CN104130091A - Method for reducing diyne compounds - Google Patents
Method for reducing diyne compounds Download PDFInfo
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- CN104130091A CN104130091A CN201410336803.4A CN201410336803A CN104130091A CN 104130091 A CN104130091 A CN 104130091A CN 201410336803 A CN201410336803 A CN 201410336803A CN 104130091 A CN104130091 A CN 104130091A
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Abstract
The invention provides a method for reducing diyne compounds. The method for reducing the compounds represented by a formula I comprises the following steps: (1) a system of a borane reagent and tetrahydrofuran is provided, wherein the borane reagent is a borane dimethylsulfide solvent; (2) cyclohexene is dropped into the system of borane reagent and tetrahydrofuran, such that a borane system comprising active hydrogen is obtained; (3) the compound represented by the formula I is added into the borane system comprising active hydrogen, and a reduction reaction is carried out, such that a compound represented by a formula II can be obtained. With the method, diyne compounds can be effectively reduced into diene compounds. In the entire process of the method, reaction materials are easy to obtain; reaction post-treatment is simple; industrial three-waste treatment is easy; and target product yield is high. The method is suitable for industrialized productions.
Description
Technical field
The present invention relates to the field of chemical synthesis, particularly, the present invention relates to reduce the method for two acetylene compounds.
Background technology
Dienes compound has a wide range of applications in chemical, if some pheromone are exactly dienes compound.The synthetic method of pertinent literature report dienes compound has multiple, for example, can be reduced and be prepared dienes compound by two acetylene compounds.At present, by reducing two acetylene compounds, prepare the method for dienes compound, most of borine tetrahydrofuran solution or borine nitrogen nitrogen dimethyl benzene amine compound of adopting reduces two acetylene compounds, but, borine nitrogen nitrogen Diethyl Aniline borane complexes is expensive, and borine consumption is bigger than normal, be not easy to suitability for industrialized production, in addition, the concentration of borine tetrahydrofuran solution is lower, the borine tetrahydrofuran solution that only has in the market 1M, cause tetrahydrofuran (THF) borine solution usage larger, price is also more expensive, and reaction volume is bigger than normal, cause the volume utilization of reactor lower.
Therefore, reduce at present the method for two acetylene compounds, still have much room for improvement.
Summary of the invention
The present invention is intended to solve at least to a certain extent one of technical problem in correlation technique.For this reason, one object of the present invention is to propose that a kind of cost is low, and productive rate is high, and three industrial wastes are easily processed, simple operation, and be easy to realize the method for reduction two acetylene compounds of suitability for industrialized production.
The invention provides the method for compound shown in a kind of reduction-type I.According to embodiments of the invention, the method comprises: (1) provides the system of borane reagent and tetrahydrofuran (THF), and wherein, described borane reagent is borine dimethyl sulphide solution; (2) tetrahydrobenzene is added drop-wise in the system of described borane reagent and tetrahydrofuran (THF), to obtain the borine system that contains active hydrogen; (3) in the borine system that contains active hydrogen described in compound shown in formula I is joined, carry out reduction reaction, so that compound shown in the formula of acquisition II.
Wherein, R, R ' are respectively independently for being selected from any one in following each group: C
1-C
5alkyl, phenyl, naphthyl, xenyl, alkyl phenyl, alkoxyl phenyl.Contriver finds, utilize the method effectively two acetylene compounds to be reduced to dienes compound, the method is added drop-wise to the mode in the system of borane reagent and tetrahydrofuran (THF) by adopting by tetrahydrobenzene, more easily obtain the borine system that contains an active hydrogen, can reduce to greatest extent borine usage quantity, and this step reaction is without monitoring, compound shown in formula I to be restored directly can be added in the borine system that contains an active hydrogen obtained above, carry out next step reaction, simple operation.On the other hand, the method adopts borine dimethyl sulphide, can greatly reduce production costs.In addition, in the whole technique of the method, reaction mass is easy to get, and post-reaction treatment is simple, and three industrial wastes are more easily processed, and target product productive rate is higher, is applicable to very much suitability for industrialized production.
