CN1019295B - Preparation process of high-purity high-carbon-alkyl alpha-cyanoacrylate - Google Patents
Preparation process of high-purity high-carbon-alkyl alpha-cyanoacrylateInfo
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- CN1019295B CN1019295B CN 87103468 CN87103468A CN1019295B CN 1019295 B CN1019295 B CN 1019295B CN 87103468 CN87103468 CN 87103468 CN 87103468 A CN87103468 A CN 87103468A CN 1019295 B CN1019295 B CN 1019295B
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- Prior art keywords
- formaldehyde
- carbon
- alkyl
- temperature
- gram
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Links
- 238000002360 preparation method Methods 0.000 title claims description 12
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims abstract description 57
- 238000000034 method Methods 0.000 claims abstract description 25
- 239000000178 monomer Substances 0.000 claims abstract description 20
- IJVRPNIWWODHHA-UHFFFAOYSA-N 2-cyanoprop-2-enoic acid Chemical compound OC(=O)C(=C)C#N IJVRPNIWWODHHA-UHFFFAOYSA-N 0.000 claims abstract description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 13
- 238000010992 reflux Methods 0.000 claims abstract description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 238000006068 polycondensation reaction Methods 0.000 claims abstract description 12
- 239000002904 solvent Substances 0.000 claims abstract description 12
- 238000009833 condensation Methods 0.000 claims abstract description 11
- 230000005494 condensation Effects 0.000 claims abstract description 11
- 229920000642 polymer Polymers 0.000 claims abstract description 10
- 238000009835 boiling Methods 0.000 claims abstract description 9
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 8
- 239000003112 inhibitor Substances 0.000 claims abstract description 8
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 239000003054 catalyst Substances 0.000 claims abstract description 5
- GNTDGMZSJNCJKK-UHFFFAOYSA-N divanadium pentaoxide Chemical compound O=[V](=O)O[V](=O)=O GNTDGMZSJNCJKK-UHFFFAOYSA-N 0.000 claims description 32
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 27
- 238000005336 cracking Methods 0.000 claims description 16
- MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 claims description 15
- 150000004054 benzoquinones Chemical class 0.000 claims description 13
- 238000005984 hydrogenation reaction Methods 0.000 claims description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- 150000002500 ions Chemical class 0.000 claims description 8
- 150000003053 piperidines Chemical class 0.000 claims description 8
- 238000010526 radical polymerization reaction Methods 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 4
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 claims description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- -1 butyl diphenol Chemical group 0.000 claims description 3
- FXZJKVODWNYPKK-UHFFFAOYSA-N 3-[3-[4-(3-chlorophenyl)piperazin-1-yl]propyl]-1h-quinazoline-2,4-dione Chemical compound ClC1=CC=CC(N2CCN(CCCN3C(C4=CC=CC=C4NC3=O)=O)CC2)=C1 FXZJKVODWNYPKK-UHFFFAOYSA-N 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 150000001721 carbon Chemical group 0.000 claims description 2
- 230000018044 dehydration Effects 0.000 claims description 2
- 238000006297 dehydration reaction Methods 0.000 claims description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 2
- 229920000137 polyphosphoric acid Polymers 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- CQOZJDNCADWEKH-UHFFFAOYSA-N 2-[3,3-bis(2-hydroxyphenyl)propyl]phenol Chemical compound OC1=CC=CC=C1CCC(C=1C(=CC=CC=1)O)C1=CC=CC=C1O CQOZJDNCADWEKH-UHFFFAOYSA-N 0.000 claims 1
- 150000001450 anions Chemical class 0.000 claims 1
- 229920006389 polyphenyl polymer Chemical group 0.000 claims 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims 1
- 239000008096 xylene Substances 0.000 claims 1
- 230000001476 alcoholic effect Effects 0.000 abstract description 4
- 238000006116 polymerization reaction Methods 0.000 abstract description 4
- 239000000463 material Substances 0.000 abstract description 2
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 abstract 2
- 239000003513 alkali Substances 0.000 abstract 1
- 239000003921 oil Substances 0.000 description 13
- 238000003756 stirring Methods 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 238000004821 distillation Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- REHUGJYJIZPQAV-UHFFFAOYSA-N formaldehyde;methanol Chemical compound OC.O=C REHUGJYJIZPQAV-UHFFFAOYSA-N 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 238000005292 vacuum distillation Methods 0.000 description 3
