CN104628562A - Preparation method for 2-ethyl-2-adamantanol acrylate - Google Patents
Preparation method for 2-ethyl-2-adamantanol acrylate Download PDFInfo
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- CN104628562A CN104628562A CN201310557602.2A CN201310557602A CN104628562A CN 104628562 A CN104628562 A CN 104628562A CN 201310557602 A CN201310557602 A CN 201310557602A CN 104628562 A CN104628562 A CN 104628562A
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- adamantanol
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- 238000002360 preparation method Methods 0.000 title claims abstract description 31
- NLNVUFXLNHSIQH-UHFFFAOYSA-N (2-ethyl-2-adamantyl) prop-2-enoate Chemical compound C1C(C2)CC3CC1C(CC)(OC(=O)C=C)C2C3 NLNVUFXLNHSIQH-UHFFFAOYSA-N 0.000 title claims abstract description 24
- 238000006243 chemical reaction Methods 0.000 claims abstract description 69
- ARJOQCYCJMAIFR-UHFFFAOYSA-N prop-2-enoyl prop-2-enoate Chemical compound C=CC(=O)OC(=O)C=C ARJOQCYCJMAIFR-UHFFFAOYSA-N 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 16
- 229910052744 lithium Inorganic materials 0.000 claims abstract description 13
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229910052751 metal Inorganic materials 0.000 claims abstract description 7
- 239000002184 metal Substances 0.000 claims abstract description 7
- 230000035484 reaction time Effects 0.000 claims abstract description 6
- 239000007788 liquid Substances 0.000 claims description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 39
- -1 diamantane ketone Chemical class 0.000 claims description 28
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical group CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 claims description 14
- 238000000605 extraction Methods 0.000 claims description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- 238000004821 distillation Methods 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 7
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 4
- 238000005516 engineering process Methods 0.000 claims description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 3
- 230000003197 catalytic effect Effects 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 claims description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 2
- 150000004053 quinones Chemical class 0.000 claims description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 3
- NCJGJDNWSHATQH-UHFFFAOYSA-N 2-adamantyl prop-2-enoate Chemical class C1C(C2)CC3CC1C(OC(=O)C=C)C2C3 NCJGJDNWSHATQH-UHFFFAOYSA-N 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 6
- 238000009776 industrial production Methods 0.000 abstract description 2
- 238000000746 purification Methods 0.000 abstract description 2
- IYKFYARMMIESOX-SPJNRGJMSA-N adamantanone Chemical compound C([C@H](C1)C2)[C@H]3C[C@@H]1C(=O)[C@@H]2C3 IYKFYARMMIESOX-SPJNRGJMSA-N 0.000 abstract 1
- RDHPKYGYEGBMSE-VQEHIDDOSA-N bromoethane Chemical group C[13CH2]Br RDHPKYGYEGBMSE-VQEHIDDOSA-N 0.000 abstract 1
- 239000000376 reactant Substances 0.000 abstract 1
- 238000001308 synthesis method Methods 0.000 abstract 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 27
- 239000000741 silica gel Substances 0.000 description 27
- 229910002027 silica gel Inorganic materials 0.000 description 27
- 239000000243 solution Substances 0.000 description 17
- 239000000047 product Substances 0.000 description 16
- 238000003756 stirring Methods 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- 239000012535 impurity Substances 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 11
- 239000010410 layer Substances 0.000 description 10
- 238000009413 insulation Methods 0.000 description 9
- 238000005070 sampling Methods 0.000 description 9
- 239000008367 deionised water Substances 0.000 description 8
- 229910021641 deionized water Inorganic materials 0.000 description 8
- 238000010790 dilution Methods 0.000 description 8
- 239000012895 dilution Substances 0.000 description 8
- 239000012452 mother liquor Substances 0.000 description 8
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 5
- 150000001336 alkenes Chemical class 0.000 description 5
- 239000011630 iodine Substances 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 238000002791 soaking Methods 0.000 description 5
- 230000003068 static effect Effects 0.000 description 5
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 4
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 230000006837 decompression Effects 0.000 description 4
- ZICQBHNGXDOVJF-UHFFFAOYSA-N diamantane Chemical compound C1C2C3CC(C4)CC2C2C4C3CC1C2 ZICQBHNGXDOVJF-UHFFFAOYSA-N 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000010025 steaming Methods 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- NPSSWQJHYLDCNV-UHFFFAOYSA-N prop-2-enoic acid;hydrochloride Chemical compound Cl.OC(=O)C=C NPSSWQJHYLDCNV-UHFFFAOYSA-N 0.000 description 3
- 239000004065 semiconductor Substances 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001312 dry etching Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 239000013307 optical fiber Substances 0.000 description 1
- 230000005693 optoelectronics Effects 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/68—Preparation of metal alcoholates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/56—Ring systems containing bridged rings
- C07C2603/58—Ring systems containing bridged rings containing three rings
- C07C2603/70—Ring systems containing bridged rings containing three rings containing only six-membered rings
- C07C2603/74—Adamantanes
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a preparation method for 2-ethyl-2-adamantanol acrylate. The method is characterized in that under a low temperature condition, adamantanone and bromoethane form an active intermediate under the action of metal lithium, and then the active intermediate reacts with acrylic anhydride to obtain 2-ethyl-2-adamantanol acrylate. According to the synthesis method provided by the invention, by selecting the reaction conditions of each step like reaction temperature, reactant ratio, reaction time, reaction raw materials and the like, the problems of difficult purification, high cost, low reaction yield, low product purity, inapplicability to large-scale industrial production and the like in existing technical disclosures can be overcome.
