Search

This paper describes the synthesis of a novel series of 2-aryl-6-(1H-indol-1-yl)-4-(trifluoromethyl)quinolines, in which aryl = C6H5, 4-CH3C6H4, 4-FC6H4, 4-CF3C6H4 and heteroaryl = 2-thienyl, by an Ullmann-type cooper-catalyzed amination cross-coupling reaction. Photophysical properties of indolyl-quinolines were investigated using absorption and emission analysis. The emission fluorescence analysis showed a blue to cyan region emission in the 400–650 nm range. Large Stokes shifts values were observed for all new quinolines and attributed to the ICT state and to the electron-substituent properties. The ability to generate 1O2 species after being exposed to white light and biomolecule-binding DNA / HSA properties were also investigated.

The present paper describes first an efficient methodology for an easy O -functionalization (alkylation) of tetracyclic hydroxyisoxazolines 1 applied to the synthesis of eight examples of new 3-(alkoxy)-3-(trifluoromethyl)-3,3a-dihydrospiro[chromeno [4,3- c ]isoxazole-4,1′-cycloalkanes] ( 6-9 ) at 61–84% yields, in which the alkoxy substituents were methoxy, benzyloxy, allyloxy, or prop-2-yn-1-yloxy; while the cycloalkanes were 5-, 6-, and 7-membered carbocycles, as well as 4′-methyl- and 4′- t -butyl-cyclohexane. The reaction medium used 1 , four alkyl halides ( 2 - 5 ), K 2 CO 3 , and KI in DMF at room temperature. The selected 3-(prop-2-yn-1-yloxy)-substituted isoxazolines 6 were successfully used as a CC -fragment in the construction of another series of five examples of 3-((1-benzyl-1 H -1,2,3-triazol-4-yl)methoxy)-3-(trifluoromethyl)-3,3a-dihydrospiro[chromeno[4,3- c ]isoxazole-4,1′-cycloalkanes] ( 10 ), at 36–84% yields, through a regioselective 1,3 dipolar cycloaddition reaction catalyzed by copper iodide (CuAAC), using benzyl azide as an NNN -building block (Click Chemistry).

This paper firstly describes the synthesis of a series of (Z)-4-((3-chloro-4-fluorophenyl)amino)-1,1,1-trifluorobut-3-en-2-ones (3a–f) as well as 1-(1-((3-chloro-4-fluorophenyl)amino)-3,4-dihydronaphthalen-2-yl)-2,2,2-trifluoroethanone (3g), from the O,N-exchange reaction of some 4-methoxy-4-alkyl(aryl)-1,1,1-trifluoroalk-3-en-2-ones (1) with 3-chloro-4-fluoroaniline (2), at 70–90% yields. Subsequently, in concentrated sulfuric acid, the enaminoketones 3 underwent a successful and regioselective intramolecular cyclocondensation reaction, which furnished a novel series of 2-alkyl(aryl)-7-chloro-6-fluoro-4-(trifluoromethyl)-quinolines (4) at 70–85% yields. To demonstrate synthetic applicability through the Sonogashira coupling reaction for obtaining quinolines with potential antimicrobial activity, the synthesis of a novel series of 2-alkyl(aryl)-6-fluoro-7-(phenylethynyl)-4-(trifluoromethyl)-quinolines (5) was performed, using quinolines 4 and phenylacetylene, via a regioselective Sonogashira coupling reaction (25–50% yield). Unfortunately, the new series of heterocycles 4 and 5 did not produce significant results against bacteria and fungi at the concentrations of 80–0.31 μg/mL.

This paper reports the results of the synthesis and structural elucidation by multinuclear NMR spectroscopy and single crystal X-ray diffraction of a new series of four examples of 1,1-difluoro-3-methyl-9-(aryl/heteroaryl)-7-(trifluoromethyl)-1H-[1,3,5,2]oxadiazaborinino[3,4-a][1,8]naphthyridin-11-ium-1-uides, which were obtained, at good yields (60–66%), from the reaction of 7-substituted N-(5-(trifluoromethyl)-1,8-naphthyridin-2-yl)acetamides — in which the 7-substituents are C6H5, 4-CH3C6H4, 4-FC6H4, and 2-Thienyl — with BF3·Et2O solution. One-dimensional multinuclear NMR spectroscopy (1H, 13C, 19F, and 11B) and two-dimensional 1H–15N HMBC are presented as powerful tools for an easy and secure NMR chemical shift assignments and structural characterization of fluorinated 1,8-naphthyridine-based boron complexes. Additionally, investigations of photophysical, electrochemical and DNA-binding properties were done.

