Stabilisation of 1-chloro-3,3,3-trifluoropropene

CA 02979946 2017-09-15 WO 2016/146940 PCT/FR2016/050577 1 STABILIZATION OF 1-CHLOR0-3,3,3-TRIFLUOROPROPENE FIELD OF THE INVENTION The present invention relates to compounds for stabilizing 1-chloro-3 ,3,3-tritluoropropene and more precisely to limit or prevent the isomerization of the trans form into the cis form. The invention also relates to the use of such stabilizers in heat transfer applications.

TECHNICAL BACKGROUND Trans-1-chloro-3,3,3-tritluoropropene (HCF0-1233zdE) is a product with a low global warming potential (GWP).

It has very favorable thermodynamic and thermophysical properties for use as a heat transfer fluid in cooling, air conditioning, power generation (including organic Rankine cycles) and high temperature heat pump applications. .

HCF0-1233zdE exhibits instability which manifests itself especially at relatively high temperatures.

This instability consists of an isomerization of a fraction of the initial charge resulting in the formation of cis-1chloro3,3,3-trifluoropropene (HCF0-1233zdZ).

However, HCF0-1233zdZ is a less volatile product than HCF01233zdE.

The boiling temperature is around 40°C for the Z isomer, and around 18.3°C for the E isomer.

This difference implies a change in the thermodynamic and thermophysical properties of the product in the installations, and a loss of performance, when isomerization occurs.

Document WO 2009/003165 describes the risks of degradation of hydrofluoroolefins and hydrochlorofluoroolefins, as well as stabilizers making it possible to combat this degradation.

These stabilizers include free radical scavenging compounds, acid scavenging compounds, oxygen scavenging compounds and polymerization inhibitors.

The following are mentioned in particular: 1,2-epoxybutane, glycidyl methyl ether, d1 oxide CA 02979946 2017-09-15 WO 2016/146940 PCT / FR2016/050577 2 limonene, 1,2-epoxymethylpropane, nitromethane, alpha methylstyrene, isoprene, phenol, hydroquinones and hydrazine.

US 7,795,480 describes a process for the manufacture of 2-chloro3,3,3-tritluoropropene (HCF0-1233xf).

A compound polymerization phenomenon is mentioned (but not an isomerization phenomenon).

Suggested stabilizers are p-tap(4-tert-amylphenol), methoxyhydroquinone, 4-methoxyphenol, triethylamine, di-isopropylamine, butylated hydroxyanisole and thymol.

Document US Pat. No. 8,217,208 describes the phenomenon of isomerization of HF0-1233zdE under the effect of temperature, but it does not teach stabilizers making it possible to limit this isomerization.

Document US 2012/0226081 describes the risks of degradation of hydrochloroolefins and hydrochloroalkanes, and proposes a set of possible stabilizers: alpha-methylstyrene, alpha-pinoxide, beta pinoxide, 1,2-epoxybutane, 1 ,2-hexadecene oxide and oxygen scavenging compounds such as diethylhydroxylamine, hydroquinone, methylethylketooxime and p-methoxyphenol.

Document US 2015/0034523 describes the risks of degradation of hydrochloroolefins and proposes two families of stabilizers, namely morpholines or trialkyl phosphates.

Almost all of the stabilizers proposed in the state of the art are solid products, or liquid products having a high boiling point.

For example, the boiling temperature of alpha-methylstyrene is 165 C, the boiling temperature of limonene-oxide is above 200 C, etc.

Isoprene, mentioned in document WO 2009/003165, is itself an unstable product, which must generally be combined with a compound such as 4-tert-butylpyrocatechol to prevent its polymerization.

The characteristics described above make the stabilizers unsuitable for certain applications in which HCF0-1233zdE is likely to be used. This is particularly the case for applications using flooded evaporators (especially with compressors without lubricating oil).

In such applications, the prior art, high boiling temperature stabilizers are ineffective because they concentrate in the evaporator and do not migrate with the heat transfer fluid to the condenser.

CA 02979946 2017-09-15 WO 2016/146940 PCT/FR2016/050577 3 There is therefore a need to provide stabilizers making it possible to limit or prevent the isomerization of HCF0-1233zdE into HCF0-1233zdZ, in particular in systems of vapor compression such as air conditioning, refrigeration, heat pump and organic Rankine cycle systems, and especially systems with a flooded evaporator.

