Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C67/00—Preparation of carboxylic acid esters
  • C07C67/03—Preparation of carboxylic acid esters by reacting an ester group with a hydroxy group
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C67/00—Preparation of carboxylic acid esters
  • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
  • C07C67/303—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by hydrogenation of unsaturated carbon-to-carbon bonds
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C67/00—Preparation of carboxylic acid esters
  • C07C67/48—Separation; Purification; Stabilisation; Use of additives
  • C07C67/52—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
  • C07C67/54—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation by distillation
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
  • C07C69/74—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring
  • C07C69/75—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring of acids with a six-membered ring
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
  • C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
  • C07C69/80—Phthalic acid esters
  • C07C69/82—Terephthalic acid esters
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C2601/00—Systems containing only non-condensed rings
  • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
  • C07C2601/14—The ring being saturated

Definitions

• the present invention relates to the field of organic synthesis. More particularly, it provides a continuous process for the transesterification of a compound comprising at least one Ci-4 carboxylic ester group in a presence of a Ci-4 alcohol and a transesterification catalyst wherein the transesterification step is performed in at least two subsequent reactors separated by a separation unit.
• the invention further relates to a process for preparing diethyl 1,4-cyclohexanedicarboxylate comprising a transesterification step of dimethyl terephthalate in the presence of ethanol and a reduction step of diethyl terephthalate.
• the present invention provides a solution to the above problem by performing the transesterification under continuous conditions in at least two subsequent reactors separated by a separation unit wherein the alcohol formed during the process is removed. To the best of our knowledge, in the prior art there is no report of such a continuous process as disclosed in the present invention.
• Figure 1 is a schematic process flow sheet illustrating an embodiment of the invention. Description of the invention
• the first object of the present invention is a continuous process for the transesterification of a compound comprising at least one Ci-4 carboxylic ester group in a presence of a Ci-4 alcohol and a transesterification catalyst wherein the transesterification step is performed in at least two subsequent reactors separated by a separation unit.
• the first object of the present invention is a continuous process for the transesterification of a compound comprising at least one Ci-4 carboxylic ester group wherein the compound comprising at least one Ci-4 carboxylic ester group is reacted with a Ci-4 alcohol in a presence of a transesterification catalyst and wherein the transesterification step is performed in at least two subsequent reactors separated by a separation unit.
• transesterification it is intended the usual meaning in the art, i.e. that the starting material and the produced compound comprise at least one carboxylic ester group.
• the transesterification is, for example, the preparation of a compound of formula R-COO-R 2 starting from a compound of formula R-COO-R 1 wherein R 1 and R 2 groups are different.
• an alcohol of formula HOR 1 is also formed being different than the Ci-4 alcohol used in the invention’s process.
• a compound comprising at least one Ci-4 carboxylic ester group is understood as a compound comprising at least a group of formula -COO-R 1 wherein R 1 is a Ci-4 alkyl group.
• the compound comprising at least one Ci-4 carboxylic ester group is a compound of formula
• R-COO-R 1 (I) wherein R 1 is a Ci-4 alkyl group and R is a Ci-is hydrocarbon group optionally comprising one or more Ci-4 carboxylic ester groups.
• ... hydrocarbon group consists of hydrogen and carbon atoms and can be in the form of an aliphatic hydrocarbon, i.e. linear or branched saturated hydrocarbon (e.g. alkyl group), a linear or branched unsaturated hydrocarbon (e.g. alkenyl or alkynyl group), a saturated cyclic hydrocarbon (e.g. cycloalkyl) or an unsaturated cyclic hydrocarbon (e.g. cycloalkenyl or cycloalkynyl), or can be in the form of an aromatic hydrocarbon, i.e. aryl group, or can also be in the form of a mixture of said type of groups, e.g.
• a specific group may comprise a linear alkyl, a branched alkenyl (e.g. having one or more carbon-carbon double bonds), a (poly)cycloalkyl and an aryl moiety, unless a specific limitation to only one type is mentioned.
• a group when a group is mentioned as being in the form of more than one type of topology (e.g. linear, cyclic or branched) and/or being saturated or unsaturated (e.g. alkyl, aromatic or alkenyl), it is also meant a group which may comprise moieties having any one of said topologies or being saturated or unsaturated, as explained above.
