The present invention relates to a method for the preparation of diaminoresorcinol. 4,6-Diaminoresorcinol is a monomer used in preparing polybenzoxazoles (PBO).

Although there are a number of known methods for preparing 4,6-diamino-resorcinol, there continues to be a need to find more efficient and cost effective routes to obtain 4,6-diaminoresorcinol.

One known method involves synthesizing the monomer from 1,2,3-trichlorobenzene as described in U.S. Patent No. 4,766,244 issued to Lysenko. However, 1,2,3-trichlorobenzene has limited availability.

Another method for preparing 4,6-diaminoresorcinol involves treating 1 ,3-dichloro-4,6-dinitro-benzene with base, to form 4,6-dinitroresorcinol. Although 4,6-dinitroresorcinol may be reduced to form 4,6-diaminoresorcinol, the product recovery is prohibitively low for commercial value.

In yet another method, the appropriate aryl ether such as di-arylmethoxy- dinitrobenzene can be cleaved to produce 4,6-diaminoresorcinol. U.S. Patent No. 5,072,053, issued to Blank et al., describes cleaving arylethers by converting diarylmethoxy- dinitrobenzenes to 4,6-diaminoresorcinol by catalytic reduction using a platinum metal supported catalyst, which cleaves the diethers and reduces the nitro groups to amines. However, the method also produces toluene as an unwanted by-product which must be removed or converted back to benzyl alcohol for recycle.

Accordingly, it remains highly desirable to provide an efficient and cost effective method for producing 4,6-diaminoresorcinol which does not have the foregoing disadvantages.

The present invention is a method for preparing 4,6-diaminoresorcinol comprising a) reducing a dinitroarylether of the formula:

(A)n

wherein R is hydrogen, C.-£ ₆ alkyl, cycloalkyl or CH = CH ₂ , R' is hydrogen or CH ₂ -R, each A is independently CI, Br, or I, and n is 0, 1 or 2; to form a diaminoarylether, and

b) cleaving the ether group(s) from the diaminoarylether under conditions such that 4,6-diaminoresorcinol is formed as a salt or other stabilized form thereof. The preferred dinitroarylethers advantageously employed in the method of the present invention correspond to the formula:

wherein R is hydrogen, C.-C. alkyl, cycloalkyl, or CH = CH ₂ and R' is hydrogen or CH ₂ -R.

In a preferred embodiment of the present invention 5-methoxy-2,4-dinitrophenol is converted to 4,6-diaminoresorcinol by contacting 5-methoxy-2,4-dinitrophenol with hydrogen in the presence of a palladium on carbon catalyst followed by hydrochloric acid.

Using the process of the present invention, an efficient, cost effective alternative route to 4,6-diaminoresorcinol is achieved.

Dinitroarylethers appropriate for the process of the present invention include dinitroarylethers of the formula:

(A)n

wherein R is hydrogen, C.-C ₆ alkyl, cycloalkyl or CH = CH ₂ ; R' is hydrogen or CH -R; each A is independently CI, Br, or I and n is O, 1 or 2. Preferably n is 0; R is hydrogen or C.-C ₆ alkyl, and R' is hydrogen or CH ₂ -R. More preferably n is 0; R is methyl, ethyl, or hydrogen and R' is hydrogen. Most preferably n is 0 and R and R' are hydrogen.

The dinitroarylethers used can be prepared by techniques well-known in the art for preparing such ethers. Either a mono- or diether of 4,6-dinitro-resorcinol can be used. In one embodiment, a monoether of 4,6-dinitroresorcinol can be advantageously prepared by contacting 1,3-dichloro-4,6-dinitrobenzene or 1 ,2,3-trichloro-4,6-dinitrobenzene with an aqueous hydroxy-containing compound in the presence of hydroxide base, preferably sodium hydroxide, under conditions sufficient to produce a monoether, specifically 5-alkoxy- 2,4-dinitrophenol or 6-chloro-5-alkoxy-2,4-dinitro-phenol. A diether of 4,6-dinitroresorcinol can be similarly prepared by contacting 1 ,3-dichloro-4,6-dinitrobenzene or 1 ,2,3-trichloro-4,6- -dinitrobenzene with a hydroxy-containing compound in the presence of hydroxide base. (Greater amounts of hydroxy-containing compounds can be employed than in preparing the monoether.) Alternatively, the diether can be formed by contacting 1 ,3-dichloro-4,6-

-dinitrobenzene or 1 ,2,3-trichloro-4,6-dinitrobenzene with an alkanolic metal alkoxide, preferably methanolic sodium methoxide, under conditions sufficient to produce a diether, specifically 1 ,3-dimethoxy-4,6-dinitrobenzene or 1 ,3-dimethoxy-2-chloro-4,6-dinitrobenzene. 1 ,3-Dichloro-4,6-dinitrobenzene an be prepared by dinitrating m-dichlorobenzene as described in Boyer and Buriks, Organic Synthesis Collective Vol. 5, p. 1067, John Wiley & Sons Inc., New York 1973 and 1 ,2,3-trichlorobenzene may be dinitrated under equivalent conditions.

