CN106748943B - The method and device that a kind of continuous hydrolysis of the double grignard condensation products of vitamin A intermediate neutralizes - Google Patents
The method and device that a kind of continuous hydrolysis of the double grignard condensation products of vitamin A intermediate neutralizes Download PDFInfo
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- CN106748943B CN106748943B CN201611262269.2A CN201611262269A CN106748943B CN 106748943 B CN106748943 B CN 106748943B CN 201611262269 A CN201611262269 A CN 201611262269A CN 106748943 B CN106748943 B CN 106748943B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C403/00—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone
- C07C403/06—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by singly-bound oxygen atoms
- C07C403/08—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by singly-bound oxygen atoms by hydroxy groups
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/24—Stationary reactors without moving elements inside
- B01J19/2415—Tubular reactors
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/30—Loose or shaped packing elements, e.g. Raschig rings or Berl saddles, for pouring into the apparatus for mass or heat transfer
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/19—Details relating to the geometry of the reactor
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/30—Details relating to random packing elements
- B01J2219/302—Basic shape of the elements
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Abstract
The invention discloses the method and device that a kind of continuous hydrolysis of the double grignard condensation products of vitamin A intermediate neutralizes.Step is that the ethers solution containing the double grignard condensation products of vitamin A intermediate is pumped into tubular reactor respectively with sour water, and being sufficiently mixed progress continuous hydrolysis through tubular reactor obtains hydrolyzate；Buck is pumped into tubular reactor through another charging aperture of tubular reactor, carried out with the hydrolyzate in tubular reactor it is continuous in and obtain neutralizer；The neutralizer is discharged from the product outlet of tubular reactor, is separated into aqueous phase and organic phase, is removed the aqueous phase, after the organic phase is washed to neutrality, evaporation recovery organic solvent, obtains vitamin A intermediate condensation product.High using the method mixing efficiency of the present invention, the time is short, the purity and high income of product；Content is high, pure high income.Continuous operation can be realized simultaneously, securely and reliably, improves the working environment of production operation personnel, improves production efficiency and utilization rate of equipment and installations.
Description
Technical field
The present invention relates to the field of chemical synthesis, more particularly to a kind of continuous water of the double grignard condensation products of vitamin A intermediate
Solve the method and device neutralized.
Background technology
The double grignard condensation products of vitamin A intermediate, for the hydrolysis precursor of vitamin A intermediate condensation product, structural formula
Formula is as follows：
The preparation technology of double grignard condensation products is as follows：Under the conditions of ether solvent, grignard is prepared with halogenated alkane in magnesium
Reagent, six carbyne alcohol are added dropwise, obtain double carbon alcohol of grignard six, then 2-methyl-4-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2-butenal is added dropwise, double grignard condensation products are prepared in reaction.
Double grignard condensation products obtain product vitamin A intermediate condensation product after sour water hydrolyzes, buck neutralizes.
It is batch process that traditional hydrolysis, which neutralizes technique,：Sour water is added in double grignard condensation product solution and stirred into water-filling
Solution, after stratification, water layer is removed, after adding soda lye wash to neutrality, removes water layer, recycling design, obtain condensation product,
The content of condensation product is about 88~92%, and yield is about 90% (with respect to 2-methyl-4-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2-butenal).
Traditional batch hydrolysis neutralizes technique and had the following disadvantages：
1) reaction is hydrolyzed using tank reactor in traditional batch hydrolysis process, and the organic solution of double grignard condensation products
It is generally not miscible with sour water, it is receivable in order to obtain industry because hydrolysis is generally occurred mainly at liquid interface
Reaction rate nevertheless, reaction effect is still not fully up to expectations, often occurs back mixing, caused, it is necessary to tempestuously blended liquid phase
The formation of undesirable accessory substance, even result in the generation of raw material overreaction；
2) hydrolysis time of batch process hydrolysis neutralization technique is longer, and sour water concentration is higher, whole system acidity is unbalanced,
So that condensation product is long with acid residence time, easily it is destroyed because condensation product is extremely unstable in acid, therefore the purity of condensation product,
Yield is low, while brings difficulty to subsequent purification；
3) in traditional batch technique, before buck neutralizes, it is necessary to by hydrolyzate stratification, as time of repose is long, easily production
Raw accessory substance, as time of repose is too short, easily condensation product is brought into spent acid water layer, therefore operation difficulty is larger, is not easy precisely to control
System.
