CN1809550A - Polycyclic lactones, (meth)acrylates having polycyclic lactone structures, and process for production thereof - Google Patents
Polycyclic lactones, (meth)acrylates having polycyclic lactone structures, and process for production thereof Download PDFInfo
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Abstract
The invention aims at providing polycyclic lactones and (meth)acrylates having polycyclic lactone structures which are free from impurities originating from reducing agents used in the production and therefore permit stable industrial production. The invention relates to polycyclic lactones represented by the general formula (1) and having contents of a group 13 or 14 element of the periodic table of 500ppm or below: (1) wherein R<1> and R<2> are each independently hydrogen or alkyl of 1 to 12 carbon atoms; and n is 0 or 1.
Description
Technical field
The present invention relates to have the lactone compound of polynuclear plane and pass through (methyl) acrylate that obtains to the acid of lactone compound addition acrylic or methacrylic and preparation method thereof.
These compounds are not only as the sense chemical intermediate of medicine and sterilant for example, and their (particularly (methyl) acrylate) be suitable as electronic material or with the acrylic resin initial monomers of the material of optical correlation.
Background technology
By reducing the cyclic acid anhydride that has carbon-to-carbon double bond in a part, known have several different methods as only optionally reducing acid anhydrides and keeping the two methods (referring to non-patent literature 1-3) of key to be translated into many macrolide compounds.In these methods, sodium borohydride/dimethyl formamide system, lithium aluminum hydride etc. are used acidic aqueous solution processing reaction solution according to conventional methods as reductive agent with after metal with similar semiconductor property or nonmetallic hydride reaction, with the hydrolysis complex compound, obtain product thus.
In addition, known in the presence of acid catalyst, the addition reaction acquisition between many cyclic lactones and the carboxylic acid have many cyclic lactones structure (methyl) acrylic compound (referring to patent documentation 1 and 2 and non-patent literature 4 and 5).
[patent documentation 1]
JP-A-3-148239
[patent documentation 2]
JP-A-63-8355
[non-patent literature 1]
People's such as M.M.Kayser Canadian Journal of Chemistry, 1978, vol.56, p.1524-1532
[non-patent literature 2]
People's such as E.M.Mangnus Synthetic Communications, 1992, vol.22, p.783-786
[non-patent literature 3]
People's such as J.Haslouin Tetrahedron Letters, 1976, p.4651-4654
[non-patent literature 4]
People's such as A.Heidekum Journal of Catalysis, 1999, vol.181, p.217-222
[non-patent literature 5]
People's such as J-M.N.Mebah New Joumal of Chemistry, 1993, vol.17, p.835-841
Summary of the invention
Yet the compound for the raw material that is used as electronic material or optical correlation material need reduce impurity as far as possible, for example has the metal or the nonmetallic content of semiconductor property.But, using reductive agent to reduce in the method for above-mentioned polycyclic acid acid anhydride, find that the many macrolide compounds of gained contain in a large number the impurity from reductive agent, and these impurity can not be removed by simple operations.
In addition, owing to contain a large amount of impurity from reductive agent, when in the presence of acid catalyst, making gained annular lactone compound and (methyl) vinylformic acid carry out addition reaction, because (methyl) acrylic compound of many macrolide compounds has formed very unsettled system as target compound and (methyl) vinylformic acid as raw material, and polyreaction is easy to carry out in reaction process and in the reacted lock out operation technology, finds to be difficult to stably carry out suitability for industrialized production.
(methyl) acrylic compound that the purpose of this invention is to provide many macrolide compounds and have many cyclic lactones structure, it does not contain the impurity from reductive agent, and the result can stably carry out suitability for industrialized production, and its preparation method also is provided.
The present inventor furthers investigate for addressing the above problem, found that in many macrolide compounds in the presence of acid catalyst and the addition reaction step between (methyl) vinylformic acid and the reduction reaction by comfortable above-mentioned polycyclic acid acid anhydride in the future in the amount of element-specific of the reductive agent that uses be reduced in specified amount or the lower ensuing purification step, might carry out suitability for industrialized production stably.The contriver also finds can be by carrying out an open loop and closed loop once more to the many macrolide compounds that obtain by reduction polycyclic acid acid anhydride, will be at many macrolide compounds and have the amount that contains in (methyl) acrylic compound of many cyclic lactones structure and reduce from the element-specific of reductive agent, described (methyl) acrylic compound with many cyclic lactones structure obtains by the many macrolide compounds of addition and (methyl) vinylformic acid.Thus, finished the present invention.
That is, of the present invention first will be intended to many macrolide compounds of following formula (1) expression, and the content that wherein is selected from the element of periodictable 13-14 family is 500ppm or littler:
R wherein
1And R
2The alkyl and the n that represent hydrogen atom independently of one another or have a 1-12 carbon atom represent 0 or 1.
Of the present invention second will be intended to prepare the method for above-mentioned many macrolide compounds,
Wherein use the unsaturated polycyclic acid acid anhydride of reductive agent reduction following formula (2) expression contain the element that is selected from periodictable 13-14 family, and the concentration that is selected from the element of periodictable 13-14 family is 500ppm or littler:
R wherein
1, R
2Have and the identical implication of formula (1) with n.
The of the present invention the 3rd will be intended to (methyl) acrylic compound with many cyclic lactones structure of following formula (3) and/or (4) expression,
The content that wherein is selected from the element of periodictable 13-14 family is 500ppm or littler:
R wherein
1, R
2Have the implication identical with n and R is hydrogen atom, methyl or trifluoromethyl with general formula (1).
The of the present invention the 4th will be intended to prepare the method for (methyl) acrylic compound with many cyclic lactones structure, wherein prepares the compound of following formula (3) and/or (4) expression by the addition reaction between above-mentioned many macrolide compounds and (methyl) vinylformic acid.
The of the present invention the 5th will be intended to prepare the method for external form acid anhydrides (exo-acid anhydride), wherein uses solvent from R wherein
1And R
2Configuration all be the unsaturated polycyclic acid acid anhydride (hereinafter being called the external form acid anhydrides) of interior type and R wherein
1And R
2Configuration all be the main crystal of precipitation (predominantly precipitated) external form acid anhydrides in the mixture of unsaturated polycyclic acid acid anhydride (hereinafter be called in type acid anhydrides) of external form.
Many macrolide compounds of the present invention and (methyl) acrylic compound with many cyclic lactones structure do not contain the impurity from reductive agent, and the result can stably carry out suitability for industrialized production.
In addition, many macrolide compounds of preparation according to the present invention and have a method of (methyl) acrylic compound of many cyclic lactones structure can reduce the impurity from reductive agent in the compound by simple operations.
Embodiment
To describe the present invention in detail below.
(many macrolide compounds)
Many macrolide compounds of the present invention are the compounds of following general formula (1) expression.
In general formula (1), R
1And R
2Represent hydrogen atom independently of one another; Or has an alkyl of 1-12 carbon atom.
As alkyl, can mention straight chain, side chain or cyclic alkyl, for example methyl, ethyl, n-propyl, sec.-propyl or normal-butyl.Wherein, preferred hydrogen atom or have the straight chained alkyl of 1-4 carbon atom, and especially preferred hydrogen atom.