- 238000010792 warming Methods 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 206010016717 Fistula Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 208000031320 Teratogenesis Diseases 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000010539 anionic addition polymerization reaction Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000004305 biphenyl Chemical group 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000010504 bond cleavage reaction Methods 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- WQPDQJCBHQPNCZ-UHFFFAOYSA-N cyclohexa-2,4-dien-1-one Chemical class O=C1CC=CC=C1 WQPDQJCBHQPNCZ-UHFFFAOYSA-N 0.000 description 1
- 125000005265 dialkylamine group Chemical group 0.000 description 1
- 230000010102 embolization Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000003890 fistula Effects 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 230000001473 noxious effect Effects 0.000 description 1
- 150000007530 organic bases Chemical group 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- SXRFXXNXVPFXDU-UHFFFAOYSA-N pentyl 2-cyanoprop-2-enoate Chemical compound CCCCCOC(=O)C(=C)C#N SXRFXXNXVPFXDU-UHFFFAOYSA-N 0.000 description 1
- 238000012643 polycondensation polymerization Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 231100000456 subacute toxicity Toxicity 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000003106 tissue adhesive Substances 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to a method for preparing high-purity alpha-cyanoacrylate high-carbon octadecy l phosphite. The method of the present invention has the steps that cyanoacetic high-carbon octadecy l phosphite carries out polycondensation reaction with a low-grade formaldehyde alcoholic solution at a certain temperature under the existence of alkali polycondensation catalysts; low-grade alcohol is recovered; then, organic solvents which have a low boiling point and has the azeotropy with water are added into obtained materials; refluxing and dehydrating are carried out; the solvents are recovered; condensation polymers are cracked under the conditions of a certain vacuum degree, the sufficient temperature and the existence of polymerization inhibitors; finally, obtained crude monomers are rectified.
Description
The present invention relates to the preparation method of α-Qing Jibingxisuanzhi.Specifically, the present invention relates to high-purity alpha-high-carbon-alkyl alpha-cyanoacrylate, particularly the preparation method of α-Qing Jibingxisuanzhengxinzhi.
As everyone knows, α-Qing Jibingxisuanzhidanti need not to heat or catalysis or just polymerization at an easy rate in the presence of the negatively charged ion of denier, so autohemagglutination brings difficulty for α-Qing Jibingxisuanzhi, especially monomeric preparation of alpha-cyanoacrylate high-carbon-alkyl and storage.United States Patent (USP) 3,254, the preparation method who discloses α-Qing Jibingxisuanzhi No. 111, this method comprises cyan-acetic ester and formaldehyde with 1～2: 1 mol ratio, the basic polycondensation catalyzer and resemble this class low boiling point solvent of benzene in the presence of react, thereby generate a kind of low-molecular-weight transition polycondensate.After reaction was finished, steaming desolventized, and obtains anhydrous rough liquid polycondensate.Directly add thermal depolymerization with resulting polycondensate (drying-free) in the presence of the stopper having then, the monomer vapours that steams is required α-Qing Jibingxisuanzhidanti after condensation.The molecular weight of the polycondensation intermediate that obtains with this method is quite low, be cracked into the α that only contains α-Qing Jibingxisuanzhi basically and no longer further decompose under certain condition, α '-dicyano is defended two acid esters, and is very little because of water content with the monomer that this method is produced, so the danger of no autohemagglutination.United States Patent (USP) 3,465, No. 027 above-mentioned patent improved, when they find thermo-cracking, if there is the basic catalyst existence can make reaction product decomposes become raw material, i.e. cyan-acetic ester, but also can react with the acidic anionic stopper, so polluted reaction product, they also find to exist trace soluble phosphoric acid in condensation polymer, can reduce paying reaction and guaranteeing that thermo-cracking obtains the result of satisfaction of thermo-cracking generation.Therefore pass through the amount of control reaction conditions and additive, thereby make highly purified α-Qing Jibingxisuanzhidanti.
