Reactions and Syntheses: In the Organic Chemistry Laboratory

868 Pages·2015·25.41 MB·English

by  Lutz F. Tietze

Table of Contents
Cover
Related Titles
Title Page
Copyright
Preface to the First Edition
1 Background
2 Organization of the Book and Directions for Its Use
References
Preface to the Second Edition
Reference
Acknowledgments
About the Authors
Abbreviations and Symbols
Chapter 1: C–C Bond Formation
1.1 Nucleophilic Addition to Aldehydes, Ketones, Carboxylic Acid
Derivatives (Esters, Anhydrides), and α,β-Unsaturated Carbonyl
Compounds; Carbonyl Olefination
1.2 Alkylation of Aldehydes/Ketones, Carboxylic Acids, and β-
Dicarbonyl Compounds
1.3 Reactions of the Aldol and Mannich Type
1.4 Electrophilic and Nucleophilic Acylation
1.5 Reactions of Alkenes Via Carbenium Ions
1.6 Transition-Metal-Catalyzed Reactions
1.7 Pericyclic Reactions
1.8 Radical Reactions
Chapter 2: Oxidation and Reduction
2.1 Epoxidation of C=C Bonds
2.2 Dihydroxylation of C=C Bonds
2.3 Oxidation of Alcohols to Carbonyl Compounds
2.4 Enantioselective Reduction of Ketones
2.5 Biomimetic Reductive Amination
2.6 Enantioselective Wacker Oxidation
Chapter 3: Heterocyclic Compounds
3.1 Three-and Four-Membered Heterocycles
3.2 Five-Membered Heterocycles
3.3 Six-Membered Heterocycles
3.4 Condensed Heterocycles
3.5 Other Heterocyclic Systems, Heterocyclic Dyes
Chapter 4: Selected Natural Products
4.1 Isoprenoids
4.2 Carbohydrates
4.3 Amino Acids and Peptides
4.4 Nucleotides and Oligonucleotides
Chapter 5: Domino Reactions
5.1 Domino Reactions in Synthetic Methodology
5.2 Domino Reactions in the Synthesis of Alkaloids
5.3 Domino Reactions in the Synthesis of Isoprenoids
5.4 Domino Reactions for the Synthesis of Chromans and Dioxins
5.5 Domino Reactions in the Synthesis of Chiroptical Switches
Index of Reactions
Index of Products
Subject Index
End User License Agreement
List of Tables
Table 3.1
Table 3.2
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Lutz F. Tietze, Theophil Eicher, Ulf Diederichsen, Andreas Speicher, and Nina
Schützenmeister
Reactions and Syntheses
In the Organic Chemistry Laboratory
Second, Completely Revised and Updated Edition
Preface to the First Edition
1 Background
The book Reaktionen und Synthesen im organisch-chemischen Praktikum und
Forschungslaboratorium was first published in German in 1981, with a second
edition in 1991, and was translated into Japanese in 1984 (second edition 1995),
English in 1989, Chinese in 1999, Russian in 2000, and Korean in 2002. The
intention was
to associate classes of compounds and functionalities with reaction types and
mechanisms,
to offer a great number of reliable preparative procedures of general
importance, and
to show the usefulness and robustness of the offered procedures for the
synthesis of selected interesting compounds of relevance in biology,
pharmacy, and medicine.
Since the last German edition, many new preparative procedures have been
developed showing high chemo, regio, diastereo, and enantioselectivity, which
frequently approach the selectivity of enzymatic transformations with the
advantage of lower substrate specificity. In addition, new methods such as
combinatorial chemistry, solid-phase chemistry, high-pressure chemistry, and
the use of microwaves for heating have been introduced. Moreover, the
efficiency of a synthesis, which can be defined as the increase in complexity per
transformation, the avoidance of toxic reagents and solvents, and the
preservation of resources are important issues in modern preparative organic
chemistry. Significant developments in the last years have been realized in
transition-metal catalysis, organocatalysis, and domino reactions. This progress
has been impressively documented in Classics of Total Synthesis [1], Organic
Synthesis Highlights [2], and Domino Reactions in Organic Synthesis [3].
As a consequence, we now present this book Reactions and Syntheses in the
Organic Chemistry Laboratory in a new form with respect to its concept and
organization and extensively renewed with respect to its content.
Its major highlights are as follows:
1. The basic units as well as the main objectives are syntheses (up to multistep
syntheses with more than five steps) of interesting and instructive target
molecules from various fields of organic chemistry. Each synthesis is
centered around one or more methods and reaction principles of general
synthetic relevance.
2. As before, the users of the new book are provided with carefully elaborated
experiments, which are described in preparative and analytical detail.
However, experiments and syntheses are accompanied throughout in
concentrated form by the required general, theoretical, and mechanistic
background and explanations. Special attention is given to retrosynthetic
analysis and alternative approaches of synthesis for a given target molecule.
3. To allow the inclusion of a representative and qualified spectrum of
contemporary synthetic methods, more than 70% of the content of the former
book has been replaced by more recent and more relevant experimental
