JPS5850204B2 - Method for producing benzyl alcohol and/or benzaldehyde derivatives having an ether bond - Google Patents

Description

Detailed Description of the Invention The present invention provides an alkyl or aryl ether of 0-cresol or p-cresol with a lower saturated fatty acid and/or anhydride thereof as a solvent, and a solubility of at least 0.01 times the mole of the oxidized product. In the coexistence of a cobalt salt and a soluble bromine compound, or in the coexistence of a co-oxidant,
This invention relates to a method for producing benzyl-V-col and/or benzaldehyde derivatives having an ether bond, which is characterized by liquid phase oxidation with molecular oxygen under an oxygen partial pressure of 0.1 to 2 kg/car (absolute pressure). .

Benzyl alcohol and benzaldehyde derivatives, which have an ether bond, are important compounds as raw materials for the organic fine chemical industry, but they have not been of great industrial interest until now, partly because their production methods are difficult. Ta.

However, recently, important organic fine chemical products derived from the above-mentioned compound groups have been appearing one after another, and there is a demand for the development of synthetic techniques for them.

In particular, p-methoxybenzaldehyde is an extremely important compound as a perfume, a pharmaceutical intermediate, etc., but no industrially advantageous synthesis method has been published at present.

The present inventors investigated a liquid phase autoxidation method of alkyl or aryl ethers of cresol, which is considered to be a rational method for synthesizing benzyl alcohol and benzaldehyde derivatives having ether bonds, and investigated lower saturated fatty acids and/or their anhydrous When an oxidation reaction is carried out using a relatively large amount of heavy metal salts, especially cobalt salts, as a catalyst in the presence of oxygen, aldehydes are mainly produced under oxygen-excess reaction conditions, and alcohols are mainly produced under oxygen-deficient reaction conditions. I applied for a patent under the heading (Patent application 1972-
42419, Showa 5l-127047).

This method is extremely effective for oxidizing the methyl group of toluene derivatives that have an ether bond at the p-position, but when the ether bond is at the m- or 〇-position, it is more effective than when oxidizing the p-substituted product. The reaction rate was drastically reduced, the reaction under low oxygen pressure did not occur, and the reaction under high oxygen pressure did not proceed smoothly unless under harsh conditions.

However, under harsh reaction conditions, side reactions inevitably increase,
Since decomposition of ether bonds is also likely to occur, the reaction may not proceed midway through the process, and in the oxidation of m- and 〇-compounds, experimental results can vary widely due to slight differences in reaction conditions. - There was also a drawback that the selectivity decreased significantly during monolithic oxidation.

In addition, during oxidation of m-units and ○-units, the experimental results vary greatly due to very small impurities, and these appear to be poor compatibility.

This phenomenon is remarkable even when m-phenoxytoluene is difficult to oxidize. For example, when m-phenoxytoluene is oxidized in liquid phase under pressurized oxygen, the reaction rate reaches a maximum of 68%.
Although a m-phenoxybenzaldehyde selectivity of 35 mo1% was obtained, there are many cases where the reaction does not occur even if the reaction is performed under the same conditions, or the reaction stops at a reaction rate of about 10%, and when the selectivity is less than 10 mo1%. were the majority.

The present inventors conducted various searches regarding the poor reproducibility, but were unable to reach a clear conclusion.

Therefore, we investigated more stable oxidation methods and found that a method using cobalt ions and nickel ions as catalysts under oxygen pressure, and a method in which cerium ions coexisted were effective, but the reaction results were It was not very good, and only a m-phenoxybenzaldehyde selectivity of 13 to 17 mo1% was obtained with good reproducibility at a reaction rate of about 20%.

Therefore, as a result of repeated research focusing on the method of adding a third component, we found that an extremely effective improvement was achieved by using a soluble cobalt salt as well as a soluble bromine compound and/or co-oxidant as a reaction accelerator. I found out that this is done.

In addition, this improved method can be advantageously applied to p-integrations, not limited to m-integrations and 〇-integrations, and when applied to p-integrations, it is better than the method previously proposed by the present inventors. It has been found that the reaction proceeds more smoothly and that good reaction results can be obtained at lower reaction temperatures and shorter reaction times.

