Essentials of Organic Chemistry E-Book

Paul M. Dewick

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 1038

Veröffentlichungsjahr: 2013

Beschreibung

Essentials of Organic Chemistry is an accessible introduction to the subject for students of Pharmacy, Medicinal Chemistry and Biological Chemistry. Designed to provide a thorough grounding in fundamental chemical principles, the book focuses on key elements of organic chemistry and carefully chosen material is illustrated with the extensive use of pharmaceutical and biochemical examples.

In order to establish links and similarities the book places prominence on principles and deductive reasoning with cross-referencing. This informal text also places the main emphasis on understanding and predicting reactivity rather than synthetic methodology as well as utilising a mechanism based layout and featuring annotated schemes to reduce the need for textual explanations.
* tailored specifically to the needs of students of Pharmacy Medical Chemistry and Biological Chemistry
* numerous pharmaceutical and biochemical examples
* mechanism based layout
* focus on principles and deductive reasoning

This will be an invaluable reference for students of Pharmacy Medicinal and Biological Chemistry.

Leseprobe

Contents

Preface

1 Molecular representations and nomenclature

1.1 Molecular representations

1.2 Partial structures

1.3 Functional groups

1.4 Systematic nomenclature

1.5 Common groups and abbreviations

1.6 Common, non-systematic names

1.7 Trivial names for complex structures

1.8 Acronyms

1.9 Pronunciation

2 Atomic structure and bonding

2.1 Atomic structure

2.2 Bonding and valency

2.3 Atomic orbitals

2.4 Electronic configurations

2.5 Ionic bonding

2.6 Covalent bonding

2.7 Bond polarity

2.8 Conjugation

2.9 Aromaticity

2.10 Resonance structures and curly arrows

2.11 Hydrogen bonding

2.12 Molecular models

3 Stereochemistry

3.1 Hybridization and bond angles

3.2 Stereoisomers

3.3 Conformational isomers

3.4 Configurational isomers

3.5 Polycyclic systems

4 Acids and bases

4.1 Acid–base equilibria

4.2 Acidity and pKa values

4.3 Electronic and structural features that influence acidity

4.4 Basicity

4.5 Electronic and structural features that influence basicity

4.6 Basicity of nitrogen heterocycles

4.7 Polyfunctional acids and bases

4.8 pH

4.9 The Henderson–Hasselbalch equation

4.10 Buffers

4.11 Using pKa values

5 Reaction mechanisms

5.1 Ionic reactions

5.2 Radical reactions

5.3 Reaction kinetics and mechanism

5.4 Intermediates and transition states

5.5 Types of reaction

5.6 Arrows

6 Nucleophilic reactions: nucleophilic substitution

6.1 The SN2 reaction: bimolecular nucleophilic substitution

6.2 The SN1 reaction: unimolecular nucleophilic substitution

6.3 Nucleophilic substitution reactions

6.4 Competing reactions: eliminations and rearrangements

7 Nucleophilic reactions of carbonyl groups

7.1 Nucleophilic addition to carbonyl groups: aldehydes and ketones

7.2 Oxygen as a nucleophile: hemiacetals, hemiketals, acetals and ketals

7.3 Water as a nucleophile: hydrates

7.4 Sulfur as a nucleophile: hemithioacetals, hemithioketals, thioacetals and thioketals

7.5 Hydride as a nucleophile: reduction of aldehydes and ketones, lithium aluminium hydride and sodium borohydride

7.6 Carbon as a nucleophile

7.7 Nitrogen as a nucleophile: imines and enamines

7.8 Nucleophilic substitution on carbonyl groups: carboxylic acid derivatives

7.9 Oxygen and sulfur as nucleophiles: esters and carboxylic acids

7.10 Nitrogen as a nucleophile: amides

7.11 Hydride as a nucleophile: reduction of carboxylic acid derivatives

7.12 Carbon as a nucleophile: Grignard reagents

7.13 Nucleophilic substitution on derivatives of sulfuric and phosphoric acids

8 Electrophilic reactions

8.1 Electrophilic addition to unsaturated carbon

8.2 Electrophilic addition to conjugated systems

8.3 Carbocations as electrophiles

8.4 Electrophilic aromatic substitution

9 Radical reactions

9.1 Formation of radicals

9.2 Structure and stability of radicals

9.3 Radical substitution reactions: halogenation

9.4 Radical addition reactions: addition of HBr to alkenes

9.5 Radical addition of oxygen: autoxidation reactions

9.6 Phenolic oxidative coupling

10 Nucleophilic reactions involving enolate anions

