Functional Group Chemistry the arrow should terminate where the centre of the new bond will be;if a leaving group departs with the bonding electrons.the arrow should terminate on the ator receiving the charge 1.2 Reagents and Reactions 1.2.1 Making and Breaking Bonds The reactions of functional groups involve the making and breaking of bonds.In homolytic reactions the bonding pair of electrons is separat- ed to generate two free radicals,whereas in heterolytic reactions the bonding pair stays with parner.The reagents that bring about these reactions are thus involved in one-or two-electron process In the laboratory,most reactions take place in solution.What may be considered to be a high-energy process of placing two bonding electrons on to one atom is influenced by the solvent.The solvent can play a major role in the stabilization of the reacting species by associating with the ions which are formed.Thus heterolytic reactions.which produce ionic species are favoured in dipolar solvents with a high dicl onstant such ormamide (DMF,HCONMe) or dim thyl sulfoxide (DMSO.Me,SO).whereash omolytic reactions are favoured by non-pola solvents such as petroleum ether or carbon tetrachloride 1.2.2 Nucleophiles and Electrophiles The reagents that bring about heterolytic reactions may be classified as hiles and electrophiles.Nucleophiles are electron-rich,sometime reagen s which participate in s of electron defi ciency in a molecule. hile forms a bor e electron defi. cient centre by donating both bonding electrons.On the other hand. electrophiles are electron-deficient,sometimes cationic,reagents that react with regions of higher electron density within a molecule.The elec- trophile forms a bond by accepting both bonding electrons from the other component of the reaction.In Table 1.4.nucleophiles and elec. ophiles are listed in terms of their position in the Peri odic Table here are some gaps in term ple.athough especies. species or their equivalents can be gene electrophiles based on oxygen(OH)and amide nitrogen (NH,")are not commonly used. 1.2.3 Radical Reagents electron.They are formed by homolytic,or one electron transfer,reac
12 Functional Group Chemistry the arrow should terminate where the centre of the new bond will be; if a leaving group departs with the bonding electrons, the arrow should terminate on the atom receiving the charge. L2 Reagents and Reactions 1.2.1 Making and Breaking Bonds The reactions of functional groups involve the making and breaking of bonds. In homolytic reactions the bonding pair of electrons is separated to generate two free radicals, whereas in heterolytic reactions the bonding pair stays with one partner. The reagents that bring about these reactions are thus involved in one- or two-electron processes. In the laboratory, most reactions take place in solution. What may be considered to be a high-energy process of placing two bonding electrons on to one atom is influenced by the solvent. The solvent can play a major role in the stabilization of the reacting species by associating with the ions which are formed. Thus heterolytic reactions, which produce ionic species, are favoured in dipolar solvents with a high dielectric constant such as water, dimethylformamide (DMF, HCONMe,) or dimethyl sulfoxide (DMSO, Me2SO), whereas homolytic reactions are favoured by non-polar solvents such as petroleum ether or carbon tetrachloride. I .2.2 Nucleophiles and Electrophiles The reagents that bring about heterolytic reactions may be classified as . Nucleophiles are electron-rich, sometimes anionic, reagents which participate in reactions at centres of electron deficiency in a molecule. A nucleophile forms a bond to the electron-deficient centre by donating both bonding electrons. On the other hand, electrophiles are electron-deficient, sometimes cationic, reagents that react with regions of higher electron density within a molecule. The electrophile forms a bond by accepting both bonding electrons from the other component of the reaction. In Table 1.4, nucleophiles and electrophiles are listed in terms of their position in the Periodic Table. There are some gaps in terms of common reactive species. For example, although such species or their equivalents can be generated, simple electrophiles based on oxygen (OH') and amide nitrogen (NHJ are not commonly used. and 1.2.3 Radical Reagents are atomic or molecular entities possessing an unpaired electron. They are formed by homolytic, or one-electron transfer, reac-
