FIELD OF THE INVENTION
The present invention provides a process for purification of 1,1-difluoroethane for use as propellent in pharmaceutical compositions.

BACKGROUND OF THE INVENTION
Hydrofluorocarbons (HFCs) have found widespread use in many commercial and industrial applications including as refrigerants, aerosol propellants, blowing agents, heat transfer media, gaseous dielectrics and as working fluids in air conditioning, heat pump and refrigeration systems.
The processes for manufacturing of R152a usually results in one or more undesired products alongside a desired product. The desired product is then separated from the undesired or peripheral products by means of several methods such as distillation, adsorption, and extraction etc.
PCT Pub. No. 2021043989 provides a process for purification of hydrohalocarbon by compressing and converting it to liquid form and then carrying out distillation in a pressurized distillation device comprising one or more rotary-packed bed. The use of distillation column equipped with rotary-packed bed makes the process complex and tedious at commercial scale.
PCT Pub. No. 1998019982 provides a process for separating 1,1-difluoroethane from a mixture of 1,1-difluoroethane and vinyl chloride by extractive distillation using an extractive agent such as hydrocarbon, alcohol or chlorocarbon.
U.S. Patent No. 9828316 provides a process for purifying a composition comprising 1,1-difluoroethane and one or more undesired halogenated hydrocarbon by contacting the composition with an adsorbent comprising a carbon molecular sieve.
Similarly, U.S. Patent No. 7696392 provides a process for purifying 1,1-difluoroethane, by contacting the crude composition with a zeolite having an average pore size of 3 to 6 Å and a silica/aluminium ratio of 2.0 or less and/or a carbonaceous adsorbent having an average pore size of 3.5 to 6Å.
The above processes either use extractive distillation which require extracting agent like n-hexane or adsorption technique which require carbon molecular sieve or zeolite which makes the process costlier at commercial scale.
Recently, R152a is being explored as a potential candidate for aerosol industry especially for delivery of medicaments such as beclomethasone, fluticasone, salbutamol, formoterol, mometasone, tiotropium, indacaterol, a combination of beclomethasone dipropionate and formoterol fumarate dehydrate etc.
The commercial grade R152a has a purity of about 99.0% and is not suitable for application as a propellant in the pharmaceutical compositions.
The present invention provides an alternative process for purifying 1,1 difluoroethane to produce the propellant grade R152a of at least 99.95% purity.

OBJECT OF THE INVENTION
The object of the present invention is to provide a simple, cost effective and commercially viable process for purifying 1,1-difluoroethane to produce the propellant grade R152a of at least 99.95% purity.

SUMMARY OF THE INVENTION
First aspect of the present invention provides a propellent grade R152a comprising one or more additional component selected from a group consisting of chlorotrifluoromethane (R13), 1,1,1-trifluoroethane (R143a), 1,1,1,2,2-pentafluoroethane (R125); 2,3,3,3-tetrafluoropropene (R-1234yf), 1,3,3,3-tetrafluoropropene (R-1234ze), 1,1,1,2-tetrafluoroethane (R134a); 1,1,2-trifluoroethane (R-123a), 2,2-dichloro-1,1,1-trifluoroethae (R-123) and 1,1-difluoropropane, wherein the additional components are present in a range of 5 parts per million to 1000 parts per million.
Second aspect of the present invention provides a process for purifying 1,1-difluoroethane, comprising the steps of:
a) providing a composition comprising 1,1-difluoroethane, low boiling components and high boiling components in a distillation column;
b) maintaining a high reflux ratio in the range of 5 to 100 at head of the distillation column;
c) allowing removal of a fraction of low boiling components from the top of distillation column;
d) optionally repeating step b) and c) at least once, till the low boiling component become substantially nil; and
e) distilling the remaining composition in distillation column to separate pure 1,1-difluoroethane from the top of distillation column by maintaining a reflux ratio in the range of 5 to 100.

