Cyclocondensation of 2-Amino-1,3,4-thiadiazoles with β-Sulfonylvinyltrifluoromethyldiols

A series of CF₃-containing 6,7-dihydro-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-7-ols was obtained by the interaction of 2-amino-1,3,4-thiadiazoles with -sulfonylvinyltrifluoromethyldiols and their stereochemistry was established. The structure of 5-(phenylsulfonyl)-7-(trifluoromethyl)-6,7-dihydro-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-7-ol was confirmed by X-ray crystallography.     

Reaction of 2-Aminothiazoles and Their Benzo- and Naphtho Derivatives with β-Sulfonyltrifluoromethylvinyldiols

By cyclocondensation of 2-aminothiazoles and their benzo and naphtho analogs with -sulfonyltrifluoromethylvinyldiols, we have obtained a series of novel CF₃-containing 6,7-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidines. In the case of the sterically hindered 2-aminothiazoles, heterocyclization does not occur and the corresponding enamino ketones are formed.     

Synthesis of new fluorine-containing pyrazolo[3,4-<Emphasis Type="Italic">b</Emphasis>]pyridinones as promising drug precursors

Methods for the synthesis of 4-R-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-6-ones (R = CF₂SAr and 4-CFHSAr) were developed. The derivatives with R = CF₂SAr were obtained by both heterocyclization of 1-substituted 5-aminopyrazoles with ethyl 4,4-difluoro-3-oxo-4-phenylsulfanylbutanoate and replacement of the Br atom in 4-bromodifluoromethyl-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-6-ones by sodium arenethiolates. The fragment 4-CF-HSAr was introduced by replacement of the Cl atom in 4-chlorofluoromethyl-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-6-ones by sodium arenethiolates. Oxidation of 4-CF₂SPh-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-6-ones gave the corresponding sulfoxides; their structures were confirmed by X-ray diffraction data.     

Zur Umsetzung von 8a-Methoxy-3,4-dihydro-2H-1,4-benzoxazin-6(8aH)-onen mit Diazoalkanen, 2. Mitt.

Summary 8a-Methoxy-3,4-dihydro-2H-1,4-benzoxazin-6(8aH)-ones2 undergo regio- and stereospecific 1,3-dipolar cycloaddition reactions with diazomethane or diazoethane to yield 3,4,6a,9,9a,9b-hexahydro-pyrazolo[3,4-h][1,4]benzoxazin-6(2H)-ones3, which slowly isomerize in solution to give the 3,4,8,9,9a,9b-hexahydro-pyrazolo[3,4-h][1,4]benzoxazin-6(2H)-ones5. The carbon of the diazoalkane dipole is attached to carbon C-8 of the benzoxazinone. The structures of the obtained products were determined by¹H- and¹³C-NMR spectroscopy. An X-ray crystal structure analysis of3 a was carried out at room temperature:C₁₁H₁₅N₃O₃,M _r =237.26, orthorhombic, Pc2₁n,a=9.173 (5),b=9.133 (4),c=13.281 (6),V=1112.6 (9) ų,Z=4,d _x =1.416 g/cm^–3, =0.93 cm^–1,R=4.33%,R _w =3.95% (919 observations, 168 parameters).

Herrn Prof. Dr. W. Fleischhacker zum 60. Geburtstag gewidmet     

10-(3-Hydroxypropyl)-1,4,6,8-tetraphenyl-1,4,7,8-tetraaza-5-phosphoniaspiro[4.5]deca-6,9-diene chloride: synthesis and molecular structure

The reaction of 2-(3,4-dihydro-2H-pyran-5-yl)-1,3-diphenyl-1,3-diaza-2³-phospholidine with C,N-diphenylnitrilimine yields 10-(3-hydroxypropyl)-1,4,6,8-tetraphenyl-1,4,7,8-tetraaza-5-phosphoniaspiro[4.5]deca-6,9-diene chloride. Its structure was determined by X-ray diffraction analysis.     