examples. The remaining (older) syntheses have been “updated” with respect
to description of their general background.
Considering the various types of users of the book in the past, there has been a
definite and broad acceptance among chemists and pharmacists on a more
advanced level, besides graduate students and researchers in universities and
industry. From these considerations, the following consequences have emerged
for the third edition:
General laboratory information, such as safety, first aid, performance of
chemical reactions, instrumentation and standard apparatus, and isolation and
purification of products, has been omitted. Methods for the formation and
transformation of basic functional groups in organic compounds, regarded as
important at the elementary education level in organic laboratory practice,
are not described. These topics are comprehensively covered in other
relevant textbooks [4–6].
The deletion of these elementary aspects of organic chemistry has allowed us
to describe in more detail of the advanced synthetic methods and to include
mechanistic aspects and to incorporate total syntheses and retrosynthetic
analyses.
2 Organization of the Book and Directions for Its
Use
The book is divided into four chapters with several sections:
Chapter 1: C–C bond formation
Chapter 2: Oxidation and reduction
Chapter 3: Heterocyclic compounds
Chapter 4: Selected natural products.
The sections (e.g., 1.1 and 1.2) contain procedures and syntheses (e.g., 1.1.1 and
1.1.2) as specified at the beginning of the section and in the Table of Contents
(cf. p. II). Each synthesis is organized as follows:
1. In the general part (a), the structural formula of the target molecule and the
topics of the presented synthesis (important for rapid information!) are given,
which is followed by introductory information on the target molecule,
retrosynthesis [7], and planning of the synthesis (possibilities, strategies, and
synthetic alternatives; considerations on practicability for laboratory use).
2. In part (b), the synthesis of the target molecule and the synthetic steps
performed in the experimental part are described. This is accompanied by
information about the mechanism(s), the stereochemical outcome, and the
selectivity of the transformations (specific reaction principles). Finally, the
number of steps performed and the yields obtained are summarized. In
general, Section (b) contains a complete scheme of the synthesis performed.
3. In Section (c), individual experimental procedures are described. Each
procedure has the following structure:
a. An identification number, which characterizes the prepared compound
according to chapter, section, and synthesis (e.g., 1.1.1.1 and 1.1.1.2); the
identification number carries one or more asterisks (*, **, ***) according
to the degree of difficulty of the procedure.
b. Literature reference(s) for the prepared compound.
c. A formula equation, which gives structures of reactants and products, and
their relative molecular masses. In general, apparatus is not discussed in
detail; however, in special cases, information about specialized
equipment (photochemical, high-pressure, microwave, etc.) is given.
d. Throughout, the procedures are presented in two parts. The first,
describing the reaction, often includes additional notes about purification
and characteristics of the substrates, such as toxicity and safety aspects.
The second describes the work-up, isolation, and purification of the
product, along with criteria of purity (mp, bp, n , TLC/R , [α] ), notes
D f D
about characteristics of the product, and other crucial experimental
details.
e. Characterization of the product by spectral data (IR, UV–vis, 1H and 13C
NMR, MS). In selected cases, the preparation of derivatives together
with their instrumental and chemical analysis is given.
4. The presentation of each synthesis is concluded by a compilation of the
literature references cited in Sections (a–c). They cover the primary
literature on the synthesis, its steps, and its topics, and refer to important
collective articles, reviews, and textbooks of advanced organic chemistry [8].
References
1. (a) Nicolaou, K.C. and Sorensen, E.J. (1997) Classics in Total Synthesis,
Wiley-VCH Verlag GmbH, Weinheim;(b) Nicolaou, K.C. and Snyder, S.A.
(2003) Classics in Total Synthesis II, Wiley-VCH Verlag GmbH, Weinheim.
2. Mulzer, J., Altenbach, H.-J., Braun, M., Krohn, K., Reissig, H.-U.,
Waldmann, H., Schmalz, H.-G., and Wirth, Th. (eds) (1991-2003) Organic
Synthesis Highlights I–V, Wiley-VCH Verlag GmbH, Weinheim.
3. Tietze, L.F., Brasche, G., and Gericke, K.M. (2006) Domino Reactions in
Organic Synthesis, Wiley-VCH Verlag GmbH, Weinheim.
4. (2001) Organikum, 21st edn, Wiley-VCH Verlag GmbH, Weinheim.
5. Hünig, S., Kreitmeier, P., Märkl, G., and Sauer, J. (2007) Arbeitsmethoden in
der Organischen Chemie (mit Einführungs-praktikum), 2nd edn, Verlag
Lehmanns, Berlin.
6. Larock, R.C. (1999) Comprehensive Organic Transformations (A Guide to
Functional Group Preparations), 2nd edn, Wiley-VCH Verlag GmbH,
Weinheim.