JPH0193561A - Production of o-nitrobenzoic acids - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as a synthetic intermediate for agricultural chemicals and pharmaceuticals, in high yield, by reacting an o-halogenated benzoic acids with a nitrite in the presence of a copper catalyst. CONSTITUTION:The objective compound of formula II can be produced by reacting o-halogenated benzoic acids of formula I (X is halogen; Y is halogen or lower alkyl; Z is H, alkali metal or alkaline-earth metal; n is 0-4) with a nitrous acid salt in the presence of a copper catalyst (e.g. cuprous chloride) in a mixed solvent (preferably dimethyl sulfoxide-toluene mixture, etc.), at 80-200 deg.C. The amounts of the nitrite and the catalyst are 1-2mol and 0.05-0.5mol per 1mol of the compound of formula I, respectively. The compound of formula I is e.g. o-chlorobenzoic acid and the nitrite is e.g. sodium nitrite.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention relates to a method for industrially producing 0-nitrobenzoic acids with good yield, which are useful as intermediates for pharmaceuticals and agricultural chemicals.

(Prior art) Conventionally, as a method for producing O-nitrobenzoic acids, O-
BACKGROUND ART There are known methods for producing 0-nitrobenzoic acids by using nitrotoluene as a raw material and oxidizing it in various ways. For example, a method of oxidizing with sodium hypochlorite in the presence of ruthenium oxide and a phase transfer catalyst [The Journal of Organic Chemistry (T
he Jour-nal of Organic Ch.
ea+1stry) + Volume 51, 2880-288
3, (1986)) or a method of electrode oxidation of o-nitrotoluene [Chemistry Letters (Che+5)
istry Letters), pp. 793-796.

(1977)] have been proposed.

(Problems to be Solved by the Invention) However, although the method of oxidizing with sodium hypochlorite has a high yield of 95%, it requires the use of expensive ruthenium oxide and the use of hypochlorite as an oxidizing agent, which is difficult to operate. Industrially, it requires a process to recover the phase transfer catalyst and ruthenium oxide used in the reaction, and electrode oxidation requires expensive equipment. There were problems with the manufacturing method.

(Means for Solving the Problems) In view of the current situation, the present inventors have developed a method for industrially producing 0-nitrobenzoic acids by a method other than the oxidation reaction of O-nitrotoluene. As a result of intensive research, we found that in the presence of an organic solvent and a copper catalyst, 0
- It has been discovered that 0-nitrobenzoic acids can be produced in good yield by using halogenated benzoic acids as raw materials and reacting them with nitrite, and based on this knowledge, the present invention has been completed.

That is, the present invention provides the following method: in the presence of an organic solvent and a copper catalyst, , n represents O or an integer from 1 to 4) and a nitrite (wherein Y, Z and n are the above-mentioned This is a method for producing 0-nitrobenzoic acids represented by ).

Used in the method of the present invention, −0 expressed by formula (1)
-Specific examples of halogenated benzoic acids include 0
-chlorobenzoic acid, 2,4-dichlorobenzoic acid, 2.5
-dichlorobenzoic acid, 2゜3-dichlorobenzoic acid, 2,
6-dichlorobenzoic acid, 2,3.4-trichlorobenzoic acid, 2,3゜5-trichlorobenzoic acid, 2,4.5-)
dichlorobenzoic acid, 2,4.6-1 dichlorobenzoic acid,
2.5.6-) dichlorobenzoic acid, 2.3,4゜5-tetrachlorobenzoic acid, 2-chloro-4-methylbenzoic acid, 2-chloro-3-methylbenzoic acid, 2-chloro-6-
Examples include methylbenzoic acid and 2-chloro-4,6-dimethylbenzoic acid.

The above-mentioned benzoic acids may be used as they are, but it is preferable to use them in the reaction as alkali metal salts such as potassium or sodium salts or alkaline earth metal salts such as calcium. can be obtained. These alkali metal salts or alkaline earth metal salts may be isolated in advance, or salts may be formed by reacting benzoic acids with alkali hydroxides in a reaction system.

Further, as the nitrite used in the method of the present invention, a salt of nitrous acid and an alkali metal atom or an alkaline earth metal atom can be used. Specific examples include sodium nitrite, potassium nitrite, calcium nitrite, and the like.

The amount of nitrite to be used may be equimolar or in excess relative to the 0-halogenated benzoic acid, but it is usually 1.
It is preferable to use up to 2 times the mole.

The organic solvents used in the method of the present invention include dimethylformamide, dimethylsulfoxide, N-methylpyrrolidone, dimethylimidazolitone, aprotic polar solvents such as sulfolane, yohibenzene, toluene, xylene, chlorobenzene, dichlorobenzene, chlorotoluene, Examples include aromatic hydrocarbon solvents that are inert to the reaction, such as nitrobenzene. Although these solvents can be used alone in the reaction, it is preferable to use a mixture of an aprotic polar solvent and an aromatic hydrocarbon solvent inert to the reaction to obtain 0-nitrobenzoic acids with higher yield. Obtainable. When using a mixture of these solvents, the ratio of the two solvents is not particularly limited, but the volume ratio of the aprotic polar solvent and the aromatic hydrocarbon solvent inert to the reaction is 1:1 to 1. :25 is preferable.

Copper catalysts used in the reaction include, for example, inorganic copper such as cuprous chloride, cupric chloride, cupric iodide, cupric sulfate, and cupric nitrate, organic copper such as copper acetate, and oxine copper. Examples include organic copper complexes such as The amount of these copper catalysts to be used is usually selected in the range of 0.01 times or more, preferably 0.05 to 0.5 times, by mole, relative to the 0-halogenated benzoic acid.

