General Principles 17 transition states Free intermediate nerg ctivatior energy ctants Reaction- 1.2.8 Inductive and Mesomeric Effects The electronic factors which affect the ground state of a molecule by operating through the o-bond system,such as the electron-withdrawing effect of a halogen,are known as inductive effects.Electronic factors. which operate by the overlap of the p-or it-orbitals of a substituent with The me omeric effect may modify the reactivity a the reaction is in progress.these effects may stabiliz an intermediate by enhancing charge delocalization,leading to the res. onance stabilization of an intermediate.The resonance stabilization of a carbanion by an adjacent carbonyl group (1.65)is an important exam- ple of this.A double-ended arrow (is used to indicate the existence of these resonance structures. 22 1.65 1.2.9 Kinetic versus Thermodynamic Control The features that control the eventual outcome of a reaction may also be illustrated by the sible reactio s with o opportunity t the product that has the owest activa on energy(and d hence is formec the fastest)will be formed preferentially.The reaction is under kineti control.On the other hand,if the products can equilibrate so that the most stable product is formed (i.e.AG predominates),the reaction is said to be subject to thermodynamic control
General Principles 17 Figure 1.1 The reaction coordinate 9.2.8 Inductive and Mesomeric Effects The electronic factors which affect the ground state of a molecule by operating through the 0-bond system, such as the electron-withdrawing effect of a halogen, are known as . Electronic factors, which operate by the overlap of the p- or norbitals of a substituent with the n;-orbitals of the rest of the molecule, are known as The mesomeric effect may modify the reactivity of the ground state of a molecule. Once the reaction is in progress, these effects may stabilize an intermediate by enhancing charge delocalization, leading to the of an intermediate. The resonance stabilization of a carbanion by an adjacent carbonyl group (1.65) is an important example of this. A double-ended arrow (++) is used to indicate the existence of these resonance structures. 1.65 I I .2.9 Kinetic versus Thermodynamic Control The features that control the eventual outcome of a reaction may also be illustrated by the reaction coordinate diagram. If there are two possible reaction products with no opportunity to equilibrate between them, the product that has the lowest activation energy (and hence is formed the fastest) will be formed preferentially. The reaction is under . On the other hand, if the products can equilibrate so that the most stable product is formed (i.e. AG predominates), the reaction is said to be subject to
18 Functional Group Chemistry 1.2.10 Steric Factors Hitherto we have considered electronic features which affect the reac- tivity of a functional group.However,there are a number of general which d to be dered in te reaction e volume on stereochemistry,some general points need to be made.steric The pathway of the incoming reagent approaching an sp centre may strongly influence the chance of a reaction.Obstruction of this pathway by other parts of the molecule will reduce the rate of reaction by Such steric factors can affect the face of a double bond to group m attached when n a reagent attacks an sp2 centre or a carb bonyl roup from the less-hin a reagent may als favour attack on a particular face.Since an addition leads to the con version of an sp2 to a more bulky sp centre,the steric consequences of this have also to be considered. Many reactions have stereochemically demanding intermediates.The ments for the optimum overlap of the participating orbitals in many reactions may lead to spe cific ste och mical relationshi ps betweer groups in the products of a reaction Neighbo nctio may participate in many reactions,affecting not only th rate the products of a reaction.Each of these general stereochemical points needs to be considered for a specific reaction.Functional groups do not exist in isolation,but in real molecules in which the general pattern of reactivity may be modified by their particular environment. 1.3 Learning Organic Functional Group Chemistry Learning organic chemistry involves rationalizing the reactivity of functional groups in a systematic way so that reactions can be seen to follow a pattern.Recognition of this pattern not only aids the under- standing of organic reaction mechanisms,but also reveals those reac. tions which do not follow the predicted pattern and for which a special explanation must be sought A useful method fo g funct ional group chemistry is to prepare a template,such as the one illustrated in Scheme 1.4.The fo rmula o typical example of a compound bearing a functional group,for exampl a ketone such as propanone (acetone),is placed in the centre of a sheet of paper.The template containing three groups of questions is then superimposed on this.The first questions lead to the identification of the sites of electron excess and deficiency in the compound.In the case of propanone these are the oxygen atom and the carbon atom of the car. .Secondly,the types of reaction that the com-
18 Functional Group Chemistry I .2.10 Steric Factors Hitherto we have considered electronic features which affect the reactivity of a functional group. However, there are a number of general steric factors which need to be considered in terms of the reaction coordinate. Although the topic will be dealt with in detail in a companion volume on stereochemistry, some general points need to be made. The pathway of the incoming reagent approaching an sp3 centre may strongly influence the chance of a reaction. Obstruction of this pathway by other parts of the molecule will reduce the rate of reaction by . Such steric factors can affect the face of a double bond to which groups become attached when a reagent attacks an sp’ centre. Reagents will attack an alkene or a carbonyl group from the less-hindered face. Hydrogen bonding interactions with a reagent may also favour attack on a particular face. Since an addition leads to the conversion of an sp2 to a more bulky sp3 centre, the steric consequences of this have also to be considered. Many reactions have stereochemically demanding intermediates. The requirements for the optimum overlap of the participating orbitals in many reactions may lead to specific stereochemical relationships between groups in the products of a reaction. Neighbouring functional groups may participate in many reactions, affecting not only the rate but also the products of a reaction. Each of these general stereochemical points needs to be considered for a specific reaction. Functional groups do not exist in isolation, but in real molecules in which the general pattern of reactivity may be modified by their particular environment. 