1.Jonathan Clayden (Mancheter University) Nick Greevs (Liverpool University) Stuart Warren (Cambridge University) Peter Wothers (Cambridge University) ORGANIC CHEMISTRYC o n t e n t sChemical reactions 113Organic chemists use curly arrows to represent 1.What is organic chemistry? 1reaction mechanisms123Drawing your own mechanisms with curlyarrows 127Organic chemistry and you1Problems 133Organic compounds1Organic chemistry and industry 6 6.Nucleophilic additiontotheOrganic chemistry and the periodic table 11 carbonyl group Organic chemistry and this bookMolecular orbitals explain the rteactivityof the carbonylgroup 135Connections14Cyanohydrins from the attack of cyanide on aldehydesBoxes and margin notes 15 and ketones137End-of-chapter problems15The angle of nucleophilic attack on aldehydes andColour 16ketones 139Nucleophilic attack by hydride on aldehydes and 2.Organic structuresketones 13919Addition of organometallic reagents to aldehydes andHydrocarbon frameworks and functionalgroups20 ketones142Drawing molecules21Addition of water to aldehydes and ketones143Hydrocarbon frameworks 26Hemiacetals from reaction of alcohols withaldehydesFunctional groups31and ketones 145Carbon atoms carrying functional groups canAcid and base catalysis of hemiacetal and hydratebe classified byoxidation level35formation 146Naming compounds 37Bisulfite addition compounds148Systematic nomenclature37Problems150What do chemists really call compounds?40How should you name compounds? 43 7.Delocalization and conjugationProblems 45Introduction 151 3.Determining organic structuresThe structure of ethane (ethylene,CH2=CH2) 151Molecules with more than one C-C doublebond153Introduction 47Conjugation156Mass spectrometry50The allyl system 158Nuclear magnetic resonance 56Other allyl-like system163Infrared spectra 65The conjugation of two bonds 166Mass spectra, NMR, and IR combined make quick identification possible 72 UV and visible spectra 169Aromaticity171Looking forward to Chapter 11 and 14 78Problems 179Problems 78 8.Acidity, basicity, and pKa 4.Structure of moleculesIntroduction81Introduction 181Atomic structure83Acidity182The definition of pKa185Summary of the importance of the quantum numbers86Basicity 197Atomic orbitals 87Molecular orbitals homonuclear diatomics95Neutral nitrogen bases 199Neutral oxygen bases 203Heteronuclear diatomics100pKa in action the development of the drug cimetidine 204Hybridization of atomic orbitals 105Conclusion 110Problems 207Problems 110 9.Using organometallic reagents to make C-C bonds 5.Organic reactions

2. Introduction 209 Problems336Organometallic compounds contain a carbon-metalbond 20914. Nucleophilic substitution at C=O withMaking organometallics 211loss of carbonyl oxygenUsing organometallics to make organic molecules218Introduction339A closer look at some mechanisms 223 Aldehydes can react with alcohols to form hemiacetrals 340Problems 224 Acetals are formed from aldehydes or ketones plusalcohols in the presenceof acids 342 10. Conjugate additionAmines react with carbonyl compounds348 Amines from imines: reduction amination 354Conjugation changes the reactivity of carbonyl group 227 Substitution of C=O for C=C: a brief look at the WittigAlkenes conjugated with carbonyl groups arereation 357polarized229 Summary 358Polarization is detectable spectroscopically 229 Problems358Molecular orbitals control conjugate addition230Ammonia and amines undergo conjugate addition23115. Review of spectroscopic methodsConjugate addition of alcohols can be catalysed by acid or base233 There are three reasons for this chapter361Conjugate addition or direct addition to the carbonylDoes spectroscopy help with the chemistry of thegroup? 234 carbonyl group? 361Copper (I) salts have a remarkableeffect onAcid derivatives are best distinguished by infrared 364organometallic reagents239 Small rings introduce strain inside the ring and higherConclusion 240s character outside it 365Problems 241 Simple calculations of C=O stretching frequencies in IR spectra367 11. Proton nuclear magnetic resonance Interactions between different nuclei can give enormous coupling constsants368The differences between carbon and protonNMR 243 Identifying products spectroscopically371Integration tells us the number of hydrogen atomsTables374 in each peak244 Problems379Regions of the proton NMR spectrum 245Protons on saturated carbon atoms24616. StereochemistryThe alkene region and the benzene region 251The aldehyde region: unsaturated carbon bonded toSome compounds can exist as a pair of mirror-image oxygen255 forms 381Coupling in the proton NMR spectrum258 The rotation of plane-polarized light is known as opticalTo conclude274activity 388Problems 275 Diastereoisomers are stereoisomers that are not enantiomers 390 12. Nucleophilic substitutionattheInvestigating the stereochemistry of a compound 397 carbonyl (C=O) groupSeparating enantiomers is called resolution 399 Problems404The product of nucleophilic addition to a carbonylgroup is notalways stable compound 27917. Nucleophilic substitution atCarboxylic acid derivatives280saturated carbonNot all carboxylic acid derivatives are equally reactive 286Making other compounds by substitution reactionNucleophilic substitution 407of acid derivatives297 Structure and stability of carbocations 407Making ketones from esters: the problem297 The SN1 and SN2 mechanisms for nucleophilicMaking ketones from esters: the solution 299 substitution411To summarize 301 How can we decide which mechanism(SN1 or SN2)Problems 302 will apply to a given organic compound? 414 The SN2 reaction420 13. Equilibria, rates and mechanisms: The leaving group 429 summary of mechanistic principles Nucleophiles436 Nucleophiles in the SN2 reaction437How far and how fast?305 Nucleophile and leaving groups compared 441How the equilibrium constant varies withthe difference Looking forward: elimination and rearrangement in energy between reactants and products307 reactions 443How to make the equilibrium favour the product you Problems444 want310Entropy is important in determining equilibrium 18. Conformational analysisconstant 312Equilibrium constant vary with temperature 314 Bond rotation allows chains of atoms to adopt aMaking reactions go faster: the real reason reactionsnumber of conformations 447are heated 315 Conformation and configuration448Kinetics 319 Barriers to rotation449Catalysis in carbonyl substitution ractions323 Conformations of ethane 450The hydrolysis of amides can have termolecular kinetics325 Conformations of propane450The cis-trans isomerization of alkenes 326 Conformations of butane 450Kinetic versus thermodynamic products328 Ring strain 452Low temperatures prevent unwanted reations fromA closer look at cyclohexane455 occurring 331 Substituted cyclohexanes460Solvents 332 Looking groups t-butyl groups, decalins, and steroids 463Summary of mechanisms from Chapters 6-12 334 Axially and equatorially substituted rings react 3. differently464 donor substituents 561Rings containing sp2 hybridized carbon atoms:Electronegative substituents give meta products 564cyclohexanone and cyclohexene471 Halogens (F, Cl, Br, and I) both withdraw and donateMultiple rings 473 electrons 566To conclude473 Why do some reactions stop cleantly atProblems 474 monosubstitution? 568 Rewiew of important reactions including selectivity 571 19. Elimination reactions Electrophilic substitution is the usual route to substituted aromatic compounds576Substitution and elimination477Problems577Elimination happens when the nucleophilic attackshydrogen instead of carbon478 23. Electrophilic alkenesHow the nucleophile affects elimination versussubstitution479Introduction electrophilic alkenes 581E1 and E2 mehanisms 480Nucleophilic conjugate addition to alkenes 582Substrate structure may allow E1482Conjugate substitution reactions 585The role of the leaving group 484Nucleophilic epoxidation 588E1 reactions can be stereoselective 487Nucleophilic aromatic substitution 589E1 reactions can be regioselective489The additionelimination mechanism 590E2 eliminations have anti-peroplanar transition state 490Some medicinal chemistry preparation of an antibiotic595E2 eliminations can be stereospecific 491The SN1 mechanism for nucleophilic aromaticE2 eliminations from cyclohexanes 492substitutiondiazonium compounds 597E2 elimination from vinyl halides: how to make alkynes493The benzyne mechanism600The regioselectivity of E2 eliminations 494Nucleophilic attack on allylic compounds 604Anion-stabilizing groups allow another mechanism To conclude 611E1cB495Problems 612To conclude 500Problems501 24. Chemoselectivity: selective reactionsand protection 20. Electrophilic addition to alkenes Selectivity615Alkenes react with bromine 503 Reducing agents616Oxidation of alkenes to form epoxides505 Reduction of carbonyl groups 617Electrophilic addition to unsymmetrical alkenes is Catalytic hydrogenation623 regioselective509 Getting rid of functional groups 627Eletrophilic addition to dienes510 Dissolving metal reduction 628Unsymmetrical bromonium ions open regioselectively 512 One functional group may be more reactive thanEletrophilic additions to alkenes can be tereoselctive 514 another for kineticor forthermodynamic reasons 630Bromonium ions as intermediates in stereoselective Oxidizing agents 637synthesis516 To conclude640Iodolactonization and bromolactonization make newProblems 640rings517How to add water across a double bond51825. Synthesis in actionTo conclude 520Problems 520 Introduction 643 Benzocaine 644 21. Formation and reactions of enols andSaccharin644 enolatesSalbutamol 645 Thyroxine646Would you accept a mixture of compounds as a pureMuscalure: the sex pheromone of the house-fly648substance? 