Synthesis of Halogenated Anilines by Treatment of N,N-Dialkylaniline N-Oxides with Thionyl Halides

Abstract

The special reactivity of N,N-dialkylaniline N-oxides allows practical and convenient access to electron-rich aryl halides. A complementary pair of reaction protocols allow for the selective para-bromination or ortho-chlorination of N,N-dialkylanilines in up to 69% isolated yield. The generation of a diverse array of halogenated anilines is made possible by a temporary oxidation level increase of N,N-dialkylanilines to the corresponding N,N-dialkylaniline N-oxides and the excision of the resultant weak N- O bond via treatment with thionyl bromide or thionyl chloride at low temperature.

Palladium-Catalyzed Synthesis of N,N-Dimethylanilines via Buchwald–Hartwig Amination of (Hetero)aryl Triflates

“…IR (ATR, neat, cm –1 ): 3378 (w), 3038 (w), 2954 (w), 2495 (m), 2442 (m), 1995 (w), 1813 (w), 1495 (m), 1461 (s), 1381 (s), 1210 (w), 1180 (m), 1140 (m), 1116 (m), 1098 (m), 1051 (m), 983 (m), 895 (m), 804 (w), 770 (s), 715 (s), 597 (s), 556 (m), 499 (m), 455 (s). The analytical data is in accordance with that reported in the literature …”

Catalytic Disproportionation of Hydrazine Promoted by Biomimetic Diiron Complexes with Benzene‐1,2‐Dithiolate Bridge Modified by Different Substituents

“…Anhydrous FeCl 2 (Aldrich), 1,2,3,4‐tetrafluorobenzene (Energy Chemical), 4‐( tert ‐butyl)benzenethiol (Energy Chemical), 4‐methoxybenzenethio (Energy Chemical), 1,2‐dibromo‐4,5‐dimethoxybenzene (Energy Chemical), 3‐bromo‐ N,N ‐dimethylaniline (Energy Chemical), n BuLi (Energy Chemical), Fc (J&K Scientific) and hydrazine (Aldrich) were used as received without further purification. Bdt‐bridged diiron complex [Cp*Fe(µ‐η 2 :η 4 ‐bdt)FeCp*] ( 1a ), [ 16 ] pentamethylcyclopentadiene, [ 21 ] 3,4,5,6‐tetrafluorobenzene‐1,2‐dithiol, [ 22 ] 4‐( tert ‐butyl)benzene‐1,2‐dithiol, [ 23 ] 4,5‐dimethoxybenzene‐1,2‐dithiol [ 24 ] and 4‐(dimethylamino)benzene‐1,2‐dithiol [ 25,26 ] were prepared according to the literatures.…”

Transformation of N,N-Dimethylaniline N-Oxides into Diverse Tetrahydroquinoline Scaffolds via Formal Povarov Reactions

“…We report here a practical synthesis of the tetrahydroquinoline scaffold as part of our broader research program investigating the special reactivity of N , N -dialkylaniline N -oxides (Scheme 1, eq 4). 10 The aniline N -oxides undergo O -acylation events with a host of electrophiles, and we have developed chemistry by which the weak N–O bond is excised in a Polonovski-type reaction to give an iminium ion. 11 Following that event, the imine is captured by an electron-rich alkene, and the resultant cation is then attacked by the pendant aniline.…”

“…As part of our study, we found these N -oxides to be far easier to handle and manipulate as complexes with m -chlorobenzoic acid. Following oxidation of the anilines with m -CPBA, 10 the N -oxides cocrystallize with the acid byproduct to give robust crystalline solids that are bench stable and nonhygroscopic (see the Supporting Information, SI). Moreover, the m -chlorobenzoic acid does not interfere with the capture of iminium ions by exogenous nucleophiles, provided that excess activating agent is employed.…”

“…Thus, the reaction constitutes the stepwise formal [4 + 2] cycloaddition (aza-Diels–Alder reaction) of the Povarov reaction. In the case of aniline N -oxides, O -acylation requires an electrophile that will not undergo the N → C group transfer we have previously described; , elimination can be achieved efficiently under the action of a Lewis acid to give a stable iminium ion (Scheme ). The elimination pathway is favored over group transfer by employing di- tert -butyl dicarbonate (Boc 2 O) as the acylating agent (which does not undergo N → C group transfer at a significant rate, Scheme b, 2 → 3b ), followed by treatment with tin­(IV) chloride as a Lewis acid.…”