10.1 Enols and enolization

10.2 Alkylation of enolate anions

10.3 Addition–dehydration: the aldol reaction

10.4 Other stabilized anions as nucleophiles: nitriles and nitromethane

10.5 Enamines as nucleophiles

10.6 The Mannich reaction

10.7 Enolate anions from carboxylic acid derivatives

10.8 Acylation of enolate anions: the Claisen reaction

10.9 Decarboxylation reactions

10.10 Nucleophilic addition to conjugated systems: conjugate addition and Michael reactions

11 Heterocycles

11.1 Heterocycles

11.2 Non-aromatic heterocycles

11.3 Aromaticity and heteroaromaticity

11.4 Six-membered aromatic heterocycles

11.5 Five-membered aromatic heterocycles

11.6 Six-membered rings with two heteroatoms

11.7 Five-membered rings with two heteroatoms

11.8 Heterocycles fused to a benzene ring

11.9 Fused heterocycles

11.10 Some classic aromatic heterocycle syntheses

12 Carbohydrates

12.1 Carbohydrates

12.2 Monosaccharides

12.3 Alditols

12.4 Glycosides

12.5 Cyclic acetals and ketals: protecting groups

12.6 Oligosaccharides

12.7 Polysaccharides

12.8 Oxidation of sugars: uronic acids

12.9 Aminosugars

12.10 Polymers containing aminosugars

13 Amino acids, peptides and proteins

13.1 Amino acids

13.2 Peptides and proteins

13.3 Molecular shape of proteins: primary, secondary and tertiary structures

13.4 The chemistry of enzyme action

13.5 Peptide biosynthesis

13.6 Peptide synthesis

13.7 Determination of peptide sequence

14 Nucleosides, nucleotides and nucleic acids

14.1 Nucleosides and nucleotides

14.2 Nucleic acids

14.3 Some other important nucleosides and nucleotides: ATP, SAM, Coenzyme A, NAD, FAD

14.4 Nucleotide biosynthesis

14.5 Determination of nucleotide sequence

14.6 Oligonucleotide synthesis: the phosphoramidite method

14.7 Copying DNA: the polymerase chain reaction

15 The organic chemistry of intermediary metabolism

15.1 Intermediary metabolism

15.2 The glycolytic pathway

15.3 The Krebs cycle

15.4 Oxidation of fatty acids

15.5 Synthesis of fatty acids

15.6 Amino acids and transamination

15.7 PLP-dependent reactions

15.8 TPP-dependent reactions

15.9 Biotin-dependent carboxylations

16 How to approach examination questions: selected problems and answers

16.1 Examination questions: useful advice

16.2 How to approach the problem: ‘Propose a mechanism for…’

16.3 Worked problems

Index

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Preface

For more years than I care to remember, I have been teaching the new intake of students to the Nottingham pharmacy course, instructing them in those elements of basic organic chemistry necessary for their future studies. During that time, I have also referred them to various organic chemistry textbooks for additional reading. These texts, excellent though they are, contain far too much material that is of no immediate use to pharmacy students, yet they fail to develop sufficiently areas of biological and medicinal interest we would wish to study in more detail. The organic chemistry needs of pharmacy students are not the same as the needs of chemistry students, and the textbooks available have been specially written for the latter group. What I really wanted was an organic chemistry textbook, considerably smaller than the 1000–1500-page tomes that seem the norm, which had been designed for the requirements of pharmacy students. Such a book would also serve the needs of those students on chemistry-based courses, but who are not specializing in chemistry, e.g. students taking medicinal chemistry and biological chemistry. I have wanted to write such a book for a long time now, and this is the result of my endeavours. I hope it proves as useful as I intended it.

Whilst the content is not in any way unique, the selection of topics and their application to biological systems should make the book quite different from others available, and of especial value to the intended readership. It is a combination of carefully chosen material designed to provide a thorough grounding in fundamental chemical principles, but presenting only material most relevant to the target group and omitting that which is outside their requirements. How these principles and concepts are relevant to the study of pharmaceutical and biochemical molecules is then illustrated through a wide range of examples.

