Haloacetylated enol ethers. 11. Synthesis of 1-methyl- and 1-phenyl pyrazole-3(5)-ethyl esters. A one-pot procedure

A one-pot synthesis of 1-methyl- and 1-phenylpyrazole-3(5)-ethyl esters 2,3a-e by the cyclocondensation of β-alkoxyvinyl trichloromethyl ketones 1a-e with methyl and phenyl hydrazine hydrochloride under mild conditions, is reported. A study using compounds 1a-e with different substituents proved that these are versatile building blocks for the synthesis of pyrazole derivatives, having a 3(5)-ethoxycarbonyl substituent in good yields (60–89%). The hydrazine and β-alkoxyvinyl trichloromethyl ketone substituent effects on the reaction regiochemistry on the formation of the 1,3- and 1,5-isomer were observed.     

Cycloaromatization Reaction of 4‐Alkoxy‐1,1,1‐trifluoroalk‐3‐en‐2‐ones with 2,6‐Diaminotoluene: The Unexpected Regioselective Synthesis of 2,4,7,8‐Tetrasubstituted Quinolines

This article reports a convenient and general method for the regioselective synthesis of a new series of 2‐alkyl(aryl)‐8‐methyl‐4‐trifluoromethyl‐7‐aminoquinolines in 86–93% yields, from cycloaromatization reactions of N‐(oxotrifluoroalkenyl)‐2,6‐diaminotoluenes in a strongly acidic medium polyphosphoric acid and absence of solvent. The enaminoketone intermediates were easily isolated from the reaction of 4‐alkoxy‐4‐alkyl(aryl)‐1,1,1‐trifluoroalk‐3‐en‐2‐ones [CF₃C(O)CH═C(R)OR¹, where R = H, Me, Ph, 4‐FPh, 4‐BrPh, 4‐MePh, and R¹ = Me, Et] with 2,6‐diaminotoluene (2,6‐DAT) in methanol under mild conditions, in 46–70% yields. Another synthetic route also allowed the regioselective synthesis of 2‐aryl(heteroaryl)‐4‐methyl‐4‐trifluoromethyl‐7‐aminoquinolines from direct cyclocondensation reactions of 4‐alkoxy‐4‐aryl(heteroaryl)‐1,1,1‐trifluoroalk‐3‐en‐2‐ones with 2,6‐diaminotoluene in methanol under mild conditions, in 21–36% yields.     

An Efficient Two‐Step Synthesis of New 5‐Substituted‐1H‐tetrazoles of Biological Interest

A simple procedure for the synthesis and characterization of new 3‐alkoxy‐3‐(1H‐tetrazol‐5‐yl)propionic acids and 2‐(1H‐tetrazol‐5‐yl)tetrahydrofuran‐ and ‐(1H‐tetrazol‐5‐yl)‐2H‐pyran‐3‐carboxylic acids from the [2 + 3] cycloaddition reactions between the nitrile group of β‐cyanocarboxylic acids with sodium azide in the presence of zinc chloride is described. The tetrazolic acids were isolated in moderate to good yields and are structurally analogous to succinic acid.     

13C NMR Chemical Shifts of β-Alkoxyvinyl Ketones: III✠-Empirical Substituent Effects in 1-Alkylamino-6-Ethoxy-1,5-Hexadien-3,4-Diones and 1,6-bis(Alkylamino)-1,5-Hexadien-3,4-diones

Evaluation by empirically derived equations for the substituent effect (E_Xn and E_Yn, n = 1 to 6) on the ¹³C NMR chemical shifts for C-1, C-2, C-3, C-4, C-5 and C-6 in 1-alkylamino-6-ethoxy-1,5-hexadien-3,4-diones 1a-f and 1,6-bis(alkylamino)-1,5-hexadien-3,4-diones 2a-f [XCH=CHC(O)-C(O)CH=CHY, where X, Y = OEt, NH₂, PhCH₂NH, n-BuNH, i-PrNH, cyclo-C₆H₁₁NH, t-BuNH], taking as reference the 1,6-diethoxy-1,5-hexadien-3,4-dione (3), is reported. From the calculated values for the E_Xn and E_Yn effects for each substituent it was possible to estimate the chemical shift of each carbon of the compounds 1,2 with excellent precision: 100% of the calculated chemical shifts are found to be within ±0.5ppm. The carbon-13 chemical shifts of C-1, C-2 and C-3 of compounds 1a,2a,3 led a good correlation with carbon charge densities (qr).     

Haloacetylated enol ethers. 14 [6]. Reaction of β-alkoxyvinyl trifluoromethyl ketones with N-methylhydroxylamine

The reaction of a series of β-methoxyvinyl trifluoromethyl ketones [CF₃COC(R²)?C(OMe)R¹, where R¹ = Me, -(CH₂)₃-C3, -CH₂)₄-C3, Ph and R² = H, Me, -(CH₂)₃-C4, -(CH₂)₄-C4] with N-methylhydroxylamine is reported. The regiochemistry of the reaction are explained by MO calculation data.