Electrochemically generated tetraethylammonium peroxy-corresponding N-alkylated pyrroles in high yields. C-Alkylated pyrroles have not been isolated in any case dicarbonate (TEAPC) and tetraethylammonium carbonate (TEAC) react under very mild conditions with pyrroles reported. affording, after addition of a suitable alkylating agent, the A fair number of 1-substituted pyrroles have been identified among natural substances or their metabolites, [1] aroma compounds of foodstuffs [2] and in tobacco; [3] in addition, they have considerable importance in the pharmaceutical field as, for example, inhibitors of enzymes [4] or as anti-inflammatory, [5a] analgesic, [5a] and antirheumatic drugs. [5b] In order to undergo N-substitution, the pyrrole nitrogen atom must be deprotonated. This deprotonation may occur either on a radical-cationic species formed in the presence of a suitable acceptor upon photostimulation of the pyrrole moiety [6] or by the use of deprotonating agents such as alkali metals, [7] alkali metal alkoxides, [7] or potassium hydroxide; [8] N-deprotonation can also be achieved under phase-transfer catalytic conditions. [9] Generally, pyrryl anions act as ambident nucleophiles and alkylation can thus Scheme 1. Electrochemical reduction of dioxygen in the presence take place either at the nitrogen atom or at the carbon of carbon dioxide and electrochemical reduction of carbon dioxide atoms. Polar aprotic solvents, large counterions and hard electrophiles favour N-alkylation. [10] Recently, we found that solutions of tetraethylammonium anions formed by means of electrogenerated tetraethylamperoxydicarbonate [TEAPC, obtained by electrochemical monium peroxydicarbonate and carbonate. reduction of dioxygen in the presence of carbon dioxide in Diethyl 5-formyl-3-methylpyrrole-2,4-dicarboxylate [16] MeCN/tetraethylammonium perchlorate (TEAP); [11aฯช11d] was used as a model compound to compare the reactivity of Equations 1 and 2] or tetraethylammonium carbonate the two electrogenerated bases. The results of the reactions (TEAC, obtained by electrochemical reduction of carbon between the model pyrrole and TEAPC or TEAC in differdioxide in MeCN/TEAP; [12a,b] Equations 3 and 4) may act ent ratios are reported in Figures 1 and2. From these figboth as bases and as carboxylating agents. Actually, upon ures it can be seen that in the case of TEAPC one equivaaddition of amines, alcohols, or phenols to these solutions lent of base is sufficient to convert all the starting pyrrole (followed by addition of alkyl halides), carbamates, [12] [13] into the N-alkylated derivative, while in the case of TEAC organic carbonates, [14] [15] and ethers [14] could be isolated, 2.5 equivalents are necessary. respectively.
The evaluation of the effect of different alkylating re-These results prompted us to study the reactivity of these agents and solvents on the reaction yields was performed solutions towards pyrroles. Since carboxylation products on the system diethyl 5-formyl-3-methylpyrrole-2,4-dicarwere not found at all, this investigation has been directed boxylate and TEAPC. The results are reported in Table 1. towards the study of the possibility of N-alkylating pyrryl It can be seen that all the alkylating reagents taken into account work well, with the only exception of 3-bromo- [a] Dipartimento di Ingegneria Chimica, Materiali, Materie Prime e Metallurgia, Universita `"La Sapienza", propionitrile (Entry 7), which undergoes an elimination re-