CN104292394B - Preparation method of Rink amide resin - Google Patents
Preparation method of Rink amide resin Download PDFInfo
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- CN104292394B CN104292394B CN201410488419.6A CN201410488419A CN104292394B CN 104292394 B CN104292394 B CN 104292394B CN 201410488419 A CN201410488419 A CN 201410488419A CN 104292394 B CN104292394 B CN 104292394B
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Abstract
The invention discloses a preparation method of Rink amide resin. The method comprises the following steps: swelling an Fmoc-amide monomer with double bonds, styrene and divinyl benzene by adopting polystyrene microspheres seeds; and with benzoyl peroxide as an initiator, polyvinyl alcohol as a stabilizing agent and lauryl sodium sulfate as an emulsifier, preparing Rink amide resin microspheres. Due to the scheme, uniform and monodispersed Rink amide resin is prepared on the basis of a 'seed method'; the method is simple, high in conversion ratio, controllable in carrying capacity and low in cost; meanwhile, a little of Fmoc-NH2 is used; the production cost is low; and the method has high market application value.
Description
Technical field
The present invention relates to solid phase synthesis resin, more particularly, to, a kind of preparation method of Rink amide resin.
Background technology
Rink Amide Resin, i.e. Rink amide resin, it is a kind of solid phase synthesis resin, be widely used in the conjunction of solid-phase peptide
Cheng Zhong；This resin details refers to http://www.rinkamideresin.com/；It is connected to aminomethyl resin or first
Rink Amide AM resin, Rink Amide mbha resin can be obtained after base benzhydrylamine resin.
Rink (transliteration is woods gram) amide resin is widely used, and the example of two applications is given below.
For example, Chinese patent 200510025924.8 discloses a kind of preparation side of Solid phase peptide synthssis terlipressin
Method, comprises the steps：With Rink Amide resin (including Rink Amide mbha resin, Rink Amide AM resin) it is
Initiation material, with the aminoacid of Fmoc protection as monomer, with TBTU or HBTU/HOBt as condensing agent, connects amino successively one by one
Acid, last peptide chain adopts Boc-Gly-OH；It is subsequently adding and cuts peptide reagent and carry out cutting peptide, add ether precipitation, obtain reduction
Type crude product, adds alkaline matter, blowing air oxidation under conditions of pH is for 7.5-10.0, obtains oxidized form crude product, finally adopts
C18 (or C8) post is isolated and purified, and obtains target product.The method of this invention, low production cost, process is simple, environment is dirty
Contaminate low, high income, be easy to industrializing implementation.
And for example, Chinese patent 200910189087.0 discloses a kind of method preparing vapreotide, comprises the following steps：1、
By Fmoc-Trp (Boc)-OH and Rink Amide resin, obtain Fmoc-Trp (Boc)-RinkAmide resin；2nd, will
Fmoc-Trp (Boc)-Rink Amide resin is coupled by peptide sequence using solid-phase synthesis and obtains linear vapreotide-Rink Amide
Resin；3rd, adopt phase oxidative vapreotide-Rink Amide resin；4th, vapreotide-Rink Amide resin, purification, jelly are cracked
Dry obtain vapreotide.This invention employs the linear vapreotide resin of iodine oxidation in solid phase, it is to avoid traditional liquid phase oxidation band
Carry out operational trouble, and improve the oxidization-hydrogenation ratio of 10%-20%.Present invention process has that operation is simple, raw material puts into
Less, the features such as low cost, yield are higher, the Gross Output rate of reaction up to 68%, thick peptide purity 85%, have considerable economical real
With being worth.
As can be seen here, Rink amide resin is with a wide range of applications.
But, these patented methods, only with Rink amide resin, it is not related to the synthesis side of Rink amide resin
Method.After the synthetic method of Rink amide resin is the multistep that Hans Rink reports on tetrahedron Letters in 1987
Modification method, the method route is long, and often step conversion ratio is low, thus leading to that functional group type on resin is many, carrying capacity is low；Meanwhile, this side
Method is used Fmoc-NH2 (fluorenes methoxy carbonyl amide) as raw material in a large number, and production cost is high.
Therefore, prior art needs to improve.
Content of the invention
The technical problem to be solved is to provide a kind of preparation method of new Rink amide resin.
Technical scheme is as follows：A kind of preparation method of Rink amide resin, it comprises the following steps：Using poly-
The Fmoc- amide monomer with double bond for the phenylethylene micro ball seed swelling, styrene and divinylbenzene, with benzoyl peroxide for drawing
Send out agent, polyvinyl alcohol is stabilizer, sodium lauryl sulphate is emulsifying agent, prepares Rink amide resin microsphere.
Preferably, after preparing Rink amide resin microsphere, described microsphere is carried out, then dries.
Preferably, the Fmoc- amide monomer with double bond is (2,4- Dimethoxyphenyl)-(4 ' (4 ' vinyl benzyl epoxides)
Phenyl)-(fluorenyl oxygen carbonyl acylamino-) methane.
Preferably, 2,4- dimethoxy-4 ' ' (4 ' vinyl benzyl epoxide) benzhydrol addition fluorenyl oxygen carbonyl amide, add
Benzenesulfonic acid, is placed in reaction in 60 DEG C of -65 DEG C of oil baths, obtains (2,4- Dimethoxyphenyl)-(4 ' (4 ' vinyl benzyl epoxide) benzene
Base)-(fluorenyl oxygen carbonyl acylamino-) methane.
Preferably, 2,4- dimethoxy-4 ' ' the addition methanol dissolving of (4 ' vinyl benzyl epoxide) benzophenone, it is slowly added to boron
After sodium hydride, reaction obtains 2,4- dimethoxy-4 ' ' (4 ' vinyl benzyl epoxide) benzhydrol.
Preferably, 2,4- dimethoxy-4 ' '-dihydroxy benaophenonel with to vinyl benzyl chloride mixing after add potassium carbonate and four
Hydrogen furan, reaction at 50 DEG C obtains 2,4- dimethoxy-4 ' ' (4 ' vinyl benzyl epoxide) benzophenone.
Preferably, aluminum chloride and phosphorus oxychloride are added after P-hydroxybenzoic acid and a phenylene dimethyl ether mixing, will after reaction
Product is poured in frozen water, stirs and terminates to heat release；Adjust pH value to 6.0 with sodium hydroxide solution again, add ethyl acetate extraction, so
Afterwards to ethyl acetate layer anhydrous sodium sulfate drying, 50 DEG C of decompression rotary evaporations, to residual liquid, stop revolving, standing, obtain
2,4- dimethoxy-4 ' '-dihydroxy benaophenonel.