Studies on sulfinatodehalogenation. XX. Sodium dithionite-initiated addition of per- and polyfluoroalkyl iodides to cyclic enol ethers and chemical conversions of the products

Per- and polyfluoroalkyl iodides [R_FI, R_F=Cl(CF₂)₄, 1a ; Cl(CF₂)₆, 1b ; Cl(CF₂)₈, 1c ; n-C₆F₁₃, 1d ; n-C₈F₁₇, 1e ] reacted with cyclic enol ethers such as 2,3-dihydrofuran (2) and 3,4-dihydro-2H-pyran (3) in aqueous acetonitrile in the presence of sodium dithionite and sodium bicarbonate at room temperature (10–15°C) to give the corresponding 2-(F-alkyl) hemiacetals in high yields. The adducts were oxidized with Ce(NH₄)₂(NO₃)₆ in acetonitrile or reduced with LiAlH₄ in ether to form the corresponding 2-(F-alkyl)lactones or diols respectively in good yields. In the presence of p-toluenesulfonic acid, the adducts were refluxed in benzene and CH₃CN to produce the corresponding 2,3-dihydro-4-(F-alkyl) furan and 3,4-dihydro-5-(F-alkyl)-2H-pyran. This is a new and effective method for preparing these useful organofluorine compounds.     

Synthesis of (R)-3,4-dihydro-2H-pyran-2-carboxaldehyde: application to the synthesis of potent adenosine A2A and A3 receptor agonist

Synthesis of potent adenosine A_2A and A₃ receptor agonist from the modification of adenosine-5′-N-ethylcarboxamide (NECA) has been reported. Diastereoisomer possessing an (R)-3,4-dihydro-2H-pyranyl (DHP) moiety exhibited the highest affinity at the A_2A and A₃ receptors. The key steps involve the synthesis of (R)-3,4-dihydro-2H-pyran-2-carboxaldehyde (7), which was obtained through the enzyme-catalyzed kinetic resolution of (±)-2-acetoxymethyl-3,4-dihydro-2H-pyran (5).     

Studies on the γ-effects. Part 3. Variations in the γ-effects ofN-substituted benzylamines,o-aminomethylphenols and 3,4-dihydro-2H-1,3-benzoxazines against theE s ′ substituent constants

The magnitude of the -effects on¹³C chemical shifts was studied as function of theN-substitution [Me, Et, Bu, CH₂C₆H₅, CH₂CH₂C₆H₅, Prⁱ, Bu^t, Bu^s, c-C₆H₁₁, CH(CH₃)C₆H₅, Bu^t, or Ph] for several benzylamines,o-aminomethylphenols and 3,4-dihydro-2H-1,3-benzoxazines. A correlation between the _c-values and the steric substituent constants (E _s ) of theN-substituents proved useful in characterizing the variation of the -effects along with the conformational factors. The diastereospecificity of the -effects is discussed for purposes of configurational assignments.For part 2, see Ref. 1. This paper is also Part 5 in the series Studies on the Benzoxazine Series.     

Substituted and fused spiro[benzo-2-azepine-3,1′-cyclohexanes]

5-Methyl-4,5-dihydro-3H-spiro[benzo-2-azepine-3,1-cyclohexane] N-oxide was rear- ranged into 5-methyl-1-oxo-1,2,4,5-tetrahydro-3H-spiro[benzo-2-azepine-3,1-cyclohexane]. The latter was used for the synthesis of spiro{triazolo[3,4-a]- and-tetrazolo[5,1-a]benzo-2- azepinecyclohexanes}.Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1647–1651, August, 2004.     

Reaction of CF3 radicals with H2S

Hydrogen abstration from H₂S by CF₃ radicals, generated by the photolysis of both CF₃COCF₃ and CF₃I, has been studied in the temperature range 314–434 K. The rate constant, based on the value of 10^13.36 cm³/mol · s for the recombination of CF₃ radicals, is given by with CF₃COCF₃ as the radical source, and with CF₃I as the radical source, where k₂ is in cm³/mol · s and E is in J/mol. These results resolve a previously existing controversy concerning the values of the rate constants for this reaction. They show that CF₃ radicals are less reactive than CH₃ radicals in attacking H₂S, and this behavior indicates that polar effects play a significant role in the hydrogen transfer reactions of CF₃ radicals.     

Synthesis of 2-oxohexahydrothieno[3,4-d]imidazole derivatives

Conclusions We synthesized the cis-3- and 4-methyl-2-oxo-6-(-carboxybutyl) hexahydro [3,4-d]-imidazoles by the reduction of the 3- and 4-methyl-2-oxo-2,3-dihydro-6-(carboxybutyl)-1H-thieno [3,4-d] imidazoles with HSiEt₃ in CF₃COOH and subsequent alkaline hydrolysis of the intermediate methyl ethers.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1634–1636, July, 1980.The authors express their gratitude to Prof. A. Mark (France) for supplying the sample of 2-oxo-4-methyl-6-(6-carboxybutyl)hexahydrothieno[3,4-d]imidazole.     