The present invention has been made based on such knowledge.

The method of oxidizing refractory compounds by adding a bromine compound to a liquid phase auto-oxidation system of methylbenzenes in acetic acid using cobalt as a catalyst is well known as the terephthalic acid production method and has been turned into a large-scale industrial process. However, there have been no published examples of adding a small amount of bromine compounds to this system to greatly improve the selectivity for the production of oxidized intermediates.

However, according to the research of the present inventors, in the atmospheric liquid phase autooxidation reaction of alkyl or aryl ether of 0-cresol using cobalt as a catalyst and acetic acid as a solvent, the reaction does not occur in the absence of a bromine compound. Even if a reaction initiator is added to start the reaction, the oxidation intermediate selectivity is 1.
It is surprising that oxidized intermediates are produced with high selectivity when a trace amount of bromine compound is added, even though the amount was only 0 mo1% or less, which is unbelievable from conventional common sense.

When p-cresol ether is subjected to liquid-phase autooxidation near normal pressure, no significant effect is observed in the case of 〇 integrated, but the effects of lowering the reaction temperature and shortening the reaction time are clear. As a result, atmospheric pressure oxidation of compounds with a large number of carbon atoms (compounds with a large number of carbon atoms are generally more difficult to oxidize than compounds with a smaller number of carbon atoms) did not actually occur in the absence of bromine compounds.

(See Examples). In addition, in connection with this phenomenon, an effect of increasing the production selectivity of oxidized intermediates was also observed, and this effect was also observed more markedly for compounds with a large number of carbon atoms.

That is, since the effect of adding a bromine compound is most pronounced for compounds that are difficult to oxidize, it can be said that the effect is quite small in the case of oxidizing p-methoxytoluene, which is easily oxidized.

Any bromine compound can be used as long as it dissolves in the reaction solution and provides bromine ions to the reaction system, and examples show that organic bromine compounds such as benzene bromide and alkyl bromide also show excellent results. However, salts of alkali metals and alkaline earth metals or hydrogen bromide are particularly effective, and when considering solubility, price, and ease of handling, potassium bromide and bromide It is also advantageous to use soda.

The amount of the bromine compound added is from o, oooi to 0 of the raw material compound.
．． 5 mol times - especially 0.001 to 0.3 mol times -
If the amount is too low, the effect will not be recognized, and if it is too high, the amount of carboxylic acid etc. produced increases and the selectivity of oxidation intermediates decreases, and a large amount of organic bromine compounds are produced as by-products, which increases the cost of separation and purification of the product. Increasing drawbacks are recognized.

It is also important to regulate the amount of bromine compound added by the amount of cobal I salt added, and 0.001 of soluble cobalt salt.
~10 times by mole - A range of 0.005 to 5 times by mole is particularly good. If the amount added is too small from this range, no effect of the addition of the bromine compound will be observed, and if it is too much, the induction period will greatly increase and the selectivity will decrease. It dropped dramatically.

Any co-oxidant can be used as long as it is easily oxidized under the reaction conditions to generate peroxy radicals, and n-butene, cyclohexanone, etc. can also be used, but the effect of addition, ease of use, Considering the price and the compounds produced by oxidation of the co-oxidizing agent, acetaldehyde, paraldehyde, and methyl ethyl ketone are particularly good, and among these, the first two are particularly good.

The amount of co-oxidant added is generally 0.0001 of the raw material compound.
~0.5 times by mole, preferably about 0.001 to 0.2 times by mole; if it is too little, the effect will not be observed, and if it is too much, there will be no particular adverse effect, but do not add more than necessary. It is disadvantageous in terms of cost, and addition of a large amount increases the calorific value, making it difficult to control the reaction, so it is not preferable to add a larger amount than necessary.

The effect of adding a co-oxidant is similar to the effect of adding a bromine compound, and it is observed that the reaction temperature is lowered, the reaction time is shortened, and the selectivity of oxidized intermediates is improved. This effect is also noticeable when oxidizing a difficult-to-oxidize compound.

