Оглавление
Surya K. De. Applied Organic Chemistry
Table of Contents
List of Tables
List of Illustrations
Guide
Pages
Applied Organic Chemistry. Reaction Mechanisms and Experimental Procedures in Medicinal Chemistry
Copyright
Preface
About the Book
About the Author
Acknowledgments
List of Abbreviations
Polarity of Solvents
Common Solvents in Chemistry
References
List of Cooling Baths
Further Reading
1 Rearrangement Reactions
Baeyer–Villiger Oxidation or Rearrangement
Mechanism
Application
Experimental Procedure (from patent US 5142093A)
Dakin Oxidation (Reaction)
Mechanism
Application
Experimental Procedure (from patent EP0591799B)
Bamberger Rearrangement
Mechanism
Experimental Procedure (from patent CN102001954B)
Beckmann Rearrangement
Mechanism
Application
Experimental Procedure (general)
Preparation of Caprolactam (from patent US 3437655A)
Benzilic Acid Rearrangement
Mechanism
Application
Experimental Procedure (from patent US20100249451B)
Baker–Venkataraman Rearrangement
Mechanism
Application
Experimental Procedure (from patent CN105985306B)
Claisen Rearrangement
Mechanism
Application
Experimental Procedure (from patent WO2016004632A1)
Eschenmoser–Claisen Rearrangement
Mechanism
Ireland–Claisen Rearrangement
Mechanism
Johnson–Claisen Rearrangement
Mechanism
Overman Rearrangement
Mechanism
Cope Rearrangement
Mechanism
Application
Experimental Procedure (from patent US 4421934A)
Curtius Rearrangement
Mechanism
Application
Experimental Procedure (from patent EP2787002A1)
Demjanov Rearrangement
Mechanism
Application
Experimental Procedure (from Reference [14], copyright 2008, American Chemical Society)
Tiffeneau–Demjanov Rearrangement
Mechanism
Application
Experimental Procedure (from Reference [10], copyright, The Royal Society of Chemistry)
Fries Rearrangement
Mechanism
Application
Experimental Procedure (from patent US9440940B2)
Favorskii Rearrangement
Mechanism
Application
Experimental Procedure (from patent EP3248959A2)
Fischer–Hepp Rearrangement
Mechanism
Experimental Procedure (general)
Hofmann Rearrangement (Hofmann degradation of amide)
Mechanism
Application
Experimental Procedure (from patent CN105153023B)
Hofmann–Martius Rearrangement
Mechanism
Experimental Procedure (from patent DD295338A5)
Lossen Rearrangement
Mechanism
Application
Experimental Procedure (from patent EP2615082B1)
Orton Rearrangement
Mechanism
Pinacol–Pinacolone Rearrangement
Mechanism
Application
Experimental Procedure (general)
Rupe Rearrangement/Meyer–Schuster Rearrangement
Rupe Rearrangement
Meyer–Schuster Rearrangement
Mechanism
Application
Experimental Procedure (from patent US4088681A)
Schmidt Rearrangement or Schmidt Reaction
Mechanism
Application
Experimental Procedure (from patent WO2009026444A1)
Wagner–Meerwein Rearrangement
Mechanism
Application
Wolff Rearrangement
Mechanism
Alternatively
Application
Experimental Procedure (from patent US9175041B2)9175041B2
Arndt–Eistert Homologation or Synthesis
Mechanism
Application
Experimental Procedure (from patent US9399645B2)
Step 1
Step 2
Zinin Rearrangement or Benzidine and Semidine Rearrangements
Mechanism
Experimental Procedure (from patent US20090069602A1)
References. Baeyer–Villiger Oxidation or Rearrangement
Dakin Oxidation or Reaction
Bamberger Rearrangement
Beckmann Rearrangement
Benzilic Acid Rearrangement
Baker–Venkataraman Rearrangement
Claisen Rearrangement/Eschenmoser–Claisen Rearrangement/Ireland–Claisen Rearrangement/Johnson–Claisen Rearrangement/Overman Rearrangement
Cope Rearrangement
Curtius Rearrangement
Demjanov Rearrangement
Tiffeneau–Demjanov Rearrangement
Fries Rearrangement
Favorskii Rearrangement
Fischer–Hepp Rearrangement
Hofmann Rearrangement (Hofmann Degradation of Amide)
Hofmann–Martius Rearrangement
Lossen Rearrangement
Orton Rearrangement
Pinacol–Pinacolone Rearrangement
Rupe Rearrangement/Meyer–Schuster Rearrangement
Schmidt Rearrangement or Schmidt Reaction
Wagner–Meerwein Rearrangement
Wolff Rearrangement
Arndt–Eistert Homologation or Synthesis
Zinin Rearrangement or Benzidine and Semidine Rearrangements
2 Condensation Reaction
Aldol Condensation Reaction
Application
Experimental Procedure (general)
Enantioselective Aldol Reaction (from patent US 6919456B2)
Mukaiyama Aldol Reaction
Mechanism
Application
Experimental Procedure (from patent DE102013011081A1)
Evans Aldol Reaction
Mechanism
Application
Experimental Procedure (from patent WO2013151161A1)
Henry Reaction
Mechanism
Application
Experimental Procedure (from patent US 6919456B2)
Preparation of Chiral Catalyst
Nitro‐Aldol Reaction
Benzoin Condensation
Mechanism
Application
Experimental Procedure (from patent DE3019500C2)
Claisen Condensation
Mechanism
Application
Experimental Procedure (from patent US9884836B2)
Darzens Glycidic Ester Condensation
Mechanism
Application