• a group when a group is mentioned as being in the form of one type of saturation or unsaturation, (e.g. alkyl), it is meant that said group can be in any type of topology (e.g. linear, cyclic or branched) or having several moieties with various topologies.
• R group can or cannot comprise a certain functional group.
• one or more is understood as comprising 1 to 7, preferably 1 to 5, preferably 1 to 3 and more preferably 1 to 2 of a Ci-4 carboxylic ester group.
• Ci-4 alcohol is understood as an alcohol of formula R 2 0H wherein R 2 is a Ci-4 alkyl group.
• the Ci-4 alcohol comprises only one hydroxy group and does not comprise any other functional group; i.e. the Ci-4 alcohol is a mono alcohol.
• the Ci-4 alcohol is not glycerine or a fatty alcohol.
• alkyl is understood as comprising branched and linear alkyl group.
• separation unit is understood as any means allowing to separate molecules from a reaction mixture comprising several molecules, in particular to separate molecules having a different boiling points.
• suitable separation unit may include distillation column, rectification device, a membrane, a pervaporation device, an adsorption unit, an absorption unit.
• the compound comprising at least one Ci-4 carboxylic ester group is not a fatty acid ester, a monoglycerides, a diglycerides, or a triglycerides.
• the compound comprising at least one Ci-4 carboxylic ester group is a diester compound. Particularly the diester is a compound of formula
• R 1 may be a C1.3 alkyl group, particularly, a methyl or ethyl group, more particularly, a methyl group.
• the carboxylic ester group may be a C1.3 carboxylic ester group and the alcohol formed/released during the invention’ process may be a C1.3 alcohol, particularly a C1.2 carboxylic ester group and a C1.2 alcohol , even more particularly, a Ci carboxylic ester group and methanol.
• the alcohol formed/released during the invention’ process is not glycerine or ethylene glycol.
• R may be a Ci-i6 hydrocarbon group optionally comprising one or more C1.4 carboxylic ester groups.
• R may be a Ci-i4 hydrocarbon group optionally comprising one or more C1.4 carboxylic ester groups.
• R may be a C1.12 hydrocarbon group optionally comprising one or more C1.4 carboxylic ester groups.
• R may be a CMO hydrocarbon group optionally comprising one or more C1.4 carboxylic ester groups.
• R may be a Ci-8 hydrocarbon group optionally comprising one or more C1.4 carboxylic ester groups.
• R may be a Ci-8 alkyl, a C3-8 cycloalkyl, a C2-8 alkenyl group or a phenyl group; each optionally substituted by one or more C1.4 carboxylic ester groups.
• R may be a Ci-6 alkyl, a C3-6 cycloalkyl, a C2-6 alkenyl group or a phenyl group; each optionally substituted by one or more C1.4 carboxylic ester groups.
• R may be a Ci-6 alkyl, a C3-6 cycloalkyl, a C2-6 alkenyl group or a phenyl group; each optionally substituted by one or two C1.4 carboxylic ester groups.
• R may be a Ci-6 alkyl, a C3-6 cycloalkyl, a C2-6 alkenyl group or a phenyl group optionally substituted by one C1.4 carboxylic ester group. Even more particularly, R may be a Ci-6 alkyl, a C5-6 cycloalkyl, a C2-6 alkenyl group or a phenyl group optionally substituted by one C1.4 carboxylic ester group.
• R’ may be a Ci-i6 hydrocarbon group.
• R’ may be a C1.14 hydrocarbon group.
• R’ may be a C1.12 hydrocarbon group.
• R’ may be a Ci-io hydrocarbon group.
• R’ may be a Ci-s hydrocarbon group.
• R’ may be a Ci-s alkanediyl, a C3-8 cycloalkanediyl, a C2-8 alkenediyl group or a phenylene group.
• R’ may be a Ci-6 alkanediyl, a C3-6 cycloalkanediyl, a C2-6 alkenediyl group or a phenylene group.
• R’ may be a Ci-6 alkanediyl, a C5-6 cycloalkanediyl, a C2-6 alkenediyl group or a phenylene group.