523 Grandisol: the sex pheromoneof the male cotton bollTautomerism: formation of enols by transfer proton 524weevil649Why dont simple aldehydes and ketones exist as enols?525Peptide synthesis: carbonyl chemistry in action651Evidence for equilibriation of carbonyl compoundsThe synthesisi of dofetilide, a drug to combat erraticwith enols 525 heartbeat658/Enolization is catalysed by acids and bases526 Looking forward661The intermediate in the base-catalysed reaction is the Problems 661enolate ion527Summary of types of enol and enolate 52826. Alkylation of enolatesStable enols 531Consequences of enolization534 Carbonyl groups show diverse reactivity663Reaction with enols or enolates as intermediates 535 Some important considerations that affect all alkylations664Stable enolate equivalents 540 Nitriles and nitrolkenes can be alkylated664Enol and enolate reactions of oxygen: preparation of Choise of electrophile for alkylation667enol ethers541 Lithium enolates of carbonyl compounds 667Reaction of enol ethers542 Alkylations of lithium enolates668To conclude 544 Using specific enol equivalents to alkylate aldehydesProblems 544 and ketones671 Alkylation of -dicarbonyl compounds 676 22. Electrophilic aromatic substitution Ketone alkylation poses a problem in regioselectivity 680 Enones provide a solution to regioselectivity problems 683Introduction: enols and phenols547 To conclude 687Benzene and its reaction with electrophiles549 Problems 688Electrophilic substitution of phenols555A nitrogen lone pair activates even more strongly55827. Reactions of enolates with aldehydesAlkyl benzenes react at the orto and para positions: 4. and ketones: the aldol reaction The Peterson reaction is a stereospecific elimination812 Perhaps the most important way of making alkenes Introduction: the aldol reaction 689 the Wittig reaction814Cross-condensation 694 E- and Z- alkenes can be made by stereoselective addition toCompounds that can enolize but that are notalkynes 818 electrophilic 696 Problems 82Controlling aldol reaction with specific enol1equivalents69732. Determination of stereochemistry bySpecific enol equivalents for carboxylic acid derivatives704spectroscopic methodsSpecific enol equivalents for aldehydes707Specific enol equivalents for ketones709 Introduction 823 3The Mannich reaction 712 J values vary with H-C-C-H dihedral angle824Intramolecular aldol reaction715 Stereochemistry of fused rings 828To conclude: a summary of equilibrium and directed The dihedral angle is not the only angle worthaldol methods718 measuring830Problems 721 Vicinal (3J) coupling constants in other ring sizes831 Geminal (2J) coupling834 28. Acylation at carbon Diastereotopic CH2 groups835 Geminal coupling in six-membered rings 841Introduction: the Claisen ester condensation comparedA surprising reaction product842to the aldol reaction723 The contribution to geminal coupling 844Problems with acylation at carbon725 The nuclear Overhauser effect844Acylation of enolates by esters726 To conclude 848Crossed ester condensations728 Problems 848Summary of preparation of keto-esters by Claisenreaction 73333. Stereoselective reactions of cyclicIntramolecular crossed Claisen ester condensations 734compoundsDirected C-acylation of enols and enolates 736The acylation of enamines `739 Introduction 851Acylation of enols under acidic conditions 740 Reations of small rings852Acylation at nucleophilic carbon (other than enols and Stereochemical control in six-membered rings 856 enolates) 742 Conformational control in the formation of six-How nature makes fatty acids 743 membered rings 861To conclude 746 Stereochemistry of bicyclic compounds862Problems 746 Fused bicyclic compounds 863 Spirocyclic compounds870 29. Conjugate addition of enolatesReactions with cyclic intermediates or cyclic transition states871Introduction: conjugate addition of enolates is aTo conclude 879Powerful synthetic transformation749 Problems879Conjugate addition of enolates is the result ofthermodynamic control74934. DiastereoselectivityA variety of electrophilic alkenes will acceptenol(ate) nucleophiles 757 Looking back 881Conjugate addition followed by cyclization makes Making single diastereoisomers using stereospecificsixmembered rings 760 reactions of alkenes 882Nitroalkanes are superb at conjugate addition766 Stereoselective reactions884Problems 768 Prochirality 884 Additions to carbonyl groups can be diastereoselective 30. Retrosynthetic analysiseven without rings887 Chelation can reverse stereoselectivity892Creative chemistry 771 Stereoselective reactions of acyclic alkenes 895Retrosynthetic analysis: synthesis backward772 Aldol reactions can be stereoselective898Disconnections must correspond to known, Problems 903reliabile reactions773Synthons are idealized reagents77335. Pericyclic reactions 1: cycloadditionsChoosing a disconnection 775Multiple step syntheses: avoid chemoselectivityA new sort of reation 905problems 776 General description of the Diels-Alderreaction907Functional group interconversion 777 The frontier orbital description of cycloadditions914Two-group disconnections are better than one 780 The Diels-Alder reaction in more detail 916C-C disconnections 784 Regioselectivity in Diels-Alder reactions 919Donor and acceptor synthons791 The Woodward-Hoffmann description of the Diels-Two-group C-C disconnections 791 Alder reaction 9221,5 Related functional groups798 Trapping reactive intermediates by Diels-AlderNatural activity and umpolung 798 reactions 923Problems 801 Other thermal cycloadditions924 Photochemical [2+2] cycloadditions927 31. Controlling the geometry of doubleThermal [2+2] cycloadditions929 bonds Making five-membered rings 1,3-dipolar cyclo- additions 932The properties of alkenes depend on their geometry 803 Two very important synthetic reactions: cycloadditionElimination reations are often unselective 803 of alkenes with osmium tetroxide and with ozone 936The Julia olefination is regiospecific and connective810 Summary of cycloaddition reactions940Stereospecific eliminations can give pure single isomers Problems940of alkenes 812 5. 36. Pericyclic reactions 2: sigmatropicDeterminating reaction mechanisms the Cannizzaro and electrocyclic reactionsreaction 1081Be sure of the structure of the product1084Sigmatropic rearrangements 943Systematic structural variation1089Orbital description of [3,3]- sigmatropic rearrangements 946The Hammett relationship 1090The direction of [3,3]- sigmatropic rearrangements 947Other kinetic evidence 1100[2,2]- Sigmatropic rearrangements951Acid and base catalysis1102[1,3]- Sigmatropic hydrogen shifts 953The detection of intermediates 1109Electrocyclic reactions956Stereochemistry and mechanism1113Problems 966Summary of methods for the investigation ofmechanism1117 37. Rearrangements Problems 1118Neighbouring groups can accelerate substitution42. Saturatedheterocycles andreactions969 stereoelectronicsRearrangements occurs when a participatinggroupsends up bonded to a different atom975 Introduction 1121Ring expansion means rearrangement982 Reactions of heterocycles1121Carbocations rearrangements: blessing or course?983 Conformation of saturated heterocycles: the anomericThe pinacol rearrangement 984effect1128The dienone-phenol rearrangement988 Making heterocycles: ring-closing reactions1134The benzilic acid rearrangement 989 Problems 1144The Favorskii rearrangement 990Migration to oxygen: the Baeyer-Villigerreaction99243. Aromatic heterocycles 1: structuresThe Beckmann rearrangement997and reationsProblems 1000Introduction 1147 38. FragmentationAromatcity survives when parts of benzenes ring arereplaced by nitrogen atoms 1148Polarization of C-C bonds helps fragmentation1003 Pyridine is a very unreactive aromatic imine 1149Fragmentations are controlled by stereochemistry 1005 Six-membered aromatic heterocycles can have oxygenA second synthesis of longifolene1010 in the ring1156The synthesis of nootkatone1011 Five-membered heterocycles are good nucleophiles 1157A revision example: rearrangements andFuran and thiophene are oxygen and sulfur analoguesfragmentation1014of pyrrole1159Problems 1017 More reactions of five-membered heterocycles1162Five-membered rings with two or more nitrogen atoms1165 39. Radical reactionsBenzo-fused heterocycles 1169Putting more nitrogen atoms in a six-membered ring 1172Radicals contain unpaired electrons1021 Fusing rings to pyridines: quinolines andisoquinolines 1174Most radicals are extremely reactive 1022 Heterocycles can have many nitrogens but only oneHow to analyse the structure of radicals: electron spinsulfur or oxygen in any ring1176resonance1024 There are thousands more heterocycles out there1176Radicals have singly occupied molecular orbitals 1025 Which heterocyclic structures should you learn?1180Radical stability1026 Problems 1182How do radicals react? 1029Titanium promotes the pinacol couplingthen 44. Aromatic heterocycles 2: synthesisdeoxygenates the products: the McMurry reaction1031Radical chain reactions1033 Thermodynamics is one our side 1185Selectivity in radical chain reactions 1035 Disconnect the carbon-heteroatom bonds first11186Selective radical bromination: allylic substitution of HPyrroles, thiophenes, and furans from 1,4-dicarbonylby Br1039compounds 1188Controlling radical chains 1041 How to make pyridines: the Hantzsch pyridineThe reactivity pattern of radicals is quite different synthesis1191from that of polar reagents1047 Pyrazoles and pyridazines from hydrazine andAn alternative way of making alkyl radicals: the mercurydicarbonyl compounds 1195 method1048 Pyrimidines can be made from 1,3-dicarbonyl compoundsIntramolecular radical reactions are moreefficientand amidines 1198that intermolecular ones 1049 Unsymmetrical nucleophiles lead to selectivityProblems 1051 questions1199Izoxazoles are made from hydroxylamine or by 40. Synthesis and reactions of carbenes1,3-dipolar cycloadditions 1200Tetrazoles are also made by 1,3-dipolar cycloadditions 1202Diazomethane makes methyl esters from carboxylicThe Fischer indole synthesis 1204Acids1053 Quinolines and isoquinolines 1209Photolysis of diazomethane produces a carbene1055 More heteroatoms in fused rings mean more choise inHow are carbenes formed? 1056 synthesis1212Carbenes can be devided into two types 1060 Summary: the three major approaches to the synthesisofHow do carbenes react? 1063 aromatic heterocycles1214Alkene (olefin) metathesis 1074 Problems 1217Summary1076Problems 107645. Asymmetric synthesis 41. Determining reaction mechanismsNature is asymmetrical Nature in the looking-glass 1219Resolution can be used to separateenantiomers1221There are mechanisms and there are mechanisms1079 The chiral pool Natures ready-made chiral centers 1222 6. Asymmetric synthesis 1225 Natures enols lysine enamines and coenzyme A 1388Chiral reagents and chiral catalysts 1233 Natures acyl anion equivalent (d1 reagent) is thiamineProblems 1244 pyrophosphate 1392Rearrangements in the biosynthesis of valine and 46. Organo-main-group chemistry 1: isoleucine1397 sulfur Carbon dioxide is carried by biotin 1399The shikimic acid pathway 1400Sulfur: an element of contradictions 1247 Haemoglobin carries oxygen as an iron (II) complex1406Sulfur-stabilized anions 1251 Problems1411Sulfonium salts1255Sulfonium ylids1258 51. Natural productsThiocarbonyl compounds 1264Sulfoxides 1265Introduction1413Other oxidations with sulfur and selenium1270Natural products come from secondary metabolism 1414To conclude: the sulfur chemistry of onions and garlic 1272Alkaloids are basic compounds from amino acidProblems 1273metabolism1414Fatty acids and other poliketides are made from 47. Organo-main-group chemistry2: acetyl CoA 1425 boron, silicon, and tinAromatic poliketides come in great variety1433Terpenes are volatile constituents of plant resins andOrganic chemists make extensive use of the periodicessential oils1437table1277Steroids are metabolites of terpene origin1441Boron1278Biomimetic synthesis: learning from Nature1446Silicon and carbon compared1287Problems1447Organotin compounds1304Problems 1308 52. Polymerization 48. Organometallic chemistryMonomers, dimmers, and oligomers1451Polimerazation by carbonyl substitution reactions 1453Transition metals extend the range of organic reactions 1311Polimerazation by electrophilic aromatic substitution 1455Transition metal complexes exibit special bonding 1315Polimerazation by the SN2 reaction1456Palladium (0) is most widely used in homogenousPolimerazation by nucleophilic attack on isocyanates1458catalysis 1319Polimerazation of alkenes 1459Alkenes are attacked by nucleophiles when coordinatedCo-polymerization 1464to palladium (II) 1336Cross-linked polymers 1466Palladium catalysis in the total synthesis of a naturalReactions of polymers 1468alkaloid1338Biodedegradable