FORM 2
THE PATENTS ACT 1970
(39 OF 1970)
&
The patent Rules, 2003
COMPLETE SPECIFICATION
A Process for Preparation of l,3,5-Trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl) benzene
SeQuent Scientific Limited
A Company Incorporated Under The Companies Act, 1956
Having Registered Office at 301, 'Dosti Pinnacle', 3rd Floor,
Plot No.E7, Road No.22, Wagle Industrial Area,
Thane(W)-400 604
The following specification particularly describes the nature of the invention and the manner in which it is to be performed:

Field of Invention
The present invention relates to a novel, cost-effective process for preparation of an antioxidant l,3,5-Trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl) benzene.
Background of the Invention
l,3,5-Trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl) benzene
represented by formula I is a phenolic antioxidant. Phenolic antioxidants are widely used in food, animal feed, and stock chemicals. Such antioxidant use has also been proven especially valuable and effective in polymeric materials and rubbers.

When these antioxidants are added to fuels, and/or used in the production thereof, phenolic antioxidants can extend storage life and protect fuel systems, increase resistance to oxidation, help control insoluble gum formation, and help petroleum and biofuel refiners and marketers meet stringent government regulations and OEM standards, including those requiring reduced emissions.
When these antioxidants are added to lubricants, and/or used in the production thereof, phenolic antioxidants can enhance thermal stability, improve lubricant performance and reduce sludge formation, extending the useful life of

lubricants in virtually any application. They reduce thickening and inhibit acid formation in a variety of applications, including engine oils, automatic transmission fluids, industrial oils, as well as compressor oil and gear and hydraulic oils.
When these antioxidants are added to polymers, and/or used in the production thereof, phenolic antioxidants can maintain the performance integrity and processing stability of plastics, elastomers, adhesives and other materials. These antioxidants are widely used in food, packaging materials, stock chemicals, plastics and the like.
There are number of literatures available which describe the process
for preparation of phenolic antioxidant. The US patent 4992597 describes a
process for the preparation of l,3,5-trimethyI-2,4,6-tris(3,5-dialkyl-4-
hydroxybenzyl)benzenes. 1,3,5-trimethyl- 2,4,6-tris(3,5-dialkyI-4-
hydroxybenzyl)benzenes is prepared by reacting mesitylene with the appropriate 2,6-dialkyl-4-methoxymethylphenol in the presence of an acidic catalyst.
US patent 3026264 describes the process for the preparation of 3,5-dialkyI-4-hydroxybenzyl-substituted benzenes such as 2,4,6-tri(3,5-di-tert-butyl-4-hydroxybenzyl)mesitylene. They are made by the reaction of 2,6-dialkyl-4-hydroxymethyl phenols with a benzene compound in an inert solvent at -15 to 100 °C in the presence of sulfuric acid or a Friedel Crafts catalyst.
GB patent 1202762 discloses a process for making 2,4,6-tri(3,5-dialky 1-4-hydroxybenzyl)benzenes by reacting a 2,6-dialkyl-4-methoxymethyl phenol with formaldehyde and acetic acid in presence of diethyl amine to form 3,5-di-tert-butyl-4-hydroxybenzyl acetate, which is further reacted with mesitylene in presence of sulphuric acid to give l,3,5-Trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl) benzene. The drawback of this process is that reaction of 2,6-dialkyl phenol with formaldehyde and acetic acid in presence of diethyl amine liberates water, which make the recovery and reuse of acetic acid on industrial scale very difficult and moreover the reaction time for the next stage becomes long.

GB patent 1327542 discloses a process for making 2,4,6-tri(3,5-diaIkyl-4-hydroxybenzyl)benzenes by reacting a 2,6-dialkyI-4-methoxymethyl phenol with an alkylbenzene compound in an inert solvent in the presence of an acidic catalyst such as sulfuric acid. According to this patent, this process uses 364 parts by weight 94% sulfuric acid per mole part mesitylene. In a commercial operation this presents a severe spent sulfuric acid disposal problem. However, merely reducing the amount of sulfuric acid results in a reaction wherein less than all of the reactive positions on the benzene compound become substituted. In the case of mesitylene and 2,6-di-tert-butyl-4-methoxymethyl phenol, lowering the amount of sulfuric acid gives a product which contains both mono- and di-3,5-di-tert-buty1-4-hydroxybenzyl-substituted mesitylene by-products, making it unacceptable for commercial sale. Thus, a need exists for a process which allows reduction in the amount of sulfuric acid used as catalyst and at the same time gives a product suitable for commercial use.
US patent 3925488 describes the process for the preparation of 3,5-dialkyl-4-hydroxybenzyl-substituted benzenes comprising reacting 3,5-di-tert-aIkyl-4-hydroxybenzyl alcohol with mesitylene in the presence of an acid whereby said acid is a catalytic amount of a sulfonic acid selected from the group consisting of lower alkane sulfonic acids, haloalkane sulfonic acids and benzene sulfonic acids.
None of the prior art processes mention the purification process to get pure product and hence required purity of the product is not achieved. Various techniques to improve yields have been tried but proved to be inconsistent at best. Equipment modifications and reaction mass agitation have not resulted in consistently good yields. Thus, any improvement which would reliably yield increased amounts of product and decreased amounts of by-products would be extremely valuable. The demand for the antioxidant products is high, in some cases so great as to justify additional capital expenditure for new plant facilities.
Thus, it is apparent that method for effective preparation of 1,3»5-Trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl) benzene in a more economical way while achieving high yield and high purity is still to be sought.

