20 Organic Chemistry William H Brown Christopher S
20 Organic Chemistry William H. Brown & Christopher S. Foote 20 -1
20 Aromatics I Chapter 20 20 -2
20 Benzene - Kekulé u The first structure for benzene was proposed by August Kekulé in 1872 u This structure, however, did not account for the unusual chemical reactivity of benzene 20 -3
20 Benzene - MO Model u The concepts of hybridization of atomic orbitals and theory of resonance, developed in the 1930 s, provided the first adequate description of benzene’s structure • the carbon skeleton is a regular hexagon, with all C-C -C and H-C-C bond angles 120° 20 -4
20 Benzene - MO Model 20 -5
20 Benzene - MO Model u Combination of six 2 p atomic orbitals gives six molecular orbitals • three bonding MOs and • three antibonding MOs u In the ground state, the six pi electrons of benzene occupy the three bonding MOs 20 -6
20 Benzene MO Model • the stability of benzene results from the fact that these three bonding MOs are much lower in energy than the six uncombined 2 p atomic orbitals 20 -7
20 Benzene - Resonance u We often represent benzene as a hybrid of two equivalent Kekulé structures • each makes an equal contribution to the hybrid and thus the C-C bonds are neither double nor single, but something in between 20 -8
20 Benzene - Resonance u Resonance energy: the 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 u One way to estimate the resonance energy of benzene is to compare the heats of hydrogenation of benzene and cyclohexene 20 -9
20 Benzene 20 -10
20 Concept of Aromaticity u The underlying criteria for aromaticity were recognized in the early 1930 s by Erich Hückel, based on MO calculations u To be aromatic, a compound must • be cyclic • have one p orbital on each atom of the ring • be planar or nearly planar so that there is continuous or nearly continuous overlap of all p orbitals of the ring • have a closed loop of (4 n + 2) pi electrons in the cyclic arrangement of p orbitals 20 -11
20 Frost Circles u Inscribe a polygon of the same number of sides as the ring to be examined such that one of the vertices is at the bottom of the ring u The relative energies of the MOs in the ring are given by where the vertices touch the circle u Those MOs • below the horizontal line through the center of the ring are bonding MOs • on the horizontal line are nonbonding MOs • above the horizontal line are antibonding MOs 20 -12
20 Frost Circles u Following are Frost circles describing the MOs for monocyclic, planar, fully conjugated four-, five-, and six-membered rings 20 -13
20 Aromatic Hydrocarbons u Annulene: a cyclic hydrocarbon with a continuous alternation of single and double bonds u [10]Annulene: according to Hückel’s criteria, this unsaturated hydrocarbon should be aromatic • it is cyclic • it has one 2 p orbital on each carbon of the ring, • it has 4(2) + 2 = 10 pi electrons u It is not aromatic, however, because it is not planar 20 -14
20 [10]Annulene • 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 the ten 2 p orbitals is no longer continuous 20 -15
20 [14]Annulene • this unsaturated hydrocarbon meets the Hückel criteria and is aromatic 20 -16
20 [18]Annulene u This unsaturated hydrocarbon is also aromatic 20 -17
20 Antiaromatic Hydrocbn u Antiaromatic hydrocarbon: a monocyclic, planar, fully conjugated hydrocarbon with 4 n pi electrons (4, 8, 12, 16, 20. . . ) • an antiaromatic hydrocarbon is especially unstable relative to an open-chain fully conjugated hydrocarbon of the same number of carbon atoms u Cyclobutadiene is antiaromatic. In the groundstate electron configuration of this molecule, • two electrons fill the 1 bonding MO • the remaining two electrons lie in the 2 and 3 nonbonding MOs 20 -18
20 Cyclobutadiene • planar cyclobutadiene has two unpaired electrons, which make it highly unstable and reactive 20 -19
20 Cyclobutadiene • cyclobutadiene is trapped within the cage of a larger molecule called a hemicarcerand (to rotate this molecule, see the accompanying CD) 20 -20
20 Cyclooctatetraene u Planar cyclooctatetraene, if it existed, would be antiaromatic; it would have two unpaired electrons in 4 and 5 nonbonding MOs 20 -21
20 Heterocyclic Aromatics u 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 are other than carbon u Pyridine and pyrimidine are heterocyclic analogs of benzene; each is aromatic. 20 -22
20 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 • pyridine has a resonance energy of 134 k. J (32 kcal)/mol, slightly less than that of benzene 20 -23
