Alkylation of Nitroarenes via Vicarious Nucleophilic Substitution – Experimental and DFT Mechanistic Studies

Abstract

Alkylation of nitroarenes via Vicarious Nucleophilic Substitution (VNS) was tested experimentally and modelled with DFT calculations. Mechanistic studies reveal intrinsic differences between reactions of archetypal carbanion precursor PhSO2CH2Cl, and alkyl phenyl sulfones, in which benzenesulfinate acts as a leaving group. Accordingly, for the latter precursors steric hindrance develops at the β‐elimination step, that raises energy barrier and results in the formation of byproducts.

Reactions of Nitroarenes with Corey–Chaykovsky Reagents

“…21 Therefore, we reckoned that reactions of secondary carbanion precursors (e.g., Et, iBu) 21 run from alternate conformer by syn-elimination pathway (to E-isomer of the anion), featured with higher, but still reasonable energy barrier. Although DFT calculations gave no conclusive data about the actual mechanism, 25 predicting similar barrier of (unconstrained) synand (crowded) anti-elimination pathways, literature data on related systems 9 and product distribution observed with the sulfonium salts (Scheme 2, right) 20 supported the postulated model. In exploratory studies of the alkylation reaction 25 we also observed formation of unexpected products, as anthranils or alkenylated arenes, formed for selected substrates (Scheme 4, bottom).…”

“…To reveal intriguing effect of the carbanion order 21 on the reaction course we focused on the mechanism and stereochemistry, which stays behind the elimination process. 25 First, using low temperature and short reaction time (-60 °C, 3 min) we isolated intermediate N-protonated adduct of 3-nitropyridine with ethyl phenyl sulfone and assigned its stereochemistry with X-ray studies. The adduct was formed as a single diastereoisomer, and cross-experiments with Scheme 2 Corey-Chaykovsky cyclopropanation of bicyclic nitroarenes with alkyl phenyl selenones (left) and alkyl diphenyl sulfonium salts (right).…”

Expected and unexpected products from reacting Sanger’s reagent with p-phenylenediamine

“…The displacement of hydrogen, rather than a halogen, has previously been called vicarious nucleophilic substitution where the leaving group is attached to the nucleophile. 18,19…”

“…λ max (EtOH)/ nm 237 (log ε 3.7) and 356 (3.5); ν max (diamond)(cm −1 ) 3423w, 3349w, 3266w, 1614s, 1577s, 1511s, 1486s, 1413s, 1329s, 1300s, 1250vs, 1220vs, 1142s, 1122s, 1059s, 917s, 837s, 746s, 699s, 653s, 515s and 495s; δ H (400 MHz; CDCl 3 ) 3.88 (2H, s, br), 6.78 (2H, d, J = 8.0, B part of AB system), 7.04 (1H, d, J = 8.0, B part of AB system), 7.08 (2H, d, J = 8.0, A part of AB system), 8.15 (1H, d, J = 8.0, A part of AB system), 9. 19 The reaction was repeated with p-phenylenediamine 6 (100 0.93 mmol) and Et 3 N (187 mg, 1.85 mmol) in i PrOH (30 mL) with 2,4-dinitrofluorobenzene 1 (345 mg, 1.85 mmol) and heated at 70 o C for 20 h. After cooling the mixture was diluted with water (180 mL), left standing for 1 h, filtered with a sinter No 4 and washed with water (10 mL). This gave the second title compound 8 as a crude product which was air dried (363 mg, 89%).…”

“…The displacement of hydrogen, rather than a halogen, has previously been called vicarious nucleophilic substitution where the leaving group is attached to the nucleophile. 18,19 DNFB 1 was reacted with aniline 14 to compare with the products formed from p-phenylenediamine 6 (Figure 8). The expected and known substitution product 15 was formed 20 in which the fluorine atom has been displaced.…”