CN104610034B - The preparation method of the chloro-5-fluoro acetophenone of a kind of 2,4-bis- - Google Patents
The preparation method of the chloro-5-fluoro acetophenone of a kind of 2,4-bis- Download PDFInfo
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Abstract
The present invention relates to a kind of method being suitable for the chloro-5-fluoro acetophenone of synthesis 2,4-bis-of suitability for industrialized production, product 2 can be significantly improved, the yield of the chloro-5-fluoro acetophenone of 4-bis-, reduce the yield of the chloro-3-fluoro acetophenone of by product 2,6-bis-, and catalyst recycling is better.
Description
Technical field
The present invention relates to the preparation method of the chloro-5-fluoro acetophenone of a kind of 2,4-bis-, particularly relate to a kind of working load phospho-wolframic acid/ZrO
2the method of zeolite magnetic coupling carried catalyst synthesis 2,4-bis-chloro-5-fluoro acetophenone.
Background technology
Quinolone is a class synthetic antibacterial drug, mainly acts on the antibacterials of Gram-negative bacteria, and does not have cross resistance between most antibacterials, and has the features such as efficient, spectrum, low toxicity, has better development prospect.
2, the chloro-5-fluoro acetophenone of 4-bis-is the important intermediate of synthesis quinolones (norfloxicin, Ciprofloxacin, Abbott 56619 etc.), for white or light yellow crystalline solid, molecular weight is 207.03, fusing point is 33.5-34 DEG C, CAS registration number is 704-10-9, can be dissolved in benzene, methylene dichloride, ethyl acetate, acetone and other organic solvent, water insoluble.Because the demand of 2,4-bis-chloro-5-fluoro acetophenone is increasing, develop multiple synthesis route, but the problem that domestic production ubiquity productive rate is low, quality is unstable, consumption of raw and auxiliary materials is high.
Current this acylation reaction of Knut Fridell-Kerafyrm is one of important method of preparation aromatic ketone compounds, and conventional acylating reagent has acetic acid, aceticanhydride, Acetyl Chloride 98Min., usually uses aluminum chloride as catalyzer.This reaction, while the chloro-5-fluoro acetophenone of generation 2,4-bis-, inevitably produces isomeric by-products 2, the chloro-3-fluoro acetophenone of 6-bis-, wherein the content of 2,4-bis-chloro-5-fluoro acetophenones is about 80%, the content of the chloro-3-fluoro acetophenone of by product 2,6-bis-is about 20%.The fusing point of the two differs 10 DEG C, is separated by the mode of periodic crystallisation at low temperatures at present usually, but along with the increase of the chloro-3-fluoro acetophenone content of by product 2,6-bis-, is just difficult to by the mode of periodic crystallisation the separation carrying out the two.
Containing 2, the chloro-5-fluoro acetophenone of 4-bis-and 2, the separation of the crystalline mother solution of the chloro-3-fluoro acetophenone of 6-bis-is studied, such as, the CN101747167A of Zhejiang Polytechnical University relates to a kind of high efficiente callback 2 from crystalline mother solution, the method of the chloro-5-fluoro acetophenone of 4-bis-, containing 2, the chloro-5-fluoro acetophenone of 4-bis-and 2, the crystalline mother solution of the chloro-3-fluoro acetophenone of 6-bis-needs by reacting preparation 2 with neopentyl glycol under the existence of an acidic catalyst, the chloro-3-fluoro acetophenone of 6-bis-and 2, 4-bis-chloro-5-fluoro acetophenone ketal, then 2, 4-bis-chloro-5-fluoro acetophenone ketal is hydrolyzed and obtains 2 through aftertreatment under the existence of another an acidic catalyst, the chloro-5-fluoro acetophenone of 4-bis-.
Zhang Qixing (" research of chlorofluorobenzene ethyl ketone synthesis technique ", Zhang Qixing, print during chemical industry, 11st volume the 6th phase, 22-24 page, 1997) and Ke Baojia (CN1634890A) relate separately to and under the existence of aluminum chloride, prepare 2 by 2,4 dichloro fluorobenzene and Acetyl Chloride 98Min., the method of the chloro-5-fluoro acetophenone of 4-bis-, wherein productive rate can reach 80%.But it employs aluminum chloride respectively as catalyzer, the cohesion but aluminum chloride easily distils also absorbs water from air, unfavorable to reaction.In addition, 1 mole of acyl chloride consumes the aluminum chloride of more than 1 mole usually, and the non-renewable use of aluminum chloride, add the difficulty of refuse process, contaminate environment.Finally, the chloro-3-fluoro acetophenone content of the method inevitable aforementioned auxiliary product 2,6-bis-is higher, and occurs that crystalline mother solution is difficult to the problem be separated.
As above existing technique all exist by product 2,6-bis-chloro-3-fluoro acetophenone content higher so that produce crystalline mother solution separation problem, refuse is difficult to process and causes the problems such as contaminate environment.
Summary of the invention
For the above-mentioned problems in the prior art, technical problem to be solved by this invention is to provide a kind of synthesis 2 newly, the method of the chloro-5-fluoro acetophenone of 4-bis-, the inventive method can significantly improve product 2, the yield of the chloro-5-fluoro acetophenone of 4-bis-, reduce the yield of the chloro-3-fluoro acetophenone of by product 2,6-bis-, and catalyst recycling is better.