polymers and plastics 1472Other transition metals: cobalt 1339Chemical reagents can be bonded to polymers 1473Problems1341Problems1478 49. The chemistry of life 53. Organic chemistry todayPrimary metabolism 1345Modern science is based on interaction betweenLife begins with nucleic acids 1347disciplines 1481Proteins are made of amino acids 1353The synthesis of Crixivan 1483Sugars just energy sources?1359The future of organic chemistry 1487Glycosides are everywhere in nature1368Most sugars are embedded in carbohydrates1372 Index1491Lipids 1374Bacteria and people have slightly different chemistry1377Problems 1379 50. Mechanisms in biological chemistryNatures NaBH4 is a nucleotide: NADH or NADPH1381Reductive amination in nature1384 7. What is organic chemistry?1Organic chemistry and youYou are already a highly skilled organic chemist. As you read these words, your eyes are using anorganic compound (retinal) to convert visible light into nerve impulses. When you picked up thisbook, your muscles were doing chemical reactions on sugars to give you the energy you needed. AsH Oyou understand, gaps between your brain cells are being bridged by simple organic molecules (neuro-transmitter amines) so that nerve impulses can be passed around your brain. And you did all that 11-cis-retinal absorbs light when we seewithout consciously thinking about it. You do not yet understand these processes in your mind aswell as you can carry them out in your brain and body. You are not alone there. No organic chemist,NH2however brilliant, understands the detailed chemical working of the human mind or body very well. HOWe, the authors, include ourselves in this generalization, but we are going to show you in thisbook what enormous strides have been taken in the understanding of organic chemistry since the Nscience came into being in the early years of the nineteenth century. Organic chemistry began as a Htentative attempt to understand the chemistry of life. It has grown into the confident basis of vast serotoninmultinational industries that feed, clothe, and cure millions of people without their even being human neurotransmitteraware of the role of chemistry in their lives. Chemists cooperate with physicists and mathemati-cians to understand how molecules behave and with biologists to understand how moleculesdetermine life processes. The development of these ideas is already a revelation at the beginning ofWe are going to give youthe twenty-first century, but is far from complete. We aim not to give you the measurements of thestructures of organic compoundsin this chapterotherwise itskeleton of a dead science but to equip you to understand the conflicting demands of anwould be rather dull. If you do notadolescent one. understand the diagrams, do notLike all sciences, chemistry has a unique place in our pattern of understanding of the universe. It worry. Explanation is on its way.is the science of molecules. But organic chemistry is something more. It literally creates itself as itgrows. Of course we need to study the molecules of nature both because they are interesting in theirown right and because their functions are important to our lives. Organic chemistry often studies lifeby making new molecules that give information not available from the molecules actually present inliving things.This creation of new molecules has given us new materials such as plastics, new dyes to colour ourclothes, new perfumes to wear, new drugs to cure diseases. Some people think that these activities areunnatural and their products dangerous or unwholesome. But these new molecules are built byhumans from other molecules found on earth using the skills inherent in our natural brains. Birdsbuild nests; man makes houses. Which is unnatural? To the organic chemist this is a meaningless dis-tinction. There are toxic compounds and nutritious ones, stable compounds and reactive onesbutthere is only one type of chemistry: it goes on both inside our brains and bodies and also in our asksand reactors, born from the ideas in our minds and the skill in our hands. We are not going to setourselves up as moral judges in any way. We believe it is right to try and understand the world aboutus as best we can and to use that understanding creatively. This is what we want to share withyou.Organic compoundsOrganic chemistry started as the chemistry of life, when that was thought to be different from thechemistry in the laboratory. Then it became the chemistry of carbon compounds, especially thosefound in coal. Now it is both. It is the chemistry of the compounds of carbon along with other ele-ments such as are found in living things and elsewhere. 8. 21 . What is organic chemistry? The organic compounds available to us today are those present in living things and those formedYou will be able to read towards the over millions of years from dead things. In earlier times, the organic compounds known from natureend of the book (Chapters 4951) were those in the essential oils that could be distilled from plants and the alkaloids that could beabout the extraordinary chemistry thatallows life to exist but this is known extracted from crushed plants with acid. Menthol is a famous example of a avouring compoundonly from a modern cooperationbetween chemists and biologists. from the essential oil of spearmint and cis-jasmone an example of a perfume distilled from jasmine owers. O N HOOH cis-jasmonementhol MeO quinine N Even in the sixteenth century one alkaloid was famousquinine was extracted from the bark of the South American cinchona tree and used to treat fevers, especially malaria. The Jesuits who did this work (the remedy was known as Jesuits bark) did not of course know what the structure of quinine was, but now we do. The main reservoir of chemicals available to the nineteenth century chemists was coal. Distil- lation of coal to give gas for lighting and heating (mainly hydrogen and carbon monoxide) also gave a brown tar rich in aromatic compounds such as benzene, pyridine, phenol, aniline, and thiophene.OH NH2SN benzene phenolaniline thiophenepyridinePhenol was used by Lister as an antiseptic in surgery and aniline became the basis for the dyestuffs industry. It was this that really started the search for new organic compounds made by chemists rather than by nature. A dyestuff of this kindstill availableis Bismarck Brown, which should tell you that much of this early work was done in Germany. H2NNH2H2N NH2NNNNBismarck Brown YIn the twentieth century oil overtook coal as the main source of bulk organic compounds so that simple hydrocarbons like methane (CH4, natural gas) and propane (CH3CH2CH3, calor gas)You can read about polymers andbecame available for fuel. At the same time chemists began the search for new molecules from newplastics in Chapter 52 and about ne sources such as fungi, corals, and bacteria and two organic chemical industries developed in paral-chemicals throughout the book. lelbulk and ne chemicals. Bulk chemicals like paints and plastics are usually based on simple molecules produced in multitonne quantities while ne chemicals such as drugs, perfumes, andCH3 (CH2)nCH3 avouring materials are produced in smaller quantities but much more protably.n = an enormous numberlength of molecule is n + 2 At the time of writing there were about 16 million organic compounds known. How many morecarbon atoms are possible? There is no limit (except the number of atoms in the universe). Imagine youve justCH3 (CH2)nCH2CH3 made the longest hydrocarbon ever madeyou just have to add another carbon atom and youven = an enormous number made another. This process can go on with any type of compound ad innitum.length of molecule is n + 3 But these millions of compounds are not just a long list of linear hydrocarbons; they embrace allcarbon atoms kinds of molecules with amazingly varied properties. In this chapter we offer a selection. 9. Organic compounds 3 What do they look like? They may be crystalline solids, oils,HOOwaxes, plastics, elastics, mobile or volatile liquids, or gases. HOHOFamiliar ones include white crystalline sugar, a cheap naturalHO Ocompound isolated from plants as hard white crystals when pure, OHand petrol, a mixture of colourless, volatile, ammable hydrocar- HO CH3CH3 OCH3bons. Isooctane is a typical example and gives its name to the OHCCHoctane rating of petrol.CH3C CH3 The compounds need not lack colour. Indeed we can soonH2HOdream up a rainbow of organic compounds covering the wholespectrum, not to mention black and brown. In this table we have sucrose ordinary sugar isooctane (2,3,5-trimethylpentane)isolated from sugar canea major constiuent of petrolavoided dyestuffs and have chosen compounds as varied in struc- or sugar beetvolatile inflammable liquidture as possible. white crystalline solidsColourDescriptionCompoundStructure red dark red hexagonal plates3-methoxybenzocycloheptatriene- O2-onepMeO orangeamber needlesdichloro dicyano quinone (DDQ) O ClCNe ClCN Oc yellowtoxic yellow explosive gas diazomethane CH2 N N green green prisms with a9-nitroso julolidine N t steel-blue lustre r NO bluedeep blue liquid with aazulene peppery smellu purpledeep blue gas condensing nitroso triuoromethaneF N to a purple solidCO F FmColour is not the only characteristic by which we recognize compounds. All too often it is theirodour that lets us know they are around. There are some quite foul organic compounds too; thesmell of the skunk is a mixture of two thiolssulfur compounds containing SH groups.skunk spray contains: SH +SH 10. 