CN102295578B - Synthetic method of 3,3-diethoxypropionitrile - Google Patents
Synthetic method of 3,3-diethoxypropionitrile Download PDFInfo
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Abstract
The invention discloses a synthetic method of 3,3-diethoxypropionitrile so as to solve the problems of large reaction operating pressure and low reaction yield in the synthesis of 3,3-diethoxypropionitrile by present acetalation methods. According to the invention, acetonitrile, carbon monoxide gas and a C1-C4 alcohol alkali metal salt are used as raw materials, C1-C3 alcohol is used as a reaction catalyst, and a non-polar solvent is used as a reaction solvent for a pressure reaction; a product obtained by the pressure reaction is subjected to an acetal reaction in acidic alcohol; and a post-processing separation process is finally carried out to complete the synthetic method. The synthetic method requires a low CO gas reaction pressure at 0.3-1.5MPa, thus substantially minimizing unsafe factors in the production; economic cost is low; the yield is high; and the post-processing is easy and the reaction solvent can be recovered and reused.
Description
Technical field
The present invention relates to a kind of 3, the synthetic method of 3-diethoxy propionitrile.
Background technology
3,3 one diethoxy propionitrile (or 3-ethoxy propylene nitrile) are the acetal form of cyanoacetaldehyde, can through cyclization, prepare the multiple heterocycles compounds such as pyrazoles, pyridine derivate, are the important medicine intermediates of synthetic drug and spices.In recent years 3, the wide model of 3-diethoxy propionitrile (or, 3-ethoxy propylene nitrile) is applied to the derivative of synthesizing cytimidine, cytosine(Cyt) and the precursor compound of VITMAIN B1.Along with expiring of the best-selling drugs patent protections such as a collection of anti AIDS virus, hepatitis B virus, the consumption of cytosine intermediate will significantly promote and increase along with corresponding pharmaceutical production ability.Under this compound room temperature, be colorless oil, molecular formula: C
7h
13nO
2(or C
5h
7nO), structural formula is:
The synthesis technique of 3,3-diethoxy propionitrile becomes the focus of domestic and international research, and at present, the method for synthetic 3,3-dialkoxy propionitrile mainly contains both at home and abroad:
(1) dehydration of amide nitrile method processed
Jourmal of the American Chemical Society, 69,2657-60; 1947 bibliographical informations, take ethyl formate, ethyl acetate is raw material, under sodium ethylate effect, through claisen condensation, then through aldol condensation, then with azanol reaction 40h, generate 3,3-diethoxy propionic acid amide, then dehydration generates 3,3-oxyethyl group propionitrile.This method technical process is long, and by product is many, and the yield of final product only has 8%.
(2), metal cyanides replaces nitrile method processed
Jourmal of the American Chemical Society, 97,7152-7157; 19757 bibliographical informations, with bromoacetaldehyde diethyl acetal and sodium cyanide reaction, can make 3,3-diethoxy propionitrile, yield approximately 80%, but due to raw material sources difficulty, reaction not exclusively, contains a large amount of problems such as sodium cyanide in waste liquid.
(3) acetal acetal method processed
German Patent Ger.Offen.3641604,16 Jun 1988 reports, in closed reactor, add acetonitrile, sodium methylate, ethyl formate etc., at 5MPa, 60 ℃, be constantly filled with CO gas until saturated, and then reaction generates acetal with monochloroethane, this overall yield of reaction is about 73.4%.Because needs carry out under high pressure and catalyzer existence, reaction conditions is relatively harsh.
⑷ oxazole open loop method
The Cai Dong of Shenyang Chemical Engineering Inst etc. are at < < fine-chemical intermediate > > 2007,37(6): 65-68 report, with 1,1,3, the mixture of isoxazole is produced in 3-tetraethoxypropane and hydroxylamine hydrochloride reaction, then with ethyl sulfate reaction, through aftertreatment, can obtain 3, the mixture of 3-diethoxy propionitrile and 3-ethoxy propylene nitrile, total recovery 85～90%.Raw materials used 1,1,3,3-tetraethoxypropane price is higher, has limited the industrial prospect of this method.
(5) benzene sulphur sulfone propionitrile method
Zhejiang University's material and Hao of engineering college precious jade etc. are at < < dyestuff and dyeing > > 2005,41(5): 41-41 report, with the chloro-3-phenyl of 2-sulphur sulfuryl propionitrile, through elimination and addition two-step reaction, synthesize 3,3-diethoxy propionitrile, yield approximately 88%.Because the chloro-3-phenyl of 2-sulphur sulfuryl propionitrile will be through the addition of vinyl cyanide chloro, displacement, the preparation of oxidation three-step reaction, in fact reactions steps is very long.
