JPS6075443A - Manufacture of halogen benzole - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides (a) - reacting anilines with a halogenating agent by a container method to produce halogenated anilines, and subsequently reacting the reaction mixture thus produced in the presence of water and an acid. or (b) by similarly reacting halogenanilines prepared by the above-mentioned or other means and separated from the reaction mixture. , concerning a new method for producing halogen pensoles.

According to Haupen-Weyl, ``Methoden der Organitsien Hemi-j'', volume 10/'y, p. 116 et seq., it is known that aromatic diazonium salts can be converted into the corresponding aromatic hydrocarbons in alcohol when heated. Therefore, it is recommended to use the diazonium salt solution as concentrated as possible and add 5 to 10 times the volume of alcohol to it.The alcohol is then converted to the corresponding aldehyde, thus increasing the aldehyde content. This prevents the reuse of the unreacted part of the alcohol.Depending on the structure of the diazonium salt, it must be operated water-free, or an 80% by weight aqueous ethanol solution can be used.Similarly [organic - Reactions Ju Vol. 1, p. 274 (Wiley Publishing, New York) teaches that the reaction does not have to be carried out absolutely without water, but the amount of water is limited to about 5-10%.

In addition to the hydrocarbons, as a by-product, there is also phenolniteryl, which corresponds to the alcohol used, cited in Book 12.
6-124), especially in alcohol diluted with water.

The yield and purity of the target substance are often unsatisfactory in this process, especially even on an industrial scale.

For example, yields of the desired substance of 46% for 2,4-dichloroaniline as the starting amine and 56% for anthranilic acid have been shown (Houben-Fill, cited above, p. 125). Angewante Hemi - Volume 70 (19
According to the miscellaneous text on page 211 of 1995, in order to avoid the formation of by-products and improve the yield of the target substance, an ether such as dioxane must be used instead of alcohol. Similarly, instead of an aqueous diazotization solution, the diazonium salt itself can be separated and reacted with alcohol (Saunders, The Aromatic Diazo Combinations, published by E. Arnold).
London, 1949, p. 271), all these processes are unsatisfactory, especially on an industrial scale, in terms of economy and simplicity of operation, which at the same time give the best possible yield of the target substance.

Science Vol. 117, pp. 379 and 680 (1956
According to a miscellaneous text published in 2013, the reaction of penzole diazonium salts with alcohols mostly yields the corresponding phenyl alkyl ethers, and no or only a very small amount of penzole derivatives remain after elimination of the diazonium group. Only. This teaching is also discussed in "Azo and Diazo Chemistry" by Etsch Zollinger, Interscience Publishing, New York and London, 19
61, p. 141. The book by Houben-Weyl (mentioned volume, p. 124) shows that the decomposition of a number of diazonium salts proceeds with the exchange of diazonium groups and ethoxy groups by heating in ethanol. According to this teaching, the exchange of diazonium groups with hydrogen requires certain reaction conditions, such as the addition of zinc or UV irradiation. In order to obtain higher yields of pensoles in the reduction with alcohols, it is recommended to add alkali or copper or zinc compounds (cited above, pp. 119-127). In the book of Haupen-Weyl (cited above, p. 128 of the above volume), it is stated that with increasing temperature the ratio of both reaction products, phenol ether and hydrocarbon, increases as follows:
It is shown that there is a shift in favor of the former.

Since the product mixtures are often difficult to work up and the yields of the desired hydrocarbons are poor, the use of other reducing agents is preferred (Sollinger, supra, 168).
page).

According to Journal 0 of the American Chemical Society, Vol. 72, p. 798 (1950), 2,
It is known that 6-dichloro-4-nitroaniline, ethanol and sodium nitrite can be converted to 6,5-dichloronitropenzole in the absence of water and in the presence of concentrated sulfuric acid at boiling temperature with a yield of 84%. ing. A similar reaction to obtain the 6,5-dibrome derivative gives a yield of 91%. This process is also unsatisfactory with respect to the yield and purity of the target substance, as well as with regard to simple, safe and economical operation, especially in industrial applications.

According to Houben-Weill, "Methoden der Orkanitsien Hemi", Vol. 5/6, pp. 705-713,
It is known that by direct chlorination of aromatic amines with free amino groups, the corresponding chloro derivatives can only be obtained in low yields. This is because free amine groups react with chlorine to form chlorine-nitrogen compounds which are unstable and decompose during chlorination to form tar-like products.

Journal of Chemical Conflict Society ^-96, 1
776 (1908) describes the reaction of 4-nitroaniline with chlorine in the presence of hydrochloric acid at high and low temperatures in a very dilute aqueous solution using, for example, a 0.8% by weight aqueous solution of the acid. 2,6-dichloro-4
- It is stated that nitroaniline is always obtained in impure form and can only be obtained in pure form by recrystallizing this crude product. This reaction requires 2-10g
It was only carried out using starting materials. When the conditions of the process described above are applied on an industrial scale, for example with at least 500 kg of starting material for each reaction, a considerable proportion of resinous colored residues and resinous residues are already formed at low temperatures and an even greater proportion at high temperatures. Decomposition products are obtained. This observation can be inferred from the instruction on page 1776 of the aforementioned Journal of the Chemical Society that even on a laboratory scale, low temperatures should always be used and the target substance should be recrystallized.