• R’ may be a 1,4-phenylene group.
• the C1.4 alcohol may be a C2-3 alcohol, preferably ethanol.
• the released alcohol from the compound comprising at least one C1.4 carboxylic ester; i.e. the compound of formula R'OH has a lower boiling point than the C1.4 alcohol; i.e. compound of formula R 2 OH.
• the difference between the boiling point of the C1.4 alcohol; i.e. compound of formula R 2 OH and the boiling point of the released alcohol from the compound comprising at least one C1.4 carboxylic ester; i.e. the compound of formula R'OH is comprised between 10 and 30°C , particularly, between 10 and 20°C, even more particularly, between 12 and 18°C.
• the compound comprising at least one C1.4 carboxylic ester group is dimethyl terephthalate or dimethyl 1,4- cyclohexanedicarboxylate.
• the released alcohol from the compound comprising at least one C1.4 carboxylic ester group is totally or partly removed in the separation unit and the C1.4 alcohol is added in each reactor.
• the C1.4 alcohol added in each reactor is the same; i.e. in each reactor ethanol is added.
• the reactors used in the invention process may be any reactors suitable for continuous process.
• the reactors may be identical or different.
• suitable reactor may include plug-flow reactor, continuously stirred tank reactor, Laminar flow reactor, loop reactor, micro reactor, reactor divided into a plurality of sections and a combination thereof.
• the reactors may be plug-flow reactor, continuously stirred tank reactor and a combination thereof.
• the continuous process is performed in two reactors.
• the residence time in each reactor will depend of the type of reactors.
• the residence time may be comprised between 0.01 hrs and 100 hrs, particularly between 0.2 hrs and 20 hrs.
• the separation unit may be a distillation column.
• Said distillation column used in the invention process may be any distillation column suitable for continuous process.
• the distillation column may comprise plates or trays or packing material. A person skilled in the art is able to select and sized the distillation column as a function of the melting and boiling point of the starting and final products.
• the distillation may be carried out at atmospheric pressure or at reduced pressure, in particular at a pressure of less than 200xl0 5 Pa (200 bars), for example at a pressure comprised between 5 xlO 5 Pa and 100xl0 5 Pa (5 and 100 bars).
• the invention’s process comprises a) the reaction of a transesterification of a compound comprising at least one Ci-4 carboxylic ester group with a Ci-4 alcohol in a presence of a transesterification catalyst in a first reactor; b) then the reaction mixture of step a) is distilled in a distillation column wherein the released alcohol is totally or partly removed; and c) then the reaction mixture is flowed in a second reactor wherein the Ci-4 alcohol is added.
• the Ci-4 alcohol added in step a) and in step c) is identical.
• the second reactor is followed by at least one separation unit wherein the unreacted or partially reacted compound comprising at least one Ci-4 carboxylic ester group, the released alcohol, the excess added Ci-4 alcohol and the transterification catalyst are removed.
• the second reactor is followed by two separation units. Said separation units are distillation column.
• the transesterification catalyst is a Lewis acid, a Bronsted acid or a base, particularly a Lewis acid.
• Specific and non-limiting examples of transesterification catalyst may be selected from the group consisting of tinorganic or titaniumorganic compounds, in situ formed tinorganic compounds via reaction of dialkyltin oxides with acid of the ester being transesterified, preferably dialkyltin derivatives such as oxides (TUH ⁇ SnO, (CsHn ⁇ SnO, dicarboxylates such as dibutyltin dilaurate, dioctyltin dicarboxylate and mixtures thereof.
• the transesterification catalyst can be added into the reaction medium of the invention’s process in a large range of concentrations.
• concentration values those ranging from about 0.001 to about 5 mol%, relative to the amount of the compound comprising at least one Ci-4 carboxylic ester, preferably from 0.02 to about 0.5 mol%, relative to the amount of the compound comprising at least one Ci-4 carboxylic ester.
• concentration of the transesterification catalyst will depend, as the person skilled in the art knows, on the nature of the latter, on the nature of the compound comprising at least one Ci-4 carboxylic ester, on the nature of the Ci-4 alcohol , on the reaction temperature as well as on the flow of the process.
