Molecular Structure of Heterocycles: 3. Semiempirical MO Calculations and Karplus-Type Dihedral Angle Dependence for the Coupling Constant Relationship of Some 4,5-Dihydro-5-Hydroxy- 5(3)-Halomethylisoxazoles

Molecular modeling by semiempirical MO calculations (AM1) was used to predict configurational and conformational preferences of a series of 4,5-dihydro-5- hydroxy-5(3)-halomethylisoxazoles. The relationship among dihedral angles calculated and the experimental ¹H NMR coupling constants, J³{Ha,b-H}, are established with Karplus-Type Equation.

     

Reactions of β-methoxyvinyl trifluoromethyl ketones with 2-pyridinecarboxamidrazone: A convenient route to trifluoromethylated 4,5-dihydro-1H-1-picolinoylpyrazole hydrochlorides

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 NMR data from the pyrazole hydrochlorides are reported.     

Synthesis of new halo-containing acetylenes and their application to the synthesis of azoles

The convenient synthesis of ten halo- and an isoxazole-containing acetylenes from the reaction of acetylenes with n-butyl lithium and subsequent reaction with an electrophile agent (ethyl trichloroacetate, ethyl dichloroacetate, trifluoroacetic anhydride, 3-methylisoxazol-5-carbonyl chloride, carbon tetrachloride and 1,1,1-trifluoro-4-ethoxy-3-buten-2-one) in moderated to good yields is reported. The application of 1,1,1-trichloro-4-phenyl-3-butyn-2-one on the synthesis of two azoles is also showed.     

Cyclocondensation reaction of 4-aryl-4-methoxy-1,1,1-trifluoro-3-buten-2-ones with urea: Synthesis of novel 6-aryl(5-methyl)-4-trifluoromethyl-2(1H)-pyrimidinones

The synthesis of a novel series of eleven 6-aryl(5-methyl)-4-trifluoromethyl-2(1H)-pyrimidinones, where aryl=Ph, 4-CH₃Ph, 4-FPh, 4-ClPh, 4-BrPh, 4-OCH₃Ph and alkyl=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.     

Haloacetylated enol ethers. 5 [5]. Heterocyclic ring closure reactions of β-alkoxyvinyl dichloromethyl ketones with hydroxylamine

The β-alkoxyvinyl dichloromethyl ketones 1a-d are cyclocondensed with hydroxylamine hydrochloride in pyridine to afford the 5-hydroxy-5-dichloromethyl-4,5-dihydroisoxazoles 2a-d in good yield. The cyclo-condensation of compound 1c gave, together with 2c , 3-cyano-2-hydroxy-2-dichloromethyltetrahydrofuran 5c. The dehydratation of compounds 2a,b , derived from acyclic enol ethers, with concentrated sulfuric acid at 30°, led the corresponding 5-dichloromethylisoxazoles 3a,b. The dehydratation of compounds 2c,d , derived from cyclic enol ethers, with concentrated sulfuric acid at 30°, led the bicyclic 4,5-dihydroisoxazoles 4c,d , and at 55°, a competitive rearrangement reaction gives the 3-cyano-2-hydroxy-2-dichloromethyl-2H-pyran 5d.     

Haloacetylated enol ethers. 7 . Synthesis of 3-aryl-5-trihalomethylisoxazoles and 3-aryl-5-hydroxy-5-trihalomethyl-4,5-dihydroisoxazoles

β-Aryl-β-methoxyvinyl trihalomethyl ketones 1a-g, 2a-g [aryl = p-YC₆H₄ where Y= H, Me, OMe, F, Cl, Br, NO₂] are cyclocondensed with hydroxylamine hydrochloride to afford the 3-aryl-5-hydroxy-5-trihalomethyl-4,5-dihydroisoxazoles 3a-g, 4a-f in good yield. The dehydratation of compounds 3a-g with concentrated sulfuric acid, led the corresponding 3-aryl-5-trichloromethylisoxazoles 5a-g . An alternative one-pot procedure yields 3-aryl-5-trihalomethylisoxazoles 5,6a-g directly by cyclocondesation of 1,2a-g with hydroxylamine hydrochloride in the presence of an excess of concentrated hydrochloric acid.     

Efficient synthesis of 6-aryl-4-trifluoromethyl/ethoxycarbonyl-2H-pyran-2-ones through self-condensation of penta-2,4-dienenitriles

An efficient synthesis of two new series of 6-aryl-4-trifluoromethyl-2H-pyran-2-ones and 6-aryl-4-carboxyethyl-2H-pyran-2-ones, obtained through the self-condensation reaction of 5-aryl-5-methoxy-3-(trifluoromethyl)penta-2,4-dienenitriles 3 and ethyl 4-aryl-2-(cyanomethylene)-4-methoxybut-3-enoates 4 respectively, is reported. The self-condensation reaction of the enoates 4 was performed in water in the presence of hydrochloric acid whereas the self-condensation reaction of the penta-2,4-dienenitriles 3 required the use of zinc bromide and hydrochloric acid in order to give the respective 2H-pyran-2-ones. Products were obtained up to 97% yield.     

Chemoselective fluorination of 2-hydroxy-3,4,7,8-tetrahydro-2H-chromen-5(6H)-ones using DAST

In this study, diethylaminosulfur trifluoride (DAST) was successfully applied in monofluorination reactions of some trifluoromethyl substituted 2-hydroxy-2H-chromenones, employing a general, mild, and efficient methodology. The fluorinated compounds (2-fluoro-2H-chromenones) were synthesized as unique products by a chemoselective reaction in 63-81% yield despite the presence of different reactive sites subjected to reactions with DAST.