(6) manthanoate method
A kind of synthesis route of Chinese patent CN1594187A report.Take acetonitrile, manthanoate is initial feed, generates the mixture of 3,3-diethoxy propionitrile and 3-ethoxy propylene nitrile.
(7) vinyl cyanide oxidation style
Japanese Laid-Open Patent 06087781 in 1994 and U.S. Jourmal of Molecular Catalysis A bibliographical information in 1996, take vinyl cyanide, ethanol and oxygen as raw material, by Palladous chloride and cuprous chloride catalyst, obtain 3 of very high yield, 3-ethoxy propionitrile.
From above-mentioned discussion, to domestic and international report a lot of of the synthetic method of 3,3-diethoxy propionitrile, but at present industrialization degree the highest be (3) acetal acetal method processed in aforesaid method; This technique is updated through descendant, and after reaction, a step is with acidic alcohol as acetal reagent, and its reaction equation is as follows:
It is initial feed that the method be take acetonitrile, CO gas, sodium ethylate, take ethyl formate as catalyzer, and reaction synthetic route is shorter, and related raw materials cost is cheap, on market, also easily buys.But the main drawback operation pressure that this synthesis route exists is larger, and CO gas reaction pressure requires 5 MPa, and production unit is had relatively high expectations, and reaction yield is lower in addition.
summary of the invention
The object of this invention is to provide a kind of 3, the synthetic method of 3-diethoxy propionitrile, larger to solve the operation pressure that synthetic 3, the 3-diethoxy propionitrile of existing acetal acetal method processed exists, the problem that reaction yield is lower.
Synthetic method of the present invention is comprised of following steps:
A, compressive reaction process: with acetonitrile, CO (carbon monoxide converter) gas and C
1～C
4alcohols an alkali metal salt is raw material, uses C
1～C
3alcohol, as catalysts, is usingd non-polar solvent as reaction solvent, and in reaction, CO (carbon monoxide converter) gas operation pressure is 0.3～1.5MPa, 50～100 ℃ of temperature of reaction, the reaction times needs 5～10 hours, after having reacted, isolate and generate 3-hydroxyl vinyl cyanide metal-salt, described C
1～C
4alcohols an alkali metal salt is selected from C
1～C
4alcohols basic metal sodium salt or C
1～C
4a kind of in alcohols sylvite;
B, aldolization process: 3-hydroxyl vinyl cyanide metal-salt and acidic alcohol that the steps A compressive reaction of take is produced are raw material, with the vitriol oil as catalyzer, 10～25 ℃ of temperature of reaction, reaction times needs 4～8 hours, generate target product 3, the mixture of 3-diethoxy propionitrile and 3-ethoxy propylene nitrile;
C, aftertreatment sepn process: after aldolization completes, to reaction system, add non-polar solvent as extraction solvent, after fully stirring, proceed to separating funnel, stratification, isolates upper organic phase; Lower floor's solution adds same extraction solvent to extract again 2 times, merges separated upper organic phase, with after sodium hydrogen carbonate solution washing, then isolates 3,3-diethoxy propionitrile by underpressure distillation.
So far can realize the object of the invention, in order to make the present invention reach better effect, the catalyzer C in steps A compressive reaction
1～C
3alcohol is selected from a kind of in methyl alcohol, ethanol or propyl alcohol.
In order to make the present invention reach better effect, the non-polar solvent adopting in described steps A and step B is C
6-C
9aromatics, be selected from a kind of in benzene,toluene,xylene or trimethylbenzene.
In order to make the present invention reach better effect, acetonitrile and C in described steps A compressive reaction
1～C
4the weight ratio of alcohols an alkali metal salt is 1:1.2～2.5, acetonitrile and C
1～C
3the weight ratio of alcohol catalyst is 1:2～5.
In order to make the present invention reach better effect, in described step B aldolization, acidic alcohol consumption is 5～10 times of amounts of steps A initial feed acetonitrile weight, and catalyzer vitriol oil add-on is 5% of acidic alcohol weight.
In order to make the present invention reach better effect, in described step B aftertreatment sepn process, underpressure distillation 3, during 3-diethoxy propionitrile, requires vacuum tightness lower than 0.07MPa, to collect the cut of 110 ~ 125 ℃.
In order to make the present invention reach better effect, the C in described steps A compressive reaction
1～C
4alcohols basic metal sodium salt is selected from a kind of in sodium methylate, sodium ethylate, sodium propylate, sodium isopropylate, sodium butylate or sodium tert-butoxide.
