Novel route of the reaction of trifluoromethyl-containing N-methyl(4-ethoxyphenyl)imidazolidin-2-ones with urea

The reactions of perfluorobiacetyl with N-(4-ethoxyphenyl)- and N-methylurea afforded cis- and trans-isomers of 1-methyl-4,5-dihydroxy-4,5-bis(trifluoromethyl)imidazolidin-2-one and 1-(4-ethoxyphenyl)-4,5-dihydroxy-4,5-bis(trifluoromethyl)imidazolidin-2-one in a yield of ～60—75%. N-Alkyl(aryl)bis(trifluoromethyl)imidazooxazoles were obtained as unexpected products in the reaction of 1-alkyl(aryl)-4,5-dihydroxy-4,5-bis(trifluoromethyl)imidazolidin-2-ones with urea in dimethylacetamide. The reaction is accompanied by the rearrangement of imidazolidin-2-ones to N-alkyl(aryl)-5,5-bis(trifluoromethyl)hydantoins with CF₃ group migration from position 5 to position 4 of the starting heterocycle. A similar rearrangement is observed on boiling of the studied imidazolidin-2-ones in dimethylacetamide. The molecular structures of 3-(4-ethoxyphenyl)-5,5-bis(trifluoromethyl)imidazolidine-2,4-dione and 6-(4-ethoxyphenyl)-3a,6a-bis(trifluoromethyl)tetrahydroimidazo[4,5-d]oxazole-2,5-dione were studied by X-ray diffraction analysis.     

Reactions of polyfluorinated thietanes: Selective synthesis of 4-R-2,2-bis(trifluoromethyl)thietane-1-S-oxides and 2-substituted 5-fluoro-4-(trifluoromethyl)-2,3-dihydrothiophenes

Oxidation of 4-substituted 2,2-bis(trifluoromethyl)thietanes by m-chloroperoxybenzoic acid results in selective formation of the corresponding S-oxides in 65-86% yield. Oxidation of 4-C₂H₅S-2,2-bis(trifluoromethyl)thietane under mild conditions led to selective formation of 4-C₂H₅SO₂-2,2-bis(trifluoromethyl)thietane, which under more rigorous conditions was selectively converted into trans-4-C₂H₅SO₂-2,2-bis(trifluoromethyl)thietane-1-S-oxide. Reaction of 4-substituted 2,2-bis(trifluoromethyl)thietanes with activated aluminum powder results in a highly selective ring expansion process, producing the corresponding 5-fluoro-4-(trifluoromethyl)-2,3-dihydro-2-alkoxythiophenes in 58-93% yield. These compounds were also prepared in 61-85% yield using a “one-pot” procedure, starting from sulfur, hexafluoropropene and the corresponding vinyl ether without isolation of any intermediates. Both 2-i-C₃H₇O- and 2-t-C₄H₉O- 5-fluoro-4-(trifluoromethyl)-2,3-dihydrothiophenes were converted into 2-fluoro-3-trifluormethylthiophene by reaction with P₂O₅.     

Reaction of 2,5-bis(trifluoromethyl)-1,3,4-oxadiazole with primary amines. Synthesis of 4-substituted-3,5-bis(trifluoromethyl)-4H-1,2,4-triazoles

Reaction of 3,5-bis(trifluoromethyl)-1,3,4-oxadiazole ( 1a ) with primary amines under a variety of conditions conveniently produced 4-substituted-3,5-bis(trifluoromethyl)-4H-1.2,4-triazoles 4a in 26-85% yield. Alkyl amines reacted with 1a in methanol at ?42° to provide hydrogen-bonded monoadduct-methanol complexes 5a , as determined by X-ray. The reaction of 1a with sterically hindered or strongly electron deficient anilines required high temperatures in the absence of solvent.     

Regioselective nucleophilic 1,4-trifluoromethylation of 2-polyfluoroalkylchromones with (trifluoromethyl)trimethylsilane. Synthesis of fluorinated analogs of natural 2,2-dimethylchroman-4-ones and 2,2-dimethylchromenes

Reactions of 2-polyfluoroalkylchromones with (perfluoroalkyl)trimethylsilanes proceed as a 1,4-nucleophilic perfluoroalkylation to give 2,2-bis(polyfluoroalkyl)chroman-4-ones with high regioselectivity and good yields after acid hydrolysis. Oxidation of 6-methyl-2,2-bis(trifluoromethyl)chroman-4-one with a mixture of K2S2O8 and CuSO4 in aqueous acetonitrile leads to fluorinated analogues of natural lactarochromal and the corresponding acid. Reduction of substituted 2,2-bis(trifluoromethyl)chroman-4-one with sodium borohydride in methanol and subsequent dehydration of chromanols in refluxing xylene in the presence of p-toluene sulfonic acid gives 2,2-bis(trifluoromethyl)chromenes, which are fluorinated analogues of natural precocenes.     