General Principles 13 Table 1.4 Nucleophies and electrophiles Nucleophies Eectrophiles H(HO) Sulfur HS.SH,SR Nitrogen NH NH2,HNR NONO Carbon RC-,CN-,RC=C R,C',RCO tions.The tendency for an unpaired electron to seek a partner means that,in the absence of special stabilizing features,free radicals are high- ly reactive species.Nevertheless,it is possible to design situations in which this reactivity can be turned to useful advantage radicals may be generated by thermal means using as initiators,com strongly bonded product such as nitrogen gas.Azobisisobutyronitrile(1.59)falls into this class.After the loss of the nitrogen,the nitrile stabilizes the adjacent carbon radical by delocalization. +N2 C=N CN 1.59 When a molecule is irradiated,particularly with ultraviolet light,some bonds within the molecule can absorb this energy and undergo homolyt- ic cleavage to generate free radicals.These reactions include the forma- tion of alkoxyl (RO.)radicals from alkyl hypoiodites (RO)or nitrites (RONO)or thegeneration of bromine atoms from bromine or N-bro- mo umber of radicals may be fomed by reactions using a metal ion.These may be either oxidations in which transition metal ion such as iron(III)accepts a single electron from the organic substrate to become iron(II),or the reaction may be a reduction in which a strongly electropositive metal such as sodium donates an elec- tron to the substrate Many radical ro actions differ from ionic processes in that they involve nce in one radical reacts with another mol in turn generates a third radical and so on,thus propagating the chain until ultimately it is terminated by the combination of two radicals
General Principles 13 Table 1.4 Nucleophiles and electrophiles Nucleophiles Elec trophiles H- H' (H,O+) Halogens F-, CI-, Br, I- (F+), CI+, Br+, I' Sulfur H,S, SH-, SR- SO,H+ Nitrogen NH,, NH,-, HNR, NO,', NO+ Carbon R,C-, CN-, RCd- R,C+, RCO+ Oxygen H,O, OH-, OMe-, OAc- (OH+) tions. The tendency for an unpaired electron to seek a partner means that, in the absence of special stabilizing features, free radicals are highly reactive species. Nevertheless, it is possible to design situations in which this reactivity can be turned to useful advantage. Radicals may be generated by thermal means using, as initiators, compounds which possess either a weak 0-0 bond such as a peroxide, or which, on fragmentation, generate a stabilized radical and a strongly bonded product such as nitrogen gas. Azobisisobutyronitrile (1.59) falls into this class. After the loss of the nitrogen, the nitrile stabilizes the adjacent carbon radical by delocalization. 1.59 When a molecule is irradiated, particularly with ultraviolet light, some bonds within the molecule can absorb this energy and undergo homolytic cleavage to generate free radicals. These reactions include the formation of alkoxyl (RO*) radicals from alkyl hypoiodites (RO) or nitrites (RONO) or the generation of bromine atoms from bromine or N-bromosuccinimide. A number of radicals may be formed by one-electron transfer redox reactions using a metal ion. These may be either oxidations in which a transition metal ion such as iron(II1) accepts a single electron from the organic substrate to become iron(II), or the reaction may be a reduction in which a strongly electropositive metal such as sodium donates an electron to the substrate. Many radical reactions differ from ionic processes in that they involve a chain of reactions. Once initiated, one radical reacts with another molecule to generate a further radical by breaking another electron pair. This in turn generates a third radical and so on, thus propagating the chain until ultimately it is terminated by the combination of two radicals