4 1 . What is organic chemistry?S But perhaps the worst aroma was that which caused the evacuation of the city of Freiburg in 1889.Attempts to make thioacetone by the cracking of trithioacetone gave rise to an offensive smell whichspread rapidly over a great area of the town causing fainting, vomiting and a panic evacuationthethioacetonelaboratory work was abandoned.It was perhaps foolhardy for workers at an Esso research station to repeat the experiment of crack-ing trithioacetone south of Oxford in 1967. Let them take up the story. Recentlywe found ourselves?with an odour problem beyond our worst expectations. During early experiments, a stopper jumpedfrom a bottle of residues, and, although replaced at once, resulted in an immediate complaint of nau- Ssea and sickness from colleagues working in a building two hundred yards away. Two of ourchemists who had done no more than investigate the cracking of minute amounts of trithioace- SStonefound themselves the object of hostile stares in a restaurant and suffered the humiliation ofhaving a waitress spray the area around them with a deodorant. The odours deed the expectedtrithioacetone;effects of dilution since workers in the laboratory did not nd the odours intolerable . . . and genu-Freiburg was evacuatedinely denied responsibility since they were working in closed systems. To convince them otherwise,because of a smell fromthe distillation this compoundthey were dispersed with other observers around the laboratory, at distances up to a quarter of amile, and one drop of either acetone gem-dithiol or the mother liquors from crude trithioacetonecrystallisations were placed on a watch glass in a fume cupboard. The odour was detected downwindin seconds.HS SH O There are two candidates for this dreadful smellpropane dithiol (called acetone gem-dithiol HSabove) or 4-methyl-4-sulfanylpentan-2-one. It is unlikely that anyone else will be brave enough toresolve the controversy.4-methyl-4-propane sulfanylpentan- Nasty smells have their uses. The natural gas piped to our homes contains small amounts of delib- dithiol 2-oneerately added sulfur compounds such as tert-butyl thiol (CH3)3CSH. When we say small, we meanvery smallhumans can detect one part in 50 000 000 000 parts of natural gas. two candidates for the worst smell in the world Other compounds have delightful odours. To redeem the honour of sulfur compounds we mustcite the trufe which pigs can smell through a metre of soil and whose taste and smell is so delightfulno-one wants to find the winner!that trufes cost more than their weight in gold. Damascenones are responsible for the smell of roses.SSIf you smell one drop you will be disappointed, as it smells rather like turpentine or camphor, but CH3CH3 next morning you and the clothes you were wearing will smell powerfully of roses. Just like the com-the divine smellpounds from trithioacetone, this smell develops on dilution.of the black truffleHumans are not the only creatures with a sense of smell. We can nd mates using our eyes alone comes from this compound(though smell does play a part) but insects cannot do this. They are small in a crowded world andO they nd others of their own species and the opposite sex by smell. Most insects produce volatilecompounds that can be picked up by a potential mate in incredibly weak concentrations. Only 1.5mg of serricornin, the sex pheromone of the cigarette beetle, could be isolated from 65 000 femalebeetlesso there isnt much in each beetle. Nevertheless, the slightest whiff of it causes the males togather and attempt frenzied copulation.damascenone - the smell of rosesThe sex pheromone of the Japanese beetle, also given off by the females, has been made bychemists. As little as 5 g (micrograms, note!) was more effective than four virgin females in attract-ing the males.O O OH OHserricornin japonilurethe sex pheromone of the cigarette beetlethe sex pheromone of the Japanese beetleLasioderma serricorne Popilia japonica The pheromone of the gypsy moth, disparlure, was identied from a few g isolated from themoths and only 10 g of synthetic material. As little as 2 1012 g is active as a lure for the males ineld tests. The three pheromones we have mentioned are available commercially for the specictrapping of these destructive insect pests. 11. Organic compounds5 Dont suppose that the females always do all the work; bothmale and female olive ies produce pheromones that attract theother sex. The remarkable thing is that one mirror image of disparluredisparlurethe molecule attracts the males while the other attracts theO the sex pheromone of the Gypsy moththPortheria hdispar f th Gthfemales! OOO O O O oleanthis mirror image isomer this mirror image isomersex pheromone of the olive flyattracts the males attracts the femalesBacrocera oleae What about taste? Take the grapefruit. The main avour comes from another sulfur compound HSand human beings can detect 2 105 parts per billion of this compound. This is an almost unimag-inably small amount equal to 104 mg per tonne or a drop, not in a bucket, but in a good-sized lake.Why evolution should have left us abnormally sensitive to grapefruit, we leave you to imagine. For a nasty taste, we should mention bittering agents, put into dangerous household substances flavouring principle of grapefruitlike toilet cleaner to stop children eating them by accident. Notice that this complex organic com-pound is actually a saltit has positively charged nitrogen and negatively charged oxygen atomsand this makes it soluble in water.O H NO N O bitrex denatonium benzoatebenzyldiethyl[(2,6-xylylcarbamoyl)methyl]ammonium benzoateOther organic compounds have strange effects on humans. Various drugs suchCO2Meas alcohol and cocaine are taken in various ways to make people temporarily happy. CH3OH N alcoholCH3OThey have their dangers. Too much alcohol leads to a lot of misery and any cocaine(ethanol)at all may make you a slave for life. OAgain, lets not forget other creatures. Cats seem to be able to go to sleep at any cocainetime and recently a compound was isolated from the cerebrospinal uid of cats that makes them, or - an addictive alkaloidrats, or humans go off to sleep quickly. It is a surprisingly simple compound. O NH2 a sleep-inducing fatty acid derivativecis-9,10-octadecenoamide This compound and disparlure are both derivatives of fatty Oacids, molecules that feature in many of the food problems peopleare so interested in now (and rightly so). Fatty acids in the diet are1OH11a popular preoccupation and the good and bad qualities of satu-189rates, monounsaturates, and polyunsaturates are continually in 1210the news. This too is organic chemistry. One of the latest mole-cules to be recognized as an anticancer agent in our diet is CLACLA (Conjugated Linoleic Acid)cis-9-trans-11 conjugated linoleic acid(conjugated linoleic acid) in dairy products. dietary anticancer agent 12. 61 . What is organic chemistry?Another fashionable molecule is resveratrole, which mayOH be responsible for the benecial effects of red wine in pre- HO venting heart disease. It is a quite different organic com- pound with two benzene rings and you can read about it in Chapter 51.OHFor our third edible molecule we choose vitamin C. This is an essential factor in our dietsindeed, that is why it is called resveratrole from the skins of grapesVitamin C (ascorbic acid) is avitamin for primates, guinea-pigs, a vitamin. The disease scurvy, a degeneration of soft tissues, whichthis theto prevent heart disease? is helps compound in red wineand fruit bats, but other mammalsparticularly in the mouth, from which sailors on long voyagescan make it for themselves.like those of Columbus suffered, results if we dont have vitamin C. It also is a universal antioxidant,OH scavenging for rogue free radicals and so protecting us against cancer. Some people think an extra H large intake protects us against the common cold, but this is not yet proved.HO O O Organic chemistry and industryHOOH Vitamin C is manufactured on a huge scale by Roche, a Swiss company. All over the world there are vitamin C (ascorbic acid) chemistry-based companies making organic molecules on scales varying from a few kilograms to thousands of tonnes per year. This is good news for students of organic chemistry; there are lots of jobs around and it is an international job market. The scale of some of these operations of organic chemistry is almost incredible. The petrochemicals industry processes (and we use the products!) over 10 million litres of crude oil every day. Much of this is just burnt in vehicles as petrol or diesel, but some of it is puried or converted into organic compounds for use in the rest of the chemical industry. Multinational companies with thousands of employees such as Esso (Exxon) and Shell dominate this sector. Some simple compounds are made both from oil and from plants. The ethanol used as a starting material to make other compounds in industry is largely made by the catalytic hydration of ethylene from oil. But ethanol is also used as a fuel, particularly in Brazil where it is made by fermentation of sugar cane wastes. This fuel uses a waste product, saves on oil imports, and has improved the quality of the air in the very large Brazilian cities, Rio de Janeiro and So Paulo. Plastics and polymers take much of the production of the petro-monomers for polymer chemical industry in the form of monomers such as styrene, acry- manufacture lates, and vinyl chloride. The products of this enormous industry are everything made of plastic including solid plastics for household goods and furniture, bres for clothes (24 million tonnes per annum), elastic polymers for car tyres, light bubble-lled polymers styrene for packing, and so on. Companies such as BASF, Dupont, Amoco, X Monsanto, Laporte, Hoechst, and ICI are leaders here. Worldwide Cl polymer production approaches 100 million tonnes per annum and O PVC manufacture alone employs over 50 000 people to make over 20acrylates vinyl chloride million tonnes per annum. The washing-up bowl is plastic too but the detergent you put in it belongs to another branch of the chemical industrycompanies like Unilever (Britain) or Procter and Gamble (USA) which produce soap, detergent, cleaners, bleaches,Ingredients polishes, and all the many essentials for the aqua, palmitic acid, modern home. These products may be lemontriethanolamine, and lavender scented but they too mostly come glycereth-26, isopentane, oleamide-DEA, oleth-2, from the oil industry. Nowadays, most pro- stearic acid, isobutane, ducts of this kind tell us, after a fashion, what is inPEG-14M, parfum, them. Try this examplea well known brand ofallantoin, shaving gel along with the list of contents on the hydroxyethyl-cellulose, hydroxypropyl-cellulose, container: PEG-150 distearate, Does any of this make any sense?CI 42053, CI 47005 13. Organic chemistry and industry7 It doesnt all make sense to us, but here is a possible interpretation. We certainly hope the bookwill set you on the path of understanding the sense (and the nonsense!) of this sort of thing.IngredientChemical meaningPurposeaquawater solventpalmitic acid CH3(CH2)14CO2Hacid, emulsiertriethanolamine N(CH2CH2OH)3baseglycereth-26glyceryl(OCH2CH2)26OH surfactantisopentane(CH3)2CHCH2CH3propellantoleamide-DEACH3(CH2)7CH=CH(CH2)7CONEt2oleth-2 Oleyl(OCH2CH2)2OH surfactantstearic acidCH3(CH2)16CO2Hacid, emulsierisobutane (CH3)2CHCH3 propellantPEG-14M polyoxyethylene glycol estersurfactantparfumperfumeallantoinHpromotes healing inH2NNcase you cutNHyourself while shaving O ON allantoinHhydroxyethyl-cellulosecellulose bre from wood pulp gives bodywith OCH2CH2OH groups addedhydroxypropyl-cellulose cellulose bre from wood pulpgives bodywith OCH2CH(OH)CH3 groups addedPEG-150 distearatepolyoxyethylene glycol diestersurfactantCI 42053Fast Green FCF (see box)green dyeCI 47005Quinoline Yellow (see box)yellow dye The structures of two dyes Fast Green FCF and Quinoline Yellow are colours permitted to be used in foods and cosmetics and have the structures shown here. Quinoline Yellow is a mixture of isomeric sulfonic acids in the two rings shown. EtEt O N N OO2SSO2O N2NaOHSO2OHOO2SSO2OH Fast Green FCF Quinoline Yellow OH The particular acids, bases, surfactants, and so on are chosen to blend together in a smooth emul-sion when propelled from the can. The result should feel, smell, and look attractive and a greenishcolour is considered clean and antiseptic by the customer. What the can actually says is this:Superior lubricants within the gel prepare the skin for an exceptionally close, comfortable and effec-tive shave. It contains added moisturisers to help protect the skin from razor burn. Lightlyfragranced. 14. 