CN102408284A - Method for converting cis-substituted cyclohexyl in organic molecules into trans-substituted cyclohexyl - Google Patents
Method for converting cis-substituted cyclohexyl in organic molecules into trans-substituted cyclohexyl Download PDFInfo
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Abstract
The invention relates to a method for converting cis-substituted cyclohexyl into trans-substituted cyclohexyl. The cis-substituted cyclohexyl has a structural formula shown in the specifications, wherein R and R' are the same or different and are an H atom, fatty hydrocarbyl with 1 to 10 carbon atoms, or aromatic hydrocarbyl with 1 to 10 carbon atoms; X and X' are the same or different and are an H element, 1 to 3 halogens, cyan, alkyl, alkoxy, trifluoromethyl or trifluoromethoxy; a catalyst converted from an isomer is weakened aluminum trichloride of which the activity is weakened by a weakening additive, or tetrachloroaluminate; and the reaction temperature is between -20 and +50 DEG C. The conversion method is simple and practicable, other isomerization side reactions in the cyclohexyl conversion process can be effectively inhibited when cyclohexyl conversion reaction is performed, a few isomerization byproducts are generated, yield is high, and a wide application prospect is achieved.
Description
Technical field
The present invention relates to a kind of transposition method of organic cpds cis-trans-isomer, particularly the cis substituted cyclohexyl is converted into the method for trans substituted cyclohexyl.
Background technology
The organism that contains one or more substituted cyclohexyls is one type of extremely useful material.The molecule of used liquid crystal monomer in the current liquid crystal material all contains one even a plurality of substituted cyclohexyl more than 70%., in the preparation process, often have along anti-isomers to generate simultaneously at this quasi-molecule, wherein trans product just can be used in the liquid crystal, and cis-product is a by product, generally accounts for the 30%-60% of total recovery, need remove.In removing the process of cis-product, can lose more trans product simultaneously, cause the production cost of this type of liquid crystal monomer to improve greatly.
Therefore, the cis-structure of the substituted cyclohexyl in the organic molecule, being converted into transconfiguration (promptly hereinafter said " transposition "), keeping simultaneously stablizing of other groups in the molecule constant again, is a very important technology that using value is also arranged very much.In general, when a side of cyclohexyl contains phenyl ring equiconjugate group, than being easier to carry out transposition.
In existing cyclohexyl transposition technology and patent, it is that catalyzer carries out transposition that a kind of method is to use Lewis acid such as aluminum trichloride (anhydrous).But there is defective in this technology, and when carrying out transposition, aluminum chloride also can cause other groups in the molecular structure that complicated isomerization side reaction takes place, and makes part material be converted into miscellaneous, nugatory impurity.When containing these substituted radicals such as halogen (like fluorine), cyanic acid in the molecule of transposition, the isomerization side reaction that aluminum chloride causes is more.In order to remove these impurity, in the process of purified product, to lose yield.
Patent CN00123925.2 discloses a kind of Lewis acid that uses passivation carries out the isomer transposition as catalyzer method; Formed the activity that complex compound has reduced lewis acid catalyst thereby principle is anhydrous A1C13 and ethers; In reaction process, hexanaphthene and phenyl ring form the midbody of two dimensional structure, eliminate cis-trans-isomer; Reset then, generate stable trans-isomer(ide).But not enough below this method exists: 1. this method is only applicable to the method for transformation of the cis-trans-isomer of alkyl-cyclohexyl benzene derivative.2. the transposition catalyst consumption is too big in this method, has increased the complex compound that inactive catalyst in production cost 3. these methods is merely aluminum chloride and ethers, and for different substituted cyclohexyl verivates, the selection of catalyst deactivation is limited.4. the temperature of translocation reaction is-15 ℃～5 ℃, and the tolerance of reaction pair temperature is not strong.
Given this special proposition the present invention.
Summary of the invention
The objective of the invention is to overcome the deficiency of above-mentioned technology and provide a kind of the cis substituted cyclohexyl is converted into the method for trans substituted cyclohexyl, this method is applicable to all organic translocation reactions of substituted cyclohexyl that contain.
For realizing above-mentioned purpose, the present invention adopts following technical scheme:
A kind of the cis substituted cyclohexyl is converted into the method for trans substituted cyclohexyl, wherein: the structural formula of cis substituted cyclohexyl does
Wherein R, R ' are identical or different, for H atom, carbonatoms are that 1～10 aliphatic group or carbonatoms are 3～10 aryl radical;
X, X ' are identical or different, are H element, 1～3 halogen, cyanic acid, alkyl, alkoxyl group, trifluoromethyl or trifluoromethoxy;
Catalyzer used in this method is: weakened active reduction aluminum chloride or tetrachloro aluminate with the reduction additive.
According to aforesaid method, wherein, described tetrachloro aluminate is tetrachloro-lithium aluminate, sodium terachloroaluminate, tetrachloro potassium aluminate or tetrachloro iron aluminate could, preferred tetrachloro-lithium aluminate.
According to aforesaid method, wherein, said reduction additive is the salt of the organism, alkali metal halide or the organic bases that contain nitro.
According to aforesaid method, wherein, the said organism that contains nitro is oil of mirbane, Nitromethane 99Min., nitroethane, nitro-chlorobenzene or dinitrobenzene, preferred oil of mirbane; Said alkali metal halide is Lithium chloride (anhydrous), sodium-chlor, Repone K or lithium fluoride, Sodium Fluoride, Potassium monofluoride, preferred Lithium chloride (anhydrous); The salt of said organic bases is the hydrogen bromide salt of hydrochloride, pyridine hydrochloride, pyridine or the triethylamine of triethylamine, the hydrochloride of preferred triethylamine.
According to aforesaid method, wherein, said catalyst consumption be main raw material mole number 1%～10%, preferred 1%～5%.