In order to make the present invention reach better effect, the C in described steps A compressive reaction
1～C
4alcohols basic metal sylvite is selected from a kind of in potassium methylate, potassium ethylate, potassium propylate, sodium isopropylate, butanols potassium or potassium tert.-butoxide.
Mechanism of the present invention is as follows: in the present invention 3, in the synthesis technique of 3-diethoxy propionitrile, in compressive reaction process, with the C of more economical cheapness
1～C
3low-carbon alcohol has replaced the catalyzer ethyl formate in original technique, not only makes CO operation pressure greatly reduce, and reaction yield is increased; With the acidic alcohol aldolization stage, add dense H
2sO
4make catalyzer, also make reaction yield further improve; In the post-reaction treatment stage, utilize some non-polar solvent (as toluene, dimethylbenzene etc.) and not the dissolving each other of acidic alcohol, and 3,3-diethoxy propionitrile (or the rare nitrile of 3-ethoxy-c) high characteristic of solubleness in non-polar solvent, directly from acidic alcohol reaction system, extract the method for required target product, make excessive acidic alcohol recovery, production cost is reduced greatly.
In the present invention 3, in the synthesis technique of 3-diethoxy propionitrile, in compressive reaction process, with the C of more economical cheapness
1～C
3low-carbon alcohol has replaced the catalyzer ethyl formate in original technique, not only makes CO operation pressure greatly reduce, and reaction yield is increased; With the acidic alcohol aldolization stage, add dense H
2sO
4make catalyzer, also make reaction yield further improve; In the post-reaction treatment stage, utilize some non-polar solvent (as toluene, dimethylbenzene etc.) and not the dissolving each other of acidic alcohol, and 3,3-diethoxy propionitrile (or the rare nitrile of 3-ethoxy-c) high characteristic of solubleness in non-polar solvent, directly from acidic alcohol reaction system, extract the method for required target product, make excessive acidic alcohol recovery, production cost is reduced greatly.
Reaction equation after improvement is as follows:
R, R': representative be C
1～C
4saturated fatty alkyl; M is sodium ion or potassium ion.
Details are as follows for summary of the invention:
(1), in above-mentioned compressive reaction, ROH catalytic mechanism is as follows:
Because low-carbon alcohol is under the katalysis of alcohol an alkali metal salt, and CO reaction can generate manthanoate, and its reaction equation is:
R:C
1～C
3straight chain saturated fatty alkyl; R': representative be C
1～C
4saturated fatty alkyl; M is basic metal particle.
Due to the generation of above-mentioned reaction, reaction system generates automatically to having reacted the manthanoate of katalysis; In addition, in reaction system, add after low-carbon alcohol, the polarity of reaction system changes to some extent, the alcohol an alkali metal salt and the CO gas that in reaction, add have better been dissolved, so further accelerated speed of response, also make CO gas-operated pressure in reaction greatly reduce, and molecular balance is moved right improved the yield of reaction.
(2) in aldolization, dense H
2sO
4catalytic mechanism:
At NaOCH=CHCN and acidic alcohol, carry out in aldolization, have a large amount of byproduct of reaction NaCl to generate.In system, add dense H
2sO
4after, have following reaction to occur:
Added a certain amount of dense H
2sO
4not only make negative product NaCl in reaction process generate HCl, and the HCl in the used up acidic alcohol of postreaction, the concentration that acidic alcohol loses in reaction is supplemented, thereby molecular balance is moved to right, increased the yield of reaction.
(3) post-reaction treatment process:
3,3-diethoxy propionitrile is very unstable in acidic alcohol system, when system temperature is during higher than 30 ℃, reacts required product 3, and 3-diethoxy propionitrile can continue with acidic alcohol the reaction following side reaction that responds and occur:
Therefore, can not reclaim excessive acidic alcohol by the method for routine distillation.How from acidic alcohol reaction system, to isolate reaction target product 3,3-diethoxy propionitrile (or the rare nitrile of 3-ethoxy-c), and reclaim excessive acidic alcohol recycling, be the difficult point of this process optimization.The present invention utilizes acidic alcohol and non-polar solvent (toluene or dimethylbenzene) not to dissolve each other, and 3,3-diethoxy propionitrile (or the rare nitrile of 3-ethoxy-c) high characteristic of solubleness in non-polar solvent, reaction target product is extracted from acidic alcohol system, the acidic alcohol reclaiming passes into after HCl gas improves concentration and can repeat to apply mechanically, thereby greatly reduce the Financial cost that 3,3-diethoxy propionitrile (or the rare nitrile of 3-ethoxy-c) is produced.