In addition, many macrolide compounds of the present invention contain the element that is selected from periodictable 13-14 family from the reductive agent of the reduction reaction that is used for carbonyl, for example boron atom or aluminium atom, boron atom particularly, the content of described element is 500ppm or littler, is preferably 200ppm or littler, 100ppm or littler more preferably, be preferably 50ppm or littler especially, be preferably 20ppm or littler especially, be preferably 5ppm or littler especially.
Simultaneously, in many macrolide compounds of following formula (1) expression, (hereinafter be called the external form lactone compound: the compound of type formula (5)) and in wherein being configured as (hereinafter is called interior type lactone compound: general formula (6)) the compound that is configured as external form of lactone part wherein.In the present invention, in the total amount of above-mentioned two kinds of compounds, the amount of external form lactone compound is preferably 70 moles of % or bigger of two kinds of total amount of compound.The amount of external form lactone is preferably 90 moles of % or bigger, and 95 moles of % more preferably most preferably are 99 moles of % or bigger:
R wherein
1, R
2Have and the identical implication of general formula (1) with n.
According to contriver's research, find n wherein be 0 interior type lactone compound about 35 ℃ for solid and wherein n be that 0 external form lactone compound is the solution form at about 35 ℃.Therefore,,, by many macrolide compounds of distillation purifying the time, when the cooling condensation, can not solidify, thereby handle easily, therefore have industrial value by increasing the amount of external form compound because the external form lactone compound is liquid at ambient temperature.
In addition, by increasing the amount of external form compound, can when carrying out esterification with (methyl) acrylate and have (methyl) acrylic compound of crosslinked lactone structure, suppress the carrying out of side reaction, therefore can improve degree of purity of production and productive rate with preparation.
(method for preparing many macrolide compounds)
(a) reduction reaction of unsaturated polycyclic acid acid anhydride
Can obtain many macrolide compounds according to currently known methods or with the carbonyl of unsaturated polycyclic acid acid anhydride of its similar methods by reduction following formula (2) expression.Can be according to currently known methods, for example Diels-Alder reaction between dienophile compound (for example corresponding maleic anhydride) and the diene (for example cyclopentadiene), the compound of preparation following formula (2) expression:
R wherein
1, R
2Have and the identical implication of general formula (1) with n.
The reductive agent that is used for above-mentioned reduction reaction is not particularly limited, as long as it is used for reducing carbonyl, but its preferred embodiment comprises the hydride of periodictable 13-14 family element, for example sodium borohydride and lithium aluminum hydride or the compound that obtains by the part active hydrogen in the hydride that replaces above-mentioned periodictable 13-14 family element with alkoxide, for example two (2-methoxy ethoxy) sodium aluminum hydrides (Red-Al).At this moment, can prepare the alkoxide group reductive agent by the respective metal hydride and the alcohol of mixed chemical metered amount before reduction reaction.
With respect to regard to the compound of following formula (1) expression, reductive agent is generally 1 or bigger with molar ratio computing, is preferably 1.5 or bigger with regard to hydride, and more preferably 2 or bigger, be preferably more than 2 especially, more preferably 3 or bigger.
On the other hand, when the amount of reductive agent is too big, cause industrial disadvantageous problem, for example aftertreatment problem, therefore its consumption is 40 or littler with molar ratio computing usually, is preferably 30 or littler, more preferably 20 or littler, be preferably 10 or littler especially, in hydride.
General by with in reductive agent and the acid anhydrides any solution or suspension by part adding in alternative solution or the suspension, carry out the reaction between reductive agent and the acid anhydrides.After adding fully, the preset time that stirs the mixture under the temperature condition identical or different with adding fashionable temperature condition is to finish reaction.Add fashionable temperature and ensuing whipping temp and be generally-50 ℃-100 ℃, but when the derivative that uses lithium aluminum hydride or its part alkoxide to replace, be preferably-20-50 ℃, when the derivative that uses sodium borohydride or its part alkoxide to replace, be preferably 0-80 ℃.
Churning time after reaction times and the addition reaction is based on such as conditions such as temperature of reaction and change, but reaction times and churning time lower limit separately is generally 0.1 hour or bigger, be preferably 0.2 hour or bigger, the upper limit separately is generally 100 hours or littler, is preferably 80 hours or littler.At rare gas element, for example react in the atmosphere of the helium of thorough drying, nitrogen or argon gas.
For reaction solvent, Canadian Journal of Chemistry people such as for example M.M.Kayser, vol.56, p.1524 recommend dimethylformaldehyde in the method for descriptions such as (1978), but when considering whole accessibility, for example during the separation of product, reaction is preferably carried out in following solvent: aliphatic straight chain ether, for example diethyl ether, dipropyl ether, dibutyl ether or 1, the 2-glycol dimethyl ether; Or cyclic ether, for example tetrahydrofuran (THF), pyrans, 1,3-dioxolane or 1,4-diox.The absolute qualification of its consumption right and wrong and optional, but as material concentration, lower limit is generally 0.1 weight % or bigger, is preferably 0.5 weight % or bigger, and the upper limit is generally 80 weight % or littler, is preferably 70 weight % or littler.
(b) inactivation of reductive agent is handled
After finishing above-mentioned reduction reaction, preferably carry out following steps: by mixed reaction solution and mineral acid, for example sulfuric acid or hydrochloric acid decompose and the complex compound of the unreacted reductive agent of inactivation and matrix intermediate and reductive agent, then use and the immiscible organic solvent extraction target product of water.
As with the immiscible organic solvent of water, can mention for example aliphatic hydrocrbon, for example hexane, heptane and octane; Aromatic hydrocarbon, for example benzene, toluene and dimethylbenzene; Ester, for example methyl acetate, ethyl acetate and butylacetate; Ether, for example diethyl ether, dipropyl ether and dibutyl ether.And when with water with the miscible solvent of any ratio (for example tetrahydrofuran (THF)) when the reaction solvent, extraction efficiency reduces, therefore if necessary talk about preferably by ordinary method for example underpressure distillation before extraction, remove part or all of reaction solvent.
The concentration of above-mentioned mineral acid is not particularly limited, but uses the 0.1-5N aqueous solution usually.Using the solution that obtains after these aqueous acid hydrolysis to be preferably tart, for example pH is 2 or lower.Temperature of reaction that decomposition reaction is required and the reaction times kind with parent material changes, and with the time effects productive rate of mineral acid treatment be difficult to the amount of isolating by product.Usually, the lower limit of temperature is generally-5 ℃ or higher, be preferably 0 ℃ or higher, the upper limit is generally 80 ℃ or lower, be preferably 50 ℃ or lower, the lower limit of time is generally 0.1 hour or bigger, is preferably 0.2 hour or bigger, the upper limit is generally 100 hours or littler, is preferably 80 hours or littler.
(c) reductive agent is being carried out after inactivation handles, be lower than the carrying out washing treatment of 12 alkaline aqueous solution with pH
In preparation method of the present invention, after making the reductive agent inactivation with mineral acid as mentioned above, by the washing step that is lower than 12 alkaline aqueous solution with pH is provided, can reduce from reductive agent and be attached to general formula (2) and/or many macrolide compounds of (3) expression in, the amount that is selected from the element of periodictable 13-14 family, these many macrolide compounds are as the product of above-mentioned reduction reaction.
