University:
Rutgers University Newark
Course:
CHEM 336 | Organic Chemistry ||
Academic year:

2024
Views:

117

Pages:

90
Author:

Mahitab S.

CHAPTER 21 BENZENE AND THE CONCEPT OF AROMATICITY ©2018 Cengage Learning. All Rights Reserved. Chapter Outline • • • • • (21.1) (21.2) (21.3) (21.4) (21.5) The structure of benzene The concept of aromaticity Nomenclature Phenols (Ar-OH) Reactions at a benzylic position (Ar-CH2-R) ©2018 Cengage Learning. All Rights Reserved. Aromatic Compounds • Term used initially to (1) classify benzene and its derivatives and to (2) classify any compound that meets the Hückel criteria for aromaticity • Refers now to the fact that these compounds are (1) highly unsaturated and (2) unexpectedly stable toward reagents that attack alkenes and alkynes • Arene - Term used to describe aromatic hydrocarbons, by analogy with alkane, alkene, and alkyne • Benzene is the parent arene • Aryl group - Group derived by removal of an H from an arene, symbol - Ar– ©2018 Cengage Learning. All Rights Reserved. Benzene's molecule Highly unsaturated Building a Model for the Structure of Benzene Evidence Available in the Mid-19th Century • Benzene’s molecular formula denoted that it is highly unsaturated • Did NOT show the chemical properties of alkenes • Characteristic reaction is substitution rather than addition • In the reaction below, only one bromobenzene is formed • Reaction helps conclude that all six hydrogens of benzene must be equivalent • When bromobenzene is treated with bromine in the presence of FeCl3 as a catalyst, three isomeric dibromobenzenes are formed ©2018 Cengage Learning. All Rights Reserved. Kekulé’s Model of Benzene ED • In 1865, Kekulé proposed that benzene consisted of a six-membered ring with one H bonded to each C • Proposed in 1872 that the ring contains three double bonds that shift back and forth so rapidly that the two forms cannot be separated • Interconversion was regarded as an equilibrium, each structure in which has become known as a Kekulé structure • Did NOT account for the unusual chemical behavior of benzene ©2018 Cengage Learning. All Rights Reserved. Molecular Orbital Model of Benzene • Carbon skeleton forms a regular hexagon with C—C —C and H—C—C bond angles of 120° • Each C forms σ bonds to two adjacent carbons by overlap of sp2-sp2 hybrid orbitals and one σ bond to H by overlap of sp2-1s orbitals • Each C has a single unhybridized 2p orbital perpendicular to the plane of the ring and contains one electron ©2018 Cengage Learning. All Rights Reserved. Figure 21.2 - Molecular Orbital Representation of the p Bonding in Benzene • According to molecular orbital theory, the combination of six parallel 2p atomic orbitals gives a set of six π MOs, three π-bonding MOs, and three πantibonding MOs ©2018 Cengage Learning. All Rights Reserved. Figure 21.3 - Orbitals for the π System of Benzene ©2018 Cengage Learning. All Rights Reserved. Resonance Model of Benzene • Benzene is represented as a hybrid of two equivalent contributing (Kekulé) structures • Each makes an equal contribution to the hybrid • C—C bonds are neither double nor single bonds but something intermediate • Actual structure is a superposition of both • Comparing the heats of hydrogenation of cyclohexene and benzene to estimate benzene’s resonance energy • Resonance energy: Difference in energy between a resonance hybrid and the most stable of its hypothetical contributing structures in which electrons are localized on particular atoms and in particular bonds ©2018 Cengage Learning. All Rights Reserved. hexone Cycolo cyclohexane whenusing Transitionmetal Ni inpresenceof Hydrogen H Resonance Model of Benzene • Cyclohexene is readily reduced to cyclohexane by hydrogen in the presence of a transition metal catalyst Nil • Benzene is reduced very slowly under these conditions to cyclohexane • Reduced more rapidly when heated and under a pressure of several hundred atmospheres of hydrogen ©2018 Cengage Learning. All Rights Reserved. Benzene