In the inventive method, to the lower 0.3～1.5MPa of CO gas reaction pressure, Financial cost is low, and productive rate is high, is 76～83%, aftertreatment easily and reaction solvent can recycle and reuse.
the impact of technique of the present invention to 3,3-diethoxy propionitrile (or the rare nitrile of 3-ethoxy-c) building-up reactions
(1) in compressive reaction, the impact of ROH catalyzer on reaction:
Take acetonitrile as initial feed synthetic 3, the method of 3-diethoxy propionitrile (or the rare nitrile of 3-ethoxy-c), bibliographical information have a German Patent Ger.Offen.3641604,16 Jun 1988 reports and Chinese patent CN1594187A reports, now compare the present invention with this two classes invention list:
Table 1 is various take the comparison of acetonitrile as synthetic 3, the 3-diethoxy propionitrile method of initial feed
As can be seen from Table 1, this technique and German Patent Ger.Offen.3641604,16 compare, and operation pressure is much lower, and used catalyst market cost is also low, has very large advantage; This technique and Chinese patent CN1594187A relatively can find out, the initial feed market cost adopting has very large advantage, and operation pressure is not high yet.Be separately C
1～C
3adding of alcohol catalyst, can better dissolve the alcohol an alkali metal salt and the CO gas that add in reaction, so further accelerated speed of response, and molecular balance is moved right improved the yield of reaction.
(2) in aldolization, dense H
2sO
4the impact of catalyzer on reaction:
When the 3-hydroxyl vinyl cyanide metal-salt of producing in compressive reaction is carried out to aldolization in acidic alcohol, add dense H
2sO
4reaction is had to a larger impact, and its result is as following table 2:
| Test number | Dense H2SO4 add-on (acidic alcohol % by weight) | Reaction times (hour) | Reaction yield (%) |
| 1 | ? | 8 | 63.5 |
| 2 | 2 | 8 | 79.2 |
| 3 | 5 | 8 | 83.3 |
| 4 | 5 | 4 | 83.2 |
| 5 | 8 | 4 | 83.2 |
As can be seen from Table 2, dense H
2sO
4the introducing of catalyzer, the change that reaction times and reaction yield have been had, its add-on is 5% the best of acidic alcohol weight.The present invention is to the added dense H of reaction system
2sO
4after by product NaCl reaction, supplemented in time the concentration of acidic alcohol loss in a part of reaction process, also reduced by product in reaction, thereby molecular balance is moved to right, accelerate the reaction times, improved reaction yield receipts.
(3) comparison of the various separation methods of post-reaction treatment process:
3,3-diethoxy propionitrile is very unstable in acidic alcohol system, when system temperature is during higher than 30 ℃, reacts required product 3, and 3-diethoxy propionitrile can continue and acidic alcohol reaction, generates other by products; Therefore, can not reclaim excessive acidic alcohol by the method for routine distillation.How from acidic alcohol reaction system, to isolate reaction target product 3,3-diethoxy propionitrile, and reclaim excessive acidic alcohol recycling, be the difficult point of this process optimization.In order to address this problem, by experiment good several method.Wherein ideal technique is: utilize the immiscible characteristic of acidic alcohol and toluene, will react target product 3,3-diethoxy propionitrile extracts from acidic alcohol system.Now several separation method lists are contrasted as following table 3:
Determining of table 3 pair product postprocessing separation method
| Sequence number | Separation method to product | Productive rate/% | The problem of subsequent disposal and generation |
| 1 | To acidic alcohol reaction system, add frozen water, then extract target product 3,3-diethoxy propionitrile with toluene | 82.3. | There is a large amount of strongly-acid alcohol-water mixtures to produce |
| 2 | In ℃ situation of system temperature T≤10, first use NaHCO 3Neutralization reaction system, after filtration, by fractionation by distillation target product 3,3-diethoxy propionitrile | 42.7 | Can reclaim a certain amount of ethanol, but reaction yield reduction to consume a large amount of NaHCO simultaneously 3 |
| 3 | In ℃ situation of system temperature T≤10, utilize high vacuum reclaiming excessive acidic alcohol | ? | Organic efficiency is very poor, and a large amount of sour gas also can etching apparatus |
| 4 | Utilize the immiscible characteristic of acidic alcohol and toluene (or benzene, dimethylbenzene, trimethylbenzene), by repeatedly extracting separated product 3,3-diethoxy propionitrile | 82.1 | Can reclaim a large amount of acidic alcohols, by passing into after HCl gas improves concentration, repeat to apply mechanically, solve blowdown problem, and reduced production cost |
From the comparison of the listed separation method of table 3, final choice utilize the immiscible characteristic of acidic alcohol and toluene (or benzene, dimethylbenzene, trimethylbenzene), extraction product 3, the method for 3-diethoxy propionitrile; The method makes excessive hydrochloric acid ethanol be able to recovery, has reduced the discharge of three industrial wastes, also greatly reduces the Financial cost of production.
