JPH0227977B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing m-nitrophenyl alkyl ether, and more specifically, to a method for producing m-dinitrobenzene and lower saturated or unsaturated aliphatic alcohol, aromatic lower alkyl alcohol, alicyclic The present invention relates to a method for producing m-nitrophenyl alkyl ether, which involves reacting alcohols such as group alcohols.

Although m-nitrophenyl alkyl ether is an important compound as a synthetic intermediate for pharmaceuticals and dyes, there is no simple industrial production method, and its development is desired. For example, known methods for synthesizing m-nitroanisole include hydrolyzing m-nitrobenzenesulfonic acid obtained by sulfonating nitrobenzene to synthesize m-nitrophenol and reacting it with methanol;
After synthesizing a diazonium salt from m-nitroaniline obtained by half-reducing dinitrobenzene, m-
A method for producing m-nitroanisole by reacting it with nitrophenol and then methanol is known. In these methods, since the former uses sulfuric acid, the manufacturing equipment is likely to be corroded, and there are problems in the selection of the material and in the treatment of by-product sulfate. On the other hand, the latter method requires a complicated synthetic method, including semi-reduction of dinitrobenzene and synthesis of a diazonium salt. Furthermore, as these known improvement methods, J.Org.Chem.41,
1560 (1976) describes a method for obtaining the corresponding nitroanisole by reacting m-dinitrobenzene and sodium methylate at 25°C for 16 hours using hexamethylphosphoramide as a solvent, and in JP-A No. 54-39030. discloses a method of reacting dinitrobenzene with an alkali metal alcoholate in the presence of a macrocyclic polyether to obtain the corresponding nitrophenyl alkyl ether or nitrophenyl aryl ether.

However, although the former method is simple, it requires a long reaction time, and the solvent used is expensive and carcinogenic.The latter method also requires the use of expensive crown ether, which cannot be recovered. This method is also difficult and cannot necessarily be said to be an advantageous method from an industrial perspective.

As a result of intensive studies on an industrially advantageous method for producing m-nitrophenyl alkyl ether, the present inventors have discovered that a direct reaction between dinitrobenzene and alcohol in the presence of an alkali metal carbonate or bicarbonate is carried out. We have discovered a method for producing nitrophenyl alkyl ether.

That is, the present invention provides m-dinitrobenzene and alcohols in water and/or a polar organic solvent in the presence of an alkali metal carbonate or hydrogen carbonate.
This is a method for producing m-nitrophenyl alkyl ether, which is characterized by carrying out the reaction at a temperature of 100°C or higher.

Examples of the alkali metal carbonate or hydrogen carbonate used in the present invention include carbonates such as lithium carbonate, sodium carbonate, potassium carbonate, lithium hydrogen carbonate, sodium hydrogen carbonate, and potassium hydrogen carbonate. Of course, the alkali metal carbonate or hydrogen carbonate that can be used in the present invention is not limited to those exemplified here, and among these, sodium carbonate, sodium hydrogen carbonate, potassium carbonate, and potassium hydrogen carbonate are particularly preferred.

The carbonate or hydrogen carbonate of these alkali metals is used in an amount of 0.5 or more molar ratio, preferably 1.0 to 10 molar ratio, to m-dinitrobenzene. m-
In the reaction of dinitrobenzene and alcohols, it is not possible to synthesize m-nitrophenyl alkyl ether in the absence of alkali metal carbonate or hydrogen carbonate, but if they are added in a molar ratio of 0.5 or more to m-dinitrobenzene, m by adding
-Nitrophenyl alkyl ether can be synthesized. Also, these for m-dinitrobenzene
Although it may be used in a molar ratio of 10 or more, the effect hardly changes even if the molar ratio is more than 10, and it is economical to use within this range and the effect is sufficient.

