Synthesis of 1‐Arylethyl‐2‐arylethylamino‐5‐trifluoroacetyl‐1,2,3,4‐tetrahydropyridines and Related Compounds with Potential Cell Efflux Pump Inhibition

This study reports a simple, fast, and efficient method for the synthesis of a new series of 1‐arylethyl‐2‐arylethylamino‐5‐trifluoroacetyl‐1,2,3,4‐tetrahydropyridines and related compounds from the reaction of 2‐alkoxy‐5‐trifluoroacetyl‐3,4‐dihydro‐2H‐pyrans with 2‐arylethanamines and related 2‐ethanamines. The desired tetrahydropyridines were obtained in excellent yields (90–98%), through a reaction that can be described as an AAB′ three‐component reaction protocol following an ANRORC‐type mechanism.     

Microwave assisted regiospecific synthesis of 5‐trifluoromethyl‐4,5‐dihydropyrazoles and—pyrazoles

The regiospecific synthesis of a series of twelve 5‐trifluoromethyl‐4,5‐dihydropyrazoles and ‐pyrazoles from the cyclocondesation reaction of 4‐alkoxy‐1,1,1‐trifluoro‐3‐alken‐2‐ones [F₃CC(O)CH=C(R¹)OR, where R¹ = Me, Et, Pr, iso‐Pr, Bu, iso‐Bu, Ph, H; and R = Me, Et] with phenylhydrazine in toluene by environmentally benign microwave induced techniques is reported. It is shown that under appropriated conditions, the variation of microwave irradiation power leads to 4,5‐dihydropyrazole or pyrazole derivatives. This paper also includes the use of montmorillonite K‐10 as a solid support for the synthesis of pyrazoles under solvent free conditions.     

Haloacetylated enol ethers: 15. Study of the regiochemistry of the cyclo‐condensation of β‐alkoxyvinyl trihalomethyl ketones with N‐methyl thiourea

A study of the regiochemistry of the cyclo‐condensation reaction of ß‐alkoxyvinyl trihalomethyl ketones with an unsymmetric dinucleophile N‐methyl thiourea to afford a series of 1‐methyl‐3‐(4,4,4‐trifluoro[chloro]‐3‐oxo‐1‐butenyl)thioureas and the corresponding N‐methyl pyrimidinethione derivatives is reported. The absolute assignment of the position of the N‐methyl group in the pyrimidine ring was obtained through a nmr study based on two dimensional HMBC and NOESY experiments.     

New succinyl‐spaced pyrazoles: Regioselective synthesis of 1,4‐bis[5‐(trichloromethyl)‐1H‐pyrazol‐1‐yl]butane‐1,4‐diones

The facile and convenient access by a conventional procedure in ethanol as solvent to a new series of succinyl‐spaced pyrazoles including 1,4‐bis[5‐(trichloromethyl)‐5‐hydroxy‐4,5‐dihydro‐1H‐pyrazol‐1‐yl]butane‐1,4‐diones (64–82%) and the respective dehydrated derivatives as 1,4‐bis[5‐(trichloromethyl)‐1H‐pyrazol‐1‐yl]butane‐1,4‐diones in 57–82% yields, from the regioselective cyclocondensation reactions of 4‐substituted 4‐methoxy‐1,1,1‐trichloroalk‐3‐en‐2‐ones with succinic acid dihydrazide, where the 4‐substituents are Me, Ph, 4‐FC₆H₄, 4‐ClC₆H₄, 4‐NO₂C₆H₄, 2‐furyl, and 2‐thienyl, is reported. J. Heterocyclic Chem., 2011.     

Regioselective synthesis and characterization of new 3‐aryl‐7‐trifluoromethyl‐[1,2,4]triazolo[4,3–a]pyrimidines

The regioselective synthesis and characterization of a new series of 3‐aryl‐7‐trifluoromethyl[1,2,4]triazolo[4,3–a]pyrimidines from the oxidative heterocyclization of 2‐(N′‐benzylidenehydrazino)‐4‐trifluoromethylpyrimidines with copper dichloride is described. J. Heterocyclic Chem., (2011).     