I have assumed that readers will have some knowledge of organic chemistry and are familiar with the basic philosophy of bonding and reactivity as covered in pre-university courses. The book then presents material appropriate for the first 2 years of a university pharmacy course, and also provides the fundamental chemical groundwork for courses in medicinal chemistry, biological chemistry, etc. Through selectivity, I have generated a textbook of more modest size, whilst still providing a sufficiently detailed treatment for those topics that are included.

I have adopted a mechanism-based layout for the majority of the book, an approach that best enables the level of detail and selection of topics to be restricted in line with requirements. There is a strong emphasis on understanding and predicting chemical reactivity, rather than developing synthetic methodology. With extensive use of pharmaceutical and biochemical examples, it has been possible to show that the same simple chemistry can be applied to real-life complex molecules. Many of these examples are in self-contained boxes, so that the main theme need not be interrupted. Lots of cross-referencing is included to establish links and similarities; these do not mean you have to look elsewhere to understand the current material, but they are used to stress that we have seen this concept before, or that other uses are coming along in due course.

I have endeavoured to provide a friendly informal approach in the text, with a clear layout and easy-to-find sections. Reaction schemes are annotated to keep material together and reduce the need for textual explanations. Where alternative rationalizations exist, I have chosen to use only the simpler explanation to keep the reasoning as straightforward as possible. Throughout, I have tried to convince the reader that, by applying principles and deductive reasoning, we can reduce to a minimal level the amount of material that needs be committed to memory. Worked problems showing typical examination questions and how to approach them are used to encourage this way of thinking.

Four chapters towards the end of the book diverge from the other mechanism-oriented chapters. They have a strong biochemical theme and will undoubtedly overlap with what may be taught separately by biochemists. These topics are approached here from a chemical viewpoint, using the same structural and mechanistic principles developed earlier, and should provide an alternative perspective. It is probable that some of the material described will not be required during the first 2 years of study, but it could sow the seeds for more detailed work later in the course.

There is a measure of intended repetition; the same material may appear in more than one place. This is an important ploy to stress that we might want to look at a particular aspect from more than one viewpoint. I have also used similar molecules in different chapters as illustrations of chemical structure or reactivity. Again, this is an intentional strategy to illustrate the multiple facets of real-life complex molecules.

I am particularly grateful to some of my colleagues at Nottingham (Barrie Kellam, Cristina De Matteis, Nick Shaw) for their comments and opinions. I would also like to record the unknowing contribution made by Nottingham pharmacy students over the years. It is from their questions, problems and difficulties that I have shaped this book. I hope future generations of students may benefit from it.

Finally, a word of advice to students, advice that has been offered by organic chemistry teachers many times previously. Organic chemistry is not learnt by reading: paper and pencil are essential at all times. It is only through drawing structures and mechanisms that true understanding is attained.

Paul M DewickNottingham, 2005

1

Molecular representations and nomenclature

1.1 Molecular representations

From the beginnings of chemistry, scientists have devised means of representing the materials they are discussing, and have gradually developed a comprehensive range of shorthand notations. These cover the elements themselves, bonding between atoms, the arrangement of atoms in molecules, and, of course, a systematic way of naming compounds that is accepted and understood throughout the scientific world.

The study of carbon compounds provides us with the subdivision ‘organic chemistry’, and a few simple organic compounds can exemplify this shorthand approach to molecular representations. The primary alcohol propanol (systematically propan-1-ol or 1-propanol, formerly n-propanol, n signifying normal or unbranched) can be represented by a structure showing all atoms, bonds, and lone pair or nonbonding electrons.

Lines are used to show what we call single bonds, indicating the sharing of one pair of electrons. In writing structures, we have to remember the number of bonds that can be made to a particular atom, i.e. the valency of the atom. In most structures, carbon is tetravalent, nitrogen trivalent, oxygen divalent, and hydrogen and halogens are univalent. These valencies arise from the number of electrons available for bonding. More often, we trim this type of representation to one that shows the layout of the carbon skeleton with attached hydrogens or other atoms. This can be a formula-like structure without bonds, or it can be one showing just the principal bonds, those of the carbon chain.

