the analysis of dark brown mass of phenyl acetylchloride by gas
chromatography-mass spectroscopy (GC-MS).
Figure 4 shows spectrum obtained during the gas chromatography-mass spectroscopy
(GC-MS) analysis of dark brown mass of phenyl acetylchloride.
Figure 5 shows the gas chromatographic analysis of DEPA.
Figure 6 shows the analysis of purity of DEPA by gas chromatography-mass
spectroscopy (GC-MS)
Figure 7 shows the NMR spectrum of DEPA.
DETAILED DESCRIPTION
The present disclosure relates to an improved process for the preparation of N,N-diethyl Phenyl Acetaminde (DEPA) comprising :
a) Refluxing a mixture of phenylacetic acid and thionylchloride with
constant stirring for a duration of 3-4 hrs to form
phenylacetylchloride;
b) stirring phenyl acetylchloride dissolved in dry ether alongwith
diethylamine for a duration ranging from 2-3 hours to obtain crude
DEPA
c) processing the crude DEPA to obtain pure DEPA.
An embodiment the present disclosure relates to an improved process for the preparation of wherein processing comprises extracting crude DEPA by dichloromethane to obtain a concentrate solution, evaporating the dichloromethane and vaccum distilling to obtain pure DEPA.
An embodiment of the present disclosure relates to a process for the preparation of DEPA wherein, the amount of phenylacetic acid is in the range of 0.1-2.0 moles.
Another embodiment of the present disclosure relates to a process for the preparation of DEPA wherein, the amount of thionylchloride is in the range of 0.1-4 moles.
Further embodiment of the present disclosure relates to an improved process for preparation of DEPA wherein, the ratio of phenyl acetic acid to thionylchloride ranges from 1:1 to 1:2.
Still another embodiment of the present disclosure relates to an improved process for preparation of DEPA wherein, the ratio of phenyl acetic acid to thionylchloride is 1:2.
One embodiment of the present disclosure is a process for the preparation of N,N-diethyl Phenyl Acetaminde (DEPA), wherein after of refluxing of phenylacetic acid and thionylchloride for a duration of 3-4 hrs, the excess thionyl chloride is removed from the reaction mixture by distillation under reduce pressure using NaOH trap to obtain purified phenylacetylchloride.
Another embodiment of the present disclosure is a process for the preparation of N,N-diethyl Phenyl Acetaminde (DEPA), wherein phenyl acetylchloride is dissolved in 3-6 parts of dry ether.
Further embodiment of the present disclosure relates to a process for the preparation of DEPA wherein, the amount of phenyl acetylchloride dissolved in dry ether is in the range of 0.1-2.0 moles.
Still another embodiment of the present disclosure relates to a process for the preparation of DEPA wherein, the diethyl amine is in the range of 0.2-3.0 moles.
Yet another embodiment of the present disclosure relates to a process for the preparation of DEPA wherein the addition of diethyl amine to phenyl acetylchloride is carried out drop wise with constant stirring in a duration of 0.5-3.0 hrs at a temperature in the range of 0-10°C.
One embodiment of the present disclosure is a process for the preparation of N,N-diethyl Phenyl Acetamide (DEPA) comprising of adding phenylacetic acid to thionylchloride to form a reaction mixture; stirring the mixture and refluxing to form phenylacetylchloride; removing excess thionyl chloride from the mixture by distillation under reduced pressure using NaOH trap to obtain purified phenylacetylchloride; adding purified phenyl acetylchloride to dry ether ranging from 3-6 parts and adding effective amount of diethyl amine drop wise with constant stirring for a duration ranging from 3-5 hrs at a temperature ranging from 0-10°C and further stirring for a duration ranging 2-3
hours to obtain crude DEPA solution; washing the DEPA solution with water and extracting DEPA from the solution by adding dichloromethane to obtain a DEPA concentrate solution; evaporating the dichloromethane and distilling the DEPA concentrate solution under vacuum to obtain pure DEPA.
Further another embodiment of the present disclosure relates to a process for the preparation of DEPA wherein, the yield of the pure DEPA is 85%.
Another embodiment of the present disclosure relates to a process for the preparation of DEPA wherein, pure DEPA has a purity of more than 95%.
Still another embodiment of the present disclosure relates to an improved process for the preparation of DEPA wherein, pure DEPA has a purity of more than 99.5%.
Further another embodiment of the present disclosure relates to an improved process for the preparation of DEPA wherein, the boiling point of the pure DEPA is in the range of 288-291°C, preferably 288°C.
Yet another embodiment the present disclosure is to provide an improved process for the preparation of DEPA that is time-efficient and involves lesser number of steps.
Further embodiment of the present disclosure is to provide an improved process for the preparation of DEPA that involves the use of low cost, indigenously available chemicals so as to make the process cost effective.
Still another embodiment of the present disclosure is to provide an improved process for the preparation of DEPA that does not require the use of any moisture-sensitive, fire hazard reagents.
Yet another embodiment of the present disclosure is to provide an improved process for the preparation of DEPA that does not use low boiling, highly inflammable solvents.
Further embodiment of the present disclosure is to provide an improved process for the preparation of DEPA that gives better yield in high purity.
Still another embodiment of the present disclosure is to provide an improved process for the preparation of DEPA that is environment friendly and does not possess occupational hazards.
Yet another embodiment of the present disclosure is to provide an improved process for the preparation of DEPA that can be used for large scale preparations.
Further another object of the present disclosure is to provide an improved process for the preparation of DEPA that leads to reduction of effluent load as compare to the processes known in the art.
Still another embodiment of the present disclosure is to provide an improved process for the preparation of DEPA that has low cost as compared to those presently available in the market.