α-Qing Jibingxisuanzhi, particularly resemble this class high-carbon-alkyl of α-Qing Jibingxisuanzhengxinzhi and have purposes widely, particularly they have good medical performance, in clinical applications such as sterilization, stomach hemostasis, vascular embolization, sealing fistula hole, five palace sections, splicing skin surface, be used as tissue adhesive, demonstrate unique result of treatment.Purpose of the present invention just provides highly purified medical alpha-cyanoacrylate high-carbon-alkyl.Therefore, the present invention is to United States Patent (USP) 3,465, and No. 027 described method is improved, and the method for more effective preparation alpha-cyanoacrylate high-carbon-alkyl, particularly α-Qing Jibingxisuanzhengxinzhi is provided.The chemical reaction of the inventive method can be expressed as follows:
R " high-carbon alkyl " promptly described herein speech is meant the straight or branched alkyl with 5-10 carbon atom in the formula, and straight chained alkyl is better, preferably n-octyl; N is the positive integer of 5-12.
Specifically, the inventive method comprises that elder generation is dissolved in formaldehyde in the lower alcohols solvent, adds the basic polycondensation catalyzer, stirs.Heat up gradually then, drip the cyanoacetic acid high-carbon-alkyl again, then fully reflux, reclaim lower alcohol, add low boiling point organic solvent then, reflux dewatering reclaims above-mentioned organic solvent, adding resembles Vanadium Pentoxide in FLAKES this anionoid stopper and free radical polymerization inhibitor rapidly again, removes remaining trace water.Then adopt underpressure distillation, when vacuumizing, heating up removes residual organic solvent, and condensation polymer cracking under certain vacuum degree and temperature obtains the crude monomer of alpha-cyanoacrylate high-carbon-alkyl.And then carry out rectifying, can obtain high-purity alpha-high-carbon-alkyl alpha-cyanoacrylate.With method for preparing alpha-cyanoacrylate high-carbon-alkyl, productive rate is up to 71%-82%, and total reaction times shortened in 4 hours, thereby enhances productivity significantly.
One of improvement of the inventive method is Paraformaldehyde 96 to be dissolved in forming homogeneous reaction system in the alcoholic solvent earlier, adds the basic polycondensation catalyzer then, stirs.Then be that cyanoacetic acid high-carbon-alkyl 95% or more is added drop-wise in the said mixture, steam except that alcoholic solvent again purity.Above-mentioned alcoholic solvent can be lower alcohols such as methyl alcohol, ethanol and propyl alcohol, preferably methyl alcohol; The mol ratio of cyanoacetic acid high-carbon-alkyl and formaldehyde is decided according to the character of used cyan-acetic ester, and this mol ratio is to monomeric synthetic and the monomeric stability of synthetic is very important, and this mol ratio is 1～1.25: 1 usually, is preferably 1.02～1.05: 1; The temperature of polycondensation is generally 20-130 ℃, and is better in 60 °-80 ℃ scope, is preferably 70-74 ℃, should prevent that temperature fluctuates up and down; Used basic polycondensation catalyzer is an organic bases, as dialkylamine of quinoline, piperidines, pyridine, diethylamine and so on etc., is preferably piperidines, and the consumption of piperidines is every moles of formaldehyde 0.2-0.4 milliliter; Adding ester to the reaction times of reclaiming before the methyl alcohol increases with the ester group carbonatoms, is generally 5-20 minute, is preferably about 10 minutes.Temperature is the highest in the flask when reclaiming methyl alcohol is controlled at 90 ℃ ± 5 ℃, should be above 100 ℃.
