DESC:FIELD OF THE INVENTION

The present invention relates to a process for preparing N-(1,3-dimethylbutyl)-N'-phenyl-1,4-benzenediamine (6PPD). In particular, the present invention provides an energy efficient, commercially viable and green process for the preparation of 6PPD wherein the process provides 6PPD in high yield, higher purity. 6PPD of the present invention is prepared from 4- aminodiphenylamine (4-ADPA), wherein the selectivity towards formation of 4NODPA+4NDPA in the preparation of 4-ADPA is maximum, and formation of side products, in particular phenazine, tars and azobenzene is minimal.

BACKGROUND OF THE INVENTION

6PPD is an organic chemical widely used as stabilising additive (or Antidegradants) in rubbers, such as NR, SBR and BR; all of which are common in vehicle tyres. Although it is an effective antioxidant it is primarily used because of its excellent antiozonant performance. It is one of several antiozonants based around p-phenylenediamine. 4-ADPA is used as a chemical intermediate in the preparation of 6PPD.

6PPD can be prepared from different starting materials. Most popularly discussed methods in the literature disclose the following routes:

(i) Reaction of 4-chloronitrobenzene with aniline and reduction of the formed 4-nitrodiphenylamine (4-NDPA) to 4-ADPA; followed by hydrogenation of 4-ADPA.
(ii) Condensation of Aniline with nitrobenzene (NB) in the presence of a base (the so-called NASH process) followed by hydrogenation, separation, Azobenzene reduction, purification to get good quality 4-ADPA and subsequent condensation with MIBK and hydrogenation of resultant Schiff base to yield 6PPD.
(iii) N-nitrosation of diphenylamine followed by the Fischer Hepp’s rearrangement to 4-nitrosodiphenylamine (4- NODPA) and its reduction to 4-ADPA; further condensation followed by hydrogenation to convert it to 6PPD.
(iv) The NASH process for 4-ADPA route is economically lucrative and hence many variations have been made in the originally developed process. Here the first step is condensation wherein Aniline and nitrobenzene condense in the presence of a base (tetramethylammonium hydroxide - TMAH) to form 4-nitrosodiphenylamine (4-NODPA) and 4-nitrodiphenylamine (4-NDPA) (and/or their salts) and some by products such as phenazine and azobenzene. The second step is hydrogenation, where NODPA is catalytically hydrogenated to 4-ADPA. The 4-ADPA further undergoes washing, purification, Azo-reduction (converting Azo-benzene by hydrogenation to Aniline), purification to remove Phenazine & tars and subsequent condensation with MIBK and hydrogenation of resultant Schiff base to yield 6PPD.

Bochkarev et al in Resource-Efficient Technologies, 2016, 2, 215-224 discloses the reaction mechanism of the NASH process. It discloses that condensation of aniline with NB serves as an example of nucleophilic aromatic substitution of hydrogen, or NASH. Stern et al., upon the research of NB with aniline-d5 reaction, have proposed a mechanism of condensation of NB with aniline in strongly basic media. In anhydrous, highly polar solvents, a very active nucleophile, anilide anion P1, is generated from aniline by deprotonation with tetraalkylammonium hydroxide (TMAH). The attack of anilide ion on the NB molecule mostly happens in the para-position and leads to the formation of anionic p-s-complex P2 (Fig a). The attack of anilide-ion in the ortho-position of NB leads to the formation of phenazine. The authors suppose that further transformations of P2 are connected with the oxidation–reduction process of hydride ion abstraction with two possible mechanisms: the intermolecular mechanism of elimination and transfer of hydride from s-complex P2 to the nitro group of another molecule, forming water and salt 4-NO2DPA P3. The corresponding intramolecular mechanism transfers hydride to the nitro group of NB and leads to the formation of water and salt 4-NODPA P4.

Fig:a
Based on the above mechanism it is understood that since 4-nitrosodiphenylamine (4-NODPA) and 4-nitrodiphenylamine (4-NDPA) (and/or their salts) are the target product at step 1, there is a need to develop industrially feasible processes which give high yield of the 4-nitrosodiphenylamine (4-NODPA) and 4-nitrodiphenylamine (4-NDPA) (and/or their salts) and minimize the formation of undesired products such as phenazine and azobenzene.

Further, US 9102585B2 discloses a process of preparing 4-ADPA by the optimizing the reaction condition of the coupling and hydrogenation reaction. The optimal conditions for conducting the stage of condensation of aniline with Nitrobenzene have been defines in terms of temperature, molar ratio between aniline and nitrobenzene and the molar ratio between water and the base (TMAH).