Experimental Procedure (from patent JP2009512630A)
Dieckmann Condensation
Mechanism
Application
Experimental Procedure (from patent US 7132564 B2)
Knoevenagel Condensation
Mechanism
Application
Experimental Procedure (from patent WO2010136360A2)
Pechmann Condensation (synthesis of coumarin) (also called von Pechmann condensation)
Mechanism
Application
Experimental Procedure (from patent US7202272B2)
Perkin Condensation or Reaction
Mechanism
Application
Experimental Procedure (from patent US4933001A)
Stobbe Condensation
Mechanism
Application
Experimental Procedure (from patent US20160137682A1)
References. Aldol Condensation Reaction
Mukaiyama Aldol Reaction
Evans Aldol Reaction
Henry Reaction
Benzoin Condensation
Claisen Condensation
Darzens Glycidic Ester Condensation
Dieckmann Condensation
Knoevenagel Condensation
Pechmann Condensation
Perkin Condensation or Reaction
Stobbe Condensation
3 Olefination, Metathesis, and Epoxidation Reactions. Olefination. Corey–Winter Olefin Synthesis
Mechanism
Application
Experimental Procedure (from patent US5807866A)
Horner–Wadsworth–Emmons Reaction
Mechanism
Application
Experimental Procedure (from patent JPWO2015046403A1)
Julia–Lythgoe Olefination
Mechanism
Modified Julia Olefination
Mechanism
Application
Experimental Procedure (from patent CN103313983A)
Julia–Kocienski Olefination
Application
Experimental Procedure (from patent WO2016125086A1)
Kauffmann Olefination
Mechanism
Application
Experimental Procedure (from patent WO2014183211A1)
Peterson Olefination
Mechanism
Application
Experimental Procedure (from patent WO2017149091A1)
Petasis Olefination
Mechanism
Application
Experimental Procedure (from patent US5087790A)
Tebbe Olefination
Mechanism
Application
Experimental Procedure (from patent US8809558B1)
Wittig Reaction or Olefination
Mechanism
Application
Experimental Procedure (from patent WO2006045010A2)
Metathesis. Olefin Metathesis
Ring‐Closing Metathesis
Mechanism
Experimental Procedure (from patent US20022018351A1)
Cross Metathesis
Ring‐Opening Metathesis
Ring‐Opening Metathesis Polymerization (ROMP)
Asymmetric Epoxidation. Sharpless Asymmetric Epoxidation
Mechanism
Application
Experimental Procedure (from patent DE102014107132A1) (For more experimental procedures see Chapter 15)
Jacobsen–Katsuki Asymmetric Epoxidation
Mechanism
Application
Experimental Procedure (from patent US7501535B2)
Shi Asymmetric Epoxidation
Mechanism
Application
Experimental Procedure (from patent EP1770095A1)
Sharpless Asymmetric Dihydroxylation
Mechanism
Application
Experimental Procedure (from patent US7472570B1)
Sharpless Asymmetric Aminohydroxylation
Mechanism
Application
Experimental Procedure (from patent US8987504B2)
Woodward cis‐Dihydroxylation
Mechanism
Application
Experimental Procedure (from patent WO1997013780A1)
Prévost trans‐Dihydroxylation Reaction
Mechanism
Application
References. Corey–Winter Olefin Synthesis
Horner–Wadsworth–Emmons Reaction
Julia–Lythgoe Olefination
Julia–Kocienski Olefination
Kauffmann Olefination
Peterson Olefination
Petasis Olefination
Tebbe Olefination
Wittig Reaction or Olefination
Metathesis
Sharpless Asymmetric Epoxidation
Jacobsen–Katsuki Asymmetric Epoxidation
Shi Asymmetric Epoxidation
Sharpless Asymmetric Dihydroxylation
Sharpless Asymmetric Aminohydroxylation
Woodward cis‐Dihydroxylation
Prévost trans‐Dihydroxylation Reaction
4 Miscellaneous Reactions. Alder‐Ene Reaction
Mechanism
Application
Experimental Procedure (from patent WO2015149068A1)
Appel Reaction
Mechanism
Application
Experimental Procedure (from patent WO2015134973A1)
Barton Decarboxylation
Mechanism
Application
Experimental Procedure (from patent US6080563A)
Barton Nitrite Photolysis (Barton nitrite ester reaction)
Mechanism
Application
Experimental Procedure (from patent US3214427A)
Brown Hydroboration
Mechanism
Application
Experimental Procedure (from patent WO1995013284A1)
Bucherer Reaction
Mechanism
Application
Experimental Procedure (from Reference [7], copyright 2020, American Chemical Society)
Chichibabin Reaction
Mechanism
Application
Experimental Procedure Amination of 3‐Picoline (from patent EP0098684B1)
Chugaev Elimination Reaction
Mechanism
Application
Experimental Procedure (from Reference [10], copyright 2008, American Chemical Society)
Cannizzaro Reaction
Mechanism
Application
Experimental Procedure (general)
Cope Elimination Reaction
Mechanism
Application
Experimental Procedure (from Reference [3], copyright, Organic Syntheses)
Corey–Fuchs Reaction
Mechanism
Application
Experimental Procedure (from patent JP2015500210A)
Formation of Compound B
Formation of Compound C
Corey–Nicolaou Macrolactonization
Mechanism
Application
Experimental Procedure (patent US20060004107A1)
Danheiser Annulation
Mechanism
Danheiser Benzannulation
Mechanism
Application