14 Functional Group Chemistry 1.2.4 Pericyclic Reactions states which are c aracterized by the maintenance throughout of an over. lap between orbitals of the correct symmetry.These reactions are known as pericyclic reactions and the rules that govern them are known as the Woodward-Hoffmann rules.A typical example of a reaction of this type is the Diels-Alder reaction of a diene and a dienophile. 1.2.5 Acids and Bases The Bronsted theory of acids and bases defines an acid as a proton donor and a base as a proton acceptor,i.e.a protic acid such as hydrochloric acid is a source of protons.Although the idea of an acidic hydrogen in organic compounds may initially be understood in terms of a carboxyl hydroxyl group,a hydrogen atom may become weakly acidic in a num- ber of other circumstances.eg.when it is attached to a carbon atom that is adjacent to a carbonyl group.On the other hand,a base such as an anion, capable of a ccepting by G.N Lewis.Protons can accept electron pairs from bases;Lewis acids are gen eralized electron-pair acceptors.For example,aluminium trichloride (1.60)behaves as a Lewis acid and reacts with the chloride ion (a Lewis 1.60 base).Boron trifluoride may react with the lone pair of the oxygen of diethyl ether to form boron trifluoride etherate (1.61).A Lewis base is BF3+OEt2 an pair donor.in this case the ether oxyg The d soft acids and bas s useful in classifying reagent nature of the ou electron shell of an atom determines its reactivity.If the electron shell is firmly bound and the orbitals are rigidly directed and of low polarizability.then the atom is said to be hard.If the orbitals are less rigidly held and are more polarizable,the atom is said to be softer.Hard acids tend to react with hard bases.and soft acids react with soft bases.Some typical hard and soft acids and bases are given in Table 1.5. Table 1.Hard and soft acids and bases Hard Soft Acids H".L".Na'.Mg?,Ce4.T,Cr-,Fe2.Cu Cu.Ag".Cd .CN-.R,S
14 Functional Group Chemistry 1.2.4 Pericyclic Reactions AlC13 + C1- AlC14- 1.60 BF3 + OEt2 BF3:OEtZ 1.61 There are a number of concerted reactions involving cyclic transition states which are characterized by the maintenance throughout of an overlap between orbitals of the correct symmetry. These reactions are known as pericyclic reactions and the rules that govern them are known as the . A typical example of a reaction of this type is the of a diene and a dienophile. 1.2.5 Acids and Bases The Bronsted theory of acids and bases defines an acid as a proton donor and a base as a proton acceptor, i.e. a protic acid such as hydrochloric acid is a source of protons. Although the idea of an acidic hydrogen in organic compounds may initially be understood in terms of a carboxyl hydroxyl group, a hydrogen atom may become weakly acidic in a number of other circumstances, e.g. when it is attached to a carbon atom that is adjacent to a carbonyl group. On the other hand, a base such as an amine, or a carboxylate anion, is capable of accepting a proton. The idea of the proton as the acidic entity was extended by G. N. Lewis. Protons can accept electron pairs from bases; are generalized electron-pair acceptors. For example, aluminium trichloride (1.60) behaves as a Lewis acid and reacts with the chloride ion (a Lewis base). Boron trifluoride may react with the lone pair of the oxygen of diethyl ether to form boron trifluoride etherate (1.61). A Lewis base is an electron pair donor, in this case the ether oxygen. is useful in classifying reagents. The nature of the outer electron shell of an atom determines its reactivity. If the electron shell is firmly bound and the orbitals are rigidly directed and of low , then the atom is said to be hard. If the orbitals are less rigidly held and are more polarizable, the atom is said to be softer. Hard acids tend to react with hard bases, and soft acids react with soft bases. Some typical hard and soft acids and bases are given in Table 1.5. The concept of I Table 1.5 Hard and soft acids and bases Hard Borderline soft Acids H+, Li+, Na+, Mg2+, Ce4+, Ti4+, CP+, Fe2+, Cu2+ Cu+, Ag+, Cd2+, Fe3+, BF,, AICI,, Me,Si+ Hg2+ Bases NH,, RNH,, H,O, OH-, F- C,H,N (pyridine), H-, CN-, R,S, Br RS-, 1-
General Principles 15 Acid-Base Catalysis Many organic reactions are subject to acid or base catalysis.For exam- ple,protonation of the oxygen atom of a carbonyl group may enhance the electron deficiency of the carbonyl carbon atom and increase its sensitivity to nucleophilic attack. The catalyst may serve to generate the reactive species.For example many electrophiles are generated by mineral acid or Lewis acid catalysts Bromine reacts with iron bre the brom 1ion(1.62 whilst acetyl chlor in the presence of aluminium trichloride reacts as an acylium ion(1.63) Br+FeBr3→ Base catalysis operates in a similar manner.An acidic proton of a cart oonyl group may rat the reactive uo removed by a base to 0- 1.64 1.2.6 Reaction Types Having considered the types of bonding.,the different functional groups and the types of reagent,it is helpful to divide organic reactions into several large groups.The first group are substitution reactions in which one groun ectly displaces another(Scheme 1.la).These reactions are typical.Elimination reactions (Scheme 1.b) (b)Elimination B+=+X (e)Addition Scheme1.1
