Title of Invention

AN IMPROVED PROCESS FOR THE PREPARATION OF 2,2,2-TRIFLUOROETHANOL

Abstract The present invention relates to an improved process for the preparation of 2,2,2-Trifluoroethanol. More particularly, the present invention provides a liquid phase process for the preparation of 2,2,2-trifluoroethanol via esterification of l,l,l-trifluoro-2-chloroethane using metal salt of carboxylic acid in presence of homogenous catalyst followed by alkaline hydrolysis. The invention utilizes polyethylene glycol (PEG) or crown ether catalysts for high yield of the product. The process utilizes an effective separation of unreacted l,l,l-trifluoro-2-chloroethane, solvent, product ester and byproduct KCI.
Full Text FIELD OF THE INVENTION
The present invention relates to an improved process for preparation of 2,2,2-trifluoroethanol from l,l,l-trifluoro-2-chloroethane. More particularly, the present invention provides a liquid phase process for the preparation of 2,2,2-trifluoroethanol via esterification of l,l,l-trifluoro-2-chloroethane using metal salt of carboxylic acid in presence of homogenous catalyst followed by alkaline hydrolysis. BACKGROUND OF THE INVENTION
The 2,2,2-trifluoroethanol (CF3CH20H or TFE) is mainly used in pharmaceutical industry, a key raw material for the production of inhalation anesthetics isoflurane and desflurane. Other uses of TFE are as a solvent, an intermediate in chemical synthesis and as a working fluid in heat absorption pumps and transformers. The preparation of 2,2,2-Trifluoroethanol is broadly classified into three strategies, however each strategy has its own limitation. First strategy US, 4,273,947 (1981), FR 2,544,712 (1984), EP 365,403 (1990), US 502,3384 (1990), JP 61,268,639 (1996) discloses the reduction of trifluoroacetic acid or trifluoroacetyl chloride to trifluoroethanol using noble metals like Rh, Ru, Ir, Pt and under high pressure. As the cost of noble metals being high and the material of construction for highly corrosive trifluoroacetic acid requires high capital investment and therefore the process has limitation in commercialization of technology.
Another reference may be made to HU 41,722 (1987), which discloses esterification of trifluoroacetic acid using benzyl alcohol followed by reduction with NaBH4 produces
several azeotropes of alcohol and water, which are difficult to separate. Yet another reference may be made to US 4,647,706,
discloses the hydrogenolysis of the trifluoroacetaldehyde to obtain trifluoroethanol, which requires initial preparation of the aldehyde by an oxidation. Yet another reference may be made to US, 4,396,784 (1983), which discloses the hydrogenation of trifluoroacetic acid to trifluoroethanol using Re-supported on fluorinated AI2O3 under pressure. The methods EP 177,393 (1986), Neth. 6,512,355 (1966), DE 3,510,883 (1986) disclose the reduction of fluorinated esters using metal oxides. It requires preparation of ester, which is of cumbersome process.
The second strategy, references may be made to US 4,434,297 (1984), JP 58,140,031 (1983), JP 58,134,043 (1983), EP 171,248 (1986), CN 1,190,092 (1998) discloses the preparation of trifluoroethanol by esterification of 1,1,1-trifluoro-2-chloroethane (HCFC-133a) with potassium acetate followed by hydrolysis. The unit operation associated with isolation of products is tedius and commercially cannot be exploited. Another reference may be made to FR 2,635,101 (1990) discloses the hydrolysis of HCFC-133a with H2O over metal phosphates, however low conversion and low selectivity.
The third method, reference may be made to US 5,629,458 (1997), discloses the preparation of trifluoroethanol by oxidation of 1,1,1-trifluoroethane which in turn should be made from methylchloroform by halogen exchange reaction. The separation of trifluoroethane from HCI generated in halogen exchange reaction is a major constraint.
Based on the above limitations, none of the methods are viable for commercial exploitation. The present invention provides a novel, clean and green process for trifluoroethanol starting from 1,1,1-trifluoro-2-chloroethane (HCFC-133a).
OBJECTIVES OF THE INVENTION
The main objective of the present invention is to provide an improved process for the preparation of 2,2,2-trifluoroethanol in two steps starting from l,l,l-trifiuoro-2-chloroethane by esterification using homogenous catalyst followed by the intermediate ester hydrolysis by an economically viable process.
Another object of the present invention is utilization of polyethylene glycol (PEG) or crown ether catalysts in step 1 of process for high yield of the product. Yet another object is an effective separation of unreacted HCFC-133a, solvent, product ester and byproduct KCI.
Yet another objective of the present invention is of reaction carried at 180°C with a mole ratio of potassium acetate to HCFC-133a is 1:2.5 with mechanical stirring. DESCRIPTION OF THE INVENTION
Accordingly, the present invention provides an improved process for preparation of 2,2,2-
trifluoroethanol from l,l,l-trifluoro-2-chloroethane, which comprises reacting 1,1,1-
trifluoro-2-chloroethane with a metal salt of carboxylic acid with a molar ratio of 1,1,1-
trifluoro-2-chloroethane to metal salt of carboxylic acid in the range 1.5:1 to 2.5:1, in an
organic solvent, in the presence of homogenous catalyst, in an autoclave under vacuum,
at a temperature in the range of 60-300°C, for a period of 6-24 hrs, under stirring, at a
speed ranging between 20-1000 rpm, distilling the above said reaction mixture to remove
the unreacted 1,1,1-trifluorochloroethane to obtain ethanol-
2,2,2-trifluoroacetate, hydrolysing the above said ethanol-2,2,2-