For this purpose, the technical solution used in the present invention is: 2,4-dichlor fluorbenzene reacts under agitation with Acetyl Chloride 98Min. under the existence of composite zeolite solid super acid catalyst, reaction to terminate in backward reaction mixture directly feeding extraction agent and water and proceeds to stir, reaction terminates rear stratification and by organic phase and aqueous phase separation, aqueous phase extraction agent extracts further, and whole organic phase is merged, by distillation removing extraction agent, 100-120 DEG C/1.33kPa cut is collected in underpressure distillation, and last freezing and crystallizing obtains white crystal.
According to one embodiment of the invention, 2,4 dichloro fluorobenzene reacts 40 minutes-180 minutes under agitation, preferred reaction 60 minutes-120 minutes with Acetyl Chloride 98Min. under the existence of composite zeolite solid super acid catalyst, temperature of reaction is 80-140 DEG C, preferred 90-120 DEG C.
According to one embodiment of the invention, the mol ratio of 2,4 dichloro fluorobenzene and Acetyl Chloride 98Min. is 1:1-1:3, preferred 1:1-1:1.3.
According to one embodiment of the invention, use 40-200 gram of composite zeolite solid super acid catalyst relative to every mole of 2,4 dichloro fluorobenzene, preferably use 80-150 gram of composite zeolite solid super acid catalyst relative to every mole of 2,4 dichloro fluorobenzene.
According to one embodiment of the invention, the extraction agent of use is acetone, methylene dichloride or toluene, but methylene dichloride has serious toxicity, and acetone easily volatilizees, in actual production, preferably use toluene.
According to one embodiment of the invention, composite zeolite solid super acid catalyst used in this application is prepared as follows: step 1: Natural Zeolite Support pre-treatment; Step 2: synthesizing porous level zeolite; Step 3: the magnetic of zeolite is modified; Step 4: prepare load phosphotungstic acid/ZrO
2zeolite magnetic coupling carried catalyst.
Step 1 carries out the pre-treatment of Natural Zeolite Support, comprises following operation:
(1.1) to Natural Zeolite Support after 450 DEG C of-650 DEG C of calcination process, carry out exchange process with the ammonium salt solution containing ammonium nitrate, volatile salt or ammonium sulfate that ammonium concentration is 0.05 ~ 1.0mol/L, the liquid-solid volume ratio of ammonium salt solution and zeolite is 3:1 ~ 5:1; Swap time is 30 minutes to 60 hours, the zeolite after exchanging with deionized water wash, then carries out drying and 450 DEG C-650 DEG C calcination process again;
(1.2) carrier reaming: the zeolite that step (1.1) obtains is put into HCl, HNO that concentration is 0.05 ~ 6mol/L
3, H
2sO
4or the solution of citric acid; Soak 6-10 hour, with deionized water wash to neutral, dry, obtain pretreated carrier 450 DEG C of-650 DEG C of roastings.
According to one embodiment of the invention, wherein said natural zeolite is mordenite, natrolite, chabazite, faujusite, is preferably mordenite.
Step 2 carries out the synthesis of porous level zeolite, comprises following operation:
(2.1) under protection of inert gas, comonomer and initiator are joined dissolving in medium and obtain reaction solution, and in 70 ~ 80 DEG C of reaction 6 ~ 10h, obtain the dispersion system of polymer microballoon;
(2.2) mix by the mass ratio 1: 10 ~ 20: 0.5 ~ 3 of dispersion system, silicon sol, non-silicon sol, then stir, at room temperature naturally place, to complete its gelation process;
(2.3) again through centrifugation, be cooled to room temperature, washing, suction filtration, drying, 450 DEG C of-650 roasting obtain porous level zeolite;
Wherein, described comonomer is vinyl monomer, comprises maleic anhydride, vinylbenzene and vinyl acetate between to for plastic, and the mol ratio of comonomer is maleic anhydride: vinylbenzene: vinyl acetate between to for plastic is 1:1-2:1-2, and in reaction solution, the mass concentration of monomer is 10% ~ 30%;
Described initiator is organo-peroxide or azo-compound, the preferred dialkyl peroxide of organic peroxide evocating agent (such as di-t-butyl peroxide, dicumyl peroxide), acyl class superoxide (such as dibenzoyl peroxide, lauroyl peroxide), hydroperoxide (such as isopropyl benzene hydroperoxide, tertbutyl peroxide), ester class superoxide (such as peroxidized t-butyl perbenzoate, the peroxidation trimethylacetic acid tert-butyl ester), two carbonic ether superoxide (such as di-isopropyl peroxydicarbonates, di-cyclohexylperoxy dicarbonate), the preferred Diisopropyl azodicarboxylate of azoic compound initiator (AIBN), 2,2'-Azobis(2,4-dimethylvaleronitrile), in reaction solution, the mass concentration of initiator is 0.1% ~ 0.5%.