Cyclometallated complexes derived from pyrimidin- and pyridazinehydrazones: Structural evidence of intermolecular “chelate metal ring” π-π interactions

Reaction of 3,4-(Me)₂C₆H₃C(Me)NN(H)[3′-(CF₃)C₄H₂N₂] (a) and 3,4-(Me)₂C₆H₃C(Me)NN(H)(4′-ClC₄H₂N₂) (b) with palladium(II) acetate gave the mononuclear cyclometallated complexes [Pd{3,4-(Me)₂C₆H₂C(Me)NN(H)[3′-(CF₃)C₄H₂N₂]}(OAc)] (1a) and [Pd{3,4-(Me)₂C₆H₂C(Me)NN(H)(4′-ClC₄H₂N₂)}(OAc)] (1b) with the ligand as terdentate [C,N,N]. Treatment of a and b with Li₂[PdCl₄] and sodium acetate in methanol at room temperature yielded the mononuclear cyclometallated complexes [Pd{3,4-(Me)₂C₆H₂C(Me)NN(H)[3′-(CF₃)C₄H₂N₂]}(Cl)] (2a) and [Pd{3,4-(Me)₂C₆H₂C(Me)NN(H)(4′-ClC₄H₂N₂)}(Cl)] (2b), respectively. Recrystallization of 2b from a dimethylsulfoxide solution gave [Pd{3,4-(Me)₂C₆H₂C(Me)NN(4′-ClC₄H₂N₂)}][(CH₃)₂SO] after deprotonation of the hydrazine nitrogen. The reaction of 2a and 2b with silver trifluoromethanesulfonate and triphenylphosphine, yielded [Pd{3,4-(Me)₂C₆H₂C(Me)NN(H)[3′-(CF₃)C₄H₂N₂]}-(PPh₃)][CF₃SO₃] (3a) and [Pd{3,4-(Me)₂C₆H₂C(Me)NN(H)(4′-ClC₄H₂N₂)}(PPh₃)]-[CF₃SO₃] (3b) with the phosphine ligand occupying the vacant coordination position after chlorine abstraction; these were deprotonated at the hydrazine nitrogen after treatment with sodium acetate. Reaction of 2a with Ph₂P(CH₂)₂AsPh₂ (arphos), after AgCl removal gave mononuclear complex Pd{3,4-(Me)₂C₆H₂C(Me)NN(H)[3′-(CF₃)C₄H₂N₂]}(Ph₂P(CH₂)₂AsPh₂)][ClO₄] (5a) with a non-coordinated As atom. Reaction of 2a and 2b with a Ag(I) salt and the tertiary diphosphine Ph₂P(CH₂)₄PPh₂ (dppb) in 2:1 molar ratio gave the dinuclear complexes [{Pd{3,4-(Me)₂C₆H₂C(Me)NN(H)[3′-(CF₃)C₄H₂N₂]}}₂(μ-Ph₂P(CH₂)₄PPh₂)][CF₃SO₃]₂ (6a) and [{Pd{3,4-(Me)₂C₆H₂C(Me)NN(H)(4′-ClC₄H₂N₂)}}₂(μ-Ph₂P(CH₂)₄PPh₂)][ClO₄]₂ (6b) with the diphosphine as a bridging ligand. Similarly, treatment of 1b with silver triflate followed by reaction with the tertiary triphosphine (Ph₂PCH₂CH₂)₂PPh (triphos), in a 3:1 molar ratio, gave the new trinuclear complex [{Pd[3,4-(Me)₂C₆H₂C(Me)NN(H)(4′-ClC₄H₂N₂)]}₃{μ₃-(Ph₂PCH₂CH₂)₂PPh}][CF₃SO₃]₃ (8b). However, reaction of 2a and 2b with (triphos), in 1:1 molar ratio gave the mononuclear complexes [Pd{3,4-(Me)₂C₆H₂C(Me)NN(H)[3′-(CF₃)C₄H₂N₂]}{(Ph₂PCH₂CH₂)₂PPh-P,P,P}][ClO₄] (7a) and [Pd{3,4-(Me)₂C₆H₂C(Me)NN(H)(4′-ClC₄H₂N₂)}-{(Ph₂PCH₂CH₂)₂PPh-P,P,P}][ClO₄] (7b) with a is five-coordinated palladium. The crystal structures of 2b, 3a, 3b, 7a and 7a have been determined by X-ray crystallography and they show π-π interactions between the metallacycle and the heterocyclic pyrimidine or pyridazine rings, which controls the crystal packing.     

