JPH05246957A - Production of m-nitroacetophenone - Google Patents

Abstract

PURPOSE:To obtain the subject compound having high quality in high yield at a low cost by nitrating acetophenone and purifying the nitrated product by neutralizing in water or an alcohol. CONSTITUTION:Acetophenone is nitrated in an organic solvent (e.g. methylene chloride) with a mixed acid (e.g. sulfuric acid) containing nitric acid at <=0 deg.C, preferably -20 to 0 deg.C to obtain crude m-nitroacetophenone containing a mixture of isomers. The crude product is purified by treating with a neutralizing agent (e.g. NaOH) in water and/or an alcohol at 0-100 deg.C. The nitration of acetophenone can be carried out without using a particular reaction apparatus. A high-quality product containing little by-product can be obtained since the reaction is carried out at a minimized nitric acid consumption. The selectivity of m-site is high to enable the separation of m-nitroacetophenone at a low cost.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a method for producing m-nitroacetophenone. m-nitroacetophenone (hereinafter abbreviated as m-NAP) is induced to m-aminoacetophenone by catalytic reduction,
It is used as a starting material for medicines and agricultural chemicals. Further, by reducing-aminating a carbonyl group, α- (3-
Aminophenyl) ethylamine-derived. this is,
As a novel aromatic diamine, it is used as a raw material for polyamide, polyimide, polyamideimide, bismaleimide and epoxy resin. It is also used as a curing agent for other maleimide compounds and epoxy compounds.

[0002]

2. Description of the Related Art Conventionally, a number of known techniques have been reported as a method for producing NAP. For example, Journal of Organic Chemistry (J. Org. Chem.) Vo
l. 11,409 (1946) describes a method of nitrating acetophenone with fuming nitric acid. That is, 94% fuming nitric acid (1.8 kg, 26.8 mol) was cooled to -20 ° C, and then acetophenone (300 g, 2.5 mol) was added to the inside temperature of -15 to -8 ° C.
It takes 30 minutes to charge. Furthermore, -10 to -15 ℃
After reacting for 1 hour with ice water, the mixture is discharged into 4 l of ice water, crude m-nitroacetophenone is precipitated and filtered. The filtrate is neutralized with sodium carbonate and the oily substance is extracted with ether. After removing the ether and distilling under reduced pressure, nitroacetophenones are distilled at 133 to 135 ° C / 4 mmHg after a large amount of the previous fraction. This fraction was cooled in an ice bath to solidify m-
The body is filtered off to obtain 120 g of o-body. Further, the front fraction is redistilled to recover 32.7 g (0.272 mol) of raw material acetophenone. The crude m-NAP in the filter cake was purified with ethanol to obtain 197 g of purified m-NAP (yield 55.4%). However, this method is a method of nitrating while charging acetophenone into fuming nitric acid, and the heat of nitration is so intense that it is difficult to control the reaction temperature. Further, since acetophenone is added to a large excess of fuming nitric acid, there is a drawback that the reacted NAP and acetophenone as a raw material are susceptible to nitric acid oxidation. In addition, since the selectivity to the m-form is low, the yield is low. Further, industrially, this method of introducing acetophenone into nitric acid has a risk of causing a runaway reaction due to oxidation of nitroacetophenone or the like when a large amount is added at one time or the reaction temperature rises during the addition. ..

