JPH0256345B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to an improved method for producing nitriles from aldehydes, and more specifically, the present invention relates to an improved method for producing nitriles from aldehydes, and more specifically, an aldehyde represented by the general formula () RCHO () (where R represents a substituted or unsubstituted aryl group) and hydroxyl. The present invention relates to a method for synthesizing corresponding nitriles () from inorganic acid salts of amines. RCHO hydroxylamine inorganic acid salt――――――――――――――――――→ RCN
() Nitriles, which are the subject of the present invention, are important raw materials for pharmaceutical and agricultural intermediates. For example, P-cyanophenol, one of the target products of the present invention, is produced from cyanox (O,O-dimethyl- O-P
-cyanophenyl phosphorothioate) and bromoxynil (4-cyano-2,6-dibromophenol). There are various methods for synthesizing nitriles from aldehydes, but the most representative one is to first synthesize oximes from aldehydes and hydroxylamine/inorganic acid salts, isolate them, and then dehydrate them in the coexistence of acid catalysts. A method of producing a nitrile through a reaction (this is abbreviated as the two-step method), and a method of producing a nitrile through a direct dehydration reaction without isolating the oxime consisting of an aldehyde and a hydroxylamine inorganic acid salt (this is a one-step method). There are two methods. The present inventors previously reported (Japanese Patent Application No. 56-194128) that by carrying out the reaction while performing azeotropic dehydration in a two-stage process, the amount of acid catalyst used could be greatly reduced compared to the conventional method. We have also found that nitriles can be obtained in good yields, and that when an amide is present in the process, side reactions can be suppressed and the selectivity of the reaction can be further improved, and we are currently applying for a patent. Furthermore, in the synthesis of nitriles from aldehydes, we have noticed that a one-step method for directly producing nitriles from aldehydes has many advantages, such as a simpler process, compared to a two-step method for isolating an oxime intermediate. and continued to consider the matter earnestly. By the way, the corresponding nitrile can be obtained directly from the aldehyde without isolating the aldoxime (1
Various methods are also known for the step method. for example
Methods disclosed in Ger, Offen 2014984, “Synthesis
(1979) 722”, “Chem. Ben 107 ,
1221 (1974)”, “Synthesis (1981)”
739, the method disclosed in Japanese Patent Application Laid-Open No. 169664, and the method disclosed in Helv.Chim.Acta 59 , 2786 (1976). However, these methods Using large amounts of formic acid,
Using highly toxic selenium dioxide as a catalyst,
Alternatively, it is necessary to use special hydroxylamine derivatives that are difficult to obtain industrially, or to use an expensive dehydrating agent in an amount equal to or more than the aldehyde.
None of these methods are satisfactory for implementation as an industrial process. The present inventors have developed a reaction to obtain a nitrile from an aldehyde and an inorganic acid salt of hydroxylamine (one-step method).
As a result of detailed studies, it was surprisingly discovered that a nitrile can be easily obtained by heating and mixing an aldehyde and an inorganic acid salt of hydroxylamine in the presence of a solvent capable of azeotroping with water. That is, in the dehydration reaction of an aldehyde and an inorganic acid salt of hydroxylamine to a nitrile, the present invention quickly azeotropically distills water generated as the reaction progresses out of the reaction system together with a solvent that is azeotropic with water. As a result, the dehydration reaction can be achieved without adding a catalyst or dehydrating agent, and furthermore, by adding a small amount of amides to the reaction system, the selectivity from aldehyde to nitrile can be improved, achieving the desired goal. The present invention relates to a method characterized in that a nitrile is obtained in high yield. The method of the present invention was previously applied for by the present inventors.
The azeotropic dehydration method and the addition of an amide in the step method are the same in terms of effect and methodology, but the azeotropic dehydration method and the addition of an amide are also used when synthesizing a nitrile from an aldehyde and a hydroxylamine/inorganic acid salt in one step. It was unimaginable that it would be effective. Furthermore, there is a big difference in that the two-stage method requires the addition of an acid catalyst separately, whereas the one-stage method of the present invention does not require the addition of an acid catalyst.
