Greener Synthesis of Organic Compounds

Ahindra Nag

• Publisher: CRC Press
• Year: 2022
• Print ISBN: 9780367544034
• eBook ISBN: 9781000545128
• Topic: Physical Sciences
• Subtopic: Chemistry
• Index: Chemistry

This book provides an interdisciplinary, integrative overview of environmental problem-solving using mild reaction conditions, green reagents, waste free and energy efficient synthesis in both industry and academic world. Discussions include a broad, integrated perspective on sustainability, integrated risk, multi-scale changes and impacts taking place within ecosystems worldwide.

Features:

• This book serves as a reference book for scientific investigators who need to do greener synthesis of organic compounds, drugs and natural products under mild reaction condition using green reagents, eco-friendly catalysts and benign reaction mediums over traditional synthetic processes which is a key driving force of scientists.
• Greener synthesis of multiple value-added heterocycles opens up a new horizon towards the organic catalysis and for this purpose, development of natural resources acts as an effective catalyst. Using environmentally friendly reaction medium e.g. ACC, WETSA, WEBSA have been used for the synthesis of some crucial heterocyclic scaffolds such as bisenols and 2-amino-4H-pyrans, tetraketones, pyrans, and biaryls.
• This book can also be used as a textbook for graduate and post graduate level courses for students. Furthermore, the problems with answers in book will add better understanding for students.

1 Green Chemistry and Green Catalysts

Ahindra Nag and Himadri Sekhar Maity

DOI: 10.1201/9781003089162-1

Contents

1. 1.1 Green Chemistry
   • 1.1.1 Water as a Greener Solvent
   • 1.1.2 Photochemistry
   • 1.1.3 Microwave-assisted Synthesis
   • 1.1.4 Tandem Reaction
   • 1.1.5 Click Reactions
   • 1.1.6 Multicomponent Reactions
   • 1.1.7 Flow Chemistry Reactions
   • 1.1.8 Versatile, Small and Biologically Active Molecules with Diverse Functionality
   • 1.1.9 Phenolic Compounds
   • 1.1.10 Heterocyclic Compounds
2. 1.2 Green Catalysts
   • 1.2.1 Lipase, Esterase and Yeast as Biocatalysts
     • 1.2.1.1 Lipase
     • 1.2.1.2 Esterase
     • 1.2.1.3 Yeast
   • 1.2.2 Plant as Biocatalyst
   • 1.2.3 Waste Feedstock as Green Catalyst
     • 1.2.3.1 Biomass Waste as Catalyst (Homogenous or Heterogeneous)
   • 1.2.4 Heterogeneous Catalysts from Waste Materials
   • 1.2.5 Green Nanoparticles as Heterogeneous Catalyst
   • 1.2.6 Ecocatalyst as Heterogeneous Catalyst from Plant Parts
   • 1.2.7 Carbon Nanoparticles as Heterogeneous Catalysts
3. References

1.1 Green Chemistry

The 21st century is recognized as the new era of green chemistry which overlaps with all sub-disciplines of chemistry. It is a swiftly developing field that provides us a proactive track for the sustainable progress of future science and technology.¹ Green chemistry is a practical as well as philosophical concept which significantly focuses on the invention, design and application of environmentally friendly chemical products and processes to reduce or to eliminate negative impacts on human health and the environment by avoiding the use and generation of hazardous substances.² Its goal is to improve the quality of life and the competitiveness of industry, by developing safer and more eco-friendly chemistry. Paul T. Anastas for the first time in 1991 coined the term green chemistry.³ In 1998, Paul T. Anastas and John C. Warner⁴ provided a set of principles known as the “Twelve Principles of Green Chemistry” to guide chemists in achieving this goal via the practice of green chemistry. The 12 principles address a range of ways to reduce the environmental and health impacts of chemical production and also guide research priorities for the development of green chemistry technologies. For this, Paul T. Anastas is regarded as the father of green chemistry. In 1995, Paul T. Anastas also helped to persuade US President Bill Clinton to launch the Presidential Green Chemistry Challenge, which encourages still by offering president’s environmental youth award (PEYA) of five citations each year to best youth scientists of companies as well as academics who have done an outstanding job of implementing the principles.³ From the perspective of green chemistry as a central issue in both academic and industrial research in the 21st century and considering the increase of environmental pollution and its intensive impact on living systems, the world is revolving around the sustainable development of environmentally benign, clean and economically feasible organic syntheses using green reagents, eco-friendly catalysts, benign reaction mediums and greener reaction conditions (e.g. microwave heating, ultrasound irradiation, infrared radiation, flow chemistry, electrolysis, grinding method and twin screw extrusion) to meet the fundamental scientific challenges of shielding the environment. Environmental factor (E-factor) is directly related to greener synthesis. E-factor is the actual amount of all waste materials [Kgs (raw materials) – Kgs (product)] formed in the process including solvent losses and waste from energy production.⁵

$$\begin{array}{c}\mathrm{E}-\mathrm{factor}=\left[\mathrm{K}\mathrm{g}\mathrm{s}\left(\mathrm{raw}\mathrm{materials}\right)-\mathrm{K}\mathrm{g}\mathrm{s}\left(\mathrm{product}\right)\right]\\ /\left[\mathrm{K}\mathrm{g}\mathrm{s}\left(\mathrm{product}\right)\right]\end{array}$$