SUMMARY OF THE INVENTION The invention relates firstly to the use of an alkene compound at 03 to 06 and comprising a single double bond, to limit or prevent the isomerization of trans-1-chloro-3,3,3 -tritluoropropene to cis-1-chloro-3,3,3 trifluoropropene.

According to one embodiment, the alkene compound is a butene or a pentene.

According to one embodiment, the alkene compound has:

¨ a boiling point less than or equal to 100 C, preferably less than or equal to 75 C, and more particularly preferably less than or equal to 50 C; and/or ¨ a solidification temperature less than or equal to 0 C, preferably less than or equal to -25 C, and more particularly preferably less than or equal to -50 C.

According to one embodiment, the alkene compound is 2-methyl-but-2ene.

According to one embodiment, the alkene compound is 3-methyl-but-1-ene.

A subject of the invention is also a composition comprising 1chloro-3,3,3-tritluoropropene and a C 3 to C 6 alkene compound and comprising a single double bond.

According to one embodiment, the alkene compound is a butene or a pentene.

According to one embodiment, the alkene compound has:

¨ a boiling point less than or equal to 100 C, preferably less than or equal to 75 C, and more particularly preferably less than or equal to 50 C; and/or - a solidification temperature less than or equal to 0° C., preferably less than or equal to -25° C., and more particularly preferably less than or equal to -50° C.

CA 02979946 2017-09-15 WO 2016/146940 PCT/FR2016/050577 4 According to one embodiment, the alkene compound is 2-methyl-but-2ene.

According to one embodiment, the alkene compound is 3-methyl-but-1ene.

According to one embodiment, the composition comprises from 0.01 to 5%, preferably from 0.1 to 2% and more particularly from 0.2 to 1%, by mass, of alkene compound.

According to one embodiment, the 1-chloro-3,3,3-trifluoropropene is in trans form in a mass proportion greater than or equal to 90%, preferably greater than or equal to 95%, more particularly preferably greater than or equal to 98%, even more preferably greater than or equal to 99%, and ideally greater than or equal to 99.5% or even greater than 99.9%.

According to one embodiment, the composition further comprises one or more heat transfer compounds other than 1-chloro-3,3,3-trifluoropropene and/or one or more additives chosen from stabilizers other than the alkene compound, lubricants, surfactants, tracers, fluorescent agents, odorants, solubilizers and mixtures thereof.

A subject of the invention is also the use of the above composition as a heat transfer fluid in a vapor compression system.

According to one embodiment, the vapor compression system is:

- an air conditioning system; or ¨ a refrigeration system; or ¨ a freezing system; or ¨ a heat pump system.

According to one embodiment, the above use is a use as a heat transfer fluid in a heat engine.

According to one embodiment, the heat transfer fluid is at a temperature greater than or equal to 100 C, preferably greater than or equal to 140 C, more particularly preferably greater than or equal to 180 C, for at least a fraction of its duration of use.

According to one embodiment, the heat transfer fluid is evaporated in a flooded evaporator.

CA 02979946 2017-09-15 WO 2016/146940 PCT/FR2016/050577 The invention also relates to a heat transfer installation comprising a circuit containing the above composition as heat transfer fluid.

According to one embodiment, the installation is chosen from among the 5 mobile or stationary installations for heating by heat pump, air conditioning, refrigeration, freezing and heat engines.

According to one embodiment, the installation comprises a flooded evaporator.

The invention also relates to a method for heating or cooling a fluid or a body by means of a vapor compression system containing a heat transfer fluid, said method comprising successively the evaporation of the fluid heat transfer fluid, compression of the heat transfer fluid, condensation of the heat fluid and expansion of the heat transfer fluid, wherein the heat transfer fluid is the composition described above.

The invention also relates to a method for producing electricity by means of a heat engine, said method successively comprising the evaporation of the heat transfer fluid, the expansion of the heat transfer fluid in a turbine making it possible to generate electricity, condensing the heat fluid and compressing the heat transfer fluid, wherein the heat transfer fluid is the composition described above.

The present invention makes it possible to overcome the drawbacks of the state of the art.

It more particularly provides stabilizers making it possible to limit or prevent the isomerization of HCF0-1233zdE into HCF0-1233zdZ, in particular in vapor compression systems such as air conditioning, refrigeration, heat pump and engine systems. heat, and especially systems with a flooded evaporator.

