Organic Transformations in Water E-Book

• Herausgeber: Wiley-VCH
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 570

Veröffentlichungsjahr: 2024

Beschreibung

Harness sustainable, environmentally friendly chemical processes with this timely volume

Green chemistry has played a leading role in the broader search for environmentally sustainable industry. One of its most important goals is the shift from volatile, hazardous organic solvents to environmentally friendly ones, of which by far the most promising is water. Cultivating organic transformations using water as a solvent is one of the most crucial steps towards the creation of green, sustainable chemical production processes.

Organic Transformations in Water provides a cutting-edge overview of water as a reaction medium for synthesis and catalysis. After a brief introduction, the book moves through each of the most important classes of organic transformation before concluding with a survey of industrial applications.

The book will also cover:

• Chemistry and physicochemical aspects of “on-water” and “in-water” reactions
• C–H activation, metathesis, nucleophilic addition and substitution, oxidation and reduction, and many more
• Asymmetric organic reactions in water
• Applications in organocatalysis, electrocatalysis, and photocatalysis

Timely and comprehensive, Organic Transformations in Water is a must-own volume for researchers and industry professionals looking to revolutionize their work in a sustainable way.

Leseprobe

Table of Contents

Cover

Table of Contents

Title Page

Copyright

Dedication

About the Editors

Preface

List of Abbreviations

1 An Introduction to Organic Transformations in Water

1.1 The Emergence of Water as a Solvent in Organic Chemistry

1.2 Green Chemistry and Water

1.3 Conclusion

References

2 Chemistry of “On-Water” Reactions

2.1 Introduction

2.2 Broadening the Scope of On-Water Reactions

2.3 Conclusions

References

3 Chemistry of “In-Water” Reactions: Spotlights on Micellar and Phase-Transfer Catalysis

3.1 Introduction

3.2 Understanding the Concept of Micellar Catalysis

3.3 Basic Principles of Phase-Transfer Catalysis

3.4 Highlights of Micellar Catalysis

3.5 Highlights of PTC

3.6 Conclusion

References

4 Physicochemical Aspects of “On-Water” and “In-Water” Reactions

4.1 Introduction

4.2 Phase Behaviors of Realistic Reactions

4.3 Mechanistic Considerations

4.4 Green Processes Based on Water-Accelerated Reactions

4.5 Summary and Conclusions

References

5 C–H Activation Reactions in Aqueous Medium

5.1 Introduction

5.2 C–H Bond Activation Reactions in Aqueous Medium

5.3 Summary and Conclusion

Acknowledgments

References

6 Recent Developments in Multicomponent Reactions in Water

6.1 Introduction

6.2 I-MCRs

6.3 Knoevenagel-Initiated MCRs

6.4 Summary and Conclusions

References

7 Pericyclic Reactions in Aqueous Medium

7.1 Introduction

7.2 Cycloaddition Reactions in Aqueous Medium

7.3 Miscellaneous Cycloaddition Reactions In-Water

7.4 Electrocyclic Reactions In-Water (Ring Closure and Ring Opening)

7.5 Sigmatropic Rearrangements In-Water

7.6 Ene Reactions

7.7 Summary and Conclusions

References

8 Olefin Metathesis In-Water: Recent Progress and Challenges

8.1 Introduction

8.2 Ionic, Non-Ionic, and Amphiphilic Group-Tagged Olefin Metathesis Catalysts

8.3 Biopolymer Integrated Olefin Metathesis Catalysts

8.4 Conclusion

Acknowledgments

References

9 Oxidation and Reduction Reactions in Water

9.1 Introduction

9.2 Oxidation Reactions in Water

9.3 Reduction Reactions in Water

9.4 Summary and Conclusions

References

10 Radical Reactions in Water

10.1 Introduction

10.2 Transition Metal-Catalyzed Radical Reaction in Water

10.3 Transition Metal-Free Radical Reaction in Water

10.4 Photoredox Reactions Excited by Visible Light in Water

10.5 Conclusions

References

Note

11 Carbene Reactions in Water

11.1 Introduction

11.2 Carbene Reaction in Water

11.3 Conclusions

References

Note

12 Nucleophilic Addition and Substitution Reactions In-Water

12.1 Introduction

12.2 Nucleophilic Addition Reactions

12.3 Nucleophilic Substitution Reactions

12.4 Summary and Conclusions

References

13 Asymmetric Organic Reactions in Water

13.1 Introduction

13.2 Asymmetric Metal (Lewis Acid) Catalysis in Water

13.3 Asymmetric Lewis Base Organocatalysis in Water

13.4 Asymmetric Brønsted Acid Organocatalysis in Water

13.5 Asymmetric Brønsted Base Organocatalysis in Water

13.6 Summary and Conclusions

Acknowledgments

References

14 Organocatalytic Reactions in Water

14.1 Introduction

14.2 Organocatalyzed Synthesis of Biologically Promising

N

-Heterocycles in Water

14.3 Organocatalyzed Synthesis of Biologically Promising

O

-Heterocycles in Water

14.4 Organocatalyzed Synthesis of Biologically Promising

N

,

O

-Heterocycles in Water

14.5 Organocatalyzed Synthesis of Biologically Promising

N

,

S

-Heterocycles in Water

14.6 Organocatalyzed Miscellaneous Reactions in Water

14.7 Asymmetric Synthesis Using Organocatalysts

14.8 Conclusions

Acknowledgments

References

15 Organic Electrocatalysis in Water

15.1 Introduction

15.2 Direct vs. Mediated Reductive Oxidation and Oxidative Reduction

15.3 Water as a Solvent and an Electrolyte

15.4 Electrocatalysis

15.5 Water Electrolysis

15.6 Organic Transformations in Water: Principles and Applications

15.7 Benefits of Electrochemical Conversions

15.8 Conclusion

15.9 Future Perspectives

References

16 Visible Light Photocatalysis in Water

16.1 Introduction

16.2 In-Water Reactions

16.3 On-Water Reactions

16.4 Photobiocatalysis

16.5 Summary and Conclusions

References

17 Industrial Applications of Organic Reactions in Water

17.1 Introduction

17.2 Oxidative Esterification of Alcohols

17.3 Green Oxidation of Methylarenes to Benzoic Acids with Bromide/Bromate in Water

17.4 Environment-Friendly Synthesis of Bromoxynil and Iodoxynil

17.5 Synthesis of 2,6-Dibromo-4-Nitroaniline from 4-Nitroaniline in an Aqueous Medium

17.6 HBr–H

2

O

2

for Regioselective Synthesis of Bromohydrins and α-Bromoketones and Oxidation of Benzylic/Secondary Alcohols to Carbonyl Compounds in Aqueous Medium

17.7 Water-Mediated Synthesis of Imidazo[1,2-

a

]Pyridines

17.8 Sulfenylation of N-Heteroarenes in Water (Rice Cooking Method)

17.9 Summary and Conclusions

Acknowledgments

References

Index

End User License Agreement

List of Tables

Chapter 1

Table 1.1 Selected EHS values of solvents.

Chapter 4

Table 4.1 Rate constants for Diels–Alder reaction between cyclopentadiene an...

Table 4.2 1,3-Dipolar cycloaddition reactions of phthalazinium-2-dicyanometh...

Chapter 7

Table 7.1 Solvent-dependent rate constants for the Diels–Alder reaction of c...

Table 7.2 Rate constants and Gibbs energies of activation for the D–A reacti...

Chapter 8

Table 8.1 G1-catalyzed RCM of diethyl diallylmalonate using various surfacta...

Table 8.2 G2-catalyzed cross-metathesis of allyl benzene using various non-i...

Chapter 10

Table 10.1 Effect of the solvent on radical cyclization of allyl iodoacetate...

Chapter 15

Table 15.1 Physical and chemical properties of water at different temperatur...

Table 15.2 Electrolytic conductivities of aqueous electrolyte solutions, mea...

List of Illustrations

Chapter 1

Scheme 1.1 Acceleration of reaction rate by on-water protocol.

Scheme 1.2 Comparison of the reactivity of quadricyclane with dimethyl azodi...

Figure 1.1 Diagrammatic representation of green chemistry principles.

Scheme 1.3 1,3-Rearrangement of cyclic alcohols promoted by hot water.

Scheme 1.4 Synthesis of polyether marine natural product in water.

Scheme 1.5 Synthesis of diaryl ethers in water using iron catalysis.

Scheme 1.6 Single-step synthesis of β-C glycosidic ketone in water.

Scheme 1.7 Oxidative hydroxylation of aromatic boronic acids to phenols.

Scheme 1.8 Energy-efficient synthesis of perimidines in water.

Scheme 1.9 Ullmann C–S coupling using ALA14 in aqueous solution.

Chapter 2

Scheme 2.1 Rates of Diels–Alder 4 + 2 cycloaddition reaction of cyclopentadi...

Scheme 2.2 Diels–Alder 4 + 2 cycloaddition of cyclopentadiene with methyl ac...

