15. Benzene and Aromaticity Aromatic Compounds
Benzene is the parent of the family of aromatic compounds. Its six carbons lie in a plane in a hexagon, each carbon has one hydrogen attached. Benzene is a resonance hybrid of two Kekulé structures.
Note: It’s okay to use circle representation if explicitly showing π electrons is not necessary, since circle doesn’t indicate number of π
electrons in ring 2 Aromatic Compounds
In orbital terms, each carbon is sp2-hybridized. These orbitals form σ bonds to hydrogen and the two neighboring carbons are all in the ring plane. A p orbital at each carbon is perpendicular to this plane, and the six electrons, one from each carbon, form an electron cloud of π bonds, which lie above and below the plane.
The bond angles in benzene are 120. All CC bond distances are equal (1.39 Å). The compound is more stable than either of the contributing Kekulé structures and has a resonance or stabilization energy of about 36 kcal/mol. 3 Aromatic Compounds
The origin of the term aromatic comes from the description of fragrant substances such as benzaldehyde present in cherries, peaches, and almonds.
Benzaldehyde
Today aromatic refers to benzene and its structural relatives. Many compounds synthetic and isolated from nature are aromatic in part, including estrone, morphine and Valium.
4 15.1 Sources of Aromatic Hydrocarbons Coal and petroleum are two main sources for simple aromatic compounds. Coal has an array of benzene like rings joined together and some compounds that coal tar yields are benzene, toluene, naphthalene, and xylene. Petroleum yields mainly alkanes and only a few aromatic compounds.
5 15.2 Naming Aromatic Compounds: Common names and structures to memorize include
benzene toluene phenol aniline xylene (methylbenzene) (hydroxybenzene) (aminobenzene) (o,m,p) (pronounced feenol)
benzyl phenyl benzoic acid benzaldehyde benzonitrile (pronounced fenyl)
benzene sulfonic acid ortho meta para 15.2 Naming Aromatic Compounds
Monosubstituted benzenes systematic names as hydrocarbons with –benzene
C H Br 6 5 C6H5NO2 bromobenzene nitrobenzene
1-propylbenzene
7 The Phenyl and Benzyl Groups
When a benzene ring is a substituent (when the alkyl group has more carbons), the term phenyl is used (for C6H5 )
You may also see “Ph” or “f” in place of “C6H5”
” “Benzyl” refers to “C6H5CH2
8 Disubstituted Benzenes
Relative positions on a benzene ring ortho- (o) on adjacent carbons (1,2) meta- (m) separated by one carbon (1,3) para- (p) separated by two carbons (1,4)
Describes reaction patterns (“occurs at the para position”)
9 Naming Benzenes With More Than Two Substituents Choose numbers to get lowest possible values List substituents alphabetically with hyphenated numbers
4-chloro-1,2-dimethylbenzene 1-bromo-3-ethyl-2-nitrobenzene Common names, such as “toluene” can serve as root name
2,4,6-trinitrotoluene 5-bromo-2-chlorophenol o-bromobenzoic acid TNT
10 Naming Benzenes
A. Br B. NO2 C. F I
Cl Br NO2
C2H5 Br H2N D. E. H F.
Cl Cl C O
A. B. C. D. E. F. 11 15.3 Structure and Stability of Benzene
Benzene is very stable it undergoes a slow substitution reaction, where the ring itself does not react. The addition product is not formed
Evidence of Stability Heat of hydration is 150 kJ/mol less than expected, so it is 150 kJ/mol more stable than expected. All carbon-carbon bonds (double and single) are the same length.
Resonance 12 15.4 Molecular Orbital Description of Benzene
The 6 p-orbitals combine to give Three bonding orbitals with 6 electrons, Two nonbonding and two antibonding orbitals Orbitals with the same energy are degenerate
13 Aromaticity and the 4n + 2 Rule
Huckel’s rule, based on calculations – a planar cyclic molecule with alternating double and single bonds has aromatic stability if it has 4n+ 2 electrons (n is 0,1,2,3,4)
Benzene Three double bonds Six π electrons
For benzene = 6 4n+2 = 6, n = 1 and is aromatic
14 Compounds With 4n Electrons Are Not Aromatic (May be Anti-aromatic)
Planar, cyclic molecules with 4 n electrons are much less stable than expected (anti-aromatic) They will distort out of plane and behave like ordinary alkenes 4- and 8-electron compounds are not delocalized (single and double bonds) cyclobutadiene Cyclobutadiene is so unstable that it dimerizes by a self-Diels-Alder reaction at low temperature Cyclooctatetraene has four double bonds, and will distort out of plane and behave like an ordinary alkene, it reacts with Br2, KMnO4, and HCl as if it were four alkenes
cyclooctatetraene 15 15.6 Aromatic Ions
The 4n + 2 rule applies to ions as well as neutral species Both the cyclopentadienyl anion and the cycloheptatrienyl cation are aromatic The key feature of both is that they contain 6 electrons in a ring of
continuous p orbitals 16 15.7 Aromatic Heterocycles: Pyridine and Pyrrole
Heterocyclic compounds contain elements other than carbon in a ring, such as N,S,O,P Aromatic compounds can have elements other than carbon in the ring
Pyridine: The nitrogen Pyrrole: Nitrogen atom is sp2- lone pair electrons are not hybridized, and lone pair of part of the aromatic system electrons occupies a p orbital (6 (perpendicular orbital) electrons)
17 15.8 Why 4n +2?