DESCRIPTION OF EMBODIMENTS OF THE INVENTION The invention is now described in more detail and in a non-limiting manner in the description which follows.

Unless otherwise stated, throughout the application the proportions of compounds indicated are given in mass percentages.

The invention is based on the discovery that C3 to C6 alkene compounds containing a single double bond make it possible to stabilize the that is, to limit or prevent its isomerization to HCF0-1233zdZ, in particular at high temperatures.

The stabilizing compounds of the invention are therefore propene, butenes, pentenes and hexenes.

Butenes and pentenes are preferred.

The pentenes are even more particularly preferred.

The stabilizing compounds of the invention can be straight chain or branched and preferably branched.

Preferably, they have a boiling point less than or equal to 100 C, more preferably less than or equal to 75 C, and more particularly preferably less than or equal to 50 C.

Boiling temperature means the boiling temperature at a pressure of 101.325 kPa, as determined according to standard NF EN 378-1 of April 2008.

Also preferably, they have a solidification temperature of less than or equal to 0° C., preferably less than or equal to -25° C., and more particularly preferably less than or equal to -50° C.

The solidification temperature is determined according to Test No. 102:

Melting Point/Melting Range (OECD Guidelines for the Testing of Chemicals, Section 1, OECD Publishing, Paris, 1995, available at http://dx.doi.orgil 0.17871978926406953440.

Stabilizing compounds of the invention are in particular:

¨ but-1-ene;

¨ cis-but-2-ene;

¨ trans-but-2-ene;

- 2-methylprop-1-ene;

¨ pent-1-ene;

¨ cis-pent-2-ene;

¨ trans-pent-2-ene;

¨ 2-methylbut-1-ene;

- 2-methylbut-2-ene; and ¨ 3-methylbut-1-ene.

Among the preferred compounds, there are in particular 2-methyl-but-2ene, of formula (CH3)2C=CH-CH3 (boiling temperature of approximately 39° C.);

and 3-methyl-but-1-ene, of formula CH3-CH(CH3)-CH=CH2 (boiling temperature of approximately 25° C.).

Two or more of the above compounds can also be used in combination.

CA 02979946 2017-09-15 WO 2016/146940 PCT / FR2016 / 050577 7 The stabilizing compounds according to the invention are thus advantageously used in combination with HCF0-1233zd, and more particularly with HCF0-1233zdE, in transfer applications heat.

Thus, the invention provides a composition, in particular useful for heat transfer applications, comprising at least HCF0-1233zd and a stabilizing compound described above.

The proportion by mass of the above stabilizing compounds in the composition may in particular be: from 0.01 to 0.05%; or 0.05 to 0.1%; or 0.1 to 0.2%, or 0.2 to 0.3%; or 0.3 to 0.4%; or 0.4 to 0.5%; or 0.5 to 0.6%; or 0.6 to 0.7%; or 0.7 to 0.8%; or from 0.8 to 0.9 μVo;

or from 0.9 to 1%; or 1 to 1.2%; or 1.2 to 1.5%, or 1.5 to 2%; or 2 to 3%; or 3 to 4%; or 4 to 5%.

The composition may comprise HCF0-1233zdE and optionally HCF0-1233zdZ.

Advantageously, the proportion of HCF0-1233zdE, relative to the total of HCF0-1233zd, is greater than or equal to 90%, or 91%, or 92%, or 93%, or 94%, or 95% , or 96%, or 97 'Vo, or 98%, or 99%, or 99.1%, or 99.2%, or 99.3%, or 99.4%, or 99.5%, or 99.6%, or 99.7%, or 99.8%, or 99.9%, or 99.91%, or 99.92%, or 99.93%, or 99.94%, or 99.95%, or 99.96%, or 99.97%, or 99.98%, or 99.99%.

The presence of the stabilizing compound makes it possible to limit or prevent an increase in the proportion of HCF0-1233zdZ in the composition over time and/or in the event of application of relatively high temperatures.

The composition of the invention may also comprise various additives.

In the case where it is a heat transfer composition, the additives can in particular be chosen from lubricants, nanoparticles, stabilizers (different from the stabilizing compounds of the invention), surfactants, tracers, fluorescent agents, odorants and solubilizing agents.

The stabilizer(s), when present, preferably represent at most 5% by mass in the heat transfer composition.

