Iron can do it too! A novel, experimentally simple procedure for the N‐arylation of primary amides with aryl iodides involving an in situ formed iron‐based catalyst is reported. The success of the reaction relies on the use of cheap and environmentally friendly FeCl3 in combination with an inexpensive diamine ligand as catalyst system (see scheme).

Flow me a Ritter: Ritter reactions are performed in a simple microreactor setup using tert‐butylacetate as versatile carbocation source. The protocol avoids the handling of large amounts of hot concentrated sulfuric acid as low concentrations are optimal for rapid access tert‐butyl‐ or diphenylmethyl‐protected amides.

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Efficient mixing, temperature control and small environmental exposures allow reactions carried out in microfluidic devices to perform superior to their batch-type counterparts in conventional flasks. The Ritter reaction has been optimised for flow conditions leading to short reaction times and higher yields and also is more feasible with regards to safety, productivity and tolerance towards substrate functionalities.One of the foremost advantages of microflow procedures in synthetic chemistry is the superior kinetic and thermodynamic control over the course of a reaction when compared to the batch process. Microfluidic mixing has been proven to be much more efficient and quicker than even rapid stirring in a flask. Additionally, the dimensions of the microstructured devices together with the flow rate can allow very short and very accurately adjusted reaction times. Thermodynamic control is facilitated as the large surface to volume ratio of the microreactor leads to optimal temperature exchange between the surrounding heat/ cold source and the reactor. Constant reaction temperature can be easily implemented and the development of unwanted hotspots, which might occur in a flask, is suppressed. Therefore microreactors can help to gain better control over the avoidance or promotion of parallel and consecutive reactions, and recent publications have summarised these efforts. 1The Ritter reaction involves the nucleophilic attack of a nitrile or cyanide onto a carbenium ion and a subsequent hydrolysis resulting in the formation of amides. 2 Carbenium ions can be generated either from alkyl alcohols or alkenes by protonation. The generation of primary carbenium ions is difficult except for benzylic alcohols. The use of other primary alcohols is very limited and requires rigorous reaction conditions. 3 Secondary and tertiary alcohols are best suited as starting materials in the Ritter reaction, which serves as an excellent tool for the oxygento-nitrogen conversion. Very strong acidic conditions, hazards such as toxicity, especially for the use of cyanides, and the large exothermic character of the reaction are of concern especially when operating on a large scale, where the latter aspect allows the occurrence of hot-spots or even thermodynamic runaways. The problems appear to rise significantly with increasing batch size. 4 Several interesting protocols have been published recently that demonstrate strategies to improve and optimise the process, such as the use of mild Lewis acids or microwave irradiation 5 and diastereoselective Ritter reactions using trifluoromethanesulfonic acid in dichloromethane have been described 6 as well as fluoro Ritter reactions in microreactors. 7 Best conversions are achieved with excess of concentrated sulfuric acid, i.e. the conditions of the original work. 8 The Ritter reaction is therefore a challenging subject for microreactor technology 9 and we report herein that this approach is advantageous with regards to safety, productivity and tolerance towards substrate functionalities.Second...

2008 N-Arylation O 0268Iron-Catalyzed N-Arylations of Amides. -A variety of aromatic and aliphatic amides is arylated with aromatic and heteroaromatic iodides using FeCl 3 /DMEDA as catalysts. An intramolecular version affords oxindole (Va) or quinolinone (Vb). -(CORREA, A.; ELMORE, S.; BOLM*, C.; Chem. Eur.