US8293673B2 discloses a five process stages as follows: (1) condensation of aniline with NB; (2) hydrogenation of the condensation products; (3) the stage of separating a complex base catalyst and hydrogenation catalyst from the products of hydrogenation; (4) hydrogenation stage of hydrogenation solvent and aniline; (5) purification stage of crude 4-ADPA.

While literature is replete with various processes for the preparation on 6-PPD and its key intermediate 4-ADPA, there is still a need for more innovative process that gives products of high purity and yield. It is also important that the process is robust so that it can be used at industrial scale.

OBJECT OF THE INVENTION

It is an object of the present invention to provide an in-situ process for preparing high quality 6PPD via 4-ADPA.

It is another object of the present invention to provide a process for preparing 4-ADPA wherein the side products are less than 0.5% in whole mass.

It is another object of the present invention to provide a process for preparing 4-ADPA wherein the formation of one or more side products and tars, in particular phenazine is less than 0.1% in whole mass.

It is another object of the present invention to provide a process for preparing 4-ADPA wherein the retention time of reaction mass during reaction between nitrobenzene and aniline is less than 2 Hrs.

It is yet another object of the present invention to provide a process for preparing 4- ADPA wherein the process is carried out in continuous mode.

It is yet another object of the present invention to provide a process for preparing 4- ADPA wherein the process generates negligible effluent.

It is yet another object of the present invention to provide a process for preparing 4- ADPA wherein the process is energy efficient and has high atom efficiency.

SUMMARY OF THE INVENTION

Accordingly, the present invention provides a process for the preparation of N-(1,3-dimethylbutyl)-N'-phenyl-1,4-benzenediamine (6-PPD) comprising:

a) treating aniline with a base to obtain a mixture containing reactive anilide;

b) treating the mixture obtained in step (a) with nitrobenzene to obtain a reaction mixture comprising 4- NODPA, 4- NDPA and side products comprising azobenzene and phenazine;

c) treating the reaction mixture of step (b) with a hydrogenation catalyst at a temperature 50 0C to 90 °C and between 10 kg/cm2 to 25 kg/cm2 Hydrogen pressure to obtain 4- aminodiphenylamine;

d) treating 4- aminodiphenylamine with Methyl isobutyl ketone in the presence of a hydrogenation catalyst to obtain the N-(1,3-dimethylbutyl)-N'-phenyl-1,4-benzenediamine.

In one embodiment, the total impurity at step (b) is less than 0.5% and Phenazine is less than 0.1%

Here, reactive anilide will mean anilide ion or its TMAH salt.

The present invention also provides an in-situ process for the preparation of 4- aminodiphenylamine comprising:

a) treating aniline with a base to obtain a mixture containing reactive anilide;

b) treating the mixture obtained in step (a) with nitrobenzene to obtain a reaction mixture comprising 4- NODPA, 4- NDPA and side products comprising azobenzene and phenazine;

c) treating the reaction mixture of step (b) with a hydrogenation catalyst at a temperature 50 0C to 90 °C and between 10 kg/cm2 to 25 kg/cm2 Hydrogen pressure to obtain 4- aminodiphenylamine.

BRIEF DESCRIPTION OF DRAWINGS
a) Fig 01 shows the IR spectra of the reaction mixture
b) Fig 02 shows the IR spectra of the reaction mixture
c) Fig 03 shows the UV-VIS spectra of the reaction mixture
d) Fig 04 shows the 1H NMR spectra of the reaction mixture
e) Fig 05 shows the 13C NMR spectra of the reaction mixture

DETAILED DESCRIPTION OF THE INVENTION WITH NON-LIMITING EMBODIMENTS AND EXAMPLES

The present invention provides a process for the preparation of highly pure 6PPD (N-(1,3-dimethylbutyl)-N'-phenyl-1,4-benzenediamine) and its key starting material 4- aminodiphenylamine (4-ADPA).

The preparation of 4-ADPA involves the introduction of aniline and nitrobenzene into a reactor leading to irreversible reaction of aniline and nitrobenzene under suitable optimized reaction conditions with respect to temperature, pressure, mole ratio, catalyst, base, solvent, etc. to synthesize 4-NODPA and its salt &/or 4 -NDPA or its salt. The process step of 4-ADPA preparation is crucial as the impurity and yields at this step further affects the quality of 6PPD. The 4-ADA can be isolated or it can be used further in-situ.

In one embodiment, the present invention provides a process for the preparation of 6PPD, said process comprising condensation of 4- aminodiphenylamine (4-ADPA) with Methyl isobutyl ketone (MIBK) in the presence of a hydrogenation catalyst.