Described medium is C
1-C
12the mixing solutions of alkyl alcohol and acetone, volume ratio is: 1:1-1.5.Wherein said C
1-C
12alkyl alcohol particular methanol, ethanol, butanols, Virahol, especially preferred alcohol and Virahol.
Described silicon sol is selected from tetraethoxy, isopropyl titanate or zirconium-n-propylate, and described non-silicon sol is selected from sodium aluminate, aluminum nitrate, aluminium secondary butylate, trimethyl carbinol aluminium, aluminum ethylate and aluminum isopropylate.
Or step 2 comprises following operation:
(2.1) HNO is used
3solution and H
2o
2solution carries out modification to carbon nano tube surface, obtains the carbon nanotube of surface modification.
(2.2) by non-silicon precursor sol solution and cetyl trimethylammonium bromide (CTAB), after being dissolved in dehydrated alcohol respectively, remix together and stir 0.5-1.5 hour, obtains mixed system 1; By the triblock copolymer (P123) of polyoxyethylene-poly-oxypropylene polyoxyethylene with add H through above-mentioned modified carbon nano-tube
2sO
4with in HCl mixing solutions, in stirred at ambient temperature until P123 melts completely, add the precursor aqueous solution that the silicon sol that is dissolved in dehydrated alcohol obtains, stir 2-3 hour, obtain mixed system 2;
(2.3) by mixed system 1 and 2-in-1 and and after mixing, at 95-105 DEG C, Hydrothermal Synthesis 40-50 hour, finally takes out, and is cooled to room temperature, washing, suction filtration, drying, roasting, obtain the Porous materials of two kinds of presomas with double-pore structure.
Described silicon sol is selected from tetraethoxy, isopropyl titanate or zirconium-n-propylate, and non-silicon sol is selected from sodium aluminate, aluminum nitrate, aluminium secondary butylate, trimethyl carbinol aluminium, aluminum ethylate and aluminum isopropylate.
Step 3 is that magnetic is modified, and comprises the following steps: be n (Fe by mol ratio
3+): n (Fe
2+) be the FeSO of 1:0.7-0.5
47H
2o, Fe
2(SO
4)
3, or n (Fe
3+): n (Fe
2+) be the FeCl of 1:0.7-0.5
36H
2o, FeCl
2dissolve in deionized water, add cetyl trimethylammonium bromide, under an inert atmosphere, regulate pH to 9-10; In the solution after adjustment pH, add the zeolite deriving from step 1 and step 2, after dropping tetraethyl orthosilicate completes, stir 6 hours, then add TiSO
4, adjust pH to 13, dropping limit, limit is stirred, and leaves standstill, utilize magnetic resolution, and wash away impurity with acetone, afterwards, the magnetic solid super acidic catalyst obtained is put into baking oven after completing, and dries at 105 DEG C.
According to one embodiment of the invention, the weight ratio that adds of the zeolite of step 1 and step 2 is 1:4-1:1, and the weight ratio that adds of the zeolite of preferred steps 1 and step 2 is 2:3.
Step (4) is load phosphotungstic acid/ZrO
2, comprise the following steps: by Zr (NO
3)
4be dissolved in deionized water, be mixed with the zirconium nitrate aqueous solution that mass concentration is 30-40% (preferably 40%), join in the zirconium nitrate aqueous solution by the zeolite that abovementioned steps (3) obtains, violent stirring, to even suspension, then instills ammoniacal liquor and makes Zr (OH)
4uniform deposition on zeolite, leach throw out and wash, 100-110 DEG C dries, then in air atmosphere 350-450 DEG C of roasting; The Salkowski's solution being 10 % by weight by aforementioned zeolite concentration in air atmosphere after 350-450 DEG C of roasting floods 8 hours, then evaporating water, 100-110 DEG C of oven dry, then 200-400 DEG C of (preferably 300 DEG C) roasting in air atmosphere, obtains load phosphotungstic acid/ZrO
2zeolite.
According to one embodiment of the invention, zirconic charge capacity is the 5-10% of weight zeolite, and phospho-wolframic acid charge capacity is the 5-10% of weight zeolite.
The catalyzer adopting present method to prepare has following beneficial effect:
1. adopt natural zeolite to mix mutually with synthetic zeolite, reduce use cost, simultaneously multistage pore size distribution avoids homogeneous narrow and small duct in single molecular sieve and is unfavorable for that macromole participates in reaction, hinders generation diffusion and the generation carbon distribution of product and reactant.
2., owing to having carried out expanding treatment to zeolite, be both beneficial to the catalytic activity improving zeolite, be more conducive to, after follow-up coated magneticsubstance, still keeping the rate of diffusion in duct.
3. adopt template original position to prepare zeolite molecular sieve, cosolvent made by the alcohol that have employed corresponding hydrolyzate, not only in the process of synthesis, hydrolytic process has been relaxed by the adjustment of solvent, and be conducive to the sedimentation growth of copolymer microsphere, polyalcohol microspherulite diameter is homogeneous, and the single template of molecular weight distribution is orderly, by controlling reaction times and solvent ratio, the size of adjustable ethene copolymer, can obtain the macropore template of different size.
4. utilize modified carbon nano-tube to obtain mesoporous material for template.