As a method for improving the above-mentioned method, Chemical Abstracts (Chem. Abst.) Vol. 62, 11725 (196
There is a method described in 5). This method is a continuous process of nitration. Fuming nitric acid (1.54) 210 ml, 90%
Mixture (A) consisting of sulfuric acid 1460 ml, 62% fuming sulfuric acid 370 ml, 95% acetophenone 500 ml, 90% sulfuric acid (1.8
2) Add 0 ml of mixed solution (B) consisting of 1460 ml and fuming sulfuric acid 270 ml.
Cool to -5 ° C and then charge solution A and solution B in equal proportions at -8 to -3 ° C into the reactor. After reacting for 30 to 35 minutes, the solution is transferred to a reaction apparatus cooled to -6 to -3 ° C, and a certain amount is discharged into ice water to precipitate crystals. The precipitated crystals are filtered and the filter cake is washed with water until neutral. afterwards,
Further, by washing with 75% hydrous ethanol, m-NAP was obtained with a yield of 77%. This method is a nitration method by simultaneous dropping, and although the crude yield of m-NAP is high,
Using a large excess of sulfuric acid to suppress reaction heat as much as possible,
Further, since fuming nitric acid is used, there is a defect that the target NAPs are easily oxidized. Industrially, not only is a device with a high cooling efficiency required, but also a treatment cost for excess acid waste liquid is required, so it cannot be said to be an economically advantageous method. Further, in order to obtain high quality m-NAP, a purification step such as removal of isomers and acid components contained in the crystal is required.

On the other hand, German Patent 1284958 also describes a continuous process for nitration. Specifically, 3.0 l (A) of a mixed acid of sulfuric acid and nitric acid (volume ratio: 5.25: 1.0) was cooled to 0 ° C., and 360 g (3.0 mol) of acetophenone was added to 2 g.
It is cooled to 0 ° C. (B), and this A: B is flown into the reactor at a rate of 8.3: 1 at a rate of 10 ml / sec. Cooling water of 11.5 ℃ is flown outside the reactor, but the internal temperature is 60
Rise to ℃. The reaction time during this period is 8 to 9 minutes. Immediately after the reaction, the crystals are discharged into ice water and the precipitated crystals are filtered. The filter cake was washed, extracted with methylene chloride, and the methylene chloride layer was further washed with water, and then the solvent was distilled off to obtain 450 g of semi-crystalline crude NAP. Most of the o-form contained in this was recovered. After that, crude m-NAP is obtained. By refining the obtained crude crystals with ethanol,
-260 g of NAP (54% yield) is obtained. In addition, as the o-form, the recovered o-form is purified by distillation to obtain 1
02g (yield 20%) is obtained. This method is also a continuous process similar to the above, but since it is carried out at a relatively high reaction temperature, it is expected that a large amount of oxidized by-products and the like will be mixed in addition to the o-form, and by-products are generated. Since it is removed, the purification yield of the target product must be reduced. Also,
In order to carry out industrially, the target product is once extracted with an organic solvent, so that a step of recovering the organic solvent is required. Although the crude yield is improved, it contains many by-products, which complicates the purification operation and makes it difficult to obtain a target product of high quality.

The above-mentioned publicly known documents and the methods of the prior arts all involve nitration of acetophenone by using sulfuric acid and nitric acid in excess, so that there are problems such as waste acid treatment and cooling efficiency is high. Special reactors are needed to improve. Further, in terms of selectivity to m-form and yield, it is still insufficient and no industrially advantageous method has been found. German patent 93514 is a further improvement of the above nitration continuous process. Specifically, a mixed solution of concentrated sulfuric acid and 65% nitric acid (volume ratio 11: 4) (A),
Mixture of concentrated sulfuric acid and acetophenone (4: 1 by volume)
(B) is cooled to 20 ° C., and the mixed liquids A and B are charged at a volume ratio of 1: 2 into a DC reaction tube cooled to −8 to −5 ° C. The residence time of the reaction solution at this time is 9 to 12 minutes. After the reaction solution was discharged into ice water, the precipitated crystals were filtered, the filter cake was thoroughly washed with water, then washed with 80% water-containing methanol and dried to obtain m-NAP (yield 78
%). In this method, the reaction tube must be cooled sufficiently, the nitration time is short, and the temperature rise due to heat generation cannot be avoided, and it is expected that the target substance will be decomposed. Industrially, since sulfuric acid is used in a large excess, the cost of acid treatment affects the cost of the target product. Further, it is clear that a step of removing the isomers and acid components contained in the crystal is required to improve the quality of the target product.

[0006]

The object of the present invention is to nitrate acetophenone to produce m-nitroacetophenone, which is a method for producing industrially high quality m-nitroacetophenone at a high yield and at a low cost. Is to provide.