Hypervalent tetracoordinate organobismuth compounds (10-Bi-4)

A stable hypervalent 10-Bi-4 species, tetraethylammonium bis[α,α-bis(trifluoromethyl)benzenemethanolato(2-)-C²],Obismuthanate(1-), was prepared by the reaction of bismuth trichloride with 2 equiv of lithium 2-(2-lithiophenyl)-2-propoxide derivatives. The ate complex was inert toward MeI, instead, the corresponding nonfluorinated analogue, bis[α,α-bis(dimethyl)benzenemethanolato(2-)-C², O]bismuthanate(1-), was reactive enough toward MeI to give O-methylated product. Regioselective methylation at the nonfluorinated methanolate was observed in the reaction of unsymmetrically substituted ate complex, [α,α-bis(dimethyl)benzenemethanolato(2-)-C², O[]α,α-bis(trifluoromethyl) benzenemethanolato(2-)-C², O]bis-muthanate(1-). Mechanism of isomerization of these ate complexes and related protonated compounds and the synthesis and stability of [α,α-bis(trifluoromethyl)-benzenemethanolato (2-) -C², O]diarylbismuthanate-(1-) were also described.     

Nucleophilic trifluoromethylation of RF-containing 4-quinolones, 8-aza- and 1-thiochromones with (trifluoromethyl)trimethylsilane

Reactions of N-substituted 2-polyfluoroalkyl-4-quinolones and 8-aza-5,7-dimethyl-2-polyfluoroalkylchromones with (trifluoromethyl)trimethylsilane proceed mainly as a 1,4-nucleophilic trifluoromethylation to give N-substituted 2,2-bis(polyfluoroalkyl)-2,3-dihydroquinolin-4(1H)-ones and 5,7-dimethyl-2,2-bis(polyfluoroalkyl)-2,3-dihydro-4H-pyrano[2,3-b]pyridin-4-ones after acid hydrolysis. Similar reaction with 2-trifluoromethyl-4H-thiochromen-4-one proceeds as a 1,2-addition to give 2,4-bis(trifluoromethyl)-4H-thiochromen-4-yl trimethylsilyl ether.     

Bis(trifluoromethyl)-containing 1-azatricycloheptanes

6-Substituted 7-halo-3,3-bis(trifluoromethyl)-2-azabicyclo[2.2.1]heptanes were synthesized by the addition of water, alcohols, and acetic acid to 3-halo-7,7-bis(trifluoromethyl)-1-azatricyclo[2.2.1.0^2,6]heptanes in the presence of H₂SO₄. 5,6-Disubstituted 3,3-bis(trifluoromethyl)-2-azabicyclo[2.2.1]heptanes were prepared by oxymercuration of 3,3-bis(trifluoromethyl)-2-azabicyclo[2.2.1]hept-5-ene.     

Remarkable effect of metal fluoride catalyst on reaction of hexafluoropropene, sulfur and vinyl ethers. Convenient synthesis of 2,2-bis(trifluoromethyl)-4-R-thietanes, 3,3-bis(trifluoromethyl)-5-R-1,2-dithiolanes and 2,2-bis(trifluoromethyl)-4-R-1,3-dithiolanes

It was demonstrated that the outcome of the reaction of hexafluoropropene, sulfur and vinyl ether strongly depends on the catalyst and reaction conditions. The reaction of HFP and S_x leading to the formation of 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithietane (1) when it is catalyzed by CsF, proceeds under milder conditions and is easier to control compared to KF catalyzed process. The order of addition of reagents plays a crucial role on the outcome of the reaction. For example, the addition of vinyl ether to pregenerated solution of 1 in DMF solvent results in slow reaction, leading to the corresponding 2,2-bis(trifluoromethyl)-4-R-thietanes in 8-91% yield, and it is catalyzed by either by KF or CsF. The addition of second mole of sulfur to the solution of 2,2-bis(trifluoromethyl)-4-R-thietanes in the presence MF catalyst leads to insertion of sulfur into thietane ring with the formation of the corresponding cyclic disulfides—3,3-bis(trifluoromethyl)-5-R-1,2-dithietanes. On the other hand, the addition of second mole of sulfur to the solution of 1 in DMF in the presence of CsF catalyst, followed by addition of vinyl ether results in exothermic reaction, and it produces the corresponding 2,2-bis(trifluoromethyl)-4-alkoxy-1,3-dithiolanes in good yield.It was also demonstrated that 2,2-bis(trifluoromethyl)-4-R-thietanes can undergo disproportionation under action of fluoride anion, producing a mixture of the corresponding 1,2-dithiolane and CF₂C(CF₃)CH₂CFHOR. The nucleophilic attack of fluoride anion in this case proceeds selectively on the carbon of the thietane ring, bearing alkoxy group.The structure of 2,2-bis(trifluoromethyl)-4-R-thietanes forming as the result of 2 + 2 cycloaddition reaction between hexafluorothioacetone generated “in situ” from dimer 1 and vinyl ether was firmly supported by single crystal X-ray diffraction data, obtained for thietane bearing t-BuO-group.     

