Curtius Rearrangement of Aromatic Carboxylic Acids to Access Protected Anilines and Aromatic Ureas

Abstract

The reaction of a chloroformate or di-tert-butyl dicarbonate and sodium azide with an aromatic carboxylic acid produces the corresponding acyl azide, presumably through the formation of an azidoformate. The acyl azide undergoes a Curtius rearrangement to form an isocyanate derivative which is trapped either by an alkoxide or by an amine to form the aromatic carbamate or urea. The reaction conditions are compatible with a variety of functional groups and allow the synthesis of a number of aniline derivatives containing alkyl, halide, nitro, ketone, ether, and thioether substituents. [reaction: see text]

Recent Development about the Use of Pyrocarbonates as Activator in Organic Synthesis: A Review

“…Nevertheless, solvent optimization in order to increase the solubility of the various ( species and intermediates leads to high conversion when 1,2-dimethoxyethane (DME) is used [53]. A temperature increase up to 75 °C is also necessary, so the acid catalyst cannot be added, since fast decomposition of Boc 2 O occurs.…”

MethylN-(2-bromo-4-chlorophenyl)carbamate

“…They can be synthesized using a variety of convenient processes (Blaser et al, 2012;Smith et al, 2012;Ibrahim et al, 2011;Porzelle et al, 2009;Lee et al, 2009;Lebel & Leogane, 2006;Caddick et al, 2003). The X-ray crystal structure of the related tert-butyl 2-phenylethylcarbamate was published recently (El-Hiti et al, 2016).…”

Recent Developments on the Carbamation of Amines

“…The reaction of carboxylic acid 162 with di-tert-butyl dicarbonate 123 and sodium azide allowed the formation of an acyl azide 159, which undergoes a Curtius rearrangement in the presence of tetrabutylammonium bromide and zinc(II)triflate afforded the corresponding carbamates 6 through the trapping of isocyanate intermediate (Scheme 140). They have also extended the same protocol for the direct synthesis of carbamates of aromatic amines using aromatic acid [202,203] Dussault and Xu have reported a direct conversion of various acid azides 159 to their corresponding carbamates 6 through Curtius rearrangement using an alcohol 5 (Scheme 141) [204]. Similar kind of approach was adopted by Saigo and coworkers for the synthesis of fullerene carbamates through reaction of corresponding fullerene acid azide with an alcohol [205].…”