Simple Syntheses of 3-Trifluoroacetyl-4-Quinolylamines, Sulfides, and Ethers Starting From N,n-Dimethyl-4-Quinolylamine

Computational Study for the Aromatic Nucleophilic Substitution of 4-Dimethylamino-3-trifluoroacetyl- quinoline with Various Nucleophiles

“…Energy change E3 from 1 to VI (Path A) is calculated to be 59.2 kcal/mol 14 which is deemed too large to undergo the reaction from 1 to 8 under the reported experimental conditions (100 °C). 8 In contrast, order (in parentheses) are also put up in Figure 3.…”

“…Based on the energy value of TSN-S, activation energy Ea of the process from 1 to VII is estimated to be 29.5 kcal/mol, which is compatible with the experimental fact that the N-S exchange reaction of 1 with n-butanethiol should be performed at 100 °C for reaction completion. 8…”

“…All calculation results in this section are afforded under butyronitrile medium condition which is adopted as a solvent for this N-S exchange. 8 Energy values of geometrically optimized two intermediates VI and VII are indicated in Figure 3.…”

“…For computationally explaining the reaction of 1 with n-butanol as a representative case, we have referring to our previous study. 8 Energy values of geometrically optimized two intermediates VIII and IX are indicated in Figure 5.…”

“…The key step on the above studies is a unique aromatic nucleophilic substitution of 4-dimethylamino moiety of trifluoroacetylated quinoline 1 with N-, S-, and O-nucleophiles (Scheme 1). 8 Previously, we reported highly selective nucleophilic substitutions on 4-(dimethylamino)-2-methoxy-3-(trifluoroacetyl)quinoline 2 giving 3 9,10 together with some computational studies on their reaction course. [11][12][13] Here we wish to describe the DFT calculation (RB3LYP/6-31G*) study on the reaction of 1 as the more simplified substrate than 2 bearing electron donative methoxy group at the 2-position in order to elucidate the essential reactivity of 3-trifluoroacetylquinoline system with various nucleophiles.…”