After above-mentioned condensation polymerization step is finished, there is water to generate in the reaction mixture, this moisture content can make monomer generation anionoid polymerization, causes the cracking difficulty, even fully scission reaction does not take place.Therefore, need add anhydrous organic solvent in reaction mixture, make itself and water form azeotropic mixture and remove the moisture content that remains in the mixture with distillation, this solvent also can be used to dissolve the condensation polymer of generation.Obviously, the distillation temperature of entrainer must be lower than the cracking temperature of condensation polymer, usually select for use benzene, toluene or dimethylbenzene etc. to make azeotropic solvent, but preferably selecting boiling range for use is that 60-90 ℃ sherwood oil is as azeotropic solvent, because this solvent is except that having suitable distillation temperature, nontoxicity is compared with benzene one class noxious solvent and to be had superiority, be convenient to operation, reduce and pollute.The addition of sherwood oil is 100～400 milliliters of every moles of formaldehyde, is preferably 120～250 milliliters.Usually the component distillation temperature is 70-80 ℃, is preferably 72-76 ℃, and dewatering time is 1～2 hour, after dewatering fully, reclaims sherwood oil, adds negatively charged ion stopper and free radical polymerization inhibitor then rapidly, stirs fast.The negatively charged ion stopper that adds can in and basic catalyst, the monomer generation anionic polymerization that suppresses generation, the example of this stopper has acidic substance such as Vanadium Pentoxide in FLAKES, tetra-sodium, polyphosphoric acid, preferably use Vanadium Pentoxide in FLAKES, because this negatively charged ion stopper can be removed the basic catalyst in the reaction mixture, because of it has very strong water separation capability, can remove remaining trace water, thereby prevent to generate unwanted pair of product again.The Vanadium Pentoxide in FLAKES that uses should be slightly excessive, but also should avoid excessive too many, pays the formation of product because of excessive acid can cause some volatility, thus the purity and the monomeric productive rate of the alpha-cyanoacrylate high-carbon-alkyl that influence makes.The consumption of Vanadium Pentoxide in FLAKES is every moles of formaldehyde 4-12 gram, is preferably the 6-8 gram; The adding of above-mentioned free radical polymerization inhibitor can suppress the radical polymerization that causes because of heating, and this stopper can be hydrogenation benzoquinones, pyrocatechol, tertiary butyl diphenol, biphenyl 3 phenol, hydrogenation benzoquinones preferably, and its consumption is every moles of formaldehyde 0.02 gram.
After above-mentioned dehydration is finished, do not need filtering separation, in careful slowly gas clean-up, elevated temperature, remove the remaining sherwood oil in the material,, preferably reach 130～150 ℃ as 120～160 ℃ of flask Nei Wenduda, vacuum tightness is during less than 10 mmhg, indicates that low boilers taken off.Then improve heat-up rate, when temperature reaches 185-230 ℃, vacuum tightness is the 1-10 mmhg, and preferably temperature is 190～210 ℃, and when vacuum tightness was the 1-6 mmhg, condensation polymer began cracking, and the cracking time is 20-60 minute.The crude monomer of the alpha-cyanoacrylate high-carbon-alkyl that steams under the vacuum condition is collected in the flask that is added with free radical polymerization inhibitor such as hydrogenation benzoquinones and negatively charged ion stopper such as Vanadium Pentoxide in FLAKES, the consumption of hydrogenation benzoquinones is every mole of crude monomer 0.01～0.1 gram, and the consumption of Vanadium Pentoxide in FLAKES is every mole of crude monomer 0.001～0.01 gram.With the further rectifying of gained crude monomer, be rapidly heated, carefully slowly vacuumize, when vacuum tightness is the 1-6 mmhg, the fraction when collecting the corresponding boiling point of each monomer.In the cracking of condensation polymer and the stage of rectification of crude product, the general sulfurous gas that feeds is as the negatively charged ion stopper, but because of sulfurous gas meeting severe corrosion equipment, influence unfavorable factors such as normal running and contaminate environment, the present invention does not adopt, but suppresses the anionoid polymerization of α-Qing Jibingxisuanzhi effectively by the amount of control reaction conditions and additive.This also is one of characteristics of the present invention.