reducedmorerapidlyunderpressureofheatedseveralhydrogen Figure 21.5 - Resonance Energy of Benzene ResonanceofBenzene heatsofHydrogenationofcyclohexanebenzeneand1,315 cycolohexatrian I Tokailmol 28kcalmoi 14kcalmy Resonance energy of benzene as determined by comparison of the heats of hydrogenation of cyclohexene, benzene, and the hypothetical compound 1,3,5-cyclohexatriene ©2018 Cengage Learning. All Rights Reserved. Example • The heats of hydrogenation of cyclohexene, 1,3cyclohexadiene, and benzene are −28, −55, and −49 kcal/mol, respectively • To what amount is benzene stabilized when compared to a hypothetical 1,3,5-cyclohexatriene? 1. 6 kcal/mol Theheathydrogenationofcycolohexene 28kcalnot 13Cyclohexadiene 55kcalmil 2. 21 kcal/mol b 3. 27 kcal/mol cyclohexane almost twiceof Benzene 49kcalImo 4. 35 kcal/mol Kallman 84kcalmy 28 1 3 cycolohexatriene 5. 49 kcal/mol 1,315 is by 497 184 Hencebenzene stabilized ©2018 Cengage Learning. All Rights Reserved. 35kcal'm Hückel Criteria for Aromaticity • Proposed by Erich Hückel based on molecular orbital (MO) energy calculations • To be aromatic, a compound must: • (1) Be cyclic • (2) Have one 2p orbital on each atom of the ring • (3) Be planar or nearly planar so that there is continuous or nearly continuous overlap of all 2p orbitals of the ring • (4) Have a closed loop of (4n + 2)π electrons in the cyclic arrangement of 2p orbitals ©2018 Cengage Learning. All Rights Reserved. Frost Circle • Graphic method for determining the relative energies of the π MOs for planar, fully conjugated, monocyclic compounds • Steps involved in construction • (1) Draw a circle and then (2) inscribe in it a polygon of the same number of sides as the ring in question, with one of its vertices being at the bottom of the circle • Relative energies of the MOs in the ring are given by points where the vertices of the polygon touch the circle • MOs below the horizontal line through the center of the ring are bonding MOs • MOs on the horizontal line are nonbonding MOs • MOs above the horizontal line are antibonding MOs ©2018 Cengage Learning. All Rights Reserved. Figure 21.6 - Frost circles • Frost circles showing the number and relative energies of the π MOs for planar, fully conjugated four-, five-, and six-membered rings ©2018 Cengage Learning. All Rights Reserved. Aromatic Hydrocarbons - Annulene • Cyclic hydrocarbon with a continuous alternation of single and double bonds • Cyclobutadiene, benzene, and cyclooctatetraene are members of annulene family • [14]Annulene and [18]annulene are aromatic according to Hückel’s criteria • Resonance energy of [18]annulene - 418 kJ (100 kcal)/mol) ©2018 Cengage Learning. All Rights Reserved. Aromatic Hydrocarbons - Annulene • An induced ring current occurs in aromatic molecules, which causes protons on benzene and other arenes to deshield and appear far downfield (higher shift) • Characteristic of all compounds that meet the Hückel criteria for aromaticity • Predicts that: • H atoms outside the ring should come into resonance at higher shift • H atom inside the ring should come into resonance farther upfield (lower shift) ©2018 Cengage Learning. All Rights Reserved. Aromatic Hydrocarbons - Annulene • [10]annulene is found to be nonaromatic even though it should be aromatic according to Hückel’s criteria • (1) Is cyclic and (2) has one 2p orbital on each carbon of the ring and (3) 10 electrons in its π system • (4) Nonbonded interactions between the two hydrogens that point inward toward the center of the ring force the ring into a nonplanar conformation in which overlap of ten 2p orbitals is not continuous Hackel's criteria 1 cyclic 2 one 2porbitaloneachcarbon ofthering ©2018 Cengage Learning. All Rights Reserved. 