5., after coated magnetic material, by magnetic force, catalyzer high efficiency separation from product out, can be overcome the shortcoming of catalyzer not easily Separation and Recovery after the reaction.
6. magneticsubstance appearance is coated with protective layer, can protect magnetic particle when reacting.
7. modified component in-situ preparation can be overlying on zeolite surface by the inventive method, each component disperses is effective, and be conducive to the effect playing each component, synergy is better.
8., in the preparation process of the chloro-5-fluoro acetophenone of 2,4-bis-, avoid aforementioned use aluminum chloride Problems existing, and the agent of the application's partially catalyzed effectively can improve 2, the selectivity of the chloro-5-fluoro acetophenone of 4-bis-, reduces mother liquor crystallization subsequently and is separated the cost of the chloro-5-fluoro acetophenone of 2,4-bis-.
Embodiment
In order to make object of the present invention, technical scheme and advantage clearly understand, the following specific embodiment of the present invention is described, but the present invention is limited to absolutely not these examples.The following stated is only the good embodiment of the present invention, only for explaining the present invention, therefore can not be interpreted as the restriction to the scope of the claims of the present invention.It should be pointed out that all any amendments done within the spirit and principles in the present invention, equivalent replacement and improvement etc., all should be included within protection scope of the present invention.
The test of zeolite catalyst strength of acid of the present invention is undertaken by Hammett indicator method.Use anhydrous cyclohexane as solvent, compound concentration is 0.1%-0.5% indicator solution.Drip indicator to dry catalyst surface and observe colour-change during mensuration: if color changes, showing that catalyzer reaches the strength of acid of the indicator of use, now changing acid stronger indicator and measure, until color no longer changes.The maximal acid intensity that can reach is the strength of acid of this catalyzer.
Below by way of concrete test examples, preparation method of the present invention and effect thereof are described.
The preparation of composite zeolite solid super acid catalyst
Step (1): zeolite pre-treatment
A1
To mordenite carrier after 450 DEG C of calcination process, adding with containing ammonium concentration is that 1.0mol/L ammonium nitrate solution carries out exchange process, ammonium salt solution and the liquid-solid volume ratio of zeolite are 4:1, swap time is 6 hours, repeat 4 times, mordenite after exchanging with deionized water wash, then carry out drying and 450 DEG C of calcination process again;
The zeolite of aforementioned calcination process is again put into the H that concentration is 6mol/L
2sO
4soak 6 hours in solution, with deionized water wash to neutral, drier, within 8 hours, obtain pretreated carrier 450 DEG C of roastings.
A2
To mordenite carrier after 650 DEG C of calcination process, adding with containing ammonium concentration is that 0.05mol/L ammoniumsulphate soln carries out exchange process, ammonium salt solution and the liquid-solid volume ratio of zeolite are 3:1, swap time is 30 hours, repeat 10 times, mordenite after exchanging with deionized water wash, then carry out drying and 650 DEG C of calcination process again;
The zeolite of aforementioned calcination process again being put into concentration is that the salpeter solution of 0.05mol/L soaks 12 hours, with deionized water wash to neutral, drier, within 8 hours, obtain pretreated carrier 650 DEG C of roastings.
A3
To mordenite carrier after 550 DEG C of calcination process, adding with containing ammonium concentration is that 0.5mol/L sal volatile carries out exchange process, ammonium salt solution and the liquid-solid volume ratio of zeolite are 4:1, swap time is 60 hours, mordenite after exchanging with deionized water wash, then carry out drying and 550 DEG C of calcination process again;
The zeolite of aforementioned calcination process again being put into concentration is that the hydrochloric acid soln of 4mol/L soaks 10 hours, with deionized water wash to neutral, drier, within 8 hours, obtain pretreated carrier 550 DEG C of roastings.
Step (2): the synthesis 1 of porous level zeolite
B1
Under protection of inert gas, the maleic anhydride of mol ratio 1:1:1, vinylbenzene and vinyl acetate between to for plastic and dibenzoyl peroxide are joined ethanol and acetone volume ratio is dissolve in the mixed solvent of 1:1 to obtain reaction solution, in reaction solution, the mass concentration of initiator is 0.1%, and in 70 DEG C of reactions 6 hours, obtain the dispersion system of polymer microballoon;
By dispersion system, tetraethoxy silicon sol and aluminum nitrate according to 1: 10: 0.5 mass ratio mix, then stir, at room temperature naturally place, to complete gelation process;
Again through centrifugation, be cooled to room temperature, washing, suction filtration, drying, 450 DEG C of roastings obtain porous level zeolite for 6 hours.
B2
Under protection of inert gas, the maleic anhydride of mol ratio 1:2:2, vinylbenzene and vinyl acetate between to for plastic and dibenzoyl peroxide are joined ethanol and acetone volume ratio is dissolve in the mixed solvent of 1:1.5 to obtain reaction solution, in reaction solution, the mass concentration of initiator is 0.5%, and in 80 DEG C of reactions 10 hours, obtain the dispersion system of polymer microballoon;
By dispersion system, tetraethoxy silicon sol and aluminum nitrate according to 1: 20: 3 mass ratio mix, then stir, at room temperature naturally place, to complete gelation process;
Again through centrifugation, be cooled to room temperature, washing, suction filtration, drying, 650 DEG C of roastings obtain porous level zeolite for 5 hours.
