DESC:CONTINUOUS METHOD FOR MANUFACTURING P-AMINO PHENOL AND DERIVATIVES THEREOF
Field of Invention:
The present invention relates to a continuous process for production of p-Aminophenol by catalytic hydrogenation of nitrobenzene (NB) and removal of undesirable impurities. This invention also relates to an improved process for the preparation of N-acetyl-p-aminophenol (APAP) by acetylation of p-Aminophenol (PAP) wherein the process operations are minimized during the acetylation reaction.

Background of the Invention:
p-Aminophenol (PAP) and its derivatives are well-known and extensively used industrial chemicals with wide variety of industrial applications in pharmaceuticals, dying agents such as sulphur dyes and in making photographic chemicals. p-Aminophenol (PAP) is used as an important chemical intermediate in the preparation of the analgesic, acetaminophen. The most common method for preparing p-Aminophenol (PAP) involves the catalytic hydrogenation of nitrobenzene in an acid medium via the formation of phenylhydroxylamine, which promptly rearranges in acid reaction medium to form p-Aminophenol (PAP). Two 1894 reports by Bamberger (Ber. 27, 1347 and 1548) were the first to observe and describe this rearrangement.
Henke, et al. (US. Pat. No. 2198249) discloses a process for the preparation of p-Aminophenol (PAP) by the catalytic hydrogenation of nitrobenzene (NB) in an acid medium. However, the process yields were found to be low and the final product was contaminated with impurities.
A number of improvements have since been reported; for instance, Spiegler (US. Pat. No. 2765342) studied the reaction extensively. Among the factors explored by Spiegler was the effect on reduction rate and p-Aminophenol (PAP) yield of including a surfactant selected from among several quaternary ammonium compounds and several non-quaternary compounds. Among the quaternary ammonium compounds used was dodecyltrimethylammonium chloride; the non-quaternary compounds investigated included two simple tertiary amine salts: triethylamine sulfate and tributylamine sulfate, as well as dioctadecyl propyleneamine dioleate. From a plot of rate and yield data, Spiegler concluded that the rate/yield performance of all of the quaternary ammonium compounds examined was superior to that of the non-quaternary compounds. However, the reagents are expensive and recovery of the unused reagents was cumbersome and lead to a lot of wastage.
G. Benner (U.S. Pat. No. 3383416) used the Henke et al. approach of charging all the nitrobenzene at once and used a carbon-supported platinum catalyst and quaternary ammonium surfactant, preferably dodecyl trimethylammonium chloride, as disclosed by Spiegler. Benner purposely interrupted the hydrogenation well before all the nitrobenzene had been consumed. In the presence of two liquid phases, aqueous and nitrobenzene, a carbon-supported platinum catalyst is preferentially wetted by the nitrobenzene, so most of the catalyst is suspended in the nitrobenzene phase. Thus, when hydrogenation is interrupted while there is still a distinct nitrobenzene phase, the catalyst preferentially remains suspended in the lower nitrobenzene layer, permitting the removal of the upper aqueous solution of PAP and aniline by decantation. The p-Aminophenol (PAP) is later recovered from the aqueous layer and purified.
Although p-Aminophenol (PAP) is the principal product of the process discussed above, the by-product aniline is also of commercial significance. While the relative yields of p-Aminophenol (PAP) and aniline are sensitive to a number of variables, such as hydrogen pressure, acidity, catalyst, temperature, surfactant, degree of agitation, etc., the by-product aniline yield will often amount to 10 to 25% or more of the yield of p-Aminophenol (PAP). Thus, the marketability of the by-product aniline is a significant factor in the overall economy of the p-Aminophenol (PAP) process.
Various sulfides of certain heavy metals such as cobalt, molybdenum and tungsten have also been proposed as hydrogenation catalysts; platinum and platinum on carbon and/or alumina have conventionally been used in the conversion of nitrobenzene to p-Aminophenol. However, over time the conventional platinum catalysts was found to be well suited for the preparation of commercially significant quantities of p-Aminophenol (PAP), they are capable of further hydrogenating the p-aminophenol to alicyclic compounds which are undesirable by-products. This is particularly the case where hydrogenation takes place in the presence of a quantity of platinum catalysts. Further, the nitrobenzene cannot be hydrogenated to completion without over hydrogenation by use of platinum catalysts. Thus, in the conventional hydrogenation reaction, the process must be stopped prior to completion to avoid the formation of undesired alicyclic compounds. This requires the additional step of recovering the unconsumed nitrobenzene by steam distillation. Moreover, conventional platinum catalysts are easily poisoned and are not reusable unless returned to a precious metal refiner to recover the metal.
W. R. Clingan (U.S. Pat. No. 4440954), had also provided a process to extract the impurities such as 4,4'-diaminodiphenyl ether and other small amine by-products from the final product of p-aminophenol by taking the aqueous solution of p-aminophenol and neutralizing the product with a base, adding an organic solvent like toluene and separating and recovering p-aminophenol of improved purity from said aqueous phase.
Most of the drawbacks in the prior-art for the preparation of p-Aminophenol (PAP) is related to the use of electrochemical reduction of nitrobenzene in acidic environment and undergoes the Bamberger rearrangement of phenyl hydroxylamine in acidic environment above 80ºC leading to PAP with all other impurities like DADPE/ODA (Diaminodiphenylether), aniline and OAP (Ortho-aminophenol).
Also, it was observed that at low temperatures catalytic reduction of nitrobenzene (NB), aniline is the only product formed. The limitations in this conversion methodology is that overall there is a four phase reaction system viz. liquid acidic water phase, liquid nitrobenzene as the second phase, solid catalyst embedded in the nitrobenzene (NB) as the third phase and hydrogen gas as the fourth phase. These operations are usually carried out in conventional batch reactor. The scale of such four phased reaction system is difficult and the output in terms of selectivity towards p-Aminophenol (PAP) gets affected. The other draw back that inventors have observed during the conversion of nitrobenzene (NB) to p-Aminophenol (PAP) is that inefficient extraction of an intermediate phenyl hydroxylamine. This phenylhydroxylamine in acidic aqueous phase gets embedded or dissolved in nitrobenzene (NB) resulting in drastic reduction of selectivity to p-Aminophenol (PAP).
In the present day and age where the world consumption of drugs have, spiked rapidly pharmaceutical industries are on a constant mission to find ways and means to improve the production of various drugs while maintaining the quality and purity levels. A continuous and economical process not only helps yield low contamination level but also increase the rate of production significantly. This has lead our inventors to design a process wherein the continuous production of p-aminophenol has an increase yield while separating the impurities and reusing the unconsumed catalysts. This has addressed the requirement of purification and was also found to be highly economical and ecofriendly.