According to aforesaid method, wherein, the consumption of said reduction additive be catalyzer mole number 1%～200%.
According to aforesaid method, wherein, used conversion solvent is halohydrocarbon, aliphatic hydrocarbon, aromatic hydrocarbon or its mixture in this method.
According to aforesaid method, wherein, the temperature of reaction that adopts in this method is between-20 ℃～+ 50 ℃; Preferred 5～15 ℃.
Below be detailed description of the present invention:
A kind of the cis substituted cyclohexyl is converted into the method for trans substituted cyclohexyl, wherein: the structural formula of cis substituted cyclohexyl does
Wherein R, R ' are identical or different, for H atom, carbonatoms are that 1～10 aliphatic group or carbonatoms are 3～10 aryl radical;
X, X ' are identical or different, are H element, 1～3 halogen, cyanic acid, alkyl, alkoxyl group, trifluoromethyl or trifluoromethoxy;
Catalyzer used in this method is: weakened active reduction aluminum chloride or tetrachloro aluminate with the reduction additive.
In the structural formula of above-mentioned cis substituted cyclohexyl; R and R ' can be identical, also can be different, and can be that 3～10 aryl radical or carbonatoms are 1～10 aliphatic group for H atom, carbonatoms; Said aliphatic group can be for saturated; Also can substituting group can be had, also substituting group can be with for undersaturated.
Patent CN00123925.2 discloses a kind of complex compound that adopts Lewis acid and ethers and has carried out the method that the cis-trans-isomer of alkyl-cyclohexyl benzene derivative transforms as catalyzer.But this method is only applicable to the method for transformation of the cis-trans-isomer of alkyl-cyclohexyl benzene derivative, and applicable scope is limited; The transposition catalyst consumption is too big in this method, has increased production cost, has also brought trouble for the purification processes of title product; Inactive catalyst is merely the complex compound of aluminum chloride and ethers in this method, and for different substituted cyclohexyl verivates, the selection of catalyst deactivation is limited; This method is limited to the tolerance of temperature of reaction.
Method of the present invention is with suitable reduction additive, after the reduction of the activity of aluminum chloride, remakes the catalyzer into transposition, or directly uses the tetrachloro aluminate, like the catalyzer as transposition such as tetrachloro-lithium aluminate.
Specifically, method of the present invention adopts following two kinds of synthetic routes:
Among the present invention, the reduction additive that is adopted is the salt of the organism, alkali metal halide or the organic bases that contain nitro.
Among the present invention, the said organism that contains nitro is oil of mirbane, Nitromethane 99Min., nitroethane, nitro-chlorobenzene or dinitrobenzene, preferred oil of mirbane;
In the prior art, nitro-compound is because general toxicity is bigger, and has color, in subsequent disposal, is difficult to remove.And in the general technology report, all be to use nitro-compound as solvent, and consumption is very big, this more aggravates to have manifested its above-mentioned defective, so when the isomer translocation reaction, generally all will not adopt.Only adopt the very little nitro-compound of consumption among the present invention; Not only can make its above-mentioned defective be attenuated to the acceptable scope as far as possible; The more important thing is still can play and weaken the active effect of aluminum chloride fully, can be used as a kind of good position rotaring catalyst, in translocation reaction, play good effect and weakened active aluminum chloride with this; Transformation efficiency is improved, reduce the decomposition that raw material takes place because of side reaction.
Said alkali metal halide is Lithium chloride (anhydrous), sodium-chlor, Repone K or lithium fluoride, Sodium Fluoride, Potassium monofluoride, preferred Lithium chloride (anhydrous);
Most of metal halides since in organic solvent solvability very poor, also not with the aluminum chloride complexing, so do not have attenuation basically, also not as aluminum chloride reduction adopted report of additive or precedent.But the present invention find Lithium chloride (anhydrous), sodium-chlor, Repone K or lithium fluoride, Sodium Fluoride, Potassium monofluoride etc. can with aluminum chloride generation complexing, generate the tetrachloro aluminate, not only increased its solubleness, also played effect near 100% reduction aluminum chloride.
Said the salt of basic alkali is arranged is the hydrogen bromide salt of hydrochloride, pyridine hydrochloride, pyridine or the triethylamine of triethylamine, the hydrochloride of preferred triethylamine.
The salt of organic bases and the mixture of aluminum chloride are in a liquid state, and are called as ionic liquid, are the model mixtures that occurs in the recent period, generally are used as extraordinary reaction solvent and use; And its proportioning is a lot, and must adjust certain proportioning just has the transposition effect.Up to the present, its katalysis aspect transposition, not report or application.
Among the present invention, described tetrachloro aluminate is tetrachloro-lithium aluminate, sodium terachloroaluminate, tetrachloro potassium aluminate or tetrachloro iron aluminate could etc., preferred tetrachloro-lithium aluminate.
In the prior art; Directly also do not appear in the newspapers as position rotaring catalyst with the tetrachloro aluminate, the tetrachloro aluminate is the lower position rotaring catalyst of a kind of specific activity, with respect to aluminum trichloride catalyst; The transformation efficiency that cis-trans-isomer transforms is high, and other isomerization side reaction is few.
Among the present invention, said catalyst consumption be main raw material mole number 1%～10%, preferred 1%～5%.
Among the CN00123925.2 catalyst consumption be the main raw material mole number 0.5-1 doubly; Main raw material for identical mole number; Catalyst consumption is 10-100 times of catalyst levels among the present invention among the CN00123925.2; Not only improve production cost, reduced production efficiency, also be unfavorable for the purification processes of follow-up title product.
Among the present invention, the consumption of said reduction additive be catalyzer mole number 1%～200%.
Among the present invention, used conversion solvent is halohydrocarbon, aliphatic hydrocarbon, aromatic hydrocarbon or its mixture in this method.
