Sustainable Organic Synthesis: Tools and Strategies

Cover
Sustainable Organic Synthesis: Tools and Strategies
Preface
Biographies
Contents
Section 1 - Activation of Chemical Substrates under Sustainable Conditions
	Chapter 1 - Assessing the Sustainability of Syntheses of the Anti- tuberculosis Pharmaceutical Pretomanid by Green Metrics
		1.1 Introduction
		1.2 Syntheses of Pretomanid
		1.3 Sustainability Index
		1.4 Ranking Analysis of the Pretomanid Synthesis Plans
		1.5 Conclusion
		References
	Chapter 2 - Homogeneous Catalysis
		2.1 Introduction
		2.2 Catalysis
		2.3 Homogeneous Catalysis
		2.4 Model Examples
			2.4.1 Hydrogenation Reactions
			2.4.2 C–C Bond Forming Reactions
			2.4.3 C–Heteroatom Bond Forming Reactions
			2.4.4 Polymerisation Reactions
		2.5 Conclusions
		References
	Chapter 3 - Heterogeneous Catalysis
		3.1 Basic Concepts from a Historical Perspective
			3.1.1 Heterogeneous Catalysts
				3.1.1.1 Bulk Inorganic Catalysts
				3.1.1.2 Bulk Organic Catalysts
				3.1.1.3 Supported Catalysts
			3.1.2 Heterogeneity Test
				3.1.2.1 Recycling Test
			3.1.3 Examples of the Application of Heterogeneous Catalysis
				3.1.3.1 Lewis Acid- supported Catalysts: A3/KA2 Coupling and Nitro- Mannich Reactions
				3.1.3.2 Heteropolyacid- supported Catalysts: Aza- Friedel- Crafts Reaction
		3.2 Conclusions
		References
	Chapter 4 - Biocatalysis, an Introduction. Exploiting Enzymes as Green Catalysts in the Synthesis of Chemicals and Drugs
		4.1 Introduction
		4.2 Lipases
			4.2.1 Lipase- catalysed Hydrolysis of Esters
			4.2.2 Lipase- catalysed Esterification Reactions
			4.2.3 Lipase- catalysed Aminolysis Reactions
			4.2.4 Lipase- catalysed Oxidation Reactions
		4.3 Nitrilases
		4.4 Monoamine Oxidases (MAOs)
		4.5 Ketoreductases (KRED)
		4.6 Monooxygenases and Baeyer–Villiger Monooxygenases (BVMO)
		4.7 Transaminases
		4.8 Other Enzymes and Perspectives
		List of Abbreviations
		References
	Chapter 5 - Activation of Chemical Substrates Under Sustainable Conditions: Electrochemistry and Electrocatalysis
		5.1 Introduction
		5.2 Principles of Synthetic Organic Electrochemistry
			5.2.1 General Setup
			5.2.2 Potential vs. Current
				5.2.2.1 Potentiostatic Conditions
				5.2.2.2 Galvanostatic Conditions
			5.2.3 Reaction Setup
				5.2.3.1 Power Supply
				5.2.3.2 Reaction Vessels
				5.2.3.3 Electrodes
				5.2.3.4 Solvents
				5.2.3.5 Supporting Electrolytes
				5.2.3.6 Modes of Electron Transfer
		5.3 Application of Electrochemical Procedures for Sustainable Activation of Substrates
			5.3.1 Shono Oxidation
			5.3.2 Dehydrogenative Aryl–Aryl Coupling
			5.3.3 Electroreductive Difunctionalisation of Alkenes
			5.3.4 Electrochemical Birch Reduction
		5.4 Conclusion
		References
	Chapter 6 - Colored Compounds for Eco- sustainable Visible- light Promoted Syntheses
		6.1 Introduction
		6.2 Classes of Colored Compounds Applied in Photochemical Syntheses
			6.2.1 Thioketones
			6.2.2 α-­Diketones
			6.2.3 Barton Esters
			6.2.4 Cyanoarenes
			6.2.5 Azoderivatives of Formulae R–N=N–R
			6.2.6 4- Substituted- 1,4- dihydropyridines
			6.2.7 Other Radical Precursors
			6.2.8 Carbene Precursors
			6.2.9 Nitrene Precursors
		6.3 Conclusions
		References
	Chapter 7 - Activation of Chemical Substrates Under Sustainable Conditions: Mechanochemistry
		7.1 Introduction
		7.2 Methodology in Mechanochemistry
			7.2.1 Laboratory Instrumentation
			7.2.2 Sample Preparation
			7.2.3 Control of Solid- State Reactivity
				7.2.3.1 Liquid- Assisted Grinding (LAG)