Objectives of the Invention:
The main objective of the present invention is to provide a continuous process for the preparation and purification of p-Aminophenol (PAP) from nitrobenzene by use of catalytic hydrogenation wherein the apparatus was designed to include a loop Venturi reactor that results in creating a very large interfacial area that causes a rapid reaction rate. It also relates to downstream adsorption processing technique to isolate pure quality of p-Aminophenol (PAP).
Another objective of the present invention is to increase the selectivity to p-Aminophenol and to maintain a high conversion of nitrobenzene, while still being able to recover and reuse unreacted Nitrobenzene (NB), other reactants such as ammonium sulphate by employing high purity stabilizers and help contain the hydrogen atmosphere without any loss.

Summary of the Invention:
The main aspect of the present invention is to provide a continuous process for the preparation and purification of p-Aminophenol (PAP) from nitrobenzene by use of catalytic hydrogenation wherein the apparatus was designed to include a loop Venturi reactor type that results in creating a very large interfacial area causing rapid reaction rate.
The second aspect of the present invention is to increase the selectivity to p-Aminophenol (PAP) and to maintain a high conversion of nitrobenzene.
The third aspect of the present invention relates to the recovery of the Nitrobenzene (NB) employing simple acid base treatment in a continuous operation.
The fourth aspect of the present invention relates to downstream adsorption processing technique to isolate pure quality p-Aminophenol (PAP).
The fifth aspect of the present invention relates to a continuous process for the preparation of N-acetyl-p-aminophenol from p-Amino phenol employing acetic acid as an acetylating agent.
The sixth aspect of the present invention relates to continuous process for the recovery of ammonium sulphate with high purity employing stabilizers.

List of abbreviations:
NB - Nitro Benzene
PAP - p-Aminophenol
APAP - N-acetyl-p-aminophenol
PARA - Paracetamol
ABS - Ammonium bi-sulfate
DADPE - Diaminodiphenyl Ether
DMSO - Dimethyl sulfoxide
OAP - Ortho-aminophenol
MSGL - MS Glass Lined
MSPTFE - MS Polytetrafluoroethylene
RPM - Rotations per Minute
CAPEX - Capital expenditures
OPEX - Operating Expense
DBE - Di-butyl ether
DM - De-mineralized
CSTR - Continuous Stirred Tank Reactor
CSA - battery grade sulfuric acid
FFE - Falling Film Evaporator
HPLC - High-performance liquid chromatography
LLE - Liquid-Liquid Extraction