The content of the invention
It is an object of the invention to provide it is a kind of it is simple to operate, reaction yield is high, the vitamin A intermediate of good product quality
The method that the continuous hydrolysis of double grignard condensation products neutralizes.
To achieve the above object, the present invention provides a kind of continuous hydrolysis neutralization of the double grignard condensation products of vitamin A intermediate
Method, it is characterised in that step is,
1) the ethers solution containing the double grignard condensation products of vitamin A intermediate is pumped into tubular reactor respectively with sour water,
Progress continuous hydrolysis, which is sufficiently mixed, through tubular reactor obtains hydrolyzate；
2) buck is pumped into tubular reactor through another charging aperture of tubular reactor, with the hydrolyzate in tubular reactor
Carry out continuous neutralize and obtain neutralizer；
3) neutralizer is discharged from the product outlet of tubular reactor, separates into aqueous phase and organic phase, described in removing
Aqueous phase, after the organic phase is washed to neutrality, evaporation recovery organic solvent, obtain vitamin A intermediate condensation product.
Further, in the 1) step, packing section and clear band, institute have been arranged alternately in the pipeline of the tubular reactor
State the section that packing section is filled with filler in the duct, the clear band is the section of non-filler in pipeline, packing section and
Clear band alternates；Preferably, the length ratio of the packing section and clear band is 1:(0.5~2)；It is furthermore preferred that described fill out
The length ratio for expecting section and clear band is 1:(1~1.5)；Pipeline is provided with charging aperture 1, charging aperture 2 and charging aperture 3 and product discharge
Mouthful；Its middle charging aperture 1, charging aperture 2 and charging aperture 3 are respectively used to entering for pair ethers solution of grignard condensation products, sour water and buck
Material；Preferably, the position of charging aperture 3 is arranged at hydrolysis and completes or be basically completed part；The pipeline periphery is provided with folder
Set, for leading to heat transferring medium, reaction is exchanged heat.
Further, the filler is quartz sand, Raschig ring or graphite nodule；
Optional, the tubular reactor is straight pipe type tubular reactor, U-tube formula tubular reactor, coiled tubular type
Reactor or multitube tubular reactor.
Further, in the 1) step, the ethers be 2 to 10 carbon composition straight or branched ether or tetrahydrofuran and
Its derivative, the straight or branched ether are selected from least one of isopropyl ether, ether, propyl ether；The tetrahydrofuran and its spread out
Biology is tetrahydrofuran or 2- methyltetrahydrofurans；
It is optional, the concentration of the ethers solution containing the double grignard condensation products of vitamin A intermediate for 0.4~
1.6mol/L；Preferably, it is 0.5~1.2mol/L；It is furthermore preferred that it is 0.8~1.0mol/L；
Optional, the sour water is sulfuric acid, hydrochloric acid, phosphoric acid or aqueous ammonium chloride solution；
Optional, [H+] concentration in the sour water is 0.5~2mol/L；Preferably, it is 0.5~1.8mol/L；It is more excellent
Choosing, be 1.4~1.6mol/L；
Optional, the ethers solution containing the double grignard condensation products of vitamin A intermediate and the charging of sour water unit interval
Volume ratio is：Ethers solution containing the double grignard condensation products of vitamin A intermediate：Sour water=1:(1.1~2)；Preferably, it is 1:
(1.1~1.7)；It is furthermore preferred that it is 1:(1.4~1.5)；
Optional, the reaction temperature of the hydrolysis is 0~60 DEG C；Preferably, it is 15~45 DEG C；It is furthermore preferred that for 25~
35℃；
Optional, the reaction time of the hydrolysis is 10~100 seconds；Preferably, it is 20~80 seconds；It is furthermore preferred that it is 30
~60 seconds.
Further, in the 2) step, the buck is aqueous sodium carbonate or sodium bicarbonate aqueous solution；
Optional, the concentration of the buck is 0.1~1mol/L；
Optional, the ethers solution containing the double grignard condensation products of vitamin A intermediate and the charging of buck unit interval
Volume ratio is：Ethers solution containing the double grignard condensation products of vitamin A intermediate：Buck=1：(0.5~2)；Preferably, it is 1:
(1~1.5)；
Optional, the reaction temperature of the neutralization is 0~60 DEG C；Preferably, it is 15~45 DEG C；It is furthermore preferred that for 25~
35℃；
Optional, the reaction time of the neutralization is 10~90 seconds；Preferably, it is 20~70 seconds；It is furthermore preferred that for 40~
60 seconds.