Therefore, when an easily oxidizable compound such as p-methoxytoluene is oxidized at around 100°C, no effect is observed; When reacting, the effect of addition is clearly recognized, so take into account the reactivity of the oxidized material and reaction conditions.
It is only necessary to decide whether or not to use a co-oxidizing agent.

In addition, in the oxidation of refractory compounds, it has been observed that depending on the reaction conditions, the reaction may not proceed smoothly unless a co-oxidizing agent is used or a mixed solvent of a lower saturated fatty acid and its anhydride is used. (described later), and the method of using a co-oxidant in combination is often more advantageous in terms of cost. Therefore, it can be said that it is generally more advantageous to use a co-oxidant in combination when oxidizing a refractory compound.

In the method of the present invention, the catalyst seems to act in the form of a lower saturated fatty acid as a ligand dissolved in the reaction solution, and no positive effect is observed even if the catalyst is added in an amount greater than the dissolved amount.

Furthermore, for the reasons mentioned above, it is desirable to add cobalt as a salt of lower saturated fatty acids, especially acetate, but soluble cobalt salts that easily form cobalt ions coordinated with lower saturated fatty acids in the reaction system should be used as catalysts. Can be used as acetylacetonate, naphthenate, benzoate,
Stearates, nitrates, etc. can also be used.

However, cobalt halides often do not cause the reaction and cannot be said to be a preferable catalyst.

The optimum amount of catalyst to be added varies depending on reaction conditions such as raw materials, solvent, co-oxidizing agent, type and amount of bromine compound added, and reaction temperature, but it varies greatly depending on the type of solvent. When oxidizing difficult-to-oxidize compounds such as
．． The reaction will not occur unless the catalyst is added in an amount of 0.05 times the mole or more, and it is desirable to add more than 0.05 times the mole of O,OS in order to make the reaction proceed smoothly, but in a mixed solvent of acetic acid and acetic anhydride, the reaction does not occur. The reaction proceeded with twice the addition.

When oxidizing easily oxidizable compounds such as p-methoxytoluene, the amount of catalyst added may be smaller than when oxidizing difficult-to-oxidize compounds. It is clear from the examples that addition of approximately twice as much soluble cobalt salt is sufficient, but even when using an easily oxidizable compound as a raw material, the amount of soluble cobalt salt added is approximately 0.0 times that of the raw material compound.
It is preferable that the amount is 0.01 mole or more.

Taking these into account, it can be said that the minimum amount of soluble cobalt salt to be added is 0.001 times, preferably 0.01 times by mole, the amount of the raw material compound, and the maximum amount to be added is the saturated dissolved amount under the reaction conditions, but particularly preferred is is 0.05 to 0.0 of the raw material compound.
It was 3 times the mole amount.

If the amount of the catalyst added is too small, the reaction rate and selectivity will both decrease, and if the amount is about 0.001 times the amount of the starting compound by mole, the reaction will not start if the oxidizable compound is used as the starting material.

If the amount of catalyst added is too large, there will not be much negative effect on reactions outside of chamfering in terms of reaction engineering, but a large amount of catalyst will precipitate during product separation and recovery, reducing the yield of the target product. There are negative points such as this, so it is not a desirable thing.

In order to obtain substituted benzaldehyde or substituted benzyl alcohol with good yield by the method of the present invention, it is essential to use a lower saturated fatty acid having 2 to 4 carbon atoms and/or its anhydride as a solvent. As mentioned above, acetic acid is particularly excellent as a lower saturated fatty acid anhydride, and acetic anhydride is particularly excellent as a lower saturated fatty acid anhydride, and even better results are obtained when these are used in combination.

However, it goes without saying that if a sufficient amount of cobalt salt is added without using acetic anhydride in combination, it is more advantageous to use acetic acid alone.

Furthermore, it has been observed that lower saturated fatty acid esters of substituted benzyl alcohol tend to grow more easily when an anhydride is used in combination than when lower saturated fatty acids are used alone, so whether or not an anhydride should be used in combination depends on the reaction conditions. It may be determined as appropriate, taking into consideration the purpose and purpose.

The amount of solvent added varies depending on the type of solvent, reaction conditions, and type of oxidized product, but it is generally about 0.2 to 20 times the mole of the raw material compound, and a particularly good range is 2.
It is about 15 mole times.

