CN1183062C - Process for separating o-and p-substituted benzene compounds - Google Patents
Process for separating o-and p-substituted benzene compounds Download PDFInfo
- Publication number
- CN1183062C CN1183062C CNB008134111A CN00813411A CN1183062C CN 1183062 C CN1183062 C CN 1183062C CN B008134111 A CNB008134111 A CN B008134111A CN 00813411 A CN00813411 A CN 00813411A CN 1183062 C CN1183062 C CN 1183062C
- Authority
- CN
- China
- Prior art keywords
- ion exchange
- compound
- formula
- exchange resin
- solvent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/54—Preparation of compounds containing amino groups bound to a carbon skeleton by rearrangement reactions
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B63/00—Purification; Separation; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/79—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/80—Separation; Purification; Stabilisation; Use of additives by liquid-liquid treatment
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/47—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B40/00—Libraries per se, e.g. arrays, mixtures
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to a method for using a binary mixture of an o-substituted benzene compound and a p-substituted benzene compound in an optional proportion to prepare the o-substituted benzene compound and the p-substituted benzene compound separately. The o-substituted benzene compound and the p-substituted benzene compound comprise a 1, 2-substituted benzene compound represented by an isomeric formula 1 and a 1, 4-substituted benzene compound represented by the isomeric formula 2, wherein R1 is selected from-OH,-COOH,-NH2 and N(R3)(R4), and R3 and R4 are-H and (CH2)nCH3, wherein n is an integer from 0 to 4; R2 is selected from-(CO-CH3),-(NH2),-(OH),-(NO2),-(X),-(OCH3),-COOH,-CHO, and-(OCH2CH3), and X is selected from F, Cl, Br and the halogen of I. The method basically comprises the following steps: (1). the binary mixture is firstly processed by an organic solvent to carry out phase separation, and one of the two compounds is dissolved into a solution phase preferentially; (2). the solution phase comes into contact with ion exchange resin to adsorb and recover all the existing undissolved compound preferentially, the other compound is taken as a basically pure undissolved compound, and the phase separation of the other compound and the compound in the solution phase is further carried out; (3). the desolvation of the solution phase is carried out by a conventional method, and the dissolved compound is recovered from the solution phase of step (2) by a basically pure mode. The method for preparing pure compounds represented by the formula 1 and the formula 2 separately has the advantages of high yield, simpleness and low cost.
Description
Invention field
The present invention relates to from any ratio the neighbour-, the binary mixture of right-substituted benzene compound prepares the method for neighbour's-and right-replace benzene compound respectively.
Background of invention
Isomery that boiling point is approaching and non-heterogeneous mixture separate a normally industrial problem, what this paper cherished a special interest is heterogeneous mixture, for example the method for splitting of the benzoic mixture of the phenol of Qu Daiing (as hydroxyacetophenonum), the aniline that replaces and replacement.Being separated in the chemical preparation industry of heterogeneous mixture is important, by physical method, is difficulty or infeasible economically as this class materials of separation such as distillation, crystallization, solvent extractions.Some known chemistry that are used to separate closely-related organic compound are arranged now, for example utilize the dissociation extraction of dissociation constant difference, reaction distillation, with the isolating reactive crystallization of complexing agent, [Gaikar, V.G. and Sharma, the M.M. such as reaction precipitation of chemical complexing or use sulfonic acid, Sep.Purif.Methods, 18 (2) 111 (1989)].The reactivity of all these method utilization acidity/phenolic compound/tart difference is effectively separated, yet it is incomplete separating by these methods, needs MULTI CONTACT.
Phenol acidylate Fries is subsequently reset and to be obtained neighbour-and the mixture of right-hydroxy acetophenone (HAP), and the composition of product is changed to 95% according to reaction conditions and catalyzer by 10% of o-HAP.P-hydroxy acetophenone (p-HAP) is the solid white crystalline powder, 148 ℃/3mmHg of boiling point, and o-hydroxy acetophenone (o-HAP) is the liquid that at room temperature is green-yellow, 213 ℃/717mmHg of boiling point.Therefore these materials have significant industrial significance as pharmaceutical intermediate.P-HAP is used to produce the bufexamac (4-butoxy-N-hydroxybenzene ethanamide) as anti-inflammatory, pain relieving and febrifugee, also be used to produce pifoxime as antiphlogistic drug (1-[[4-[1-(oxyimino) ethyl] phenoxy group] ethanoyl] piperidines).O-HAP is used to produce 4 hydroxy coumarin, it is a basic raw material, is used to produce Syncumar [3-(α-acetonyl-p-nitrobenzyl)-4 hydroxy coumarin] as antithrombotics and vitamin K antagonist, as the tioclomarol of antithrombotics (3-[3-(4-chloro-phenyl-)-1-(5-chloro-2-thienyl)-3-hydroxypropyl]-4-hydroxyl-2H-1-chromen-2-one) be used as the Warnerin (3-(α-acetonyl benzyl)-4 hydroxy coumarin sodium salt) of antithrombotics equally.
