DD253997A1 - PROCESS FOR PREPARING SUBSTITUTED 2-ARYLUREIDOPHENOLES - Google Patents

Abstract

The process for the preparation of substituted 2-Arylureidophenolen (I) has to indicate the task of a new, uncomplicated and energetically inexpensive access to this class of substances. The object is achieved by acylation of substituted 2-aminophenols (II) with substituted N-phenylcarbamic acid chlorides (III) in an absolute aprotic solvent at room temperature. The substances produced according to the invention are obtained in good yield and high purity and are reactive intermediates for organic syntheses. B. be used with a suitable substituent pattern for the production of color couplers for color recording materials.

Description

in which R ¹ , R ² and R ^{3 have} the abovementioned meaning, with substituted N-phenylcarbamic acid chlorides of the general formula III,

ITH-COCI

wherein R ⁴ also has the above meaning, in an absolute aprotic solvent in the temperature range of 15 to 30 ⁰ C implemented.

2. The method according to claim 1, characterized in that the aprotic solvent is preferably a cyclic ether, such as. As dioxane is used.

Field of application of the invention

The invention relates to a process for preparing substituted 2-arylureidophenols of the general formula I

OH

-NH-CO -Mt

in the R ¹ , R ² , R ³ and R ^{4 is} a hydrogen atom, an alkyl, cycloalkyl, aryl, cyano, alkoxy, cycloalkoxy, aryloxy, nitro, alkoxycarbonyl, cycloalkoxycarbonyl or aryloxycarbonyl group or a halogen atom could be.

Characteristic of the known technical solutions

For the synthesis of substituted 2-Arylureidophenolen so far three synthesis routes are known, all emanating from substituted 2-aminophenols. The construction of a urea structure from these educts is difficult due to the principle bifunctionality of 2-aminophenols as binucophiles and hitherto, despite special reaction conditions with process-related disadvantages and limitations afflicted.

Thus, in DE 3300412, DE 3315012 and JP 60/49335 the synthesis of 5-nitro-2-arylureidophenolen by aminolysis of N-Arylcarbamidsäurephenylestern with 2-amino-5-nitrophenol described.

EH-GO-NH

The reworking of this synthetic route gave unsatisfactory yields due to incomplete reaction of the starting materials. Another possibility for the preparation of substituted 2-Arylureidophenolen is the nucleophilic ring opening of substituted benzoxazolones with anilines.

OH OH *-*

SSHC

D 0

EH-CO-NH

(D.R. P. 487014, Chem. Zentralblatt 1930 II, 135)

In the investigation of this reaction variant on the example of the anilinolysis of 6-nitrobenzoxazolone, however, the desired urea derivative was obtained only in a yield of 30%. Among the numerous impurities resulting from side reactions, als, Ν'-diphenylurea was identified as the main constituent, the formation of which can be understood by undesired further reaction of already formed product with still unreacted aniline. Efforts to circumvent the difficulties described have led to the development of a synthesis of substituted 2-arylureidophenols starting from substituted 2-aminophenols which add to substituted phenyl isocyanates.

NH-CO-NH

For this, z. For example, in DE 3429257, DE 3429576 and JP 59/59656 reactions which occur at moderately elevated temperature in absolute solvents such as acetonitrile or toluene, satisfactory to good yields, but which are still capable of improvement, are given. When reworking the regulations, the results indicated were only partially confirmed.

Object of the invention

The object of the invention is to provide a synthetic route by which substituted 2-arylureidophenols of the formula I can be prepared from reactive, readily available starting materials in a low-cost, low-energy solvent in a generally applicable, uncomplicated process.

Explanation of the essence of the invention

The invention has the object to enable in a technically simpler and easy to dominate a new synthesis of substituted 2-Arylureidophenole, z. B. represent interesting intermediates in the synthesis of phenol derivatives, which can be used as photographic color couplers

 The object is achieved in that substituted 2-aminophenols of the general formula II,

in which R ¹ , R ² and R ^{3 have} the abovementioned meaning, with substituted phenylcarbamic acid chlorides of the general formula III,

wherein R ⁴ also has the meaning given above, in an absolute aprotic solvent, for. As a cyclic ether, be reacted at room temperature.

Surprisingly, the acid chloride used shows a reactivity which is not inferior in the reaction with 2-aminophenols that of the isocyanate, so that, in contrast to the difficulties described in the previous methods for the synthesis of substituted 2-Arylureidophenolen the acylation process described the synthesis of pure products in good until very good yields possible.

The substituted phenylcarbamic acid chlorides (general formula III) used according to the invention are readily obtainable by addition of dry hydrogen chloride gas to the corresponding substituted phenylisocyanates in quantitative yield. The high propensity, present as heterocubes in a substituted phenylisocyanate, for the addition of acidic compounds to the C-N double bond of the isocyanate (to be used, for example, in DE 3429257 and DE 3429576) is utilized in this hydrogen chloride addition to add substances with the substituted phenylcarbamic acid chlorides III which are very effective acylating reagents.

