WO2020136678A1

WO2020136678A1 - A process for preparation of tertiary butyl hydroquinone

Info

Publication number: WO2020136678A1
Application number: PCT/IN2019/050951
Authority: WO
Inventors: Rajiv Ashokbhai Shah; Rasiklal Amulakhbhai Vora
Original assignee: Milestone Preservatives Pvt. Ltd.
Priority date: 2018-12-24
Filing date: 2019-12-23
Publication date: 2020-07-02

Abstract

A PROCESS FOR PREPARATION OF TERTIARY BUTYL HYDROQUINONE The present invention relates to a process for preparation of tertiary butyl hydroquinone. More particularly, it relates to a process for preparation 5 of TBHQ by eradicating the consumption of hazardous solvents like toluene and eliminating hazardous impurities like hydroquinone, tertiary butyl‐p‐benzoquinone and also drastically reducing the presence of heavy metals like lead and arsenic. The present invention includes stages I‐IV in which TBHQ is more purified and precipitated with a high scale purity results. TBHQ has 10 application in food additives, animal feeds, as an antioxidant, emulsifier and in edible oils, effectively as antioxidant.

Description

A PROCESS FOR PREPARATION OF TERTIARY BUTYL HYDROQUINONE

FIELD OF INVENTION

The present invention relates to a process for preparation of tertiary butyl hydroquinone (also termed as TBHQ). More particularly, the present invention relates to a process for preparation of highly effective, purified and efficient tertiary butyl hydroquinone by eliminating the consumption of hazardous solvents.

BACKGROUND OF THE INVENTION

Tertiary butyl hydroquinone is highly used as an anti oxidant especially for unsaturated vegetable oils and severable edible animal fats. It prevents any sort of rancidification i.e. discoloration, change flavor or odor of food in which it is added. It is synthetic and is also incorporated due to its effectiveness in polyunsaturated oils, nuts, inedible animal fats, butterfat and packaged fried foods in addition to foods packaging substances such as glassine as well as paraffin wax. It is well-known in the food industry for its potential to increase the shelf life of the food products.

Although a natural antioxidant called tocopherol already exists in almost all kinds of vegetable oils and fats. It has negligible potential to offer stabilization of the product. It makes no difference on adding tocopherol externally to enhance the shelf-life of the product. These fats and oils require synthetic antioxidants. TBHQ very ideally preserves unsaturated fats especially polyunsaturated vegetable oils and inedible animal fats. It is more appropriate for saturated fats, nuts, essential oils and food packaging material as well. It is also a healthier alternative for these types of fat and oils.

TBHQ has high oxidation resistance for unsaturated fats and oils which are more effective than other commonly used antioxidants. TBHQ is excellent oil-soluble wherein the copper and iron metals do not change color and flavor; adding any fat in foods does not lead to change in odor and stench. This makes it gain a wide use in oil and oil-containing food in addition. TBHQ is also used as intermediates for organic synthesis and raw materials of polyester and photosensitive agents, cosmetic additives can also be synthesized. Another important food antioxidants is butoxy hydroxy anisole.

The conventional process for the preparation of TBHQ involves raw material hydroquinone wherein TBHQ is generated by reaction of isobutylene or tertiary butanol in the presence of a catalyst. In this reaction, the catalyst uses more acid as catalyst; useful lewis acid catalysts are used for research due to its low industrial activity. It is difficult to increase the selectivity wherein the by-products obtained have many disadvantages relating to high production cost, when combined with phenolic byproduct the utilization value is not high and easy to cause environmental pollution. One such process for preparation of tertiary butyl hydroquinone has been disclosed in patent document CN1762944 that determines the preparation of tertiary butyl hydroquinone with methyl tert-butyl ether as alkylating agent using a solvent and an acid catalyst with hydrogen. The hydrazine reaction produces 2-tert butyl hydroquinone and a hydrocarbyl transfer reagent is added under reflux. The problem associated in this preparation process is a specific maintenance of temperature, very complex process and a constant monitoring is needed to monitor the dropping time of the funnel. Another such document for preparation of tertiary butyl hydroquinone has been disclosed in patent document US4323713 that determines the preparation of hydroquinone with an oxidation-reduction process. The process involves stirring means along with temperature measuring means, compressed air source, steam distillation, gas inlet and outlet tubes. The limitation of this invention is incorporation of several processes which is a time consuming process, very costly method for preparation of TBHQ and also involves utilization of catalysts in the process making the process more lengthy and complex in nature.