If the amount of solvent used is too small, the characteristics of the method of the present invention will be lost, a significant decrease in reaction rate and selectivity will be observed, and the reaction will often not occur.

However, even if the amount of solvent used is excessive, there is no major change, and the highest selectivity may be obtained when the solvent is added in an amount of 15 moles or more of the raw material compound, but if it is used in an excessive amount, the oxidation rate may decrease. There are drawbacks such as lower productivity, an increase in the optimum amount of catalyst, and an increase in post-treatment costs for the produced liquid.
That's not a good thing.

In the method of the present invention, if acetaldehyde, paraldehyde, or methyl ethyl ketone is used as a co-oxidizing agent,
Its oxidation produces acetic acid.

Therefore, when such co-oxidants are used in relatively large amounts, the required amount can be obtained within the system relatively early after the reaction starts, even if no lower saturated fatty acids or their anhydrides are present at the start of the reaction. Since acetic acid is produced, the oxidized intermediate can be obtained in fairly good yield.

That is, it is also possible to generate lower saturated fatty acids in situ by using a large amount of co-oxidizing agent in advance.

However, as is clear from the examples, this method generally has a lower selectivity of oxidized intermediates than the case where a lower saturated fatty acid and/or its anhydride is added at the start of the reaction, and it cannot be said that it is advantageous in terms of cost. do not have.

In addition, in this method, it is desirable to add about 0.5 to 5 moles of the co-oxidant, but when adding such a large amount, it is difficult to control the reaction unless an inert solvent is added as a diluent.
It is also recognized that the range of optimal reaction conditions is quite narrow, and from these points of view it cannot be said to be a particularly preferred method.

The oxidation reactivity of the alkyl or aryl ether of cresol using cobalt as a catalyst and a lower saturated fatty acid and/or its anhydride as a solvent decreases as the alkyl or aryl group becomes more complex. (formation reactions) tend to occur relatively easily, so unless reaction conditions are selected that allow the reaction to proceed smoothly at low temperatures, the reaction will not occur, and complex compounds such as bromine compounds and It can be said that the effect of adding an oxidizing agent is remarkable.

However, it is difficult to synthesize raw materials for very complex compounds, and even if a bromine compound is added, the reactivity and selectivity decrease, probably because the decomposition reaction is easier than the oxidation reaction. It is best to limit the number of carbon atoms in the or aryl group to 12 or less, and the effect of adding a bromine compound is particularly remarkable in phenyl, cyclohexyl, and o-cresol.
or m-)lyl, or a C1-C8 linear alkyl ether as a raw material.

In p-meth)oxytoluene, cobalt catalyst alone produces oxidized intermediates with high selectivity, so the effect of adding bromine compounds and co-oxidants is not very large. was phenyl, tolylcyclohexyl, or an alkyl ether of 04-CI2.

According to the present invention, the methyl group bonded to the benzene nucleus of the above-mentioned raw material compound is oxidized to a hydroxyl group or an aldehyde group, and is converted into the corresponding oxidized derivative. In this case, the oxygen pressure is 0.1 to 2 kg. There is a clear difference in the product composition and optimal reaction solution composition between the reaction when the /ca is low and the reaction when it is higher. It is necessary to appropriately select reaction conditions such as temperature, solvent composition, and amount of catalyst.

For example, regarding the solvent, as mentioned above, when using a low oxygen pressure of about 0.1 to 2 kg/crA (absolute pressure) according to the present invention, a mixed solvent of fatty acids and fatty acid anhydrides may be used in the absence of a co-oxidant. However, it was rarely advantageous to use a mixed solvent at high oxygen pressures.

There is also a large difference in the combined effect of co-oxidants between low oxygen pressure and high oxygen pressure; in the former case, the addition of a co-oxidant is often necessary to obtain a high yield of oxidized intermediates. However, in many cases the latter could not be said to be a necessary condition.

Regarding the amount of catalyst, when the oxygen pressure is low, the amount of oxidized material is 0.
．． Although it was necessary to add 0.01 mole or more, it was sufficient to add 0.001 mole or more at high oxygen pressure.

