Acetic acid production increased with the use of a flow system due to steady-state long-term operation versus batch cycling.

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. Continuousflow 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 O 2 and 1 % Au/TiO 2 , 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.

In the present paper we report the synthesis of condensed pyrimidone heterocycles (including novel ones) prepared by the Gould−Jacobs reaction using an in-house-built vacuum-to-high pressure multipurpose "three-mode" pyrolysis reactor. Four of the ring systems have not been described in the literature to date. The pyrolysis reactor has (i) a flash vacuum pyrolysis (FVP) module that applies high vacuum (10 −3 mbar), letting the starting material through the reactor chamber heated up to 1000 °C; (ii) a pneumatic spray pyrolysis (PSP) module that can inject nonvolatile reactants to the heated reactor zone; and (iii) a high-pressure pyrolysis (HPP) continuous-flow module that operates from atmospheric to 400 bar pressure and between room temperature and 600 °C. The capabilities of the pyrolysis reactor were demonstrated by comparison experiments on two different condensed pyrimidone bicyclic ring systems, and the established reaction conditions were then successfully applied to the synthesis of another six condensed pyrimidone bicyclic systems.

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 W 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).

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