Albrecht Marhold

A new method for the trifluoromethylation of aromatics

Abstract A new method is discribed for introducing a CF3-group, by a single-step synthesis, into aromatic compounds. This trifluoromethylation is done by means of a mixture consisting of HF/CCL4 and the aromatic compound. The reaction is thought to be of a Friedel-Crafts type and limited to aromatics which are not substituted by electron withdrawing groups.

A new synthesis of 5-trifluoromethyluracil

Abstract 5-Trifluoromethyluracil, an important intermediate for the preparation of the antiviral trifluridine, is obtained by chlorinating thymine to give the new 2,4-dichloro-5-trichloromethylpyrimidine. Reacting the latter with hydrogen fluoride yields the new 2, 4-difluoro-5-trifluoromethylpyrimidine, and hydrolysis with water gives 5-trifluoromethyluracil in high purity and good yield.

A new family of delocalized lipophilic cations

A new family of delocalized lipophilic cations containing one to three carbimino, sulfimino and phosphinimino units with Cl−, Br−, HF2− and Me3SiF2− as counterions has been designed. The compounds synthesized demonstrate high performance and thermal stability in the ‘Halex’ fluorination reactions. For the first time sulfur tetrachloride pregenerated at −78°C was successfully applied in reactions with N-nucleophiles to afford straightforwardly sulfonium chlorides with three S–N bonds.

Synthese von α-Fluoracrylsäure und Derivaten

Zusammenfassung Three new routes to derivatives of α-fluoracrylic acid, including a laboratory synthesisand a large-scale method, are reported. The processes are (i) addition of elementaryfluorine to acrylic esters and subsequent elimination of HF; (ii) addition of difluorocarbeneto isopropenyl methyl ether, oxidation via ring opening and dehalogenation; and (iii)‘nitrofluorination’ of 2,3-dichloropropene, hydrolysis and dechlorination.

A new method for the trifluoromethylation of aromatic compounds

Abstract Trifluoromethyl groups attached to aromatic compounds are usually prepared by perchlorinating a methyl group and is subsequently perfluorinated by halogen exchange using a fluorinating agent. In addition to this method, which is also used in industry, there are also a number of different synthesis methods which are however only of limited importance owing to the costly reagents required. The disadvantage of the above-mentioned two-step synthesis lies in the restricted range of application since many of the substituents attached to the aromatic compound hinder the chlorination of the methyl group or they are themselves changed (e. g. methyl, bromine …). By means of a new one-step process, the trifluoromethylation of aromatic compounds is made possible by using the reagent HF/CCl4. RH, alkyl, aryl, halogen, phenoxy The anhydrous hydrofluoric acid acts as a Friedel-Crafts-catalyst, solvent and fluorinating agent. The fange of application of the reaction is discussed. Apart from indicating the influence of the concentration of the reaction components, temperature and pressure, details are also given concerning catalysts and side reactions.

Fluorid-katalysierte michael-addition von 2,2,2,-trifluornitroalkanen an aktivierte monoolefine☆

Abstract The fluoride catalyzed addition of the 2,2,2,-trifluoronitroalkanes CF 3 CH 2 NO 2 (Ia) and CF 3 CH(CH 3 )NO 2 (Ib) to activated carbon-carbon double bonds was applied to the synthesis of functionalized trifluoromethyl nitroalkanes CF 3 C(R)NO 2 C(R 1 R 2 )CH(R 3 ) Y (II) (R=H, CH 3 ). The influence of steric and electronic factors on the formation of the adducts (II) was investigated via systematic variation of the activating group Y, and the substituents (R 1 , R 2 , R 3 ) on the double bond. The trifluoromethyl nitroalkanes reported represent a class of compounds which are possible intermediates for the synthesis of biologically active compounds.

Alkylation of Benzotriflourides

Abstract The alkylation of benzotrifluorides under Friedel-Crafts conditions will be described. In addition to this a detailed discussion of the range of application and in particular examples for controlling the isomer distribution will be given. Also the isomerisation of reaction products and the influence of temperature, pressure, solubility, substituents ect. is discussed.

1,1,1,4,4,4-Hexafluorbutane (R 356), a potential CFC substitute

Abstract As part of the world-wide efforts to limit the antropogenic depletion of the stratospheric ozone layer, there is an intensive search for substitutes for all chlorine-containing compounds used in refrigeration. Beside the H-CFCs with reduced ozone depletion potential (ODP), to date only perfluoroalkanes with a high greenhouse potential have been put forward as blowing agents in PUR rigid foams. We consider 1,1,1,4,4,4-hexafluorbutane (R 356) to be the better alternative than the above-mentioned substitutes. In spite of the C4-carbon framework, the physical properties of hexafluorbutane are very similiar to those of R 11. R 356 is not combustible, nor is a gas-air-mixture explosive. Hexafluorbutane also seems to be well-suited from the ecological point of view: by definition, its ozone depletion potential is zero. Due to the partial hydrocarbon character, R 356 is rapidly decomposed in the atmosphere, and thus contributes only minimally to the greenhouse effect. A synthetic route is presented, and an overview given of properties of the technical application of R 356 in PUR rigid foam.

Substitution reactions on halogenated benzotrifluorides with n-nucleophiles

Abstract Fluorine-containing anilines and phenyl hydrazines are well known versatile intermediates for biologically active compounds. In a program for screening various classes of herbicides, it was neccessary to synthesize new compounds with particular substitution pattern as intermediates. Benzotrifluoride precursors substituted by fluorine and chlorine in the required positions were synthesized by catalytical hydrogenolysis. Subsequent substitution with ammonia or hydrazine led to the expected compounds. To optimize the reaction, the reaction conditions (solvent, temperature and amount of reagent) have been examinated and will be discussed in comparison to similar reactions. The influence of the substitution pattern of the benzotrifluoride as well as of the type of nucleophile will be treated in terms of the products obtained.

On the influence of the trifluoromethyl group in the selectivity of nucleophilic substitution in aromatic compounds

Abstract The trifluoromethyl group is known to be a weakly activating substituent in aromatic nucleophilic substitution reactions. Nucleophile-dependent discrimination between ortho - and para -substitution is observed but with a reversal in selectivity as compared to the nitro group. This will be shown in the case of the halex reactions and substitution reactions with C -nucleophiles. Depending on the reaction conditions, high yields of mono fluoro-chlorotrifluoromethyl- benzaldehydes or the respective difluoro compounds can be obtained. The carbon nucleophiles are more selective than the much-studied nitrogen nucleophiles, and give excellent yields of p -trifluoromethylphenyl malonic acid derivatives.