However, for many complex structures, even these approaches become too tedious, and we usually resort to a shorthand version that omits most, if not all, of the carbon and hydrogen atoms. Propanol is now shown as a zig-zag chain with an OH group at one end. The other end of the chain, where it stops, is understood to represent a methyl group; three attached hydrogens have to be inferred. At a point on the chain, two hydrogens are assumed, because two bonds to carbons are already shown. In a structure where three bonds joined, a single additional hydrogen would be assumed (see vinyl chloride, below).

The zig-zag arrangement is convenient so that we see where carbons are located (a long straight line would not tell us how many carbons there are), but it also mimics the low-energy arrangement (conformation) for such a compound (see Section 3.3.1). Note that it is usual to write out the hydroxyl, or some alternative group, in full. This group, the so-called functional group, tends to be the reactive part of the molecule that we shall be considering in reactions. When we want an even more concise method of writing the molecule, abbreviations for an alkyl (or aryl) group may be used, in which case propanol becomes PrOH. Some more common abbreviations are given later in Table 1.3.

Double bonds, representing the sharing of two pairs of electrons, are inferred by writing a double line. Vinyl chloride (systematically chloroethene) is shown as two different representations according to the conventions we have just seen for propanol. Note that it is customary always to show the reactive double bond, so that CH2CHCl would not be encountered as an abbreviation for vinyl chloride.

The six-membered cyclic system in aromatic rings is usually drawn with alternating double and single bonds, i.e. the Kekulé form, and it is usually immaterial which of the two possible versions is used. Aniline (systematically aminobenzene or benzenamine) is shown with and without carbons and hydrogens. It is quite rare to put in any of the ring hydrogens on an aromatic ring, though it is sometimes convenient to put some in on the substituent, e.g. on a methyl, as in toluene (methylbenzene), or an aldehyde group, as in benzaldehyde.

Benzene strictly does not have alternating double and single bonds, but the aromatic sextet of electrons is localized in a π orbital system and bond lengths are somewhere in between double and single bonds (see Section 2.9.4). To represent this, a circle may be drawn within the hexagon. Unfortunately, this version of benzene becomes quite useless when we start to draw reaction mechanisms, and most people continue to draw benzene rings in the Kekulé form. In some cases, such as fused rings, it is actually incorrect to show the circles.

Thus, naphthalene has only 10 π electrons, one from each carbon, whereas the incorrect two-circle version suggests it has 12 π electrons.

We find that, in the early stages, students are usually happier to put in all the atoms when drawing structures, following earlier practices. However, you are urged to adopt the shorthand representations as soon as possible. This saves time and cleans up the structures of larger molecules. Even a relatively simple molecule such as 2-methylcyclohexanecarboxylic acid, a cyclohexane ring carrying two substituents, looks a mess when all the atoms are put in. By contrast, the line drawing looks neat and tidy, and takes much less time to draw.

Do appreciate that there is no strict convention for how you orientate the structure on paper. In fact, we will turn structures around, as appropriate, to suit our needs. For example, the amino acid tyrosine has three functional groups, i.e. a carboxylic acid, a primary amine, and a phenol. How we draw tyrosine will depend upon what modifications we might be considering, and which functional group is being altered.

You will need to be able to reorientate structures without making mistakes, and also to be able to recognize different versions of the same thing. A simple example is with esters, where students have learnt that ethyl acetate (ethyl ethanoate) can be abbreviated to CH3CO2C2H5. When written backwards, i.e. C2H5OCOCH3, the ester functionality often seems less recognizable.

1.2 Partial structures

We have just seen that we can save a lot of time and effort by drawing structures without showing all of the atoms. When we come to draw reaction sequences, we shall find that we are having to repeat large chunks of the structure each time, even though no chemical changes are occurring in that part of the molecule. This is unproductive, so we often end up writing down just that part of the structure that is of interest, i.e. a partial structure. This will not cause problems when you do it, but it might when you see one and wish to interpret it.

In the representations overleaf, you can see the line drawing and the version with methyls that stresses the bond ends. Both are satisfactory. When we wish to consider the reactivity of the double bond, and perhaps want to show that reaction occurs irrespective of the alkyl groups attached to the double bond, we put in the abbreviation R (see below), or usually just omit them. When we omit the attached groups, it helps to show what we mean by using wavy lines across the bonds, but in our urge to proceed we tend to omit even these indicators. This may cause confusion in that we now have what looks like a double bond with four methyls attached, not at all what we intended. A convenient ploy is to differentiate this from a line drawing by putting in the alkene carbons.

