DD281187A5 - PROCESS FOR PREPARING POLYFLUORIZED N, N-DISUBSTITUTED PHENAZINE - Google Patents

Abstract

The invention relates to a novel preparation process of novel N, N-disubstituted phenazines of the general formula I, wherein R 1 and R 2 are a straight-chain or branched alkyl radical having one to four carbon atoms; R3 to R6 are each fluorine or a perfluorinated C1-C4 alkyl radical; or R3 and R4 and / or R5 and R6 together with the fluorinated phenyl part of the phenazine form a fully fluorinated alicyclic ring having a total of 4 to 7 carbon atoms, which is optionally substituted by CF3. The compounds are prepared from N-alkylated anilines with sodium hydride and are suitable for the preparation of polyfluorinated compounds with application in medicine and biochemistry. Formula I {phenazine; fluorinated compounds; Method; polyfluorinated phenazines; Medicine; Biochemistry}

Description

Field of application of the invention

The invention relates to eh process for the preparation of new polyfluorinated Ν, Ν'-disubstituted phenazines. The phenazines prepared according to the invention can be used as starting materials for the preparation of new polyfluorinated compounds which can be used in biology and medicine.

Characteristic of the known solutions

Polyfluorinated Ν, Ν'-dihydrophenazines are prepared in two stages by oxidation of polyfluorinated anilines or polyfluorinated diphenylamines with subsequent N-reduction.

As the oxidizing agent lead tetraacetate (J.M. Birchall et al., J. ex Soc, [C] [1970], 449) or the electrochemical oxidation (A.G.Hudson et al., Tetrahedron 26 (1979) 3791.5781) are used. The yields are 28-40%.

Object of the invention

The aim of the invention is to produce new polyfluorinated N, N'-disubstituted phenazines more easily and in higher yield.

Essence of the invention

The invention has for its object to provide a novel process for the preparation of new polyfluorinated Ν, Ν'-disubstituted phenazines.

According to the invention, compounds of the general formula I are prepared

(I)

wherein R ¹ and R ^{2 are} each a straight-chain or branched alkyl radical having one to four carbon atoms; R ^J , R ⁴ , R ⁵ and R ⁶ are each fluorine or a perfluorinated straight-chain or branched alkyl radical having one to four carbon atoms; or Λ ³ and R ⁴ and / or R ⁵ and R ⁶ ) together with the fluorinated phenyl moiety of the phenazine form a fully fluorinated ring with a total of from 4 to 7 carbon atoms, optionally substituted by trifluoromethyl.

Preferred Verbin ^ · strength of "Ormei I are those in which R ³ to R ⁶ are each fluoro. Also preferred are compounds in which R ³ and R '.". Srad! "Are sltige or branched perfluorinated alkyl groups and R ⁴ and R ⁶ is fluorine, wherein compounds of which R ⁴ mil unc n ^s jlDich trifluoromethyl are particularly preferred.

Preferred compounds are also those in which R ³ to R ^{6 are} each straight-chain or branched perfluorinated alkyl groups, in particular R ³ to R ^{6 are} each trifluoromethyl.

A further preferred group preparable according to the invention are those compounds of the formula I in which R ³ and R ⁴ and also R ⁵ and R ⁶ together with the respective fluorinated phenyl moiety! of the phenazine form an acyclic ring, wherein the resulting compounds of the formula III

(III)

η is preferably 0.1 or 1. Particular preference is given to η = 1.

In the context of the present invention, "straight-chain or branched alkyl having 1 to 4 carbon atoms" means methyl, ethyl, propyl, isopropyl, butyl, isobutyl and tert-butyl.

represents an aromatic ring on which hydrogen is completely replaced by fluorine.

The erfindungsgemäSe process for the preparation of the new Ν, Ν'-disubstituted phenazines of the general formula I is that polyfluorinated N-alkylated anilines of the general formula M

(II)

wherein R ^{7 has} the meaning given for R 'or R ² and R ⁸ and R ^{0 have} the meaning mentioned for R ³ to R ⁶ , in a concentration of at least 1.5 mol / l with sodium hydride in dipolar aprotic solvents.