Embodiment
Embodiment 1
In 2L stainless steel pressure reactor, add 41 grams of acetonitriles, 500 grams of toluene, 70 grams of sodium ethylates, 200 grams of ethanol, after having fed in raw material, closed reactor, heats up in 70 ℃, passes into CO gas 0.3MPa pressurize reaction 8 hours, stopped reaction.Reaction generates 3-hydroxyl vinyl cyanide sodium salt (NaOCH=CHCN) and from mother liquor, with solid form, separates out in reaction process, by filter method, separates, standby.
The there-necked flask that 300 grams of acidic alcohols is added to 2L, keeps 15 ℃ of system temperatures with ice-water bath, opens 3-hydroxyl vinyl cyanide sodium salt (NaOCH=CHCN) substep stirring producing in above-mentioned reaction and adds, and reacts and adds dense H after 10 minutes
2sO
4(add-on is acidic alcohol 5%), keeps 15 ℃ of degree reactions 4 hours.To reaction system, add toluene 200ML again, stratification after fully stirring, separates upper strata, then repeats twice of this operation (adding altogether toluene three times, toluene total amount 600ML); With mother liquor to the pH value that saturated sodium bicarbonate solution neutralization separates, be 7, underpressure distillation, collects the cut of 110 ~ 125 ℃, and vacuum tightness must not be lower than 0.07MPa, and the calculated yield of weighing is 82.5%.
Embodiment 2
In 2L stainless steel pressure reactor, add 41 grams of acetonitriles, 500 grams of toluene, 49 grams of sodium methylates, 200 grams of methyl alcohol, after having fed in raw material, closed reactor, heats up in 50 ℃, passes into CO gas 0.3MPa pressurize reaction 10 hours, stopped reaction.Reaction generates 3-hydroxyl vinyl cyanide sodium salt (NaOCH=CHCN) and from mother liquor, with solid form, separates out in reaction process, by filter method, separates, standby.
The there-necked flask that 410 grams of acidic alcohols is added to 2L, with ice-water bath, keeping system temperature is 15 ℃, opens 3-hydroxyl vinyl cyanide sodium salt (NaOCH=CHCN) substep stirring producing in above-mentioned reaction and adds, and reacts and adds dense H after 10 minutes
2sO
4(add-on is acidic alcohol 5%), keeps 15 ℃ of degree reactions 4 hours.To reaction system, add toluene 200ML again, stratification after fully stirring, separates upper strata, then repeats twice of this operation (adding altogether toluene three times, toluene total amount 600ML); With mother liquor to the pH value that saturated sodium bicarbonate solution neutralization separates, be 7, underpressure distillation, collects the cut of 110 ~ 125 ℃, and vacuum tightness must not be lower than 0.07MPa, and the calculated yield of weighing is 81.6%.
Embodiment 3
In 2L stainless steel pressure reactor, add 41 grams of acetonitriles, 500 grams of dimethylbenzene, 102 grams of sodium isopropylates, 205 grams of propyl alcohol, after having fed in raw material, closed reactor, heats up in 100 ℃, passes into CO gas 1.5MPa pressurize reaction 8 hours, stopped reaction.Reaction generates 3-hydroxyl vinyl cyanide sodium salt (NaOCH=CHCN) and from mother liquor, with solid form, separates out in reaction process, by filter method, separates, standby.
The there-necked flask that 410 grams of acidic alcohols is added to 2L, with ice-water bath, keeping system temperature is 15 ℃, opens 3-hydroxyl vinyl cyanide sodium salt (NaOCH=CHCN) substep stirring producing in above-mentioned reaction and adds, and reacts and adds dense H after 10 minutes
2sO
4(add-on is acidic alcohol 5%), keeps 15 ℃ of degree reactions 4 hours.To reaction system, add dimethylbenzene 200ML again, stratification after fully stirring, separates upper strata, then repeats twice of this operation (adding altogether dimethylbenzene three times, dimethylbenzene total amount 600ML); With mother liquor to the pH value that saturated sodium bicarbonate solution neutralization separates, be 7, underpressure distillation, collects the cut of 110 ~ 125 ℃, and vacuum tightness must not be lower than 0.07MPa, the calculated yield 76.8% of weighing.
