179. A new synthesis of fluoro-ketones

Abstract

Trifluoroacetic acid, when treated with a Grignard reagent (RMgX ; where R = Me, Et, Pri, Bun, But, Ph), afforded the corresponding ketone, CF,*COR. Heptafluorobutyric acid and methylmagnesium iodide gave heptafluoropropyl methyl ketone. The ketones underwent haloform reactions, to give acids, R*CO,H, identified as S-benzylthiuronium salts.SEVERAL methods have been used hitherto for the synthesis of fluoro-ketones. Ester condensations, followed by hydrolyses of the derived p-keto-esters or p-diketones, have been employed most frequently.1 For the synthesis of mixed aromatic fluoroalkyl ketones, Friedel-Crafts reactions have been utilised.2 Fluoroacyl derivatives of reactive aromatic or heterocyclic compounds were made by Hoesch reaction^.^ Grignard-type syntheses involving fluorocarboxylic acid derivatives such as esters, acyl halides, etc. , have been used for ketone production, but suffer from certain limitations. The chief of these is the formation, at the same time, of tertiary alcohols and, where the Grignard reagents have p-hydrogen atoms, secondary alcohols by reduction of any carbonyl groups present in the intermediates4 Very recently, it was shown by McBee, Pierce, and Meyer that the reaction of Grignard reagents with perfluoro-nitriles proceeds normally, and hence may be used for ketone synthesis.Experience in this Department has shown that the ester condensation route, though rather laborious, is satisfactory for the preparation of trifluoroacetone. However, when it was applied to the production of ethyl trifluoromethyl ketone, only poor yields of a very impure product were obtained. Accordingly, we considered possible alternative syntheses for fluoro-ketones , and it appeared likely that fluoro-acids themselves might react with Grignard reagents to give carbonyl compounds.The acidic hydrogen of acids is of course removed by organomagnesium compounds in the well-known Zerewitinoff reaction. Alkanecarboxylic acids have long been known to give tertiary alcohols when treated with excess of organomagnesium halides,6 but the process does not seem to have been used at all widely. However, ketones were obtained, in yields below 25% , by Salkind and Beburischwili 7 from sodium salts, and by Huston and Bailey from acids themselves, though in the latter case tertiary alcohols were the major products. Highly fluorinated carbonyl compounds can give various quite well-defined compounds in which one carbon atom is linked to two oxygen atoms, e g . , R*CF,*CR'(OR"),. The stabilities of these relative to the hydrocarbon-type analogues are greatly enhanced by the presence of the electronegative fluorine substituents. For a reaction between a fluoroacid and a Grignard reagent, it seemed possible that, after the former had undergone elimination of the active hydrogen and addition to the carbonyl group, the resulting complex might resist further reaction , in particular any replacement of oxygen-containing functions (such as OeMgX).This supposition was confirmed experimentally. Anhydrous trifluoroacetic acid reacted readi...

Detection of fluoroalkyl and acyl radicals in the gas-phase photolysis of ketones and aldehydes by electron spin resonance gas-phase spin trapping techniques

“…romethyl radicals are; readily detected in the photolysis of acetone,2 1,1,l-trifluoroacetone or hexafluoroacetone (see Table I for wavelength dependence on the structure of radical produced in the photolysis of trifluoroacetone), no acetyl radicals could be detected by this method. In a solution experiment in benzene at room temperature the acetyl spin adduct can be obtained by allowing terf-butoxy radicals (from di-tert-butylperoxalate, a thermal source of fert-butoxy radicals (BuO•) at room temperature) to react with acetaldehyde in the presence of PBN This approach was unsuccessful with trifluoroacetaldehyde and the following reaction sequence was used to make the trifluoroacetyl spin adduct of PBN in solution 14.0, 0/ = 5.4 G It is clear from the difference in splitting constants that the spectra of the acetyl spin adducts could be recognized in the presence of the methyl or trifluoromethyl spin adducts if present in significant quantities. Formyl radicals were detected by PBN in the photolysis of formaldehyde in the gas phase.…”

Fungistatic activity of cations of nonaromatic amines

“…l-(Trifluoromethyl)propylamine was prepared by catalytic hydrogenation of the oxime of l,l,l-trifluoro-2-butanone. Synthesis of the ketone was described by Sykes et al (1956).…”

Some Fluorine Containing D.D.T. Analogues

“…It seemed, therefore, worthwhile to study analogously substituted 1,1,I-trifluoro-2,2-diphenylethanes (I), thus continuing previous work. For the preparation of I, a suitably substituted trifluoroacetophenone (II), which was synthetized from trifluoroacetic acid and 3 moles of the appropriate arylmagnesium halide [2,3], was reduced to the corresponding secondary alcohol (III), either catalytically or by means of lithium aluminium hydride, both methods having been used previously [3]. The secondary alcohol (III) was finally condensed with the appropriate disubstituted benzene derivative in the presence of cone.…”