Scheme 2.3 On-water reactions described by Sharpless and coworkers explore t...

Scheme 2.4 On-water models proposed by (a) Marcus and Jung show H-atoms prot...

Scheme 2.5 3+2 cycloaddition reaction of phthalazinium-2-dicyanomethanide wi...

Scheme 2.6 Reaction of 2-methylindole with benzoquinone using various solven...

Scheme 2.7 Addition of

n

-butyl lithium to imines using on-water conditions w...

Scheme 2.8 Comparison of the reactions of benzyl azide and BrESF in-flask re...

Scheme 2.9 Light-mediated reaction of indole and isoquinoline-1-carbonitrile...

Scheme 2.10 (a) Electrochemical synthesis of a metal-free Reformatsky reacti...

Scheme 2.11 (a) Thin film processing in the VFD enhances the on-water effect...

Scheme 2.12 (a) Passerini reaction explored by Shapiro and Vigalok and depen...

Chapter 3

Scheme 3.1 Commonly used surfactants.

Scheme 3.2 Ligands/precatalysts for micellar Suzuki–Miyaura couplings.

Scheme 3.3 Micellar sp

2

–sp

2

and sp

2

–sp

3

Suzuki–Miyaura couplings and DEL fun...

Scheme 3.4 Micellar Suzuki–Miyaura couplings under flow conditions.

Scheme 3.5 Initial reports on micellar C–N couplings.

Scheme 3.6 Micellar C–N couplings employing (a) ppm levels of [Pd] and (b) h...

Scheme 3.7 Micellar Sonogashira couplings using (a) initial reports [Pd] and...

Scheme 3.8 Micellar Sonogashira couplings using cBRIDP/Pd(OAc)

2

or Pd-G3-Cat...

Scheme 3.9 Micellar α-arylation reactions.

Scheme 3.10 Micellar nanocatalysis in the context of Fe/ppm Pd NPs.

Scheme 3.11 Micellar nanocatalysis enabling ligand-free catalysis.

Scheme 3.12 Micellar catalysis in the context of S

N

Ar reactions.

Scheme 3.13 Micellar catalysis in the context amide couplings.

Scheme 3.14 Micellar catalysis in the context of biocatalysis.

Scheme 3.15 Asymmetric α-hydroxylation of α-aryl-δ-lactams.

Scheme 3.16 Asymmetric nucleophilic aromatic substitution...

Scheme 3.17 Catalytic asymmetric alkylation of 3-arylpiperidin-2-ones using ...

Scheme 3.18 Csp

3

–Csp

3

bond formation through the synergistic effect of Palla...

Scheme 3.19 PTC-mediated enantioselective α-benzoxylation.

Scheme 3.20 PTC-mediated SM couplings.

Chapter 4

Scheme 4.1 Tandem aldehyde oxidation/Passerini reaction “on-water”.

Figure 4.1 Simplified phase complexity scenarios of water-accelerated reacti...

Scheme 4.2 A water-accelerated Henry reaction.

Figure 4.2 Classification of catalytic reactions performed in water: when al...

Scheme 4.3 Rapid, metal-free, and aqueous water-accelerated synthesis of imi...

Figure 4.3 A scaled-up setup for reaction from

8

to

9

. (a) Before reaction; ...

Figure 4.4 Effects of salts on the kinetics of a Henry reaction.

Scheme 4.4 (a) Cycloaddition of quadricyclane with DEAD. (b) The ene reactio...

Figure 4.5 (a) Experimental set up: plugs form at the junction between a tol...

Figure 4.6 Kinetic profile of Henry reaction in batch at a 1 : 1 phase ratio...

Figure 4.7 1,3-Dipolar cycloaddition reactions of pthalazinium-2-dicyanometh...

Figure 4.8 (a) Reaction rate constants for reaction between phthalazinium-2-...

Figure 4.9 Reaction progress of the Michael addition of dimethyl 2-methylmal...

Figure 4.10 Plot of the % yield of product from the reaction of 5-nitroindol...

Scheme 4.5 Water-accelerated reactions reported by Sharpless and coworkers....

Figure 4.11 Energy diagram (in kcal/mol) of the cycloaddition of DMAD and qu...

Figure 4.12 Energy profile of Henry reaction under (a) water-accelerated con...

Figure 4.13 Pictures of the catalyst recovery (HQN-SQA) and product separati...

Chapter 5

Scheme 5.1 Sonogashira coupling in aqueous medium for the synthesis of aryle...

Scheme 5.2 C(sp)–H bond activation by transition metal catalysts.

Scheme 5.3 The alkynylation of aldehydes catalyzed by bimetallic Ru-In catal...

Scheme 5.4 Ru-Cu-catalyzed A

3

coupling for the synthesis of propargylamines ...

Scheme 5.5 Gold-catalyzed A

3

coupling via C–H activation in water.

Scheme 5.6 Cu-catalyzed asymmetric addition of phenylacetylene to imines in ...

Scheme 5.7 Ag-catalyzed A

3

coupling in water and phosphorus ligand effect on...

Scheme 5.8 Cu-catalyzed functionalization of amino acids and peptides via A

3

Scheme 5.9 Au-catalyzed cascade reaction of terminal alkyne with

ortho

-alkyn...

Scheme 5.10 Cu-mediated coupling of alkynes with N-acylimines and N-acylimin...

Scheme 5.11 Pd-catalyzed coupling reactions of acid chlorides with terminal ...

Scheme 5.12 Ag-catalyzed alkynylation of ketones in water.

Scheme 5.13 Ag-catalyzed synthesis of dihydrobenzofuran derivatives from sal...

Scheme 5.14 The alkynylation of cyclic ketones catalyzed by silver-Ruphos in...

Scheme 5.15 Ag-NHC catalyzed alkynylation of isatins via on-water approach....

Scheme 5.16 Pd-NHC catalyzed alkynylation of MBH carbonates in water.

Scheme 5.17 Cu-catalyzed conjugate addition of terminal alkyne and alkyliden...

Scheme 5.18 Pd-catalyzed conjugate addition of terminal alkynes with enones ...

Scheme 5.19 Pd-catalyzed conjugate addition of terminal alkynes to acrolein ...

Scheme 5.20 Cu-Pd-catalyzed nucleophilic addition of terminal alkyne to acti...

Scheme 5.21 Transition-metal-free coupling of alkynes and alkyl iodides unde...

Scheme 5.22 The synthesis of aryl-substituted 1,4-benzoquinone via In(OTf)

3

-...

Scheme 5.23 The direct coupling of indoles with 1,4-benzoquinones using “on-...

Scheme 5.24 The addition of naphthols to 3,4-dihydroisoquinoline via aza-Fri...

Scheme 5.25 Rh-catalyzed synthesis of 3-substituted phthalides via a cascade...

Scheme 5.26 The

ortho

-phenylation catalyzed by Ru via C(sp

2

)–H bond activati...

Scheme 5.27 Ru-catalyzed tandem cyclization between aniline derivative and a...

Scheme 5.28 Ru-catalyzed direct arylation in water with phenol as the aryl s...

Scheme 5.29 Ru-based MCAT-53 catalyst for the synthesis of anacetrapib inter...

Scheme 5.30 Pd-catalyzed

para

-selective arylation of phenols with aryl iodid...

Scheme 5.31 Pd-catalyzed

ortho

-arylation of benzoic acid in water.

Scheme 5.32 Rh-catalyzed 2-phenylation of indole derivatives in water.

Scheme 5.33 The homo-coupling of aryl carboxylic acid catalyzed by Rh in wat...

Scheme 5.34 The regioselective synthesis of biaryl acids catalyzed by Rh in ...

Scheme 5.35 The regiospecific CDC of aryl carboxylic acids catalyzed by Rh i...

Scheme 5.36 The metal-free oxidative coupling for the synthesis of xanthone ...

Scheme 5.37 Palladium-catalyzed

ortho

-acylation reactions in water.

Scheme 5.38 Palladium-catalyzed C(sp

2

)–H bond activation in water for carbaz...

Scheme 5.39 Rh-catalyzed synthesis of isoquinoline derivatives in water.

Scheme 5.40 Pd-catalyzed synthesis of tetrahydro-β-carbolines in water.

Scheme 5.41 Ru-catalyzed C–H alkylation of aromatic acids with maleimides in...

Scheme 5.42 Pd-catalyzed chelation-assisted arylation and methylation reacti...

Scheme 5.43 Rh-catalyzed and a visible-light-induced C(sp

2

)–H bond activatio...

Scheme 5.44 Ligand effect on the Ru-catalyzed arylation reactions in water....

Scheme 5.45 Ru-catalyzed

in situ

olefin migration reaction in water.

Scheme 5.46 Cu-catalyzed CDC reactions of tertiary amines with nitroalkanes ...

Scheme 5.47 Cu-catalyzed CDC reaction between N-aryl tetrahydroisoquinolines...

Scheme 5.48 The photocatalyst (Fe

3

O

4

-RB/LDH) catalyzed CDC reaction under vi...

