Trans-1,4-cyclohexyl organic compounds and their purification methods

Abstract

This application relates to a trans-1,4-cyclohexyl organic compound and a purification method thereof. The method includes: providing a composite catalyst, which is a mixture composed of one or more of an alkyl aluminum chloride-magnesium chloride complex, an alkyl zirconium chloride-magnesium chloride complex, and an alkyl titanium chloride-magnesium chloride complex; adding a mixed system containing a trans-1,4-cyclohexyl organic compound and a cis-1,4-cyclohexyl organic compound to a first solvent and mixing under a protective atmosphere, and then adding the composite catalyst to carry out a cyclohexyl rearrangement reaction to convert the cis-1,4-cyclohexyl organic compound into a trans-1,4-cyclohexyl organic compound to obtain a product. The method described in this application can improve the purification rate of the trans-1,4-cyclohexyl organic compound.

Description

Technical Field

[0001] This application relates to the technical field of material production, and more specifically, to trans-1,4-cyclohexyl organic compounds and their purification methods. Background Art

[0002] When preparing trans-1,4-cyclohexyl organic compounds, a mixture of cis-1,4-cyclohexyl organic compounds and trans-1,4-cyclohexyl organic compound isomers is always obtained first, resulting in a low purity of the trans-1,4-cyclohexyl organic compounds. Therefore, the mixture needs to be further purified. Summary of the Invention

[0003] This application provides a trans-1,4-cyclohexyl organic compound and its purification method, and the method can improve the purification rate of the trans-1,4-cyclohexyl organic compound.

[0004] In a first aspect, this application proposes a method for purifying trans-1,4-cyclohexyl organic compounds, and the method includes:

[0005] Providing a composite catalyst, the composite catalyst includes a mixture composed of one or more of an alkyl aluminum chloride-magnesium chloride complex, an alkyl zirconium chloride-magnesium chloride complex, and an alkyl titanium chloride-magnesium chloride complex;

[0006] Adding a mixed system containing trans-1,4-cyclohexyl organic compounds and cis-1,4-cyclohexyl organic compounds to a first solvent for mixing under a protective atmosphere, and adding the composite catalyst after mixing to carry out a cyclohexyl rearrangement reaction to convert the cis-1,4-cyclohexyl organic compounds into the trans-1,4-cyclohexyl organic compounds to obtain a product.

[0007] In some embodiments, the step of providing the composite catalyst includes: adding an anhydrous chloride salt to a second solvent under a protective atmosphere, and then adding a solution of a Grignard reagent of a straight-chain alkyl chloride. The solution of the Grignard reagent of the straight-chain alkyl chloride includes a third solvent, and the anhydrous chloride salt includes a mixture of one or more of anhydrous aluminum trichloride, anhydrous zirconium tetrachloride, and anhydrous titanium tetrachloride; removing the second solvent and the third solvent from the catalytic system to obtain the composite catalyst.

[0008] In some embodiments, based on the total molar amount of the catalytic system, the molar percentage content of the anhydrous chloride salt is A%, and the molar percentage content of the Grignard reagent of the straight-chain alkyl chloride is B%, and 1.0 ≤ B / A ≤ 1.5.

[0009] In some embodiments, the Grignard reagent of the straight-chain alkyl chloride includes a Grignard reagent of a substituted or unsubstituted C1 to C10 straight-chain alkyl chloride.

[0010] In some embodiments, the Grignard reagent of the linear alkyl chloride comprises one or a mixture of two or more of methyl chloride Grignard reagent, ethyl chloride Grignard reagent, propyl chloride Grignard reagent, butyl chloride Grignard reagent, pentyl chloride Grignard reagent, hexyl chloride Grignard reagent, heptyl chloride Grignard reagent, octyl chloride Grignard reagent, n-nonyl chloride Grignard reagent, and n-decyl chloride Grignard reagent.

[0011] In some embodiments, based on the total mass of the first solvent, the mixed system, and the composite catalyst, the mass percentage content of the first solvent is C%, the mass percentage content of the mixed system is D%, and 3 ≤ C / D ≤ 10.

[0012] In some embodiments, based on the total mass of the first solvent, the mixed system, and the composite catalyst, the mass percentage content of the mixed system is D%, and the mass percentage content of the composite catalyst is E%, and 0.5% ≤ E / D ≤ 2%.

[0013] In some embodiments, the temperature is controlled at -20°C to 10°C in the step of providing the composite catalyst.

[0014] In some embodiments, during the process of adding the mixed system containing trans-1,4-cyclohexyl organic compounds and cis-1,4-cyclohexyl organic compounds to the first solvent and mixing under a protective atmosphere, the temperature is controlled at -20°C to 10°C.

[0015] In some embodiments, during the process of the cyclohexyl rearrangement reaction, the temperature is controlled at -20°C to 10°C.

[0016] In some embodiments, during the process of the cyclohexyl rearrangement reaction, the reaction time is controlled at 3 hours to 10 hours.

[0017] In some embodiments, the method further includes: subjecting the product to crystallization treatment.

