CN1615291A - Preparation of 3,5,5-trimethyl-cyclohex-2-ene-1,4-dione - Google Patents
Preparation of 3,5,5-trimethyl-cyclohex-2-ene-1,4-dione Download PDFInfo
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- CN1615291A CN1615291A CNA028274202A CN02827420A CN1615291A CN 1615291 A CN1615291 A CN 1615291A CN A028274202 A CNA028274202 A CN A028274202A CN 02827420 A CN02827420 A CN 02827420A CN 1615291 A CN1615291 A CN 1615291A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
- C07C45/32—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen
- C07C45/33—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen of CHx-moieties
- C07C45/34—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen of CHx-moieties in unsaturated compounds
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
- C07C49/603—Unsaturated compounds containing a keto groups being part of a ring of a six-membered ring
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
Abstract
The present invention relates to an improved process for the preparation of 3,5,5-trimethylcyclohex-2-ene-1,4-dione by oxidation of 3,5,5-trimethylcyclohex-3-en-1-one in the presence of an oxidizing agent and a catalyst system comprising a transition metal complex, catalyst, an auxiliary base, possibly water, and a catalytically active co-additive, characterized in that carboxylic acid amides are employed as the solvent.
Description
Technical field
The present invention relates to by oxidation 3,5,5-trimethylammonium-hexamethylene-3-alkene-1-ketone (β-isophorone) prepares 3,5,5-trimethyl-cyclohex-2-en-1, the improving one's methods of 4-diketone (Oxophorone).
Background technology
Oxophorone (KIP) is the important intermediate in synthetic Trimethylhydroquinone or the Trimethylhydroquinone ester, and Trimethylhydroquinone or the Trimethylhydroquinone ester intermediate product during to be vitamin-E synthetic.In addition, KIP is the many carotenoid of preparation, for instance as the intermediate product of astaxanthin, zeaxanthin and canthaxanthin.
It is known that (β-IP) produces KIP by oxidation α-isophorone or β-isophorone.
According to Hosokawa etc. (Chem.Lett., 1983,1081-1082), in the presence of 10 moles of % acid chlorides and auxiliary alkali, realize α-isophorone is oxidized to KIP by t-butyl hydroperoxide, maximum yield is 55%.Except high catalytic amount and the low yield that can realize, particularly use the expensive oxidants hydrogen peroxide tertiary butyl to make this method not attractive for industrial reaction.
There is same problem in the reaction of WO 96/154094, wherein uses Ib, Vb, VIb or VIII subgroup metal, particularly vanadium oxide (V) and iron(ic) chloride (III) as the catalyzer with the t-butyl hydroperoxide oxidation.
Herein, the oxidation economy by oxygen or oxygen-containing gas mixture many.DE 25 26 851 discloses may be under the situation of adding copper (II) salt or molybdic oxide, the correlation method of oxidation α-isophorone under the catalysis of for example phospho-molybdic acid or silicomolybdic acid.But,, need 96 hours very long reaction times and 100 ℃ high temperature in order to realize transforming fully.The yield that can realize only is 45% under these conditions.
Freer etc. (Chem.Lett., 1984,2031-2032) and in EP 0 425 976 yield is described.
Also described and in acetone, added triethylamine (DE 26 57 386) or heterocyclic nitrogenous bases as solvent, as under the situation of pyridine (JP Hei 11-49717/1999) by the oxidation of the catalytic β-IP of activated carbon to KIP.But the flash-point of solvent acetone is-17 ℃, and 100 ℃ temperature of reaction far surpasses this temperature, and for security reasons this is unacceptable for industrial realization.
The amount of the catalyzer that is just adopted and reaction conditions (low temperature, short reaction times), and the yield that under height conversion (highly selective), can realize, β-IP is produced as catalyst for reaction by the complex compound that uses transition metal and polydentate ligand to the improvement of the oxidation of KIP.
Except with triethylamine as alkali and water as the additive, EP-B 0 311 408 adopts the tetraphenylporphyrin manganese as catalyzer.Use the solvent mixture of glycol dimethyl ether and methylene dichloride to obtain 98% optimum thick yield herein.From economy and secure context, using solvent mixture is unsuitable for industrial realization.
The article of delivering afterwards in same authors (Ito etc., Synthesis 1997,2,153-155) in, reported that maximum selectivity only is 93% when adopting glycol dimethyl ether under optimal conditions.Because-6 ℃ low-flash and relevant explosion hazard use glycol dimethyl ether not expect for industrial realization as solvent.In addition, use is synthesized very expensive and must the porphyrin catalyst with low yield preparation is a shortcoming in independent dual stage process.If use salung (salen) manganese (III) muriate as catalyzer, under described condition, can only obtain 81% yield.
According to JP Sho 64-90150/1989 and JP Hei 01-175955/1989, under the selection condition of optimum, use salung manganese (III) compound and derivative can realize just surpassing 90% KIP yield.Also use glycol dimethyl ether as solvent herein, thereby also relate to the shortcoming of having described.