				7.2.3.2 Ion-  and Liquid- Assisted Grinding (ILAG)
				7.2.3.3 Polymer- Assisted Grinding (POLAG)
				7.2.3.4 Ionic Liquid- Assisted Grinding (IL- AG)
				7.2.3.5 Liquid- Assisted Resonant Acoustic Mixing (LA- RAM)
		7.3 Analysis of Mechanochemical Reactions
			7.3.1 Powder X- Ray Diffraction
			7.3.2 Raman Spectroscopy
			7.3.3 TRIS- XANES and Solid- State NMR
			7.3.4 Temperature Measurement during Milling
		7.4 Organic Synthesis Under Mechanochemical Conditions
			7.4.1 Metal Catalysis
			7.4.2 Organocatalysis
			7.4.3 Photocatalysis
		References
	Chapter 8 - Sustainable Activation of Chemical Substrates Under Sonochemical Conditions
		8.1 Introduction
		8.2 Sonochemistry, a Chemistry based on Power Ultrasound
			8.2.1 Acoustic Cavitation and Associated Effects
			8.2.2 Ultrasonic Parameters and Experimental Factors Affecting Cavitation
				8.2.2.1 Ultrasonic Frequency
				8.2.2.2 Dissipated Ultrasonic Power
				8.2.2.3 Hydrostatic Pressure
				8.2.2.4 Temperature
				8.2.2.5 Nature of the Solvent
				8.2.2.6 Dissolved Gas
				8.2.2.7 External Pressure
				8.2.2.8 Ultrasonic Intensity
			8.2.3 Mode of Irradiation and Sonoreactors
				8.2.3.1 Modes of Irradiation
				8.2.3.2 Equipment
				8.2.3.3 Characterization of the Ultrasonic Parameters
		8.3 Organic Sonochemistry: beneficial Effects and New Reactivities
			8.3.1 Green Organic Sonochemistry
			8.3.2 Cases Studies in Organic Sonochemistry
				8.3.2.1 Examples of Oxidation Reactions
				8.3.2.2 Examples of Reduction Reactions
				8.3.2.3 Examples of Fused Heterocycles
				8.3.2.4 Examples of Organometallic Reactions
			8.3.3 Scale- up and Industrial Applications
		8.4 Conclusions: from the Challenges to New Perspectives of Organic Sonochemistry
		List of Abbreviations
		References
Section 2 - Benign Media for Organic Synthesis
	Chapter 9 - Biomass- derived Solvents
		9.1 Introduction
		9.2 Methyltetrahydrofuran (2- MeTHF)
			9.2.1 2- MeTHF as a Solvent in Organic Chemistry Reactions
			9.2.2 2- MeTHF as a Solvent in Biotransformations
		9.3 Gamma- Valerolactone (GVL)
			9.3.1 GVL as a Solvent in Organic Chemistry Reactions
			9.3.2 GVL as a Solvent in Biotransformations
		9.4 Dihydrolevoglucosenone
			9.4.1 Dihydrolevoglucosenone as a Solvent in Organic Chemistry Reactions
			9.4.2 Dihydrolevoglucosenone in Biotransformations
		9.5 Glycerol and Glycerol- based Solvents (GBs)
			9.5.1 Glycerol and Glycerol- based Solvents (GBs) in Organic Chemistry Reactions
			9.5.2 Glycerol and Glycerol- based Solvents (GBs) in Biotransformations
		References
	Chapter 10 - Supercritical Solvents
		10.1 Definition of Supercritical State
		10.2 Properties of Supercritical Fluids as Pure Substances
			10.2.1 SCFs in Practice
		10.3 Tailoring SCF Properties
			10.3.1 Selected Applications of Supercritical Solvents in Organic Synthesis
			10.3.2 Olefin Metathesis Using scCO2 as a Solvent
			10.3.3 Platform Chemicals from Glucose in SCW
			10.3.4 Biodiesel Production in SC- Methanol/Ethanol
			10.3.5 The Enzyme- catalyzed Synthesis of Butyl Levulinate from Levulinic Acid and Butanol: Green Metrics Evaluation
		References
	Chapter 11 - Challenges of Using Fluorous Solvents for Greener Organic Synthesis
		11.1 Introduction
		11.2 Perfluorinated Solvents
			11.2.1 Physical Properties of Perfluorocarbons and Perfluorinated Polyethers
			11.2.2 Organic Synthesis Using Perfluorinated Solvents
		11.3 Fluorous- organic Hybrid Solvents
			11.3.1 Physical Properties of Fluorous- organic Hybrid Solvents
			11.3.2 Organic Synthesis Using Fluorous- organic Hybrid Solvents