Preferably, described polystyrene microsphere seed is 25 μm of polystyrene microspheres of uniform particle diameter.
Preferably, described preparation method comprises the following steps：Prepare the aqueous phase of polystyrene polymeric microsphere reaction system
Solution, wherein 10g/L containing polyvinyl alcohol, 2.5g/L containing sodium lauryl sulphate；Take partly described aqueous phase solution, will be monodispersed
The polystyrene microsphere suspended dispersed of 25 μm of uniform particle diameter in aqueous phase solution, wherein 2.5g/L containing polystyrene microsphere, obtain
Polystyrene seed microsphere suspended dispersed solution；Benzoyl peroxide is dissolved in containing styrene monomer, (2,4- dimethoxy benzenes
Base) in-(4 ' (4 ' vinyl benzyl epoxide) phenyl)-(fluorenyl oxygen carbonyl acylamino-) methane, and the mixed liquor of divinylbenzene, obtain
To oily solution, wherein, the mass percent of benzoyl peroxide is 0.9% to 1.1%；Separately take partly described aqueous phase solution,
Described oily solution is added in aqueous phase solution, obtains the mixed system of water-oil phase layering, emulsion is made in ultrasonic mixing,
Wherein, scattered oiliness droplet diameter is less than 1 μm；Polystyrene seed microsphere suspended dispersed solution is added to described milkiness
Liquid, is placed in 20 DEG C to 45 DEG C oil baths, after swelling 15 to 30 hours under mechanical agitation, is warmed up to 66 DEG C to 82 DEG C and keeps
Mechanical agitation carries out polyreaction 20 to 32 hours, with the classification of lauryl sodium sulfate aqueous solution gravitational settling, removes small particle
Polystyrene microsphere, obtain the Rink amide resin microsphere of uniform particle diameter.
Preferably, benzoyl peroxide and the mass percent of described mixed liquor are 0.98% to 0.99%:1；Profit two
In the mixed system being mutually layered, the volume ratio of water-oil phase is 1:(1.8 to 4.2)；The temperature of described oil bath is 30 DEG C；Described machine
Tool speed of agitator is 150rpm, and under mechanical agitation, swelling time is 18 hours, is warmed up to 75 DEG C and keeps mechanical agitation
Carry out polyreaction 24 hours, the product obtaining is classified 3 with the lauryl sodium sulfate aqueous solution 500mL gravitational settling of 2.5g/L
Secondary, remove a small amount of polystyrene microsphere of nominal particle size, obtain the Rink amide resin microsphere of uniform particle diameter.
Using such scheme, the inventive method is simple, high conversion rate, and carrying capacity is controlled, with low cost, simultaneously using Fmoc-
NH2 is few, low production cost.There is very high market using value.
Brief description
Fig. 1 is the reaction schematic diagram of one embodiment of the present of invention；
Fig. 2 is the monomer preparation reaction schematic diagram of one embodiment of the present of invention；
Fig. 3 is the Rink amide resin preparation reaction schematic diagram of one embodiment of the present of invention；
The Rink amide resin microphotograph that Fig. 4 is obtained for one embodiment of the present of invention.
Specific embodiment
For the ease of understanding the present invention, below in conjunction with the accompanying drawings and specific embodiment, the present invention will be described in more detail.
It should be noted that when element is expressed " being fixed on " another element, it can directly on another element or therebetween
There may be one or more elements placed in the middle.When an element is expressed " connection " another element, it can directly be connected
It is connected to another element or there may be one or more elements placed in the middle therebetween.The term that this specification is used is " vertical
", " level ", "left", "right" and similar statement for illustrative purposes only.
Unless otherwise defined, all of technology that this specification is used and scientific terminology are led with the technology belonging to the present invention
The implication that the technical staff in domain is generally understood that is identical.The term being used in the description of the invention in this specification is simply
The purpose of description specific embodiment, is not intended to limit the present invention.The term "and/or" that this specification is used includes one
The arbitrary and all of combination of individual or multiple related Listed Items.
As shown in figure 1, one embodiment of the present of invention is, a kind of preparation method of Rink amide resin, it includes following
Step：Using the Fmoc- amide monomer with double bond for the polystyrene microsphere seed swelling, styrene and divinylbenzene, with peroxide
Change benzoyl is initiator, and polyvinyl alcohol is stabilizer, and sodium lauryl sulphate is emulsifying agent, prepares Rink amide resin
Microsphere.For example, preparation method is divided into three below step：1st, prepare polystyrene microsphere seed；2nd, prepare the Fmoc with double bond
(fluorenylmethyloxycarbonyl)-amide monomer；3rd, press different proportion and adjust with the Fmoc- amide monomer of double bond, styrene, divinylbenzene
Join, obtain the different degrees of cross linking, Rink amide (amide) the solid phase synthesis resin microsphere of different carrying capacity, there is very high practicality
It is worth.Wherein, the degree of cross linking and carrying capacity can determine according to logical reasoning or limited experimentation.
