JPS63275548A - Production of o-aminobenzoyl compound - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as a raw material for pharmaceuticals, perfumes, agricultural chemicals, synthetic resins, additives, etc., by reacting an aromatic amine with a nitrile in the presence of a specific amine having steric hindrance substituent using a boron fluoride compound catalyst. CONSTITUTION:An aromatic amine of formula X-C6H4-NHR (X is H, R, RO, F, Cl, Br, C6H5, C6H5CH2, etc.; R is H, CH3, C2H5, C3H5, C4H9, C5H11, etc.) is made to react with a nitrile of formula Y-C6H4-CN (Y is same as X). The reaction is carried out in the presence of a secondary amine or tertiary amine having steric hindrance substituent using a boron fluoride compound selected from boron fluoride or its complex as a catalyst in the absence of solvent or in an inert solvent at 50-300 deg.C, preferably 100-250 deg.C for 0.5-50hr. The reaction product is hydrolyzed in the presence of an acidic substance or a halogen ion to obtain the objective compound.

Description

[Detailed description of the invention] [Industrial application field] The present invention is applicable to pharmaceuticals, fragrances, agricultural chemicals, industrial chemicals 1, synthetic resins,
The present invention relates to a new method for producing 0-aminobenzoyl compounds, which have high industrial value as raw materials for special resins, additives, etc.

[Prior Art] O-aminobenzoyl compounds are produced by reduction of O-nitrobenzoyl compounds (Ber, 18.2400.188
5 years and 29.1303.1896; J, pr
akt, Chem+ (2) + 65+308, 1
902), Hofmann degradation of 0-benzoylbenzamide (Ann, 291, 13. 1896; J, Ch.
em, Soc, .

85.386.1904), the Ullmann-Pryor process (Organi), which is a five-step process from anthranilic acid.
c 5yntheses+32.9+ 1952),
Stern-Bach method using the high-temperature Friedel-Krach reaction of aniline (Ko Himochi, 1978-15788),
Sugazawa method in which benzonitrile or benzaldehyde is condensed with anilines using boron trichloride as a catalyst (Journal of the Society of Organic Synthetic Chemistry, 36.!lh6, 480.1978; Chem, Phar+++).

Bull, 33. I'h5, 1836. 1985). However, these conventional methods either require expensive reagents, have low yields of the target product, have many work steps and are complicated to operate, or have poor reproducibility depending on the raw material. However, it was difficult to say that it was an industrially advantageous method, as it had drawbacks such as being unable to do so.

[The problem that the invention attempts to solve]

The inventors of the present invention sought to overcome the drawbacks of the conventional methods as described above, searched for a method for producing 0-aminobenzoyl compounds easily and in large quantities, and finally achieved the present invention. The main objective of the present invention is to be able to use an inexpensive boron fluoride compound consisting of either boron fluoride (BF3) or its complex salt (BP+tff salt) as a catalyst for the condensation reaction. As a result of intensive efforts, it was discovered that, contrary to expectations, secondary amines or tertiary amines with sterically hindered substituents exhibit excellent effects, and they have found that the conventional Lewis acid catalyst (BCl
We have now completed the method of the present invention, which exhibits effects that could not be achieved with AlCl2 or AlCl.

[Means and operations for solving the problems] The present inventor has solved the drawbacks related to the conventional method by the following means and has completed the present invention.

That is, an aromatic amine represented by the general formula % formula % (1) and a nitrile represented by the general formula % formula % () (however, in formula 1 and ■2, X, Y are II,
R.

RO + F, CI, Br + CaHs, C
6115CI+2, chl! So, c, 1lsc
o, RNHC6114+RN It Cb)! 4
C11□, RNHCJ140. RNHC6114
CO, and X and Y may be the same or different (,
Also, R is )l, Clh.

