Although most alkanes react with chlorine by a radical chain mechanism when reaction

Construct a Frost circle for a planar eight-membered ring with one 2p orbital on each atom of the ring and show the relative energies of its eight p molecular orbitals. Which are bonding MOs, which are antibonding, and which are nonbonding?

Which compound gives a signal in the 1H-NMR spectrum with a larger chemical shift, furan or cyclopentadiene? Explain.

Describe the ground-state electron configuration of the cyclopentadienyl cation and radical. Assuming each species is planar, would you expect it to be aromatic or antiaromatic?

Describe the ground-state electron configuration of the cycloheptatrienyl radical and anion. Assuming each species is planar, would you expect them to be aromatic or antiaromatic?

Write names for these compounds.

Arrange these compounds in order of increasing acidity: 2,4-dichlorophenol, phenol, cyclohexanol.

Predict the products resulting from vigorous oxidation of each compound by H2CrO4.

Name the following compounds and ions.

Draw a structural formula for each compound. (a) 1-Bromo-2-chloro-4-ethylbenzene (b) m-Nitrocumene (c) 4-Chloro-1,2-dimethylbenzene (d) 3,5-Dinitrotoluene (e) 2,4,6-Trinitrotoluene (f) (2S,4R)-4-Phenyl-2-pentanol (g) p-Cresol (h) Pentachlorophenol (i) 1-Phenylcyclopropanol (j) Triphenylmethane (k) Phenylethylene (styrene) (l) Benzyl bromide (m) 1-Phenyl-1-butyne (n) (E)-3-Phenyl-2-propen-1-ol

Molecules of 6,69-dinitrobiphenyl-2,29-dicarboxylic acid have no tetrahedral chiral center, and yet they can be resolved to a pair of enantiomers. Account for this chirality.

Following each name is the number of Kekul structures that can be drawn for it. Draw these Kekul structures and show, using curved arrows, how the first contributing struc- ture for each molecule is converted to the second and so forth. (a) Naphthalene (3) (b) Phenanthrene (5)

Each molecule in this problem can be drawn as a hybrid of five contributing structures: two Kekul structures and three that involve creation and separation of unlike charges. Draw these five contributing structures for each molecule. (a) Chlorobenzene (b) Phenol (c) Nitrobenzene

Following are structural formulas for furan and pyridine. (a) Draw four contributing structures for furan that place a positive charge on oxygen and a negative charge first on carbon 3 of the ring and then on each other carbon of the ring. (b) Draw three contributing structures for pyridine that place a negative charge on nitrogen and a positive charge first on carbon 2, then on carbon 4, and finally on carbon 6.

State the number of 2p orbital electrons in each molecule or ion.

Which of the molecules and ions given in Problem 21.15 are aromatic according to the Hckel criteria? Which, if planar, would be antiaromatic?

Construct MO energy diagrams for the cyclopropenyl cation, radical, and anion. Which of these species is aromatic according to the Hckel criteria?

Naphthalene and azulene are constitutional isomers of molecular formula C10H8. Naphthalene is a colorless solid with a dipole moment of zero. Azulene is a solid with an intense blue color and a dipole moment of 1.0 D. Account for the difference in dipole moments of these constitutional isomers.

Compound A (C9H12) shows prominent peaks in its mass spectrum at m/z 120 and 105. Compound B (also C9H12) shows prominent peaks at m/z 120 and 91. On vigorous oxi- dation with chromic acid, both compounds give benzoic acid. From this information, deduce the structural formulas of compounds A and B.

Following are IR and 1H-NMR spectra of compound D. The mass spectrum of com- pound D shows a molecular ion peak at m/z 136, a base peak at m/z 107, and other prominent peaks at m/z 118 and 59. (a) Propose a structural formula for compound D. (b) Propose structural formulas for ions in the mass spectrum at m/z 118, 107, and 59.

Compound E (C8H10O2) is a neutral solid. Its mass spectrum shows a molecular ion at m/z 138 and prominent peaks at M-1 and M-17. Following are IR and 1H-NMR spectra of compound E. Deduce the structure of compound E.

Following are 1H-NMR and 13C-NMR spectral data for compound F (C12H16O). From this information, deduce the structure of compound F.

Following are 1H-NMR and 13C-NMR spectral data for compound G (C10H10O). From this information, deduce the structure of compound G.