DE 26 10 254 discloses use salung manganese (II) or cobalt or related compound as the β-IP of the catalyzer oxidation to KIP.Herein, reported in one embodiment 100% by the catalytic reaction preference of salung manganese.Under described condition, this per hour is equivalent to space/time yield of every liter of 0.09 kilogram of KIP.In open back several years of this patent application, identical author use the similar result of phospho-molybdic acid as catalyzer.
According to JP Sho 61-191645/1986, by also adopting organic amine or an alkali metal salt as additive except that the phospho-molybdic acid of catalytic amount or silicomolybdic acid, the selectivity of this method can be increased to 96%.But the maximum conversion that can realize only is 59% by this way, therefore needs to handle (work up) product solution, and this is expensive and not too expectation from economic aspect.
According to JP Hei 10-182543/1998, when employing comprises the catalyst system of platinum salt and heteropolyacid or its salt, also realize similar result.But the high price of platinum salt makes this method not have rentability extraly.
According to DE 24 59 148, can adopt the acetylacetonate of many transition metal, preferably the vanadium acetylacetonate is as the catalyzer by molecular oxygen oxidation α-isophorone.But, need long reaction times more than 40 hours and 100 ℃ to 130 ℃ high temperature equally, and only obtain 20% to 40% not satisfied yield.
Generally speaking, because the reaction yield of described method is low, so also do not know α-isophorone is direct oxidation into the method for the economy of KIP.The oxidation of the β-IP that can obtain by currently known methods can more effectively be carried out.Herein, the most economical variant of this oxidation also is to use oxygen or the oxygen-containing gas program as oxygenant.
Therefore, according to DE 24 57 157, by isomerization formerly by the sodium acetate mediation, can be increased to 56% by the catalytic α-isophorone of transition metal acetylacetonate to the yield of the oxidizing reaction of β-IP, only need 25 ℃-75 ℃ summary low temperature and＞26 hours shorter reaction time simultaneously.Yet these results are still unsatisfactory.
According to DE 25 15 304, by except that the transition metal acetylacetonate, also adding pyridine or pyridine derivate, will realize significant the improvement, the bearing reaction time shortens to 2 hours to 3.5 hours, and obtain KIP with 70% to 80% yield, in one embodiment even reach 91%.Prove that needing a large amount of alkali (based on β-IP, reaching 250 moles of %) and catalyzer (based on β-IP, reaching 10% weight) is a shortcoming herein.
According to DE 38 42 547, if in the presence of pyridine, use specific copper acetylacetonate, can significantly reduce the amount of the above-mentioned alkali that adopted and catalyzer and obtain similar KIP at scientific literature (M.Constantini etc., J.Mol.Catal., 1980,7, but do not mention this result again in 89-97).In the document, reported and under optimal conditions, used salung manganese can realize 85% maximum KIP yield as oxide catalyst.According to the document, under optimal conditions, space/time yield may be increased to 0.16kg KIP/ (h*l), but this is still unsatisfactory.
Solvent has also been proposed to the space/time yield of reaction and optionally influence in the document.Author's conclusion is, if the employing aprotic solvent, along with polarity and alkalescence increase, speed of reaction increases really, but not increase of selectivity.Confirm that many ethers and ketone, particularly glycol dimethyl ether and acetone are the optimum solvent for selectivity.But, because can only be by very expensive safety precaution, it means very big economic cost then, just can avoid the explosion hazard of reaction mixture, so consider secure context not consider to use flash-point be-17 ℃ acetone or flash-point to be-6 ℃ glycol dimethyl ether solvent as the industrial method for oxidation in described temperature range.In addition, use ether to cause forming the danger of high explosive superoxide usually as solvent in the presence of alkali and oxygen, this relates to further danger.
US 5,874,632 describe for the first time educt concentration in the reaction mixture in detail and the selectivity that can realize between relation.Discovery by in the catalytic reaction of salung manganese, only could realize 91% good selectivity under low β-IP concentration of maximum 10 weight % in glycol dimethyl ether (diglyme) in the presence of triethylamine and the water as reaction accelerator as alkali.Under greater concn, selectivity takes place significantly to reduce.Herein, disclose as solving and used ether and ketone, particularly diglyme is as the solution of the problem of solvent, but interpolation is particularly added methyl ethyl diketone from the organic acid of the pKa value with 2-7 or the catalytic active substance of corresponding aldehyde, the compound or the Lithium Sulphate of various enolizations.By this measure, can realize very high educt concentration, and needn't accept optionally significantly to reduce.Can realize reaching space/time yield of 0.34kg KIP/ (h*l) by this way.