The separation of two kinds of isomer adopts decompression to carry out fractionation by efficient fractional column/tower down, or adopts steam distillation, because o-isomer (being chelated) tool steam-volatile more.But to separate these materials be incomplete to this method usually, and do not have magnetism economically.For steam distillation, required quantity of steam is very big, and is polluted by institute's dissolved phenol.Therefore, people still need seek to split by chemical process the method for mono-substituted phenol isomer.
Goal of the invention
Therefore, basic purpose of the present invention provides from the heterogeneous mixture of the formula 1 of any ratio and 2 compounds and prepares shown in the pure basically formula 11 respectively, shown in benzene compound that 2-replaces and the formula 21, and the method for the benzene compound that 4-replaces, wherein R
1Be selected from-OH ,-COOH ,-NH
2, N (R
3) (R
4), R wherein
3And R
4Be-H, (CH
2)
nCH
3N=0-4; R
2Be selected from-(CO-CH
3) ,-(NH
2) ,-(OH) ,-(NO
2) ,-(X) ,-(OCH
3) ,-COOH ,-CHO ,-(OCH
2CH
3) and X be the halogen that is selected from F, Cl, Br and I.
Formula 1 formula 2
Another object of the present invention provides the method for distinguishing the described pure compound of preparation formula 1 and formula 2 from the described mixture of formula 1 and 2 described compounds with high yield.
Another purpose provides from the mixture difference preparation formula 1 of formula 1 and 2 described compounds and the simple and low cost method of formula 2 described pure compounds.
Summary of the invention
The invention provides the method for preparing 1,4 benzene compound that replaces shown in 1,2 benzene compound that replaces shown in the formula 1 of isomery and the formula 2 from the binary mixture of the formula 1 of any ratio and 2 described isomeric compounds respectively, wherein R
1Be selected from-OH ,-COOH ,-NH
2, N (R
3) (R
4), R wherein
3And R
4Be-H, (CH
2)
nCH
3N=0-4; R
2Be selected from-(CO-CH
3) ,-(NH
2) ,-(OH) ,-(NO
2) ,-(X) ,-(OCH
3) ,-COOH ,-CHO ,-(OCH
2CH
3) and X be the halogen that is selected from F, Cl, Br and I.
Formula 1 formula 2
Described method comprises the steps:
I) use-case as described herein organic solvent handle described binary mixture and be separated, the optimum solvation of one of described two kinds of compounds in solution mutually in, another kind is pure basically not dissolved compound;
The solution that above-mentioned steps (i) is obtained contacts with ion exchange resin described herein, further preferentially adsorbed and reclaim and anyly be present in the described undissolved compound of above-mentioned (i) described solution in mutually, thus further carry out the pure basically not dissolved compound of another compound conduct and described solution mutually described in being separated of compound;
Iii) reclaim described dissolved compound from the (ii) described solution of above-mentioned steps with pure basically form by the desolventizing that carries out the solution phase with ordinary method.
Preferred aspect according to aforesaid method of the present invention, in step (i) thus in handle described binary mixture with described organic solvent described step also comprise with the isolated described undissolved compound of fresh solvent wash and obtain containing another part solution phase of dissolved compound and further isolated pure basically not dissolved compound; Described solution is comprised with the described step of described ion exchange resin contact contacts described solution mutually mutually together with described ion exchange resin with described another part solution.
Also preferred following by adsorbed formula 1 of described ion exchange resin recovery and 2 component described ion exchange treatment after in aforesaid method of the present invention:
Thereby iv) use the compound of one of organic polar solvent, aqueous base and sour solvent treatment step described sorbent material ion exchange resin (ii) from the described formula 1 of described resin desorption and 2;
The v) solution desolventizing by above-mentioned steps (a) is obtained, the mixture of compound that reclaims the compound of described formula 1 and 2 and the described formula 1 that will reclaim and 2 are as described binary mixture add-back as mentioned above in the step (i).
