Organic Chemistry: 100 Must-know Mechanisms: In Organic Chemistry

Book Preface

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   post-doctoral 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), and 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 comprehensive anthology. The book is intended to be a visual guide as distinguished from a traditional text book. The presentation of each mechanism constitutes a complete InfoGraphic (or “MechanoGraphic”)  and provides distilled information focusing on key concepts, rules, acronyms, and  terminology. It heavily focuses on the basic core – the starting amount of information,  the extract – that a good organic chemist can commit to memory and understanding.  Starting initially as a daily micro-blog post with a “hash tag” (#100MustKnowMechanisms) that gained a lot of support from students and chemists around the world,  the book is really intended to bring together an array of mechanisms, organize them,  provide additional historical context, and enable a conceptual space where the reader  can focus on learning them as well as serve as a desk-reference or a “flip-book”. The book is color-coded: each key reaction is enclosed in a dark blue frame; each  key mechanism (the center piece of the book) is presented in a red frame; other reactions and mechanisms related to the core 100 mechanisms covered in this book are  usually summarized in grey frames. The book also collects a few useful rules, facts,  and concepts that are presented in green frames. The reader may find several star  diagrams, representing synthetic diversity, for example, throughout the book as well.

Relevant comments and clarifications can be found in footnotes. Sources. The underlying information stays very close to information usually  covered in classic or key organic chemistry text books [1]. More specialized literature  may be necessary in some cases (for organometallic or photochemical transformations, for example) [2]. The reader is also encouraged to familiarize themselves with  some other supporting bibliography [3]. Where appropriate, it also references texts  that the author trusts and cites for further in-depth study if the reader so chooses.
Since this book strives to be an abridged visual illustration, students are encouraged  to use other, more comprehensive books on the subject, especially those related to the  named reactions in organic chemistry [4]. Additionally, open on-line sources, when  thoughtfully selected, can also be very useful [5]. Such sources may be mentioned  here when the information was deemed accurate, thorough, and supported by the  references. This is further supplemented by the author’s aggregate knowledge and  education gained through college, graduate school, and post-doctoral academic rese arch. The author also found the encyclopedia of organic reagents [6] to be an extremely useful “go-to” starting point in his personal experience and professional career,  especially when embracing a new chemistry topic or using a new reagent. Moreover,  each MechanoGraphic is supported by reference to the likely first original publication  where the related reaction or mechanism was first mentioned (see the time-scale  after each mechanism). Finally, several key and fundamental reviews; publications  on recently elucidated mechanisms; and other research articles are referenced, as  needed. The author uses his best judgement in each case. However, even though the provided information was carefully checked, and presented in agreement with standard and accepted chemistry rules, this does not guarantee that it is free of all errors.

A further caveat, the variety of text and scholarly references does not imply a comprehensive and chronological review of the literature and history – it is not a global historic review of mechanisms from 1800‒2020. Mechanisms and our understanding of  them can also change as this book is being prepared and the corresponding literature  revised. Thus, the reader should supplement the use of the book with primary source  reading and deeper study through a comprehensive textbook prepared by a cohort of  experienced professors and experts. Here, the most common and known pathways,  those that do not violate basic standard chemistry rules and that are frequently referenced in the classic and contemporary literature, are summarized visually.

A Few Things to Keep in Mind. It is also important that the reader remain flexible and mindful that mechanisms are represented based on our current understanding, taking into consideration basic chemistry rules, valency, electron pushing rules, charge preservation, Lewis dot structures, etc. They may not be the most  “cutting-edge” or up-to-date (e.g., cross coupling reactions that may not be wellunderstood). They may also be substrate-dependent and each reaction may undergo  a slightly different pathway. Thus, the reader should not treat the book as a dogmatic  guide, and should keep an open mind for new data, creativity, and view the book as  part of a continuous debate in the subject.