Hence, to overcome the above mention problems it is desperately needed to invent a simple preparation process of TBHQ which is not subjected to above mention problems so that the finally obtained TBHQ is more effective , efficient and is highly purified as when compared to prior art. OBJECT OF THE INVENTION

The principle object of the present invention is to provide a process for preparation of tertiary butyl hydroquinone. Further object of the present invention is to provide a process for preparation of tertiary butyl hydroquinone with 99.95% purity through HPLC assay technique.

Another object of the present invention is to provide an effective process for preparation of TBHQ by eradicating the use of any hazardous solvents or chemicals which causes the environmental pollution and health hazards.

Another object of the present invention is to provide a process for preparation of TBHQ conferring to a lesser extent of side reactions and providing high yields. Yet another object of the present invention is to provide a process for preparation of TBHQ whereby the shelf life of TBHQ is 3 years from date of manufacturing when the container is intact.

SUMMARY OF THE INVENTION The present invention relates to a process for preparation of tertiary butyl hydroquinone. More particularly, it relates to a process for preparation of TBHQ by eradicating the consumption of hazardous solvents. The present invention includes stages I-IV in which TBHQ is more purified and precipitated with a high scale purity results and also the process involves the steps for incorporation of a nutch filter to purify the collected TBHQ in the each of the foregoing stages that provides highly effective, efficient and purified tertiary butyl hydroquinone. TBHQ has application in food additives, animal feeds, as an antioxidant, emulsifier and in edible oils.

BRIEF DESCRIPTION OF DRAWINGS Fig. 1 illustrates a purity test pattern showing the retention time of tertiary butyl hydroquinone.

Fig. 2 illustrates a purity test pattern showing the retention time of tertiary butyl p-benzoquinone.

Fig. 3 illustrates a purity test pattern showing the retention time of hydroquinone.

Fig. 4 illustrates a purity test pattern showing the retention time of 2, 5 di tertiary butyl hydroquinone.

DETAILED DESCRIPTION

Before explaining the present invention in detail, it is to be understood that the invention is not limited in its application to the details. The invention is capable of other embodiment and of being practiced or carried out in a variety of ways. It is to be understood that the phraseology and terminology employed herein is for the purpose of description and not of limitation.

It is to be understood that tertiary butyl hydroquinone has a molecular formula of C10H14O2 and molecular weight of 166.24. TBHQ is a synthetic aromatic organic compound which is a type of phenol. It is a derivative of hydroquinone, substituted with a tert-butyl group.

TBHQ has chemical names 2 Tertiary Butyl 1-4 dihydroxy benzene 1, 4-Benzenediol; 2-(l, 1-dimethylethyl) Mono-tert-butylhydroquinone t- butylhydroquinone; 2-(l, l-dimethylethyl)-l 4-benzenediol. TBHQ is a white crystalline powder having characteristic odor. It is soluble in alcohol and is practically insoluble in water. It is also used as food additives, animal feeds, an antioxidant, emulsifier, in edible oils, in perfumery, as a stabilizer also added to varnishes, lacquers and resins.

The present invention provides a process for preparation of TBHQ comprises following stages and steps: Stage I:

(a) In a reactor vessel 12% to 16% hydroquinone and 48% to 52% toluene are added and are heated at a temperature 70-10CTC.

(b) 8% to 12% tertiary butanol and 23% to 27% phosphoric acid are added to the above prepared reaction mixture of step (a) slowly within 10 to

20 hours and heated at 85-105°C.

(c) The phosphoric acid layer is separated from the bottom and toluene layer is transferred to crystallizer and cooled at 30-40°C.

(d) Impure TBHQ is precipitated and that is transferred to a nutch filter for further purification.

Stage II:

(e) Above prepared TBHQ from stage (I) is mixed with acetone and water mixture (0.70 to 1.30 times of weight of collected TBHQ) into the reactor vessel and heated at the temperature 75-95°C.