The pH of above-mentioned alkaline aqueous solution is greater than 7, be preferably 8 or the bigger upper limit less than 12, be preferably 11.5 or littler.As the alkaline matter that is used for this aqueous solution, preferred as alkali supercarbonate, for example sodium bicarbonate or alkaline carbonate yellow soda ash for example.
Amount as above-mentioned alkaline aqueous solution to be used, its consumption is 2 weight equivalents (weightequivalents) or bigger, is preferably 3 weight equivalents or bigger, more preferably 5 weight equivalents or bigger, be preferably 10 weight equivalents or bigger especially, with respect to lactone compound.On the other hand,, do not obtain and increase the consumption corresponding effects, so the upper limit is generally 200 weight equivalents or littler, be preferably 100 weight equivalents or littler, more preferably 50 weight equivalents or littler because using when too a large amount of.
The concentration of alkaline matter in alkaline aqueous solution is not particularly limited, but because too low concentration will cause the detersive efficiency of difference, so concentration is set in 1% of saturation concentration usually.When concentration approaches saturation concentration, might be under washing operation neutral and alkali species precipitate, so this concentration preferably set saturation concentration 99% or littler, be preferably 95% or littler, more preferably 90% or littler.
In addition, above-mentioned alkaline aqueous solution can once be applied to lactone compound, perhaps is divided into and repeatedly is used for carrying out washing treatment.The number of times of washing this moment depends on the total amount of alkaline aqueous solution to be used, perhaps whether with carrying out washing treatment and the distillation processing of the many macrolide compounds that describe below or the open loop and the reconstruction operation combination of lactonic ring, but preferably carry out repeatedly carrying out washing treatment, this processing is carried out twice or repeatedly usually, be preferably three times or more times, more preferably five times or more times.
Usually at 0 ℃ or higher, be preferably 10 ℃ or the higher washing operation that carries out.On the other hand,,, be preferably 40 ℃ or lower, more preferably 30 ℃ or lowlyer carry out this operation usually at 50 ℃ or lower because too high temperature can cause the decomposition of lactone compound.
Washing time is 5 minutes or longer, is preferably 10 minutes or longer, and more preferably 30 minutes or longer and fully, it was 5 hours or shorter, is preferably about 2 or 3 hours or shorter.
Can be with before the organic solvent extraction, and after above-mentioned acid treatment, use alkaline aqueous solution to carry out carrying out washing treatment, perhaps can carry out carrying out washing treatment after the extraction, but preferably after extraction, carry out with an organic solvent.
In addition, occur in order to prevent remaining alkaline matter, preferably after carrying out carrying out washing treatment with alkaline aqueous solution, water carries out carrying out washing treatment.
(d) distillation lactone compound
For many macrolide compounds of the present invention, also can handle and reduce the element that is selected from periodictable 13-14 family by distillation.Distillating method can be for known distillating method and without limits.The physicals that depends on lactone compound can be distilled by selecting decompression degree and temperature.
Particularly, outer-3-oxo (oxo)-4-oxatricyclo [5.2.1.0
2,6] last of the ten Heavenly stems-8-alkene is compared the fusing point that has near room temperature with endo isomer, and because therefore it can be preferred easily by the above-mentioned element of industrial easy distillation processing minimizing.
(e) open loop of lactonic ring
For many macrolide compounds of the present invention, can reduce from amount reductive agent, that be selected from the element of periodictable 13-14 family in the many macrolide compounds that are attached to formula (2) and/or (3) expression by following steps are provided: the step of an open loop of many macrolide compounds lactonic ring; The compound of open loop is extracted into the step of water layer; Separate water layer and organic layer organic layer is discharged to the step of system outside; With the compound of open loop once more closed loop become the step of lactonic ring; And the closed loop compound that adds organic solvent and will form lactonic ring is extracted into the step in the organic solvent, the step of a described open loop be by water and with the immiscible organic solvent of water in, make the solution that contains many macrolide compounds that obtains by aforesaid method and pH be 12 or higher alkaline aqueous solution contact and carry out.In many macrolide compounds of the present invention, because have many have high boiling point and dystectic compounds, so there is the situation that can not easily carry out being undertaken by distillation industrial purification, therefore process of the present invention is effective especially.
Kind as the basic cpd that in alkaline aqueous solution, uses, can mention for example oxyhydroxide, carbonate and the supercarbonate of basic metal (for example lithium, sodium and potassium), perhaps oxyhydroxide, carbonate and the supercarbonate of alkaline-earth metal (for example calcium and magnesium).Wherein, preferred especially sodium hydroxide or potassium hydroxide.
The pH of the alkaline aqueous solution of Shi Yonging is preferably 12 or higher herein, and more preferably 13 or higher.
The amount of basic cpd to be used is 0.1 equivalent or bigger, is preferably 0.5 equivalent or bigger, and more preferably 1 equivalent or bigger is preferably 1.05 moles or bigger, especially with respect to the mole number of pending lactonic ring.On the other hand, when basic cpd is too many, aspects such as cost and aftertreatment work existing problems, so the consumption of this compound is 100 equivalents or littler, is preferably 20 equivalents or littler, more preferably 10 equivalents or littler.
The lower limit of treatment temp is generally-5 ℃ or higher, is preferably 0 ℃ or higher, more preferably 10 ℃ or higher, the upper limit is generally 200 ℃ or lower, be preferably 150 ℃ or lower, more preferably 100 ℃ or lower, but exist preferred process temperature along with the number of n increases and trend of rising.Treatment time is not particularly limited, but the optimum handling time is depended on the amount and the treatment temp of alkali, but lower limit is generally 0.01 hour or bigger, be preferably 0.02 hour or bigger, more preferably 0.1 hour or bigger, that the upper limit is generally is 50 little, the time or littler, be preferably 20 hours or littler, more preferably 10 hours or littler.
After above-mentioned processing, preferred water layer separated from one another and organic layer, and dilute with water gained water layer if necessary, be used in then describe in above-mentioned (b) with the immiscible organic solvent washing of water, thus above-mentioned opened loop compound is extracted in the water layer and with impurity and is extracted in the organic layer, from system, remove organic layer.
(f) form lactonic ring again
By the aqueous solution that acidifying obtains after the ring-opening reaction of lactonic ring, the open ring lactone environment-development is given birth to closed loop and is formed lactonic ring once more.Acid to be used is not particularly limited, as long as it is a protonic acid, but is generally mineral acid, for example hydrochloric acid or sulfuric acid.Select concentration arbitrarily, still produce strong heat for fear of neutralization, the common operation of this step preferably maybe joins this aqueous acid in the another kind of aqueous solution by part by add any alkaline aqueous solution after ring-opening reaction.
The amount of the acid that decision is used according to the pH of reaction system, and the pH that adds the reactive system after finishing is preferably less than 7, more preferably less than 2.
In order to finish neutralization reaction and cyclization, if necessary, can be after interpolation continuously stirring 0.1-50 hour again.Churning time after adding temperature and adding needn't be carried out under extra high temperature, and they can be any temperature and time.
After reaction is finished, separating organic substances.Thus, separate each layer, and, then merge, separate from water layer then with the organic substance that reclaims previously with the remaining water layer of suitable organic solvent extraction.
After the separation, preferably wash with pure water.Usually uses and the volume ratio of oil reservoir is preferably twice or more times as pure water and the washing times of 0.1-10.