The appropriate temperature for the method of the present invention varies widely depending on the type of oxidized product, reaction conditions, and target product, and is 30 to 60°C when p-methoxytoluene is oxidized in the coexistence of acetaldehyde for the purpose of anisaldehyde synthesis. is particularly good, but 0-phenoxytoluenya p-n with only the bromine compound added
When oxidizing -dodecyloxytoluene, good results could not be obtained by oxidizing it at 100°C or higher.

Therefore, it is difficult to indicate the appropriate temperature range for the method of the present invention, but the general reaction temperature range is 30 to 180°C,
It can be said that the optimum temperature for oxidation-resistant compounds shifts to the higher temperature side.

When oxidizing an alkyl or aryl ether of cresols according to the present invention, as understood from the experimental results shown in the examples below, in order to obtain the desired oxidized intermediate with high selectivity, the alkyl or aryl ether of 0-cresol must be Or, when aryl ether is used as a raw material, the reaction rate is preferably 80% or less, preferably about 15 to 75%, and when p-cresol alkyl or aryl ether is used as raw material, the reaction rate is 90% or less, preferably It is better to set it to 30-80%.

Considering the economic efficiency of the process, it is generally better to set the minimum reaction rate to 10% or more, but of course, even if the reaction rate is lower than that, e.g. 5 to 10%, depending on the type of product (product Depending on the value (value), sufficient economic efficiency may be obtained, so it is not particularly limited to this.

As the oxidizing agent, in addition to oxygen, various oxygen-containing gases such as air or a mixed gas of air and oxygen can be used.

Further, the reaction format may be either a batch type or a continuous type, and may be appropriately determined in consideration of productivity, equipment cost, etc.

The catalyst, solvent, raw materials, products, etc. can be separated and recovered from the reaction products using methods known to those skilled in the art, such as distilling off the majority of the lower saturated fatty acids in the reaction solution under reduced pressure, and adding toluene to the remaining solution. This can be easily done in high yield by adding water and separating the aqueous layer containing the catalyst and lower saturated fatty acids and the toluene layer containing the raw materials and products, and rectifying the toluene layer under reduced pressure. can.

Furthermore, it goes without saying that the solvent and catalyst thus recovered can be used again in the reaction.

Next, the method of the present invention will be explained in more detail with reference to Examples.

In addition, "aldehyde", "acetic acid ester", and "alcohol" shown in the table below all mean those corresponding to the raw materials used.

Example 1 0-Methoxytoluene:200 acetic acid (OAc) 2. 4H20: Bromine compound = 1:8:
Add 200ml of raw material solution having a composition of 0.1 : 0.01 (molar ratio), and adjust the reaction temperature to 60 to 65°C in a hot water bath.
The reaction was carried out for a predetermined time by supplying oxygen at a rate of 3.6 J/hr while stirring the solution vigorously at r, p, m of 1000 to 1200.

The reaction product liquid was analyzed by heating gas chromatography using silane-treated Celite 545 supported with 10% by weight silicone oil 0V-17 as a filler.

The experimental results are shown in Table 1. Note that when no bromine compound was added, no reaction occurred under these conditions.

The raw material 0-methoxytoluene was synthesized from 0-cresol and dimethyl sulfuric acid by a conventional method, and was sufficiently purified by repeated alkali washing and rectification before use.

Example 2 Using NaBr as the bromine compound, the same oxidation experiment as in Example 1 was carried out, and the effects of reaction temperature and reaction rate were studied, and the results shown in Table 2 were obtained.

Example 3 Using acetic acid as a solvent, co(OAc)2.4H20 and N
0 in exactly the same manner as in Example 1 using aBr as a catalyst.
- The results shown in Table 3 were obtained by examining the amount of acetic acid, the amount of Co, the amount of NaBr, the effect of adding acetaldehyde, etc. without performing normal pressure oxygen oxidation of methoxytoluene.

* * * 1 Paraldehyde was used instead of AcH.

Cobalt benzoate was used in place of 2Co(OAc)2.4H20.