The 4-ADPA is obtained in high yield and purity and the process significantly reduces the formation of side products.

In another embodiment, the present invention provides a process for the preparation of 4-ADPA, said process comprising:
a) Treating aniline with a strong base to obtain a mixture containing reactive anilide;
b) Treating the mixture obtained in step (a) with nitrobenzene to obtain a reaction mixture comprising 4- NODPA, 4- NDPA and one or more side products like azobenzene and phenazine;
c) Treating the reaction mixture of step (b) with a hydrogenation catalyst at a temperature 50 0C to 90 0C and between 10 kg/cm2 to 25 kg/cm2 Hydrogen pressure to obtain 4-ADPA.

In another embodiment the present invention provides a process for the preparation of 4-ADPA, said process comprising:
a) reacting aniline and nitrobenzene in presence of Tetramethylammonium hydroxide (TMAH) and water (20% to 35% solution) to obtain a reaction mixture comprising 4- NODPA, 4- NDPA and one or more side products like azobenzene and phenazine;

b) treating the reaction mixture of step (a) with a hydrogenation catalyst at a temperature between 50 0C -100 0C to obtain 4-ADPA, wherein the concentration of side products is less than 0.5%.

The deprotonation of Aniline resulting from reacting Aniline with TMAH, generates the Anilide ion, which is required for nucleophilic attack on Nitrobenzene forming the complex. This Anilide then has the tendency to dissociate back to Aniline.

According to Le Châtelier's principle, removing a product from a system at equilibrium causes the equilibrium to shift to the right, favouring the formation of more products to compensate for the loss. The present invention uses ATFE, applies constant vacuum and constantly removes the water in order to evaporate the moisture under vacuum so that the above-mentioned equilibrium will completely lie onto the product side. This shifts the equilibrium so that 95-100 % of the Anilide is formed.

In another embodiment, the present invention provides a process for the preparation of 4-ADPA, said process comprising:

a) Treating aniline with a base in an agitated thin film evaporator (ATFE) to obtain a mixture containing reactive anilide; (ATFE operating under 20 mm Hg to 50 mm Hg abs pressure and 50 0C to 80 0C temperature);
b) Treating the mixture obtained in step (a) with nitrobenzene in a reactor at temperature between 50 °C -80° C to obtain a reaction mixture comprising 4- NODPA, 4- NDPA and one or more side products like azobenzene and phenazine;
c) Treating the reaction mixture of step (b) with a hydrogenation catalyst at a temperature between 50 °C -100 °C and Hydrogen pressure of 10 to 25 kg/cm2 to obtain 4-ADPA; wherein the reactor at step (b) is selected from one or more continuous stirred tank reactor (CSTR) or plug flow reactor or “forced circulation rising film evaporator” (FCRFE).

In another embodiment, the present invention provides a process for the preparation of (N-(1,3-dimethylbutyl)-N'-phenyl-1,4-benzenediamine) 6-PPD, said process comprising:

a) reacting aniline and nitrobenzene in presence of Tetramethylammonium hydroxide in ATFE to obtain a reaction mixture comprising 4- NODPA, 4- NDPA and one or more side products like azobenzene and phenazine;

b) treating the reaction mixture of step (a) with a hydrogenation catalyst in a suitable reactor at a temperature between 50 0C -100 0C to obtain 4-ADPA,

c) separating the catalyst by filtration followed by separation of organic and aqueous phase,

d) dehydrating the organic phase followed by its fractional distillation to remove Aniline, preferably between 5-10% w/w,

e) hydrogenation in presence of a hydrogenation catalyst to reduce azobenzene to aniline and filtering,

f) subjecting the filtrate to fractional distillation at 150 0C -250 0C to obtain 4-ADPA and remove aniline and phenazine,

g) reacting the 4-ADPA and Methyl isobutyl ketone (MIBK) in the presence of a hydrogenation catalyst to obtain (N-(1,3-dimethylbutyl)-N'-phenyl-1,4-benzenediamine) 6-PPD.