EXAMPLES
It should be understood that the following examples described herein are only for illustrative purposes and all the possible modifications or changes suggested to a person skilled in the art are included within the scope and purview of this application and appended claims.
Example 1
Phenyl acetic acid (13.6 g, 0.1 moles) and thionyl chloride (24 g, 0.2moles) were taken in a 100 ml two necked round bottom flask fitted with a double wall condenser and a guard tube. The reaction mixture was stirred and refluxed on a water bath for 2-3 hours. After the completion of the reaction, which was conformed by GC (Fig. 1) and GC-MS (Fig. 2),the excess thionyl chloride was removed by distillation under reduced pressure using sodium hydroxide trap to obtain the crude dark brown mass of phenyl acetyl chloride which was analyzed using GC-MS (Fig. 3 and 4). The phenyl acetyl chloride (15.4 g, 0.1 mole) obtained was taken in dry ether (50 ml) and added to a 100 ml two necked round bottom flask fitted with a double wall condenser and a guard tube. To this mixture excess of diethyl amine (21 ml, 0.2 moles) was added drop wise with constant stirring by keeping temperature in the range of 0-10°C. This addition was completed in 30 minutes. The stirring of this mixture was continued for further 2 hours, and a light yellow colored diethylamine hydrochloride precipitated out. The mixture was washed twice with water and extracted with dichloromethane. The diethylamine hydrochloride was completely soluble in water and thus, was completely removed by washing with excess water. The extract of dichloromethane was evaporated and N, N-Diethyl Phenyl Acetamide (DEPA) obtained was distilled under vacuum. DEPA obtained was in pure form and it was analyzed using GC/MS (Fig. 5 and 6) and H-NMR (Fig. 7). The yield obtained was 85% and the boiling point of DEPA was 288°C.
Example 2
Phenyl acetic acid (68 g, 0.5 moles) and thionyl chloride (60 g, 0.5 moles) was taken in a 500 ml two necked round bottom flask fitted with a double wall condenser and a guard tube. Then this reaction mixture was stirred and refluxed on a water bath for 2-3 hours. After the completion of the reaction the excess of thionyl chloride was removed by distillation under reduced pressure using sodium hydroxide trap to obtain the crude dark brown mass of phenyl acetyl chloride. The phenyl acetyl chloride (11%, 0.5 mole) obtained was taken in dry ether (250 ml) and added to a 500 ml two necked round bottom flask fitted with a double wall condenser and a guard tube. To this mixture excess of diethyl amine (105 ml, 1 moles) was added drop wise with constant stirring by keeping temperature in the range of 0-10°C. This addition was completed in 60 minutes. The stirring of this mixture was continued for further 2 hours, and a light yellow colored diethylamine hydrochloride precipitated out. Then this mixture was washed twice with water and extracted with dichloromethane. The diethylamine hydrochloride was completely soluble in water and thus was completely removed by washing with excess water. The extract of dichloromethane was evaporated and the product thus obtained was distilled under vacuum. DEPA was then obtained in pure form which was checked by using NMR and GC/MS. The yield obtained was 85% and the boiling point was 288°C.
Example 3
Phenyl acetic acid (136 g, 1 moles) and thionyl chloride (236 g, -150, 2moles) was taken in a 1000 ml two necked round bottom flask fitted with a double wall condenser and a guard tube. Then this reaction mixture was stirred and refluxed on a water bath for 2-3 hours. After the completion of the reaction the excess of thionyl chloride was removed by distillation under reduced pressure using sodium hydroxide trap to obtain the crude dark brown mass of phenyl acetyl chloride. The phenyl acetyl chloride (154 g,l mole) obtained was taken in dry ether (500 ml) and then added to a 1000 ml two necked round bottom flask fitted with a double wall condenser and a guard tube. To this mixture excess of diethyl amine (210 ml, 2 moles) was added drop wise with constant stirring by keeping temperature in the range of 0-10°C. This addition was completed in 2-3 hours. The stirring of this mixture was continued for further 2 hours, and a light yellow colored diethylamine hydrochloride precipitated out. Then this mixture was washed twice with water and extracted with dichloromethane. The diethylamine hydrochloride was completely soluble
in water and thus was completely removed by washing with excess water. The extract of dichloromethane was evaporated and the product thus obtained was distilled under vacuum. DEPA was then obtained in pure form which was checked by using NMR and GC/MS. The yield obtained was 85% and the boiling point was 288°C.

We claim:
1. A process for the preparation of N,N-Diethyl Phenyl Acetamide (DEPA), said
process comprising
a) Refluxing a mixture of phenylacetic acid and thionylchloride
with constant stirring for a duration of 3-4 hrs to form
phenylacetylchloride;
b) stirring phenyl acetylchloride dissolved in dry ether
alongwith diethylamine for a duration ranging from 2-3
hours to obtain crude DEPA; and
c) processing the crude DEPA to obtain pure DEPA.

2. The process as claimed in claim 1, wherein processing comprises extracting crude
DEPA by dichloromethane to obtain a concentrate solution, evaporating the
dichloromethane and vaccum distilling to obtain pure DEPA
3. The process as claimed in claim 1, wherein the phenylacetic acid is in the range of
0.1-2.0 moles.
4. The process as claimed in claim 1, wherein the thionylchloride is in the range of
0.1-4.0 moles.
5. The process as claimed in claim 1, wherein the ratio of phenyl acetic acid to
thionylchloride ranges from 1:1 to 1:2.
6. The process as claimed in claim 1, wherein the phenyl acetylchloride is in the
range of 0.1-2.0 moles.
7. The process as claimed in claim 1, wherein the diethylamine is in the range of 0.2-
3.0 moles.