Detailed Description:
The present invention provides a continuous process for the preparation and purification of p-Aminophenol (PAP) from nitrobenzene by use of catalytic hydrogenation.
An embodiment of the present invention is employing a venturi loop reactor, installed in the recycle loop. This creates a very large interfacial area resulting in very rapid reaction rate. The inventors have found that nitrobenzene (NB) conversion to p-Aminophenol (PAP) is seven times faster when venturi loop reactor was used compared to conventional batch mode reaction.
Simultaneously, the inventors have found the nitrobenzene (NB) conversion to be limited to the tune of 70-75% since the catalyst remains occluded by nitrobenzene phase.
Another embodiment of the present invention provides for a separation process of nitrobenzene (NB) catalyst mixture, wherein the apparatus consists of venturi loop reactor which is subjected to a continuous hydrogenation set-up via small phase separator/decanter on the side stream. This enables separation of the heavier nitrobenzene (NB) catalyst layer from the lighter aqueous layer containing the product that is taken out of the system continuously while the heavier organic layer is recycled back into the reactor. In this system at any given point of time, all the reactants are pumped into the reaction zone continuously, while the product in aqueous phase consisting of high purity product is collected out. By this method the advantage that inventors have been able to show that catalyst as well as unconverted nitrobenzene is easily recoverable.
The present method also provides for the reaction to be carried out in a batch mode using venturi-loop reactor system, wherein the inventors have gained very rapid reaction rate. After the batch, the reaction mass is allowed to settle. Again the batch can be started with fresh catalyst and after the reaction is complete, the reaction mass is allowed to settle in another tank. Subsequently, another batch can be started using the catalyst used for the first batch. In this way continuously several batches can be run wherein the inventors have been able to achieve TON of catalyst as 2371 (on dry basis of catalyst).
The above procedure has the following advantages
i) The above describe continuous process will have significant advantages in terms of CAPEX and OPEX.
ii) The above described continuous process is very safe more so while transferring all the raw materials to the reactor which is done under pressure. This way there is no scope for venting the gases as there will be always hydrogen environment.
iii) This continuous process setup makes it easy for automation resulting in good process safety and process control.
iv) The consumption of hydrogen gas which is the main reactant is greatly reduced by using the above mentioned loop-venturi system compared to that of conventional batch reaction system.
v) The inventors have also observed that selectivity between p-Aminophenol (PAP) and aniline will be higher for the loop-venturi system as compared to the conventional batch reaction system.
An embodiment of the present invention is to increase the selectivity to p-Aminophenol (PAP) and to maintain a high conversion of nitrobenzene by employing a base, preferably ammonium bi-sulfate.
An embodiment of the present invention provides for a process to recover Nitrobenzene by employing an acid-base treatment in a continuous operation. Most of the prior art reveals that recovery of undissolved nitrobenzene (NB) in the reaction medium is achieved by solvent extraction technique which has the drawback of complex extraction procedure with many organic solvents like toluene etc. Moreover, the recovered the nitrobenzene (NB) has still been purified which is troublesome. The inventors have observed that dissolved nitrobenzene (NB) in the reaction medium is almost amounts to 3-4 % of NB used for the reaction. So it is imperative that this undissolved nitrobenzene (NB) has to be recovered as far as economics and ecology is considered. Moreover, the inventors have found that this reaction medium is highly acidic, from a commercial viewpoint and it will be difficult to install and operate corrosion proof equipment. So the inventors have established a simple neutralization of the reaction mass by employing liquid/gaseous ammonia till the pH is in the range of 4.0 to 4.5. Finally the reaction mixture is concentrated over falling/rising film/ or both in combination partial evaporator that is made of Duplex/SS316.
The above describe partial neutralization procedure has the following advantages
i) By this method of partial neutralization, simple industrial equipment can be designed and used for recovery of nitrobenzene and excess water.
ii) The inventors have found that the recovered of nitrobenzene (NB) of this partial neutralization process is of very high purity.
iii) In this above technique the recovered nitrobenzene (NB) is in the lower layer and water form an upper layer and both can be easily recycled back to the reaction zone.
iv) A lot of effluent is reduced making the process ecologically better.
v) In this system the quality of p-Aminophenol (PAP) remains intact due to less residence time in the evaporator resulting in better downstream recovery of p-Aminophenol (PAP).
vi) This process also is suitable for process automation and better safety.
In yet another embodiment of the present invention provides for a downstream processing technique to isolate pure quality p-Aminophenol (PAP). This embodiment of the invention also involves p-Aminophenol (PAP) purification. The reaction mixture of nitrobenzene (NB) contains lot of impurities like aniline, nitrobenzene (NB), p-Aminophenol (PAP), DADPE and OAP etc. These are normally purified by employing extraction techniques which is troublesome. Removal of these impurities also involved pH adjustment and extractions in extractions columns. To avoid all these problems inventors have employed adsorption techniques for removal of the above mentioned impurities more particularly DADPE. This technique is followed by extraction at 4.5 to 5.0 pH employing solvents like isobutanol or di-butyl ether (DBE).
An embodiment of the present invention relates to the continuous process for the preparation of N-acetyl-p-aminophenol (APAP) from p-Aminophenol (PAP) using acetic acid as an acetylating agent. Normally in the prior-art, acetylation reactions of p-Aminophenol (PAP) produced by Bamberger reaction employs acetic anhydride which is controlled substance. Moreover, the use of acetic anhydride has man drawback like use of excess of acetic anhydride, difficulty in restricting to mono-acetylation of the amino group, longer reaction times, oligomerization of the hydroxyl aromatic amine and colour formation of the product.
The inventors studied the above drawbacks and came with a solution wherein acetic acid is used as the main acetylating agent and also employing reactive distillation technique. Reactive distillation (RD) is a combination of reaction and distillation in one unit operation owing to which it enjoys a number of specific advantages over conventional sequential approach of reaction followed by distillation. Reactive distillation technique may be effectively used to improve the conversion of a reversible reaction by continuously removing one or more of the products. Prior-art does not report reactive distillation process to carry out p-aminophenol and acetic acid reaction for the preparation of N-acetyl-p-aminophenol (APAP).
The p-Aminophenol (PAP) produced by Bamberger process contains < 250 ppm of DADPE when acetic acid was the main acetylating agent. The N-acetyl-p-aminophenol (APAP) produced by using acetic acid as acetylating agent showed less of di-acetylated DADPE. Further, this di-acetylated DADPE is soluble in acetic acid-water mother liquor. The obtained mother liquor was subjected to removal of di-acetylated DADPE impurity by adsorption over alumina/silica columns. In this method adsorbents could adsorb the impurities to the desired level, and the mother liquor could be recycled to next batch resulting in the enhancement of N-acetyl-p-aminophenol (APAP) with high quality and high purity. The product N-acetyl-p-aminophenol (APAP) if desired can be further purified.
Another embodiment of the present invention provides for a continuous process for the recovery of ammonium sulphate with high purity employing stabilizers. During the conversion of p-Aminophenol (PAP) almost >80% of nitrobenzene (NB) goes to p-Aminophenol (PAP) while 20 % of nitrobenzene (NB) converts to aniline. The batch is performed in acidic medium and at the end the acidity is eliminated by ammonia which results in the formation of ammonium sulphate. The recovered ammonium sulphate is not very pure and it is very essential that this ammonium has to be recovered in pure manner for sustainability of p-Aminophenol (PAP) production. The by-product i.e., ammonium sulphate also contains dissolved p-Aminophenol (PAP) which if removed can yield good quality ammonium sulphate. The inventors have found that this can be achieved by employing a proper stabilizer and avoid the use of surfactants. The obtained ammonium sulphate has to undergo extractions step followed by air oxidation to get good quality ammonium sulphate.
Various modifications of the present invention may be made to the embodiments disclosed herein, therefore the above description should not be construed as limiting, but merely as exemplifications of preferred embodiments. The present invention is exemplified by the following example, which is provided for illustration only and should not be construed to limit the scope of the invention.

EXAMPLES
Example-1 NB to PAP using CSTR
Experimental set-up for batch mode hydrogenation of NB: The hydrogenation reaction was carried out in 50-L capacity jacketed stirred tank MSGL or MSPTFE lined reactors. The reactor was equipped with agitator and a RPM variator, thermo-well, temperature indicator, baffles, pressure indicator, safety relief valve, nitrogen and hydrogen gas auto injection arrangement, sampling arrangement etc. The reactor was equipped with 20-L capacity hydrogen gas storage vessel. The hydrogen supply to the reactor was through this hydrogen gas storage vessel. The hydrogen storage vessel also had pressure and temperature indicator. The pressure indicator was helpful to monitor the hydrogen gas consumption.
The reactor was charged with 27 kg of DM water; to this water 1.485 kg of battery grade sulfuric acid (CSA) was charged. Nitrobenzene (NB) 3.375 kg was charged followed by 27 gm of Pt/C catalyst was charged. Reactor was closed. Agitation was adjusted at 700 RPM. The reactor was flushed by pressurizing with nitrogen to 1.5 kg-g/cm2 pressure for seven times. Then the reaction mixture was heated till 85oC. The hydrogen supply to the reactor was started and the pressure of the reactor was maintained at 3.0 kg-g/cm2. The reaction being exothermic the temperature was maintained by providing mild cooling by intermittent circulation of water through the jacket of the reactor. After around 3.5 hours, the hydrogen consumption was found to be low and the reaction was stopped. The pressure reduction of hydrogen storage vessel was 65 kg-g/cm2.
After cooling the reaction mixture both the layers; organic (heavy layer) and aqueous layers (light layer) were separated. The catalyst was present in organic (nitrobenzene layer); this layer was preserved for recycle of catalyst in next batches. The aqueous layer was stored under inert atmosphere. The aqueous layer was subjected to analysis by HPLC. The reports of HPLC analysis are shown in the Table-1.