CzHs, C3)! 7. C4H9, C3lI lr
,C61(+z,Ca1(l 1C6115,0(C
II□CI+□)2CI(,CHJ(CHzCHz)
zcH, cJsN (indicates either (jlzcL2)zcll. Hereinafter, the same symbols have the same meaning.)
Condensation using a boron fluoride compound consisting of either boron fluoride (BF3) or its complex salt (BP, complex salt) in the presence of a secondary or tertiary amine having a sterically hindered substituent, and then He invented a method for producing an 0-aminobenzoyl compound, which is characterized by hydrolyzing the condensation reaction product obtained here.

Here, the aromatic amine represented by the general formula % formula % (1) is aniline, p-halogenoaniline, N-methylaniline, p-halogeno-N-methylaniline, N-ethylaniline, p-halogeno- N-ethylaniline, p-methoxyaniline, benzidine, p.

Preferably, it is at least one compound selected from the group consisting of p'-diaminodiphenyl ether, p,p'-diaminodiphenylmethane, p,p'-diaminobenzophenone, m,m''-diaminobenzophenone, and the like.

Also, the general formula %formula%() The nitrile represented by Benzonitrile, p-halogenobenzonitrile.

Preferably, it is at least one compound selected from the group consisting of p-methylbenzonitrile, p-methoxybenzonitrile, p-ethybenzonitrile, p-phenylbenzonitrile, p-phenoxybenzonitrile, and the like.

Further, the secondary amine or tertiary amine having a sterically hindered substituent preferably exhibits any of the following structures (Ill) to (■).

R1-N-R3・ ・ ・ ・ ・ ・ ・ ・ ・
(I[[)g.

(However, in formulas ■ to ■, R2 is HlC) lz, C2
H5, Cx! I+.

Indicates either C41C41l, RZ, R3, R4, R
5 is CH3, C2H5°C3H? , C4H9, and they may be the same or different, but in formula (■), R1+ R2+R3 are all CH3, CJ
Neither of s can be. ) Furthermore, the boron fluoride compound is BF3. BF, Koichiro complex salt, BF3
Alcohol complex salt, BP, water complex salt, BF, phenol complex salt, BF3 nitrile complex salt, BF3 ammonia complex salt, BF3
Amine complex salt, BF3 organic acid complex salt, BF3 ester complex salt,
and BF3 acid amide complex salt.

The reaction is promoted by performing the hydrolysis in the presence of an acidic substance or a halogen ion.

The reaction included in the method of the present invention can be expressed as a film as shown in the following formula (■).

Given the current level of chemical knowledge, it is difficult to give a theoretical explanation as to why this reaction proceeds so favorably, but in any case, it has been thought that such a reaction would not be successful. This is what I used to do. As a result of conducting multiple experiments, the inventor discovered that the process (■) is possible.

Now, specific examples of the compound represented by the general formula (1) are as follows (provided that the substituents o +,
The prefixes m- and p- are omitted, and the normal of the substituents,
(Distinctions such as iso, secondary, tertiary, etc. are also omitted). That is, the main compounds are aniline, toluidine, ethylaniline, propylaniline, butylaniline, amylaniline, hexylaniline, cyclohexylaniline, diphenylamine, and N-methylaniline.

N-ethylaniline, N-methyltoluidine, N-ethyltoluidine, anisidine, phenetidine.

Fluoroaniline, chloraniline, bromoaniline,
Phenylaniline, benzylaniline, phenoxyaniline, benzoylaniline, benzidine, N, N'-
These include dimethylbenzidine, diaminodiphenylamine, diaminodiphenyl ether, and diaminobenzophenone.

Specific examples of the compound represented by the -C formula (II) are as follows (provided that the substituents.

-, m-, p- prefixes are omitted, and substituent groups such as normal, iso, secondary, tertiary, etc. are also omitted). That is, the main compounds are benzonitrile, methylbenzonitrile, methoxybenzonitrile, and ethoxybenzonitrile.

Fluorobenzonitrile, chlorobenzonitrile.

Phenylbenzonitrile, benzylbenzonitrile, phenoxybenzonitrile, benzoylbenzonitrile,
Phenylaminophenylbenzonitrile, Phenylaminobenzylbenzonitrile.

These include phenylaminophenylbenzonitrile, phenylaminobenzoylbenzonitrile, and the like.