8 1 . What is organic chemistry? CNAnother oil-derived class of organic chemical business includes adhesives, sealants, coatings, andO so on, with companies like CibaGeigy, Dow, Monsanto, and Laporte in the lead. Nowadays aircraftCH3 are glued together with epoxy-resins and you can glue almost anything with Superglue a polymer ofO methyl cyanoacrylate.Superglue bonds things togetherThere is a big market for intense colours for dyeing cloth, colouring plastic and paper, paintingwhen this small moleculewalls, and so on. This is the dyestuffs and pigments industry and leaders here are companies like ICIjoins up with hundreds of its fellows in a polymerization reaction and Akzo Nobel. ICI have a large stake in this aspect of the business, their paints turnover alonebeing 2 003 000 000 in 1995.The most famous dyestuff is probably indigo, an ancient dye that used to be isolated from plantsThe formation of polymers is discussedbut is now made chemically. It is the colour of blue jeans. More modern dyestuffs can be representedin Chapter 52.by ICIs benzodifuranones, which give fashionable red colours to synthetic fabrics like polyesters. We see one type of pigment around us all the time in the form of the colours on plastic bags.Among the best compounds for these are the metal complexes called phthalocyanines. Changing themetal (Cu and Fe are popular) at the centre and the halogens round the edge of these moleculeschanges the colour but blues and green predominate. The metal atom is not necessary for intensepigment coloursone new class of intense high performance pigments in the orangered range arethe DPP (1,4-diketopyrrolo[3,4-c]pyrroles) series developed by CibaGeigy. Pigment Red 254 isused in paints and plastics. ORClClClClCl Cl ClCl NClO O ON NNH O HN OON CuNNHN NOClClO HN NClCl Cl Cl ORClCl Cl ICIs Dispersolindigo benzodifuranone ICIs Monastral Green GNA Ciba Geigys Pigment Red 254the colour of blue jeans red dyes for polyestera good green for plastic objectsan intense DPP pigment Colour photography starts with inorganic silver halides but they are carried on organic gelatin.You can read in Chapter 7 why someLight acts on silver halides to give silver atoms that form the photographic image, but only in blackcompounds are coloured and others and white. The colour in lms like Kodachrome then comes from the coupling of two colourlessnot.organic compounds. One, usually an aromatic amine, is oxidized and couples with the other to give acoloured compound.RH NH2NH N NOPhR Nlight, silver HNN OPh photographicOSO2O Na developer O NaSO2O NEt2 NEt2colourless magenta pigment from two colourless cyclic amide aromatic amineNEt2 colourless compounds 15. Organic chemistry and industry 9 That brings us to avours and fragrances. Companies like International Flavours and Fragrances O(USA) or GivaudanRoure (Swiss) produce very big ranges of ne chemicals for the perfume, cos-metic, and food industries. Many of these will come from oil but others come from plant sources. Atypical perfume will contain 510% fragrances in an ethanol/water (about 90:10) mixture. So the cis-jasmonethe main compoundperfumery industry needs a very large amount of ethanol and, you might think, not much perfumeryin jasmine perfumematerial. In fact, important fragrances like jasmine are produced on a >10 000 tonnes per annumscale. The cost of a pure perfume ingredient like cis-jasmone, the main ingredient of jasmine, may beseveral hundred pounds, dollars, or euros per gram.The world of perfumeryPerfume chemists use extraordinary language to describe achieve the required effect, the perfumer blendedtheir achievements: Paco Rabanne pour homme washerbaceous oils with woody accords and the syntheticcreated to reproduce the effect of a summer walk in the aroma chemical dimethylheptanol which has aopen air among the hills of Provence: the smell of herbs, penetrating but indenable freshness associated withrosemary and thyme, and sparkling freshness with cool open air or freshly washed linen. (J. Ayres, Chemistry andsea breezes mingling with warm soft Alpine air. ToIndustry, 1988, 579) Chemists produce synthetic avourings such as smoky bacon and even chocolate. Meatyavours come from simple heterocycles such as alkyl pyrazines (present in coffee as well as roastmeat) and furonol, originally found in pineapples. Compounds such as corylone and maltol givecaramel and meaty avours. Mixtures of these and other synthetic compounds can be tuned to tastelike many roasted foods from fresh bread to coffee and barbecued meat. O N HO O HOOHO NOOan alkyl pyrazine corylonemaltolfrom coffee and furonol caramel E-636 for cakes roast meat roast meat roasted tasteand biscuits Some avouring compounds are also perfumes and may also be used as an intermediate inmaking other compounds. Two such large-scale avouring compounds are vanillin (vanilla avouras in ice cream) and menthol (mint avour) both manufactured on a large scale and with manyuses.O OH vanillin mentholfound in vanilla pods;CH3Oextracted from mint;manufacturedH 25% of the worlds supply on a large scale manufacturedHO Food chemistry includes much larger-scale items than avours. Sweeteners such as sugar itself areisolated from plants on an enormous scale. Sugars structure appeared a few pages back. Othersweeteners such as saccharin (discovered in 1879!) and aspartame (1965) are made on a sizeablescale. Aspartame is a compound of two of the natural amino acids present in all living things and ismade by Monsanto on a large scale (over 10 000 tonnes per annum).methyl ester ofphenylalanineCO2H CO2HO OHHN is made from N H2N OCH3 two amino acids H2N OCH3OOaspartame (NutraSweet) aspartic200 sweeter than sugar acid 16. 10 1 . What is organic chemistry?The pharmaceutical businesses produce drugs and medicinal products of many kinds. One of the great revolutions of modern life has been the expectation that humans will survive diseases because of a treatment designed to deal specically with that disease. The most successful drug ever is raniti- dine (Zantac), the GlaxoWellcome ulcer treatment, and one of the fastest-growing is Pzers silde- nal (Viagra). Success refers both to human health and to prot!You will know people (probably older men) who are on -blockers. These are com- pounds designed to block the effects of adrenaline (epinephrine) on the heart and hence to prevent heart disease. One of the best is Zenecas tenormin. Preventing high blood pressure also pre- vents heart disease and certain specic enzyme inhibitors (called ACE-inhibitors) such as Squibbs captopril work in this way. These are drugs that imitate substances naturally present in the body.The treatment of infectious diseases relies on antibiotics such as the penicillins to prevent bacteria from multiplying. One of the most successful of these is Smith Kline Beechams amoxycillin. The four-membered ring at the heart of the molecule is the -lactam. EtOMe NO2NN N Me2NSSO NNHMeNH NH OO N Glaxo-Wellcomes ranitidine Methe most successful drug to dateOO Pfizers sildenafil (Viagra)Pfizers sildenafil (Viagra) world wide sales peaked >1,000,000,000 per annum three million satisfied customers in 1998three million satisfied customers in 1998NH2 OHH HH HON NS HSN ON O CO2HHOO Zenecas tenorminSquibbs captoprilCO2H cardioselective -blocker specific enzyme inhibitor SmithKline Beechams amoxycillin for treatment and prevention for treatment and-lactam antibioticof heart diseaseprevention of hypertensionfor treatment of bacterial infectionsWe cannot maintain our present high density of population in the developed world, nor deal with malnutrition in the developing world unless we preserve our food supply from attacks by insects and fungi and from competition by weeds. The world market for agrochemicals is over 10 000 000 000 per annum divided roughly equally between herbicides, fungicides, and insecticides.At the moment we hold our own by the use of agrochemicals: companies such as Rhne- Poulenc, Zeneca, BASF, ScheringPlough, and Dow produce compounds of remarkable and specic activity. The most famous modern insecticides are modelled on the natural pyrethrins, stabilized against degradation by sunlight by chemical modication (see coloured portions of decamethrin) and targeted to specic insects on specic crops in cooperation with biologists. Decamethrin has a safety factor of >10#000 for mustard beetles over mammals, can be applied at only 10 grams per hectare (about one level tablespoon per football pitch), and leaves no signicant environmental residue.OBrOOO Br O OO CNa natural pyrethin decamethrinfrom pyrethrum - daisy-like flowers from East Africaa modified pyrethrin - more active and stable in sunlight 17. Organic chemistry and the periodic table 11 As you learn more chemistry, you will appreciate how remarkable it is that Nature should pro-duce three-membered rings and that chemists should use them in bulk compounds to be sprayed oncrops in elds. Even more remarkable in some ways is the new generation of fungicides based on ave-membered ring containing three nitrogen atomsthe triazole ring. These compounds inhibitan enzyme present in fungi but not in plants or animals. One fungus (potato blight) caused the Irish potato famine of the nineteenth century and the vari-ous blights, blotches, rots, rusts, smuts, and mildews can overwhelm any crop in a short time.Especially now that so much is grown in Western Europe in winter, fungal diseases are a realthreat. NCO2MeClClN NHN N O ON NO Hbenomyl a fungicide which controlspropiconazolemany plant diseases a triazole fungicide You will have noticed that some of these companies have ngers in many pies. These companies,or groups as they should be called, are the real giants of organic chemistry. RhnePoulenc, theFrench group which includes pharmaceuticals (RhnePoulencRorer), animal health, agrochemi-cals, chemicals, bres, and polymers, had sales of about 90 billion French Francs in 1996. Dow, theUS group which includes chemicals, plastics, hydrocarbons, and other bulk chemicals, had sales ofabout 20 billion US dollars in 1996.Organic chemistry and the periodic tableAll the compounds we have shown you are built up on hydrocarbon (carbon and hydrogen) skele-tons. Most have oxygen and/or nitrogen as well; some have sulfur and some phosphorus. These arethe main elements of organic chemistry but another way the science has developed is an explorationof (some would say take-over bid for) the rest of the periodic table. Some of our compounds also haduorine, sodium, copper, chlorine, and bromine. The organic chemistry of silicon, boron, lithium,the halogens (F, Cl, Br, and I), tin, copper, and palladium has been particularly well studied andthese elements commonly form part of organic reagents used in the laboratory. They will crop upthroughout this book. These lesser elements appear in many important reagents, which are used inorganic chemical laboratories all over the world. Butyllithium, trimethylsilyl chloride, tributyltinhydride, and dimethylcopper lithium are good examples.The halogens also appear in many life-saving drugs. The recently discovered antiviral com-pounds, such as aluridine (which contains both F and I, as well as N and O), are essential for theOght against HIV and AIDS. They are modelled on natural compounds from nucleic acids. TheInaturally occurring cytotoxic (antitumour) agent halomon, extracted from red algae, contains BrNHand Cl.CH3 C4H9CH3NOCl ClBrO Li CH3 SiClC4H9 Sn H Cu Li HOCH3 C4H9CH3Bu3SnH Me2CuLi Br Cl HOF BuLi Me3SiClbutyllithiumtrimethylsilyl chloride tributyltin hydride dimethylcopper lithiumhalomon fialuridine naturally occurring antiviral compound antitumour agent Another denition of organic chemistry would use the periodic table. The key elements inorganic chemistry are of course C, H, N, and O, but also important are the halogens (F, Cl. Br, I), 18. 