[0018] In a second aspect, the present application provides a trans-1,4-cyclohexyl organic compound, which is prepared by the method according to any one of the embodiments of the first aspect of the present application.

[0019] According to the method of the embodiments of the present application, the composite catalyst is a composite composed of composite molecules. After the composite catalyst is prepared, it can be applied to the cyclohexyl rearrangement reaction without separation and purification; and it can significantly improve the conversion rate of cis-1,4-cyclohexyl organic compounds, increase the proportion of trans-1,4-cyclohexyl organic compounds in the product, and control the content of isomerization impurities; and the dosage of the composite catalyst is relatively smaller and the cost is lower. Detailed Embodiments

[0020] Embodiments of the present application will be described in detail below. Throughout the specification of the present application, the embodiments of the present application should not be construed as limiting the present application.

[0021] In addition, quantities, ratios, and other numerical values are sometimes presented herein in a range format. It should be understood that such range formats are for convenience and brevity and should be interpreted flexibly to include not only the explicitly specified numerical values as range limits but also all individual numerical values or sub-ranges subsumed within the range as if each numerical value and sub-range were explicitly specified.

[0022] In the detailed description and claims, a list of items joined by terms such as "one or more of", "one or more of", "a mixture of one or two or more of", or other similar terms can mean any combination of the listed items. For example, if items A and B are listed, then the phrase "at least one of A and B" means only A; only B; or A and B. In another example, if items A, B, and C are listed, then the phrase "at least one of A, B, and C" means only A; or only B; only C; A and B (excluding C); A and C (excluding B); B and C (excluding A); or all of A, B, and C. Item A can include a single element or multiple elements. Item B can include a single element or multiple elements. Item C can include a single element or multiple elements.

[0023] The term "saturated alkyl" encompasses straight-chain and branched-chain alkyls. For example, a chain alkyl can be a C1-C50 alkyl, C1-C40 alkyl, C1-C30 alkyl, C1-C20 alkyl, C1-C12 alkyl, C1-C10 alkyl, C1-C6 alkyl, C1-C4 alkyl. In some embodiments, the alkyl includes methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl, octyl, etc. Additionally, the chain alkyl can be optionally substituted.

[0024] The term "cyclic alkyl" refers to a cyclic structure composed of three or more carbon atoms. For example, a cyclic alkyl can be a C3-C50 cycloalkyl, C3-C40 cycloalkyl, C3-C30 cycloalkyl, C3-C20 cycloalkyl, C3-C12 cycloalkyl, C3-C10 cycloalkyl, C3-C6 cycloalkyl, C3-C4 cycloalkyl. In some embodiments, the cyclic alkyl includes cyclopropyl, cycloisopropyl, cyclobutyl, cycloisobutyl, cyclotert-butyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, etc. Additionally, the cyclic alkyl can be optionally substituted.

[0025] The term "aryl group" refers to a closed aromatic ring or ring system. For example, the aryl group can be a C6-C50 aryl group, a C6-C40 aryl group, a C6-C30 aryl group, a C6-C20 aryl group, or a C6-C10 aryl group. Among them, the C6-C30 aryl group refers to a group containing 6 to 30 carbon atoms and including an aromatic cyclic structure. In some embodiments, the aryl group includes phenyl, naphthyl, phenanthryl, anthryl, biphenyl, triphenylene, pyrenyl, spirobifluorene, perylene, indenyl, and azulene, etc. Additionally, the aryl group can be optionally substituted.

[0026] The term "halogen atom" refers to a fluorine atom, a chlorine atom, a bromine atom, etc.

[0027] The term "heteroatom" refers to a nitrogen atom, a sulfur atom, a phosphorus atom, etc.

[0028] The term "hydrogen" refers to 1H (protium, H), 2H (deuterium, D), or 3H (tritium, T). In various embodiments, "hydrogen" can be 1H (protium, H).

[0029] Throughout this specification, the substituents of a compound are disclosed in groups or ranges. It is expressly contemplated that such a description includes every individual sub-combination of the members of these groups and ranges. For example, it is expressly contemplated that the term "C1-C8 alkyl" discloses C1, C2, C3, C4, C5, C6, C7, C8, C1-C8, C1-C7, C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, C2-C8, C2-C7, C2-C6, C2-C5, C2-C4, C2-C3, C3-C8, C3-C7, C3-C6, C3-C5, C3-C4, C4-C8, C4-C7, C4-C6, C4-C5, C5-C8, C5-C7, C5-C6, C6-C8, C6-C7, and C7-C8 alkyls individually.

[0030] As other examples, it is expressly contemplated that the integers in the range of 5 to 40 are disclosed individually as 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, and 40; it is expressly contemplated that the integers in the range of 1 to 20 are disclosed individually as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, and 20. Accordingly, other groups or ranges can be expressly contemplated.

[0031] When the above groups are substituted, the substituting group can be a halogen atom or a heteroatom. The halogen atom can be optionally a fluorine atom.