Further, the ethers solution containing the double grignard condensation products of vitamin A intermediate, sour water, hydrolyzate, buck and
Flow velocity of the neutralizer in tubular reactor is 0.4-6m/s；Preferably, it is 1-4m/s；It is furthermore preferred that it is 2-3m/s.
The present invention also provides the side that a kind of continuous hydrolysis suitable for the double grignard condensation products of the vitamin A intermediate neutralizes
The device of method, described device are a kind of tubular reactor, it is characterised in that have been arranged alternately in the pipeline of the tubular reactor
Packing section and clear band, the packing section are filled with the section of filler in the duct, and the clear band is without filling in pipeline
The section of thing, packing section and clear band alternate；There are charging aperture 1, charging aperture 2 and charging aperture 3 and product outlet on pipeline；
Its middle charging aperture 1, charging aperture 2 and charging aperture 3 are respectively used to pair charging of the ethers solution of grignard condensation products, sour water and buck；
The pipeline periphery is provided with chuck, and for leading to heat transferring medium, reaction is exchanged heat.
Further, the length ratio of the packing section and clear band is 1:(0.5~2)；Preferably, the packing section and blank
The length ratio of section is 1:(1~1.5)；
Optional, the position of charging aperture 3 is arranged at hydrolysis and completes or be basically completed part.
Further, the filler is quartz sand, Raschig ring or graphite nodule.
Further, the tubular reactor is straight pipe type tubular reactor, U-tube formula tubular reactor, coiled tubular type
Reactor or multitube tubular reactor.
The distance of charging aperture 1 and 2 of the present invention is as far as possible near, because two kinds of raw materials are to be passed through pipeline simultaneously, charging aperture closes on
It is provided with to meet early beneficial to the two and is sufficiently mixed.
When reactant mixture flows through the packing section of tubular reactor, out of phase liquid reactant is thoroughly mixed, cut
Cut, be separated into small droplet, when mixture flows through clear band, out of phase liquid reactant is layered or part because of Action of Gravity Field
Layering, is divided into the upper and lower, when it is again introduced into next packing section, the upper and lower part is sheared simultaneously again
Mixing, redisperse is smaller droplet.The step of reactant mixture is by a series of mixing, shearing, combination, until described anti-
It should be basically completed.
Beneficial effects of the present invention：
(1) continuous hydrolysis that double grignard condensation products are carried out using the tubular reactor of the present invention is neutralized, and mixing efficiency is high, acid
The acidity of water hydrolyzation system is low compared with traditional batch Hydrolyze method, and hydrolysis time is short, the when compole that hydrolysate condensation product contacts with acid
It is short, so as to the purity and high income of product；Final product outward appearance is pale yellow oil, and content is pure up to 96%~98%
Yield is up to 98%~99%.
(2) continuous operation can be achieved, production process is easily controlled by automaton, operation facilitates, securely and reliably,
The error of manually operated can be avoided, greatlys save manpower, the working environment of production operation personnel is improved, improves life
Produce efficiency and utilization rate of equipment and installations.
Brief description of the drawings
Fig. 1 is the schematic device of coiled tubular reactor of the present invention.
Fig. 2 is the detection spectrogram of condensation product.
Embodiment
Embodiments of the invention are described below in detail, the example of the embodiment is shown in the drawings, wherein from beginning to end
Same or similar label represents same or similar element or the element with same or like function.Below with reference to attached
The embodiment of figure description is exemplary, it is intended to for explaining the present invention, and is not considered as limiting the invention.Embodiment
In unreceipted particular technique or condition person, according to the technology described by document in the art or condition or according to the description of product
Book is carried out.Agents useful for same or the unreceipted production firm person of instrument, being can be by the conventional products of acquisition purchased in market.
The content of condensation product is detected using following methods in following examples：
Method name：SHW- reversed-phased high performace liquid chromatographics；Pillar be Dalian Yi Lite Hypersil ODS2 5um ×
4.6mm×150mm；Detection wavelength 205nm；Flow velocity 1.0ml/min；Mobile phase is acetonitrile：Water：Tetrahydrofuran：Methanol=40：
50：0.7：1.2；Sample treatment is：Sample 0.04g accurately is weighed, is dissolved in 50ml methanol.Detection spectrogram is shown in Fig. 2.
