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![BS-Organic Chemistry-I 15-Jan-20
Dr Ahmad Raza (PhD, QAU Islamabad) 2
Aromaticity
Examples:…………
Cycloheptatriene
Dr Ahmad Raza 5
Aromaticity
Examples:…………
Naphthalene
aromatic
Cyclodecapentaene
Non-aromatic Not planar
cyclooctatetraene
Non-aromatic
Dr Ahmad Raza 6
Aromaticity
Annulenes
• monocyclic compounds containing alternating ring double bonds,
such as benzene, but of different sizes.
• According to systematic nomenclature, cyclobutadiene is
[4]annulene, benzene is a [6]annulene, and cyclooctatetraene is an
[8]annulene
• Digit within brackets indicate no. of pi electrons
• [10]-Annulene was expected to be aromatic but is non-aromatic due to
ring strain e.g. Cyclodecapentaene
• Higher annulnes i.e. 14, 18 etc are aromatic
Dr Ahmad Raza 7
Electrophilic substitution
• The exposed pi electrons of benzene are susceptible to electrophilic (E+)
attack, hence undergoes electrophilic aromatic substitution
• The reactions in which a proton (H+) of aromatic ring is substituted by an
elctrophile (E+) is called as electrophilic aromatic substitution
Mechanism
• In the first step, an electrophile (E+) attacks the π-electrons of benzene ring
• A carbocation (arenium ion or σ-complex) is generated which is delocalized
over the ring
• This carbocation is non-aromatic (has 4 π-electrons)
1. Step one
Dr Ahmad Raza 8](https://image.slidesharecdn.com/8-240508162547-a2c712d3/75/8-_Aromaticity-_Substitution_Reactions-Nadir-pdf-2-2048.jpg)
8._Aromaticity,_Substitution_Reactions Nadir.pdf
- 1. BS-Organic Chemistry-I 15-Jan-20 DrAhmad Raza (PhD, QAU Islamabad) 1 Aromaticity • The term “Aromatic” was initially associated with benzene • Now linked with cyclic compounds having chemical properties similar to benzene • The characteristic behavior exhibited by aromatic compounds is called “Aromaticity” • Property of sp2 hybridized planar ring • p-orbital on each atom allow cyclic delocalization of π-electrons • Aromatic compounds exhibit high degree of unsaturation and undergo substitution reactions rather than addition • Have extra stability (resonance energy) Dr Ahmad Raza 1 Aromaticity • The aromatic system possess closed system of π-electrons Huckle’s rule • Given by Huckle in 1931 for monocyclic compounds • Cyclic system having 4n+2 delocalized π-electrons exhibit aromatic character Where n = 0, 1, 2, 3, 4, 5……etc. • In general planar cyclic structures with 2, 6, 10, 14, 18, 22 etc. will be aromatic n = 0 we get (4 × 0) + 2 = 2 n = 1 we get (4 × 1) + 2 = 6 n = 2 we get (4 × 2) + 2 = 10 n = 3 we get (4 × 3) + 2 = 14 Note: The system can also be an ion Dr Ahmad Raza 2 Aromaticity The necessary conditions for aromaticity • For a compound to be aromatic, it must fulfill following requirements: 1. Must have cyclic and planar structure 2. Each atom of ring must be sp2 hybridized 3. Must obey Huckle’s rule Examples: H H Non-aromatic H Aromatic • Although cyclopropane is cyclic, planar and have 2 pi electrons, yet is non-aromatic • It does not have delocalization of pi electrons Cyclopropene Cyclopropenyl cation Dr Ahmad Raza 3 Aromaticity Examples:………… Pyrrole N H O Furan S Thiophene N Pyridine Benzene H H 1,3-cyclopentadiene Non-aromatic H 1,3-cyclopentadienyl cation Non-aromatic H 1,3-cyclopentadienyl anion aromatic Dr Ahmad Raza 4
- 2. BS-Organic Chemistry-I 15-Jan-20 DrAhmad Raza (PhD, QAU Islamabad) 2 Aromaticity Examples:………… Cycloheptatriene Dr Ahmad Raza 5 Aromaticity Examples:………… Naphthalene aromatic Cyclodecapentaene Non-aromatic Not planar cyclooctatetraene Non-aromatic Dr Ahmad Raza 6 Aromaticity Annulenes • monocyclic compounds containing alternating ring double bonds, such as benzene, but of different sizes. • According to systematic nomenclature, cyclobutadiene is [4]annulene, benzene is a [6]annulene, and cyclooctatetraene is an [8]annulene • Digit within brackets indicate no. of pi electrons • [10]-Annulene was expected to be aromatic but is non-aromatic due to ring strain e.g. Cyclodecapentaene • Higher annulnes i.e. 14, 18 etc are aromatic Dr Ahmad Raza 7 Electrophilic substitution • The exposed pi electrons of benzene are susceptible to electrophilic (E+) attack, hence undergoes electrophilic aromatic substitution • The reactions in which a proton (H+) of aromatic ring is substituted by an elctrophile (E+) is called as electrophilic aromatic substitution Mechanism • In the first step, an electrophile (E+) attacks the π-electrons of benzene ring • A carbocation (arenium ion or σ-complex) is generated which is delocalized over the ring • This carbocation is non-aromatic (has 4 π-electrons) 1. Step one Dr Ahmad Raza 8
- 3. BS-Organic Chemistry-I 15-Jan-20 DrAhmad Raza (PhD, QAU Islamabad) 3 Electrophilic substitution Mechanism……. • E+ may be positive ion or dipole • Arenium ion is resonance stabilized and hybrid of three structures • First step is slow and is therefore rate determining step Dr Ahmad Raza 9 Electrophilic substitution Mechanism……. 2. Step two • In the second step, arenium ion looses a proton to base present in mixture • The proton is lost from the carbon which bears E+ • The released electron pair of C-H bond becomes part of cyclic π-system and restore the six π-electrons to regain aromatic character • Since stability is gained by the molecule hence this step is fast • The driving force of substitution is rearomatization Dr Ahmad Raza 10 Electrophilic substitution Energy diagram Dr Ahmad Raza 11 Electrophilic substitution reactions 1. Nitration of benzene • Commonly carried out by heating benzene with mixture of conc. HNO3 and conc. H2SO4 • The nitronium ion (NO2 +) is generated as electrophile (observed spectroscopically) Dr Ahmad Raza 12
- 4. BS-Organic Chemistry-I 15-Jan-20 DrAhmad Raza (PhD, QAU Islamabad) 4 Electrophilic substitution reactions Nitration of benzene……… Mechanism Dr Ahmad Raza 13 Electrophilic substitution reactions 2. Sulphonation of benzene • By heating benzene with conc. H2SO4 at 80 °C Or Fuming sulphuric acid (H2SO4 +SO3) at 25 °C • Although SO3 is neutral but still act as E+ since S is electron deficient Dr Ahmad Raza 14 Electrophilic substitution reactions Sulphonation of benzene………. Mechanism 1 = Generation of E+ 2 = Attack of E+ 3 = Restoration of aromaticity by abstraction of proton form sp3 carbon by HSO4 -1 4 = Proton transfer from H2SO4 to benzene sulphonate ion Dr Ahmad Raza 15 Electrophilic substitution reactions 3. Halogenation of benzene • The substitution of halogen atom (Cl, Br or I) in place of hydrogen is called halogenation • Benzene reacts with halogens in the presence of Lewis acid (FeCl3 or FeBr3) • Fe reacts wit halogen to from ferric halide 2Fe + 3X2 2FeX3 25°C Heat Dr Ahmad Raza 16
- 5. BS-Organic Chemistry-I 15-Jan-20 DrAhmad Raza (PhD, QAU Islamabad) 5 Electrophilic substitution reactions Halogenation of benzene………….. Mechanism • Aromatic halogenation reactions are carried out in the absence of light since side chain substitution is catalyzed by light Dr Ahmad Raza 17 Electrophilic substitution reactions Halogenation of benzene………….. • However in the absence of light toluene reacts with Cl2 or Br2 in the presence of AlCl3 or FeCl3 to give mixture of o- and p- derivatives Dr Ahmad Raza 18 Electrophilic substitution reactions • Developed by Charles Friedel and James Crafts in 1877 • Involves the introduction of alkyl or acyl group into benzene ring in the presence of anhydrous AlCl3 or any other Lewis acid i.e. BF3, FeCl3 etc. Friedal-Crafts reactions 4. Friedal-Crafts alkylation • Carried out by treating benzene with alkylating reagent like alkyl halide (R- X), alcohols (R-OH), or alkenes • Used for introducing alkyl group in the benzene ring • Reaction is carried out in inert solvent like nitrobenzene or carbon disluphide Dr Ahmad Raza 19 Electrophilic substitution reactions Friedal-Crafts alkylation…… Examples CH3Cl AlCl3 5 o C CH3 HCl (CH3)2CHOH BF3 -10 o C CH H2O H3C CH3 CH3-CH=CH2 AlCl3 HCl CH H3C CH3 Dr Ahmad Raza 20