For example, a kind of preparation method of Rink amide resin, it comprises the following steps：Molten using polystyrene microsphere seed
The Fmoc- amide monomer of expansible band double bond, styrene and divinylbenzene, with benzoyl peroxide as initiator, polyvinyl alcohol is
Stabilizer, sodium lauryl sulphate is emulsifying agent, prepares Rink amide resin microsphere；And for example, also include step：Using institute
State Rink amide resin microsphere preparation Rink amide resin, i.e. after preparing Rink amide resin microsphere, adopt these
Rink amide resin prepared by Rink amide resin microsphere.For example, divinylbenzene is p-divinyl benzene.Preferably, described poly-
Phenylethylene micro ball seed is 25 μm of polystyrene microspheres of uniform particle diameter；For example, using the PS microsphere of 4.5 μm of uniform particle diameter, molten
Swollen styrene (Styrene, C8H8), it is polymerized again, obtain the PS microsphere of 25 μm of uniform particle diameter.Preferably, prepare Rink acyl
After polyimide resin microsphere, described microsphere is cleaned with organic reagent, then dries；Described organic reagent includes acetone, dichloromethane
Alkane and/or methanol etc..For example, after preparing Rink amide resin microsphere, to described microsphere acetone, dichloromethane and/
Or methanol cleaning, then dry；Then adopt the microsphere preparation Rink amide resin after these drying.Wherein, with double bond
Fmoc- amide monomer is (2,4- Dimethoxyphenyl)-(4 ' (4 ' thiazolinyl benzyloxy) phenyl)-(fluorenyl oxygen carbonyl acylamino-) first
Alkane, such as (2,4- Dimethoxyphenyl)-(4 ' (4 ' vinyl benzyl epoxide) phenyl)-(fluorenyl oxygen carbonyl acylamino-) methane.Below
Example mainly with (2,4- Dimethoxyphenyl)-(4 ' (4 ' vinyl benzyl epoxide) phenyl)-(fluorenyl oxygen carbonyl acylamino-) methane
As a example, the Fmoc- amide monomer with double bond is except (2,4- Dimethoxyphenyl)-(4 ' (4 ' vinyl benzyl epoxide) phenyl)-(fluorenes
Base oxygen carbonyl acylamino-) can also select that other structures are stable, the especially low-cost Fmoc- acyl with double bond outside methane
Amine monomers.Preferably, (2,4- Dimethoxyphenyl)-(4 ' (4 ' vinyl benzyl epoxide) phenyl)-(fluorenyl oxygen carbonyl acylamino-) first
The mass ratio of alkane, styrene and divinylbenzene is (1 to 5):(1 to 5):(0.05 to 0.1), for example, the mass ratio of three is
(1 to 4):(1 to 4):(0.05 to 0.1)；And for example, the mass ratio of three is (2 to 3):(2 to 3):(0.05 to 0.075)；Preferably
, (2,4- Dimethoxyphenyl)-(4 ' (4 ' vinyl benzyl epoxide) phenyl)-(fluorenyl oxygen carbonyl acylamino-) methane with cinnamic
Gross mass (i.e. both quality sum values), the mass ratio with divinylbenzene is 8:0.1, for example, (2,4- Dimethoxyphenyl)-
(4 ' (4 ' vinyl benzyl epoxide) phenyl)-(fluorenyl oxygen carbonyl acylamino-) methane and cinnamic mass ratio are (2 to 3):(2 to 3)；
Preferably, both mass ratioes are 1:1.
For example, a kind of preparation method of Rink amide resin, it comprises the following steps：Molten using polystyrene microsphere seed
The Fmoc- amide monomer of expansible band double bond, styrene and divinylbenzene, with benzoyl peroxide as initiator, polyvinyl alcohol is
Stabilizer, sodium lauryl sulphate is emulsifying agent, prepares Rink amide resin microsphere；Wherein, polystyrene microsphere seed
It is placed in the aqueous phase solution of polystyrene polymeric microsphere reaction system；For example, 8- containing polyvinyl alcohol in described aqueous phase solution
20g/L, 1.5-4g/L containing sodium lauryl sulphate；And for example, 8-15g/L containing polyvinyl alcohol in described aqueous phase solution, contain dodecane
Base sodium sulfate 2-3g/L；Preferably, described aqueous phase solution 10g/L containing polyvinyl alcohol, 2.5g/L containing sodium lauryl sulphate.So
Afterwards, by monodispersed, uniform particle diameter polystyrene microsphere suspended dispersed in aqueous phase solution, obtain polystyrene seed microsphere
Suspended dispersed solution.For example, polystyrene microsphere particle diameter is 20 μm to 30 μm, and and for example, polystyrene microsphere particle diameter is for 22 μm extremely
28μm；Preferably, polystyrene microsphere particle diameter is 25 μm.For example, wherein, polystyrene seed microsphere suspended dispersed solution contains and gathers
Phenylethylene micro ball 1.5-5g/L, and for example, polystyrene seed microsphere suspended dispersed solution 2-4g/L containing polystyrene microsphere, preferably
, polystyrene seed microsphere suspended dispersed solution 2.5g/L containing polystyrene microsphere.And for example, polystyrene seed microsphere suspends
In dispersion soln, polystyrene microsphere is identical with Sodium Dodecyl Sulfate, so, is conducive to obtaining dispersibility preferably poly-
Styrene seed microsphere suspended dispersed solution.
Preferably, 2,4- dimethoxy-4 ' ' (4 ' vinyl benzyl epoxide) benzhydrol addition fluorenyl oxygen carbonyl amide, add
Benzenesulfonic acid, is placed in reaction in 60 DEG C of -65 DEG C of oil baths, obtains (2,4- Dimethoxyphenyl)-(4 ' (4 ' vinyl benzyl epoxide) benzene
Base)-(fluorenyl oxygen carbonyl acylamino-) methane, for example, it is placed in reaction in the oil bath of 60 DEG C, 62 DEG C, 63 DEG C or 65 DEG C, obtains (2,4-
Dimethoxyphenyl)-(4 ' (4 ' vinyl benzyl epoxide) phenyl)-(fluorenyl oxygen carbonyl acylamino-) methane.Preferably, in nitrogen or
Under the protection of noble gases, it is placed in reaction in 60 DEG C of -65 DEG C of oil baths；In view of cost of implementation, preferably nitrogen.And for example, 2,4- bis-
Methoxyl group -4 ' the addition methanol dissolving of (4 ' vinyl benzyl epoxide) benzophenone, after being slowly added to sodium borohydride, reaction obtains 2,4-
Dimethoxy-4 ' ' (4 ' thiazolinyl benzyloxy) benzhydrol；For example, described it is slowly added to sodium borohydride, including sodium borohydride is light
Lightly it is placed in methanol and its related solution or be lentamente poured in methanol and its related solution.Wherein, 2,4- diformazan
Epoxide -4 '-dihydroxy benaophenonel adds potassium carbonate and oxolane with to after vinyl benzyl chloride mixing, and react at 50 DEG C and obtain
2,4- dimethoxy-4 ' ' (4 ' vinyl benzyl epoxide) benzophenone.Wherein, add after P-hydroxybenzoic acid and a phenylene dimethyl ether mixing
Enter aluminum chloride and phosphorus oxychloride, after reaction pour product in frozen water into, stir and terminate to heat release；Adjusted with sodium hydroxide solution again
PH value, to 6.0, adds ethyl acetate extraction, then to ethyl acetate layer anhydrous sodium sulfate drying, 50 DEG C of decompression rotary evaporations
To residual liquid, stop revolving, standing, obtain 2,4- dimethoxy-4 ' '-dihydroxy benaophenonel；For example, revolving is to residual liquid
Less than 180mL, 150mL or 100mL etc., and for example, revolving to residual liquid starts naked eyes visible solid state etc..