Examples of alcohols to be reacted with m-dinitrobenzene in the present invention include methanol, ethanol, n-propanol, iso-propanol,
Allyl alcohol, n-butanol, iso-butanol, sec-butanol, t-butanol, n
-amyl alcohol, iso-amyl alcohol,
t-amyl alcohol, buten-2-ol-
1. Lower saturated or unsaturated aliphatic alcohols such as propargyl alcohol and 3-methylbuten-1-ol 3, lower alkyl-substituted aromatic alcohols such as benzene alcohol and ethylbenzene alcohol, and alicyclic alcohols such as cyclohexanol etc. can be used. Of course, the alcohols that can be used in the present invention are not limited to those exemplified here. Further, the amount of alcohol used is preferably at least 1 molar ratio to m-dinitrobenzene, and a large amount can also be used to serve as a reaction solvent.

The solvent used in the reaction of the present invention is water and/or a polar organic solvent, and any polar organic solvent may be used as long as it dissolves at least carbonate or hydrogen carbonate to some extent at a temperature of 100°C or higher. , these include, for example, formamide, N-methylformamide, N,N-dimethylformamide, N,N-diethylformamide, acetamide, N-methylacetamide, N,N-dimethylacetamide, N-methylpropionamide,
Amides such as N, N, N', N'-tetramethylurea, 2-pyrrolidone, N-methylpyrrolidone, hexamethylphosphoramide, 1,3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, In addition, dioxane, trioxane, tetrahydrofuran, diethylene diglycol, dimethyl ether, methanol, ethanol, n-propanol, iso-propanol, n-butanol, iso-butanol, Sec-butanol, t-butanol, n-amyl alcohol, iso- amyl alcohol, t-amyl alcohol, butene-2
-ol-1, propargyl alcohol, 3-methylbuten-1-ol-3, benzyl alcohol, etc., and these are used alone or as a mixed solvent with water. Among polar solvents, aprotic polar solvents are particularly preferable, such as amide organic solvents and dimethyl sulfoxide, which not only dissolve carbonates and hydrogen carbonates but also have good solubility in m-dinitrobenzene. It is a preferred solvent, which can shorten the reaction time and improve the yield of the reaction product.

In the present invention, water alone can be used as a solvent, but when alcohols with high solubility in water are used for the reaction, the alcohol can also be used as a mixed solvent with water, so the alcohol used for the reaction can be used for the reaction. Use at least an equivalent amount depending on the concentration of m-dinitrobenzene in the system.

In the present invention, the reaction hardly progresses at low temperatures, and the reaction temperature is at least 100°C or higher, preferably
It is necessary to maintain the temperature within the range of 120°C to 180°C. Any temperature above 100°C may be used, but unnecessary high temperatures should be avoided since by-products will be produced at high temperatures. Especially when using amides as a solvent,
The reaction is carried out at a temperature below the decomposition temperature of the amide compound used, since the amide decomposes and reacts with the target product, resulting in an increase in by-products. For example, when using N,N-dimethylformamide as a solvent,
Since decomposition of NN-dimethylformamide occurs at around 155°C, in this case, the reaction may be carried out at 140-150°C. Furthermore, when water, a low-boiling organic solvent, or a low-boiling alcohol is used in the reaction, the reaction must be carried out under pressure in order to maintain the reaction temperature at 100°C or higher.

The time required for the reaction depends on the type of reactants, temperature,
It varies depending on the amount of carbonate and hydrogen carbonate, but usually 3
~20 hours is sufficient. For example, when m-nitroanisole is synthesized using methanol in NN-dimethylformamide, a reaction time of 4 to 8 hours is preferred.

In addition, in the present invention, when a lower aliphatic secondary alcohol such as isopropyl alcohol is used in the reaction or as a solvent, the alcohol acts to reduce m-dinitrobenzene in the reaction system, resulting in by-products such as azoxy compounds. Since the concentration of m-dinitrobenzene tends to increase, it is preferable to conduct the reaction at a dilute concentration of m-dinitrobenzene.

