General Principles 7 reactivity.The electronegativity of an element is a measure of the power of an element to attract electrons to itself in a chemical bond.It increas- es across a period in the Periodic Table from lithium to fluorine and decreases down a group.Electronegativity differences between atoms lead sharing of the bonding between the atoms concerned tron exce on the Pauling scale (lithium=1 and fluorine=4)are given in Table 1.1. Table 1.1 Some Pauling electronegativity values Mg1.2 B2.0 C2.5 N3.0 03.5 91.8 P2.1 S2.5 c3.0 Ge1.8As2.0 Se2.4 Br2.9 12.5 The halogens,oxygen and nitrogen are more electronegative than car- bon and hence mine groups may berep the full-headed represent the shift of an electron pair. 1.42 However,this is not a complete picture of the factors that contribute to the reactivity of functional groups.For example,the electronegativi ty difference between carbon and iodine is relatively small.In the much larger iodine atom the bonding orbitals are further from the nucleus than 1.43 1.44 in chlorine and are more polarizable during the course of a reaction. These differences affect both the g-and n-bonds.Thus many of the reac- tions of the alkyl halide ay he rational ied in terms of the poo the onds the polriabilit the component atoms. 1.1.5 The Role of Lone Pairs The non-bonding 'lone pairs'of electrons,particularly on oxygen and nitrogen are far from i ert and play an important role in directing the H outcome of many r actions. The may accept a pr oton or a Lewis acid and thus increase the electron deficiency of on atom to which they are attached.Secondly,they are available for donatio to ar 1A5 attached electron-deficient carbon,and thus they may reduce the sensi tivity of this carbon to nucleophilic attack.Thirdly,they are available cò for conjugation with the n-electrons of an alkene or arene,thus increas- ing its electron-rich character.These effects may be summarized in 1.45-1.47.When two oxygen atoms,each possessing lone pairs,are 146 1.47
General Principles 7 reactivity. The of an element is a measure of the power of an element to attract electrons to itself in a chemical bond. It increases across a period in the Periodic Table from lithium to fluorine and decreases down a group. Electronegativity differences between atoms lead to an unequal sharing of the bonding electrons between the atoms concerned and consequently to regions of electron deficiency and electron excess in a molecule. Some electronegativities on the Pauling scale (lithium = 1 and fluorine = 4) are given in Table 1.1. Table 1 .l Some Pauling electronegativity values H 2.1 Li 1.0 Mg 1.2 B 2.0 C 2.5 N 3.0 0 3.5 F 4.0 Si 1.8 P 2.1 S 2.5 CI 3.0 Ge 1.8 As 2.0 Se 2.4 Br 2.8 I 2.5 The halogens, oxygen and nitrogen are more electronegative than carbon and hence the alkyl halides, carbonyl and imine groups may be represented as in 1.42-1.44, where the full-headed arrows represent the shift of an electron pair. However, this is not a complete picture of the factors that contribute I --C--Cl 1.42 I to the reactivity of functional groups. For example, the electronegativity difference between carbon and iodine is relatively small. In the much \P \P/ /C=O /C=N larger iodine atom the bonding orbitals are further from the nucleus than in chlorine and are more polarizable during the course of a reaction. These differences affect both the 0- and n-bonds. Thus many of the reactions of the alkyl halides and of carbonyl compounds may be rationalized in terms of the of the component atoms. 1.43 1.44 of the bonds and the 1.1.5 The Role of Lone Pairs The non-bonding of electrons, particularly on oxygen and I .9,+ I x nitrogen, are fa from inert and play an important role in directing the outcome of many reactions. They may accept a proton or a Lewis acid --c-0 and thus increase the electron deficiency of the carbon atom to which they are attached. Secondly, they are available for donation to an attached electron-deficient carbon, and thus they may reduce the sensitivity of this carbon to nucleophilic attack. Thirdly, they are available 1.45 \ r* \ q-R r,C=O R 1.46 for conjugation with the n-electrons of an alkene or arene, thus increasing its electron-rich character. These effects may be summarized in -0, ?TC\ E+ 1.45-1.47. When two oxygen atoms, each possessing lone pairs, are 1.47