3 10electronsin its ti system Aromatic Hydrocarbons - Annulene • The ring of [10]annulene can assume a conformation close enough to planar that it becomes aromatic if the two hydrogen atoms facing inward toward the center of the ring are replaced by a CH2 group (bridged [10]annulene) InRing 2hydrogenfacing inwardtowardthecenter cHzgroup ©2018 Cengage Learning. All Rights Reserved. Antiaromatic Hydrocarbons • Monocyclic, planar molecules with 4n π electrons (4, 8, 12, 16, 20, . . .) are especially unstable relative to an open-chain fully conjugated hydrocarbon of the same number of carbon atoms Cycolobutadiene 1 4T electrons 2 24 electrons • Cyclobutadiene fill T • (1) Has 4 π electrons • (2) In the ground-state electron configuration, two π electrons fill the π1-bonding MO • The third and fourth π electrons lie in the π2and π3-nonbonding MOs ©2018 Cengage Learning. All Rights Reserved. bondingM Antiaromatic Hydrocarbons • Cyclooctatetraene • (1) Shows reactions typical of alkenes and has 8 π electrons • (2) X-ray studies show that the most stable conformation is a nonplanar tub conformation • Although overlap of 2p orbitals occurs to form double bonds, there is almost no overlap between 2p orbitals at the ends of carbon-carbon single bonds since they are not parallel • π system is not conjugated despite having continuous sp2 hybridized carbon atoms Nonpolarconfirmation isthemoststabletab ©2018 Cengage Learning. All Rights Reserved. Figure 21.8 - Molecular Orbital Energy Diagram for a Planar Conformation of Cyclooctatetraene ©2018 Cengage Learning. All Rights Reserved. Heterocyclic Aromatic Compounds • Compounds containing more than one kind of atom in a ring (N, S, O) • Pyridine and pyrimidine are heterocyclic analogs of benzene • Five-membered ring heterocyclic compounds furan, thiophene, sp pyrrole, and imidazole are also aromatic ©2018 Cengage Learning. All Rights Reserved. Figure 21.10 - Pyridine • Nitrogen atom in pyridine is sp2 hybridized • The unshared pair of electrons occupies an sp2 orbital and is not a part of the six π electrons of the aromatic system (the aromatic sextet) • Resonance energy is 134 kJ (32 kcal)/mol ©2018 Cengage Learning. All Rights Reserved. Figure 21.11 - Furan and Pyrrole • The heteroatom is sp2 hybridized • In furan, one unshared pair of electrons of heteroatom lies in an unhybridized 2p orbital and is a part of the π system, other unshared pair lies in an sp2 hybrid orbital perpendicular to the 2p orbitals and is not a part of the π system • In pyrrole, the unshared pair of electrons on nitrogen is part of the π system • Resonance energy • Furan - 67 kJ (16 kcal)/mol • Pyrrole - 88 kJ (21 kcal)/mol ©2018 Cengage Learning. All Rights Reserved. Heterocyclic Aromatic Compounds In Biology • Indole contains a pyrrole ring fused with a benzene ring • Derivatives include the essential amino acid ʟ-tryptophan and the neurotransmitter serotonin • Purine contains a six-membered pyrimidine ring fused with a five-membered imidazole ring • Caffeine is a trimethyl derivative of an oxidized purine • Compounds derived from purine and pyrimidine are building blocks of DNA and RNA ©2018 Cengage Learning. All Rights Reserved. Aromatic Hydrocarbon Ions • Any neutral monocyclic unsaturated hydrocarbon with an odd number of carbons in the ring must have at least one CH2 group in the ring and thus cannot be aromatic • Cyclopropene has the correct number of π electrons to be aromatic, 4(0) + 2 = 2, but has no closed loop of 2p orbitals • If the CH2 group becomes a CH+ group in which the C atom is sp2 hybridized and has a vacant 2p orbital, then the overlap of orbitals is continuous and the cyclopropenyl cation will be aromatic according to MO theory ©2018 Cengage Learning. All Rights Reserved. Aromatic Hydrocarbon Ions • Example: 3-chlorocyclopropene reacts readily with antimony(V) chloride to form a stable salt ©2018 Cengage Learning. All Rights Reserved. Aromatic Hydrocarbon Ions • Chemical behavior of 3-chlorocyclopropene is to be contrasted with that of 5-chloro-1,3-cyclopentadiene, which cannot be made to form a stable salt 21 345 • A cyclic, planar, conjugated cyclopentadienyl cation has four π electrons and would be antiaromatic if synthesized • Five equivalent contributing structures can be drawn for the