Transcript Organic Chemistry - City University of New York
Heterocyclic Aromatics
Heterocyclic compound:
A compound that contains more than one kind of atom in a ring.
•
In organic chemistry, the term refers to a ring with one or more atoms that differ from carbon.
Pyridine and pyrimidine are heterocyclic analogs of benzene; each is aromatic.
4 4 3 5 3 N 5 2 6 1 N •• Pyridine 6 2 1 N •• Pyrimidine
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Database for unknown compounds
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Pyridine
• • •
The nitrogen atom of pyridine is
sp
2 hybridized.
The unshared pair of electrons lies in an
sp
2 hybrid orbital and is not a part of the six pi electrons of the aromatic system (the aromatic sextet).
Resonance energy of pyridine is134 kJ (32 kcal)/mol.
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Furan and Pyrrole
• • • •
The oxygen atom of furan is
sp
2 hybridized.
one unshared pairs of electrons on oxygen lies in an unhybridized
2p
orbital and is a part of the aromatic sextet.
The other unshared pair lies in an
sp
2 hybrid orbital and is not a part of the aromatic system.
The resonance energy of furan is 67 kJ (16 kcal)/mol.
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Other Heterocyclics
N Indole H N N N N Purine H CH 2 CH 2 NH 2 HO N H Serotonin (a neurotransmitter) H 3 C N O N CH 3 O N CH 3 Caffeine N
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Aromatic Hydrocarbon Ions
Any neutral, monocyclic, unsaturated hydrocarbon with an odd number of carbons must have at least one CH 2 cannot be aromatic.
group and, therefore, CH 2 CH 2 Cycloprop ene Cyclop entadien e CH 2 Cycloh eptatriene
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Cyclopropene, for example, has the correct number of pi electrons to be aromatic, 4(0) + 2 = 2, but does not have a closed loop of 2
p
orbitals.
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Cyclopropenyl Cation
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If, however, the CH 2 group of cyclopropene is transformed into a CH + group in which carbon is
sp
2 hybridized and has a vacant 2
p
orbital, the overlap of orbitals is continuous and the cation is aromatic.
H H H + + H H H H H + H Cycloprop enyl cation represented as a h yb rid of three equ ivalen t contributin g s tru ctures
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Cyclopropenyl Cation
•
When 3-chlorocyclopropene is treated with SbCl 5 , it forms a stable salt.
H Cl 3-Chloro cyclopropene + Sb Cl 5 Antimony(V) chloride (a Lewis acid) + H Sb Cl 6 Cyclopropenyl hexachloroantimonate
•
This chemical behavior is to be contrasted with that of 5-chloro-1,3-cyclopentadiene, which cannot be made to form a stable salt.
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Cyclopentadienyl Cation
H Cl 5-Chloro-1,3 cyclopentadiene + A gBF 4 + H BF 4 + Ag Cl Cyclopentadienyl tetrafluoroborate
• •
If planar cyclopentadienyl cation were to exist, it would have 4 pi electrons and be antiaromatic.
Note that we can draw five equivalent contributing structures for the cyclopentadienyl cation. Yet this cation is not aromatic because it has only 4 pi electrons.
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Cyclopentadienyl Anion, C
5
H
5 -
To convert cyclopentadiene to an aromatic ion, it is necessary to convert the CH 2 group to a CH group in which carbon becomes
sp
2 hybridized and has 2 electrons in its unhybridized 2
p
orbital.
H • H • • • H H H th e origin of th e 6 pi electrons in the cyclopen tadienyl anion H H H H : H H H H H Cyclopentad ienyl anion (aromatic) H n = 1
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Cyclopentadienyl Anion, C
5
H
5 -
•
As seen in the Frost circle, the six pi electrons of cyclopentadienyl anion occupy the
p
1 ,
p
2 , and
p
3 molecular orbitals, all of which are bonding.
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Cyclopentadienyl Anion, C
5
H
5 -
The p
K
a
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of cyclopentadiene is 16.
In aqueous NaOH, it is in equilibrium with its sodium salt.
H H CH 2 p
K
a 16.0
+ NaOH H H : H Na + + H 2 O p
K
a 15.7
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It is converted completely to its anion by very strong bases such as NaNH 2 , NaH, and LDA.
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Cycloheptatrienyl Cation, C
7
H
7 +
Cycloheptatriene forms an aromatic cation by conversion of its CH 2 its
sp
2 group to a CH carbon having a vacant 2
p
+ group with orbital.
H H H H H H + H + H H H H Cyclohep tatrien yl cation (Tropylium ion ) (aromatic) H H H
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Nomenclature
Monosubstituted alkylbenzenes are named as derivatives of benzene.