8 Functional Group Chemistry attached to the same carbon atom,the interactions between the lone pairs become important in determining the stereochemistry of reactions. 1.1.6 Resonance The structures of a number of compounds that contain a conjugated n- system can be written as the combination of a number of contributory valence bond structures.Thus benzene can be written as a combination of the two valence hond str ctures 1.48 and 1.49.These contributory bu 1.48 1.49 n-iso The delocal bond structures.leads to enhanced stability. Examination of the contributory resonance structures can shed a use- ful light on the regions of electron deficiency and electron excess in a molecule and hence on its reactivity.The delocalization of charge through a conjugated system can give significant stabilization to reac the delocali zation of the rrrbontocarbony group (e1 m1 There are a number of rules that distinguish meaningful contributory 1.50 resonance structures.Firstly,the atoms involved must not move between resonance structures:secondly.the same number of paired electrons should exist in each structure contributing to the resonance hybrid;and thirdly.structures that have adiacent like charges will not make a maior contribution to the overall resonance hybrid.,neither will those involv Finally, framewor between the contributory resonance structures. 1.1.7 Tautomerism Compounds whose structures differ in the arrangement of hydrogen atoms and which are in rapid equilibrium are called tautomer s It is portan t to draw a ion between resona ce forms and tautome toobtain information on the tence of the individual tautomeric forms,resonance forms are not dis tinguishable.The difference can be illustrated by considering an amide (1.52).The resonance form(1.53)shows a difference in the position of charge,while the tautomer(1.54)shows a difference in the position of a hydrogen atom. OH 1.52 resonance 1.53 tautomerism 1.54
8 Functional Group Chemistry 1.48 8 1.49 \/ \I c-c - c=c /-d / \o- 1.50 1.51 attached to the same carbon atom, the interactions between the lone pairs become important in determining the stereochemistry of reactions. 1.1.6 Resonance The structures of a number of compounds that contain a conjugated nsystem can be written as the combination of a number of contributory valence bond structures. Thus benzene can be written as a combination of the two valence bond structures 1.48 and 1.49. These contributory but non-isolable structures are known as , The delocalization of the n;-electrons, arising from the combination of these valence bond structures, leads to enhanced stability. Examination of the contributory resonance structures can shed a useful light on the regions of electron deficiency and electron excess in a molecule and hence on its reactivity. The delocalization of charge through a conjugated system can give significant stabilization to reaction intermediates. An example is the delocalization of the negative charge of a carbanion adjacent to a carbonyl group (see 1.50 and 1.51). There are a number of rules that distinguish meaningful contributory resonance structures. Firstly, the atoms involved must not mo\7e between resonance structures; secondly, the same number of paired electrons should exist in each structure contributing to the resonance hybrid; and thirdly, structures that have adjacent like charges will not make a major contribution to the overall resonance hybrid, neither will those involving multiple isolated charges. Finally, it is important that the 0-bond framework, and in particular steric factors, permit a planar relationship between the contributory resonance structures. I .I .7 Tautomerism Compounds whose structures differ in the arrangement of hydrogen atoms and which are in rapid equilibrium are called . It is important to draw a distinction between resonance forms and tautomers. Whereas it is possible to obtain spectroscopic information on the existence of the individual tautomeric forms, resonance forms are not distinguishable. The difference can be illustrated by considering an amide (1.52). The resonance form (1.53) shows a difference in the position of charge, while the tautomer (1.54) shows a difference in the position of a hydrogen atom. 1.52 resonance 1.53 tautomerism 1.54
General Principles 9 A number of common tautomeric relationships are shown in Box 1.2. Box 1.2 Tautomeric Relationships Enol N-R Imine Enamin Nitroso Oxime OH Nitro Soaioy 1.1.8 Naming of Compounds Many simple common compounds are known by both a ivial and a systematic name.The systematic names are helpful in learning the struc tures of organic compounds,but the trivial names are often simpler and can reflect the source or dominant reactivity of the compound concerned. The systematic name for a compound has a stem that describes the car- bon skeleton,prefixes and suffixes that indicate the functional groups. and mmbers (locants)that define their position.Prefixes may also be stereochemistr is given in Table12. A list of the more com prefixes,and stems Thus the various CHo alcohols are named as butan-1-ol [CH,CH,CH,CH,OH],butan-2-ol [CH,CH,CH(OH)CH ]2-methyl- propan-1-ol [(CH ),CHCH,OH]and 2-methylpropan-2-ol [(CH)COH]. In selecting a stem,note that this includes the carbon atom of the sub- stituent described by the suffix.For example,ethanoic acid (acetic acid) is ChCO H not CH,CH.CO,H(Propa oic acid).Where there is chain ong nain is selected as the sten example CH,CH,CH(CH)CH,OH is named as 2-methylbutan-1-ol and not as 2 ethylpropan-1-ol. The relative positions of substituents on an aromatic ring(e.g.ben- zene)are indicated by numbers(see 1.55).When only two substituents 1.55