Equally, in order to make method of the present invention more economical, recycle solvent with ion exchange resin regeneration with in aforesaid method.
The term " heterogeneous mixture " that is used for this paper comprises that substituting group occupies the mixture of the disubstituted benzenes of different positions on the phenyl.Main substituting group normally forms the hydroxyl of fortified phenol (OH) with the amino (NH that forms substituted aniline
2), second substituting group is nitro, chlorine, methoxyl group, oxyethyl group, hydroxyl etc.
Term " optimum solvation " is meant compares one of component (o-isomer) obvious higher solvability in organic solvent with another component (p-isomer).Owing to there is the o-isomer, the p-isomer also can be dissolved in the organic solvent, but as long as the ratio of the meltage of o-isomer and p-isomer meltage is very high, this solvency action will can not have a negative impact to sepn process.The choice of Solvent that is used for first step must be based on solubility data and other character, for example boiling point, toxicity etc.Selected solvent should make a kind of component solubleness therein very high, and the solubleness of another kind of component is low relatively.And solvent should not dissolve the ion exchange resin that is selected to the absorption of step in (iii).
The organic solvent that is used for step (i) is selected from aliphatic series, alicyclic, aromatic hydrocarbon, their chlorinated derivatives, ether, ester, acid amides and ketone and their mixture.For example normal heptane, hexanaphthene, toluene are used for these compounds of selectivity/optimum solvation, and positive aliphatic hydrocrbon is a preferred solvent.
Be used for step ion exchange resin (iii) and be selected from and have the paradigmatic structure of vinylbenzene-Vinylstyrene as polymer backbone, contain be useful on acidic mixture primary, the second month in a season or tertiary amine or quaternary ammonium group and be used for the sulfonic acid or the carboxylic acid functional of amine mixt.
Some the commercially available ion exchange resin that is used for present method is Indion 850, Indion810, Indion 925, Tulsion A-2X MP, Dowex MSA-1 (these are trade(brand)names of commercial ion exchange resin).
Term " preferentially adsorbed " is meant compares the obviously higher absorption on ion exchange resin of one of component with the another kind of component in the mixture.The amount that second component that should understand extract phase also can be less than main absorbed component is adsorbed on the identical ion exchange resin.If the ratio height of the adsorptive capacity of preferentially adsorbed component and the adsorptive capacity of other component, this adsorption is harmless to splitting.
To be considered to for these ion-exchange resin absorptions be important in the existence of the character of these amino and acidic-groups and quantity and aromatic nucleus in the paradigmatic structure of resin.Method of the present invention is particularly useful for the heterogeneous mixture of separating organic acid and alkali.The example of mixture comprises o-/p-hydroxy acetophenone, o-/p-N-methyl-p-nitroaniline, o-/p-chloroaniline, o-/p-nitrophenols, o-/p-chlorophenol, o-/p-hydroxy-benzoic acid, o-/p-hydroxy benzaldehyde, o-/p-aminoacetophenone etc.Usually in the mixture of o-and p-substitution compound, the o-isomer optionally is dissolved in the organic solvent, and when mixture contacted with ion exchange resin, the p-isomer was by preferentially adsorbed.Such two kinds of special selective binding in the method so that these mixtures separate fully.Following table shows can use coordinative solvent and ion exchange resin isolated compound.
| R 1 | R 2 | Solvent (i) | Resin functional group | Solvent (iv) |
| -OH | -COCH 3 | Normal heptane | Tertiary amine | Methyl alcohol |
| -NO 2 | -NH 2 | Normal heptane | Sulfonic acid | Methyl alcohol |
| -Cl | -NH 2 | Normal heptane | Sulfonic acid | Methyl alcohol |
| -NH 2 | -COCH 3 | Normal heptane | Sulfonic acid | Methyl alcohol |
| -OH | -COOH | Normal heptane | Tertiary amine | Methyl alcohol |
| -OH | -CHO | Normal heptane | Tertiary amine | Methyl alcohol |
| -COOH | -Cl | Normal heptane | Tertiary amine | Methyl alcohol |
| -COOH | NO 2 | Normal heptane | Tertiary amine | Methyl alcohol |
| -COOH | -NH 2 | Normal heptane | Tertiary amine | Methyl alcohol |
| -OH | -NO 2 | Normal heptane | Tertiary amine | Methyl alcohol |
Be used for step organic polar solvent (iv) and be selected from fatty alcohol, alicyclic ring alcohol, aromatic alcohol, ester, ether, ketone, acid amides and aqueous alcohol, acid, alkali and their mixture.For example, methyl alcohol, ethanol, ether, diisopropyl ether, acetone, methylethylketone are used for these compounds of desorption.Methyl alcohol, ethanol, acetone are preferred solvent.