This is presumably due to the following reasons. In other words, even in the one-stage process, assuming that the reaction mechanism goes through an oxime intermediate, an acid catalyst would be required for the dehydration reaction (according to conventional knowledge), but in the one-stage process, an acid catalyst would be required for the dehydration reaction, but in the one-stage process, aldehyde and The idea is that the inorganic acid that would be liberated at the same time as the oxime is produced from the hydroxylamine inorganic acid salt plays the role of an acid catalyst and produces a nitrile. It is believed that the effect of azeotropic dehydration in the method of the present invention is to prevent the action of the acid catalyst from being weakened by the produced water and to shift the equilibrium toward nitrile production. On the other hand, the effect of amides useful for improving reaction selectivity is considered as follows. That is, one is to control the acid strength of the acid catalyst, and the other is to control the solubility. For example, when hydroxymamine hydrochloride is used as the hydroxymamine inorganic acid salt, this may be because the acid strength of hydrogen chloride liberated as the reaction progresses is relatively mild, or because some HCl gas is released during the azeotropic reaction. Nitrile can sometimes be obtained with good selectivity even without the addition of amides, perhaps because it escapes from the system as Otherwise, the selectivity of the reaction decreases slightly. The reason why the effect of adding amides is especially remarkable when using this hydroxylamine sulfate is presumed to be due to the neutralizing effect of amides on sulfuric acid. Furthermore, when using an aqueous solution of hydroxylamine/sulfate, the reaction system becomes a two-layer system with the azeotropic solvent, hydrocarbon or halogenated hydrocarbon, as the upper layer (the aldehyde is distributed in both layers). It can also be considered that amides are useful in improving the contact between the two layers. Examples of amides used in this reaction include formamide, N-methylformamide, N,N
- Dimethylformamide, acetamide, N-methylacetamide, N,N-dimethylacetamide, N-methylpyrrolidone, hexamethylphosphoric triamide (HMPA), etc., and the amount used is 0.05 part to 1 part of aldehyde.
1.5 parts, preferably 0.1 to 0.75 parts. Examples of solvents that are azeotropic with water include benzene, toluene, xylene, chlorobenzene, and heptane. The reaction temperature is the temperature at which the azeotropic solvent and water are azeotropically distilled out of the system depending on the reaction conditions. Generally, it will be between 60℃ and 120℃. The reaction is usually carried out under normal pressure, but it can also be carried out under increased pressure or reduced pressure. Specific examples of substituted or unsubstituted aryl aldehydes represented by the general formula () that are the subject of the present invention include (o-, m-, p-)oxybenzaldehyde, (o-, m-, p-) nitro Benzaldehyde, (o-,m-,p-)cyanobenzaldehyde, (o-,m-,p-)methoxybenzaldehyde, (o-,m-,p-)acetoxybenzaldehyde, (o-,m-,p- ) formylbenzamide, (o-,m-,p-)formyl-N,N-dimethylbenzamide, (o-,m-,
p-) Chlorbenzaldehyde, (2,4-,2,
5-,2,6-,3,4-)dichlorobenzaldehyde, (o-,m-,p-)brombenzaldehyde, (2,4-,2,5-,2,6-,3,
4-) Dibromobenzaldehyde or substituted arylbenzaldehyde having two or more types of the above substituents. Among them, p-oxybenzaldehyde and p-nitrobenzaldehyde are particularly effective for the method of the present invention. The inorganic acid salt of hydroxylamine used in the present invention is hydroxylamine sulfate or hydroxylamine hydrochloride. The nitrile obtained by the method of the present invention can be easily recovered from the reaction system by operations such as extraction or distillation, and depending on the purpose of use, it can be further purified by known purification techniques. The present invention will be described in detail below using specific examples, but the present invention is not limited thereto. Example 1 P-oxybenzaldehyde in a 50ml flask
503 mg of hydroxylamine hydrochloride, 323 mg of hydroxylamine hydrochloride, and 10 ml of toluene were charged, a Dean Stark dehydrator was attached to the flask, and the water in the distillate was decomposed by heating for 4 hours while stirring with a magnetic stirrer, and the toluene was refluxed. After the reaction was completed, water and methyl isobutyl ketone were added to the reaction solution, and the mixture was stirred and then separated. The aqueous layer was extracted again with methyl isobutyl ketone, combined with the previous organic layer, and subjected to gas chromatography (5% PEG20M, 0.5 m, 190° (held for 4 minutes) to 220° (held for 5 minutes), 2°C/min). The product was analyzed by . As a result of analysis, the conversion rate of p-oxybenzaldehyde was 100%, p-cyanophenol was 449 mg (yield 91%), and p-oxybenzaldehyde oxime was 6.1 mg (yield 1.1).