1.3 Functional groups

The reactivity of a molecule derives from its functional group or groups. In most instances the hydrocarbon part of the molecule is likely to be unreactive, and the reactivity of the functional group is largely independent of the nature of the hydrocarbon part. In general terms, then, we can regard a molecule as R–Y or Ar–Y, a combination of a functional group Y with an alkyl group R or aryl group Ar that is not participating in the reaction under consideration. This allows us to discuss reactivity in terms of functional groups, rather than the reactivity of individual compounds. Of course, most of the molecules of interest to us will have more than one functional group; it is this combination of functionalities that provides the reactions of chemical and biochemical importance. Most of the functional groups we shall encounter are included in Table 1.1, which also contains details for their nomenclature (see Section 1.4).

It is particularly important that when we look at the structure of a complex molecule we should visualize it in terms of the functional groups it contains. The properties and reactivity of the molecule can generally be interpreted in terms of these functional groups. It may sometimes be impossible to consider the reactions of each functional group in complete isolation, but it is valuable to disregard the complexity and perceive the simplicity of the structure. With a little practice, it should be possible to dissect the functional groups in complex structures such as morphine and amoxicillin.

Table 1.1 Functional groups and IUPAC nomenclature (arranged in order of decreasing priority)

1.4 Systematic nomenclature

Organic compounds are named according to the internationally accepted conventions of the International Union of Pure and Applied Chemistry (IUPAC). Since these conventions must cover all eventualities, the documentation required spans a book of similar size to this volume. A very much-abbreviated version suitable for our requirements is given here:

the functional group provides the suffix name;

with two or more functional groups, the one with the highest priority provides the suffix name;

the longest carbon chain containing the functional group provides the stem name;

the carbon chain is numbered, keeping minimum values for the suffix group;

side-chain substituents are added as prefixes with appropriate numbering, listing them alphabetically.

The stem names are derived from the names of hydrocarbons. Acyclic and cyclic saturated hydrocarbons (alkanes) in the range C1 – C12 are listed in Table 1.2.

Aromatic systems are named in a similar way, but additional stem names need to be used. Parent aromatic compounds of importance are benzene, naphthalene, anthracene, and phenanthrene. The last three contain fused rings, and they have a fixed numbering system that includes only those positions at which substitution can take place.

Table 1.2 Names of parent hydrocarbons

It is anticipated that readers will already be familiar with many of the general principles of nomenclature and will be able to name a range of simple compounds. It is not the object of this section to provide an exhaustive series of instructions for naming every class of compound. Instead, the examples chosen here (Box 1.1) have been selected to illustrate some of the perhaps less familiar aspects that will be commonly encountered, and to foster a general understanding of the approach to nomenclature.

Alternative names are shown in some cases; this should emphasize that there is often no unique ‘correct’ name. Sometimes, it can be advantageous to bend the rules a little so as to provide a neat name rather than a fully systematic one. Typically, this might mean adopting a lower priority functional group as the suffix name. It is important to view nomenclature as a means of conveying an acceptable unambiguous structure rather than a rather meaningless scholastic exercise. Other examples will occur in subsequent chapters, and specialized aspects, e.g. heterocyclic nomenclature, will be treated in more detail at the appropriate time (see Chapter 11). Stereochemical descriptors are omitted here, but will be discussed under stereochemistry (see Sections 3.4.2 and 3.4.3).