Scheme 5.49 The β-C(sp

3

)–H bond hydroxylation of...

Scheme 5.50 Pd-catalyzed β-arylation of alanine with water as a co-solvent....

Scheme 5.51 The direct addition of cycloalkanes to imines is mediated by the...

Scheme 5.52 I

2

-catalyzed oxidative CDC reactions of N-aryl tetrahydroisoquin...

Scheme 5.53 Metal-free oxidative CDC reaction of N-aryl tetrahydroisoquinoli...

Chapter 6

Figure 6.1 Schematic overview of a three-component reaction (3-CR). For the ...

Figure 6.2 Schematic representation for the preparation of MWCNTs MNCs.

Scheme 6.1 The most common I-MCRs.

Scheme 6.2 Overview of heterocyclic scaffolds described in the review of Nas...

Scheme 6.3 Preparation of β-lactam derivatives via an Ugi-4C-3CR in water.

Scheme 6.4 Preparation of various β-lactam derivatives in water.

Scheme 6.5 Preparation of furan derivatives via a Knoevenagel/Michael additi...

Scheme 6.6 Preparation of various furan derivatives using different cyclic d...

Scheme 6.7 Preparation of furo[2,3-

d

]pyrimidines via a 3-CR in the presence ...

Scheme 6.8 Preparation of pyrrole derivatives via a 4-C Knoevenagel/Michael ...

Scheme 6.9 Preparation of thioimidazolidinonesvia a 3-CR in water.

Scheme 6.10 Preparation of five-membered lactams via an Ugi reaction in wate...

Scheme 6.11 Spiropyrrolopyrrolizines via a 5-CR catalyzed by TiO

2

/Fe

3

O

4

/MWCN...

Scheme 6.12 Preparation of selenazolines via an I-MCR in water.

Scheme 6.13 Preparation of selenazolines using various 3-aminooxetanes via a...

Scheme 6.14 Preparation of thiophene derivatives via a 3-CR in water.

Scheme 6.15 Preparation of pyran derivatives using a 3-CR catalyzed...

Scheme 6.16 Preparation of pyrancoumarin derivatives using a 3-CR in the pre...

Scheme 6.17 Preparation of pyrazine derivatives via a 3-CR in water.

Scheme 6.18 Preparation of pyrazine derivatives via a 3-CR using Meldrum’s a...

Scheme 6.19 Preparation of dihydroquinoxalin-2-amine derivatives via a 3-CR ...

Scheme 6.20 Preparation of pyrimidoisoquinoline via a 4-CR supported with KF...

Scheme 6.21 Preparation of diazepine derivatives using a 4-CR in water.

Scheme 6.22 Preparation of pyrimidobenzazepine via a 7-CR catalyzed by Ag/Fe

Scheme 6.23 Preparation of oxazolopyrimidoazepines via a 6-CR in the presenc...

Scheme 6.24 Tandem Knoevenagel–Michael addition/cyclization and Knoevenagel–...

Scheme 6.25 Preparation of

trans

-2,3-substituted dihydrofurans via a 3-CR ca...

Scheme 6.26 Preparation of 5-aminopyrazole-4-carbonitrile via a 3-CR in the ...

Scheme 6.27 Preparation of isoxazoles via a 3-CR in water.

Scheme 6.28 Overview of isoxazoles prepared via a 3-CR using different catal...

Scheme 6.29 Overview of fused pyranopyrimidines, tetrahydrobenzopyrans, and ...

Scheme 6.30 Synthesis of 7-amino-6-cyano-1,5-dihydro-

1

H-pyrano[2,3-

d

]pyrimid...

Scheme 6.31 Preparation of pyrano[3,2-

c

]chromene derivatives via a 3-CR in w...

Scheme 6.32 Preparation of tetrahydrobenzo[

b

]pyran derivatives via a 3-CR in...

Scheme 6.33 Preparation of pyrano[3,2-

b

]pyran derivatives via ultrasound-ass...

Scheme 6.34 Preparation of 2-amino-4

H

-benzo[

h

]chromene-3-carbonitrile deriva...

Scheme 6.35 Preparation of chromene derivatives via a 3-CR in the presence o...

Scheme 6.36 Preparation of pyranopyridocarbazole derivatives via an ultrasou...

Scheme 6.37 Preparation of spirooxindole derivatives via N-doped graphene ox...

Scheme 6.38 Preparation of spirooxindoles via an ultrasound-assisted 3-CR in...

Scheme 6.39 Preparation of spiropyrrolooxindole via a 5-C Knoevenagel/cycliz...

Scheme 6.40 Preparation of spiropyran derivatives via an SDS-catalyzed 3-CR ...

Scheme 6.41 Preparation of pyrazolopyranopyrimidines using ultrasound condit...

Scheme 6.42 Preparation of 1,4-dihydropyrano[2,3-

c

]pyrazole derivatives via ...

Scheme 6.43 Preparation of aminocyanopyridines using microwave conditions in...

Scheme 6.44 Preparation of fused pyrimidines in the presence of

L

-proline in...

Scheme 6.45 Preparation of pyrido[2,3-

d

]pyrimidines and 1,6-naphthyridine-2,...

Scheme 6.46 Preparation of thiadiazoloquinazolinone-coumarin hybrids using m...

Scheme 6.47 Preparation of 1,4-dihydropyridines using microwave conditions i...

Scheme 6.48 Preparation of 1,4-dihydropyridines using microwave conditions i...

Scheme 6.49 Preparation of tetrahydrodipyrazolopyridines via a 6-CR in water...

Scheme 6.50 Preparation of spiropyridoindolepyrrolidines via a 6-CR in the p...

Scheme 6.51 Preparation of spiropyridoindoles via a 6-CR in the presence of ...

Scheme 6.52 Preparation of spiro-1,2,4-triazine derivativesvia a 6-CR in the...

Chapter 7

Scheme 7.1 General representation of various pericyclic reactions.

Scheme 7.2 (a) The first ever [4+2] cycloaddition by Diels and Alder; (b) ea...

Scheme 7.3 Enhanced reaction rates in water for an intermolecular Diels–Alde...

Scheme 7.4 D–A reaction of 2-PyMe

2

Si-substituted 1,3-dienes with

p-

benzoquin...

Scheme 7.5 Comparison of e

ndo-/exo

-product ratios during the Diels–Alder rea...

Scheme 7.6 First example of intramolecular Diels–Alder reactions in water.

Scheme 7.7 “On-water” Diels–Alder reaction.

Scheme 7.8 Rate enhancement for the [3+2] cycloaddition of norbornene and ph...

Scheme 7.9 The water-mediated, 1,3-dipolar cycloaddition reactions of (a) 5-...

Scheme 7.10 Synthesis of functionalized pyridines using [2+2+2] cycloadditio...

Scheme 7.11 [4+3] Cycloaddition reactions in water.

Scheme 7.12 [5+2] Cycloaddition reactions in-water.

Scheme 7.13 [2+2] Cycloaddition of coumarin in-water.

Scheme 7.14 (a) First 4π-electrocyclic reaction in...

Scheme 7.15 Transformation of furfural into 4,5-dimorpholinocyclopent 2-enon...

Scheme 7.16 (a) One-pot, domino Knoevenagel-6π-elec...

Scheme 7.17 (a) First aqueous Claisen rearrangement of chorismate to prephen...

Scheme 7.18 The [2,3]-sigmatropic rearrangement of (a) allylic sulfoxides (M...

Scheme 7.19 On-water ene reaction of azodicarboxylates and olefins.

Chapter 8

Figure 8.1 Ruthenium-based olefin metathesis catalysts.

Figure 8.2 Ionic and non-ionic group-tagged ruthenium-based metathesis catal...

Scheme 8.1 RCM reactions of hydrophilic dienes catalyzed by a PEG-substitute...

Figure 8.3 Water-soluble first-generation Grubbs catalyst derivatives.

Figure 8.4 Hoveyda–Grubbs catalysts bearing quaternary ammonium groups.

Scheme 8.2 Latent ruthenium metathesis catalysts for aqueous ROMP and RCM re...

Figure 8.5 PEG-substituted Hoveyda–Grubbs second-generation catalysts.

Scheme 8.3 ROMP of hydrophilic norbornene derivative in water using PEG-subs...

Figure 8.6 Grubbs and Hoveyda–Grubbs catalysts immobilized on amphiphilic po...

Scheme 8.4 Hoveyda–Grubbs second-generation catalyst supported on poly(4-oxa...

Figure 8.7 Various ionic and non-ionic surfactants for aqueous olefin metath...

Scheme 8.5 Sequential cross-metathesis and transfer hydrogenation in water....

Figure 8.8 Dextrin and alginate-based olefin metathesis catalyst systems.

Scheme 8.6 RCM reactions catalyzed by

33

and

34

.

Chapter 9

Scheme 9.1 Mn-catalyzed partial oxidation of aryl and aliphatic alcohols.