[0032] In the process of synthesizing trans - 1,4 - cyclohexyl organic compounds, cis - 1,4 - cyclohexyl organic compounds are often co - produced. To improve the purity of trans - 1,4 - cyclohexyl organic compounds, it is necessary to remove cis - 1,4 - cyclohexyl organic compounds or convert cis - 1,4 - cyclohexyl organic compounds into trans - 1,4 - cyclohexyl organic compounds through the "cyclohexyl rearrangement reaction".

[0033] In the related art, a catalyst is required in the cyclohexyl rearrangement reaction. In the related art, Lewis acid is usually used. The inventor found that Lewis acid with weak activity cannot catalyze the "cyclohexyl rearrangement reaction"; Lewis acid with too strong activity will cause side reactions such as carbocation rearrangement and cyclohexyl ring opening of the substrate while catalyzing the "cyclohexyl rearrangement reaction", thereby generating more isomerization impurities; moreover, the molecular structures of these isomerization impurities are also similar to those of the target product, resulting in low efficiency and large yield loss in removing these impurities during subsequent purification. The inventor further studied and found that the cyclohexyl rearrangement reaction can be better completed by optimizing and modifying Lewis - type catalysts. For example, catalysts such as trifluoroacetic acid or trifluoromethanesulfonic acid, a mixture of anhydrous aluminum trichloride and an activity - reducing additive, lithium (or sodium, potassium) tetrachloroaluminate composite salts, etc. can be used.

[0034] However, through in - depth research by the inventor, it is found that the above - mentioned catalysts all have certain problems. For example, trifluoroacetic acid or trifluoromethanesulfonic acid - type catalysts are expensive; the dosage needs to be as much as 15 - 30% of the mass ratio of the substrate, and the use cost is high; the hydrolysis products have strong corrosiveness to equipment, etc.

[0035] The mixture of anhydrous aluminum trichloride and an activity - reducing additive has the following defects: Some activity - reducing additives, such as nitrobenzene, triethylamine hydrochloride, quaternary ammonium salts, etc., have too strong an inhibitory effect on the activity of aluminum trichloride, and the "cyclohexyl rearrangement reaction" is often difficult to initiate; often, the total amount of such mixed additives needs to be increased to 10 - 20% of the mass ratio of the substrate to produce a relatively stable catalytic effect; resulting in high use cost and a large amount of three wastes generated during post - treatment. Another part of the activity - reducing additives, such as lithium chloride (or sodium, potassium), etc., have poor solubility in the reaction solution (usually various organic solvents), making it difficult to weaken the activity of all aluminum trichloride molecules; the inhibitory effect on side reactions such as carbocation rearrangement and cyclohexyl ring opening is very unstable.

[0036] Lithium (sodium, potassium) tetrachloroaluminate composite salt catalysts have the following problems: Sodium tetrachloroaluminate and potassium tetrachloroaluminate have poor solubility in various organic solvents, and the catalytic action is mainly achieved by a solid-liquid two-phase reaction; when the dosage is too small, the rate of the "cyclohexyl rearrangement reaction" is too slow, and it is even difficult to initiate the reaction; often, the dosage needs to be increased to 5% mass ratio of the substrate or even higher to achieve better catalytic effect. Lithium tetrachloroaluminate has sufficient solubility in organic solvents to stably catalyze the "cyclohexyl rearrangement reaction"; however, due to the increasing demand for lithium batteries, the market price of lithium tetrachloroaluminate has increased by more than 500% from 2012 to 2022, and the use cost is getting higher and higher.

[0037] Based on the above problems, the inventor further studied the catalyst and proposed a method for purifying trans-1,4-cyclohexyl organic compounds. The method will be described in detail below.

[0038] Method for purifying trans-1,4-cyclohexyl organic compounds

[0039] The method includes: Step S100, providing a composite catalyst; Step S200, cyclohexyl rearrangement reaction.

[0040] In step S100, the composite catalyst may include one or a mixture of two or more of alkylaluminum chloride-magnesium chloride complex, alkylzirconium chloride-magnesium chloride complex, and alkyltitanium chloride-magnesium chloride complex.

[0041] The composite catalyst can be self-made or directly purchased. In some embodiments, the step of providing the composite catalyst may further include:

[0042] Step S110, adding anhydrous chloride salt to the second solvent under a protective atmosphere, and then adding a solution of a Grignard reagent of a straight-chain alkyl chloride, and mixing to form a catalytic system, where the solution of the Grignard reagent of the straight-chain alkyl chloride includes a third solvent;

[0043] Step S120, removing the second solvent and the third solvent from the catalytic system to obtain the composite catalyst.

[0044] In some embodiments, the anhydrous chloride salt may include one or a mixture of two or more of anhydrous aluminum trichloride, anhydrous zirconium tetrachloride, and anhydrous titanium tetrachloride.

[0045] In some embodiments, the second solvent may be an inert organic solvent that basically does not react with the anhydrous chloride salt and the Grignard reagent. For example, the second solvent may include one or a mixture of two or more of petroleum ether, cyclohexane, methylcyclohexane, benzene, toluene, and xylene.

[0046] The amount of the second solvent can be adjusted according to the amount of the anhydrous chloride salt, and the added amount of the second solvent can enable the added chloride salt and the second solvent to be stirred to form a suspension.