When electrons fill the various molecular orbitals, it takes two electrons (one pair) to fill the lowest-lying orbital and four electrons (two pairs) to fill each of n succeeding energy level This is a total of 4n + 2
18 15.9 Polycyclic Aromatic Compounds: Naphthalene Aromatic compounds can have rings that share a set of carbon atoms (fused rings) Compounds from fused benzene or aromatic heterocycle rings are themselves aromatic, if the follow Huckel’s rule
19 Naphthalene Orbitals
Three resonance forms and delocalized electrons
20 15.10 Spectroscopy of Aromatic Compounds
IR: Aromatic ring C–H stretching at 3030 cm1 and peaks 1450 to 1600 cm1
UV: Peak near 205 nm and a less intense peak in 255-275 nm range
21 15.10 Spectroscopy of Aromatic Compounds
1H NMR: Aromatic H’s strongly deshielded by ring and absorb between 6.5 and 8.0
22 Ring Currents
Ring Current: The circulation of electrons induced in aromatic rings by an external magnetic field. This effect accounts for the downfield shift of aromatic ring protons (6.5 to 8.0 ) compared to vinylic protons (4.5 to 6.5 ). The presence of a ring current is a characteristic of all Hückel aromatic molecules and is a good test for aromaticity.
23 13C NMR of Aromatic Compounds
Carbons in aromatic ring absorb at 110 to 140 Shift is distinct from alkane carbons but in same range as alkene carbons
24 16. Chemistry of Benzene: Electrophilic Aromatic Substitution Substitution Reactions of Benzene and Its Derivatives Reactions of benzene lead to the retention of the aromatic core Electrophilic aromatic substitution replaces a hydrogen on benzene with another electrophile
Typical reactions include chlorination, bromination, iodination, nitration, sulfonation, alkylation, and acylation ( the last two are Friedel- Crafts reactions)
26 Substitution Reactions of Benzene and Its Derivatives
Electrophilic substitution reactions occur on aromatic compounds other than benzene and are a good test for aromaticity. 27 Substitution Reactions of Benzene and Its Derivatives
The mechanism involves two steps: addition of the electrophile to a ring carbon, to produce an intermediate benzenonium ion, followed by proton loss to again achieve the (now substituted) aromatic system.
General Mechanism
benzenonium ion
28 16.1 Bromination of Aromatic Rings
Benzene’s electrons participate as a Lewis base in reactions with Lewis acids The product is formed by loss of a proton, which is replaced by bromine
FeBr3 is added as a catalyst to polarize the bromine reagent
29 Mechanism: Formation of Product from Intermediate
The addition of bromine occurs in two steps
In the first step the electrons act as a nucleophile toward Br2 (in a complex with FeBr3) This forms a cationic addition intermediate from benzene and a bromine cation - The cationic addition intermediate transfers a proton to FeBr4 - (from Br and FeBr3) This restores aromaticity (in contrast with addition in alkenes)
slow fast
Aromatic rings are less reactive towards electrophiles than alkenes. Alkenes undergo addition reactions while aromatic compounds prefer to undergo substitution reactions. 30 16.2 Other Aromatic Substitutions
The reaction with bromine involves a mechanism that is similar to many other reactions of benzene with electrophiles The cationic intermediate was first proposed by G. W. Wheland of the University of Chicago and is often called the Wheland intermediate
George Willard Wheland 1907-1974
31 Aromatic Chlorination and Iodination
Chlorination:
Iodination: Iodine itself is unreactive towards an aromatic ring and requires an oxidizing agent (H2O2 or CuCl2). I2 is oxidized and it becomes a more powerful electrophile that reacts as I+.