%) was found to be generated. Example 2 Using 1.0 g of p-oxybenzaldehyde, 768 mg of hydroxylamine sulfate and 10 ml of toluene,
The reaction was carried out in the same manner as in Example 1 except that the reaction time was changed to 30 minutes. As a result, it was found that the conversion rate of p-oxybenzaldehyde was 100%, the yield of p-cyanophenol was 72%, and the yield of p-oxybenzaldehyde oxime was 0%. Examples 3-8 1.0 g of p-oxybenzaldehyde, 672 mg of hydroxylamine sulfate, 10 ml of toluene and
The reaction was carried out in the same manner as in Example 2, except that the amide, reaction temperature, and reaction time shown in the table were used, and the results shown in Table 1 were obtained.

[Table] Example 9 300 g of p-oxybenzaldehyde, 72 ml of 10% hydroxylamine sulfate aqueous solution (hydroxylamine content 0.247 mol), 15 ml of formamide, and 300 ml of toluene were charged into a 500 ml 4-necked flask, and a reaction apparatus similar to that of Example 1 was set up. The reaction was carried out for 4 hours at 110°C. After the reaction is complete, add 9.2g of 28% caustic soda aqueous solution and water.
When 25 ml of p-cyanophenol was added and stirred, the reaction solution separated into three layers, with 99% of the produced p-cyanophenol present in the top layer and middle layer, and 1% p-cyanophenol in the aqueous layer.
- Contains cyanophenols. The conversion rate of p-oxybenzaldehyde was 100%, the yield of p-cyanophenol was 94%, and the yield of p-oxybenzaldehyde oxime was 0.2%. Example 10 501 mg of p-nitrobenzaldehyde, 272 mg of hydroxylamine sulfate, 0.1 ml of DMF, and 5 ml of toluene were charged into a 25 ml flask, and heated under reflux for 6 hours with stirring using the same reaction apparatus as in Example 1. After the reaction was completed, the same post-treatment as in Example 1 was carried out,
As a result of gas chromatography analysis, p-
It was found that the conversion of nitrobenzaldehyde was 88% and the yield of p-nitrobenzonitrile was 80%.

Claims (1)

[Claims] 1 Aldehyde represented by the general formula () (in the formula,
R represents a substituted or unsubstituted aryl group. ) In the reaction of synthesizing the corresponding nitriles from RCHO () and an inorganic acid salt of hydroxylamine, water generated as the reaction progresses in a heated reactor is discharged from the reaction system together with a solvent that is azeotropic with water. A method for producing nitriles, characterized by azeotropic distillation. 2. The method for producing nitriles according to claim 1, wherein the reaction for synthesizing nitriles is carried out in the presence of amides. 3 The substituent of the substituted aryl group represented by the general formula () is a hydroxyl group, a nitro group, a cyano group,
The method according to claim 1 or 2, which is an alkoxyl group, an alkoxycarbonyl group, an amide group, or a halogen atom. 4 The substituted aryl aldehyde represented by the general formula () is parahydroxybenzaldehyde,
3. The method according to claim 1, wherein the nitrile compound obtained therefrom is balacyanophenol. 5 Claims in which the amides are formamide, N-methylformamide, N,N-dimethylformamide, acetamide, N-methylacetamide, N,N-dimethylacetamide, N-methylpyrrolidone, or hexamethylphosphorictriamide. The method according to item 2, 3 or 4. 6 Solvents that azeotrope with water include benzene, toluene,
The method according to claim 1, 2, 3, 4 or 5, wherein xylene, chlorobenzene or heptane is used.