General Principles 9 A number of common tautomeric relationships are shown in Box 1.2. 1.1.8 Naming of Compounds Many simple common compounds are known by both a trivial and a systematic name. The systematic names are helpful in learning the structures of organic compounds, but the trivial names are often simpler and can reflect the source or dominant reactivity of the compound concerned. The systematic name for a compound has a stem that describes the carbon skeleton, prefixes and suffixes that indicate the functional groups, and numbers (locants) that define their position. Prefixes may also be added to indicate modifications to the carbon skeleton and to define the stereochemistry. A list of the more common prefixes, suffixes and stems is given in Table 1.2. Thus the various C4H,,0 alcohols are named as butan-1-01 [CH,CH,CH,CH,OH], butan-2-01 [CH,CH,CH(OH)CH,], 2-methylpropan- f-01 [(CH,),CHCH,OH] and 2-methylpropan-2-01 [(CH,),COH]. In selecting a stem, note that this includes the carbon atom of the substituent described by the suffix. For example, ethanoic acid (acetic acid) is CH,CO,H, not CH,CH,CO,H (propanoic acid). Where there is chain branching, the longest chain is selected as the stem. For example, CH,CH,CH(CH,)CH,OH is named as 2-methylbutan- 1-01 and not as 2- ethylpropan- 1-01. The relative positions of substituents on an aromatic ring (e.g. benzene) are indicated by numbers (see 1.55). When only two substituents X 4 P 1.55
10 Functional Group Chemistry Table 1.2 Common stems,suffixes and prefixes meth- hept(a) Co dec(a)- eth pent(a)- oct(a)- prop(a)- hex(a)- non(a) -oic acid carboxvic acid -ene alkene -oate ester or salt -0y acyl derivative y aky derivative -one ketone two or three of Examples of prefixes chioro- flucro- nitro- are pres place of 1,3 and 1 respectively.These may also be used two particular substituents in a polyfunctional molecule.The lowest numbers possible are given to the substituents(e.g.1-bromo-4-methyl- 2-nitrobenzene,1.56)and the substituents are listed in alphabetical order. The reactivity of the positions adjacent to a functional group is often modified by the functional group.Specific names are given to these posi- 1.56 tions.The position adjacent to an alkene is know as the allylic po tion,whilst that adjacent to a b ene ng is know position.In more gen the designate positions adjacent to and progressively further from a func tional group.The @-position is that at the end of a chain.Thus the com- mon amino acids such as alanine (1.57)are a-amino acids and 0 but-3-en-2-one(1.58)is an o,B-unsaturated ketone.The Greek letters a CH2=CHC and b may also have a different stereochemical meaning.but the con text usually makes this clear 158 When twe for exa ple two hydroxyl groups,are adjac cent to 芒含 An asymmetric centre may be described systematically using the sequence rules.The atoms attached to the asymmetric centre are ranked according to their atomic number.The highest number is given the pri- ority 'a'and the lowest'd'.If,on viewing the carbon-d bond from the side remote from d,the sequence of the three higher atoms around the
10 Functional Group Chemistry Table 1.2 Common stems, suffixes and prefixes ~ ~~ ~~~ Examples of stems for carbon chain length C, meth- C, but(a)- C, hept(a)- C,, dec(a)- C, eth- C, pent(a)- C, oct(a)- c, ProP(a)- C, hex(a)- C, non(a)- Examples of suffixes -ane alkane -oic acid carboxylic acid -ene alkene -oate ester or salt -yne alkyne -0yl acyl derivative -01 alcohol -Y I alkyl derivative -al aldehyde -amine amine -one ketone -di-. -tri- two or three of Examples of prefixes cyclo- aminocisltrans- bromo- (*I- chlorofluoroh yd roxyiodomethylnitroBr 3”” CH3 1.56 C02H / CH3CH \ NH2 1.57 0 // CH2=CHC \ CH3 1.58 are present, o- (ortho), m- (meta) and p- (para) are sometimes used in place of 1,2-, 1,3- and 1,4-, respectively. These may also be used to relate two particular substituents in a polyfunctional molecule. The lowest numbers possible are given to the substituents (e.g. 1 -bromo-4-methyl- 2-nitrobenzene, 1.56) and the substituents are listed in alphabetical order. The reactivity of the positions adjacent to a functional group is often modified by the functional group. Specific names are given to these positions. The position adjacent to an alkene is known as the position, whilst that adjacent to a benzene ring is known as the position. In more general cases the Greek letters a, p and y are used to designate positions adjacent to and progressively further from a functional group. The o-position is that at the end of a chain. Thus the common amino acids such as alanine (1.57) are a-amino acids and but-3-en-2-one (1.58) is an a$-unsaturated ketone. The Greek letters a and p may also have a different stereochemical meaning, but the context usually makes this clear. When two groups, for example two hydroxyl groups, are adjacent to each other, they are known as groups, whilst two groups attached to the same atom are referred to as An asymmetric centre may be described systematically using the . The atoms attached to the asymmetric centre are ranked according to their atomic number. The highest number is given the priority ‘a’ and the lowest ‘d’. If, on viewing the carbon-d bond from the side remote from d, the sequence of the three higher atoms around the groups