Can carry out inactivation to reductive agent by combination (c) suitably and handle the back and use the carrying out washing treatment of alkaline aqueous solution and (d) distillation lactone compound and (e) and (f) open loop and form lactonic ring again, reduction is selected from the amount of the element of periodictable 13-14 family.
Many macrolide compounds by aforesaid operations preparation have can be in statu quo as the purity of product, perhaps this compound has the purity as the parent material of (methyl) acrylic acid addition reaction, but if necessary, can be by using usual method, for example crystallization or chromatographic separation are further purified.
(g) preparation method of many macrolide compounds, wherein external form is 70 moles of whole % or bigger
(g-1) parent material of many macrolide compounds
In order to prepare many macrolide compounds, wherein the amount of external form is 70 moles of % or bigger of external form and interior type total amount, is necessary to control the configuration as the unsaturated polycyclic acid acid anhydride of parent material.For unsaturated polycyclic acid acid anhydride, there is wherein R
1And R
2Configuration all be that the unsaturated polycyclic acid acid anhydride of interior type (hereinafter is called the external form acid anhydrides: R following formula (7)) and wherein
1And R
2Configuration all be external form unsaturated polycyclic acid acid anhydride (type acid anhydrides in hereinafter being called: following formula (8)), but usually commercially available be interior type.Therefore, when by aforesaid method it being reduced, when preparing many macrolide compounds, type is as main ingredient in forming.In order to obtain the external form lactone compound, be necessary to increase the external form for the treatment of as the unsaturated polycyclic acid acid anhydride of parent material
Amount:
R wherein
1, R
2Have and the identical implication of formula (1) with n.
In order to obtain the mixture of external form acid anhydrides and interior type acid anhydrides, enumerate the following method of explanation.
(g-1-1) isomerization reaction of interior type acid anhydrides
By type acid anhydrides in the thermal treatment, form the external form acid anhydrides, the mixture of type acid anhydrides and external form acid anhydrides in forming thus.The lower limit of heated perimeter is generally 140 ℃ or higher, is preferably 160 ℃ or higher, is preferably 170 ℃ or higher especially, and the upper limit is generally 300 ℃ or lower, is preferably 270 ℃ or lower, is preferably 250 ℃ or lower especially.
The isomerization reaction time is preferably 1 minute or bigger, is preferably 5 minutes-10 hours.Preferably in appropriate solvent, carry out this reaction.
The kind of useable solvents is not particularly limited, as long as it is inactive to parent material, intermediate and product, but the example comprises aliphatic hydrocrbon, for example hexane, heptane and octane; Aromatic hydrocarbon, for example benzene, toluene and dimethylbenzene; Ester, for example ethyl acetate and butylacetate; Lactone, for example butyrolactone and valerolactone; Straight chain or cyclic ether, for example dibutyl ether, diethylene glycol dimethyl ether and tetrahydrofuran (THF); Deng.
(g-1-2) reaction of the Diels-Alder between acid anhydrides and the diene
By in the presence of acid anhydrides and diene common, heating, form the mixture of external form acid anhydrides and interior type acid anhydrides.
As acid anhydrides, can mention maleic anhydride and interior-3,5-dioxo-4-oxatricyclo [5.2.1.0
2,6] last of the ten Heavenly stems-8-alkene.As diene, can mention Dicyclopentadiene (DCPD), cyclopentadiene or the like.
By use maleic anhydride as acid anhydrides and Dicyclopentadiene (DCPD) as diene, when obtaining the mixture of external form acid anhydrides and interior type acid anhydrides (wherein n is 0), form outer-3,5-dioxo-4-oxatricyclo [5.2.1.0
2,6] last of the ten Heavenly stems-8-alkene and interior-3,5-dioxo-4-oxatricyclo [5.2.1.0
2,6] last of the ten Heavenly stems-8-alkene.
At this moment, the amount of acid anhydrides to be added is selected from 0.1 molar equivalent-10 molar equivalent usually, with respect to cyclopentadienyl skeleton, but is preferably 0.5 molar equivalent-5 molar equivalent, more preferably 0.7 molar equivalent-2 molar equivalent is preferably 0.8 molar equivalent-1.5 molar equivalent especially.
When obtaining the mixture of external form acid anhydrides and interior type acid anhydrides (wherein n is 1), using maleic anhydride as acid anhydrides and Dicyclopentadiene (DCPD) during as diene, the consumption of acid anhydrides can be selected from 0.05 molar equivalent-1 molar equivalent usually, with respect to cyclopentadienyl skeleton, but be preferably 0.1 molar equivalent-0.8 molar equivalent, more preferably 0.2 molar equivalent-0.75 molar equivalent is preferably 0.3 molar equivalent-0.7 molar equivalent especially.
When obtaining the mixture of external form acid anhydrides and interior type acid anhydrides (wherein n is 1), in using-3,5-dioxo-4-oxatricyclo [5.2.1.0
2,6] last of the ten Heavenly stems-8-alkene is as acid anhydrides and Dicyclopentadiene (DCPD) during as diene, it is 0.1 molar equivalent-10 molar equivalent that the consumption of acid anhydrides can be selected from usually, with respect to cyclopentadienyl skeleton, but be preferably 0.5 molar equivalent-5 molar equivalent, more preferably 0.7 molar equivalent-2 molar equivalent is preferably 0.8 molar equivalent-1.5 molar equivalent especially.
When obtaining the mixture of external form acid anhydrides and interior type acid anhydrides (wherein n is 1), can use obtain in the present invention outer-3,5-dioxo-4-oxatricyclo [5.2.1.0
2,6] last of the ten Heavenly stems-8-alkene, but preferred use commercially available interior-3,5-dioxo-4-oxatricyclo [5.2.1.0
2,6] last of the ten Heavenly stems-8-alkene.
The lower limit of temperature of reaction is generally 140 ℃ or higher, is preferably 160 ℃ or higher, is preferably 170 ℃ or higher especially, and the upper limit is generally 300 ℃ or lower, is preferably 270 ℃ or lower, is preferably 250 ℃ or lower especially.
Reaction times is preferably 1 minute or longer, is preferably 5 minutes-10 hours.In the reaction, the solvent that (f-1-1) enumerates above can existing simultaneously.
In addition, when acid anhydrides and cyclopentadiene reaction, also might be by using another equipment, Dicyclopentadiene (DCPD) generation cracking reaction (oppositely Diels-Alder reaction) forms cyclopentadiene, and it is contacted under these conditions with acid anhydrides.
The lower limit of temperature of reaction is generally 140 ℃ or higher, and the upper limit is generally 300 ℃ or lower, is preferably 160 ℃ or higher and be preferably 270 ℃ or lower, is preferably 170 ℃ or higher and further preferred 250 ℃ or lower especially.Reaction times is preferably 1 minute or longer, preferred 5 minutes-10 hours.During reaction, the solvent that (f-1-1) enumerates above can existing simultaneously.
(f-2) mainly precipitate external form acid anhydrides crystalline method
Can mainly make the crystallization of external form acid anhydrides by using the mixture of solvent treatment external form acid anhydrides and interior type acid anhydrides.
Under-20 ℃-100 ℃ arbitrary temp, the external form acid anhydrides solubleness of the solvent that use this moment is less than the solubleness of interior type acid anhydrides.