Specific examples of secondary amines or tertiary amines represented by (II) to (■) having sterically hindered substituents are as follows (provided that the o-, m- , p
The prefix - is omitted, and the distinction between normal, iso, secondary, tertiary, etc. of substituents is also omitted)
. i.e. methyldipropylamine, ethyldipropylamine.

Tripropylamine, methyldibutylamine, ethyldibutylamine, tributylamine, methyldiphenylamine, ethyldiphenylamine, methyldibenzylamine, ethyldibenzylamine.

Methylphenylbenzylamine, ethylphenylbenzylamine, tribenzylamine, 2,6-dimethylpyridine 22,6-dimethylpyridine, 2,6-methylethylpyridine, 2,2,6.6-titramethylbiperidine, 1 ,2,2.6.6-pentamethylpiperidine,
2,2.6.6-tetramethylmorpholine, 1,2
゜2.6.6-pentamethylmorpholine, 2.2.4
．． 6.6-pentamethylpiperazine, C2,2,4,
6,6-hexamethylpiperazine and the like.

Specific examples of boron fluoride or its complex salts are as follows (however, distinctions of substituents such as normal, iso, secondary, tertiary, etc. are omitted, and the compounds are shown by chemical formulas).

That is, BF3.8F30 (C113) z, BF+
0 (CJs) 218F30' (C3t17)z,
BhO(CJJz, BF3C1+30H, Bh(C
1+301riz.

BF3CztlsOH,BF3 (C2H5OH) Z
+ BFJzO, BF3 (H2O) z.

BhO(CJs)z)lzO,BF3C6)ISOH,
BF3(CJbO)1)z3BF3C6H5CN,
BFJIIz, BF3RNH2, BF3RR' N
H, BF3RR' R”N.

BF:1RCOOH, BF3(RCOOH)z, BF3
RCOOR', BF3C1+30H" (However, in these formulas, R represents either H, C113, C2H5, C6H5, and R', R" represents CH3, CzHs, CzHt,
CJq, and they may be the same or different. ) The fact that hydrolysis is carried out in the presence of an acidic substance or halogen ion means that the pH of the aqueous solution is ≧1 to 1, depending on the presence of a water-soluble inorganic acid, a water-soluble acidic inorganic salt, a water-soluble organic acid, etc.
7. Particularly preferably an aqueous solution whose pH is maintained at 1 to 6, or F-, CI-.

The hydrolysis treatment is carried out at 0 to 100° C. in an aqueous solution whose pH is maintained at 1 to 8, particularly preferably at 1 to 7, in the presence of Br.

This treatment is usually easily accomplished by dissolving or dispersing the imino compound shown in formula (■) in an aqueous solution and bringing it into sufficient contact with water.This imino compound is pre-dissolved in an organic solvent. There is no harm in leaving it as is.

Now, the reaction between the aromatic amine represented by the formula (1) and the nitrile represented by (n) is carried out in the presence of the secondary amine or tertiary amine referred to in the present invention.
P, using a complex salt as a catalyst under solvent-free conditions or in the presence of an inert solvent at 50 to 300°C, particularly preferably 10
This is achieved by keeping it at 0 to 250°C for 0.5 to 50 hours, and the amounts of (I)/(n)/amine/catalyst used are 1 to 2/1/1 if expressed in molar ratio. ~2/1~5
This is often done within a range of percentages. This reaction is carried out under reduced pressure, normal pressure, or increased pressure. However, if it is necessary to remove the low-boiling fractions produced by the reaction (this may be necessary to maintain the reaction temperature), the reaction mixture may be removed at an appropriate time. It is desirable to distill away more.

Many reactions are carried out in an inert gas atmosphere, if necessary with strong stirring, but it is best to avoid direct sunlight. The imino compound shown in formula (■) or its salt may be temporarily collected from this reaction mixture as an intermediate, but it may be subjected to a hydrolysis process as it is, and after the reaction is completed, the target product can be extracted by washing, extraction, or distillation. It can be collected by a method such as a crystallization method or a recrystallization method. At this time, unreacted raw materials and by-products are effectively separated from the target product, and the formation of the product can be detected at each stage during the reaction by chromatography or the like.