Method according to compound shown in the reduction-type I of the embodiment of the present invention, can also have following additional technical feature:
According to embodiments of the invention, the system of described borane reagent and tetrahydrofuran (THF) is prepared by following steps: tetrahydrofuran (THF) is carried out to nitrogen replacement processing, to obtain the tetrahydrofuran (THF) of processing through nitrogen replacement; Under nitrogen protection, described borine dimethyl sulphide solution and the described tetrahydrofuran (THF) of processing through nitrogen replacement are mixed, to obtain the system of described borane reagent and tetrahydrofuran (THF).Thus, can fast and effeciently obtain the system of borane reagent and tetrahydrofuran (THF), be conducive to raise the efficiency.
According to embodiments of the invention, in described borine dimethyl sulphide solution, the volumetric molar concentration of borine dimethyl sulphide is 10mol/L.
According to embodiments of the invention, in step (2), under 0～10 degree Celsius, preferably under 0～5 degree Celsius, described tetrahydrobenzene is added drop-wise in the system of described borane reagent and tetrahydrofuran (THF).Thus, tetrahydrobenzene and borane reagent are reacted under optimal temperature condition, be conducive to two tetrahydrobenzene in conjunction with two hydrogen above borane reagent, effectively obtain the borine system containing active hydrogen, reduce side reaction and occur, in addition, tetrahydrobenzene is added drop-wise in the system of described borane reagent and tetrahydrofuran (THF), is conducive to the generation containing the borine system of active hydrogen, not only can effectively reduce the consumption of borane reagent, and can effectively reduce production costs, improve reaction efficiency.
According to embodiments of the invention, in step (2), according to the mol ratio of described tetrahydrobenzene and borine dimethyl sulphide, be 7.5～10.5:3.5～5.5, preferably the ratio of 8.0～9.0:4.0, is added drop-wise to described tetrahydrobenzene in the system of described borane reagent and tetrahydrofuran (THF).Thus, the generation of the borine system that is conducive to contain active hydrogen, and then be conducive to raise the efficiency.
According to embodiments of the invention, in step (2), further comprise: after described tetrahydrobenzene being added drop-wise in the system of described borane reagent and tetrahydrofuran (THF), by resulting mixing solutions under 0～10 degree Celsius, preferably be incubated 3～5 hours under 0～5 degree Celsius, so that the borine system that contains active hydrogen described in obtaining.Thus, tetrahydrobenzene is reacted under optimal condition with borane reagent, be conducive to improve the efficiency that obtains the borine system that contains active hydrogen.
According to embodiments of the invention, in step (3), under subzero 15 degrees Celsius～subzero 5 degrees Celsius, preferably under subzero 10 degrees Celsius～subzero 5 degrees Celsius, in the borine system that contains active hydrogen described in compound shown in described formula I is joined.Thus, be conducive to the carrying out of reduction reaction, reduce by product and generate, improve reaction efficiency and productive rate.
According to embodiments of the invention, in step (3), by the mol ratio of compound shown in described formula I and described tetrahydrobenzene, be 1:7.5～10.5, the ratio of preferred 1:8.0～9.0, in the borine system that contains active hydrogen described in compound shown in described formula I is joined.Thus, be conducive to the carrying out of reduction reaction, reduce by product and generate, improve reaction efficiency and target product productive rate.
According to embodiments of the invention, in step (3), carry out described reduction reaction and further comprise: under subzero 5 degrees Celsius～0 degree Celsius, carry out the first reduction reaction 3～7 hours, preferably 4～6 hours, to obtain the first reduction reaction product; Under 5～10 degrees Celsius, described the first reduzate is carried out to the second reduction reaction 2～5 hours, preferably 4 hours, to obtain compound shown in described formula II.Thus, can under optimal condition, compound shown in formula I be reduced to compound shown in formula II, reduce by product and generate, be conducive to improve the productive rate of reaction efficiency and target product.
According to embodiments of the invention, further comprise: compound shown in formula II is carried out to purification process.Thus, can effectively obtain compound shown in the formula II that purity is higher.