[0047] In some embodiments, the temperature of step S110 can be controlled to be from -20°C to 10°C, such as -20°C, -15°C, -10°C, -5°C, 0°C, 5°C, 8°C, 10°C or a range composed of any two of the above values.

[0048] In some embodiments, the straight-chain alkyl chloride in the Grignard reagent of the straight-chain alkyl chloride can be one or a mixture of two or more of chloromethane, chloroethane, chloropropane, chlorobutane, chloropentane, chlorohexane, chloroheptane, chlorooctane, chlorononane and chlorodecane.

[0049] In some embodiments, the Grignard reagent of the straight-chain alkyl chloride includes one or a mixture of two or more of chloromethane Grignard reagent, chloroethane Grignard reagent, chloropropane Grignard reagent, chlorobutane Grignard reagent, chloropentane Grignard reagent, chlorohexane Grignard reagent, chloroheptane Grignard reagent, chlorooctane Grignard reagent, chlorononane Grignard reagent and chlorodecane Grignard reagent.

[0050] In some embodiments, based on the total molar amount of the catalytic system, the molar percentage content of the anhydrous chloride salt is A%, and the molar percentage content of the Grignard reagent of the straight-chain alkyl chloride is B%, and 1.0 ≤ B / A ≤ 1.5.

[0051] If the content of the Grignard reagent is too small, there may not be enough equivalent alkyl groups and magnesium atoms to form complexes with aluminum trichloride, zirconium tetrachloride or titanium tetrachloride molecules. Excessive aluminum trichloride, zirconium tetrachloride or titanium tetrachloride molecules may remain in the composite catalyst, and since aluminum trichloride, zirconium tetrachloride or titanium tetrachloride are all strong Lewis acids, they will cause more cyclohexyl ring-opening and rearrangement side reactions in the rearrangement reaction.

[0052] If the content of the Grignard reagent is too large, in the prepared composite catalyst, there will be more metal (aluminum, zirconium, or titanium) complex molecules with two or more alkyl groups. These metal complex molecules with two or more alkyl groups have a very low catalytic effect on the cyclohexyl rearrangement reaction, or even no catalytic effect.

[0053] Combining the above analysis, the inventor preferably selects 1.0 ≤ B / A ≤ 1.5 to ensure that not too many metal complex molecules with two or more alkyl groups are generated; for example, B / A can be 1.0, 1.1, 1.2, 1.3, 1.4, 1.5 or a range composed of any two of the above values.

[0054] In some embodiments, the third solvent may be an organic solvent. For example, the third solvent may include one or a mixture of two or more of diethyl ether, tetrahydrofuran, methyltetrahydrofuran, petroleum ether, cyclohexane, methylcyclohexane, benzene, toluene, and xylene.

[0055] The amount of the third solvent can be adjusted according to the amount of the Grignard reagent of the linear alkyl chloride so that the Grignard reagent of the linear alkyl chloride can be substantially completely dissolved.

[0056] In some embodiments, after adding the Grignard reagent of the linear alkyl chloride in step S100, it can be kept warm for a certain period of time, such as 1 h to 5 h.

[0057] In some embodiments, the protective atmosphere refers to an atmosphere that does not react with the raw materials and products in the catalytic system. Gases such as nitrogen, helium, and argon can be used as protective gases to achieve a protective atmosphere.

[0058] In some embodiments, the removal of the second solvent and the third solvent can be carried out by means such as reduced pressure concentration or evaporation.

[0059] In some embodiments, the composite catalyst includes one or a mixture of two or more of a complex of alkylaluminum chloride - magnesium chloride, a complex of alkylzirconium chloride - magnesium chloride, and a complex of alkyltitanium chloride - magnesium chloride.

[0060] As a specific example of step S100, step S100 may include adding a second solvent to a reaction vessel, stirring and cooling under nitrogen protection, controlling the temperature of the reaction system at -20°C to 10°C, and then adding an anhydrous chloride salt. Then, continue to control the temperature at -20°C to 10°C, and slowly dropwise add a solution of the Grignard reagent of the linear alkyl chloride. After the dropwise addition is completed, continue to keep warm at -20°C to 10°C and stir for 1 hour to 5 hours. Finally, remove the second solvent and the third solvent by reduced pressure concentration; the concentrated residue is the composite catalyst.

[0061] The temperature range of -20°C to 10°C is adopted in step S100, which has the following beneficial effects:

[0062] When the temperature is too low, the solubility of the anhydrous chloride salt in the second solvent decreases, and the reaction rate of forming the composite catalyst with the Grignard reagent becomes slower and even difficult to react completely. When the temperature is too high, the anhydrous chloride, as a strong Lewis acid, may catalyze and cause the cleavage of ether solvents; or side reactions such as Friedel - Crafts alkylation of aromatic solvents. Therefore, the inventors preferably set the reaction temperature of step S100 at -20°C to 10°C.

