This invention relates to an improved process for preparing N- (3-amino-4-chlorophenyl) acylamides which are useful as intermediates for couplers for preparing disperse azo dyes for dyeing textile fibers and for preparing couplers which are useful in color photography. The process involves the selective acylation of the 4-amino group in l-chloro-2,4- diaminobenzene using certain acyl chlorides in the presence of an acid acceptor.

Prior Art U.S. Patent 4,448,719 (Example 28) teaches the selective acylation of l-chloro-2,4-diaminobenzene using 2-methoxyethyl chlorocarbonate in a reaction mixture of chlorobenzene and water. No yields are given. The use of the reaction conditions of this method to produce the N- (3-amino-4-chlorophenyl) acylamides of this invention gives very low yields of product (see Comparative Example 1) .

U.S. Patent 4,283,556 teaches the selective mono acylation of l-methoxy-2,4-diaminobenzene using anhydrides in alcohols as solvents. Using anhydrides to introduce the acyl group is inherently less efficient than acylation with acyl halides, since approximately- one half of the weight of anhydride is lost during the reaction in the form of the corresponding acid. This is particularly disadvantageous in preparing the intermediates for photographic couplers, since the acylating agent is usually used to introduce a complicated and expensive ballast group into the coupler. Similarly, U.S. Patent 4,540,815 describes the selective acylation of 1,3-diaminobenzene and l-C^ -C ₄

alkoxy-2,4-diaminobenzenes using anhydrides in the presence of C _x -C ₄ alkanols and hydrogen halides to precipitate the monoacylated compounds when formed to prevent further acylation.

Detailed Description of the Invention

This invention relates to a process for preparing N- (3-amino-4-chlorophenyl) acylamides of Formula I:

comprising reacting, in a solvent comprising at least one polar solvent, in the presence of an acid acceptor, l-chloro-2,4-diaminobenzene with at least one acyl chloride of formula II: Cl-X-R wherein X is -CO- or -S0 ₂ -; R is selected from the group Ci-C _js alkyl; C ₁ -C _2S alkyl substituted with one or more groups selected from C^-C^ alkoxy, aryl, aryloxy and C ₅ -C ₇ cycloalkyl; aryl; C ₅ -C ₇ cycloalkyl. The N-(3- amino-4-chlorophenyl) acylamides I, are useful as intermediates for producing disperse textile dyes and couplers for color photography. The reaction of 1- chloro-2,4-diaminobenzene with acyl chlorides II is as follows:

wherein X and R are as defined above.

It has been discovered that high yields of useful compounds 'I having high purity are obtained by reacting the l-chloro-2,4-diaminobenzene II with acyl chlorides III as described above in certain polar solvents. If the reaction is conducted in a polar solvent the purification is generally conducted in a non-polar solvent. Preferably mixtures of certain nonpolar solvents and certain polar solvents present at up to 50% by weight are used. The nonpolar solvent is selected from C ₅ -C ₇ alkanes, benzene, toluene, ethylbenzene, cumene and xylenes, or mixtures thereof, with toluene being preferred. Useful polar solvents include alkanols, with methanol being preferred. Preferably, the solvent mixture contains from 20 to 50% by weight of the polar solvent.

The mixed solvents as described above are particularly useful for promoting the completion of the acylation reaction and further for removing any bis acylated product, which may occur as an undesired impurity, during isolation of the desired product.

The monoacylation reactions are carried out in the presence of one or more acid acceptors, usually selected from tertiary amines, e.g. triethylamine, tri-n- butylamine, tetraalkylethylenediamines,- N,N-dialkylanilines, e.g. N,N-dimethylanilines; nitrogen containing heterocyclic compounds, e.g. pyridine, picolines, lutidines, quinolines, isoquinolines, pyrroles, imidazoles and mixtures thereof. Preferred acid acceptors are' triethylamine, pyridine, picolines, lutidines, imidazole and mixtures thereof.

The acylation reaction is usually carried out at temperatures ranging from -15 to +75°C, preferably from -5 to +50°C. Prior to the present invention the N- (3-amino-4- chlorophenyl) acylamides were made from chloro nitro anilines via a difficult multi step process (e.g. as disclosed in U.S. 3,265,506, Example 8). The selective acylation of 1-chloro-2,4-diaminobenzene according to the process of this invention provides an alternative process which offers high yields of desired products having excellent purity. Since the starting 1-chloro- 2,4-diaminobenzene for this method is derived by reduction of l-chloro-2,4-dinitrobenzene, which is readily available and cheap, the method offers improved economics versus previously disclosed methods.