A series of seven novel scaffolds of 2-substituted 4-trifluoromehyl-5H-chromeno[4,3-b]pyridin-5-ones (3a-g), where R (2-substituents) = Me, Ph, 4-tolyl, 4-NO2C6H4, 4-FC6H4, 4-BrC6H4, and 2-thienyl, were easily and regioselectively synthesized by employing a [3 + 3] cyclocondensation reaction of 4-methyl(aryl/thienyl)-4‑methoxy-1,1,1-trifluoroalk-3-en-2-ones (1) with 4-aminocoumarin (2) in up to 66% yields. The photophysical and electrochemical analysis of 3a-g revealed large Stokes shifts (30 to 130 nm) due to the ICT state and low redox oxidation processes. Additionally, the antioxidant activity evaluated by DPPH assays (aided by cyclic voltammetry) showed that compounds 3b (R = Ph, EC50 (µM) = 19.6) and 3e (R = 4-FC6H4, EC50 (µM) = 19.1) had the most significant radical scavenging capacity (ref. ascorbic acid = 10.9 µM).

This paper describes firstly an effective protocol for the synthesis of a new series of five examples of 3-(trifluoromethyl)-3,3a-dihydrospiro[chromeno[4,3-c]isoxazole-4,1′-cycloalkan]-3-ols (4), in which the cycloalkanes — cyclopentane, cyclohexane, cycloheptane, and 4′-methyl- and 4′-t-butyl-cyclohexane — were isolated at yields of 65–84%. The dihydro-isoxazolinols 4 were obtained regioselectively from the reactions of 2,2,2-trifluoro-1-[4-methoxy-spiro(2H-chromen-2,1′-cycloalkane)-3-yl]ethanones (3) with hydroxylamine hydrochloride, in the presence of sodium bicarbonate and methanol as solvent, for 24 h at 60 °C. The ethanone precursors 3 were synthesized by trifluoroacetylation reaction, employing trifluoroacetic anhydride and mixtures of enolethers and/or acetals derived from spiro[chroman-2,1′-cycloalkan]-4-ones (2) (Kabbe’s adducts), which were obtained beforehand from the reaction of cycloalkanones 1 with 2-hydroxyacetophenone and pyrrolidine. Subsequently, dehydration reactions of isoxazolinols 4, employing thionyl chloride and pyridine, enabled the isolation of another series of five novel spiro-isoxazoles 5 (76–95% yield). The structural features of the two series of new spiro heterocycles (4 and 5) were unequivocally determined with the aid of: one-dimensional 1H, 13C, and 19F NMR spectroscopy; two-dimensional 1H and 13C NMR spectroscopy (NOESY, gHMBC, and gHMQC); single crystal X-ray diffraction; and GC–MS.

A convergent synthesis of a series of 16 new polysubstituted (5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl)(quinolin-4-yl)methanones, starting from isatin and alky(aryl/heteroaryl) ketones, is described. The diheteroaryl methanones were achieved at yields of up to 95% by a [3 + 2] cyclocondensation reaction involving 4-alkyl(aryl/heteroaryl)-4-methoxy-1,1,1-trifluorobut-3-en-2-ones (by two-step reaction) and 2-alkyl(aryl/heteroaryl)-4-carbohydrazides (by three-step reaction). Subsequently, representative dehydrated heterocyclic derivatives were obtained from the respective 5-hydroxy-2-pyrazoline moieties by classical dehydration reactions, which resulted in the corresponding (5-(trifluoromethyl)-1H-pyrazol-1-yl)(quinolin-4-yl)methanones (three examples) at yields of 69–82%. The subsequent cytotoxicity evaluation showed that compounds with aromatic groups at the 2-position of the quinoline and a methyl moiety at the 3-position of the pyrazole have significant cytotoxicity in human leukocytes at high concentrations (200 μM).