Background Knowledge. To fully benefit from the book, the reader should have  basic knowledge of organic chemistry. Figures are presented with an assumption that  the reader understands common terms and symbols. Thus, basic concepts are not  introduced or explained. Undergraduate students, graduate students, scientists, teachers, and professors in the discipline should be able to utilize the book. The book can  also serve as a good condensed “refresher” for the experienced organic chemist who  wants to “zero-in” on the most basic and fundamental core mechanisms as judged by  the author.

The Inspiration and Further Reading. The author heavily draws upon his personal  experience as a student of chemistry and later an academic researcher. Never having  taken a formal course on mechanisms in organic chemistry, he approached the material initially through memorization as opposed to derivation. The first impression was  fear and a sense of being overwhelmed. However, after many years of experience,  more obvious patterns, trends, rules, and dependencies appear to have crystallized  providing an inductive ability to navigate and identify the mechanisms behind reactions. This personal experience has definitely shaped the teaching philosophy of the  book, and is further enhanced by the efficient way in which information can be conveyed through visuals and space.

Moreover, as most individuals have a predisposition  for visual learning – this book is more intuitively aligned with the way that we seem to  learn the fastest. It strives to be a focused collection of the most useful, basic, and fundamental mechanisms. Started initially as a micro-blog post, the discussion, engagement, and interest it sparked indicated a clear need for a more-carefully prepared, provided information was carefully checked, and presented in agreement with stan dard and accepted chemistry rules, this does not guarantee that it is free of all errors.

A further caveat, the variety of text and scholarly references does not imply a comprehensive and chronological review of the literature and history – it is not a global historic review of mechanisms from 1800‒2020. Mechanisms and our understanding of  them can also change as this book is being prepared and the corresponding literature  revised. Thus, the reader should supplement the use of the book with primary source  reading and deeper study through a comprehensive textbook prepared by a cohort of  experienced professors and experts. Here, the most common and known pathways,  those that do not violate basic standard chemistry rules and that are frequently referenced in the classic and contemporary literature, are summarized visually.

A Few Things to Keep in Mind. It is also important that the reader remain flexible and mindful that mechanisms are represented based on our current understanding, taking into consideration basic chemistry rules, valency, electron pushing  rules, charge preservation, Lewis dot structures, etc. They may not be the most  “cutting-edge” or up-to-date (e.g., cross-coupling reactions that may not be wellunderstood). They may also be substrate-dependent and each reaction may undergo  a slightly different pathway. Thus, the reader should not treat the book as a dogmatic  guide, and should keep an open mind for new data, creativity, and view the book as  part of a continuous debate in the subject.

Background Knowledge. To fully benefit from the book, the reader should have  basic knowledge of organic chemistry. Figures are presented with an assumption that  the reader understands common terms and symbols. Thus, basic concepts are not  introduced or explained. Undergraduate students, graduate students, scientists, teachers, and professors in the discipline should be able to utilize the book. The book can  also serve as a good condensed “refresher” for the experienced organic chemist who  wants to “zero-in” on the most basic and fundamental core mechanisms as judged by  the author.

The Inspiration and Further Reading. The author heavily draws upon his personal  experience as a student of chemistry and later an academic researcher. Never having  taken a formal course on mechanisms in organic chemistry, he approached the material initially through memorization as opposed to derivation. The first impression was  fear and a sense of being overwhelmed. However, after many years of experience,  more obvious patterns, trends, rules, and dependencies appear to have crystallized  providing an inductive ability to navigate and identify the mechanisms behind reactions. This personal experience has definitely shaped the teaching philosophy of the  book, and is further enhanced by the efficient way in which information can be conveyed through visuals and space. Moreover, as most individuals have a predisposition  for visual learning – this book is more intuitively aligned with the way that we seem to  learn the fastest. It strives to be a focused collection of the most useful, basic, and fundamental mechanisms. Started initially as a micro-blog post, the discussion, engagement, and interest it sparked indicated a clear need for a more-carefully prepared,