Furthermore, according to Houben-Weill's aforementioned book, page 706,
If the free amino groups of the aromatic amine to be chlorinated are protected by substitution in a reaction step prior to the chlorination reaction, e.g. by acetylation, undesirable chlorine-
It is known to avoid the formation of nitrogen compounds. However, in this case, after the chlorination, the acyl group must be eliminated again in a third reaction step.

In some cases (see page 710) it may be advantageous to lead the free aromatic amine by sulfonation to the corresponding sulfonic acid before chlorination, which sulfonic acid is subsequently chlorinated at low temperature and finally by increasing the temperature. The sulfonic acid group is removed again. In this way, 2,6-dichloro-4-nitroaniline is obtained via 4-nitroaniline sulfonic acid with a yield of 87%. Houben-Weyl's miscellaneous text states that when 2-nitroaniline or 4-nitroaniline is reacted with sulfuric acid, sodium chloride, and sodium hypochlorite solution at room temperature, a chlorine atom appears at the 4- or 2-position relative to the amine group. It is detailed that a corresponding monochloronitroaniline having

4-nitroaniline in 47 wt% hydrochloric acid and 60 wt% H
Direct chlorination with 2O2 produces 2,6-dichloro-4-nitroaniline in a yield of 74% (Houben-Weyl, supra, p. 710).

The invention of Japanese Patent Application No. 148327/1980 is to combine a halogen nitroaniline represented by the general formula (in which R1 and R2 have the meanings given below) with an aliphatic, alicyclic, or araliphatic alcohol at a temperature of at least 65°C. At temperature,
by reacting a halogen nitroaniline with an alcohol and a nitrosating agent in the presence of an acid at elevated temperature, characterized in that the reaction is carried out with the addition of water.
This is a method for producing no-rogennitrobenzole represented by the general formula (in the formula, R1 and R2 may be the same or different and each represents a halogen atom, and R2 may represent a hydrogen atom).

The present inventors (a) in the first step, react aniline represented by the general formula (in which R3 and R4 have the meanings given below) with a halogenating agent in the presence of water and an acid,
The thus produced halogenaniline represented by the general formula (in which R', Rs and R4 have the meanings given below) is removed from the reaction mixture (in the second step, in the presence of an acid) or react with an aliphatic, cycloaliphatic or araliphatic alcohol and a nitrosating agent by adding water at a temperature of 65°C; When a halogenated aminobenzoic acid compound represented by The method of Application No. 51-148327 is further modified by the general formula (in the formula, R' and R4 may be the same or different and each represents a halogen atom, and R3 is a nitro group or a group -CO
means OR5, and R4 may also mean a hydrogen atom (
, when R3 means the group -COOR', R4 may mean a nitro group, and R5 means a hydrogen atom or an aliphatic, cycloaliphatic, araliphatic or aromatic residue) He developed a method for producing the halogen pensol represented by the formula and discovered scales.

Furthermore, in the first step, the present inventors reacted nitroaniline represented by the general formula (in which R4 has the meaning given below) with a halogenating agent in the presence of water and an acid, and the thus produced general The halogen nitroaniline of the formula (R1 and R4 have the meanings given below) is added in a second stage to water in the presence of an acid at a temperature of at least 65° C. without separating it from the reaction mixture. When reacting with an aliphatic, alicyclic or araliphatic alcohol and a nitrosating agent, the general formula (wherein R1 and R4 may be the same or different, each means a halogen atom, and R4 is It has now been found that halogen nitropenzoles represented by (which may also mean atoms) are advantageously obtained.

Furthermore, the present inventors prepared a halogenamine benzoic acid compound represented by the general formula (in which ul, R' and R4 have the meanings given below) in the presence of an acid by adding water at a temperature of at least 65°C. When reacting with an aliphatic, alicyclic or araliphatic alcohol and a nitrosating agent, the general formula (wherein R1 means a halogen atom, R4 is a hydrogen atom,
A halogen benzoic acid compound represented by a halogen atom or a nitro group, and R5 is a hydrogen atom or an aliphatic, alicyclic, araliphatic or aromatic residue is advantageously obtained. I found out.

Halogen penzole■ is halogen nitropenzole■′
and halogen benzoic acid compound I〃, halogen aniline (2) includes halogen nitroaniline IIa and halogen amine benzoic acid compound (2), and aniline (2) includes nitroaniline N' and aminobenzoic acid compound r.

15 One reaction is sodium hypochlorite, 4-nitroaniline,
When sulfuric acid, sodium nitrite and ethanol are used, the following reaction formula can be used.

This reaction can be shown by the following reaction formula when sodium nitrite, 6,5-dichloro-4-aminebenzoic acid, sulfuric acid and ethanol are used.

16-H2 According to the process of the invention, halogen nitropenzoles are obtained in improved yields and purities by simple and economical means, especially on an industrial scale, in view of the state of the art. The addition of copper salts or other catalysts or large amounts of alcohol is unnecessary.

The amount of halogenated nitrophenol produced is 0.5% relative to the reaction mixture despite the high water content of the reaction mixture.
06% by weight or less. The formation of resinous by-products is not observed to any substantial extent.