Experimental Procedure (from Reference [22], Copyright 2013, American Chemical Society)
Diels–Alder Reaction
Normal Electron Demand Diels–Alder Reaction
Inverse electron Demand Diels–Alder Reaction
Hetero–Diels–Alder Reaction
Mechanism
Application
Experimental Procedure (from patent CA 2361682A1)
Dutt–Wormall Reaction
Mechanism
Étard Reaction
Mechanism
Application
Experimental Procedure (US8957255B2)
Finkelstein Reaction
Mechanism
Application
Experimental Procedure (from patent WO2019134765A1)
Fischer–Speier Esterification
Mechanism
Experimental Procedure (general)
Mukaiyama Esterification
Mechanism
Application
Experimental Procedure (from patent US4206310A)
Yamaguchi Esterification
Mechanism
Application
Experimental Procedure (from patent WO 2019033219A1)
Grignard Reaction
Mechanism
Application
Experimental Procedure (general)
Experimental Procedure (from patent WO1994028886A1)
Gabriel Synthesis
Mechanism
Application
Experimental Procedure (from patent US9540358B2)
Hell–Volhard–Zelinsky Reaction
Mechanism
Application
Experimental Procedure (from patent WO199101199A1)
Hofmann Elimination or Exhaustive Methylation
Mechanism
Application
Hosomi–Sakurai Reaction
Mechanism
Application
Experimental Procedure (from patent WO2019093776A1)
Huisgen Cycloaddition Reaction
Click Chemistry
Mechanism
Experimental Procedure (from patent WO2008124703A2)
Hunsdiecker Reaction
Mechanism
Application
Experimental Procedure (from patent WO2017060906A1)
Keck Asymmetric Allylation
Mechanism
Application
Experimental Procedure (from patent US6603023B2)
Thionation Reaction (Lawesson's Reagent)
Mechanism
Application
Experimental Procedure (general)
Michael Addition or Reaction
Mechanism
Application
Experimental Procedure (Aza‐Michael Addition) (from patent CN102348693B)
Mitsunobu Reaction
Mechanism
Application
Experimental Procedure (from patent US20170145017A1)
Morita–Baylis–Hillman Reaction (Baylis–Hillman Reaction)
Mechanism
Application
Experimental Procedure (from patent US20060094739A1)
Nozaki–Hiyama–Kishi Reaction
Mechanism
Application
Experimental Procedure (from patent US20190337964A1)
Paterno–Büchi Reaction
Mechanism
Application
Experimental Procedure (from Reference [29], copyright 2019, American Chemical Society)
Pauson–Khand Reaction
Mechanism
Application
Experimental Procedure (from patent WO2003080552A2)
Reformatsky Reaction
Mechanism
Application
Experimental Procedure (from patent US6924386B2)
Ritter Reaction
Mechanism
Application
Experimental Procedure (from patent WO1996036629A1)
Robinson Annulation
Mechanism
Application
Experimental Procedure (from patent WO2018226102A1)
Sandmeyer Reaction
Mechanism
Application
Experimental Procedure (from patent WO20100234652A1)
Schotten–Baumann Reaction
Mechanism. Amide Formation
Ester Formation
Application
Simmons–Smith Reaction
Mechanism
Application
Experimental Procedure (from patent US7019172B2)
Stork Enamine Synthesis
Mechanism
Application
Experimental Procedure (from patent US2773099A)
Tishchenko Reaction
Mechanism
Application
Experimental Procedure (from Reference [38], copyright 2012, American Chemical Society)
Ullmann Coupling or Biaryl Synthesis
Mechanism
Application
Ullmann Biaryl Ether and Biaryl Amine Synthesis/Ullman Condensation
Ullmann Biaryl Ether Synthesis
Goldberg Reaction (biaryl amines)
Ullmann‐Type Reaction/Ullmann Condensation
Mechanism
Application
Experimental Procedure (from Patent WO1999018057A1)
Weinreb Ketone Synthesis
Mechanism
Application
Experimental Procedure (from patent US9399645B2)
Step 1
Step 2
Williamson Ether Synthesis
Mechanism
Application
Experimental Procedure (from patent WO1994028886A1)
Wurtz Coupling or Reaction
Mechanism
Application
Wurtz–Fittig Reaction
Mechanism
References. Alder‐Ene Reaction
Appel Reaction
Barton Decarboxylation
Barton Nitrite Photolysis (Barton Nitrite Ester Reaction)
Brown Hydroboration
Bucherer Reaction
Chichibabin Reaction
Chugaev Elimination Reaction
Cannizzaro Reaction
Cope Elimination Reaction
Corey–Fuchs Reaction
Corey–Nicolaou Macrolactonization
Danheiser Annulation/Danheiser Benzannulation
Diels–Alder Reaction
Dutt–Wormall Reaction
Étard Reaction
Finkelstein Reaction
Fischer–Speier Esterification
Mukaiyama Esterification
Yamaguchi Esterification
Grignard Reaction
Gabriel Synthesis
Hell–Volhard–Zelinsky Reaction
Hofmann Elimination or Exhaustive Methylation
Hosomi–Sakurai Reaction
Huisgen Cycloaddition Reaction/Click Chemistry
Hunsdiecker Reaction
Keck Asymmetric Allylation
Thionation Reaction (Lawesson's Reagent)
Michael Addition or Reaction
Mitsunobu Reaction
Morita–Baylis–Hillman Reaction (Baylis–Hillman Reaction)
Nozaki–Hiyama–Kishi Reaction
Paterno–Büchi Reaction
Pauson–Khand Reaction
Reformatsky Reaction
Ritter Reaction
Robinson Annulation
Sandmeyer Reaction
Schotten–Baumann Reaction
Simmons–Smith Reaction
