Brominated Trihalomethylenones as Versatile Precursors to 3‐Ethoxy, ‐Formyl, ‐Azidomethyl, ‐Triazolyl, and 3‐Aminomethyl Pyrazoles

Abstract

5‐Bromo[5,5‐dibromo]‐1,1,1‐trihalo‐4‐methoxy‐3‐penten[hexen]‐2‐ones are explored as precursors to the synthesis of 3‐ethoxymethyl‐5‐trifluoromethyl‐1H‐pyrazoles from a cyclocondensation reaction with hydrazine monohydrate in ethanol. 3‐Ethoxymethyl‐carboxyethyl ester pyrazoles were formed as a result of a substitution reaction of bromine and chlorine by ethanol. The dibrominated precursor furnished 3‐acetal‐pyrazole that was easily hydrolyzed to formyl group. In addition, brominated precursors were used in a nucleophilic substitution reaction with sodium azide to synthesize the 3‐azidomethyl‐5‐ethoxycarbonyl‐1H‐pyrazole from the reaction with hydrazine monohydrate. These products were submitted to a cycloaddition reaction with phenyl acetylene furnishing the 3‐[4(5)‐phenyl‐1,2,3‐triazolyl]5‐ ethoxycarbonyl‐1H‐pyrazoles and to reduction conditions resulting in 3‐aminomethyl‐1H‐pyrazole‐5‐carboxyethyl ester. The products were obtained by a simple methodology and in moderate to good yields.

Brominated β-Alkoxyvinyl Trihalomethyl Ketones as Promising Synthons in Heterocyclic Synthesis

“…Additionally, the nature of the trihalomethyl group (CF 3 , CCl 3 , or CClF 2 ) directed the diene that was formed, by eliminating ethyl bromide (C=C formed at the 5position, in which R = CF 3 ) or ethyl chloride (C=C formed at the 1-position, in which R ≠ CF 3 ). 20 These brominated enones have been directly used in cyclocondensation reactions for preparing a series of pyrazoles, 21,22 isoxazoles, 9,23 thiazoles, 9 and pyrimidines 9,24 (Scheme 4). One can see that despite the electrophilic centers at C2, C4, and C5, the reaction proceeds selectively at C2 and C4 when reacting with 1,2-and 1,3-dinucleophiles in most cases (compounds 6, 7, and 13).…”

“…The reaction of 14 with triethyl phosphite furnishes enylphosphonate 17 (Scheme 5). 25 The reaction of 5-bromoenone 2 with alcohols catalyzed by p-toluenesulfonic acid (PTSA) gives 4-alkoxy-5-bromo-enones 15, and the reaction of this with sodium azide furnishes 4-alkoxy-5-azido-enones 18, 26,27 which are easily converted into the corresponding pyrimidine, pyrazole, and 1,2,3-triazoles from reaction with 2-methylisothiourea, hydrazine, and alkynes (copper-catalyzed alkyne-azide [CuAAC] reaction), respectively, 22,28 thus furnishing third-generation intermediates.…”

Efficient Synthesis of (1,2,3‐Triazol‐1‐yl)methylpyrimidines from 5‐Bromo‐1,1,1‐trifluoro‐4‐methoxypent‐3‐en‐2‐one

“…One such enone, 1,1,1‐trifluoro‐4‐methoxypent‐3‐en‐2‐one, can be converted through a bromination reaction into the derivative 5‐bromo‐4‐methoxy‐1,1,1‐trifluoropent‐3‐en‐2‐one ( 1 ), whose utility in organic synthesis has been much less explored. [2a], Brominated enone 1 is a versatile building block as it is a highly functionalized structure with diverse reactive sites, as shown in Figure . The carbon atoms shown in red (i.e., A, B, and C) are electrophilic centers.…”

“…[4b] All these compounds – represented by structures I – IV – are important chemical intermediates that can be useful for the construction of various classes of heterocyclic compounds. Thus, brominated enone 1 has been used by our research group to prepare series of heterocyclic compounds, including pyrazoles,, [2a] pyrroles, thiopyrimidines, and pyrazolinium cations . Another research group used brominated enone 1 as the starting material for the synthesis of pyrazole, isoxazole, and oxy‐ and thiopyrimidines,[4b] thus demonstrating its great synthetic potential.…”

New strategy for the synthesis of 4-amine-2-trifluoromethyl pyrroles N-substituted

“…2 The introduction of fluorine atoms and fluorinated groups into organic molecules often confers significant and useful changes in their chemical and physical properties. 3 Fluorinated enaminones are also very attractive synthons with high potential for the synthesis of fluorinated heterocycles. 4 In this work, we present a versatile approach for the synthesis of a new series of 4-amine-3-trifluoromethyl pyrroles N-substituted from β-enaminones trifluoromethylate 2 with amines.…”