Accompanying drawing explanation
Fig. 1 has shown according to the schematic flow sheet of the method for compound shown in the reduction-type I of the embodiment of the present invention;
Fig. 2 has shown according to embodiments of the invention 1, the high-efficient liquid phase chromatogram of products obtained therefrom;
Fig. 3 has shown according to embodiments of the invention 2, the high-efficient liquid phase chromatogram of products obtained therefrom; And
Fig. 4 has shown according to embodiments of the invention 3, the high-efficient liquid phase chromatogram of products obtained therefrom.
Embodiment
Describe embodiments of the invention below in detail.The embodiment the following describes is exemplary, only for explaining the present invention, and can not be interpreted as limitation of the present invention.Unreceipted concrete technology or condition in embodiment, according to the described technology of the document in this area or condition or carry out according to product description.The unreceipted person of production firm of agents useful for same or instrument, being can be by the conventional products of commercial acquisition.
The invention provides the method for compound shown in a kind of reduction-type I.According to embodiments of the invention, the method comprises the following steps:
(1) provide the system of borane reagent and tetrahydrofuran (THF), wherein, described borane reagent is borine dimethyl sulphide solution.
According to embodiments of the invention, the system of borane reagent and tetrahydrofuran (THF) can prepare by following steps: tetrahydrofuran (THF) is carried out to nitrogen replacement processing, to obtain the tetrahydrofuran (THF) of processing through nitrogen replacement; Under nitrogen protection, described borine dimethyl sulphide solution and the described tetrahydrofuran (THF) of processing through nitrogen replacement are mixed, to obtain the system of described borane reagent and tetrahydrofuran (THF).Thus, can fast and effeciently obtain the system of borane reagent and tetrahydrofuran (THF), be conducive to raise the efficiency.
According to embodiments of the invention, in borine dimethyl sulphide solution, the concentration of borine dimethyl sulphide is not particularly limited, and those skilled in the art can select flexibly according to practical situation.According to one embodiment of present invention, in borine dimethyl sulphide solution, the volumetric molar concentration of borine dimethyl sulphide is 10mol/L.Thus, can effectively control reaction volume, improve the volume utilization of reactor.
(2) tetrahydrobenzene is added drop-wise in the system of described borane reagent and tetrahydrofuran (THF), to obtain the borine system that contains active hydrogen.
According to embodiments of the invention, in step (2), under 0～10 degree Celsius, preferably under 0～5 degree Celsius, described tetrahydrobenzene is added drop-wise in the system of described borane reagent and tetrahydrofuran (THF).Thus, tetrahydrobenzene and borane reagent are reacted under optimal temperature condition, be conducive to two tetrahydrobenzene in conjunction with two hydrogen above borane reagent, effectively obtain the borine system containing active hydrogen, reduce side reaction and occur, in addition, tetrahydrobenzene is added drop-wise in the system of described borane reagent and tetrahydrofuran (THF), is conducive to the generation containing the borine system of active hydrogen, not only can effectively reduce the consumption of borane reagent, and can effectively reduce production costs, improve reaction efficiency.
According to embodiments of the invention, in step (2), according to the mol ratio of described tetrahydrobenzene and borine dimethyl sulphide, be 7.5～10.5:3.5～5.5, preferably the ratio of 8.0～9.0:4.0, is added drop-wise to described tetrahydrobenzene in the system of described borane reagent and tetrahydrofuran (THF).Thus, the generation of the borine system that is conducive to contain active hydrogen, and then be conducive to improve reaction efficiency.
According to embodiments of the invention, in step (2), further comprise: after described tetrahydrobenzene being added drop-wise in the system of described borane reagent and tetrahydrofuran (THF), by resulting mixing solutions under 0～10 degree Celsius, preferably be incubated 3～5 hours under 0～5 degree Celsius, so that the borine system that contains active hydrogen described in obtaining.Thus, tetrahydrobenzene is reacted under optimal condition with borane reagent, be conducive to improve the efficiency that obtains the borine system that contains active hydrogen.
(3) in the borine system that contains active hydrogen described in compound shown in formula I is joined, carry out reduction reaction, so that compound shown in the formula of acquisition II.
Wherein, R, R ' are respectively independently for being selected from any one in following each group: C
1-C
5alkyl, phenyl, naphthyl, xenyl, alkyl phenyl, alkoxyl phenyl.