Embodiment 4
In 2L stainless steel pressure reactor, add 41 grams of acetonitriles, 500 grams of toluene, 92 grams of potassium ethylates, 200 grams of ethanol, after having fed in raw material, closed reactor, heats up in 60 ℃, passes into CO gas 1.0MPa pressurize reaction 5 hours, stopped reaction.Reaction generates 3-hydroxyl vinyl cyanide sylvite (KOCH=CHCN) and from mother liquor, with solid form, separates out in reaction process, by filter method, separates, standby.
The there-necked flask that 205 grams of acidic alcohols is added to 2L, with ice-water bath, keeping system temperature is 15 ℃, opens 3-hydroxyl vinyl cyanide sylvite (KOCH=CHCN) substep stirring producing in above-mentioned reaction and adds, and reacts and adds dense H after 10 minutes
2sO
4(add-on is acidic alcohol 5%), keeps 15 ℃ of degree reactions 4 hours.To reaction system, add toluene 600ML to add (each 200ML) three times again, stratification after fully stirring, separate upper toluene phase, adding saturated sodium bicarbonate solution to be neutralized to pH value is 7, underpressure distillation, collect the cut of 110 ~ 125 ℃, vacuum tightness must not be lower than 0.07MPa, and the calculated yield of weighing is 78.6%.
Embodiment 5
In 2L stainless steel pressure reactor, add 41 grams of acetonitriles, 500 grams of trimethylbenzenes, 92 grams of potassium methylates, 200 grams of methyl alcohol, pass into CO gas 0.3MPa pressurize reaction 8 hours at 60 ℃, stopped reaction, generate 3-hydroxyl vinyl cyanide sylvite (KOCH=CHCN), separate, standby.
The there-necked flask that 300 grams of acidic alcohols is added to 2L, with ice-water bath, keeping system temperature is 15 ℃, opens 3-hydroxyl vinyl cyanide sylvite (KOCH=CHCN) substep stirring producing in above-mentioned reaction and adds, and reacts and adds dense H after 10 minutes
2sO
4(add-on is acidic alcohol 5%), keeps 15 ℃ of degree reactions 4 hours.To reaction system, add trimethylbenzene 200ML again, stratification after fully stirring, separates upper strata, then repeats twice of this operation (adding altogether trimethylbenzene three times, trimethylbenzene total amount 600ML); With mother liquor to the pH value that saturated sodium bicarbonate solution neutralization separates, be 7, underpressure distillation, collects the cut of 110 ~ 125 ℃, and vacuum tightness must not be lower than 0.07MPa, and the calculated yield of weighing is 83.1%.
Embodiment 6
In 2L stainless steel pressure reactor, add 41 grams of acetonitriles, 500 grams of toluene, 102 grams of potassium isopropoxides, 200 grams of propyl alcohol, after having fed in raw material, closed reactor, heats up in 90 ℃, passes into CO gas 1.0MPa pressurize reaction 10 hours, stopped reaction.Reaction generates 3-hydroxyl vinyl cyanide sylvite (KOCH=CHCN) and from mother liquor, with solid form, separates out in reaction process, by filter method, separates, and dries, standby.
The there-necked flask that 410 grams of acidic alcohols is added to 2L, with ice-water bath, keeping system temperature is 15 ℃, opens 120 grams of 3-hydroxyl vinyl cyanide sylvite (KOCH=CHCN) substep stirring producing in above-mentioned reaction and adds, and reacts and adds dense H after 10 minutes
2sO
4(add-on is acidic alcohol 5%), keeps 15 ℃ of degree reactions 4 hours.To reaction system, add toluene 200ML again, stratification after fully stirring, separates upper strata, then repeats twice of this operation (adding altogether toluene three times, toluene total amount 600ML); With the mother liquor pH value that saturated sodium bicarbonate solution neutralization separates, be 7, underpressure distillation, collects the cut of 110 ~ 125 ℃, and vacuum tightness must not be lower than 0.07MPa, the calculated yield 82.7% of weighing.
Embodiment 7
In 2L stainless steel pressure reactor, add 41 grams of acetonitriles, 500 grams of toluene, 102 grams of potassium propylates, 200 grams of propyl alcohol, after having fed in raw material, heat up in 100 ℃, pass into CO gas 1.5MPa pressurize reaction 5 hours, reaction generates 3-hydroxyl vinyl cyanide sylvite (KOCH=CHCN).