The solvent of translocation reaction is merely halohydrocarbon, aliphatic hydrocarbon among the CN00123925.2, and the transposition choice of Solvent is wider among visible the present invention.
Among the present invention, the temperature of reaction that adopts in this method is between-20 ℃～+ 50 ℃; Preferred 5～15 ℃.
The scope of temperature of reaction is that the temperature of reaction interval has comprised the scope of room temperature between-20 ℃～+ 50 ℃ among the present invention, and temperature of reaction is controlled easily and realized, the tolerance of reaction pair temperature is more intense.The temperature of reaction of patent CN00123925.2 is-15 ℃～+ 5 ℃, and the temperature range of temperature of reaction is in 20 ℃, and scope is smaller, and a little less than room temperature, the tolerance of reaction pair temperature is not strong.
Compared with prior art, beneficial effect of the present invention is:
1. the suitability of the method for translocation reaction is very wide among the present invention, and substituent R no longer only is defined as alkyl, can also be the H element, or one to a plurality of saturated or undersaturated, have and replace or the aliphatic hydrocarbon or the arene substituting group of unsubstituted group.
2. the kind of catalyzer is more, and for different cyclohexyl derivatives, catalyzer has bigger selectivity in the translocation reaction.
3. catalyst consumption is less among the present invention, both can reduce production costs, and helps the purification processes of later stage target compound again.
4. the temperature of translocation reaction is that the scope of temperature of reaction is big, and has comprised the scope of room temperature between-20 ℃-+50 ℃ among the present invention, and temperature of reaction is controlled easily and realized, the tolerance of reaction pair temperature is better.
5. the translocation reaction among the present invention is fabulous to the restraining effect of isomerization side reaction; Tolerable reaction time range is very long; Even after having experienced the reaction times more than 120 hours, still have only isomery by product seldom, can carry out the analysis and the aftertreatment of quality at leisure.
6. present method can suppress the generation of other isomerization side reaction in the cyclohexyl transposition process effectively when carrying out the reaction of cyclohexyl transposition; Not only effective to molecule simple in structure, simultaneously also the molecule of the more complicated that contains substituted radicals such as halogen (like fluorine), cyanic acid there is obvious effects.
7. after the method among use the present invention; Can be so that contain the material of substituted cyclohexyl; Other impurity that produced by isomerization reaction in translocation reaction but maintain ratio seldom all the time, and the difficulty when purifying trans product in the later stage so also descends with loss greatly.Carry out transposition with simple use aluminum trichloride (anhydrous) and compare, overall yield has obtained very big lifting.
Transposition method of the present invention is simple, and yield is very high, is with a wide range of applications.
Embodiment
Through specific embodiment summary of the invention of the present invention is further explained below, but therefore do not limited content of the present invention.
The transposition (cis in the raw material: trans=70: 30) of synthetic instance 1:4-(4 '-propyl group cyclohexyl) phenylcyclohexane.
Embodiment 1
Adopt the synthetic route of synthetic instance 1.Use aluminum trichloride (anhydrous)-triethylamine hydrochloride mixture to be catalyzer; Solvent is a sherwood oil, and temperature is 5-10 ℃.
Experimental implementation:
In the 100ml there-necked flask, add triethylamine and the 60ml sherwood oil (90-120 ℃) of 0.1mol earlier.Stir the aqueous hydrochloric acid that accurately drips 0.105mol down then.Drip off back stirring at room 30 minutes.Be heated to sherwood oil under stirring and reflux, and divide the clean water that refluxes and take out of with water trap.To anhydrous telling, be cooled to room temperature, stir the aluminum trichloride (anhydrous) that adds 0.105mol down.Added the continued stirring at room 1 hour.Stop stirring, find that solid all dissolves, reaction solution is divided into two-layer: the upper strata is colourless sherwood oil; Lower floor is a brown liquid.When taking aluminum trichloride (anhydrous)-triethylamine hydrochloride mixture, directly draw lower floor with dropper.
Cis: trans=70: 30 material sample oven dry, thoroughly remove clean moisture and polar solvent.Get wherein 10g, join in the 250ml there-necked flask, be stirred to the solid dissolving under the room temperature with the sherwood oil (90-120 ℃) of 100ml.Be cooled to 5-10 ℃ of liquid temperature.Aluminum trichloride (anhydrous)-triethylamine hydrochloride the mixture that adds 0.5g rapidly.Keep 5-10 ℃ of argon shield, stirring and liquid temperature after adding.Take out about 5ml reaction solution at regular intervals, with the 5% salt acid elution of 20ml, wash 3 times with the tap water of 20ml the back earlier.Organic layer after washing finishes carries out gas chromatographic detection, measures the content of wherein cis-product, trans product and isomerizing impurity (a plurality of impurity summation).
Experimental result:
After transposition amounts to 5 hours, cis: trans: impurity=40: 59: 1
After transposition amounts to 10 hours, cis: trans: impurity=18: 78: 3
After transposition amounts to 15 hours, cis: trans: impurity=7: 89: 4
After transposition amounts to 20 hours, cis: trans: impurity=3: 92: 5
Embodiment 2
Adopt the synthetic route of synthetic instance 1.Use aluminum trichloride (anhydrous)-oil of mirbane mixture to be catalyzer; Solvent is a methylene dichloride, and temperature is 10-15 ℃.
Experimental implementation:
Cis: trans=70: 30 material sample oven dry, it is subsequent use thoroughly to remove clean moisture and polar solvent.