According to embodiments of the invention, in step (3), under subzero 15 degrees Celsius～subzero 5 degrees Celsius, preferably under subzero 10 degrees Celsius～subzero 5 degrees Celsius, in the borine system that contains active hydrogen described in compound shown in described formula I is joined.Thus, be conducive to the carrying out of reduction reaction, reduce by product and generate, improve reaction efficiency and productive rate.
According to embodiments of the invention, in step (3), by the mol ratio of compound shown in described formula I and described tetrahydrobenzene, be 1:7.5～10.5, the ratio of preferred 1:8.0～9.0, in the borine system that contains active hydrogen described in compound shown in described formula I is joined.Thus, be conducive to the carrying out of reduction reaction, reduce by product and generate, improve reaction efficiency and target product productive rate.
According to embodiments of the invention, in step (3), carry out described reduction reaction and further comprise: under subzero 5 degrees Celsius～0 degree Celsius, carry out the first reduction reaction 3～7 hours, preferably 4～6 hours, to obtain the first reduction reaction product; Under 5～10 degrees Celsius, shown in inciting somebody to action, the first reduzate carries out the second reduction reaction 2～5 hours, and preferably 4 hours, to obtain compound shown in described formula II.Thus, can under optimal condition, compound shown in formula I be reduced to compound shown in formula II, reduce by product and generate, be conducive to improve the productive rate of reaction efficiency and target product.
According to embodiments of the invention, further comprise: compound shown in formula II is carried out to purification process.Thus, can effectively obtain compound shown in the formula II that purity is higher.
According to embodiments of the invention, can to compound shown in formula II, carry out purification process by following steps: utilize diethanolamine to wash compound shown in formula II, then add diatomite, and filter, organic phase is washed through weak acid, so that the compound shown in purifying formula II.
According to a concrete example of the present invention, with compound shown in diethanolamine washing type II 1 hour, then add diatomite to stir 30min, and filter, obtain organic layer, organic layer after washing, sodium bisulfate washing, sodium bicarbonate washing, concentrates compound shown in the formula II that obtains purifying successively.
Contriver finds, utilize the method effectively two acetylene compounds to be reduced to dienes compound, the method is added drop-wise to the mode in the system of borane reagent and tetrahydrofuran (THF) by adopting by tetrahydrobenzene, more easily obtain the borine system that contains an active hydrogen, can reduce to greatest extent borine usage quantity, and this step reaction is without monitoring, compound shown in formula I to be restored directly can be added in the borine system that contains an active hydrogen obtained above, carry out next step reaction, simple operation.On the other hand, the method adopts borine dimethyl sulphide, can greatly reduce production costs.In addition, in the whole technique of the method, reaction mass is easy to get, and post-reaction treatment is simple, and three industrial wastes are more easily processed, and target product productive rate is higher, is applicable to very much suitability for industrialized production.
General method
(1) preparation of the system of borane reagent and tetrahydrofuran (THF)
In reaction flask, add tetrahydrofuran (THF), then, tetrahydrofuran (THF) is carried out to nitrogen replacement, then, under nitrogen protection, the tetrahydrofuran (THF) of borine dimethyl sulphide solution and process nitrogen replacement is mixed, obtain the system of borane reagent and tetrahydrofuran (THF).
(2) synthesizing of the borine system that contains active hydrogen
The system of borane reagent obtained above and tetrahydrofuran (THF) is cooled to 0～10 ℃, then tetrahydrobenzene is slowly added drop-wise in the system of borane reagent and tetrahydrofuran (THF), dropping process has white solid and separates out, and controls that temperature is the highest is no more than 12 ℃ in dropping process.After dropwising, resulting mixture, in 0～10 ℃ of insulation 3～5 hours, is obtained to the borine system that contains active hydrogen, this step does not need monitoring.
(3) dienes compound is synthetic
The borine system that contains active hydrogen obtained above is cooled to-15～-5 ℃, then, add wherein compound shown in formula I (being reduced substrate), in adition process, control temperature and be no more than-5 ℃, then, by resulting mixture stirring reaction 3～7 hours at-5～0 ℃, preferably 4～6 hours, then be warming up to 5～10 ℃ of stirring reactions 2～5 hours, preferably 4 hours, GC follows the tracks of reaction process, after completion of the reaction, add acetic acid cancellation, then through heptane extraction, pickling, alkali cleaning, the concentrated crude product that obtains, after crude product is washed with diethanolamine, add diatomite, filter, filtrate is through S-WAT washing, after sodium bicarbonate washing, concentrate and obtain compound shown in formula II.