[0063] In step S200, a mixed system containing trans-1,4-cyclohexyl organic compounds and cis-1,4-cyclohexyl organic compounds is added to a first solvent under a protective atmosphere and mixed. After mixing, a composite catalyst is added for a cyclohexyl rearrangement reaction to convert the cis-1,4-cyclohexyl organic compounds into trans-1,4-cyclohexyl organic compounds, obtaining a product.

[0064] In this application, the trans-1,4-cyclohexyl organic compounds and the cis-1,4-cyclohexyl organic compounds are isomers.

[0065] In some embodiments, the first solvent may include one or a mixture of two or more of petroleum ether, cyclohexane, methylcyclohexane, benzene, toluene, xylene, dichloromethane, 1,2-dichloroethane, chloroform, and carbon tetrachloride.

[0066] In some embodiments, based on the total mass of the first solvent, the mixed system, and the composite catalyst, the mass percentage content of the first solvent is C%, and the mass percentage content of the mixed system is D%, with 3 ≤ C / D ≤ 10. Since many raw materials or products corresponding to this application may only be partially soluble in the first solvent; the raw materials or products that cannot be completely dissolved will be in a suspension state with the first solvent. When the amount of the first solvent used is too small, the suspension may be too viscous and difficult to stir; when the amount of the first solvent used is more, no more beneficial effects will be produced. Therefore, this application preferably has 3 ≤ C / D ≤ 10. Exemplarily, C / D can be 3, 5, 6, 8, 9, 10, or a range composed of any two of the above values.

[0067] In some embodiments, based on the total mass of the first solvent, the mixed system, and the composite catalyst, the mass percentage content of the mixed system is D%, and the mass percentage content of the composite catalyst is E%, with 0.5% ≤ E / D ≤ 2%.

[0068] The smaller the amount of the composite catalyst used, the slower the rate of the cyclohexyl rearrangement reaction; while increasing the amount of the composite catalyst can accelerate the reaction rate, it will also lead to an increase in cost and an increase in the three wastes when separating and removing the composite catalyst during post-treatment. For the above reasons, the inventor preferably has 0.5% ≤ E / D ≤ 2%. Exemplarily, E / D can be 0.5%, 0.8%, 1%, 1.2%, 1.5%, 1.8%, 2%, or a range composed of any two of the above values.

[0069] In some embodiments, the temperature for adding raw materials and the reaction temperature in step S200 can be controlled to be from -20°C to 20°C.

[0070] When the temperature in step S200 is too low, the rate of the cyclohexyl rearrangement reaction will slow down and it may even be difficult to occur; when the temperature is too high, the proportion of side products of cyclohexyl ring opening and rearrangement will increase significantly. Therefore, the inventors of the present application preferably set the reaction temperature of step S200 to be from -20°C to 20°C. Exemplarily, the temperature can be -20°C, -10°C, -5°C, 0°C, -5°C, -10°C, -12°C, -15°C, -18°C, -20°C, or a range composed of any two of the above values.

[0071] In some embodiments, in step S200, the reaction time of the cyclohexyl rearrangement reaction can be from 3 hours to 10 hours.

[0072] Combined with the reaction temperature of step S200, the corresponding cyclohexyl rearrangement reaction in the present application can generally be completed within 3 hours to 10 hours. When the reaction time is too short, the cyclohexyl rearrangement reaction may still not be complete; when the reaction time is too long, no more beneficial effects will be produced. Therefore, the inventors of the present application preferably set the reaction time of step S200 to be within 3 hours to 10 hours. Exemplarily, the reaction time can be 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 9 hours, 10 hours, or a range composed of any two of the above values.

[0073] As a specific example of step S200, step S200 may include:

[0074] Into the reaction vessel, first add a first solvent and a mixed system containing trans-1,4-cyclohexyl organic compounds and cis-1,4-cyclohexyl organic compounds, stir and cool down to -20°C to 20°C under nitrogen protection, then add a composite catalyst, and continue to keep the temperature between -20°C and 20°C for reaction for 1 hour to 10 hours.

[0075] The general formula of the reaction equation corresponding to the present application is as follows:

[0076] R3MgCl + AlCl3 → R3AlCl2MgCl2 + (R3)2AlCl MgCl2 + MgAlCl5 Alkyl zirconium chloride - magnesium chloride complex

[0077] R3MgCl + ZrCl4 → R3ZrCl3MgCl2 + (R3)2ZrCl2MgCl2 + MgZrCl6 Alkyl zirconium chloride - magnesium chloride complex

[0078] R3MgCl + TiCl4 → R3TiCl3MgCl2 + (R3)2TiCl2MgCl2 + MgTiCl6 Alkyl titanium chloride - magnesium chloride complex

[0079]

[0080] In the above equations, R1 and R2 are each independently selected from substituted or unsubstituted saturated alkyl groups, substituted or unsubstituted cycloalkyl groups, or substituted or unsubstituted aromatic groups; when substituted, the substituents may include halogen atoms.

[0081] Optionally, R1 and R2 are each independently selected from substituted or unsubstituted C1-C10 saturated alkyl groups, substituted or unsubstituted C3-C10 cycloalkyl groups, or substituted or unsubstituted C6-C10 aromatic groups.