20 Furan • the oxygen atom of furan is sp 2 hybridized • one unshared pairs of electrons on oxygen lies in an unhybridized 2 p 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 k. J (16 kcal)/mol 20 -24
20 Other Heterocyclics 20 -25
20 Aromatic Hydrcbn Ions u Any neutral, monocyclic unsaturated hydrocarbon with an odd number of carbons must have at least one CH 2 group and, therefore, cannot be aromatic • 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 20 -26
20 Cyclopropenyl Cation • 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 20 -27
20 Cyclopropenyl Cation u When 3 -chlorocyclopropene is treated with Sb. Cl 5, it forms a stable salt • this chemical behavior is to be contrasted with that of 5 -chloro-1, 3 -cyclopentadiene, which cannot be made to form a stable salt 20 -28
20 Cyclopentadienyl C+ • if planar cyclopentadienyl cation existed, 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. 20 -29
20 Cyclopentadienyl Anion u To convert cyclopentadiene to an aromatic ion, it is necessary to convert the CH 2 group to a CHgroup in which carbon becomes sp 2 hybridized and has 2 electrons in its unhybridized 2 p orbital 20 -30
20 Cyclopentadienyl Anion u The p. Ka of cyclopentadiene is 16 • in aqueous Na. OH, it is in equilibrium with its sodium salt • it is converted completely to its anion by very strong bases such as Na. NH 2 , Na. H, and LDA 20 -31
20 Cycloheptatrienyl C+ u Cycloheptatriene forms an aromatic cation by conversion of its CH 2 group to a CH+ group with its sp 2 carbon having a vacant 2 p orbital 20 -32
20 Nomenclature u Monosubstituted alkylbenzenes are named as derivatives of benzene • many common names are retained 20 -33
20 Nomenclature u Benzyl and phenyl groups 20 -34
20 Disubstituted Benzenes u Locate the two groups by numbers or by the locators ortho (1, 2 -), meta (1, 3 -), and para (1, 4 -) • where one group imparts a special name, name the compound as a derivative of that molecule 20 -35
20 Disubstituted Benzenes • where neither group imparts a special name, locate the groups and list them in alphabetical order 20 -36
20 Polysubstituted Derivs • 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 20 -37
20 NMR Spectroscopy u Hydrogens bonded to a benzene ring appear in the region 6. 5 to 8. 5 u Aryl hydrogens absorb further downfield than vinylic hydrogens, which is accounted for by an induced ring current • the induced ring current has an associated magnetic field which opposes the applied field in the middle of the ring but reinforces it on the outside of the ring • thus, hydrogens on the benzene ring come into resonance at a lower applied field; that is, at a larger chemical shift than vinylic hydrogens 20 -38
20 NMR Spectroscopy u There are, of course, no hydrogens on the inside of a benzene ring. But there are in larger annulenes, for example [18]annulene 20 -39
20 Phenols u The functional group of a phenol is an -OH group bonded to a benzene ring 20 -40
20 Phenols • hexylresorcinol is 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 20 -41
20 Acidity of Phenols u Phenols are significantly more acidic than alcohols, compounds that also contain the OH group 20 -42
20 Acidity of Phenols • the greater acidity of phenols compared with alcohols is due to the greater stability of the phenoxide ion relative to an alkoxide ion 20 -43
20 Acidity of Phenols u Alkyl and halogen substituents effect acidities by inductive effects • alkyl groups are electron-releasing • halogens are electron-withdrawing 20 -44
20 Acidities of Phenols • nitro groups increase the acidity of phenols by both an electron-withdrawing inductive effect and a resonance effect 20 -45
20 Acidities of Phenols • part of the acid-strengthening effect of -NO 2 is due to its electron-withdrawing inductive effect • in addition, -NO 2 substituents in the ortho and para positions help to delocalize the negative charge 20 -46
20 Acidity of Phenols u Phenols are weak acids and react with strong bases to form water-soluble salts • water-insoluble phenols dissolve in Na. OH(aq) 20 -47
20 Acidity of Phenols • most phenols do not react with weak bases such as Na. HCO 3; they do not dissolve in aqueous Na. HCO 3 20 -48
20 Alkyl-Aryl Ethers u Alkyl-aryl ethers can be prepared by the Williamson ether synthesis • but only using phenoxide salts and alkyl halides • aryl halides are unreactive to SN 2 reactions u The following two examples illustrate • the use of a phase-transfer catalyst • the use of dimethyl sulfate as a methylating agent 20 -49