Embodiment 1
A, the borine system that contains active hydrogen are synthesized
In 500mL reaction flask, add tetrahydrofuran (THF) 150g (2.08mol); nitrogen replacement three times; under nitrogen protection, add borine dimethyl sulphide solution 35mL (0.35mol); be cooled to 0 ℃; slowly drip tetrahydrobenzene 63.3g (0.77mol), control temperature and be no more than 12 ℃, dropwise rear insulation reaction 5 hours; stopped reaction, obtains the borine system that contains active hydrogen.
B, 15,15-diethoxy hexadecyl-3, the reduction of 5-diine
The borine system that contains active hydrogen obtained above is cooled to-10 ℃, slowly drip 15, 15-diethoxy hexadecyl-3, 5-diine 29.2g (0.1mol), after being added dropwise to complete, at-5～0 ℃, stirring reaction is 5 hours, then be warming up to 5～10 ℃, stirring reaction 4 hours, GC follows the tracks of reaction process, control raw material and be less than 1.5% (full integration), react qualified after, add acetic acid 122.4g cancellation 1 hour, then add water 306.0g, heptane 198.3g, organic layer adds aqueous acetic acid washed twice, sodium bicarbonate aqueous solution washing, the concentrated crude product that obtains, crude product rejoins after heptane, with diethanolamine washing 1 hour, add diatomite to stir 30min, filter, obtain organic layer, successively through washing, sodium bisulfate washing, sodium bicarbonate washing, organic layer is concentrated obtains product (15, 15-diethoxy hexadecyl-3, 5-diene) 41.5g, purity: 80.9%, content: 59.6%, yield: 83.6%, the high performance liquid chromatography of products obtained therefrom (HPLC) figure is shown in Fig. 2.
Embodiment 2
The borine system of a, active hydrogen is synthetic
In 500mL reaction flask, add tetrahydrofuran (THF) 150g (2.08mol), nitrogen replacement three times; under nitrogen protection, add borine dimethyl sulphide solution 40mL (0.4mol); be cooled to 10 ℃; slowly drip tetrahydrobenzene 69.8g (0.85mol); control temperature and be no more than 12 ℃; dropwise rear reaction 4 hours, stopped reaction, obtains the borine system that contains active hydrogen.
B, 15,15-diethoxy hexadecyl-3, the reduction of 5-diine
The borine system that contains active hydrogen obtained above is cooled to-10 ℃, slowly drip 15, 15-diethoxy hexadecyl-3, 5-diine 29.2g (0.1mol), after being added dropwise to complete, at-5～0 ℃, stirring reaction is 5 hours, then be warming up to 5～10 ℃, stirring reaction 4 hours, GC follows the tracks of reaction process, control raw material and be less than 1.5% (full integration), react qualified after, add acetic acid 120.4g cancellation 1 hour, add water 310.0g, heptane 200.3g, organic layer adds aqueous acetic acid washed twice, sodium bicarbonate aqueous solution washing, the concentrated crude product that obtains, crude product rejoins after heptane, with diethanolamine washing 1 hour, add diatomite to stir 30min, filter, obtain organic layer, successively through washing, sodium bisulfate washing, sodium hydrogen carbonate solution washing, organic layer is concentrated obtains product (15, 15-diethoxy hexadecyl-3, 5-diene) 39.5g, purity: 75.9%, content: 55.6%, yield: 74.2%, the high performance liquid chromatography of products obtained therefrom (HPLC) figure is shown in Fig. 3.
Embodiment 3
The borine system of a, active hydrogen is synthetic
In 500L reactor, add tetrahydrofuran (THF) 54.0kg (0.75kmol), nitrogen replacement three times; under nitrogen protection, add borine dimethyl sulphide solution 14.0L (0.14kmol); be cooled to 0 ℃; slowly drip tetrahydrobenzene 24.4kg (0.30kmol); control temperature and be no more than 12 ℃; dropwise rear reaction 4 hours, stopped reaction, obtains the borine system that contains active hydrogen.