Box 1.1

Systematic nomenclature: some examples

alkenes have higher priority than halides; suffix is -enelongest carbon chain is seven carbons: heptanenumbering is chosen to give lowest numbers for the double bonds; 2-ene denotes 2,3-double bond, 4-ene denotes 4,5-double bondthe European system hepta-2,4-diene is less prone to errors than the US system 2,4-heptadienean additional syllable -a- is used but is not obligatory; heptadiene is easier to say than heptdienealcohols have higher priority than alkynes; suffix is -ollongest carbon chain is six carbons: hexanenumbering is chosen to give lowest number for alcoholthe European system hex-5-yn-2-ol keeps numbers and functionalities togetheracids have higher priority than amines; remember ‘amino acids’suffix is -oic acidone of the methyls is part of the five carbon chain, the others are substituentsnote the use of 4,4-, which shows both methyls are attached to the same carbon; 4-dimethyl would not be as precisehighest priority group is ketone; suffix -onelongest carbon system is the ring cyclohexanenumbering is around the ring starting from ketone as position 12,5-diene conveys 2,3- and 5,6-double bondsnote 2,5-dienone means two double bonds and one ketone; contrast endione which would be one double bond and two ketoneshighest priority group is aldehyde; suffix -alamino group at 4 is also substituted; together they become ethylaminothe alternative name invokes a seven-carbon chain with one carbon (C-5) replaced by nitrogen; this is indicated by using the extra syllable -aza-, so the chain becomes 5-azaheptanesimple ethers are best named as an alkyl alkyl etherthe phenylmethyl group is commonly called benzylan acceptable alternative is as an alkoxy alkane: the alternative ethoxytoluene would require an indication of the point of attachmentthe second alternative invokes a three-carbon chain with one carbon replaced by oxygen; this is indicated by using the extra syllable -oxa-, so the chain becomes 2-oxabutaneesters are named alkyl alkanoate – two separate words with no hyphen or commaalkyl signifies the alcohol part from which the ester is constructed, whilst alkanoate refers to the carboxylic acid partbut-2-yl means the ester is constructed from the alcohol butan-2-ol; 3-phenylpropanoate means the acid part is 3-phenylpropanoic acidnote the numbers 2 and 3 are in separate words and do not refer to the same part of the moleculethis is a methyl ester of a substituted benzoic acid; the ring is numbered from the point of attachment of the carboxylthe acid portion for the ester is 2-substitutedthe ether group is most easily treated as a methoxy substituent on the benzene ringthe carboxylic acid takes priority; suffix usuallyoic acidthe carboxylic acid is here treated as a substituent on the cyclohexane ring; the combination is called cyclohexanecarboxylic acidthis is a secondary amide of butanoic acid; thus the root name is butanamidetwo methyl substituents are on position 3, and one on the nitrogen, hence N,3,3-trimethyl; the N is given in italicsa ketone in which the longest chain is two carbons; thus the root name is ethanonethe phenyl substituent is on the carbonyl, therefore at position 1without the 1-substituent, ethanone is actually an aldehyde, and would be ethanal!the alternative methyl phenyl ketone is a neat and easy way of conveying the structurethis structure has a common name, acetophenone, which derives from an acetyl (CH3CO) group bonded to a phenyl ringan amine; suffix usually -aminethe root name can be phenylamine, as an analogue of methylamine, or the systematic benzenamine; in practice, the IUPAC accepted name is anilinethe ring is numbered from the point of attachment of the amino groupthe prefixes ortho-, meta-, and para- are widely used to denote 1,2-, 1,3-, or 1,4-arrangements respectively on an aromatic ring; these are abbreviated to o-, m-, and p-, all in italicsthis could be named as an alcohol, or as a phenolas an alcohol (butanol), there is a substituted phenyl ring attached at position 2note the phenyl and its substituents are bracketed to keep them together, and to separate their numbering (shown underlined) from that of the alcohol chainas a phenol, the substituted butane side-chain is attached through its 2-position so has a root name but-2-yl to show the position of attachment; again, this is in brackets to separate its numbering from that of the phenoldi-, tri-, tetra-, etc. are not part of the alphabetical sequence for substituents; dimethoxy comes under m, whereas trihydroxy would come under h, etc.this is a thioether, which can be named as a thioether or as a sulfidean alternative invokes a four-carbon chain with one carbon replaced by sulfur using the extra syllable -thia-; this chain thus becomes 2-thiabutanenote how the (trimethyl)methyl group is most frequently referred to by its long-established name of tertiary-butyl, abbreviated to tert-butyl, or t-butylthis contains an amine, an amide, and a carboxylic acid; the acid takes prioritythe amide group as a substituent is termed carbamoyl; this includes one carbon, so the chain length remaining to name is only four carbons – butaneit is rather easier to consider the amide as amino and ketone substituents on the five-carbon chainthe ketone is indicated by oxo-; do not confuse this with -oxa-, which signifies replacement of one carbon by oxygenthe common name is glutamic acid; it is an amino acid found in proteins

There now follow a number of examples demonstrating how to convert a systematic name into a structure, with appropriate guidance hints (Box 1.2). For added relevance, these are all selected from routinely used drugs. Again, any stereochemical aspects are not included.