Fluorination: Poor yields of monofluoro-aromatic compounds are made since fluorine is so reactive. 32 Aromatic Nitration
Nitration:
+ The combination of nitric acid and sulfuric acid produces NO2 (nitronium ion)
33 Aromatic Sulfonation
Sulfonation:
Reaction with a mixture of sulfuric acid and SO3 Reactive species is sulfur trioxide or its conjugate acid Reaction occurs via Wheland intermediate and is reversible
34 Alkali Fusion of Aromatic Sulfonic Acids
Sulfonic acids are useful as intermediates Heating with NaOH at 300 ºC followed by
neutralization with acid replaces the SO3H group with an OH Must be alkyl substituted (17.10) Example is the synthesis of p-cresol
35 16.3 Alkylation of Aromatic Rings: The Friedel–Crafts Reaction
Alkylation: The attachment of an alkyl group to a benzene ring. Carbocation R+ is the electrophile
The catalyst is Aluminum chloride (or CuCl3) which promotes the formation of the carbocation
36 16.3 Alkylation of Aromatic Rings: The Friedel–Crafts Reaction
Mechanism: (Where R = 2-chloropropane) Cl AlCl AlCl - + 3 4
AlCl - H 4 - AlCl4
+ HCl + AlCl3
37 Limitations of the Friedel-Crafts Alkylation
Only alkyl halides can be used (F, Cl, I, Br) Aryl halides and vinylic halides do not react (their carbocations are too hard to form)
Will not work with rings containing an amino group substituent or a strongly electron-withdrawing group Often difficult to stop after a single substitution. Occasional skeletal rearrangement of alkyl group forming a mixture of products
38 16.4 Acylation of Aromatic Rings
Reaction of an acid chloride (RCOCl) and an
aromatic ring in the presence of AlCl3 introduces acyl group, COR
Benzene with acetyl chloride yields acetophenone
39 Mechanism of Friedel-Crafts Acylation
Similar to alkylation An acyl cation does not rearrange No multiple substitutions
40 16.5 Substituent Effects in Aromatic Rings A substituent already present on a benzene ring has two effects:
1. Reactivity of the ring.
Some substituents activate the ring and make it more reactive than benzene. (Reactivity increases )
Phenyl, -CH3, -NHCOCH3, -OCH3, -OH, -NH2 (O, P)
Some substituents deactivate the ring and make it less reactive than benzene. (Reactivity increases ) + -N R3, -NO2, -CN, -SO3H, carbonyl (M) Halogens, Hydrogens (O,P)
41 16.5 Substituent Effects in Aromatic Rings A substituent already present on a benzene ring has two effects:
2. Orientation of the reaction. The three possible disubstituted products - ortho, para and meta - are not formed in equal amounts. The substituent already on the ring determines the position of the second substituent (see labels on 1). Substituents are classified into three groups; ortho-para directing activators ortho-para directing deactivators meta directing deactivators Note: there are no meta directing activators Inductive and resonance effects control the reactivity and orientation in electrophilic aromatic substitutions.
42 Inductive Effects
Controlled by electronegativity and the polarity of bonds in functional groups
Halogens, C=O, CN, and NO2 withdraw electrons through s bond connected to ring - δ- δ+ δ δ+
Alkyl groups donate electrons
43 Resonance Effects – Electron Withdrawal & Donation The withdrawal or donation of electrons through bond due to the overlap of the p orbital on the substituent with a p orbital on the aromatic ring. Carbonyl, cyano, and nitro substituents withdraw electrons from the aromatic ring through resonance. Halogen, hydroxyl alkoxy (-OR) and amino substituents donate electrons to the ring.
44 Summary Table: Effect of Substituents in Aromatic Substitution (Table 16.2)
45 Problems:
1. Devise the synthesis for each of the following, starting from benzene: a. m-bromobenzenesulfonic acid
Hint: Since meta product, introduce the meta- directing substituent first
46 Problems:
1. Devise the synthesis for each of the following, starting from benzene: b. p-nitrotoluene
The methyl substituent is ortho, para-directing; the two isomers obtained in the final step would have to be separated. Usually the para isomer, in which the two substituents are furthest apart, predominates.
47 Problems:
2. Is it possible to prepare m- bromochlorobenzene by two successive electrophilic aromatic substitutions? Explain.
48 16.7 Trisubstituted Benzenes: Additivity of Effects
If the directing effects of the two groups are the same, the result is additive
49 Substituents with Opposite Effects
If the directing effects of two groups oppose each other, the more powerful activating group decides the principal outcome Usually gives mixtures of products
-CH3, -OH both OP directors -OH stronger activating group
50 Meta-Disubstituted Compounds Are Unreactive Between the Substituents Meta: The reaction site is too hindered
Ortho: To make aromatic rings with three adjacent substituents, it is best to start with an ortho-disubstituted compound
51 Problems
1. For a one step synthesis of 3-bromo-5-nitrobenzoic acid, which is a better starting material, 3-bromobenzoic acid or 3- nitrobenzoic acid? Why? 3-nitrobenzoic acid is better because both substituents are meta-directing:
52 Problems
2. Show how 3,5-dinitrocholorobenzene can be prepared starting from a disubstituted benzene.
53 Problems
3. Devise a synthesis for the following using toluene as the starting material.
CH3 CH3 CH3 Cl HONO2 Cl2
H+ FeCl3
NO2 NO2 If the chlorination were performed first, a considerable portion of product would have the chlorine para to the methyl group. Also, note that in the second step, both substituents direct the
chlorine to the desired position (CH3 is o, p-directing, NO2 is m-directing).