The there-necked flask that 300 grams of acidic alcohols is added to 2L, with ice-water bath, keeping system temperature is 15 ℃, opens 3-hydroxyl vinyl cyanide sylvite (KOCH=CHCN) substep stirring producing in above-mentioned reaction and adds, and reacts and adds dense H after 10 minutes
2sO
4(add-on is acidic alcohol 5%), keeps 15 ℃ of degree reactions 4 hours.To reaction system, add toluene 500ML again, add water 300Ml, stratification after fully stirring, separate upper toluene phase, adding saturated sodium bicarbonate solution to be neutralized to pH value is 7, underpressure distillation, collect the cut of 110 ~ 125 ℃, vacuum tightness must not be lower than 0.07MPa, the calculated yield 82.0% of weighing.
Embodiment 8
In 2L stainless steel pressure reactor, add 41 grams of acetonitriles, 500 grams of dimethylbenzene, 96 grams of sodium ethylates, 200 grams of ethanol, after having fed in raw material, closed reactor, heats up in 60 ℃, passes into CO gas 0.3MPa pressurize reaction 8 hours, stopped reaction.It is separated standby that reaction generates 3-hydroxyl vinyl cyanide sodium salt (NaOCH=CHCN).
The there-necked flask that 205 grams of acidic alcohols is added to 2L, with ice-water bath, keeping system temperature is 10 ℃, opens 3-hydroxyl vinyl cyanide sodium salt (NaOCH=CHCN) substep stirring producing in above-mentioned reaction and adds, and reacts and adds dense H after 10 minutes
2sO
4(add-on is acidic alcohol 5%), keeps 10 ℃ of degree reactions 8 hours.To reaction system, add dimethylbenzene 200ML again, stratification after fully stirring, separates upper strata, then repeats twice of this operation (adding altogether dimethylbenzene three times, toluene total amount 600ML); With mother liquor to the pH value that saturated sodium bicarbonate solution neutralization separates, be 7, filter to isolate mother liquor, underpressure distillation, collects the cut of 110 ~ 125 ℃, and vacuum tightness must not be lower than 0.07MPa, the calculated yield 81.0% of weighing.
Embodiment 9
In 2L stainless steel pressure reactor, add 41 grams of acetonitriles, 500 grams of trimethylbenzenes, 80 grams of sodium ethylates, 200 grams of ethanol, after having fed in raw material, closed reactor, heats up in 70 ℃, passes into CO gas 1.0MPa pressurize reaction 6 hours, stopped reaction.It is separated standby that reaction generates 3-hydroxyl vinyl cyanide sodium salt (NaOCH=CHCN).
The there-necked flask that 300 grams of acidic alcohols is added to 2L, with ice-water bath, keeping system temperature is 15 ℃, by 3-hydroxyl vinyl cyanide sodium salt (NaOCH=CHCN) substep add, react and add dense H after 10 minutes
2sO
4(add-on is acidic alcohol 5%), keeps 10 ℃ of degree reactions 8 hours.To reaction system, add trimethylbenzene 200ML again, stratification after fully stirring, separates upper strata, then repeats twice of this operation (adding altogether trimethylbenzene three times, toluene total amount 600ML); With mother liquor to the pH value that saturated sodium bicarbonate solution neutralization separates, be 7, underpressure distillation, collects the cut of 110 ~ 125 ℃, and vacuum tightness must not be lower than 0.07MPa, the calculated yield 78% of weighing.
Embodiment 10
In 2L stainless steel pressure reactor, add 41 grams of acetonitriles, 500 grams of benzene, 70 grams of sodium ethylates, 200 grams of ethanol, after having fed in raw material, closed reactor, heats up in 70 ℃, passes into CO gas 0.3MPa pressurize reaction 8 hours, stopped reaction.Reaction generates 3-hydroxyl vinyl cyanide sodium salt (NaOCH=CHCN) and from mother liquor, with solid form, separates out in reaction process, by filter method, separates, standby.
The there-necked flask that 300 grams of acidic alcohols is added to 2L, keeps 15 ℃ of system temperatures with ice-water bath, opens 3-hydroxyl vinyl cyanide sodium salt (NaOCH=CHCN) substep stirring producing in above-mentioned reaction and adds, and reacts and adds dense H after 10 minutes
2sO
4(add-on is acidic alcohol 5%), keeps 15 ℃ of degree reactions 4 hours.To reaction system, add benzene 200ML again, stratification after fully stirring, separates upper strata, then repeats twice of this operation (adding altogether benzene three times, benzene total amount 600ML); With mother liquor to the pH value that saturated sodium bicarbonate solution neutralization separates, be 7, underpressure distillation, collects the cut of 110 ~ 125 ℃, and vacuum tightness must not be lower than 0.07MPa, and the calculated yield of weighing is 81.8%.