Embodiment 1
Using straight pipe type tubular reactor, quartz sand used in the packing section in pipeline, the length ratio of packing section and clear band
For 1：1.
Compound concentration is the diethyl ether solution of the double chlorine magnesium condensation products of 0.8mol/L, forms material 1；Prepare [H+] concentration is
1.6mol/L aqueous hydrochloric acid solutions, form material 2；It is 0.5mol/L aqueous alkalis to prepare sodium acid carbonate concentration, forms material 3.
Simultaneously by material 1 and material 2 using unit interval volume ratio as 1:1.1 ratio is respectively through charging aperture 1 and charging aperture 2
Tubular reactor is pumped into, it is 25 DEG C to control hydrolysis temperature, hydrolysis time 20 seconds；After hydrolysis time arrives, by material 3 through charging aperture 3
Tubular reactor is pumped into, material 1 is 1 with 3 unit interval of material volume ratio:0.6, it is 25 DEG C to control neutralization reaction temperature, is neutralized
40 seconds time；Above-mentioned hydrolysis and neutralization reaction, it is 1m/s to control flow velocity of the reaction mass in tubular reactor.In continuous
With after the completion of, neutralizer is discharged from the product outlet of tubular reactor, the water layer of neutralizer point is gone, ether layer is washed with water into
After property, concentration and recovery ether, faint yellow oily condensation product, content 97.6%, the pure yield 98.6% of product are obtained.
Embodiment 2
Using U-tube formula tubular reactor, quartz sand used in the packing section in pipeline, the length ratio of packing section and clear band
For 1：0.5.
Compound concentration is the tetrahydrofuran solution of the double chlorine magnesium condensation products of 1.2mol/L, forms material 1；Compound concentration is
1.8mol/L aqueous ammonium chloride solutions, form material 2；It is 0.1mol/L aqueous alkalis to prepare sodium acid carbonate concentration, forms material 3.
Simultaneously by material 1 and material 2 using unit interval volume ratio as 1:1.4 ratio is respectively through charging aperture 1 and charging aperture 2
Tubular reactor is pumped into, it is 45 DEG C to control hydrolysis temperature, hydrolysis time 80 seconds；After hydrolysis time arrives, by material 3 through charging aperture 3
Tubular reactor is pumped into, material 1 is 1 with 3 unit interval of material volume ratio:2, it is 45 DEG C to control neutralization reaction temperature, during neutralization
Between 70 seconds；Above-mentioned hydrolysis and neutralization reaction, it is 4m/s to control flow velocity of the reaction mass in tubular reactor.It is continuous to neutralize
After the completion of, neutralizer is discharged from the product outlet of tubular reactor, the water layer of neutralizer point is gone, ether layer is washed with water to neutrality
Afterwards, concentration and recovery tetrahydrofuran, faint yellow oily condensation product, content 97.2%, the pure yield 98.4% of product are obtained.
Embodiment 3
Using coiled tubular reactor, Raschig ring used in the packing section in pipeline, the length ratio of packing section and clear band
For 1：1.5.Structure is as shown in Figure 1.
Compound concentration is the diethyl ether solution of the double chlorine magnesium condensation products of 1.0mol/L, forms material 1；Prepare [H+] concentration is
1.4mol/L aqueous sulfuric acids, form material 2；It is 0.1mol/L aqueous alkalis to prepare sodium acid carbonate concentration, forms material 3.
Simultaneously by material 1 and material 2 using unit interval volume ratio as 1:1.5 ratio is respectively through charging aperture 1 and charging aperture 2
Tubular reactor is pumped into, it is 35 DEG C to control hydrolysis temperature, hydrolysis time 30 seconds；After hydrolysis time arrives, by material 3 through charging aperture 3
Tubular reactor is pumped into, material 1 is 1 with 3 unit interval of material volume ratio:1.5, it is 35 DEG C to control neutralization reaction temperature, is neutralized
60 seconds time；Above-mentioned hydrolysis and neutralization reaction, it is 2m/s to control flow velocity of the reaction mass in tubular reactor.In continuous
With after the completion of, neutralizer is discharged from the product outlet of tubular reactor, the water layer of neutralizer point is gone, ether layer is washed with water into
After property, concentration and recovery ether, faint yellow oily condensation product, content 98.8%, the pure yield 99.6% of product are obtained.