Preferably, described preparation method comprises the following steps：Prepare the aqueous phase of polystyrene polymeric microsphere reaction system
Solution, wherein 10g/L containing polyvinyl alcohol, 2.5g/L containing sodium lauryl sulphate；Take partly described aqueous phase solution, will be monodispersed
The polystyrene microsphere suspended dispersed of 25 μm of uniform particle diameter in aqueous phase solution, wherein 2.5g/L containing polystyrene microsphere, obtain
Polystyrene seed microsphere suspended dispersed solution；Benzoyl peroxide is dissolved in containing styrene monomer, (2,4- dimethoxy benzenes
Base) in-(4 ' (4 ' vinyl benzyl epoxide) phenyl)-(fluorenyl oxygen carbonyl acylamino-) methane, and the mixed liquor of divinylbenzene, obtain
To oily solution, wherein, the mass percent of benzoyl peroxide is 0.9% to 1.1%；For example, the matter of benzoyl peroxide
Amount percentage ratio is 1%；Preferably, benzoyl peroxide and the mass percent of described mixed liquor are 0.98% to 0.99%:1；
And for example, mass percent in oily solution for the benzoyl peroxide is 0.95% to 1%.Separately take partly described aqueous phase solution,
Described oily solution is added in aqueous phase solution, obtains the mixed system of water-oil phase layering, emulsion is made in ultrasonic mixing,
Wherein, scattered oiliness droplet diameter is less than 1 μm.Preferably, when preparing emulsion, the ratio of oily solution liquid compatible with water
For 1:(1 to 5) is it is preferred that the volume ratio of water-oil phase is 1:(1.8 to 4.2), and for example, the ratio of oily solution liquid compatible with water
Example is 1:(1.5 to 2.5).Then, polystyrene seed microsphere suspended dispersed solution is added to described emulsion, is placed in 20 DEG C
To 45 DEG C of oil baths, for example, it is placed in 25 DEG C to 40 DEG C oil baths it is preferred that being placed in 28 DEG C to 32 DEG C oil baths；Preferably, described oil bath
Temperature be 30 DEG C；And swelling 15 to 30 hours under mechanical agitation, for example, swelling 15 under mechanical agitation, 18,
21st, 22,25,28 or 30 hours；And for example, churned mechanically rotating speed is 100 to 200 revs/min, and for example, churned mechanically rotating speed is
120 to 180 revs/min；Preferably, churned mechanically rotating speed is 140 to 160 revs/min；Then, it is warmed up to 66 DEG C to 82 DEG C and protect
Hold mechanical agitation and carry out polyreaction 20 to 32 hours, for example, be warmed up to 72 DEG C to 78 DEG C, and for example, be warmed up to 75 DEG C or 76 DEG C；
And for example, churned mechanically rotating speed is kept to be 120 to 180 revs/min；Preferably, churned mechanically rotating speed is 140 to 160 revs/min；
Preferably, mechanical agitation when swelling and mechanical agitation when being polymerized, both rotating speeds are identical；For example, described mechanical agitation rotating speed
For 150rpm, under mechanical agitation, swelling time is 18 hours, is warmed up to 75 DEG C and keeps mechanical agitation to carry out polymerization instead
Answer 24 hours；Then, it is classified with lauryl sodium sulfate aqueous solution gravitational settling, remove the polystyrene microsphere of small particle, obtain
Rink amide microsphere to uniform particle diameter.Preferably, with the classification of lauryl sodium sulfate aqueous solution gravitational settling repeatedly, so
Removal effect is preferable.Preferably, the product obtaining is classified with the lauryl sodium sulfate aqueous solution 500mL gravitational settling of 2.5g/L
3 times, remove a small amount of polystyrene microsphere of nominal particle size, obtain the Rink amide microsphere of uniform particle diameter, i.e. Rink amide tree
Lipoid microsphere.
For example, a kind of preparation method of Rink amide resin, it comprises the following steps：
1st, PS seed preparation, dispersed polymeres prepare 4.5 μm of uniform particle diameter PS microspheres, swelling styrene, gather again
Close, obtain 25 μm of uniform particle diameter PS microspheres, this PS microsphere is as the seed of solid phase synthesis resin microsphere.
2nd, monomer preparation
Between P-hydroxybenzoic acid and 1.2eq, phenylene dimethyl ether carries out friedel-crafts acylation and obtains 2,4- dimethoxy-4 ' '-hydroxyl
Base benzophenone, product re-crystallizing in ethyl acetate, yield 90%.2,4- dimethoxy-4 's '-dihydroxy benaophenonel with to ethylene
Base benzyl chloride is reacted, then uses NaBH4Reduction, obtains intermediate；This intermediate again with Fmoc-NH2Reaction just can get final product,
Gross production rate up to 100% or is similar to 100%.
Each monomer and preparation flow as shown in Fig. 2 the synthetic method of correlation can be realized using prior art with reaction condition,
Under different material ratio, product can be obtained, the present invention does not claim specific method for preparing monomer, but for whole
Preparation flow and its preparation method subsequently preparing Rink amide resin, belong to scope of the claimed of the present invention.Each monomer and
It is preferred that a kind of raw material is relatively excessive in preparation flow, so, to the yield of final product than advantageous.For example, isophthalic two
Methyl ether is The more the better, but increases cost too much, and 1.2 equivalents are to react more preferably to select.
3rd, solid phase synthesis resin-made is standby
With the Fmoc- amide monomer with double bond of the PS seed swelling different proportion prepared by above-mentioned steps 1, styrene,
Divinylbenzene, with BPO (Benzoyl peroxide, benzoyl peroxide) for initiator, PVA (polyvinyl alcohol) is stable
Agent, SDS (sodium lauryl sulphate) is emulsifying agent, and the trityl group chlorine solid phase synthesis resin preparing 80 to 120 μm is micro-
Ball, microsphere is cleaned with acetone and/or methanol, dries, and completes to produce.
For example, microsphere cleaning step is as follows：Microsphere after 100g staged care, is cleaned one time with 500mL acetone first, takes out
Filter；Add 500mL methanol to clean one time, sucking filtration；Repeat and cleaned with acetone, methanol, repeat procedure above three times.Product exists
At 60 DEG C, 12h is dried, and directly packs, as product.
The preparation method of PS seed is exemplified below.
For example, the polystyrene microsphere preparation of 4.5 μm of uniform particle diameter, detailed process is as follows：290mg radical initiator is even
Nitrogen bis-isobutyronitrile (AIBN) is dissolved in 8mL (7.248g) styrene (Styrene) monomer, makes AIBN account for the quality of styrene monomer
Percentage ratio is 4%.It is anhydrous that 0.624g Polyvinylpyrrolidone (PVP) and 0.6g Triton X-100 (0.572mL) are dissolved in 32mL
In ethanol, 8mL is added in above-mentioned ethanol solution so that final dissolved with the styrene monomer solution of azodiisobutyronitrile
In mixed solution, the concentration of Polyvinylpyrrolidone and Triton X-100 is respectively 15.6g/L and 15.0g/L, styrene monomer
The percent by volume accounting for whole solution is 20%.Under nitrogen protection, by above-mentioned mixed solution with the mechanical agitation speed of 150rpm.
