Alkylation of perfluoro-2-methyl-2-pentylcarbanion with alkyl and allyl halides

Perfluoro-2-methyl-2-pentylcarbanion, generated from perfluoro-4-methyl-2-pentene in an aprotic solvent, reacted with halides RX, where R = alkyl or allyl and X = I, Br, or Cl, to give fluorohydrocarbons of the general formula CF₃CF₂CF₂C(CF₃)₂R. No reaction with iso-propyl iodide and with 1-iodo-2,2,2,-trifluoroethane occurred. The reaction with 1-iodo-3,3,3,-trifluoropropene resulted in the formation of 3,3,3,-trifluoropropene and 2-H-perfluoro-2-methyl-pentane.     

Diels-Alder reactions of trifluoromethyl alkenes with 5-ethoxyoxazoles: synthesis of trifluoromethylated pyridine derivatives

Cycloaddition reactions between 5-ethoxyoxazole derivatives [2,4-dimethyl 5-ethoxyoxazole and 4-methyl 5-ethoxyoxazole] and various trifluoromethyl alkenes [ethyl 4,4,4-trifluorocrotonate CF₃CHCHCO₂Et, 3,3,3-trifluoro 1-(phenylsulfonyl)-1-propene CF₃CHCHSO₂Ph and 2-(trifluoromethyl) propenoic acid CF₃(HO₂C)CCH₂] gave several trifluoromethyl-substituted pyridine systems in moderate yield (20-56%). Their structures were determined by multinuclear NMR techniques including ¹H-¹³C HETCOR spectroscopy.     

Radical reactions of ethyl orthoformate with 3,3,3-trifluoropropene

Conclusions The radical reaction of 3,3,3-trifluoropropene with ethyl orthoformate largely leads to the formation of the adduct, EtOC(O)OCH(Me)CH₂CH₂CF₃ due to rearrangement of the intermediate radicals with 1,5 hydrogen atom migration.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 6, pp.1418–1420, June, 1985.     

Radical reaction of ethyl orthoacetate with 3,3,3-trifluoropropene

Summary The reaction of 3,3,3-trifluoropropene with ethyl orthoacetate leads to the formation of an acetate CH₃C(O)OCH(CH₃)CH₂CH₂CF₃ and a ketone CH₃C(O)CH₂CH(CF₃)CH₂CH₂CF₃. A reaction mechanism is proposed which involves rearrangement of the radicals CR₃C(OC₂H₅)₂OCH(CH₃) (CH₂CHCF₃) _n ^. with 1,7- and 1,5-migration of an H atom and stabilization by fragmentation.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1583–1586, July, 1986.     

The chemistry of tetrafluoroallene: nucleophilic addition reactions with phenols and amines

Treatment of tetrafluoroallene or its precursor, ICF₂CH₂CF₂I, with phenols in the presence of K₂CO₃ gave the corresponding unsaturated ethers. Tetrafluoroallene also reacted readily with amines in THF at room temperature to afford 3,3,3-trifluoropropionamides.     

The substrate specificity of the heat-stable stereospecific amidase from Klebsiella oxytoca

The substrate specificity of the heat-stable stereospecific amidase from Klebsiella oxytoca was investigated. In addition to the original substrate, 3,3,3-trifluoro-2-hydroxy-2-methylpropanamide, the amidase accepted 2-hydroxy-2-(trifluoromethyl)-butanamide and 3,3,3-trifluoro-2-amino-2-methylpropanamide as substrates. Compounds with larger side chains and compounds where the hydroxyl group was substituted with a methoxy group, or in which the CF₃ group was substituted by CCl₃, were not accepted. The biotransformation is a new synthetic route to (R)-(+)-3,3,3-trifluoro-2-amino-2-methylpropanoic acid, and its related (S)-(−)-amide, and to (R)-(+)-2-hydroxy-2-(trifluoromethyl)-butanoic acid and its related (S)-(−)-amide.     

1,3‐Dipolar Cycloadditions of Ethyl 2‐Diazo‐3,3,3‐trifluoropropanoate to Alkynes and [1,5] Sigmatropic Rearrangements of the Resulting 3H‐Pyrazoles: Synthesis of Mono‐, Bis‐ and Tris(trifluoromethyl)‐Substituted Pyrazoles

The 1,3‐dipolar cycloadditions of ethyl 2‐diazo‐3,3,3‐trifluoropropanoate with electron‐rich and electron‐deficient alkynes, as well as the van Alphen? Hüttel rearrangements of the resulting 3H‐pyrazoles were investigated. These reactions led to a series of CF₃‐substituted pyrazoles in good overall yields. Phenyl‐ and diphenylacetylene proved to be unreactive, but, at high temperature, the diazoalkane and phenylacetylene furnished a cyclopropene derivative. As expected, the 1,3‐dipolar cycloaddition to the ynamine occurred much faster than those to electron‐deficient alkynes. With one exception, all cycloadditions proceeded with excellent regioselectivities. The [1,5] sigmatropic rearrangement of the primary 3H‐pyrazoles provided products with shifted acyl groups; products resulting from the migration of a CF₃ group were not detected. In agreement with literature reports, this rearrangement occurs faster with 3H‐pyrazoles bearing electron‐withdrawing substituents.     