Embodiment 4
Using coiled tubular reactor, Raschig ring used in the packing section in pipeline, the length ratio of packing section and clear band
For 1：1.5.Structure is as shown in Figure 1.
Compound concentration is the propyl ether solution of the double chlorine magnesium condensation products of 0.4mol/L, forms material 1；Prepare [H+] concentration is
0.5mol/L aqueous sulfuric acids, form material 2；Preparation concentration of sodium carbonate is 0.1mol/L aqueous alkalis, forms material 3.
Simultaneously by material 1 and material 2 using unit interval volume ratio as 1:1.7 ratio is respectively through charging aperture 1 and charging aperture 2
Tubular reactor is pumped into, it is 60 DEG C to control hydrolysis temperature, hydrolysis time 10 seconds；After hydrolysis time arrives, by material 3 through charging aperture 3
Tubular reactor is pumped into, material 1 is 1 with 3 unit interval of material volume ratio:1, it is 60 DEG C to control neutralization reaction temperature, during neutralization
Between 10 seconds；Above-mentioned hydrolysis and neutralization reaction, it is 0.4m/s to control flow velocity of the reaction mass in tubular reactor.In continuous
With after the completion of, neutralizer is discharged from the product outlet of tubular reactor, the water layer of neutralizer point is gone, ether layer is washed with water into
After property, concentration and recovery propyl ether, faint yellow oily condensation product, content 96.2%, the pure yield 98.0% of product are obtained.
Embodiment 5
Using coiled tubular reactor, graphite nodule used in the packing section in pipeline, the length ratio of packing section and clear band
For 1：2.
Compound concentration is the isopropyl ethereal solution of the double chlorine magnesium condensation products of 1.6mol/L, forms material 1；Prepare [H+] concentration is
2.0mol/L aqueous sulfuric acids, form material 2；Preparation concentration of sodium carbonate is 1mol/L aqueous alkalis, forms material 3.
Simultaneously by material 1 and material 2 using unit interval volume ratio as 1:1.7 ratio is respectively through charging aperture 1 and charging aperture 2
Tubular reactor is pumped into, it is 0 DEG C to control hydrolysis temperature, hydrolysis time 100 seconds；After hydrolysis time arrives, by material 3 through charging aperture 3
Tubular reactor is pumped into, material 1 is 1 with 3 unit interval of material volume ratio:0.5, it is 0 DEG C to control neutralization reaction temperature, during neutralization
Between 90 seconds；Above-mentioned hydrolysis and neutralization reaction, it is 6m/s to control flow velocity of the reaction mass in tubular reactor.It is continuous to neutralize
After the completion of, neutralizer is discharged from the product outlet of tubular reactor, the water layer of neutralizer point is gone, ether layer is washed with water to neutrality
Afterwards, concentration and recovery isopropyl ether, faint yellow oily condensation product, content 96.3%, the pure yield 98.1% of product are obtained.
Embodiment 6
Using U-tube formula tubular reactor, graphite nodule used in the packing section in pipeline, the length ratio of packing section and clear band
For 1：2.
Compound concentration is the 2- methyltetrahydrofuran solution of the double chlorine magnesium condensation products of 0.5mol/L, forms material 1；Prepare [H+]
Concentration is 0.5mol/ phosphate aqueous solutions, forms material 2；Preparation concentration of sodium carbonate is 0.1mol/L aqueous alkalis, forms material 3.
Simultaneously by material 1 and material 2 using unit interval volume ratio as 1:2 ratio is respectively through charging aperture 1 and the pump of charging aperture 2
Enter tubular reactor, it is 15 DEG C to control hydrolysis temperature, hydrolysis time 60 seconds；After hydrolysis time arrives, by material 3 through the pump of charging aperture 3
Enter tubular reactor, material 1 is 1 with 3 unit interval of material volume ratio:0.5, it is 15 DEG C to control neutralization reaction temperature, during neutralization
Between 20 seconds；Above-mentioned hydrolysis and neutralization reaction, it is 3m/s to control flow velocity of the reaction mass in tubular reactor.It is continuous to neutralize
After the completion of, neutralizer is discharged from the product outlet of tubular reactor, the water layer of neutralizer point is gone, ether layer is washed with water to neutrality
Afterwards, concentration and recovery 2- methyltetrahydrofurans, faint yellow oily condensation product, content 97.5%, the pure yield 98.4% of product are obtained.