General Principles 11 asymmetric carbon,a>b>c.is clockwise,the centre is described as R(right handed tus).If the C IS ticlockwise,the re is de of these rules for the designation of stereochemistry,including that of alkenes,is described in books on stereochemistry. In a number of cases,particularly with simple molecules,the com- monly accepted trivial name is more clearly indicative of their proper- ties.source and reactivity.The iupac rule s indicate that some of these trivial na ad and the e in the scientific literature and on the bot he laboratory.How systematic nomenclature is used for more complex structures,for index ing and for abstracting.Consequently,both have to be known.In this book we will use the common trivial names,giving where appropriate the systematic name as well. Abbreviations are often used for parts of structures,particularly when these do not participate in a reaction.Thus the symbol R may be used for the rem cule.The abb Ar ay be used for (CH).Some common abbreviations for alkyl groups are given in Table 1.3. Table 1.3 Common abbreviations for alkyl groups Me tertiary butyl (fert-buty) Dropv 名 acetyl Pr or iPr isopropyl Bz benzoyl Another abbreviation used in drawing structures is to draw only the bonds of the carbon framework,leaving out the atoms.Bonds between carbon and hydrogen atoms are also left out.Thus.butane is drawn as e as a hexagon.Double and triple bonds are as .In this book,benzene rings will be drawn as cyclo hexatrienes rather than with a circle,because this valence bond repr sentation makes it much easier for the student to understand the mechanism of aromatic substitution.Furthermore,in polycyclic aro- matic compounds the use of circles can be misleading. Electron movement is symbolized by a double-headed 'curly arrow' for the movement of an electron pair.and a single-headed arrow or'fish- hook'for the movement of a single electron ein re resenting electrot mo ent,the must start from the hond o om that provide electron(s)and the arrow should end where the electron mo terminates,either to form a bond or on the particular atom or group that receives the charge.Thus if the electron movement creates a bond
General Principles 11 asymmetric carbon, a -+ b -+ c, is clockwise, the centre is described as R (right handed or rectus). If the order a + b + c is anticlockwise, the centre is described as S (left handed or sinister). The full implementation of these rules for the designation of stereochemistry, including that of alkenes, is described in books on stereochemistry. In a number of cases, particularly with simple molecules, the commonly accepted trivial name is more clearly indicative of their properties, source and reactivity. The IUPAC rules indicate that some of these trivial names are preferred and they are in current common usage in the scientific literature and on the bottles found in the laboratory. However, systematic nomenclature is used for more complex structures, for indexing and for abstracting. Consequently, both have to be known. In this book we will use the common trivial names, giving where appropriate the systematic name as well. Abbreviations are often used for parts of structures, particularly when these do not participate in a reaction. Thus the symbol R may be used for the remainder of a molecule. The abbreviation Ar may be used for an aromatic ring while Ph is used for phenyl (C,H,). Some common abbreviations for alkyl groups are given in Table 1.3. Table 1.3 Common abbreviations for alkyl groups Me methyl Bu butyl Et ethyl But or t-Bu tertiary butyl (tert-butyl) Pr ProPYl AC acetyl Pr‘ or iPr isopropyl 82 benzoyl Another abbreviation used in drawing structures is to draw only the bonds of the carbon framework, leaving out the atoms. Bonds between carbon and hydrogen atoms are also left out. Thus, butane is drawn as a ‘zigzag’ and cyclohexane as a hexagon. Double and triple bonds are included as = or =. In this book, benzene rings will be drawn as cyclohexatrienes rather than with a circle, because this valence bond representation makes it much easier for the student to understand the mechanism of aromatic substitution. Furthermore, in polycyclic aromatic compounds the use of circles can be misleading. Electron movement is symbolized by a double-headed ‘curly arrow’ used for an for the movement of an electron pair, and a single-headed arrow or ‘fish- electron pair hook’ for the movement of a single electron. In representing electron movement, the arrow must start from the bond or atom that provides the electron(s) and the arrow should end where the electron movement terminates, either to form a bond or on the particular atom or group that receives the charge. Thus if the electron movement creates a bond, 7. -3 used for a single electron