In the method of the present invention, it is important to appropriately select the reaction raw materials and reaction conditions in order to suppress side reactions, and the yield of the target product is influenced by the combination thereof. It will be shown.

〔Example〕

The present inventor conducted numerous experiments regarding the method of the present invention described above and confirmed the superiority of the final method.Examples will be shown below to further explain the technical content of this method. .

Example 1 47.0 g (0.5 mol) of aniline, 129 g (1.0 mol) of ethyldiisopropylamine, and 51.0 g (0.5 mol) of benzonitrile were mixed, cooled, and stirred. BF3 gas 101.7 g (1,
If 5 mol) is blown into the mixture, a paste-like material with crystals dispersed therein will be created. Then, gradually warm it up to 200-220
After reacting at ℃ for 20 hours, the reaction mixture was cooled, poured into 500 ml of 10% aqueous hydrochloric acid solution, and boiled for 20 hours to convert unreacted benzonitrile to benzoic acid. A concentrated sodium hydroxide solution is added to the reaction mixture to make it alkaline, and unreacted aniline and ethyldiisopropylamine are recovered by fume distillation. When ice water is added to the residue and stirred, a large amount of crystals precipitates, which are filtered off and recrystallized from ether to yield aminobenzophenone (mp,
106°C) 46.0g (yield 46%) was obtained.

Example 2 In Example 1, benzidine 46. was used instead of aniline.
When 0 g (0.25 mol) was used in the same manner, 3,3°-dibenzoylbenzidine was obtained in a yield of 23%.

Examples 3 to 11 If the same procedure as in Example 1 is carried out using 5 mol of p-substituted aniline shown in the following table instead of aniline, the corresponding 2-amino-5-substituted benzophenone can be obtained with the yield shown in the following table. sell.

Examples 12 to 16 If the same procedure as in Example 1 is carried out using 5 moles of nuclear-substituted benzonitrile shown in the following table and an amine having a sterically hindered substituent in place of benzonitrile and ethyldiisopropylamine, the results shown in the following table are obtained. The yield corresponds to 2-
Obtain amino-benzophenones.

Examples 17-24 If the same procedure as in Example 1 was performed using the catalyst shown in the following table instead of BF and gas, the corresponding 0
- Obtain aminobenzphenone.

The catalysts shown in the following table are synthesized by blowing BF3 gas into the corresponding organic compounds immediately before use, and then concentrated under reduced pressure.
It is a pure product that has been purified as much as possible by vacuum distillation or recrystallization, and is a colorless liquid or colorless crystal. Note that when a commercially available product (reagent) is used, the yield of the target product tends to decrease.

〔Effect of the invention〕

As described above, according to the present invention, in order to synthesize an 0-aminobenzoyl compound, anilines and benzonitriles are synthesized in the presence of amines having specific sterically hindered substituents using a boron fluoride compound catalyst. An effective process was developed to react the condensate and hydrolyze the condensate. This method has the advantage of easily producing useful 0-aminobenzoyl compounds, which are raw materials for pharmaceuticals, organic synthesis intermediates, polymeric compounds, etc., and can be said to have tremendous industrial value.

Claims (6)