Mixture of isomers contacts with the organic solvent of selection, stirs time enough to dissolve.Employed quantity of solvent is calculated by the solvability of more diffluent isomer, is used for the enough time of dissolved to be generally 30 minutes.Be stirred under the temperature of selection and the normal atmosphere and carry out, after stirring,, from organic solution, isolate sedimentary component by filtering or decant.The organic phase that will contain nearly all o-isomer and the p-isomer that is dissolved in organic solvent on a small quantity contacts with pulpous state ion exchange resin (IER), maybe can be by the post/tower of filling ion exchange resin.
Slurry stirs time enough so that adsorption to take place, and adsorption time is 12 minutes-2 hours usually.Be blended under the temperature of selection and the normal atmosphere and carry out, after mixing, by decant or filtration or centrifugal with ion exchange resin and liquid separation.Isolating ion exchange resin is handled to discharge the organic compound of absorption with polar solvent (for example methyl alcohol) or alkali aqueous solution.This dispose procedure can carry out under the temperature of selecting.Reclaim ion exchange resin, dry and circulation is used for sepn process subsequently.
Reclaim by fractionation from the organic compound that ion exchange resin discharges with polar solvent, if use alkali aqueous solution to discharge the oxybenzene compound of absorption, then solution is at first handled with neutralization bases with inorganic acid aqueous solution, organic compound is separated as second, can pass through decant or filtration or this organic compound of centrifugation.
In other method, be seated in ion exchange resin for the inflow that mixture is arranged and flow out in the post/tower of logistics, the organic phase that contains almost whole o-isomer and the p-isomer of minimal amounts of dissolved in organic solvent is passed through the ion exchange resin bed layer with specific flow pumping, and the preferentially adsorbed of p-HAP takes place therein.So the effluent of post/tower is pure o-HAP, the effluent of collecting post/tower begins to increase until the concentration of p-HAP in effluent.After this concentration, stop mixture solution stream, from post/tower, discharge any residual liquid.Begin the fluid of alcohol is passed through post/tower with direction identical with mixture solution or opposite direction, collect the solution of outlet, the concentration of hydroxy acetophenone is reduced to zero in effluent, discharges solution subsequently from post/tower, and drying is used for next sorption cycle.
In other method, after stopping mixture solution and flowing, from post/tower, discharge residual liquid, alkali aqueous solution is reduced to zero by post/tower concentration of HAP in effluent.Discharge the solution in post/tower subsequently, use methanol wash, drying also is used for next sorption cycle.
The major advantage of this method is by taking this two step strategy, and o-and p-mixture of isomers can be separated into pure o-and p-isomer in single equilibrium stage operation.Method of the present invention is particularly useful for the heterogeneous mixture of separating organic acid and alkali.
Be easy to comprise the compound that o-and p-replace with the heterogeneous mixture that method of the present invention is handled, these mixtures comprise o-/p-hydroxy acetophenone, o-/p-N-methyl-p-nitroaniline, o-/p-chloroaniline, o-/p-nitrophenols, o-/p-chlorophenol, o-/p-hydroxy-benzoic acid, o-/p-hydroxy benzaldehyde, o-/p-aminoacetophenone etc.
This method obtains the disconnected from each other of the extra high rate of recovery and heterogeneous mixture, and this will be impossible in single stage distillation.In addition, can easily reclaim solvent, but its recirculation and do not have the significantly sacrificing of component.Another advantage is that specific energy consumption is obviously lower mutually with the physical sepn that relates to vacuum distilling/vapor distillation process that is used for mixture separation.
Embodiment
Nonrestrictive embodiment is for a more detailed description for example referring to following for purpose of the present invention, advantage and the means that reach them, and embodiment only illustrates, rather than limits the scope of the invention.Employed chemical
P-hydroxy acetophenone (p-HAP) (extra-pure grade, 98% purity)
O-hydroxy acetophenone (o-HAP) (synthetic level, 95% purity)
Normal heptane (LR level)
Methylene dichloride (LR level)
Ion exchange resin: Indion 850 (Ion Exchange India, Ltd.)