Rate stirs 30min, then the three neck round bottom flask filling above-mentioned mixed solution is placed in the oil bath that temperature is 70 DEG C, by machinery
Stir speed (S.S.) reacts 24h after being adjusted to 100rpm.Product monodisperse polystyrene (PS) polymer microsphere is used after terminating by reaction
Absolute ethanol washing 3-5 time, obtains the polystyrene microsphere of 4.5 μm of uniform particle diameter.
And for example, 25 μm of uniform particle diameter polystyrene microsphere preparations are as follows：
1st, prepare containing polyvinyl alcohol (PVA) is 10g/L and the aqueous solution 1L for 2.5g/L containing sodium lauryl sulphate (SDS)
As the aqueous phase solution preparing polystyrene polymeric microsphere reaction system.
2nd, by the polystyrene microsphere suspended dispersed of 4.5 μm of uniform particle diameter of 0.4g single dispersing in 20mL above-mentioned containing 10g/L
In the aqueous solution of PVA and 2.5g/L SDS, obtain PS seed microsphere suspended dispersed solution.
3rd, 857mg radical initiator azodiisobutyronitrile (AIBN) is dissolved in containing 85.7g (86.6mL) styrene list
In body, the mass percent that radical initiator accounts for high molecular polymerization monomer is 1%.The oily solution obtaining is added to
173mL contains in 10g/L PVA and the aqueous solution of 2.5g/L SDS, obtains the mixed system of water-oil phase layering, wherein, profit
Biphase volume ratio is 1:2.The mixed system that this water-oil phase is layered is made by emulsion by ultrasonication, used is super
Acoustical power is 300W, and ultrasonic time is 9s, and interval time is 3s, and number of repetition is 90 times, observes final under an optical microscope
Emulsion in scattered oiliness droplet diameter be less than 1 μm.
4th, 20mL polystyrene seed microsphere aaerosol solution is added in above-mentioned emulsion, by this swollen mixt system
It is placed in 30 DEG C of oil baths, swelling 18h under the mechanical agitation of 150rpm, polystyrene seed microsphere absorbs in emulsion
After oiliness droplet, diameter dimension increases.Absorb the oiliness droplet in most emulsion to polystyrene seed microsphere
Afterwards, temperature is risen to 70 DEG C, be kept stirring for speed polyreaction 24h, the 25 μm of uniform particle diameter polystyrene microspheres of product obtaining,
With the polystyrene microsphere being less than 1 μm of particle diameter on a small quantity, it is classified 3 times with the aqueous solution 500mL gravitational settling of 2.5g/L SDS and removes 1
The polystyrene microsphere of μm particle diameter, obtains the polystyrene microsphere seed of 25 μm of uniform particle diameter.
Continue with the preparation method of the reaction and wherein each monomer illustrating in Fig. 2, these monomers can also be adopted
Realized with additive method.
Compound 5 (2,4- dimethoxy-4 's '-dihydroxy benaophenonel) preparation：100g P-hydroxybenzoic acid (1) is and between 120g
Phenylene dimethyl ether (2) 1.2eq, adds 500mL round-bottomed flask, adds 10.5g aluminum chloride (3) 1.1eq, 22g phosphorus oxychloride
2eq；It is placed in reaction 2h in 60 DEG C of -65 DEG C of oil baths.After reaction terminates, product is poured in 1000mL frozen water, stir to heat release knot
Bundle.Adjust pH value to 6.0 with 30% sodium hydroxide solution again, add 500mL ethyl acetate to extract three times, ethyl acetate layer is with anhydrous
Sodium sulfate is dried 12h.50 DEG C of decompression rotary evaporations, to remaining 150mL liquid, stop revolving, standing, separate out 168g product 5, produce
Rate is about 90%.
Compound 8 (2,4- dimethoxy-4 's '-(4 ' vinyl benzyl epoxide) benzophenone) preparation：100g compound 5 with
58.9g adds in 500mL round-bottomed flask to vinyl benzyl chloride (6), adds 107g potassium carbonate (7) 2eq, adds 200mL tetrahydrochysene
Furan, 50 DEG C of reaction 3h.Obtain 144.5g compound 6, yield is about 99%-100%, can generally achieve 100%.
Compound 10 (2,4- dimethoxy) -4 '-(4 ' vinyl benzyl epoxide) benzhydrol) preparation：100g compound 5 adds
Enter the dissolving of 200mL methanol, be slowly added to 12g sodium borohydride (9) 1.2eq under room temperature, after adding, then react 20min, obtain 100g
Product 10, yield is about 99%-100%.
Compound 13 ((2,4- Dimethoxyphenyl), (4 '-(4 ' vinyl benzyl epoxide) phenyl), (fluorenyl oxygen carbonyl acyl ammonia
Base) methane) preparation：100g compound 10, adds 95.3g fluorenyl oxygen carbonyl amide (11) 1.5eq, adds 8.4g benzenesulfonic acid (12)
0.2eq, is placed in 60 DEG C of -65 DEG C of oil baths and reacts 6h so that it may obtain 158g final product 13, yield is about 99%-100%.
Solid phase synthesis resin-made is standby as shown in figure 3, for example, the change of the PS seed swelling different proportion of method described above preparation
Compound 13 monomer, styrene, divinylbenzene, with BPO (Benzoyl peroxide, benzoyl peroxide) for initiator, PVA
(polyvinyl alcohol) be stabilizer, SDS (sodium lauryl sulphate) be emulsifying agent, prepare particle size range be 80-120 μm and
Then microsphere is cleaned by the Rink amide microsphere of uniform particle diameter with acetone, methanol, dries, and completes to produce, under the microscope
Photograph is as shown in figure 4, from this photograph, the Rink amide resin microspherulite diameter homogeneity obtained by this preparation method is very
Good.
Provide some embodiments below again and contrasted, the preparation method of Rink amide resin of the present invention is described.
Prepare containing PVA be 10g/L and containing SDS be 2.5g/L aqueous solution 10L as preparing polystyrene polymeric microsphere
The aqueous phase solution of reaction system.
By the polystyrene microsphere suspended dispersed of 25 μm of uniform particle diameter of single dispersing containing 0.85g in the above-mentioned aqueous phase solution of 350mL
In, obtain PS seed microsphere suspended dispersed solution.