Example-2 to 7 NB to PAP using CSTR – Catalyst recycles
Experimental set-up for batch mode hydrogenation of NB: Similar experimental set-up as mentioned under Example-1 was used for all these experiments.
The reactor was charged with 27 kg of DM water; to this water 1.485 kg of battery grade sulfuric acid was charged. Nitrobenzene layer 739 gm; along with catalyst obtained under Example-1 was charged. To it fresh NB 2.636 kg was charged so that the total NB was 3.375 in each run; which was followed by 1.35 gm of fresh Pt/C catalyst (as mentioned under Experiment-1) was charged. Reactor was closed. Agitation was adjusted at 700 RPM. The reactor was flushed by pressurizing with nitrogen to 1.5 kg-g/cm2 pressure for seven times. Then the reaction mixture was heated till 85 to 90oC. The hydrogen supply to the reactor was started and the pressure of the reactor was maintained at 3.0 kg-g/cm2. The reaction being exothermic the temperature was maintained by providing mild cooling by intermittent circulation of water through the jacket of the reactor. Once the reaction or hydrogen up-take was lower the reaction was stopped. The pressure reduction of hydrogen storage vessel was noted. The rest of the experimental details were same as mentioned under Example-1. The results are recorded in the Table-1.
After cooling the reaction mixture both the layers; organic (heavy layer) and aqueous layers (light layer); were separated. The catalyst was present in organic (nitrobenzene layer); this layer was preserved for recycle of catalyst in next batches. The aqueous layer was subjected to analysis by HPLC. The results of input and HPLC analysis are shown in the Table-1.

Table-1 Shows the batch mode hydrogenation of NB to PAP, input quantities
Example No. 1 2 3 4 5 6 7
DM Water, kg 27.00 27.00 27.00 27.00 27.00 27.00 27.00
CSA, kg 1.485 1.485 1.485 1.485 1.485 1.485 1.485
Fresh NB, Kg 3.375 2.636 2.442 2.333 2.415 2.469 2.465
Recycle NB layer, kg 0.00 0.739 0.933 1.042 0.96 0.906 0.91
Fresh Catalyst, gm 27.00 1.35 1.35 1.35 1.35 1.35 1.35
Hydrogen consumption in terms of kg-g/cm2 65.0 61.0 57.9 59.9 61.2 61 61.7
Reaction time, hr. 3.5 3.3 3.0 3.0 3.0 3.0 3.0
Conversion of NB% 78.1 72.4 69.1 71.6 73.1 73 73.8
HPLC analysis
PAP% 6.38 5.99 5.83 6.0 6.06 5.99 6.02
OAP% 0.085 0.081 0.082 0.082 0.088 0.08 0.089
Aniline% 0.91 0.78 0.66 0.71 0.81 0.89 0.88
NB% 0.1 0.17 0.15 0.17 0.21 0.26 0.17
DADPE (ODA), ppm 152 160 147 149 155 152 187
Selectivity towards PAP 85.6% 85.56% 86.93% 86.58% 85.79% 84.91% 84.48%

Example-8 to 15 NB to PAP using CSTR with inline gas-liquid mixer and auto decanter
Experimental set-up for batch mode hydrogenation of NB: The hydrogenation reaction was carried out in 50-L capacity jacketed stirred tank MSGL or MSPTFE lined reactors. The reactor was equipped with agitator with agitator RPM variator, thermo-well, temperature indicator, baffles, reaction mixture circulation pump, in-line gas-liquid mixer, auto decanter, pressure indicator, safety relief valve, nitrogen and hydrogen gas auto injection arrangement, sampling arrangement etc. The reactor was equipped with 20-L capacity hydrogen gas storage vessel. The hydrogen supply to the reactor was through this hydrogen gas storage vessel. The hydrogen storage vessel also had pressure and temperature indicator. The pressure indicator was helpful to monitor the hydrogen gas consumption.
The reactor was charged with DM water; to this DM water; battery grade sulfuric acid (CSA) was charged. In few experiments ammonium sulfate was charged to dilute sulfuric acid to generate in-situ ammonium bi-sulfate. Nitrobenzene (NB) charged followed by Pt/C catalyst (as mentioned under Experiment-1) was charged. See all the quantities in the Table-2. Reactor was closed. Agitation was adjusted at 700 RPM. The reactor was flushed by pressurizing with nitrogen to 1.5 kg-g/cm2 pressure for seven times. The in-line reaction circulation pump was started and it was allowed to pass through the in-line gas-liquid mixer as well as auto decanter. Then the reaction mixture was heated till 85oC. The hydrogen supply to the reactor was started and the pressure of the reactor was maintained at 3.0 kg-g/cm2. The reaction being exothermic the temperature was maintained by providing mild cooling by intermittent circulation of water through the jacket of the reactor. After the hydrogen consumption was low enough; the reaction was stopped. The pressure reduction of hydrogen storage vessel was noted.
After cooling the reaction mixture both the layers; organic (heavy layer) and aqueous layers (light layer); were separated. The catalyst was present in organic (nitrobenzene layer); this layer was preserved for recycle of catalyst in next batches. The aqueous layer was stored under inert atmosphere. The aqueous layer was subjected to analysis by HPLC. The results of inputs and HPLC analysis are shown in the Table-2.

Table-2 Shows the batch mode hydrogenation of NB to PAP using in-line gas-liquid mixer and auto decanter, input quantities
Example No. 8 9 10 11 12 13 14 15
DM Water, kg 27 27 27 27 23.825 23.825 27 27
CSA, kg 1.488 1.488 2.97 2.97 3.946 3.946 2.976 2.976
Ammonium sulfate, kg 0 0 0 0 0 0 3.923 3.923
Fresh NB, Kg 3.375 3.375 6.754 6.754 8.939 8.939 3.375 3.375
Fresh Catalyst, gm 27 27 54 54 91 91 27 27
Recycle Catalyst, gm 0 0 0 0 15 15 0 0
Hydrogen consumption in terms of kg-g/cm2 63 63 138 138 221 182 64 65
Reaction time, hr. 1.5 1.5 1.8 1.8 2.0 0.75 1.5 1.5
Conversion of NB% 74.8 75 73 73.2 75.2% 61% 69.8 71
HPLC analysis
PAP% 6.17 6.24 10.54 10.48 12.85 11.78 5.47 5.07
OAP% 0.09 0.09 0.16 0.16 0.21 0.17 0.08 0.08
Aniline% 0.8 0.78 1.5 1.56 2.43 1.97 0.63 0.58
NB% 0.26 0.255 0.20 0.17 0.24 0.25 0.17 0.21
DADPE (ODA), ppm 163 158 678 800 3300 2620 110 104
Selectivity towards PAP 85.56% 86.33% 84.24% 83.54% 80.2% 81% 86.84% 86.8%

