Efficient Route to Deuterated Aromatics by the Deamination of Anilines

Abstract

One-step replacement of NH2 groups in ring-substituted anilines by deuterium is reported. Approaches comprising both solid-phase and solution-phase syntheses can be used on a large variety of substrates. The method uses diazotization in a mixture of water and either dichloromethane or chloroform, which serve as a source of hydrogen. This protocol can be used as a general method for fast and easy incorporation of deuterium into an aromatic system using deuterated chloroform.

Salicylic Acid‐Catalyzed One‐Pot Hydrodeamination of Aromatic Amines by tert‐Butyl Nitrite in Tetrahydrofuran

“…One common drawback in most of the existing methods is that they rely on the isolation of unstable aryl diazonium salts. In this context, a more limited number of one‐pot procedures have been developed, including: (a) the use of NaNO 2 in H 3 PO 2 , (b) the reaction with alkyl nitrites in THF or DMF at 65 °C, (c) NaNO 2 in AcOH/H 2 O followed by NaHSO 3 , and recently, NaNO 2 /AcOH in CHCl 3 /H 2 O . Importantly, the use of a deuteride equivalent as the hydrogen source would give access to regioselectively deuterated aromatic compounds.…”

One-Pot, Metal-Free Conversion of Anilines to Aryl Bromides and Iodides

“…14 Free-radical generation offers halogen abstraction in solution under mild reaction conditions compatible with sensitive substrates. Recently Burglova et al 15 described a procedure for one-step deuterium introduction by deamination of anilines (Scheme 1). Using this as a springboard, we explored the conversion of anilines to the corresponding aryl bromides and iodides.…”

“…Although a single-phase CH 3 CN/H 2 O system (Table 1, entry 9) gave a yield similar to that of the biphasic CH 2 Cl 2 /H 2 O system (Table 1, entry 5), the latter is preferred due to the solubilizing power of CH 2 Cl 2 , easy diazotization in the water layer, and convenient separation of final products from inorganics and salts. 9,15 …”

Hydro/Deutero Deamination of Arylazo Sulfones under Metal- and (Photo)Catalyst-Free Conditions

“…However, these transition metal-based approaches often lack regioselectivity [8,9,12], and when using substituted iodoarenes, a dehalogenation and/or alkyl group shift under acid conditions may take place [18]. On the other hand, the Ar–X/Ar–D conversion was achieved via deuterodehalogenation of (hetero)aryl halides (mainly bromides) catalyzed by Pd-complexes [19,20,21] (Scheme 1b), mediated by the potassium methoxide/disilane system [22], by Pd-catalyzed deborylation of boronate esters in THF/D 2 O 4:1 [23] or via deamination of anilines (via in situ prepared diazonium salts) [24].…”