Among the stabilizers, mention may in particular be made of nitromethane, ascorbic acid, terephthalic acid, azoles such as tolutriazole or benzotriazole, phenolic compounds such as tocopherol, hydroquinone, t-butyl hydroquinone, 2,6-di-ter-butyl-4-methylphenol, epoxides (optionally fluorinated or perfluorinated alkyl or alkenyl or aromatic) such as butyl glycidyl ether, hexanediol diglycidyl ether, allyl glycidyl ether, butylphenylglycidyl ether, phosphites, phosphonates, thiols and lactones.

As lubricants, it is possible in particular to use oils of mineral origin, silicone oils, paraffins of natural origin, naphthenes, synthetic paraffins, alkylbenzenes, poly-alpha olefins, polyalkene glycols, polyol esters and/or polyvinyl ethers.

According to an advantageous embodiment of the invention, the composition of the invention is however devoid of lubricant.

As nanoparticles, carbon nanoparticles, metal oxides (copper, aluminum), Ti02, A1203, Mo52, etc. can be used in particular.

As tracers (capable of being detected), mention may be made of deuterated or non-deuterated hydrofluorocarbons, deuterated hydrocarbons, perfluorocarbons, fluoroethers, brominated compounds, iodine compounds, alcohols, aldehydes, ketones, nitrous oxide and combinations thereof. The tracing agent is different from the heat transfer compound(s) making up the heat transfer fluid.

Mention may be made, as solubilizing agents, of hydrocarbons, dimethyl ether, polyoxyalkylene ethers, amides, ketones, nitriles, chlorocarbons, esters, lactones, aryl ethers, fluoroethers and 1,1 ,1-trifluoroalkanes. The solubilizing agent is different from the heat transfer compound(s) making up the heat transfer fluid.

As fluorescent agents, mention may be made of naphthalimides, perylenes, coumarins, anthracenes, phenanthracenes, xanthenes, thioxanthenes, naphthoxanhthenes, fluoresceins and derivatives and combinations thereof.

As odorous agents, mention may be made of alkylacrylates, allylacrylates, acrylic acids, acrylesters, alkylethers, alkylesters, alkynes, aldehydes, thiols, thioethers, disulphides, allylisothiocyanates, alkanoic acids , amines, norbornenes, norbornene derivatives, cyclohexene, heterocyclic aromatic compounds, ascaridole, o-methoxy(methyl)-phenol and combinations thereof.

The composition according to the invention may also comprise at least one other heat transfer compound, in addition to HCF0-1233zd.

Such another optional heat transfer compound may in particular be a hydrocarbon, ether, hydrofluoroether, hydrofluorocarbon, hydrochlorofluorocarbon, hydrochloroolefin, hydrochloroolefin or hydrochlorofluoroolefin compound.

By way of example, said other heat transfer compound can be chosen from 1,1,1,4,4,4-hexafluorobut-2-ene (HF0-1336mmz, E or Z isomer), 3,3 ,4,4,4-pentafluorobut-1-ene (HF0-1345fz), 2,4,4,4-tetrafluorobut1ene (HF0-1354mfy), 1,1,1,3,3-pentafluoropropane (HFC-245fa ), 2,3,3,3-tetrafluoropropene (HF0-1234yf), 1,3,3,3-tetrafluoropropene (HF0-1234ze), difluoromethane (HFC-32), 1,1,1,2 -tetrafluoroethane (HFC134a), 1,1,2,2-tetrafluoroethane (HFC-134), 1,1-difluoroethane (HFC 152a), pentafluoroethane (HFC-125), 1,1,1,3,3-pentafluorobutane (HFC365mfc), methoxynonafluorobutane (HFE7100), butane (HC-600), 2methylbutane (HO-601a), pentane (HC-601), ethyl ether, methyl acetate and combinations thereof.

In the composition of the invention, the HCF0-1233zd may in particular represent from 1 to 5% of the composition; or from 5 to 10% of the composition;

or from 10 to 15% of the composition; or from 15 to 20% of the composition; or from to 25% of the composition; or from 25 to 30% of the composition; or from 30 to 35% of the composition; or from 35 to 40% of the composition; or from 40 to 45% of the composition; or from 45 to 50% of the composition; or from 50 to 55% of the composition or from 55 to 60% of the composition or from 60 to 65% of the composition or from 65 to 70% of the composition or from 70 to 75% of the composition or from 75 to 80% of the composition or from 80 to 85% of the composition or from 85 to 90% of the composition or from 90 to 95% of the composition or from 95 to 99% of the composition; or from 99 to 99.5% of the composition or from 99.5 to 99.9% of the composition; or more than 99.9% of the composition.