1.3 Learning Organic Functional Group Chemistry Learning organic chemistry involves rationalizing the reactivity of functional groups in a systematic way so that reactions can be seen to follow a pattern. Recognition of this pattern not only aids the understanding of organic reaction mechanisms, but also reveals those reactions which do not follow the predicted pattern and for which a special explanation must be sought. A useful method for learning functional group chemistry is to prepare a template, such as the one illustrated in Scheme 1.4. The formula of a typical example of a compound bearing a functional group, for example a ketone such as propanone (acetone), is placed in the centre of a sheet of paper. The template containing three groups of questions is then superimposed on this. The first questions lead to the identification of the sites of electron excess and deficiency in the compound. In the case of propanone, these are the oxygen atom and the carbon atom of the carbony1 group, respectively. Secondly, the types of reaction that the com-
General Principles 19 pound undergoes are identified.In the example of propanone,these would be addition reactions.Thirdly,the results of using various reagents for reactions are drawn on to the sheet of paper.For propanone,these would be the products of the addition of various nucleophiles to the car- bonyl group.Once a series of reactions have been outlined,it is impor- tant to rationalize them in mechanistic terms. Reaction types:substitution.elimination addition.oxidation.reduction? Electrophile Products Nucleophile Reactant Reagents antd Products Scheme 1.4 Reaction template A second strategy is to replace one atom by another close to it in the Periodic table to reveal analogies and patterns of reactivity.for exam- ger eal analogies ity of nitri and carbonyl com ds nd bet ic methods. A number of summary charts showing the inter-relationship of func tional groups are placed at the end of the sections in Chapters 2,3 and 4.Students should copy these and place the formulae of appropriate reagents and conditions above the arrows linking the functional groups The creation of'spiders webslinking specific pounds provides a useful method of learning functional group chemistry
General Principles 19 pound undergoes are identified. In the example of propanone, these would be addition reactions. Thirdly, the results of using various reagents for reactions are drawn on to the sheet of paper. For propanone, these would be the products of the addition of various nucleophiles to the carbony1 group. Once a series of reactions have been outlined, it is important to rationalize them in mechanistic terms. Scheme 1.4 Reaction template A second strategy is to replace one atom by another close to it in the Periodic Table to reveal analogies and patterns of reactivity. For example, replacing a nitrogen atom by an oxygen atom may reveal analogies between the reactivity of nitriles and carbonyl compounds and between enamines and enols. It may also provide some useful ideas for synthetic methods. A number of summary charts showing the inter-relationship of functional groups are placed at the end of the sections in Chapters 2, 3 and 4. Students should copy these and place the formulae of appropriate reagents and conditions above the arrows linking the functional groups. The creation of ‘spider’s webs’ linking specific compounds provides a useful method of learning functional group chemistry
20 Functional Group Chemistry Summary of Key Points 1.The 2s and 2p orbitals of carbon may be hybridized to give the tetrahedral sp,planar sp2 and linear sp arrangements.Carbon may form o-and n-bonds to other atoms.Two or more n- bonds may be coniugated.A cyclic coniugated system con- taining (4n+2)n electrons possesses a particular stability known as aromaticity 2.Functional groups are inter-related by a series of redox and substitutive transformations.The reactions of functional groups may be determined by the electronegativity differences between the component atoms. 3.Nucleophiles are electron-rich,sometimes anionic,reagents which articipate in reactions at centres of electron defic iency 4.Electrophiles are electron-deficient,sometimes cationic. reagents that react with regions of higher electron density with- in a molecule. 5.Free radicals are atomic or molecular species which possess unpaired electrons. 6. Reactions may be grouped into substitution,elimination addition,oxidation.reduction and rearrangement reactions. 7.Acids and bases can play an important part in the catalysis of organic reactions. owns inductive whilst those operating thou the n-bonding system are mesomeric effects. 9.Resonance effects may stabilize an intermediate. 10.Steric factors may influence both the products and rates of reactions
20 Functional Group Chemistry
General Principles 21 Worked Problems Q Identify the o-and n-bonds in 1. C=0 1 H A See 2.The o-bonds are derived from the overlap between the sp2hybridized orbitals of the carbon and the Is orbital of the hydro- gen atoms and a 2p orbital of the oxygen.These orbitals lie between the atoms.The nt-orbital lies above and below the plane of the C=O zroup and arise from the overlap of the 2p orbitals on the carbon and the oxygen. Q Name compound 3. CH-C-OH E 3 Me A The longest chain is six carbons and hence the compound is named as a substituted hexane:3.4-dimethylhexan-3-o1. QDraw the preferred conformation of 1-iodo-2-phenylethane. A See 4.There is a staggered conformation about the ethane C-C bond with the two bulky groups trans to each other. H 4P% Q From a consideration of the Pauling electronegativity values predict the charge distribution in the carbon-silicon bond. A Carbon has a Pauling electronegativity of 2.5 whilst silicon is Conel the chare b
General Principles 21