Hypervalent Iodine Chemistry:  Mechanistic Investigation of the Novel Haloacetoxylation, Halogenation, and Acetoxylation Reactions of 1,4-Dimethoxynaphthalenes

Abstract

Treatment of 1,4-dimethoxynaphthalenes with iodosobenzene diacetate and trimethylsilyl chloride or bromide furnished the haloacetoxylated, acetoxylated, and halogenated 1,4-dimethoxynaphthalenes in excellent yield. The reaction pathway for each transformation was shown to be a function of reagent stoichiometry. A mechanistic hypothesis is presented that rationalizes the reaction pathways and explains the subtle differences in the halogenation reactions. The acetoxylation, for example, is thought to involve the formation of an iodonium ion that promotes the nucleophilic addition of acetate ion and subsequent 1,2-acetyl migration. Bromination occurs as a direct result of the oxidation of trimethylsilyl bromide to bromine, followed by electrophilic aromatic substitution. Chlorination is thought to proceed via a radical process and not the formation of molecular chlorine from the dissociation of iodosobenzene dichloride. The haloacetoxylation reaction also appears to be fairly specific for 1,4-dimethoxynaphthalenes, since the analogous reaction with a 1,4-dimethoxybenzene derivative was unsuccessful.

A magnetic nanobead‐based bioassay provides sensitive detection of single‐ and biplex bacterial DNA using a portable AC susceptometer

“…Thus, a simple ligand exchange of iodine(III) can provide a radical halogen reagent, PhI(OAc)Cl, from both PhICl 2 and PhI(OAc) 2 , as shown in Scheme . Previously, Evans and Brandt reported 1 H NMR spectra of this mixed iodine(III) species formed from PhI(OAc) 2 and trimethylsilyl chloride (TMSCl), but proposed that radical chlorination occurred by PhICl 2 , not PhI(OAc)Cl 16…”

Design and Synthesis of Novel Quinone Inhibitors Targeted to the Redox Function of Apurinic/Apyrimidinic Endonuclease 1/Redox Enhancing Factor-1 (Ape1/Ref-1)

“…Rf = 0.17 (1:9 EtOAc:hexanes); 0.50 (CH2Cl2) Mp = oil (Lit. 38 – 40 °C)20 1H NMR (CDCl3): δ 3.91 (s, 3H); 3.98 (s, 3H); 3.99 (s, 3H); 6.63 (s, 1H); 7.40 (m, 2 H); 8.09 (dd, 2H) According to the procedure by Syper et al,23 1,2,4-trimethoxynaphthalene(1.07 g, 4.90 mmol) was dissolved in THF (20.0 mL) at 0 °C under argon, and then nBuLi (1.6 M in hexanes, 4.0 mL, 10.0 mmol) was added at 0 °C. The reaction was stirred at 0 °C for 5 h before DMF (0.850 mL, 11.0 mmol) was added at 0 °C.…”

“…Rf = 0.25 (1:9 EtOAc:hexanes); 0.20 (CH2Cl2) mp = 43 – 45 °C (Lit. 53 °C d)231H NMR (CDCl3): δ 3.99 (s, 3H); 4.00 (s, 3H); 4.03 (s, 3H); 7.55 (m, 2H); 8.15 (dd, 2H); 10.57 (s, 1H)…”

Organic synthesis using (diacetoxyiodo)benzene (DIB): Unexpected and novel oxidation of 3-oxo-butanamides to 2,2-dihalo-N-phenylacetamides

“…Based on this result, we developed a simple and efficient approach to the synthesis of 2,2-dihalo- N -phenylacetamides, on which we report herein (Scheme 2). To the best of our knowledge, there are several reports on chlorination and bromination reactions with PhI(OAc) 2 and a halogen source such as TMSBr, lithium halide or pyridinium halide [32–34]. Also, there are several reports on the synthesis of difunctionalized acetamide derivatives [35–38], but this report is the first to describe the synthesis of 2,2-dihalo- N -phenylacetamides through an oxidative process with PhI(OAc) 2 and Lewis acids as the halogen source.…”