12 1 . What is organic chemistry? p-block elements such as Si, S, and P, metals such as Li, Pd, Cu, and Hg, and many more. We can construct an organic chemists periodic table with the most important elements emphasized:1the organic chemistsYou will certainly know something H periodic tableabout the periodic table from your213 14 15 1617previous studies of inorganicLiB C NO Fchemistry. A basic knowledge ofthe groups, which elements areMgNa AlSiPS Clmetals, and roughly where the345 67 8910 11 12elements in our table appear will KTi CrCu ZnSeBrbe helpful to you.Pd Sn I Os Hg So where does inorganic chemistry end and organic chemistry begin? Would you say that the antiviral compound foscarnet was organic? It is a compound of carbon with the formula CPO5Na3 but is has no CH bonds. And what about the important reagent tetrakis triphenyl phos- phine palladium? It has lots of hydrocarbontwelve benzene rings in factbut the benzene rings are all joined to phosphorus atoms that are arranged in a square around the central palladium atom, so the molecule is held together by CP and PPd bonds, not by a hydrocarbon skeleton. Although it has the very organic-looking formula C72H60P4Pd, many people would say it is inorganic. But is it? OP tetrakis O PONa Ptriphenylphosphine O3 Pd palladiumO PP [(C6H5)3P]4Pd foscarnet antiviral agent(Ph3P)4Pd The answer is that we dont know and we dont care. It is important these days to realize that strict boundaries between traditional disciplines are undesirable and meaningless. Chemistry continues across the old boundaries between organic chemistry and inorganic chemistry on the one side and organic chemistry and biochemistry on the other. Be glad that the boundaries are indistinct as that means the chemistry is all the richer. This lovely molecule (Ph3P)4Pd belongs to chemistry. 19. Organic chemistry and this bookWe have told you about organic chemistrys history, the types of compounds it concerns itself with, thethings it makes, and the elements it uses. Organic chemistry today is the study of the structure and reac-tions of compounds in nature of compounds, in the fossil reserves such as coal and oil, and of thosecompounds that can be made from them. These compounds will usually be constructed with a hydro-carbon framework but will also often have atoms such as O, N, S, P, Si, B, halogens, and metals attachedto them. Organic chemistry is used in the making of plastics, paints, dyestuffs, clothes, foodstuffs,human and veterinary medicines, agrochemicals, and many other things. Now we can summarize all ofthese in a different way. Structure determinationhow to nd outathe structures of new compounds The main components of organic chemistry as discipline are these even if they are available only in invisibly small amounts Theoretical organic chemistryhow to understand those structures in terms of atoms and the electrons that bind them together Reaction mechanismshow to nd out how these molecules react with each other and how to predict their reactions Synthesishow to design new moleculesand then make them Biological chemistryhow to nd out what Nature does and how the structures of biologically active molecules are related to what they doThis book is about all these things. It tells you about the structures of organic molecules and thereasons behind them. It tells you about the shapes of those molecules and how the shape relates totheir function, especially in the context of biology. It tells you how those structures and shapes arediscovered. It tells you about the reactions the molecules undergo and, more importantly, how andwhy they behave in the way they do. It tells you about nature and about industry. It tells you howmolecules are made and how you too can think about making molecules.We said it tells in that last paragraph. Maybe we should have said we tell because we want tospeak to you through our words so that you can see how we think about organic chemistry and toencourage you to develop your own ideas. We expect you to notice that four people have written thisbook and that they dont all think or write in the same way. That is as it should be. Organic chemistryis too big and important a subject to be restricted by dogmatic rules. Different chemists think in dif-ferent ways about many aspects of organic chemistry and in many cases it is not yet possible to besure who is right.We may refer to the history of chemistry from time to time but we are usually going to tell you aboutorganic chemistry as it is now. We will develop the ideas slowly, from simple and fundamental onesusing small molecules to complex ideas and large molecules. We promise one thing. We are not goingto pull the wool over your eyes by making things articially simple and avoiding the awkward ques-tions. We aim to be honest and share both our delight in good complete explanations and our puzzle-ment at inadequate ones. So how are we going to do this? The book starts with a series of chapters onthe structures and reactions of simple molecules. You will meet the way structures are determined andthe theory that explains those structures. It is vital that you realize that theory is used to explain what isknown by experiment and only then to predict what is unknown. You will meet mechanismsthedynamic language used by chemists to talk about reactionsand of course some reactions. 20. 14 1 . Organic chemistry and this book The book starts with an introductory section of four chapters: 1What is organic chemistry? 2Organic structures 3Determining organic structures 4Structure of moleculesIn Chapter 2 you will look at the way in which we are going to present diagrams of molecules on the printed page. Organic chemistry is a visual, three-dimensional subject and the way you draw molecules shows how you think about them. We want you too to draw molecules in the best way available now. It is just as easy to draw them well as to draw them in an old-fashioned inaccurate way.Then in Chapter 3, before we come to the theory of molecular structure, we shall introduce you to the experimental techniques of nding out about molecular structure. This means studying the interactions between molecules and radiation by spectroscopyusing the whole electromagnetic spectrum from X-rays to radio waves. Only then, in Chapter 4, will we go behind the scenes and look at the theories of why atoms combine in the ways they do. Experiment comes before theory. The spectroscopic methods of Chapter 3 will still be telling the truth in a hundred years time, but the the- ories of Chapter 4 will look quite dated by then.We could have titled those three chapters: 2 What shapes do organic molecules have? 3 How do we know they have those shapes? 4 Why do they have those shapes?You need to have a grasp of the answers to these three questions before you start the study of organic reactions. That is exactly what happens next. We introduce organic reaction mechanisms in Chapter 5. Any kind of chemistry studies reactionsthe transformations of molecules into other molecules. The dynamic process by which this happens is called mechanism and is the language of organic chemistry. We want you to start learning and using this language straight away so in Chapter 6 we apply it to one important class of reaction. This section is: 5Organic reactions 6Nucleophilic addition to the carbonyl groupChapter 6 reveals how we are going to subdivide organic chemistry. We shall use a mechanistic classication rather than a structural classication and explain one type of reaction rather than one type of compound in each chapter. In the rest of the book most of the chapters describe types of reac- tion in a mechanistic way. Here is a selection. 9Using organometallic reagents to make CC bonds 17 Nucleophilic substitution at saturated carbon 20 Electrophilic addition to alkenes 22 Electrophilic aromatic substitution 29 Conjugate Michael addition of enolates 39 Radicals Interspersed with these chapters are others on physical aspects, organic synthesis, stereochem- istry, structural determination, and biological chemistry as all these topics are important parts of organic chemistry. Connections section Chemistry is not a linear subject! It is impossible simply to start at the beginning and work through to the end, introducing one new topic at a time, because chemistry is a network of interconnecting ideas. But, unfortunately, a book is, by nature, a beginning-to-end sort of thing. We have arranged the chapters in a progression of difculty as far as is possible, but to help you nd your way around 21. Boxes and margin notes 15we have included at the beginning of each chapter a Connections section. This tells you three thingsdivided among three columns:(a) what you should be familiar with before reading the chapterin other words, which previouschapters relate directly to the material within the chapter (Building on column)(b) a guide to what you will nd within the chapter (Arriving at column)(c) which chapters later in the book ll out and expand the material in the chapter (Lookingforward to column)The rst time you read a chapter, you should really make sure you have read any chapter mentionedunder (a). When you become more familiar with the book you will nd that the links highlighted in(a) and (c) will help you see how chemistry interconnects with itself.Boxes and margin notesThe other things you should look out for are the margin notes and boxes. There are four sorts, andthey have all appeared at least once in this chapter.HeadingSometimes the main text of theThe most important looks like this. Anything in this sort of box is verybook needs clarication orexpansion, and this sort of marginimportanta key concept or a summary. Its the sort of thing you would do well to note will contain such little extrashold in your mind as you read or to note down as you learn. to help you understand difcultpoints. It will also remind you ofthings from elsewhere in the book Headingthat illuminate what is beingdiscussed. You would do well to Boxes like this will contain additional examples, amusing you might want to miss out this sort of box, and only read read these notes the rst time background information, and similar interesting, butthem later on to esh out some of the main themes of the you read the chapter, though inessential, material. The rst time you read a chapter,chapter. later, as the ideas become morefamiliar, you might choose to skipthem.End-of-chapter problems This sort of margin note will mainlyYou cant learn organic chemistrytheres just too much of it. You can learn trivial things contain cross-references to otherlike the names of compounds but that doesnt help you understand the principles behind theparts of the book as a further aid tonavigation. You will nd an examplesubject. You have to understand the principles because the only way to tackle organic chemistry on p. 000.is to learn to work it out. That is why we have provided end-of-chapter problems. They areto help you discover if you have understood the material presented in each chapter. In general,the 1015 problems at the end of each chapter start easy and get more difcult. They comein two sorts. The rst, generally shorter and easier, allow you to revise the material in that chap-ter. The second asks you to extend your understanding of the material into areas not coveredby the chapter. In the later chapters this second sort will probably revise material from previouschapters. If a chapter is about a certain type of organic reaction, say elimination reactions (Chapter 19), thechapter itself will describe the various ways (mechanisms) by which the reaction can occur and itwill give denitive examples of each mechanism. In Chapter 19 there are three mechanisms andabout 65 examples altogether. You might think that this is rather a lot but there are in fact millions ofexamples known of these three mechanisms and Chapter 19 only scrapes the surface. Even if youtotally comprehended the chapter at a rst reading, you could not be condent of your understand-ing about elimination reactions. There are 13 end-of-chapter problems for Chapter 19. The rstthree ask you to interpret reactions given but not explained in the chapter. This checks that you canuse the ideas in familiar situations. The next few problems develop specic ideas from the chapterconcerned with why one compound does one reaction while a similar one behaves quite differently. 