Scheme 9.2 Mo

VI

complex-catalyzed epoxidation of alkenes in water.

Scheme 9.3 Titanosilicate/H

2

O

2

catalyzed epoxidation of propylene in water....

Scheme 9.4 Ir-catalyzed partial oxidation of aryl and aliphatic alcohols.

Scheme 9.5 Photocatalyzed oxidation of alcohol to the corresponding aldehyde...

Scheme 9.6 Ru-catalyzed oxidation of aryl and aliphatic primary alcohols to ...

Scheme 9.7 I

2

/NaOH/TBHP-catalyzed oxidation of alcohols and aldehydes to car...

Scheme 9.8 Cl

−

ion-catalyzed oxidation of alcohols to carboxylic acids...

Scheme 9.9 Oxidation of aryl ketones and benzyl nitrile derivatives to carbo...

Scheme 9.10 Oxidation of furfural to furancarboxylic acid in water.

Scheme 9.11 Oxidation of aldehydes to carboxylic acids in water.

Scheme 9.12 Transfer hydrogenation of ketones utilizing formic acid as the h...

Scheme 9.13 Chemoselective reduction of α,β-...

Scheme 9.14 Asymmetric transfer hydrogenation of quinolines and

N

-heteroaryl...

Scheme 9.15 Asymmetric transfer hydrogenation of quinolone derivatives.

Scheme 9.16 Ruthenium-catalyzed transfer hydrogenation of carbonyl compounds...

Scheme 9.17 Hydrogenation of olefins.

Scheme 9.18 Palladium(0)nanoparticle-catalyzed reduction of epoxides.

Scheme 9.19 Reduction of nitroarenes via heterogeneous Pd catalysis.

Scheme 9.20 Surfactant-type catalyst for the asymmetric transfer hydrogenati...

Scheme 9.21 Nano-Ni

2

P as hydrogenation catalyst.

Scheme 9.22 Selective reduction of furfural to furfuryl alcohol catalyzed by...

Scheme 9.23 Electrocatalytic reduction of nitrite catalyzed by iron complex....

Scheme 9.24 Co nanocluster-catalyzed hydrogenation of furfural.

Scheme 9.25 Reduction of 2- and 4-nitroanilines.

Scheme 9.26 Selective reduction of cinnamaldehyde to cinnamyl alcohol using ...

Scheme 9.27 Reduction of carbonyl compounds in water utilizing hydrogen sulf...

Chapter 10

Scheme 10.1 Oxidation of benzylic sp

3

C–H in water.

Scheme 10.2 Cobalt-catalyzed peroxidation of 2-oxindoles in water.

Scheme 10.3 Oxidative radical addition of aryl hydrazines in water.

Scheme 10.4 Copper(II)-catalyzed trifluoromethylation of

N

-aryl acrylamides ...

Scheme 10.5 Metal-catalyzed C–H bond trifluoromethylation in water.

Scheme 10.6 Silver-catalyzed decarboxylative allylation in water.

Scheme 10.7 Silver-catalyzed decarboxylative trifluoromethylthiolation in wa...

Scheme 10.8 Copper-catalyzed difunctionalization of alkene in water.

Scheme 10.9 Copper-catalyzed S-methylation of sulfonyl hydrazidesin water.

Scheme 10.10 Atom transfer radical cyclization of 2-iodoacetamidein water.

Scheme 10.11 DEPO-mediated arylation of lactamsin water.

Scheme 10.12 Radical deoxygenation of alcohols and intermolecular C–C bond f...

Scheme 10.13 C–S bond formation in water.

Scheme 10.14 Intramolecular oxidative radical cyclization of

N

-substituted 2...

Scheme 10.15 Na

2

S

2

O

8

-mediated efficient synthesis of isothiocyanates in wate...

Scheme 10.16 K

2

S

2

O

8

-mediated synthesis and functionalization of heterocycles...

Scheme 10.17 Radical cyclization reaction of 1,6-enynes with sulfonyl hydraz...

Scheme 10.18 Three types of radical cyclization of 1,6-enynes with sulfonyl ...

Scheme 10.19 Radical cyclization of 2-arylbenzoimidazoles with unactivated a...

Scheme 10.20 C(sp

3

)−H hydroxylation of 2-oxindoles in water.

Scheme 10.21 Ionic liquid promoted C–H bond oxidant cross-coupling reaction ...

Scheme 10.22 KI/TBHP-catalyzed C(sp

3

)–H functionalization/C–O/C–N bond forma...

Scheme 10.23 Hydrosilylation of triple-bonded substrates in water.

Scheme 10.24 Three-component reactions of naphthol, aldehyde, and tetrahydro...

Scheme 10.25 Radical coupling reactions of oxindoles with

t

-BuONO.

Scheme 10.26 Catalyst-free fluorination in water.

Scheme 10.27 Iodine-catalyzed amination of benzothiazolesin water.

Scheme 10.28 Addition of diaryl phosphine oxide to alkyne in water.

Scheme 10.29 Visible-light-driven epoxyacylation and hydroacylation of olefi...

Scheme 10.30 Remote 1,5-trifluoromethylthio-sulfonylation of vinylcyclopropa...

Scheme 10.31 Visible-light-induced sulfonylation of alkenes with sulfonyl ch...

Scheme 10.32 An amphiphilic iridium catalyst mediated difunctionalization of...

Scheme 10.33 Visible light induced Meerwein hydration reaction in water.

Scheme 10.34 Visible light induced dehydrogenative aza-coupling of 1,3-dione...

Scheme 10.35 Visible light induced cross-dehydrogenative coupling in water....

Chapter 11

Scheme 11.1 Iron-catalyzed cyclopropanation of trifluoroethylamine hydrochlo...

Scheme 11.2 Iron-catalyzed cyclopropanation with

in situ

generation of diazo...

Scheme 11.3 Rhodium-catalyzed cyclopropenation in water.

Scheme 11.4 Blue light-promoted cyclopropenizations in water.

Scheme 11.5 Rh(II)-catalyzed intramolecular C–H insertion of diazo substrate...

Scheme 11.6 Iridium-catalyzed carbene insertion into N–H bonds in water.

Scheme 11.7 Difluoromethylation of alcohols with TMSCF

2

Br in water.

Scheme 11.8 C2-Functionalization of 1-substituted imidazoles in water.

Scheme 11.9 Silver(I)-promoted intramolecular addition in water.

Scheme 11.10

N

-Heterocyclic carbene-catalyzed asymmetric benzoin reaction in...

Scheme 11.11 Aza-Michael addition reaction in water.

Scheme 11.12 NHC-catalyzed reactions of enalsin water.

Scheme 11.13 Reaction of enals with isatins with the use of brine as reactio...

Chapter 12

Scheme 12.1 [Nmm-PDO][OAc] and [Nmp-PDO][OAc]-catalyzed reactions in-water....

Scheme 12.2 Pharmaceutically relevant cyano compounds were synthesized

via

t...

Scheme 12.3 Cu-catalyzed Michael addition reaction in aqueous media.

Scheme 12.4 Synthesis of

β-

amino carbonyl compounds via HybPOM/HPW

12

an...

Scheme 12.5 Synthesis of 3,4-dihydro-2-quinolones using Cu-catalyzed alkyne ...

Scheme 12.6 Synthesis of 4-hydroxy-4H-chromene barbiturates and 4-hydroxy-4H...

Scheme 12.7 S

N

Ar reaction using TPGS-750-M and K

3

PO

4

in water.

Scheme 12.8 S

N

Ar reactions of various N, O, and S nucleophiles in the HMPC–w...

Scheme 12.9 Palladium-catalyzed nucleophilic substitution of alcohols and th...

Scheme 12.10 Bu

4

NHSO

4

-catalyzed pyrazole

N

-allylation in an aqueous medium....

Chapter 13

Scheme 13.1 Asymmetric reduction of ketones in water using chiral surfactant...

Scheme 13.2 Asymmetric transfer hydrogenation of imines and iminiums in wate...

Scheme 13.3 Asymmetric epoxidation of allylic alcohols in water using chiral...

Scheme 13.4 Asymmetric sulfoxidation of sulfides in water using [Fe(salan)] ...

Scheme 13.5 Asymmetric Barbier-type allylation of ketones in water using chi...

Scheme 13.6 Asymmetric three-component alkynylation of aldehydes in water us...

Scheme 13.7 Asymmetric Friedel–Crafts-type reaction of indoles in water usin...

Scheme 13.8 Asymmetric aldol reaction of formaldehyde in water using chiral ...

Scheme 13.9 Asymmetric ring opening of

meso

-epoxides using amines in water u...

Scheme 13.10 Asymmetric thia-Michael addition/protonation of thiols in water...

Scheme 13.11 Asymmetric boron conjugate additions in water using a [Cu] cata...

Scheme 13.12 Asymmetric silyl conjugate additions in water using a [Cu] cata...

Scheme 13.13 Asymmetric direct aldol reaction of ketones to aldehydes in wat...