For the rentability of catalysis process, particularly use homogeneous catalyst, except space/time yield (every liter of reaction volume is the kilogram number of product per hour) and required catalytic amount, additive and choice of Solvent are most important.When repeating currently known methods, find to form a large amount of by products by using preferred solvent and described additive in response matrix, this has the effect that reduces catalyzer output in cycle period, if therefore this method cyclical operation then reduces the selectivity of expecting product KIP.The mass consumption of solvent and additive is relevant therewith, needs simultaneously to remove formed by product by suitable technology operation, and this needs a large amount of installation costs.
In aforesaid method, the β-IP under salung manganese known in the prior art and metalloporphyrin and phthalocyanine catalyst composition exist and the reaction and display best choice and the space/time yield of oxygen.Based on the high spatial/time yield that can realize, simple relatively catalyzer, described Preparation of Catalyst is cheap and when to add the fashionable conversion fully that has just caused highly selective on a small quantity, and based on the high relatively flash-point of 53 ℃ of preferred solvent diglymes, according to US 5, as if 874,632 method be suitable for industrial realization most.But this method has some shortcomings, and this will explain below.
When this method conduct has the distillation processing and remove the circulation means operation of the diglyme that desolvates from product, find to use diglyme may have the selectivity of extraordinary yield and＞90% really as solvent, but the decomposition of solvent, alkali and additive causes carboxylic acid to form, carboxylic acid is circulated again in the reactor during solvent cycle, perhaps must spend a large amount of expenses to be removed.To mention formic acid and acetate especially herein, and methoxyacetic acid and 2-methoxy ethoxy acetate.These by products are concentrated in circulating solvent and cause oxidizing reaction optionally to continue to reduce.
Another important shortcoming is the unstable that is pre-mixed the catalyst component in solvent for industrial procedure.Directly be metered into catalyzer because will avoid usually with solid, so ideally before reaction at first with catalyzer with catalyzer alkali and catalytic activity altogether additive in solvent, introduce in the reaction vessel, and this solution contact continuously and with β-IP with in its adding reactive moieties.If use glycol ether optimum for selectivity, find that catalyst solution is significantly aging along with the premixture time limit of service increases, reaction preference acutely reduces in continuation method himself showing as for this.
Another also dissatisfied up to now problem that solves is that the by product between oxidation period forms, and particularly hydroxy isophorone depends on response procedures, and hydroxy isophorone amount with 5%-20% in conventional preparation method forms.Under optimal conditions, if at NEt
3Use salung manganese as catalyzer in/water/diglyme system, can obtain 5% minimum hydroxy isophorone and form (based on the β that adopts-IP).By product on this order of magnitude forms not to be expected from economic aspect.
In addition, use ether to relate to the danger of the high explosive superoxide that formation described as the solvent of oxidizing reaction.In addition, diglyme is very expensive solvent, and it has disadvantageous effect for the setting up cost of this method, therefore uses diglyme not too to expect as the solvent of the reaction of being studied from economic aspect.
In a word, also do not find gratifying comprehensive notion for industrial reaction, it need consider following standard simultaneously:
A) use the favourable solvent that obtains easily,
B) use inert solvent stability under reaction conditions,
C) only use a kind of homogeneous solvent, avoiding during handling expensive separating substances,
D) use the solvent that under reaction conditions, is not tending towards forming explosive superoxide,
E) use the appropriate solvent of stopping reaction matrix (solution of any additives and catalyzer), so be formed on the solution of long-time relatively interior shelf-stable.
Summary of the invention
Therefore, the objective of the invention is to find suitable stopping reaction system based on prior art, solvent particularly, it avoids the important in some cases shortcoming at the currently known methods description, keep simultaneously or increase good selectivity and reaction yield, particularly in the catalyst for additives system of the water of salung manganese/auxiliary alkali/optional/altogether.
The invention provides by oxidation 3 in the presence of oxygenant and catalyst system, 5,5-trimethylammonium-hexamethylene-3-alkene-1-ketone (β-isophorone, β-IP) prepare 3,5,5-3-methyl cyclohexanol-2-alkene-1,4-diketone (Oxophorone, improving one's methods KIP), described catalyst system comprise transition metal complex catalyst, auxiliary alkali, possible water, and the catalytic activity that is selected from down group additive altogether:
1.pKa be the organic acid of 2-7, perhaps corresponding aldehyde;
2. the fatty alcohol or the phenol that have 1-4 carbon atom;
3. can form the compound of enol structure; And
4. Lithium Sulphate;
It is characterized in that adopting carboxylic acid amide as solvent.
Description of drawings
Fig. 1 is the figure of demonstration as the KIP yield of the function of β-IP concentration.
Fig. 2 is the figure of demonstration as the KIP yield of the function of the oxygen of being supplied with.
Embodiment
Following equation has clearly been set forth this reaction:
Proved that weak organic acid or bidentate complex compound are particularly advantageous additives altogether aspect reaction kinetics.Particularly preferred additive altogether is acetate, butyric acid, Whitfield's ointment, oxalic acid, toxilic acid, citric acid and other aliphatic series or aromatics one, two or tricarboxylic acid.Amino acid also suits as glycine, leucine, methionine(Met) or aspartic acid.