Description
Technical field
The present invention relates to organic synthesis field, specifically provide a kind of preparation method of 2-ethyl-2-adamantanol acrylate.
Background technology
Diamantane is a kind of straight, symmetrical, high stability caged hydrocarbon, because have the structure that four cyclohexane rings are condensed into cage type, so, be the compound that a kind of symmetry is high and stable.Its derivative known relates to the fields such as medicine, aerospace, functional materials, refining of petroleum.
It is worth mentioning that, because diamantane has the such as character such as optical characteristics, thermotolerance, therefore, its derivative is often used in optic disc base board, optical fiber or lens lamp.Can be used as semi-conductor photo-resist, photosemiconductor sealing agent, optoelectronic component (photoconductive tube, optical communication lens and optical thin film etc.) and their caking agent.
Wherein, the electronic component manufactured using alkyl adamantane esters of acrylic acid as raw material, the dry etching patience in semiconductor fabrication process is high, and the development prospect as semi-conductor material is wide.
In prior art, in the manufacture method of known alkyl diamantane ester, be adopt the alkylating reagent of organometallic compound formation to after diamantane ketoalkylation, by the adamantyl alkoxide obtained, obtained by the method for esterifying halide.
Many employings acyl chlorides carries out esterification as etheride, thus just causes the by product of this reaction to be muriate.Ancestor institute is known, as being mixed into as magazine in the materials such as electronic component by muriate, even content is lower also can there is the problem reducing the performance of electronics unit's material own.
In addition, because acetyl halide compound activity is higher, often in the process of producing, existing enchashment is needed to use.And, with regard to the character of this type compound itself, there is corrodibility high, the problem that production requirement is strict.So, use the raw material of the type to there is the difficulty on preserving and producing.
Summary of the invention
The present invention is intended to overcome above-mentioned defect, provides a kind of high yield, high purity, environmental protection, cheap, the preparation method that can carry out industrial 2-ethyl-2-adamantanol acrylate.
For achieving the above object, the preparation method of the 2-ethyl-2-adamantanol acrylate that the present invention relates to, it is characterized in that, under cryogenic, after diamantane ketone and monobromethane form active intermediate under the effect of metal, be obtained by reacting 2-ethyl-2-adamantanol acrylate by this active intermediate and acrylic anhydride.
The temperature of 2-ethyl-2-adamantanol acrylate preparation process should control below 15 DEG C.
Metal involved in above-mentioned preparation method can be selected from MAGNESIUM METAL or metallic lithium.
Concrete reaction equation is as follows:
M can be Mg, Li.
The concrete technology step of the preparation method of above-mentioned 2-ethyl-2-adamantanol acrylate is as follows:
Step one, monobromethane is dripped in diamantane ketone, form preparation liquid one.
In practice, it is in the anhydrous tetrahydrofuran solution of diamantane ketone of 30-40% that monobromethane is added dropwise to mass percent concentration when stirring by general employing, stirs until clearly molten.Vice versa, diamantane ketone solution can be dripped in monobromethane solution.
Herein, it should be noted that the mol ratio of monobromethane and diamantane is 1:0.8-1.9; Preferred molar ratio is 1:1.3-1.9.