Methyl alcohol (AR level)
Analytical procedure: the high performance liquid chromatography that adopts C18 anti-phase post
Embodiment 1:
In having the reaction vessel of agitator (200ml), add the mixture that contains 2.68g o-HAP and 0.22gp-HAP, in this mixture, add normal heptane.Mixture stirred 30 minutes under the room temperature of 303K, filtering mixt, and the p-HAP of precipitation separation from organic phase obtains the pure product of 0.176g (80% rate of recovery) (100% purity) with pure heptane wash subsequently.The extraction solution that contains 0.044g p-HAP and 2.6g o-HAP that employing is measured through HPLC adds 5g weakly alkaline macroporous ion exchange resin mutually in this solution, Indion 850, keep vibration 8 hours.With solution and resin isolation, solution contains 2.55g o-HAP (95.15% rate of recovery) by decant, removes and desolvates its recovery, and purity 100% is reused with regenerating resin with the methanol wash resin subsequently.
Embodiment 2:
This embodiment is identical with embodiment 1, is employed HAP different amts.Mixture contains 3.6g o-HAP and 0.34g p-HAP, and absorption back extract phase contains 0.067g p-HAP and the 3.5go-HAP residual solution contains 3.48g o-HAP (96.67% rate of recovery), without any the p-HAP of trace.
Embodiment 3:
In having the reactor of whipping appts, add the dichloromethane solution that 23ml contains 0.61g o-HAP and 0.62gp-HAP, in this solution, add the dry ion exchange resin Indion850 of 2.0g to form slurry, under 303K, stir this mixture and adsorbed in 8 hours.The suction filtration mixture separates liquor with ion exchange resin.Isolated ion exchange resin washed with dichloromethane, filtrate contain 0.21g p-HAP and 0.58g o-HAP (using high effective liquid chromatography for measuring).
Embodiment 4:
In having the reactor of agitator (200ml), add the mixture that contains 35g o-HAP and 1.75g p-HAP, in this mixture, add the 500ml normal heptane.Mixture was stirred 30 minutes under the room temperature of 303K, filtering mixt, the p-HAP of precipitation separation from organic phase uses pure heptane (55ml) washing to obtain the pure product of 1.567g (89.5% rate of recovery) (100% purity) subsequently.Extracting solution is measured through HPLC and is contained 0.183g p-HAP and 35g o-HAP.
The pumping subsequently of extracting solution phase is by post (the 2.0cm diameter of filling ion exchange resin Indion 850, the 37cm height), extraction solution phase (555ml) for all passing through does not detect p-HAP in effluent liquid, the rate of recovery of o-HAP is 78.5% (100% purity) in extracting solution.
Carry out desorption with methyl alcohol, when 220ml methyl alcohol passes through post, desorption 7.5g o-HAP and 1.83gp-HAP.
Employed chemical
O-nitrophenols (o-NP) (100% is pure)
P-nitrophenols (p-NP) (100% is pure)
Normal heptane (LR level)
Ion exchange resin: Indion 850, and weakly base resin (Ion Exchange India, Ltd.)
: Indion 810, and basic resin (Ion Exchange India, Ltd.)
Embodiment 5:
In having the reactor of agitator (200ml), add the mixture that contains 0.48g o-NP and 0.4g p-NP, in this mixture, add the 50ml normal heptane.Mixture was stirred 30 minutes under the room temperature of 303K, and filtering mixt is used pure heptane wash subsequently with the p-NP of precipitation separation from organic phase, obtains the pure product of 0.3995g (99.88% rate of recovery) (100% purity).The UV-spectrophotometric determination of learning from else's experience contains the extraction liquid phase of 0.0005g p-NP and 0.47g o-NP, adds 1g weakly alkaline macroporous ion exchange resin in this solution, and Indion 850, keep vibration 8 hours.With resin and solution separating, except that desolvating, reclaim 0.45g o-NP (95.47% rate of recovery) by decant from solution evaporation.
Embodiment 6:
This embodiment is identical with embodiment 5, and the resin that is employed NP quantity and use is different.Mixture contains 5g o-NP and 5g p-NP, and extract phase contains 0.006g p-NP and 4.7g o-NP, and behind absorption p-NP on Indion 810 resins, residual solution contains 4.55g o-NP (96.8% rate of recovery), without any the p-NP of trace.