This short study reports firstly the synthesis of a new series of six 1-substituted 6-((4,4,4-trihalo-3-oxo-alk-1-en-1-yl)amino)-2H-chromen-2-ones (4 and 5) and three 4- substituted 2,2-difluoro-3-(2-oxo-2H-chromen-6-yl)-6-(trichloromethyl)-2H-1,3,2-oxazaborinin-3-ium-2-uides (7), in which the selected 1- and 4-substituents are Me, Ph, and thien-2-yl. Both series (4 and 5) were synthesized from the reaction of 6-aminecoumarin (3) with (Z)-1,1,1-trihaloalk-3-en-2-ones (1 and 2), at 50–95 % yields. Subsequently, reactions of the coumarins 4 and 5 with boron (BF3·OEt2) gave only the corresponding 6-trichlorometylated heterocycles (7), at 65–78 % yields. Absorption and emission properties were investigated for the new coumarin derivatives. The results for UV–vis, emission fluorescence, quantum yield, and Stokes shift analysis indicated important relationships between the β-enaminone skeletons and their substituents.

The results of the chemical behavior of three substituted cyanoacetylazoles and some salicylic aldehydes used to obtain new trifluoromethylated azolecarbonyl-2H-chromen-2-ones through Knoevenagel condensation reactions, are reported. First, a new series of four 3-(5-hydroxy-3-methyl-5-trifluoromethyl-4,5-dihydro-1H-pyrazole-1-carbonyl)-2-imino-2H-chromenes were efficiently synthesized, in yields of 50–78%, using 0.4 M NaOH/EtOH as the catalyst. They were then subjected to an acid hydrolysis reaction, which produced the respective trifluoromethyl-substituted pyrazolinecarbonyl coumarins in good yields (80–91%). In order to study the influence of the CF3 substituent, reactions involving 1-cyanoacetyl-3,5-dimethyl-5-hydroxy-4,5-dihydro-1H-pyrazole were also performed, but they did not provide the desired coumarins. On the other hand, attempts to synthesize some pyrrolecarbonyl coumarins not containing trifluoromethyl groups, but using the same methodology, directly resulted in a new series of five 3-(1-methyl-1H-pyrrol-2-carbonyl)-2H-chromen-2-ones in good yields (40–60%).

This paper reports a synthetic and NMR spectroscopic studies of two new series of 4-fluorinated 1,3,5-substituted 1H-pyrazoles. Firstly, an efficient synthesis of new series of 3-aryl-4-(di)fluoromethyl-1H-1-phenylpyrazoles, where [aryl = Ph, 4-NO2C6H4, 4-CH3OC6H4] is described, from fluorination reactions of 4-(formyl)- and 4-(hydroxymethyl)-1H-1-phenylpyrazoles in dichloromethane as solvent at room temperature, employing diethylaminosulfur trifluoride (DAST) as fluorinating agent in 41 to 73% yield. The 4-formyl-pyrazoles are obtained in 54–58% yield by Vilsmeier–Haack reaction using a mixture of POCl3/DMF with arylhydrazones, which were derived from the respective aryl methyl ketones and phenylhydrazine. The 4-hydroxymethyl-pyrazole precursors were easily obtained from the reduction of 4-formyl-pyrazoles by sodium borohydride (NaBH4) in 52–87% yield. Subsequently, the present work also discusses the 1H, 13C and 19F NMR spectroscopic data.

This paper firstly describes an efficient and regioselective method for the synthesis of a new series of 2,2,2-trifluoro-1-[4-methoxy-spiro(2 H -chromen-2,1′-cycloalkane)-3-yl]ethanones from spiro[chroman-2,1′-cycloalkan]-4-ones (Kabbe's adduct). Yields of 38–61% were obtained when trifluoroacetylation reactions of mixtures of enolethers and/or acetals derived from four spiro ketones (Kabbe's adduct) were performed at a temperature of 45 °C, employing anhydrous chloroform as the solvent. Subsequently, when the respective trifluoroacetylated Kabbe adducts reacted with phenylhydrazine and methylhydrazine at a 1:1 molar ratio in refluxing ethanol for 24 h, a new series of seven examples of a new spiro-condensed heterocyclic system, namely 1(2)-methyl(phenyl)-3-(trifluoromethyl)-1,4(2,4)-dihydro-spiro(chromen[4,3- c ]pyrazole-4, n ′-cycloalkanes) – where cycloalkanes are cyclopentane, cyclohexane, and cycloheptane for n = 1; and tetrahydro-2 H -pyran for n = 2 – were isolated at yields of between 35% and 51%. Finally, the structures of new spiro heterocycles were determined with the aid and simultaneous application of 1 H, 13 C and 19 F one-dimensional and gHMBC NMR experiments, X-ray monocrystal diffraction, and mass spectrometry techniques.