22. 16 1 . Organic chemistry and this book Finally there are some more challenging problems asking you to extend the ideas to unfamiliar molecules.The end-of-chapter problems should set you on your way but they are not the end of the journey to understanding. You are probably reading this text as part of a university course and you should nd out what kind of examination problems your university uses and practise them too. Your tutor will be able to advise you on suitable problems for each stage of your development. The solutions manual The problems would be of little use to you if you could not check your answers. For the maximum benet, you need to tackle some or all of the problems as soon as you have nished each chapter without looking at the answers. Then you need to compare your suggestions with ours. You can do this with the solutions manual (Organic Chemistry: Solutions Manual, Oxford University Press, 2000). Each problem is discussed in some detail. The purpose of the problem is rst stated or explained. Then, if the problem is a simple one, the answer is given. If the prob- lem is more complex, a discussion of possible answers follows with some comments on the value of each. There may be a reference to the source of the problem so that you can read further if you wish. Colour You will already have noticed something unusual about this book: almost all of the chemical struc- tures are shown in red. This is quite intentional: emphatic red underlines the message that structures are more important than words in organic chemistry. But sometimes small parts of structures are in other colours: here are two examples from p. 000, where we were talking about organic compounds containing elements other than C and H. OI NH BrCl Cl fialuridine NO antiviral compoundO HO BrClHalomonHO Fnaturally occurring antitumour agentWhy are the atom labels black? Because we wanted them to stand out from the rest of the molecule. In general you will see black used to highlight important details of a moleculethey may be the groups taking part in a reaction, or something that has changed as a result of the reaction, as in these examples from Chapters 9 and 12.O HO1. 1. EtMgBrMgBrO2. H3O+ HO2. H+, H2O new CC bondWe shall often use black to emphasize curly arrows, devices that show the movement of elec- trons, and whose use you will learn about in Chapter 5. Here is an example from Chapter 10: notice black also helps the + and charges to stand out.OOO CN MeMe CNMeCN H 23. Colour 17 Occasionally, we shall use other colours such as green, or even orange, yellow, or brown, to high-light points of secondary importance. This example is part of a reaction taken from Chapter 19: wewant to show that a molecule of water (H2O) is formed. The green atoms show where the watercomes from. Notice black curly arrows and a new black bond. new C=CHH double bond OH O HH HH NNNN + H2O Other colours come in when things get more complicatedin this Chapter 24 example, we wantto show a reaction happening at the black group in the presence of the yellow H (which, as you willsee in Chapter 9, also reacts) and also in the presence of the green protecting groups, one of thetopics of Chapter 24.PhPhOH OHMeO2C N N MeMgBr HO (excess)BnO BnO And, in Chapter 16, colour helps us highlight the difference between carbon atoms carrying fourdifferent groups and those with only three different groups. The message is: if you see something in acolour other than red, take special notethe colour is there for a reason.4 H 1 3 except glycine NH2 NH2 1 plane of paper is aamino acids H are chiral plane of symmetry3 RCO2H 2 3 HCO2H 2 through C, N, and CO2HThat is all we shall say in the way of introduction. On the next page the real chemistry starts, andour intention is to help you to learn real chemistry, and to enjoy it. 24. Organic structures Connections 2Building on: Leading to:Looking forward to: This chapter does not depend on The diagrams used in the rest of the book Ascertaining molecular structureChapter 1 spectroscopically ch3Why we use these particular diagramsHow organic chemists name What determines a molecules molecules in writing and in speech structure ch4What is the skeleton of an organic moleculeWhat is a functional groupSome abbreviations used by all organic chemistsDrawing organic molecules realistically in an easily understood styleThere are over 100 elements in the periodic table. Many molecules contain well over 100 atomspalytoxin, for example (a naturally occurring compound with potential anticancer activity) containsPalytoxin was isolated in 1971 in129 carbon atoms, 221 hydrogen atoms, 54 oxygen atoms, and 3 nitrogen atoms. Its easy to see how Hawaii from Limu make o Hane (deadlychemical structures can display enormous variety, providing enough molecules to build even theseaweed of Hana) which had beenused to poison spear points. It is one ofmost complicated living creatures. But how can we understand what seems like a recipe for confu-the most toxic compounds knownrequiring only about 0.15 microgramsion? Faced with the collection of atoms we call a molecule, how can we make sense of what we see?per kilogram for death by injection. TheThis chapter will teach you how to interpret organic structures. It will also teach you how to draw complicated structure was determineda few years later.organic molecules in a way that conveys all the necessary information and none of the superuous.OH HO OH OH OH OH HOO OHH HO OHOH OHH O OHO HO HOHOHHOOH OHH H HH ONN OHHO HO HOH OH OHO O OHOOHH OHHOOH NH2 HOOH HOHOOH H O HOH OHOH H HHO HO OH O OOHOHHOpalytoxin H 25. 202 . Organic structuresHydrocarbon frameworks and functional groupsAs we explained in Chapter 1, organic chemistry is the study of compounds that contain carbon. Nearlyall organic compounds also contain hydrogen; most also contain oxygen, nitrogen, or other elements.Organic chemistry concerns itself with the way in which these atoms are bonded together into stablemolecular structures, and the way in which these structures change in the course of chemical reactions.Some molecular structures are shown below. These molecules are all amino acids, the con-stituents of proteins. Look at the number of carbon atoms in each molecule and the way they arebonded together. Even within this small class of molecules theres great varietyglycine and alaninehave only two or three carbon atoms; phenylalanine has nine. HH NH2 H NH2 HCH C C HNH2C OHCOHHCCH3C C CC OHHCC C O O H HH OLysine has a chain of atoms; tryptophan has rings. H HH H H H H NH2N H CHCCH NH2C C C OH CH2N C CC C C C OHH H H HC CC O C HHH HOIn methionine the atoms are arranged in a single chain; in leucine the chain is branched. In proline,the chain bends back on itself to form a ring. H HH H H NH2CH3 HHWe shall return to amino acids asNH2examples several times in this chapter, H3C C COHHC N Hbut we shall leave detailed discussions S C CC COHHH3CCC C C OHabout their chemistry till Chapters 24Cand 49, when we look at the way inH H O C H HO Hwhich they polymerize to form peptidesH H Oand proteins.Yet all of these molecules have similar propertiesthey are all soluble in water, they are all bothacidic and basic (amphoteric), they can all be joined with other amino acids to form proteins. This isbecause the chemistry of organic molecules depends much less on the number or the arrangement ofcarbon or hydrogen atoms than on the other types of atoms (O, N, S, P, Si) in the molecule. Wecall parts of molecules containing small collections of these other atoms functional groups, simplybecause they are groups of atoms that determine the way the molecule works. All amino acids con-tain two functional groups: an amino (NH2 or NH) group and a carboxylic acid (CO2H) group(some contain other functional groups as well).and biologically.groups determine the way the molecule works both chemically The functionalH NH2H H H H H NH2H H H NH2C OH C C COH H3CC C OHH3C CH2N C CC S CCOH H H HO H HOalaninelysinemethioninecontains just the amino has an additional also has a sulfideand carboxylic acid amino groupfunctional group functional groups 26. Drawing molecules21That isnt to say the carbon atoms arent important; they just play quite a different role from thoseof the oxygen, nitrogen, and other atoms they are attached to. We can consider the chains and rings Organic skeletonsof carbon atoms we nd in molecules as their skeletons, which support the functional groups andOrganic molecules left to decompose for millions of years inallow them to take part in chemical interactions, much as your skeleton supports your internal the absence of light and oxygenorgans so they can interact with one another and work properly.become literally carbon skeletonscrude oil, for example, is a mixture of moleculesit acts as a support for the functional groups.chains and rings of carbon atoms, and The hydrocarbon framework is made up of consisting of nothing but carbon and hydrogen, while coal consists of little else but carbon. AlthoughH Hthe molecules in coal and oil differH Hwidely in chemical structure, theyCH H HH HH have one thing in common: noH H HH HH H C C Hfunctional groups! Many are very CCCCCCH C C H unreactive: about the onlyH C C H H C C Hchemical reaction they can takeCH C H H C H part in is combustion, which, inH H H H H HH Hcomparison to most reactions that H H H H take place in chemical laboratories a chaina ringa branched chain or in living systems, is an extremely violent process. In Chapter 5 we will start to look atWe will see later how the interpretation of organic structures as hydrocarbon frameworks