The substituted 2-aminophenols II to be acylated are in principle both O- and N-acylatable by an acylating agent. In order to preclude acylation on the hydroxyl oxygen, the use of an auxiliary base usually added as an acid-binding agent, such as a tertiary amine (e.g., triethylamine or pyridine), is avoided thereby avoiding deprotonation to the phenolate anion which would be more nucleophilic than an amino group. The execution of the acylation reaction under neutral conditions in absolute dioxane proved to be extremely advantageous. This causes on the one hand that due to the higher neutral nucleophilicity of the amino group relative to the hydroxyl group, the desired N-acylation takes place, on the other hand, the solvent used dioxane acts by reaction with the liberated in the reaction of hydrogen chloride to an oxonium salt as an acid-binding agent, but without to change the starting materials undesirable.

It is furthermore favorable for the energy balance of the process that the reaction described already and best proceeds at room temperature (at elevated temperature, side reactions gain in importance).

The yields obtained with the specified method are good to very good and mean effective utilization of the high-quality starting materials.

It has been demonstrated that with a suitable substituent pattern R ¹ , R ² , R ³ , R ^4, the inventively synthesized substituted 2-Arylureidophenole z. B. can be used as valuable intermediates for the synthesis of phenolic cyan couplers for color recording materials use.

The invention will be explained below with reference to exemplary embodiments:

Production Example 1

5-nitro-2-phenylureidophenol

6.5 g (0.042 mol) of N-phenylcarbamoyl chloride are dissolved in 30 ml of dry dioxane and added dropwise to a solution of 6.45 g (0.042 mol) of 2-amino-5-nitrophenol in 150 ml of dry dioxane and stirred for 2 hours at room temperature. Then it is slowly poured into 225ml of water. The crystalline precipitating product is filtered off and is pure after washing with water.

Yield: 11.4 g (80% of theory) mp 184-186 ° C

Analog were shown:

5-nitro-2- (2-methylphenyl) ureidophenol

Yield: 70% d. Th. Mp. 192-194 ⁰ C

5-nitro-2- (2-cyanophenyl) ureidophenol

Yield: 65% d. Th. Mp. 209-211 ⁰ C

Production Example 2

4-chloro-5-nitro-2-phenylureidophenol

10.8 g (0.07 mol) of N-phenylcarbamoyl chloride are dissolved in 35 ml of dry dioxane, added all at once to a suspension of 12.8 g (0.068 mol) of 2-amino-4-chloro-5-nitrophenol in 400 ml of dry dioxane and Stirred for 12 hours at room temperature. It forms a yellow precipitate. After adding 3 ml of concentrated hydrochloric acid, the precipitate is filtered off and washed with hot water until the washing liquid is almost colorless. Another portion of crude product is obtained by dropping the clear organic filtrate with stirring into 11 ice-water. The crystalline precipitating yellow-green product is filtered off and washed with water. Both fractions of the crude product are recrystallized from aqueous ethanol. Yield: 14.2 g (68% of theory) mp.201 ° C.

Production Example 3

2-Phenylureidophenol

10.8 g (0.07 mol) of N-phenylcarbamoyl chloride are dissolved in 25 ml of dry dioxane, added all at once to a solution of 7.4 g (0.068 mol) of 2-aminophenol in 200 ml of dry dioxane and stirred at room temperature for 5 hours. A light oil settles. After adding 3 ml of concentrated hydrochloric acid, the reaction mixture is filtered. The resulting filtrate and oil are worked up by treatment with water. To this, the filtrate and oil are poured slowly into 250 ml of water, precipitating a white precipitate, which is filtered off and washed with water, after which it is pure.

Yield: 10.1 g (65% of theory) mp 202-203 ° C

Production Example 4

4,6-dichloro-5-methyl-2-phenylureidophenol

15.5 g (0.068 mol) of S ^ -dichloro-e-hydroxy ^ -methylaniline hydrochloride are suspended in 300 ml of dry dioxane. To release the amine, 5.5 g (0.068 mol) of dry pyridine are added. Thereafter, 10.8 g (0.07 mol) of N-phenylcarbamoyl chloride in 25 ml of dry dioxane are added and the mixture is stirred at room temperature for 7 hours. After addition of 3 ml of concentrated hydrochloric acid, the reaction mixture is slowly stirred into .11 water. The precipitated white crystalline precipitate is filtered off and recrystallized from aqueous ethanol.

Yield: 19.6 g (93% of theory) mp 178-181 ° C. '

Claims (2)

claims: 1. Process for the preparation of substituted 2-Arylureidophenolen of the general formula I, OH J wherein R ¹ , R ² , R ³ and R ^{4 are} a hydrogen atom, an alkyl, cycloalkyl, aryl, cyano, alkoxy, cycloalkoxy, aryloxy, nitro, alkoxycarbonyl, cycloalkoxycarbonyl or aryloxycarbonyl group or a halogen atom can, characterized in that substituted 2-aminophenols of the general formula II,