The 3rd Frontiers in Organic Synthesis Technology” (FROST3) focusing on the “Progress in Flow Chemistry”, organized jointly by the Flow Chemistry Society and Akadémiai Kiadó Zrt. (a Wolters Kluwer company – publisher of the Journal of Flow Chemistry) was held in Budapest on the 11th–13th October 2011. 58 people attended from all over the world, and 11 internationally renowned speakers presented their latest results. Since the last conference held in 2009 we have witnessed a rapid development of flow chemistry technologies, both in the applications and the reactor design.
Authors:Gellért Sipos, Viktor Gyollai, Tamás Sipőcz, György Dormán, László Kocsis, Richard V. Jones and Ferenc Darvas
The atom economy concept is one of the earliest recognition for green and sustainable aspects of organic synthesis. Over the years, novel technologies emerged that made this important feature of reactions into practice. Continuous-flow devices increased the efficiency of the chemical transformations with novel process windows (high T, high p and heterogeneous packed catalysts etc.) and increased safety which turned the attention to reexamine old, industrial processes. Oxidation can be performed under flow catalytic conditions with molecular oxygen; alcohols can be oxidized to carbonyl compounds with high atom economy (AE = 87 %). Using O2 and 1 % Au/TiO2, alcohol oxidation in flow was achieved with complete conversion and >90 % yield. N-alkylation is another good example for achieving high atom economy. Under flow catalytic conditions (Raney Ni), amines were successfully reacted with alcohols directly (AE = 91 %) with >90 % conversion and selectivity. In both examples, the effective residence time was less than 1 min. These two examples demonstrate the significant contribution of flow technology to the realization of key principles in green and sustainable chemistry.
Authors:Tamás Sipőcz, László Lengyel, Gellért Sipos, László Kocsis, György Dormán, Richard V. Jones and Ferenc Darvas
A novel method for C–H functionalization of heteroaromatic rings by using continuous-flow reactors is reported. Direct alkylation reactions were investigated under heterogeneous catalytic conditions using simple transition metal catalysts at elevated temperature and pressure. As a model reaction, the alkylation of indole was attempted using cheap Raney® Nickel catalyst. Alcohols served both as alkylating agent and as reaction media. The targeted 3-alkyl-indoles were obtained in moderate to good yield with reasonable selectivity. Transient protection on the N-atom increased the selectivity up to 80%. The scope and limitations were also investigated. In summary, direct alkylation with alcohols represents a rapid (residence time of <1 min) and traceless process with high atom economy (88–92%, in those cases where transient protection was not applied).