Diamantane ketone also dissolves in the composition of one or more in anhydrous tetrahydro furan, Anaesthetie Ether, ethylbenzene, benzene, alkane, and its mass percent concentration is preferably 33-40%.The excessive concentration of reaction system, cause reaction too violent, form unnecessary by product, the concentration of reaction system is too low, then cause solute too to disperse, thus causes reaction efficiency to reduce.
In addition, monobromethane herein can also be replaced by other liquid halogenated compounds, thus obtains other substituent 2-adamantanol acrylate derivatives.Wherein, preferably as the halogenated aliphatics of halogenated alkane, haloolefin etc.
Step 2, metal is added in solvent, form preparation liquid two.
This solvent can be selected from the mixture of one or more in anhydrous tetrahydro furan, Anaesthetie Ether, ethylbenzene, benzene, alkane, and the mass percent concentration of metallic lithium is 2-6%, is preferably 4-6%.
Wherein, the mol ratio of diamantane ketone and metallic lithium is 1:1.8-2.8, preferred 1:2.3-2.8.
In addition, in the present invention, preferably use metallic lithium, also can use MAGNESIUM METAL in addition.
Step 3, slowly drop in preparation liquid two by preparation liquid one, temperature of reaction is 5-15 DEG C, reaction times 0.5-1.5 hour.
In practice, preparation liquid two should be kept to be in whipped state, be cooled to sub-zero zero while stirring, preferable temperature is-5 DEG C ~ 0 DEG C.
It should be noted that due to product of the present invention or its intermediate quite responsive to temperature, be improve the productive rate of product, in the process of reaction, the control problem of temperature should be paid close attention to.
In addition, preparation liquid one drops in the process of preparation liquid two, drips the speed that speed should control at 0.6-1.2%/min, drips practice and is about 2-3 hour, period, crosses reacting phenomenon, temperature of reaction should be controlled between 5 DEG C ~ 15 DEG C for what avoid product.
After dropping operation completes, insulation 0.5-1.5 hour.Period, the judgement of reaction end, by sampling the rear TLC(PE:EA=10:1 of cancellation reaction that adds water in process, iodine develops the color, water soaking), the qualified rear confirmation of sample presentation GC detection simultaneously.
Step 4, reaction system is cooled to less than-5 DEG C, adds the poly-resist of catalytic amount.
After above-mentioned reaction terminates, carry out cooling process to system, preferable temperature is-10--8 DEG C.
Poly-resist can be selected from the composition of one or more in phenolic inhibitor, quinones stopper, arene nitro compound stopper.Usage quantity is the 0.5-3% of diamantane ketone quality.
Step 5, dropping acrylic anhydride, temperature of reaction is-10 DEG C ~-5 DEG C, and reaction times 0.5-1.5 hour, the cancellation that adds water was reacted.
Wherein, the mol ratio of diamantane ketone and acrylic anhydride is 1:0.6-1.4, is preferably 1.2-1.4.
The method that the judgement of reaction end preferably adopts GC to detect.
It should be noted that the temperature added water in the process of cancellation reaction controls below-5 DEG C, is preferably-10--8 DEG C.The speed dripping water when cancellation is reacted will be no more than-5 DEG C with reacting liquid temperature and be advisable, otherwise may have the generation of impurity alkene.
The consumption of water is 2-4 times of diamantane ketone quality, is preferably 2.5-3 doubly.
Step 6, obtain 2-ethyl-2-adamantanol acrylate through aftertreatment.
This last handling process comprises extraction at least one times, filtration at least one times and underpressure distillation.
Wherein, the quality of solvent is 5-50 times of diamantane ketone, is preferably 8-15 doubly.
In practice, after the cancellation that adds water reaction, preferred static separatory 30-60 minute, underpressure distillation organic layer, water layer extraction liquid extracts at least one times, merges concentration of organic layers.Wherein, one or more being selected from alkane, ethers, naphthenic hydrocarbon, ester class of extraction liquid obtain mixture.
After repeatedly adding alkane, filter, merging organic layer is concentrated obtains product, and productive rate is 66-99%.
