JPS58172357A - Preparation of nitrile - Google Patents

Abstract

PURPOSE:To prepare a nitrile useful as an intermediate of agricultural chemicals, etc., easily, by heating an aldehyde and an inorganic acid salt of hydroxylamine in the presence of a solvent which forms azeotropic mixture with water, and removing the produced water from the reaction system by azeotropic distillation. CONSTITUTION:An aldehyde of formula RCHO (R is substituted or unsubstituted aryl) is made to react with an inorganic acid salt of hydroxylamine to obtain the corresponding nitrile of formula RCN. The reaction is carried out by heating the reaction mixture in the presence of a solvent (e.g. benzene, toluene, etc.) which forms an azeotropic mixture with water, thereby removing the produced water from the system by azeotropic dehydration. Addition of an amide (e.g. formamide) to the system improves the selectivity of nitrile. The addition of an acid catalyst is not necessary in the above process, and it is supposed that the inorganic acid which is expected to be separated by the production of oxime serves as an acid catalyst. The lowering of the catalytic effect can be prevented, and the equilibrium of the reaction can be shifted toward the nitrile-formation side by the azeotropic dehydration.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an improved method for producing nitriles such as aldehyde λ, etc. ! Look closely at the general formula (
1) A method for synthesizing nitriles (II) with Hr5 from the aldehyde RcHo (1) (where R represents a conversion or a conversion of aryl) and hydroxylamine. It is.

-2H2O([) The nitrile that is the object of the present invention! iFl is an important fk raw material for pharmaceutical and agricultural intermediates; It is known to be an important intermediate for capsule drugs such as -cyanophenyl phospho(Omega) ate) and bromoxynil (q-cyano-2,〆-co)bromophenol). .

There are various methods for synthesizing nitriles from aldehydes, but the most representative one is to synthesize oximes from aldehydes and hydroxylamine/inorganic*i, and then to synthesize oximes in the coexistence of acid catalysts after isolation. A method of producing a nitrile through a dehydration reaction (this is abbreviated as the two-step method) and a method of producing a nitrile through a direct dehydration reaction of an aldehyde and hydroxylamine/inorganic IW salt without removing the oxime (
This is abbreviated as the 7-step method).

The present inventors have developed a two-stage method (Patent Application Show! 1/9/2/2013) in which the reaction is carried out while performing azeotropic dehydration, and the acid catalyst used is different from the conventional method. We discovered that nitriles can be obtained with a large reduction in yield and in good yields, and that by coexisting amides, side reactions can be suppressed and the selectivity of the 7 reactions can be further improved, and we applied for a patent. It's inside. Furthermore, we
In the synthesis of nitriles from aldehydes, we focused on the fact that a seven-step method for directly producing nitriles from aldehydes has many advantages, such as simplicity and simplicity, compared to a two-step method for isolating oxime intermediates. , continued to consider the chapter.

By the way, various K4 methods are known for directly obtaining the corresponding nitrile from an aldehyde without isolating the fludoxime (seven-step method). For example Gep, nffq#
2. θ/&, the one who disclosed to Akira? ! -,” 5ynth*e
l s(/?7?) 722'Disclosure method,'
Chpm, B@n /θ7°/, 22J (/974t
) “The method of disclosure, '5ynthesis (/97
/ ) 739' discloses the method, JP-A-Sho! 6-/Iwo, the method of disclosure to the funeral,” Re1v, C!him, Acta
! 9, br4 (/?7+)' and the like are known. However, these methods require the use of large amounts of highly corrosive formic acid, the use of highly toxic selenium dioxide as a catalyst, and the use of unique hydroxylamine derivatives that are difficult to obtain industrially. Since it is necessary to use an arbitrary dehydrating agent in an amount equal to or more than the aldehyde in moles, XA-r is too difficult to implement as an industrial process.

The present inventors have discovered that inorganic P of aldehydes and hydroxylamine
As a result of investigation into the reaction (7-step method) for obtaining nitriles from Phanawa, it was found that in the presence of a solvent that can azeotrope with water, the inorganic acid of aldehyde and hydroxylamine It has been found that nitrile can be easily obtained by mixing nitrile with salt.

That is, the present invention is directed to the dehydration reaction of an aldehyde and an inorganic acid salt of hydroxylamine to a nitrile, in which water generated as the reaction progresses is quickly distilled out of the reaction system at a certain point together with a solvent that is azeotropic with water. As a result, the Sakisui reaction can be achieved without adding a catalyst or dehydrating agent, and the selectivity from aldehydes to nitriles is improved by adding a small amount of amides to the reaction system. The present invention relates to a method characterized in that the desired nitrile can be obtained in high yield.