The dinitroarylethers can be prepared using any hydroxy-containing compound which will form an ether when reacted with a dinitroaryl compound. The preferred hydroxy- containing compounds are cycloalkyl alcohols, branched- or straight-chain C.-C. alkyl alcohols, and allyl alcohol. More preferred are alkyl alcohols, such as methanol and ethanol, with methanol being the most preferred.

The alkanolic metal alkoxide which can be employed in preparing the dinitroarylether is an alkanolic solution containing an alkali metal alkoxide which can be prepared by dissolving an alkali metal in an alkanol. The alkanol can be a C.-C ₇ alkanol, is preferably a C.-C ₃ alkanol and is most preferably methanol. The metal can be any alkali metal and is most preferably sodium. The solution may contain any effective amount of alkali metal but it preferably contains from 20 to 40, most preferably approximately 25 weight percent, said weight percent being based on the total weight of the solution.

In another embodiment, a monoether of 4,6-dinitroresorcinol can advantageously be prepared by contacting 1-chloro-2,4-dinitrobenzene with a hydroperoxide in the presence of an anhydrous alkali metal hydroxide, (as described in Makosza and Sienkiewicz, Journal of Organic Chemistry, Vol. 55 No. 17, August 17, 1990, "Hydroxylation of Nitroarenes with Alkyl Hydroperoxide Anions via Vicarious Nucleophilic Substitution of Hydrogen"), and further reacted with an alkyl alcohol to form a 5-alkoxy-2,4-dinitrophenol. The hydroperoxide may be any tertiary alkyl or aralkyl hydroperoxide. The term aralkyl refers to a radical in which an alkyl hydrogen atom is substituted by an aryl group. Preferred hydroperoxides are cumene, tert-butyl, and neopentyl hydroperoxides. More preferred are cumene hydroperoxide and tert-butyl hydroperoxide. Most preferred is cumene hydroperoxide. The alkali metal hydroxide is preferably sodium hydroxide, potassium hydroxide, lithium hydroxide or cesium hydroxide. More preferred is sodium hydroxide or potassium hydroxide, wherein the most preferred is sodium hydroxide.

In the method of the present invention dinitroarylethers are reduced to form diaminoarylethers followed by an ether cleavage reaction to form diaminoresorcinol. Both the reduction and cleavage can be maintained within a single reaction vessel without isolation of intermediates, thus simplifying the reaction. Alternatively, but less preferably, the reactions can be conducted sequentially in two or more reaction vessels.

It is not particularly critical to the practice of the present invention how the reduction of the nitro groups of the dinitroarylethers is accomplished provided the desired number of the nitro groups are reduced to amino groups. Preferably, the reduction comprises contacting the dinitroarylether with hydrogen in the presence of a reduction catalyst.

5 The reduction catalyst can be any catalyst which will reduce the nitro groups to amines in the presence of hydrogen. Typical reduction catalysts include transition metal catalysts such as nickel, palladium, ruthenium and platinum. Preferably, the catalysts are supported, for example, metal catalysts supported on carbon, and are palladium, ruthenium or platinum metal catalysts. The most preferred is palladium on carbon.

10 The amount of catalyst employed will depend on a number of factors including the specific catalyst selected. Typically, the catalyst is employed in an amount of 0.1 to 10 mole percent relative to the dinitroarylether. Preferably, the amount of catalyst employed is from 2 to 7, most preferably approximately 5 mole percent based on the amount of dinitroarylether. The reduction reaction can be conducted at any temperature at which the

15 reduction occurs and will depend upon a number of factors including the pressure and catalyst used. The pressure is not critical to the process of the present invention and any pressure may be used which will allow reduction to occur. Typically, atmospheric pressure is employed. The reaction is normally conducted at temperatures from 20°Cto 1 10°C. Preferably, the reaction is conducted at temperatures from 40°C to 80°C, most preferably at temperatures from 50°C to

20 60°C. The time required for the reduction reaction is also dependent upon the reaction conditions including temperature, pressure, catalyst used and desired conversion, but is generally the amount of time needed to convert substantially all the dinitroarylether to the diaminoarylether. In general the reaction requires from 1 to 10 hours for complete conversion. More preferably the reaction is conducted for 2 to 8 hours. Most preferably, the reaction is

25 conducted for approximately 4 hours.

The catalytic reduction is preferably conducted in a solvent for the diaminoarylether. Preferred solvents include water and ethylene glycol. The most preferred solvent is water.

