Study of regioselectivity in cyanomethylation of 4-(trifluoromethyl)pyrimidin-2(1Н)-ones

Substituent-Driven Selective N-/O-Alkylation of 4-(Trihalomethyl)pyrimidin-2(1H)-ones Using Brominated Enones

“…To our surprise, the product was obtained in the pure form after simple extraction in yields of 85 and 80% when R = Ph and H, respectively. The structures of N-and O-alkylated derivatives were unambiguously determined by 1 H− 13 C and HMBC NMR spectraScheme 2 shows the large differences in chemical shifts for each isomer. It is also important to mention that the configuration of the double bond originates from the starting (E)-5-bromo enone 3/enaminone 4a, 28 and no isomerization was observed during the course of the reaction (determined by 2D NOESY NMR).…”

“…The compounds 5a−g were obtained in moderate to excellent yields (72−92%, Table 2), which shows the tolerance to several substituents (e.g., small and longer alkyl chains such as Et, n-Pr, n-Bu, and i-Bu, as well as cycloalkanes with fiveand six-membered heterocyclic ringssee Table 2) at the amino moiety. It is important to note that, during the experiments, for all compounds, only the formation of Oalkylated product was observed by 1 H and 13 C NMR analyses.…”

“…Several derivatization techniques have already been reported for the synthesis of trihalomethyl (−CCl 3 or −CF 3 ) pyrimidines, − with the most widely explored derivatization technique being alkylation (usually N - or O -) using alkyl halides or esters . However, the selectivity of the reaction (to furnish N - or O -alkylated products) in the absence of protecting groups or catalysts is still a problem .…”

A computational study for the reaction mechanism of metal-free cyanomethylation of aryl alkynoates with acetonitrile

“…[1][2][3] In addition, cyanomethyl moieties obtained via cyanomethylation are found as versatile motifs in some important bioactive natural products and drugs. 4,5 A variety of protocols have been reported, including transition-metalcatalyzed methods [6][7][8][9][10][11][12][13][14][15][16] and metal-free catalyzed methods [17][18][19][20][21][22] for the synthesis of cyanomethyl-containing compounds. Compared to the toxic metal used, metal-free catalyzed methods used acetonitrile [9][10][11][12]17,18 and its analogs such as bromoacetonitrile, [13][14][15][16] cyanoacetic acid 19,20 and ethyl cyanoacetate 5 have drawn considerable attention due to its inexpensive and environmental-friendly properties.…”

Chan–Evans–Lam N1-(het)arylation and N1-alkеnylation of 4-fluoroalkylpyrimidin-2(1H)-ones

“…Our interest in the development of N-arylation methods resonated with recent studies focused on the addition of various C-nucleophilic reagents to 4-trifluoromethylpyrimidin-2(1H)ones I, heterocyclic analogues of activated ketimines (Figure 1), thus offering potential applications in the design of new heterocyclic chemotypes [21][22][23][24][25]. Compounds I are precursors of trifluoromethyl-substituted dihydropyrimidine derivatives which appear as original and potent scaffolds in medicinal chemistry, given the great importance of fluorinated groups in drug discovery [26][27][28][29].…”