Example-16 to 19 NB to PAP Continuous manufacturing of PAP using CSTR with inline gas-liquid mixer and auto decanter
Experimental set-up for batch mode hydrogenation of NB: The hydrogenation reaction was carried out in 50-L capacity jacketed stirred tank MSGL or MSPTFE lined reactors. The reactor was equipped with agitator with agitator RPM variator, thermo-well, temperature indicator, baffles, reaction mixture circulation pump, in-line gas-liquid mixer, auto decanter, pressure indicator, safety relief valve, nitrogen and hydrogen gas auto injection arrangement, sampling arrangement etc. The reactor was equipped with 20-L capacity hydrogen gas storage vessel. The hydrogen supply to the reactor was through this hydrogen gas storage vessel. The hydrogen storage vessel also had pressure and temperature indicator. The pressure indicator was helpful to monitor the hydrogen gas consumption. The reactor was equipped with CSA metering tank with CSA metering pump, NB metering tank with NB metering pump and DM Water metering tank with DM Water metering pump. The CSA metering tank was charged with adequate CSA quantity; the NB metering tank was charged with adequate NB with 0.2% of catalyst and the DM Water metering tank was charged with adequate DM Water quantity. All the metering tanks were maintained under nitrogen pressure and were placed on the load cell to measure the quantities of raw material. In the DM Water supply line to hydrogenator in-line heater (hot oil circulated) was provided to heat the DM Water feed to the reaction temperature.
In all the three examples i.e. Example 16 to 19, initially the reactor was charged with 27 kg DM water; to this DM water; 1.485 kg battery grade sulfuric acid (CSA) was charged. Then 3.375 kg of Nitrobenzene (NB) charged followed by 27 gm Pt/C catalyst (as mentioned under Experiment-1) was charged. Reactor was closed. Agitation was adjusted at 700 RPM. The reactor was flushed by pressurizing with nitrogen to 1.5 kg-g/cm2 pressure for seven times. The in-line reaction circulation pump was started and the reaction mixture was allowed to pass through the in-line gas-liquid mixer as well as through auto decanter. Then the reaction mixture was heated till 85oC. The hydrogen supply to the reactor was started and the pressure of the reactor was maintained at 3.0 kg-g/cm2. The reaction being exothermic the temperature was maintained by providing mild cooling by intermittent circulation of water through the jacket of the reactor. As soon as the hydrogen consumption was around 60 kg/cm2, the other raw materials continuous pumping / metering were started. The NB along with catalyst pumping rate was maintained at 2.52 kg/h. CSA pumping rate was maintained at 1.11 kg/h. The DM Water pumping rate was maintained at 25.7 kg/h. The DM Water temperature was maintained at 100 to 105o C. After the hydrogen consumption was low enough; the reaction was stopped. Simultaneously the clean reaction mixture was removed out of the auto-decanter at the rate of 28 to 30 kg/h. The reaction mixture was cooled to 40 to 45oC with the help of in-line product cooler installed on the product withdrawal line. The NB layer along with catalyst got separated in the auto-decanter and was recycled back in to the reaction system. The pressure reduction of hydrogen storage vessel was noted. See all the quantities and results in the Table-3.

Table-3 Shows the continuous hydrogenation of NB to PAP using in-line gas-liquid mixer and auto decanter, input quantities
Example No. 16 17 18 19
DM Water total input, kg 74.116 46.700 49.983 59.883
CSA total input, kg 3.520 3.509 3.288 4.061
Fresh NB total input, Kg 7.995 8.000 6.743 8.175
Fresh Catalyst total input, gm 50 50 50 50
Hydrogen consumption in terms of kg-g/cm2 105 103 120 110
Reaction time, hr. 2.9 2.9 2.0 2.9
Conversion of NB% 74% 73% 78% 74.8%
HPLC analysis
Product removed (aqueous layer) total, kg 83.45 56.00 58.50 69.98
PAP% 5.31 7.87 6.65 6.58
OAP% 0.08 0.12 0.10 0.10
Aniline% 0.75 1.04 1.02 0.88
NB% 0.18 0.17 0.21 0.18
DADPE (ODA), ppm 90 250 207 257
Selectivity towards PAP 84.73% 85.3% 83.54% 85.20%

Example No. 20 to 24 - Continuous removal of dissolved nitrobenzene and concentration of reaction mass using Falling Film Evaporator
Experimental set-up for extraction of impurities: The set-up consisted of 200-L MSGL / MSPVDF lined reactor for pH adjustment (if required) by using liquid ammonia (25% ammonia in water). The reactor was equipped with agitator, thermo-well, liquid ammonia metering system and in-line pH measurement electrode. This reactor was used for partial neutralization of reaction mass to pH 2 to 4.5. The partially neutralized reaction mass was concentrated using oil heated Falling Film Evaporator (FFE). The FFE was equipped with cyclone separator fitted in vapor line, oil heated pre-heater for pre-heating the feed / reaction mass entering into FFE, concentrate receiver, distillate receiver condenser in vapor line, reaction mass metering / feed pump etc.
200-kg of reaction mass obtained in Examples 1 to 19 was taken in a 200-L MSGL reactor and agitator of the reactor was started. The reaction pH was adjusted to the desired value by transferring liquid ammonia with the help of peristaltic pump. Meantime the pre-heater of the FFE was heated by circulating hot oil at 95oC and also the FFE was heated by passing hot oil at 130oC through the jacket of FFE. Also the cooling water through the jacket of vapor condenser was started. The heating bath of concentrate receiver was also started so as to maintain the concentrate in hot conditions at 75 to 80oC. The reaction mass (at different pH for different set of reaction conditions) was fed at the rate of 56 to 57 kg/h to the pre-heater for FFE. The distillate was collected in distillate receiver and concentrate was collected in concentrate receiver. The distillate and the concentrate were analyzed by HPLC. The results are shown in the following Table-4.