Thus it is highly desirable to develop a process which overcomes most of the drawbacks of the prior art. The present inventors have developed easy, single step and very cost effective process, which overcomes most of the above stated drawbacks.
Summary of the Invention
The principal aspect of the present invention is to provide a process for the preparation of l,3,5-Trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyI) benzene of formula I comprising:
a) reacting 2,6-di-t-butyl phenol of formula III with paraformaldehyde in a acetic acid and ethylenedichloride (EDC) in presence of base to form 3,5-di-tert-butyl-4-hydroxybenzyl acetate of formula II;
b) condensing the obtained 3,5-di-tert-butyl-4-hydroxybenzyl acetate with mesitylene using acid to form l,3,5-Trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl) benzene of formula I; and
c) purifying the crude l,3,5-Trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl) benzene of formula I using a solvent to form pure 1,3,5-Trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl) benzene of formula I.
The present invention can be illustrated by the below reaction scheme:


Figure 1: X-Ray diffractogram of l,3,5-Trimemyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl) benzene
Detail Description of the Invention
Accordingly in an embodiment of the invention, the reaction of 2,6-di-t-butyl phenol of formula III with paraformaldehyde is carried out in a solvent mixture of acetic acid and ethylene dichloride (EDC). The base for the reaction is an amine preferably secondary amine more preferably di-n -propylamine. The reaction is carried out at a temperature in the range of about 80-110°C, preferably at90-100°C.
In another embodiment of the invention, water liberated during the reaction is removed by azeotropic distillation. This removal of water reduces the reaction time in the next condensation step drastically. Moreover, acetic acid used as a solvent can be recycled and reused in next reaction.

In another embodiment of the invention, condensation of 3,5-di-tert-butyl-4-hydroxybenzyl acetate of formula II with mesitylene to form 1,3,5-Trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl) benzene of formula I is carried out using acid catalyst selected from the group comprising hydrochloric acid, sulphuric acid and the like, preferably sulphuric acid. The condensation is carried out in presence of a solvent preferably acetic acid in the temperature range of about 50-80 °C, preferably 60-70 °C.
In another embodiment of the invention, condensation of 3,5-di-tert-butyl-4-hydroxybenzyl acetate of formula II with mesitylene to form 1,3,5-Trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl) benzene of formula I is carried out insitu i.e. without isolating 3,5-di-tert-butyl-4-hydroxybenzyl acetate.
In yet another embodiment of the invention, purification of crude 1,3,5-
trimethyI-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl) benzene of formula I in step
c) is carried out using a solvent preferably halogenated solvent selected from the
group comprising chlorobenzene, carbon tetrachloride, dichloromethane, ethylene
dichloride and the like, more preferably ethylene dichloride. The obtained pure
l,3,5-trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl)benzene is
recrystallized from a solvent selected from the group comprising methanol, ethanol, isopropanol, butanol, n-butanol, acetonitrile, acetic acid and mixture thereof, preferably acetic acid at 70-80°C.
In another embodiment of the invention, l,3,5-trimethyl-2,4,6-tris(3,5-di-tert-butyI-4-hydroxybenzyl) benzene obtained after purification is crystalline and characterised by X-ray powder diffraction pattern as given in figure 1 and having major 26 peaks at 6.05, 10.28, 10.78, 12.91, 13.48, 13.87, 14.06,16.54, 18.21, 18.52, 18.86, 19.28, 19.84 and 20.09±0.2. This is carried out using X-ray diffractometer using Cu anode having 45kV, 40mA at 25 °C. This crystalline form is very stable and the form doesn't change with time for a considerably long time.