Also have been found that fatty alcohol, as methyl alcohol, ethanol, butanols, isopropylcarbinol and the trimethyl carbinol, or phenol can be as being total to additive.Can form the common additive of enol structure, for example methyl aceto acetate, phenyl-acetone, particularly methyl ethyl diketone are particularly advantageous.Methyl ethyl diketone is particularly preferably as additive altogether, because its allows to realize than with other suitable higher reaction preference of common additive in addition.
Use methyl ethyl diketone to show the higher β-IP concentration that to use based on amount of the mixture, therefore can realize higher space/time yield, and not take place optionally seriously to reduce.
Based on catalyzer, can adopt preferred 4: 1 to 40: the 1 common additive and the mol ratio of catalyzer 1: 1 to 100: 1.
Carboxylic acid amide also is not familiar with in any publication so far as the outstanding character of the solvent of the oxidizing reaction of being studied and is found.On the contrary, in all open reports related to the present invention, preferably mentioned and adopted ether and ketone solvent, caused above-mentioned shortcoming as optimum.
In the method for the invention, suitable carboxylic acid amide is dimethyl formamide, diethylformamide, N,N-DIMETHYLACETAMIDE, diethyl acetamide or their mixture.Dimethyl formamide is particularly preferred carboxylic acid amide.The amount of operable suitable carboxylic acid amide is not crucial for implementing method of the present invention, but is based on the total amount of reaction mixture, preferably uses 50 weight % to 95 weight %, the carboxylic acid amide of the amount of preferred 65 weight % to 85 weight %.
Have been found that the KIP selectivity that can realize unexpectedly has the sensitive reaction for lower oxygen supply in the oxidation of carboxylic acid amide.In the tentative bubble post of introducing gas by the pore frit very effectively (Pilot bubble column), only from the per hour high relatively oxygen metering introducing of 0.5 liter of oxygen (particular value of used prototype system) of every gram β-IP, it is obvious that the great potential of this kind solvent just becomes.Below the value, selectivity takes place significantly to reduce at this.At the solvent that routine adopts, in the situation as diglyme, can not observe influence so far.
In order to realize optimum yield, the oxygen in carboxylic acid amide is supplied with even must be increased to the per hour about 0.8 liter of oxygen of every at least gram β-IP.Therefore, do not consider or do not know that these situations cause the bad result of response procedures in carboxylic acid amide inevitably, supposed improperly with being described as top-priority ether from it and compared that carboxylic acid amide has the low adaptability of supposition as the solvent of the reaction of being studied with ketone.
The fact is, carrying out oxidation in carboxylic acid amide not only allows to prepare KIP with highly selective and yield and reduces by product simultaneously and form, and catalyst system is significantly lower than reaction sensibility in the situation of ether for the existence of carboxylic acid in carboxylic acid amide, described carboxylic acid is when the cyclical operation method, obtains inevitably.
This catalyst system also has obviously better stability in carboxylic acid amide than in ether, this allows premixing reaction matrix in the method for operate continuously, and the selectivity that do not react in for some time reduces.
Another main advantages of carboxylic acid amide is, the described catalytic activity that optionally can realize under the situation in not serious loss altogether additive to the ratio that influences of educt concentration as obviously more remarkable in diglyme, this causes economic interests with regard to the space/time yield of reaction.Therefore, even under β-IP concentration of 40 weight %, still observe the selectivity more than 85%, this value only could realize when educt concentration reaches maximum 20 weight % in diglyme.
Simultaneously, because the weak base character of carboxylic acid amide solvent, based on the β-IP that is adopted, the consumption of auxiliary alkali can be reduced to 10 moles of %, and the not serious reaction preference that can realize that reduces.
In addition, use carboxylic acid amide, particularly Lian Jia dimethyl formamide as solvent, than using very expensive glycol ether, have huge economic interests as diglyme and glycol dimethyl ether, thought that up to now these solvents are the preferred solvent that realize highly selective.
In order to react, β-IP is contacted with response matrix continuously or discontinuously, response matrix comprises catalyzer and auxiliary alkali, and catalytic activity is total to additive and optional water, and it is dissolved or suspended in the carboxylic acid amide as solvent, at normal pressure or add and depress and oxygen or oxygen-containing gas mixture reaction.
Employed catalyzer is the complex compound catalyst of mentioning in the prior art that contains transition metal, and as salung manganese, tetraphenylporphyrin manganese and manganese phthalocyanine, salung manganese is preferred.Based on β-IP, this catalyzer is usually with 0.001-3 weight %, and the amount of preferred 0.05-1 weight % adds.