[0082] When the above groups can be substituted, the substituents may include halogen atoms, and further, the substituents include fluorine atoms.

[0083] Exemplarily, R1 and R2 are each independently selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, cyclopropyl, cyclopentyl, cyclohexyl, phenyl, naphthyl or fluorophenyl.

[0084] R3 may be selected from straight-chain alkyl groups, such as C1-C20 straight-chain alkyl groups.

[0085] Exemplarily, R3 may be selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, n-nonyl or n-decyl, etc.

[0086] According to the method of the embodiment of the present application, the composite catalyst is a composite composed of composite molecules. After the composite catalyst is prepared, it can be applied to the cyclohexyl rearrangement reaction without separation and purification; and it can significantly improve the conversion rate of cis-1,4-cyclohexyl organic compounds, increase the proportion of trans-1,4-cyclohexyl organic compounds in the product, and control the content of isomerization impurities; and the dosage of the composite catalyst is relatively smaller and the cost is lower.

[0087] The composite catalyst described in the present application also has the following advantages:

[0088] First, by introducing alkyl groups and complexed magnesium chloride into the molecular structure of the composite catalyst of the present application, the activity of Lewis acids such as aluminum trichloride, zirconium tetrachloride, and titanium tetrachloride is moderately weakened. The obtained composite catalyst can not only catalyze the "cyclohexyl rearrangement" reaction, but also will not generate too many isomerization impurities. The composite catalyst of the present application can make the product contain more than 90% of trans-1,4-cyclohexyl organic compounds (target products), for example, it can reach more than 99.5%; at the same time, control the isomerization impurities that are difficult to purify and remove ≤1%.

[0089] Second, by introducing straight-chain alkyl groups into the molecular structure of the composite catalyst of the present application, the solubility of some of their components in various organic solvents is enhanced. Therefore, the dosage of the composite catalyst is relatively smaller, and the effect of stably catalyzing the "cyclohexyl rearrangement reaction" can be achieved.

[0090] Thirdly, various raw materials required for preparing the composite catalyst, such as Grignard reagents of various linear alkyl chlorides, aluminum trichloride or titanium tetrachloride, zirconium tetrachloride, etc., have a wide range of interchangeable selectivity, and most of them are abundantly supplied in the market and inexpensive. Combining with the aforementioned low dosage, the preparation and use costs of these types of catalysts preferred in the present application are more advantageous.

[0091] In order to further improve the purity of trans-1,4-cyclohexyl organic compounds, in some embodiments, after step S200, the method further includes step S300 for further purification.

[0092] The means of further purification can utilize the boiling point difference between cis- and trans-isomers and be separated by atmospheric distillation or vacuum distillation; crystallization and other means can also be used for purification; or a combination of multiple means can be used for purification.

[0093] Specifically, the crystallization means is as follows: In step S300, after the reaction in step S200 is completed, water can be added to the reaction system in step S200 for hydrolysis; then the water layer is separated by liquid separation. After the organic layer is washed with water until the water layer is neutral, the organic solvent is then concentrated and removed. The residue is mainly a mixture containing compounds with trans-1,4-substituted cyclohexyl, and the remaining components are compounds containing cis-1,4-substituted cyclohexyl and a small amount of rearrangement by-products. After further crystallization purification, a compound containing trans-1,4-substituted cyclohexyl with a purity ≥ 99.5% can be obtained.

[0094] The step of further crystallization purification includes: using thiourea or cyclodextrin to perform inclusion crystallization on the product to be separated; then using methods such as heating dissociation, extraction, and water washing to separate the molecules containing trans-1,4-cyclohexyl organic compounds and thiourea or cyclodextrin. Due to the large steric hindrance of cis-1,4-cyclohexyl organic compounds, the molecules containing cis-1,4-cyclohexyl organic compounds are difficult to enter the crystal cavities of thiourea and cyclodextrin crystals; the steric hindrance of trans-1,4-cyclohexyl organic compounds is smaller, and the molecules containing trans-1,4-cyclohexyl organic compounds can enter the crystal cavities of thiourea and cyclodextrin crystals; thus, this means can be used for recrystallization purification.

[0095] In some embodiments, the temperature during the hydrolysis by adding water dropwise, as well as during subsequent liquid separation and water washing, is between room temperature and 60°C.

[0096] In some embodiments, there is no strict requirement for the dosage of water during hydrolysis, as long as it can completely dissolve the composite catalyst added in step S200 and their hydrolysis products.

[0097] In some embodiments, the hydrolysis time is 0.5 hour to 1 hour.

[0098] In some embodiments, there are no strict requirements for the amount of water used during the water washing or the number of washing times, and the water layer during liquid separation after washing should be neutral.

[0099] In some embodiments, there are no fixed requirements for conditions such as the type, amount, and temperature of the solvent during crystallization purification, and these can be determined according to properties such as the solubility of the substrate.

[0100] Trans-1,4-cyclohexyl organic compounds

[0101] In a second aspect of the present application, a trans-1,4-cyclohexyl organic compound is proposed, and the trans-1,4-cyclohexyl organic compound can be synthesized by the method described in any of the embodiments of the first aspect of the present application.