[0007]

In order to solve the above-mentioned problems, the present inventors diligently studied the nitration conditions of acetophenone and the purification method of m-nitroacetophenone. As a result, acetophenone was added at a temperature below 0 ° C.
After carrying out the nitration, it was found that the objective can be achieved by neutralizing the obtained crude NAP in water or alcohol, and the present invention has been completed. That is, the present invention is to nitrate acetophenone at a temperature of 0 ° C. or lower,
The present invention relates to a method for producing m-nitroacetophenone, which comprises purifying a crude m-nitroacetophenone containing an obtained isomer compound by neutralizing in water or alcohol, and further, to provide a crude m-nitroacetophenone. -The present invention relates to a method for producing m-nitroacetophenone by neutralizing and purifying nitroacetophenone in an aqueous alcohol solution.

When nitrating acetophenone,
By using a mixed acid containing nitric acid slightly exceeding the theoretical amount, m-nitroacetophenone (m-NAP) can be obtained in good yield without lowering the selectivity to m-form. Then, the crude m-NAP containing the obtained isomer is neutralized in water or an aqueous alcohol solution to separate and remove by-products such as o-NAP, o-, m-nitrobenzoic acid, and acid components. Is a method of obtaining highly pure m-NAP. The acetophenone used in the production method of the present invention has a purity of 98% or more and is easily available industrially.

The sulfuric acid used in the present invention has a DVS (ratio of the total amount of sulfuric acid to the total amount of water) in the range of 15 to 100, and the amount used is 1 with respect to acetophenone.
~ 9 times by weight. Even if the amount used exceeds 8 times, there is no problem in the reaction, but not only the volume efficiency is lowered, but it is economically unfavorable in terms of waste acid treatment cost and the like. Preferably 3 to
6 times the amount. The nitric acid used in the present invention is 60 to 98.
% Concentration range is used. When the nitric acid concentration is high, the target substance tends to be easily oxidized, and therefore a high concentration is not preferable. The amount of nitric acid used is 0.9 to 1.3 equivalents to 1 equivalent of acetophenone. 1.
There is no problem even if it is 3 equivalents or more, but if it is used in an excessively large amount, NAP is likely to be oxidized and the yield tends to be lowered, which is not preferable. The amount of sulfuric acid used for preparing the mixed acid is preferably 1.0 to 3.0 equivalents to 1 equivalent of nitric acid. In this case, the sulfuric acid concentration and the amount used differ depending on the concentration of nitric acid used, but the sulfuric acid concentration is generally set within the range of 70 to 100%.

In the nitration reaction of the present invention, an organic solvent inert to the reaction can be used in combination, and the amount of sulfuric acid used can be reduced by using the organic solvent in combination. Examples of the organic solvent that can be used in combination include methylene chloride, chloroform, carbon tetrachloride, 1,1-dichloroethane, ethylene chloride, 1,1,1-trichloroethane,
Halogenated hydrocarbons such as 1,1,2-trichloroethane, 1,1,1,2-tetrachloroethane and tetrachloroethylene are used. When such an organic solvent is used in combination, the amount used is 1 to 10 with respect to acetophenone.
Double amount is preferred. When an organic solvent is used in combination, for example, when ethylene chloride is used, acetophenone is initially dissolved in the organic solvent, but upon contact with sulfuric acid, a salt of acetophenone and sulfuric acid is formed, and the salt is transferred to the sulfuric acid layer. After the reaction, the reaction mixture has two layers, so that the crude m-NAP can be easily isolated by allowing the lower sulfuric acid layer to discharge into water after standing. Further, the ethylene chloride in the upper layer can be reused as it is.

The nitration reaction temperature in the present invention is 0 ° C.
It is below, preferably in the range of -20 to 0 ° C, and more preferably in the range of -10 to -5 ° C. At -20 ° C or lower, there is no problem in the reaction, but an efficient device such as cooling equipment is required. At 0 ° C. or higher, there is a tendency that the number of o-forms and by-products accompanying oxidation increase. The reaction time depends on the amount of sulfuric acid and the sulfuric acid concentration, but is about 1 to 10 hours, and about 2 to 5 hours is sufficient.

