The Literature of Organic Chemistry

chapter 26 The Literature of Organic Chemistry Getting a grasp on the chemical literature is a serious challenge, with hundreds of journals already in existence and more being created on a frequent basis. Any one of the publications might contain that kernel of knowledge that will help you solve a problem in the teaching or research laboratory. Before you think you will be buried in paper, however, take heart in knowing that there are both high- and lowtechnology strategies for efficiently browsing the literature. This chapter is intended to show you how. 26.1 Introduction Every serious chemistry student needs to understand and navigate scientific information. In the past this meant knowing one s way around the library, but today more and more information is now accessed via a computer. This makes it tempting to rely on online information to the exclusion of everything else, which can be dangerous. Despite rapid advances in information technology, most published knowledge in the sciences still exists only in printed form, and the chemist must be careful not to neglect these resources. This chapter is not intended to be a comprehensive guide to the literature of organic chemistry. Rather, it aims to provide a general overview of the important literature sources of organic chemistry that may be used as starting points for research. 26.2 Classification of the Literature Most of the literature of organic chemistry can be divided into eight major categories: (1) primary research journals, (2) review serials, (3) abstracting and indexing sources, (4) handbooks and dictionaries, (5) general multivolume references, (6) reference works on synthetic procedures and techniques, (7) sources of spectral data, and (8) advanced textbooks and monographs. (Chemical patents, which form another important segment of the organic literature, are outside the scope of this chapter.) In this section, selected examples from each of these classes are given, along with brief explanatory notes. In Section 26.3, examples are provided to illustrate how the literature may be used to find information about a specific organic compound. 991 80461_ch26_ptg01_991-1008.indd 991

992 Experimental Organic Chemistry Gilbert and Martin Journals have been the lifeblood of scientific communication for centuries. Taken together, they serve as the cumulative memory of scientific research, allowing scientists to build on the work of others and avoid unnecessary repetition of past work. Thus journals are in a sense both a starting point and endpoint for research: Scientists must know the literature of their field well and read continually to keep up to date. This informs their own research from its very beginning. Ultimately, they publish their finished work in the same journals for others to learn from, in what is essentially an unending cycle. Untold thousands of scientific journals have been published over the centuries, in all languages. Today, Chemical Abstracts Service scans over 9000 journals for new chemical information. However, the majority of significant articles are likely to be found in a few hundred of the best and most widely read journals. From their origins in the mid-seventeenth century, scientific journals remained largely unchanged for over 300 years. In the mid-twentieth century, two major shifts occurred: (1) an explosion in the number of published journals, and (2) the emergence of English as the standard international language of science. Over 85% of new chemistry papers today are written in English, regardless of their country of origin. In the 1990s, the Internet brought profound changes to the way journals are disseminated and read. Many journals in the sciences are now available to subscribers electronically. Most electronic journals, commonly called e-journals, are digital clones of the printed originals, offering full text of articles and other content in various formats, primarily in HTML (hypertext markup language) and the proprietary PDF (portable document format). The electronic journal offers a number of obvious advantages over the paper version. An authorized user may access an article any time of day or night, from any location no trip to the library is necessary. Publishers typically make the electronic version of new articles available days or weeks before the print version appears. Online journals cannot be lost or mutilated like physical volumes can. It is easy to search the full text of articles, either within a particular journal or across a number of titles from the same publisher. More significantly, index databases can link directly to the full text of an article, eliminating several steps in obtaining it. The first electronic journals started their coverage in the mid-1990s, and most publishers have now digitized their older volumes, in many cases all the way back to the first issue of the journal. At the present stage of their development, electronic journals mainly save time and reduce inconvenience, but there hopefully will be further advantages to this format in the future as technology advances. For example, publishers and scientists are exploring enhancements to the traditional journals that are made possible by the multimedia environment of the Web. Interactive features, manipulatable 3-D chemical structures, spreadsheets, hypertext links, and raw data are appearing in some e-journals. Indeed, the digital copy is now often viewed as the archival copy of record, and the printed journal itself is gradually disappearing. Another aspect of scientific journals that deserves mention is their cost. Traditional journals are sold on a subscription basis, primarily to libraries, and journals in chemistry are typically among the most expensive of any discipline. Before the 1970s, most scientists could count on having ready access to almost all of the published literature through their libraries. But in the decades since, journals have become far more numerous and costly, resulting in decreased access for many. In recent years, there has been a movement to make more of the literature open access, meaning that the articles are freely available online to anyone at any time. Many of the publishing costs, including that of peer review (see below), still 80461_ch26_ptg01_991-1008.indd 992