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Many common names are retained.
Toluene OH Ethylbenzene N H 2 CHO Cumene COOH Styrene OCH 3 Phenol Aniline Benzaldehyde Benzoic acid Anisole
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Nomenclature
Benzyl and phenyl groups Benzene Phenyl group, Ph O 1-Phenyl-1-pentanone H 3 CO CH 3 Toluene O CH 2 Benzyl group, Bn 4-(3-Methoxyphenyl) 2-butanone Ph (Z)-2-Phenyl 2-butene
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Disubstituted Benzenes
Locate two groups by numbers or by the locators
ortho
(1,2-),
meta
(1,3-), and
para
(1,4-).
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Where one group imparts a special name, name the compound as a derivative of that molecule.
CH 3 NH 2 COOH NO 2 CH 3 Cl Br 4-Bromotolu ene (
p
-Bromotoluen e) 3-Chloroan iline (
m
-Chloroan iline) 2-N itrobenzoic acid (
o
-N itrob enzoic acid ) CH
m
-Xylene 3
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Disubstituted Benzenes
•
Where neither group imparts a special name, locate the groups and list them in alphabetical order.
CH 2 CH 3 NO 2 4 2 Br 3 1 2 1 Cl 1-Chloro-4-ethylben zene (
p
-Ch loroethylbenzen e) 1-Bromo-2-nitrob enzene (
o
-Bromon itroben zene)
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Polysubstituted Derivatives
• •
If one group imparts a special name, name the molecule as a derivative of that compound.
If no group imparts a special name, list them in alphabetical order, giving them the lowest set of numbers.
CH 3 1 2 N O 2 Br 6 OH 1 2 Br N O 2 4 Cl 4 4-Chloro-2-nitro toluene 4 Br 2,4,6-Tribromo phenol 2 1 Br CH 2 CH 3 2-Bromo-1-ethyl-4 nitrobenzene
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Phenols
The functional group of a phenol is an -OH group bonded to a benzene ring.
OH OH OH OH OH CH 3 Phenol 3-Methylphenol (
m-
Cresol) 1,2-Benzenediol (Catechol) OH 1,4-Benzenediol (Hydroquinone)
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Acidity of Phenols
Phenols are significantly more acidic than alcohols.
OH + H 2 O CH 3 CH 2 OH + H 2 O O + H 3 O + CH 3 CH 2 O + H 3 O + p
K
a = 9.95
p
K
a = 15.9
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Acidity of Phenols
Separation of water insoluble phenols from water-insoluble alcohols.
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Acidity of Phenols (Resonance)
•
The greater acidity of phenols compared with alcohols is due to the greater stability of the phenoxide ion relative to an alkoxide ion.
H These 2 Kekulé s tru ctures are equivalent These th ree con trib utin g s tru ctures delocalize th e negative charge on to carb on atoms of th e rin g
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Phenol Subsitituents (Inductive Effect)
Alkyl and halogen substituents effect acidities by inductive effects:
• •
Alkyl groups are electron-releasing.
Halogens are electron-withdrawing.
OH OH OH OH OH Phen ol p
K
a 9.95
m-
p
K
Cres ol a CH 3 10.01
CH 3
p-
Cres ol p
K
a 10.17
Cl Cl
m-
Chlorop henol p
K
a 8.85
p-
Chororophen ol p
K
a 9.18
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Phenol Subsitituents(Resonance, Inductiion)
•
Nitro groups increase the acidity of phenols by both an electron-withdrawing inductive effect and a resonance effect.
OH OH OH Ph e no l p
K
a 9.95
NO 2
m -
N itrop h e n ol p
K
a 8.28
NO 2
p-
N itrop h e n ol p
K
a 7.15
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Acidity of Phenols
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Part of the acid-strengthening effect of -NO 2 its electron-withdrawing inductive effect.
is due to In addition, -NO 2 substituents in the ortho and para positions help to delocalize the negative charge.
O O delocalization of negative charge onto oxygen further increases the resonance stabilization of phenoxide ion N + N + O O O O
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Synthesis : Alkyl-Aryl Ethers
Alkyl-aryl ethers can be prepared by the Williamson ether synthesis:
• •
but only using phenoxide salts and haloalkanes.
haloarenes cannot be used because they are unreactive to S N 2 reactions.
X + RO N a + no reaction
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Synthesis : Alkyl-Aryl Ethers
Phenol OH + CH 2 = CHCH 2 Cl N aOH, H 2 O, CH 2 Cl 2 3-Chloropropene (Allyl chloride) OCH 2 CH= CH 2 Phenyl 2-propenyl ether (Allyl phenyl ether) Phenol OH + O CH 3 OSOCH 3 O D imethyl sulfate N aOH, H 2 O, CH 2 Cl 2 OCH 3 + N a 2 SO 4 Methyl phenyl ether (Anisole)
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Synthesis : Kolbe Carboxylation
Phenoxide ions react with carbon dioxide to give a carboxylate salt.