The HCF0-1233zd content may also vary within several of the above ranges: for example 50-55% and 55-60%, i.e. 50-60%, etc.

The composition of the invention can be used in a heat transfer process.

The heat transfer method according to the invention is based on the use of an installation comprising a vapor compression system which contains the composition of the invention as heat transfer fluid.

The heat transfer process can be a process of heating or cooling a fluid or a body.

CA 02979946 2017-09-15 WO 2016/146940 PCT/FR2016/050577 The composition of the invention can also be used in a process for producing mechanical work or electricity, in particular in accordance with a Rankine cycle.

For heating and cooling applications, the vapor compression system includes at least one evaporator, one compressor, one condenser and one expander, as well as heat transfer fluid transport lines between these elements. The evaporator and the condenser include a heat exchanger allowing heat exchange between the heat transfer fluid and another fluid or body.

10 As a compressor, it is possible in particular to use a centrifugal compressor with one or more stages or a centrifugal mini-compressor.

Rotary, scroll, piston or screw compressors can also be used.

The compressor can be driven by an electric motor or by a gas turbine (for example powered by the exhaust gases of a vehicle, for mobile applications) or by gear.

The vapor compression system then operates according to a conventional vapor compression cycle.

The cycle involves changing the state of the heat transfer fluid from a liquid (or two-phase liquid/vapor) phase to a vapor phase at a relatively low pressure, then compressing the vapor phase fluid to a relatively low pressure. high, the change of state (condensation) of the heat transfer fluid from the vapor phase to the liquid phase at a relatively high pressure, and the reduction of the pressure to start the cycle again.

The installation may also optionally comprise at least one heat transfer fluid circuit used to transmit heat (with or without change of state) between the heat transfer fluid circuit and the fluid or body to be heated or cooled.

The installation may also optionally comprise two (or more) vapor compression systems, containing identical or distinct heat transfer fluids.

For example, vapor compression systems can be coupled together.

The cooling methods and installations according to the invention include air conditioning methods and installations (with mobile installations, for example in vehicles, or stationary), refrigeration (with mobile installations, for example in containers, or stationary) and freezing or cryogenics.

CA 02979946 2017-09-15 WO 2016/146940 PCT/FR2016/050577 The heating installations according to the invention include heat pumps.

For mechanical work or electricity generation applications, the installation is a heat engine, which includes at least an evaporator, a turbine, a condenser and a pump, as well as heat transfer fluid transport lines between these elements. The installation can then operate according to a Rankine cycle.

It is possible to use any type of heat exchanger for the implementation of the heat transfer fluids according to the invention, and in particular co-current heat exchangers or, preferably, countercurrent heat exchangers. -fluent.

In particular, the evaporator used in the context of the invention can be an overheating evaporator or a flooded evaporator.

In a superheated evaporator, all of the heat transfer fluid is evaporated at the outlet of the evaporator, and the vapor phase is superheated.

In a flooded evaporator, the heat transfer fluid in liquid form does not evaporate completely.

A flooded evaporator comprises a liquid phase and vapor phase separator.

The invention is particularly useful when such an evaporator is used.

Indeed, the state of the art high boiling temperature stabilizers are ineffective when such an evaporator is employed, because they concentrate in the evaporator and do not migrate with the heat transfer fluid to the condenser.

The invention is also particularly useful when a high temperature exists at at least one point of the fluid circuit, and more particularly a temperature greater than or equal to 100 C, or 110 C, or 120 C, or 130 C, or at 140 C, or at 150 C, or at 160 C, or at 170 C, or at 180 C, or at 190 C, or at 200 C.

Indeed, it is under these conditions that HCF01233zdE is most likely to convert to HCF0-1233zdZ.

In particular, in air conditioning appliances, the general operating temperature is below 10000; but hot spots at the compressor outlet can reach temperatures in excess of 100°C, affecting the heat transfer fluid for a small proportion of its full circulation time (e.g. less than 1%).

In heat pumps, the condensation temperature can reach around 140°C.

In this case, the heat transfer fluid may be at a temperature of approximately 140 C over a significant proportion of its duration of complete circulation (for example approximately 50%).