Stork Enamine Synthesis
Tishchenko Reaction
Ullmann Coupling or Biaryl Synthesis
Ullmann Biaryl Ether and Biaryl Amine Synthesis/Ullman Condensation
Weinreb Ketone Synthesis
Williamson Ether Synthesis
Wurtz Coupling or Reaction
Wurtz–Fittig Reaction
5 Aromatic Electrophilic Substitution Reactions. Bardhan–Sengupta Synthesis
Mechanism
Bogert–Cook Reaction or Synthesis of Phenanthrene
Mechanism
Friedel–Crafts Reaction
Friedel–Crafts acylation
Friedel–Crafts alkylation
Mechanism
Mechanism for Friedel–Crafts Alkylation
Application
Experimental Procedure (from patent US4814508A)
Gattermann Aldehyde Synthesis
Mechanism
Experimental Procedure (from patent US2067237A)
Gattermann–Koch Aldehyde Synthesis
Mechanism
Experimental Procedure (from patent WO2002020447A1)
Haworth Reaction
Mechanism
Experimental Procedure (from patent CN106977377A)
Houben–Hoesch Reaction
Mechanism
Application
Experimental Procedure (from patent EP0431871A2)
Kolbe–Schmitt Reaction
Mechanism
Application
Experimental Procedure (from patent US7582787B2)
Reimer–Tiemann Reaction
Mechanism
Application
Experimental Procedure (from patent US4324922A)
Vilsmeier–Haack Reaction
Mechanism
Application
Experimental Procedure (from patent US5599966A)
References. Bardhan–Sengupta Synthesis
Bogert–Cook Reaction or Synthesis of Phenanthrene
Friedel–Crafts Reaction
Gattermann Aldehyde Synthesis
Gattermann–Koch Aldehyde Synthesis
Haworth Reaction
Houben–Hoesch Reaction
Kolbe–Schmitt Reaction
Reimer–Tiemann Reaction
Vilsmeier–Haack Reaction
6 Pd‐Catalyzed CC Bond‐Forming Reactions. Suzuki Coupling Reaction
Mechanism
Application
Experimental Procedure (General)
Heck Coupling Reaction (Mizoroki–Heck Reaction)
Mechanism
Application
Experimental Procedure (from patent WO2008138938A2)
Negishi Coupling Reaction
Mechanism
Application
Experimental Procedure (from patent WO2010026121)
Stille Coupling Reaction (Migita–Kosugi–Stille Coupling Reaction)
Mechanism
Application
Experimental Procedure (from patent WO2008012440A2)
Sonogashira Coupling Reaction
Mechanism
Application
Experimental Procedure (General)
Kumada Cross‐Coupling
Mechanism
Application
Experimental Procedure (from patent WO2015144799)
Hiyama Coupling Reaction
Mechanism
Application
Experimental Procedure (from patent US20022018351A1)
Liebeskind–Srogl Coupling Reaction
Mechanism
Application
Experimental Procedure (from patent WO2008030840A2)
Fukuyama Coupling Reaction
Mechanism
Application
Experimental Procedure (from patent US20150336915A1)
Buchwald–Hartwig Coupling Reaction (Buchwald–Hartwig Amination)
Mechanism. Buchwald–Hartwig Amination
Application
Experimental Procedure (from patent US7442800B2)
Tsuji–Trost Allylation
Mechanism
Application
Experimental Procedure (from patent US20190270700A1)
References. Suzuki Coupling Reaction
Heck Coupling Reaction (Mizoroki–Heck Reaction)
Negishi Coupling Reaction
Stille Coupling Reaction (Migita–Kosugi–Stille Coupling Reaction)
Sonogashira Coupling Reaction
Kumada Cross‐Coupling
Hiyama Coupling Reaction
Liebeskind–Srogl Coupling Reaction
Fukuyama Coupling Reaction
Buchwald–Hartwig Coupling Reaction (Buchwald–Hartwig Amination)
Tsuji–Trost Allylation
7 Multicomponent Reaction
Biginelli Reaction (3‐Component Reaction [3‐CR])
One of Plausible Mechanisms
Application
Experimental Procedure (from patent US810606062B1)
Gewald Reaction (3‐Component Reaction [3‐CR])
Mechanism
Application
Experimental Procedure (from patent US20100081823A1)
Hantzsch Pyridine Synthesis
Mechanism
Application
Experimental Procedure (from patent US8106062B1)
Mannich Reaction
Mechanism
Application
Experimental Procedure (from patent WO2007011910A2)
Passerini Reaction (3‐Component Reaction [3‐CR])
Mechanisms. Ionic Mechanism
Concerted Mechanism
Lactone Formation [3]
Application
Experimental Procedure (from patent WO1995002566A1)
Strecker Amino Acid Synthesis
Mechanism. Part 1: Formation of α‐Aminonitrile
Part 2: Hydrolysis of the Nitrile
Application
Experimental Procedure (from patent US5169973A)
Ugi Reaction (4‐Component Reaction [4‐CR])
Plausible Reaction Mechanism
Application
Experimental Procedure (from patent US20150087600A1)
Asinger Reaction (4‐Component Reaction [A‐4CR])
Application
References. Biginelli Reaction
Gewald Reaction
Hantzsch Pyridine Synthesis
Mannich Reaction
Passerini Reaction
Strecker Amino Acid Synthesis
Ugi Reaction
Asinger Reaction
8 Oxidations and Reductions. Oxidation Reactions. Corey–Kim Oxidation
Mechanism
Application
Experimental Procedure (from patent US9212136B2)
Dess–Martin Oxidation
Mechanism
Application
Experimental Procedure (General)
Experimental Procedure (from patent US9212136B2)
Jones Oxidation
Mechanism
Application
Experimental Procedure (General)
Swern Oxidation
Mechanism
Experimental Procedure (from patent US9212136B2)
Pfitzner–Moffatt Oxidation