3 Air instead of oxygen (flow rate 300 ml/mi!L)
was used as the oxidizing agent.

4 Orthobutyric acid was used instead of AcOH.

5 Orthobutyric acid ester 6 KBr was used instead of NaBr.

7 Co(OAc)2.4H20 was replaced with 2-valent cobalt acetylacetonate.

8 Propionic acid was used instead of AcOH.

9 Propionate ester 10 Cobalt stearate was used in place of Co(OAc)2.4H20.

co(NO3)2.6H20 was used instead of 11Co(OAc)2.4H20.

Methyl ethyl ketone was used instead of 12AcH.

Example 4 Example 3 except that the oxidized substance is p-methoxytoluene
An experiment was conducted in exactly the same manner as above, and the results shown in Table ※※4 were obtained.

Note that p-methoxytoluene was a commercially available product that was sufficiently purified in the same manner as in Example 1 before use.

*Paraldehyde was used instead of IAcH.

*2 Orthobutyric acid was used instead of AcOH.

*3 Methyl ethyl ketone was used instead of AcH.

*4 Cobalt naphthenate (cobalt content 10 wt%) was used instead of Co(OAc)2.4H20.

*5 Air instead of oxygen (flow rate 300rrLl/m11
t) was used as oxidizing agent.

*6 Co(NOAc) instead of Co(OAc)2.4H20
3) 2.6H20 was used.

*7 In these experiments, benzene was used as a solvent instead of AcoHO, and divalent cobalt acetylacetonate was used as a catalyst instead of co(OAc)2.4H20. The production of aldehydes was observed, probably because of the production of , but in the reference example, no production of aldehydes was observed at all, probably because lower fatty acids were not produced even in 5 situ.

Example 5 In exactly the same manner as in Example 1, acetic acid was used as a solvent, and Co
(OA c ) 2 ・4 Various compounds were oxidized with oxygen at atmospheric pressure using H20 as a catalyst, and a comparison was made between cases where a bromine compound, or a bromine compound and a co-oxidant, coexisted in the reaction system and cases where a co-oxidant did not exist. , Table 5 was obtained.

The raw material compound was synthesized from 0-cresol or p-cresol and a brominated hydrocarbon by a conventional method using copper powder as a catalyst and caustic alkali as a condensing agent, and was sufficiently purified in the same manner as in Example 1 before use. did.

In addition, the reaction product was confirmed by GC-MS method.

Example 6 300r equipped with stirrer, thermometer and gas inlet
Add 150 ml of raw material solution of the specified composition to a 5US-316 stainless steel autoclave, and heat at 1600 r.
, p, m, stir the liquid vigorously to bring it to the specified liquid temperature, and then
Oxygen* was introduced from the pressure accumulator through the pressure regulator, and the oxygen pressure was maintained at 1.5 kg/ca (absolute pressure).

The amount of oxygen consumed was determined from the amount of oxygen pressure decrease in the pressure accumulator, and when a predetermined amount of oxygen had been absorbed, the reactor was rapidly cooled to stop the reaction.

Table 6 shows the results of analyzing the produced liquid in exactly the same manner as in Example 1.

Using Example 7 as a raw material, AcOH, as a solvent, a bromine compound, and a cobalt salt.
Exactly the same experiment as in Example 1 was conducted using NaBr and co(OAc)2.4H20, respectively.
The results shown in Table 7 were obtained.

Claims (1)

[Scope of Claims] An alkyl or aryl ether of 10-cresol or p-cresol is mixed with a soluble cobalt salt in an amount of 0.01 times or more mole of the amount of the oxidized substance, using a lower saturated fatty acid and/or its anhydride as a solvent. In the coexistence of a soluble bromine compound of 0.001 to 0.3 times the mole of the cobalt salt and 0.005 to 5 times the mole of the cobalt salt, or
In the coexistence of a co-oxidant with ooi~0.2 times the mole of co-oxidant, under an oxygen partial pressure of 0.1~2 kg/c4 (absolute pressure), 0
- When the alkyl or aryl ether of cresol is used as a raw material, the reaction rate is 10 to 80%, and when the alkyl or aryl ether of p-cresol is used as a raw material, the reaction rate is 10 to 90%. Characterized by oxidation. A method for producing benzyl alcohol and/or benzaldehyde derivatives having an ether bond.