After the reaction, the reaction solution obtained in the above reaction is
Place in ice water to precipitate the product, filter to obtain crude m
-Get NAP. About the obtained crude m-NAP,
Purification by neutralization in water and / or alcohol according to the method of the present invention. Examples of alcohols used for purification of crude NAP include methanol, ethanol, n-propyl alcohol, iso-propyl alcohol, n-butyl alcohol, sec-butyl alcohol, iso-butyl alcohol, tert-butyl alcohol, 1- Pentanol, 2-pentanol, 3-pentanol, 1-hexanol, cyclohexanol, etc. are mentioned. Preferably, methanol, ethanol or iso-propyl alcohol is used. The amount of water or alcohol used during purification is preferably 1 to 5 parts by weight based on the crude NAP. There is no problem even if it is used in excess, but the solubility of the target substance lowers the yield, and it is economically disadvantageous in terms of volumetric efficiency reduction and solvent recovery.

As the neutralizing agent used in the method of the present invention, an alkali metal or alkaline earth metal hydroxide,
Carbonates or bicarbonates, ammonia or usual organic amines are used. For example, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium hydrogen carbonate, potassium hydrogen carbonate, magnesium oxide, lithium hydroxide, ammonia, triethylamine,
Examples include triethanolamine and pyridine. These neutralizing agents may be dissolved in water as long as they are solid. The amount to be used may be an amount necessary to neutralize the pH value within the range of 5 to 7. When the pH value is 7 or more, the amount of coloring components increases, the quality deteriorates and the yield decreases.
This neutralization treatment is carried out in the temperature range of 0 to 100 ° C., but can be carried out in an alcohol or an aqueous alcohol solution in a dispersed or dissolved state.

[0014]

EXAMPLES The present invention will now be described in more detail by way of examples, which should not be construed as limiting the invention.
The analysis of the reaction solution and m-NAP was carried out by gas chromatography and liquid chromatography. Gas chromatography analysis conditions GC-12A (Shimadzu) Column: 10% Silicon OV-17 Filler: Celite 545, AW, DMCS, 60-80
mesh, 2 m Col temperature: 210 ° C. Inj temperature: 230 ° C. Liquid chromatography analysis conditions Column: YMC-pack, A-303 (S-5, 12
Mobile phase: Acetonitrile: Water = 60:40 (Water adjusts 0.005 mol / l of sodium heptane sulfonate to pH 2.2-2.5 with 85% phosphoric acid) Detector: 875-UV , 254 nm (JASCO) Flow rate: 0.45 ml / min (53.0 kg / cm ² )

Example 1 In a container equipped with a stirrer, 180 g of 94% sulfuric acid (DVS
15.67, 6 times amount), and after cooling to -10 to -15 ° C, 30 g of 99.2% acetophenone at the same temperature.
(0.248 mol) was charged over 1 hour. Next, at the same temperature, mixed acid (98% sulfuric acid 33 g (0.33 mol) and 98%
Nitric acid (17.5 g, consisting of 0.273 mol) was charged over 2 hours and reacted at the same temperature for 2 hours. As a result of analyzing this reaction mass by gas chromatography and liquid chromatography, the m-form: o-form ratio = 84.6: 15.4,
The production rates are m-NAP 82.9% and o-NAP 15.1.
%, And the unreacted acetophenone was 1%.
In addition, partially oxidized m- and o-forms of benzoic acid were confirmed. The reaction mass was added to 1.1 liter of ice water at 0 to 15 ° C.
The mixture was discharged at 1, the mixture was stirred at the same temperature for 1 hour, and the pale yellow crystals were filtered. The filter cake was washed with 41 ml of water to obtain 44.5 g of a crude m-NAP wet body. As a result of the analysis, the purity of m-NAP is 7
It was 3.6% and the yield was 80% based on acetophenone. The m-form: o-form ratio was 93: 7. Then, in a container equipped with a stirrer, 44.5 g of crude m-NAP
70.6 g of methanol (2 times amount / NA
P) and 8.5 g of water were charged (adjusted to 80% aqueous methanol solution). Under stirring, at 20 to 25 ° C., 13.2 g (0.0063 mol) of 4% sodium hydrogen carbonate solution was added to adjust the pH.
Was neutralized from 1.6 to 6.7. Then 55-60
After the temperature was raised to 0 ° C. to dissolve it, at the same temperature, 3.2 g (0.0015 mol) of a 4% sodium hydrogen carbonate solution was further added to adjust the pH to 5.6 to 6.7. After cooling to 10 ° C., the mixture was filtered at the same temperature, and the filter cake was washed with 35 g of 80% aqueous methanol solution and dried. Yield 31.8g, purity 9
9.8%, purity conversion yield (vs. acetophenone) 77.5
%, Melting point 76.5 to 78.0 ° C. (manufactured by Metra: fully automatic melting point measuring device PF61 type).

