Dialkyl Carbonates as Sacrifical Molecules: from Heterocycles to Macrocycles

Dialkyl carbonate (DACs) are well recognized green reagents and solvents for new synthetic pathways. In particular dimethyl carbonate (DMC), nowadays synthesized by CO2 insertion into epoxides, has shown surprising high selectivity with different nucleophiles acting either as methoxycarbonylation (BAc2 mechanism) or methylaing (BAl2 mechanism) agent. In this lecture recent advances in DMC chemistry for chlorine-free synthesis of five- and six-membered heterocycles will be presented. Reaction of 1,4-diols with DMC in the presence of a base resulted in the chlorine-free synthesis of five-membered cyclic compounds. This synthetic procedure can be also used for the quantitative intramolecular heterocyclisation of bifunctional compounds, i.e., 4-amino-1-butanol to achieve pyrrolidine. Six-member cyclic carbamates have also been synthesized by chlorine-free approach employing DMC chemistry. In fact, reacting a primary amine or a hydrazine with a di(methylcarbonate) derivative of 1,3-diols oxazinan-2-ones can be synthesized in a one-pot chlorine-free reaction. Recently we also investigated the replacement of the chlorine by a carbonate moiety in half-nitrogen and -sulphur mustard compounds. Results collected demonstrated that the novel mustard carbonates are easily synthesized, don’t show any toxicity and react with a wide range of nucleophiles in the absence of any base. These novel compounds can be employed for the synthesis of piperidines and thiopyrans. Furthermore, the polycondensation of a nitrogen mustard carbonate analogue with aromatic diols under dilution conditions resulted in a new synthetic approach to azacrowns previously not accessible.