Fluorosilicone elastomer based on the poly[(3,3,3‐trifluoropropyl)methyl‐siloxane‐co‐(3,3,4,4,5,5,6,6,6‐nonafluorohexyl)methylsiloxane]

Fluorosilicone elastomer based on the poly[(3,3,3‐trifluoropropyl)methylsiloxane‐co‐(3,3,4,4,5,5,6,6,6‐nonafluorohexyl)methylsiloxane] was studied. First, the synthesis of fluorosilicone polymer based on the poly[(3,3,4,4,5,5,6,6,6‐nonafluorohexyl)methylsiloxane] (PNFHMS) was examined by the polymerization of 1,3,5‐tris(3,3,4,4,5,5,6,6,6‐nonafluorohexyl)‐1,3,5‐trimethylcyclotrisiloxane (C₄F₉D3) by sodium hydroxide. On the contrast of the polymerization of the commercially available 1,3,5‐tris(3,3,3‐trifluoropropyl)‐1,3,5‐trimethylcyclotrisiloxane (CF₃D3), the polymerization of C₄F₉D3 with sodium hydroxide resulted in the formation of 1,3,5,7‐tetrakis(3,3,4,4,5,5,6,6,6‐nonafluorohexyl)‐1,3,­5,7‐tetramethylcyclotetrasiloxane : [C₄F₉CH₂CH₂(CH₃)SiO]₄ (C₄F₉D4) as the major product. It was due to the easy occurrence of the depolymerization by the back‐biting mechanism, because C₄F₉D4 is more stable ­than 1,3,5,7‐tetrakis(3,3,3‐trifluoropropyl)‐1,3,5,7‐tetramethylcyclotetrasiloxane : [CF₃CH₂CH₂(CH₃)SiO]₄ (CF₃D4). The above result made us to conclude that it was difficult to apply the polymer based on PNFHMS to heat vulcanizable elastomers and to investigate the elastomer based on the poly[(3,3,3‐trifluoropropyl)methylsiloxane‐co‐(3,3,4,4,5,5,6,6,6‐nonafluorohexyl)methylsiloxane]. C₄F₉D3 and CF₃D3 were co‐polymerized successfully by sodium hydroxide and formulated with the silica treated by CF₃D3. The use of silica treated with methylsilyl unit failed, because creep‐hardening phenomenon occurred. This elastomer was evaluated about some mechanical properties, and the resistance to organic solvents, and a fuel. The advantage that can be detected from the introduction of [C₄F₉C₂H₄‐(CH₃)SiO] unit was that the resistance to the polar solvents such as acetone and dimethylformamide was improved. Copyright © 2001 John Wiley & Sons, Ltd.     

Reaction of benzyl chloride with propylene and trifluoropropene under metallocomplex initiation conditions

The reactions of benzyl chloride with propylene and 3,3,3-trifluoropropene in the presence of Fe(CO)₅ ` + DMF were studied. With propylene, the reaction stops at the addition stage with the simultaneous formation of dibenzyl. In the case of 3,3,3-trifluoropropene, a telomerization takes place, whereby the second growing radical C₆H₅CH₂CH₂CH(CF₃)CH₂HCF₃ practically completely isomerizes with a 1,5-migration into the radical C₆H₅HCH₂CH(CF₃)CH₂CH₂CF₃. To confirm the structure of the isolated compounds, chromato-mass-spectrometry and¹³C NMR were used.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 6, pp. 1384–1388, June, 1991.     