Example 2 In a container equipped with a stirrer, 360 g of 96% sulfuric acid (DVS
24.0, 6 times amount) was charged, and after cooling to -5 to -9 ° C, 60 g of 99.2% acetophenone (0.
(495 mol) was charged over 1 hour. Next, 102.8 g of mixed acid (consisting of 66 g of 96% sulfuric acid (0.647 mol) and 36.8 g of 94% nitric acid (0.549 mol)) was charged over 3 hours at the same temperature, and 2 Reacted for hours. As a result of analyzing this reaction mass by gas chromatography and liquid chromatography, the m-form: o-form ratio = 84.7: 1.
5.3, the production rate is m-NAP 82.0%, o-N
AP was 14.8% and unreacted acetophenone was 2%. In addition, partially oxidized m- and o-forms of benzoic acid were confirmed. This reaction mass was added to 2.3 liters of ice water.
After discharging at -15 ° C and stirring at the same temperature for 1 hour, pale yellow crystals were filtered. The filter cake was washed with 82 ml of water to give a crude m-N
94.5 g of AP wet body was obtained. As a result of analyzing this crude m-NAP, the purity of m-NAP was 69.2%, and the yield was 80%.
(Vs. acetophenone). The m-body: o-body ratio was 92: 7. Next, in a container equipped with a stirrer,
After charging 94.5 g of crude m-NAP, methanol 14
0.8 g (2 volumes / NAP) and 11.1 g of water were charged (adjusted to 80% aqueous methanol solution). 20-2 under stirring
28.5 g of 4% sodium hydrogen carbonate solution (0.
(0136 mol) was added to neutralize the pH from 1.5 to 6.6. After that, the temperature is raised to 55 to 60 ° C. to dissolve,
At the same temperature, 3.1 g of 4% sodium hydrogen carbonate solution (0.0
015 mol) was added to adjust the pH from 6.2 to 6.5. After cooling to 10 ° C., the mixture was filtered at the same temperature, and the filter cake was filtered to 8
It was washed with 70 g of 0% aqueous methanol solution and dried. Yield 6
It was 2.9 g, purity 99.8%, purity conversion yield (relative to acetophenone) 77.0%, and melting point 76.3 to 78.0 ° C.