B3
Under protection of inert gas, the maleic anhydride of mol ratio 1:2:2, vinylbenzene and vinyl acetate between to for plastic and dibenzoyl peroxide are joined ethanol and acetone volume ratio is dissolve in the mixed solvent of 1:1.5 to obtain reaction solution, in reaction solution, the mass concentration of initiator is 0.3%, and in 80 DEG C of reactions 8 hours, obtain the dispersion system of polymer microballoon;
By dispersion system, tetraethoxy silicon sol and aluminum nitrate according to 1: 15: 1.5 mass ratio mix, then stir, at room temperature naturally place, to complete gelation process;
Again through centrifugation, be cooled to room temperature, washing, suction filtration, drying, 550 DEG C of roastings obtain porous level zeolite for 5 hours.
Step (2): the synthesis 2 of porous level zeolite
B'1
Use dense HNO
3with 30% mass concentration H
2o
2modification is carried out to carbon nano tube surface (external diameter about 6nm), obtains the carbon nanotube of surface modification.
Stir 0.5 hour together with remix after aluminum nitrate is dissolved in dehydrated alcohol respectively with cetyl trimethylammonium bromide (CTAB), obtain mixed system 1; By the triblock copolymer (P123) of polyoxyethylene-poly-oxypropylene polyoxyethylene with add dense H through above-mentioned modified carbon nano-tube
2sO
4with in HCl mixing solutions, in stirred at ambient temperature until P123 melts completely, add the teos solution being dissolved in dehydrated alcohol, stir 3 hours, obtain mixed system 2;
By mixed system 1 and 2-in-1 and and after mixing, reinstall reactor, in 95 DEG C of Hydrothermal Synthesiss 50 hours, finally take out, be cooled to room temperature, washing, suction filtration, drying, roasting, obtain the zeolite of two kinds of presomas with double-pore structure,
Amount ratio is, carbon nanotube: aluminum nitrate: CTAB: triblock copolymer: tetraethyl silicate=2g:2g:3g:1g:2ml.
B'2
Use dense HNO
3with 30% mass concentration H
2o
2modification is carried out to carbon nano tube surface (external diameter about 6nm), obtains the carbon nanotube of surface modification.
Stir 1.5 hours together with remix after aluminum nitrate is dissolved in dehydrated alcohol respectively with cetyl trimethylammonium bromide (CTAB), obtain mixed system 1; By the triblock copolymer (P123) of polyoxyethylene-poly-oxypropylene polyoxyethylene with add dense H through above-mentioned modified carbon nano-tube
2sO
4with in HCl mixing solutions, in stirred at ambient temperature until P123 melts completely, add the teos solution being dissolved in dehydrated alcohol, stir 2 hours, obtain mixed system 2;
By mixed system 1 and 2-in-1 and and after mixing, reinstall reactor, in 105 DEG C of Hydrothermal Synthesiss 40 hours, finally take out, be cooled to room temperature, washing, suction filtration, drying, roasting, obtain the zeolite of two kinds of presomas with double-pore structure.
Amount ratio is, carbon nanotube: aluminum nitrate: CTAB: triblock copolymer: tetraethyl silicate=2g:2g:3g:1g:2ml.
B'3
Use dense HNO
3with 30% mass concentration H
2o
2modification is carried out to carbon nano tube surface (external diameter about 6nm), obtains the carbon nanotube of surface modification.
Stir 1 hour together with remix after aluminum nitrate is dissolved in dehydrated alcohol respectively with cetyl trimethylammonium bromide (CTAB), obtain mixed system 1; By the triblock copolymer (P123) of polyoxyethylene-poly-oxypropylene polyoxyethylene with add dense H through above-mentioned modified carbon nano-tube
2sO
4with in HCl mixing solutions, in stirred at ambient temperature until P123 melts completely, add the teos solution being dissolved in dehydrated alcohol, stir 2.5 hours, obtain mixed system 2;
By mixed system 1 and 2-in-1 and and after mixing, reinstall reactor, in 100 DEG C of Hydrothermal Synthesiss 45 hours, finally take out, be cooled to room temperature, washing, suction filtration, drying, roasting, obtain the zeolite of two kinds of presomas with double-pore structure.
Amount ratio is, carbon nanotube: aluminum nitrate: CTAB: triblock copolymer: tetraethyl silicate=2g:2g:3g:1g:2ml.
Step (3): magnetic is modified
C1
Be n (Fe by mol ratio
3+): n (Fe
2+) be the FeSO of 1:0.7
47H
2o and Fe
2(SO
4)
3dissolve in deionized water, add cetyl trimethylammonium bromide, under an inert atmosphere, regulate pH to 9; In the solution after adjustment pH, add the zeolite deriving from step 1 and step 2, after dropping tetraethyl orthosilicate completes, stir 6 hours, then add TiSO
4, adjust pH to 13, dropping limit, limit is stirred, and leaves standstill, utilize magnetic resolution, and wash away impurity with acetone, afterwards, the magnetic solid super acidic catalyst obtained is put into baking oven after completing, and dries at 105 DEG C.