General Principles 15 Acid-Base Catalysis Many organic reactions are subject to acid or base catalysis. For example, protonation of the oxygen atom of a carbonyl group may enhance the electron deficiency of the carbonyl carbon atom and increase its sensitivity to nucleophilic attack. The catalyst may serve to generate the reactive species. For example, many electrophiles are generated by mineral acid or Lewis acid catalysts. Bromine reacts with iron(II1) bromide to give the bromonium ion (1.62), whilst acetyl chloride in the presence of aluminium trichloride reacts as an acylium ion (1.63). 0 // + \ 31-2 + FeBq - Br+ + FeBr4- CH3C + A1Cl-j + CH3CrO + AIC14- 1.62 c1 1.63 Base catalysis operates in a similar manner. An acidic proton of a methylene adjacent to a carbonyl group may be removed by a base to generate the reactive nucleophilic carbanion (1.64). - I 113 0 1.2.6 Reaction Types Having considered the types of bonding, the different functional groups and the types of reagent, it is helpful to divide organic reactions into several large groups. The first group are in which one group directly displaces another (Scheme 1. la). These reactions are typical of o-bonded C-X systems. (Scheme 1.1 b) Scheme 1.1
16 Functional Group Chemistry form a second group.Elimination reactions lead to the formation of an unsaturated n-bonded system.The converse of these are addition reac. tions.in which sp or sp2centres are converted to spor sp'centres,respec tively(Scheme 1.lc).These eactions are typical of -bonds. aci particularly t elimination mechanism (e.g.Scheme 1.2).Oxidation and reduction reac- tions may often be regarded as subsets of elimination and addition reac- tions,respectively.Other oxidation reactions may involve the substitution of a hydrogen atom by an oxygen atom,while some reduc- onscment of a substituent by nyarogen Rear (Scheme 1.3)may Addition-elimination 8→56 →Nu-C=0+Y Scheme1.2 一 Scheme 1.3 Finally,there is the large family of industrially important polymer- ization reactions. 1.2.7 The Reaction Coordinate Asa reaction from starting materils toproducts,it is pos ble to show the change of the free energy against the progress of reaction(the reaction coordinate)and thus identify various stages in the reaction(see Figure 1.1).The activation energy needed to reach the tran- sition state determines the rate of the reaction.In a multi-step process, we can often identify the rate-limiting step
16 Functional Group Chemistry Scheme 1.2 form a second group. Elimination reactions lead to the formation of an unsaturated n-bonded system. The converse of these are , in which sp or sp2 centres are converted to sp2 or sp3 centres, respectively (Scheme 1. lc). These reactions are typical of n-bonds. A number of reactions which at first sight appear to be substitution reactions, particularly at sp2 centres, in fact proceed via an additionelimination mechanism (e.g. Scheme 1.2). Oxidation and reduction reactions may often be regarded as subsets of elimination and addition reactions, respectively. Other oxidation reactions may involve the substitution of a hydrogen atom by an oxygen atom, while some reductions involve the displacement of a substituent by hydrogen (hydrogenolysis). Rearrangement reactions (Scheme 1.3) may be considered as internal substitution reactions. I Addition-elimination Scheme 1.3 Finally, there is the large family of industrially important polymerization reactions. I .2.7 The Reaction Coordinate As a reaction proceeds from starting materials to products, it is possible to show the change of the free energy against the progress of the reaction (the reaction coordinate) and thus identify various stages in the reaction (see Figure 1.1). The activation energy needed to reach the transition state determines the rate of the reaction. In a multi-step process, we can often identify the rate-limiting step