Microwave-assisted synthesis of 5-trichloromethyl substituted 1-phenyl-1H-pyrazoles and 1,2-dimethylpyrazolium chlorides

A series of five 5-trichloromethyl-1-phenyl-1H-pyrazoles and six 5-trichloromethyl-1,2-dimethylpyrazolium chlorides have been synthesized in 80-98% yield by environmentally benign microwave induced techniques involving the cyclocondensation of 4-alkoxy-1,1,1-trichloro-3-alken-2-ones [Cl₃C(O)C(R²)=C(R¹)OR, where R²=H, Me; R¹=H, alkyl, phenyl and R=Me, Et] with phenyl hydrazine and 1,2-dimethylhydrazine dihydrochloride, respectively, using toluene as solvent. The use of microwave and classical methods are comparable for making pyrazoles, but the formation of pyrazolium chlorides can be achieved in a significant shorter time, and in some cases better yield.     

Preparation of new 2‐amino‐ and 2,3‐diamino‐pyridine trifluoroacetyl enamine derivatives and their application to the synthesis of trifluoromethyl‐containing 3H‐pyrido[2,3‐b][1,4] diazepinols

The synthesis of a novel series of the intermediates N²(N³)‐[1‐alkyl(aryl/heteroaryl)‐3‐oxo‐4,4,4‐trifluoroalk‐1‐en‐1‐yl]‐2‐aminopyridines [F₃CC(O)CH?CR¹(2? NH?C₅H₃N)] and 2,3‐diaminopyridines [F₃CC(O)CH?CR¹(2‐NH₂‐3‐NH? C₅H₃N)], where R¹ = H, Me, C₆H₅, 4‐FC₆H₄, 4‐CIC₆H₄, 4‐BrC₆H₄, 4‐CH₃C₆H₄, 4‐OCH₃C₆H₄, 4,4′‐biphenyl, 1‐naphthyl, 2‐thienyl, 2‐furyl, is reported. The corresponding series of 2‐aryl(heteroaryl)‐4‐trifluoromethyl‐3H‐pyrido[2,3‐b][1,4]diazepin‐4‐ols obtained from intramolecular cyclization reaction of the respective trifluoroacetyl enamines or from the direct cyclocondensation reaction of 4‐methoxy‐1,1,1‐trifluoroalk‐3‐en‐2‐ones with 2,3‐diaminopyridine, under mild conditions, is also reported.     

An efficient synthesis of 1-cyanoacetyl-5-halomethyl-4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrazoles in ionic liquid

The synthesis of eleven 1-cyanoacetyl-5-hydroxy-5-halomethyl-4,5-dihydro-1H-pyrazoles from the reaction of 4-alkoxy-3-alken-2-ones f(R ³C(O)C(R ²) = C(R ¹)OR, where R ³ = CF₃, CCl₃, CHCl₂, CO₂ Et; R ²/R ¹ = H/H, H/Me, H/Et, -(CH₂)₄-, Me/H, H/Pr, and R = Me, Et) with cyanoacetohydrazide is reported. The reaction was carried out in the ionic liquid ([bmim][BF₄]) and molecular solvents. The results showed that when the ionic liquid was used as reaction medium, the reaction time was drastically decreased and the yield was improved. Correspondence: Marcos A. P. Martins, Núcleo de Química de Heterociclos – NUQUIMHE, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.     

Microwave-assisted synthesis and antimicrobial activity of 5-trihalomethyl-3-arylisoxazoles

A series of twelve 5-trihalomethyl-3-arylisoxazoles was synthesized and screened for antibacterial and antifungal activities. The compounds were synthesized from the cyclondensation of 1,1,1-trihalo-4-alkoxy-3-alken-2-ones [CX ₃C(O)C(R ²)=C(R ¹)OR, where X = Cl and F; R=Me; R ²=H; R ¹=H, Me, F, Cl, Br, and NO₂] with hydroxylamine hydrochloride through a rapid one-pot reaction via microwave irradiation. Some of the 5-trihalomethyl-3-arylisoxazoles exhibited good in vitro anti-Cryptococcus activity. Correspondence: Marcos A. P. Martins, Núcleo de Química de Heterociclos (NUQUIMHE), Centro de Ciências Naturais e Exatas, Departamento de Química, Universidade Federal de Santa Maria, 97.105-900 Santa Maria, RS, Brazil.