Reformatsky Reaction of Methyl α-Bromoisobutyrate with 2-Oxo-2H-benzo[f]chromene-3-carboxylic Acid Esters and N-Benzylamide

Reformatsky reagent derived from methyl -bromoisobutyrate reacts with methyl and ethyl 2-oxo-2H-benzo[f]chromene-3-carboxylates and N-benzyl-2-oxo-2H-benzo[f]chromene-3-carboxamide to afford the corresponding derivatives of 4-(1-methyl-1-methoxycarbonylethyl)-2-oxo-3,4-dihydro-2H-benzo[f]chromene-3-carboxylic acid as a single stereoisomer.     

Mono-, Bi-, and Trinuclear Triarylantimony Organylsulfonate Derivatives: Synthesis and Structure

The reactions of tris(3-methylphenyl)antimony with trifluoromethanesulfonic acid and of triphenylantimony with 3,4-dimethylbenzenesulfonic acid in the presence of tert-butylhydroperoxide in ether (molar ratio of initial reagents, 3: 2: 3) have been performed to synthesize nona(3-methylphenyl)tristiboxane-1,5- diyl-bis(trifluoromethanesulfonate) CF₃OSO₂Sb(3-MeC₆H₄)₃OSb(3-MeC₆H₄)₃OSb(3-MeC₆H₄)₃OSO₂CF₃. PhH (I) separated after recrystallization from a benzene–octane mixture in the form of a benzene solvate and, at an equimolar ratio of initial reagents, hexaphenyldistiboxane-1,3-diyl-bis(3,4-dimethylbenzenesulfonate) separated after recrystallization from toluene in the form of a toluene solvate 3,4-Me₂C₆H₃OSO₂SbPh₃OSbPh₃OSO₂C₆H₃Me₂-3,4. TolH (II). The similar reactions of tris(5-bromo-2- methoxyphenyl)antimony and tris(4-methylphenyl)antimony with 2,5-dimethylbenzenesulfonic and 3,4- dimethylbenzenesulfonic acids, respectively in the presence of tert-butylhydroperoxide (molar ratio, 1: 2: 1) lead to the formation of triarylantimony bis(arenesulfonates) (5-Br,2-MeO,C₆H₃)₃Sb(OSO₂C₆H₃Me₂-2,5)₂ (III) and (4-MeC₆H₄)₃Sb(OSO₂C₆H₃Me₂-3,4)₂ (IV). The Sb atom in the structures of complexes I–IV has a distorted trigonal bipyramidal coordination to the oxygen atoms in axial positions.     

A highly efficient and ecofriendly procedure for tetrahydropyranylation of alcohols and phenols in the presence of in-situ generated I2 under heterogeneous and neutral conditions

Abstract  Molecular iodine generated in situ from Fe(NO₃)₃·9H₂O/NaI acts as a highly efficient catalyst for tetrahydropyranylation of various alcohols and phenols with 3,4-dihydro-2H-pyran in almost quantitative yields. The reaction occurs rapidly in dichloromethane at room temperature, and use of toxic molecular iodine is avoided. Graphical Abstract        

Voltammetric studies of the Kolbe synthesis with perfluorocarboxylic acids prepared from hexafluoropropene oxide oligomers

Carboxylic acids prepared from hexafluoropropene oxide CF₃CF₂CF₂O[CF(CF₃)CF₂O]_nCF (CF₃)COOH [n = 0, 2,5-bis(trifluoromethyl)-3,6-dioxaperfluorononanoic acid; n = 1, 2,5,8- tris(trifluoromethyl)-3,6,9-trioxaperfluorododecanoic acid], according to voltammetric data, enter the Kolbe reaction both at the Pt anode and at anodes from carbon materials in H₂O-CH₃CN and CH₃OH-CH₃CN solutions. The critical potential appreciably depends both on the anode material and on the solvent composition. Favorable effect of pyridine additions in H₂O-CH₃CN solutions is due to replacement of water molecules from the electrical double layer. The sodium ions exert a negative effect on the Kolbe synthesis.Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 11, 2004, pp. 1842–1846.Original Russian Text Copyright © 2004 by Chechina, Sokolov, Tomilov.This revised version was published online in April 2005 with a corrected cover date.     