Employed chemical
P-phenylenediamine (p-PDA) (100% is pure)
O-phenylenediamine (o-PDA) (100% is pure)
1,2 ethylene dichloride (LR level)
Ion exchange resin: Indion 840, and highly acidic resin (Ion Exchange India, Ltd.)
Embodiment 7:
In having the reactor of whipping appts, add and contain 0.12g (0.93%w/w) p-PDA and 0.1g (0.8%w/w) o-PDA and 9.8ml as 1 of phenylenediamine solvent, the 10ml solution of 2-ethylene dichloride adds the dry ion exchange resin of 0.1g (Indion 840) to form paste mixture in this reactor.At room temperature stir this mixture adsorbed in 8 hours.The suction filtration mixture, isolating ions exchange resin from liquid.Measure with the GC that uses SE-30 post (Perkin Elmer type), filtrate is contained 0.042% (w/w) p-PDA and 0.69% (w/w) o-PDA.
Embodiment 8:
This embodiment is identical with embodiment 7, is employed PDA different amts.Mixture contains 0.23g (1.8%w/w) o-PDA and 0.21g (1.66%w/w) p-PDA, after the absorption, is measured by GC, and filtrate is contained 0.718% (w/w) p-PDA and 1.64% (w/w) o-PDA.
Claims (18)
1. produce the method for 1,4 benzene compound that replaces shown in 1,2 benzene compound that replaces shown in the formula 1 of isomery and the formula 2 respectively from the binary mixture of the formula 1 of any ratio and 2 described isomeric compounds, wherein R
1Be selected from-OH ,-COOH ,-NH
2, N (R
3) (R
4), R wherein
3And R
4Be-H, (CH
2)
nCH
3N=0-4; R
2Be selected from-(CO-CH
3) ,-(NH
2) ,-(OH) ,-(NO
2) ,-(X) ,-(OCH
3) ,-COOH ,-CHO ,-(OCH
2CH
3) and X be the halogen that is selected from F, Cl, Br and I
Formula 1 formula 2
Described method comprises the steps:
I) handle described binary mixture with organic solvent and be separated, described formula 1 compound optimum solvation in solution mutually in, formula 2 compounds are pure basically not dissolved compound;
The solution that above-mentioned steps (i) is obtained contacts with ion exchange resin, further preferentially adsorbed and reclaim and anyly be present in described undissolved formula 2 compounds of above-mentioned (i) described solution in mutually, thus further carry out the pure basically not dissolved compound of formula 2 compounds conduct and described solution mutually described in being separated of compound;
Iii) reclaim described dissolved formula 1 compound from the (ii) described solution of above-mentioned steps with pure basically form by the desolventizing that carries out the solution phase with ordinary method.
2. the method for claim 1, wherein, in step (i) thus in handle described binary mixture with described organic solvent described step also comprise with isolated described undissolved formula 2 compounds of fresh solvent wash and obtain containing another part solution phase of formula 1 compound and further isolated pure basically not dissolution type 2 compounds; Described solution is (ii) comprised with the described step of described ion exchange resin contact contacts described solution mutually mutually together with described ion exchange resin with described another part solution.
3. method as claimed in claim 1 or 2 comprises:
Followingly after described ion exchange treatment reclaim adsorbed formula 1 and 2 component, comprising by described ion exchange resin:
Thereby iv) use ion exchange resin after the described absorption (ii) of one of organic polar solvent, aqueous base and sour solvent and composition thereof treatment step from the compound of the described formula 1 of described resin desorption and 2;
The v) solution desolventizing by above-mentioned steps is (iv) obtained, the mixture of compound that reclaims the compound of described formula 1 and formula 2 and the described formula 1 that will reclaim and 2 are as described binary mixture add-back as mentioned above in the step (i).
4. method as claimed in claim 1 or 2 comprises regenerating ion exchange resin and recirculation solvent.
5. method as claimed in claim 1 or 2, wherein the organic solvent that is adopted in step (i) is selected from aliphatic series, alicyclic, aromatic hydrocarbon, their chlorinated derivatives and their mixture.
6. method as claimed in claim 1 or 2, wherein be used for step ion exchange resin (iii) and be selected from and have the paradigmatic structure of vinylbenzene-Vinylstyrene as polymer backbone, contain be useful on acidic mixture primary, the second month in a season or tertiary amine or quaternary ammonium group and be used for the sulfonic acid or the carboxylic acid functional of amine mixt.
