Trifluoromethyl imidazoles

Some imidazole derivatives with trifluoromethyl substituents have been made, as part of a programme on the synthesis of fluorine-containing annyti-cancer agents. This work is a joint project between ourselves and Professor A.B. Foster's group at the Institute of Cancer Research, Royal Cancer Hospital, London. Imidazole carboxylic acids have been treated with sulphur tetrafluoride to give 2-trifluoromethyl-, 2,4-bis(trifluoromethyl)-, and 2,4,5-tris(trifluoromethyl)-imidazole. Some reactions of these trifluoromethyl derivatives have been studied. Ranges of N-substituted derivatives have been synthesised using the imidazole silver salts and the appropriate alkyl halide derivative. Hydrolytic stabilities of the CF₃ groups in the patent imidazoles have been studied.The 2-trifluoromethyl derivative is the least stable hydrolytically.     

The Trifluoromethyl Anion

First evidence for the existence of free trifluoromethyl anion CF₃⁻ has been obtained. The 3D‐caged potassium cation in [K(crypt‐222)]⁺ is inaccessible to CF₃⁻, thus rendering it uncoordinated (“naked”). Ionic [K(crypt‐222)]⁺ CF₃⁻ has been characterized by single‐crystal X‐ray diffraction, solution NMR spectroscopy, DFT calculations, and reactivity toward electrophiles.     

The Trifluoromethyl Anion

First evidence for the existence of free trifluoromethyl anion CF₃^? has been obtained. The 3D‐caged potassium cation in [K(crypt‐222)]⁺ is inaccessible to CF₃^?, thus rendering it uncoordinated (“naked”). Ionic [K(crypt‐222)]⁺ CF₃^? has been characterized by single‐crystal X‐ray diffraction, solution NMR spectroscopy, DFT calculations, and reactivity toward electrophiles.     

Trifluoromethyl Derivatives of Benzooxatellurole

Replacement of the iodine atom in an iodine (III) CF₃‐transfer reagent with a Te‐aryl moiety was accomplished in a three‐step synthetic sequence. Three compounds of this type have been prepared, two of which were characterized by X‐ray diffraction. Single crystal structures were also obtained for three related Te(IV) compounds unreported so far ( 4a , 4b , 6b ). Comparison with the iodine (III) analogues indicate a large degree of structural similarity, however these species display an interesting decomposition pathway under thermal conditions. In addition to the expected Te?CF₃ bond cleavage, C?F bond cleavage is also observed, unlike in the case of iodine (III) compounds.     

Trifluoromethyl derivatives of cerium endohedral metallofullerenes

A method was developed for the synthesis of trifluoromethyl derivatives of endohedral metallofullerenes (EMF) encapsulating cerium based on the high-temperature solid-state reaction of silver trifluoroacetate with a DMF extract of EMF enriched with Ce@C₈₂. The trifluoromethyl derivatives Ce@C₈₂(CF₃)₅ (isomers I–III) with high purity (98–99%) were synthesized and isolated for the first time. These compounds were characterized by HPLC, S8-MALDI-TOF mass spectrometry, and optical spectroscopy.     

Reactions of Bis(Trifluoromethyl)Phosphine and Tetrakis(Trifluoromethyl)Phosphine with Ruthenium Carbonyl Clusters

Abstract

The reaction of (CF₃)₂P-P(CF₃)₂ with [Ru₃(CO)₁₂] yielded compounds : [Ru₁₄(CO)₁₃{μ-P(CF₃)₂)₂] (1), [Ru₄(CO)₁₄{μ-P(CF₃)₂}₂] (2), and [Ru₄(CO)₁₁{μ-P(CF₃)₂}₄] (3); reaction with [μ-H)₄Ru₄(CO)₁₂] yielded (1) and [(μ-H)₃Ru₄(CO)₁₂{μ-P(CF₃)₂}] (4). The reaction of (CF₃)₂PH with [Ru₃(CO)₁₂] yielded compounds (1) and (4) and compounds (1) and (2) using cluster : ligand ratios of 1:1 and 1:2 respectively. All the compounds have been characterised by X-ray crystallography; a schematic diagram of their structures is shown in Figure 1. The fluxional behaviour of the hydrides in (4) was studied using variable temperature ¹H NMR spectroscopy (see Figure 2). The result of this study was used in the assignment of hydride positions of (4) in the solid state.     