The method of the present invention is the same in terms of methodology as the two-step method previously filed by the present inventors with the addition of azeotropic amide. It was unexpected that the azeotropic dehydration method and the addition of an amide would be effective even in the case of synthesizing nitriles in seven stages from acid pipes. Furthermore, there is a major difference in that while the one- and two-stage process requires the addition of an acid catalyst, the seven-stage process of the present invention does not require the addition of an acid catalyst. This is presumably due to hFF as described below.

In other words, if we assume that the membrane properties go through an oxime intermediate in the reaction contact, an acid catalyst will be necessary for the dehydration reaction (according to conventional knowledge), but one of the seven-step methods is The idea is that when oxime is produced from aldehyde and hydroxylamine/mmp salt, oxime is liberated at the same time, and nitrile is produced by acting as an acid catalyst.

The effect of mutual bird tax water at the intersection of wood inventions is the above-mentioned Wj111
It is thought that the purpose is to prevent the 1# fh stage from being weakened by the water produced and to shift the equilibrium to the nitrile production side.

On the other hand, the effects of amides that are useful in improving reaction selectivity can be considered as follows. That is, one is the control of the acid strength of the dipping acid catalyst, and the other is the one-time control. For example, hydroxymamine
When Hananchu is used, this may be because the acid strength of the Hanaka suiho, which is liberated as the reaction progresses, is relatively strong fk, or because some of it escapes from the system as Hc-e gas during the azeotropic reaction. mosquito,
In some cases, nitriles can be obtained with good selectivity even without adding amides to the reaction, but when hydroxylamine/sulfate is used, the selectivity of the reaction is poor, probably due to the strong acid strength of the liberated sulfuric acid. It will decrease slightly. The reason why the effect of adding amides is particularly pronounced when this hydroxylamine sulfuric acid bed is used is presumed to be due to the neutralizing effect of amide clusters on sulfuric acid. More hydroxylamine! When using an aqueous solution of R# Hanawa, the reaction system should be a two-dimensional system in which the azeotropic solvent is a hydrocarbon or a halogenated hydrocarbon (the aldehyde should be placed in both layers), It is also possible that the 7-amides are useful for improving the weldability between the single layers.

(Amides used in this reaction include, for example, formamide, jl-methylformamide, and N.

Examples include N-dimethylformamide, acetamide, N-methylacetamide, N,N-dimethylacetamide, N-methylpyrrolidone, hexamethylphosphoric triamide (1 (ifP)), and the amount used is aldehyde/Ikuni. 0.0j parts to /, ! parts, preferably θ
,/~Q, is Shibe.

Examples of pestles that are azeotropic with water include benzene, toluene, xylene, chlorobenzene, and hebutane.

The reaction temperature q is @11 at which the azeotropic solvent is azeotropically distilled out of the system depending on the reaction conditions. Generally 10℃～/
Between 2o'c and power.

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 the substituted or unsubstituted aryl aldehyde represented by the general formula (1), which is the counterpart of the present invention, are as follows:
0+ ”-+ p) size xybenzaldehyde, (o −
, rn-, v-) nitrobenzaldehyde, (Osm
+p) cyanobenzaldehyde, (or ” r
T” methoxybenzaldehyde, (o−+ m +
p) Acetoxybenzaldehyde, (o-, m-
.

Mi p-)*Rumirubenzaagogo4do, (o-, m-.

p-) * Lumiru N, N-dimethylbenzamide, (o
-+ m-r p-) chlorobenzaldehyde, (co,4t-,co,!-,co,ni-13Iter)dichlorobenzaldehyde, (o-,m+.

p-)Propentabenzaldehyde, (Ko, Ku1.2.j
-, Ko, J-1! , 4t-) Dibromobenzaldehyde is a substituted arylbenzaldehyde having one or more of the above-mentioned gastric groups.3. It is y. Among them, the effect of the method of the present invention! [The most significantly expressed are p-oxybenzaldehyde and p-nitrobenzaldehyde.

The inorganic acid group of hydroxylamine used in the present invention is hydroxylamine sulfate or hydroxylamine salt.

The nitrile obtained by the method of the present invention can be easily recovered from the reaction system by operations such as paper extraction or distillation, and depending on the purpose of use, it can be further purified by known purification techniques.

The present invention will be explained in detail below using specific examples, but the present invention is not limited thereto.