In the there-necked flask of 100ml, add the methylene dichloride of 60ml and the oil of mirbane of 0.50g.The aluminum trichloride (anhydrous) that adds 0.5g under the room temperature rapidly.Keep room temperature and argon shield after adding, stir more than 1 hour.Be cooled to reacting liquid temperature 10-15 ℃ under stirring, argon shield adds the above-mentioned subsequent use material sample of 30g down rapidly.Keep 10-15 ℃ of stirring and liquid temperature.Take out about 5ml reaction solution at regular intervals, with the 5% salt acid elution of 20ml, wash 3 times with the tap water of 20ml the back earlier.Organic layer after washing finishes carries out gas chromatographic detection, measures the content of wherein cis-product, trans product and isomerizing impurity (a plurality of impurity summation).
Experimental result:
After transposition amounts to 5 hours, cis: trans: impurity=34: 65: 1
After transposition amounts to 10 hours, cis: trans: impurity=9: 90: 1
After transposition amounts to 15 hours, cis: trans: impurity=3: 94: 3
After transposition amounts to 20 hours, cis: trans: impurity=2: 94: 4
Embodiment 3
Adopt the synthetic route of synthetic instance 1.Use aluminum trichloride (anhydrous)-Lithium chloride (anhydrous) mixture to be catalyzer; Solvent is a methylene dichloride, and temperature is 5-10 ℃.
Experimental implementation:
Cis: trans=70: 30 material sample oven dry, it is subsequent use thoroughly to remove clean moisture and polar solvent.
In the there-necked flask of 100ml, add the methylene dichloride of 60ml.After the argon replaces, add the aluminum trichloride (anhydrous) of 0.3g under the room temperature rapidly; Lithium chloride (anhydrous) with 0.14g.Keep room temperature and argon shield after adding, stir more than 1 hour.Be cooled to reacting liquid temperature 5-10 ℃ under stirring, argon shield adds the above-mentioned subsequent use material sample of 30g down rapidly.Keep 5-10 ℃ of stirring and liquid temperature.Take out about 5ml reaction solution at regular intervals, with the 5% salt acid elution of 20ml, wash 3 times with the tap water of 20ml the back earlier.Organic layer after washing finishes carries out gas chromatographic detection, measures the content of wherein cis-product, trans product and isomerizing impurity (a plurality of impurity summation).
Experimental result:
After transposition amounts to 5 hours, cis: trans: impurity=30: 69: 1
After transposition amounts to 10 hours, cis: trans: impurity=3: 96: 1
After transposition amounts to 15 hours, cis: trans: impurity=3: 95: 2
After transposition amounts to 20 hours, cis: trans: impurity=2: 95: 3
Embodiment 4
Adopt the synthetic route of synthetic instance 1.Use anhydrous tetrachloro-lithium aluminate to be catalyzer, solvent is methylene dichloride, perhydronaphthalene, and temperature is 5-10 ℃.
Experimental implementation (option A):
Cis: trans=70: 30 material sample oven dry, it is subsequent use thoroughly to remove clean moisture and polar solvent.
In the there-necked flask of 100ml, add the perhydronaphthalene of 60ml.After the argon replaces, add the aluminum trichloride (anhydrous) of 0.3g under the room temperature rapidly; Lithium chloride (anhydrous) with 0.14g.After adding, the dimension argon shield is heated to 180 ℃, and the fusing of bottle end solid is stirred more than 1 hour.Argon shield and stirring are lowered the temperature near room temperature down, and a bottle end solid solidifies again.
Stop to stir, under the argon shield, pour out most liquid perhydronaphthalenes rapidly with decantation earlier, still stay in the bottle bottle end solid; The methylene dichloride that adds 60ml then rapidly.Recover to stir and argon shield, be cooled to reacting liquid temperature 5-10 ℃, add the above-mentioned subsequent use material sample of 30g rapidly.Continue to keep 5-10 ℃ of stirring and liquid temperature.Take out about 5ml reaction solution at regular intervals, with the 5% salt acid elution of 20ml, wash 3 times with the tap water of 20ml the back earlier.Organic layer after washing finishes carries out gas chromatographic detection, measures the content of wherein cis-product, trans product and isomerizing impurity (a plurality of impurity summation).
Experimental result:
After transposition amounts to 5 hours, cis: trans: impurity=32: 68: 0
After transposition amounts to 10 hours, cis: trans: impurity=7: 92: 1
After transposition amounts to 15 hours, cis: trans: impurity=4: 94: 2
After transposition amounts to 20 hours, cis: trans: impurity=4: 94: 2
Experimental implementation (option b):
Cis: trans=70: 30 material sample oven dry, thoroughly remove clean moisture and polar solvent.Get wherein 10g, join in the 100ml there-necked flask with the sherwood oil (90-120 ℃) of 60ml.After the argon replaces, be stirred to most of solid dissolving under the room temperature.Under the argon shield, be cooled to 5-10 ℃ of liquid temperature, add the anhydrous tetrachloro-lithium aluminate of 0.5g rapidly.Continue to keep 5-10 ℃ of argon shield, stirring and liquid temperature.Take out about 5ml reaction solution at regular intervals, with the 5% salt acid elution of 20ml, wash 3 times with the tap water of 20ml the back earlier.Organic layer after washing finishes carries out gas chromatographic detection, measures the content of wherein cis-product, trans product and isomerizing impurity (a plurality of impurity summation).
Experimental result:
After transposition amounts to 5 hours, cis: trans: impurity=32: 68: 0
After transposition amounts to 10 hours, cis: trans: impurity=10: 90: 0
After transposition amounts to 15 hours, cis: trans: impurity=6: 93: 1
After transposition amounts to 20 hours, cis: trans: impurity=4: 94: 2
Embodiment 5
Adopt the synthetic route of synthetic instance 1.Use aluminum trichloride (anhydrous)-pyridine hydrochloride mixture to be catalyzer; Solvent is a sherwood oil, and temperature is 5-10 ℃.
