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The chemical industry has moved into the third millennium with the ambitious goal of designing greener synthetic processes. In this chapter, we discuss the challenges inherent in this transition and the great potential that enabling technologies and hybrid reactors have in hastening its completion. A general overview of solvents, chemical selection and economic driving forces is also presented (economic incentives, green solvents, innovative purification, etc.). The industrial applications of supercritical fluids, ionic liquids and bio-based solvents have been explored as well as the promoting effects of ultrasound, hydrodynamic cavitation, photochemistry and microwaves. When these techniques are applied in continuous flow, they are able to dramatically improve reaction rates and efficiency, providing improved reaction-parameter control. In this current decade of the European “Green Deal”, the urgent need for sustainability also requires that action be taken on several fronts and that business models are rethought. Examples of industrial interest in innovative synthetic reactors and new downstream technologies are reported and discussed.

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