Mechanism
Application
Experimental Procedure (from patent WO2019202345A2)
Tamao–Fleming Oxidation
Fleming Oxidation
Tamao Oxidation
Mechanism
Application
Experimental Procedure (from patent WO2005113558A2)
Tamao–Kumada Oxidation
Mechanism
Oppenauer Oxidation
Mechanism
Application
Experimental Procedure (from patent US3506692A)
Riley Oxidation
Mechanism
Application
Experimental Procedure (from patent US20140341799A1)
Ley–Griffith Oxidation
Mechanism
Application
Experimental Procedure (from patent WO1998008849A1)
Criegee Oxidation (Criegee Glycol Cleavage)
Mechanism
Application
Experimental Procedure (from patent US5208036)
Criegee Ozonolysis
Mechanism
Application
Experimental Procedure (from patent US20030232989A1)
Reduction Reactions. Birch Reduction
Mechanism
Application
Experimental Procedure (from patent US20090247756A1)
Bouveault–Blanc Reduction
Mechanism
Application
Experimental Procedure (from patent US2883424A)
Clemmensen Reduction
Mechanism
Carbanionic Mechanism
Carbenoid/Radical Mechanism
Application
Experimental Procedure (from patent WO1994028886A1)
Corey–Bakshi–Shibata Reduction (also known as Itsuno–Corey reduction)
Mechanism
Application
Experimental Procedure (from patent WO2013040068A2)
Noyori Asymmetric Hydrogenation
Mechanism
Application
Experimental Procedure (from patent US20020173683A1)
Luche Reduction
Mechanism
Application
Experimental Procedure (from patent US20180134650A1)
Meerwein–Ponndorf–Verley Reduction
Mechanism
Application
Experimental Procedure (from patent US8674120B2)
Mozingo Reduction
Application
Rosenmund Reduction
Mechanism
Experimental Procedure (from patent US3517066A)
Preparation of 3,4,5‐Trimethoxybenzaldehyde
Wolff–Kishner Reduction
Mechanism
Application
Experimental Procedure (from Patent US20060128691A1)
References. Corey–Kim Oxidation
Dess–Martin Oxidation
Jones Oxidation
Swern Oxidation
Pfitzner–Moffatt Oxidation
Tamao–Fleming Oxidation
Tamao–Kumada Oxidation
Oppenauer Oxidation
Riley Oxidation
Ley–Griffith Oxidation
Criegee Oxidation (Criegee Glycol Cleavage)
Criegee Ozonolysis
Birch Reduction
Bouveault–Blanc Reduction
Clemmensen Reduction
Corey–Bakshi–Shibata Reduction (also known as Itsuno–Corey Reduction)
Noyori Asymmetric Hydrogenation
Luche Reduction
Meerwein–Ponndorf–Verley Reduction
Mozingo Reduction
Rosenmund Reduction
Wolff–Kishner Reduction
9 Nomenclature and Application of Heterocyclic Compounds
The Hantzsch–Widman Nomenclature
Examples
Saturated System
Partial Unsaturation
Unsaturated System
Priority of Heteroatoms for Numbering Purposes When More Than One Heteroatom in the Ring
Extra Hydrogen Atom
Heterocycles with Fused Rings
Common Names
The Replacement Nomenclature
Application of Heterocyclic Compounds
Drugs for Oxirane Derivatives
Drugs for Aziridine Derivatives
Drugs for Azetidine Derivatives
Drugs for Oxetane Derivatives
Drugs for Furan Derivatives
Drugs for Thiophene Derivatives
Drugs for Pyrrole and Pyrrolidine Derivatives
Drugs for Imidazole, Imidazoline, and Imidazolidine Derivatives. Antibacterial
Antifungal
Other
Drugs for Triazole Derivatives
Drugs for Isoxazole Derivatives
Drugs for Thiazole Derivatives
Drugs for Pyridine Derivatives
Drugs for Pyrimidine Derivatives
Drugs for Pyrazine Derivatives
Drugs for Piperidine Derivatives
Drugs for Quinoline/Isoquinoline Derivatives
Drugs for Oxazole/Isoxazole/Thiazole/Thiadiazole Derivatives
Drugs for Chromane Derivatives
Drugs for Indole Derivatives
Drugs for Benzimidazole Derivatives
Drugs for Indazole Derivatives
Drugs for Azepin/Diazepine Derivatives
Drugs for Xanthine Derivatives
Drugs for Lactone Derivatives
Drugs for β‐Lactam Derivatives
References
10 Synthesis of Some Heterocyclic Compounds Using Named Reactions. Bartoli Indole Synthesis
Mechanism
Application
Experimental Procedure (from patent US9567339B2)
Bischler–Napieralski Reaction
Mechanism
Alternative Mechanism
Application
Experimental Procedure (from patent US6048868A)
Combes Quinoline Synthesis
Mechanism
Application
Experimental Procedure (from patent WO2018234184A1)
Conrad–Limpach Synthesis
Mechanism
Application
Experimental Procedure (from patent US20120010237A1)
Doebner–Miller Reaction
Mechanism
Application
Feist–Benary Synthesis of Furan
Mechanism
Application
Experimental Procedure (from patent CN106243072A)
Fischer Indole Synthesis
Mechanism
Application
Experimental Procedure (General)
Friedländer Synthesis or Annulation
Mechanism
Application
Experimental Procedure (General)
Knorr Pyrrole Synthesis
Mechanism
Application
Madelung Indole Synthesis
Mechanism
Application
Experimental Procedure (General)
Paal–Knorr Furan Synthesis
Mechanism
Experimental Procedure (General)
Paal–Knorr Pyrrole Synthesis
Mechanism
Application
Experimental Procedure (an intermediate for Atorvastatin, from patent WO2009023260A2)