The terms "aryl" and "aryloxy" are used to denote aromatic monovalent radicals selected from the classes of benzene and naphthalene and these radicals substituted with one or more groups selected from C _j -C _j r, alkyl; C ₁ -C ₁₂ alkoxy; hydroxy; nitro; halogen; C ₅ -C ₇ cycloalkyl; alkanesulfonamido; phenylsulfonyl and phenylsulfonyl substituted by one or more groups selected from C^C^ alkoxy, C- _. -C ₁₂ alkanoyloxy, benzyloxy, OR_, and OCORi,

wherein R is phenyl or phenyl substituted by C -C ₁₂ alkyl, ^-C^ alkoxy or halogen.

The term C _x -C ₂₅ alkyl is used to denote a straight or branched chain hydrocarbon radical having 1 to 25 carbons.

In the terms ⁿ C ₁ -C ₁₂ alkoxy", "C^-C^, alkanoyloxy", alkanoylamino" and alkanesulfonamido", the alkyl portion of the group is a straight or branched chain hydrocarbon moiety containing 1 to 12 carbon atoms.

The term "halogen" is used to include fluorine, chlorine, bromine and iodine.

In a preferred embodiment of the invention, X is - CO-, and R is preferably Ci-Cj _o alkyl substituted with a phenoxy radical containing one or more groups selected from C ₁ -C ₂₀ alkyl, hydroxy, nitro, C ₁ -C ₁₂ alkanesulfonamido, Cj-C ₁₂ alkanoyloxy and halogen. In another preferred embodiment, X is CO and R is phenyl or phenyl substituted with C ₁ -C ₂₀ alkyl, C _x -C ₁₂ alkoxy or nitro. In another preferred embodiment of the invention, X is -S0 ₂ - and R is a C ₁ -C ₂₀ alkyl radical. Typical acyl chlorides III which are useful in the practice of the invention are provided in Table I. The N- (3-amino-4-chlorophenyl) acylamides of Formula I may be readily converted to provide useful derivatives IV.

I IV

The above reaction may be conducted via a number of methods'which are generally known in the art. The class of compounds within Formula IV wherein X is CO; R is C ₁ -C ₄ alkyl, substituted C^-C* alkyl or aryl; R ² is hydrogen unsubstituted or substituted Cj-Cg alkyl, or unsubstituted or substituted C ₃ -C ₄ alkenyl are known to be useful as couplers for producing azo disperse dyes for textile fibers (U.S. Patent 4,448,719; Dyes and Pigments 4 (1983) 195-211) .

The class of compounds within Formula IV wherein X is -CO- and -S0 ₂ -; R is C^-C^ alkyl, substituted C^-C^ alkyl or aryl; R ² an active methylene moiety such as 1- aryl-5-pyrazolone-3-yl or pivaloyl are useful intermediates for color photography [U.S. Patent 5,008,179 (See Columns 7,8,9); U.S. Patent 3,265,506 (See Columns 5,7,8); U.S. Patent 3,894,875 (See Columns 4,5,6,7,8); U.S. Patent 3,408,194 (See Column 6)] . The following examples illustrate further the practice of the invention.

Example 1

A room temperature solution of 1-chloro-2,4- diaminobenzene (1.43g, 10 mmol), 1-hexadecanesulfonyl chloride (3.24g, 10 mmol), imidazole (0.68g, 10 mmol) and toluene (20mL) was stirred for 1 hr. Isopropyl alcohol (20 mL) was added and the reaction mixture was heated at 60°C for 2 hours. Analysis by thin layer chromatography (tic) (40% ethyl acetate and 60% heptane) indicated incomplete acylation and additional

1-hexadecanesulfonyl chloride (0.7g, 2 mmol) was added and the reaction mixture was stirred at 60-62°C for an additional hour, at which time the reaction appeared to be complete by tic analysis. The reaction solution was treated with hot water (50 mL) and the layers separated. The toluene layer was further washed twice with 50 mL of hot water. Heptane (20 mL) was added to the recovered toluene layer to precipitate the product, N~(3-amino- 4-chlorophenyl) -1-hexadecanesulfonamide, which was isolated by cooling the mixture to 0°C and collecting the product by vacuum filtration. After being washed with cold heptane, the product was dried (yield=3.12g, 72% of the theoretical yield) and it melted at 103- 104°C. No impurities were observed by IrtTMR analysis.