7. method as claimed in claim 3 wherein is used for step organic polar solvent (iv) and is selected from aliphatic series, alicyclic, aromatic alcohol, ester, ether, ketone, acid amides and aqueous alcohol.
8. method as claimed in claim 1 or 2, wherein R
1=-(OH); R
2=-(CO-CH
3); Organic solvent is a normal heptane in step (i); Step (iii) the intermediate ion exchange resin be have SDVB as polymeric skeleton, have the weakly alkaline macroporous resin of tertiary amine functional group; Step (iv) in organic polar solvent be methyl alcohol.
9. method as claimed in claim 1 or 2, wherein R
1=-(NO
2); R
2=-(NH
2); Organic solvent is a normal heptane in step (i); Step (iii) the intermediate ion exchange resin be have SDVB as polymeric skeleton, have sulfonic acid functional group's acid macroporous resin; Step (iv) described in organic polar solvent be methyl alcohol.
10. method as claimed in claim 1 or 2, wherein R
1=-(Cl); R
2=-(NH
2); At organic solvent described in the step (i) is normal heptane; Step (iii) the intermediate ion exchange resin be have SDVB as polymeric skeleton, have sulfonic acid functional group's acid macroporous resin, step (iv) in organic polar solvent be methyl alcohol.
11. method as claimed in claim 1 or 2, wherein R
1=-(OH); R
2=-(NO
2); Organic solvent is a normal heptane in step (i); Step (iii) the intermediate ion exchange resin be have SDVB as polymeric skeleton, have the weakly alkaline macroporous resin of tertiary amine functional group, step (iv) in organic polar solvent be methyl alcohol.
12. method as claimed in claim 1 or 2, wherein R
1=-(OH); R
2=-(Cl); Organic solvent is a normal heptane in step (i); Step (iii) neutral and alkali ion exchange resin be have SDVB as polymeric skeleton, have the weakly alkaline macroporous resin of tertiary amine functional group, step (iv) in organic polar solvent be methyl alcohol.
13. as the described method of one of claim 1-12, wherein R
1=-(COOH); R
2=-(Cl); Organic solvent is a normal heptane in step (i); Step (iii) neutral and alkali ion exchange resin be have SDVB as polymeric skeleton, have the weakly alkaline macroporous resin of tertiary amine functional group, step (iv) in organic polar solvent be methyl alcohol.
14. method as claimed in claim 1 or 2, wherein R
1=-(COOH); R
2=-(NO
2); Organic solvent is a normal heptane in step (i); Step (iii) neutral and alkali ion exchange resin be have SDVB as polymeric skeleton, have the weakly alkaline macroporous resin of tertiary amine functional group, step (iv) in organic polar solvent be methyl alcohol.
15. method as claimed in claim 1 or 2, wherein R
1=-(CHO); R
2=-(OH); Organic solvent is a normal heptane in step (i); Step (iii) neutral and alkali ion exchange resin be have SDVB as polymeric skeleton, have the weakly alkaline macroporous resin of tertiary amine functional group, step (iv) in organic polar solvent be methyl alcohol.
16. method as claimed in claim 1 or 2, wherein R
1=-(COOH); R
2=-(CHO); Organic solvent is a normal heptane in step (i); Step (iii) neutral and alkali ion exchange resin be have SDVB as polymeric skeleton, have the weakly alkaline macroporous resin of tertiary amine functional group, step (iv) in organic polar solvent be methyl alcohol.
17. method as claimed in claim 1 or 2, wherein R
1=-(COOH); R
2=-(NH
2); Organic solvent is a normal heptane in step (i); Step (iii) neutral and alkali ion exchange resin be have SDVB as polymeric skeleton, have the weakly alkaline macroporous resin of tertiary amine functional group, step (iv) in organic polar solvent be methyl alcohol.