It should be noted that filtration supports multiselect silica gel, due to other impurity may be produced during the course, answer the number of times of controlled filter.Find through experiment, a not clear impurity is had to produce (the not aobvious fluorescence of this impurity) with acrylic anhydride reaction, this impurity recrystallization method not easily removes, although, this impurity can remove by underpressure distillation, but as not high enough in vacuum tightness during underpressure distillation (cause interior temperature too high) can produce a large amount of alkene (impurity), find that this impurity can remove by silica gel through experiment, therefore, silica gel is selected to coordinate the mode of underpressure distillation to carry out in the present invention, but as too low in strength of solution when crossing silica gel, impurity-eliminating effect is not good so substantially impurity can be removed after silica gel after solution will being concentrated after crossing twice silica gel.
The consumption of silica gel is 5-20 times of diamantane ketone quality.
In addition, because product involved in the present invention is very responsive to heat, temperature during underpressure distillation should not exceed 20 DEG C, otherwise has impurity (as: alkene) generation.
the effect of invention and effect
The present invention prepares 2-ethyl-2-adamantanol acrylate by the reaction scheme selected acrylic anhydride and replace the halogenating agent in routine techniques to carry out esterification.
Empirical tests finds, acrylic anhydride reaction is more excellent than acrylate chloride.A large amount of polymkeric substance is had to produce after the raw material propylene acyl chloride reaction used in traditional technology, but, use acrylic anhydride then to there is not the too much problem of above-mentioned polymkeric substance.In addition, the halogenide of acrylate chloride class often deposits the problem being difficult to after the completion of reaction reject completely, and the existence of this material has had a strong impact on the application prospect of this product at electronics production field.
Therefore, acrylate chloride is replaced with acrylic anhydride and carried out the reaction of this one-tenth ester afterwards by the present invention, and this raw material is not only easy to obtain, and byproduct of reaction is few, and is easy to be separated in the process of aftertreatment, and then also can not have influence on the application of this product.
Especially it is worthy of note, also point out because this product is very responsive to heat in the present invention, so require to want strict temperature control when reacting; The present invention carries out under advocating temperature of reaction to be controlled the cold condition below 20 DEG C, thus avoids the generation of impurity (alkene), ensure that the purity of product, improves the productive rate of product.
In addition, consider the said products characteristic, for ensureing conversion rate of products, reduce production cost further, cancellation step of reaction after completion of the reaction, the speed dripping water will be no more than-5 DEG C with reacting liquid temperature and be advisable, otherwise may have the generation of impurity alkene.
In sum, in synthetic method provided by the invention, by the selection of each step reaction condition, as: temperature of reaction, reaction ratio, reaction times, reaction raw materials etc., overcome prior art open in, purification difficult, high cost, reaction yield are low, product purity is low, be not suitable for the problems such as large-scale industrial production.
Embodiment
Embodiment one,
Step one, 120g diamantane ketone is dissolved in 360ml anhydrous tetrahydro furan, under stirring, adds 120g monobromethane, molten clear after stand-by.
Step 2, the metallic lithium of 13g and 300ml anhydrous tetrahydro furan (moisture is less than 200ppm) added in the churned mechanically 1000ml reaction flask of band, be cooled to-5 DEG C ~ 0 DEG C while stirring to start to drip above-mentioned mixing solutions and drip off for about 2 hours, control temperature is at 5 DEG C ~ 15 DEG C, drip off rear insulation and after 1 hour, sample the rear TLC(PE:EA=10:1 of cancellation reaction that adds water, iodine develops the color, water soaking), sample presentation GC detects qualified rear (middle control 1) simultaneously, is cooled to-10 DEG C ~-8 DEG C.
Step 3, add 2g thiodiphenylamine stir 10min.
Step 4, dropping acrylic anhydride control rate of addition and temperature are controlled at-10 DEG C ~-5 DEG C, drip off rear insulation and after 1 hour, sample control 2 in the rear sample presentation GC(of cancellation reaction that adds water), after near for temperature of reaction system-10 DEG C ~-8 DEG C being dripped in 1000ml reaction flask 300ml deionized water cancellation reaction, reaction solution is transferred to static 1 hour branch vibration layer after solution is distinguished (lower floor) in 1000ml separating funnel.