54 16.8 Nucleophilic Aromatic Substitution
Aryl halides are inert to both SN1 and SN2 conditions;
SN1 : Unfavorable dissociation of the aryl halide and the aryl cation is unstable.
SN2: Halo-substituted carbon atom is sterically shielded from back-side attack by the aromatic ring. Nucleophilic Aromatic Substitution Reaction: Addition/elimination to activated aryl halide
55 16.8 Nucleophilic Aromatic Substitution
The reaction occurs in two steps and involves a resonance- stabilized carbanion intermediate. The addition/elimination mechanism.
Cl OH Cl OH + Cl- + OH- NO NO 2 NO2 2 carbanion intermediate
Nucleophilic aromatic substitution occurs only if the aromatic ring has an electron-withdrawing group in the ortho or para position relative to the halogen where the anion intermediate is stabilized through resonance. The meta position does not provide this stabilization.
56 16.8 Nucleophilic Aromatic Substitution Differences between electrophilic and nucleophilic aromatic substitutions: Electrophilic substitutions are favored by electron donating substituents, which stabilize the carbocation intermediate. Nucleophilic substitutions are favored by electron withdrawing substituents, which stabilize the carbanion intermediate. The electron withdrawing groups that deactivate rings for electrophilic substitution (NO2, carbonyl, cyano, etc.), activate them for nucleophilic substitution. These groups are meta directors in electrophilic substitution, but ortho, para directors in nucleophilic substitution.
57 16.9 Benzyne
The benyne intermediate is highly reactive and the triple bond is very weak. Nucleophilic aromatic substitution by benzyne intermediate.
Mechanism: At high temperatures, pressures and a strong base, aryl halides without electron-withdrawing groups can be converted to phenols. This reaction occurs by an elimination/addition reaction that involves a benzyne intermediate. - Cl OH OH H - HCl H2O elimination addition
chlorobenzene phenol benzyne 58 16.10 Oxidation of Aromatic Compounds
The benzene ring cannot be oxidized, but the alkyl side chains can Many of the reactions happen at the benzylic position.
Reactions occur with 1º, 2º but not 3º, alkyl side chains. A mixture of products may be formed.
59 16.10 Oxidation of Aromatic Compounds
Alkyl side chains can be oxidized to CO2H by strong reagents such as KMnO4 and Na2Cr2O7 if they have a C-H next to the ring Converts an alkylbenzene into a benzoic acid
KMnO4 COOH CH3 H2O
H KMnO4 C CH2CH2CH3 COOH
H H2O
60 16.10 Oxidation of Aromatic Compounds
CH3 KMnO4 C CH NO Reaction CH3 3 KMnOH O 4 CH 2 NO Reaction C 3 CH3 H2O CH CH3 CH3 3 KMnO4 HOOC C CH H C C CH CH3 3 3 CH3 3 KMnOH O 4 2 CH3 CH H C CCH3 CH HOOC C 3 3 3 COOH CH3 H O 2 CH3 CH3 COOH CH3
61 Bromination of Alkylbenzene Side Chains Reactions occur at the benzylic position and do not give a mixture of products.
(NBS)
62 Comparing Bromination reactions
NBS, (PhCO2)2, CCl4
CH2CH2CH3 Br2,
Br2, FeBr3
63 16.11 Reduction of Aromatic Compounds Aromatic rings are inert to catalytic hydrogenation under conditions that reduce alkene double bonds Can selectively reduce an alkene double bond in the presence of an aromatic ring
64 16.11 Reduction of Aromatic Compounds An aromatic ring can be hydrogenated under the conditions of a Pt catalyst with hydrogen gas at very high pressures or use a powerful catalyst such as rhodium on carbon. The aromatic ring is reduced to a cyclohexane.
CH3 H2, Pt, EtOH
2000 psi, 25oC CH3
65 Reduction of Aryl Alkyl Ketones
The aromatic ring activates a neighboring carbonyl group. The reaction is specific for alkyl aryl ketones; dialkyl ketones are not affected. Ketone is converted into an alkylbenzene by catalytic hydrogenation over Pd catalyst
66 Brief Review of Organic Reactions & Mechanisms For Chapters 6-16 Look over this review, It is a good summary for what you will need for this semester. I suggest writing a reaction summary for you to review.
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