This paper describes an efficient method for synthesis of rufinamide analogs from the 1,3-dipolar cycloaddition and/or electrocyclization reactions under conventional thermal conditions of 4-alkyl(aryl/heteroaryl)-4-alkoxy-1,1,1-trifluoroalk-3-en-2-ones (1) with 2,6-difluorobenzyl azide, where 4-alkyl = H, Me; 4-aryl = Ph, 4-NO2C6H4, 4-OCH3C6H4, 4-FC6H4, 4,4′-BiPh; and 4-heteroaryl = 2-thienyl; for the efficient preparation of a series of ten new trifluoroacetyl(trifluoromethyl) substituted 1H-1,2,3-triazoles. Yields in the range of 30–71% were obtained when the reactions were performed at high temperatures (130–150 °C) under solvent-free conditions. The pure regioisomers or mixtures of triazoles could be isolate with dependency of the 4-substituent of the enones 1. Finally, two mechanisms are proposed and the results are discussed in accordance with the X-ray diffraction results and FMO theory, which describes the possible HOMO/LUMO interactions via DFT calculations for both precursors.

This paper describes firstly the synthesis of a new series of 3-hydroxy-2-[(3(5)-(methyl/phenyl)-5(3)-(trifluoromethyl)-1 H -pyrazol-4-yl)arylmethyl]-cyclohex-2-en-1-ones (2), where aryl = C 6 H 5 , 4-NO 2 C 6 H 4 , 4-OCH 3 C 6 H 4 , from an ANRORC ring transformation reaction of 3-acyl-4-aryl-2-(trifluoromethyl)-2-hydroxy-3,4,7,8-tetrahydro-2 H -chromen-5(6 H )-ones (1), where acyl = acetyl and benzoyl, in the presence of hydrazine hydrate, at 63–90% yields. In subsequent steps, an oxidative aromatization reaction from 2 was done in an iodine/methanol medium for the preparation of 3(5)-trifluoromethyl-5(3)-methyl-4-[(2,6-dimethoxyphenyl)-(4-methoxyphenylmethyl)]-1 H -pyrazole (3) at 72% yields. Also, the alkylation reaction using benzyl chloride easily converted a pyrazole like 2 to its N -benzyl derivative (4), at 69% yield. Finally, the structural assignment of compounds 2–4 was deduced by mass spectrometry, X-ray crystal diffraction and density functional theory (DFT) calculations, which clearly and unambiguously furnished values very close to those determined from 1 H, 13 C and 19 F NMR data.

This paper describes a mild method for regioselective reduction of 3-acyl-4-aryl-2-(trifluoromethyl)-2-hydroxy-3,4,7,8-tetrahydro-2 H -chromen-5(6 H )-ones, where acyl = Ac, Bz, 2-thenoyl; and aryl = Ph, 4-NO 2 C 6 H 4 , 4-OCH 3 C 6 H 4; employing sodium borohydride as the reducing reagent for successful preparation of a series of nine new 3-acyl-4-aryl-2-(trifluoromethyl)-8a-hydroxy-octahydrochromen-5-ones. Yields in the range of 25–63% were obtained when the reduction reactions were performed at room temperature using ethanol as the solvent. When 3-acetyl-2-hydroxy-5-methoxy-4-phenyl-2-(trifluoromethyl)chromane was also tested under similar conditions, the 3-(1-hydroxyethyl)-3,4-dihydro-2 H -chromane derivative was obtained at 83% yield. A representative X-ray diffraction ORTEP for an example of 2-(trifluoromethyl)-octahydrochromen-5-one is shown and the reduction mechanisms discussed.