sup-the way that functional groups direct the chemical reactions of aporting functional groups helps us to understand and rationalize the reactions of organic molecules. molecule.It also helps us to devise simple, clear ways of representing molecules on paper. You saw in Chapter 1how we represented molecules on paper, and in the next section we shall teach you ways to draw(and ways not to draw) moleculesthe handwriting of chemistry. This section is extremely impor-tant, because it will teach you how to communicate chemistry, clearly and simply, throughout yourlife as a chemist.Drawing molecules Be realistic Three fatty acid molecules and one glycerol molecule combine to form theBelow is another organic structureagain, you may be familiar with the molecule it represents; it is fats that store energy in our bodies anda fatty acid commonly called linoleic acid.are used to construct the membranes around our cells. This particular fattyH H HHH H H H H H H H HH acid, linoleic acid, cannot be manufactured in the human body, andH3C CCC CCCC OHis an essential part of a healthy dietCC CC C C CC C C found, for example, in sunower oil. carboxylic acid Fatty acids differ in the length of theirH H H H HH HH H H HH H H O functional groupchains of carbon atoms, yet they have very similar chemical propertieslinoleic acid because they all contain the carboxylic acid functional group. We shall comeWe could also depict linoleic acid asback to fatty acids in Chapter 49.H OHCH3CH2CH2CH2CH=CHCH2CH=CHCH2CH2CH2CH2CH2CH2CH2CO2H HO COHCC linoleic acidH H HHor asglycerolH H H HHH HHH HH H HH C C C CCC C C C C CCC CC C C CO2HH H H HHH H H H H HHH HH H H X-ray crystallography discoverslinoleic acidthe structures of molecules by observing the way X-rays bounceYou may well have seen diagrams like these last two in older booksthey used to be easy to print (in off atoms in crystalline solids. Itthe days before computers) because all the atoms were in a line and all the angles were 90. But are gives clear diagrams with thethey realistic? We will consider ways of determining the shapes and structures of molecules in moreatoms marked a circles and thedetail in Chapter 3, but the picture below shows the structure of linoleic acid determined by X-raybonds as rods joining them together.crystallography. 27. 22 2 . Organic structures You can see that the chain of carbon atoms is not linear, but a zig-zag. Although our diagram is just a two-dimensional representation of this three-dimensional structure, it seems reasonable to draw it as a zig-zag too. H H H H H H H H H H HH HH H3C C C C C CCC OH CCC C C CCC C C H H HH HH H H HH HH H H O linoleic acid This gives us our rst guideline for drawing organic structures. Draw chains of atoms as zig-zagsGuideline 1 Realism of course has its limitsthe X-ray structure shows that the linoleic acid molecule is in fact slightly bent in the vicinity of the double bonds; we have taken the liberty of drawing it as a straight zig-zag. Similarly, close inspection of crystal structures like this reveals that the angle of the zig-zag is about 109 when the carbon atom is not part of a double bond and 120 when it is. The 109 angle is the tetrahedral angle, the angle between two vertices of a tetrahedron when viewed from its centre. In Chapter 4 we shall look at why carbon atoms take up this particular arrangement of bonds. Our realistic drawing is a projection of a three-dimensional structure onto at paper so we have to com- promise. Be economical When we draw organic structures we try to be as realistic as we can be without putting in superuous detail. Look at these three pictures.123 (1) is immediately recognizable as Leonardo da Vincis Mona Lisa. You may not recognize (2)its also Leonardo da Vincis Mona Lisathis time viewed from above. The frame is very ornate, but the picture tells us as much about the painting as our rejected linear and 90 angle diagrams did about 28. Drawing molecules 23our fatty acid. Theyre both correctin their waybut sadly useless. What we need when we drawmolecules is the equivalent of (3). It gets across the idea of the original, and includes all the detailnecessary for us to recognize what its a picture of, and leaves out the rest. And it was quick to drawthis picture was drawn in less than 10 minutes: we havent got time to produce great works ofart! Because functional groups are the key to the chemistry of molecules, clear diagrams must empha-size the functional groups, and let the hydrocarbon framework fade into the background. Comparethe diagrams below:H H H H H H H H H H H H HHH3C C C C C C CC OHOHCCC C C CC C C CH H HH HH H H HH H H H H O linoleic acidOlinoleic acidThe second structure is the way that most organic chemists would draw linoleic acid. Notice how theimportant carboxylic acid functional group stands out clearly and is no longer cluttered by all thoseCs and Hs. The zig-zag pattern of the chain is much clearer too. And this structure is much quickerto draw than any of the previous ones!To get this diagram from the one above weve done two things. Firstly, weve got rid of all thehydrogen atoms attached to carbon atoms, along with the bonds joining them to the carbon atoms.Even without drawing the hydrogen atoms we know theyre therewe assume that any carbon atomthat doesnt appear to have its potential for four bonds satised is also attached to the appropriatenumber of hydrogen atoms. Secondly, weve rubbed out all the Cs representing carbon atoms. Wereleft with a zig-zag line, and we assume that every kink in the line represents a carbon atom, as doesthe end of the line. every kink in this H is shown the end of the line the chain representsbecause it is represents a C atom a C atomattached to an atom other than COHO What is a good reason not to? all four bonds One is if the C or H is part of a this C atom mustare shown to this also carry 3 H atoms these C atoms must these C atoms must functional group. Another is if the also carry 1 H atom also carry 2 H atomsC atom, so no because only 1 bondC or H needs to be highlighted in because only 3 bonds because only 2 bonds H atoms are is shownimpliedsome way, for example, becauseare shown for each atomare shown for each atomits taking part in a reaction. Dontbe too rigid about these We can turn these two simplications into two more guidelines for drawing organic structures.guidelines: theyre not rules.Better is just to learn by example(youll nd plenty in this book): if itMiss out the Hs attached to carbon atoms, along with the CH bonds Guideline 2helps clarify, put it in; if it cluttersand confuses, leave it out. Onething you must remember,(unless there is a good reason not to)though: if you write a carbon atomMiss out the capital Cs representing carbon atoms Guideline 3as a letter C then you must add allthe H atoms too. If you dont wantto draw all the Hs, dont write C(unless there is a good reason not to)for carbon.Be clear CH3 H NH2Try drawing some of the amino acids represented on p. 000 in a similar way, using the three guide- H C C OHlines. The bond angles at tetrahedral carbon atoms are about 109. Make them look about 109 pro-H3C CCjected on to a plane! (120 is a good compromise, and it makes the drawings look neat.)H HO Start with leucine earlier we drew it as the structure to the right. Get a piece of paper and do itnow; then see how your drawing compares with our suggestions.leucine 29. 24 2 . Organic structures It doesnt matter which way up youve drawn it, but your diagram should look something like one of these structures below.ONH2NH2OHOH HO2C N O HH NH2leucine leucineleucineHOOCleucine The guidelines we gave were only guidelines, not rules, and it certainly does not matter which way round you draw the molecule. The aim is to keep the functional groups clear, and let the skeleton fade into the background. Thats why the last two structures are all rightthe carbon atom shown as C is part of a functional group (the carboxyl group) so it can stand out.Now turn back to p. 000 and try redrawing the some of the other eight structures there using the guidelines. Dont look at our suggestions below until youve done them! Then compare your draw- ings with our suggestions. NH2NH2 NH OH H2N OH OHOHOOOO glycine alanine phenylalanineproline NH2 NH2 NH2OHOH HNSH2 NOH OOOtryptophanmethionine lysine Remember that these are only suggestions, but we hope youll agree that this style of diagram looks much less cluttered and makes the functional groups much clearer than the diagrams on p. 000. Moreover, they still bear signicant resemblance to the real thingcompare these crystal structures of lysine and tryptophan with the structures shown above, for example. Structural diagrams can be modied to suit the occasion Youll probably nd that you want to draw the same molecule in different ways on different occa- sions to emphasize different points. Lets carry on using leucine as an example. We mentioned before that an amino acid can act as an acid or as a base. When it acts as an acid, a base (for example, hydroxide, OH) removes H+ from the carboxylic acid group in a reaction we can represent as NH2 NH2Not all chemists put circles round theirOOplus and minus chargesits a matterHOH + H2Oof personal choice. OOThe product of this reaction has a negative charge on an oxygen atom. We have put it in a circle toThe wiggly line is a graphical way ofmake it clearer, and we suggest you do the same when you draw charges: +s and s are easilyindicating an incomplete structure: itshows where we havemislaid. We shall discuss this type of reaction, the way in which reactions are drawn, and what thementally snappedO curly arrows in the diagram mean in Chapter 5. But for now, notice that we drew out the CO2H asoff the CO2H groupHfrom the rest of the the fragment left because we wanted to show how the OH bond was broken when the base attacked.molecule. O We modied our diagram to suit our own purposes. 30. Drawing molecules 25 When leucine acts as a base, the amino (NH2) group is involved. The nitrogen atom attaches itselfto a proton, forming a new bond using its lone pair. We can represent this reaction asH H H H HOH H N NH+ H2O CO2H A lone pair is a pair of electrons that is CO2H not involved in a chemical bond Weshall discuss lone pairs in detail in Notice how we drew the lone pair at this time because we wanted to show how it was involved in Chapter 4. Again, dont worry aboutthe reaction. The oxygen atoms of the carboxylic acid groups also have lone pairs but we didnt drawwhat the curly arrows in this diagrammeanwe will cover them in detail inthem in because they werent relevant to what we were talking about. Neither did we feel it was nec-Chapter 5.essary to draw CO2H in full this time because none of the atoms or bonds in the carboxylic acidfunctional group was involved in the reaction.Structural diagrams can show three-dimensional information on atwo-dimensional pageOf course, all the structures we have been drawing only give an idea of the real structure of themolecules. For example, the carbon atom between the NH2 group and the CO2H group ofleucine has a tetrahedral arrangement of atoms around it, a fact which we have so far completely H NH2ignored. CO2HWe might want to emphasize this fact