Pictet–Gams Isoquinoline Synthesis
Mechanism
Application
Pictet–Spengler Reaction
Mechanism
Application
Experimental Procedure (from patent CN107552089A)
Skraup Quinoline Synthesis
Mechanism
Experimental Procedure (from patent WO2011022928A1)
Preparation of 7‐Trifluoromethyl‐5‐nitroquinoline
References. Bartoli Indole Synthesis
Bischler–Napieralski Reaction
Combes Quinoline Synthesis
Conrad–Limpach Synthesis
Doebner–Miller Reaction
Feist–Benary Synthesis of Furan
Fischer Indole Synthesis
Friedländer Synthesis or Annulation
Knorr Pyrrole Synthesis
Madelung Indole Synthesis
Paal–Knorr Furan Synthesis
Paal–Knorr Pyrrole Synthesis
Pictet–Gams Isoquinoline Synthesis
Pictet–Spengler Reaction
Skraup Quinoline Synthesis
11 Protection and Deprotection of Common Functional Groups
Amines
tert‐Butyloxycarbonyl (Boc)
2‐(Trimethylsilyl)ethoxymethyl (SEM)
Carbobenzyloxy/Carboxybenzyl/Benzyloxycarbonyl (Cbz or Z)
9‐Fluorenylmethyloxycarbonyl (Fmoc)
Allyloxycarbonyl (Alloc)
Benzyl (Bn)
p‐Methoxybenzyl (PMB)
Acetyl (Ac)
Trifluoroacetyl
Tosyl (Ts)
Trityl (Trt)
2,2,2‐Tricholoethoxycarbonyl (Troc)
Methyl Carbamate
Formamide
Alcohols
Methyl Ether
Methoxymethyl (MOM) Ether
2‐Methoxyethoxymethyl (MEM) Ether
Benzyloxymethyl (BOM) Ether
Tetrahydropyranyl (THP) Ether
Benzyl (Bn) Ether
tert‐Butyl (t‐Bu) Ether
Silyl Ether. Trimethylsilyl (TMS) Ether
Triisopropylsilyl (TIPS) Ether
tert‐Butyldimethylsilyl (TBS or TBDMS)
tert‐Butyldiphenylsilyl (TBDPS)
2‐(Trimethylsilyl)ethoxymethyl (SEM) Ether
Ester Formation. Acetate or Acetyl (Ac) Ester
Methanesulfonate (Mesylate)
Tosylation
Benzoate (Bz) Ester
Pivaloate (piv) Ester
For 1,2‐Diols. Acetonide (Isopropylidene Ketal)
Carbonate
Benzylidene Acetal
For 1,3‐Diols
For Phenols
Protection and Deprotection for the Carboxylic Acid Group
From Primary or Secondary Alcohol
For tert‐Butyl Ester
Benzyl Ester
Silyl Ester
2‐(Trimethylsilyl)ethoxymethyl Ester (SEM Ester)
Protection and Deprotection of Carbonyl Group
Dimethyl Acetals and Ketals
1,3‐Dioxolane (Cyclic Acetals and Ketals)
1,3‐Dioxane
1,3‐Dithiolane (Cyclic Dithioacetals and Ketals)
1,3‐Dithiane
Protection and Deprotection of Terminal Alkyne
References. Amines
Alcohols
Protection and Deprotection for the Carboxylic Acid Group
Protection and Deprotection of Carbonyl Group
Protection for the Terminal Alkyne CH
12 Amino Acids and Peptides. Natural Amino Acids
Amino Acids with Nonpolar Side Chain
Amino Acids with Polar Side Chain
Amino Acids with Positive Charged (Basic) Side Chain
Amino Acids with Negatively Charged (Acidic) Side Chain
Nonnatural Amino Acids
Solution‐Phase Peptide Synthesis
Experimental
Mechanism of DIC–HOBt Coupling Reaction
Mechanism of Boc Deprotection with TFA
Mechanism of Fluorenyl‐9‐methoxycarbonyl (Fmoc) Deprotection with Piperidine
Solid‐Phase Peptide Synthesis. Merrifield Resin
Solid‐Phase Peptide Synthesis Fmoc Strategy
Amino Acids with Side‐Chain Protecting Groups for Fmoc Strategy. General Considerations
Standard Fmoc Strategy for SPPS
Cleavage Cocktail
Cleavage Cocktail A
Cleavage Cocktail B
Reagents and conditions
Covalent Peptides
Staple Peptides
Building Blocks for Stapled Peptides (Both L and D Analogs of Amino Acids Are Available)
Hydrocarbon Stapled Peptide Examples
Experimental Procedure
Stapled Peptide by Click Chemistry
Building Blocks for Click Chemistry (Both L and D Analogs Are Available)
Side‐Chain Modification
References
13 Functional Group Transformation
Alcohol to Aldehyde
Secondary Alcohol to Ketone
Primary Alcohol to Carboxylic Acid
1,2‐Diol Oxidation
Alcohol to Fluoride [11,14,15]
Alcohol to Chloride
Alcohol to Bromide
Alcohol to Iodide [13]
Alcohol to Ester
Alcohol to Ether
Alcohol to Sulfonic Ester
Alcohol to Methylene
Alcohol to Azide
Azide to Amine
Aldehyde to Alcohol
Aldehyde to Carboxylic Acid
Aldehyde to Difluoro [14, 15]
Ketone to Alcohol
Ketone to Ester
Ketone to Difluoro [14,15]
Ketone to Methylene
Ketone to Thioketone
Acid (Carboxylic) to Ester
Acid to Amide
Acid to Ketone
Ester to Acid
Ester to Aldehyde
Ester to Alcohol
Ester to Ketone
Nitro to Amine
Alkene to Epoxide
Alkene to Alkane
Alkyne to Alkane
Alkyne to Alkene
Cyano to Carboxylic Acid
Cyano to Amine [16]
Cyano to Amide
Methyl Phenyl Ether to Phenol [17, 18]
Toluene to Benzyl Halides
Alkylbenzene to Benzoic Acid
Aromatic Amine to Azide
Aromatic Halide to Aldehyde [21]
Aromatic Halide to Benzoic Acid [22]
Thioether to Sulfoxide
Thioether to Sulfone
Thiol to Disulfide [23–25]
Unsymmetrical Disulfide
Reductive Amination
Amine to Urea and Thiourea
Urea Formation from Two Amines
References
14 Synthesis of Some Drug Molecules
References
15 Common Laboratory Methods. Acetylation of Alcohol (patent WO2013040068A2)
Deacetylation (patent WO2013040068A2)
Tosylation of Alcohol (patent US9399645B2)
Benzoylation of Alcohol (patent WO2019093776A1)