(f) Above prepared solution is filtered out and cooled at 20-40°C in the crystallizer.

(g) From the above prepared solution 2, 5-di TBHQ is separated as filtrate and remaining TBHQ is further crystallized out with acetone and water mixture distilled out at 110°C.

(h) TBHQ is separated for further purification and is transferred to stage III. Stage III:

(i) Above collected TBHQ is reacted with isopropyl benzene (3 to 5 times of weight of collected TBHQ) in the reactor vessel and is heated at 100- 125°C.

(j) Above prepared solution is filtered out and cooled at 15-25°C in the crystallizer.

(k) Pure TBHQ is been reprecipitated and is transferred to the nutch filter for drying. Stage IV:

(l) The above prepared TBHQ from stage III is added to a dryer and heated upto 80°C under vacuum of 700-760 mm.

(m) Dried TBHQ is collected as a finished product. The present invention relates to a process for preparation of TBHQ wherein the solvents is selected but not limited to acetone, ethanol, isopropyl alcohol, ethyl acetate, isopropyl benzene, ethyl benzene, methanol and water are used as solvent. It should be appreciated that there is considerable overlap between the above-listed solvents in common usage, since a given solvent is often classified differently by different practitioners in the field, or is commonly used for any of several different functions. Thus, the above-listed solvents should be taken as merely exemplary, and not limiting, of the types of solvents that can be included in process for preparation of TBHQ of the present invention. One or more of these solvents can be selected and used by the skilled artisan having regard to the particular desired properties of the dosage form by routine experimentation without any undue burden.

The present invention relates to a process for preparation of TBHQ wherein the acetone and water mixture is 0.70 to 1.30 times weight of collected TBHQ which is mentioned in step (e) of stage II; the acetone is in the range of 25% to 50% and water is in the range of 40% to 75%.

The invention is illustrated more in detail in the following example. The example describes and demonstrates embodiment within the scope of the present invention. This example is given solely for the purpose of illustration and is not to be construed as limitations of the present invention, as many variations thereof are possible without departing from the spirit and scope.

Example 1:

The present invention provides a process for preparation of TBHQ comprises following stages and steps:

Stage I:

(a) In a reactor vessel 14.25% hydroquinone and 50% toluene were added and heated at a temperature 70-100°C. (b) 10.72% tertiary butanol and 25% phosphoric acid were added to the above prepared reaction mixture of step (a) slowly within 10 to 20 hours and heated at 85-105°C.

(c) The phosphoric acid layer was separated from the bottom and toluene layer was transferred to crystallizer and cooled at 30-40°C.

(d) Unpurified TBHQ was precipitated and transferred to a nutch filter for further purification.

Stage II:

(e) Above prepared TBHQ from stage (I) and mixed with acetone and water mixture (0.70 to 1.30 times of weight of collected TBHQ) into the reactor vessel and heated at the temperature 75-95°C.

(f) Above prepared solution was filtered out and cooled at 20-40°C in the crystallizer.

(g) From the above prepared solution 2, 5-di TBHQ was separated as filtrate and remaining TBHQ was further crystallized out with acetone and water distilled out at 110°C.

(h) TBHQ was transferred for further purification to stage III. Stage III:

(i) Above collected TBHQ was reacted with isopropyl benzene (3 to 5 times of weight of collected TBHQ) in the reactor vessel and heated at 100- 125°C. (j) The above prepared solution was filtered out and cooled at 15-25°C in the crystallizer.

(k) Pure TBHQ was reprecipitated and transferred to the nutch filter for drying.

Stage IV:

(l) The above prepared TBHQ from stage III was added to a dryer and heated upto 80°C under vacuum of 700-760 mm.

(m) Dried TBHQ was collected as a finished product.