cyclopentadienyl cation, but it is not aromatic since it has only 4n π electrons rather than (4n + 2) π electrons ©2018 Cengage Learning. All Rights Reserved. Cyclopentadiene • To form an aromatic ion from cyclopentadiene, it is necessary to convert the CH2 group to a CH– group in which carbon becomes sp2 hybridized and has two electrons in its unhybridized 2p orbital • Resulting cyclopentadienyl anion is aromatic • pKa value is 16 • When treated with aqueous NaOH, an equilibrium is established in which some of the hydrocarbon is converted to its aromatic anion (next slide) ©2018 Cengage Learning. All Rights Reserved. Cyclopentadiene • Converted completely to its anion by treatment with sodium amide ©2018 Cengage Learning. All Rights Reserved. Cycloheptatriene • Forms an aromatic cation, cycloheptatrienyl cation, by conversion of its CH2 group to a CH+ group with its sp2 carbon having a vacant 2p orbital • Cycloheptatrienyl cation has six π electrons in seven 2p atomic orbitals ©2018 Cengage Learning. All Rights Reserved. Example 21.3 - MO Energy Diagrams I • Construct an MO energy diagram for the cyclopentadienyl anion and describe its ground-state electron configuration • Solution • Refer to the Frost circle shown in Figure 21.6 for a planar, fully conjugated five-membered ring • The six π electrons occupy the π1, π2, and π3 molecular orbitals, all of which are bonding MOs ©2018 Cengage Learning. All Rights Reserved. Example • Which of the following is not a condition for aromaticity? 1. 2. 3. 4. 5. The molecule must be a six-membered ring The molecule must have planar or nearly planar π system The molecule must have (4n + 2) π electrons in the ring The molecule must show the effects of ring currents in its NMR spectrum Each atom in the ring must contribute one p orbital to the system ©2018 Cengage Learning. All Rights Reserved. Example • Which process would convert 1,3,5-cycloheptatriene into an aromatic substance? 1. 2. 3. 4. 5. Addition of one electron Removal of one electron Abstraction of a hydrogen atom Abstraction of a proton Abstraction of a hydride ©2018 Cengage Learning. All Rights Reserved. Example • Which of the following compounds is not aromatic? 1. 2. 3. DO Ogp2 4. 5. ©2018 Cengage Learning. All Rights Reserved. Aromatic cyclic B Example • Which of the following compounds is antiaromatic? 1. 2. 4. 3. 5. ©2018 Cengage Learning. All Rights Reserved. Example • How many π electrons are in imidazole? 1. 2. 3. 4. 5. 0 2 4 6 8 The number of 4n t 2 ti e 6 6 4n 4 h 44 1 So it's Aromatic ©2018 Cengage Learning. All Rights Reserved. Example • What is the correct ranking of the pKa values for the following carbon acids? 1. 2. 3. 4. 5. A< B< C A< C< B B< A< C B< C< A C< A< B ©2018 Cengage Learning. All Rights Reserved. Example • Which of the following is the best characterization of the cyclopentadienyl cation? 1. 2. 3. 4. 5. Hyperconjugated Antiaromatic Vinylic Allylic Benzylic ©2018 Cengage Learning. All Rights Reserved. Example • The coronene shown below is planar • What is true about it? 1. 2. 3. 4. 5. It is aromatic because it has (4n + 2) π electrons It is antiaromatic because it has (4n) π electrons It is aromatic because it has π rings each with (4n + 2) π electrons It is antiaromatic because Hückel rule applies only to single rings It is nonaromatic ©2018 Cengage Learning. All Rights Reserved. Nomenclature - Monosubstituted Alkylbenzenes • Named as derivatives of benzene • Many common names are retained by IUPAC • Examples - Toluene (for methylbenzene), cumene (for isopropylbenzene), and styrene (for vinylbenzene) ©2018 Cengage Learning. All Rights Reserved. Nomenclature - Monosubstituted Alkylbenzenes • Phenyl group: Derived by loss of an H atom from benzene is a phenyl group, abbreviation -Ph • Phenyl group and its derivatives are named as substituents in molecules containing other functional groups • Benzyl group: Derived by loss of an H atom from the methyl group of toluene, abbreviation -Bn ©2018 Cengage Learning. All Rights Reserved. Nomenclature - Disubstituted Benzenes • When two substituents occur on a benzene ring, three constitutional isomers are possible • Locate the substituents by numbering the atoms of the ring or by using the locators ortho (1,2-), meta (1,3-), and para (1,4-) • When one group imparts a special name to the compound, name the compound as a derivative of that parent molecule, and the special substituent is assumed to occupy ring position number 1 I 2 1 2 3 3 4 metal para 4 bromotoulene 3choloraniline 72 ortho 2nitrobenzonic ©2018 Cengage Learning. All Rights Reserved. 