The ratio of 4-NDPA to 4-NODPA produced in the reaction of the present invention can be controlled by varying the ratio of aniline to nitrobenzene. The higher the ratio of aniline to nitrobenzene, the higher is the ratio of 4-NODPA to 4-NDPA. Conversely, the higher the ratio of nitrobenzene to aniline, the higher is the ratio of 4-NDPA to 4-NODPA. In one embodiment of the present invention, the mole ratio aniline to nitrobenzene at the beginning of the reaction is in the range of 6:1 to 10:1.
The in-process separation can be done by any by any conventional method in the literature, selected from but not limited to (a) filtration for removing the solids, like catalyst, from reaction media; (b) separation by allowing residence time to a mixture containing organics and solvent, density difference separates both liquids; (c) separation by using liquid - liquid extraction where solubility & density plays a role; (d) separation by atmospheric, vacuum distillation of binary mixture vapor pressure play a role; (e) separation by fractional distillation two or more components vapor pressure play a role; (f) using resin to adsorb Anions and Cations as well as noble metals; (g) using centrifuge to separate solids or liquids by density difference and the like
The hydrogenation catalyst can be selected from, but not limited to, iridium, nickel, Raney Nickel, palladium, platinum, rhodium, ruthenium, their oxides and hydroxides etc. The catalyst can be supported on a support such as carbon, activated carbon, charcoal and silica.

In one embodiment, the water formed during step a) is quickly removed in an ATFE.

In one embodiment a suitable reactor is selected from one or more continuous stirred tank reactor (CSTR) or plug flow reactor or “forced circulation rising film evaporator” (FCRFE).

In one embodiment, the mole ratio of TMAH and nitrobenzene at the beginning of the reaction is in the range of 0.95:1 to 1.1:1.

In one embodiment, the hydrogenation temperature is between 50 0C -100 0C.

In one embodiment, the hydrogenation pressure is between 10 kg/cm2 to 25 kg/cm2.

In one embodiment, the hydrogenation reaction time is between 30 min to 180 min.

In one embodiment, TMAH is purified using resins (ion-exchange) to remove accumulated anions in TMAH during 4-ADPA manufacturing process.

In one embodiment, the present invention provides a process of preparing 4-ADPA wherein the selectivity of the reaction is 95% to 100%.

In one embodiment, the present invention provides a process of preparing 4-ADPA wherein the reaction has very high atom efficiency leading to highly economical process, due to reduced formation of undesired products like phenazine and azobenzene.

In one embodiment, the present invention provides a process of preparing 6-PPD wherein the process is carried in continuous mode.

In one embodiment, the present invention provides a process of preparing 6PPD where the yield and purity of 6PPD is 95-100 %.

In one embodiment, the present invention provides a process of preparing 6PPD from 4-ADPA wherein the process achieves 95% to 100% conversion.

In one embodiment, the process of the present invention provides more than 95% pure 4-ADPA.

In one embodiment, the present invention provides a process of preparing 4-ADPA where the yield of 4-ADPA is 95% to 100 %.

It will nevertheless be understood that no limitation of the scope of the invention is thereby intended by way of embodiments and examples. Such alterations and further modifications in the present invention, and such further applications of the principles of the invention as would normally occur to those skilled in the art are to be construed as being within the scope of the present invention.

It will be understood by those skilled in the art that the summary of the invention provided herein is exemplary and explanatory of the invention and are not intended to be restrictive thereof. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention belongs. The composition, methods, processes, and examples provided herein are only illustrative and not intended to be limiting.

The terms "comprises", "comprising", or any other variations thereof, are intended to cover a non-exclusive inclusion, such that a process or method that comprises a list of steps does not include only those steps but may include other steps not expressly listed or inherent to such a process or method. Similarly, one or more steps of method or components preceded by "comprises... a" does not, without more constraints, preclude the existence of other, steps or components. Appearances of the phrase "in a preferred embodiment”, “in an embodiment", “in another embodiment” and similar language throughout this specification may, but not necessarily do, all refer to the same embodiment.

EXAMPLE 1: Condensation reaction
Tetramethylammonium hydroxide TMAH and Aniline were fed to Agitated thin film reactor (ATFE). The temperature of the ATFE bottoms was set to 70-75 °C. The reaction between TMAH and Aniline was monitored using a ‘infrared spectroscopy’ and water was continuously removed for shifting the reaction in the forward direction towards Anilide formation. The reaction mixture obtained in ATFE was then pumped to a one or more reactor (CSTR/Plug flow/FCRFE) and Nitrobenzene was added continuously at required mole ratio. CSTR/Plug flow/FCRFE outlet is continuously withdrawn and taken to a buffer tank for sampling (HPLC analysis) and for next step of reaction. The analysis results are as below:
Table 1
Reaction temp °C Reaction time Aniline Nitrobenzene Phenazine 4-NODPA 4-NDPA Azobenzene Moisture
70-73
60 min
60-65%
<0.01%
<0.05%
17-18%
1-1.5%
<0.5%
2-4%

