JPS5850970B2 - 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 cresol, using a lower saturated fatty acid and/or its anhydride as a solvent, together with a soluble cobalt salt in an amount of 0.01 times or more mole of the amount to be oxidized. , a soluble bromine compound, and a co-oxidizer, under an oxygen partial pressure of 0.1 to 2 kg/ff1 (absolute pressure), and is characterized by liquid phase oxidation with molecular oxygen to a point where the reaction rate is 60% or less. The present invention relates to a method for producing benzyl alcohol and/or benzaldehyde derivatives having an ether bond.

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, m-phenoxybenzyl alcohol and m-phenoxybenzaldehyde are extremely important compounds as agricultural chemical intermediates, but the importance of compounds in this field has only recently increased, so there are currently no industrially advantageous synthetic methods. The law has not been announced.

The present inventors investigated a liquid phase autoxidation method for 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 When an oxidation reaction is carried out in the presence of anhydride using a relatively large amount of heavy metal salts, especially cobalt salts, as a catalyst, aldehydes are mainly produced under oxygen-excess reaction conditions, and alcohols are mainly produced under oxygen-deficient reaction conditions. A patent application was filed under the heading ← Patent 1973
-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-position or the The reaction rate decreased dramatically, the reaction under low oxygen pressure did not occur, and the reaction under high oxygen pressure did not proceed smoothly unless under harsh conditions.3However, under harsh reaction conditions, side reactions inevitably increase. However, since ether bonds are likely to break down, the reaction may stop progressing midway through, and in the oxidation of m- and 〇-compounds, the experimental results can vary widely due to slight differences in reaction conditions, and p- There was also the drawback that the selectivity decreased significantly during integral oxidation.

In addition, during m-integral and ○-integral oxidation, there are large fluctuations in experimental results due to extremely small impurities, and these appear to impair reproducibility.

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 mol was obtained, there were many cases in which the reaction did not occur even if the reaction was carried out under the same conditions, or the reaction stopped at a reaction rate of about 10 φ, and the selectivity was often less than 10 mol φ. It was a part.

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, including one that uses cobalt ions and nickel ions as catalysts for oxygen pressurization,
In addition, we found that a method in which cerium ions are not allowed to coexist is effective, but the reaction results are not very good.The reaction rate is about 20φ, and the m-phenoxybenzaldehyde selectivity is 13 to 17 mol with good reproducibility. It was just something to be gained.

Therefore, various studies were conducted, mainly focusing on the method of adding the tertiary component, and the method of the present invention was arrived at.

The method of oxidizing refractory compounds by adding bromine compounds and co-oxidants 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 is widely used. Although it has been industrialized, there have been no published examples of adding a small amount of a bromine compound and a co-oxidizing agent to this system to significantly improve the production selectivity of oxidized intermediates.

However, according to the research conducted by the present inventors, during the atmospheric liquid phase autooxidation reaction of alkyl or aryl ethers of m-cresol using cobalt as a catalyst and acetic acid as a solvent, a trace amount of a bromine compound and a co-oxidant were added as a sprig. At the same time, it was found that by suppressing the reaction rate to 60φ or less, oxidized intermediates were produced with high selectivity.

If a bromine compound or co-oxidant is not present, no reaction will occur under the same conditions, and even if the reaction is started by adding a reaction initiator, the oxidized intermediate selectivity will be low at a reaction rate of 20 to 30. This result is surprising when considered together with the experimental results showing that the amount was only 10 mo1% or less, and is unbelievable from conventional common sense.

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, the salts of alkali metals and alkaline earth metals or hydrogen bromide are particularly effective, and considering solubility, price, and ease of handling, potassium bromide and bromide are the most effective. It is also advantageous to use soda.

Moreover, the bromine compound in this case can also be formed in a reaction system.

The amount of bromine compound added is 0.0001 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 cannot be tolerated for a period of time, and if it is too high, the amount of carboxylic acid etc. produced increases, reducing the selectivity of oxidized intermediates, and a large amount of organic bromine compounds are produced as by-products, making it difficult to separate and purify the product. There are some drawbacks that increase costs.

It is also important to regulate the amount of calories added to the bromine compound by the amount of cobalt salt added, and the o, ooi of soluble cobalt salt
A range of ~10 moles - especially 0.005 to 5 moles - is good; if the amount added is less than this range, the effect of the addition of the bromine compound will not be recognized, and if it is too much, the induction period will increase by a wide range. As a result, the selection rate decreased significantly.