C2
Be n (Fe by mol ratio
3+): n (Fe
2+) be the FeSO of 1:0.5
47H
2o and Fe
2(SO
4)
3dissolve in deionized water, add cetyl trimethylammonium bromide, under an inert atmosphere, regulate pH to 10; In the solution after adjustment pH, add the zeolite deriving from step 1 and step 2, after dropping tetraethyl orthosilicate completes, stir 6 hours, then add TiSO
4, adjust pH to 13, dropping limit, limit is stirred, and leaves standstill, utilize magnetic resolution, and wash away impurity with acetone, afterwards, the magnetic solid super acidic catalyst obtained is put into baking oven after completing, and dries at 100 DEG C.
C3
Be n (Fe by mol ratio
3+): n (Fe
2+) be the FeCl of 1:0.7
36H
2o and FeCl
2dissolve in deionized water, add cetyl trimethylammonium bromide, under an inert atmosphere, regulate pH to 9; In the solution after adjustment pH, add the zeolite deriving from step 1 and step 2, after dropping tetraethyl orthosilicate completes, stir 6 hours, then add TiSO
4, adjust pH to 13, dropping limit, limit is stirred, and leaves standstill, utilize magnetic resolution, and wash away impurity with acetone, afterwards, the magnetic solid super acidic catalyst obtained is put into baking oven after completing, and dries at 110 DEG C.
Step (4): phospho-wolframic acid/ZrO
2load
D1
By Zr (NO
3)
4be dissolved in deionized water, be mixed with the zirconium nitrate aqueous solution that mass concentration is 30%, join in the zirconium nitrate aqueous solution by the zeolite that abovementioned steps (3) obtains, violent stirring, to even suspension, then instills ammoniacal liquor and makes Zr (OH)
4uniform deposition on zeolite, leach throw out and wash, 100 DEG C of oven dry, then 450 DEG C of roastings in air atmosphere.The Salkowski's solution being 10 % by weight by aforementioned zeolite concentration in air atmosphere after 350 DEG C of roastings floods 8 hours, then evaporating water, 100 DEG C of oven dry, and then 300 DEG C of roastings in air atmosphere, obtain load phosphotungstic acid/ZrO
2zeolite.
D2
By Zr (NO
3)
4be dissolved in deionized water, be mixed with the zirconium nitrate aqueous solution that mass concentration is 40%, then join in the zirconium nitrate aqueous solution by the zeolite that abovementioned steps (3) obtains, violent stirring, to even suspension, then instills ammoniacal liquor and makes Zr (OH)
4uniform deposition on zeolite, leach throw out and wash, 105 DEG C of oven dry, then 350 DEG C of roastings in air atmosphere.The Salkowski's solution being 10 % by weight by aforementioned zeolite concentration in air atmosphere after 350 DEG C of roastings floods 8 hours, then evaporating water, 110 DEG C of oven dry, and then 400 DEG C of roastings in air atmosphere, obtain load phosphotungstic acid/ZrO
2zeolite.
D3
By Zr (NO
3)
4be dissolved in deionized water, be mixed with the zirconium nitrate aqueous solution that mass concentration is 35%, then join in the zirconium nitrate aqueous solution by the zeolite that abovementioned steps (3) obtains, violent stirring, to even suspension, then instills ammoniacal liquor and makes Zr (OH)
4uniform deposition on zeolite, leach throw out and wash, 110 DEG C of oven dry, then 400 DEG C of roastings in air atmosphere.The Salkowski's solution being 10 % by weight by aforementioned zeolite concentration in air atmosphere after 350 DEG C of roastings floods 8 hours, then evaporating water, 105 DEG C of oven dry, and then 200 DEG C of roastings in air atmosphere, obtain load phosphotungstic acid/ZrO
2zeolite.
Table 1: catalyst characterization
Wherein, preparation process refers to the step that catalyst preparing uses, such as A1B1C1D1 refers to and uses abovementioned steps A1, B1, C1 and D1 preparation respectively, natural zeolite and synthetic zeolite ratio refer to by step (3) middle select the zeolite ratio of different step 1 and step 2 to obtain natural zeolite and synthetic zeolite ratio.
The preparation of the chloro-5-fluoro acetophenone of 2,4-bis-
The preparation of the chloro-5-fluoro acetophenone of embodiment 1:2,4-bis-
33 grams of (0.2mol) 1 are added in reactor, the chloro-4-fluorobenzene of 3-bis-and 20.4 grams of (0.26mol) Acetyl Chloride 98Min.s, then in reactor, add the catalyzer 11 in 30 grams of aforementioned tables 1, react to 120 DEG C of stirring reactions 60 minutes, subsequently to charging in reaction mixture 500 ml deionized water and 200 milliliters of toluene and proceed stir, by organic phase and aqueous phase separation after layering, gained aqueous phase 200 milliliters of toluene extract further, whole for gained organic phase is merged, by distillation removing toluene, reactor temperature carries out underpressure distillation after reaching 90 DEG C, collect 100-120 DEG C of cut, last freezing and crystallizing obtains 42.0 grams of white crystals, , fusing point is 33.5-34 DEG C, yield is 92.1%.