Scheme 13.14 Asymmetric direct aldol reaction in water using a polymer-suppo...

Scheme 13.15 Asymmetric direct Michael reaction of...

Scheme 13.16 Asymmetric direct Michael reaction in water using a superparama...

Scheme 13.17 Asymmetric Diels–Alder reaction in water using a chiral imidazo...

Scheme 13.18 Asymmetric Diels–Alder reaction in water using a chiral diarylp...

Scheme 13.19 Asymmetric transfer hydrogenation in water using a chiral phosp...

Scheme 13.20 Asymmetric Michael addition of malonates to...

Scheme 13.21 Asymmetric Michael addition of DTMs to β...

Scheme 13.22 Asymmetric Mannich reaction of DTMs...

Scheme 13.23 Asymmetric Mannich reaction of malonates to aryl

N

-Boc imines o...

Scheme 13.24 Asymmetric thiolation in water using chiral

tert

-amine squarami...

Scheme 13.25 Asymmetric protonation in water using a chiral

tert

-amine thiou...

Scheme 13.26 Synergistic Brønsted acid-hydrogen bonding...

Chapter 14

Scheme 14.1 Synthesis of decahydroacridine-1,8-diones (

5

) and dihydropyrido[...

Scheme 14.2 Microwave-assisted synthesis of the DCGS.

Scheme 14.3 DCGS-catalyzed one-pot four-component synthesis of 2-amino-4-sub...

Scheme 14.4 Citric acid-catalyzed one-pot pseudo five-component synthesis of...

Scheme 14.5 Ascorbic acid-catalyzed synthesis of 2-substituted-2,3-dihydroqu...

Scheme 14.6 Taurine-catalyzed synthesis of novel 1,2-(dihydroquinazolin-3(4

H

Scheme 14.7 Squaric acid-catalyzed synthesis of 2,3-dihydro-1

H

-perimidines (

Scheme 14.8 Iodine-catalyzed synthesis of 2-arylimidazo[1,2-

a

]pyridines (

25

)...

Scheme 14.9 Thiamine hydrochloride-catalyzed synthesis of 1,2,4-triazolidine...

Scheme 14.10 Ultrasound-assisted, triethylamine-catalyzed synthesis of dieth...

Scheme 14.11 SDS-catalyzed synthesis of 2-amino-3-cyano-4-aryltetrahydrobenz...

Scheme 14.12 Plausible mechanism and the role of SDS as catalyst for the syn...

Scheme 14.13 SDS-catalyzed synthesis of spiropyrans in water.

Scheme 14.14

L

-prolinamide-catalyzed synthesis of 2-aryl-3-nitro-2

H

-chromene...

Scheme 14.15 4-Dimethylaminopyridine-catalyzed synthesis of 2-amino-4-aryl-4

Scheme 14.16 SDS-catalyzed synthesis of 2-amino-3-cyano-4-substitued-4

H

-chro...

Scheme 14.17 Proposed mechanism for the synthesis of 2-amino-3-cyano-4-subst...

Scheme 14.18 Baker’s yeast-catalyzed synthesis of tetrahydrobenzo[

a

]xanthene...

Scheme 14.19 Taurine-catalyzed synthesis of pyrano[3,2-

c

]quinolone derivativ...

Scheme 14.20

L

-proline-catalyzed synthesis of chromeno[4,3-

d

]pyrimidines in ...

Scheme 14.21 Succinic acid-catalyzed synthesis of 3,4-disubstituted isoxazol...

Scheme 14.22

L

-proline-catalyzed synthesis of chromeno[4,3-

b

]pyrano[3,4-

e

]py...

Scheme 14.23 DBU-catalyzed 4

H

-pyrimido[2,1-

b

]benzothiazole derivatives in mi...

Scheme 14.24

L

-proline-catalyzed synthesis of spiro[benzothiazolo[3,2-

a

]pyri...

Scheme 14.25 Choline hydroxide-catalyzed synthesis of...

Scheme 14.26

L

-proline-catalyzed synthesis of (

E

)-nitroalkenes in water

via

...

Scheme 14.27 Guanidine hydrochloride-catalyzed synthesis of

bis

(pyrazol-4-yl...

Scheme 14.28 Benzo[

d

]pyrazolo[5,1-

b

][1,3]iodazol-4-ium salt-catalyzed synthe...

Scheme 14.29

L

-valine-catalyzed synthesis of 2-aminobenzothiazolomethyl naph...

Scheme 14.30 Synthesis of

bis

(coumarin-3-yl)arylmethanes using proline-deriv...

Scheme 14.31 Mandelic acid or itaconic acid-catalyzed synthesis of 2-aminobe...

Scheme 14.32

L

-proline-catalyzed synthesis of 4-hydroxy-4

H

-chromene-function...

Scheme 14.33 Asymmetric

exo

-selective Diels–Alder reaction in water. OTMS, o...

Scheme 14.34 D-Glucosamine-based β-CD inclusion...

Scheme 14.35 A novel proline-based amide-catalyzed asymmetric Aldol reaction...

Scheme 14.36 Asymmetric Aldol reaction in water using an isothiouronium salt...

Scheme 14.37 C

2

-symmetric tertiary amine-squaramide-catalyzed asymmetric Mic...

Scheme 14.38 Asymmetric Michael addition in water using pyrrolidine-based tr...

Scheme 14.39 Asymmetric Michael addition reaction using proline-derived hydr...

Scheme 14.40 Asymmetric Michael addition reaction using aDPEN-based thiourea...

Scheme 14.41 Asymmetric Michael addition reaction between phenylmaleimide de...

Scheme 14.42 Asymmetric Michael addition reaction between...

Scheme 14.43 Asymmetric Michael addition reaction using proline-derived bifu...

Chapter 15

Scheme 15.1 (a) Direct vs. mediated reductive oxidation; (b) direct vs. medi...

Figure 15.1 Electron conduction, the mobility of species and ions, and elect...

Figure 15.2 (a) Traditional water electrolysis; (b) overall water electrolys...

Figure 15.3 Flow chart of single-pass Kolbe electrolysis in water.

Scheme 15.2 Kolbe reaction for the conversion of: (a) valeric acid to

n

-Octa...

Figure 15.4 Diagramv showing the formation of hydrogen during the electrocat...

Figure 15.5 Electrochemical set up for the synthesis of thick Zn films.

Scheme 15.3 (a) Electrochemical deoxygenation of epoxidesinto alkenes; (b) z...

Scheme 15.4 (a) Cu/Pd-catalyzed allylic alkylations; (b) Co-catalyzed C–H/N–...

Scheme 15.5 (a) Electrochemical oxidation of benzylic C–H and its proposed m...

Scheme 15.6 (a) Electrochemical Birch reduction on aqueous media; (b) electr...

Scheme 15.7 The anodic oxidation of primary amine to nitrile in aqueous medi...

Scheme 15.8 (a) Electrochemical atom transfer radical polymerization (ATRP);...

Scheme 15.9 (a) Possible products of the ECH of furfural (

6

). (b) ECH of

39

...

Scheme 15.10 (a) The oxidative electrochemical synthesis of bromohydrin in D...

Scheme 15.11 (a) Hydrodeoxygenation of levulenic acid

52

to valeric acid

53

;...

Chapter 16

Scheme 16.1 (a) Water-soluble Ir-based photocatalysts; (b) trifluoromethylat...

Scheme 16.2 PQS-attached photocatalyst and conversion of alkenes

4

and enol ...

Scheme 16.3 Conversion of

o

-chlorobenzamides

10

to either

11

or

12

depending...

Scheme 16.4 Use of meglumine as an additive for photochemical cross-coupling...

Scheme 16.5 Deboronative cyanation is promoted by a Ru-based photocatalyst....

Scheme 16.6 LUMO-lowering effect of water in the photocatalytic cross-coupli...

Scheme 16.7 (a) Effect of water in the chemoselective formation of alkylated...

Scheme 16.8 Cross-coupling cleavage of C(

sp

2

)–Y bonds at the water-oil inter...

Scheme 16.9 Discovery of fatty acids decarboxylase (FAP).

Scheme 16.10 Dynamic kinetic resolution of amines by using lipases.

Scheme 16.11 Merging of photoredox and enzyme catalysis for the C–H function...

Chapter 17

Scheme 17.1 Oxidative esterification of primary alcohols.

Scheme 17.2 Conversion of methylarenes to aromatic carboxylic acids.

Figure 17.1 Regeneration of bromide/bromate.

Scheme 17.3 Synthesis of bromoxynil and ioxynil

.

Scheme 17.4 Synthesis of 2,6-dibromo-4-nitroaniline in an aqueous acidic med...

Scheme 17.5 Synthesis of bromohydrins, α...

Scheme 17.6 Intramolecular hydroamination in water.

Scheme 17.7 Labeling studies with D

2

O.

Scheme 17.8 Mechanism for water-mediated intramolecular hydroamination.

Scheme 17.9 Sulfenylation of imidazo[1,2-

a

]pyridine.