Step 5, organic layer is transferred to 20 DEG C of decompression steamings on Rotary Evaporators and takes off when absence of liquid reserves, water layer 300ml n-hexane extraction, by organic layer and merging also evaporate to dryness (about 300g yellow liquid), adding the dilution of 500ml normal hexane has a large amount of sticky solid to separate out, after filtering, filtrate is with branch vibration layer after the deionized water wash of 300 × 2, rinse with 1000ml normal hexane afterwards with crossing silica gel (200g) after 30g anhydrous sodium sulfate drying, after a silica gel (200g) rinses silica gel with 300ml normal hexane afterwards, 20 DEG C, mother liquor is evaporated to absence of liquid and reserves, sampling and delivery GC, obtain colourless transparent liquid 190g, silica gel (200g) is crossed afterwards with after 300ml normal hexane flushing silica gel after using the dilution of 1000ml normal hexane again, 3 are controlled) in sampling and delivery GC(, 20 DEG C, mother liquor is evaporated to absence of liquid and reserves, obtain colourless transparent liquid 150.36g(water pump and draw dry 3 hours).
Embodiment two,
Step one, 150g diamantane ketone is dissolved in 475ml anhydrous tetrahydro furan, add under stirring 207g monobromethane molten clear after stand-by.
Step 2, the metallic lithium of 19.6g and 330ml anhydrous tetrahydro furan (moisture is less than 200ppm) added in the churned mechanically 1000ml reaction flask of band, be cooled to-5 DEG C ~ 0 DEG C while stirring to start to drip above-mentioned mixing solutions and drip off for about 2.5 hours, control temperature is at 5 DEG C ~ 15 DEG C, drip off rear insulation and after 1.5 hours, sample the rear TLC(PE:EA=10:1 of cancellation reaction that adds water, iodine develops the color, water soaking), sample presentation GC detects qualified rear (middle control 1) simultaneously, is cooled to-10 DEG C ~-5 DEG C.
Step 3, add 4.5g thiodiphenylamine stir 20min.
Step 4, start to drip 176g acrylic anhydride and control rate of addition and temperature is controlled at-10 DEG C ~-5 DEG C, drip off rear insulation and after 1.5 hours, sample control 2 in the rear sample presentation GC(of cancellation reaction that adds water), after near for temperature of reaction system-10 DEG C ~-8 DEG C being dripped in 1000ml reaction flask 450ml deionized water cancellation reaction, reaction solution is transferred in 1000ml separating funnel static 1.5 hours and treats that solution is distinguished.
Step 5, extraction organic layer, the temperature decompression steaming being transferred on Rotary Evaporators less than 20 DEG C is taken off when absence of liquid reserves, water layer 300ml hexanaphthene extracting twice, by organic layer and merging also evaporate to dryness (about 389g yellow liquid), adding the dilution of 500ml hexanaphthene has a large amount of sticky solid to separate out, after filtering, filtrate is with branch vibration layer after the deionized water wash of 300 × 2, rinse with 1000ml hexanaphthene afterwards with crossing silica gel (200g) after 45g anhydrous sodium sulfate drying, after a silica gel (250g) rinses silica gel with 400ml hexanaphthene afterwards, 20 DEG C, mother liquor is evaporated to absence of liquid and reserves, sampling and delivery GC, obtain the thick product of colourless transparent liquid 262g().
Step 6, with crossing after silica gel (250g) rinses silica gel with 350ml hexanaphthene afterwards after the dilution of 1200ml hexanaphthene, 3 are controlled) in sampling and delivery GC(, the temperature that mother liquor is less than 20 DEG C is evaporated to absence of liquid and reserves, and obtains colourless transparent liquid 201.2g(purity > 98.3%) (water pump draws dry 3 hours).
Embodiment three,
Step one, 150g diamantane ketone is dissolved in 300ml dry-out benzene, add under stirring 88g monobromethane molten clear after stand-by.
Step 2, the metallic lithium of 13g and 220ml dry-out benzene added in the churned mechanically 1000ml reaction flask of band, be cooled to-5 DEG C ~ 0 DEG C while stirring to start to drip above-mentioned mixing solutions and drip off for about 3 hours, control temperature is at 5 DEG C ~ 15 DEG C, drip off rear insulation and after 1 hour, sample the rear TLC(PE:EA=10:1 of cancellation reaction that adds water, iodine develops the color, water soaking), sample presentation GC detects qualified rear (middle control 1) simultaneously, is cooled to-10 DEG C ~-8 DEG C.
Step 3, add 1g thiodiphenylamine stir 10min.
Step 4, start to drip 75g acrylic anhydride and control rate of addition and temperature is controlled at-10 DEG C ~-5 DEG C, drip off rear insulation and after 0.5 hour, sample control 2 in the rear sample presentation GC(of cancellation reaction that adds water), after near for temperature of reaction system-10 DEG C ~-8 DEG C being dripped in 1000ml reaction flask 200ml deionized water cancellation reaction, reaction solution is transferred in 1000ml separating funnel static 1 hour and treats that solution is distinguished.