In addition, can preferably use following solvent, wherein the external form acid anhydrides amount that is dissolved in 100 parts by weight solvent 25 ℃ the time is 30 weight parts or littler.More preferably, this solvent is following solvent, and wherein this amount is that 20 weight parts or littler and preferred especially this amount are that 10 weight parts or littler solvent are as solvent.
As the example of the solvent that satisfies this requirement, can enumerate aromatic hydrocarbon, for example benzene, toluene and dimethylbenzene; Aliphatic hydrocrbon, for example hexane, heptane and octane; Straight chain or cyclic ether, for example dibutyl ether, diethylene glycol dimethyl ether and tetrahydrofuran (THF); Ester, for example ethyl acetate and butylacetate; Lactone, for example butyrolactone and valerolactone.Particularly, aromatic hydrocarbons and aliphatic hydrocrbon, more preferably monocyclic aromatic hydrocarbon, for example benzene, toluene and dimethylbenzene.
Exist under the situation of solvent when preparation feedback solution, when the solvent that uses had utmost point lower boiling, vapour pressure uprised, and therefore needed high voltage bearing equipment, so preferably consider the boiling point selective solvent of solvent.
Obtain high-purity external form acid anhydrides in order to handle, importantly according to the solvent design temperature by this.When the temperature when passing through the filtering separation crystal from mother liquor was too high, purity was high but output reduces.On the contrary, when liquid is cooled too lowly, the high still purity drop of productive rate.For Tc, select top condition based on solvent types and quantity.The lower limit of temperature is generally-20 ℃ or higher, is preferably 0 ℃ or higher, is preferably 10 ℃ or higher especially, and the upper limit is generally 100 ℃ or lower, is preferably 50 ℃ or lower, is preferably 40 ℃ or lower especially.
In addition, under the situation of using solvent, when the amount of solvent was excessive, productive rate reduced.The lower limit of preferable range is generally 0.1 weight equivalent or bigger, is preferably 0.5 weight equivalent or bigger, and with respect to the gross weight of interior type acid anhydrides and external form acid anhydrides, the upper limit is generally 20 weight equivalents or littler, is preferably 10 weight equivalents or littler.When carrying out recrystallization, if necessary, can further improve purity.When crystallization or recrystallization, it also is suitable adding kind of a crystalline substance.
(f-3) after crystallization, reuse mother liquor
In by the solution behind the crystal of filtering separation acid anhydrides, there are the interior type acid anhydrides and the dissolved external form acid anhydrides that are removed.By this solution is handled once more, for example isomerization reaction etc. if desired, can increase the amount of the external form acid anhydrides of existence.In addition, by carrying out crystallization treatment and optional recrystallization processing as required once more, can obtain the external form acid anhydrides.
Can obtain corresponding external form lactone compound by reduction by the external form acid anhydrides that aforesaid method obtains as parent material.
(preparation has the method for many cyclic lactones structure (methyl) acrylic compound)
Can will be converted into the compound of following formula (3) and/or (4) expression by many macrolide compounds that aforesaid method obtains according to currently known methods (wherein in the presence of acid catalyst, carrying out) or its similar approach with (methyl) acrylic acid addition reaction:
R wherein
1, R
2Have and the identical implication of formula (1) with n.
As R, can mention hydrogen atom, methyl or trifluoromethyl and preferred hydrogen atom or methyl.
The acid catalyst that is suitable for is not particularly limited, and its specific examples comprises 1) mineral acid, for example hydrochloric acid, sulfuric acid and phosphoric acid; Organic sulfonic acid, for example Phenylsulfonic acid, toluenesulphonic acids and cresol sulfonic acid; Br φ nsted acid, sulfonic acid ion exchange resin for example, 2) normally used Lewis acid, for example boron trifluoride and complex compound thereof (hereinafter being abbreviated as boron trifluoride (complex compound) sometimes), anhydrous zinc halide, anhydrous aluminum halide, anhydrous iron halide, tin halides, the metal-salt of trifluoromethanesulfonic acid, for example Ytterbiumtriflate; The anhydrous halide or the alkoxide of family's 4 metals (for example titanium, zirconium and hafnium).Wherein, the pKa of preferred above-mentioned acid or its aqueous solution is 6 or lower those.These acid catalysts can be used singly or in combination.In the mineral acid, preferably sulfuric acid.In the Lewis acid, preferred boron trifluoride.
In addition, the usage quantity of acid catalyst becomes with the kind of catalyzer, but is limited to 0.01 mole of % or bigger usually, is preferably 0.1 mole of % or bigger; The upper limit is generally 100 moles of % or littler, is preferably 50 moles of % or littler, with respect to the many macrolide compounds as parent material.
Temperature of reaction changes with the kind of catalyzer, but its lower limit is generally-50 ℃ or higher, is preferably 0 ℃ or higher; Its upper limit is generally 200 ℃ or lower, is preferably 150 ℃ or lower.
For (methyl) acrylic acid consumption, when considering the process yield of many macrolide compounds, lower limit is generally 0.1 molar equivalent or bigger, be preferably 1 molar equivalent or bigger, be generally 20 molar equivalents or littler with the upper limit, be preferably 10 molar equivalents or littler, with respect to equivalent or bigger.
In addition, if desired, can there be solvent simultaneously during reaction.
After reaction, can separate (methyl) acrylate by ordinary method.For example, can be set forth in behind the neutralizing acid catalyzer to operate and carry out isolating method by for example extraction and distillatory.
((methyl) acrylic compound) with many cyclic lactones structure
In many rings (methyl) acrylate that contains lactonic ring that obtains by above-mentioned preparation method, the amount reductive agent that uses when coming many macrolide compounds of comfortable preparation following formula (2) and/or (3) expression, periodictable family 13 or 14 element is 500ppm or littler, be preferably 200ppm or littler, 100ppm or littler more preferably, be preferably 50ppm or littler especially, be preferably 20ppm or littler especially, be preferably 5ppm or littler especially.This amount is more little, and stability is good more.
In addition, when the compound that obtains by aforesaid method during as many macrolide compounds parent material with high-content external form lactone compound, can prepare (methyl) acrylic compound with many cyclic lactones structure, the compound that is configured as external form of lactone part (hereinafter be called outer-(methyl) acrylic compound) and wherein in the total amount of the compound of type in being configured as of lactone part (in hereinafter being called-(methyl) acrylic compound) wherein, the amount of (methyl) acrylic compound is 70 moles of % or bigger outward.In this application, in the total amount of two kinds of compounds, the amount of outer (methyl) acrylic compound is preferably 70 moles of % or bigger of the total amount of two kinds of compounds.The amount of (methyl) acrylic compound is preferably 90 moles of % or bigger outward, and more preferably 95 moles of % most preferably are 99 moles of %.
Embodiment
To describe the present invention in more detail below, but the present invention is not limited in the following examples, unless exceeded its essence.
Embodiment 1
(preparing many macrolide compounds)
In reactor, add 1083g tetrahydrofuran (THF) (THF) and 84gNaBH
4, begin then to stir.
On the other hand, by mix 328g commercially available in-3,5-dioxo-4-oxatricyclo [5.2.1.0
2,6] last of the ten Heavenly stems-solution that 8-alkene (interior-5-norbornylene-2, the 3-dicarboxylic anhydride) and 64g methyl alcohol and 1313g obtain in advance dropwise added in the above-mentioned reactor in 2 hours.Simultaneously, the interior temperature control of reactor is at 25 ℃.dropwise add finish after, under agitation total material is remained on 25 ℃ 2 hours.
