Synthesis of Carbamates and Ureas Using Zr(IV)-Catalyzed Exchange Processes

Link: http://pubs.acs.org/cgi-bin/abstract.cgi/orlef7/asap/abs/ol0702728.html

From Prof. John A. Porco, Jr's group at Boston University

A report appeared in Org Lett ASAP on the synthesis of carbamates and ureas from dialkyl carbonates by exchange reaction catalyzed by Zr(IV) catalyst.

In their study of the exchange process for the formation of carbobates from dialkyl carbonates with amines. Zr(Ot-Bu)4 was chosen as the catalyst. In their synthesis of carbamates, an additive was required and they found 2-hydroxypyridine (or HYP) to be optimal. The following table shows the scope of the reaction.

In this series of reaction, it was found that the reaction could not be accelerated with microwave. The typical reaction conditions are: performed neat with 1.0 equiv of amine and 1.5 equiv of dialkyl carbonate in the presence of 5 mol % Zr(Ot-Bu)4 and 10 mol % HYP at 80 °C (12 h). The reaction was found to perform well both with aliphatic and aromatic amines.

Next, the optimal conditions for the carbamate-urea exchange (for the synthesis of ureas) were screened. In the model reactions between 3,4-dimethoxyphenethylamine and N-ethyl urethane
to give urea 9, 4-methyl-2-hydroxyquinoline (Me-HYQ) was found to be an optimal additive.

The scope of the urea formation was then studied and the results are summarized in the table below.

In contrast to the carbamate formation, the carbamate-urea exchange process can be accelerated using microwave. Some of the ureas can also be synthesized in one pot from dialkyl carbonate.