[0102] Examples

[0103] Hereinafter, the embodiments of the present application will be described. The embodiments described below are exemplary and are only used to explain the present application and should not be construed as a limitation of the present application. For those without specific techniques or conditions indicated in the embodiments, the techniques or conditions described in the literature in the art or according to the product specifications shall be followed. For reagents or instruments without the manufacturer indicated, they are all conventional products that can be obtained through commercial purchase.

[0104] Example 1

[0105] Prepare an ethyl zirconium chloride-magnesium chloride complex.

[0106] C2H5MgCl + ZrCl4 → C2H5ZrCl3MgCl2 + (C2H5)2ZrCl2MgCl2 + MgZrCl6 Ethyl zirconium chloride-magnesium chloride complex

[0107] Step 1.1: Add 200 ml of methylcyclohexane to a 500 ml reaction flask. Protect with nitrogen, stir, and cool down. Control the temperature of the reaction mixture between 0 and 10 °C. First, add 23.0 g (0.1 mol) of anhydrous zirconium tetrachloride; then slowly add dropwise a solution of 0.1 mol of ethyl Grignard reagent dissolved in 60 ml of tetrahydrofuran. After the addition is complete, continue to stir at 0 to 10 °C for 1 hour.

[0108] Step 1.2: Concentrate under reduced pressure to remove methylcyclohexane and tetrahydrofuran from the reaction solution obtained in Step 1.1; the concentrated residue is the ethyl zirconium chloride-magnesium chloride complex, approximately 34.2 g (wet weight).

[0109] Example 2

[0110] Prepare a n-nonyl titanium chloride-magnesium chloride complex.

[0111] C 10 H21 MgCl + TiCl4 → C 10 H 21 TiCl3MgCl2 + (C 10 H 21 )2TiCl2MgCl2 + MgTiCl6 Nonyltitanium chloride - magnesium chloride complex

[0112] Step 2.1: Add 100 ml of toluene into a 500 ml reaction flask. Protect with nitrogen, stir and cool down the temperature. Control the temperature of the reaction mixture between -20°C and -10°C. First, add 18.8 g (0.1 mol) of anhydrous titanium tetrachloride, and then slowly dropwise add a solution of 0.15 mol of nonyl Grignard reagent dissolved in 200 ml of toluene. After the addition is complete, continue to stir at -20°C to -10°C for 5 hours.

[0113] Step 2.2: Concentrate under reduced pressure to remove toluene from the reaction solution obtained in Step 2.1; the concentrated residue is nonyltitanium chloride - magnesium chloride complex, about 53.1 g (wet weight).

[0114] Example 3

[0115] Prepare (trans, trans)-4-ethyl-4'-(3'',4'',5''-trifluoro)phenylbicyclohexane.

[0116]

[0117] Step 3.1: Add into a 500 ml reaction flask: 324 g of cyclohexane; a mixture of 32.4 g (0.1 mol) of (trans, cis)-4-ethyl-4'-(3'',4'',5''-trifluoro)phenylbicyclohexane (about 86%) and (trans, trans)-4-ethyl-4'-(3'',4'',5''-trifluoro)phenylbicyclohexane (about 13%). Stir and cool down the temperature to 10 - 20°C, and then add 0.16 g of ethyl zirconium chloride - magnesium chloride complex; after the addition is complete, continue to stir at 10 - 20°C for 3 hours.

[0118] Step 3.2: Add 20 g of water into the reaction solution obtained in Step 3.1, then heat to 50 - 60°C and stir for 30 minutes, and separate the layers. The obtained organic layer is washed with water twice at 50 - 60°C; each time about 50 g of water is used; the pH of the water layer after the second water wash is about 7.

[0119] Step 3.3: Concentrate the organic layer obtained after the water washing in Step 3.2 under reduced pressure to remove cyclohexane; the residue is about 38 g (wet weight). Sampling and analyzing by gas chromatography, it is found that the content of (trans, cis)-4-ethyl-4'-(3'',4'',5''-trifluoro)phenylbicyclohexane is about 4.2%; the content of (trans, trans)-4-ethyl-4'-(3'',4'',5''-trifluoro)phenylbicyclohexane is about 94.3%.

[0120] Step 3.4: Crystallize the concentrated residue obtained in Step 3.3 twice with a toluene / ethanol mixed solvent with a mass ratio of 5, and then dry the crystallized filter cake. About 26.6 g of (trans, trans)-4-ethyl-4'-(3'',4'',5''-trifluoro)phenylbicyclohexane is obtained, with a purity of about 99.6% and a (purified) yield of 82%.

[0121] Example 4:

[0122] Prepare (trans, trans)-4-propyl-4'-ethylbicyclohexane.

[0123]

[0124] Step 4.1: Add to a 500 ml reaction flask: 141.6 g of chloroform; a mixture of 47.2 g (0.2 mol) of (trans, cis)-4-propyl-4'-ethylbicyclohexane (about 53%) and (trans, trans)-4-propyl-4'-ethylbicyclohexane (about 47%). Cool the mixture to -10 to -20 °C with stirring, and then add 0.94 g of n-nonyltitanium chloride-magnesium chloride complex; after adding, continue to stir at -10 to -20 °C for 10 hours.