Then, stir down, the 2N aqueous sulfuric acid with 1200g in 2 hours time dropwise adds wherein.The interior temperature control to 25 of reactor ℃.In addition, add 657g water.Then, under agitation total material is remained on 25 ℃ 3 hours.
In reactor, add 164g toluene, after stirring, total material is left standstill.Content in the reactor is divided into two-layer.Remove water layer, and only take out oil reservoir.Interior ester concentration in the oil reservoir is 6.4%.
In the oil reservoir that takes out, wherein 543g is put into flask, remove by distillation on vaporizer and desolvate.Strengthen temperature and decompression degree gradually, and finally remove by distillation under the condition of 50 ℃ and 30torr the component that is removed by distillation.
(using the washing of alkaline aqueous solution)
Enriched material, 151g toluene and 65.7g 5%NaHCO with whole amounts of obtaining above
3Solution is poured in the reactor as alkaline aqueous solution.After the stirring at room, mixture is left standstill, remove water layer then and obtain oil reservoir.Repeat these operations altogether 6 times to obtain to contain in the 21g-3,5-dioxo-4-oxatricyclo [5.2.1.0
2,6] last of the ten Heavenly stems-oil reservoir of 8-alkene.
(open loop of lactonic ring)
This oil reservoir is poured in the reactor, stirred down, the 72.6g10%NaOH aqueous solution was at room temperature dropwise added wherein in 30 minutes, then total material was remained on room temperature 30 minutes.Then, mixture is left standstill, remove oil reservoir, take out water layer.In this water layer of whole amounts, add 65.7g toluene.After stirring total material and leaving standstill, take out water layer and remove oil reservoir.In water layer, have the compound that is following form: lactone compound is open loop.
(forming lactonic ring again)
In reactor, add above-mentioned water layer and 65.7g toluene, then total material under agitation is heated to 50 ℃.In 30 minutes,, then total material was kept 30 minutes to the 2N sulfuric acid that wherein adds 109g.Then, mixture is left standstill, remove water layer and obtain oil reservoir.Then, add 65.7g water.After total material is stirred and leaves standstill, remove water layer and obtain oil reservoir.Repeat similar water treatment three times altogether.Concentrate the oil reservoir that so obtains, desolvate, obtain the lactone (18.9g) of purifying thus to remove.
The concentration of contained boron is 9ppm in the lactone of purifying.
(esterification)
After 95% sulfuric acid with 0.83g dropwise adds in 6.6g toluene and the 6.9g methacrylic acid, under agitation total material is heated to 110 ℃.Type wherein dropwise adds the lactone of the above-mentioned purifying of 3g and the mixing solutions of 4.2g toluene in 30 minutes.Finish dropwise add after, stir down total material is remained on 110 ℃ 6 hours, cooling reactor then.At this moment, in reactor, do not find polymerisate.
Then, in above-mentioned reaction soln impouring 20g water, add 10.8g toluene then.After stirring, mixture is left standstill, remove water layer then, obtain oil reservoir.Repeat following steps three times: with the 5%NaHCO of 18g
3The step that the aqueous solution adds this oil reservoir and remove water layer after total material is stirred and leaves standstill.Then, repeat following steps 3 times: the water with 18g adds in the gained oil reservoir and the step of removing water layer after stirring total material and leaving standstill again.Afterwards, desolvate by distilling to remove.At this moment, strengthen temperature and decompression degree gradually, remove under the condition of 50 ℃ and 30torr the component that is removed by distillation.Simultaneously, polymerization in enriched material, do not occur, and acquisition 3.5g contains the enriched material of methacrylic ester as main ingredient.The concentration of boron is 0.14ppm in esterification products.
Comparative Examples 1
After preparing the annular lactone compound according to the mode identical, only carry out the primary alkali solution washing with embodiment 1.The oil reservoir that obtain this moment is called thick interior ester solution-1.Boron concentration is 1370ppm in this thick lactone-1.
When using it to carry out esterification in the mode identical with embodiment 1, the content of reactor forms agglomerate rather than solution, and polymerization has taken place in this expression.
Embodiment 2
After preparing the annular lactone compound according to the mode identical, only carry out three alkaline aqueous solutions washings with embodiment 1.The oil reservoir that obtain this moment is called thick interior ester solution-2.The concentration of boron is 170ppm in this thick lactone-2.
When using it to carry out esterification, obtained to contain the target enriched material of methacrylic ester as main ingredient in the mode identical with embodiment 1.
Embodiment 3
Obtain in the mode identical with embodiment 2 thick in behind the ester solution-2, in the mode identical lactone structure is carried out that open loop is handled and reconstruction with embodiment 1.At this moment, the concentration of boron is 15ppm.Use it to carry out esterification according to embodiment 1 identical mode.Behind cooling reactor, in reactor, do not find polymerisate.
Reference example 1
Use purifying lactone of the foregoing description 1 and the thick interior ester solution-2 of embodiment 2, similarly carry out esterification, obtain methacrylic ester.At this moment, reactor is remained on 110 ℃ 6 hours and the cooling after, its continuation was at room temperature kept 14 hours.When stating the purifying lactone of embodiment 1 in the use, the content of not observing reactor changes, but in using embodiment 2 thick ester solution-2 o'clock, the viscosity of the content of reactor increases slightly, and thinks and partly carried out polymerization.Therefore, find to compare with other situation, when stating the purifying lactone (boron concentration is reduced to 9ppm) of embodiment 1 in the use, the stability in storage of reaction soln is higher.
Embodiment 4
(isomerization of acid anhydrides)
In reactor, add in 150g commercially available-3,5-dioxo-4-oxatricyclo [5.2.1.0
2,6] last of the ten Heavenly stems-8-alkene (interior-5-norbornylene-2, the 3-dicarboxylic anhydride) and 150g toluene.When the stirring system is inner, total material is heated to 190 ℃ and kept 2 hours.Afterwards, when reactor cooling to 25 ℃, in reaction soln, precipitate crystal.By after removing by filter crystal, dried crystals finds that its weight is 61g.With this dissolution of crystals in THF and the result by gc analysis be, find outer-3,5-dioxo-4-oxatricyclo [5.2.1.0
2,6] last of the ten Heavenly stems-8-alkene (outer-5-norbornylene-2,3-dicarboxylic anhydride) exists with the purity of 82.3 weight %.
(precipitation external form acid anhydrides)
In Glass Containers, add this crystal of 51g and 51g toluene.Total material is heated to 95 ℃, to dissolve crystal fully.Afterwards, solution is cooled to 25 ℃.In reactor, precipitate crystal, then by removing by filter crystal.Afterwards, when dried crystals, find that its weight is 39g.As the result who this crystal is dissolved in THF and analyzes by gas-chromatography body method, find outer-3,5-dioxo-4-oxatricyclo [5.2.1.0
2,6] last of the ten Heavenly stems-8-alkene exists with the purity of 94.2 weight %.