1,3Dimethylbenzene Nomenclature - Disubstituted Benzenes • Where neither group imparts a special name, locate the two substituents and list them in alphabetical order before the ending -benzene • Carbon of the benzene ring with the substituent of lower alphabetical ranking is numbered C-1 para 1 cholor 4ethyl benzene ortho 1 Bromo 2 nitrobenzene ©2018 Cengage Learning. All Rights Reserved. 1,3 Dinitrobenzene Nomenclature - Polysubstituted Benzenes • When three or more substituents are present on a ring, their locations are specified by numerals • If one substituent imparts a special name, name the compound as a derivative of that parent molecule • If none of the substituents imparts a special name, number the substituents to give the smallest set of numbers and list them in alphabetical order before the ending -benzene 4choir 2 nitrotoulene 2,4,6 Tribromopheno ©2018 Cengage Learning. All Rights Reserved. 2 bromo l ethly 4 nitro benzene Nomenclature - Polysubstituted Derivatives • Polynuclear aromatic hydrocarbons (PAH) • Hydrocarbon containing two or more fused benzene rings • Examples: Naphthalene, anthracene, and phenanthrene • In numbering polynuclear aromatic hydrocarbons (PAHs), carbon atoms common to two or more rings are not numbered because they have no replaceable hydrogens ©2018 Cengage Learning. All Rights Reserved. Example 21.5 - Benzene Nomenclature • Write names for these compounds • Solution a. b. c. d. Ethyl 4-aminobenzoate (ethyl p-aminobenzoate) 3,4-Dimethoxybenzaldehyde 4-Nitrophenyl ethanoate (p-nitrophenyl acetate) 3-Phenylpropene (allyl benzene) ©2018 Cengage Learning. All Rights Reserved. Example • What is the IUPAC name of the following compound? 4 I 2 3 4bromo 3cholor 1. 2. 3. 4. 5. 4-Bromo-3-chloro-1-methylbenzene 1-Chloro-2-bromo-5-methylbenzene 1-Bromo-2-chlorotoluene 4-Bromo-3-chlorotoluene 2-Bromo-1-chlorotoluene ©2018 Cengage Learning. All Rights Reserved. Example • Which of the following names incorrectly describes the relationship between the substituents for the derivative shown below? 21 2. 3. I 5. m-xylene 1,3-Dimethylbenzene 3-Methyltoluene m-methyltoluene Ortho-xylene ©2018 Cengage Learning. All Rights Reserved. Example • What is the name of the class of compounds to which the molecule shown belongs? 1. 2. 3. 4. 5. Annulenes Heterocyclic aromatics Bicyclic compounds Polycyclic aromatic hydrocarbons Trisubstituted benzenes ©2018 Cengage Learning. All Rights Reserved. Phenols • Contain an —OH bonded to a benzene ring (Ar-OH) • Substituted phenols are named as derivatives of phenol, as benzenols, or by common names phenol z 12 3 43 3 methypheno Benzema 1,2 113benzendid 114 Benzenedi • Low-melting solids that are soluble in water ©2018 Cengage Learning. All Rights Reserved. Phenols • Medical uses • Hexylresorcinol is used as a mild antiseptic and disinfectant • Eugenol is used as a dental antiseptic and analgesic • Urushiol is the main component of the oil of poison ivy ©2018 Cengage Learning. All Rights Reserved. Acidity of Phenols • Phenols are significantly more acidic than alcohols • Acid ionization constant of phenol is 106 times larger than that of ethanol (pKa = 10) ©2018 Cengage Learning. All Rights Reserved. Acidity of Phenols pls10 • Greater acidity of phenols in comparison with alcohols is due to the greater stability of the phenoxide ion relative to an alkoxide ion • Negative charge on the phenoxide ion is delocalized by resonance, whereas