Example 2

A solution of l-chloro-2,4-diaminobenzene (1.43g _γ 0.01 mole) and triethyl amine (l.lg, 0.011 mole) in a mixture of methyl alcohol (5.0 mL) and toluene (10.0 L) was stirred and cooled to -5°C. To this solution was added 4- (2,4-di-tert-pentylphenoxy)butyryl chloride (3.60g, 0.0107m) at less than +5°C. The reaction mixture was stirred overnight and allowed to warm to room temperature. The mixture was examined via HPLC and found to be 87% desired product and 10% of the undesired

bis-acylated compound. The methanol and hydrochloride salt of the amine were removed by washing the toluene layer with water. After evaporating the toluene layer to dryness the crude product was recrystallized from a solution of 10 mL of heptane and 5 mL of toluene. The yield of solid product was 4.10g. High pressure liquid chromatography, analysis (HPLC) indicated that the crude product consisted of 98.4% by weight (90.7% of the theoretical yield) of the desired monoacylated product N- (3' -amino-4' -chlorophenyl) -4- (2,4-di-tert- pentylphenoxy)butyramide shown below,

NHCqCH) ₃

0.1% by weight of the starting l-chloro-2,4- diaminobenzene and 0.6% by weight of the bis acylated product. None of the isomeric product resulting from acylation of the 2-amino group of the starting material was observed.

Example 3

Example 2 was repeated using lutidine(1.2g, 0.011 mol) as the acid acceptor to yield 3.38g of product which by HPLC was shown to consist of 96.8% by weight (73.5% of the theoretical yield) of the desired

monoacylated product, 0.65% by weight of starting 1- chloro-2,4-diaminobenzene and 0.9% by weight of the bis acylated product.

Example 4

A solution of l-chloro-2,4-diaminobenzene (1.43g, 0.01 mol) and imidazole (0.7g) in a mixture of toluene (10.0 mL) and methyl alcohol (5.0 mL) was stirred and treated with benzoyl chloride at 0-5°C. The reaction mixture was stirred at 0-5°C for 1 hour and then allowed to stir overnight at room temperature. Water (20 mL) and ethyl acetate (30 mL) were added and the mixture was then heated until all of the solid had dissolved. The water layer was separated and the organic layer was evaporated to dryness. After recrystallization from toluene, 2 13 grams of product were obtained (86.3% of the theoretical yield) . The product, which showed only one component present by thin layer chromatography and which melted at 160-161°C, had the following structure:

The product was high quality by H ¹ NMR.

Example 5

A solution of l-chloro-2,4-diaminobenzene (l.43g, 0.01 mol) and imidazole (0.0113 mol) in toluene (10.0 mL) and methyl alcohol (5.0 mL) was stirred and treated at 0-5°C with a solution of p-toluene sulfonyl chloride (2.1 g, 0.0108 mol) in toluene (10.0 mL) . The reaction mixture was stirred overnight at room temperature and then washed with water (40.0 mL) . The aqueous layer was discarded and the solvent was removed from the organic layer by evaporation. After recrystallization of the residue from a mixture of toluene-ethyl acetate, the product was obtained in 88.3% yield by weight. By H ¹ NMR, the product was 97.2% pure by weight and had the following 'structure:

Thus, an actual yield of 85.8% of the theoretical yield was obtained.

Comparative Example 1 (U.S. 4,448,719, Ex. 28)

A mixture of l-chloro-2,4-diaminobenzene (4.27g, 0.03 mol), chlorobenzene (15 mL) and water (15 mL) was stirred vigorously and treated with a solution of 4- (2,4-di-tert-pentylphenoxy)butyryl chloride (0.03 mol) at 8-10°C, while the pH was kept at 6-7 by the addition of a 5% by weight aqueous sodium carbonate solution. The reaction mixture was stirred for 0.5 hour and was examined by HPLC and found to be a mixture of 63% of the desired product and 30% of the undesired bis-acylated compound. The mixture was heated to 70°C to dissolve the solids present. The aqueous layer was separated off and the organic layer washed with hot water (50.0 mL) . The solvent was removed under vacuum from the organic layer to yield a solid residue which was recrystallized from a mixture of heptane (30.0 mL) and toluene (15.0 mL) to yield 3.67g (33.0% of the theoretical yield) of product which was high quality (by tic) product having the following structure:

Compared to the procedure of this invention utilized in Example 2 above (90.7 % of the theoretical yield, 87% desired product in the reaction mixture) , a much lower yield of product was obtained using the reaction conditions of known process (33% of theoretical yield, 63% desired product in the reaction mixture) . Thus, the process of the present invention is nearly three times more efficient than the prior art process.

13 -

TABLE I

Typical Acyl Halides

^R 3 - ^C I- ^C 12 ^aUc y alkanoyloxy, benzyioxy, aryl or aroy _l oxy

Table I continued

(CH ₃ ) ₂ CHCθα

CH ₃ (CH ₂ ) ₃ CH(C2H ₅ OCl

n-C ₁₃ H ₂₇ Cθα

Coα

Table I continued . . .

o- CH _j COCl