According to the invention, different compounds of the formula II can be used in a reaction in order to arrive at final products of the formula I, for. B. R 'and R ² or R ³ and R ^e each have different meanings. However, this is easily varied by the skilled person depending on the desired end product.

The starting compounds of the formula II are known and can be prepared by known processes.

You get it z. Example by reacting polyfluoroaromatics with alkylamines or with tetrafluoroethylene under the respective conditions described in the literature.

The compounds of the general formula i are new and are particularly suitable for the preparation of new perfluorinated compounds for medicine and biology. The preparation of these compounds by known methods is associated with great difficulty and possible only with low yield. In addition to the ease of manufacture of the novel compounds using the new method, this method has the advantage that also known compounds are available in one stage, which can otherwise be prepared only in multi-step reactions. The yield is generally much higher than ice in the known processes; it is over 80% in the case of the new Ν, Ν'-dialkylphenazines.

Preferred compounds are

1. Those of the formula I in which R ¹ and R ^{2 represent} an alkyl group having one to three carbon atoms of R ³ to R ^{6 are} trifluoromethyl groups, for. B

 2,7-Bis (trifluoromethyl) -5,10-dimethylhexafluorophenazine 2,7-Bis (trifluoromethyl) -5, '' 0-diethyl-3,5-carbo- inazine 2,7-bis (trifluoromethyl) -5,10-dipropylhexafluorophenazine 2,7- Bis (trifluoromethyl) -5,10-diisopropylhexafluorophenazine 5,10-dimethyltetrakis (trifluoromethyl) tetrafluorophenazine 5,10-diethyltetrakis (trifluoromethyl) tetrafluorophenazine 5,10-dipropyltetrakis (trifluoromethyl) tetrafluorophenazine 5,10- diisopropyl-tetrakis (trifluoromethyl) -tetrafluorphenazin

2. those "of the formula III in which R 'and R ^{2 are} an alkyl radical having one to three carbon atoms and η = 0.1 or 2, for example

öJO-dimethyl-bisftetrafluorcyclobutanol-tetrafluorphenazin

öJO-diethyl-bisftetrafluorcyclobutanol-tetrafluorphenazin

N, N'-dimethyl-bisfhexafluorcyclopentaiiol tetrafiuorphenazin

N, N'-dimethyl-bisfoctafluorcyclohexanol tetrafluorphenazin

N, N'-diethyl-bislhexafluorcyclopentanol tetrafluorphenazin

N, N'-dimethyl-bisfoctafluorcyclohexanoJ tetrafluorphenazin

The reaction is preferably at a concentration of derAusgangskornponenten 2mol / l to IOmol / 1, in particular 2-3mol / l and temperatures of -10 ^c C to 40 ^c C, preferably carried out in dipolar aprotic solvents in DMF. The polyfluorinated phenazines precipitate a'c insoluble substances in DMF. They are filtered off after completion of the reaction and recrystallized acetone / water. The identification takes place by means of ¹ H and ¹⁹ F NMR as well as MS and elemental analysis.

Ausfühningsbeispiole

example 1

5,10-Dimothyl-2,4,7,9-tetrakls (trifluoromethyl) -tetrafluorphenazin

1.2 g (50 mmol) of NaH were suspended in 15 ml of dried DMF in a three-necked flask equipped with a reflux condenser, stirrer and dropping funnel. With stirring, a solution of 14.5 g (49 mmol) of N-methylamino-m-perfluorxylol in 10 ml of DMF was added dropwise to this suspension. There was a strong foaming exothermic reaction. By cooling with ice, the temperature was maintained at about 20 ^c C. After completion of the dropping, stirring was continued for another hour. Subsequently, the precipitate was filtered off and washed with ethanol. Not Drying gave 11 g (84%) of a light yellow solid having a melting point of 185 ⁰ C. In ^1S F-NMR spectrum, two multiplets were at -1C7,0ppm (CF, phenyl), and -123,8ppm (CF, phenyl ) and two singlets at 3.2 ppm (-CF ₂ ) and 53.7 ppm (-CF ₃ ) in a ratio of 1: 1: 3: 3. In the 'H NMR spectrum, only one singlet occurred at 3.48 ppm. Mass spectroscopy determined a molar mass of 554 g / mol.