Reaction of 1,2-diarylhydrazines with acetic anhydride catalyzed by 4-(dimethylamino)pyridine

Summary A new method for the synthesis of 1,2-diaryl-1,2-dihydro-5-methyl-3H-pyrazol-3-ones3 and 4-acetyl-1,2-diaryl-1,2-dihydro-5-methyl-3H-pyrazol-3-ones5 is presented. The reaction of 4,4-disubstituted 1,2-diarylhydrazines1 with acetic anhydride in the presence of an equimolar amount of 4-(dimethylamino)pyridine leads to mixtures of the corresponding acetyl derivatives2 and3. Under the same conditions, 2,2-disubstituted 1,2-diarylhydrazines yield mixtures of3 and5.

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4-(Dimethylamino)pyridin-katalysierte Reaktion von 1,2-Diarylhydrazinen mit Essigsäureanhydrid

Zusammenfassung Eine neue Methode zur Synthese von 1,2-Diaryl-1,2-dihydro-5-methyl-3H-pyrazol-3-onen3 und 4-Acetyl-1,2-diaryl-1,2-dihydro-5-methyl-3H-pyrazol-3-onen5 wird beschrieben. Die Reaktion von 4,4-disubstituierten 1,2-Diaryl-hydrazinen1 mit Essigsäureanhydrid führt in Gegenwart eines Äquivalentes 4-(Dimethylamino)pyridin zu Gemischen der entsprechenden Acetylderivate2 und3. Unter den gleichen Bedingungen werden aus 2,2-disubstituierten 1,2-Diarylhydrazinen Gemische aus3 und5 erhalten.

     

The gas phase reaction of CF3 radicals with C6F5H in the temperature range 373–658 K

CF₃ radicals were generated by the photolysis of perfluoroacetic anhydride. In the presence of pentafluorobenzene, the CF₃ radicals react according to the following mechanism: It was found that the addition reaction (3) becomes reversible above ca. 453 K. The addition rate parameters have been revised and they satisfactorily agree with those reported previously. At temperatures higher than 593 K, only true H-abstraction occurs. The rate constant k_H for reaction (5) is given by: where θ = 2.303 RT kJmol^?1 and k_c is the rate constant for combination of CF₃ radicals. The reactions of CF₃ with benzene and pentafluorobenzene are compared.     

Theoretical study of the reaction of CF3O radicals with CO

The potential energy surface for the reaction of the CF₃O radicals with CO was investigated. The geometries and vibrational frequencies of the reactants, transition states, intermediates, and products were calculated at the UB3LYP/6-311+G(2d,p), UB3LYP/6-311+G(3df,2p) and UMP2/6-311+G(2d,p) levels of theory. The energies were improved by using the G2M(CC2) and G3B3 methods. The calculation suggests the reaction proceeds via either the fluorine abstraction of CF₃O by CO to produce FCO + CF₂O with a high energy barrier or the barrierless association of the reactants to form the trans-CF₃OCO intermediate. The trans-CF₃OCO is predicted to undergo subsequent isomerization to cis-CF₃OCO or dissociate directly to the products FCO + CF₂O and CF₃ + CO₂. The collisional stabilization of trans-CF₃OCO is dominant at room temperature, while trans-CF₃OCO isomerizing to cis-CF₃OCO followed by dissociating to CF₃ + CO₂ is accessible when temperature rises. The reason for only trans-CF₃OCO without cis-CF₃OCO observable in Ashen’s experiment [S.V. Ahsen, J. Hufen, H. Willner, J.S. Francisco, Chem. Eur. J. 8 (2002) 1189] is cis-CF₃OCO can be produced only via the isomerization of trans-CF₃OCO, and its yield is inappreciable at a low experimental temperature. The enthalpies of formation for the two conformations of CF₃OCO have been deduced: (trans-CF₃OCO) = −196.25 kcal mol⁻¹, (trans-CF₃OCO) = −197.46 kcal mol⁻¹, (cis-CF₃OCO) = −193.64 kcal mol⁻¹, and (cis-CF₃OCO) = −194.90 kcal mol⁻¹.     

The reaction of C2F5 radicals with H2S

The reaction of C₂F₅ radicals with H₂S was studied over the range 1°?123°C using C₂F₅ radicals generated by photolysis of perfluoropropionic anhydride. The rate constant k_H for reaction (2) is given by where θ = 2.303RT/cal mole^?1. The relevance of this result to conflicting published data on the analogous reaction between CF₃ radicals and H₂S is discussed. It is concluded that there is little difference in the Arrhenius parameters for reaction of CF₃ and C₂F₅ radicals with H₂S.