All these advantageous results are due in particular to the instructions given by the said publications, namely to prepare the diazonium salts first by the usual procedure of diazotization in the cold and then to add auxiliaries such as copper in the absence of water or in the presence of as little water as possible. This is unexpected considering that the reduction is carried out using alcohol with the use of salt. Also, in view of Houben-Weyl's writings, it could be expected that the target substance could be obtained in improved yield and purity without prior preparation of the diazonium salt and at elevated temperatures in the presence of large amounts of water. That was not the case.

Furthermore, in view of the state of the art, according to the method of the present invention, it is possible to produce dichloroaniline and monochloroaniline and to carry out these reactions simultaneously in a single container method, especially on an industrial scale, thereby making it easier and more economical. Target substance ■ is obtained. No special purification operations and conversion of the starting material (1) to its acyl or sulfonic acid derivative are necessary. The formation of resinous or tarry by-products or decomposition products is not observed to any substantial extent even in the first stage. All these advantageous results are unexpected in view of the state of the art, since under the conditions of the invention the target substances are obtained with improved yields and purity.

The preferred starting materials (1) and (2) and the corresponding preferred target materials (2) are such that R1 and R4 in their formulas may be the same or different (respectively an iodine atom, preferably a bromine atom or a chlorine atom). , R3 means a nitro group or a group -COOR', R4 may further mean a hydrogen atom, and when R3 means a group -COOR5, R4 may mean a nitro group. , and R5 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, a cyclohexyl group, a cyclopentyl group, an aralkyl group having 7 to 12 carbon atoms, or a phenyl group. The radicals may be further substituted by groups which are inert under the reaction conditions, for example alkyl groups or alkoxy groups each having 1 to 3 carbon atoms.The halokenenitroaniline is usually substituted in the 2-position on the nucleus. or has a nitro group at the 4-position and a halogen atom at the 2-position, 4-position, or 6-position.Halogenamine = 1so-benzoic acid compound ■ has a carboxyl group and/or two chlorine atoms or The groups R1 and R4 can be located at any position on the nucleus, preferably these substituents are in the 2-, 4- or 6-position relative to the amino group.

For example, the following starting material (1) is suitable. 6-chlor-1
6-bromo-16-iodo-16,5-dichloro-13
, 5-dibrome-16,5-short-12,6-dichloro-12,6-dibrome- and 2,6-diiodo4
-Aminobenzoic acid; 2-aminobenzoic acid monosubstituted in the 6-, 5- or 6-position or di-substituted in the 3,5- or 4,6-position with a chlorine, bromine or iodine atom Aminobenzoic acid; 2 at the above two positions
Corresponding 4-aminobenzoic acids and 2-aminobenzoic acids substituted with different halogen atoms or one nitro group and one halogen atom; similar methyl-, ethyl-1n- of the above aminobenzoic acids 7'ropyru, isopropyl-1n-butyl-, isobutyl-1 secondary butyl 20
- Ru, tertiary butyl, pentyl, hexyl, cyclohexyl, cyclobenzyl, benzyl, phenyl, phenylethyl-10-methylphenyl-1m-methylphenyl-1p-methylphenyl-10-methoxyphenyl- 1 m-methoxyphenyl- and p-methoxyphenyl-ester. The following are preferred. 6,5-dichloro-2-aminobenzoic acid, 3,5-cyclo-2-aminobenzoic acid ester of methyl- or ethyl alcohol, 6,5-dichloro-4-aminobenzoic acid, 6, of methyl- or ethyl alcohol 5-dichloro-4-amine benzoic acid ester, 3,5-dibrom-2-amine benzoic acid, 6,5-dibrom-2-aminobenzoic acid ester of methyl- or ethyl alcohol/l/, 3,5-dibrome -4-Aminobenzoic acid, 6,5-dibrom-4-aminebenzoic acid ester of methyl- or ethyl alcohol, 3,5-short-2-aminebenzoic acid, 3,5-short- of methyl- or ethyl alcohol 2-aminobenzoic acid ester, 6,5-short-4-aminobenzoic acid, 3,5-short-4-aminobenzoic acid ester of methyl- or ethyl alcohol.

For example, the following starting material ■ is suitable. 2-nitro- or 4-nitroaniline and mixtures of 2-nitro- and 4-nitroaniline; 2-chloro-4-nitroaniline, 2-bromo-4-nitroaniline and 2-iodo-
4-nitroaniline; 4-10-2-nitroaniline, 6-chloro-2-nitroaniline, 4-bromo-2-
--407='J-n, 6-bromo-2-nitroaniline, 4-iodo-2-nitroaniline and 6-iodo-2
-Nitroaniline. Particularly preferred are 2-nitro- or 4-nitroanilines and mixtures of 2-nitro- and 4-nitroanilines; aminobenzoic acids (1) and aminobenzoic acid esters (2) corresponding to the starting materials (1) above.