This paper describes the one-pot simple and efficient oxidative aromatization reaction employing an iodine/alcohol medium for the preparation of a series of 11 new 3-acyl-2-hydroxy-5-alkoxy-4-aryl-2-(trifluoromethyl)chromanes, where acyl = Ac, Bz, furan-2-oyl; aryl = Ph, 4-NO 2 C 6 H 4 , 4-OCH 3 C 6 H 4 and alkoxy = OMe, O-Pr n , EtO and OBn from the respective 3-acyl-4-aryl-2-(trifluoromethyl)-2-hydroxy-3,4,7,8-tetrahydro-2 H -chromen-5(6 H )-ones. Yields in the range of 50–89% were obtained when the oxidative reactions were performed using both conventional thermal heating (CTH) and microwave (MW) procedures. In general, the MW method produced similar yields with shorter reaction times and easier reaction workups. As an example, a representative X-ray diffraction ORTEP for 3-benzoyl-2-hydroxy-5-methoxy-4-methoxyphenyl-2-(trifluoromethyl)chromane is also shown.

A new series of twenty-one trifluoromethyl-containing ( E )- N ′-arylidene-1 H -pyrazole-1-carbohydrazides ( 4 ) was synthesized by the cyclocondensation reactions of six 3-alkyl(aryl/heteroaryl)-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1 H -pyrazole-1-carbohydrazides ( 2 ) with eleven aryl/heteroaryl aldehydes and acetophenone ( 3 ) in 52–97% yields and six new carbohydrazides 2 were easily obtained from the reaction of 1,1,1-trifluoro-4-alkyl(aryl/heteroaryl)-4-methoxy-3-alken-2-ones ( 1 ) with carbohydrazide. Subsequently, four examples of carbohydrazides 4 were fully studied by X-ray diffraction and the twenty-seven pyrazolyl-carbohydrazides 2 and 4 screened for their antioxidant and antimicrobial proprieties and evaluated by DPPH and MIC methods, respectively. Both series 2 and 4 showed ability to capture DPPH free radical for IC 50 from 47.57 to 487 μg/mL. Most of the compounds presented fungistatic and bacteriostatic activity only for high MIC levels ranging from 0.25 mg/mL to 0.5 mg/mL.

This study describes a simple and efficient procedure to synthesize a novel series of fourteen 4-substituted N-(5-pyridinyl-1H-1,2,4-triazol-3-yl)-6-(trifluoromethyl)pyrimidin-2-amines, where the 4-substituents are H, CH3, C6H5, 4-FC6H4, 4-CH3C6H4, 4-CH3OC6H4 and 2-Furyl; from the cyclocondensation reaction of N-[5-(pyridinyl)-1H-1,2,4-triazol-3-yl]guanidines with 4-alkoxy-4-alkyl(aryl/heteroaryl)-1,1,1-trifluoroalk-3-en-2-ones. The reactions were carried out in ethanol under reflux for 18 h and led to 40–68% yields. N-(Pyridyl-triazolyl)guanidine precursors were further obtained from reactions of cyanoguanidine with nicotinic or isonicotinic acid hydrazides and the halogenated enones from trifluoroacetylation of enolethers or acetals.

The regiospecific synthesis of a novel series of nine 4-phenyl- and 3-alkyl(aryl)-5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-tosylpyrazoles (pyrazolinyl p-tolyl sulfones), as well as their antimicrobial activity against yeast, such as fungi, bacteria, and alga are reported. The 1-p-tosyl-2-pyrazolines were obtained from the cyclocondensation reaction of 3-phenyl- and 4-alkyl(aryl)-1,1,1-trifluoro-4-alkoxy-3-alken-2-ones, [where alkyl = H, Me and aryl are -C6H5, 4-CH3C6H4, 4-OCH3C6H4, 4-FC6H4, 4-ClC6H4, 4-BrC6H4,] with p-tosylhydrazine in a yield of 58–92% when toluene was employed as solvent. The best activity was obtained when the structure possessed a 4-fluorophenyl substituent linked at the carbon-3 of the pyrazoline ring. Subsequently, the dehydration reaction of 3-(4-fluorophenyl) substituted 2-pyrazoline with thionyl chloride/pyridine in benzene as solvent furnished the corresponding 1H-pyrazole in only a moderate yield (49%).