B, 15,15-diethoxy hexadecyl-3, the reduction of 5-diine
The borine system that contains active hydrogen obtained above is cooled to-5 ℃, slowly drip 15 wherein, 15-diethoxy hexadecyl-3, 5-diine 11.7kg (0.04kmol), after being added dropwise to complete, at-5～0 ℃, stirring reaction is 4 hours, then be warming up to 5～10 ℃, stirring reaction 4 hours, GC follows the tracks of reaction process, control raw material and be less than 1.5% (full integration), react qualified after, add acetic acid 35.4kg cancellation 1 hour, add water 110.0kg, heptane 85.7kg, organic layer adds aqueous acetic acid washed twice, sodium bicarbonate aqueous solution washing, the concentrated crude product that obtains, crude product rejoins after heptane, with diethanolamine washing 1 hour, add diatomite to stir 30min, filter, obtain organic layer, successively through washing, sodium bisulfate washing, sodium hydrogen carbonate solution washing, organic layer is concentrated obtains product (15, 15-diethoxy hexadecyl-3, 5-diene) 17.5kg, purity: 75.5%, content: 49.2%, yield: 72.5%, the high performance liquid chromatography of products obtained therefrom (HPLC) figure is shown in Fig. 4.
Embodiment 4
The borine system of a, active hydrogen is synthetic
In 500L reactor, add tetrahydrofuran (THF) 54.0kg (0.75kmol), nitrogen replacement three times; under nitrogen protection, add borine dimethyl sulphide solution 14.0L (0.14kmol); be cooled to 0 ℃; slowly drip tetrahydrobenzene 22.8kg (0.28kmol); control temperature and be no more than 12 ℃; dropwise rear reaction 5 hours, stopped reaction, obtains the borine system that contains active hydrogen.
B, 15,15-diethoxy hexadecyl-3, the reduction of 5-diine
The borine system that contains active hydrogen obtained above is cooled to-5 ℃, slowly drip 15 wherein, 15-diethoxy hexadecyl-3, 5-diine 8.8kg (0.03kmol), after being added dropwise to complete, at-5～0 ℃, stirring reaction is 4 hours, then be warming up to 5～10 ℃, stir 4 hours, GC follows the tracks of reaction process, control raw material and be less than 1.5% (full integration), react qualified after, add acetic acid 35.4kg cancellation 1 hour, add water 110.0kg, heptane 85.7kg, organic layer adds aqueous acetic acid washed twice, sodium bicarbonate aqueous solution washing, the concentrated crude product that obtains, crude product rejoins after heptane, with diethanolamine washing 1 hour, add diatomite to stir 30min, filter, obtain organic layer, successively through washing, sodium bisulfate washing, sodium hydrogen carbonate solution washing, organic layer is concentrated obtains product (15, 15-diethoxy hexadecyl-3, 5-diene) 13.7kg, purity: 80.9%, content: 51.4%, yield: 79.1%.
Embodiment 5
The borine system of a, active hydrogen is synthetic
In 500mL reaction flask, add tetrahydrofuran (THF) 150g (2.08mol), nitrogen replacement three times; under nitrogen protection, add borine dimethyl sulphide solution 35mL (0.35mol); be cooled to 0 ℃; slowly drip tetrahydrobenzene 63.3g (0.77mol); control temperature and be no more than 12 ℃; dropwise rear reaction 4～5 hours, stopped reaction, obtains the borine system that contains active hydrogen.
B, 15,15-diethoxy hexadecyl-3, the reduction of 5-diine
The borine system that contains active hydrogen obtained above is cooled to-15 ℃, slowly drip 15, 15-diethoxy hexadecyl-3, 5-diine 29.2g (0.1mol), after being added dropwise to complete, at-5～0 ℃, stirring reaction is 6 hours, then be warming up to 5～10 ℃, stir 4 hours, GC follows the tracks of reaction process, control raw material and be less than 1.5% (full integration), react qualified after, add acetic acid 122.4g cancellation 1 hour, add water 306.0g, heptane 198.3g, organic layer adds aqueous acetic acid washed twice, sodium bicarbonate aqueous solution washing, the concentrated crude product that obtains, crude product rejoins after heptane, with diethanolamine washing 1 hour, add diatomite to stir 30min, filter, obtain organic layer, successively through washing, sodium bisulfate washing, sodium hydrogen carbonate solution washing, organic layer is concentrated obtains product (15, 15-diethoxy hexadecyl-3, 5-diene) 41.0g, purity: 82.0%, content: 58.6%, yield: 81.2%.