Embodiment 5
(isomerization reaction)
In reactor, add 100g commercially available in-3,5-dioxo-4-oxatricyclo [5.2.1.0
2,6] last of the ten Heavenly stems-8-alkene and 50g toluene.Under agitation reactor heating is to remove toluene by distillation.Continue reactor heating and remain on 190 ℃ 1 hour.
With after the reactor cooling to 100 ℃, to wherein adding toluene.With the interior temperature of reactor be cooled to 50 ℃ and add a spot of kind brilliant.Afterwards, with reactor cooling to 25 ℃.In reactor, precipitate crystal.By after removing by filter crystal, when dried crystals, find that its weight is 28g.As this crystal being dissolved in THF and the result by gc analysis, find outer-3,5-dioxo-4-oxatricyclo [5.2.1.0
2,6] last of the ten Heavenly stems-8-alkene exists with the purity of 87.9 weight %.
(precipitation external form acid anhydrides)
In Glass Containers, add this crystal of 23g and 34.5g toluene.Total material is heated to 100 ℃, to dissolve crystal fully.Add a small amount of crystalline substance of planting down at 95 ℃.Afterwards, solution is cooled to 25 ℃.In reactor, precipitate crystal, then by removing by filter crystal.Afterwards, when dried crystals, find that its weight is 18.4g.As this crystal being dissolved in THF and the result by gc analysis, find outer-3,5-dioxo-4-oxatricyclo [5.2.1.0
2,6] last of the ten Heavenly stems-8-alkene exists with the purity of 97.5 weight %.
(preparing many macrolide compounds)
In reactor, add the THF of 33g and the NaBH of 2.3g
4, begin then to stir.On the other hand, will in 1 hour, dropwise add in the above-mentioned reactor by mixing the solution that above-mentioned crystal of 10g and 2g methyl alcohol and 60g THF obtain in advance.Simultaneously, with the interior temperature control of reactor at 25 ℃.After dropwise adding finishes, under agitation total material is remained on 25 ℃ and reach 2 hours.
Then, stir down, the 2N aqueous sulfuric acid with 36.5g in 1 hour time dropwise adds wherein.With the interior temperature control to 25 of reactor ℃.In addition, add 20g water.
Then, in reactor, add 5g toluene, total material is left standstill.Content in the reactor is divided into two-layer.Remove water layer, and only take out oil reservoir.Desolvate by on vaporizer, distilling to remove.
Except that after desolvating, with the 5%NaHCO of 45g toluene and 20g
3The aqueous solution adds in the resistates that removes after desolvating, and stirs the mixture then and makes it and leave standstill, and removes water layer.In addition, the 5%NaHCO that adds 20g
3The aqueous solution is removed water layer similarly.Repeat six times this NaHCO
3Solution washing.When the solvent on vaporizer, removed in the gained toluene layer, obtained the 5.6g fluid cpds by distillation.The result of gas chromatographic analysis is, obtained the mixture of lactone compound, and is outer-3,5-dioxo-4-oxatricyclo [5.2.1.0
2,6] last of the ten Heavenly stems-8-alkene/interior-3,5-dioxo-4-oxatricyclo [5.2.1.0
2,6] last of the ten Heavenly stems-ratio=97.9/2.1 of 8-alkene.
Above-mentioned lactone compound is poured in the flask.Under the low pressure of 15mmHg, use simple distillation equipment to distill.Under 148 ℃ of the interior Wen Weiyue of flask, the distillation lactone compound.In being cooled to 25 ℃ still tube, lactone compound flows and does not adhere to, to obtain through the distillatory lactone compound.
Embodiment 6
Obtain identical external form acid anhydrides by the method for describing among the embodiment 5, the step of going forward side by side is carried out identical reduction reaction.With the washing of 5% sodium bicarbonate aqueous solution once, wash with water once.When the solvent on vaporizer, removed in the gained toluene layer by distillation, measure the concentration of removing boron contained in the fluid cpds that the back obtains at solvent, find that boron concentration is 940ppm.This liquid of method purifying by embodiment 5 describes obtains to contain the lactone compound of external form as main ingredient.Find that the boron concentration in the lactone compound is 3.5ppm.Use the lactone compound that so obtains, carry out (the lactone open loop) and (forming lactonic ring again) described among the embodiment 1.The boron concentration of finding the last lactone compound that obtains is less than detection limit (less than 0.1ppm).
Comparative Examples 2 (in using-3,5-dioxo-4-oxatricyclo [5.2.1.0
2,6] last of the ten Heavenly stems-8-alkene prepares the annular lactone compound)
Use commercially available in-3,5-dioxo-4-oxatricyclo [5.2.1.0
2,6] last of the ten Heavenly stems-8-alkene, carry out reduction reaction by the method that embodiment 2 describes.Using NaHCO
3Behind the solution washing, concentrate toluene layer, obtain white crystal.With gas chromatographic analysis gained white crystal, found that crystal be purity be 99.3% interior-3,5-dioxo-4-oxatricyclo [5.2.1.0
2,6] last of the ten Heavenly stems-8-alkene.
Embodiment 7 (methacrylic ester of lactone compound forms reaction)
Will outer-3-oxo-4-oxatricyclo [5.2.1.0
2,6] last of the ten Heavenly stems-8-alkene is dissolved in the 4 normal methacrylic acids, then to wherein adding 95% sulfuric acid, is 0.2 with respect to the mol ratio of lactone, then stirred 1 hour at 85 ℃.When content is carried out gas chromatographic analysis, find that the transformation efficiency of parent material is 50%, and observe and formed outer-3-oxo-4-oxatricyclo [5.2.1.0
2,6] last of the ten Heavenly stems-8-ylmethyl acrylate and outer-3-oxo-4-oxatricyclo [5.2.1.0
2,6] last of the ten Heavenly stems-9-ylmethyl acrylate.
On the other hand, with interior-3-oxo-4-oxatricyclo [5.2.1.0
2,6] last of the ten Heavenly stems-8-alkene is dissolved in the 4 equivalent methacrylic acids, then to wherein adding 95% sulfuric acid, is 0.2 with respect to the mol ratio of lactone, then stirred 1 hour at 85 ℃.When content is carried out gas chromatographic analysis, find that the transformation efficiency of parent material is 5% or littler.
As mentioned above, clearly the methacrylic ester of external form lactone formation reaction is carried out to such an extent that carry out obviously soon than interior type lactone.
Therefore, by using external form lactone that reduction external form acid anhydrides obtains, can effectively prepare the derivative of lactone compound with aliphatic polynuclear plane as parent material.
Though described the present invention, for those skilled in the art clearly, can carry out various improvement and change to it without departing from the spirit and substance in the present invention with reference to specific embodiment.
The application is based on the Japanese patent application 2003-137371 of Japanese patent application 2003-124292 that submitted on April 28th, 2003 and submission on May 15th, 2003, and its content is hereby incorporated by.
Industrial applicibility
Many macrolide compounds of the present invention and (methyl) acrylate chemical combination with many cyclic lactones structure Thing does not contain the impurity from reducing agent, therefore may stably carry out suitability for industrialized production.
In addition, the many macrolide compounds of preparation according to the present invention and (methyl) with many cyclic lactones structure The method of acrylate compounds, can by simple and easily operation reduce in the compound from The impurity of reducing agent.