And, 0.95g BPO is dissolved in containing 50g styrene monomer, 50g compound 13,0.95g 80% divinyl
In benzene, the oily solution obtaining is added in the above-mentioned aqueous phase solution of 248mL, obtains the mixed system of water-oil phase layering.Logical
Cross ultrasonication and the mixed system that this water-oil phase is layered is made emulsion, the ultrasonic power being used is 450W, when ultrasonic
Between be 10s, interval time be 2.5s, number of repetition be 100 times, oiliness droplet diameter be less than 1 μm.
350mL polystyrene seed microsphere aaerosol solution is added in above-mentioned emulsion, by this swollen mixt system
It is placed in oil bath, as shown in table 1 below by following reaction condition preparation Rink amide resin microsphere.
Table 1
It is further continued for illustrating the preparation method of Rink amide resin of the present invention below, micro- including Rink amide resin
The preparation method of ball, with these Rink amide resin microspheres, can prepare Rink amide resin.
It should be noted that for the ease of test compare, below each example employ many identical experiment conditions, these
Identical experiment condition not as the extra restriction of the preparation method scope of the claimed for the present invention, and as just it
In example, for the preparation method of the present invention and its prepared Rink amide resin microsphere are described.
Example 1 carrying capacity 0.335mmol/g, 100 μm of uniform particle diameter Rink amide microsphere preparations：
1st, prepare containing polyvinyl alcohol (PVA) is 10g/L and the aqueous solution for 2.5g/L containing sodium lauryl sulphate (SDS)
10L is as the aqueous phase solution preparing polystyrene polymeric microsphere reaction system.
2nd, by the polystyrene microsphere suspended dispersed of 25 μm of uniform particle diameter of single dispersing containing 1g in 400mL above-mentioned containing 10g/L
In the aqueous solution of PVA and 2.5g/L SDS, obtain PS seed microsphere suspended dispersed solution.
3rd, 0.8g benzoyl peroxide (BPO) is dissolved in containing 64g styrene monomer, 16g compound 13,1g 80% 2
In vinyl benzene, the mass percent that radical initiator accounts for high molecular polymerization monomer is 1%.The oily solution obtaining is added
Contain in 10g/L PVA and the aqueous solution of 2.5g/L SDS to 165mL, obtain the mixed system of water-oil phase layering, wherein oil
The biphase volume ratio of water is about 1:2.The mixed system that this water-oil phase is layered is made by emulsion by ultrasonication, is used
Ultrasonic power be 500W, ultrasonic time be 9s, interval time be 3s, number of repetition be 90 times, observe under an optical microscope
In final emulsion, scattered oiliness droplet diameter is less than 1 μm.
4th, 400mL polystyrene seed microsphere aaerosol solution is added in above-mentioned emulsion, by this swollen mixt body
System is placed in 30 DEG C of oil baths, swelling 18h under the mechanical agitation of 150rpm, and polystyrene seed microsphere absorbs in emulsion
Oiliness droplet after diameter dimension increase.Absorb the oiliness droplet in most emulsion to polystyrene seed microsphere
Afterwards, temperature is risen to 75 DEG C, be kept stirring for speed polyreaction 24h, the 100 μm of uniform particle diameter of product obtaining contain 20% compound
13 polystyrene microsphere, and it is less than the polystyrene microsphere of 1 μm of particle diameter on a small quantity, with the aqueous solution 500mL weight of 2.5g/L SDS
The polystyrene microsphere of power classification of sedimentation 1 μm of particle diameter of 3 removals, obtains particle diameter and is 100 μm, carrying capacity 0.335mmol/g, 1% friendship
The Rink amide microsphere of the uniform particle diameter of connection degree.
Example 2 carrying capacity 0.67mmol/g, 100 μm of uniform particle diameter Rink amide microsphere preparations：
1st, prepare containing polyvinyl alcohol (PVA) is 10g/L and the aqueous solution for 2.5g/L containing sodium lauryl sulphate (SDS)
10L is as the aqueous phase solution preparing polystyrene polymeric microsphere reaction system.
2nd, by the polystyrene microsphere suspended dispersed of 25 μm of uniform particle diameter of single dispersing containing 1g in 400mL above-mentioned containing 10g/L
In the aqueous solution of PVA and 2.5g/L SDS, obtain PS seed microsphere suspended dispersed solution.
3rd, 0.8g benzoyl peroxide (BPO) is dissolved in containing 48g styrene monomer, 32g compound 13,1g 80% 2
In vinyl benzene, the mass percent that radical initiator accounts for high molecular polymerization monomer is 1%.The oily solution obtaining is added
Contain in 10g/L PVA and the aqueous solution of 2.5g/L SDS to 165mL, obtain the mixed system of water-oil phase layering, wherein, oil
The biphase volume ratio of water is about 1:2.The mixed system that this water-oil phase is layered is made by emulsion by ultrasonication, is used
Ultrasonic power be 500W, ultrasonic time be 9s, interval time be 3s, number of repetition be 90 times, observe under an optical microscope
In final emulsion, scattered oiliness droplet diameter is less than 1 μm.
4th, 400mL polystyrene seed microsphere aaerosol solution is added in above-mentioned emulsion, by this swollen mixt body
System is placed in 30 DEG C of oil baths, swelling 18h under the mechanical agitation of 150rpm, and polystyrene seed microsphere absorbs in emulsion
Oiliness droplet after diameter dimension increase.Absorb the oiliness droplet in most emulsion to polystyrene seed microsphere
Afterwards, temperature is risen to 75 DEG C, be kept stirring for speed polyreaction 24h, the 100 μm of uniform particle diameter of product obtaining contain 60% compound
13 polystyrene microsphere, and it is less than the polystyrene microsphere of 1 μm of particle diameter on a small quantity, with the aqueous solution 500mL weight of 2.5g/L SDS
The polystyrene microsphere of power classification of sedimentation 1 μm of particle diameter of 3 removals, obtains particle diameter and is 100 μm, carrying capacity 0.67mmol/g, and 1% is crosslinked
The Rink amide microsphere of the uniform particle diameter of degree.
Example 3 carrying capacity 1.0mmol/g, the Rink amide microsphere preparation of 100 μm of uniform particle diameter：
1st, prepare containing polyvinyl alcohol (PVA) is 10g/L and the aqueous solution for 2.5g/L containing sodium lauryl sulphate (SDS)
10L is as the aqueous phase solution preparing polystyrene polymeric microsphere reaction system.