• the Ci-4 alcohol can be added into the reaction medium of the invention’s process in a large range of concentrations.
• Ci-4 alcohol values those ranging from about 2 to about 20 equivalents, relative to the amount of the compound comprising at least one Ci-4 carboxylic ester, preferably at least 5 equivalents, relative to the amount of the compound comprising at least one Ci-4 carboxylic ester.
• concentration of the Ci-4 alcohol will depend, as the person skilled in the art knows, on the nature of the latter, on the nature of the compound comprising at least one Ci-4 carboxylic ester, on the nature of the transesterification catalyst, on the reaction temperature as well as on the flow of the process.
• the Ci-4 alcohol is added in each reactor of the invention’s process, in particular, the same Ci-4 alcohol is added in each reactor.
• the invention’s process is carried out at a temperature comprised between 20°C and 250°C.
• the temperature is in the range between 70°C and 200°C.
• a person skilled in the art is also able to select the preferred temperature as a function of the melting and boiling point of the starting and final products as well as the desired time of reaction or conversion.
• the invention’s process may be performed at a pressure comprised between 0.1xl0 5 Pa and 100xl0 5 Pa (0.1 to 100 bars) or even more if desired.
• a person skilled in the art is well able to adjust the pressure as a function of the catalyst load and of the compound comprising at least one Ci-4 carboxylic ester.
• the invention’s process may be performed under inert atmosphere such as nitrogen and/or argon.
• the invention processes can be carried out in the presence or absence of a solvent.
• a solvent is required or used for practical reasons, then any solvent current in such reaction type can be used for the purposes of the invention.
• the choice of the solvent is function of the nature of the compound comprising at least one Ci-4 carboxylic ester group and/or catalyst and the person skilled in the art is well able to select the solvent most suitable in each case to optimize the reaction.
• the Ci-4 alcohol and the transesterification catalyst are recycled.
• the invention’s process for compound comprising more than one Ci-4 carboxylic ester involves the formation of mono transesterified compound as an intermediate; such intermediate may be present at a certain level in the final reaction mix, and may be recycled in the invention’s process. In addition, unreacted starting materials may be also recycled in the invention’s process.
• a second object of the present invention is the use of the process as defined above to produce perfumery, cosmetic or pharmaceutic products, particularly, perfumery products.
• the perfumery product may be diethyl 1,4- cycl ohexanedi carb oxyl ate .
• a further object of the present invention is a process for preparing diethyl 1,4- cyclohexanedicarboxylate comprising the step of a) the transesterification as defined above of dimethyl terephthalate in the presence of ethanol providing diethyl terephthalate; and b) the reduction of diethyl terephthalate obtained in step a).
• a further object of the present invention is a process for preparing diethyl 1,4-cyclohexanedicarboxylate comprising the step of a) the transesterification as defined above wherein dimethyl terephthalate reacts with ethanol in the presence of a transesterification catalyst providing diethyl terephthalate; and b) the reduction of diethyl terephthalate obtained in step a).
• the reduction is a hydrogenation using molecular H2 and a hydrogenation catalyst.
• the hydrogenation catalyst may be a metal in elemental metallic form, in particular palladium or ruthenium in elemental metallic form.
• said palladium (Pd) or Ruthenium (Ru) is supported on a carrying material.
• carrying material is carbon, silica or aluminum oxide.
• Such supports are well known to a person skilled in the art.
• the supported palladium (Pd) or ruthenium (Ru) catalysts are known compounds and are commercially available. A person skilled in the art is able to select the preferred kind of metal as the way that it was deposit on the support, as the proportion of metal on support material, as the form (powder, granules, pellets, extrudates, mousses.%) and as the surface area of the support.
• the hydrogenation catalyst is alumina supported ruthenium.
• the amount of metal relative to the support can range between 0.05% and 25% w/w, or even between 0.4% and 6%, relative to the weight on the support used.
• the hydrogenation catalyst can be added into the reaction medium of the invention’s process in a large range of concentrations.
• concentration values those ranging from 0.001 mol% to lmol%, relative to the total amount of diethyl terephthalate.