Carry out mass spectroscopy and ultimate analysis to product, acquired results is as follows:
Mass spectrum: m/z:205.97 (100.0%), 207.97 (64.1%), 209.96 (10.2%), 206.97 (8.7%), 208.97 (5.6%).
Results of elemental analyses: C, 46.41; H, 2.43; Cl, 34.25; F, 9.18; O, 7.73.Molecular weight of product is: 207.03.
The preparation of the chloro-5-fluoro acetophenone of embodiment 2:2,4-bis-
Repeat embodiment 1, difference is the catalyzer 11 using regeneration 5 times later, and final reaction obtains 39.8 grams of white crystals, yield 87.4%.
The preparation of the chloro-5-fluoro acetophenone of embodiment 3:2,4-bis-
Repeat embodiment 1, difference is that temperature of reaction is 115 DEG C, and final reaction obtains 41.8 grams of white crystals, yield 91.8%.
The preparation of the chloro-5-fluoro acetophenone of embodiment 4:2,4-bis-
Repeat embodiment 1, difference is that temperature of reaction is 90 DEG C, and final reaction obtains 41.3 grams of white crystals, yield 90.8%.
The preparation of the chloro-5-fluoro acetophenone of embodiment 5:2,4-bis-
Repeat embodiment 1, difference is the catalyzer 17 in use 30 grams of aforementioned tables 1, and final reaction obtains 38.8 grams of white crystals, yield 85.2%.
The preparation of the chloro-5-fluoro acetophenone of embodiment 6:2,4-bis-
Repeat embodiment 1, difference is the catalyzer 2 in use 30 grams of aforementioned tables 1, and final reaction obtains 41.5 grams of white crystals, yield 91.2%.
The preparation of the chloro-5-fluoro acetophenone of embodiment 7:2,4-bis-
Repeat embodiment 1, difference is the catalyzer 8 in use 30 grams of aforementioned tables 1, and final reaction obtains 38.9 grams of white crystals, yield 85.4%.
Comparative example 1, embodiment 5, embodiment 6 and embodiment 7, contriver finds unexpectedly, even if use the catalyzer in the application's table 1 all can effectively improve product 2, the selectivity of the chloro-5-fluorobenzoyl chloride of 4-bis-, but catalyzer 11 and catalyzer 17 still obviously will be better than catalyzer 2 and catalyzer 8 in selectivity.
The preparation of the chloro-5-fluoro acetophenone of embodiment 8:2,4-bis-
Repeat embodiment 1, difference is the catalyzer 17 using regeneration 5 times later, and final reaction obtains 39.7 grams of white crystals, yield 87.2%.
According to embodiment 2 and embodiment 8, the application's catalyzer, after regeneration several times, still can reach good effect, reduce catalyzer cost, decrease refuse process.
The preparation of the chloro-5-fluoro acetophenone of embodiment 9:2,4-bis-
Repeat embodiment 1, difference is use 15.7 grams of (0.26mol) Acetyl Chloride 98Min.s, and final reaction obtains 41.6 grams of white crystals, yield 91.4%.
The preparation of the chloro-5-fluoro acetophenone of embodiment 10:2,4-bis-
Repeat embodiment 1, difference is the catalyzer 11 in use 16 grams of aforementioned tables 1, and final reaction obtains 41.0 grams of white crystals, yield 90.2%.
Claims (11)
1. the method for the chloro-5-fluoro acetophenone of synthesis 2,4-bis-, said method comprising the steps of:
2,4-dichlor fluorbenzene reacts under agitation with Acetyl Chloride 98Min. under the existence of composite zeolite solid super acid catalyst, reaction to terminate in backward reaction mixture directly feeding extraction agent and water and proceeds to stir, reaction terminates rear stratification and by organic phase and aqueous phase separation, aqueous phase extraction agent extracts further, and whole organic phase is merged, by distillation removing extraction agent, product frac is collected in underpressure distillation, and last freezing and crystallizing obtains white crystal
Wherein said composite zeolite solid super acid catalyst is prepared by following steps:
(1) Zeolite support pre-treatment, comprises following operation:
(1.1) to Natural Zeolite Support after 450 DEG C of-650 DEG C of calcination process, carry out exchange process with the ammonium salt solution containing ammonium nitrate, volatile salt or ammonium sulfate that ammonium concentration is 0.05 ~ 1.0mol/L, the liquid-solid volume ratio of ammonium salt solution and zeolite is 3:1 ~ 5:1; Swap time is 30 minutes to 60 hours, the zeolite after exchanging with deionized water wash, then carries out drying and 450 DEG C-650 DEG C calcination process again; Described natural zeolite is mordenite;
(1.2) carrier reaming: the zeolite that step (1.1) obtains is put into HCl, HNO that concentration is 0.05 ~ 6mol/L
3, H
2sO
4or soak 6-10 hour in citric acid, with deionized water wash to neutral, dry, obtain pretreated carrier 450 DEG C of-650 DEG C of roastings;
(2) synthesis of porous level zeolite, comprises following operation:
(2.1) HNO is used
3and H
2o
2modification is carried out to carbon nano tube surface, obtains the carbon nanotube of surface modification,
