JPH0788341B2 - Method for producing carboxamides - Google Patents

Description

The present invention relates to a method for producing aromatic or heterocyclic carboxylic acid amides.

More specifically, general formula (IV): R ¹ (Cl) m (IV) (wherein, R ¹ represents an aromatic hydrocarbon group or a heterocyclic hydrocarbon group which may have a substituent, and m Represents an integer of 1 or more.) The organic chloride represented by (In the formula, R ⁵ R ⁶ and R ⁷ may be the same or different and each represents an alkyl group which may have a substituent, a phenyl group, a phenyl group which may have a substituent or a phenoxy group. ) Is used as a catalyst in the presence of a base in the presence of carbon monoxide and the general formula (III) (In the formula, R ² and R ³ may be the same or different, and may have a hydrogen atom or a substituent, and represent an aliphatic hydrocarbon group, an aromatic hydrocarbon group or a heterocyclic hydrocarbon group. , R ² and R ³
Together represent an alkylene group which may be interrupted by an oxygen atom or a nitrogen atom. ) Is reacted with an amine represented by the formula (I-1) at a reaction temperature of 180 ° C to 300 ° C: (In the formula, R ¹ , R ² , R ³ and m are the same as above.) The present invention relates to a process for producing a carboxylic acid amide.

The carboxylic acid amides according to the present invention are compounds which are themselves useful as agricultural chemicals, and also provide a novel method for producing carboxylic acid amides which are also useful in medicine and the like.

As a method for producing an aromatic or heterocyclic carboxylic acid amide, a method of reacting an aromatic or heterocyclic halogen compound and a primary or secondary amine with palladium / triarylphosphine and reacting with carbon monoxide Have been proposed (see US Pat. No. 3,588,358 and US Pat. No. 4,128,554).

However, in these methods, reaction with iodide or bromide as an aromatic halide is performed, but reaction with an aromatic chloride is not performed. As a reaction of a chlorinated compound, 2-chloropropene, which has a double bond and is easily reacted, is reacted with aniline in the presence of a tertiary amine under pressure to form N-phenylmethacrylamide. However, the reaction of aromatic chloride is not described at all, and the phosphine compound used as a catalyst is a triarylphosphine which is completely different from the present invention.

Further, a method of reacting an organic halide, carbon monoxide and phosphoric acid triamides in the presence of a carbonylation catalyst (Japanese Patent Laid-Open Publication No. S60-12065)
57-200338) is known. However, this method also does not disclose any reaction with an aromatic chlorinated compound in which the aromatic ring is directly substituted with chlorine, and phosphoric acid triamide is used in the reaction. This phosphoric acid triamide is expensive and highly toxic, and therefore has problems in industrialization.

Japanese Unexamined Patent Publication (Kokai) No. 61-293950 discloses a method for producing a carboxylic acid and an ester thereof using a chloro or promarene carbonyl chromium compound, but it is possible to produce a tricarbonyl chromium complex as a reaction substrate. It is expensive and has toxicity issues.

As described above, the reaction of aromatic iodide or bromide with carbon monoxide is known, but the method of synthesizing aromatic carboxylic acid amides by the reaction of aromatic chloride and carbon monoxide is completely unknown. Not not.

In view of the above situation, the present inventors have conducted intensive studies on the reaction of aromatic or heterocyclic chlorides with carbon monoxide, and as a result, established a method for obtaining aromatic or heterocyclic carboxylic acid amides in good yield. The present invention has been completed.

The reaction of the present invention can be represented schematically as follows, for example.

(In the formula, R ¹ , R ² , R ³ , R ⁵ , R ⁶ , R ⁷ and m are the same as above.) That is, the organic chloride represented by the general formula (IV) is converted into a palladium compound and a general formula (V ) Is used as a catalyst to react with carbon monoxide and the amines represented by the general formula (III) in the presence of a base or in the presence or absence of a solvent at a reaction temperature of 180 ° C to 300 ° C. By
The desired carboxylic acid amide represented by the general formula (I-1) can be produced.