Pivaloylation of Alcohol (patent WO2019093776A1)
Silylation of Alcohol (patent WO1998008849A1)
Desilylation (patent WO1998008849A1)
Esterification (ester formation)
Ester Formation from Acid and Alcohol (patent US9399645B2)
Carboxylic Acid to Benzyl Ester (patent WO2019134765A1)
Hydrolysis (saponification) of Ester
Carboxylic Acid to Acid Chloride (patent US20070197544A1)
Acid Chloride to Amide (patent US20070197544A1)
Amide Bond Formation Using Carboxylic Acid and PBr3 (patent US20070197544A1)
Buchwald–Hartwig Amination (patent US20070197544A1)
Ester to Carboxylic Acid (patent WO2019134765A1)
Benzyl Ester to Carboxylic Acid (patent WO2019134765A1)
Boc‐ Protection of Amino Group (patent US20090054548A1)
Deprotection of Boc Group (patent US20090054548A1)
Sulfonation of Aromatic Compound (patent WO2002030878A1)
Nitration of Aromatic Compound (mild and noncorrosive conditions) (patent WO1994019310A1)
Nitration of Aromatic Compound (regular method)
Nitration of Aromatic Compound (regular method) (patent WO2016118450A1)
Reduction of Nitro Group (patent WO2018167800A1)
Reduction of Nitro Group by Hydrogenation (patent US6329380B1)
Reduction of Nitro Group Using Hydrazine Raney Nickel (patent US20070197544A1)
Reduction of Nitro Group Using Fe and NH4Cl (patent US20070197544A1)
Reduction of Ketone with NaBH4 (patent WO2013040068A2)
Reduction of Ester to Alcohol (patent US9399645B2)
Reduction of Ester to Alcohol with DIBAL‐H (patent WO2016037566A1)
Ester to Aldehyde (patent US20190337964A1)
Selective Oxidation of Primary Alcohol (patent WO2013040068A2)
Oxidation of Alcohol Using DMP
Oxidation of Primary Alcohol Using TEMPO (patent US10407378B2)
Benzylation of Phenol
Debenzylation by Hydrogenation (Patent WO1994028886A1)
Iodination of Aromatic Compound (patent US7951832B2)
Methylation of Phenol
Demethylation to Phenol (patent US6924310B2)
Bromide to O‐Benzyl (patent WO2019134765A1)
Tosylate to Fluoride (patent WO2019134765A1)
Iodide to Tosylate (patent WO2019134765A1)
Ozonolysis of Alkene (patent WO2013040068A2)
Asymmetric Dihydroxylation of Alkene (Sharpless Method) (WO2019093776A1)
Alcohol to Fluoride (WO2019134765A1)
Alcohol to Iodide (patent US9399645B2)
Alcohol to Bromide (patent WO2016037566A1)
Alcohol to Iodide via Tosylation (patent WO2016037566A1)
Alkene to Aldehyde (patent WO1998008849A1)
Amine to Azide via Diazotization (patent WO20030135050A1)
Azide to Amine (patent US6329380B1)
Reductive Amination (patent WO2005118525A1)
Asymmetric C‐Alkylation (patent WO2005118525A1)
Aldehyde to 1,1‐Difluoroalkane (WO2018167800A1)
Free Radical Reaction (patent WO2013040068A2)
Umpolung
Silylation of 1,3‐Dithiane (C‐Silylation) (Model reactions for education purpose only)
Alkylation on 2‐Diphenylmethyl‐1,3‐Dithiane
Deprotection of 1,3‐Dioxolane
Preparation of Grignard Reagent and Reaction with an Aldehyde
Alcohol to Bromide
Deprotection of 1,3‐Dithiane
16 Common Reagents in Organic Synthesis
Acetic Acid (CH3CO2H)
Uses
Acetic Anhydride
Uses
Acetyl Chloride
Uses
AlkylFluor
Uses
Aluminum Chloride (Aluminium Chloride; AlCl3)
Uses
Aluminum Isopropoxide (Aluminium Isopropoxide)
Uses
Ammonium Chloride (NH4Cl)
Uses
Ammonium Formate
Uses
Ascorbic Acid (Vitamin C) Sodium Salt (Sodium L‐Ascorbate)
Uses
9‐Azabicyclo[3.3.1]nonane N‐Oxyl, (2‐Azaadamantane‐N‐oxyl) (AZADO)
Uses
Azobisisobutyronitrile (AIBN)
Uses
[1,1′‐(Azodicarbonyl)dipiperidine] (ADDP)
Uses
Benzoyl Peroxide
Uses
[1,1′‐Bis(diphenylphosphino)ferrocene] palladium(II) dichloride, Pd(dppf)Cl2
Uses
[Bis(triphenylphosphine)palladium(II) dichloride], Pd(Ph3P)2Cl2
Uses
Bismuth Chloride (BiCl3)
Uses
(Bis(trifluoroacetoxy)iodo)benzene
Uses
9‐Borabicyclo[3.3.1]nonane (9‐BBN)
Uses
Boron Tribromide (BBr3)
Uses
Boron Trifluoride Diethyl Etherate (BF3‐OEt2)
Uses
Bromine (Br2)
Uses
N‐Bromosaccharin (NBSa)
Uses
N‐Bromosuccinimide (NBS)
Uses
Burgess Reagent [Methyl N‐(triethylammoniosulfonyl)carbamate]
Uses
tert ‐Butyldimethylsilyl Chloride (TBDMS‐Cl)
Uses
tert‐Butyldimethylsilyl Trifluoromethanesulfonate (TBS‐OTf)
Uses
tert‐Butyl Hydroperoxide (TBHP)
Uses
n‐Butyllithium (n‐BuLi)
Uses
tert‐Butyllithium
tert‐Butyl Nitrite (TBN)
Uses
Carbon Tetrabromide (CBr4)
Uses
Carbonyldiimidazole (CDI)
Uses
Ceric Ammonium Nitrate (CAN; (NH4)2Ce(NO3)6)
Uses
Cesium Carbonate (Cs2CO3)
Uses
Cesium Fluoride (CsF)
Uses
Chloramine‐T,N‐chloro Tosylamide Sodium Salt
Uses
m‐Chloroperbenzoic Acid (m‐CPBA)
Uses
N‐Chlorosuccinimide (NCS)
Uses
Chromium Trioxide
Uses
Cobalt Chloride
Uses
Copper Iodide (CuI)
Uses
Dess–Martin Periodinane (DMP)
Uses
(Diacetoxyiodo)benzene (DAIB)
Uses
1,4‐Diazabicyclo[2.2.2]octane (DABCO)
Uses
1,8‐Diazabicyclo[5.4.0]undec‐7‐ene (DBU)
Uses
Diazomethane
Uses
Di‐tert‐butyl Azodicarboxylate (DBAD)
Uses
2,3‐Dichloro‐5,6‐dicyanobenzoquinone (DDQ)
Uses
N,N′‐Dicyclohexylcarbodiimide (DCC)
