The Chemistry of Process Development in Fine Chemical and Pharmaceutical Industry, 2nd Edition

Acknowledgements.

Abbreviations.

1. The Nature of Process Development.

1.1 Introduction.

1.2 Desirable Goals of Process Development.

1.3 Evolution of an R & D Process into a Process Technology.

1.4 Scope and Limitations of Process Development.

1.5 The Role of Chemical Engineers.

1.6 Exploratory (Investigative) Approach to Optimization.

1.7 Statistical Approaches and Automated Works Stations.

1.8 Scale–up Considerations.

1.9 Process Development in Relation to Plant Equipment.

2. Survey of Some Organic Reactions in Relation to Process Development.

2.1 Introduction.

2.2 Preparation of Acid Chlorides from Carboxylic Acids.

2.3 Friedel–Crafts Acylations Acylations.

2.4 Grignard Reagents.

2.5 The Wittig Reaction.

2.6 Ozonolysis.

2.7 The Mitsunobu Reaction.

2.8 Photochemistry in Process Industry.

2.9 Very Low Temperature (Cryogenic) Chemistry (–70° to –100°).

2.10 Reactions Under Very High Pressures.

3. Chiral Technology.

3.1 Introduction.

3.2 Nature of Chirality.

3.3 Basic Assumptions of Chiral Technology.

3.4 Factors Responsible for the Rapid Growth of Chiral Technology.

3.5 Techniques for Obtaining Single Enantiomers.

3.6 The Chiral Pool.

3.7 Biotechnology.

3.8 Racemate Resolution Strategies.

3.9 Simplified Methodologies for Optical Resolution.

3.9 A Other Strategies for Racemati Resolution.130-

3.9 B Asymmetric Synthesis.

4. Strategies for Simplification of Organic Reactions and Processes.

4.1 Introduction.

4.2 Reaction Simplification Through in situ Generation of components.

4.3 Process Simplification.

5. Reagent Modification and Rate and Order of Addition of Reagents.

5.1 Introduction.

5.2 Supported Regents.

5.3 Complex formation to Modify Reagent Reactivity.

5.4 Effect of Aging of Reagents on Reactivity.

5.5 Rate of Addition of Reagents.

5.6 Order of Addition of Reagents.

6. Additives for Reagents–Fine Tuning of Organic Reactions.

6.1 Introduction.

6.2 Water as an Additive.

6.3 Covalent Organic Compounds as Additives.

6.4 Ionic Organic Compounds as Additives.

6.5 Metallorganics and Organolithiums as Additives.

6.6 Inorganics as additives.

7. Choosing A Reagent.

7.1 Introduction.

7.2 Safety Issues.

7.3 Toxicity Consideration.

7.4 Cost Consideration.

7.5 Nasty By-products.

7.6 Efficacy Rather Than Cost.

7.7 Strategy Rather Than Reagent.

7.8 Operational and Work–up Convenience.

7.9 Improved Performance.

7.9A Environmental Options in choosing a Reagent.

8. By-Products from Side Reactions.

8.1 Introduction.

8.2 Sources of By-product Formation.

9. Solvents and Solvents Effects.

9.1 Introduction.

9.2 Solvation and its Effect on Solubility and Reactivity.

9.3 Solvent effects in Organic Reactions.

9.4 Choosing a Solvent.

9.5 Impurities in Solvents.

9.6 Utility of Mixed Solvents.

9.7 Liquid Products as Solvents.

9.8 Some Relatively New Solvents.

9.9 Aqueons Medium for Organic Reactions.

9.10 No solvent is The Best Solvent.

9.11 Molten Salts as Solvents.

9.12 Room Temperature Ionic Liquids as Solvents.

9.13 Supercritical Carbon Dioxide-a Safe and Green Solvent.

10. Phase Transfer Catalysis.

10.1 Introduction.

10.2 Nature of PTC Reactions.

10.3 Mechanistic Aspects.

10.4 Factors Affecting PTC Reactions.

10.5 Choosing a Phase Transfer Catalyst.

10.6 Phase Transfer of Neutral Uncharged Molecules.

10.7 Organometallic PTC.

10.8 Exercising the PTC Option.

11. Work–up, Purity, and Purification.

11.1 Introduction.

11.2 Classical Work-up.

11.3 Environmental Problems.

11.4 Two Typical Reactions Involving Classical Work–up.

11.5 Work-up Procedures for a Variety of Reactions.

11.6 Simplification of Reaction Work-up.

11.7 Aqueous Biphasic Liquid Systems for Reactions.

11.8 Other Types of Aqueous Biphasic Liquid Systems.

11.9 Fluorous Biphasic Catalysis and Synthesis.

11.10 Purity.

11.11 Purification.

12. Safety Assessment of Chemical Process Technology.

12.1 Introduction.

12.2 Early Detection and Prevention of Chemical Accidents.

12.3 Principles of Chemical Process Safety.

12.4 Reaction Runaway Scenarios.

12.5 Chemical Reaction Hazards.

12.6 Quantification of Chemical Hazards.

References.

Index.

General.

Reaction Type.

Reagents.