The organic chloride represented by the general formula (IV) of the present invention is an organic chloride having at least one chlorine atom on the ring of an aromatic hydrocarbon or heterocyclic hydrocarbon which may have a substituent. As long as it is a condensed ring hydrocarbon and a condensed heterocyclic hydrocarbon, and representative examples are, for example, chlorobenzene, dichlorobenzene, trichlorobenzene, tetrachlorobenzene, pentachlorobenzene, hexachlorobenzene, trifluoromethyl. Chlorbenzene, chlorotoluene, dichlorotoluene, trichlorotoluene, chloroxylene, dichloroxylene, trichloroxylene, chlorophenol, chloroanisole, chloronitrobenzene, dichloronitrobenzene,
Chlorocyanobenzene, chlorophenylacetic acid ester,
N-acetylchloroaniline, chloroacetophenone,
Aromatic organic chlorides such as chlorobenzophenone, chloromethylthiobenzene, chlorobenzoic acid ester, chlorodiphenyl ether, chloronaphthalene, chloromethylnaphthalene, chloroanthraquinone, chlorothiophene,
Heterocyclic organic chlorides such as chlorofuran, chloroindole, chloropyridine, dichloropyridine, chloropicoline, chloroquinoline, chloroquinoxaline and dichloroquinoxaline can be mentioned. The organic chloride may be used in a predetermined amount, or may be used in excess and used as a solvent.

Examples of the amines represented by the general formula (III) used in the present invention include aliphatic amines such as ammonia, methylamine, ethylamine, dimethylamine and diethylamine, aniline, alkylaniline, haloaniline, haloalkylaniline and alkoxyaniline ( Methoxyaniline, ethoxyaniline, isopropoxyaniline), aromatic amines such as benzylamine, pyrrole,
Heterocyclic amines such as imidazole, triazole, indole, aminopyridine, aminotriazole, aminoimidazole, aminothiophene, aminothiazole, aminofuran, aminobenzimidazole and aminoquinoline can be mentioned.

Amines represented by the general formula (III) are organic chlorides 1
It may be present in the reaction system in an equimolar amount to a molar amount or in a molar amount corresponding to the number of chlorine atoms on the ring of the organic chloride or in an excess amount.

The amines represented by the general formula (III) can also act as a base by using in excess.

The palladium compound used as a catalyst in the present invention may be used in combination with a phosphine compound, and examples of the palladium compound include metallic palladium, palladium carbon, palladium alumina, palladium chloride, palladium bromide, palladium acetate, dichlorobiscyanophenyl. Examples thereof include palladium, dichlorobistriphenylphosphine palladium, tetrakistriphenylphosphine palladium and the like.

Examples of the phosphine compound represented by the general formula (V) that can be used in combination with the palladium compound in the present invention include triisopropylphosphine, tributylphosphine,
Triphenylphosphine, triparafluorophenylphosphine, tri-pentafluorophenylphosphine,
Examples thereof include triparatolyl phenylphosphine, triphenoxyphosphine, dimethylphenylphosphine, methyldiphenylphosphine, di-pentafluorophenylphosphine and the like.

The amount of phosphine compound added is based on the palladium compound
0.01 to 10,000 times mol may be used, preferably 0.1 to 1
It is sufficient to use 00 times mole.

In the present invention, the palladium compound and the phosphine compound represented by the general formula (V) may be used in combination, and may be used alone in the reaction system, or may be prepared in the form of a complex in advance and used.

The addition amount is not particularly limited, but the amount of the palladium compound and the phosphine compound added to the reaction system is 1 mol based on 1 mol of the organic chloride represented by the general formula (IV).
It suffices to use 0.0001-fold to 0.5-fold moles, preferably
It may be selected from the range of 0.001 times mole to 0.1 times mole.

The base that can be used in the present invention may be selected from inorganic bases and organic bases, for example, inorganic bases such as sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, triethylamine, tributylamine, diisopropylethylamine, triisooctyl. Amine, pyridine, N-methylpyrrolidine, N-methylmorpholine, N
There may be mentioned organic bases such as ethylmorpholine.

As the amount of the base used, it is preferable to use the amount necessary for neutralizing the produced hydrogen chloride, but it is of course at least better or higher than this.

The reaction in the present invention can be carried out in the presence or absence of a solvent, the solvent that can be used may be a solvent that does not significantly inhibit the reaction, for example, hexane, benzene, ether, tetrahydrofuran, acetonitrile, Examples thereof include organic solvents such as dimethylformamide, hexamethylphosphotriamide, and acetone.

The reaction of the present invention is carried out under atmospheric pressure to increased pressure, and the pressure of carbon monoxide is appropriately selected within the range of 1 to 200 atm, preferably within the range of 1 to 50 atm.

The present invention is carried out at a reaction temperature of 180 ° C to 300 ° C, preferably 180 ° C to 250 ° C.

The reaction vessel used in the present invention may be a normally used vessel, and in the case of a pressure reaction, any vessel can be used as long as it can withstand the reaction pressure, and a metal or glass vessel is usually used.

The reaction time varies depending on the amount of the reaction reagent and the reaction temperature, but may be selected from the range of several minutes to 48 hours.

After the completion of the reaction, the desired compound can be obtained by the usual treatment.

Examples of the present invention will be shown below, but the present invention is not limited thereto.