Chapter 26 The Literature of Organic Chemistry 993 remain, so new business models are being explored to pay for open access without compromising the quality of the literature. It s a big challenge, and the end result is still unknown. In chemistry, almost all of the top-tier journals are still accessible only to subscribing institutions. Primary Research Journals Primary research journals are the ultimate source of most of the information in chemistry. These journals publish original research results in several formats. Articles are full papers that provide historical discussions together with a presentation of the important findings, conclusions, and experimental details for preparing new compounds. Communications and Letters are short articles, sometimes with brief experimental details, that are restricted to a single topic or important discovery. Such articles must be especially timely and of general interest to the chemical community. Some journals also publish short papers called Notes that contain limited discussions and experimental details. The defining trait of primary scientific journals is the process of peer review. Authors submit a paper to the editor of a journal, who in turn sends the manuscript to selected reviewers, or referees, who evaluate the paper for originality, accuracy, relevance, and value to the scientific community. The reviewers may approve the paper for publication as-is, or they may reject it outright, but commonly they request revisions, after which it is accepted. To reduce bias, some journals keep the identity of reviewers and authors confidential this is called double-blind peer review. Others only keep the identity of the reviewers confidential. The following are some of the most important current journals for the practicing organic chemist, with their CASSI abbreviations in brackets: 1. Advanced Synthesis & Catalysis [Adv. Synth. Catal.] (2001 present). Formerly Journal für praktische Chemie, this German journal, which started in 1834, covers practical synthetic and catalytic methods from both an academic and an industrial perspective. 2. Angewandte Chemie, International Edition in English [Angew. Chem. Int. Ed.] (1962 present). This is an outstanding high-impact journal that publishes critical reviews of selected topics and communications covering all areas of chemistry. 3. Biochemistry [Biochemistry] (1962 present). Articles and communications in biochemistry, but many of the contributions tend toward the biological side of organic chemistry. Published by the American Chemical Society. 4. Bioorganic & Medicinal Chemistry [Bioorg. Med. Chem.] (1993 present). Full articles on bio-organic and medicinal chemistry topics. 5. Bioorganic & Medicinal Chemistry Letters [Bioorg. Med. Chem. Lett.] (1991 present). As the title implies, this companion to the preceding entry publishes letters and short communications on these topics. 6. Bulletin of the Chemical Society of Japan [Bull. Chem. Soc. Jpn.] (1926 present). Articles and notes in English covering all areas of chemistry. 7. Canadian Journal of Chemistry [Can. J. Chem.] (1951 present). Articles in English and French in all areas of chemistry. 8. Chemical Communications [Chem. Commun. (Cambridge, UK)] (1965 present). This Royal Society of Chemistry title publishes timely brief communications and is one of the most important general chemistry letters journals. 9. Chemistry: A European Journal [Chem.-Eur. J.] (1995 present). A spin-off from Angewandte Chemie, this newer journal has emerged as a leading title. 80461_ch26_ptg01_991-1008.indd 993

994 Experimental Organic Chemistry Gilbert and Martin 10. Chemistry Letters [Chem. Lett.] (1972 present). Communications in English covering all areas of organic chemistry. Published by the Chemical Society of Japan. 11. European Journal of Organic Chemistry [Eur. J. Org. Chem.] (1998 present). Formed by the merger of the organic sections of a number of established European chemistry journals. 12. Helvetica Chimica Acta [Helv. Chim. Acta] (1918 present). Articles and notes in English, French, or German covering all areas of organic chemistry. Official journal of the Swiss Chemical Society. 13. Heterocycles [Heterocycles] (1973 present). Reviews, communications, and articles in all areas of heterocyclic chemistry. Published in Japan by the Sendai Institute of Heterocyclic Chemistry. 14. Journal of the American Chemical Society [ J. Am. Chem. Soc.] (1879 present). Articles and communications covering all areas of chemistry. One of the foremost chemical journals in the world, JACS has a broad scope across all of chemistry. 15. Journal of Medicinal Chemistry [ J. Med. Chem.] (1959 present). Articles, communications, and notes in English covering the preparation of new organic compounds having biological activity. 16. Journal of Organic Chemistry [ J. Org. Chem.] (1936 present). Articles, communications, and notes in all areas of organic chemistry; this is arguably the best journal in the world dedicated to publishing work covering organic chemistry. It is published by the American Chemical Society. 17. Nature [Nature (London, UK)] (1869 present). This prestigious British journal is analogous to the U.S.-based Science and publishes papers in all fields of science, including chemistry. 18. Organic & Biomolecular Chemistry [Org. Biomol. Chem.] (2003 present). Formed by the merger of the two sections of Journal of the Chemical Society, Perkin Transactions. Primarily articles and some communications, in all areas of organic and bio-organic chemistry. 19. Organic Letters [Org. Lett.] (1999 present). This letters journal is published by the American Chemical Society and has rapidly become a leading title. 20. Organometallics [Organometallics] (1982 present). Published by the American Chemical Society, this is the premier journal covering all aspects of organometallic chemistry. 21. Proceedings of the National Academy of Sciences of the U.S.A. [Proc. Natl. Acad. Sci. U.S.A.] (1915 present). Major multidisciplinary journal that emphasizes the life sciences. 22. Science [Science (Washington DC, U.S.)] (1883 present). The official journal of the American Association for the Advancement of Science (AAAS), Science is one of the most prestigious, widely read and cited journals in the world. As its title implies, it is multidisciplinary in scope and publishes papers in all fields. 23. Synlett [Synlett] (1990 present). Articles and communications in the general area of synthetic organic chemistry. 24. Synthesis [Synthesis] (1969 present). Reviews, articles, and communications in the general area of synthetic organic chemistry. 25. Tetrahedron [Tetrahedron] (1957 present). An international journal dedicated to publishing articles, reviews, and symposia in print in the general areas of organic and bio-organic chemistry. 80461_ch26_ptg01_991-1008.indd 994

Chapter 26 The Literature of Organic Chemistry 995 26. Tetrahedron: Asymmetry [Tetrahedron: Asymmetry] (1990 present). Reviews, articles, and communications in the specialized area of asymmetric synthesis and methods. 27. Tetrahedron Letters [Tetrahedron Lett.] (1959 present). An international journal dedicated to publishing brief two- or four-page communications in all areas of organic and bio-organic chemistry. Review Serials Abstracting and Indexing Sources Review serials publish longer articles covering specific topics. They can be journals or periodic book series, such as those published annually. As a rule, review articles do not present new research but rather summarize and synthesize recent original work published previously in primary journals. They can be very useful as a point of entry into the literature on a less familiar topic because they contain substantial bibliographies. Reviews are often commissioned from expert authors and can take a great deal of time and effort to prepare. Some review serials publish reviews in all areas of chemistry, while others cover only specific areas. In addition to the review serials listed below, a number of the primary research journals listed above also publish excellent reviews. These include Angewandte Chemie International Edition in English, Heterocycles, Synthesis, and Tetrahedron. 1. Accounts of Chemical Research [Acc. Chem. Res.] (1968 present). Provides concise reviews of areas of active research in all areas of chemistry. It is published by the American Chemical Society. 2. Advances in Heterocyclic Chemistry [Adv. Heterocycl. Chem.] (1963 present). Publishes lengthy reviews on this topic. 3. Advances in Organometallic Chemistry [Adv. Organomet. Chem.] (1964 present). One or two volumes per year with lengthy review articles. 4. Chemical Reviews [Chem. Rev. (Washington DC, U.S.)] (1924 present). A review journal published by the American Chemical Society that covers all areas of chemistry. 5. Chemical Society Reviews [Chem. Soc. Rev.] (1972 present). A review journal with broad scope published by the Royal Society of Chemistry. 6. Natural Product Reports [Nat. Prod. Rep.] (1984 present). Comprehensive reviews of natural products chemistry. 7. Organic Reaction Mechanisms [Org. React. Mech.] (1965 present). Annual survey of the literature on this topic. 8. Organic Reactions [Org. React.] (1942 present). Annual. Each volume contains lengthy reviews that deal with an organic reaction of wide applicability. Typical experimental procedures are given in detail, and extensive tables of examples with references are provided. Each volume contains a cumulative author and chapter title index. The vast body of scientific literature would be useless without a way to find what you re looking for within it. Abstracting and indexing sources provide systematic indexing of the literature within a given subject area. Articles, patents, books, conference papers, reports, and other types of documents are regularly scanned by expert indexers, who analyze documents for pertinent content, assign subject terms, and write a concise summary called an abstract. This information is then input into a database that can be searched online. 80461_ch26_ptg01_991-1008.indd 995

996 Experimental Organic Chemistry Gilbert and Martin Chemical Abstracts is the world s largest index, providing the key to the world s chemical literature. It began in 1907 and annually abstracts over a million documents that are drawn from about 9000 technical journals as well as from books, conferences, dissertations, and patents. Chemical Abstracts (CA), which appeared weekly in print until 2009, provides by far the most complete coverage of the chemical literature after 1940. The most important contribution of Chemical Abstracts is the systematic registration of chemical compounds in the Registry file, a database that is the key piece of the Chemical Abstracts online system. Once a new chemical substance has been reported and characterized in the literature, it is assigned a specific CA Index Name and a unique Registry Number. Index names follow CA s own nomenclature rules, and these may change over time. Registry numbers (CAS RNs), however, do not change. They have the recognizable format 1234-56-7, where the first segment contains between two and seven digits. RNs themselves carry no chemical meaning they merely represent records in the CAS Registry database. Registry numbers are widely used throughout the chemical literature, and by the chemical industry, as a standard way to identify chemical structures without the confusing and contradictory problems of nomenclature. Known synonyms, trade names, and molecular and structural formulas for a given structure are listed in its Registry record, thus providing an effective link to an unambiguous identifier that can be used in indexing the literature. Over 90 million substances, including chemicals, polymers, alloys, and multicomponent mixtures, have been registered by Chemical Abstracts since 1965. Nearly a million new substances are registered each year, the majority of them organic. In addition, the database contains records for over 65 million biosequences. There are several different ways to search Chemical Abstracts electronically, and the most common are described below. 1. SciFinder. SciFinder is an interface to the Chemical Abstracts family of databases. The CAPLUS file is the equivalent to the printed Chemical Abstracts from 1907 to the present. The Registry file of chemical substances is described above. CASREACT is a file of single- and multistep organic reactions drawn from selected organic journals. SciFinder provides a user-friendly, graphical interface that permits searching by topic, author, chemical structure, and substructure. Search results can be refined, analyzed, and displayed in a number of ways. SciFinder also provides links to the electronic full text of many papers. 2. CAS Online. This database service is available through STN, the online system operated by Chemical Abstracts Service (CAS) that provides access to several related files with a choice of interfaces. Because using CAS Online incurs significant time- and query-based costs, it is advisable to obtain training and assistance from a search specialist before beginning searching. That assistance will improve the quality and the cost-effectiveness of the search. In addition to Chemical Abstracts, many other databases provide access to other specialized types of literature in related fields, including medicine, patents, polymers, toxicology, and pharmacy. These major resources deserve mention here: 1. Inspec. The primary index for physics, astronomy, and electrical and computer engineering. Includes strong coverage of chemical physics, physical chemistry, and spectroscopy. 2. Medline. Broad coverage of the biomedical journal literature. Available in several different incarnations, including PubMed, which is provided free of charge by the National Library of Medicine. It is also included in SciFinder. 80461_ch26_ptg01_991-1008.indd 996

Chapter 26 The Literature of Organic Chemistry 997 3. Web of Science. Produced by Thomson-Reuters, this is a unique reference tool that provides an alternative method to traditional subject-based literature searching. It enables you to search forward from a particular literature reference. For example, to find later applications of a reaction or method that was described in a specific paper, you simply look up the entry for that paper to identify papers that subsequently cited the original article. Visit your library or its website to learn more about these and other scientific databases that may be available to you. Handbooks and Dictionaries Handbooks and dictionaries of organic chemistry provide specific information, such as physical properties and uses of known compounds. Most of these tools are now accessed online, though most are derived from earlier printed works. 1. SigmaAldrich.com. The Aldrich Handbook is the sales catalog of the Aldrich Chemical Co., a leading supplier of research chemicals. It is also useful as a source of CAS RNs, formulas, structures, and basic physical data on thousands of products, including cross-references to the Merck Index and the Aldrich spectra and regulatory reference sets. 2. CRC Handbook of Chemistry and Physics, annual editions. CRC Press, Boca Raton, FL. The CRC is probably the best-known single-volume handbook, and it contains a wealth of useful data in all areas of chemistry and physics. The most useful part for organic chemists is the section headed Physical Constants of Organic Compounds, which provides formulas, structures, molar masses (molecular weights), densities, refractive indexes, solubilities, color, and melting and boiling points for about 11,000 compounds. There are indexes by synonym, molecular formula, and CAS RN. Many institutions also subscribe to the Web version of the CRC. 3. Combined Chemical Dictionary. The CCD is not really a dictionary, but is an excellent source for basic physical and chemical data on over 600,000 organic, organometallic, and inorganic compounds, natural products, and derivatives. Entries also provide literature references for synthesis, characterization, spectra, and properties, making the CCD useful as a starting point in a literature search. The CCD is part of the ChemNetBase system provided by CRC Press. 4. Properties of Organic Compounds. A database containing brief factual entries for about 25,000 compounds. A good source for chemical structures and numeric spectral data. It is part of the CRC ChemNetBase system. 5. Hawley s Condensed Chemical Dictionary, 15th ed., Lewis, R., ed. Wiley, New York, 2007. One of the better general chemistry dictionaries. 6. Lange s Handbook of Chemistry, 16th ed., Dean, J. A., ed. McGraw-Hill, New York, 2005. Gives physical properties for about 4300 organic compounds. Very similar to the CRC in scope and arrangement. 7. Merck Index,15th ed. Royal Society of Chemistry, Cambridge, 2013. Gives a concise summary of the physical, chemical, and pharmacological properties of more than 10,000 compounds, including pharmaceuticals, organic chemicals and reagents, inorganic substances, agricultural chemicals, and naturally occurring substances. Organization is alphabetical by name; it is best to consult the synonym index first. Also includes indexes by CAS RN and therapeutic category. 80461_ch26_ptg01_991-1008.indd 997

998 Experimental Organic Chemistry Gilbert and Martin 8. NIST Chemistry WebBook (webbook.nist.gov/chemistry). A free and authoritative online database of reliable physical, chemical, and spectral data for several thousand chemical species. Provided by the National Institute of Standards and Technology (NIST). 9. Name Reactions: A Collection of Detailed Reaction Mechanisms, 5th ed., Li, J., ed. Springer, Berlin, 2014. A useful compilation of data for name reactions, giving general scheme, mechanism of reaction, examples, and references. The German Handbuch Tradition General Treatises Distinct from the familiar American handbook publication, which is intended as a handy bench-top reference tool, the German Handbuch concept dates from the early nineteenth century, when chemists began to make attempts to catalog, summarize, and organize comprehensively the existing literature on chemical substances. This involved the systematic indexing of compounds, extraction and critical assessment of reported data and methods of preparation, and republishing pertinent data in a single, highly organized reference work. Friedrich Konrad Beilstein (1838 1906) and Leopold Gmelin (1788 1853) were pioneers of the Handbuch format, and the works that bear their names are two of the most important resources in the sciences. Today, however, the literature of chemistry is far too vast to be covered completely in handbooks, and many modern chemists are unfamiliar with them, preferring their much faster and more powerful database versions. Gmelin s Handbook deals with inorganic and organometallic compounds and is outside the scope of this chapter. Beilstein s Handbuch der Organischen Chemie is perhaps the most extensive reference work in any branch of science. It was first published in 1881 1883 in two volumes. Publication of the fourth and last edition began in 1918 and ended in 1998. In contrast to most other collections of physical and chemical data, those included in Beilstein were critically evaluated and checked for internal consistency. Although familiarity with the printed Beilstein Handbook is a useful skill for an organic chemist to have, in reality few chemists still use the printed version today. In the mid-1990s, the Beilstein Institute launched an online service that revolutionized the use of this extraordinary tool. The latest version of the system is called Reaxys, and provides online access to the database of over 25 million substances and 37 million reactions. Reaxys is best searched by drawing a chemical structure or reaction. It is also searchable by identifying elements, such as chemical name, name fragment, CAS RN, and molecular formula, as well as by numeric and keyword searches in various data fields. Reaxys is now the tool of choice for many organic and medicinal chemists seeking rapid access to the organic literature. Its primary strength is its thorough retrospective coverage of the organic literature as far back as 1771, up to 1959. The post-1960 content of Beilstein is more selective and comes from scanning a smaller number of journals and patents in organic and medicinal chemistry, seeking newly reported substances and reactions. Physical and chemical data about new and old compounds are extracted from articles and added to the database along with references to the literature source. Reaxys is owned by Elsevier. Unlike indexes or handbooks, these tools provide encyclopedic review chapters on specific subjects, with plentiful literature references, and act as an overview of the field. 1. Chemistry of Functional Groups, Patai, S., ed. Wiley-Interscience, New York. A long-running book series devoted to in-depth reviews of functional groups. 2. Chemistry of Heterocyclic Compounds (1950 present). Wiley Interscience, New York. A series of review volumes that cover specific types of heterocyclic compounds. 80461_ch26_ptg01_991-1008.indd 998

Chapter 26 The Literature of Organic Chemistry 999 3. Comprehensive Heterocyclic Chemistry, Katritzky, A. R.; Rees, C. W., eds. Pergamon Press, Oxford, 1984. An eight-volume treatise covering the reactions, structure, synthesis, and uses of heterocyclic compounds. It is supplemented by Comprehensive Heterocyclic Chemistry II, Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V., eds. Pergamon Press, Oxford, 1996, an 11-volume treatise updating the literature coverage through 1995; and Comprehensive Heterocyclic Chemistry III, Katrizky A.R., ed. Elsevier, Amsterdam, 2008, a 15-volume set. 4. Comprehensive Organic Chemistry, Barton, D. H. R.; Ollis, W. D., eds. Pergamon Press, Oxford, 1978. A six-volume treatise on the synthesis and reactions of organic compounds. 5. Comprehensive Organic Functional Group Transformations, Katritzky, A. R.; MethCohn, O.; Rees, C. W., eds. Pergamon Press, Oxford, UK, 1995. A sevenvolume set that comprehensively reviews transformations of functional groups. A seven-volume update was published in 2005. 6. Comprehensive Organic Synthesis, Trost, B. M.; Fleming, I., eds. Pergamon Press, Oxford, 1991. A nine-volume treatise that covers all aspects of synthetic organic chemistry, including carbon-carbon bond formation, heteroatom manipulation, and oxidation and reduction. A second edition was published in 2014. 7. Comprehensive Organometallic Chemistry, Wilkinson, G., ed. Pergamon Press, Oxford, 1982. A nine-volume treatise covering the synthesis, reactions, and structure of organometallic compounds. It is supplemented by Comprehensive Organometallic Chemistry II, Wilkinson, G., ed. Pergamon Press, Oxford, 1996, a 14-volume treatise updating the literature coverage through 1994; and Comprehensive Organometallic Chemistry III, Mingos, D. M. P., ed. Elsevier, Amsterdam, 2007, a 13-volume update. It is often necessary to survey the scope and limitations of a reaction, a synthetic method, a reagent, or a technique to determine whether it may be applied to solving a specific problem. To facilitate access to this information, a number of reference works are available that contain reviews of reactions, reagents, techniques, and methods in organic chemistry; these are often serial in nature. 1. Comprehensive Organic Transformations: A Guide to Functional Group Preparations, 2nd ed., Larock, R. C. John Wiley & Sons, New York, 1999. A one-volume compilation of reactions of functional groups. 2. Fieser s Reagents for Organic Synthesis. Wiley-Interscience, New York, 1967 present. These volumes describe thousands of reagents and solvents, in terms of methods of preparation or source, purification, and use in typical reactions. 3. Encyclopedia of Reagents for Organic Synthesis, 2nd ed. Paquette, L. A. John Wiley & Sons, New York, 2009. A 14-volume set, also available online, that covers important reagents used in synthetic organic chemistry. 4. Organic Syntheses. John Wiley & Sons, New York, 1921 present. An annual publication collecting detailed synthetic procedures that have been thoroughly checked by independent investigators. The procedures are general and can be applied to the synthesis of related compounds other than those described. The Collective Volumes revise, index, and republish the methods originally appearing in the annual volumes. The collective volumes contain indexes of formulas, names, types of reaction, types of compounds, purification of solvents and reagents, and illustrations of special apparatus. This useful series is freely available on the Web at orgsyn.org. 80461_ch26_ptg01_991-1008.indd 999

1000 Experimental Organic Chemistry Gilbert and Martin 5. Purification of Laboratory Chemicals, 7th ed., Armarego, W. L. F. et al. Butterworth- Heinemann, Amsterdam, 2013. Brief procedures for purifying organic solvents and reagents in the laboratory. 6. Science of Synthesis. Thieme, Stuttgart, 2000 present. A revised edition of Houben-Weyl Methoden der Organischen Chemie, providing systematic coverage of organic synthetic techniques. This resource is also available electronically by subscription. Sources of Spectral Data A problem commonly encountered in organic chemistry is identifying a compound that has been obtained from a chemical reaction or isolated from a natural source or the environment. The spectroscopic characteristics of a sample provide important clues to the identity of the substance. Collections of spectral data of known compounds provide a source of such information that may be used either to identify known compounds or to assist in the determination of the structure of an unknown substance. Two major publishers of chemical reference spectra are the Aldrich Chemical Company and Bio-Rad Sadtler Research Laboratories. Aldrich has published a number of compact compilations of infrared and NMR spectra based largely on organic chemicals sold through their catalog. These sets are commonly found in academic libraries and are easy to use, with indexes by chemical name, molecular formula, CAS RN, and Aldrich catalog number. The Aldrich sets are organized by chemical class, making it relatively easy to locate spectra similar to that of an unknown. The various Sadtler series, in contrast, are much larger and somewhat more complex to use. The spectra sheets are filed in random order, and separate index volumes must be used to locate desired compounds. The indexes provide access by name, molecular formula, or chemical class. Some important printed sets of reference spectra found in many libraries are listed below. 1. 1 H NMR Spectra Aldrich Library of NMR Spectra, 2nd ed., Pouchert, C. J., ed. Aldrich Chemical Company, Milwaukee, 1983; two volumes. A collection of about 37,000 spectra. Aldrich Library of 13 C and 1 H FT-NMR Spectra, Pouchert, C. J.; Behnke, J., eds. Aldrich Chemical Company, Milwaukee, 1993; three volumes. A collection of about 12,000 spectra. Nuclear Magnetic Resonance Spectra. Sadtler Research Laboratories, Philadelphia. Proton NMR spectra of more than 64,000 compounds. Peaks are assigned to the hydrogen nuclei responsible for the absorptions, and integration of the signals is shown on many of the spectra. 2. 13 C NMR Spectra Atlas of Carbon-13 NMR Data, Breitmaier, E.; Haas, G.; Voelter, W. Heyden, Philadelphia, 1979; two volumes. Tabular data on 3017 compounds, with chemical shifts for 13 C given and 1 H 13 C multiplicities indicated. Sadtler Standard Carbon-13 NMR Spectra. Sadtler Research Laboratories, Philadelphia, 1976 1996. Compilation of proton-decoupled spectra. 3. IR Spectra Aldrich Library of Infrared Spectra, 3rd ed., Pouchert, C. J., ed. Aldrich Chemical Company, Milwaukee, 1981. A collection of about 12,000 spectra. 80461_ch26_ptg01_991-1008.indd 1000

Chapter 26 The Literature of Organic Chemistry 1001 Aldrich Library of FT-IR Spectra, Pouchert, C. J., ed. Aldrich Chemical Co., Milwaukee, 1985 1989; three volumes. Sadtler Standard Infrared Prism Spectra. Sadtler Research Laboratories, Philadelphia. Compilation of 91,000 spectra. Sadtler Standard Infrared Grating Spectra. Sadtler Research Laboratories, Philadelphia. Compilation of 91,000 spectra. Sigma Library of FT-IR Spectra, Keller, R. J., ed. Sigma Chemical Company, St. Louis, 1986; two volumes. A collection of 10,400 spectra of biological compounds. 4. Ultraviolet Spectra Ultra Violet Spectra. Sadtler Research Laboratories, Philadelphia, 1968 1996. The Reaxys system (see Beilstein, above) indexes and provides literature references for spectral data of organic compounds, although the spectra themselves are not included. While most spectral libraries are fee-based, the Web offers a few free options for locating chemical spectra as well. One is the NIST Chemistry WebBook (webbook.nist.gov/chemistry), maintained by the National Institute of Standards and Technology. Another worthwhile free tool is the Integrated Spectral Data Base System for Organic Compounds (SDBS), maintained by the National Institute of Advanced Industrial Science and Technology in Japan (www.aist.go.jp/riodb / SDBS/menu-e.html). Advanced Textbooks and Monographs Advanced textbooks in organic chemistry provide useful information for students who are interested in a more sophisticated or advanced treatment of the information than that found in a typical undergraduate organic textbook. Monographs are books in which specific topics are examined in depth for a readership of practicing specialists and advanced students. Some monographs are written entirely by one or two authors, but most are collections of chapters written by a variety of experts under the oversight of an editor. Monographs do not present new research results, but rather serve as full-length reviews of current knowledge. Both textbooks and monographs include extensive bibliographies of primary literature references for further reading. 1. Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry; Part A: Structure and Mechanisms; Part B: Reactions and Synthesis, 5th ed. Springer, New York, 2007. An excellent survey of reactions and their applications. 2. Carruthers, W. Some Modern Methods of Organic Synthesis, 3rd ed. Cambridge University Press, Cambridge, UK, 1986. A detailed discussion of selected reactions used in synthetic organic chemistry. 3. Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G. Principles and Applications of Organotransition Metal Chemistry, 2nd ed. University Science Books, Mill Valley, CA, 1987. An excellent survey of organometallic chemistry. 4. Eliel, E. L.; Wilen, S. H.; Doyle, M. P. Basic Organic Stereochemistry, Wiley- Interscience, New York, 2001. An excellent treatise on all aspects of stereochemistry. 5. Kocienski, P. J. Protecting Groups, 3rd ed. Thieme, New York, 2005. An extensive compilation of methods for protection and deprotection of various functional groups together with insights on compatibility in polyfunctional molecules. 80461_ch26_ptg01_991-1008.indd 1001