trifluoroacetate by slowly adding an aqueous solution of base to the cooled ethanol-2,2,2-trifluoroacetate and maintaining the temperature ranging between 30 - 100°C, for a period of 2-8 hrs, followed by distillation to obtain the desired product and metal salt of carboxylic acid.
In an embodiment of the present invention the metal salt of carboxylic acid used is
selected from potassium acetate and sodium acetate.
In yet another embodiment of the present the organic solvent used is selected from NMP,
DMSO and DMF.
In yet another embodiment the homogenous catalyst used is selected from PEG-600 and
crown ether.
In yet another embodiment the temperature used for estrification is in the range 100-
250°C.
In yet another embodiment the mechanical stirrer speed used is in the range 200-1000
rpm, preferably in the range of 500 - 800 rpm.
In yet another embodiment the time period used for estrification is in the range of 12 -
18hrs.
In yet another embodiment the products obtained are effectively separated by distillation
using high performance sectors packing material in distillation column.
In yet another embodiment the organic solvent used is recovered and is recyclable or
further use.
In yet another embodiment the yield of ethanol-2,2,2-trifluoroacetate obtained is in the
range 80-96%.
In yet another embodiment the base used for hydrolysation is selected from the group consisting of KOH, NaOH, K2C03 and Na2C03.
In yet another embodiment the temperature used in hydrolysation is in the range 30-100°C.
In still another embodiment the byproduct potassium acetate is recovered for further recycle in hydrolysation reaction.
The present invention is related to the process for the preparation of Trifluoroethanol in two steps. Step 1 involves esterification of 1,1,1 -trifluoro-2-chloroethane using metal salt of carboxylic acid in a medium of solvent. The metals are mainly sodium, potassium and the solvents such as NMP, DMF & DMSO are used. The reaction is mainly between gas and solid in presence of solvent under anhydrous conditions. In order to promote reaction, the solubility of solid and gas in a solvent/medium using homogenous catalyst is desirable. The catalysts such as PEG-600&crown ether are used in reaction. Thus in a typical reaction, solvent, catalyst and solid metal salt of carboxylic acid is charged into an autoclave equipped with mechanical stirrer, thermowell and pressure gauge. Air is removed from autoclave under reduced pressure and desired quantity of 1,1,1-trifluoro-2-chloroethane is charged. Mole ratio of metal salt of carboxylic acid to 1,1,1-trifluoro-2-chloroethane is in the range 1:1.5 to 1:2.5 and solvent verses reactants is 1:2.5. The reaction is conducted in batch mode at temperature in the range 60-300°C, more preferably 100 -250°C and most preferably 150 - 190°C with stirring speed in the range 200 -1000 rpm, more preferably 350 - 900 rpm and most preferably 500 - 800 rpm. The reaction time is in the range 6 - 24 h, more preferably 9 - 20 h and
most preferably 12 - 18h. The reaction product mixture is distilled into a still equipped with distillation column maintaining condenser coolant temperature in the range 0 to -50°C more preferably -5°C to -40°C and most preferably -10 to -30°C. During distillation the autoclave temperature is in the range 100 to 200°C, more preferably 110 to 190°C and most preferably 130 to 175°C. The residue left after distillation, a mixture of solvent and byproduct (KCI) are recovered by filtration followed by distillation. The mixture of ester and unreacted HCFC-133a is further distilled using distillation column to recover HCFC-133a for recycle and product ester for use in next step.
Step 2 involves hydrolysis of ester using a metal hydroxide such as KOH, NaOH or metal carbonate such as K2CO3 and Na2C03 at a temperature range of 30 - 100°C, more preferably 40 - 80°C and most preferably 55 - 75°C. The hydrolysed product is analysed by using Gas chromatography and product 2,2,2-trifluoroethanol is distilled from aqueous mixture in pure form using a distillation column packed with high performance sectors material.
The following examples are given by the way of illustration and therefore should not be construed to limit the scope of the invention.
Example 1
The experimental setup consists of a 2 litre autoclave equipped with a mechanical stirrer, thermowell, pressure gauge, rupture disc and suitable control instrumentation for heating and cooling. The reactor is charged with N-methyl-2-pyrrolidone (NMP) (560g, 99%), potassium acetate (377g, 3.85moles), PEG-600 (5g) and system is evacuated for 10 min. at 200 mm vacuum. 2-chloro-1,1,1-trifluoroethane (HCFC-133a) (683g, 5.76 moles) is charged and the reactor is slowly heated to 180°C and maintained under autogenic pressure. As the reaction progresses, the pressure drops slowly and attains a constant value. The reaction duration is nearly 12 h. Unreacted
HCFC-133a and product ester is distilled into a still equipped with distillation column. The HCFC-133a (276g, 2.33 moles) is recovered by further distillation and ethanol -2,2,2-trifluoroacetate (458.5g, 3.23moles) obtained in 94% yield. The left over slurry in autoclave is filtered and solid byproduct KCI is washed with NMP and dried. The mother liquor is distilled for the recovery of NMP solvent.
Example 2
The experimental conditions and product recovery is almost similar as discussed in example 1 except the catalyst used is crown ether. The yield of product is 96%.
Example 3
As in example 1, the reactor is charged with N-methyl-2-pyrrolidone (NMP) (180g, 99%), potassium acetate (120g, 1.22 moles), PEG-600(1g) and 2-chloro-1,1,1-trifluoroethane (HCFC-133a) (210g, 1.77 moles). The reaction is conducted at 150°C under autogenic pressure for 12 h. The HCFC-133a (189g, 1.59 moles) is recovered by distillation. Ethanol-2,2,2-trifluoroacetate (22.65g, 0.16 moles) obtained in 13% yield.
Example 4
As in example 1, the reactor is charged with DMSO (296g, 99%), potassium acetate (90.4g, 0.92 moles), PEG-600 (1.5g) and 2-chloro-1,1,1-trifluoroethane (296g, 2.5 moles). The reaction is conducted at 180°C under autogenic pressure for 15 h. The HCFC-133a (266g, 2.24 moles) is recovered by distillation. Ethanol-2,2,2-trifluoroacetate (105g, 0.74 moles) obtained in 80.4%.
Example 5
As in example 1, the reactor is charged with N-methyl-2-pyrrolidone (NMP) (415g, 99%), sodium acetate (236.6g, 2.88 moles), crown ether (1g) and 2-chloro-1,1,1-trifluoroethane (HCFC-133a) (511g, 4.31 moles). The reaction is conducted at 200°C under autogenous pressure for 18hrs. The HCFC-133a (254g, 2.14moles) is recovered by distillation. Ethanol-2,2,2-trifluoroacetate (295g, 2.08 moles) obtained in 72% yield.
Example 6
Ethanol-2,2,2-trifluoroacetate (508.4g (94%), 3.36 moles) is taken in a 2 litre 4-neck round bottomed flask equipped with mechanical stirrer, thermowell, condensor and dropping funnel. The flask is cooled to 0 - 5°C and aqueous potassium hydroxide solution (544.7g, 34.6%, 3.37 moles) is slowly added over a period of 3 h, allowed for another 3 h for completion of reaction during which due to exothermicity the temperature of reaction rose to 75°C and product formation is verified by G.C. The product 2,2,2-trifluoroethanol is distilled through a column packed with high performance sectors packing material and obtained 268g with a yield of 80%. The residue after distillation of TFE is an aqueous solution of KOAc is neutralized with known quantity of acetic acid. Nearly 600 gms of toluene was added and azeotropically water was removed. The residue is filtered, wet cake is washed with toluene and dried to obtain potassium acetate which is sufficiently pure for recycle in step 1.
Example 7
Ethanol-2,2,2-trifluoroacetate (528.7g(94%), 3.5 moles) is taken as in example 6 and aqueous sodium hydroxide solution (411g, 35%, 3.6moles) is slowly added at 0-5°C over a period of 4 h, allowed for another 5 h, for completion of reaction during which due to exothermicity the temperature of reaction rose to 55°C and product formation is verified by GC. The product
2,2,2-trifluoroethanol is distilled as in example 6 and obtained 255.5g with a yield of 73%. The recovery of sodium acetate is as cited in example 6.
Example 8
Ethanol-2,2,2-trifluoroacetate (114g, 94%, 0.75moles) is taken as in example 6 and aqueous potassium carbonate solution (172.6g, 50%, 0.62 moles) was slowly added at 75°C over a period of 6 h and continued for another four hours for completion of reaction. The product is as distilled in example 6 and obtained 52g with a yield of 69%. The recovery of potassium acetate is as cited in example 6.
Example 9
The experimental conditions and product recovery is similar as discussed in example 1 except recovered potassium acetate is used and conducted the experiment. The yields are comparable with experiment 1.


We claim:
1. An improved process for preparation of 2,2,2-trifluoroethanol from 1,1,1-trifluoro-2-chloroethane, which comprises reacting l,l,l-trifluor-2-ochloroethane with a metal salt of carboxylic acid with a molar ratio of 1,1,1-trifluorochloroethane to metal salt of carboxylic acid in the range 1.5:1 to 2.5:1, in an organic solvent, in the presence of homogenous catalyst, in an autoclave under vacuum, at a temperature in the range of 60-3 00°C, for a period of 6-24 hrs, under stirring, at a speed ranging between 20-1000 rpm, distilling the above said reaction mixture to remove the unreacted l,l,l-trifluoro-2-chloroethane to obtain ethanol-2,2,2-trifluoroacetate, hydrolysing the above said ethanol-2,2,2-trifluoroacetate by slowly adding an aqueous solution of base to the cooled ethanol-2,2,2-trifluoroacetate and maintaining the temperature ranging between 30 - 100°C, for a period of 2-8 hrs, followed by distillation to obtain the desired product and metal salt of carboxylic acid.
2. An improved process as claimed in claim 1, wherein the metal salt of carboxylic acid used is selected from potassium acetate and sodium acetate.
3. An improved process as claimed in claims 1&2, wherein the organic solvent used is selected from N-methyl-pyrollidone (NMP), Dimethyl sulfoxide(DMSO), and Dimethylformamide(DMF).
4. An improved process as claimed in claims 1-3, wherein the homogenous catalyst used is selected from PEG-600 and crown ether.

5. An improved process as claimed in claims 1-4, wherein the temperature used for esterification is in the range 100-250°C.
6. An improved process as claimed in claims 1-5, wherein the mechanical stirrer speed used is in the range 200-1000 rpm, preferably in the range of 500 - 800 rpm.
7. An improved process as claimed in claims 1-6, wherein the time period used for esterification is in the range of 12 - 18hrs.
8. An improved process as claimed in claims 1-7, wherein the products obtained are effectively separated by distillation using high performance sectors packing material in distillation column.
9. An improved process as claimed in claims 1-8, wherein the yield of ethanol-2,2,2-trifluoroacetate obtained is in the range 80-96%.
10. An improved process as claimed in claims 1-9, wherein the base used for hydrolysation is selected from the group consisting of KOH, NaOH, K2C03 and Na2C03.
11. An improved process as claimed in claims 1-10, wherein the temperature in hydrolysation is in the range of 30-100°C.
12. An improved process as claimed in claims 1-11, wherein the byproduct potassium acetate is recovered for further recycle in hydrolysation reaction.

13. An improved process for preparation of 2,2,2-trifluoroethanol from l,l,l-trifluoro-2-chloroethane, as herein described with reference to the examples.

Documents:

476-del-2005-Abstract-(11-03-2011).pdf

476-del-2005-abstract.pdf

476-del-2005-Claims-(11-03-2011).pdf

476-del-2005-claims.pdf

476-del-2005-Correspondence-Others-(11-03-2011).pdf

476-del-2005-correspondence-others.pdf

476-del-2005-Description (Complete)-(11-03-2011).pdf

476-del-2005-description (complete).pdf

476-del-2005-form-1.pdf

476-del-2005-form-18.pdf

476-del-2005-form-2.pdf

476-del-2005-Form-3-(11-03-2011).pdf

476-del-2005-Form-3-(27-03-2012).pdf

476-del-2005-form-3.pdf

476-del-2005-form-5.pdf

476-del-2005-Petition-137-(27-03-2012).pdf


Patent Number 247629
Indian Patent Application Number 476/DEL/2005
PG Journal Number 17/2011
Publication Date 29-Apr-2011
Grant Date 28-Apr-2011
Date of Filing 04-Mar-2005
Name of Patentee COUNCIL OF SCIENTIFIC & INDUSTRIAL RESEARCH
Applicant Address ANUSANDHAN BHAWAN, RAFI MARG, NEW DELHI-110 001, INDIA
Inventors:
# Inventor's Name Inventor's Address
1 BANDA NARSAIAH INDIAN INSTITUTE OF CHEMICAL TECHNOLOGY, HYDERABAD, 500 007, INDIA
2 PAMULAPARTHY SHANTHAN RAO INDIAN INSTITUTE OF CHEMICAL TECHNOLOGY, HYDERABAD, 500 007, INDIA
3 SRIPATHY NARAYAN REDDY INDIAN INSTITUTE OF CHEMICAL TECHNOLOGY, HYDERABAD, 500 007, INDIA
4 PUNNAMRAJU VENKATA SATYA SRINIVAS INDIAN INSTITUTE OF CHEMICAL TECHNOLOGY, HYDERABAD, 500 007, INDIA
PCT International Classification Number C07C 29/124
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 NA