含三氟甲基和双希夫碱化合物的合成与表征

利用1,4-双(4-氨基-2-三氟甲基苯氧基)苯与苯甲醛或其衍生物的反应,合成了一系列含三氟甲基和双希夫碱的新化合物,其结构经UV,1HNMR,IR和元素分析表征。     

Iron-Catalyzed Halogen Exchange of Trifluoromethyl Arenes**

The facile production of ArCF₂X and ArCX₃ from ArCF₃ using catalytic iron(III)halides is reported, which constitutes the first iron-catalyzed halogen exchange for non-aromatic C−F bonds. Theoretical calculations suggest direct activation of C−F bonds by iron coordination. ArCX₃ and ArCF₂X products of the reaction are synthetically valuable due to their diversification potential. In particular, chloro- and bromodifluoromethyl arenes (ArCF₂Cl, ArCF₂Br respectively) provide access to a myriad of difluoromethyl arene derivatives (ArCF₂R). To optimize for mono-halogen exchange, a statistical method called Design of Experiments was used. Optimized parameters were successfully applied to electron rich and electron deficient aromatic substrates, and to the late stage diversification of flufenoxuron, a commercial insecticide. These methods are highly practical, being run at convenient temperatures and using inexpensive common reagents.     

Reduction of Aryl Trifluoromethyl Oximes

Borane-tetrahydrofuran complex reduces trifluoromethyl oximes to trifluoromethyl hydroxylamines in good yields.     

Catalytic Synthesis of Trifluoromethyl Cyclopropenes and Oligo-Cyclopropenes

The synthesis of trifluoromethylated cyclopropenes is often associated with important applications in drug discovery and functional materials. In this report, we describe the use of readily available chiral rhodium(II) catalysts for a highly efficient asymmetric cyclopropenation reaction of fluorinated donor–acceptor diazoalkanes with a broad variety of aliphatic and aromatic alkynes. Further studies highlight the unique reactivity of fluorinated donor–acceptor diazoalkanes in the synthesis of oligo-cyclopropenes. Subsequent C−H functionalization of trifluoromethyl cyclopropenes furnishes densely substituted cyclopropene frameworks and also allows the alternative synthesis of bis-cyclopropenes.     

Anodic Processes Involving Trifluoromethyl Cobaloxime and Nucleophiles

Anodic oxidation of trifluoromethyl cobaloxime (CF₃)Co(DH)₂Py in the presence of such nucleophiles as pyridine or NO^– ₃ and C₆F₁₃COO^– anions is studied. A controlled-potential electrolysis and ¹⁹F NMR spectroscopy show the anodic reaction products to contain compounds with the bond >N–CF₃. A mechanism for the reaction between a labile Co(+4) complex and pyridine is offered. At potentials more positive than that of the Co(+3) Co(+4) oxidation, secondary products of electrochemical reaction form and are revealed by a cathodic reduction peak.     

Structure and Properties of 2,2-Dibromovinyl Trifluoromethyl Ketone

It was established by IR spectroscopy and quantum-chemical calculations along nonempirical DFT method in B3LYP version with the basis set 6-311 G(d,p) that 2,2-dibromovinyl trifluoromethyl ketone consisted of a mixture of s-cis planar conformer and s-trans-form deviating from a plane by 13°, whereas the s-cis-form is more energetically stable than the s-trans one (E -5.07 kcal mol^{- 1}). Also in 2,2-dibromovinyl methyl ketone the planar s-cis conformer is more stable. Chlorine-containing analogs, 2,2-dichlorovinyl trifluoromethyl ketone and 2,2-dichlorovinyl methyl ketone, are more stable in the planar s-trans-conformation. Charge distribution and polarization in the dibromovinyl ketones are analogous to those in dichlorovinyl ketones in agreement with the established reactivity of dibromovinyl trifluoromethyl ketone. By reaction of 2,2-dibromovinyl trifluoromethyl ketone with 2,4-dinitrophenyl-, alkylhydrazines, N,N-dimethylhydrazine, N,N-, N,O-, N,S-binucleophiles were respectively obtained hydrazone, derivatives of pyrazole, imidazole, oxazole, and 1,3-thiazine containing a trifluoromethyl group.     

Trifluoromethyl substituted 4-pyrones via self-condensation of trifluoroacetoacetates

When 3-(acetoxy)-4,4,4-trifluoro-2-butenoates 7 and 8 are heated at 100°, in the presence of catalytic amounts of zinc chloride, they undergo self-condensation to yield 2,6-bis(trifluoromethyl)-4-pyrones 1 and 2 respectively. Compounds 1 and 2 were further converted to the corresponding pyridine derivatives 3 and 4 via ammoniolysis.     

Trifluoromethyl Sulfones and Perfluoroalkanesulfonamides of the Azole Series

2-Phenyl-4-trifluoromethylsulfonylmethyl-2H-1,2,3-triazole was synthesized from 4-bromo-methyl-2-phenyl-2H-1,2,3-triazole and sodium trifluoromethanesulfinate CF₃SO₂Na. 1(2)-Ethyl-4-nitro-1(2)H-1,2,3-triazoles and 4-nitro-2-phenyl-2H-1,2,3-triazole were reduced to the corresponding amines. Intermediate 1,2-bis(1-ethyl-1H-1,2,3-triazol-4-yl)diazene 1-oxide exists as a mixture of syn and anti isomers, the former being stabilized via formation of a strong intramolecular hydrogen bond. The reduction of 2-ethyl-4-nitro-2H-1,2,3-triazole in the presence of HCl afforded the target 4-amino-2-ethyl-2H-1,2,3-triazole and also 4-amino-5-chloro-2-ethyl-2H-1,2,3-triazole. Treatment of alkyl-substituted 4-amino-1,2,3-triazoles with trifluoromethanesulfonyl chloride and pentafluoroethanesulfonyl chloride gave N-triazolyl-substituted trifluoromethane- and pentafluoroethanesulfonamides and -imides.     