there is no possibility for delocalization of charge in an alkoxide ion (only inductive stabilization) Resonance stability ©2018 Cengage Learning. All Rights Reserved. Acidity of Phenols • Affected by ring substituents through a combination of (1) induction and (2) resonance • Alkyl substituents are electron releasing toward the aromatic ring • Destabilize phenoxide ion contributing structures and reduce the acidity of substituted phenols ©2018 Cengage Learning. All Rights Reserved. Acidity of Phenols • Halogens are electron withdrawing • The more highly electronegative halogens withdraw electron density from the aromatic ring and provide greater stability to the halophenoxide ion • Both inductive and resonance effects are observed in nitrophenols • Both m-nitrophenol and p-nitrophenol are stronger acids ©2018 Cengage Learning. All Rights Reserved. Acidity of Phenols Nitrogroup ara • Acid-strengthening effect of the nitro group is greater in the metapara position than in the meta position, even though it is farther away from the —OH group • Part of the strengthening property stems from its electronwithdrawing inductive effect • Nitro substitution in the ortho or para position increases acidity (induction and resonance) • Caused by the delocalization of the negative charge of the phenoxide ion onto an oxygen of the nitro group ©2018 Cengage Learning. All Rights Reserved. Example 21.6 - Acidity of Phenols • Arrange these compounds in order of increasing acidity: 2,4-dinitrophenol, phenol, and benzyl alcohol • Solution • pKa of benzyl alcohol, a primary alcohol, is approximately 16–18 (Section 10.3) • pKa of phenol is 9.95 • Nitro groups are electron withdrawing and increase the acidity of the phenolic —OH group • In order of increasing acidity, they are as follows: ©2018 Cengage Learning. All Rights Reserved. Acid-Base Reactions of Phenols • Phenols are weak acids and react with strong bases such as NaOH to form water-soluble salts • Most phenols do not react with weaker bases such as sodium bicarbonate and do not dissolve in its aqueous solution • Carbonic acid is a stronger acid than phenol • Equilibrium for the reaction of phenol and bicarbonate ion lies far to the left ©2018 Cengage Learning. All Rights Reserved. Figure 21.14 - Separation of Water-Insoluble Phenols from Water-Insoluble Alcohols (important) ©2018 Cengage Learning. All Rights Reserved. Alkyl-Aryl Ethers (Ar-O-alkyl) • Can be prepared from a phenoxide salt and a haloalkane (Williamson ether synthesis), but NOT from a haloarene and alkoxide salt, because haloarenes are unreactive under the conditions of Williamson synthesis • Haloarenes do not undergo nucleophilic displacement by either an SN1 or SN2 mechanism Note • Examples on the next slide ThisReactiondon't other workonthe andalso electrophile direction thearomatic ©2018 Cengage Learning. All Rights Reserved. Alkyl-Aryl Ethers (Ar-O-alkyl) • Example of Williamson synthesis of alkyl-aryl ethers Hal • Synthesis of anisole illustrates the use of dimethyl sulfate as a methylating agent ©2018 Cengage Learning. All Rights Reserved. Kolbe Carboxylation • Phenoxide ions react with carbon dioxide to give a carboxylic acid salt • Phenol is dissolved in aqueous NaOH, and this solution is then saturated with CO2 under pressure to give sodium salicylate • Upon acidification of the alkaline solution, salicylic acid is isolated as a solid, mp 157–159°C ©2018 Cengage Learning. All Rights Reserved. Kolbe Carboxylation of Phenol - Mechanism • Step 1: Make a new bond between a nucleophile (arene ring) and an electrophile (key step) • Phenoxide ion reacts like an enolate anion, and the phenoxide anion attacks the carbonyl carbon • Step 2: Keto-enol tautomerism • Keto-enol tautomerism of the cyclohexadienone intermediate gives the product salicylate anion • Enol is the more stable of the two tautomers because of its aromatic character ©2018 Cengage Learning. All Rights Reserved. Oxidation of Phenols to Quinones • Phenols are susceptible to