In the method of the present invention, the catalyst seems to act in the form of a lower saturated fatty acid dissolved in the reaction solution as a ligand, 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 lower saturated fatty acid salt, especially acetate, but soluble cobalt salts that easily form cobalt ions coordinated with lower saturated fatty acids in the reaction system are not suitable for use as catalysts. Can be used as acetylacetonate, naphthene hydrochloride, benzoate,
Stearates, nitrates, etc. can also be used.

However, cobalt halides often do not cause the reaction, and are not considered to be preferred catalysts.

The optimum amount of catalyst added is that in the absence of co-oxidizer,
Although it fluctuates considerably depending on the reaction conditions such as the type of solvent and bromine compound, reaction temperature, and amount of solvent, the fluctuation is reduced by adding a co-oxidant, and when no co-oxidant is added, lower fatty acids and their anhydrides In many cases, the reaction did not proceed smoothly unless a mixed solvent was used, but this drawback was overcome by the combined use of a co-oxidizing agent.

The minimum amount of soluble cobalt salt added is 0.01 of the raw material compound.
The mole times and maximum addition amount are the saturated dissolution amount under the reaction conditions, and it is particularly preferable that the raw material compound be 0.05 to 0.
．． It was 3 times the mole amount.

If the amount of catalyst is too small. Both the reaction rate and selectivity decrease, and the reaction does not start at about 0.001 times the mole of the starting compound.

If the scale of the catalyst temperature is too large, there is not much negative effect on the reaction outside the chamfer from a reaction engineering perspective, but a large amount of catalyst may precipitate during product separation and recovery, resulting in a decrease in the yield of the target product. This is not a desirable thing because it has negative points such as reducing the number of people.

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. Acetic acid is particularly excellent, and acetic anhydride is particularly excellent as a lower saturated fatty acid anhydride.

It has also been observed that lower saturated fatty acid esters of substituted benzyl alcohol tend to be more likely to be produced when an anhydride is used in combination than when lower saturated fatty acids are used alone.

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 1.
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.

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, etc. 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 to 0.0001 of the raw material compound.
0.5 is preferably about 0.001 to 0.2 mole times; if it is too small, the effect will not be recognized, and if it is too large, there will be no particular negative effect, but adding more than necessary is costly. Addition of a larger amount than necessary is not preferable because it is disadvantageous in terms of the amount of addition, and it is recognized that the calorific value increases when a large amount is added, making it difficult to control the reaction.

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 oxidizing substituted toluene that has an ether bond at the m-position, which is less likely to be oxidized than p-substituted toluene, the effect of using a co-oxidant in combination can be large. Even in cases where the temperature is below 50°C or when the amount of cobalt salt added is too small when lower saturated fatty acids are used as a sole solvent, the reaction proceeds smoothly by using a co-oxidant, and oxidized intermediates can be obtained with high selectivity. cases were often observed.

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 reaction) has a tendency to occur relatively easily, so unless reaction conditions are selected that allow the reaction to proceed smoothly at a low temperature, the reaction will not occur, and complex compounds will not coexist with bromine compounds. The effect of the combined use of oxidizing agents can be said to be remarkable.

However, it is difficult to synthesize raw materials for compounds that are too complex, and even if a bromine compound and a co-oxidizing agent are used together, the reactivity and selectivity will decrease, probably because the decomposition reaction is easier than the oxidation reaction. It is best to limit the number of carbon atoms in the alkyl group or aryl group to 12 or less, and the combined effect of a bromine compound and a co-oxidizing agent is particularly remarkable for phenyl, cyclohexyl, m-tolyl, or C0 to C3 straight chain alkyl groups. This was the case when ether was used as the raw material.

When the alkyl or aryl ether of m-cresol is oxidized according to the present invention, the reaction rate must be increased to obtain the desired oxidized intermediate with high selectivity, as understood from the experimental results shown in the practical example below. 60fb or less, preferably 15
It is best to set it to about 50%.

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, for example 5 to 10%, it is possible depending on the type of product (commodity). Depending on the value (value), sufficient economic efficiency may be obtained, so it is not particularly limited to this.