Table-4 Shows the continuous concentration of reaction mass at various pH for Nitrobenzene recovery using FFE
Example No. 20 21 22 23 24
pH value of reaction mass <1.00 2.00 2.50 3.00 4.50
Total feed to FFE, kg 84 70 75.6 68 73
Weight of distillate (aqueous layer) collected, kg 15.12 12.95 13.99 10.53 10.45
Weight of distillate (organic NB layer) collected, kg 0.094 0.11 0.06 0.093 0.09
Weight of concentrate, Kg
HPLC analysis of concentrate
PAP% 7.36 7.12 7.11 4.21 4.2
OAP% 0.21 0.20 0.20 0.16 0.16
Aniline% 1.52 1.44 1.39 0.86 0.76
NB, ppm - - - 7 20
DADPE (ODA), ppm 470
HPLC analysis of distillate
PAP% 0 0 0 0 0
OAP% 0 0 0 0 0
Aniline% 0.044 0.15 0.38 0.66 1.3
NB, % 0.28 0 0.49 0.28 0.61
DADPE (ODA), ppm 0 0 0 0 0

Example No. 25 and 26 - Continuous extraction of impurities in PAP reacting mass using Liquid-Liquid Extractor
Experimental set-up for extraction of impurities: The set-up consisted of 200-L MSGL / MSPVDF lined reactor. The reactor was equipped with agitator, thermo-well, liquid ammonia metering system and in-line pH measurement electrode. This reactor was used for partial neutralization of reaction mass (obtained from Examples 1 to 24) to pH 4 to 4.5. The partially neutralized reaction mass was extracted in a counter current manner using jacketed, packed column, 24 L capacity extractor. The extractor at the top and bottom of extractor had calming zones to facilitate phase separation. The extraction was carried out using hot solvent / solvent mixture. The extractor was facilitated with metering pumps for feeding of both aqueous phase as well as extracting solvent phase. The extractor was equipped with two in-line heaters for pre-heating of incoming aqueous phase and solvent phase. The extractor was initially filled with solvent phase, which was maintained at 75 to 80o C. Once the extractor was filled completely with the solvent phase, the aqueous reaction phase continuous metering was started through the oil heated pre-heater from the top of column and the solvent phase continuous feeding was started through the oil heated pre-heater at the bottom phase of extractor. The extract and raffinate were collected through the calming zone from the top and bottom respectively. The raffinate stream was monitored for DADPE content by HPLC. The extract was recycled for three to five times in subsequent extraction batches till the DADPE concentration in the raffinate was in the limit. The following Table-5 shows the results of Liquid-Liquid Extraction (LLE) of reaction mixture.

Table-5 Shows the continuous extraction of reaction mass using Toluene + Aniline mixture
Example-25 Example-26
Aq. Layer flow rate – 25.7 LPH, Solvent flow rate – 12.5 LPH, Solvent Toluene: Aniline ratio – 75%:25%. Following table shows HPLC analysis results of raffinate with time Aq. Layer flow rate – 25.7 LPH, Solvent flow rate – 7.8 LPH, Solvent Toluene: Aniline ratio – 75%:25%. Following table shows HPLC analysis results of raffinate with time
Time, h PAP % OAP % Aniline % DADPE, ppm Time, h PAP % OAP % Aniline % DADPE, ppm
1 3.64 0.067 3.2 Nil 1 3.32 0.015 2.91 5.0
2 5.52 0.07 5.1 Nil 2 4.36 0.08 2.56 33.0
3 5.21 0.09 5.15 3.0 3 4.26 0.09 2.35 42.0
4 0.25 0.06 49.06 3.0 4 4.53 0.12 2.52 38.0
5 3.98 0.09 3.56 5.0 5 4.54 0.11 2.38 45.0
6 7.57 0.004 4.73 1.0 6 4.53 0.13 2.17 42.0
7 3.27 0.06 2.8 1.0 7 4.63 0.07 2.13 33.0
8 3.85 0.06 3.05 6.7 8 4.67 0.12 1.98 21.0
9 2.82 0.05 2.4 2.7 9 4.32 0.11 2.15 5.0
10 2.77 0.004 2.24 2.6 10 4.56 0.11 2.00 3.0
11 2.83 0.04 2.51 4.0 11 4.54 0.12 2.05 2.0
12 3.87 0.06 3 Nil
13 2.76 0.04 2.6 7.6
14 3.16 0.06 2.02 3.8
15 2.52 0.03 2 Nil
16 3.6 0.04 2.9 Nil
17 3.1 0.025 2.26 5.0
18 3.39 0.037 3.11 2.0
19 4.07 0.042 3.68 Nil
20 3.36 0.03 3.2 Nil

Example No. 27 – Isolation of Para-Amino Phenol (PAP)
Experimental set-up for isolation of PAP The set-up consisted of 200-L MSGL/SS316 / MSPVDF lined reactor. The reactor was equipped with agitator, thermo-well, liquid ammonia metering system and in-line pH measurement electrode, solvent addition system, reaction mass charging system, Nutsch filter to filter crude PAP, vacuum pump, Olsa type vacuum drier etc.
150 kg of reaction mixture with pH of 4.5 and free from impurities like DADPE obtained from Example 25 and 26 was charged in to the reactor. Into this reactor 5 kg of toluene was charged followed by 1.5 kg of ammonium bi-sulfite solution was charged and the pH of solution was made to 7.0 with the help of 5.6 kg of 25% ammonia solution using metering pump. The slurry of PAP was filtered using Nutsch filter using vacuum, the crude wet cake of PAP was washed with 5 kg of toluene followed by 10 kg of 2.5% solution of ammonium bi-sulfite in water. The wet cake was dried in vacuum drier at 60o C. The analysis of dry PAP showed 8.0 PPM of DADPE.

Example No. 28 – Isolation of Para-Amino Phenol (PAP)
Experimental set-up for isolation of PAP Similar set-up as mentioned under Example-27 as used.
150 kg of reaction mixture with pH of 4.5 and free from impurities like DADPE obtained from Example 25 and 26 was charged in to the reactor. Into this reactor 5 kg of toluene was charged followed by 4.0 kg of 10% sodium bi-sulfite solution was charged and the pH of solution was made to 7.0 with the help of 5.59 kg of 25% ammonia solution using metering pump. The slurry of PAP was filtered using Nutsch filter using vacuum, the crude wet cake of PAP was washed with 5 kg of toluene followed by 10 kg of 2.5% solution of sodium bi-sulfite in water. The wet cake was dried in vacuum drier at 60o C. The analysis of dry PAP showed 10.0 PPM of DADPE.