• the metal concentration will be comprised between 0.02 mol% to lmol%, or even between 0.04 mol% to lmol%. It goes without saying that the optimum concentration of metal will depend, as the person skilled in the art knows, on the nature of the latter, if the process is run in batch or continuously, on the temperature and on the pressure of H2 used during the process, as well as the desired time of reaction.
• the hydrogenation catalyst may be recycled at the end of the invention’s process. In other words, the hydrogenation catalyst may be recovered at the end of the invention’s process and use several times in the invention’s process.
• the molecular hydrogen can be used pure or mixed with an inert gas.
• inert gas are nitrogen or argon.
• the EE/inert gas volume ratio is comprised between 1/1 to 0.01/1 and more preferably the ratio is 0.05/1.
• the molecular hydrogen can be added into the reaction medium of the invention’s process in a large range of ratios relative to the substrate.
• molecular hydrogen ratio values those ranging from 100 mol% to 5000 mol%, relative to the amount of diethyl terephthalate.
• the molecular hydrogen concentration will be comprised between 300 mol% to 2000 mol% relative to the amount of diethyl terephthalate.
• a person skilled in the art is well able to adjust the pressure or the flow (e.g. in a continuous process) of molecular hydrogen to obtain this range of concentration as a function of the process is batch or continuous.
• concentration of molecular hydrogen as a function of the catalyst load and of dilution of diethyl terephthalate in the solvent.
• the reduction can be carried out under batch or continuous conditions. According to a particular embodiment of the invention, the reduction is a continuous one, as it allows higher productivity.
• any solvent current in such reaction type can be used for the purposes of the invention.
• Non-limiting examples include Ce-i2 aromatic solvents such as toluene, 1,3-diisopropylbenzene, p-cymene, cumene, pseudocumene, benzyl acetate, xylene or a mixture thereof, C3-16 alkane such as hexadecane, ether solvents such as tetrahydrofuran, butyl ether, methyltetrahydrofuran or a mixture thereof, esters such as ethyl acetate or diethyl cyclohexyl di carb oxylate(reacti on product), the latter being the preferred solvent.
• the choice of the solvent is a function of the hydrogenation catalyst and the person skilled in the art is well able to select the solvent most convenient in each case to optimize the reaction.
• the temperature at which the reduction can be carried out is comprised between 90°C and 300°C. More preferably in the range of between 100 °C and 200°C for a continuous process.
• a person skilled in the art is also able to select the preferred temperature as a function of the melting and boiling point of the starting and final products as well as the desired time of reaction or conversion.
• the reduction may be performed at a pressure comprised between O.lxlO 5 Pa and 100xl0 5 Pa (0.1 to 100 bars) or even more if desired.
• a person skilled in the art is well able to adjust the pressure as a function of the catalyst load and the desired time of reaction or conversion. As examples, one can cite typical pressures of 1 to 50xl0 5 Pa (1 to 50 bars).
• the reduction is performed in a fix-bed reactor.
• the reduction is performed in the absence of transesterification catalyst.
• a further object of the present invention is a process for preparing diethyl 1,4- cyclohexanedicarboxylate comprising the step of a) the reduction of dimethyl terephthalate; and b) the transesterification as defined above of dimethyl 1,4- cyclohexanedicarboxylate obtained in step a) in the presence of ethanol providing diethyl 1,4-cyclohexanedicarboxylate.
• Diethylterephthalate had been continuously hydrogenated in a trickle-bed catalytic reactor R-3 over the supported precious-metal catalyst at 55 bar and 120°C with about 75% of the reaction mix returned back to the top of the reactor to avoid undesirably high temperatures due to the exothermicity of hydrogenation.
• reaction mix contained (excluding ethanol and methanol) 91% of diethylterephthalate, and about 11,000 kg of alcohol byproduct (about 50% each of methanol and ethanol) had been distilled out.
• alcohol byproduct about 50% each of methanol and ethanol

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• 2023
  • 2023-09-21 JP JP2025517219A patent/JP2025532099A/ja active Pending
  • 2023-09-21 WO PCT/EP2023/076018 patent/WO2024062008A1/en not_active Ceased
  • 2023-09-21 CN CN202380068097.7A patent/CN119947824A/zh active Pending
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