Example 3 In a container equipped with a stirrer, 360 g of 98% sulfuric acid (DVS
(49.0, 6 times amount) was charged, and after cooling to -5 to -8 ° C, 60 g of 99.2% acetophenone (0.
(495 mol) was charged over 1 hour. Next, 140.2 g of mixed acid (composed of 90 g of 98% sulfuric acid (0.90 mol) and 50.2 g of 69% nitric acid (0.549 mol)) was charged at the same temperature over 4.5 hours, and at the same temperature. The reaction was carried out for 2 hours.
As a result of analyzing this reaction mass by gas chromatography and liquid chromatography, the m-form: o-form ratio = 85.0: 15.
0, production rate is m-NAP 82.0%, o-NAP
It was 14.8% and unreacted acetophenone was 3%. In addition, partially oxidized m- and o-forms of benzoic acid were confirmed. This reaction mass was added to 0.
After discharging at 15 ° C and stirring at the same temperature for 1 hour, pale yellow crystals were filtered. The filter cake was washed with 82 ml of water to give a crude m-NA.
93.0 g of P wet body was obtained. As a result of analyzing this crude m-NAP, the m-NAP purity was 69.4%, and the yield was 7
It was 9.0% (vs. acetophenone). Also, m-
The body: o-body ratio was 92.1: 7.9. After charging 93.0 g of crude m-NAP into a container equipped with a stirrer,
140.0 g of methanol (double amount / NAP) and water 12.
0 g was charged (adjusted to 80% aqueous methanol solution). 4% sodium hydrogen carbonate solution 2 at 20 to 25 ° C under stirring
The pH was neutralized from 2.0 to 5.5 by adding 4.4 g (0.012 mol). Thereafter, the temperature was raised to 55 to 60 ° C. to dissolve it, and then a 4% sodium hydrogen carbonate solution was added at the same temperature.
2 g (0.003 mol) was added to adjust the pH from 5.2 to 6.
Adjusted to 2. After cooling to 10 ° C., the mixture was filtered at the same temperature, and the filter cake was washed with 70 g of 80% aqueous methanol solution and dried. Yield 62.2 g, purity 99.8%, purity conversion yield (relative to acetophenone) 75.9%, melting point 76.7-7.
It was 8.0 ° C.

Example 4 In a container equipped with a stirrer, 180 g of 98% sulfuric acid (DVS
49.0, 3 times amount), 180 g of ethylene chloride (3 times amount)
Was charged, and after cooling to -5 to -8 ° C, at the same temperature,
60 g (0.495 mol) of 9.2% acetophenone was added to 1
Charged over time. Next, 102.5g of mixed acid at the same temperature
(66 g of 98% sulfuric acid (0.66 mol) and 3% of 94% nitric acid)
6.5 g (consisting of 0.545 mol) was charged over 4.5 hours and reacted at the same temperature for 2 hours. As a result of analyzing this reaction mass by gas chromatography and liquid chromatography, the m-form: o-form ratio = 85.0: 15.0, and the production rates were m-NAP80.8% and o-NAP14.2%. Yes, unreacted acetophenone was 3%. In addition, partially oxidized m- and o-forms of benzoic acid were confirmed. After the reaction, the mixture was left standing for 3 hours, and then the sulfuric acid layer was added with 2.5 l of ice water
The mixture was discharged at 0 to 15 ° C. and stirred at the same temperature for 1 hour, and then pale yellow crystals were filtered. The filter cake is washed with 82 ml of water to obtain a coarse m
91.5 g of NAP wet body was obtained. As a result of analyzing this crude m-NAP, the m-NAP purity was 69.7%, and the yield was 78.0% (vs acetophenone). Also, m
The-body: o-body ratio was 92.1: 7.9. A container equipped with a stirrer was charged with 91.5 g of crude m-NAP, and then 138.6 g of methanol (2 times amount / NAP) and 1 part of water.
2.5 g was charged (adjusted to 80% methanol aqueous solution). With stirring, 24.4 g (0.012 mol) of 4% sodium hydrogen carbonate solution was added at 20 to 25 ° C. to adjust the pH to 2.
Neutralized from 0 to 5.5. After that, the temperature was raised to 55 to 60 ° C. to dissolve it, and then 6.2 g (0.003 mol) of a 4% sodium hydrogen carbonate solution was added at the same temperature to adjust the pH to 5.2 to 6.2. After cooling to 10 ° C, the mixture was filtered at the same temperature, and the filter cake was washed with 70 g of 80% aqueous methanol solution and dried. Yield 61.4 g, purity 99.8%, purity conversion yield (relative to acetophenone) 75.0%, melting point 76.
It was 8-78.0 degreeC.