As the halogenating agent, a halogen or a substance that generates a halogen under reaction conditions is generally used. As halogen, it is particularly advantageous to use iodine, preferably bromine and especially chlorine. The halogenating agent is used in stoichiometric amounts or in excess, preferably from 1.0 to 5.0 molar per mole of starting material.
0 moles, especially 1.0 to 2.0 moles of halogen, or 1
The reaction can be carried out at a ratio of 0 to 5.0 equivalents, particularly 1.0 to 2.0 equivalents of the halogenating agent. Equivalents are based on the above reaction formula, for example 2 moles of hypochlorous acid)
IJum is equivalent to 1 mole of nitroaniline.

As halogen-forming substances, halides are particularly preferably used together with oxidizing agents and acids. It is also possible to use oxidizing agents and hydrogen halides, preferably hydrogen iodide, especially hydrogen bromide and especially hydrogen chloride, particularly preferably in the form of aqueous solutions of hydrogen halides, such as hydrochloric acid. The halides are preferably used in the form of their alkaline earth metal salts, especially their alkali metal salts, such as calcium bromide, calcium iodide, magnesium bromide, magnesium iodide, lithium bromide, lithium iodide, calcium chloride. ,
Mention may be made of magnesium chloride, lithium chloride and especially sodium bromide, thorium iodide, potassium bromide, potassium iodide, preferably sodium chloride and potassium chloride.

As oxidizing agents, preference is given to using chromium compounds such as potassium, sodium or ammonium dichromate, chromic acid and chromyl chloride, permanganates such as potassium permanganate, or MnO2 or oxygen. The oxidizing agent is used in an amount of 1.0 to 5.0% per mole of starting material (1).
It is particularly advantageous to use a proportion of 0 mol, preferably 1.0 to 2.5 mol. In a preferred embodiment,
Hydrogen peroxide as oxidizing agent is preferably used in an amount of 1.0 to 5.0 equivalents, in particular 1.0 to 2.0 equivalents, based on the starting material (1) for the halogenation. Hydrogen peroxide is preferably
It is used in the form of an aqueous solution of up to 80% by weight, especially 10 to 50% by weight. Optionally, substances which produce hydrogen peroxide under the reaction conditions are also used, such as those listed below. Inorganic or organic peroxo compounds such as sodium peroxide, potassium peroxide, magnesium peroxide, calcium peroxide,
Zinc peroxide, barium peroxide and barium superoxide, hydroperoxides such as Na0OH.0.5H202,
Corresponding hydrates such as CaO2.8H20□, peroxohtrides such as BaO2@H2O2 and Ba
O2@2H202, peroxo compounds and peroxomonosulfates and their salts such as sodium peroxocarbonate, potassium peroxocarbonate and ammonium peroxodisulfate, peroxocarbonates such as sodium peroxocarbonate and calcium peroxocarbonate, peroxophosphates such as potassium peroxophosphate.

In a preferred embodiment, halogen oxygen acids, their anhydrides, or salts thereof, such as chloric acid, hypochlorous acid, hypobromous acid, dichlorine oxide, and their sodium and potassium salts are used. Optionally, the abovementioned halogen compounds can also be used together with oxidizing agents and/or free halogens.

In a preferred embodiment, the hypochlorite is used in the form of the corresponding alkaline aqueous solution.

The hypochlorite is reacted in an amount of 1 to 1.2 equivalents, preferably 1.05 to 1.1 equivalents, per 11 moles of the starting material. The equivalent is based on the above reaction formula (for example, 2 moles of hypochlorite). One mole of calcium hypochlorite means one equivalent of one mole of nitroaniline. Particular preference is given to using calcium hypochlorite, magnesium hypochlorite, barium hypochlorite, lithium hypochlorite, preferably potassium hypochlorite and especially sodium hypochlorite. The preferably used aqueous solutions of hypochlorites, particularly preferably alkali metal hypochlorites, generally contain from 6 to 15% by weight, preferably from 12 to 14% by weight.
% by weight of hypochlorite and 1% by weight of hypochlorite.
0.2 to 2.5 moles per mole of alkali metal hydroxide can also be contained.

In all cases of halogenation, water is added to the starting mixture and is defined in the present invention as added water. Additionally, additional amounts of water are formed during the course of the reaction. Starting material H
50 to 5000% by weight, particularly preferably 50% by weight, based on the weight of
Preference is given to adding 0 to 5000% by weight, especially 1000 to 4000% by weight, of water to the starting mixture. Some, preferably all, of the water is added in the form of an aqueous solution of the corresponding acid and/or an aqueous solution of hypochlorite.

Generally, the first stage of this reaction is carried out at a temperature of 25°C or higher, usually at 25°C.
7 to 1 DO°C1 Preferably at a temperature of 27 to 80°C, more preferably 27 to 60°C, even more preferably 60 to 55°C, especially 65 to 50°C, especially 40 to 45°C, under normal pressure or increased pressure. , performed continuously or discontinuously. Usually components of the starting mixture, such as water or acid, or often the entire starting mixture, are used as solvent for the reaction, optionally all or part of the alcohol used in the second stage being added to the starting mixture of the first stage. You can also do that.

Generally, a strong acid is used as the acid for the first stage.

In the present invention, strong acid means an organic or inorganic acid which has an acid index (pKs) of -7 to +2.16 and is inert under the reaction conditions.