Higher E-factor means more waste and negative environmental impact. For example, the first laboratory synthesis of its anti-impotence drug sildenafil citrate (Viagra) by drugmaker Pfizer had an E-factor of 105. Then, Pfizer’s researchers cut Viagra’s E-factor to 8 by eliminating hazardous chlorinated solvents, hydrogen peroxide and oxalyl chloride.³ After that success, Peter Dunn, the leader of the Viagra synthesis team, became the head of the more systematic green-chemistry drive started by Pfizer in 2001. Pfizer reduced the E-factor of the anticonvulsant pregabalin (Lyrica) from 86 to 9 and modified similar improvements for the antidepressant sertraline and the non-steroidal anti-inflammatory drug celecoxib. “These three products alone have eliminated more than half a million metric tons of chemical waste”, commented Dunn.³

1.1.1 Water as a Greener Solvent

From the perspective of green chemistry, the use of environmentally friendly reaction mediums such as water, ionic liquids, polyethylene glycol (PEG), supercritical fluids (especially supercritical carbon dioxide (scCO₂)), organic carbonate solvents, perfluorinated solvents and glycerol instead of hazardous organic solvents is one of the most fundamental contents of green chemistry.⁶ Nature’s own reaction medium, i.e. water plays an essential role in life processes as well as organic syntheses. From the standpoint of green chemistry, water as a reaction solvent has gained significant attention for many organic transformations because water is considered as non-toxic, abundantly available, cheap, safe for handing, non-flammable and environmentally benign compared to other organic solvents.⁷ In addition, water not only increases the rate and yield of reactions but also enhances unique enantioselectivity in a chiral synthesis which is not observed for reactions in organic solvents.⁸ Water has emerged as a greener solvent by the significant accelerating effect on versatile organic transformations owing to its high polarity, a network of hydrogen bonds, hydrophobic interaction, trans-phase interaction, high surface tension and high specific heat capacity.⁶,⁹ Furthermore, water-mediated reactions offer the key advantage of insolubility of the final products, which facilitates their isolation by a simple filtration method. For instance, “in/on water reactions at the surface/interface” and “phase-transfer” techniques are the major platforms used in advanced synthetic chemistry for easy isolation of the products and catalyst from the aqueous reaction medium.¹⁰

The first example of organic synthesis of indigo was described by Baeyer and Drewsen in 1882 (Figure 1.1).¹¹ In the synthesis, a suspension of o-nitrobenzaldehyde in aqueous acetone was treated with a solution of sodium hydroxide. There was immediate formation of the characteristic blue color of indigo and the product subsequently precipitated.

Figure 1.1 Synthesis of indigo in aqueous medium.

Breslow and co-workers reported¹² in 1980 that an acceleration of the Diels–Alder reaction under “in water” condition was achieved at very high dilution to dissolve the reactants and also observed that the cycloaddition of cyclopentadiene (0.4 mM) and butanone (25.5 mM) was 740 times faster in water than in isooctane (Figure 1.2). The increased selectivity could be obtained with water (endo/exo = 21.4) compared to the same reaction in cyclopentadiene (endo/exo = 3.85) and the same results were obtained in protic solvent (ethanol and methanol) and hydrocarbons.

Figure 1.2 Diels–Alder reaction in aqueous medium.

Sharpless and co-workers used¹³ “on water” condition under which substantial rate enhancement was noticed when the organic reactants were insoluble in the aqueous phase. The “on water” protocol provided not only...

Table of contents

• Cover Page
• Half Title page
• Title Page
• Copyright Page
• Contents
• Preface
• Editor
• Contributors
• 1 Green Chemistry and Green Catalysts
• 2 New Greener Developments in Direct Amidation of Carboxylic Acids
• 3 Greener Methods for Halogenation of Aromatic Compounds
• 4 Microwave as a Greener Alternative in the Synthesis of Organic Compounds
• 5 Photochemical Reactions as a Useful and Easy to Implement and Scale-Up, New Method for the Synthesis of Chemicals
• 6 Biocatalysis in Green Biosolvents
• 7 Palladium-Catalyzed Suzuki–Miyaura Cross-Coupling in Continuous Flows
• 8 Synthesis of Bioactive Heterocyclic Compounds
• 9 The Use of Small Particle Catalysts in Pursuit of Green and Sustainable Chemistry
• 10 Greener Organic Transformations by Plant-Derived Water Extract Ashes
• 11 Application of Starch in the Synthesis of N-substituted Pyrroles by a Simple and Green Route
• 12 Greener Synthesis of Potential Drugs
• 13 Selected Green Efforts to Utilization of Carbohydrates
• 14 Greener Synthesis of Natural Products
• 15 The Prelude of Green Syntheses of Drugs and Natural Products
• 16 Biosynthesis of Natural Products
• Problems and Answers
• Index