Example (1-1) 3'-isopropoxy 2-α, α, α-
Production of trifluorotoluanilide Orthochlorobenzotrifluoride (12 ml), meta-isopropoxyaniline (1.5 g), palladium chloride (17.7 mg), tributylphosphine (0.4 g), potassium carbonate (1.5 g) were placed in a metal autoclave with an electromagnetic induction stirrer. Put it in, replace it with carbon monoxide several times, and then fill it with 44 kg / cm ² .
The internal temperature is set to 200 ° C and the reaction is carried out for 6 hours with stirring. After the reaction, the mixture was cooled to room temperature, washed with water, the organic layer was separated, concentrated, and reconstituted with ethyl acetate-hexane to give 3'-isopropoxy-2.
1.95 g of -α, α, α-trifluorotoranilide was obtained.

Melting point 102-103 ° C. Yield 1.95 g Example (1-2) Orthochlorobenzotrifluoride (10 ml), meta-isopropoxyaniline (1.0 g), tetrakis (triphenylphosphine) in a metal autoclave with an electromagnetic induction stirrer. Palladium (250 mg), triphenylphosphine (0.28 g) and N-methylpyrrolidine (0.84 g) were added,
After substituting several times with carbon monoxide, it was filled with 76 kg / cm ² and the internal temperature was 20
The reaction is carried out for 6 hours with stirring at 0 ° C. After the reaction, the mixture was cooled to room temperature, washed with water, the organic layer was separated, concentrated, and reconstituted with ethyl acetate-hexane to give 3'-isopropoxy 2-α,
1.56 g of α, α-trifluorotoranilide was obtained.

Yield 1.56 g Example (1-3) Orthochlorobenzotrifluoride (12 ml), meta-isopropoxyaniline (1.5 g), palladium chloride (17.7 mg), triphenylphosphine (in a metal autoclave with an electromagnetic induction stirrer) 0.52g), potassium carbonate (1.5
After adding g) and substituting with carbon monoxide several times, it is filled with 42 kg / cm ² and the temperature is kept at 200 ° C. for 6 hours with stirring. After the reaction, the mixture was cooled to room temperature, washed with water, the organic layer was separated, concentrated, and reconstituted with isopropanol-hexane to give 3'-isopropoxy 2-α, α, α-trifluorotoluanilide.
96 g was obtained.

Yield 1.96 g Example (1-4) Orthochlorobenzotrifluoride (25 ml), meta-isopropoxyaniline (3 g), palladium chloride (17.7 mg), triphenylphosphine (524 mg), N- in a metal shaking autoclave. Methylmorpholine (2.2 g) was added, carbon monoxide was substituted several times, and the mixture was filled with 42 kg / cm ² and the internal temperature was 200 ° C. in a silicone oil bath, and the mixture was reacted for 5 hours while shaking. After the reaction, the mixture was cooled to room temperature, washed with water, the organic layer was separated, concentrated, and recombined with ethyl acetate-hexane.
2.0 g of 3'-isopropoxy 2-α, α, α-trifluorotoluanilide was obtained.

Yield 2.0 g Example 2 The same conditions as in Example (1-4) were used except that N-methylmorpholine in Example (1-4) was replaced with the base shown in the table below. The results are summarized in the table below.

Claims (7)

[Claims] 1. An organic chloride having at least one chlorine atom on the ring of an aromatic hydrocarbon or a heterocyclic hydrocarbon which may have a substituent, and a palladium compound and a compound represented by the general formula (V): (In the formula, R ⁵ R ⁶ and R ⁷ may be the same or different and each represents an alkyl group which may have a substituent, a phenyl group, a phenyl group which may have a substituent or a phenoxy group. ) The method for producing carboxylic acid amides, which comprises reacting carbon monoxide and amines at a reaction temperature of 180 ° C to 300 ° C in the presence of a base using a phosphine compound represented by the formula as a catalyst. 2. The method for producing carboxylic acid amides according to claim 1, wherein the palladium compound is palladium metal, palladium metal supported on a solid, or palladium zero-valent, divalent or tetravalent complex. 3. A palladium compound is palladium carbon,
The method for producing a carboxylic acid amide according to claim 1, which is palladium chloride or palladium acetate. 4. The method for producing carboxylic acid amides according to claim 1, wherein the phosphine compound represented by the general formula (V) is trialkylphosphine or triarylphosphine. 5. The method for producing a carboxylic acid amide according to claim 1, wherein the base is an inorganic base or an organic base. 6. The method for producing a carboxylic acid amide according to claim 1 or 4, wherein the base is sodium carbonate or potassium carbonate. 7. The method for producing a carboxylic acid amide according to claim 1, wherein the pressure of carbon monoxide is 1 to 200 atm.