Synthese von Trifluoromethyl-substituierten Schwefel-Heterocyclen unter Verwendung von 3,3,3-Trifluorobrenztraubensäure-Derivaten

Synthesis of Trifluoromethyl-Substituted Sulfur Heterocycles Using 3,3,3-Trifluoropyruvic-Acid Derivatives The reaction of methyl 3,3,3-trifluoropyruvate ( 1 ) with 2,5-dihydro-1,3,4-thiadiazoles 4a, b in benzene at 45° yielded the corresponding methyl 5-(trifluoromethyl)-1,3-oxathiolane-5-carboxylates 5a, b (Scheme 1) via a regioselective 1,3-dipolar cycloaddition of an intermediate ‘thiocarbonyl ylide’ of type 3 . With methyl pyruvate, 4a reacted similarly to give 6 in good yield. Methyl 2-diazo-3,3,3-trifluoropropanoate ( 2 ) and thiobenzophenone ( 7a ) in toluene underwent a reaction at 50°; the only product detected in the reaction mixture was thiirane 8a (Scheme 2). With the less reactive thiocarbonyl compounds 9H-xanthene-9-thione ( 7b ) and 9H-thioxanthene-9-thione ( 7c ) as well as with 1,3-thiazole-5(4H)-thione 12 , diazo compound 2 reacted only in the presence of catalytic amounts of Rh₂(OAc)₄. In the cases of 7a and 7b , thiiranes 8b and 8c , respectively, were the sole products (Scheme 3). The crystal struture of 8c has been established by X-ray crystallography (Fig.). In the reaction with 12 , desulfurization of the primarily formed thiirane 14 gave the methyl 3,3,3-trifluoro-2-(4,5-dihydro-1,3-thiazol-5-ylidene)propanoates (E)-and (Z)- 15 (Scheme 4). A mechanism of the Rh-catalyzed reaction via a carbene addition to the thiocarbonyl S-atom is proposed in Scheme 5.     

Reaction of 3,3,3-trifluoropropene-1 with bromoform and methylene bromide

The radical telomerization of 3,3,3-trifluoropropene with bromoform and methylens bromide has been studied. The nature of the products with bromoform depends substantially on the method of initiation. In the presence of Fe(CO)₅ + DMF, telomers of CHBr₂(CH₅₂CHCF₃)_nBr are formed, while with initiation with benzoyl peroxide other compounds are also formed that contain two, three, or four bromine atoms per molecule. To elucidate the formation of these products a reaction scheme is proposed that involves rearrangement of CHBr₂CH₂CH(CF₃)CH₃CHCF₃ radicals to CBr₂CH₂CH(CF₃)CH₂CH₂CF₃ radicals.Deceased.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2558–2562, November, 1989.     

Reactions of CF3-enones with ethyl nitroacetate and nitromethane: synthesis of CF3-γ-nitroketones

Reactions of α,β-unsaturated CF₃-ketones with nitromethane and ethyl nitroacetate have been investigated. We found that α,β-unsaturated trifluoromethylketones react with ethyl nitroacetate in the presence of calcinated potassium fluoride to form two classes of 1,4-conjugated addition products: CF₃-γ-nitroketones and 6,6,6-trifluoro-2-nitro-5-oxohexanoates in nearly quantitative yields. The products obtained are precursors for CF₃-pyrrolidine synthesis.     

The catalytic olefination reaction of aldehydes and ketones with CBr3CF3

The new approach of catalytic olefination reaction (COR) has been used to convert aromatic and aliphatic aldehydes and ketones to 2-bromo-3,3,3-trifluoroprop-1-enes by the treatment of corresponding hydrazones with CBr₃CF₃ under copper(I) catalysis conditions. The reaction proceeds stereoselectively, the target alkenes were obtained in good yields.     

Synthesis of allenes containing geminal trifluoromethyl groups

Allenes (CF₃)₂CCC(COOMe)₂ and (CF₃)₂CCC(COOEt) Ph were prepared by Cs-catalyzed condensation of octafluoroisobutene with dimethyl malonate and ethyl phenylacetate respectively. A stable salt

is formed from (CF₃)₂CCC(COOMe)₂ and CsF. Similar salts were prepared through the condensation of octafluoroisobutene with ethyl cyanoacetate and malononitrile. Allenes (CF₃)₂CCOMe₂ and (CF₃)₂CCCHPh were synthesized by dehydrofluorination of olefines (CF₃)₂CHCFCRR′ under the action of octafluoroisobutene and CsF mixture; the latter allene has been isolated only as a cycloadduct with octafluoroisobutene.     