18. method as claimed in claim 1 or 2, wherein R
1=-(NH
2); R
2=-(COCH
3); Organic solvent is a normal heptane in step (i); Step (iii) neutral and alkali ion exchange resin be have SDVB as polymeric skeleton, have sulfonic acid functional group's acid macroporous resin, step (iv) in organic polar solvent be methyl alcohol.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/IN2000/000072 WO2002010097A1 (en) | 2000-07-27 | 2000-07-27 | A process for separating o- and p-substituted benzene compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1376140A CN1376140A (en) | 2002-10-23 |
| CN1183062C true CN1183062C (en) | 2005-01-05 |
Family
ID=11076260
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB008134111A Expired - Fee Related CN1183062C (en) | 2000-07-27 | 2000-07-27 | Process for separating o-and p-substituted benzene compounds |
Country Status (3)
| Country | Link |
|---|---|
| CN (1) | CN1183062C (en) |
| AU (1) | AU2001210522A1 (en) |
| WO (1) | WO2002010097A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100369883C (en) * | 2006-06-28 | 2008-02-20 | 乔旭 | Separation method of o-chlorobenzoic acid and p-chlorobenzoic acid mixture |
| CN106554264A (en) * | 2016-11-07 | 2017-04-05 | 北京天弘天达医药科技有限公司 | A kind of parahydroxyacet-ophenone product and preparation method thereof and purposes |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2838570A (en) * | 1954-03-26 | 1958-06-10 | Byk Gulden Lomberg Chem Fab | Process of producing pure halogeno methyl (p-hydroxy phenyl) ketones |
| US3894096A (en) * | 1971-12-07 | 1975-07-08 | American Cyanamid Co | Separation of para-nitrated phenolic compounds from crude reaction mixtures containing ortho-and para-nitrated phenolic compounds |
| US5177302A (en) * | 1990-11-27 | 1993-01-05 | Director-General, Agency Of Industrial Science And Technology | Process for separating isomers of disubstituted benzenes and agents to be used therefor |
| NL9202248A (en) * | 1992-12-23 | 1994-07-18 | Univ Delft Tech | Process for separating the ortho and para isomer of hydroxymandelic acid or a salt thereof, the ortho and para isomer of hydroxymandelic acid obtained by this method, and the use of the ortho isomer in the preparation of EDDHA. |
-
2000
- 2000-07-27 WO PCT/IN2000/000072 patent/WO2002010097A1/en active Application Filing
- 2000-07-27 AU AU2001210522A patent/AU2001210522A1/en not_active Abandoned
- 2000-07-27 CN CNB008134111A patent/CN1183062C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| AU2001210522A1 (en) | 2002-02-13 |
| WO2002010097A1 (en) | 2002-02-07 |
| CN1376140A (en) | 2002-10-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1310867C (en) | Process for the oxidative purification of terephthalic acid | |
| CN1164650C (en) | Process for preparation of polyphenylether | |
| CN111266088B (en) | Efficient porous adsorbent for treating phenolic wastewater and preparation method thereof | |
| CN1910130A (en) | Process for production of a dried carboxylic acid cake suitable for use in polyester production | |
| CN101896462B (en) | Process for the resolution of isoquinoline derivatives | |
| CN101037388A (en) | Multifunctional ion liquid system, preparation and application thereof | |
| JP2017533236A (en) | Method for extracting valuable aromatic products from compositions containing lignin | |
| CN1012812B (en) | Method for recovering gallium | |
| CN102971281A (en) | Cyclic compound purification method | |
| CN101679253B (en) | Process for purifying 2-phenyl-3, 3 -bis(4-hydroxyphenyl) phthalimidine (PPPBP) | |
| CN101065384A (en) | Method for separation and purification of hydrocodone by preparative chromatography | |
| CN1183062C (en) | Process for separating o-and p-substituted benzene compounds | |
| CN105481656B (en) | The extraction process of aldehydes matter in a kind of pyrolkigneous liquid | |
| CN1087739C (en) | Inclusion and resolution preparation process of optical purity benzimidazoles medicines resisting peptic ulcer | |
| CN104892493A (en) | Separation and purification method of 2,3-dimethylpyridine | |
| CN102276572A (en) | Method for preparing vitamin E acetate acetic ester | |
| CN1216879C (en) | Process for producing alpha-tocopheryl acetate | |
| CN86102590A (en) | The method of purification of methacrylic acid | |
| CN111153775A (en) | Preparation method of triclosan methyl ester | |
| CN1827664A (en) | Fluorescent sensing materials made of conjugated polymer and process for preparing same | |
| CN102344366A (en) | Method for extracting butyl acrylate through liquid-liquid extraction of two side feed solvents | |
| CN1131141A (en) | Process for purifying alpha, beta-unsaturated esters | |
| CN1123271A (en) | Adsorption process for amine of amine salt recovery from aqueous brine solutions | |
| KR100615931B1 (en) | Precess of the preparation of high-purity alkyladamantyl esters | |
| CN1218949C (en) | Artemisine arylether derivatives and their preparing process |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |