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:

1. Chapter 1: C-C bond formation
2. Chapter 2: Oxidation and reduction
3. Chapter 3: Heterocyclic compounds
4. 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:
   1. 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.
   2. Literature reference(s) for the prepared compound.
   3. 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.
   4. 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, nD, TLC/Rf, [a]D), notes about characteristics of the product, and other crucial experimental details.
   5. 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. 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. 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. 3. Tietze, L.F., Brasche, G., and Gericke, K.M. (2006) Domino Reactions in Organic Synthesis, Wiley-VCH Verlag GmbH, Weinheim.
4. 4. (2001) Organikum, 21st edn, Wiley-VCH Verlag GmbH, Weinheim.
5. 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. 6. Larock, R.C. (1999) Comprehensive Organic Transformations (A Guide to Functional Group Preparations), 2nd edn, Wiley-VCH Verlag GmbH, Weinheim.
7. 7. (a) Retrosynthesis is oriented toward the concepts and terminology of Warren, S. (1982) Organic Synthesis - The Disconnection Approach, John Wiley & Sons, Inc., New York;(b) Warren, S. (1978) Designing Organic Syntheses, John Wiley & Sons, Inc., New York;(c) Corey, E.J. and Cheng, X.-M. (1989) The Logic of Chemical Synthesis, John Wiley & Sons, Inc., New York.
8. 8. For example (a) Smith, M.B. (2013) March's Advanced Organic Chemistry, 7th edn, John Wiley & Sons, Inc., Hoboken, NJ;(b) Carey, F.A. and Sundberg, R.J. (1995) Organische Chemie, Wiley-VCH Verlag GmbH, Weinheim;(c) Quinkert, G., Egert, E., and Griesinger, C. (1995) Aspekte der Organischen Chemie, Wiley-VCH Verlag GmbH, Weinheim;(d) Brückner, R. (2004) Reaktionsmechanismen (Organische Reaktionen, Stereochemie, moderne Synthesemethoden), 3rd edn, Spektrum Akademischer Verlag, Heidelberg;(e) Eliel, E.L., Wilen, S.H., and Doyle, M.P. (2001) Basic Organic Stereochemistry, John Wiley & Sons, Inc., New York;(f) Fuhrhop, J.-H. and Li, G. (2003) Organic Synthesis, 3rd edn, Wiley-VCH Verlag GmbH,...