Evaluation study:

The final product was evaluated through various parameters. The final product i.e. tertiary butyl hydroquinone was used as a sample and was evaluated through various parameters. An evaluation study was based on the available form of TBHQ which was compared to the prepared TBHQ from the present claimed process. The parameters for evaluation study are as follows: i) Description:

The visual examination of sample TBHQ was done. The prepared TBHQ was white crystalline powder having characteristic odor. ii) Solubility:

The solubility of sample TBHQ was checked in water and other common solvent. The sample TBHQ was soluble in alcohol and practically insoluble in water. iii) Assay:

The HPLC assay technique was conducted and several impurities were tested. The method is described as follows:

HPLC Test Method:- Test system: Isocratic

Test preparation: 20 mg dissolved in 25 ml mobile phase

Mobile phase: 700 ml Methanol alongwith 300 ml of water

Column: Hypersil BDS C 18 (250 x 4.6 mm, 5 micrometer)

Flow rate: 0.6 ml/min

Wave length: 310 nm

Absorbance Units Full Scale: 0.08

Run time: 20 min

Detector: Ultraviolet A) Purity test of Tertiary Butyl p-Benzoquinone:

The above stated HPLC test method was conducted and result was obtained as stated in below table: Result:

Table 1: Retention time and area (%) of Tertiary Butyl p-Benzoquinone

Fig. 2 determines a graph provided by the result of a HPLC assay technique clearly pointing out a peak showing an area (%) of 87.35 and retention time of 13.373 min which indicates that the impurity was not found or NIL when purity test was performed through HPLC assay technique.

Observation:

In the standard process for preparation of TBHQ, the hazardous impurity tertiary butyl p-benzoquinone was found to be NIL at the end of the process whereas the sample TBHQ of the present invention also complies with the standard process which was resulted through HPLC technique. B) Purity test of Hydroquinone:

Table 2: Retention time and area (%) of Hydroquinone

Fig. 3 envisions a graph providing the result of HPLC assay technique clearly pointing out a peak showing a retention time of 4.627 min with an area (%) of 99.93% which complies with the standards of the Hydroquinone and clearly implies that the collected TBHQ was pure in nature.

Observation:

In the standard process for preparation of TBHQ, the hazardous impurity hydroquinone was found to be NIL at the end of the process whereas the sample TBHQ of the present invention also complies with the standard process. C) Purity test of 2, 5 di- Tertiary Butyl Hydroquinone:

Table 3: Retention time and area (%) of 2, 5 di- Tertiary Butyl Hydroquinone

Fig. 4 envisions the result which describes a graph providing the result of HPLC assay technique clearly pointing out a peak showing a retention time of 15.013 min with a area (%) of 96.04% which complies with the standards of the 2, 5 di- Tertiary Butyl Hydroquinone and clearly implies that the collected TBHQ was pure in nature.

Observation:

In the standard process for preparation of TBHQ, the hazardous solvent 2, 5 di-tertiary butyl hydroquinone was found to have maximum 0.2% at the end of the process whereas the sample TBHQ of the present invention was found to have 0.05%.

• Result of Assay method:

The above stated HPLC test method was conducted and result was obtained as stated in below table: Table 4: Retention time and area (%) of Tertiary butyl hydroquinone

Fig. 1 determines the result which describes that the obtained Tertiary butyl hydroquinone has 99.95% purity and involved only 2, 5 di-tertiary butyl hydroquinone in a minimal amount (0.05%) and had a retention time of 16.240 min in the form of an impurity and all other impurities were not found or NIL when purity test was performed through a HPLC assay technique. Observation:

The standard process for preparation of TBHQ provides a minimum 99.80% purity whereas the sample TBHQ of the present invention results into 99.95% of purity. iv) Purity test of Toluene

The purity test of Toluene was conducted through a GC Head space technique by Gas chromatography.

Table 5: Gas chromatographic parameters

Procedure:

Preparation of Solution:

1) Blank: (Air)

The "Air" was taken into a 20 ml Head Space vial, which was sealed immediately with a septum and Crimp cap. 2) Diluent: (DMF)

5.0 ml of N. N-Dimethylfomamide was transferred into Head Space vial and was sealed immediately with a septum and crimp cap.

3) Standard Solution:

89 mg of toluene and 50 mg of Isopropyl Benzene were accurately weighed and transferred into a 50.0 ml of volumetric flask. 25.0ml of diluent was added and was mixed to make volume up to mark with diluent. Pipette out 2.5 ml from this obtained solution into 50 ml of volumetric flask and make up volume to the mark with diluent. 5.0 ml of this standard solution was filed into each six-headspace vial and the vial was crimped. This vial was used for standard analysis. 4) Sample Solution:

About 500 mg of sample were accurately weighed and transferred into a headspace vial, 5.0 ml of diluent was added, the vial was swirled to disperse the sample and the vial was sealed (Sample preparation in duplicate).