Synthesis of 2-aryl-4-phenyl-5-trifluoromethylimidazoles

Several 2-aryl-4-phenyl-5-trifluoromethylimidazoles have been made from the previously unknown 1-phenyl-3,3,3-trifluoro-1,2-propanedione monohdyrate. One analog, 4-phenyl-2,5-bis(trifluoromethyl)imidazole, is quite acidic, exhibiting pK_a 8.1.     

Reaction of 2-amino-4-imino-2-perfluoropentene with ethylenediamine and diethylenetriamine

The transamination of 2-amino-4-imino-2-perfluoropentene with ethylenediamine gives the corresponding 6-fluoro-5,7-bis(trifluoromethyl)-2,3-dihydro-1H-1,4-diazepine. The transamination of 2-amino-4-imino-2-perfluoropentene by diethylenetriamine is accompanied by intramolecular nucleophilic substitution of the α-fluorine atom to form 1,9-bis(trifluoromethyl)-3,4,6,7-tetrahydro-2H-pyrazino[1,2-a]pyrazine whose structure was established by an X-ray structural investigation. Several salts of this bicyclic compound and its complex with BF₃ have been described. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1773–1776, October, 1993.     

Synthesis of imidazo[4,5-c]pyridines with a trifluoromethyl group at C-4 and/or C-6

Thermal condensation of histamine with trifluoroacetaldehyde gives 4-(trifluoromethyl)spinacamine and subsequent dehydrogenation with selenium dioxide leads to 4-(trifluoromethyl)-1H-imidazo[4,5-c]pyridine (42%). Fluorination with sulfur tetrafluoride of L-spinacine, obtained from the condensation of L-histidine with formaldehyde, affords 6-(trifluoromethyl)spinacamine, which can be converted to 6-(trifluoromethyl)-1H-imidazo[4,5-c]pyridine with selenium dioxide (49%). Application of the sequential reactions to 4-(trifluoro-methyl)-L-spinacine gives 4,6-bis(trifluoromethyl)-1H-imidazo[4,5-c]pyridine. Dehydrogenation of the tetrahydropyridine ring also occurred during the fluorination with sulfur tetrafluoride.     

Preparation and steric structure of 2-Alkoxy-2,5-dioxo-4,4-bis(trifluoromethyl)-7(8)-chloro-1,3,2λ5-benzodioxaphosphepins

The reaction of hexafluoroacetone with 2-alkoxy-6(7)-chloro-1,3,2-benzodioxaphosphorin-4-ones yielded 7-and 8-chloro-substituted 2-alkoxy-2,5-dioxo-4,4-bis(trifluoromethyl)-1,3,2λ⁵-benzodioxaphosphepines. Their steric structure was studied by single-crystal X-ray diffraction. The effect of fluorinated substituents on the crystal packing of the benzophosphepines was demonstrated. Hydrolysis of these compounds gave the corresponding 4-and 5-chloro-substituted 2-(2-hydroxyphenyl)-2-oxo-1,1-bis(trifluoromethyl)-ethanols; the structure of 2-(2-hydroxy-5-chlorophenyl)-2-oxo-1,1-bis(trifluoromethyl)ethanol was also proved by single-crystal X-ray diffraction.     

Reactions of tri- and hexafluoroacetylacetones and 4-ethoxy-1,1,1-trifluorobut-3-en-2-one with 2-aminobenzohydrazide

Reactions of 1,1,1-trifluoropentane-2,4-dione and 1,1,1,5,5,5-hexafluoropentane-2,4-dione with 2-aminobenzohydrazide afforded (2-aminophenyl)[5-hydroxy-3-methyl-5-(trifluoromethyl)- and (2-aminophenyl)[ 5-hydroxy-3,5-bis(trifluoromethyl)-4,5-dihydropyrazol-1-yl]methanones, respectively. 4-Ethoxy-1,1,1- trifluorobut-3-en-2-one reacted with 2-aminobenzhydrazide to give 2-(trifluoromethyl)-3a,4-dihydropyrazolo-[5,1-{ptb}]quinazolin-9(3{ptH})-one.     

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.     

Synthesis of 2,5-diethyl-3,4-bis(trifluoromethyl)furan and its derivatives

The addition reaction of propionaldehyde to hexafluoro-2-butyne ( 1 ) under γ-ray irradiation gave trans-6,6,6-trifluoro-4-trifluoromethyl-4-hexen-3-one ( 2 ) and 4,5-bis(trifluoromethyl)octa-3,6-dione ( 3 ). The latter compound was treated with sulfuric acid to give 2,5-diethyl-3,4-bis(trifluoromethyl)furan ( 4a ). Several reactions, such as bromination, dehydrobromination and oxidation, were carried out to prepare derivatives of 4a .     