Regarding the definition of the acid index or pKs value, see
Reference is made to Volume 15, page 2. For example, the following are suitable. Concentrated sulfuric acid, preferably 90-98% by weight sulfuric acid, phosphoric acid, preferably 85-90% phosphoric acid, hydrochloric acid, preferably 60-98% by weight
68% by weight hydrochloric acid, nitric acid, preferably 60 to 65% by weight nitric acid, perchloric acid, preferably 65 to 70% by weight, perweight acid and acidic acid, preferably 85 to 99% by weight, hydrogen chloride gas, boric acid, trichloroacetic acid Acidic ion exchangers in the form of , trifluoroacetic acid or polyfluoroethylene sulfo/acid are likewise used. Suitable acids are hydrochloric acid or sulfuric acid, especially at the concentrations mentioned. Optionally, the same substance, for example hydrochloric acid, can be chosen as the halogenating agent simultaneously with the acid. The acid is preferably used in an amount of 1 to 30 parts by weight, particularly preferably 1.0 to 20 parts by weight, especially 5 to 15 parts by weight per part by weight of starting material (1). 5-400 per weight of water added
It is particularly advantageous to use concentrations of acid of 10% to 100% by weight. The acid is calculated as 100% water-free acid in these concentration and amount indications, regardless of the actual structure or the amount of water mixed during addition of the acid.

If an excess of alkali is added together with the hypochlorite solution (which is often done to stabilize solutions of this type), the amount of particularly advantageous acid mentioned above is generally increased by an amount equivalent to the excess alkali. using the corresponding acid.

Using an alkanol and a nitrifying agent under conditions corresponding to each other, (a) the halogenaniline ■ produced in the two steps according to the procedure described above is reacted in a second step without separating it from the reaction mixture; , or (bl) the no-rogenbenzoic acid compound (2) produced in the first step by the above method and separated from the reaction mixture, optionally after purification, is reacted as the starting material (2), or (b2) Halogen benzoic acid compound (2) produced by other methods can be reacted.

The starting material (1) as its reaction mixture formed in the first step, or the halogenbenzoic acid compound prepared by (bl) or (b2), is preferably combined with a stoichiometric amount or excess of alcohol and the starting material (2) or 1 mol of (1) is reacted with 6 to 60 equivalents, particularly 5 to 15 equivalents (number of moles divided by the number of hydroxyl groups in the molecule) of alcohol.

In this connection, the starting material I+ is chosen in the case of (bl) and (b2), and the starting material ■ in the case of (a). The alcohol may be an aliphatic, cycloaliphatic or araliphatic mono- or polyalcohol.

Preferred alcohols have the general formula %. In this formula, HQ is an alkyl group having 1 to 5 carbon atoms, a cyclohexyl group, an aralkyl group having 7 to 12 carbon atoms, a residue HO-R10- (in the formula, 110 is an aliphatic residue, in particular an alkylene group having 2 to 4 carbon atoms) or a residue R"0-(R'
00) n-R''- (wherein RIO may be the same or different and each denotes an aliphatic residue, in particular an alkylene group having 2 to 4 carbon atoms, and RIl is a hydrogen atom or an aliphatic a residue, in particular an alkyl group having 1 to 4 carbon atoms, and n means a number of 4.6.2 or in particular 1.Said residues are groups which are inert under the reaction conditions; It may be further substituted, for example by alkyl or alkoxy groups each having 1 to 3 carbon atoms.

Alcohols include, for example, methanol, ethanol, n- and 1-propertool, n-butanol, butanol-2, inbutanol, ethylene glycol, diethylene glycol, methylethylene glycol, benzyl alcohol, n-pentanol, phenylethanol, and Pentyl glycol, p-methylbenzyl alcohol, p-ethoxybenzyl alcohol, 1.3-propylene glycol, 1.4-phthanediol, 1.2
- Propylene glycol, triethylene glycol and dipropylene glycol - mono-n-butyl ether or mixtures thereof are used. Preferred are ethanol, impropatol, methyl ethylene glycol, n-propatol and imbutanol.

In the second step of this reaction or the reaction according to (bl) or (b2), a nitrosating agent, such as nitrous acid or a substance that converts to nitrous acid under the reaction conditions, such as nidrose gas, a salt of nitrous acid, preferably an alkali metal salt, is added. Especially potassium nitrite or sodium nitrite, or esters of nitrous acid, preferably cycloalkyl-, aralkyl-
Or particularly preferably, alkyl esters are used. If alkyl nitrites are used, the addition of alcohol can be omitted completely or preferably partially. This is because under the reaction conditions the nitrite ester of the Cono type can replace the combination from nitrous acid and the corresponding alcohol, in which case the starting materials ■ or ■
A ratio of 1 to 5 equivalents of alcohol per mole of alcohol is preferred. In the esters, alkyl nitrites having 1 to 6 carbon atoms, such as ethyl-1n-propyl-1n-isopropyl-1n-butyl-, imbutyl-1 sec-butyl-1 tertiary-butyl, amyl-, Preference is given to using inamyl, benzyl, cyclohexyl/and especially methyl esters.

In the present invention, nidrose gas refers to nitrogen oxides known as nitrosating agents, such as nitrogen oxides, nitrogen dioxide,
Means nitrogen tetroxide or dinitrogen trioxide. These can be used alone or in mixtures with one another, particularly preferably from nitrogen monoxide and nitrogen dioxide.