Trifluoromethyl Derivatives of Elusive Fullerene C98

Data concerning the isomeric composition of C₉₈ and the chemistry of C₉₈ derivatives are scarce due to very low abundance of C₉₈ in the fullerene soot. Trifluoromethylation of C₉₈-containing mixtures followed by HPLC separation of CF₃ derivatives and single crystal X-ray diffraction study resulted in structural characterization of four compounds C₉₈(248)(CF₃)_18/20, C₉₈(116)(CF₃)₁₈, and C₉₈(120)(CF₃)₂₀. To date, these compounds represent the largest fullerenes isolated as CF₃ derivatives with experimentally determined molecular structures. The addition patterns of C₉₈(CF₃)_18/20 are discussed in detail revealing the stabilizing factors, such as isolated double C=C bonds and benzenoid rings on C₉₈ fullerene cages. A detailed comparison with the addition patterns of the known C₉₈Cl_n allowed us to contribute to the better understanding the chemistry of elusive C₉₈ fullerene.     

Photochemistry of 2-(Trifluoromethyl) cyclohexanone

The photochemical behaviour of the title compound 1a is compared to that of the non-fluorinated parent ketone 2-methylcyclohexanone ( 1b ). Substitution of the CH₃- group on C(2) by a trifluoromethyl group strongly enhances 2H- and RH- reduction product formation in cyclohexane or 2-propanol and oxetane formation in the presence of 2-methylpropene as olefinic component. Under all these conditions 1b exclusively undergoes a-cleavage, a process observed for 1a only in non-reducing solvents as benzene or tert-butyl alcohol.     

Stepwise Degradation of Trifluoromethyl Platinum(II) Compounds

The action of moisture on the homoleptic organoplatinum(II) compound [NBu₄]₂[Pt(CF₃)₄] ( 1 ) gives rise to the carbonyl derivative [NBu₄][Pt(CF₃)₃(CO)] ( 2 ), which is itself moisture stable. However, treatment of compound 2 with HCl(aq) results in the formation of [NBu₄][cis‐Pt(CF₃)₂Cl(CO)] ( 3 ), which undergoes degradation of an additional CF₃ group by further treatment with HCl(aq) in large excess, affording [NBu₄][cis‐Pt(CF₃)Cl₂(CO)] ( 4 ). The carbonyl derivatives 2 – 4 are fairly stable species, in which the CO ligand, however, can be readily extruded by reaction with trimethylamine N‐oxide (ONMe₃). Thus, compound 2 reacts with ONMe₃ in the presence of a number of neutral or anionic ligands affording a series of singly or doubly charged derivatives with the general formulae [NBu₄][Pt(CF₃)₃(L)] [L=CNtBu ( 5 ), PPh₃ ( 6 ), P(o‐tolyl)₃ ( 7 ), tht ( 8 ; tht=tetrahydrothiophene)] and [NBu₄]₂[Pt(CF₃)₃X] [X=Cl ( 9 ), Br ( 10 ), I ( 11 )], respectively. Compound 2 also reacts with ONMe₃ and pyridin‐2‐thiol (C₅H₅NS) giving rise to the five‐membered metallacyclic derivative [NBu₄][Pt(CF₃)₂(CF₂NC₅H₄S‐κC,κS)] ( 12 ), which can be viewed as a difluorocarbene species stabilized by intramolecular base coordination. On the other hand, treatment of compound 3 with ONMe₃ in the presence of C₅H₅NS yields the four‐membered metallacyclic compound [NBu₄][Pt(CF₃)₂(NC₅H₄S‐κN,κS)] ( 13 ). The geometries of the metallacycles in compounds 12 and 13 are compared. In the absence of any additional ligand, compound 3 undergoes dimerization producing the dinuclear species [NBu₄]₂[{Pt(CF₃)₂}₂(μ‐Cl)₂] ( 14 ). Halide abstraction in the latter compound with AgClO₄ in THF yields the solvento compound cis‐[Pt(CF₃)₂(thf)₂] ( 15 ). The highly labile character of the THF ligands in compound 15 makes this species a convenient synthon of the “cis‐Pt(CF₃)₂” unit.     

4‐(Trifluoromethyl)benzonitrile

4‐(Tri­fluoro­methyl)­benzo­nitrile, C₈H₄F₃N, at 123 K contains mol­ecules linked together through one C—H?F bond and two C—H?N hydrogen bonds into sheets that are further crosslinked to form a dense two‐dimensional network without π?π ring interactions. The aromatic ring is slightly deformed due to the two para‐related electronegative groups.