DD284232A5 - PROCESS FOR THE PREPARATION OF NEW 4,6-DINITROBENZOFUROXAN DERIVATIVES - Google Patents

Abstract

The invention relates to a process for the preparation of novel 4,6-dinitrobenzofuroxan derivatives of general formula I, which is obtained by reacting corresponding * Meisenheimer complexes of 4,6-dinitrobenzofuroxan with aqueous nitric acid. The compounds of general formula I are useful as intermediates for biologically active substances. Formula I {Meisenheimer complex of 4,6-dinitrobenzofuroxan; * * * 4,6-dinitrobenzofuroxan derivative; Intermediate; biologically active substance}

Description

Title of the invention

Process for the preparation of new 4,6-dinitrobenzofuroxan derivatives

Field of application of the invention

The invention relates to a process for the preparation of novel 4,6-dinitrobenzofuroxan derivatives which are useful as intermediates for biologically active substances.

Characteristic of the known state of the art

The substances produced by the process according to the invention are novel compounds for which there are no directly comparable processes.

Are known methods for the synthesis of N-arylamino-4,6-dinitrobenzofuroxanen, starting from the 7-chloro-4,6-dinitrobensofuroxan is (Austr. J. Chem. 1985, 3JL 435). However, according to this procedure, it is not possible to obtain isomer-free products, but in addition to the 7- (N-arylamino) also the 5- (N-arylamino) -4,6-dinitrobenzofuroxanes are formed. Furthermore, it is known that Meisenheimer complexes of polynitroaromatics bearing a hydrogen atom on the sp ³ -hybridized carbon atom can be converted into the corresponding rearomatization products by using oxidizing agents (Chem. Rev. 1982, S2., 427). In the case of the Meisenheimer complexes of 4,6-dinitrobenzofuroxan, this route of oxidative rearomatization was described for only a few σ-CC-linked complexes, and it succeeds only when strong oxidants, eg. B. KMnO4 in sulfuric acid solution can be used. By contrast, weaker oxidants are completely ineffective (Tetrahedron Lett. 1985, 23, 1307).

Object of the invention

The aim of the invention is to develop a technically easy to carry out process for preparing new substituted in 7-position 4,6-dinitrobenzofuroxanes.

Explanation of the essence of the invention

The object of the invention is to produce, starting from the readily available Meisenheimer complexes of 4,6-dinitrobenzofuroxan with formanilides and imides, new substituted in 7-position 4,6-dinitrobenzofuroxanes.

This object is achieved by a process for the preparation of novel 4,6-dinitrobenzofuroxan derivatives of general formula I,

in the

R denotes either an aryl radical of the formula II,

wherein -i is hydrogen, halogen, an alkyl, alkoxy, dialkyl

amino or nitro radical, and R ^{1 is} a formyl group or R and R 1 together represent a succinyl or phthaloyl radical,

according to the invention, a Meisenheimer complex of general formula III,

III

in the

R and E ^{1 have} the abovementioned meanings and M is a monovalent metal atom, in particular a

Metal atom from the I. main or subgroup of the Periodic Table of the Elements, is reacted with 30 to 70% aqueous nitric acid in the temperature range between 0 and 40 ⁰ C.

The essence of the invention in the broadest sense is that a corresponding ο -NC-linked Meisenheimer complex of 4,6-dinitrobenzofuroxan is converted under oxidative conditions in its Rearomatisierungsprodukt. Characteristic of the solution according to the invention is that it uses aqueous nitric acid. The selection of the cation in the Meisenheimer complex of the general formula III is of reaction-determining importance when using 7- (N-formyl-N-aryl-amino) -4,6-dinitro-7, x-dihydrobenzofurazanide-1-oxide sum , in which case the silver salt of the Meisenheimer complex of the general formula III is preferably used. If, on the other hand, 7-succinimido or 7-phthalimido-4,6-dinitro-7, x-dihydrobenzofurazanide 1-oxide are used, then both the silver complexes and the alkali metal complexes can be used. According to the Meisenheimer complexes of general formula III at temperatures between 0 and 40 ⁰ C with 30 to 70% aqueous nitric acid, preferably with 50 to 65% nitric acid, treated with mixing.

After dilution of the reaction mixture with water, the target products of general formula I are separated and purified by conventional methods. In the case of 7- (N-formyl-N-aryl-amino) -4,6-dinitrobenzofuroxane obtained from the nitric acid solution, first, the HNO3 adducts, which are, however, less stable and

by dissolving in a suitable solvent, e.g. As methanol, ethanol, acetone or mixtures of these, can be easily converted into the nitric acid-free product.

The Meisenheimer complexes of general formula III required for the solution according to the invention are obtainable by simple processes from 4,6-dinitrobenzofuroxan and formanilide alkali metal salts or phthalimide or succinimide alkali metal salts in high yields and can be easily converted into their silver salts with aqueous silver nitrate solution

The enriching the prior art advantage of the solution according to the invention is that you can get from readily available starting materials, in a single reaction step and by an aqueous procedure to the target products. This was not foreseeable since according to the prior art, such 7- (N-formylamino) -4,6-dinitro-benzofuroxan-Berivate are not known and was expected to cleavage reactions.