Embodiment 6
The borine system of a, active hydrogen is synthetic
In 500mL reaction flask, add tetrahydrofuran (THF) 150g (2.08mol), nitrogen replacement three times; under nitrogen protection, add borine dimethyl sulphide solution 35mL (0.35mol); be cooled to 0 ℃; slowly drip tetrahydrobenzene 63.3g (0.77mol); control temperature and be no more than 12 ℃; dropwise rear reaction 4～5 hours, stopped reaction, obtains the borine system that contains active hydrogen.
B, 3, the reduction of the pungent diine of 5-
The borine system that contains active hydrogen obtained above is cooled to-15 ℃, slowly drip 3, the pungent diine 10.6g of 5-(0.1mol), after being added dropwise to complete, at-5～0 ℃, stirring reaction is 6 hours, then be warming up to 5～10 ℃, stir 4 hours, GC follows the tracks of reaction process, control raw material and be less than 1.5% (full integration), react qualified after, add acetic acid 122.4g cancellation 1 hour, add water 306.0g, heptane 198.3g, organic layer adds aqueous acetic acid washed twice, sodium bicarbonate aqueous solution washing, the concentrated crude product that obtains, crude product rejoins after heptane, with diethanolamine washing 1 hour, add diatomite to stir 30min, filter, obtain organic layer, successively through washing, sodium bisulfate washing, sodium hydrogen carbonate solution washing, organic layer is concentrated obtains product (3, 5-octadiene) 9.6g, purity: 91.0%, content: 83.0%, yield: 78.1%.
Embodiment 7
The borine system of a, active hydrogen is synthetic
In 500mL reaction flask, add tetrahydrofuran (THF) 150g (2.08mol), nitrogen replacement three times; under nitrogen protection, add borine dimethyl sulphide solution 45mL (0.45mol); be cooled to 0 ℃; slowly drip tetrahydrobenzene 81.3g (0.99mol); control temperature and be no more than 12 ℃; dropwise rear reaction 4～5 hours, stopped reaction, obtains the borine system that contains active hydrogen.
B, 3, the reduction of the pungent diine of 5-
The borine system that contains active hydrogen obtained above is cooled to-5 ℃, slowly drip 3, the pungent diine 10.6g of 5-(0.1mol), after being added dropwise to complete, at-5～0 ℃, stirring reaction is 6 hours, then be warming up to 5～10 ℃, stir 4 hours, GC follows the tracks of reaction process, control raw material and be less than 1.5% (full integration), react qualified after, add acetic acid 122.4g cancellation 1 hour, add water 306.0g, heptane 198.3g, organic layer adds aqueous acetic acid washed twice, sodium bicarbonate aqueous solution washing, the concentrated crude product that obtains, crude product rejoins after heptane, with diethanolamine washing 1 hour, add diatomite to stir 30min, filter, obtain organic layer, successively through washing, sodium bisulfate washing, sodium hydrogen carbonate solution washing, the concentrated product (3 that obtains of organic layer, 5-octadiene) 10.2g, purity: 95.0%, content: 90.0%, yield: 90.0%.
In description of the invention, it will be appreciated that, term " first ", " second " be only for describing object, and can not be interpreted as indication or hint relative importance or the implicit quantity that indicates indicated technical characterictic.Thus, one or more these features can be expressed or impliedly be comprised to the feature that is limited with " first ", " second ".In description of the invention, the implication of " a plurality of " is two or more, unless otherwise expressly limited specifically.
In the description of this specification sheets, the description of reference term " embodiment ", " some embodiment ", " example ", " concrete example " or " some examples " etc. means to be contained at least one embodiment of the present invention or example in conjunction with specific features, structure, material or the feature of this embodiment or example description.In this manual, to the schematic statement of above-mentioned term not must for be identical embodiment or example.And, the specific features of description, structure, material or feature can one or more embodiment in office or example in suitable mode combination.In addition,, not conflicting in the situation that, those skilled in the art can carry out combination and combination by the feature of the different embodiment that describe in this specification sheets or example and different embodiment or example.