20 Alkyl-Aryl Ethers 20 -50
20 Kolbe Carboxylation u Phenoxide ions react with carbon dioxide to give a carboxylic salt 20 -51
20 Kolbe Carboxylation • the mechanism begins by nucleophilic addition of the phenoxide ion to a carbonyl group of CO 2 20 -52
20 Oxidation to Quinones u Because of the presence of the electrondonating -OH group, phenols are susceptible to oxidation by a variety of strong oxidizing agents 20 -53
20 Oxidation of Phenols 20 -54
20 Quinones u Perhaps the most important chemical property of quinones is that they are readily reduced to hydroquinones 20 -55
20 Vitamin K • both natural and synthetic vitamin K (menadione) are 1, 4 -naphthoquinones 20 -56
20 Benzylic Oxidation u Benzene is unaffected by strong oxidizing agents such as H 2 Cr. O 4 and KMn. O 4 • halogen and nitro substituents are also unaffected by these reagents • an alkyl group with at least one hydrogen on its benzylic carbon is oxidized to a carboxyl group 20 -57
20 Benzylic Oxidation u if there is more than one alkyl group on the benzene ring, each is oxidized to a -COOH group 20 -58
20 Benzylic Chlorination u Chlorination (and bromination) is by a radical mechanism 20 -59
20 Benzylic Reactions u Benzylic radicals (and cations too) are easily formed because of the resonance stabilization of these intermediates • the benzyl radical is a hybrid of five contributing structures 20 -60
20 Benzylic Halogenation u Benzylic bromination is highly regioselective 20 -61
20 Benzylic Halogenation u Benzylic chlorination is also regioselective, but less so than benzylic bromination u The order of regioselectivity is which parallels BDEs for the formation of radicals 20 -62
20 Hydrogenolysis u Hydrogenolysis: cleavage of a single bond by H 2 • among ethers, benzylic ethers are unique in that they are cleaved under conditions of catalytic hydrogenation 20 -63
20 Benzyl Ethers u The particular value of benzyl ethers is that they can serve as protecting groups for the OH groups of alcohols and phenols • 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 20 -64
20 Benzyl Ethers • protect the phenolic -OH, carry out the hydroboration/oxidation, and then remove the benzyl protecting group by hydrogenolysis 20 -65
20 Prob 20. 15 State the number of p orbital electrons in each. 20 -66
20 Prob 20. 23 From this spectral data, write a structural formula for compound F, C 12 H 16 O. 20 -67
20 Prob 20. 24 From this spectral data, write a structural formula for compound G, C 10 H 10 O. 20 -68
20 Prob 20. 29 Compound K, C 10 H 12 O 2, is insoluble in water, 10% Na. OH and 10% HCl. Given this information and the following spectral data, propose a structural formula for compound K. 20 -69
20 Prob 20. 30 Propose a structural formula for each compound. 20 -70
20 Prob 20. 31 Each compound shows strong, sharp absorption between 1700 and 1720 cm-1, and strong, broad absorption over the region 2500 -3500 cm-1. 20 -71
20 Prob 20. 35 Arrange the entries in each set in order of increasing acidity. 20 -72
20 Prob 20. 36 Explain the trends in acidity of phenol and the monofluoro derivatives of phenol. 20 -73
20 Prob 20. 38 From each pair, select the stronger base. 20 -74
20 Prob 20. 39 Describe a chemical procedure to separate a mixture of these compounds and recover each in pure form. 20 -75
20 Prob 20. 46 Account for the following order of reactivity under SN 1 conditions. 20 -76
20 Prob 20. 47 Propose a mechanism for this rearrangement. Account for the fact that the product is 2 -phenylpropanal rather than its constitutional isomer, 1 -phenyl-1 -propanone. 20 -77
20 Prob 20. 49 Synthesize these compounds from ethylbenzene. 20 -78
20 Prob 20. 50 Show to convert 1 -phenylpropane to the following compounds. 20 -79
20 Prob 20. 51 Given this retrosynthetic analysis, propose a synthesis for cabinoxamide. Note that aryl bromides form Grignard reagents much more readily than aryl chlorides. 20 -80
20 Prob 20. 52 Propose (1) a mechanism formation of I, (2) a structure for II and a mechanism for its formation, and (3) a mechanism for the formation of cromolyn sodium. 20 -81
20 Prob 20. 53 Describe the chemistry of each step. 20 -82
20 Prob 20. 53 (cont’d) describe the chemistry of each step 20 -83
20 Aromatics I End of Chapter 20 20 -84
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