Table 2
Mole Ratio (NB: TMAH: Aniline) NB
addition time: 4-NODPA 4-NDPA AzoBz Phenazine Selectivity
1 : 1.05 : 8 Continuous 17-18% 1 to 1.5% <0.3% <0.03% 98.9%

Similar experiment was repeated and the data is as below:
Table 3
S N Batch No Aniline Nitrobenzene 4-NODPA 4-NDPA Azobenzene Phenazine Conversion%
1 FC-18/PP-1 62.464 0.162 17.737 2.571 0.498 0.096 99.838
2 FC-18/PP-2 61.15 0 18.52 2.199 0.305 0.059 100
3 FC-18/PP-3 55.89 0.02 15.05 1.92 0.49 0.092 99.98
4 FC-18/PP-4 63.16 0 17.28 2.7 0.45 0.054 100
5 FC-18/PP-5 61.52 0.56 15.92 1.18 0.54 0.087 99.44

Example 2: Hydrogenation reaction (4NODPA to 4ADPA)
The reaction product obtained in example 1 is treated with a hydrogenation catalyst at a temperature between 50 °C to100 °C and pressure between 10 kg/cm2 to 25 kg/cm2 to obtain- 4-ADPA.

EXAMPLE 3: preparation of 6 PPD
The reaction product obtained in example 2 is treated with a hydrogenation catalyst and MIBK at a temperature between 125 °C to175 °C and pressure of 15 kg/cm2 to 35 kg/cm2 to obtain 6PPD. The product was 98-99 % pure and Yield was 97% to 99%.

Advantages of the invention:
1. Less reaction time during the coupling-reaction between Aniline and nitrobenzene
2. Less effluent generation (Conforming to green chemistry).
3. Better yield, purity, conversion, and selectivity
4. Formation of undesired products like azobenzene and phenazine is significantly reduced.
5. Energy efficient, more operation friendly.
6. High atom efficiency leads to competitive economic process.
7. Increased stability of 4ADPA during storage and transportation.
,CLAIMS:We Claim

1. A process for the preparation of N-(1,3-dimethylbutyl)-N'-phenyl-1,4-benzenediamine comprising
a) treating aniline with a base to obtain a mixture containing reactive anilide;
b) treating the mixture obtained in step (a) with nitrobenzene to obtain a reaction mixture comprising 4- NODPA, 4- NDPA and side products comprising azobenzene and phenazine;
c) treating the reaction mixture of step (b) with a hydrogenation catalyst at a temperature 50 0C to 90 °C and between 10 kg/cm2 to 25 kg/cm2 Hydrogen pressure to obtain 4- aminodiphenylamine;
d) treating 4- aminodiphenylamine with Methyl isobutyl ketone in the presence of a hydrogenation catalyst to obtain the N-(1,3-dimethylbutyl)-N'-phenyl-1,4-benzenediamine.

2. The process as claimed in claim 1, wherein the total impurity at step (b) is less than 0.5% and Phenazine is less than 0.1%

3. The process as claimed in claim 1 wherein 4- aminodiphenylamine is prepared and used in-situ for production of N-(1,3-dimethylbutyl)-N'-phenyl-1,4-benzenediamine.

4. The process as claimed in claim 1 wherein the base is Tetramethylammonium hydroxide (TMAH).

5. The process as claimed in claim 1 wherein the hydrogenation catalyst is selected from iridium, nickel, Raney Nickel, palladium, platinum, rhodium, ruthenium, their oxides and hydroxides.

6. The process as claimed in claim 1 wherein the hydrogenation catalyst is a supported catalyst.
7. The process as claimed in claim 1 wherein 95-100 % of aniline is converted to reactive anilide.

8. The process as claimed in claim 1 wherein the amount of phenazine is 0- 0.1%.

9. The process as claimed in claim 1 wherein the hydrogenation temperature is between 50 0C -100 0C.

10. The process as claimed in claim 1 wherein the hydrogenation pressure is between 10 kg/cm2 to 25 kg/cm2.

11. The process as claimed in claim 1 wherein the hydrogenation reaction time is between 30 to 120 min.

12. The process as claimed in claim 1 wherein at step (b) Aniline amount is between 5-10% w/w.

13. The process as claimed in claim 1 wherein the said process is carried in one or more agitated thin film evaporator (ATFE), continuous stirred tank reactor (CSTR) or plug flow reactor or “forced circulation rising film evaporator” (FCRFE).

14. The process as claimed in claim 1 wherein the said process is carried in batch or continuous mode.