oxidation by a variety of strong oxidizing agents because of the presence of the electron-donating —OH group on the ring • Quinones can also be obtained by oxidation of 1,2-benzenediol (catechol) or 1,4benzenediol (hydroquinone) ©2018 Cengage Learning. All Rights Reserved. Quinones • Are cyclohexadienediones • o-Quinones - Contain carbonyl groups ortho to each other • p-Quinones - Contain carbonyl groups para to each other • Readily reduced to benzenediols • Example: p-quinone is readily reduced to hydroquinone by sodium dithionite in neutral or alkaline solution ©2018 Cengage Learning. All Rights Reserved. Quinones • Reversible oxidation/reduction of hydroquinones or quinones is important in many examples in both chemistry and biology • Example: Coenzyme Q (ubiquinone) is a carrier of electrons in the respiratory chain • Both the oxidized and the reduced form play vital roles in the respiratory system ©2018 Cengage Learning. All Rights Reserved. Quinones • Example: Vitamin K2 • Its deficiency causes delayed clotting time of blood • Essential to the synthesis of prothrombin in the liver • Natural form of vitamin K2 has a chain of five to eight isoprene units bonded to a 1,4-naphthoquinone ring • Menadione, a synthetic material with vitamin K activity, has only hydrogen in place of the long alkyl side chain ©2018 Cengage Learning. All Rights Reserved. Commercial Application of Quinones • Black-and-white photography • Black-and-white film is coated with an emulsion containing silver bromide or silver iodide crystals, which become activated by exposure to light • Activated silver ions are reduced in the developing stage to metallic silver by hydroquinone, which at the same time is oxidized to quinone ©2018 Cengage Learning. All Rights Reserved. Reactions at a Benzylic Position • Reactions involving alkyl side chains of aromatic compounds occur preferentially at the benzylic position • Benzylic position: An sp3 hybridized carbon bonded to a benzene ring • Occur owing to the following reasons: • Benzene ring is resistant to reaction with many reagents that normally attack alkanes • Benzylic cations and benzylic radicals are easily formed because of resonance stabilization of these intermediates ©2018 Cengage Learning. All Rights Reserved. Benzylic Oxidation • Benzene is unaffected by strong oxidizing agents such as H2CrO4 and KMnO4 • Toluene reacts with these oxidizing agents under vigorous conditions to give benzoic acid • Halogen and nitro substituents on an aromatic ring are unaffected by these oxidations ©2018 Cengage Learning. All Rights Reserved. Toluene benzonicacid Benzylic Oxidation • Side chain of tert-butylbenzene is not oxidized • If a benzylic hydrogen exists, then (1) the benzylic carbon is oxidized to a carboxyl group and (2) all other carbons of the side chain are removed as CO2 • (1) If no benzylic hydrogen exists, no oxidation of the side chain occurs • (2) If more than one alkyl side chain exists, each is oxidized to —COOH ©2018 Cengage Learning. All Rights Reserved. Benzylic Oxidation • Naphthalene is oxidized to phthalic acid by molecular oxygen in the presence of a vanadium(V) oxide (vanadium pentoxide) catalyst • Illustrates the ease of oxidation of condensed benzene rings compared with benzene ©2018 Cengage Learning. All Rights Reserved. Example 21.7 - Benzylic Oxidation • Draw a structural formula for the product of vigorous oxidation of 1,4-dimethylbenzene (p-xylene) by H2CrO4 • Solution • Both alkyl groups are oxidized to —COOH groups • The product is terephthalic acid, one of two monomers required for the synthesis of Dacron polyester and Mylar (Section 29.5B) ©2018 Cengage Learning. All Rights Reserved. Benzylic Halogenation • Chlorination and bromination of toluene ©2018 Cengage Learning. All Rights Reserved. Benzylic Halogenation • Halogenation of a larger alkyl side chain is highly regioselective • Example: Bromination of ethylbenzene • Regioselectivity is dictated by the resonance stabilization of the benzylic radical