Oxalyl chloride, Stolle reaction

From 1913 to 1930, R. Stolle published several manuscripts describing the synthesis of oxindoles from anilines and a-chloroacyl chlorides. His typical substrates were chloroacetanilides or the corresponding MA -diphenylamide. The manuscripts also described the synthesis of isatines (2,3-dioxindoles) from arylamines and oxalyl chloride. The reactions require high temperatures (typically > 150 °C) to complete the cyclization step. 

Stolle synthesis. Formation of indole derivatives by the reaction of arylamines with a-haloacid chlorides or oxalyl chloride, followed by cyclization of the resulting amides with aluminum chloride. 

A related synthesis produces indolones by a different Friedel-Crafts route. The Stolle synthesis reacts with a secondary aryl amine such as diphenylamine with an a-chloro acid chloride or an a-bromo acid bromide to give an a-bromoamide (such as 315) or an a-chloroamide. An early version of the reaction used oxalyl chloride, but a more typical example is the reaction of 2-bromopropanoyl bromide with 314 to give 315. Friedel-Crafts cyclization (with AICI3) led to the indolone 316.1 ... 

The Stolle reaction is thought to occur via a typical mechanism for amide formation from an amine and acid chloride, followed by Friedel-Crafts alkylation or acylation. No definitive mechanistic work has been performed on this reaction, but incorporating the mechnistic understandings of two steps provides a firm basis for understanding the mechanism of this reaction. Formation of the mono-amide from oxalyl chloride and aniline provides intermediate 4, which in the presence of AICI3 undergoes intramolecular electrophilic aromatic substitution to the desired 2,3-dioxindole (isatin) 7 via intermediates 5 and 6. 

The Stolle reaction of arylamines with oxalyl chloride has provided interesting avenues into dioxoindoles. As shown below, reaction of 4,5-dihydro-[l,2]dithiolo[3,4-c]quinoline-l-thiones 18 with oxalyl chloride in refluxing toluene gave the corresponding quinoline-4,5-diones 20. The reaction did not require Lewis acid catalysis, as the HCl generated in the acylation step provided sufficient conditions for the cyclization step. ... 

In a very interesting application of the Stolle oxindole synthesis, reaction of (9-acylated-A-glycosylphenylamine with oxalyl chloride followed by deprotection gave the corresponding hexopyranosylisatins 23-25. ... 

---