Experimental implementation:
In the 100ml there-necked flask, add pyridine and the 60ml sherwood oil (90-120 ℃) of 0.1mol earlier.Stir the hydrochloride aqueous solution that accurately drips 0.105mol down then.Drip off back stirring at room 30 minutes.Be heated to sherwood oil under stirring and reflux, and divide the clean water that refluxes and take out of with water trap.To anhydrous telling, be cooled to room temperature, stir the aluminum trichloride (anhydrous) that adds 0.105mol down.Added the continued stirring at room 1 hour.Stop stirring, find that solid all dissolves, reaction solution is divided into two-layer: the upper strata is colourless sherwood oil; Lower floor is aluminum trichloride (anhydrous)-pyridine hydrochloride mixture.When taking aluminum trichloride (anhydrous)-pyridine hydrochloride mixture, directly draw lower floor with dropper.
Cis: trans=70: 30 material sample oven dry, thoroughly remove clean moisture and polar solvent.Get wherein 20g, join in the 500ml there-necked flask, be stirred to the solid dissolving under the room temperature with the sherwood oil (90-120 ℃) of 180ml.Be cooled to 5-10 ℃ of liquid temperature.Aluminum trichloride (anhydrous)-pyridine hydrochloride the mixture that adds 0.1g rapidly.Keep 5-10 ℃ of argon shield, stirring and liquid temperature after adding.Take out about 5ml reaction solution at regular intervals, with the 5% salt acid elution of 20ml, wash 3 times with the tap water of 20ml the back earlier.Organic layer after washing finishes carries out gas chromatographic detection, measures the content of wherein cis-product, trans product and isomerizing impurity (a plurality of impurity summation).
Experimental result:
After transposition amounts to 5 hours, cis: trans: impurity=45: 44: 1
After transposition amounts to 10 hours, cis: trans: impurity=24: 74: 2
After transposition amounts to 15 hours, cis: trans: impurity=10: 86: 4
After transposition amounts to 20 hours, cis: trans: impurity=6: 89: 5
Embodiment 6
Adopt the synthetic route of synthetic instance 1.Use aluminum trichloride (anhydrous)-Nitromethane 99Min. mixture to be catalyzer; Solvent is a methylene dichloride, and temperature is 5-10 ℃.
Experimental implementation:
Cis: trans=70: 30 material sample oven dry, it is subsequent use thoroughly to remove clean moisture and polar solvent.
In the there-necked flask of 100ml, add the methylene dichloride of 60ml and the Nitromethane 99Min. of 0.25g.The aluminum trichloride (anhydrous) that adds 0.5g under the room temperature rapidly.Keep room temperature and argon shield after adding, stir more than 1 hour.Be cooled to reacting liquid temperature 5-10 ℃ under stirring, argon shield adds the above-mentioned subsequent use material sample of 30g down rapidly.Keep 5-10 ℃ of stirring and liquid temperature.Take out about 5ml reaction solution at regular intervals, with the 5% salt acid elution of 20ml, wash 3 times with the tap water of 20ml the back earlier.Organic layer after washing finishes carries out gas chromatographic detection, measures the content of wherein cis-product, trans product and isomerizing impurity (a plurality of impurity summation).
Experimental result:
After transposition amounts to 5 hours, cis: trans: impurity=41: 58: 1
After transposition amounts to 10 hours, cis: trans: impurity=18: 81: 1
After transposition amounts to 15 hours, cis: trans: impurity=7: 90: 3
After transposition amounts to 20 hours, cis: trans: impurity=4: 92: 4
Embodiment 7
Adopt the synthetic route of synthetic instance 1.Use aluminum trichloride (anhydrous)-anhydrous potassium fluoride mixture to be catalyzer; Solvent is a methylene dichloride, and temperature is 5-10 ℃.
Experimental implementation:
Cis: trans=70: 30 material sample oven dry, it is subsequent use thoroughly to remove clean moisture and polar solvent.
In the there-necked flask of 100ml, add the methylene dichloride of 60ml.After the argon replaces, add the aluminum trichloride (anhydrous) of 0.3g under the room temperature rapidly; Anhydrous potassium fluoride with 0.20g.Keep room temperature and argon shield after adding, stir more than 1 hour.Be cooled to reacting liquid temperature 5-10 ℃ under stirring, argon shield adds the above-mentioned subsequent use material sample of 30g down rapidly.Keep 5-10 ℃ of stirring and liquid temperature.Take out about 5ml reaction solution at regular intervals, with the 5% salt acid elution of 20ml, wash 3 times with the tap water of 20ml the back earlier.Organic layer after washing finishes carries out gas chromatographic detection, measures the content of wherein cis-product, trans product and isomerizing impurity (a plurality of impurity summation).
Experimental result:
After transposition amounts to 5 hours, cis: trans: impurity=34: 65: 1
After transposition amounts to 10 hours, cis: trans: impurity=13: 86: 1
After transposition amounts to 15 hours, cis: trans: impurity=7: 90: 3
After transposition amounts to 20 hours, cis: trans: impurity=5: 92: 3
Embodiment 8
Adopt the synthetic route of synthetic instance 1.Use anhydrous tetrachloro potassium aluminate to be catalyzer, solvent is a methylene dichloride, and temperature is 5-10 ℃.
Experimental implementation:
Cis: trans=70: 30 material sample oven dry, thoroughly remove clean moisture and polar solvent.Get wherein 10g, join in the 100ml there-necked flask with the sherwood oil (90-120 ℃) of 60ml.After the argon replaces, be stirred to most of solid dissolving under the room temperature.Under the argon shield, be cooled to 5-10 ℃ of liquid temperature, add the anhydrous tetrachloro potassium aluminate of 0.5g rapidly.Continue to keep 5-10 ℃ of argon shield, stirring and liquid temperature.Take out about 5ml reaction solution at regular intervals, with the 5% salt acid elution of 20ml, wash 3 times with the tap water of 20ml the back earlier.Organic layer after washing finishes carries out gas chromatographic detection, measures the content of wherein cis-product, trans product and isomerizing impurity (a plurality of impurity summation).