1002 Experimental Organic Chemistry Gilbert and Martin 6. Wuts, P. G. M. Greene s Protective Groups in Organic Synthesis, 4th ed. Wiley- Interscience, New York, 2007. An extensive compilation of methods for protection and deprotection of various functional groups. 7. Lowry, T. H.; Richardson, K. S. Mechanism and Theory in Organic Chemistry, 3rd ed. Harper and Row, New York, 1987. An excellent treatment of mechanistic and theoretical aspects of organic chemistry. 8. Anslyn, E. V.; Dougherty, D. A. Modern Physical Organic Chemistry, University Science Books, Sausalito, CA, 2005. An advanced text that addresses topics in biochemistry and organometallic, materials, and bio-organic chemistry from a mechanistic viewpoint. 9. Smith, M. B.; March, J. March s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 7th ed. Wiley-Interscience, New York, 2013. An advanced text with broad coverage and many references to the original literature. 10. Smith, M. B. Organic Synthesis, 2nd ed. McGraw-Hill, New York, 2002. Chapters on synthetic topics contain extensive bibliographies and homework problems. 11. Crews, P.; Rodríguez, J.; Jaspars, M. Organic Structure Analysis, Oxford University Press, Oxford, UK, 1998. 26.3 Using The Literature Of Organic Chemistry The literature outline in this chapter may be used in a variety of ways, according to the aims and needs of different courses and the library facilities available. Even in those cases where the pressure of time and/or lack of facilities preclude the use of literature beyond the pages of this textbook itself, this chapter is still valuable if you decide to go further in the study of organic chemistry. In many organic laboratory courses, instructors make part of the experimental assignments open-ended encouraging the students to plan and carry out experiments with some independence. This is a desirable objective, but there is an element of risk if the experimental procedure has not been carefully checked; procedures found in the literature are not always easily reproduced. One of the better sources of experiments is Organic Syntheses; although the experiments are typically reported on a large scale, they may often be easily scaled down. The experiments that occasionally appear in the Journal of Chemical Education also deserve mention. The synthesis of known and unknown compounds is a task commonly encountered by the research organic chemist. In the course of this work, it is often necessary to determine whether a particular compound has been previously prepared; if it has, then the questions of when, how, and by whom arise. If the compound has not been reported, then the chemist searches for similar compounds, because the same synthetic methods might apply to the substance of interest. The examples that follow will illustrate two standard methods of performing literature searches to solve such problems, and the exercises at the end pose many types of problems that are routinely encountered in research. When beginning a search for information on a chemical compound, it is always best to start with the readily available, easy-to-use reference tools. If you do not find what you are looking for, you then proceed to larger, more complex tools. Although many students today are inclined to start with free Internet sites or search engines, this strategy will rarely provide the necessary information and may even result in 80461_ch26_ptg01_991-1008.indd 1002

Chapter 26 The Literature of Organic Chemistry 1003 misleading or erroneous data. In the setting of a chemistry laboratory, this can be dangerous. It is always better to stick with reliable, authoritative tools, whether online or in print. A trip to the library can actually be faster and more fruitful than browsing random websites. What Is Mustard Gas? Mustard gas is one of the names that has been applied to the compound ClCH 2 CH 2 S CH 2 CH 2 Cl. Let s say that you need to find the answers to the following questions: (1) Has this compound been synthesized or isolated; (2) by whom, and when; (3) where can the most recent information on this compound be found? How do you find this information? Starting with the Merck Index (15th edition), you may look up mustard gas in the name index in the back of the book. (Or you can use the electronic version of the Merck if it s available to you.) You see the name with the number 6401 next to it. This number is the monograph number within the Merck Index and indicates where you will find the entry on this substance. Turning to entry 6401, there is a paragraph containing basic information about this compound: its synonyms, molecular formula and molecular weight, and literature references describing its preparation, reactions, and toxicity. (Note the phrase Deadly vesicant. ) Other information includes melting and boiling points, densities, appearance and odor, refractive index, uses, and safety warnings. Note the CAS RN, 505-60-2, as this will come in handy in subsequent searches. The oldest literature reference in the preparation section is Meyer, Ber. 19, 3260 (1886), which refers to the 1886 article by Victor Meyer in Chemische Berichte that describes the preparation of this dangerous gas by treating [b, b ]-dihydroxyethyl sulfide with HCl gas. The Merck Index often cites the original paper or patent that reported the first synthesis of a chemical. To gather more extensive information and more recent references, some basic database searching is the next step. Reaxys Reaxys provides a large amount of chemical and physical data, as well as many retrospective references to preparation and reaction articles. Searching in Reaxys is compound-based: It allows searching by chemical name, name segment(s), molecular formula, Registry Number, and (sub)structure. SciFinder SciFinder (Chemical Abstracts) will provide literature citations from 1907 to the present. Within SciFinder, you may search for information about a compound in different ways. For instance, you can search the phrase preparation of mustard gas as a Research Topic, and this option will automatically locate the Registry Number of mustard gas and return a list of literature references where the preparation of this substance is discussed. Alternately, you can choose the search option Chemical Substance or Reaction and enter its Registry Number or its name. The Substance option will locate a group of Registry compound records for you to examine and choose from, after which you can retrieve the relevant literature references. Both approaches work well for this question. It is always a good idea to examine the compound s Registry record to confirm the structure and gather synonyms for use elsewhere. In the case of a well-known compound like mustard gas, a search in SciFinder will often retrieve thousands of documents, requiring you to narrow your search with additional terms or parameters. 80461_ch26_ptg01_991-1008.indd 1003

