Second Edition

This edition of Organic Chemistry: 100 Must-Know Mechanisms is an enriched and improved version of the first book with over 40 new illustrations. It builds upon the existing 100 fundamental mechanisms mentioned in the previous book and adds other mechanisms related to the original 100 with engaging, supplementary examples. The book is also fine-tuned with features that can help broaden its usefulness to earlier-stage students of chemistry and related sciences.

Formal Lewis (dot) structures are added to all the previously mentioned intermediates in each mechanism, keeping track of the movement of electrons and making the schemes more comprehensive. This improvement is a valuable enhancement for those still learning organic chemistry and expands usefulness to undergraduate students and college students in STEM fields whose area of major concentration is not chemistry. The original 100 mechanistic schemes are also visually improved: the chemical structures are more vivid and consistent throughout the book. Additionally, newly formed bonds are highlighted in red color and accentuated using bold lines for each final product or key intermediate.

In the first version, many related mechanisms were only mentioned by name. The second edition expands upon those examples and has numerous new mechanistic schemes. For example, the reader will find a new illustration of the Bouveault–Blanc reduction mechanism of esters and ketones, a separate Wolff rearrangement, which was previously mentioned only as a part of the Arndt–Eistert synthesis mechanism. Other new illustrations include the Dakin reaction mechanism, the Myers–Saito cyclization mechanism, the Pomeranz–Fritsch reaction mechanism, an example of the Benzidine rearrangement mechanism, the Delépine reaction mechanism, the Peterson olefination mechanism, the Kabachnik–Fields reaction mechanism, the Petasis reaction mechanism, the Stetter reaction mechanism for aromatic and aliphatic aldehydes, the Fischer esterification mechanism – and its comparison to the Mitsunobu ester synthesis and the stereochemical outcome of both reactions involving a chiral alcohol – the Ullmann biaryl ether coupling mechanism catalyzed by Cu(I) complex with a neutral bidentate ligand, the Reimer–Tiemann reaction mechanism, and the Clemmensen reduction mechanism. The nontraceless and traceless Staudinger ligation mechanisms are also highlighted, making them especially relevant after the announcement of the 2022 Nobel Prize in Chemistry for the development of click chemistry and bioorthogonal chemistry [30g, 30h].

Moreover, many of the original mechanistic schemes depicted in the first edition of this book were general, covering a vast scope of chemical structures and often using a general R-group representation, instead of a particular example of an actual organic compound. This edition is enhanced with a variety of real-case examples, such as the bromination and nitration of an aromatic ring (an example of the aromatic electrophilic substitution), the Beckmann rearrangement mechanism of cyclohexanone oxime, the Chichibabin amination mechanism of quinoline, a sequence of the Cope rearrangements involving (3R,4R)-3,4-dimethylhexa-1,5-diene, (2E,4R,5R,6E)-4,5-dimethylocta-2,6-diene, (2Z,4R,5R,6E)-4,5-dimethylocta-2,6-diene, and (2Z,4R,5S,6E)-4,5-dimethylocta-2,6-diene, several variations of the Diels–Alder cycloaddition reactions using various dienes and dienophiles, the Favorskii rearrangement mechanism of 2-chlorocyclohexan-1-one, the Grob fragmentation mechanism of (1R,3S)-3-chloro-1-methylcyclohexan-1-ol, the Bischler–Napieralski cyclization mechanism of N-phenethylacetamide, the Polonovski reaction mechanism (N-demethylation) of a morphinan derivative, and the Suzuki cross-coupling mechanism catalyzed by either Pd(dppf)Cl2 or tetrakis(triphenylphosphine)palladium(0): Pd(PPh3)4. Also noteworthy, an educational example of the ozonolysis reaction mechanism of (–)-α-fenchene and anomalous (interrupted) ozonolysis reaction mechanisms are presented as well, in addition to the synthesis of cubane-1,4-dicarboxylic acid (with the key Favorskii rearrangement transformation step), the rearrangement mechanism of bicyclo[2.2.2]octane system (an example of the Hell–Volhard–Zelinsky reaction), and two plausible mechanisms of adamantane rearrangement undergoing a sequence of numerous Wagner–Meerwein rearrangement steps.

This edition continues in the tradition of the first: presenting information efficiently by using clear, balanced, and intuitive visuals and infographic diagrams. Like a stone sculpture, this version is a refined and more finely chiseled version of the first. The goal is to build upon what worked well, update the content where needed, and to add key pieces of information or notation, with the ultimate objective of making the book more useful to more students of chemistry and the sciences. Of course, we cannot promise perfection, because it, like an asymptote, is unreachable, but we hope that you will find this version to be a valuable addition or update to your scientific library.

Preface and Overview

Pedagogical Principles. At first, every body of knowledge that is new to us seems to have boundless complexity and creates the initial impression of incomprehensibility and even fear. Organic chemistry provides an excellent example of this phenomenon. The discipline is replete with complex and initially abstract concepts, as a result, the information may seem overwhelming, particularly for the young chemist. But as with most new subjects, consistent study and practice reveals patterns, commonalities, rules, and an apparent logic. Eventually, an “architecture” becomes more apparent as we grow to become more experienced chemists. To develop this intuition, it requires close study, repetition, and breadth of exposure. A significant element of that learning is intrinsic and simply requires time and immersion. However, to help with the development of this intuition, an organic chemist would also be wise to focus on mechanisms for organic reactions as a foundation or anchoring point. This, in combination with deep study, can help organize knowledge into skill and expertise. An understanding of reaction mechanisms provides a solid foundation for the field and a scaffold for further study and life-long learning. Mechanisms are highly useful because they can logically explain how a chemical bond in a molecule was formed or broken and help to rationalize the formation of the final synthetic target or an undesired side-product. Moreover, as we parse an increasing number of mechanisms, we begin to see the similarities and an invisible conceptual “thread” then forms in our mind’s eye that was not previously apparent. It helps to organize thinking and brings sense to the otherwise foreign concepts such as reactive intermediates, transition states, charges, radicals, and mechanistic arrows.

The Approach. To help galvanize – and perhaps catalyze – the organic chemist’s inductive ability and to provide a “go-to” reference for closer study, this book strives to present an abridged summary of some of the most important mechanisms. In today’s terms, these are 100 MUST-KNOW mechanisms. The author draws upon scientific knowledge developed through undergraduate and graduate years, including postdoctoral research and study focused on organic synthesis. With a keen awareness of the incremental learning process, the book curates and presents mechanisms by category, starting with the fundamental and basic mechanisms (e.g., nucleophilic substitution or elimination), mechanisms associated with the most well-known named reactions (e.g., the Diels–Alder reaction or the Mitsunobu reaction). Additionally, the collection is complemented with historically important mechanisms (e.g., the diazotization or the haloform reaction). Finally, it includes some mechanisms dear to the author’s heart, which he deems elegant or simply “cool” (e.g., the Paternò–Büchi cycloaddition or the alkyne zipper reaction).

Organization. The mechanisms are organized alphabetically by chapter for ease of reference, and numbered from 1 to 100. The dedicated student will consistently proceed through every single mechanism, giving each one time to study, practice with, memorize, and ponder. At the same time, the book can be used as a quick visual reference or as a starting point for further research and reading. The 100 mechanisms are selected for being classic and famous, core or fundamental, and useful in practice. Of course, a good degree of personal intuition is involved in the selection and it is definitely not a dogmatic ordering or a...