According to the method of the present invention, the reaction is rapid, the reaction time is short, the conversion rate of m-dinitrobenzene is high, and m-nitrophenyl alkyl ether can be produced in high yield. Since there is almost no m-dinitrobenzene, cooling,
After separation, the desired product can be easily obtained by ordinary distillation or extraction separation.

Examples are shown below.

Example 1 300 g of N,N-dimethylformamide, 90 g (2.8 mol) of methanol, and m-dinitrobenzene were placed in an autoclave equipped with a sampling outlet.
84.1 g (0.5 mol) and 150 g (1.8 mol) of sodium hydrogen carbonate were charged, and the mixture was heated and stirred at 150°C for 6 hours. The internal pressure of the autoclave reached around 6 Kg/ ^cm2 , and after confirming the disappearance of m-dinitrobenzene, it was left to cool to room temperature, the insoluble matter, which was mainly sodium bicarbonate, was separated, and the liquid was distilled under reduced pressure to a boiling point of 135. ~136℃ (13
51.3 g (yield 70.4%) of a fraction (mmHg) was obtained. At room temperature, this fraction is yellow in color with a melting point of 38-39℃, and the elemental analysis values are carbonic acid, 54.50, hydrogen 4.20, nitrogen 9.42, and oxygen.
It was confirmed that it was m-nitroanisole.

Example 2 The same method as in Example 1 was used except that 300 g of water was used in place of the N,N-dimethylformamide used in Example 1, and the same amount of soda carbonate was used in place of sodium bicarbonate, at 150°C. The reaction was carried out by heating and stirring for 6 hours. After cooling to room temperature and separating the insoluble components, which are mainly high-boiling by-products, the suspension was diluted with benzene.
Extraction was performed twice with 500 ml and distilled in the same manner as in Example 1 to obtain 30.6 g (yield 40.0%) of m-nitroanisole.

Example 3 Into the same type of autoclave 2 used in Example 1, 600 g of NN-dimethylformamide, 120 g (2.0 mol) of iso-propyl alcohol, and potassium carbonate were added.
41.4g (0.3mol), m-dinitrobenzene 20.2g
(0.12 mol) was charged, and the reaction was carried out by heating and stirring at 150°C for 8 hours. After cooling to room temperature, insoluble matter, mainly potassium carbonate, was separated, and the liquid was subjected to vacuum distillation to obtain 20.4 g (yield: 94%) of a fraction with a boiling point of 150-160°C (24 mmHg).

As a result of boiling point and elemental analysis, this product was confirmed to be m-nitrophenyl isopropyl ether.

Example 4 300 g of dimethyl sulfoxide and benzyl alcohol were placed in the same autoclave as in Example 1.
108g (1.0 mol), m-dinitrobenzene 84.1g (0.5
mol) and 150 g (1.5 mol) of potassium hydrogen carbonate were added, and the mixture was heated and stirred at 180°C for 6 hours. After cooling, insoluble matter was separated, and dimethyl sulfoxide in the liquid was distilled off under reduced pressure. As a result of gas chromatographic analysis of the remaining 157 g, 57 g (yield 49.8%) of m-nitrophenylbenzyl ether was obtained.

Comparative Example 300g of water and 90g of methanol (2.8
mol), m-dinitrobenzene 84.1g (0.5 mol),
106 g (1.0 mol) of sodium carbonate was charged, and the reaction was carried out under heating under reflux for 6 hours. After reacting for 6 hours, it was left to cool to room temperature, extracted three times with 200 ml of benzene, and the benzene layer was analyzed by gas chromatography. As a result, 81.2 g of m-dinitrobenzene was determined.
No nitroanisole was detected.

Claims (1)

[Claims] 1. In the presence of an alkali metal carbonate or hydrogen carbonate, in water and/or a polar organic solvent at 100°C.
A method for producing m-nitrophenyl alkyl ether, which comprises reacting m-dinitrobenzene and an alcohol at a temperature above. 2. The method according to claim 1, which is carried out at a reaction temperature of 120 to 180°C. 3. The method according to claim 1, wherein the reaction is carried out in an aprotic polar organic solvent.