In addition, the reduction may also be carried out in the presence of a reducing

30 agent such as stannous chloride, lithium aluminum hydride or any other reducing agents known in the art. The amount of these reducing agents used will depend upon the specific reducing agent and dinitroarylether used in the reduction reaction and will typically be at least the stoichiometric amount needed for the reduction reaction to occur.

The diaminoarylether product is preferably obtained as a hydrohalide salt by

35 adding hydrohalide to the reduction reaction. The hydrohalide can be added at any time but is most preferably added after the reduction reaction has been initiated. Hydrohalides which can be used include hydrochloric, hydrobromic and hydroiodic acids, with the preferred being hydrochloric acid. The amount of hydrohalide used is the amount needed to obtain the desired

hydrohalide salt. Preferably, at least 2 equivalents of hydrohalide are used in relation to the dinitroarylether.

Upon desired completion of the reduction reaction, the reduction catalyst is removed using conventional techniques such as filtration. The filtration may be conducted such that the filtrate is maintained within the same reaction vessel.

The ether cleavage reaction may be accomplished using any reagent which will cleave ethers from aryl compounds. These reagents include hydrochloric, hydrobromic or hydroiodic acids, lithium chloride, and tertiary amide hydrohalide salts, for example,

N,N-dimethyl acetamide or N-methylpyrrolidinone. Preferably the cleavage is accomplished by saturating the reaction mixture containing the diaminoarylether hydrohalide salt with dry HCI, adjusting the temperature to a sufficient amount and for a sufficient amount of time such that the ether group(s) are cleaved and 4,6-diaminoresorcinol is formed.

The cleavage reaction can be conducted at any temperature at which the cleavage will occur and will depend on a number of factors including the specific diaminoarylether used and reaction conditions. The reaction is generally conducted at a temperature from 80°C to 200°C, more preferably at a temperature from 120°C to 180°C, and most preferably from 145°Cto 165°C.

The pressure of the cleavage reaction is not critical and may be any pressure at which the cleavage reaction will occur. Typically, the pressure is from 200 to 500 psi. Most preferably the reaction is conducted at a pressure of approximately 350 psi.

The time necessary for the cleavage reaction to occur is also dependent upon the other reaction conditions, the specific diaminoarylether used and the desired conversions. In general the reaction is continued until substantially all the diaminoarylether has been converted to diaminoresorcinol. Preferably the reaction is conducted between 12 to 36 hours. More preferably the reaction is conducted between 15 to 24 hours. Most preferably the reaction is completed in approximately 18 hours.

4,6-Diaminoresorcinol is formed as a hydrohalide salt or other stabilized form thereof. Preferably 4,6-diaminoresorcinol is recovered as a hydrochloride, hydrobromide or hydroiodide salt. Most preferably 4,6-diaminoresorcinol is recovered as a hydrochloride salt. The following examples are set forth to illustrate the present invention and should not be construed to limit its scope. In the examples, all parts and percentages are by weight unless otherwise indicated.

Preparing Ethers of Dinitroresorcinol Example 1 - Preparing 5-Methoxy-2,4-dinitrophenol from 1 ,3-Dichloro-4,6-dinitrobenzene

5

10

A 1 liter (L) round-bottom flask equipped with a mechanical stirrer and a reflux condenser was charged with 23.7 grams (g) of 1,3-dichloro-4,6-dinitrobenzene, 100 milliliters (mL) of methanol, 200 mL of water and 15 grams of sodium hydroxide and heated to approximately 65°C for approximately 8 hours. The reaction mixture was then poured into 0 ^c C aqueous hydrochloric acid, isolated by filtration and air-dried. The theoretical yield of

15 5-methoxy-2,4-dinitrophenol, a monoether of dinitro-resorcinol, was 21.4 g, and the dry weight yield was 20.5 g which gives an overall 95 percent yield of 5-methoxy-2,4-dinitrophenol. Example 2 - Preparing 1.3-Dimethoxy-4,6-di nitrobenzene from 1 ,3-Dichloro-

-4,6-dinitrobenzene

20

25

A 1-liter, 3-necked, round-bottomed flask was charged with 500 mL of methanol, 30 g of crushed potassium hydroxide, 75 mL of water, and 23.7 g (0.10 mole) of 1 ,3-dichloro- 4,6-dinitrobenzene. The reaction mixture was agitated and heated to 65°C for 8 hours and cooled to 25°C. The reaction mixture was then quenched with an excess of 0°C aqueous ^* *" hydrochloric acid. The resulting pale yellow solid was isolated by filtration and air-dried to yield 20 g (90 percent yield) of 1 ,3-dimethoxy-4,6-dinitrobenzene, a diether of dinitro¬ resorcinol.