Comparative example 1
The intermittent hydrolysis neutralization reaction of double grignard condensation products is carried out using traditional handicraft：
The diethyl ether solution that 50L concentration is the double chlorine magnesium condensation products of 0.8mol/L is put into reactor, adjustment reactor stirring
The stir speed (S.S.) of slurry is 150r/min, puts into 50L [H while stirring+] concentration is 3.0mol/L aqueous hydrochloric acid solutions, when sour water feeds intake
Between be 3Min, sour water feeds intake stratification after end, divides sub-cloud sour water；Add the sodium acid carbonate that 100L concentration is 0.3mol/L
Aqueous alkali, 30min is stirred, stood, branch vibration layer, ether layer is washed to neutrality, and be concentrated under reduced pressure recovery ether, obtains yellow oily
Condensation product, content 90.1%, the pure yield 90.2% of product.
Comparative example 2
Using straight pipe type tubular reactor, the parameter such as quartz sand filler, tube side, caliber and the phase of embodiment 1 are filled in pipeline
Together.
Compound concentration is the diethyl ether solution of the double chlorine magnesium condensation products of 0.8mol/L, forms material 1；Prepare [H+] concentration is
1.6mol/L aqueous hydrochloric acid solutions, form material 2；It is 0.5mol/L aqueous alkalis to prepare sodium acid carbonate concentration, forms material 3.
Simultaneously by material 1 and material 2 using unit interval volume ratio as 1:1.1 ratio is respectively through charging aperture 1 and charging aperture 2
Tubular reactor is pumped into, it is 25 DEG C to control hydrolysis temperature, hydrolysis time 30 seconds；After hydrolysis time arrives, by material 3 through charging aperture 3
Tubular reactor is pumped into, material 1 is 1 with 3 unit interval of material volume ratio:0.6, it is 25 DEG C to control neutralization reaction temperature, is neutralized
40 seconds time；Above-mentioned hydrolysis and neutralization reaction, it is 1m/s to control flow velocity of the reaction mass in tubular reactor.In continuous
With after the completion of, neutralizer is discharged from the product outlet of tubular reactor, the water layer of neutralizer point is gone, ether layer is washed with water into
After property, concentration and recovery ether, faint yellow oily condensation product, content 92.6%, the pure yield 94.3% of product are obtained.
Using in the vitamin A obtained by technical scheme it can be seen from embodiment 1-6 and comparative example 1-2
The double grignard condensation product high incomes of mesosome, reach more than 96%, the pure yield more than 98% of product, significantly larger than comparative example 1-2's
As a result.
Although embodiments of the invention have been shown and described above, it is to be understood that above-described embodiment is example
Property, it is impossible to limitation of the present invention is interpreted as, one of ordinary skill in the art is not departing from the principle and objective of the present invention
In the case of above-described embodiment can be changed within the scope of the invention, change, replace and modification.
Claims (31)
1. the method that a kind of continuous hydrolysis of the double grignard condensation products of vitamin A intermediate neutralizes, it is characterised in that step is,
1) the ethers solution containing the double grignard condensation products of vitamin A intermediate is pumped into tubular reactor respectively with sour water, through pipe
Formula reactor is sufficiently mixed progress continuous hydrolysis and obtains hydrolyzate；
2) buck is pumped into tubular reactor through another charging aperture of tubular reactor, is carried out with the hydrolyzate in tubular reactor
Continuous neutralize obtains neutralizer；
3) neutralizer is discharged from the product outlet of tubular reactor, is separated into aqueous phase and organic phase, is removed the aqueous phase,
After the organic phase is washed to neutrality, evaporation recovery organic solvent, vitamin A intermediate condensation product is obtained.
2. the method that the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 1 neutralizes, it is characterised in that
1) in the step, packing section and clear band have been arranged alternately in the pipeline of the tubular reactor, the packing section is i.e. in pipe
The section of filler is filled with road, the clear band is the section of non-filler in pipeline, and packing section and clear band alternate；
Pipeline is provided with charging aperture 1, charging aperture 2 and charging aperture 3 and product outlet；Its middle charging aperture 1, charging aperture 2 and charging aperture 3 divide
Not Yong Yu the ethers solution of double grignard condensation products, sour water and buck charging；The pipeline periphery is provided with chuck, is changed for logical
Thermal medium, reaction is exchanged heat.
3. the method that the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 2 neutralizes, it is characterised in that
The length ratio of the packing section and clear band is 1:(0.5~2).