2nd, by the polystyrene microsphere suspended dispersed of 25 μm of uniform particle diameter of single dispersing containing 1g in 400mL above-mentioned containing 10g/L
In the aqueous solution of PVA and 2.5g/L SDS, obtain PS seed microsphere suspended dispersed solution.
3rd, 0.8g benzoyl peroxide (BPO) is dissolved in containing 32g styrene monomer, 48g compound 13,1g 80% 2
In vinyl benzene, the mass percent that radical initiator accounts for high molecular polymerization monomer is 1%.The oily solution obtaining is added
Contain in 10g/L PVA and the aqueous solution of 2.5g/L SDS to 165mL, obtain the mixed system of water-oil phase layering, wherein, oil
The biphase volume ratio of water is about 1:2.The mixed system that this water-oil phase is layered is made by emulsion by ultrasonication, is used
Ultrasonic power be 500W, ultrasonic time be 9s, interval time be 3s, number of repetition be 90 times, observe under an optical microscope
In final emulsion, scattered oiliness droplet diameter is less than 1 μm.
4th, 400mL polystyrene seed microsphere aaerosol solution is added in above-mentioned emulsion, by this swollen mixt body
System is placed in 30 DEG C of oil baths, swelling 18h under the mechanical agitation of 150rpm, and polystyrene seed microsphere absorbs in emulsion
Oiliness droplet after diameter dimension increase.Absorb the oiliness droplet in most emulsion to polystyrene seed microsphere
Afterwards, temperature is risen to 75 DEG C, be kept stirring for speed polyreaction 24h, the 100 μm of uniform particle diameter of product obtaining contain 60% compound
13 polystyrene microsphere, and it is less than the polystyrene microsphere of 1 μm of particle diameter on a small quantity, with the aqueous solution 500mL weight of 2.5g/L SDS
The polystyrene microsphere of power classification of sedimentation 1 μm of particle diameter of 3 removals, obtains particle diameter and is 100 μm, carrying capacity 1.0mmol/g, and 1% is crosslinked
The Rink amide microsphere of the uniform particle diameter of degree.
Example 4 carrying capacity 1.0mmol/g, 80 μm of uniform particle diameter Rink amide microsphere preparations：
1st, prepare containing polyvinyl alcohol (PVA) is 10g/L and the aqueous solution for 2.5g/L containing sodium lauryl sulphate (SDS)
10L is as the aqueous phase solution preparing polystyrene polymeric microsphere reaction system.
2nd, by the polystyrene microsphere suspended dispersed of 25 μm of uniform particle diameter of single dispersing containing 1g in 400mL above-mentioned containing 10g/L
In the aqueous solution of PVA and 2.5g/L SDS, obtain PS seed microsphere suspended dispersed solution.
3rd, 0.4g benzoyl peroxide (BPO) is dissolved in containing 16g styrene monomer, 24g compound 13,0.5g 80%
In divinylbenzene, the mass percent that radical initiator accounts for high molecular polymerization monomer is 1%.The oily solution obtaining is added
Enter and contain in 10g/L PVA and the aqueous solution of 2.5g/L SDS to 165mL, obtain the mixed system of water-oil phase layering, profit
Biphase volume ratio is about 1:4.The mixed system that this water-oil phase is layered is made by emulsion by ultrasonication, is used
Ultrasonic power is 500W, and ultrasonic time is 9s, and interval time is 3s, and number of repetition is 90 times, observes under an optical microscope
In whole emulsion, scattered oiliness droplet diameter is less than 1 μm.
4th, 400mL polystyrene seed microsphere aaerosol solution is added in above-mentioned emulsion, by this swollen mixt body
System is placed in 30 DEG C of oil baths, swelling 18h under the mechanical agitation of 150rpm, and polystyrene seed microsphere absorbs in emulsion
Oiliness droplet after diameter dimension increase.Absorb the oiliness droplet in most emulsion to polystyrene seed microsphere
Afterwards, temperature is risen to 75 DEG C, be kept stirring for speed polyreaction 24h, the 100 μm of uniform particle diameter of product obtaining contain 60% compound
13 polystyrene microsphere, and it is less than the polystyrene microsphere of 1 μm of particle diameter on a small quantity, with the aqueous solution 500mL weight of 2.5g/L SDS
The polystyrene microsphere of power classification of sedimentation 1 μm of particle diameter of 3 removals, obtains particle diameter and is 80 μm, carrying capacity 1.0mmol/g, 1% degree of cross linking
Uniform particle diameter Rink amide microsphere.
Example 5 carrying capacity 1.0mmol/g, 120 μm of uniform particle diameter Rink amide microsphere preparations：
1st, prepare containing polyvinyl alcohol (PVA) is 10g/L and the aqueous solution for 2.5g/L containing sodium lauryl sulphate (SDS)
10L is as the aqueous phase solution preparing polystyrene polymeric microsphere reaction system.
2nd, by the polystyrene microsphere suspended dispersed of 25 μm of uniform particle diameter of single dispersing containing 1g in 400mL above-mentioned containing 10g/L
In the aqueous solution of PVA and 2.5g/L SDS, obtain PS seed microsphere suspended dispersed solution.
3rd, 1.4g benzoyl peroxide (BPO) is dissolved in containing 56g styrene monomer, 84g compound 13,1.75g 80%
In divinylbenzene, the mass percent that radical initiator accounts for high molecular polymerization monomer is 1%.The oily solution obtaining is added
Enter and contain in 10g/L PVA and the aqueous solution of 2.5g/L SDS to 280mL, obtain the mixed system of water-oil phase layering, wherein,
The volume ratio of water-oil phase is about 1:2.The mixed system that this water-oil phase is layered is made by emulsion by ultrasonication, is made
Ultrasonic power is 500W, and ultrasonic time is 9s, and interval time is 3s, and number of repetition is 90 times, sees under an optical microscope
Examine scattered oiliness droplet diameter in final emulsion and be less than 1 μm.
4th, 400mL polystyrene seed microsphere aaerosol solution is added in above-mentioned emulsion, by this swollen mixt body
System is placed in 30 DEG C of oil baths, swelling 18h under the mechanical agitation of 150rpm, and polystyrene seed microsphere absorbs in emulsion
Oiliness droplet after diameter dimension increase.Absorb the oiliness droplet in most emulsion to polystyrene seed microsphere
Afterwards, temperature is risen to 75 DEG C, be kept stirring for speed polyreaction 24h, the 100 μm of uniform particle diameter of product obtaining contain 60% compound
13 polystyrene microsphere, and it is less than the polystyrene microsphere of 1 μm of particle diameter on a small quantity, with the aqueous solution 500mL weight of 2.5g/L SDS
The polystyrene microsphere of power classification of sedimentation 1 μm of particle diameter of 3 removals, obtains particle diameter and is 120 μm, carrying capacity 1.0mmol/g, and 1% is crosslinked
The Rink amide microsphere of the uniform particle diameter of degree.