Although illustrated and described embodiments of the invention above, be understandable that, above-described embodiment is exemplary, can not be interpreted as limitation of the present invention, and those of ordinary skill in the art can change above-described embodiment within the scope of the invention, modification, replacement and modification.
Claims (10)
1. a method for compound shown in reduction-type I, is characterized in that, comprising:
(1) provide the system of borane reagent and tetrahydrofuran (THF), wherein, described borane reagent is borine dimethyl sulphide solution;
(2) tetrahydrobenzene is added drop-wise in the system of described borane reagent and tetrahydrofuran (THF), to obtain the borine system that contains active hydrogen;
(3), in the borine system that contains active hydrogen described in compound shown in formula I is joined, carry out reduction reaction, so that compound shown in the formula of acquisition II,
Wherein, R, R ' are respectively independently for being selected from any one in following each group: C
1-C
5alkyl, phenyl, naphthyl, xenyl, alkyl phenyl, alkoxyl phenyl.
2. method according to claim 1, is characterized in that, the system of described borane reagent and tetrahydrofuran (THF) is prepared by following steps:
Tetrahydrofuran (THF) is carried out to nitrogen replacement processing, to obtain the tetrahydrofuran (THF) of processing through nitrogen replacement;
Under nitrogen protection, described borine dimethyl sulphide solution and the described tetrahydrofuran (THF) of processing through nitrogen replacement are mixed, to obtain the system of described borane reagent and tetrahydrofuran (THF).
3. method according to claim 2, is characterized in that, in described borine dimethyl sulphide solution, the volumetric molar concentration of borine dimethyl sulphide is 10mol/L.
4. method according to claim 1, is characterized in that, in step (2), under 0～10 degree Celsius, preferably under 0～5 degree Celsius, described tetrahydrobenzene is added drop-wise in the system of described borane reagent and tetrahydrofuran (THF).
5. method according to claim 4, it is characterized in that, in step (2), according to the mol ratio of described tetrahydrobenzene and borine dimethyl sulphide, be 7.5～10.5:3.5～5.5, preferably the ratio of 8.0～9.0:4.0, is added drop-wise to described tetrahydrobenzene in the system of described borane reagent and tetrahydrofuran (THF).
6. method according to claim 5, is characterized in that, in step (2), further comprises:
After described tetrahydrobenzene being added drop-wise in the system of described borane reagent and tetrahydrofuran (THF), resulting mixing solutions, under 0～10 degree Celsius, is preferably incubated to 3～5 hours under 0～5 degree Celsius, so that the borine system that contains active hydrogen described in obtaining.
7. method according to claim 1, it is characterized in that, in step (3), under subzero 15 degrees Celsius～subzero 5 degrees Celsius, under preferred subzero 10 degrees Celsius～subzero 5 degrees Celsius, in the borine system that contains active hydrogen described in compound shown in described formula I is joined.
8. method according to claim 7, it is characterized in that, in step (3), by the mol ratio of compound shown in described formula I and described tetrahydrobenzene, be 1:7.5～10.5, the ratio of preferred 1:8.0～9.0, in the borine system that contains active hydrogen described in compound shown in described formula I is joined.
9. method according to claim 8, is characterized in that, in step (3), carries out described reduction reaction and further comprises:
(a) under subzero 5 degrees Celsius～0 degree Celsius, carry out the first reduction reaction 3～7 hours, preferably 4～6 hours, to obtain the first reduction reaction product;
(b), under 5～10 degrees Celsius, shown in inciting somebody to action, the first reduzate carries out the second reduction reaction 2～5 hours, and preferably 4 hours, to obtain compound shown in described formula II.
10. method according to claim 1, is characterized in that, further comprises:
Compound shown in formula II is carried out to purification process.
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| WO2012175398A1 (en) * | 2011-06-22 | 2012-12-27 | Dsm Ip Assets B.V. | NEW INTERMEDIATES FOR THE VITAMIN A AND β-CAROTENE SYNTHESIS |
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