35

Example 3 - Preparing 5-Methoxy-2,4-dinitrophenol from 2.4-Dinitrochlorobenzene

20 g of NaOH powder was added to a 250-mL 3-necked flask equipped with a mechanical stirrer, C0 ₂ condenser, dropping funnel and thermowell. Approximately 100 to 125 mL of liquid NH ₃ were condensed into the reactor utilizing a dry ice bath. To the stirred slurry of powdered NaOH-NH ₃ a solution of 1-chloro-2,4-dinitrobenzene (0.1 mol) and cumene hydroperoxide (0.1 mol) in 50 mL of methylene chloride was added dropwise over 1 hour maintaining the temperature at -30°C by the refluxing NH ₃ . After the addition was completed, the reaction mixture was allowed to warm to

-10°C to O°C and 75 mL of methanol containing 0.1 to 2 g of sodium hypophosphite was added dropwise over 1 hour. The resulting solution was agitated at room temperature for 3 to 4 hours.

The reaction mixture which contained precipitated Na phenolic salts was diluted with water to dissolve the salts and transferred to a 1-L separating funnel (to which a 500 mL solution of H ₂ 0 had been added) where the aqueous solution was extracted with CH ₂ C1 ₂ (2x200 mL) to remove the cumene derivatives. After extraction, the aqueous phenate salt solution was slowly acidified with concentrated HC1 at a temperature of approximately 25°C or less to precipitate the desired 5-methoxy-2,4-dinitrophenol, a monoether of dinitro-resorcinol. The crude phenol (17 to 19 g) was recrystallized from H ₂ 0-MeOH (50:50) to give 5-methoxy-2,4- -dinitrophenol in 75 percent to 80 percent yield. Preparing Diaminoarylethers from Dinitroarylethers

Example 4 - Preparing 5-Methoxy-2,4-diaminophenol Pi hydrochloride from 5-Methoxy-2,4- dinitrophenol

A 500 mL, 3-necked, round-bottomed flask was charged with 150 mL of water, 21.4 g (0.1 mole) of 5-methoxy-2,4-dinitrophenol and 1.0 g of 10 percent palladium on carbon catalyst. The reaction was stirred under a nitrogen atmosphere for 3 to 4 minutes. The stirred

reaction mixture was heated to 55°C and hydrogen gas was sparged below the surface of the reaction mixture. After 10 minutes, 19.8 g (0.2 mole) of concentrated HCI was added through the condenser while hydrogenation was continued for 4 hours. The catalyst was removed by filtration and the filtrate was passed into a solution consisting of 0.5 g of stannous chloride dihydrate and 25 mL of concentrated HCI. This solution was then saturated with dry HCI gas and cooled to 25°C. The solvent was then removed under reduced pressure (15 mm) to yield a pale, off-white solid. The product was then isolated as the dihydrochloride salt after drying in a vacuum oven for approximately 18 hours at 40°C, to give 5-methoxy-4,6-diaminophenol dihydrochloride (21.0 g, 92.5 percent yield). 0 Preparing 4,6-Diaminoresorcinol Dihydrochloride

Example 5 - Preparing 4,6-Diaminoresorcinol Dihydrochloride from 5-Methoxy-2,4- -diaminophenol

2.5 g of 5-methoxy-2,4-diaminophenol and 25 mL of concentrated HCI was placed in a 45 mL Hastalloy C autoclave. The mixture was then heated to 140°C for 16 hours at a 0 pressure of approximately 200 psi. The reaction mixture was then cooled to 25°C, the reactor was vented and the product, a white solid, was filtered and dried to yield 1.2 g of crude 4,6-diaminoresorcinol dihydrochloride. Example 6 - Preparing 4,6-Diaminoresorcinol Dihydrochloride from 5-Methoxy-2.4-

-dinitrophenol 5

2HC1

A 500 mL, 3-necked, round-bottomed flask was charged with 150 mL of water, 21.4 g (0.1 mole) of 5-methoxy-2,4-dinitrophenol and I .O g of 10 percent palladium on carbon catalyst. The reaction was stirred under a nitrogen atmosphere for 3 to 4 minutes. The stirred reaction mixture was heated to 55°C and hydrogen gas was sparged below the surface of the 5 reaction mixture. After 10 minutes, 19.8 g (0.2 mole) of concentrated HCI was added through the condenser while hydrogenation was continued for 4 hours. The catalyst was removed by filtration and the filtrate was passed into a solution consisting of 0.5 g of stannous chloride

dihydrate and 25 mL of concentrated HCI. This solution was then saturated with dry HCI gas and charged to a 600 m L Hastalloy B autoclave. The reactor was heated to 150°C for 18 hours and cooled to 25°C. The resulting product was isolated by filtration and dried under nitrogen to yield 19.7 g (90 percent yield) of crude 4,6-diaminoresorcinol dihydrochloride.