Experimental result:
After transposition amounts to 5 hours, cis: trans: impurity=37: 63: 0
After transposition amounts to 10 hours, cis: trans: impurity=11: 89: 0
After transposition amounts to 15 hours, cis: trans: impurity=7: 92: 1
After transposition amounts to 20 hours, cis: trans: impurity=3: 95: 2
Synthetic instance 2: [4 '-(4 "-the propyl group cyclohexyl) cyclohexyl]-3, the transposition of 4-two fluorobenzene (cis in the raw material: trans=70: 30).
Embodiment 9
Adopt the synthetic route of synthetic instance 2.Use aluminum trichloride (anhydrous)-triethylamine hydrochloride mixture to be catalyzer, wherein the mol ratio of aluminum trichloride (anhydrous)-triethylamine hydrochloride is 1.0: 2.0; Solvent is a sherwood oil, and temperature is 0-10 ℃.
Experimental implementation:
In the 100ml there-necked flask, add triethylamine and the 60ml sherwood oil (90-120 ℃) of 0.1mol earlier.Stir the aqueous hydrochloric acid that accurately drips 0.105mol down then.Drip off back stirring at room 30 minutes.Be heated to sherwood oil under stirring and reflux, and divide the clean water that refluxes and take out of with water trap.To anhydrous telling, be cooled to room temperature, stir the aluminum trichloride (anhydrous) that adds 0.05mol down.Added the continued stirring at room 1 hour.Stop stirring, find that solid all dissolves, reaction solution is divided into two-layer: the upper strata is colourless sherwood oil; Lower floor is a brown liquid.When taking aluminum trichloride (anhydrous)-triethylamine hydrochloride mixture, directly draw lower floor with dropper.
Cis: trans=70: 30 material sample oven dry, thoroughly remove clean moisture and polar solvent.Get wherein 10g, join in the 250ml there-necked flask with the sherwood oil (90-120 ℃) of 100ml.After the argon replaces, be stirred to the solid dissolving under the room temperature.Under the argon shield, be cooled to 0-10 ℃ of liquid temperature.Aluminum trichloride (anhydrous)-triethylamine hydrochloride the mixture that adds 0.5g rapidly.Keep 0-10 ℃ of stirring and liquid temperature.Take out about 5ml reaction solution at regular intervals, with the 5% salt acid elution of 20ml, wash 3 times with the tap water of 20ml the back earlier.Organic layer after washing finishes carries out gas chromatographic detection, measures the content of wherein cis-product, trans product and isomerizing impurity (a plurality of impurity summation).
Experimental result:
After transposition amounts to 5 hours, cis: trans: impurity=52: 45: 3
After transposition amounts to 10 hours, cis: trans: impurity=36: 57: 7
After transposition amounts to 15 hours, cis: trans: impurity=24: 65: 11
After transposition amounts to 20 hours, cis: trans: impurity=17: 69: 14
After transposition amounts to 30 hours, cis: trans: impurity=11: 72: 17
Embodiment 10
Adopt the synthetic route of synthetic instance 2.Use aluminum trichloride (anhydrous)-oil of mirbane to be mixed into the catalyzer thing, wherein the mol ratio of aluminum trichloride (anhydrous)-oil of mirbane is 1.0: 11; Solvent is a methylene dichloride, and temperature is 5-15 ℃.
Experimental implementation:
Cis: trans=70: 30 material sample oven dry, it is subsequent use thoroughly to remove clean moisture and polar solvent.
In the there-necked flask of 100ml, add the methylene dichloride of 60ml and the oil of mirbane of 0.50g.After the argon replaces, add the aluminum trichloride (anhydrous) of 0.5g under the room temperature rapidly.Keep room temperature and argon shield after adding, stir more than 1 hour.Be cooled to reacting liquid temperature 5-15 ℃ under stirring, add the above-mentioned subsequent use material sample of 30g rapidly.Continue to keep 5-15 ℃ of stirring and liquid temperature.Take out about 5ml reaction solution at regular intervals, with the 5% salt acid elution of 20ml, wash 3 times with the tap water of 20ml the back earlier.Organic layer after washing finishes carries out gas chromatographic detection, measures the content of wherein cis-product, trans product and isomerizing impurity (a plurality of impurity summation).
Experimental result:
After transposition amounts to 5 hours, cis: trans: impurity=57: 41: 2
After transposition amounts to 10 hours, cis: trans: impurity=39: 58: 3
After transposition amounts to 15 hours, cis: trans: impurity=25: 70: 5
After transposition amounts to 20 hours, cis: trans: impurity=16: 77: 7
Embodiment 11
Adopt the synthetic route of synthetic instance 2.Use aluminum trichloride (anhydrous)-Lithium chloride (anhydrous) mixture to be catalyzer.Wherein aluminum trichloride (anhydrous)-Lithium chloride (anhydrous) is 1.0: 1.5 in molar ratio; Solvent is a chloroform, and temperature is 15-25 ℃.
Experimental implementation:
Cis: trans=70: 30 material sample oven dry, it is subsequent use thoroughly to remove clean moisture and polar solvent.
In the there-necked flask of 100ml, add the chloroform of 60ml.After the argon replaces, add the aluminum trichloride (anhydrous) of 0.3g under the room temperature rapidly; Lithium chloride (anhydrous) with 0.14g.Keep room temperature and argon shield after adding, stir more than 1 hour.Be cooled to reacting liquid temperature 15-25 ℃ under stirring, add the above-mentioned subsequent use material sample of 30g rapidly.Continue to keep 15-25 ℃ of stirring and liquid temperature.Take out about 5ml reaction solution at regular intervals, with the 5% salt acid elution of 20ml, wash 3 times with the tap water of 20ml the back earlier.Organic layer after washing finishes carries out gas chromatographic detection, measures the content of wherein cis-product, trans product and isomerizing impurity (a plurality of impurity summation).