Aminophosphite und Aminophosphorane mit der 2,2,2-Trifluor-1-(trifluormethyl)ethyl-Gruppierung

Aminophosphites and Aminophosphoranes Containing the 2,2,2-Trifluoro-1-(trifluoromethyl)ethyl Grouping By the reaction of dichloroaminophosphines R₂NPCl₂ (R = Me, Et, SiMe₃; R₂ = CH₂(CH₂CMe₂)₂) and LiOCH(CF₃)₂ the phosphites 1 – 4 and LiCl were formed. Hexafluoroacetone reacted with 1 or 2 to give the monocyclic phosphoranes 5 and 7 . Compound 5 could also be obtained from the dichloroaminophosphosphorane 6 and LiOCH(CF₃)₂. The aminophosphite 2 , elementary chlorine and Li₂[OC(CF₃)₂C(CF₃)₂O] or LiOCH(CF₃)₂ gave 7 or the acyclic phosphorane 8 , respectively. Compounds 1 – 4 exhibit two magnetically inequivalent CF₃ groups in the ¹⁹F-N.M.R. spectra, the phosphoranes 5 , 7 and 8 show no ligand permutation at room temperature.     

Organic electrosynthesis using a fluoride ion mediator

Recent studies on fluoride ion-mediated anodic methoxylation of fluoroalkyl sulfides and sulfur-containing five-membered heterocyclic compounds together with its synthetic applications are summarized in this review. The first example of anodic methoxylation of 2-acyloxy-3,3,3-trifluoropropyl sulfides accompanying with [1,2]-rearrangement of acyloxy group is described. Fluoride ion-mediated anodic intramolecular cyclization of 3,3,3-trifluoropropyl sulfides bearing OH and t-BuCOO groups provides CF₃-containing 1,3-oxathiolane and ethylene carbonate derivatives, respectively. Fluoride ion mediator can be also applied to anodic intramolecular carbon–carbon coupling to form oxindole and 3-oxotetrahydroisoquinoline derivatives.     

Electron-impact studies of organometallic molecules—VII. Some transition metal complexes derived from 3,3,3-trifluoroprop-1-yne

The mass spectra of ten complexes derived from 3,3,3-trifluoroprop-1-yne, namely (CF₃C?CH)CO₂(CO)₆, (CF₃C?CH) [π? C₅H₅Ni]₂, (CF₃C?CH)₃Co₂(CO)₄, CF₃CH₂C[Co(CO)₃]₃, are discussed in terms of their structures. The major processes observed can be satisfactorily explained in terms of (i) loss of carbonyl groups, if present; (ii) loss of one fluorine atom from the parention (iii) elimination of neutral metal fluorides, with ligand transfer reactions in the case of the iron complexes; (iv) elimination of neutral fluorocarbon molecules.     

Methyl 3,3,3-trifluoro-2-diazopropionate for the synthesis of functionalized styrenes

The efficient method for the synthesis of novel trifluoromethyl-containing hydroxy- and aminostyrenes has been developed. The reaction sequence includes the selective insertion of CF₃-substituted carbene, which was catalytically derived from methyl 3,3,3-trifluoro-2-diazopropionate, into the OH- or NH-bonds of easily available o-bromophenol and o-bromoaniline derivatives followed by a bromine substitution for vinyl group via Pd-catalyzed Stille reaction.     

Synthesis of 3,3,3-trifluoroprop-1-enyl compounds from some enolizable aldehydes

2,2,2-Trifluoroethyldiphenylphosphine oxide [Ph₂P(O)CH₂CF₃] (2) is known to give no Horner reaction product with enolizable aldehydes. We found, however, that some enolizable aldehydes such as N-Boc-pyrrolidine-2-aldehyde (9) gave the expected 3,3,3-trifluoroprop-1-enyl compounds by reaction with 2. The products could be further transformed to some 2,2,2-trifluoroethyl-substituted nitrogen-containing heterocycles by using radical cyclization or Heck reaction.     

The steric and electronic effects of aliphatic fluoroalkyl groups

Ab initio calculations were performed on 18 fluorinated and unfluorinated alcohols at the B3LYP and HF levels with the 6-311G^∗∗ basis set. Molar volumes of the alcohols were computed at each level and averaged to produce a scale of relative size. From this, various isosteric replacements of potential use in drug design were suggested: ethyl by FCH₂CH₂ or HCF₂CH₂, propyl by CF₃CH₂, isopropyl by CF₃(CH₃)CH or (FCH₂)₂CH, isobutyl or t-butyl by (CF₃)₂CH, and 3-methyl-2-butyl by CF₃(CH₃)₂C. Calculation of the charge on oxygen and the Wiberg index of the CO bond allowed an electronegativity scale to be constructed for the fluoroalkyl groups. Electronegativity decreased in the order: (CF₃)₃C>(CF₃)₂CH>C₂F₅CH₂>CF₃CH₂>CH₃(CF₃)₂C>HCF₂CH₂>CF₃(CH₃)CH>(FCH₂)₂CH>FCH₂CH₂>CF₃(CH₃)₂C. This ranking agreed with literature acid dissociation data for the alcohols studied.