Further, embodiments of the invention also include, each technical characteristic of the various embodiments described above, are mutually combined formation
The preparation method of Rink amide resin, so, is prepared homogeneous, monodispersed Rink amide solid phase based on " seed law " one step
Synthetic resin, method is simple, and carrying capacity is controlled, with low cost, can obtain the different degrees of cross linking, the Rink amide solid phase of different carrying capacity
Synthetic resin microsphere.
It should be noted that giving the preferred embodiment of the present invention in the description of the present invention and its accompanying drawing, but,
The present invention can realize the embodiment however it is not limited to described by this specification by many different forms, these embodiments
Not as the extra restriction to present invention, the purpose providing these embodiments is to make the understanding to the disclosure
More thoroughly comprehensive.And, above-mentioned each technical characteristic continues to be mutually combined, form the various embodiments not being enumerated above, all
It is considered as the scope of description of the invention record；Further, for those of ordinary skills, can be according to the above description
Improved or converted, and all these modifications and variations all should be belonged to the protection domain of claims of the present invention.
Claims (10)
1. a kind of preparation method of Rink amide resin is it is characterised in that comprise the following steps：
Using the Fmoc- amide monomer with double bond, styrene and divinylbenzene swelling polystyrene microsphere seed, with peroxidating
Benzoyl is initiator, and polyvinyl alcohol is stabilizer, and sodium lauryl sulphate is emulsifying agent, prepares Rink amide resin micro-
Ball.
2. after preparation method is it is characterised in that prepare Rink amide resin microsphere according to claim 1, to institute
State microsphere to be carried out, then dry.
3. according to claim 2 preparation method it is characterised in that the Fmoc- amide monomer with double bond be (2,4- dimethoxies
Base phenyl)-(4 ' (4 ' vinyl benzyl epoxide) phenyl)-(fluorenyl oxygen carbonyl acylamino-) methane.
4. according to claim 3 preparation method it is characterised in that 2,4- dimethoxy-4 's ' (4 ' vinyl benzyl epoxide) two
Benzyl alcohol adds fluorenyl oxygen carbonyl amide, adds benzenesulfonic acid, is placed in reaction in 60 DEG C of -65 DEG C of oil baths, obtains (2,4- dimethoxies
Base phenyl)-(4 ' (4 ' vinyl benzyl epoxide) phenyl)-(fluorenyl oxygen carbonyl acylamino-) methane.
5. according to claim 4 preparation method it is characterised in that 2,4- dimethoxy-4 's ' (4 ' vinyl benzyl epoxide) two
Benzophenone adds methanol dissolving, and after being slowly added to sodium borohydride, reaction obtains 2,4- dimethoxy-4 ' ' (4 ' vinyl benzyl epoxide)
Benzhydrol.
6. according to claim 5 preparation method it is characterised in that 2,4- dimethoxy-4 's '-dihydroxy benaophenonel with to second
Potassium carbonate and oxolane is added, reaction at 50 DEG C obtains 2,4- dimethoxy-4 ' after thiazolinyl benzyl chloride mixing ' (4 ' vinyl benzyls
Epoxide) benzophenone.
7. according to claim 6 preparation method it is characterised in that adding after P-hydroxybenzoic acid and phenylene dimethyl ether mixing
Aluminum chloride and phosphorus oxychloride, after reaction pour product in frozen water into, stir and terminate to heat release；Adjust pH with sodium hydroxide solution again
It is worth to 6.0, adds ethyl acetate extraction, then to ethyl acetate layer anhydrous sodium sulfate drying, 50 DEG C of decompression rotary evaporations are extremely
Residual liquid, stops revolving, standing, obtains 2,4- dimethoxy-4 ' '-dihydroxy benaophenonel.
8. according to claim 7 preparation method it is characterised in that described polystyrene microsphere seed be uniform particle diameter 25
μm polystyrene microsphere.
9. according to described preparation method arbitrary in claim 1 to 8 it is characterised in that comprising the following steps：
Prepare the aqueous phase solution of polystyrene polymeric microsphere reaction system, wherein 10g/L containing polyvinyl alcohol, sulfur containing dodecyl
Sour sodium 2.5g/L；
Take partly described aqueous phase solution, by the polystyrene microsphere suspended dispersed of monodispersed 25 μm of uniform particle diameter in aqueous phase solution
In, wherein 2.5g/L containing polystyrene microsphere, obtain polystyrene seed microsphere suspended dispersed solution；
Benzoyl peroxide is dissolved in containing styrene monomer, (2,4- Dimethoxyphenyl)-(4 ' (4 ' vinyl benzyl epoxide) benzene
Base) in-(fluorenyl oxygen carbonyl acylamino-) methane, and the mixed liquor of divinylbenzene, obtain oily solution, wherein, benzoyl peroxide
The mass percent of formyl is 0.9% to 1.1%；
Separately take partly described aqueous phase solution, described oily solution is added in aqueous phase solution, obtain the mixed of water-oil phase layering
Fit system, emulsion is made in ultrasonic mixing, and wherein, scattered oiliness droplet diameter is less than 1 μm；
Polystyrene seed microsphere suspended dispersed solution is added to described emulsion, is placed in 20 DEG C to 45 DEG C oil baths, in machinery
After swelling 15 to 30 hours under stirring action, it is warmed up to 66 DEG C to 82 DEG C and to keep mechanical agitation to carry out polyreaction 20 to 32 little
When, with the classification of lauryl sodium sulfate aqueous solution gravitational settling, remove the polystyrene microsphere of small particle, obtain uniform particle diameter
Rink amide resin microsphere.
10. according to claim 9 preparation method it is characterised in that the quality hundred of benzoyl peroxide and described mixed liquor
Divide ratio for 0.98% to 0.99%:1；In the mixed system of water-oil phase layering, the volume ratio of water-oil phase is 1:(1.8 to
4.2)；The temperature of described oil bath is 30 DEG C；Described mechanical agitation rotating speed is 150rpm, and under mechanical agitation, swelling time is
18 hours, it is warmed up to 75 DEG C and keeps mechanical agitation to carry out polyreaction 24 hours, the product the obtaining dodecane of 2.5g/L
Base aqueous sodium persulfate solution 500mL gravitational settling is classified 3 times, removes a small amount of polystyrene microsphere of nominal particle size, obtains particle diameter equal
One Rink amide resin microsphere.
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