[0125] Step 4.2: Add 30 g of water to the reaction solution obtained in Step 4.1, then stir at room temperature for 1 hour and separate the layers. Wash the obtained organic layer with water twice at room temperature; each time about 30 g of water is used; the pH of the water layer after the second water washing is about 7.

[0126] Step 4.3: Concentrate the organic layer obtained after the water washing in Step 4.2 under reduced pressure to remove chloroform; the residue is about 55 g (wet weight). Sampling and analyzing by gas chromatography, it is found that the content of (trans, cis)-4-propyl-4'-ethylbicyclohexane is about 7.2%; the content of (trans, trans)-4-propyl-4'-ethylbicyclohexane is about 92.5%.

[0127] Step 4.4: Crystallize the concentrated residue obtained in Step 4.3 three times with isopropanol with a mass ratio of 4, and then dry the crystallized filter cake. About 33.5 g of (trans, trans)-4-propyl-4'-ethylbicyclohexane is obtained, with a purity of about 99.8% and a (purified) yield of 71%.

[0128] Although the illustrative embodiments have been shown and described, those skilled in the art should understand that the above embodiments should not be construed as a limitation on the present application, and that the embodiments can be changed, substituted, and modified without departing from the spirit, principles, and scope of the present application.

Claims

1. A method for purifying trans-1,4-cyclohexyl organic compounds, comprising: providing a composite catalyst, which is one or both of an ethyl zirconium chloride-magnesium chloride complex and a n-nonyl titanium chloride-magnesium chloride complex; adding a mixed system containing trans-1,4-cyclohexyl organic compounds and cis-1,4-cyclohexyl organic compounds into a first solvent under a protective atmosphere for mixing, and after mixing, adding the composite catalyst for cyclohexyl transposition reaction to convert the cis-1,4-cyclohexyl organic compounds into the trans-1,4-cyclohexyl organic compounds to obtain a product, wherein the first solvent is one or a mixture of two or more of petroleum ether, cyclohexane, methylcyclohexane, benzene, toluene, xylene, dichloromethane, 1,2-dichloroethane, chloroform, and carbon tetrachloride; the trans-1,4-cyclohexyl organic compound is one of (trans, trans)-4-ethyl-4'-(3'',4'',5''-trifluoro)phenylbicyclohexane and (trans, trans)-4-propyl-4'-ethylbicyclohexane; the cis-1,4-cyclohexyl organic compound is one of (trans, cis)-4-ethyl-4'-(3'',4'',5''-trifluoro)phenylbicyclohexane and (trans, cis)-4-propyl-4'-ethylbicyclohexane; wherein the step of providing the composite catalyst includes: adding an anhydrous chloride salt into a second solvent under a protective atmosphere, and then adding a solution of a Grignard reagent of a straight-chain alkyl chloride, the Grignard reagent of the straight-chain alkyl chloride being one or both of a chloroethane Grignard reagent and a chlorononane Grignard reagent, the solution of the Grignard reagent of the straight-chain alkyl chloride including a third solvent, and the anhydrous chloride salt being one or both of anhydrous zirconium tetrachloride and anhydrous titanium tetrachloride; removing the second solvent and the third solvent from the catalytic system to obtain a composite catalyst, wherein the second solvent is one or a mixture of two or more of petroleum ether, cyclohexane, methylcyclohexane, benzene, toluene, and xylene, and the third solvent is one or a mixture of two or more of ether, tetrahydrofuran, methyltetrahydrofuran, petroleum ether, cyclohexane, methylcyclohexane, benzene, toluene, and xylene; based on the total molar amount of the catalytic system, the molar percentage content of the anhydrous chloride salt is A%, and the molar percentage content of the Grignard reagent of the straight-chain alkyl chloride is B%, and 1.0 ≤ B / A ≤ 1.5; based on the total mass of the first solvent, the mixed system, and the composite catalyst, the mass percentage content of the first solvent is C%, and the mass percentage content of the mixed system is D%, and 3 ≤ C / D ≤ 10; based on the total mass of the first solvent, the mixed system, and the composite catalyst, the mass percentage content of the mixed system is D%, and the mass percentage content of the composite catalyst is E%, and 0.5% ≤ E / D ≤ 2%; In the step of providing the composite catalyst, the temperature is controlled to be -20°C to 10°C; in the process of adding a mixed system containing trans-1,4-cyclohexyl organic compounds and cis-1,4-cyclohexyl organic compounds to the first solvent and mixing under a protective atmosphere, the temperature is controlled to be -20°C to 10°C; In the process of the cyclohexyl rearrangement reaction, the temperature is controlled to be -20°C to 10°C.

2. The method according to claim 1, wherein It also includes: In the process of the cyclohexyl rearrangement reaction, the reaction time is controlled to be 3 hours to 10 hours.

3. The method according to claim 1 further comprises: Crystallize the product.

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