4. the method that the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 3 neutralizes, it is characterised in that
The length ratio of the packing section and clear band is 1:(1~1.5).
5. the method that the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 2 neutralizes, it is characterised in that
The position of the charging aperture 3 is arranged at hydrolysis and completes or be basically completed part.
6. the method that the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 2 neutralizes, it is characterised in that
The filler is quartz sand, Raschig ring or graphite nodule；
Optional, the tubular reactor is straight pipe type tubular reactor, U-tube formula tubular reactor, coiled pipe reaction
Device or multitube tubular reactor.
7. the method that the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 1 neutralizes, it is characterised in that
1) in the step, the ethers is the straight or branched ether or tetrahydrofuran and its derivative of 2 to 10 carbon compositions, described straight
Chain or branched chain ether are selected from least one of isopropyl ether, ether, propyl ether；The tetrahydrofuran and its derivative be tetrahydrofuran or
2- methyltetrahydrofurans；
Optional, the concentration of the ethers solution containing the double grignard condensation products of vitamin A intermediate is 0.4~1.6mol/L；
Optional, the sour water is sulfuric acid, hydrochloric acid, phosphoric acid or aqueous ammonium chloride solution；
Optional, [H+] concentration in the sour water is 0.5~2mol/L；
Optional, the ethers solution and sour water unit interval feed volume containing the double grignard condensation products of vitamin A intermediate
Than for：Ethers solution containing the double grignard condensation products of vitamin A intermediate：Sour water=1:(1.1~2)；
Optional, the reaction temperature of the hydrolysis is 0~60 DEG C；
Optional, the reaction time of the hydrolysis is 10~100 seconds.
8. the method that the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 7 neutralizes, it is characterised in that
The concentration of the ethers solution containing the double grignard condensation products of vitamin A intermediate is 0.5~1.2mol/L.
9. the method that the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 8 neutralizes, it is characterised in that
The concentration of the ethers solution containing the double grignard condensation products of vitamin A intermediate is 0.8~1.0mol/L.
10. the method that the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 7 neutralizes, it is characterised in that
[H+] concentration in the sour water is 0.5~1.8mol/L.
11. the method that the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 10 neutralizes, its feature exist
In [H+] concentration in the sour water is 1.4~1.6mol/L.
12. the method that the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 7 neutralizes, it is characterised in that
The ethers solution containing the double grignard condensation products of vitamin A intermediate and sour water unit interval input material volume ratio are 1:(1.1~
1.7)。
13. the method that the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 12 neutralizes, its feature exist
In the ethers solution containing the double grignard condensation products of vitamin A intermediate and sour water unit interval input material volume ratio are 1:
(1.4~1.5).
14. the method that the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 7 neutralizes, it is characterised in that
The reaction temperature of the hydrolysis is 15~45 DEG C.
15. the method that the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 14 neutralizes, its feature exist
In the reaction temperature of the hydrolysis is 25~35 DEG C.
16. the method that the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 7 neutralizes, it is characterised in that
The reaction time of the hydrolysis is 20~80 seconds.
17. the method that the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 16 neutralizes, its feature exist
In the reaction time of the hydrolysis is 30~60 seconds.
18. the method that the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 1 neutralizes, it is characterised in that
2) in the step, the buck is aqueous sodium carbonate or sodium bicarbonate aqueous solution；
Optional, the concentration of the buck is 0.1~1mol/L；
Optional, the ethers solution and buck unit interval feed volume containing the double grignard condensation products of vitamin A intermediate
Than for：Ethers solution containing the double grignard condensation products of vitamin A intermediate：Buck=1：(0.5~2)；
Optional, the reaction temperature of the neutralization is 0~60 DEG C；
Optional, the reaction time of the neutralization is 10~90 seconds.
19. the method that the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 18 neutralizes, its feature exist
In the ethers solution containing the double grignard condensation products of vitamin A intermediate and buck unit interval input material volume ratio are 1:(1
~1.5).
20. the method that the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 18 neutralizes, its feature exist
In the reaction temperature of the neutralization is 15~45 DEG C.
21. the method that the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 20 neutralizes, its feature exist
In the reaction temperature of the neutralization is 25~35 DEG C.
22. the method that the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 18 neutralizes, its feature exist
In the reaction time of the neutralization is 20~70 seconds.
23. the method that the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 22 neutralizes, its feature exist
In the reaction time of the neutralization is 40~60 seconds.