- 6. BS-Organic Chemistry-I 15-Jan-20 DrAhmad Raza (PhD, QAU Islamabad) 6 Electrophilic substitution reactions Friedal-Crafts alkylation…… Mechanism Dr Ahmad Raza 21 Electrophilic substitution reactions Friedal-Crafts alkylation…… Lmitations a) Polyalkylation • It is difficult to stop the reaction when one alkyl group has entered the ring • Often poly-alkylated benzenes are produced • For example: Benzene with excess of CH3Cl gives1,2,4,5- tetramethyl benzene C H 3 C l A lC l3 C H 3 H 3 C H 3 C C H 3 Dr Ahmad Raza 22 Electrophilic substitution reactions Friedal-Crafts alkylation…… Lmitations b) Products due to rearrangement of carbonium ion electrophile (E+) • The generated carbocation of alkyl halide may undergo rearrangement before attacking the benzene ring • This rearrangement is in the order primary secondary tertiary attributed to their relative stability Dr Ahmad Raza 23 • This rearrangement usually takes place by transfer of H- or R- • Therefore reaction of benzene with 1-chloropropane (propyl chloride) in the presence of AlCl3 produces isopropylbenzene (cumene) as major product rather than expected n-propylbenzene Electrophilic substitution reactions Friedal-Crafts alkylation…… Lmitations CH3-CH2-CH2-Cl AlCl3 CH CH3 CH3 H2 C H2 C CH3 Major product Minor product Dr Ahmad Raza 24
- 7. BS-Organic Chemistry-I 15-Jan-20 DrAhmad Raza (PhD, QAU Islamabad) 7 Electrophilic substitution reactions 5. Friedal-Crafts acylation • Carried out by treating benzene with acylating reagent like acyl halide (CH3COX), or acid anhydride, or ketenes • Used for introducing acyl group (RCO-) in the benzene ring • Reaction is carried out in inert solvent like nitrobenzene or carbon disluphide • Aromatic ketone is generated Dr Ahmad Raza 25 Electrophilic substitution reactions Friedal-Crafts acylation…….. Examples AlCl3 C CH3 O HCl H3C C Cl O AlCl3 C CH3 O CH3COOH H3C C O H3C C O O AlCl3 C CH3 O H2C C O Ketene Acetophenone Dr Ahmad Raza 26 Electrophilic substitution reactions Friedal-Crafts acylation…….. Mechanism Dr Ahmad Raza 27 Electrophilic substitution reactions Friedal-Crafts acylation…….. • Unlike alkyl group in Friedal craft alkylation, acyl does not undergo rearrangement, not it allows the introduction of another acyl group in the benzene ring Advantage of Friedal crafts acylation Dr Ahmad Raza 28 • Friedal craft acylation can be applied to prepare straight chain alkyl benzenes • Acylation of benzene gives ketone which is then reduced to n- alkylbenzenes by Clemmensen reduction or Wolf Kishner reduction
- 8. BS-Organic Chemistry-I 15-Jan-20 DrAhmad Raza (PhD, QAU Islamabad) 8 Electrophilic substitution reactions Friedal-Crafts acylation…….. Advantage of Friedal crafts acylation Dr Ahmad Raza 29 Electrophilic substitution reactions 5. Formylation • Substitution of formyl group (aldehyde) -CHO- into aromatic ring • Similar to acylation • Can not be carried out with formyl chloride or formic anhydride • Formyl chloride is stable for short time in CHCl3 at -40 °C Dr Ahmad Raza 30 • Formic anhydride decomposes at room temperature • May be accomplished by: 1. Gatterman-Koch reaction 2. Gatterman reaction 3. Formylation with formyl fluoride Electrophilic substitution reactions 1. Gatterman-Koch reaction Mechanism • Similar to Friedel-Crafts acylation • CO and HCl react to form formyl chloride which then reacts with benzene to form benzaldehyde • Formyl chloride can be generated by dropping chlorosulphonic acid on formic acid Dr Ahmad Raza 31 Electrophilic substitution reactions 2. Gatterman reaction • Gatterman used HCN in place of CO (poisonous) as source of formyl group • Direct use of HCN can be avoided by using Zn(CN)2 Dr Ahmad Raza 32
- 9. BS-Organic Chemistry-I 15-Jan-20 DrAhmad Raza (PhD, QAU Islamabad) 9 Electrophilic substitution reactions 3. With formyl fluoride • Benzene is treated with formyl fluoride (HOCF) in the presence of BF3 ether (solvent) • Formyl fluoride is stable as compared to formyl chloride Dr Ahmad Raza 33