In still another embodiment, some of the key advantages of the present invention are as below:
1. The process of the present invention uses acetic acid and ethylene dichloride for the reaction of 2,6-di-t-butyl phenol with para formaldehyde, this helps in the easy removal of water from the reaction mixture by azeotropic distillation.
2. The removal of water reduces the time cycle drastically by reducing the reaction time in condensation and makes the recovery of acetic acid easy and makes recovered acetic acid reusable.
3. The process of the present invention can be carried out in a single step, which minimises the workup and effluent generation.
4. Further the present invention provides a novel process of purification which avoids the use of column provides highly pure l,3,5-Trimethyl-2,4,6-tris(3,5-di-tert-butyI-4-hydroxybenzyl) benzene or pure 1,3,5-Trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl) benzene acceptable to the regulatory authority.
The present invention can be illustrated by the following examples, which are not to limit the scope of invention.
Example 1: Preparation of l,3,5-Trimethyl-2,4,6-tris(3,5-di-tert-butyI-4-hydroxybenzyl) benzene of formula I:
(a) Preparation of 3,5-di-tert-butyl-4-hydroxybenzyl acetate of formula II
Acetic acid (300.0 ml), 2,6-di-t-butyl phenol (200g) and EDC (100 ml) were charged into a RB flask. Para formaldehyde (45.4g) was added to the above reaction mass and stirred at 30 ± 2°C. Di-n-propylamine (17.6 g) was added slowly to the reaction mass and the reaction mas was gradually heated to 95±2°C. The setup was kept in distillation mode to remove liberated water from the reaction. The reaction mass was maintained at 95 ± 2°C till water and EDC came out from the reaction. After completion of reaction, the reaction mass was cooled to 60-70°C.

(b) Preparation of l,3,5-Trimethy]-2,4,6-tris(3,5-di-tert-butyl-4-
hydroxybenzyl) benzene of formula I
Mesitylene (30 g) and above cooled reaction mass was charged into a RB flask at 60-70°C. Sulfuric acid (10.66g) was added to the above reaction mass at 60-70°C and maintained for 1 hour. Addition of sulfuric acid (10.66g) was repeated twice. After completion of reaction, the reaction mass was slowly cooled to 25-30°C and stirred. The solid product obtained was washed with acetic acid till filtrate becomes colorless and dried under vacuum.
Yield: 170±5g Purity: 94-97% MP:224-232 °C
(c) Purification of l,3,5-Trimethyl-2,4,6-tris(3,5-di-tert-buryl-4-
hydroxybenzyl) benzene
EDC (300 ml or 1.5 volumes on DTBP) and wet material (175 ± 5 g) were charged into the RB Flask. The reaction mass was heated to a clear solution. Water (300 ml or 1.5 volumes on DTBP) was charged to the clear mass and maintained for 30 minutes at 55 ±2°C.The mass was allowed to settle for 30 minutes. The layers were separated, EDC layer was passed through 2 micron candle filter to another 500 ml RBF. EDC was distilled completely under vacuum at below 70°C. Acetic acid (300 ml or 1.5 volume on DTBP) was added and stirred for 1 hour at 70-80°C. The reaction mass was cooled to 30±2°C, stirred for 30minutes. The reaction mass was filtered under vacuum, washed with acetic acid till filtrate becomes colorless and dried at 85-90°C under vacuum.
Yield: 0.72 to 0.76w/w (144-152g)
Purity: NLT 99.5%
MP: 140-146 °C
Colour of solution 500 (nm%): min 98

We claim:
1. A process for the preparation of l,3,5-trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl) benzene of formula I, which comprises:

a) reacting 2,6-di-t-butyl phenol of formula III with paraformaldehyde in a acetic acid and ethylenedichloride (EDC) in presence of base to form 3,5-di-tert-butyl-4-hydroxybenzyl acetate of formula II;

b) condensing the obtained 3,5-di-tert-butyl-4-hydroxybenzyl acetate with mesitylene using acid to form l,3,5-Trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl) benzene of formula I; and

c) purifying the crude 1,3,5-Trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl) benzene of formula I using a solvent to form pure l,3,5-Trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl) benzene of formula I.
2. A process according to claim 1, wherein the base in step a) is di-n-propylamine.
3. A process according to claim 1, wherein the reaction in step a) is carried out at temperature 90- 100°C.
4. A process according to claim 1, wherein the acid used in step b) is selected from the group comprising hydrochloric acid, sulphuric acid and the like.
5. A process according to claim 1, wherein the acid in step b) is sulphuric acid.
6. A process according to claim I, wherein the condensation in step b) is preferably carried out at temperature 60-70 °C.
7. A process according to claim 1, wherein the solvent used for purification in step c) is selected from the group comprising chlorobenzene, carbon tetrachloride, dichloromethane, ethylene dichloride and the like.
8. A process according to claim 1, wherein the solvent used for purification in step c) is ethylene dichloride.