A convenient method for the synthesis of a novel series of 7-trifluoromethyl-5,6-dihydrobenzo[c]acridines, in 44–82% yields, by intramolecular cyclization reactions of N-aryl-2-trifluoroacetyl-3,4-dihydronaphthylamines using poly-phosphoric acid (PPA), is described on this paper. Naphthylamine derivatives are obtained by an oxygen-nitrogen exchange reaction from 1-methoxy-2-trifluoroacetyl-3,4-dihydronaphthalene with substituted anilines.

A series of 10 heterocycles was obtained from the reaction of 1,1,1-trifluoro-4,4-diethoxy-3-buten-2-one and 1,1,1,2,2-pentafluoro-4,4-diethoxy-3-penten-2-one with different dinucleofiles (hydrazine, methyl hydrazine, hydroxylamine and sodium cyanide). The pyrazoles, 4,5-dihydroisoxazoles and pyrrolidinones polyfluoroalkyl substituted were obtained in moderate to good yields under mild conditions.

A convenient method for the synthesis of eight alkyl 6-[4,5-dihydroisoxazol-3-yl(-pyrazol-3(5)-yl)]hexanoates from the cyclocondensation of methyl 10,10,10-trifluoro[chloro]-9-oxo-7-methoxydec-7-enoates and hydroxylamine hydrochloride or hydrazine hydrochloride, respectively, in ethanol as solvent is reported. The reaction of methyl 10,10,10-trichloro-9-oxo-7-methoxydec-7-enoates with hydrazines furnished the pyrazole derivatives with the simultaneous transformation of trichloromethyl to carboxyl group.

A new series of six 3-aryl-5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-picolinoylpyrazole hydrochlorides were synthesised in one-step in high yields by the reaction of β-methoxyvinyl trifluoromethyl ketones with 2-pyridinecarboxamidrazone in the presence of hydrochloric acid. The hydrochloride salts were easily converted to the respective new series of free trifluoromethylated 4,5-dihydro-1H-1-picolinoylpyrazoles using triethylamine in anhydrous diethyl ether. X-ray structure and 35 Cl NMR data from the pyrazole hydrochlorides are reported.

A multi-linear-regression analysis using the Kamlet–Abbout–Taft (KAT) solvatochromic parameters in order to elucidate and quantify the solvent effects on the 17 O chemical shifts of three 4-dimethylsulfoximide-1,1,1-trifluoro-3-buten-2-ones is reported. The predominant conformational structures of compounds has been determined by energy minimization calculations using the Austin Model (AM1) semi-empirical method, which has been used to explain the 17 O NMR chemical shifts for CO and SO groups. The chemical shifts of carbonyl and sulfoximide oxygen’s of molecules showed similar dependencies (in ppm) on the solvent polarity–polarizability and the solvent hydrogen-bond-donor (HBD) acidities. The influence of solvent hydrogen-bond-acceptor (HBA) basicities was little significant.

The synthesis of a novel series of eleven 6-aryl(5-methyl)-4-trifluoromethyl-2(1H)-pyrimidinones, where aryl ¼ Ph, 4-CH3Ph, 4-FPh, 4ClPh, 4-BrPh, 4-OCH3Ph and alkyl ¼ H, CH3, from the reaction of 4-aryl-4-methoxy-1,1,1-trifluoro-3-buten-2-ones with urea in the presence of hydrochloric acid, is reported. Trifluoroacetylation of acetophenone- and propiophenone-dimethylacetals derived from phenones, was employed to obtain the precursors. # 2002 Elsevier Science B.V. All rights reserved.

The one-pot synthesis of nine novel 5-trifluoromethyl-1,2-dimethyl-1H-pyrazolium chlorides 2 from the cyclocondensation of 4-alkoxy-1,1,1-trifluoro-3-alken-2-ones 1 [CF3C(O)CH=C(R1)OR, where R1=H, Me, n-Pr, n-Hex, Ph, 4-Me-C6H4, 4-F-C6H4, 4-Cl-C6H4, 4-NO2-C6H4, and R=Me, Et] with 1-2-dimethyl hydrazine, in quantitative yields, is reported. The 1 H , 13 C , 19 F and 35 Cl NMR chemical shifts of compounds 2 also are described.