Step 5, extraction organic layer, be transferred to 15 DEG C of decompression steamings on Rotary Evaporators to take off when absence of liquid reserves, water layer 200ml petroleum ether extraction, by organic layer and merging also evaporate to dryness (about 330g yellow liquid), adding the dilution of 300ml sherwood oil has a large amount of sticky solid to separate out, after filtering, filtrate is with branch vibration layer after the deionized water wash of 200 × 2, rinse twice with difference 400ml sherwood oil afterwards with crossing silica gel (150g) after 20g anhydrous sodium sulfate drying, after a silica gel (150g) rinses silica gel with 200ml sherwood oil afterwards, 15 DEG C, mother liquor is evaporated to absence of liquid and reserves, sampling and delivery GC, obtain the thick product of colourless transparent liquid 200.6g().
Step 6, with crossing after silica gel (150g) rinses silica gel with 300ml sherwood oil afterwards after the dilution of 800ml sherwood oil, 3 are controlled) in sampling and delivery GC(, mother liquor less than 15 DEG C temperature are evaporated to absence of liquid and reserve, and obtain colourless transparent liquid 163.1g(purity > 97%) (water pump draws dry 3 hours).
Embodiment four,
Step one, 150g diamantane ketone is dissolved in 450ml dry-out benzene, add under stirring 150g methyl iodide molten clear after stand-by.
Step 2, the metallic lithium of 13g and 220ml dry-out benzene added in the churned mechanically 1000ml reaction flask of band, be cooled to-5 DEG C ~ 0 DEG C while stirring to start to drip above-mentioned mixing solutions and drip off for about 3 hours, control temperature is at 5 DEG C ~ 15 DEG C, drip off rear insulation and after 1 hour, sample the rear TLC(PE:EA=10:1 of cancellation reaction that adds water, iodine develops the color, water soaking), sample presentation GC detects qualified rear (middle control 1) simultaneously, is cooled to-10 DEG C ~-8 DEG C.
Step 3, add 4g thiodiphenylamine stir 15min.
Step 4, start to drip 95g acrylic anhydride and control rate of addition and temperature is controlled at-10 DEG C ~-5 DEG C, drip off rear insulation and after 0.5 hour, sample control 2 in the rear sample presentation GC(of cancellation reaction that adds water), after near for temperature of reaction system-10 DEG C ~-8 DEG C being dripped in 1000ml reaction flask 200ml deionized water cancellation reaction, reaction solution is transferred in 1000ml separating funnel static 1 hour and treats that solution is distinguished.
Step 5, extraction organic layer, be transferred to 15 DEG C of decompression steamings on Rotary Evaporators to take off when absence of liquid reserves, water layer 200ml n-hexane extraction, by organic layer and merging also evaporate to dryness (about 345g yellow liquid), adding the dilution of 300mll normal hexane has a large amount of sticky solid to separate out, after filtering, filtrate is with branch vibration layer after the deionized water wash of 200 × 2, rinse twice with difference 400mll normal hexane afterwards with crossing silica gel (150g) after 20g anhydrous sodium sulfate drying, after a silica gel (150g) rinses silica gel with 200mll normal hexane afterwards, 15 DEG C, mother liquor is evaporated to absence of liquid and reserves, sampling and delivery GC, obtain the thick product of colourless transparent liquid 180.6g().
Step 6, with crossing after silica gel (150g) rinses silica gel with 300mll normal hexane afterwards after the dilution of 1000ml normal hexane, 3 are controlled) in sampling and delivery GC(, mother liquor less than 15 DEG C temperature are evaporated to absence of liquid and reserve, and obtain colourless transparent liquid 135.1g(purity > 98%) (water pump draws dry 3 hours).
Claims (10)
1. the preparation method of a 2-ethyl-2-adamantanol acrylate, it is characterized in that: under cryogenic, after diamantane ketone and monobromethane form active intermediate under the effect of metal, be obtained by reacting 2-ethyl-2-adamantanol acrylate by this active intermediate and acrylic anhydride.