Generally 1.1 to 5 alkyl nitrite, nitrite ester and/or nidrose gas per mole of starting material (i) or (i)
1.1 to 2.7 mol % of alkyl nitrite or nitrite ester per mole, preferably of starting material 1 or l K t 1 to 1.7 mol, or especially N2032 to 4
Moles are used. A gas that is inert under the reaction conditions, such as nitrogen, may be mixed with the nitrogen oxide or mixed gas.

Glycol esters of nitrous acid are likewise used as nitrosating agents. The nitrite esters can be prepared by any means, preferably by reacting glycols or glycol derivatives with nitrous acid or nitrogen oxide, according to the method described in German Patent Application No. 21 44 420. Preferred glycol esters and glycol derivatives are mono- or di-glycol esters of nitrous acid having the general formula %. In this formula, 1 (6 is a residue -R7-0-8 is an aliphatic residue, R8 is a hydrogen atom or an aliphatic residue, n is 1
．． 2.3 or 4, or a group -NO or an aliphatic, araliphatic, cycloaliphatic or aromatic residue. Preferably R7 is an alkylene group having 6 to 12 carbon atoms, especially 4 to 9 carbon atoms, R8 is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, especially a methyl group, and n is 1.2.
or the number of O, and X is a group -NO, an alkyl group having 1 to 4 carbon atoms, an aralkyl group having 7 to 12 carbon atoms, a cyclohexyl group, a cyclopentyl group,
pheni/'' group or an alkylcarbonyl group having 2 to 5 carbon atoms, in particular an acetyl group. Said alkyl and alkylene groups may be straight-chain or branched. Preferred residues of said may be further substituted by groups which are inert under the reaction conditions, for example alkoxy or alkyl groups each having from 1 to 6 carbon atoms.In general, 1. 1 to 5 moles, preferably 1.1 to 2 monoglycol esters per mole of starting material 1 or 2
．． Amounts of 7 mol, especially 1.1 to 2.2 mol, are used.

Similarly, 0.55 to 2.5 moles of diglycol ester, preferably 0.55 to 1 mole of diglycol ester, per mole of starting material (1) or (2).
．． An amount of 35 mol, in particular 0.55 to 1.1 mol, is chosen.

Suitable esters V are, for example, mono- or diesters of nitrous acid with the following compounds:

CH.

CH30-CH2CH2-OH, CH30-CH2-C
H-OH.

C2H,0-CH2CH2-OH1C3H70-CH2
CH2-OH.

CH.

CH30-(CH-CH20)2HSC4H,0-CH
2CH2-OH.

CH3CH3 HO-(CH2CH20)2H, HO-CH-CH20
-C'H2-CH-OH.

C,,H,0-(CH-CH20)2H1HO-(CH
2CH20)3H.

CH30(CH2CH2O)2H, CH3Co-0CH
2CH,, -OH.

02H,O(aH2CH2o),,nSc stop,O(C
H2CH2O)2H1C6H,,O-CH2CH,,O
H, C4I(90(aH2cH2o)2H.

CH30(CH2CH20)3■], C2H50(CH
2Cl(20)3H1 and R6 are residues -R7-0-
Diglycol ester in which 1X is a group -NO1 and R7 is an alkylene group: (CH2)3-1- (
CH2)4. -,-(CH2)",CH,CH・ (CH2)6-1-CH2-CH-CH2-1-CH2
-C-CH2-1H3 -CH2-C-CH2-1-CH-CH-C'H2-1
C2H5C3H7 C83C2N! 1-CH-C-CH2-1-CH2-C-CH2- or C3H7C■13 products (.

CH3('H,.

-C-CI, -CH- H3 The second stage of this reaction or the reaction with (bl) or (b2) is particularly advantageously carried out in an amount of from 0.2 to 10,000 mol, preferably from 0.2 to 10,000 mol per mol of the starting material 1 or 2. 0.5~1000
This is carried out by adding mol, in particular 5 to 100 mol, in particular 15 to 50 mol, of water.

Water can be added separately and/or in the form of an aqueous solution of a reaction participant, such as an aqueous solution of an acid or alkali nitrite, or a mixture of alcohol and water. In this connection, the water formed in the reaction itself is not defined as added water and is therefore not included in the preferred amounts of water mentioned above. In case (a), the water added and the water formed during the first stage is O12-1[
Water has already been added for the first stage of the reaction such that the amount of water is 1000 mol, particularly advantageously 0.5 to 1000 mol, preferably 5 to 100 mol, in particular 15 to 50 mol. It is preferable.

Second stage reaction in case of (,) or (+) 1)
The reaction according to (b 2 ) is carried out in the presence of an acid, preferably from 1.5 to 15 equivalents, especially 2
．． It is carried out in an amount of 5 to 10 equivalents of acid.

Inorganic acids are generally used. -Equivalent amounts of polybasic acids can also be used instead of basic acids. For example, the following acids are suitable: Hydrogen chloride, hydrogen bromide, hydrogen iodide, perchloric acid, sulfuric acid, nitrous acid, phosphoric acid, nitric acid, boron-containing acids such as boric acid or borofluoric acid, or mixtures of these acids. The acids can be used in concentrated form, as mixtures with each other and/or with solvents, especially water. Preferred are sulfuric acid, nitric acid, phosphoric acid or perchloric acid.