Example/ ! 7 parts by weight of p-oxybenzaldehyde, 323 parts of hydroxylamine acid salt, and 7011 toluene were placed in an O- flask, and a Dean-Stark dehydrator was attached to the flask. After the reaction was completed, water and methyl isobutyl ketone were added to the reaction solution, and the mixture was stirred and separated. Is the aqueous layer methyl isobutyl keto again? Extracted with Samai organic coral, and subjected to chromatography (jlKPKG, 20M, 0.3m).
.

/ 0° (held for 9 minutes) ~ 2.20° (held for 5 minutes),
As a result of the analysis of the product, the conversion rate of ℃-oxybenzaldehyde was /θθ〇, p-cyanophenol was 9% (yield: 9%) and p-oxybenzaldehyde was 9% (yield: 9%).・Oxime is j, /I
It was found that IF (yield/,/regret) was produced.

Example: p-oxybenzaldehyde 7.0 & hydroxylamine sulfate 176? using town and toluene IC) xl,
The reaction was carried out in the same manner as in Example except that the reaction time was changed to 30 minutes. As a result, the conversion of p-oxybenzaldehyde was $100, and the yield of p-cyanophenol was 7.21.
It can be seen that the yield of p-oxybenzaldehyde oxime is O.

! ! Example 3~! p-oxybenzaldehyde/, Of! , 7λ cape to hydroxylamine sulfate f9I salt, toluene 101 and 1s
The reaction was carried out in the same manner as in Example 1, except that the amide, reaction a, and reaction time shown in the table were used, and the results shown in Table 1 were obtained.

Table 1 Seishin results *1 In the table, 1 and abbreviations indicate the following.

FA: Formamide XMIP: N-methylformamide DMF! N,N-dimethylformamide Mum: N-methylacetamide 1: Hexamethylphosphoric triamide*2 The amount added is the amount of amide added to 7 parts by weight of p-oxybenzaldehyde (state: parts by volume) ).

Example 2 p-oxybenzaldehyde 3θogJi.

Add 72 ml of hydroxylamine sulfate aqueous solution (hydroxylamine content O-ρmo13), formamide/jt/,) toluene: 100 ml.

The mixture was charged into a wLt\Low flask and reacted at 710°C for a period of time using the same reaction apparatus as in the actual example. After the reaction 2/
When 9.2 g of % aqueous sodium hydroxide solution and 2.1% of water were added and stirred, the reaction liquid separated into 3 layers, with 99% of the p-cyanophenol produced in the top layer and middle layer 1, and water. The layer contained p-cyanophenol. The conversion rate of f&f, p-oxynzaldehyde is 10
0%, p-cyanophenol yield is 911t%%p-
The yield of oxybenzaldehyde oxime was 0.2%. Example 10 p-Nitrobenzaldehyde jj-0/"l, 2 hydroxylamine sulfate cores, DMFO0/d1 and toluene! ml f2jdy were charged in a flask and stirred using the same reaction apparatus as in Example/ After completing the reaction, which was heated under reflux for 6 hours, the same post-treatment as in Practical P1 Example 1' was carried out, and gas chromatography was performed. It was found that the yield was 10 cm.

Patent applicant: Sumitomo Chemical Niji Co., Ltd. Patent attorney Moroishi Hikaru: Station ・′ 417-

Claims (1)

[Claims] (1) A water-soluble aldehyde represented by the general formula (1) (in the formula,
Rii represents a substituted or unsubstituted 7-aryl group. )R
In the reaction of synthesizing the corresponding nitriles, the reaction between cHo (1) and hydroxylamine is such that water, which is produced as a reaction progresses in a sugar-added reactor, is removed from the reaction system together with a solvent that is azeotropic with water. A process for producing nitrile examples, characterized by azeotropic distillation to nitrile. (To) Claim P in which the reaction for synthesizing nitriles is carried out in the presence of amides! ! A method for producing nitriles according to item 1. (3) The substituent of the substituted aryl group represented by general formula (1) is a hydroxyl group, a nitro group, a cyano group, an alfxyl group, a flukoxycarponyl group, or an amide group.
-1 is a halogen atom Claim 7'! + The method described in item 1. (i) The method according to claim 1 or 1, wherein the substituted aryl aldehyde represented by the general formula (1) is parahydroxybenzaldehyde, and the nitrile compound obtained therefrom is paracyanophenol. ) Amides include formamide, N-methylformamide, N, N-dimethylformamide, acetamide, N-methylacetamide, N. Claim No. 3, which is N-dimethylacetamide, N-methylpyrrolidone or hexamethylphosphoric triamide? Or the method described in Section 9. (2) The solvent azeotropic with water is benzene, toluene, xylene chlorobenzene or hebutane, claim 7. ．． 2, 3. The method described in item 1.