Can be used as this auxiliary alkali according to the known organic and mineral alkali of prior art, alkylamine, two or trialkylamine, aromatics and aliphatic heterocyclic bases, sodium hydroxide or potassium solution or alcoholate for example, or quaternary ammonium hydroxide, preferably trialkylamine, particularly triethylamine.These alkali can adopt with convention amount, for example, based on β-IP, 5-60 mole %, the amount of preferred especially 10-35 mole %.
In the method for the invention, adopt carboxylic acid amide, for example dimethyl formamide (DMF), diethylformamide (DEFA), and corresponding ethanamide, as N,N-DIMETHYLACETAMIDE or diethyl acetamide as solvent.In particularly preferred embodiments, be reflected in the dimethyl formamide and carry out.The content of carboxylic acid amide is generally 50 weight % to 95 weight % in the reaction mixture, more preferably adopts the amount of 65 weight % to 85 weight %.
Water content in the total reaction mixture can change between 0-30 weight %.Under the situation of not adding water, realized very high selectivity, but had uneconomic reaction times.Therefore, preferably adopt water, particularly based on the gross weight of reaction mixture, between 0.05 weight % to 30 weight %, preferably between 0.5-20 weight %, between 0.5 weight % to 5 weight % as reaction promotor.
The oxygenant that can adopt among the present invention is oxygen or oxygen-containing gas mixture, air or for example by adding rare gas element, and for instance as nitrogen, and the oxygen that dilutes.
Reaction can or add at normal pressure to depress to be carried out.For instance, reaction can be carried out under the pressure of 1-12 crust, and this depends on the volume content of oxygen in the used oxygenant.
Temperature of reaction can be between-30 ℃ to 80 ℃, preferably between 10 ℃ to 45 ℃.
Method of the present invention is implemented simple and is provided reaction product with good yield and high purity.Can be by using common method, particularly vacuum distilling reaction product isolated from product mixtures.
Use 30 meters long, the J of 0.32 millimeter internal diameter and 1 micron thickness; W DB-5 capillary column is measured yield in HP 5890 or HP 6890 gas-chromatographies.Use diethyl acetamide as interior mark.To be used as reference substance by the KIP of distillation purifying.
HPLC measures and carries out in the system that comprises Biotronik BT 3035 UV detectors, Jasco 880 PU pumps and Spectra Physics Chrom Jet totalizing instrument.Used pillar is RP18,5 μ, 250 * 4mm internal diameter.Above-mentioned KIP reference substance is used as external standard.
Following examples are used for setting forth in more detail the present invention.
Embodiment 1-12
The salung manganese of the amount that at first specified 58.0 gram solvents, 1.2 gram water, 0.16 gram methyl ethyl diketone, 2.53 in the table 1 is restrained triethylamines and can see from table 1 is put into glass beaker and is stirred 15 minutes (modification A) or 16 hours (variant B).Add 15.4 gram β-IP then, and reaction mixture is stirred momently and is transferred in the bubble post.Under normal pressure and 35 ℃, with oxygen ventilation (12l/h) 2.5 hours, then with the yield of marker method by gas Chromatographic Determination KIP.The results are shown in Table 1.
Comparative examples A-F
The salung manganese of the amount that at first 58.0 gram diglymes, 1.2 gram water, 0.16 gram methyl ethyl diketone, 2.53 is restrained triethylamines and can see from table 1 is put into glass beaker and is stirred 15 minutes (modification A) or 16 hours (variant B).Add 15.4 gram β-IP then, and with the of short duration stirring of reaction mixture and be transferred in the bubble post.Under normal pressure and 35 ℃, with oxygen ventilation (12l/h) 2.5 hours, then with the yield of marker method by gas Chromatographic Determination KIP.The results are shown in Table 1.
Table 1
| Embodiment/comparative example | Solvent | Variant | The amount of catalyzer [based on the weight % of β-IP] | KIP yield [%] |
| ????1 | ????DMF | ??A | ????0.2 | ????91.4 |
| ????2 | ????DMF | ??B | ????0.2 | ????89.7 |
| ????3 | ????DEFA | ??A | ????0.2 | ????90.5 |
| ????4 | ????DEFA | ??B | ????0.2 | ????89.6 |
| ????A | Diglyme | ??A | ????0.2 | ????90.3 |
| ????B | Diglyme | ??B | ????0.2 | ????85.3 |
| ????5 | ????DMF | ??A | ????0.3 | ????92.2 |
| ????6 | ????DMF | ??B | ????0.3 | ????91.9 |
| ????7 | ????DEFA | ??A | ????0.3 | ????92.0 |
| ????8 | ????DEFA | ??B | ????0.3 | ????90.3 |
| ????C | Diglyme | ??A | ????0.3 | ????90.1 |
| ????D | Diglyme | ??B | ????0.3 | ????87.0 |
| ????9 | ????DMF | ??A | ????0.4 | ????92.8 |
| ????10 | ????DMF | ??B | ????0.4 | ????92.0 |
| ????11 | ????DEFA | ??A | ????0.4 | ????92.1 |
| ????12 | ????DEFA | ??B | ????0.4 | ????92.5 |
| ????E | Diglyme | ??A | ????0.4 | ????90.5 |
| ????F | Diglyme | ??B | ????0.4 | ????88.8 |
Embodiment 13-15
At first the acid of specified amount in 72.5 gram DMF, 1.56 gram water, 0.21 gram methyl ethyl diketone, 3.18 gram triethylamines, the tables 2 and 75 milligrams of salung manganese are put into glass beaker and stirred 15 minutes.Add 19.25 gram β-IP then, and with the of short duration stirring of reaction mixture and be transferred in the bubble post.Under normal pressure and 35 ℃, with oxygen ventilation (16l/h) 2.5 hours, then with the yield of marker method by gas Chromatographic Determination KIP.The results are shown in Table 2.