In addition, hot spots between 150 and 200 C can also be observed at the compressor outlet. The impact of a long residence time at temperatures above 100° C. and the existence of points at temperatures which may approach 200° C. therefore require a stabilizer.

Preferably also, in the installation according to the invention, the temperature of the composition used as heat transfer fluid remains higher than the solidification temperature of the stabilizing compound, in order to avoid any deposit of solid matter in the circuit. .

The composition according to the invention may also be useful as a blowing agent, propellant (for example for an aerosol), cleaning agent or solvent, dielectric gas, in addition to its use as a heat transfer fluid. .

As a propellant, the composition according to the invention can be used alone or in combination with known propellants.

The propellant comprises, preferably consists of, a composition according to the invention.

The active substance to be sprayed can be mixed with the propellant and inert compounds, solvents or other additives, to form a composition to be sprayed.

Preferably, the composition to be sprayed is an aerosol.

As a blowing agent, the composition according to the invention may be included in a blowing composition, which preferably comprises one or more other compounds capable of reacting and forming a foam or cellular structure under appropriate conditions, as is known to those skilled in the art.

In particular, the invention proposes a process for preparing an expanded thermoplastic product comprising firstly the preparation of a polymeric expansion composition.

Typically, the polymer blowing agent composition is prepared by plasticizing a polymer resin and mixing the components of a blowing agent composition at an initial pressure.

Plasticization of the polymer resin can be effected by heat, by heating the polymer resin to soften it sufficiently to mix a blowing agent composition. Generally, the plasticization temperature is close to the glass transition temperature or the melting temperature for crystalline polymers.

Other uses of the composition according to the invention include uses as a solvent, cleaning agent or the like.

Examples include CA 02979946 2017-09-15 WO 2016/146940 PCT / FR2016/050577 13 steam degreasing, precision cleaning, electronic circuit cleaning, dry cleaning, abrasive cleaning, solvents for deposition of lubricants and release agents, and other solvent or surface treatments.

EXAMPLES The following examples illustrate the invention without limiting it.

Example 1 (comparative) ¨ instability of HCF0-1233zdE in the absence of stabilizer The thermal stability tests of HCF0-1233zdE are carried out according to the ASHRAE 97-2007 standard entitled Sealed glass tube method to test the chemical stability of materials for use within refrigerant systems.

The compositions are determined by gas chromatograph on a CP-siI8-CB column.

A first series of tests is carried out at 150° C. for periods of between 10 minutes and 14 days.

The results show a slight formation of the HF0-1233zdZ isomer, reaching a content of 0.14% at 14 days.

A second series of tests is carried out at 200° C. for a period of 24 hours.

The results show a slight formation of the HCF01233zdZ isomer up to approximately 1%.

Finally, a third series of tests is carried out at 250° C. for a period of 24 hours as well.

The results show a formation of the HCF0-1233zdZ isomer of between 6 and 9%.

Example 2 (invention) ¨ stabilization of HCF0-1233zdE Thermal stability tests similar to those of example 1 are carried out, by adding 0.5% of stabilizer to HCF0-1233zdE (mass content relative to the sum of the stabilizer and HCF0-1233zdE).

The stabilizers tested are 2-methyl-but-2-ene (2m2b) and 3-methyl-but-1-ene (3m1b).

A first series of tests is carried out at 150° C. for a period of 14 days.

The tests with 3m1b show a formation of the HCF01233zdZ isomer of the order of 0.08% at the end of the period.

In the tests with 2m2b, no formation of HF0-1233zd-Z is measured.

A second series of tests is carried out at 200° C. for a period of 24 hours.

The tests with 3m1b show a slight formation of the isomer CA 02979946 2017-09-15 WO 2016/146940 PCT/FR2016/050577 14 HF0-1233zdZ of the order of 0.3%, and those with 2m2b show a formation of HCF0-1233zdZ of the order of 0.07% at the end of this period.

The following table summarizes the stabilization effect observed:

HCF0-1233zdE HCF0-1233zdE HCF0-1233zdE alone + 3m1b + 2m2b 14 days at 0.14% of 0.08% of HCF01233zdZ 150 C HCF0-1233zdZ HCF0-1233zdZ undetectable 24 hours at 1 `)/0 of HCF0- 0, 3% HCF0- 0.07% 200C 1233zdZ 1233zdZ HCF0-1233zdZ