In addition, since this reaction is carried out at the reflux temperature of the reaction mixture, it varies depending on the type and volume ratio of the solvent used in the reaction, but usually 5
The temperature is selected in the range of 0°C or higher, preferably 80 to 200°C.

There is no particular restriction on the reaction pressure, and the reaction may be carried out at normal pressure or under increased pressure; however, from an industrial perspective, it is preferable to carry out the reaction at normal pressure. Furthermore, the reaction time is 0.5~
He was a henchman for about 15 hours. The obtained reaction mixture is poured into water, precipitated with hydrochloric acid or the like, filtered, and further recondensed with water or toluene to obtain the desired nitrobenzoic acid.

(Effects of the Invention) The method of the present invention makes it possible to industrially produce O-nitrobenzoic acids in good yield by a method other than the oxidation reaction using nitrotoluene as a raw material, which requires conventional oxidation equipment. This method is extremely valuable as an industrial method for producing O-nitrobenzoic acids.

Further, the 0-nitrobenzoic acids obtained by the method of the present invention are useful compounds as intermediates in the production of agricultural chemicals and pharmaceuticals.

(Example) The present invention will be explained in more detail with reference to Examples.

Example 1 A 100 m four-loaf flask equipped with a cooling tube and a stirrer,
O-chlorobenzoic acid 7.82 g (50 mmol), 5
0% potassium hydroxide aqueous solution 5.61g (50 mmol)
After adding 50 ml of toluene and removing only water by azeotropic dehydration, 1.5 ml of dimethyl sulfoxide and 4.14 g (60 mmol) of sodium nitrite were added and after azeotropic dehydration again, 0.8 g (5 mmol) of copper sulfate was removed. ) was added thereto, and the mixture was reacted at 110°C under reflux in a nitrogen stream for 7 hours.

After the reaction is complete, the reaction solution is poured into water, precipitated with hydrochloric acid, filtered, and the resulting crystals are re-solidified with water until the melting point is 145.
7.57 g of 0-nitrobenzoic acid at ~149°C was obtained. The yield was 90.6%.

Example 2 In a 100 m four-loaf flask equipped with a cooling tube and a stirrer,
0-chlorobenzoic acid 7.82 g (50 mmol), 5
0% potassium hydroxide aqueous solution 5.61g (50 mmol)
After adding 50 ml of toluene and azeotropic dehydration, toluene was distilled off. Next, dehydrated dimethyl sulfoxide 5Qm
l and 6.9 g (100 mmol) of sodium nitrite,
Add 0.8 g (5 mmol) of copper sulfate, and in a nitrogen stream,
The reaction was carried out for 9 hours at 150-160°C under reflux.

After the reaction was completed, the reaction solution was poured into water and precipitated with hydrochloric acid, and the crystals obtained by filtration were reconsolidated with water to obtain 〇-nitrobenzoic acid 5.
．． 43g was obtained. The yield was 65%.

Example 3 50 ml of 〇-dichlorobenzene was used in place of dimethyl sulfoxide in Example 2, and the amount of sodium nitrite was adjusted to 5.
18 g (75 mmol), reaction temperature 175-1
The same procedure as in Example 2 was carried out except that the temperature was 80°C.

As a result, 5.01 g of O-nitrobenzoic acid was obtained.

The yield was 60%.

Example 4 In a 100 m fourth flask equipped with a cooling tube and a stirrer,
7.82 g (50 mmol) of O-chlorobenzoic acid, 50 ml of toluene, 2.5 ml of dimethyl sulfoxide and 10.35 g (150 mmol) of sodium nitrite.
After removing only water by azeotropic dehydration, copper sulfate 0,
8 g (5 mmol) was added, and the following procedure was carried out in the same manner as in Example 1.

As a result, 6.53 g of 0-nitrobenzoic acid was obtained.

The yield was 78.1%.

Example 5 In a 100 m four-loaf flask equipped with a cooling tube and a stirrer,
2.4-dichlorobenzoic acid 9.55 g (50 mmol)
, 5.61 g (50 mmol) of a 50% aqueous potassium hydroxide solution and 50 ml of toluene were added, and after azeotropic dehydration, the toluene was distilled off.

Next, 50 ml of 0-chlorotoluene. 5 ml of N-methylpyrrolidone and 6.9 g (100 mmol) of sodium nitrite were added, and after azeotropic dehydration, 0.8 g (5 mmol) of copper sulfate was added, and the mixture was heated at 150 to 160°C under reflux in a nitrogen stream.
The reaction was carried out for 5 hours.

After the reaction was completed, the resulting reaction solution was post-treated in the same manner as in Example 1 to obtain 7.28 g of 2-nitro-4-chlorobenzoic acid having a melting point of 14.0 to 145°C. The yield was 71.9%.

Example 6 2-chloro-4 in place of 0-chlorobenzoic acid in Example 1
The same procedure as in Example 1 was carried out except that 8.53 g (50 mmol) of -methylbenzoic acid was used.

As a result, 5.32 g of 2-nitro-4-methylbenzoic acid with a melting point of 161 to 165°C was obtained. The yield was 58.7%.

Claims (1)

[Claims] In the presence of an organic solvent and a copper catalyst, the general formula▲ includes mathematical formulas, chemical formulas, tables, etc.▼...(I) (In the formula, X is a halogen atom, Y is a halogen atom or a lower an alkyl group, Z is a hydrogen atom, an alkali metal atom, or an alkaline earth metal atom, and n is an integer from 0 or 1 to 4). o-Nitro expressed by the general formula ▲ Numerical formulas, chemical formulas, tables, etc. Method for producing benzoic acids.