Electrophilic substitution in indoles. Part 14. Azo-coupling of indoles with p-nitrobenzenediazonium fluoroborate

Abstract

~~~~ ~ lndole and its 1and 2-methyl derivatives undergo second-order azo-coupling reactions with pnitrobenzenediazonium tetrafluoroborate to afford the corresponding indole-3-azo-(4'-nitrobenzenes). Kinetic studies with related 3-deuterioindoles showed that there is no isotope effect, thus confirming that the initial attack of the electrophile is the rate-determining step, as in the majority of electrophilic aromatic substitutions.In contrast, 3-methylindole afforded 3-methylindole-2-azo-(4'-nitrobenzene) and the reaction not only showed a small deuterium isotope effect (ca. 2) but was also affected by base catalysis by water added to the acetonitrile. The difference in behaviour of the 3-methylindole from indole and its 1and 2-methyl derivatives could be accounted for by a mechanism involving primary attack of the diazonium salt at the 3-position followed by rearrangement; further evidence for this mechanism was provided by the straight line plot obtained in comparisons of the rates of reactions for the four indoles with acidity functions (which reflect protonation at the 3-position).

Strictosidine Synthase: Mechanism of a Pictet−Spengler Catalyzing Enzyme

“…The closest analogous system is the report of primary isotope effects between 2 and 3 for coupling of [2-2 H]-3-methyl-indole with electrophilic p-nitrobenzenediazonium ion at 30 °C. 45 Therefore, to provide a context for our observed enzymatic D V of 2.67, we studied a model Pictet-Spengler reaction in solution.…”

“…In other words, as the rate of the reverse reaction k −3 increases relative to deprotonation k 4 (Figure 1), the deprotonation becomes rate controlling, and the observed KIE increases. [45][46][47][48] Factors contributing to the emergence of primary KIEs include sterics, base and reactant concentrations, and the acidity of the leaving proton. 44 Assuming that the steps prior to the rate-limiting deprotonation step are reversible in the enzyme active site, a primary KIE should be expected if the rates of the reverse reaction (i.e., k −3 in Figure 1) are fast relative to the rate of deprotonation (k 4 in Figure 1).…”

Straightforward Access to Hexahydropyrrolo[2,3‐b]indole Core by a Regioselective C3‐Azo Coupling Reaction of Arenediazonium Compounds with Tryptamines

“…37 Based on the relatively small Hammett reaction constant observed for the azocyclization of 5a , the mechanism appears to be better described by the Jackson-Lynch model. This is in line with the recent mechanistic observation on the reversibility of the initial phenylselenation step in the phenylselenation/cyclization cascade reaction of tryptamines.…”

Chiral Anion Phase Transfer of Aryldiazonium Cations: An Enantioselective Synthesis of C3‐Diazenated Pyrroloindolines

“…[2] Aryldiazonium salts were recognized as candidates, as their N -electrophilicity has been exploited to diazenate several classes of carbon nucleophiles in a non-stereoselective fashion, including aromatics, [3] enolates, [4] and heteroaromatics. [5] Reports of Gomberg–Bachmann–Hey biaryl syntheses [3b] and azo-coupling reactions [3a,c] that utilize aryldiazoniums under phase-transfer conditions further encouraged our efforts in this area. Furthermore, while azo compounds have been utilized extensively in materials science, [6] commodities, [7] and chemical biology [8] for their photochemical properties, studies of enantioenriched diazenes within these contexts are rare.…”