24. the method that the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 1 neutralizes, it is characterised in that
The ethers solution containing the double grignard condensation products of vitamin A intermediate, sour water, hydrolyzate, buck and neutralizer are anti-in tubular type
It is 0.4-6m/s to answer the flow velocity in device.
25. the method that the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 24 neutralizes, its feature exist
In the ethers solution containing the double grignard condensation products of vitamin A intermediate, sour water, hydrolyzate, buck and neutralizer are in tubular type
Flow velocity in reactor is 1-4m/s.
26. the method that the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 25 neutralizes, its feature exist
In the ethers solution containing the double grignard condensation products of vitamin A intermediate, sour water, hydrolyzate, buck and neutralizer are in tubular type
Flow velocity in reactor is 2-3m/s.
27. a kind of method that continuous hydrolysis suitable for the double grignard condensation products of vitamin A intermediate described in claim 1 neutralizes
Device, described device are a kind of tubular reactor, it is characterised in that have been arranged alternately filler in the pipeline of the tubular reactor
Section and clear band, the packing section are filled with the section of filler in the duct, and the clear band is non-filler in pipeline
Section, packing section and clear band alternate；There are charging aperture 1, charging aperture 2 and charging aperture 3 and product outlet on pipeline；Wherein
Charging aperture 1, charging aperture 2 and charging aperture 3 are respectively used to pair charging of the ethers solution of grignard condensation products, sour water and buck；It is described
Pipeline periphery is provided with chuck, and for leading to heat transferring medium, reaction is exchanged heat.
28. described in claim 27 suitable for the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 1
The device of the method for sum, it is characterised in that the length ratio of the packing section and clear band is 1:(0.5~2)；
Optional, the position of charging aperture 3 is arranged at hydrolysis and completes or be basically completed part.
29. described in claim 28 suitable for the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 1
The device of the method for sum, it is characterised in that the length ratio of the packing section and clear band is 1:(1~1.5).
30. described in claim 27 suitable for the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 1
The device of the method for sum, it is characterised in that the filler is quartz sand, Raschig ring or graphite nodule.
31. described in claim 27 suitable for the continuous hydrolysis of the double grignard condensation products of vitamin A intermediate described in claim 1
The device of the method for sum, it is characterised in that the tubular reactor be straight pipe type tubular reactor, U-tube formula tubular reactor,
Coiled tubular reactor or multitube tubular reactor.
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| CN112724164B (en) * | 2021-01-05 | 2023-07-04 | 兰州康鹏威耳化工有限公司 | Continuous preparation method of Grignard reagent |
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| GB634533A (en) * | 1947-02-20 | 1950-03-22 | Deventer Matrassen En Ledikant | Improvements in and relating to wire spring mattresses |
| US2920103A (en) * | 1958-01-24 | 1960-01-05 | Ortho Pharma Corp | 11-monocis isomer of vitamin a |
| GB877556A (en) * | 1958-04-23 | 1961-09-13 | Pfizer & Co C | Purification of a vitamin a intermediate |
| NL6614558A (en) * | 1966-10-17 | 1968-04-18 | ||
| DE19925384A1 (en) * | 1999-06-02 | 2000-12-07 | Oxeno Olefinchemie Gmbh | Process for the catalytic implementation of multiphase reactions, especially hydroformylations |
| CN101104812A (en) * | 2007-08-06 | 2008-01-16 | 武汉工程大学 | Technique for hypercritical continuous preparation of biological diesel oil and equipment thereof |
| CN102531984B (en) * | 2011-12-29 | 2013-12-04 | 上虞新和成生物化工有限公司 | Continuous extracting and purifying method of vitamin A intermediate |
| WO2013132042A1 (en) * | 2012-03-09 | 2013-09-12 | Basf Se | Continuous process for the synthesis of graft polymers based on polyethers |
| CN104262077B (en) * | 2014-09-29 | 2016-08-24 | 中国海洋石油总公司 | Parallel ring cast direct chlorination produces the device of 1,2-dichloroethanes |
| CN105541549B (en) * | 2015-12-25 | 2017-11-10 | 上虞新和成生物化工有限公司 | A kind of restoring method of vitamin A intermediate |
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| CN110950736B (en) * | 2019-12-06 | 2021-04-20 | 上虞新和成生物化工有限公司 | Process for preparing alcohol substance by hydrolyzing metal organic product |
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