Comparative example G-I
At first the acid of specified amount in 72.5 gram diglymes, 1.56 gram water, 0.21 gram methyl ethyl diketone, 3.18 gram triethylamines, the tables 2 and 75 milligrams of salung manganese are put into glass beaker and stirred 15 minutes.Add 19.25 gram β-IP then, and with the of short duration stirring of reaction mixture and be transferred in the bubble post.Under normal pressure and 35 ℃, with oxygen ventilation (16l/h) 2.5 hours, then with the yield of marker method by gas Chromatographic Determination KIP.The results are shown in Table 2.
Table 2
| Embodiment/comparative example | Solvent | The acid [mg/kg solvent] that adds | KIP yield [%] |
| ????13 | ????DMF | Formic acid: 2059 | ????91.7 |
| ????14 | ????DMF | Acetate: 2011 | ????88.5 |
| ????15 | ????DMF | Formic acid: 1031 acetate: 1007 | ????92.3 |
| ????G | Diglyme | Formic acid: 1999 | ????84.6 |
| ????H | Diglyme | Acetate: 1742 | ????86.5 |
| ????I | Diglyme | Formic acid: 1044 acetate: 1028 | ????86.0 |
Reconfirmed with method of the present invention and can realize higher yield.
Embodiment 16-22
Under normal pressure and 35 ℃, in about 100 gram β-IP, triethylamines, water, methyl ethyl diketone and the solution of salung manganese in DMF that concentration can be read from table 3 in the bubble post of laboratory with oxygen ventilation (16l/h) 2.5 hours, then with the yield of marker method by gas Chromatographic Determination KIP.The results are shown in Table 3.
Table 3
| Embodiment | ??β-IP ??[mol/l] | Triethylamine [mol/l] | Water [mol/l] | Methyl ethyl diketone [mol/l] | Salung manganese [mol/l] | KIP yield [%] |
| ??16 | ??0.54 | ??0.30 | ??0.80 | ??115 | ??3.81 | ??92.6 |
| ??17 | ??1.08 | ??0.30 | ??0.81 | ??113 | ??3.79 | ??91.7 |
| ??18 | ??1.59 | ??0.30 | ??0.81 | ??167 | ??5.57 | ??89.4 |
| ??19 | ??2.11 | ??0.29 | ??0.79 | ??222 | ??7.38 | ??87.7 |
| ??20 | ??2.62 | ??0.29 | ??0.78 | ??273 | ??9.14 | ??85.7 |
| ??21 | ??3.85 | ??0.29 | ??0.78 | ??375 | ??12.55 | ??70.0 |
| ??22 | ??5.61 | ??0.28 | ??0.75 | ??571 | ??19.10 | ??64.7 |
The KIP yield of the KIP yield among the comparing embodiment 16-22 and the 5th, 874, No. 632 tables 3 of United States Patent (USP).The result as shown in Figure 1.
In Fig. 1, can clearly be seen that compared with prior art, under identical β-IP concentration, KIP yield of the present invention obviously improves, promptly increase.
Embodiment 23-26
At first 58.0 gram dimethyl formamides, 1.2 gram water, 0.16 gram methyl ethyl diketone, 2.53 gram triethylamines and 45 milligrams of salung manganese are put into glass beaker and stirred 15 minutes.Add 15.4 gram β-IP then, and with the of short duration stirring of reaction mixture and be transferred in the bubble post.Under normal pressure and 35 ℃, with the oxygen ventilation of the amount that is metered into that can from table 4, see 2.5 hours, then with the yield of external standard method by gas Chromatographic Determination KIP.The results are shown in Table 4.
Comparative Example J-M
At first 58.0 gram diglymes, 1.2 gram water, 0.16 gram methyl ethyl diketone, 2.53 gram triethylamines and 45 milligrams of salung manganese are put into glass beaker and stirred 15 minutes.Add 15.4 gram β-IP then, and with the of short duration stirring of reaction mixture and be transferred in the bubble post.Under normal pressure and 35 ℃, with the oxygen ventilation of the amount that is metered into that can from table 4, see 2.5 hours, then with the yield of external standard method by gas Chromatographic Determination KIP.The results are shown in Table 4.