(2.2) stir 0.5-1.5 hour together with remix after non-silicon sol being dissolved in dehydrated alcohol respectively with cetyl trimethylammonium bromide (CTAB), obtain mixed system 1; By the triblock copolymer (P123) of polyoxyethylene-poly-oxypropylene polyoxyethylene with join H through the carbon nanotube of above-mentioned surface modification
2sO
4with in HCl mixing solutions, in stirred at ambient temperature until P123 melts completely, add the precursor aqueous solution that the silicon sol that is dissolved in dehydrated alcohol obtains, stir 2-3 hour, obtain mixed system 2;
(2.3) by mixed system 1 and 2-in-1 and and after mixing, at 95-105 DEG C, Hydrothermal Synthesis 40-50 hour, finally takes out, and is cooled to room temperature, washing, suction filtration, drying, roasting, obtain the zeolite of two kinds of presomas with double-pore structure,
Described silicon sol is selected from tetraethoxy, isopropyl titanate or zirconium-n-propylate, and non-silicon sol is selected from sodium aluminate, aluminum nitrate, aluminium secondary butylate, trimethyl carbinol aluminium, aluminum ethylate and aluminum isopropylate;
(3) magnetic is modified, and comprises the following steps:
Be n (Fe by mol ratio
3+): n (Fe
2+) be the FeSO of 1:0.7-0.5
47H
2o, Fe
2(SO
4)
3, or n (Fe
3+): n (Fe
2+) be the FeCl of 1:0.7-0.5
36H
2o, FeCl
2dissolve in deionized water, add cetyl trimethylammonium bromide, under an inert atmosphere, regulate pH to 9-10; In the solution after adjustment pH, add the zeolite deriving from step (1) and step (2), after dropping tetraethyl orthosilicate completes, stir 6 hours, then add TiSO
4, adjust pH to 13, dropping limit, limit is stirred, and leaves standstill, utilize magnetic resolution, and wash away impurity with acetone, afterwards, the magnetic solid super acidic catalyst obtained is put into baking oven after completing, and dries at 105 DEG C; Wherein the weight ratio that adds of the zeolite of step (1) and step (2) is 1:4-1:1;
(4) phospho-wolframic acid/ZrO
2load, comprise the following steps:
By Zr (NO
3)
4be dissolved in deionized water, be mixed with the zirconium nitrate aqueous solution that mass concentration is 30-40%, join in the zirconium nitrate aqueous solution by the zeolite that abovementioned steps (3) obtains, violent stirring, to even suspension, then instills ammoniacal liquor and makes Zr (OH)
4uniform deposition on zeolite, leach throw out and wash, 100-110 DEG C dries, then in air atmosphere 350-450 DEG C of roasting;
The Salkowski's solution being 10 % by weight by aforementioned zeolite concentration in air atmosphere after 350-450 DEG C of roasting floods 8 hours, then evaporating water, 100-110 DEG C of oven dry, and then 200-400 DEG C of roasting in air atmosphere, obtains load phosphotungstic acid/ZrO
2zeolite.
2. method according to claim 1, it is characterized in that zirconic charge capacity is the 5-10% of weight zeolite, phospho-wolframic acid charge capacity is the 5-10% of weight zeolite.
3. method according to claim 1, is characterized in that in step (3), and the weight ratio that adds of the zeolite of step (1) and step (2) is 2:3.
4. method according to claim 1, is characterized in that in step (4), by Zr (NO
3)
4be dissolved in deionized water and be mixed with the zirconium nitrate aqueous solution that mass concentration is 40%.
5. method according to claim 1, is characterized in that in step (4), and the maturing temperature after dipping Salkowski's solution is 300 DEG C.
6. method according to claim 1, it is characterized in that 2,4 dichloro fluorobenzene reacts 40 minutes-180 minutes under agitation with Acetyl Chloride 98Min. under the existence of composite zeolite solid super acid catalyst, temperature of reaction is 80-140 DEG C.
7. method according to claim 1, it is characterized in that 2,4 dichloro fluorobenzene reacts 60 minutes-120 minutes under agitation with Acetyl Chloride 98Min. under the existence of composite zeolite solid super acid catalyst, temperature of reaction is 90-120 DEG C.
8. method according to claim 1, is characterized in that using 40-200 gram of composite zeolite solid super acid catalyst relative to every mole of 2,4 dichloro fluorobenzene.
9. method according to claim 1, is characterized in that using 80-150 gram of composite zeolite solid super acid catalyst relative to every mole of 2,4 dichloro fluorobenzene.
10. method according to claim 1, the extraction agent that it is characterized in that using is acetone, methylene dichloride or toluene.
11. methods according to claim 1, is characterized in that the extraction agent used is toluene.
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| 氯氟苯乙酮合成工艺的研究;张启兴;《化工时刊》;1997;第11卷(第2期);22-24 * |
| 硅胶负载磷钨酸铯催化合成对甲氧基苯乙酮;施介华等;《石油化工》;2009;第38卷(第5期);525-530 * |
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