BRIEF DESCRIPTION OF DRAWING
Figure 1 and Figure 2 describes the flow of the process.
Figure 1: A stream ‘1’ is charged in a distillation column ‘D1’ and allowed venting of non-condensable components ‘2’ through metering valve ‘V1’. After removal of ‘2’, total reflux is maintained for 2 hours in ‘D1’ and allowed removal of a fraction of low boiling components ‘3’ from the top through condenser ‘C1’ and metering valve ‘V1’. The draw rate of ‘3’ is maintained using the mass flow meters ‘MFM-1 and MFM-3’, so that the reflux ratio is 10. The total reflux is maintained again for 2 hours in ‘D1’ and allowed removal of another fraction of ‘3’ from the top. The total reflux is maintained again for 2 hours in ‘D1’ and allowed removal of remaining fraction of ‘3’ from the top. The remaining mixture in ‘D1’ is distilled to obtain pure 1, 1-difluoroethane ‘4’ from the top and high boiling components ‘5’ are removed from the bottom re-boiler ‘RB1’ passing from ‘MFM-2’.
Figure 2: A stream ‘1’ is charged in a distillation column ‘D1’ and allowed venting of non-condensable components ‘2’ through metering valve ‘V1’. After removal of ‘2’, total reflux is maintained for 2 hours in ‘D1’ and allowed removal of a fraction of low boiling components ‘3’ from the top through ‘C1’ and ‘V1’. The draw rate of ‘3’ is maintained using the mass flow meters ‘MFM-1 and MFM-3’ so that the reflux ratio is 10. The total reflux is maintained again for 2 hours in ‘D1’ and allowed removal of another fraction of ‘3’ from the top. The total reflux is maintained again for 2 hours in ‘D1’ and allowed removal of remaining fraction of ‘3’ from the top. The remaining mixture in re-boiler ‘RB1’ of distillation column ‘D1’ is charged into re-boiler ‘RB2’ of distillation column ‘D2’ controlled via ‘MFM-2’ and distilled to obtain pure 1, 1-difluoroethane ‘4’ from the top of ‘D2’ through condenser ‘C2’ and metering valve ‘V2’ and mass flow meter ‘MFM-5’. The reflux ratio in “D2’ is maintained using MFM-4 and high boiling components ‘5’ are removed from the bottom of ‘D2’ through ‘MFM-6’.

DETAILED DESCRIPTION OF THE INVENTION
The various terms used in Figures 1 & 2 are as described below.
As used herein, stream ‘1’ refers to a crude mixture of 1, 1-difluoroethane, non-condensable, low boiling and high boiling components.
As used herein, ‘2’ refers to non-condensable components.
As used herein, ‘3’ refers to low boiling components.
As used herein, ‘4’ refers to pure 1, 1-difluoroethane.
As used herein, ‘5’ refers to high boiling components.
As used herein, ‘D1’ refers to first distillation column and ‘D2’ refers to second distillation column.
As used herein, ‘C1’ refers to first condenser and ‘C2’ refers to second condenser.
As used herein, ‘V1’ refers to first metering valve and ‘V2’ refers to second metering valve.
As used herein, ‘RB1’ refers to first re-boiler and ‘RB2’ refers to second re-boiler.
As used herein, ‘MFM-1’, ‘MFM-2’, ‘MFM-3’, ‘MFM-4’, ‘MFM-5’ and ‘MFM-6’ refers to first, second, third, fourth, fifth and sixth mass flow meters respectively.
As used herein, the substantially nil amount refers 5-100 ppm of that component, when analyzed by GCMS analysis.
As used herein, the low boiling component refers to a component having boiling point lower than 1,1-difluoroethane, ranging from -70 to -25°C. The low boiling component is selected from a group consisting of acetylene, pentafluoroethane, 1,1,1-trifluoroethane, 1,1,1,2-tetrafluoroethane, 2,3,3,3-tetrafluoropropene, chlorodifluoromethane, propane and butane or the like. Preferably, the low boiling component includes pentafluoroethane, 1,1,1-trifluoroethane, 1,1,1,2-tetrafluoroethane and chlorodifluoromethane.
As used herein, the high boiling component refers to a component having boiling point higher than 1,1-difluoroethane, and may range from -20°C to 90°C. The high boiling component is selected from a group consisting of 1,3,3,3-tetrafluoropropene, isobutane, 1,2-dichloro 1,1,2-trifluoroethane (R-123a), 2,2-dichloro-1,1,1-trifluoroethae (R-123), chloromethane, methylene dichloride, ethylene dichloride and trichloroethylene or the like. Preferably, the high boiling component includes 1,2-dichloro 1,1,2-trifluoroethane (R-123a), 2,2-dichloro-1,1,1-trifluoroethae (R-123) and chloromethane or the like.
The composition of 1,1-difluoroethane may contain one or more of non-condensable components.
As used herein, the non-condensable components have very low boiling point of less than -80°C and may range from -170 to -80°C and are selected from a group consisting of acetylene, nitrogen and air or the like.
In an embodiment, the non-condensable impurities having very low boiling point as compared to R152a even lower than low boiling components are removed at the top of distillation column before high reflux is maintained. After removal of non-condensable impurities, the high reflux is maintained to enrich low boiling components at the top of distillation column and thus removed from the top. After the complete removal of low boiling component, the remaining mixture is distilled to enrich pure R152a at the top and thus is isolated from the top of distillation column. The remaining high boiling component is separated from the bottom of distillation column.
As used herein, the reflux ratio refers to L/V ratio, wherein L is the flow rate of the liquid in Kg/hour and V is the flow rate of the vapor in Kg/hour. In other words, the reflux ratio is the ratio of amount of liquid returning in distillation column to the liquid removed from the column.
As used herein, the total reflux ratio refers reflux ratio when nothing is withdrawn from the column. In other words, the total reflux ratio refers to L/V ratio = 8, wherein L is the flow rate of the liquid in Kg/hour and V is the flow rate of the vapor in Kg/hour
In an embodiment, the process is carried out while maintaining a total reflux ratio for some time prior to maintaining high reflux ratio.
As used herein, the mass flow meters are used to control the flow of streams.
In an embodiment, the high reflux is achieved by maintaining reflux ratio in the range of from 5-100. In a preferred embodiment, the high reflux is achieved by maintaining reflux ratio in the range of from 10-50. In other words, the high reflux ratio means that more liquid that has returned to the distillation column compared to the amount of liquid removed. The reflux ratio is measured through mass flow metres which is placed in reflux line and another in product removal line.
In an embodiment, the total reflux, the high reflux and distillation steps are carried out in a single distillation column or sequential distillation columns.
In another embodiment, the high reflux and distillation steps are carried out in a separate distillation column connected to each other.
In another embodiment, the distillation is carried out continuously in two or more columns connected to each other for sequential separation of non-condensable components, low boiling components and high boiling components.
The composition feed which is subjected to purification in the present invention comprises the following composition and the analysis was carried out in GCMS.
Compounds Boiling Points
(°C) Input feed (ppm) Input feed (ppm) Output
(ppm)
Acetylene -84 1 179 0
Pentafluoro-ethane (R-125) -48 18 7 0
1,1,1-Trifluoroethane (R-143a) -47 295 450 0
Propane -42 10 5 0
Chlorodifluoromethane (R-22) -42 30 350 0
1,1,1,2-Tetrafluoroethane (R-134a) -26.6 28 985 9
1,1-Difluoroethane (R-152a) -24.9 99.918 98.62 99.9971
Chloromethane -24.2 1 5 0
Isobutane -11.7 1 6 0
Butane -1 1 4 0
1,2-Dichloro-1,1,2-trifluoroethane (R-123a) 27.6 10 45 0
2,2-Dichloro-1,1,1-trifluoroethane (R-123) 27.8 381 1.1% 20
Methylene chloride 38 89 77 0
Methylene Chloride 38 3 5 0
1,2-Dichloroethane 84 11 150 0

In an embodiment, 1,1-difluoroethane is obtained with a purity greater than 99.99%, having low boiling component less than 100 ppm preferably between 10 to 100 ppm and high boiling components less than 100 ppm, preferably between 10 to 100 ppm.
In another embodiment, 1,1-difluoroethane obtained by the process of present invention has purity of 99.99% to 99.999% having total content of low and high boiling components of less than 100 ppm, preferably 10 to 100 ppm.
In an embodiment, the pure 1,1-difluoroethane contains substantially nil amount of non-condensable components.
In an embodiment, the pure 1,1-difluoroethane contains substantially nil amount of any other impurity component.
In an embodiment, the present invention provides a process for purifying 1,1-difluoroethane, comprising the steps of:
a) providing a composition comprising 1,1-difluoroethane, low boiling components and high boiling components, in a distillation column;
b) maintaining a high reflux ratio of 5 to 100 in the distillation head;
c) allowing removal of a fraction of low boiling components from the top of distillation column.
d) optionally repeating step b) and c) at least once; and
e) distilling the remaining composition in distillation column to separate pure 1,1 difluoroethane from the top of distillation column by maintaining a reflux ratio in the range of 5 to 100.
In another embodiment, the low boiling components are removed at a rate of 10g/hr to 500g/hr from the top of distillation column through metered valve.
In a specific embodiment, the low boiling components are removed at a rate of 15g/hr to 200g/hr from the top of distillation column through metered valve.
In another embodiment, the reflux ratio is measured at the head of the distillation column. The high reflux ratio enables enrichment of low boiling components, which can be later withdrawn in small portions. In a smaller scale, the low boilers can be enriched by maintaining total reflux for certain specific time and then withdrawing a small portion.
In another embodiment of the present invention, the distillation column is maintained at a temperature gradient of 1 to 5°C. The temperature gradient is the difference in the temperature of the top and the bottom of the distillation column.
In another embodiment of the present invention the process is carried out as illustrated in Figure 1.
In another embodiment of the present invention, the process is carried out as illustrated in Figure 2.
The pure product i.e., 1,1-difluoroethane is monitored by gas chromatography (GC).
Unless stated to the contrary, any of the words “comprising”, “comprises” and includes mean “including without limitation” and shall not be construed to limit any general statement that it follows to the specific or similar items or matters immediately following it.
Embodiments of the invention are not mutually exclusive but may be implemented in various combinations. The described embodiments of the invention and the disclosed examples are given for the purpose of illustration rather than limitation of the invention as set forth in the appended claims.
The crude 1,1-difluoroethane as used herein as composition feed can be prepared by any of the methods known in the art e.g., as disclosed in European Patent No. 2336101B1.
The following examples are given by way of illustration and therefore should not be construed to limit the scope of the present invention.
EXAMPLES
Example 1: Purification of crude 1,1-difluoroethane.
A crude mixture containing 1,1-difluoroethane, non-condensable, low boiling and high boiling components was charged in a distillation column and allowed venting of non-condensable components. After removal of non-condensable components, the mixture was refluxed for 2 hours and allowed removal of a fraction of low boiling components from the top. The remaining mixture was refluxed for another 2 hours and allowed removal of another fraction of low boiling components from the top. The remaining mixture in distillation column 1 was again refluxed for 2 hours and allowed removal of remaining fraction of low boiling components from the top.
The remaining mixture in distillation column was distilled to obtain pure 1,1-difluoroethane from the top and high boiling components were removed from the bottom. The pure compound was analysed by GCMS to obtain below results.
Components Output (ppm)
Acetylene 0
1,1,1-Trifluoroethane (HFC-143a) 0
1,1,1,2,2-Pentafluoroethane (HFC-125) 0
1,1,1,2-Tetrafluoroethane (HFC-134a) 9
1,1-Difluoroethane (HFC-152a) 99.9971%
1,3,3,3-Tetrafluoropropene (HFC-1234ze) 0
VCM 0
2,2-Dichloro-1,1,1-trifluoro ethane (HCFC-123) 20
Methylene Chloride (HCC-30) 0
Methylene Chloride (HCC-30) 0
1,2-Dichloro ethane (HCC 150) 0

CLAIMS:

WE CLAIM:
1. A propellent grade R152a comprising one or more additional component selected from a group consisting of chlorotrifluoromethane, 1,1,1-trifluoroethane , 1,1,1,2,2-pentafluoroethane; 2,3,3,3-tetrafluoropropene, 1,3,3,3-tetrafluoropropene , 1,1,1,2-tetrafluoroethane; 1,1,2-trifluoroethane, 2,2-dichloro-1,1,1-trifluoroethae and 1,1-difluoropropane, wherein the additional components are present in a range of 5 parts per million to 1000 parts per million.
2. A process for purifying 1,1-difluoroethane, comprising the steps of:
a) providing a composition comprising 1,1-difluoroethane, low boiling components and high boiling components in a distillation column;
b) maintaining a high reflux ratio in the range of 5 to 100 at head of the distillation column;
c) allowing removal of a fraction of low boiling components from the top of distillation column;
d) repeating step b) and c) till the low boiling component become substantially 5-100 ppm; and
e) distilling the remaining composition in distillation column to separate pure 1,1-difluoroethane from the top of distillation column by maintaining a reflux ratio in the range of 5 to 100.
3. The process as claimed in claim 2, wherein the step b) of maintaining a high reflux ratio in the range of 5 to 100 at the head of the distillation column and step c) of allowing removal of a fraction of low boiling components from the top of distillation column are repeated at least twice.
4. The process as claimed in claim 2, wherein the low boiling component used in step a) refers to a component having boiling point lower than 1,1-difluoroethane, ranging from -70 to -25°C selected from a group consisting of acetylene, pentafluoroethane, 1,1,1-trifluoroethane, 1,1,1,2-tetrafluoroethane, 2,3,3,3-tetrafluoropropene, chlorodifluoromethane, propane and butane or a mixture thereof.
5. The process as claimed in claim 2, wherein the high boiling component used in step a) refers to a component having boiling point higher than 1,1-difluoroethane, ranging from -20°C to 90°C selected from a group consisting of 1,3,3,3-tetrafluoropropene, isobutane, 1,2-dichloro 1,1,2-trifluoroethane (R-123a), 2,2-dichloro-1,1,1-trifluoroethae (R-123), chloromethane, methylene dichloride, ethylene dichloride and trichloroethylene or a mixture thereof.
6. The process as claimed in claim 2, wherein the composition of 1,1-difluoroethane to be purified contains one or more of non-condensable components selected from a group consisting of acetylene, nitrogen and air or a mixture thereof.
7. The process as claimed in claim 2, wherein the high reflux is achieved by maintaining reflux ratio in the range of from 10-50.
8. The process as claimed in claim 2, wherein the distillation column is maintained at a temperature gradient of 1 to 5°C.
9. The process as claimed in claim 2, wherein the low boiling components are removed at a rate of 10g/hr to 500g/hr from the top of distillation column through metered valve.
10. The process as claimed in claim 2, wherein the flow of the process is illustrated in Figure 1 and Figure 2.