The synthesis of a series of novel trifluoromethylated β-acetal- gem -diols, 4-alkoxy-4-ethoxy-1,1,1-trifluoro-butane-2,2-diols ( 4a = methoxy , 4b = ethoxy , 4c = allyloxy , 4d = ynyloxy ) and 1-(2-alkoxytetrahydro-furan-3-yl)-2,2,2-trifluoro-ethane-1,1-diols ( 6a = methoxy , 6b = ethoxy , 6c = allyloxy , 6d = ynyloxy ) from the reaction of 4-ethoxy-1,1,1-trifluoro-3-buten-2-one ( 1 ) and 1-(4,5-dihydro-furan-3-yl)-2,2,2-trifluoro-ethanone ( 2 ) with sodium azide in hydro-alcoholic medium, is presented. From these reactions, a small amount (ca. of 20%) of the parent trifluoromethylated β-acetal-ketones, 4-alkoxy-4-ethoxy-1,1,1-trifluoro-butan-2-ones ( 3a – d ) and 2,2,2-trifluoro-1-(2-alkoxy-tetrahydro-furan-3-yl)-ethanones ( 5a – d ) were also obtained. The synthetic potential of the trifluoromethylated β-acetal-diols was demonstrated by its application to the synthesis of 3-ethoxy-5-hydroxy-5-trifluoromethyl-pyrrolidin-2-one ( 7 ).

A convenient method to obtain β-alkyl-β-methoxyvinyl trifluoromethyl ketones [CF 3 COCHC(OMe)R, where R = Et, n -Pr, i -Pr, i -Bu, t-Bu, –(CH 2 ) 2 OMe] from the regiospecific acylation of kinetic enol ether generated in situ is reported. The unsymmetrical ketone dimethyl acetals react with trifluoroacetic anhydride in the presence of pyridine using dry chloroform as solvent with a temperature range of 25–60°C. These acetals [R–C(OMe) 2 Me] are obtained from the reaction of alkyl methyl ketones with trimethyl orthoformate in the presence of p -toluenesulfonic acid as catalyst in pure methanol as solvent. The new acetylated enol ethers proved to be versatile building blocks for the construction of interesting alkyl trifluoromethyl substituted heterocycles. Thus, examples of isoxazoline, pyrazoline, pyrazole and pyrimidinone have been obtained in good yields (62–79%).

The synthesis of 3-aryl[alkyl]-5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-pyrazolethiocarboxyamides (2a‐g) from the direct cyclocondensation reaction of b-alkoxyvinyl trifluoromethyl ketones (1a‐g) with thiosemicarbazide in methanol, under mild conditions, is reported. Similarly, the 1H-1-pyrazolethiocarboxyamide derivatives (2a‐g) were easily dehydrated and the thiocarboxyamide group hydrolyzed in a one-step reaction by stirring with concentrated sulfuric acid to give the 3-aryl[alkyl]-5-trifluoromethyl-1H-pyrazoles (3a‐g) in good yields. Specific syntheses and physical properties of 3-aryl[alkyl]-5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-pyrazolethiocarboxyamides are reported here for the first time. # 1998 Elsevier Science S.A. All rights reserved.

The one-pot, simple and efficient three-component condensation protocol for the preparation of a series of twenty-five new 3-acyl-4-aryl-2-(trifluoromethyl)-2-hydroxy-3,4,7,8-tetrahydro-2H-chromen-5(6H)-ones, where aryl = Ph, 4-tolyl, 4-ClPh, 4-NO2Ph and 4-CHOPh, and acyl = Ac, Bz, 4-FBz, furan-2-oyl, thien-2-oyl and naphth-1-oyl, employing 1,3-cyclohexanedione, five aryl aldehydes and for the first time, six 4-alkyl(aryl/heteroaryl)-4-methoxy-1,1,1-trifluoroalk-3-en-2-ones, is described. Yields in 15–75% were obtained when the MCRs were performed in the presence of a catalytic amount of triethylamine (25 mol%) and in ethanol as solvent under reflux for 16 h. A representative X-ray diffraction data for 3-acetyl-4-phenyl-2-(trifluoromethyl)-2-hydroxy-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one is also showed.