The alpha-cyanoacrylate high-carbon-alkyl that makes with the inventive method after measured, its purity is up to 97%～99.5%; Carry out toxicological experiment, acute toxicity LD with above-mentioned monomer and micro-toughner blend
50Belong to low toxicity level (9.91 gram/kg body weight), subacute toxicity is negative, and no carcinogenic, teratogenesis, mutagenesis all are suitable for clinical application.
The following example will further specify the present invention, but this does not limit the scope of the invention.
Embodiment 1
The monomeric preparation of alpha-cyanoacrylate n-pentyl ester
In being housed, 3 liter of three neck round-bottomed flask of reflux water-dividing device, condenser, whipping appts, thermometer and dropping funnel add 154 gram formaldehyde methanol solutions (containing 2 moles of formaldehyde), 0.6 milliliter of piperidines, stirring also is warming up to 40 ℃, drip 322.4 gram (2.08 moles) cyanoacetic acids and just defending ester, add in about 15 minutes, refluxed 15 minutes at 66～70 ℃.Reclaim methyl alcohol again, reclaiming top temperature is 97 ℃.Then 00 milliliter of sherwood oil of Dropwise 5 at 64～68 ℃ of scope internal reflux no droplet drippage to the water trap that dewaters, refluxes for some time again, and the recovery sherwood oil is to temperature 115.Add 14 gram Vanadium Pentoxide in FLAKESs and 0.04 gram hydrogenation benzoquinones rapidly, fully stir.Remove whipping appts, change into vacuum distillation apparatus, when slowly vacuumizing, elevated temperature removes remaining sherwood oil, when temperature reaches 120 ℃, vacuum tightness is changed receiving bottle during less than 10 mmhg, and collecting vacuum tightness with the two neck flasks that 0.02 gram hydrogenation benzoquinones and 0.004 gram Vanadium Pentoxide in FLAKES are housed is 6 mmhg, the alpha-cyanoacrylate that cracking went out when temperature was 175-210 ℃ is just being defended the ester crude monomer, lasts 40 minutes.Then the gained crude monomer is carried out rectifying, be rapidly heated and vacuumize, when vacuum tightness is 5.4 mmhg, collect the fraction of temperature when being 113 ℃, obtain rectifying product 264.5 grams, productive rate is 79.2%.
Embodiment 2
The preparation of alpha-cyanoacrylate 2-ethyl-own ester
In embodiment 1 described 3 liter of three neck round-bottomed flask, add 154 gram formaldehyde methanol solutions (containing 2 moles of formaldehyde), 0.6 milliliter of piperidines, stirring also is warming up to 40 ℃, in mixture, drip 417.6 gram (2.12 moles) cyanoacetic acid 2-ethyl-own esters, add in about 12 minutes, 68-72 ℃ of scope internal reflux 15 minutes, reclaim methyl alcohol then, reclaiming top temperature is 98 ℃.Then add 450 milliliters of sherwood oils,, reflux for some time again, reclaim sherwood oil to temperature and reach 115 ℃, add 14 gram Vanadium Pentoxide in FLAKESs and 0.04 gram hydrogenation benzoquinones rapidly, fully stir at 66～68 ℃ of scope internal reflux no droplet drippage to the water trap that dewaters.Remove whipping appts, change into vacuum distillation apparatus.When vacuumizing, elevated temperature, remove remaining sherwood oil, when temperature reaches 125 ℃, change receiving bottle, collecting vacuum tightness with the two neck flasks that a small amount of hydrogenation benzoquinones and Vanadium Pentoxide in FLAKES are housed is the 5-6 mmhg, the crude monomer of alpha-cyanoacrylate 2-ethyl-own ester that cracking went out when temperature was 180～215 ℃.Then the gained crude monomer is carried out rectifying, be rapidly heated and vacuumize, collecting vacuum tightness is 6 mmhg, the fraction when temperature is 128 ℃, rectifying product 325.4 grams, productive rate is 77.8%.