Guide

Cover

Table of Contents

Title Page

Copyright

Dedication

About the Editors

Preface

List of Abbreviations

Begin Reading

Index

End User License Agreement

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Organic Transformations in Water

Principles and Applications

Edited by Gopinathan Anilkumar, Nissy Ann Harry, and Sankuviruthiyil M. Ujwaldev

Editors

Prof. Gopinathan AnilkumarMahatma Gandhi UniversitySchool of Chemical SciencesKottayamKerala 686560India

Dr. Nissy Ann HarryCatholicate CollegePostgraduate and Research Department of ChemistryPathanamthittaKerala 689645India

Dr. Sankuviruthiyil M. UjwaldevSree Kerala Varma CollegePostgraduate and Research Department of ChemistryThrissurKerala 680011India

Cover Images: © WhiteJack/Alamy Stock Photo, © Chemical structure was kindly provided by G. Anilkumar, N.A. Harry, S.M. Ujwaldev.

All books published by WILEY-VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.

Library of Congress Card No.: applied for

British Library Cataloguing-in-Publication DataA catalogue record for this book is available from the British Library.

Bibliographic information published by the Deutsche NationalbibliothekThe Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at <http://dnb.d-nb.de>.

© 2025 WILEY-VCH GmbH, Boschstraße 12, 69469 Weinheim, Germany

All rights reserved (including those of translation into other languages, text and data mining and training of artificial technologies or similar technologies). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law.

Print ISBN: 978-3-527-35377-4

ePDF ISBN: 978-3-527-84683-2

ePub ISBN: 978-3-527-84682-5

oBook ISBN: 978-3-527-84684-9

Dedicated with profound reverence and gratitude to Professor Dr. Vijay Nair for instilling passion for organic chemistry in the minds of young researchers, nurturing and caring them, moulding them into fine organic chemists, enlightening them, profusely inspiring them through his gentle and distinguished manner, revolutionizing organic synthesis by his unique and unparalleled contributions and for touching the life of one of us (GA) by mentoring him into the fascinating world of organic synthesis.

About the Editors

Gopinathan Anilkumar was born in Kerala, India, and took his PhD in 1996 from Regional Research Laboratory (renamed as National Institute for Interdisciplinary Science and Technology NIIST-CSIR), Trivandrum, with Dr. Vijay Nair. He did postdoctoral studies at University of Nijmegen, The Netherlands (with Professor Binne Zwanenburg), Osaka University, Japan (with Professor Yasuyuki Kita), Temple University, USA (with Professor Franklin A. Davis), and Leibniz-Institut für Katalyse (LIKAT), Rostock, Germany (with Professor Matthias Beller). He was a senior scientist at AstraZeneca (India). Currently, he is a professor in Organic Chemistry at the School of Chemical Sciences, Mahatma Gandhi University in Kerala, India. His research interests are in the areas of organic synthesis, medicinal chemistry, heterocycles, and catalysis. He has published more than 210 papers in peer-reviewed journals, 7 patents, 10 book chapters, and edited two books entitled “Copper Catalysis in Organic Synthesis” (Wiley-VCH, 2020) and “Green Organic Reactions” (Springer, 2021). He has received Dr. S. Vasudev Award from Govt of Kerala, India, for best research (2016) and Evonik research proposal competition award (second prize 2016). He is a fellow of the Royal Society of Chemistry (UK).

Nissy Ann Harry was born in Kerala, India. She obtained her PhD in organic chemistry from the School of Chemical Sciences, Mahatma Gandhi University, in 2021 under the guidance of Dr. Gopinathan Anilkumar. She has published over 30 papers in peer-reviewed journals and 3 book chapters. She is currently working as an assistant professor in the Postgraduate and Research Department of Chemistry, Catholicate College, Pathanamthitta, Kerala. Her research interests include organic synthesis, catalysis, and green chemistry.

Sankuviruthiyil M. Ujwaldev was born in Kerala, India. He obtained his PhD in organic chemistry from the School of Chemical Sciences, Mahatma Gandhi University, in 2021 under the guidance of Dr. Gopinathan Anilkumar. He has published over 26 papers in peer-reviewed journals and 2 book chapters. He is currently working as an assistant professor in the Postgraduate and Research Department of Chemistry, Sree Kerala Varma College, Thrissur, Kerala.

Preface

Water forms the greenest solvent available for chemical reactions in response to nature’s plea for safer chemistry. Solvents comprise a large portion of the overall mass handled in a chemical reaction, thus selecting the right one is crucial. In addition to being inexpensive and benign for the environment, using water as a solvent also produces entirely new reactivity. Water is now employed as an imperative solvent in a wide range of reactions, including oxidation–reduction processes, C–H activations, radical reactions, pericyclic reactions, transition-metal catalysis, and so forth. The switch from conventional organic solvents to green solvents is long overdue. The prime goal of this book is to draw more attention to green organic synthesis among researchers. The chapters are designed to explicate the importance and potency of “nature’s reaction solvent” in organic synthesis. This book addresses many aspects of organic synthesis in water, and the 17 chapters demonstrate the complexity and the rapid progress of many areas in this field.

The first chapter comprises a general introduction to organic transformations in water, discussing its historical developments and contributions to green chemistry. The next chapter discusses “on-water reactions” focusing on the mechanistic aspects as well as on a range of reaction types. The third chapter deals with micellar and phase-transfer catalysis that enables the desired transformations to occur in mild aqueous conditions without the need for hazardous organic solvents. In the next chapter, physicochemical aspects and the complex phase behaviors and mechanisms of “on-water” and “in-water” reactions are explained. The fifth chapter focuses on the direct functionalization of inert C–H bonds, in aqueous environments, offering significant advantages in terms of sustainability, safety, and biocompatibility. Performing multicomponent reactions (MCRs) in water offers a more sustainable and environmentally friendly approach to the synthesis of bioactive heterocyclic compounds, which is discussed in the next chapter. The seventh chapter describes the influence of water on the reaction rates, regio- and stereochemical outcomes of pericyclic reactions such as cycloaddition reactions, electrocyclic reactions, sigmatropic rearrangements, and group transfer reactions. Recent progress in olefin metathesis in water is portrayed in Chapter 8, with special reference to water-compatible homogeneous and heterogeneous ruthenium metathesis catalyst systems. Chapter 9 addresses the advances over the past few years in oxidation and reduction reactions using water as the reaction medium. Chapter 10 aims to summarize the recent advances in radical reactions in water, categorizing them according to different catalytic modes. The next chapter primarily delves into synthetic transformations involving carbene intermediates in water. Water as a suitable medium in several nucleophilic additions and substitution reactions in water is showcased in Chapter 12. Chapter 13 explores the advancements and current state of asymmetric synthesis in bulk water using advanced small molecular catalysts, including chiral metal complexes and organocatalysts. The next chapter surveys the recent literature on the synthesis of structurally diverse organic scaffolds utilizing various metal-free organic substances in the aqueous medium. Establishing electroorganic procedures that can be performed in an aqueous solution is the main focus of Chapter 15. Chapter 16 gives an overview of photocatalytic synthetic methods by using water as a reaction medium, by merging the innate green properties of water with the exploitation of a renewable energy source, such as light. Finally, the last chapter illustrates the industrially important organic reactions carried out in the aqueous medium.

Although aqueous organic chemistry has extensive applications and a bright future, this subject is unfocused in current organic textbooks. Leading researchers in the field of organic synthesis from academics across the globe have contributed to this book. This book will be a very valuable reference source for students, postgraduates, research scholars, professors, industrialists, and scientists. We hope our vision to clutch the attention of researchers more toward green organic synthesis will be successful through this book.