Claims (26)
1. many macrolide compounds of following formula (1) expression,
The content that wherein is selected from the element of periodictable 13-14 family is 500ppm or littler:
R wherein
1And R
2The alkyl and the n that represent hydrogen atom independently of one another or have a 1-12 carbon atom represent 0 or 1.
2. according to many macrolide compounds of claim 1, the element that wherein is selected from the 13-14 of periodictable family is the boron atom.
3. claim 1 or many macrolide compounds of 2, wherein lactonic ring is configured as external form.
4. the method for preparing each many macrolide compounds among the claim 1-3,
Wherein use the unsaturated polycyclic acid acid anhydride of reductive agent reduction following formula (1) expression contain the element that is selected from periodictable 13-14 family, and the concentration that is selected from the element of periodictable 13-14 family is 500ppm or littler:
R wherein
1, R
2Have and the identical implication of formula (1) with n.
5. the method for the many macrolide compounds of preparation of claim 4, it may further comprise the steps: after the reduction reaction of finishing unsaturated polycyclic acid acid anhydride, add mineral acid make the reductive agent inactivation and then with pH less than 12 alkaline aqueous solution washing gained treatment soln.
6. the method for the many macrolide compounds of preparation of claim 5, wherein mineral acid is sulfuric acid or hydrochloric acid.
7. the method for claim 5 or 6 many macrolide compounds of preparation, wherein pH contains alkali metal hydrocarbonate or alkaline carbonate less than 12 alkaline aqueous solution.
8. the method for each the many macrolide compounds of preparation among the claim 4-7, after it is included in the reduction reaction of finishing unsaturated polycyclic acid acid anhydride, the step of many macrolide compounds of distillation type (1) expression.
9. the method for each the many macrolide compounds of preparation among the claim 4-8, after it is included in the reduction reaction of finishing unsaturated polycyclic acid acid anhydride, water with the immiscible organic solvent of water in open loop type (1) expression many macrolide compounds lactonic ring step, with opened loop compound be extracted into aqueous phase step, separates water layer and organic layer organic layer be discharged to step outside the system, the opened loop compound closed loop become the step of lactonic ring and adding organic solvent are extracted into step in the organic solvent once more with the compound that closed loop is become lactonic ring.
10. many macrolide compounds of preparation method of claim 9, wherein the open loop of lactonic ring by make this compound and pH be 12 or higher alkaline aqueous solution contact and carry out.
11. many macrolide compounds of preparation method of claim 9 or 10, wherein the closed loop of lactonic ring is undertaken by this compound is contacted with mineral acid.
12. the method for each the many macrolide compounds of preparation among the claim 4-11, wherein unsaturated polycyclic acid acid anhydride are by using solvent, from R wherein
1And R
2Configuration all be the unsaturated polycyclic acid acid anhydride (hereinafter being called the external form acid anhydrides) of interior type and R wherein
1And R
2Configuration all be that the crystalline step of main precipitation external form acid anhydrides obtains in the mixture of unsaturated polycyclic acid acid anhydride (hereinafter be called in type acid anhydrides) of external form.
13. many macrolide compounds of preparation method of claim 12, wherein solvent is following solvent: under-20 ℃-100 ℃ arbitrary temp, the solubleness of external form acid anhydrides is less than the solubleness of interior type acid anhydrides.
14. many macrolide compounds of preparation method of claim 12 or 13, wherein solvent is following solvent: wherein under 25 ℃, the amount that is dissolved in the external form acid anhydrides in 100 parts by weight solvent is 30 weight parts or littler.
15. each many macrolide compounds of preparation method among the claim 12-14, wherein solvent is aromatic hydrocarbon or aliphatic hydrocarbon.
16. each many macrolide compounds of preparation method among the claim 12-15, wherein unsaturated polycyclic acid acid anhydride is to obtain by the following steps before precipitation crystalline step: in the heating type acid anhydrides with make type acid anhydrides isomerization to the small part, to be translated into the external form acid anhydrides.
17. many macrolide compounds of preparation method of claim 16, wherein the Heating temperature during isomerization is 140-300 ℃.
18. each many macrolide compounds of preparation method among the claim 4-17, wherein unsaturated polycyclic acid acid anhydride are by to Dicyclopentadiene (DCPD) and/or cyclopentadiene and maleic anhydride and/or interior-3,5-dioxo-4-oxatricyclo [5.2.1.0
2,6] last of the ten Heavenly stems-8-alkene carries out the Diels-Alder reactions steps and obtains.
19. by (methyl) acrylic compound with many cyclic lactones structure of following formula (3) and (4) expression, the content that wherein is selected from the element of periodictable 13-14 family is 500ppm or littler:
R wherein
1, R
2Have the implication identical with n and R is hydrogen atom, methyl or trifluoromethyl with formula (1).
20. a method for preparing (methyl) acrylic compound with many cyclic lactones structure, wherein the compound by following formula (4) and/or (5) expression is to obtain by each many macrolide compounds and (methyl) acrylic acid addition reaction among the claim 1-3.
21. a method for preparing the external form acid anhydrides wherein uses solvent from R wherein
1And R
2Configuration all be the unsaturated polycyclic acid acid anhydride (hereinafter being called the external form acid anhydrides) of interior type and R wherein
1And R
2Configuration all be the crystal of main precipitation external form acid anhydrides in the mixture of unsaturated polycyclic acid acid anhydride (hereinafter be called in type acid anhydrides) of external form.
22. according to the method for preparing the external form acid anhydrides of claim 21, wherein solvent is following solvent: under-20 ℃-100 ℃ arbitrary temp, the solubleness of external form acid anhydrides is less than the solubleness of interior type acid anhydrides.
23. according to the method for preparing the external form acid anhydrides of claim 21 or 22, wherein solvent is following solvent: the amount that is dissolved in the external form acid anhydrides in 100 parts by weight solvent under 25 ℃ is 30 weight parts or littler.
24. according to each the method for preparing the external form acid anhydrides among the claim 21-23, wherein solvent is aromatic hydrocarbon or aliphatic hydrocrbon.
25. according to each the method for preparing the external form acid anhydrides among the claim 21-24, wherein unsaturated polycyclic acid acid anhydride obtains by following steps: before precipitation crystal step, type acid anhydrides and make type acid anhydrides isomerization to the small part in the heating is to be translated into the external form acid anhydrides.
26. according to the method for preparing the external form acid anhydrides of claim 25, wherein the Heating temperature during isomerization is 140-300 ℃.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP124292/2003 | 2003-04-28 | ||
| JP2003124292 | 2003-04-28 | ||
| JP137371/2003 | 2003-05-15 |
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| Publication Number | Publication Date |
|---|---|
| CN1809550A true CN1809550A (en) | 2006-07-26 |
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ID=36840922
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200480017476 Pending CN1809550A (en) | 2003-04-28 | 2004-04-27 | Polycyclic lactones, (meth)acrylates having polycyclic lactone structures, and process for production thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110305306A (en) * | 2019-07-26 | 2019-10-08 | 苏州大学 | Bicyclic lactone polymer and its preparation and application |
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2004
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|---|---|---|---|---|
| CN110305306A (en) * | 2019-07-26 | 2019-10-08 | 苏州大学 | Bicyclic lactone polymer and its preparation and application |
| CN110305306B (en) * | 2019-07-26 | 2021-04-13 | 苏州大学 | Bicyclic lactone polymers, their preparation and use |
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