In case (a,) the acid can be added at the end of the first stage, particularly preferably the same acid is chosen for both stages of the reaction and taking into account that the acid is consumed in both stages. 1.5 to 15% for the starting material ■ or ■ during the second step.
in an amount in which equivalents, especially 2.5 to 10 equivalents, of acid are always present;
Add acid to the starting mixture.

The boiling temperature of the compound, preferably 40 to 200°C, especially 45°C
It is carried out continuously or discontinuously at a temperature of ~100° C. under normal or increased pressure. Usually the components of the starting mixture, such as water, alcohol or acid, or the entire starting mixture, are
Used as a solvent in reactions.

This reaction can be carried out as follows. The mixture of starting materials (1), halogenating agent such as hypochlorite, acid and water is maintained at the first stage reaction temperature for 0.5 to 25 hours. Preferably, a halogenating agent, such as preferably an aqueous solution of sodium hypochlorite, is passed into the mixture of reactants.

This inflow can take place at any speed within a wide range. The end of the reaction often coincides with the end of the hypochlorite influx. Starting from aniline or monohalogenaniline in this first step of the reaction,
The corresponding mono- or dihalogenaniline is formed. This product remains in the reaction mixture and the second stage of the reaction begins. The alcohol, nitrosating agent and optionally acid and water are then added. Mixture from 1.0 to
Hold at second stage reaction temperature for 25 hours. Preferably, a nitrosating agent such as nitrous acid or an aqueous solution of nitrite is passed into the mixture of reactants.

This inflow can take place at any speed within a wide range. The end of the reaction often coincides with the end of the nitrosating agent flow. The target substance is separated from the reaction mixture by a conventional method such as filtering.

The reaction (bl) or (b2) can be carried out as follows. The mixture of starting material (1), alcohol, nitrosating agent, acid and water is maintained at the reaction temperature for 1.5 to 15 hours. The subsequent operations are performed in the same manner as described above.

The novel compound produced by the method of the present invention can be used as a pharmaceutical,
It is a valuable starting material for the production of dyes and pesticides. Regarding uses, please refer to the above-mentioned publications as well as Ullmann's Encyclopedia, Vol. 12, pp. 798-800, and Vol. 4, pp. 286-28.
Reference is made to page 7.

Parts in the following examples mean parts by weight.

Example 1 168 parts of 4-nitroaniline are added to 950 parts of dilute sulfuric acid (64% by weight), and then 300 parts of hydrochloric acid (66% by weight) are introduced. Hydrogen peroxide solution (50% by weight) at 59°C14
Add 0 parts to 2 hours. Next is isopropatool 500
of NaN0□2 in 600 parts of water at 60°C.
00 parts of solution is added in 180 minutes, nitrogen is evolved. After cooling, adding 600 parts of water and filtering with suction, 183 parts (95% of theory) of 6,5-dichloronitropenzole with a melting point of 58 DEG -60 DEG C. are obtained.

Example 2 168 parts of 2-nitroaniline are reacted in the same manner as in Example 1 to obtain 186 parts of 3,5-dichloronitropenzole (97% of theory) having a melting point of 57-59°C.

Example 6 168 parts of 4-nitroaniline was mixed with dilute sulfuric acid (50% by weight) 8
00 parts of chlorine-caustic alkaline solution at 65°C.
50 parts (165 parts of sodium hypochlorite and hydroxide)
(containing 2 parts of IJum). 650 parts of Impropatool and 200 parts of H2SO4 (98% by weight) are added sequentially.

A solution of 125 parts of NaNO2 in 175 parts of water at 50°C
If added for 00 minutes, nitrogen will be generated. Cool, add water 5
00 parts and filtered with suction, melting point 57-60
180 parts of 3,5-dichloronitropenzole (94% of theory) are obtained.

Example 4 168 parts of 4-nitroaniline are added to 950 parts of dilute sulfuric acid (65% by weight) and then 250 parts of hydrochloric acid (66% by weight) are rapidly introduced. A solution of 81 parts of sodium chlorate and 120 parts of water is added at 50° C. followed by 600 parts of isopropanol. Nitrogen is evolved when a solution of 200 parts of NaNO in 600 parts of water is added over 120 minutes.

Cooling, adding 600 parts of water and filtering with suction gives 6,5-dichloronitropenzole 1 with a melting point of 59-61°C.
89 parts (98% of theory) are obtained.

Example 5 138 parts of 4-nitroaniline was added to 1600 parts of water,
325 parts of bromine are then added at 45-50°C. Sulfuric acid (
NaNO2 in 300 parts of water at 50°C after sequentially adding 500 parts of
Adding 200 parts over 300 minutes generates nitrogen. After cooling, adding 1000 parts of water and filtering with suction, 267 parts (95% of theory) of 3,5-dibromnitropenzole with a melting point of 100 DEG -106 DEG C. are obtained.