The solid is 5,10-dimethyl-2,4,7,9-tetrakis (trifluoromethyl) tetrafluorophenazine.

Example 2

2-7-bis (trifluoromethyl) -5,10-dimethylhexafluorphenazin

1.9 g (79 mmol) of sodium hydride were suspended in 20 ml of DMF. To this suspension was added dropwise a solution of 20 g (81 mmol) of 4- (N-methylamino) -heptofluorotoluene in 10 ml of DMF. After completion of the dropwise addition and cooling of the vigorous foaming and exothermic reaction, the mixture was stirred for a further hour, then it was filtered off and washed with ethanol. This gave 12.3 g (90%) of a solid having a melting point of 170 ° C. In ^t9 F-NMR spectrum of a triplet occurred (CF _3, 6F) and two multiplets at -144,3ppm (CF, 4F) and -153,3ppm (CF, 2F) at -56.1 ppm. In the 'H NMR spectrum, a singlet occurs at 3.47.

The compound prepared is 2,7-bis (trifluoromethyl) -5,10-dimethylhexai'uorophenazine.

Example 3

N, N'-dimethyl-bis (hexafluorpentano) tetrafluorphenazin

0.5 g of NaH was suspended in 7 ml of dried DMF in a three-necked flask as described in Example 1. With stirring, a solution of 6.5 g (20 mmol) of 5- (methylamino) nonafluoroindane in 50 ml of DMF was added dropwise to this suspension. After stopping the dripping? was stirred for another five hours, it was 5 g (86.2%) (mp: 270 ° C.) N, N'-dimethyl bis (hexafluorpentano) tetrafluorphenazin.

Claims (10)

claims: wherein R ¹ and R ^{2 is} a straight-chain or branched alkyl radical having one to four carbon atoms; R ³ , R ⁴ , R ⁵ and R ⁶ are each fluorine or a perfluorinated straight or branched chain alkyl radical having one to four carbon atoms; orR ³ and R ⁴ and / or R ⁵ and R ⁶ together with the fluorinated phenyl moiety of the phenazine a fully fluorinated alicyclic ring having a total of 4 to 7 carbon atoms, which may optionally be substituted by trifluoromethyl, characterized in that poly-fluorinated N-alkylated anilines the general formula H wherein R ^{7 has} the meaning given for R ¹ and R ² and R ⁸ and R ^{9 have} the meaning mentioned for R ³ to R ^G , is reacted in a concentration of at least 1.5 mol / l with sodium hydride in dipolar aprotic solvents. 2. The method according to claim 1, characterized in that R ³ to R ° jewuils is fluorine. 3. The method according to claim 1, characterized in that R ³ and R ^{5 are} straight-chain or branched perfluorinated alkyl groups and R ⁴ and R ^{6 is} fluorine. 4. The method according to claim 3, characterized in that R ³ and R ^{5 are} each trifluoromethyl and R ⁴ and R ^{6 are} each fluorine. 5. The method according to claim 1, characterized in that R ³ to R ^{6 are} each straight-chain or branched perfluorinated alkyl groups. 6. The method according to claim 5, characterized in that η * to R ^{6 is in} each case trifluoromethyl. 7.A method according to claim 1, ckidurch characterized in that ^> R ³ and R ⁶ together with the fluorinated phenyl moiety of the phenazine each form an alicyclic ring and in the resulting compounds of formula IN (III) η can assume values of 0.1 or 2. 8. The method according to claim 7, characterized in that η = 1. 9. The method according to claim 1-8, characterized in that the reaction at a concentration of the starting components of 2mol / l to 10mol / l and temperatures of -1O ⁰ C to + 40 ° C is carried out in dipolar aprotic solvents. 10. The method according to claim 9, characterized in that the reaction at a Konzentratior the starting components of 2-3 mol / l and at a temperature of 20-30T <n DMF is performed.