Uses
Diethylaminosulfur Trifluoride (DAST)
Uses
Diethyl Azodicarboxylate (DEAD)
Uses
Diiodomethane (CH2I2)
Uses
Diisobutylaluminum Hydride (DIBAL‐H)
Uses
Diisopropylaminoborane
Diisopropyl Azodicarboxylate (DIAD)
Uses
N,N‐Diisopropylethylamine (DIEA) (Hünig's Base)
Uses
4‐Dimethylaminopyridine (N,N′‐Dimethylaminopyridine) (DMAP)
Uses
Diphenylphosphoryl Azide (DPPA)
Uses
Di‐tert‐butyl Peroxide (DTBP)
Uses
Ethyl Chloroformate
Uses
1‐Ethyl‐3‐(3‐dimethylaminopropyl)carbodiimide Hydrochloride (EDC·HCl)
Uses
Formic Acid
Uses
O‐(7‐Azabenzotriazol‐1‐yl)‐N,N,N′,N′‐tetramethyluronium hexafluorophosphate (HATU)
Uses
Hexafluorophosphate Benzotriazole Tetramethyl Uronium (HBTU)
Uses
Hexamethylphosphoramide (HMPA)
Uses
Hydrazine (NH2NH2·H2O)
Uses
1‐Hydroxybenzotriazole (HOBt)
Uses
Hydrogen Peroxide
[Hydroxy(tosyloxy)iodo]benzene (HTIB) (Koser's Reagent)
Uses
Imidazole
Uses
Iodine (I2)
Uses
Iodobenzene Dichloride
Uses
N‐Iodosuccinimide (NIS)
Uses
2‐Iodoxybenzoic Acid (IBX)
Uses
Iron(III) Nitrate Nonahydrate
Uses
Isoamyl Nitrite (Also Called Amyl Nitrite)
Uses
Isobutyl Chloroformate
Uses
Jones Reagent
Uses
Lawesson's Reagent
Uses
Lead Tetraacetate (Pd(OAc)4)
Uses
Lithium Aluminum Hydride (LiAlH4)
Uses
Lithium Diisopropylamide (LDA)
Uses
2,6‐Lutidine (2,6‐Dimethylpyridine)
Uses
Manganese Dioxide (MnO2)
Uses
Methanesulfonyl Chloride (Mesyl Chloride)
Uses
N‐Methylmorpholine N‐oxide (NMO)
Uses
Nitrosobenzene
Uses
Osmium Tetroxide
Uses
Oxalyl Chloride
Uses
Oxone (Potassium Peroxymonosulfate)
Uses
Ozone (O3)
Uses
PhenoFluor Mix
Uses
Palladium on Calcium Carbonate (Pd/CaCO3)
Uses
Palladium on Carbon
Uses
Phenyltrimethylammonium Perbromide (PTAB) or Phenyltrimethylammonium Tribromide (PTT)
Uses
Phosphorus Oxychloride
Uses
Phosphorus Tribromide (PBr3)
Uses
Piperidine
Uses
Platinum on Carbon
Uses
Platinum(IV) Oxide
Uses
Potassium bis(trimethylsilyl)amide (KHMDS) (Potassium Hexamethyldisilazide)
Potassium tert‐Butoxide
Uses
Potassium Carbonate
Uses
Potassium Iodide
Uses
Potassium Permanganate
Uses
Potassium Sodium Tartrate Tetrahydrate (Rochelle's Salt)
Uses
Propylphosphonic Anhydride (T3P)
Uses
PyAOP
Uses
(Benzotriazol‐1‐yloxy)tripyrrolidinophosphonium Hexafluorophosphate (PyBOP)
Uses
Pyridine
Uses
Pyridinium Chlorochromate (PCC)
Uses
Pyridinium Dichromate (PDC)
Uses
Pyridinium p‐Toluenesulfonate (PPTS)
Uses
Raney Nickel. Uses
Ruthenium(III) Chloride (RuCl3)
Uses
Scandium(III) Trifluoromethanesulfonate (Scandium Triflate)
Uses
Selectfluor
Uses
Sodium Azide
Sodium Bis(trimethylsilyl)amide (NaHMDS)
Sodium Borohydride
Uses
Sodium Cyanoborohydride
Uses
Sodium Hydride (NaH) Uses
Sodium Hypochlorite (Bleach)
Uses
Sodium Nitrite
Uses
Sodium Periodate
Uses
Sodium Sulfide (Na2S)
Uses
Sodium Triacetoxyborohydride (STAB)
Uses
Tetra‐n‐butylammonium Fluoride (TBAF)
Uses
Tetra‐n‐butylammonium Iodide (TBAI)
Uses
Tetrakis(triphenylphosphine)palladium(0) (Pd(Ph3P)4)
Uses
2,2,6,6‐Tetramethylpiperidin‐1‐yl)oxyl (TEMPO)
Uses
Tetrapropylammonium Perruthenate (TPAP)
Uses
Thionyl Chloride
Uses
Titanium(IV) Chloride
Uses
Titanium Isopropoxide
Uses
p‐Toluenesulfonic Acid
Uses
Tributyltin Hydride
Uses
Triethylamine (TEA)
Uses
Triethyl Orthoformate
Uses
Trifluoroacetic Acid (TFA)
Uses
Trimethylsilyl Chloride (TMS‐Cl)
Uses
2‐(Trimethylsilyl)ethoxymethyl Chloride (SEM‐Cl)
Uses
Trimethylsilyl Cyanide (TMS‐CN)
Uses
Trimethylsilyl Diazomethane
Uses
Trimethylsilyl Iodide
Uses
Triphenylphosphine (Ph3P)
Uses
Triphosgene [bis(trichloromethyl) carbonate (BTC)]
Uses
Tris(dibenzylideneacetone)dipalladium(0)
Trityl Chloride (Triphenylmethyl Chloride)
Uses
Urea Hydrogen Peroxide (UHP)
Uses
Zinc (Zn)
Uses
Zinc Chloride
Uses
References
Further Reading. Organic and Medicinal Chemistry Books Consulted
Appendix A List of Medicines (Partial) and Nutrients. Antibiotic (antibacterial agent)
Antiviral Medicines
Antifungal Medicines
Antimalarial Medicines
Antituberculosis Medicines
Medicines for Pain
Anticonvulsants Medication (antiepileptic drugs or as antiseizure drugs)
Anti‐infective Medicines (anthelminthics and antifilarials)
Medicines for Migraine
Antileprosy Medicines
Disinfectant and Antiseptics
Antidiabetic Medicines (diabetes medications)
Medicines for Anesthetics (anesthetics)
Antiallergics and Medicines for Anaphylaxis
Cardiovascular Medicines
Medicines for Gastrointestinal
Medicines for Mental and Behavioral Disorders
Medicine for Joint Paints
Medicines Affecting the Blood
Medicines for Cancer (antineoplastics)
Medicines for Parkinson's Disease
Medicines for Ear, Nose, and Throat
Medicines for the Respiratory Tract
Reproductive Health and Perinatal Care Medicines
Medicines for Dermatological (topical)
Antidotes in Poisonings
Vitamins
Other Nutrients
Medical Advice Disclaimer
Further Reading
Index
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