2. the preparation method of a kind of 2-ethyl-2-adamantanol acrylate as claimed in claim 1, is characterized in that, realized by following concrete technology step:
Step one, monobromethane is dripped in diamantane ketone, form preparation liquid one;
Step 2, metal is added in solvent, form preparation liquid two;
Step 3, slowly drop in preparation liquid two by preparation liquid one, temperature of reaction is 5-15 DEG C, reaction times 0.5-1.5 hour;
Step 4, reaction system is cooled to less than-5 DEG C, adds the poly-resist of catalytic amount;
Step 5, dropping acrylic anhydride, temperature of reaction is-10 DEG C ~-5 DEG C, and reaction times 0.5-1.5 hour, the cancellation that adds water was reacted;
Step 6, obtain 2-ethyl-2-adamantanol acrylate through aftertreatment,
Wherein, the metal described in step 2 can be selected from MAGNESIUM METAL or metallic lithium.
3. the preparation method of a kind of 2-ethyl-2-adamantanol acrylate as claimed in claim 2, is characterized in that: the mol ratio of described diamantane ketone, metallic lithium, monobromethane and acrylic anhydride is 1:1.8-2.8:0.8-1.9:0.6-1.4.
4. the preparation method of a kind of 2-ethyl-2-adamantanol acrylate as claimed in claim 2, is characterized in that: the mol ratio of described diamantane ketone, metallic lithium, monobromethane and acrylic anhydride is preferably 1:2.3-2.8:1.3-1.9:1.2-1.4.
5. the preparation method of a kind of 2-ethyl-2-adamantanol acrylate as claimed in claim 2, is characterized in that: described poly-resist can be selected from the composition of one or more in phenolic inhibitor, quinones stopper, arene nitro compound stopper.
6. the preparation method of a kind of 2-ethyl-2-adamantanol acrylate as claimed in claim 2, is characterized in that: the solvent in described step 2 can be selected from the mixture of one or more in anhydrous tetrahydro furan, Anaesthetie Ether, toluene, benzene, alkane.
7. the preparation method of a kind of 2-ethyl-2-adamantanol acrylate as claimed in claim 2, is characterized in that: the temperature in the process of the cancellation that adds water in described step 5 reaction controls below-5 DEG C.
8. the preparation method of a kind of 2-ethyl-2-adamantanol acrylate as claimed in claim 2, is characterized in that: the aftertreatment in described step 6 is extraction at least one times, filtration at least one times and underpressure distillation.
9. the preparation method of a kind of 2-ethyl-2-adamantanol acrylate as claimed in claim 8, is characterized in that: the temperature of described underpressure distillation is lower than 20 DEG C.
10. the preparation method of a kind of 2-ethyl-2-adamantanol acrylate as described in as arbitrary in claim 1 to 9, is characterized in that: described monobromethane can be replaced, for the preparation of the derivative of 2-adamantanol acrylate by any liquid halogenated compound.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109776311A (en) * | 2019-02-26 | 2019-05-21 | 江苏南大光电材料股份有限公司 | The preparation method and device of 2- isopropyl -2- adamantanol (methyl) acrylate |
| CN110305011A (en) * | 2019-06-10 | 2019-10-08 | 宁波南大光电材料有限公司 | 5- methyl 5- nonyl methacrylate and the preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004210745A (en) * | 2003-01-08 | 2004-07-29 | Takasago Internatl Corp | Method for producing (meth)acrylic ester |
| CN1527810A (en) * | 2001-06-07 | 2004-09-08 | 株式会社德山 | Method for producing 2-alkyl-2-adamantyl acrylate |
| CN101792389A (en) * | 2008-12-26 | 2010-08-04 | 三菱瓦斯化学株式会社 | Method for producing adamantyl (meth)acrylates |
-
2013
- 2013-11-11 CN CN201310557602.2A patent/CN104628562A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1527810A (en) * | 2001-06-07 | 2004-09-08 | 株式会社德山 | Method for producing 2-alkyl-2-adamantyl acrylate |
| JP2004210745A (en) * | 2003-01-08 | 2004-07-29 | Takasago Internatl Corp | Method for producing (meth)acrylic ester |
| CN101792389A (en) * | 2008-12-26 | 2010-08-04 | 三菱瓦斯化学株式会社 | Method for producing adamantyl (meth)acrylates |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109776311A (en) * | 2019-02-26 | 2019-05-21 | 江苏南大光电材料股份有限公司 | The preparation method and device of 2- isopropyl -2- adamantanol (methyl) acrylate |
| CN110305011A (en) * | 2019-06-10 | 2019-10-08 | 宁波南大光电材料有限公司 | 5- methyl 5- nonyl methacrylate and the preparation method and application thereof |
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