Example No. 28 to 30 –Purification of PAP by crystallization
Experimental set-up for Purification of PAP The set-up consisted of 20-L SS316 / MSPVDF lined, jacketed reactor having heating fluid circulation system to heat the material in the reactor. The reactor was equipped with reflux condenser. The reactor was equipped with agitator, thermo-well, solvent charging system and solid addition system, Nutsch filter or Centrifuge to filter pure PAP, vacuum pump, Olsa type vacuum drier etc.
8 kg of methanol or 10 kg of iso-Butanol or 10 kg of DM water was charged to the reactor. Then to it 1 kg colored PAP obtained from the Example 27 or Example 28 was charged. Then to this reactor 40 gm of ammonium bi-sulfite / ammonium sulfite solution was charged followed by 30 gm of activated carbon. The contents of the flask were heated till boiling and were maintained at solvent reflux temperature for 60 minutes. The charcoal treated mass was hot filtered over the Nutsch filter to remove the charcoal. The filtrate was charged in to another 20-L SS316 / MSPVDF lined, jacketed reactor having cooling fluid circulation system to cool the material in the reactor. The material inside reactor was cooled to 10 to 12o C under agitation and the crystallized PAP were filtered using Centrifuge. The pure PAP cake was washed with 5% solution of ammonium bi-sulfite or ammonium sulfite in water. The wet cake of pure PAP was dried in Olsa direr under vacuum at 60o C. The results are as shown in Table-6.

Table-6 Shows the results of purification of PAP
Example 28 Example 29 Example 30
Input of crude PAP, gm 1000 1000 1000
Dried crystallized PAP, gm 920 920 925
Melting point, oC 186 186 187
Moisture content, % 0.054 0.054 0.53
Appearance and color Crystalline, off white material Crystalline, off white material Crystalline, off white material
HPLC analysis results
OAP% - - -
Aniline% - - 0.0018
DADPE, ppm 2.0 8.0 7.0

Example No. 31 to 33 - Continuous extraction of impurities from ammonium sulfate solution after recovery of PAP - using LLE
Experimental set-up for Purification of ammonium sulfate Experimental set-up for extraction of impurities: The ammonium sulfate solution after recovery of PAP was extracted in a counter current manner using jacketed, packed column, 4 L capacity jacketed extractor. The extractor at the top and bottom of extractor had calming zones to facilitate phase separation. The extraction was carried out using hot solvent / solvent mixture. The extractor was facilitated with metering pumps; peristaltic type for feeding of both ammonium sulfate solution phase as well as extracting solvent phase. The extractor was equipped with two in-line heaters for pre-heating of incoming aqueous phase and solvent phase. The extractor was initially filled with solvent phase, which was maintained at 75 to 80o C. Once the extractor was filled completely with the solvent phase, the aqueous reaction phase continuous metering was started through the oil heated pre-heater from the top of column and the solvent phase continuous feeding was started through the oil heated pre-heater at the bottom phase of extractor. The extract and raffinate were collected through the calming zone from the top and bottom respectively. The raffinate stream was monitored for PAP and aniline content by HPLC. The following Table-7 shows the results of Liquid-Liquid Extraction (LLE) of ammonium sulfate solution using different solvents.

Table-7 Shows the of purification of ammonium sulfate solution
Example 31 Example 32 Example 33
Type of Solvent used Toluene Di-Butyl Ether Iso-Butanol
Aq. ammonium sulfate solution to solvent ratio / flow rate, mL/min 60 : 20 60 : 20 60 : 20
Appearance of raffinate (ammonium sulfate solution) Clear and Slightly brownish Clear and Slightly brownish Clear and colorless
HPLC analysis of input ammonium sulfate solution
PAP% 0.74 0.74 0.74
OAP% 0.006 0.006 0.006
Aniline % 1.61 1.61 1.61
HPLC analysis ammonium of sulfate solution (raffinate) after steady state condition
PAP% 0.29 0.24 0.0001
OAP% 0.002 0.002 Nil
Aniline % 0.21 0.11 0.001

Example No. 34–Isolation of pure ammonium sulfate
Experimental set-up for isolation of pure ammonium sulfate in a continuous manner: Similar experimental set-up as mentioned under Example 20 to 24 with FFE was used in two stages as described under Examples 20 to 24 in two stages. Where; 150 kg of ammonium sulfate clear and colorless solution was charged to the reactor. Then to it 400 gm of 30% hydrogen peroxide was charged, the mixture was well mixed. The solution was charged to Falling Film Evaporator at the rate 50 to 52 kg/h. The pre-heater used for heating ammonium sulfate solution was maintained at 90 to 92o C, whereas the Falling Film Evaporator was maintained at 128 to 130oC, this helped to recover the dissolved solvents like Di-Butylether or iso-Butanol as the azeotrope, the solvent layer was recycled in the ammonium sulfate solution liquid-liquid extractor. Partially concentrated ammonium sulfate solution was collected in concentrate tank.
The concentrated ammonium sulfate solution was again fed to FFE at the rate of 40 to 42 kg/h, where the pre-heater used for heating ammonium sulfate solution was maintained at 90 to 92o C, and the FFE was maintained at 133 to 135oC. The distilled water was collected in distillate receiver tank and the concentrated ammonium sulfate solution was collected in concentrate receiver and was maintained hot to avoid solidification. The concentrated ammonium sulfate solution was charged in the Olsa dryer and it was dried under vacuum at 80o C, till it gave the free flowing white powder. The ammonium sulfate solid after HPLC analysis showed 18 ppm of PAP, whereas OAP and Aniline were nil.