OH Phenol NaOH H 2 O O Na + Sodiu m phen oxid e CO 2 H 2 O OH O CO Na + Sodium salicylate HCl H 2 O OH O COH S alicylic acid
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Mechanism: Kolbe Carboxylation
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The mechanism begins by nucleophilic addition of the phenoxide ion to a carbonyl group of CO 2 .
O Sodium phenoxide + O C O (1) O O C O H keto-enol tautomerism (2) OH O C O A cyclohexadienone intermediate structure Salicylate anion Go back to aromatic
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Synthesis: Quinones
Because of the presence of the electron-donating -OH group, phenols are susceptible to oxidation by a variety of strong oxidizing agents.
OH O H 2 Cr O 4 Phenol O 1,4-Benzoquinone (
p-
Quinone)
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Quinones
OH OH 1,2-Benzen ediol (Catechol) O K 2 Cr 2 O 7 O H 2 SO 4 1,2-Benzoquin on e (
o
-Qu inone) OH O K 2 Cr 2 O 7 H 2 SO 4 OH 1,4-Ben zenediol (Hydroquin on e) O 1,4-Benzoquin on e (
p
-Qu inone)
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Quinones
Readily reduced to hydroquinones.
O OH Na 2 S 2 O 4 , H 2 O (reduction ) O 1,4-Benzoqu inone (
p
-Qu inone) OH 1,4-Benzen ediol (Hydroq uinone)
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Coenzyme Q
Coenzyme Q is a carrier of electrons in the respiratory chain.
O OH MeO MeO reduction MeO O Coenzyme Q (oxid ized form) n H oxidation MeO OH Coenzyme Q (redu ced form) n H
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Benzylic Oxidation
Benzene is unaffected by strong oxidizing agents such as H 2 CrO 4
•
and KMnO 4 Halogen and nitro substituents are also unaffected by these reagents.
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An alkyl group with at least one hydrogen on its benzylic carbon is oxidized to a carboxyl group.
CH 3 O 2 N Cl 2-Chloro-4-nitrotoluene COOH H 2 Cr O 4 O 2 N Cl 2-Chloro-4-nitrobenzoic acid
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Benzylic Oxidation
•
If there is more than one alkyl group on the benzene ring, each is oxidized to a -COOH group.
H 3 C CH 3 1,4-Dimethylbenzene (
p-
xylene) K 2 Cr 2 O 7 H 2 SO 4 O HOC O COH 1,4-Benzenedicarboxylic acid (terephthalic acid)
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Benzylic Chlorination
Chlorination and bromination occur by a radical chain mechanism.
CH 3 h eat or ligh t CH 2 Cl + Cl 2 + HCl Toluen e Benzyl ch loride Ethylbenzen e Br NBS ( PhCO 2 ) 2 , CCl 4 1-Bromo-1-p henylethan e (racemic)
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Mechanism: Benzylic Reactions
Benzylic radicals (and cations also) are easily formed because of the resonance stabilization of these intermediates.
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The benzyl radical is a hybrid of five contributing structures.
C C C C C
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Benzylic Halogenation
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Benzylic bromination is highly regioselective.
Br Eth ylb enzene NBS (PhCO 2 ) 2 , CCl 4 1-Bromo-1-phen yleth ane (the only product formed )
•
Benzylic chlorination is less regioselective.
Cl heat or ligh t + Cl 2 + Eth ylb enzene 1-Chloro-1 p henylethan e (90%) Cl 1-Ch loro-2 ph enylethan e (10%)
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Hydrogenolysis
Hydrogenolysis:
•
Cleavage of a single bond by H Benzylic ethers are unique in that they are cleaved under conditions of catalytic hydrogenation.
2 this bond is cleaved O Benzyl butyl ether + H 2 Pd/ C OH + Me 1-Butanol Toluene
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Synthesis, Protecting Group: Benzyl Ethers
The value of benzyl ethers is as protecting groups for the OH groups of alcohols and phenols.
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To carry out hydroboration/oxidation of this alkene, the phenolic -OH must first be protected; it is acidic enough to react with BH 3 and destroy the reagent.
OH 1 . ClCH 2 Ph Et 3 N 2-(2-Propen yl)p henol (2-A llylp henol) O Ph 2 . BH 3 • THF 3 . H 2 O 2 / NaOH O Ph OH H 2 Pd/ C OH OH