Box 1.2

Converting systematic names into structures: selected drug molecules

1.5 Common groups and abbreviations

In drawing structures, we are already using a sophisticated series of abbreviations for atoms and bonding. Functional groups are also abbreviated further, in that –CO2H or –CHO convey considerably more information to us than the simple formula does. Other common abbreviations are used to specify particular alkyl or aryl groups in compounds, to speed up our writing of chemistry. It is highly likely that some of these are already familiar, such as Me for methyl, and Et for ethyl. Others are included in Table 1.3.

Table 1.3 Some common structural abbreviations

1.6 Common, non-systematic names

Systematic nomenclature was introduced at a relatively late stage in the history of chemistry, and thus common names had already been coined for a wide range of chemicals. Because these names were in everyday usage, and familiar to most chemists, a number have been adopted by IUPAC as the approved name, even though they are not systematic. These are thus names that chemists still use, that are used for labelling reagent bottles, and are those under which the chemical is purchased. Some of these are given in Table 1.4, and it may come as a shock to realize that the systematic names school chemistry courses have provided will probably have to be ‘relearned’.

The use of the old terminology n- (normal) for unbranched hydrocarbon chains, with i- (iso), s- (secondary), t- (tertiary) for branched chains is still quite common with small molecules, and can be acceptable in IUPAC names.

Table 1.4 Common, non-systematic names

1.7 Trivial names for complex structures

Biochemical and natural product structures are usually quite complex, some exceedingly so, and fully systematic nomenclature becomes impracticable. Names are thus typically based on so-called trivial nomenclature, in which the discoverer of the natural product exerts his or her right to name the compound. The organism in which the compound has been found is frequently chosen to supply the root name, e.g. hyoscyamine from Hyoscyamus, atropine from Atropa, or penicillin from Penicillium. Name suffixes might be -in to indicate ‘a constituent of’, -oside to show the compound is a sugar derivative, -genin for the aglycone released by hydrolysis of the sugar derivative, -toxin for a poisonous constituent, or they may reflect chemical functionality, such as -one or -ol. Traditionally, -ine is always used for alkaloids (amines).

Structurally related compounds are then named as derivatives of the original, using standard prefixes, such as hydroxy-, methoxy-, methyl-, dihydro-, homo-, etc. for added substituents, or deoxy-, demethyl-, demethoxy-, dehydro-, nor-, etc. for removed substituents. Homo- is used to indicate one carbon more, whereas nor- means one carbon less. The position of this change is then indicated by systematic numbering of the carbon chains or rings. Some groups of compounds, such as steroids and prostaglandins, are named semi-systematically from an accepted root name for the complex hydrocarbon skeleton. Drug names chosen by pharmaceutical manufacturers are quite random, and have no particular relationship to the chemical structure.

1.8 Acronyms

Some of the common reagent chemicals and solvents are usually referred to by acronyms, a sequence of letters derived from either the systematic name or a trivial name. We shall encounter some of these in due course, and both name and acronym will be introduced when we first meet them. For reference purposes, those we shall meet are also listed in Table 1.5. Far more examples occur with biochemicals. Those indicated cover many, but the list is not comprehensive.

Table 1.5 Some common acronyms

Acronym

Chemical/biochemical name

Reagents and solvents

DCC

D

i

c

yclohexyl

c

arbodiimide

DMF

D

i

m

ethyl

f

orm amide

DMSO

D

i

m

ethyl

s

ulf

o

xide

LAH

L

ithium

a

luminium

h

ydride

LDA

L

ithium

d

i-isopropyl

a

mide

mCPBA

m

eto-

C

hloro

p

eroxy

b

enzoic

a

cid

NBS

N

-

B

romo

s

uccinimide

PTSA

p

ara

-

T

oluene

s

ulfonic

a

cid

tBOC

t

ert

-

B

utyl

o

xy

c

arbonyl

THF

T

etra

h

ydro

f

uran

Biochemicals

ADP

Adenosine diphosphate

AMP

Adenosine monophosphate

ATP

Adenosine triphosphate

CDP

Cytidine diphosphate

CTP

Cytidine triphosphate

DNA

Deoxyribonucleic acid

FAD

Flavin adenine dinucleotide

FADH

2

Flavin adenine dinucleotide (reduced)