intermediate • Mechanism of radical bromination at a benzylic position is identical to that for allylic bromination ©2018 Cengage Learning. All Rights Reserved. Benzylic Halogenation • Chlorination of alkyl side chains is also highly regioselective but not to the same degree as bromination • When ethylbenzene is treated with chlorine under radical reaction conditions, products are formed in the ratio of 9:1 • Order of stability of radicals is as follows (reflects the C—H bond dissociation enthalpies (BDE) for formation of radicals) ©2018 Cengage Learning. All Rights Reserved. Hydrogenolysis of Benzyl Ethers (Bn-OR) • Benzylic ethers are cleaved under the conditions of catalytic hydrogenation as illustrated by the hydrogenolysis of benzyl hexyl ether • Hydrogenolysis: Cleavage of a single bond by H2 • Accomplished by treating a compound with H2 in the presence of a transition metal catalyst (H2, Pd/C) ©2018 Cengage Learning. All Rights Reserved. Hydrogenolysis of Benzyl Ethers (Bn-OR) • Benzyl ethers: serve as protecting groups for the —OH groups of alcohols and phenols • For example, to carry out hydroboration/oxidation of this alkene, the phenolic —OH must first be protected; it is acidic enough to react with BH3 and destroy the reagent r ©2018 Cengage Learning. All Rights Reserved. Example • What is the most likely protonation site in the conjugated alkene shown below? 1. 2. 3. 4. 5. 1 2 3 4 5 ©2018 Cengage Learning. All Rights Reserved. Example • Benzene undergoes substitution when reacted with Br2, as contrasted with other compounds containing π bonds where addition is the norm. What is the main reason for this behavior? cyclic Sp 3 1. 2. 3. 4. 5. Addition would lead to a nonaromatic system Substitution gives a product of higher energy Production of HBr results in a very stable byproduct Aromatic systems react faster because the intermediate is stabilized by resonance The transition state of the first step is aromatic ©2018 Cengage Learning. All Rights Reserved. Example • What is the most likely mechanism of the following reaction? 1. 2. 3. 4. 5. S N1 S N2 E1 E2 E1cB ©2018 Cengage Learning. All Rights Reserved. Problem 21.62 - Albuterol • Following is a synthesis for albuterol (Proventil), currently one of the most widely used inhalation bronchodilators ©2018 Cengage Learning. All Rights Reserved. Problem 21.62 - Albuterol a. Propose a mechanism for conversion of 4hydroxybenzaldehyde to A b. Propose reagents and experimental conditions for conversion of A to B c. Propose a mechanism for the conversion of B to C • Hint: Think of trimethylsulfonium iodide as producing a sulfur equivalent of a Wittig reagent d. Propose reagents and experimental conditions for the conversion of C to D ©2018 Cengage Learning. All Rights Reserved. Problem 21.62 - Albuterol a. The first reaction is similar in mechanism to the Kolbe carboxylation and involves reaction of a phenoxide ion with a carbonyl group ©2018 Cengage Learning. All Rights Reserved. Problem 21.62 - Albuterol • Proton transfer followed by keto-enol tautomerism gives intermediate A ©2018 Cengage Learning. All Rights Reserved. Problem 21.62 - Albuterol b. The phenol and —OH of C are then protected in the form of a cyclic acetal (Intermediate B) formed by treatment of A with acetone • If the two were not protected, each would react with NaH in the following step c. Conversion of B to C begins with the formation of a sulfur equivalent of a Wittig reagent ©2018 Cengage Learning. All Rights Reserved. Problem 21.62 - Albuterol • Reaction of the sulfur ylide with the aldehyde group of compound B gives an epoxide (compound C) ©2018 Cengage Learning. All Rights Reserved. Problem 21.62 - Albuterol d. Treatment of compound C with tert-butylamine opens the epoxide ring by nucleophilic displacement of oxygen • • As a final step, acid-catalyzed removal of the acetal protecting group gives albuterol The molecule has one chiral center and is produced as a racemic mixture ©2018 Cengage Learning. All Rights Reserved.