Claims (3)
1. one kind 3, the synthetic method of 3-diethoxy propionitrile, is characterized in that it is comprised of following steps:
A, compressive reaction process: with acetonitrile, CO (carbon monoxide converter) gas and C
1～C
4alcohols an alkali metal salt is raw material, uses C
1～C
3alcohol, as catalysts, is usingd non-polar solvent as reaction solvent, and in reaction, CO (carbon monoxide converter) gas operation pressure is 0.3～1.5MPa, 60～100 ℃ of temperature of reaction, the reaction times needs 6～10 hours, after having reacted, isolate and generate 3-hydroxyl vinyl cyanide metal-salt, described C
1～C
4alcohols an alkali metal salt is selected from C
1～C
4alcohols basic metal sodium salt or C
1～C
4a kind of in alcohols sylvite;
B, aldolization process: 3-hydroxyl vinyl cyanide metal-salt and acidic alcohol that the steps A compressive reaction of take is produced are raw material, with the vitriol oil as catalyzer, 10～25 ℃ of temperature of reaction, reaction times needs 4～8 hours, generate target product 3, the mixture of 3-diethoxy propionitrile and 3-ethoxy propylene nitrile;
C, aftertreatment sepn process: after aldolization completes, to reaction system, add non-polar solvent as extraction solvent, after fully stirring, proceed to separating funnel, stratification, isolates upper organic phase; Lower floor's solution adds same extraction solvent to extract again 2 times, merges separated upper organic phase, with after sodium hydrogen carbonate solution washing, then isolates 3,3-diethoxy propionitrile by underpressure distillation;
Catalyzer C in described steps A compressive reaction
1～C
3alcohol is selected from a kind of in methyl alcohol, ethanol or propyl alcohol;
The non-polar solvent adopting in described steps A and step C is C
6-C
9aromatics, be selected from a kind of in toluene, dimethylbenzene or trimethylbenzene;
Acetonitrile and C in described steps A compressive reaction
1～C
4the weight ratio of alcohols an alkali metal salt is 1:1.2～2.5, acetonitrile and C
1～C
3the weight ratio of alcohol catalyst is 1:2～5;
C in described steps A compressive reaction
1～C
4alcohols basic metal sodium salt is selected from a kind of in sodium methylate, sodium ethylate, sodium propylate, sodium isopropylate, sodium butylate or sodium tert-butoxide;
C in described steps A compressive reaction
1～C
4alcohols basic metal sylvite is selected from a kind of in potassium methylate, potassium ethylate, potassium propylate, potassium isopropoxide, butanols potassium or potassium tert.-butoxide.
2. according to claim 1 a kind of 3, the synthetic method of 3-diethoxy propionitrile, it is characterized in that: in described step B aldolization, acidic alcohol consumption is 5～10 times of amounts of steps A initial feed acetonitrile weight, and catalyzer vitriol oil add-on is 5% of acidic alcohol weight.
3. according to claim 1 and 2 a kind of 3, the synthetic method of 3-diethoxy propionitrile, is characterized in that: in described step C aftertreatment sepn process, underpressure distillation 3, during 3-diethoxy propionitrile, require vacuum tightness lower than 0.07MPa, to collect the cut of 110 ~ 125 ℃.
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| CN105399646B (en) * | 2015-06-04 | 2018-08-24 | 新乡学院 | A kind of cytosine intermediate 3, the preparation method of 3- diethoxy propionitrile |
| CN109912454B (en) * | 2019-03-26 | 2022-01-21 | 南京欧信医药技术有限公司 | Synthesis method of mixture of 3-ethoxyacrylonitrile and 3, 3-diethoxypropionitrile |
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| US4228097A (en) * | 1977-11-30 | 1980-10-14 | Dynamit Nobel Aktiengesellschaft | Method of preparing α-hydroxymethylene nitriles |
| DE3641604A1 (en) * | 1986-12-05 | 1988-06-16 | Huels Troisdorf | Process for the synthesis of cyanoacetaldehyde acetals |
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|---|---|---|---|---|
| US4228097A (en) * | 1977-11-30 | 1980-10-14 | Dynamit Nobel Aktiengesellschaft | Method of preparing α-hydroxymethylene nitriles |
| DE3641604A1 (en) * | 1986-12-05 | 1988-06-16 | Huels Troisdorf | Process for the synthesis of cyanoacetaldehyde acetals |
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