		11.4 Phase- vanishing (PV) Methods Using a Fluorous Solvent as a Liquid- phase Membrane
			11.4.1 Concept of PV Methods
			11.4.2 PV Method Accompanied by Photo Irradiation
			11.4.3 Grignard- type Reaction Using the PV Method
			11.4.4 PV Method Accompanied by in situ Gas Evolution
		11.5 Conclusions
		References
	Chapter 12 - Ionic Liquids and Deep Eutectic Solvents
		12.1 A Very Short Introduction
		12.2 Ionic Liquids
			12.2.1 Ionic Liquid Structure, Synthesis and Basic Properties: A Brief Survey
			12.2.2 Sustainable Physical Properties
			12.2.3 Solvent Intrinsic Catalysis
			12.2.4 Ionic Liquids as a Nice Environment for Metal- based Catalysts
			12.2.5 How Sustainable are ILs
		12.3 Deep Eutectic Solvents
			12.3.1 Deep Eutectic Solvents (DESs): General Overview
			12.3.2 Preparation of DESs and Overview of their Properties and Applications
			12.3.3 DESs in Organic Synthesis
				12.3.3.1 Consecutive Reactions in DESs
				12.3.3.2 Unveiling the Role Played by the DES
				12.3.3.3 The Case of Reactive DESs
				12.3.3.4 Grignard and Organolithium Chemistry in DESs
				12.3.3.5 To What Extent are the Green Metrics of Reactions in DESs Investigated
			12.3.4 Future Perspective
		12.4 Author Credits
		References
	Chapter 13 - Environmentally Benign Media: Water, AOS, and Water/Organic Solvent Azeotropic Mixtures
		13.1 Introduction
		13.2 Water and Biphasic/Azeotropic Mixtures as Reaction Solvents
			13.2.1 Organic Synthesis Exclusively Performed in Water
			13.2.2 Organic Reactions in Aqueous Organic Solvents or a Biphasic System
		13.3 Surfactants as an Additive for Chemistry in Water
			13.3.1 Anionic Surfactants
			13.3.2 Amphiphilic Surfactants
		13.4 Use of Aqueous Reaction Media for Industrial Applications
		13.5 Academic Incorporation of Chemistry in Water
		13.6 Conclusion
		References
	Chapter 14 - Solvent- free Conditions
		14.1 Introduction
		14.2 Solvent- free Organic Reactions
			14.2.1 Neat Reactions
			14.2.2 MOF- catalysed Reactions
		14.3 Solid- state Reactions
			14.3.1 Thermal Solid- state Reactions
			14.3.2 Topochemical Reactions
			14.3.3 Solid- state Melt Reactions
			14.3.4 Mechanochemical Reactions
			14.3.5 Photochemical Reactions
		14.4 Asymmetric Reactions
		14.5 Continuous Flow Twin- Screw Extrusion
		14.6 Conclusion
		References
Section 3 - Sustainable Approaches in Organic Synthesis
	Chapter 15 - Biomass- derived Platform Chemicals
		15.1 The Platform Molecules
		15.2 Rich Diversity Across the Platforms
		15.3 Heteroatom Content
		15.4 Functional Groups/Level of Functionality
		15.5 The Challenge of Hydrophobic Platform Molecules
		15.6 Time for a New Top Twelve
		References
	Chapter 16 - Sustainable Tools for Flow Chemistry
		16.1 Introduction
			16.1.1 Flow Chemistry as a Key Tool in Green and Sustainable Chemistry
		16.2 Heterogeneous and Recyclable Catalytic Systems
			16.2.1 Pd/C Catalyzed Arylation of Indoles in a Recoverable Polarclean/Water Mixture as the Reaction Medium
			16.2.2 Heterogenized Palladium- based Catalytic Systems
			16.2.3 Polymer- supported Catalytic Systems
		16.3 Selection of Safer and Recoverable Reaction Media
			16.3.1 Biomass- derived Solvents
				16.3.1.1 Heck–Mizoroki Cross- coupling in GVL
				16.3.1.2 Fujiwara–Moritani C–H Alkenylation in GVL
			16.3.2 Recoverable Azeotropic Reaction Media
				16.3.2.1 Waste Minimized Reduction of Nitrocompounds by a Heterogenous Au- based Catalyst in an EtOH/Water Azeotrope
				16.3.2.2 Waste Minimized Ullmann- type Reaction in Biomass Derived Furfuryl Alcohol/Water Azeotrope