Experimental result:
After transposition amounts to 5 hours, cis: trans: impurity=54: 45: 1
After transposition amounts to 10 hours, cis: trans: impurity=40: 59: 1
After transposition amounts to 15 hours, cis: trans: impurity=28: 70: 2
After transposition amounts to 20 hours, cis: trans: impurity=17: 79: 4
Embodiment 12
Adopt the synthetic route of synthetic instance 2.Use anhydrous tetrachloro-lithium aluminate to be catalyzer, solvent is methylene dichloride, perhydronaphthalene, and temperature is 15-50 ℃.
Experimental implementation (option A):
Cis: trans=70: 30 material sample oven dry, it is subsequent use thoroughly to remove clean moisture and polar solvent.
In the there-necked flask of 100ml, add the perhydronaphthalene of 60ml.After the argon replaces, add the aluminum trichloride (anhydrous) of 0.3g under the room temperature rapidly; Lithium chloride (anhydrous) with 0.14g.After adding, keep argon shield, be heated to 180 ℃, the fusing of bottle end solid is stirred more than 1 hour.Argon shield and stirring are lowered the temperature near room temperature down, and a bottle end solid solidifies again.
Stop to stir, under the argon shield, pour out most liquid perhydronaphthalenes rapidly with decantation earlier, still stay in the bottle bottle end solid; The methylene dichloride that adds 60ml then rapidly.Recover to stir and argon shield, be cooled to reacting liquid temperature 25-50 ℃, add the above-mentioned subsequent use material sample of 30g rapidly.Keep 25-50 ℃ of stirring and liquid temperature.Take out about 5ml reaction solution at regular intervals, with the 5% salt acid elution of 20ml, wash 3 times with the tap water of 20ml the back earlier.Organic layer after washing finishes carries out gas chromatographic detection, measures the content of wherein cis-product, trans product and isomerizing impurity (a plurality of impurity summation).
Experimental result:
After transposition amounts to 5 hours, cis: trans: impurity=54: 45: 1
After transposition amounts to 10 hours, cis: trans: impurity=43: 56: 1
After transposition amounts to 15 hours, cis: trans: impurity=28: 70: 2
After transposition amounts to 20 hours, cis: trans: impurity=17: 79: 4
Experimental implementation (option b):
Cis: trans=70: 30 material sample oven dry, thoroughly remove clean moisture and polar solvent.Get wherein 10g, join in the 100ml there-necked flask with the sherwood oil (90-120 ℃) of 60ml.After the argon replaces, be stirred to most of solid dissolving under the room temperature.Under the argon shield, be cooled to 15-25 ℃ of liquid temperature, add the anhydrous tetrachloro-lithium aluminate of 0.5g rapidly.Keep 5-10 ℃ of stirring and liquid temperature.Take out about 5ml reaction solution at regular intervals, with the 5% salt acid elution of 20ml, wash 3 times with the tap water of 20ml the back earlier.Organic layer after washing finishes carries out gas chromatographic detection, measures the content of wherein cis-product, trans product and isomerizing impurity (a plurality of impurity summation).
Experimental result:
After transposition amounts to 5 hours, cis: trans: impurity=55: 45: 0
After transposition amounts to 10 hours, cis: trans: impurity=43: 56: 1
After transposition amounts to 15 hours, cis: trans: impurity=30: 68: 2
After transposition amounts to 20 hours, cis: trans: impurity=18: 78: 4
Embodiment 13
Adopt the synthetic route of synthetic instance 1.Use aluminum trichloride (anhydrous)-triethylamine hydrochloride mixture to be catalyzer, wherein the mol ratio of aluminum trichloride (anhydrous) and triethylamine hydrochloride is 100: 1; Solvent is a sherwood oil, temperature is-and 25-0 ℃.
Experimental implementation:
In the 100ml there-necked flask, add triethylamine and the 60ml sherwood oil (90-120 ℃) of 0.001mol earlier.Stir the aqueous hydrochloric acid that accurately drips 0.001mol down then.Drip off back stirring at room 30 minutes.Be heated to sherwood oil under stirring and reflux, and divide the clean water that refluxes and take out of with water trap.To anhydrous telling, be cooled to room temperature, stir the aluminum trichloride (anhydrous) that adds 0.1mol down.Added the continued stirring at room 1 hour.Stop stirring, find that solid all dissolves, reaction solution is divided into two-layer: the upper strata is colourless sherwood oil; Lower floor is a brown liquid.When taking aluminum trichloride (anhydrous)-triethylamine hydrochloride mixture, directly draw lower floor with dropper.
Cis: trans=70: 30 material sample oven dry, thoroughly remove clean moisture and polar solvent.Get wherein 10g, join in the 250ml there-necked flask, be stirred to the solid dissolving under the room temperature with the sherwood oil (90-120 ℃) of 100ml.Be cooled to liquid temperature-20--10 ℃.Aluminum trichloride (anhydrous)-triethylamine hydrochloride the mixture that adds 0.12g rapidly.Keep argon shield, stirring and liquid temperature-20-0 ℃ after adding.Take out about 5ml reaction solution at regular intervals, with the 5% salt acid elution of 20ml, wash 3 times with the tap water of 20ml the back earlier.Organic layer after washing finishes carries out gas chromatographic detection, measures the content of wherein cis-product, trans product and isomerizing impurity (a plurality of impurity summation).
Experimental result:
After transposition amounts to 5 hours, cis: trans: impurity=43: 55: 2
After transposition amounts to 10 hours, cis: trans: impurity=26: 70: 4
After transposition amounts to 15 hours, cis: trans: impurity=23: 72: 5
After transposition amounts to 20 hours, cis: trans: impurity=22: 72: 6.