1004 Experimental Organic Chemistry Gilbert and Martin Medline If you are also interested in the toxicity and health effects of mustard gas, searching the medical literature is the next step. Medline thoroughly indexes the medical literature, and it contains a great deal of information on the biochemical, toxicological, and clinical aspects of this poison. Medline is included in SciFinder, where it can be searched simultaneously with Chemical Abstracts. The free version of Medline is called PubMed. Web of Science (Science Citation Index) Another way to find papers that might be relevant to the mustard gas question is to search Web of Science for articles that have cited Meyer s original synthesis. The interface allows you to look up the Meyer paper as a cited reference. Several authors have cited Meyer in the last decade or so, demonstrating that the organic chemistry literature has a long shelf-life. Is a Compound of Interest Known? A second example of a search for the preparation of the compound 3-(2-furyl)- 1-(3-nitrophenyl) propenone illustrates how you can use Reaxys and Registry to find compounds that have been reported in the literature, especially those that are not likely to be found in standard handbooks such as the Merck Index and the CRC. It does not really matter which database you consult first, but you should ideally use both. An important point to realize is that the exact name you have for the compound, if you have one at all, is unlikely to be the name used in Reaxys or Registry, which use their own quite different systems of nomenclature. So it is generally unwise to rely solely on a name search in any database or index. O O NO 2 3-(2-Furyl)-1-(3-nitrophenyl)propenone First, draw the structure of the compound in the Reaxys structure editor and search it. This brings up the record for the compound in question. A method of preparation using furfural and 1-(3-nitrophenyl)ethanone is found by clicking on the Preps total in the Preparations column. If you follow the link to the Reaxys reaction record, you find two literature references: D. L. Turner, J. Am. Chem. Soc. 71, 1949, 612, and Li, Synth.Comm. 29, 1999, 965. O O CHO 2-Furaldehyde CCH 3 Acetophenone Next, follow up with a search in Chemical Abstracts/Registry. Using SciFinder, you can draw the structure in the structure editor, specify an exact search, and locate Registry records that match. Note that searching the exact name as given above results in no hits, and a molecular formula search on C 13 H 9 NO 4 retrieves hundreds 80461_ch26_ptg01_991-1008.indd 1004

Chapter 26 The Literature of Organic Chemistry 1005 of hits, neither of which is very helpful. A structure search is thus clearly the best option. From this search we find that the CAS RN for this compound is 15462-51-8, and its CA Index Name is 2-propen-1-one, 3-(2-furanyl)-1-(3-nitrophenyl)-. A related record with CAS RN 132434-55-0 has the same structure but with a double bond geometry indicated; isomers are given separate entries in CAS. From this point, you can easily retrieve further literature references, including the two papers cited through Reaxys as noted above. If thorough searches in both Beilstein and SciFinder turn up no exact matches for the structure in question, it is advisable to search the molecular formula and/ or name in the pre-1967 Chemical Abstracts printed indexes. If you still are unable to find a match, you can fairly safely assume that the compound has not been fully characterized in the literature. Further searches for similar compounds can then begin. Exercises 1. Find the melting points of the following crystalline derivatives: a. 2,4-dinitrophenylhydrazone of trichloroacetaldehyde b. semicarbazone of 3-methylcyclohexanone c. phenylurethane of 1,3-dichloro-2-propanol d. amide of 2-methyl-3-phenylpropanoic acid e. benzamide of 4-fluoroaniline 2. Locate an article or a chapter on each of the following types of organic reactions: a. the aldol reaction b. the Wittig reaction c. reactions of diazoacetic esters with unsaturated compound d. hydration of alkenes and alkynes through hydroboration e. metalation with organolithium compounds f. reactions of lithium dialkylcuprates g. asymmetric synthesis of amino acids h. the Suzuki reaction i. Click chemistry j. enantioselective alkylation of enolates k. organozinc chemistry l. multicomponent reactions m. cascade (or domino) reactions n. sigmatropic rearrangements o. transition metal-catalyzed cross-coupling reactions p. enantioselective epoxidation q. organic catalysis r. C H activation s. cyclopropanation reactions t. intramolecular Diels-Alder reactions 80461_ch26_ptg01_991-1008.indd 1005

1006 Experimental Organic Chemistry Gilbert and Martin u. diversity-oriented synthesis v. enantioselective reductions w. catalytic oxidations x. microwave-assisted synthesis y. solid-phase synthesis z. protecting groups 3. Give a literature reference for a practical synthetic procedure for each of the following compounds and state the yield that may be expected: a. 1,2-dibromocyclohexane b. a-tetralone c. 3-chlorocyclopentene d. 2-carboethoxycyclopentanone e. norcarane f. tropylium fluoborate g. 1-methyl-2-tetralone h. adamantane i. buckminsterfullerene (buckyball) 4. Locate descriptions of procedures for the preparation or purification of the following reagents and solvents used in organic syntheses: a. Raney nickel catalysts b. sodium borohydride c. dimethyl sulfoxide d. sodium amide e. diazomethane 5. Find IR spectra for the following compounds: a. N- cyclohexylbenzamide b. 4,5-dihydroxy-2-nitrobenzaldehyde c. benzyl acetate d. diisopropyl ether e. 3,6-diphenyl-2-cyclohexen-1-one f. 4-amino-1-butanol 6. Find 1 H and 13 C NMR spectra of the following compounds: a. benzyl acetate b. diisopropyl ether c. 4-amino-1-butanol d. 1-propanol e. indan 7. N-Mesityl-N-phenylformamidine was first synthesized between 1950 and 1960. Use Reaxys (if available to you) or other indexes to find the primary research article in which this compound is described, and write an equation for the reaction used to prepare it. 80461_ch26_ptg01_991-1008.indd 1006