The content of toluene was measured by the below given calculation formula: Calculation:

At x Ws x Dt x P x 10⁶

Content (ppm) =

As x DS x Wt x 100

Where:

At = The peak area of solvents peak in Sample solution

As= Average peak area of respective solvent peak in Standard solution

Ds= Dilution factor of Standard Solution

Dt= Dilution factor of Test Solution

Ws= Weight of respective standard in Standard solution (in mg)

Wt= Weight of sample in Sample solution (in mg)

P= % Purity of solvent in standard preparation

Result & Observation:

In the standard process for preparation of TBHQ, the hazardous solvent toluene was found to be practically NIL at the end of the process whereas the sample TBHQ of the present invention also complies with the standard process which was resulted through GC Head Space technique. v) Purity test of Heavy Metals (As, Pb):

The detection of heavy metals was conducted by an inductively coupled plasma optical emission spectroscopy. Table 6: Solvents and reagents used in purity test of heavy metals

Procedure:

The reagents are been incorporated in a selected procedure which involves following steps:

1) Preparation of Solution:

Diluent: 5.0 % Nitric acid

2) Preparation of 5.0 % Nitric acid:

Pipette out 5.0 ml of 69 % Nitric acid ICP Grade into 100.0 ml of volumetric flask and make up volume to the mark with HPLC grade water.

3) Preparation of mixture of Standard stock solution (1 ppm)

Pipette out 1.0 ml from Standard solution A (10 ppm -As, Pb) to 10 ml of volumetric flask. Make up volume to the mark with diluent.

4) Preparation of Standard solution A (0.1 ppm)

Pipette out 1.0 ml from standard stock solution in 10 ml of volumetric flask. Make up volume to the mark with diluent. 5) Preparation of Standard solution B (0.2 ppm)

Pipette out 2.0 ml from standard stock solution in 10 ml of volumetric flask. Make up volume to the mark with diluent.

6) Preparation of Standard solution C (0.3 ppm) Pipette out 3.0 ml from standard stock solution in 10 ml of volumetric flask Make up volume to the mark with diluent.

7) Preparation of Sample solution:

1 gm of sample was transferred into 50.0 ml of beaker. 1.0 ml of hydrogen peroxide was added to the sample then 2.0 ml of cone. Nitric acid was slowly added to the sample. The above prepared mixture was heated for few minutes. 8.0 ml of cone. Nitric acid was added and the solution was heated until sample was completely dissolved and clear solution was obtained. After digestion of sample the mixture was cooled to room temperature and make up the volume to 25 ml with HPLC grade water. The solution was filtered through whatman filter paper.

Table 7: Inductively Coupled Plasma method parameters:

The plasma was ignited and wait for about 15 minutes to get it stabilized. The blank solution was aspirated and zeros the signal. Aspirated diluent, standard, sample solution was taken in triplicate cycles in the plasma and the ionization intensity was measured as per below stated calculation formula:

Calculation: ppm per ml x volume final

(ppm) =

Sample taken

Result & Observation:

In the standard process for preparation of TBHQ, the hazardous heavy metals were found to have maximum 0.5 ppm at the end of the process whereas the heavy metals retained from the sample TBHQ of the present invention were found to have 0.25 ppm. Specifically, the hazardous metal arsenic was found to have maximum 1.0 ppm at the end of the process whereas the metal arsenic retained from the sample TBHQ of the present invention was found to have 0.85 ppm. vi) Melting range:

In the standard process for preparation of TBHQ, the melting range was found to be 126.5°C to 128.5°C whereas the melting range of prepared TBHQ of the present invention was found to be 127.0°C to 128.5°C. vii) UV Absorbance:

The sample TBHQ of the present invention passes the UV Absorbance test (poly nuclear hydrocarbons) and complies with the standard process for preparation of TBHQ. viii) Moisture content:

The moisture content of the collected tertiary butyl hydroquinone was measured by titration method.