-. - -. embodiments

example 1

7- ( N-formyl-M-phenyl-amino ") -4,6-dinitrobenz-furoxan

9.4 g (20 mmol) of the monohydrate of silver 7- (N-formyl-N-phenylamino) -4,6-dinitro-7, x-dihydrobensofurazanide 1-oxide are finely pulverized and ice-cooled with stirring in 100 ml Entered 65% nitric acid. The mixture is then warmed slowly to tree temperature and stirred for 1 hour at 20 ⁰ C. The orange-colored suspension is then under ice cooling with 100 ml of dist. Diluted water, the resulting nitric acid product was filtered off with suction, washed free of acid with water and dried in air ¹ .

Yield: 7.0 g (86%), mp 97 to 98 ⁰ C.

The nitric acid adduct is recrystallized from a heated to 40 ⁰ C mixture of one part by volume of ethanol and two parts by volume of acetone. After concentrating and cooling the solution, the target product is obtained in the form of dark red crystals.

Yield: 4.1 g, mp 165-177 ⁰ C. Analysis for C13H7M5O7.

calc .: C 45.23 H 2.04 N 20.29 Found: C 44.99 H 2.02 N 20.34

Example 2 7-rM-Formyl-N- (4-methvlphenyl) -aminol-4,6-dinitrobenaofuroxan

Analogous to the manner described in Example 1, except that 9.7 g (20 mmol) of the monohydrate of silver 7- [N-formyl-N- (4-methylphenyl) amino] -4,6 -dinitro-7, x-dihydrobenzofurazanide-1-oxide and 100 ml of 50% nitric acid are reacted.

i . J I.

This gives 6.9 g (82%) of the nitric acid adduct with a melting point of 88 to 95 ^D C.

The redissolution from a heated mixture of ethanol / acetone / diethyl ether (1: 1: 1) gives the target product in the form of dark red crystals.

Mp. 183 to 191 ° C.

Analysis for C14H9N5O7

Calc .: C 46.80 H 2.52 N 19.49 Found: C 46.80 H 2.54 N 19.30

Example 3

7-rM-formyl-N- (4-ch lorphenvl) amine ol-4,6-dinitrobensofu.roxan

8.2 g (16 mmol) of the monohydrate of silver 7- [M-formyl-N- (4-chlorophenyl) amino] -4,6-dinitro-7, x-dihydrobenzofurazanide 1-oxide are added portionwise in 100 ml Added 68% nitric acid and treated the resulting suspension for 30 minutes at room temperature in an ultrasonic bath (40 KHa, 50 W). The work-up is carried out as described in Example 1. This gives 4.6 g of the nitric acid adduct having a melting point of 100 to 104 ⁰ C. The recrystallization from acetone / ethanol / diethyl ether (1: 1: 1) provides the target product having a melting point of 146 to 155 ° C.

Analysis for C13H6CIN5O7

Calc .: C 41.12 H 1.59 N 18.45 Cl 9.34 Found: C 41.19 H 1.63 N 18.44 Cl 9.40

Example 4

7-H-succinimido-4,6-dinitrobenzofuroxan

5.5 g (15 mmol) of potassium 7-succinimido-4,6-dinitro-7, x-dihydrobenzofurazanid-1-oxide are finely pulverized and stirred

2 Γί. · ..:; 2

ml ice-cooled 60% nitric acid registered. The Geroisch is stirred for 3 hours without external cooling, the resulting yellow solid is filtered off, washed with water and dried in air.

Yield: 3.5 g (72%), mp 254-257 ⁰ C. Analysis for CioHsNsOe.

Calc .: C 37.16 H 1.56 N 21.67 F: C 36.54 H 1.60 N 21.67

Example 5

7- ( N-phthalimido ) -4.6-dinitrobensofuroxan

7.4 g (18 mmol) of potassium 7-phthali-nido-4,6-dinitro-7,10-dihydrobenzofurazanide 1-oxide are suspended in 40 ml of water and cooled in an ice-bath. The mixture is added dropwise to this suspension while stirring a mixture of 30 ml of 60% nitric acid and 10 ml of 98% nitric acid, while allowing the temperature to rise to 40 ⁰ C. It is then stirred for 1 hour at 30 ⁰ C and then diluted with 50 ml of water. The precipitate is filtered off with suction, washed acid-free with water and dried.

Yield: 4.8 g (72 sg), mp 241-244 ° C.

Calc .: C 45.30 H 1.36 N 18.87 F: C 45.38 H 1.61 N 18.34

Recrystallization from toluene gives the product as yellow needles with a melting point of 244 ° C.

Claims (3)

claims 1. A process for the preparation of novel 4,6-dinitrobenzofuroxan derivatives of general formula I, UO ₁ i in the R denotes either an aryl radical of the formula II, II if wherein J is hydrogen, halogen, an alkyl, alkoxy, dialkyl amino or Mitrorest, and R ^{1 is} a formyl group or
R and R ¹ together represent a succinyl or phthaloyl radical, characterized in that a Meisenheimer complex of the general formula III, III wherein R and R ^{1 have} the abovementioned meanings and M is a monovalent metal atom, reacted with 30 to 70% aqueous nitric acid in the temperature range between 0 and 40 ^D C. 2. The method according to claim 1, characterized in that M is a function of the meaning of the radicals R and R ^{1 is} a metal atom from the series of the I. main or subgroup of the Periodic Table of the Elements. 3. The method according to claim 1 and 2, characterized in that preferably the silver salt of Meisenheimer complex III is used when R denotes an aryl radical and BA is a formyl group.