Table 4
| Embodiment/comparative example | Solvent | The oxygen that is metered into | The KIP yield | |
| ???[l/h] | [l/h*g?β-IP] | ????[％] | ||
| ????23 | ????DMF | ????6 | ????0.40 | ????75.8 |
| ????24 | ????DMF | ????8 | ????0.53 | ????87.4 |
| ????25 | ????DMF | ????10 | ????0.66 | ????89.2 |
| ????26 | ????DMF | ????12 | ????0.80 | ????90.2 |
| ????J | Diglyme | ????6 | ????0.40 | ????86.8 |
| ????K | Diglyme | ????8 | ????0.53 | ????87.9 |
| ????L | Diglyme | ????10 | ????0.66 | ????89.0 |
| ????M | Diglyme | ????12 | ????0.80 | ????88.9 |
Embodiment 23-26 has set forth the optionally tremendous influence of oxygen supply to the Oxophorone that can realize in the DMF solvent.Comparative Example J-M shows this influence of only observing not half in the solvent diglyme that gives special priority for according to prior art.Therefore, do not know that in DMF reaction preference causes bad result (embodiment 23-24) inevitably to the susceptibility of inadequate oxygen supply, from its supposition, compare with ketone with being described as preferred ether in the prior art, carboxylic acid amide has lower adaptability as the solvent of the reaction of being studied.
On the other hand, if guarantee sufficiently high oxygen supply (embodiment 25-26), the carboxylic acid amide of describing among the present invention becomes clear as the unexpected high potentiality of the solvent of the reaction of being studied.Referring to Fig. 2.
Embodiment 27-30
At first the triethylamine of 72.5 gram dimethyl formamides, 1.5 gram water, 0.22 gram methyl ethyl diketone, the amount that can see and 75 milligrams of salung manganese are put into glass beaker and stirred 15 minutes from table 5.Add 19.3 gram β-IP then, and with the of short duration stirring of reaction mixture and be transferred in the bubble post.Under normal pressure and 35 ℃, with oxygen ventilation (16l/h) 3 hours, then with the yield of marker method by gas Chromatographic Determination KIP.The results are shown in Table 5.
Comparative example N
In this comparative example, use diglyme to replace DMF as solvent, the relative composition of solution is identical with embodiment 27-30.Measure the yield of KIP by HPLC with external standard method.The results are shown in Table 5.
Table 5
| Embodiment/comparative example | Solvent | Triethylamine concentration | The KIP yield | |
| [the mole % of β-IP relatively] | [the weight % of β-IP relatively] | ??[％] | ||
| ??27 | ??DMF | ??????????5 | ??????????3.6 | ??84.5 |
| ??28 | ??DMF | ??????????10 | ??????????7.3 | ??90.1 |
| ??29 | ??DMF | ??????????15 | ??????????10.9 | ??91.1 |
| ??30 | ??DMF | ??????????20 | ??????????14.6 | ??91.2 |
| ??N | Diglyme | ??????????11.4 | ??????????8.3 | ??86.8 |
Reconfirmed the method for the present invention of using, that is, used dimethyl formamide to replace diglyme, realized better yield as solvent.Referring to embodiment 28 and comparative example N.
Claims (14)
1, by oxidation 3 in the presence of oxygenant and catalyst system, 5,5-trimethylammonium-hexamethylene-3-alkene-1-ketone prepares 3,5,5-3-methyl cyclohexanol-2-alkene-1, the method of 4-diketone, described catalyst system comprise transition metal complex catalyst, auxiliary alkali, possible water, and the catalytic activity that is selected from down group additive altogether:
1) pKa is the organic acid of 2-7, perhaps corresponding aldehyde;
2) C
1-C
4Fatty alcohol or phenol;
3) can form the compound of enol structure; And
4) Lithium Sulphate;
Wherein adopt carboxylic acid amide as solvent.
2, according to the process of claim 1 wherein that this carboxylic acid amide is dimethyl formamide, diethylformamide, N,N-DIMETHYLACETAMIDE, diethyl acetamide or their mixture.
3, according to the method for claim 1 or 2, wherein this carboxylic acid amide is a dimethyl formamide.
4, according to claim 1,2 or 3 method, wherein use salung manganese as this catalyzer.
5, according to the method for claim 4, wherein based on β-IP, the amount of the catalyzer of adding is 0.001-3 weight %.
6, according to claim 1,2 or 3 method, wherein use triethylamine as this auxiliary alkali.
7,, wherein use methyl ethyl diketone as additive altogether according to claim 1,2 or 3 method.
8, according to the method for claim 7, wherein based on this catalyzer, the mol ratio of the methyl ethyl diketone of adding is 1: 1 to 100: 1.
