S_NAr reactions of substituted pyridines with secondary amines in aqueous solution: Kinetic and reactivity indices in density functional theory

Abstract

A kinetic study is reported for the reactions of 2-methoxy-3-nitropyridine 1a and 2methoxy-5-nitropyridine 1b with three secondary amines 2a-c (morpholine, piperidine, and pyrrolidine) in aqueous solution at 20 • C. The Brønsted-type plots are linear with nuc = 0.52 and 0.55 for pyridines 1a and 1b, respectively, indicating that the reaction proceeds through a S N Ar mechanism in which the first step is the ratedetermining step. Additional theoretical calculations using the DFT/B3LYP method confirm that the C-2 carbon being the most electrophilic center for the both pyridines 1a and 1b. The second-order rate constants have been used to evaluate the electrophilicity parameters E of 1a and 1b according to the linear free energy relationship log k (20 • C) = s N (N + E). The E parameters thus derived are compared with the electrophilic reactivities of a large variety of anisoles. The validity of these E values has been satisfactorily verified by comparison of calculated and experimental second-order rate constants for the reactions of pyridines 1a and 1b with anion of ethyl benzylacetate. K E Y W O R D S density functional theory, electrophilicity parameter (E), equation of Mayr, kinetics, S N Ar, substituted pyridine Int J Chem Kinet. 2019;51:249-257.

Electrophilic reactivities of 7‐L‐4‐nitrobenzofurazans in σ‐complexation processes: Kinetic studies and structure–reactivity relationships

“…Ben Salah and coworkers 16 have shown that the experimental rate constants of the reactions of benzoselenadiazolium cation 18 with secondary amines (morpholine, piperidine, and pyrrolidine) in acetonitrile solution at 20 ° C are 30 to 56 orders of magnitude higher than those calculated from equation (1). Recently, Mahdhaoui and coworkers 45 investigated the reactivities of a series of pyridines 19 with anion of ethyl benzylacetate in DMSO at 20 °C solution and demonstrated that calculated rate constants according to the linear free energy relationship (equation 1) deviate by more than a factor 35 from those measured.…”

Electrophilicities of 4‐Nitrobenzochalcogenadiazoles

“…The E values are listed and compared in Figure 4 with those obtained in previous studies by our Laboratory for 2,5dinitrothiophene 5, [35] 4,6-dinitrotetrazolopyridine 6, [36] 2-methoxy-5-nitropyridine 7 [31] and 1,3,5-trinitrobenzene 8, [36] together with substrates 9-12 previously investigated by Mayr and coworkers. [37][38][39][40] Comparison of Figure 4 shows that the reactivity of nitrobenzoselenadiazol 1 b compares well with that of other neutral electrophiles such as the 2,5-dinitrothiophene 5 (E =-11.57) [35] and the 2-cinnamoyl-1-mesityl-3-methyl-1H-imidazol-3-ium 9 (E =-11.48), [37] while the reactivity of 1 a is similar to that of the benzaldehyde 10 (E =-12.90) [38] and (2-phenylethene-1,1-diylsulfonyl)dibenzene 11 (E =-12.93).…”

“…[37][38][39][40] Comparison of Figure 4 shows that the reactivity of nitrobenzoselenadiazol 1 b compares well with that of other neutral electrophiles such as the 2,5-dinitrothiophene 5 (E =-11.57) [35] and the 2-cinnamoyl-1-mesityl-3-methyl-1H-imidazol-3-ium 9 (E =-11.48), [37] while the reactivity of 1 a is similar to that of the benzaldehyde 10 (E =-12.90) [38] and (2-phenylethene-1,1-diylsulfonyl)dibenzene 11 (E =-12.93). [39] On the other hand, our electrophiles 1 appear to be much more electrophilic than 2-methoxy-5-nitropyridine 7, the least electrophilic species for which an E parameter has been determined to date [31] but, have an E value more than 6 units lower than that of 4,6-dinitrotetrazolopyridine 6 (E =-4.67) [36] and 4-nitrodiazonium ion 12 (E =-5.10), [40] compounds the general behaviour of which are representative of a superelectrophilic rankings. [19,23,25,41,42] Another interesting result is the finding that nitrobenzoselenadiazole 1 b is 2 orders of magnitude more electrophilic than 1,3,5-trinitrobenzene 8 (E =-13.19), [35] the common reference aromatic electrophile in σ-complexation processes.…”

“…The slopes close to 1 indicate the applicability of Eq (1). [30][31][32][33][34] On this basis, the values of the electrophilicity parameters E of Table 3. Characteristic 13 C NMR in DMSO-d6 of the 4-nitrobenzochalcogenadiazoles 1 and σ-adducts 4 c and 4 f [a] Values reported by Miranda and al.…”

“…[56] On the other hand, one can suggest that replacement of sulfur atom by selenium atom does not affect dramatically the sensitivity of the rates to changes in the basicity of the nitroalkyl anions 2 a-c. We also note that similar β nuc values close to than 0.50 have been observed for S N Ar processes in which bond formation to the nucleophile is rate limiting. [31,54,[56][57][58] For example, β nuc value of 0.52 has been reported for reactions of 2-methoxy-3-nitropyridine with secondary cyclic amines (morpholine, piperidine, and pyrrolidine) in aqueous solution at 20°C, [31] and β nuc value of 0.51 has been measured in dimethyl sulfoxide solution at 25°C for the reactions of 4-fluoronitrobenzene with a series of phenothiazidines. [56] Kinetics data in Table 4 have also been used to determine Brønsted α elec values for the σ-complexation reaction of 4nitrobenzochalcogenadiazoles 1 a and 1 b by individual nitroalkyl anions 2 a-c.…”