Embodiment 3
The preparation of α-Qing Jibingxisuanzhengxinzhi
Add 154 gram formaldehyde methanol solutions (containing 2 moles of formaldehyde) in embodiment 1 described 3 liter of three neck round-bottomed flask, 0.6 milliliter of piperidines stirs and is warming up to 45 ℃.With the 445.8(2.08 mole) n-octyl cyanoacetate was added drop-wise in the said mixture in 15 minutes, refluxed 10 minutes at 70-75 ℃.Continue the distillation that heats up then, reclaim methyl alcohol, the top temperature of recovery is 98 ℃.Then 00 milliliter of sherwood oil of Dropwise 5 at 74～76 ℃ of scope internal reflux no droplet drippage to the water trap that dewaters, refluxes for some time again, and recovery sherwood oil to temperature reaches 116 ℃.Add 14 gram Vanadium Pentoxide in FLAKESs and 0.04 gram hydrogenation benzoquinones rapidly, fully stir.Remove whipping appts, change into vacuum distillation apparatus, when vacuumizing, elevated temperature removes remaining sherwood oil, when temperature reaches 150 ℃, change receiving bottle, collecting vacuum tightness with the two neck flasks that 0.02 gram hydrogenation benzoquinones and 0.004 gram Vanadium Pentoxide in FLAKES are housed is 6～3 mmhg, and the crude monomer of the α-Qing Jibingxisuanzhengxinzhi that cracking went out when temperature was 190～224 ℃ lasts 20 minutes.Then the crude monomer with gained carries out rectifying, is rapidly heated and vacuumizes, and when vacuum tightness is 6 mmhg, collects the fraction of temperature when being 138 ℃, obtains 340.2 gram rectifying products, and productive rate is 81.4%.
Embodiment 4
The preparation of α-Qing Jibingxisuanzhengxinzhi
Press embodiment 3 described method operations, but the consumption of cyanoacetic acid n-octyl is 417.6 grams (2.12 moles), obtains rectifying product 301.8 grams, productive rate is 72.2%.
Claims (10)
1, the method for preparation high-purity alpha-high-carbon-alkyl alpha-cyanoacrylate (the high-carbon alkyl is meant the straight or branched alkyl with 5-10 carbon atom), this method comprises:
A. the cyanoacetic acid high-carbon-alkyl is carried out polycondensation at the low-alcohol solution that is selected from the presence of the basic polycondensation catalyzer of quinoline, pyridine, diethylamine and piperidines with formaldehyde under 20-130 ℃ temperature;
B. reclaim lower alcohol, add then be selected from benzene,toluene,xylene and boiling range be 60-90 ℃ sherwood oil can with water azeotropic low boiling point organic solvent, reflux dewatering also reclaims above-mentioned solvent;
C. under the temperature of the vacuum tightness of 1-10 mmhg and 185-230 ℃, be selected from Vanadium Pentoxide in FLAKES at every moles of formaldehyde 4-12 gram, the negatively charged ion stopper of tetra-sodium and polyphosphoric acid and every moles of formaldehyde 0.02 gram is selected under the existence condition of free radical polymerization inhibitor of hydrogenation benzoquinones, pyrocatechol, tertiary butyl diphenol and polyphenyl triphenol and makes the condensation polymer cracking, obtain crude monomer, carry out rectifying again, thereby obtain highly purified alpha-cyanoacrylate high-carbon-alkyl.