KottayamSeptember 2024     

Gopinathan Anilkumar

Nissy Ann Harry

Sankuviruthiyil M. Ujwaldev

List of Abbreviations

A3

aldehyde-alkyne-amine

ABNO

9-azabicyclo[3.3.1]nonane

N

-oxyl

ADH

alcohol dehydrogenase

API

active pharmaceutical ingredient

ATRP

atom transfer radical polymerization

BIMs

bis(indolyl)methanes

BMIDA

boronic acid

N

-methyliminodiacetic acid

Bpy

bipyridine

BVMs

Baeyer–Villiger monooxygenases

C-H

carbon–hydrogen

C4A4

calix[4]arene tetracarboxylic acid

cBRIDP

di-

t

-butyl(2,2-diphenyl-1-methyl-1-cyclopropyl)phosphine

CDC

cross dehydrogenative coupling

CE

coulombic efficiency

CFP

carbon fiber paper

COMU

1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholinocarbenium hexafluorophosphate

Cryo-TEM

cryogenic transmission electron microscopy

CSTR

continuously stirred tank reactor

CTAB

cetrimonium bromide

CTAC

cetyltrimethylammonium chloride

CTF

covalent triazine framework

β-CD

β-cyclodextrin

CZA

citrazinic acid

CoQ10

coenzyme Q10

D-A

Diels–Alder

DABCO

1,4-diazabicyclo[2.2.2]octane

DBPNA

2,6-dibromo-4-nitroaniline

DBSA

4-dodecylbenzene sulfonic acid

DBU

1,8-diazabicyclo[5.4.0]undec-7-ene

DCGS

diester cationic gemini surfactant

DCILs

dicationic ionic liquids

DCM

dichloromethane

DEAD

diethyl azodicarboxylate

DELs

DNA-encoded libraries

DEPO

diethylphosphine oxide

DFT

density functional theory

DG

directing group

DIPEA

N

,

N

-di-isopropylethylamine

DLS

dynamic light scattering

DMAD

dimethyl azodicarboxylate

DMC

dimethyl carbonate

DMF

dimethylformamide

DmgH

dimethylglyox

DPBS

Dulbecco’s phosphate buffered saline

DPEN

1,2-diphenyl-1,2-ethylenediamine

DTBP

di-

tert

-butyl peroxide

DTMs

dithiomalonates

E factor

environmental factor

EAN

ethyl ammonium nitrate

ECH

electrocatalytic hydrogenation

EDA

electron donor–acceptor

EDA

ethylenediamine

EDC

1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide

EDTA

ethylenediaminetetraaceticacid

EHS

environment health safety

ERED

Ene-reductase

et al.

et alia

EnT

energy transfer

FAD

flavin adenine dinucleotide

FAP

fatty acid photodecarboxylase

FDCA

2,5-furan dicarboxylic acid

FMO

frontier molecular orbital

G1

Grubbs first-generation catalyst

G2

Grubbs second-generation catalyst

GBB

Groebke–Blackburn–Bienayme

HAT

hydrogen atom transfer

HATU

hexafluorophosphate azabenzotriazole tetramethyl uronium

HBD

hydrogen bond donors

HE

Hantzsch ester

HER

hydrogen evolution reaction

HFIP

1,1,1,3,3,3-hexafluoroisopropanol

HG

Hoveyda–Grubbs

HMPC

hydroxypropyl methylcellulose

i-GAL

innovation green aspiration level

I-MCRs

isocyanide-based multicomponent reaction

KREDs

ketoreductases

LUMO

lowest unoccupied molecular orbital

MCCA

medium-chain carboxylic acids

MCR

multicomponent reaction

MNPs

magnetic nanoparticles

MO

molecular orbital

MOF

metal-organic framework

Mpg-CN

mesoporous graphitic carbon nitride

MVK

methyl vinyl ketone

MVS

methyl vinyl sulfone

MWCNTs MNCs

multiwalled carbon nanotubes magnetic nanocomposites

MWI

microwave irradiation

NADPH

nicotinamide adenine dinucleotide phosphate hydrogen

NGO

N

-doped graphene oxide

NHC

N

-heterocyclic carbene

Ni-MPA

Ni

II

-3-mercaptopropionic acid

NMP

N

-methylpyrrolidone

NMR

nuclear magnetic resonance

NP

nanoparticle

OBBD

B-alkyl-9-oxa-10-borabicyclo[3.3.2]decane

oCB

oxidised carbon black

OEOMA

oligo(ethylene oxide) methyl ether methacrylate

OER

oxygen evolution reaction

OFRs

oscillatory plug flow reactor

o-QMs

ortho

-quinone methides

ORR

oxygen reduction reaction

PAA

polyacrylic acid

PBAM-ran-PHPAM

poly(

N

-(benzyl acrylamide))-ran-poly(

N

-(2-hydroxypropyl)acrylamide)

PCET

proton-coupled-electron-transfer

PChlide

protochlorophyllide

pDApr

polydiacetylene-proline

PEG

polyethylene glycol

pH

potential of hydrogen

PHU

1-(3,5-bis(trifluoromethyl)phenyl)-3-((R)-phenyl((S)-pyrrolidin-2-yl)methyl)urea

PIDA

poly(diiododiacetylene)

PIL

polymer ionic liquid

PILs

protic ionic liquids

PMI

process mass intensity

ppm

parts per million

PQS

polyethyleneglycol ubiquinol succinate

PTC

phase transfer catalysis

PTS

polyoxyethanyl-α-tocopheryl sebacate

RCM

ring-closing metathesis

RDS

rate determining step

ROMP

ring-opening metathesis polymerization

RT

room temperature

SCF

supercritical fluids

SDOSS

sodium dioctyl sulfosuccinate

SDS

sodium dodecyl sulfate

SERS

surface-enhanced Raman spectroscopy

SET

single electron transfer

SM

Suzuki-Miyaura

SN1

substitution nucleophilic unimolecular

SN2

substitution nucleophilic bimolecular

SNAr

nucleophilic aromatic substitution

SS

stainless-steel

STY

space-time-yield

TBAC

tetrabutylammonium chloride

TBAI

tetra-

n

-butylammonium iodide

TBAOH

tetrabutyl ammonium hydroxide

TBHP

tert

-butyl hydroperoxide

TEA

triethyl amine

TEM

transmission electron microscopy

TEMPO

(2,2,6,6-tetramethylpiperidin-1-yl)oxyl

TFA

trifluoroacetic acid

TFE

2,2,2-trifluoroethanol

THAC

tetrahexylammonium chloride

THF

tetrahydrofuran

TMEDA

N

,

N

,

N

′,

N

′-tetramethylethylenediamine

TOF

turnover frequencies

TON

turnover number

TPGS-750-M

DL-α-tocopherol methoxypolyethylene glycol succinate solution

TPP

tetraphenyl phosphonium

TPPMS

sodium diphenylphosphinobenzene-3-sulfonate

TRIP

R-3,3′-Bis(2,4,6-triisopropylphenyl)-1,1′-binaphthyl-2,2′-diyl hydrogenphosphate

Trpy

terpyridine

VFD

vortex fluidic devices

WERSA

water extract of rice straw ash

XPhos

dicyclohexyl[2′,4′,6′-tris(propan-2-yl)[1,1′-biphenyl]-2-yl]phosphane

1An Introduction to Organic Transformations in Water

Nissy Ann Harry1 and Gopinathan Anilkumar2,3

1Catholicate College, Postgraduate and Research Department of Chemistry, Pathanamthitta, Kerala 689645, India

2Mahatma Gandhi University, School of Chemical Sciences, Priyadarsini Hills PO, Kottayam, Kerala 686560, India

3Mahatma Gandhi University, Institute for Integrated programs and Research in Basic Sciences (IIRBS), Priyadarsini Hills PO, Kottayam, Kerala 686560, India

1.1 The Emergence of Water as a Solvent in Organic Chemistry

A world without the plethora of goods produced by industrial organic synthesis is inconceivable in terms of societal welfare. Environmental concerns have been raising their head since the 1940s, coinciding with the expansion of industrial activity [1]. Merely a tiny percentage of the earth’s resources are transformed into the intended goods by chemical processes, producing copious amounts of toxic elements and pollutants.

Solvents comprise a significant portion of the total mass needed in a chemical process; therefore, selecting the right one is crucial. Water is the greenest solvent readily accessible and has the least negative environmental effects. The reaction solvent utilized by nature is water. It is an inexhaustible naturally occurring, nonflammable, and abundant solvent. Other intriguing properties of water are the extensive hydrogen bonding, the pH of water can be changed, salts or surfactants can be added to provide salting-in or salting-out effects, and co-solvent or biphasic reaction systems can be used [2].

In 1828, Wohler’s urea synthesis was the first organic reaction to employ water as a solvent [3]. The synthesis of indigo by Baeyer and Drewsen in 1882 may be the first instance of real organic synthesis. A sodium hydroxide solution was added to a suspension of o-nitrobenzaldehyde in aqueous acetone during their synthesis. The distinctive blue color of indigo appeared instantly, and the product eventually precipitated. But later on, water was practically eliminated from reactions as a result of the development of organometallic chemistry. The availability of conventional solvents for several processes has improved due to advancements in the petrochemical industry. Also, there was a fallacy, “Corpora non agunt nisi fluida (or liquida) seu soluta” (“The substances do not react unless fluid or if dissolved”) [4]. This state of concern persisted until Breslow’s groundbreaking study in 1980 demonstrated how adding water could accelerate the Diels–Alder process (Scheme 1.1) [5]. Here, water continued to be the most effective medium. Furthermore, even faster rates were produced by the salting-out effect of LiCl, which further reduced the solubility of organic partners in water. In addition, the presence of guanidinium chloride acted to decrease hydrophobic interactions, which resulted in slower reactions. This eliminated the possibility that the dissolution of organic reactants was necessary.

Scheme 1.1 Acceleration of reaction rate by on-water protocol.

With the release of some masterworks by the Sharpless (Scheme 1.2) and Breslow groups, water has gained popularity as a reaction medium [6, 7]. Sharpless called these water-enhanced reactions between water-insoluble reactants “on-water reactions.”

Scheme 1.2 Comparison of the reactivity of quadricyclane with dimethyl azodicarboxylate in different solvents.