Claims (8)
1. one kind is converted into the method for trans substituted cyclohexyl with the cis substituted cyclohexyl, and it is characterized in that: the structural formula of cis substituted cyclohexyl does
Wherein R, R ' are identical or different, for H atom, carbonatoms are that 1～10 aliphatic group or carbonatoms are 1～10 aryl radical;
X, X ' are identical or different, are H element, 1～3 halogen, cyanic acid, alkyl, alkoxyl group, trifluoromethyl or trifluoromethoxy;
Catalyzer used in this method is: weakened active reduction aluminum chloride, perhaps tetrachloro aluminate with the reduction additive.
2. method according to claim 1 is characterized in that, described tetrachloro aluminate is tetrachloro-lithium aluminate, sodium terachloroaluminate, tetrachloro potassium aluminate or tetrachloro iron aluminate could, preferred tetrachloro-lithium aluminate.
3. method according to claim 1 is characterized in that, said reduction additive is the salt of the organism, alkali metal halide or the organic bases that contain nitro.
4. method according to claim 3 is characterized in that, the said organism that contains nitro is oil of mirbane, Nitromethane 99Min., nitroethane, nitro-chlorobenzene or dinitrobenzene, preferred oil of mirbane; Said alkali metal halide is Lithium chloride (anhydrous), sodium-chlor, Repone K or lithium fluoride, Sodium Fluoride, Potassium monofluoride, preferred Lithium chloride (anhydrous); The salt of said organic bases is the hydrogen bromide salt of hydrochloride, pyridine hydrochloride, pyridine or the triethylamine of triethylamine, the hydrochloride of preferred triethylamine.
5. according to any described method of claim 1-4, it is characterized in that, said catalyst consumption be main raw material mole number 1%～10%, preferred 1%～5%.
6. according to any described method of claim 1-4, it is characterized in that, the consumption of said reduction additive be catalyzer mole number 1%～200%.
7. according to any described method of claim 1-4, it is characterized in that used conversion solvent is halohydrocarbon, aliphatic hydrocarbon, aromatic hydrocarbon or its mixture in this method.
8. according to any described method of claim 1-4, it is characterized in that the temperature of reaction that adopts in this method is between-20 ℃～+ 50 ℃; Preferred 5～15 ℃.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103012083A (en) * | 2012-12-28 | 2013-04-03 | 上海天问化学有限公司 | Dicyclohexyl fluorinated tolane negative liquid crystal, and synthesis method and application thereof |
| CN110964538A (en) * | 2019-12-18 | 2020-04-07 | 江苏创拓新材料有限公司 | Transposition method of 1-cyclohexyl-2, 3-difluorobenzene |
| CN111393253A (en) * | 2019-01-02 | 2020-07-10 | 江苏广域化学有限公司 | Synthesis method of compound containing trans-substituted cyclohexyl |
| CN113548938A (en) * | 2020-12-23 | 2021-10-26 | 江苏广域化学有限公司 | Cis-trans-inversion method of non-terminal alkene liquid crystal monomer |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3281490A (en) * | 1962-03-02 | 1966-10-25 | British Petroleum Co | Catalyst and isomerisation process using said catalysts |
| US3954823A (en) * | 1975-06-02 | 1976-05-04 | Dow Corning Corporation | Interconversion of stereoisomeric cycloorganosiloxanes |
| CN1304914A (en) * | 2000-10-02 | 2001-07-25 | 烟台万润精细化工有限责任公司 | Transform process for cis (or trans)-isomer of alkyl cyclohexyl benzene derivative |
-
2010
- 2010-09-21 CN CN 201010289832 patent/CN102408284B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3281490A (en) * | 1962-03-02 | 1966-10-25 | British Petroleum Co | Catalyst and isomerisation process using said catalysts |
| US3954823A (en) * | 1975-06-02 | 1976-05-04 | Dow Corning Corporation | Interconversion of stereoisomeric cycloorganosiloxanes |
| CN1304914A (en) * | 2000-10-02 | 2001-07-25 | 烟台万润精细化工有限责任公司 | Transform process for cis (or trans)-isomer of alkyl cyclohexyl benzene derivative |
Non-Patent Citations (1)
| Title |
|---|
| 李锋等: "顺反异构化过程及其机理", 《化学试剂》, vol. 27, no. 1, 28 January 2005 (2005-01-28) * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103012083A (en) * | 2012-12-28 | 2013-04-03 | 上海天问化学有限公司 | Dicyclohexyl fluorinated tolane negative liquid crystal, and synthesis method and application thereof |
| CN103012083B (en) * | 2012-12-28 | 2014-12-03 | 福建省邵武市永晶化工有限公司 | Dicyclohexyl fluorinated tolane negative liquid crystal, and synthesis method and application thereof |
| CN111393253A (en) * | 2019-01-02 | 2020-07-10 | 江苏广域化学有限公司 | Synthesis method of compound containing trans-substituted cyclohexyl |
| CN111393253B (en) * | 2019-01-02 | 2022-11-29 | 江苏广域化学有限公司 | Synthesis method of compound containing trans-substituted cyclohexyl |
| CN110964538A (en) * | 2019-12-18 | 2020-04-07 | 江苏创拓新材料有限公司 | Transposition method of 1-cyclohexyl-2, 3-difluorobenzene |
| CN110964538B (en) * | 2019-12-18 | 2022-01-04 | 江苏创拓新材料有限公司 | Transposition method of 1-cyclohexyl-2, 3-difluorobenzene |
| CN113548938A (en) * | 2020-12-23 | 2021-10-26 | 江苏广域化学有限公司 | Cis-trans-inversion method of non-terminal alkene liquid crystal monomer |
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