		16.4 Adoption of Flow Conditions to Access Sustainable Processes
			16.4.1 Waste- minimized Synthesis of Questiomicyn- A and Related Compounds
			16.4.2 Sustainable Flow Synthesis of Benzoxazoles by Heterogeneous Manganese- based Systems
			16.4.3 Leaching- minimized Flow- assisted Protocol for Mizoroki–Heck Reaction
			16.4.4 Continuous Flow Waste Minimized C–H Arylation of 1,2,3- triazoles
		16.5 Conclusions
		References
	Chapter 17 - Step Economy
		17.1 Introduction to Step Economy
		17.2 Cascade Reactions
			17.2.1 Introduction
			17.2.2 Trifluoromethylation Reaction
			17.2.3 Trifluoromethylthiolation Reaction
		17.3 Multicomponent Reactions
			17.3.1 Introduction
			17.3.2 Construction of Fluorine- Containing Functional Groups Involving Difluorocarbene
			17.3.3 Fluorinated Functionalization of Carbon–Carbon Unsaturated Bonds
		17.4 Conclusion
		List of Abbreviations
		References
	Chapter 18 - Microwave Irradiation
		18.1 Introduction to Microwaves
			18.1.1 History and Theory
			18.1.2 How Microwaves Enhance Organic Reactions
			18.1.3 Non- thermal Effect of Microwaves
			18.1.4 Microwave Reactors
		18.2 Microwave- assisted Organic Synthesis and Green Chemistry
			18.2.1 Energy Efficiency and Microwaves
			18.2.2 Solvent- free Reactions
			18.2.3 Susceptors
			18.2.4 Heterogeneous Catalysis
			18.2.5 Green Solvents
			18.2.6 Flow Chemistry and Green Scale- up
			18.2.7 MW- assisted Reactions and the E- factor
			18.2.8 The Setup of a Green MW- assisted Chemistry Process
		18.3 Conclusions
		References
	Chapter 19 - Process Intensification: From Green Chemistry to Continuous Processing
		19.1 Process Intensification & Green Approaches to Enable a Better Future
		19.2 Process Intensification
			19.2.1 General Strategies in PI
			19.2.2 Continuous Flow Technology: an Essential Tool for PI
		19.3 Benefits and Impact of PI
			19.3.1 Business Benefits: Responsive Processing
				19.3.1.1 On Processing Flexibility
				19.3.1.2 Going from the Lab to Production Scales
			19.3.2 Sustainability Impact of PI and Continuous Flow Technology
				19.3.2.1 Continuous Technology to Improve PI of HSE Problematic Chemistries
					19.3.2.1.1
Lab Miniaturisation for Diazomethane Preparation.One illustrative example of safely handling hazardous material involves the gen...
					19.3.2.1.2
Handling Organometallics.The use of organometallics in organic synthesis programs is of fundamental importance for making carbon...
				19.3.2.2 Continuous Flow Technology to Improve PI vs. Waste Minimization
				19.3.2.3 Continuous Technology to Minimize Energy Needs from Processes
				19.3.2.4 Continuous Technology to Minimize Intermediate Inventories by Telescoping Steps
				19.3.2.5 Continuous Flow Technology to Facilitate Catalytic Processes
				19.3.2.6 Continuous Flow Technology to Improve the Output Quality of Processes
		19.4 Current Barriers and Inhibitors Towards PI
		References
	Chapter 20 - The Contribution of Green Chemistry to Industrial Organic Synthesis
		20.1 Green Chemistry: Opportunities and Driving Forces
		20.2 Green Solvents as Building Blocks for Sustainable Industrial Synthesis
			20.2.1 Supercritical CO2
			20.2.2 Ionic Liquids
			20.2.3 Bio- based Solvents
		20.3 Purification and Wastewater Treatments Under Acoustic and Hydrodynamic Cavitation
			20.3.1 Sonocrystallisation
			20.3.2 Wastewater Purification
		20.4 Innovative Reactors for Smart Chemistry
			20.4.1 Photoreactors
			20.4.2 Microwave Reactors
		20.5 Conclusions
		References
Subject Index