Reinvestigation of the reaction of ethyl 4,4,4-trifluoroacetoacetate with aldehydes and ammonia

Reaction of ethyl 4,4,4-trifluoroacetoacetate with aromatic aldehydes and ammonia gives diethyl 4-aryl-2,6-dihydroxy-2,6-bis(trifluoromethyl)-3,5-piperidinedicarboxylates ( 4 ) instead of diethyl 4-aryl-1,4-dihydro-2,6-bis(trifluoromethyl)-3,5-pyridinedicarboxylates ( 3 ) as reported previously (1).     

Synthesis of a new polyfluorinated vinylogue of tetrathiafulvalene through 1,3-dipolar cycloaddition of ethyl beta-bromoperfluorodithiocrotonate with dimethyl acetylenedicarboxylate

The ethyl ester of beta-bromoperfluorodithiocrotonic acid reacts with dimethyl acetylenedicarboxylate to give 1,4-difluoro-2,3-bis(trifluoromethyl)-but-2-ene-1,4-diylidene-2,2'-bis(4',5'-dicarbomethoxy-1',3'-dithiole) (4), a new type of vinylogue of tetrathiafulvalene. The thermal transformations of this compound lead, depending on the temperature, to the formation of the cyclization products: 11,14-difluoro-2,3,8,9-tetra(carbomethoxy)-12,13-bis(trifluoromethyl)-1,4,7,10-tetrathiadispiro[4.0.4.4]tetradeca-2,8,11,13-tetraene (8) or 5,8-difluoro-6,7-bis(trifluoromethyl)-2,3-bis(carboxymethyl)-1,4-benzodithiine (11).     

Specific Features of Reaction of 2-R-Benzo[e][1,3,2]dioxaphosphinin-4-ones with Perfluorodiacetyl. Synthesis and Steric Structure of 4′,5′-Bis(trifluoromethyl)-4-oxo-2-(2,2,3,3-tetrafluoropropoxy)-2λ 5-spiro[benzo[e][1,3,2]dioxaphosphinine-2,2′-[1,3,2]dioxaphosphole]

2-R-benzo[e][1,3,2]dioxaphosphinin-4-ones react with perfluorodiacetyl under mild conditions to form relatively labile spirophosphoranes containing a 1,3,2-dioxaphosphole ring. These compounds gradually convert to more stable 2-R-4,5-bis(trifluoromethyl)-1,3,2λ⁵-dioxaphosphole 2-oxides and diastereometic 2-R-4-(trifluoroacetyl)-4-(trifluoromethyl)benzo[f][1,3,2λ⁵]dioxaphosphepine 2-oxides, whose structure was confirmed by means of NMR and IR spectroscopy. The structure of 4′,5′ -bis(trifluoromethyl)-4-oxo-2-(2,2,3,3-tetrafluoropropoxy)-2λ ⁵-spiro[benzo[e][1,3,2]dioxaphosphinine-2,2′-[1,3,2]dioxaphosphole] was confirmed by X-ray diffraction analysis.__________Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 4, 2005, pp. 587–599.Original Russian Text Copyright © 2005 by Konovalova, Mironov, Ivkova, Zagidullina, Gubaidullin, Litvinov, Kurykin.     

A re-investigation of the reactions of pyromellitic acid and its dianhydride with sulphur tetrafluoride

The fluorination of pyromellitic acid (1) with sulphur tetrafluoride or pyromelliticdianhydride (2) by means of an SF₄---HF mixture gave, besides the expected 1,2,4,5-tetrakis(trifluoromethyl)benzene (3), considerable amounts of 5,6-bis(trifluoromethyl)-1,1,3,3-tetrafluoro-1,3-dihydroisobenzofuran (4) and detectable quantities of1,1,3,3,5,5,7,7-octafluoro-1,3,5, 7-tetrahydrobenzo[1,2-c:4,5-c′]difuran (5). Acidic hydrolysisof 4 gave 4,5-bis(trifluoromethyl)phthalic acid (6) which on treatment with SF₄ andHF yielded compounds 3 and 4.     

Photoisomerization of bis(trifluoromethyl)thiophenes

The photolysis of 2,3-bis(trifluoromethyl)thiophene gave an equilibrium mixture of 2,3- and 3,4-bis(trifluoromethyl)Dewar thiophenes, while that of 2,5-bis(trifluoromethyl)thiophene gave 2,4-bis(trifluoromethyl)-thiophene, which seemed to be formed through an intermediate other than the Dewar form.