In this way, when oxidizing the alkyl or aryl ether of m-cresol, unlike the ether oxidation of 0- and p-cresol, the oxidized intermediate cannot be obtained with high selectivity unless the reaction rate is 60φ or less. Although the reason for this is not clear, this phenomenon is observed regardless of the alkyl group or aryl group. The case was vastly different.

A more specific explanation of the relationship between reaction rate and selectivity is as follows.

That is, for the purpose of aldehyde synthesis, the reaction rate is 70.5
When methoxytoluene is oxidized to 0.30% and 20%, the aldehyde selectivity during monolithic oxidation is 58%, respectively.
．． 62.73, and 75 mol, that during p monolithic oxidation was 65.63.61, and 71 mo1%, but m monolithic acid oxidation was 16.38.70, and 67 mo1
%, and it was observed that the selectivity decreased rapidly at a reaction rate of 50% or more.

A similar phenomenon is observed when phenoxytoluene is oxidized to obtain phenoxybenzaldehyde.
In monolithic oxidation, by selecting appropriate reaction conditions, aldehydes can be obtained with a selectivity of 50 mo1% or more even at a reaction rate of 50 to 80%, but in the oxidation of m-phenoxytoluene, the reaction does not occur regardless of the reaction conditions. It is difficult to achieve a selectivity of 40 mo 1% or more when the reaction rate is 50 or more, and especially when the reaction rate is 60 f0 or more, the selectivity is 25 mo 1.
It was also difficult to calculate the percentage.

Even when oxidation is carried out for the purpose of obtaining alcohol or a mixture of alcohol and aldehyde, the relationship between reaction rate and selectivity shows the same tendency as above, and when there is a knee-thyl bond at the m-position, the reaction rate increases by 60 % or more, it was clear that an oxidized intermediate could not be obtained with good selectivity.

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 product composition and optimal reaction solution composition between the reaction when /i 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, the amount of catalyst is 0.1 to 2 according to the method of the present invention.
When using a low oxygen pressure of around kg/ffl, it is necessary to use at least 0.01 times the mole of the oxidized material.
When the oxygen pressure is high, the reaction proceeds more easily than when the oxygen pressure is low, so the amount of cobalt salt added is increased to 0.001 mole or more.

The reaction temperature varies depending on the type of material to be oxidized and the reaction conditions, but is generally 30 to 160°C, and for m-phenoxytoluene and m-methoxytoluene, which are relatively easy to oxidize, it is about 30 to 80°C. A relatively low temperature is desirable, but a higher temperature is desirable for compounds in which the alkyl or aryl groups of the raw material compound are more complex.

Particular attention must be paid to complex compounds in which the number of carbon atoms in the alkyl group or aryl group is 8 or more, since the reaction may not occur unless the reaction temperature is set to 100° C. or higher.

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 type may be a batch type or a continuous type, and may be appropriately determined in consideration of productivity, equipment cost, etc.

When carrying out the method of the present invention, the fatty acid and its anhydride used as a solvent can be produced within the reaction system.

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, by using a relatively large amount of such a co-oxidant, it can be added to the system at a relatively early stage after the start of the reaction (even if no lower saturated fatty acids or their anhydrides are present at all). Since the required amount of acetic acid is produced, the oxidized intermediate can be obtained in a 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, this method is inferior to the case where lower saturated fatty acids and/or their anhydrides are added at the beginning of the reaction;
It cannot be said that it is advantageous in terms of cost.

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, and the optimum It is also recognized that the reaction condition range is quite narrow, and from these points of view it cannot be said to be a preferable method.

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 process can be carried out easily and in high yield by calorizing and water, separating it into an aqueous layer containing dissolved catalyst and lower saturated fatty acids, and a toluene layer containing raw materials and products, and rectifying the toluene layer under reduced pressure. I can do it.

Moreover, 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 using actual flame examples.

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

Example 1 500 mA with stirrer, thermometer, gas inlet and gas outlet with reflux condenser! In a four-bottle Pyrex glass flask, m-phenoxytoluene:acetic acid:paraldehyde:Co(OAC)24H20:bromine compound-1:12.5:0.03:0.3:0
．． Add 200 TfLl of raw material solution having a composition of 0.04 (molar ratio), keep the reaction temperature at 50 to 55 °C in a hot water bath, and heat at r.
- While stirring the liquid vigorously at 1000 to 1200 p-m, air was introduced at a rate of 300 TLl/min to carry out the reaction for a predetermined time.

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

The experimental results are shown in Table 1.