Butler, Coyne, and Fokin defined water-based reactions [8]. If the transition state occurs in bulk water and the substrate solubility is more than 0.01 mol l−1, the reaction is said to occur “in water”. Substrates that have a solubility of less than 10−5 mol l−1 in water and a transition state that takes place on the organic side of the interface are considered to be “on-water” conditions. Lastly, both reaction types are likely to happen simultaneously for reactants with intermediate solubilities [9]. In a most recent review, Kitanosono and Kobayashi suggested classifying all reactions that employ water as the reaction media as “in water,” regardless of the usage of catalysts [10]. Recently, several reports, reviews, and chapters were published showing the importance of water as a green organic solvent [11,12]. However, the water as a reaction medium is less focused on books [13]. Water is now exclusively employed as a green solvent in several organic transformations, such as cross-coupling reactions, C–H activations, multicomponent reactions [14–16].

1.2 Green Chemistry and Water

Green chemistry, established about two decades ago, has drawn much attention [17]. The design of chemical processes and products to minimize or eliminate the usage or production of hazardous compounds is referred to as “green chemistry,” or sustainable chemistry [18]. The choice of green solvents to reduce toxicity and pollution is a significant step toward implementing the twelve principles of green chemistry. Solvents make up between 50% and 80% of the mass in a chemical process. Solvents are an important factor that significantly influence the total toxicity profile of a chemical process.

They typically raise the most concerns regarding process safety issues because of their volatility, flammability, and potential for explosion under specific circumstances [19]. Green alternatives include solventless systems, supercritical fluids (SCF), green solvents like water, and, more recently, ionic liquids.

Among the 12 principles of green chemistry, the use of water as a solvent always increases the greenness and sometimes the efficiency of the reaction (Figure 1.1) [20].

Prevention of waste in a reaction is crucial for sustainable development. According to estimates, solvents make up over 60% of the mass of chemicals in the pharmaceutical and chemical sectors. Reuse of solvents is still rare, and the majority of these solvents are incinerated after use to recover energy, which has a significant negative influence on the environment and waste output [21]. Furthermore, burning organic solvents produces CO2, which is largely attributed to the waste output and, to a lesser extent, to climate change. The E factor, positive material identification (PMI), and other typical green chemistry metrics used in reactions conducted in organic solvents are frequently taken into consideration in quantitative studies of waste quantity production [22].

Figure 1.1 Diagrammatic representation of green chemistry principles.

Synthetic methods should be designed in such a way that all reactants that participate in the reaction are included in the final product. Hot-water-promoted, atom economic 1,3-rearrangements of cyclic allylic alcohols were reported (Scheme 1.3) [23]. Upon raising the temperature, the pKw of water increases, indicating a greater abundance of the strong base OH− and strong acid H3O+ compared to 25 °C. Raising the temperature also lowers the dielectric constant of water, improving its suitability as a solvent for organic molecules. In contrast to high-temperature water under pressure, hot water (between 60 and 100 °C) is more readily available in both natural and laboratory settings.

Scheme 1.3 1,3-Rearrangement of cyclic alcohols promoted by hot water.

The effective use of water as a solvent paves the way toward less hazardous chemical synthesis. The development of tandem and cascade reaction techniques, which combine as many reactions as feasible to yield the end product in a single operation, is crucial to the creation of greener synthetics. Jamison and coworker synthesized the essential component of the “ladder” polyether marine natural product through a biomimetic cascade cyclization in neutral water (Scheme 1.4) [24].

Scheme 1.4 Synthesis of polyether marine natural product in water.

Along with the advent of green chemistry concepts, the phrase “green solvent” was also created and several studies on the use of safer solvents and auxiliaries arose. To identify green solvents at an early stage, Capello et al. employed the EHS (E: Environment, H: Health, and S: Safety) assessment approach to rate standard organic and novel solvents (Table 1.1). The approach ranks solvents according to an EHS value between zero and nine using nine effect categories for a solvent, including flammability, risk of explosion, decomposition, and toxicity. An elevated EHS value denotes an elevated danger linked to the solvent. The EHS values of a few chosen solvents used in chemical synthesis are displayed in (Table 1.1) [25]. Water has an EHS value of 0 and is the safest solvent.

Table 1.1 Selected EHS values of solvents.

Source: Adapted from Capello et al. [25].

Solvent

EHS

Acetone

3.1

Dimethylether

3.9

Methanol

2.7

Acetonritrile

4.5

Ethanol

2.6

THF

3.9

Cyclohexane

4.0

Water

0

Anilkumar and coworkers reported the first iron-catalyzed coupling of aryl iodides with phenols in water as a solvent [26]. Diaryl ethers are produced in good-to-exceptional yields using a 1,2-dimethylethylenediamine (DMEDA) catalytic system and inexpensive and easily accessible FeCl3·6H2O in this synthesis (Scheme 1.5). Compatibility of this reaction with a broad variety of functional groups further demonstrated its efficiency. Furthermore, the process is made easier because this conversion is done in the presence of air. Therefore, the process offers a simple, affordable, and environmentally responsible method of obtaining diaryl ethers.

Scheme 1.5 Synthesis of diaryl ethers in water using iron catalysis.

Reducing derivatives is a key step to achieving green chemistry goals. The total synthesis efficiency is increased by the removal of laborious protection-deprotection procedures for specific acidic-hydrogen-containing functional groups when water is used as a solvent. The ability to use water-soluble hydroxyl groups directly without protection or deprotection is a significant benefit of reactions in water. This characteristic is helpful in the chemistry of carbohydrates, where protection and deprotection are frequently used [27]. For example, C-glycosides are potential enzyme inhibitors commonly used in total synthesis. The traditional protocols involve the addition of nucleophiles to a protected sugar while it is anhydrous. Water is now used as a solvent in an effective protocol that eliminates the need for laborious protection and deprotection processes (Scheme 1.6). Using commercially available D-glucose and pentane-2,4-dione as starting materials, a one-step synthesis of 38 β-C glycosidic ketone from an aqueous NaHCO3 solution in nearly quantifiable quantities was achieved [28].

Scheme 1.6 Single-step synthesis of β-C glycosidic ketone in water.

Catalysis via “in water” and “on-water” processes are known approaches [29]. Surfactants and the spontaneous development of micellar aqueous media, however, offer a more widely applicable and practical way to deal with the limited solubility of organic reagents and metal catalysts in water [30]. The hydrophobic effect in water forms aggregates that function as nanoreactors [31]. Higher local concentrations with rate enhancement and particular solvation effects result from this, which favorably influences the chemo-, regio-, and stereo-selectivity of the final product [32].

Amphiphilic surfactant Brij S-100 was employed for oxidative hydroxylation of aromatic boronic acids to phenols using CuCl2 as a catalyst in water without the need for bases or ligands (Scheme 1.7) [33]. The reaction proceeded smoothly with several electron-withdrawing and electron-donating boronic acids to afford the corresponding phenols in moderate-to-excellent yields.

Scheme 1.7 Oxidative hydroxylation of aromatic boronic acids to phenols.

The use of renewable feedstock like bio-based compounds over fossil-based chemicals marks another step toward green chemistry. Research teams have just lately begun to look into the use of biosurfactants in traditional micellar catalysis reactions, such as Pd-catalyzed cross-couplings. High biodegradability and biological synthesis from renewable feedstocks are the two greatest advantages of biosurfactants; these two key benefits will further encourage the use of biosurfactants in micellar catalysis [34].

Design for energy efficiency is a significant step toward green chemistry [35]. The synthesis of 2-substituted 2,3-dihydro-1H-perimidines on water using a unique, environmentally friendly, and energy-efficient protocol was reported by Anilkumar and coworkers [36]. Using a catalyst-free on-water technique at room temperature, 1,8-diaminonaphthalene is reacted with various aldehydes to produce the 2,3-dihydro-1H-perimidine product in 30 minutes with moderate-to-good yields (Scheme 1.8). A multigram scale reaction is also carried out to guarantee the reaction’s scalability.

Scheme 1.8 Energy-efficient synthesis of perimidines in water.

Designing for degradation and designing safer chemicals that are biodegradable or less harmful to the environment is of utmost importance [37, 38]. Petrochemical compounds are the primary source of surfactants used by the chemical industry. As a result, traditional neutral or anionic surfactants do not meet these criteria. In this sense, emerging designer surfactants mark a significant shift since all newly suggested amphiphilic molecules consist of bio-based units, at least in the hydrophobic portion. For use in the Ullmann type C–S coupling reaction in water mediated by copper salt, an intriguing new surfactant bearing a sugar unit for metal catalysis in water was described (Scheme 1.9). It connects a lactose hydrophilic unit to an aliphatic alkyl chain forming the alkyl lactosamine ALA-14, which is readily synthesized and naturally degradable [39].

Scheme 1.9 Ullmann C–S coupling using ALA14 in aqueous solution.

Reactions in water thus naturally contribute to inherently safer chemistry for accident prevention