9, according to claim 1,2 or 3 method, wherein based on total reaction mixture, the amount of the water of adding is 0.05 weight % to 30 weight %.
10, adopt dimethyl formamide as solvent according to the process of claim 1 wherein, and the mixture of employing salung manganese, triethylamine, water and methyl ethyl diketone is as this catalyst system.
11, according to the process of claim 1 wherein that this oxygenant is oxygen or oxygen-containing gas mixture.
12, according to the method for claim 11, wherein this oxygenant is an oxygen.
13, according to the method for claim 11, wherein this oxygenant is an air or with the oxygen of nitrogen dilution.
14, according to the process of claim 1 wherein that this oxidizing reaction is at normal pressure or add to depress and carry out.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/EP2002/000621 WO2003062184A1 (en) | 2002-01-23 | 2002-01-23 | Process for the preparation of 3,5,5-trimethyl-cyclohex-2-ene-1,4-dione |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1615291A true CN1615291A (en) | 2005-05-11 |
| CN1267396C CN1267396C (en) | 2006-08-02 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB028274202A Expired - Fee Related CN1267396C (en) | 2002-01-23 | 2002-01-23 | Preparation of 3,5,5-trimethyl-cyclohex-2-ene-1,4-dione |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP1467961A1 (en) |
| JP (1) | JP2005526017A (en) |
| KR (1) | KR20040086284A (en) |
| CN (1) | CN1267396C (en) |
| BR (1) | BR0215533A (en) |
| CA (1) | CA2473941A1 (en) |
| MX (1) | MXPA04006987A (en) |
| WO (1) | WO2003062184A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105646196A (en) * | 2014-12-03 | 2016-06-08 | 中国科学院大连化学物理研究所 | Method for preparation of 4-methylcyclohex-3-ene-1-carboxylic acid from 4-methyl-3-cyclohexene-1-carbaldehyde |
| CN109438199A (en) * | 2018-09-20 | 2019-03-08 | 山东新和成维生素有限公司 | A kind of method that continuous high-efficient oxidation prepares 2,6,6- trimethyl -2- cyclohexene -1,4- diketone |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19619570A1 (en) * | 1996-05-15 | 1997-11-20 | Degussa | Process for the preparation of ketoisophorone |
| DE19929362A1 (en) * | 1999-06-25 | 2000-12-28 | Basf Ag | Process for the preparation of oxoisophorone using additives |
| DE10062260A1 (en) * | 2000-12-14 | 2002-06-20 | Degussa | Preparation of 3,5,5-trimethylcyclohex-2-en-1,4-dione uses a catalyst containing a coadditive from acids, 1-4C aliphatic alcohol or phenol, compounds forming an enol and lithium sulfate |
-
2002
- 2002-01-23 CA CA002473941A patent/CA2473941A1/en not_active Abandoned
- 2002-01-23 WO PCT/EP2002/000621 patent/WO2003062184A1/en not_active Application Discontinuation
- 2002-01-23 BR BR0215533-8A patent/BR0215533A/en not_active Application Discontinuation
- 2002-01-23 EP EP02701264A patent/EP1467961A1/en not_active Withdrawn
- 2002-01-23 JP JP2003562068A patent/JP2005526017A/en active Pending
- 2002-01-23 KR KR10-2004-7011365A patent/KR20040086284A/en not_active Application Discontinuation
- 2002-01-23 CN CNB028274202A patent/CN1267396C/en not_active Expired - Fee Related
- 2002-01-23 MX MXPA04006987A patent/MXPA04006987A/en not_active Application Discontinuation
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105646196A (en) * | 2014-12-03 | 2016-06-08 | 中国科学院大连化学物理研究所 | Method for preparation of 4-methylcyclohex-3-ene-1-carboxylic acid from 4-methyl-3-cyclohexene-1-carbaldehyde |
| CN105646196B (en) * | 2014-12-03 | 2018-02-23 | 中国科学院大连化学物理研究所 | A kind of method that the carboxylic acid of 4 methyl cyclohexane, 3 alkene 1 is prepared to methyl cyclohexane cyclohexene carboxaldehyde |
| CN109438199A (en) * | 2018-09-20 | 2019-03-08 | 山东新和成维生素有限公司 | A kind of method that continuous high-efficient oxidation prepares 2,6,6- trimethyl -2- cyclohexene -1,4- diketone |
Also Published As
| Publication number | Publication date |
|---|---|
| BR0215533A (en) | 2004-12-21 |
| MXPA04006987A (en) | 2004-11-10 |
| CN1267396C (en) | 2006-08-02 |
| JP2005526017A (en) | 2005-09-02 |
| CA2473941A1 (en) | 2003-07-31 |
| KR20040086284A (en) | 2004-10-08 |
| EP1467961A1 (en) | 2004-10-20 |
| WO2003062184A1 (en) | 2003-07-31 |
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