[Claims] (1) An aromatic amine represented by the general formula X-C_6H_4-NHR (I) and a general formula Y-C_6H_4-CN (II) nitrile represented by (however, in formulas I and II, X, Y are H, R,
RO, F, Cl, Br, C_6H_5, C_6H_5C
H_2, C_6H_5O, C_6H_5CO, RNHC
_6H_4, RNHC_6H_4CH_2, RNHC_
6H_4O, RNHC_6H_4CO, X and Y may be the same or different, and R is H, CH_3
, C_2H_5, C_3H_7, C_4H_9, C_5
H_1_1, C_6H_1_3, C_6H_1_1C_
6H_5, O(CH_2CH_2)_2CH, CH_3
N(CH_2CH_2)_2CH, C_2H_5N(C
Indicates either H_2CH_2)_2CH. ) and boron fluoride (BF_3) in the presence of a secondary or tertiary amine having a sterically hindered substituent.
A method for producing an o-aminobenzoyl compound, which comprises condensing the compound using a boron fluoride compound consisting of either a boron fluoride compound or a complex salt thereof (BF_3 complex salt), and then hydrolyzing the condensation reaction product obtained here. (2) Aromatic amine represented by the general formula
, Br, C_6H_5, C_6H_5CH_2, C_6
H_5O, C_6H_5CO, RNHC_6H_4, R
NHC_6H_4CH_2, RNHC_6H_4O, R
Indicates either NHC_6H_4CO, R is H, CH
_3, C_2H_5, C_3H_7, C_4H_9, C
_5H_1_1, C_6H_1_3, C_6H_1_1
C_6H_5, O(CH_2CH_2)_2CH, CH
_3N(CH_2CH_2)_2CH, C_2H_5N
Indicates either (CH_2CH_2)_2CH. ) is aniline, p-halogenoaniline, N-methylaniline, p-halogeno-N-methylaniline, N-ethylaniline, p-halogeno-N-ethylaniline, p-methoxyaniline, benzidine, p,p'-diamino diphenyl ether, p,p'-diaminodiphenylmethane,
The method for producing an o-aminobenzoyl compound according to claim (1), which is at least one compound selected from the group consisting of p,p'-diaminobenzophenone and m,m'-diaminobenzophenone. (3) Nitrile represented by the general formula Y-C_6H_4-CN (II) (however, in formula II, Y is H, R, RO, F, Cl,
Br, C_6H_5, C_6H_5CH_2, C_6H
_5O, C_6H_5CO, RNHC_6H_4, RN
HC_6H_4CH_2, RNHC_6H_4O, RN
Indicates either HC_6H_4CO, R is H, CH_
3, C_2H_5, C_3H_7, C_4H_9, C_
5H_1_1, C_6H_1_3, C_6H_1_1C
_6H_5, O(CH_2CH_2)_2CH, CH_
3N(CH_2CH_2)_2CH, C_2H_5N(
CH_2CH_2)_2CH. ) is benzonitrile, p-halogenobenzonitrile, p-
Methylbenzonitrile, p-methoxybenzonitrile,
The method for producing an o-aminobenzoyl compound according to claim (1), which is at least one compound selected from the group consisting of p-ethylbenzonitrile, p-phenylbenzonitrile, and p-phenoxybenzonitrile. (4) The o-aminobenzoyl compound according to claim (1), wherein the secondary amine or tertiary amine having a sterically hindered substituent has any of the following structures (III) to (VII). manufacturing method. ▲There are mathematical formulas, chemical formulas, tables, etc.▼......(III) ▲There are mathematical formulas, chemical formulas, tables, etc.▼......(IV) ▲There are mathematical formulas, chemical formulas, tables, etc.▼......(V) ▲Mathematical formulas , chemical formulas, tables, etc.▼......(VI) ▲Mathematical formulas, chemical formulas, tables, etc.▼...(VII) (However, in formulas III to VII, R_1 is H, CH_3,
Indicates either C_2H_5, C_3H_7, C_4H_9, and R_2, R_3, R_4, R_5 are CH_3,
C_2H_5, C_3H_7, C_4H_9, which may be the same or different, but in formula III, R_1, R_2, and R_3 are all CH_
3, C_2H_5. ) (5) The boron fluoride compound is BF_3, BF_3 ether complex salt, BF_3 alcohol complex salt, BF_3 hydrate complex salt, B
F_3 phenol complex salt, BF_3 nitrile complex salt, BF_
The o-aminobenzoyl compound according to claim (1), which is at least one compound selected from the group consisting of 3 ammonia complex salt, BF_3 amine complex salt, BF_3 organic acid complex salt, BF_3 ester complex salt, and BF_3 acid amide complex salt. manufacturing method. (6) The method for producing an o-aminobenzoyl compound according to claim (1), wherein the hydrolysis is carried out in the presence of an acidic substance or a halogen ion.