In addition, if a co-oxidizing agent is not added, a bromine compound may be added.
711 did not react at all under these conditions.

The raw material m-phenoxytoluene is m-cresol 1.
Add 1.0 mol of bromobenzene, 0 mol of KOHl, and 1 g of copper powder to 25 mol of bromobenzene, raise the temperature while stirring to expel the produced water from the system, and when the reaction temperature reaches 200°C, add 60 After reacting for several minutes, combining and extracting with benzene, alkaline washing and rectification were repeated to sufficiently purify and use.

Example 2 Using NaBr as the bromine compound, an oxidation experiment exactly similar to that in Actual Case 1 was conducted, and the relationship between reaction temperature and reaction results was investigated, and the results shown in Table 2 were obtained.

Rice 1 The reaction solution composition was m-phenoxytoluene 2: Acetic acid: Co(OAc) 2 ・4H20: NaBr:
Acetaldehyde-1=8:0.05:0.01:0.03 (molar ratio), and oxygen (feeding rate 3.61/hr) was used as the oxidizing agent.

The reaction solution composition was m-phenoxytoluene:acetic acid:Co(OAc)2.4H20:NaBr:acetaldehyde-1:8:3 rice 4 rice 0.01:0.01:0.03 (molar ratio), and the oxidizing agent Oxygen (feeding rate: 3.611/hr) was used as the gas.

The reaction solution composition was m-phenoxytoluene:acetic acid:acetic anhydride:Co(OAc)24H20:L
iBr-H2O: Paraaldehyde-1nia: 0.5
:0.1 :0.07:0.03 (molar ratio).

The reaction solution composition was m-phenoxytoluene:acetic acid:acetic anhydride:Co(OAc)24H20:LiBr-H2O:acetaldehyde=1nia:1:0.1:0.07:0.1 (molar ratio).

Example 3 Co(OAc)2''4H20 was used as a catalyst, acetic acid was used as a solvent, NaBr was added as a bromine compound, and acetaldehyde was added as a co-oxidant.
- Atmospheric pressure oxygen oxidation of methoxytoluene (feed rate 3-3.
61/hr) and obtained the results shown in Table 3.

Incidentally, the reaction apparatus and analysis method were exactly the same as in Actual Flame Example 1.

Further, m-methoxytoluene was synthesized from m-cresol and dimethyl sulfuric acid by a conventional method, or sufficiently purified by the same method as described in Example 1, and used in the reaction.

Example 4 An experiment was conducted in exactly the same manner as in Example 3 except that m-phenoxytoluene was used as the oxidizable substance, and the results shown in Table 4 were obtained.

Example 5 Various compounds were oxidized with oxygen in exactly the same manner as in Example 1, and a comparison was made between the presence and absence of a bromine compound and co-oxidant in the reaction system. In the case where no co-oxidizing agent is present, no reaction occurs at all under the reaction conditions shown in Table 5, the reaction temperature is set near the boiling point of acetic acid, and 8 to 10% of acetic anhydride is added in an amount of 2 to 3 times the mole of the raw material compound. Even when a mixed solvent of twice the molar amount of acetic acid was used, no reaction occurred within 3 hours.

Table 5 shows the experimental results when the co-oxidant and the bromine compound coexisted.

Note that the raw material compound was synthesized from m-cresol and brominated hydrocarbon in the same manner as in Example 1.

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

Counterpressure) Oxygenated at 1.5 Ke/crA.

Note that oxygen was supplied from a pressure accumulator through a pressure regulator, and the oxygen pressure was always maintained at 1.5 Ky/ffl.

Further, the stirring speed was 1600 rpm.

Claims (1)

[Claims] 1 m-cresol alkyl or aryl ether using a lower fatty acid and/or its anhydride as a solvent,
A soluble cobalt salt of o, oi times the mole of the oxidant or more, a soluble bromine compound of 0.001 to 0.3 times the mole of the oxidant and 0.005 to 5 times the mole of the cobalt salt, and a soluble bromine compound of the mole of the cobalt salt. In the coexistence of 0.001 to 0.2 moles of co-oxidant, under an oxygen partial pressure of 0.1 to 2 ny= (absolute pressure), the liquid phase is converted by molecular oxygen to a point where the reaction rate is 10 to 60 yen. A method for producing benzyl alcohol and/or benzaldehyde derivatives having an ether bond, which comprises oxidation.