Example 6 206 parts of 6,5-dichloroanthranilic acid are added to 500 parts of 45% by weight sulfuric acid and 400 parts of isopropanol. Nitrite in 140 parts of water at 80°C) IJum 10
When 0 parts of solution is introduced for 5 hours, nitrogen is evolved. Cooling, adding 1000 parts of water and filtering with suction gives 6,5-dichlorobenzoic acid 172, melting point 175-178°C.
(90% of the theoretical value) is obtained.

Example 7 When reacting in the same manner as in Example 6 using 125 parts of isopropyl nitrite instead of NaNO2, the melting point was 178.
181 parts (95% of theory) of 6,5-dichlorobenzoic acid at ~180 DEG C. are obtained.

Example 8 206 parts of 6,5-dichloroanthranilic acid are added to 200 parts of Improper Tool and 800 parts of 18% by weight hydrochloric acid. When a solution of 0 parts of NaNO21D in 140 parts of water is introduced at 80 DEG C., nitrogen is uniformly evolved. The mixture is cooled, 500 parts of water are added and the mixture is filtered with suction to give 6,5-dichlorobenzoic acid 1 with a melting point of 178-180°C.
82 parts'' (95% of theory) are obtained.

Example 9 206 parts of 6,5-dichloroanthranilic acid are added to 400 parts of ethanol, and then 400 parts of 36% by weight hydrochloric acid are added. A solution of 10 parts of NaNO2 in 150 parts of water at 758 C is introduced and nitrogen is evolved. Mixture at 75℃
After stirring for 1 hour at
186 parts (89% of theory) of 5-dichlorobenzoic acid are obtained.

Example 10 172 parts of 5-chloroanthranilic acid are added to 550 parts of 45% by weight sulfuric acid and 600 parts of isopropanol. 8
A solution of 100 parts of sodium nitrite in 140 parts of water at 0° C. is introduced for 6 hours, and nitrogen is evolved. Cool, add water 1
Adding 500 parts and filtering with suction results in a melting point of 151~
140 parts of 6-chlorobenzoic acid at 156°C (theoretical 89
%) is obtained.

Example 11 2-Aminobenzoic acid 13 in 2000 parts of 10% by weight hydrochloric acid
7 parts and 168 parts of chlorine gas are introduced at 30° C. for 6 hours. Subsequently, 800 parts of isopropanol is added. 85
Addition of a solution of 100 parts of sodium nitrite in 147-40 parts of water in 6 hours at 0C results in the evolution of nitrogen. The mixture is cooled and filtered with suction, giving 158 parts (83% of theory) of 3,5-dichlorobenzoic acid, melting point 176-179°C.

Example 12 167 parts of 2-aminobenzoic acid are added to 8 l0 parts of ethanol, 50 parts of hydrochloric acid (20% by weight) and 500 parts of water. 166 parts of chlorine gas are introduced at 80° C. over a period of 2 hours. Add 600 parts of hydrochloric acid (36% by weight) and add 125 parts of isopropyl nitrite at 80° C. for 7 hours. The mixture is cooled, 800 parts of water are added and filtered with suction, melting point 176~
143 parts (75% of theory) of 3,5-dichlorobenzoic acid at 178 DEG C. are obtained.

Example 16 137 parts of 2-aminobenzoic acid is added to 1000 parts of dilute sulfuric acid (55% by weight), and 600 parts of hydrochloric acid (36% by weight) are added. 140 parts of hydrogen peroxide solution (50% by weight) at 65℃
48- hours and then add 600 parts of isopropanol. Nitrogen is evolved when 280 parts of NaNO in 120 parts of water are added at 85°C for 8 hours. The mixture is cooled, 500 parts of water are added and filtered with suction to give 6,5
-148 parts (77% of theory) of dichlorobenzoic acid are obtained.

Applicant Basf Akchengesellschaft Agent Patent Attorney Masao Kobayashi Continuation of page 1 Priority claim [Phase] 197 Cape December 28 [Phase] West Toy @ May 11, 1977 [Phase] West Toy ○ Inventor: Ulrich Jelsak0 Inventor: Helmut Geerts (DE) [Co., Ltd.] P 2659147.9 (DE) ■
P 2721133.2 German Republic 6700 Ludwigshalfen
Zubliner Strasse 21 Federal Republic of Germany 6700 Ludwigshalfen Rubensstrasse 15

Claims (1)

[Scope of Claims] (a) In the first step, aniline represented by the general formula (wherein R3 and R4 have the meanings given below) is reacted with the norogenated wound in the presence of water and an acid. The resulting halogenaniline represented by the general formula (RI SR1 and R' have the meanings given below) is not separated from the reaction mixture (in the second step, at least 65° C. in the presence of an acid). or (b) with the general formula (wherein R', R' and R4 have the meanings given below). have)
A halogenamine benzoic acid compound represented by is reacted with an aliphatic, cycloaliphatic or araliphatic alcohol and a nitronation agent in the presence of an acid at a temperature of at least 65°C by adding water. (in the formula, R1 and R4 may be the same or different and each means a halogen atom, R3 is a nitro group or a group -CO
OR5, R4 may further mean a hydrogen atom, when R3 means a group -COOR', R4 may mean a nitro group, and R5 is a hydrogen atom or an aliphatic, aliphatic A method for producing benzole represented by a cyclic, araliphatic or aromatic residue.