Example No. 35–Preparation of PARA from PAP
Experimental set-up for manufacturing of PARA: The PARA manufacturing set-up consisted of reactive distillation set-up. The set-up consisted of 10-L capacity CSTR with 50 mm sized and 1500 mm height packed tower with the facility of azeotropic distillation for the system for separation of heterogeneous azeotrope with decanter facility. The distillation tower was packed with wire-mesh type packing. The reactor had other facilities such as thermo-well, agitator, nitrogen bubbling arrangement etc. The reactor jacket was provided with Julabo make high temperature oil circulator. Further, 20-L capacity rotary evaporator was used for drying the crude Paracetamol; also the same set-up was used to dissolve crude Paracetamol powder in aqueous acetic acid. The solution of crude Paracetamol was then crystallized with or without carbon treatment in another set-up (crystallizer) followed by filtration set-up followed by dryer.
The reactor was charged with 3.5 kg of Glacial Acetic acid. The reactor was flushed with enough nitrogen, and then to it 1 kg of PAP (as per Example 27 and Example 28) was charged. Then to it 300 gm of n-Hexane as the solvent was charged. The reaction mass was heated by circulating hot oil at 145oC. The reaction mixture started boiling and the reaction water was recovered as n-Hexane-Water azeotrope at 69 to 70oC of vapor temperature. The water was removed in decanter, whereas the partial n-Hexane layer was refluxed back to reaction zone. After about 3.5 hours of reaction almost 230 gm of reaction water containing 30% acetic acid was recovered. Then the reaction was set for normal distillation, initially excess solvent (n-Hexane) was recovered.
Then the reaction mass was charged to 20-L capacity rotary evaporator. The reaction mass was totally dried under vacuum till crude Paracetamol was isolated in powder form. The excess acetic acid recovered during isolation of crude Paracetamol was used in next Paracetamol batch. Then to the crude Paracetamol powder; 2.75 kg of 30% acetic acid in water was charged along with 0.5% of sodium di-thionate and the mixture was heated till 90 to 95o C for 30 minutes. The Paracetamol solution was subjected to cooling till 14 to 15o C in a stirred vessel. The slurry of Technical Paracetamol was filtered on the Nutsch filter. The filtrate was treated with recovered activated carbon (recovered from the Pure Paracetamol crystallization) and was recycled in next batch.
The wet cake of Technical Paracetamol was again dissolved in 5 kg of DM water, to it 12 gm sodium di-thionate was charged along with 12 gm of 48% caustic lye and 18 gm of activated carbon was charged. The mixture was heated till 95 to 97o C to dissolve the solid Paracetamol in the water. The slurry was stirred at this temperature for 30 minutes and the carbon was hot filtered. This carbon was reused in Technical Paracetamol mother liquor treatment in next batch. The Paracetamol solution was subjected to cooling till 14 to 15o C in a stirred vessel. The slurry of Pure Paracetamol was filtered on the Nutsch filter. The wet cake of Paracetamol was washed with 1.5 kg of DM water and the Pure Paracetamol cake was vacuum dried at 60o C for four hours. The dry Pure Paracetamol weighed 1.285 kg. The Pure Paracetamol cake washings and 80% of mother liquor of the Pure Paracetamol crystallization process were recycled in next batch.
The Table-8 shows the HPLC analysis results of Pure Paracetamol.

Example No. 36–Preparation of PARA from PAP – Recycle run
Experimental set-up for manufacturing of PARA: Similar set-up was used as explained under Example-35.
The reactor was charged with recovered acetic acid and fresh acetic acid to make 3.5 kg of Acetic acid. The reactor was flushed with enough nitrogen, and then to it 1 kg of PAP (as per Example 27 and Example 28) was charged. Then reactor was charged with recovered and fresh solvent to make to it 300 gm of n-Hexane. The reaction mass was heated by circulating hot oil at 145oC. The reaction mixture started boiling and the reaction water was recovered as n-Hexane-Water azeotrope at 69 to 70oC of vapor temperature. The water was removed in decanter, whereas the partial n-Hexane layer was refluxed back to reaction zone. After about 3.5 hours of reaction almost 235 gm of reaction water containing 30% acetic acid was recovered. Then the reaction was set for normal distillation, initially excess solvent (n-Hexane) was recovered.
Then the reaction mass was charged to 20-L capacity rotary evaporator. The reaction mass was totally dried under vacuum till crude Paracetamol was isolated in powder form. The excess acetic acid recovered during isolation of crude Paracetamol was used in next Paracetamol batch. Then to the crude Paracetamol powder; 2.75 kg of 30% acetic acid in water was charged along with 0.5% of sodium di-thionate and the mixture was heated till 90 to 95o C for 30 minutes. The Paracetamol solution was subjected to cooling till 14 to 15o C in a stirred vessel. The slurry of Technical Paracetamol was filtered on the Nutsch filter. The filtrate was treated with h recovered activated carbon (recovered from the Pure Paracetamol crystallization) and was recycled in next batch.
The wet cake of Technical Paracetamol was again dissolved in 80% of recovered mother liquor from earlier batch, complete cake washings from earlier batch and fresh water to make it total 5.0 kg of water, to it 12 gm sodium di-thionate was charged along with 12 gm of 48% caustic lye and 18 gm of activated carbon was charged. The mixture was heated till 95 to 97o C to dissolve the solid Paracetamol in the water. The slurry was stirred at this temperature for 30 minutes and the carbon was hot filtered. This carbon was reused in Technical Paracetamol mother liquor treatment in next batch. The Paracetamol solution was subjected to cooling till 14 to 15o C in a stirred vessel. The slurry of Pure Paracetamol was filtered on the Nutsch filter. The wet cake of Paracetamol was washed with 1.5 kg of DM water and the Pure Paracetamol cake was vacuum dried at 60o C for four hours. The dry Pure Paracetamol weighed 1.330 kg. The Pure Paracetamol cake washings and 80% of mother liquor of the Pure Paracetamol crystallization process were recycled in next batch. The Table-8 shows the HPLC analysis results of Pure Paracetamol.

Table-8 Shows the of Purified Paracetamol HPLC analysis results
Example No. Example - 35 Example - 36
HPLC Analysis results of Pure Paracetamol
p- Aminophenol (PAP) 7.0 ppm 2.4 ppm
Acetanilide 2.0 ppm 0
2-Hydroxyacetanilide Nil 0
Diacetanilide of DADPE 2.0 ppm 0
4-Acetoxy acetanilide 1.3 ppm 0

Dated this: 27th day of October, 2022.

Signature:
Name: Mr. Srinivasa Reddy Madduri
Patent Agent Reg. No.: IN/PA-1268
GRANULES INDIA LIMITED
My Home Hub, 2nd Floor, 3rd Block,
Madhapur, Hyderabad, Telangana,
INDIA-500 081

,CLAIMS:
We Claim:
1. A continuous process for the preparation of p-Aminophenol (PAP) by the catalytic hydrogenation of nitrobenzene in an acidic aqueous reaction medium.
2. The process as claimed in claim 1, wherein the catalyst comprises platinum on carbon.
3. The process as claimed in claim 2, wherein the reaction medium acidified with sulfuric acid.
4. The process as claimed in claim 3, wherein the reaction employed optionally in the presence of base, preferably ammonium bi-sulfate.
5. The process as claimed in claim 3, wherein the reaction employed in a venturi loop reactor.
6. A recovery process of the nitrobenzene comprising base treatment of acidic reaction medium comprising nitrobenzene.
7. The process as claimed in claim 6, wherein the recovery process in a continuous operation and the base is liquid or gaseous ammonia.
8. A purification process for the preparation of p-Aminophenol (PAP) by adsorption techniques.
9. The process as claimed in claim 8, wherein the adsorption over alumina/silica columns.
10. A process for the preparation of N-acetyl-p-aminophenol (APAP) comprising reacting p-Aminophenol (PAP) obtained according to claim1 with an acetylating agent selected from acetic acid and wherein the process is batch process or continuous process.