Isoindole 2-ethyl-, synthesis

The foregoing examples show that the nucleophilic attack to nitroarenes at theorr/io-posidcn followed by cyclizadon is a generid method for the synthesis of various heterocycles. When nucleophiles have an electrophilic center, heterocyclic compounds are obtained in one step. Ono and coworkers have used the anion dedved from ethyl isocyanoacetate as the reacdve anion for the preparadon of heterocyclic compounds. The carbanion reacts with various nitroarenes to give isoindoles or pyriirddines depending on the stnicture of nitroarenes fEqs. 9.56 and9.57. The synthesis of pyrroles is discussed in detail in Chapter 10. 

Bisbromomethyl derivatives are cyclized by reaction with liquid methylamine at - 80 C [2061]. Hydrazine and its simple derivatives sometimes behave as mono-functional compounds, for example, in a reaction with the dibromoarylacetic ester (81.1) [2658, 2687]. Under these conditions, phenylhydrazine ves a mixture of the isoindole and isoindoline. An unconventional synthesis of a fused pyrrole is that in which a dihalide is heated with ethyl chloroacetate and pyridine in DMF. The pyridine reacts and becomes an integral part of the product [2985]. 

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