Example 5 In a container equipped with a stirrer, 360 g of 94% sulfuric acid (DVS
(15.7, 6 times the amount) and after cooling to -5 to -8 ° C, 60 g of 99.2% acetophenone (0.
(495 mol) was charged over 1 hour. Next, 140.2 g of mixed acid (composed of 90 g of 98% sulfuric acid (0.90 mol) and 50.2 g of 69% nitric acid (0.549 mol)) was charged at the same temperature over 6.5 hours, and at the same temperature. The reaction was carried out for 2 hours.
As a result of analyzing this reaction mass by gas chromatography and liquid chromatography, the m-form: o-form ratio = 85.0: 15.
0, the production rate is m-NAP 83.3%, o-NAP
It was 14.7%. In addition, partially oxidized m- and o-forms of benzoic acid were confirmed. The reaction mass was discharged into 2.5 liters of ice water at 0 to 15 ° C., stirred at the same temperature for 1 hour, and then pale yellow crystals were filtered. The filter cake was washed with 82 ml of water to obtain 93.0 g of a crude m-NAP wet body. This rough m
As a result of analyzing -NAP, m-NAP purity is 70.4%.
And the yield was 80.0% (relative to acetophenone). The m-form: o-form ratio was 94.1: 5.9. 93.0 g of crude m-NAP in a container equipped with a stirrer
Then, 208.8 g of water (3 times amount / NAP) was charged. 4% at 70-75 ° C (NAP is oily) under stirring
24.4 g (0.012 mol) of sodium hydrogen carbonate solution
Was added to neutralize the pH from 2.0 to 5.5. After that, the temperature was raised to 55 to 60 ° C to dissolve it, and then 4% at the same temperature.
The pH was adjusted to 5.2 → 6.2 by adding 6.2 g (0.003 mol) of a sodium hydrogen carbonate solution. The oil was crystallized while allowing to cool. After cooling to 25 ° C, the mixture was filtered at the same temperature, and the filter cake was washed with 140 ml of isopropyl alcohol and dried. Yield 63.9 g, purity 99.7%,
Purity conversion yield (relative to acetophenone) 77.9%, melting point 7
It was 6.8-78.0 degreeC.

Comparative Example 1 Nitration was carried out in the same manner as in Example 3 to obtain 92.0 g of a crude m-NAP wet body. As a result of analyzing this crude m-NAP,
m-NAP purity is 69.8%, yield is 78.6%
(Vs. acetophenone). The m-form: o-form ratio was 93.0: 7.0. A container equipped with a stirrer was charged with 92.0 g of crude m-NAP, and then 138.0 g of methanol (double amount / NAP) and 11.5 g of water (80 g).
% Water-containing methanol). After that, 55-
After the temperature was raised to 60 ° C. to dissolve it, the mixture was stirred at the same temperature for 1 hour. After cooling to 10 ° C, the mixture was filtered at the same temperature, and the filter cake was removed to 8
It was washed with 70 g of 0% aqueous methanol solution and dried. Yield 64.7 g, purity 96.0% (1% of m-nitrobenzoic acid was contained by liquid chromatography analysis),
Purity conversion yield (relative to acetophenone) 76.0%, melting point 7
It was 2.1-76.6 degreeC.

[0021]

INDUSTRIAL APPLICABILITY Since the present invention is carried out without using a special reaction apparatus for nitration of acetophenone and with the amount of nitric acid used reduced as much as possible, the yield of high-quality m-nitroacetophenone with few by-products is high. You can get at a rate. Furthermore, the present invention provides a method for isolating m-nitroacetophenone, which has a high selectivity to the m-position and is industrially advantageous as compared with the conventional nitration method.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Ryuji Haseyama Mitsui Toatsu Chemical Co., Ltd. 1190 Kasama-cho, Sakae-ku, Yokohama-shi, Kanagawa

Claims (1)

[Claims] 1. A method of nitrating acetophenone at a temperature of 0 ° C. or lower, and purifying the crude m-nitroacetophenone containing the resulting isomer compound by neutralizing in water and / or alcohol. A method for producing m-nitroacetophenone.