Procedure:

1) Preparation for Factor Solution:

0.1 gm disodium tartrate was accurately weighed and was taken in Karl Fischer assembly glass. 30.0 ml of dried methanol was added and dissolved. Karl fischer reagent was added drop wise and this procedure was followed in three set. Note down the reading.

2) Procedure for Sample Solution:

0.5 gm of sample was accurately added in Karl fischer assembly glass and Karl fischer reagent was added drop wise. Note down the reading.

The moisture content was measured by the following calculation formula: Calculation:

For Factor:

Sample weight taken (mg) x 0.1566

Factor

Burette reading (ml)

For sample:

Burette reading (ml) x Factor x 100

% water = -

Sample weight taken (mg)

Result & Observation:

In the standard process for preparation of TBHQ, the moisture content was found to be maximum 0.10% whereas the moisture content retained from the sample TBHQ of the present invention was found to be 0.08% through Karl Fischer method. ix) Color of 20% TBHQ solution in propylene glycol:

The visual color test of sample TBHQ was done. In the standard process for preparation of TBHQ, the color of 20% TBHQ solution in propylene glycol was found to be clear and almost colorless at the end of the process whereas the sample TBHQ of the present invention also complies with the standard process. x) Storage and handling:

Store in a tightly closed fiber/plastic drums with LDPE liner inside and in dry and cool condition (ambient temperature 25°C).

xi) Shelf life:

Three years from the date of manufacturing in intact condition.

Although the example as well as the process of preparation and use has been specifically described, it should be understood that variations in the preferred embodiment could be achieved by a person skilled in the art without departing from the spirit of the invention. It is also to be understood that the present invention is given with the understanding that this invention is intended only to be illustrations without serving as a limitation on the scope of the invention as defined in the claims.

Claims

We claim:

1. A process for preparation of tertiary butyl hydroquinone comprises following steps:

(a) adding 12% to 16% hydroquinone and 48% to 52% toluene in a reactor vessel and heating at a temperature 70-100°C;

(b) mixing 8% to 12% tertiary butanol and 23% to 27% phosphoric acid to the above prepared reaction mixture of step (a) slowly within 10 to 20 hours and heating at 85-105°C;

(c) separating the phosphoric acid layer from the bottom and transferring toluene layer to crystallizer and cooling at 30-40°C;

(d) precipitating impure tertiary butyl hydroquinone from this reaction and transferring to a nutch filter for further purification;

(e) mixing above prepared tertiary butyl hydroquinone from step (d) with acetone and water mixture into the reactor vessel and heating at temperature 75-95°C;

(f) filtering the above prepared solution and cooling at 20-40°C in the crystallizer;

(g) separating 2, 5-di tertiary butyl hydroquinone as filtrate and crystal lizing out remaining tertiary butyl hydroquinone with acetone and water mixture distilling out at 110°C;

(h) reacting above collected tertiary butyl hydroquinone with isopropyl benzene in the reactor vessel and heating at 100-125°C; (i) filtering the above prepared solution and cooling at 15-25°C in the crystallizer;

(j) reprecipitating collected tertiary butyl hydroquinone and transferring to the nutch filter for drying;

(k) heating the dryer upto 80°C under vacuum of 700-760 mm;

(1) collecting dried tertiary butyl hydroquinone as a finished product.

2. The process for preparation of tertiary butyl hydroquinone as claimed in claim 1, wherein solvent is selected from acetone, methanol, ethanol, isopropyl alcohol, ethyl acetate, isopropyl benzene and ethyl benzene.

3. The process for preparation of tertiary butyl hydroquinone as claimed in claim 1 step (e), wherein the acetone and water mixture is 0.70 to 1.30 times with respect to weight of collected tertiary butyl hydroquinone.

4. The process for preparation of tertiary butyl hydroquinone as claimed in claim 3, wherein the acetone is in the range of 25% to 50% and water is in the range of 40% to 75%.

5. The process for preparation of tertiary butyl hydroquinone as claimed in claim 1 step (h), wherein the isopropyl benzene is 3 to 5 times with respect to weight of collected tertiary butyl hydroquinone.