FMN

Flavin mononucleotide

FMNH

2

Flavin mononucleotide (reduced)

GDP

Guanosine diphosphate

GTP

Guanosine triphosphate

NAD

+

Nicotinamide adenine dinucleotide

NADH

Nicotinamide adenine dinucleotide (reduced)

NADP

+

Nicotinamide adenine dinucleotide phosphate

NADPH

Nicotinamide adenine dinucleotide phosphate (reduced)

PLP

Pyridoxal 5′-phosphate

RNA

Ribonucleic acid

SAM

S

-Adenosylmethionine

TPP

Thiamine diphosphate

UDP

Uridine diphosphate

UTP

Uridine triphosphate

1.9 Pronunciation

As you listen to chemists talking about chemicals, you will soon realize that there is no strict protocol for pronunciation. Even simple words like ethyl produce a variety of sounds. Many chemists say ‘eethyle’, but the Atlantic divide gives us ‘ethel’ with short ‘e’s, and continental European chemists often revert to the German pronunciation ‘etool’. There is little to guide us in the words themselves, since methane is pronounced ‘meethayne’ whilst methanol tends to have short ‘e’, ‘a’, and ‘o’, except for occasional cases, mainly European, when it may get a long ‘o’. On the other hand, propanol always seems to have the first ‘o’ long, and the second one short. Vinyl can be ‘vinil’ or ‘vynyl’ according to preference, and amino might be ‘ameeno’ or ‘amyno’. Need we go on? Your various teachers will probably pronounce some common words quite differently. Try to use the most commonly accepted pronunciations, and don’t worry when a conversation with someone involves differences in pronunciation. As long as there is mutual understanding, it’s not really important how we say it. By and large, chemists are a very tolerant group of people.

2

Atomic structure and bonding

2.1 Atomic structure

Atoms are composed of protons, neutrons and electrons. Protons are positively charged, electrons carry a negative charge, and neutrons are uncharged. In a neutral atom, the nucleus of protons and neutrons is surrounded by electrons, the number of which is equal to the number of protons. This number is also the same as the atomic number of the atom. If the number of electrons and protons is not equal, the atom or molecule containing the atom will necessarily carry a charge, and is called an ion. A negatively charged atom or molecule is termed an anion, and a positively charged species is called a cation.

The inert or noble gases, such as helium, neon, and argon, are particularly unreactive, and this has been related to the characteristic number of electrons they contain, 2 for helium, 10 for neon (2 + 8), and 18 for argon (2 + 8 + 8). They are described as possessing ‘filled shells’ of electrons, which, except for helium, contain eight electrons, an octet. Acquiring a noble gas-like complement of electrons governs the bonding together of atoms to produce molecules. This is achieved by losing electrons, by gaining electrons, or by sharing electrons associated with the unfilled shell, and leads to what we term ionic bonds or covalent bonds. The unfilled shell involved in bonding is termed the valence shell, and the electrons in it are termed valence electrons.

2.2 Bonding and valency

For many years now, these types of bonding have been represented in chemistry via a shorthand notation. Ionic bonds have been shown as a simple electrostatic interaction of appropriate counter ions, so that sodium chloride and magnesium chloride are conveniently drawn as Na+Cl− and Mg2+ 2Cl− respectively. It becomes increasingly difficult to remove successive electrons from an atom, and ionic bonding is not usually encountered for some atoms, especially carbon. Organic chemistry, the study of carbon compounds, is dominated by covalent bonding and the sharing of electrons.

A covalent bond between atoms involves the sharing of two electrons, one from each atom. The sharing of two electrons is described as a single bond, and is indicated in shorthand notation by a single line. Depending upon the number of electrons an atom carries, it is able to form a certain number of bonds, and this number is called the valency of the atom. The valency of hydrogen is 1, of oxygen 2, of nitrogen 3, and carbon 4. This means that we can indicate the bonding in simple organic molecules such as methane, methanol, and methylamine via single bonds (see Section 1.1).