2, method according to claim 1, the lower alcohol that wherein dissolves formaldehyde can be methyl alcohol, ethanol and propyl alcohol; Operation be low-alcohol solution that the cyanoacetic acid high-carbon-alkyl is added drop-wise to formaldehyde smoothly with the mixture of basic catalyst in, then lower alcohol is reclaimed in backflow then.
3, method according to claim 1, wherein said can be that boiling range is 60-90 ℃ a sherwood oil with water azeotropic low boiling point organic solvent.
4, the method for preparing the high purity α-Qing Jibingxisuanzhengxinzhi according to claim 1, this method comprises:
A. n-octyl cyanoacetate under 60-80 ℃ temperature is being carried out polycondensation with the low-alcohol solution of formaldehyde with the amount of every moles of formaldehyde 1-1.25 mole in the presence of the piperidines;
B. reclaim lower alcohol, add sherwood oil then, at 70-80 ℃ of reflux dewatering and reclaim sherwood oil; In the presence of 6-8 gram Vanadium Pentoxide in FLAKES negatively charged ion stopper and 0.02 gram hydrogenation benzoquinones free radical polymerization inhibitor, be the 1-10 mmhg in vacuum tightness, temperature is to make the condensation polymer cracking under 185-230 ℃ the condition;
C. with the crude monomer that obtains in the presence of micro anion stopper and free radical polymerization inhibitor, carry out rectification under vacuum, thereby obtain highly purified alpha-cyano propylene ester n-octyl.
5, method according to claim 4, wherein lower alcohol is a methyl alcohol.
6, method according to claim 4, wherein the mol ratio of cyanoacetic acid n-octyl and formaldehyde is 1.02-1.06: 1.
7, method according to claim 4, wherein the temperature of polycondensation is 70-74 ℃, the time is 5-20 minute.
8, method according to claim 4, wherein the dehydration temperaturre with sherwood oil and water formation azeotrope is 72-76 ℃.
9, method according to claim 4, wherein Vanadium Pentoxide in FLAKES and the consumption of hydrogenation benzoquinones before cracking are respectively every moles of formaldehyde 7 grams and 0.02 gram.
10, method according to claim 4, wherein condensation polymer is that 1-6 mmhg and temperature are cracking under 190-210 ℃ the condition in vacuum tightness.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 87103468 CN1019295B (en) | 1987-05-13 | 1987-05-13 | Preparation process of high-purity high-carbon-alkyl alpha-cyanoacrylate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 87103468 CN1019295B (en) | 1987-05-13 | 1987-05-13 | Preparation process of high-purity high-carbon-alkyl alpha-cyanoacrylate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN87103468A CN87103468A (en) | 1988-11-30 |
| CN1019295B true CN1019295B (en) | 1992-12-02 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 87103468 Expired CN1019295B (en) | 1987-05-13 | 1987-05-13 | Preparation process of high-purity high-carbon-alkyl alpha-cyanoacrylate |
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| Country | Link |
|---|---|
| CN (1) | CN1019295B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1041306C (en) * | 1991-09-19 | 1998-12-23 | 西南师范大学 | Process for preparing a-cyanoacrylate |
| CN103083718B (en) | 2011-11-02 | 2015-06-10 | 中国人民解放军军事医学科学院毒物药物研究所 | Biodegradable medical adhesive, and preparation method and purpose thereof |
| CN103205206B (en) * | 2012-01-16 | 2014-11-05 | 浙江久而久化学有限公司 | Magnetic material adhesive and preparation method thereof |
| CN108689881B (en) * | 2018-07-12 | 2021-09-17 | 广州白云医用胶有限公司 | Synthesis method of alpha-n-octyl cyanoacrylate |
| CN115611772A (en) * | 2022-11-07 | 2023-01-17 | 湖南浩森胶业有限公司 | A kind of synthetic method of n-octyl α-cyanoacrylate |
-
1987
- 1987-05-13 CN CN 87103468 patent/CN1019295B/en not_active Expired
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| CN87103468A (en) | 1988-11-30 |
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