Compound H (C8H6O3) gives a precipitate when treated with hydroxylamine in aqueous ethanol and a silver mirror when treated with Tollens solution. Following is its 1H-NMR spectrum. Deduce the structure of compound H.

Compound I (C11H14O2) is insoluble in water, aqueous acid, and aqueous NaHCO3 but dissolves readily in 10% Na2CO3 and 10% NaOH. When these alkaline solutions are acidified with 10% HCl, compound I is recovered unchanged. Given this information and its 1H-NMR spectrum, deduce the structure of compound I.

Propose a structural formula for compound J (C11H14O3) consistent with its 1H-NMR and infrared spectra.

Propose a structural formula for the analgesic phenacetin, molecular formula C10H13NO2, based on its 1H-NMR spectrum.

Compound K, C10H12O2, is insoluble in water, 10% NaOH, and 10% HCl. Given this information and the following 1H-NMR and 13C-NMR spectral information, deduce the structural formula of Compound K.

Given here are 1H-NMR and 13C-NMR spectral data for two compounds. Each shows strong, sharp absorption between 1700 and 1720 cm1 and strong, broad absorption over the region 25003000 cm1. Propose a structural formula for each compound.

Account for the fact that p-nitrophenol (Ka 7.0 3 1028) is a stronger acid than is phenol (Ka 1.1 3 1010).

Account for the fact that water-insoluble carboxylic acids (pKa 45) dissolve in 10% aqueous sodium bicarbonate (pH 8.5) with the evolution of a gas, but that water- insoluble phenols (pKa 9.510.5) do not dissolve in 10% sodium bicarbonate.

Match each compound with its appropriate pKa value. (a) 4-Nitrobenzoic acid, benzoic acid, 4-chlorobenzoic acid pKa 5 4.19, 3.98, and 3.41 (b) Benzoic acid, cyclohexanol, phenol pKa 5 18.0, 9.95, and 4.19 (c) 4-Nitrobenzoic acid, 4-nitrophenol, 4-nitrophenylacetic acid pKa 5 7.15, 3.85, and 3.41

Arrange the molecules and ions in each set in order of increasing acidity (from least acidic to most acidic).

Explain the trends in the acidity of phenol and the monofluoro derivatives of phenol.

Suppose you want to determine the inductive effects of a series of functional groups (e.g., Cl, Br, CN, COOH, and C6H5). Is it best to use a series of ortho-, meta-, or para- substituted phenols? Explain.

From each pair, select the stronger base.

Describe a chemical procedure to separate a mixture of benzyl alcohol and o-cresol and to recover each in pure form.

Write a balanced equation for the oxidation of p-xylene to 1,4-benzenedicarboxylic acid (terephthalic acid) using potassium dichromate in aqueous sulfuric acid. How many milligrams of H2CrO4 are required to oxidize 250 mg of p-xylene to terephthalic acid?

Each of the following reactions occurs by a radical chain mechanism. (a) Calculate the heat of reaction, DH0, in kJ/mol for each reaction. (Consult Appendix 3 for bond dissociation enthalpies.) (b) Write a pair of chain propagation steps for each mechanism and show that the net result of each pair is the observed reaction. (c) Calculate DH0 for each chain propagation step and show that the sum for each pair of steps is identical with the DH0 value calculated in part (a).

Following is an equation for iodination of toluene.

Although most alkanes react with chlorine by a radical chain mechanism when reaction is initiated by light or heat, benzene fails to react under the same conditions. Benzene cannot be converted to chlorobenzene by treatment with chlorine in the presence of light or heat. (a) Explain why benzene fails to react under these conditions. (Consult Appendix 3 for relevant bond dissociation enthalpies.) (b) Explain why the bond dissociation enthalpy of a C!H bond in benzene is signifi- cantly greater than that in alkanes.

Following is an equation for hydroperoxidation of cumene.

Para-substituted benzyl halides undergo reaction with methanol by an SN1 mechanism to give a benzyl ether. Account for the following order of reactivity under these conditions.

When warmed in dilute sulfuric acid, 1-phenyl-1,2-propanediol undergoes dehydration and rearrangement to give 2-phenylpropanal. (a) Propose a mechanism for this example of a pinacol rearrangement (Section 10.7). (b) Account for the fact that 2-phenylpropanal is formed rather than its constitutional isomer, 1-phenyl-1-propanone.

In the chemical synthesis of DNA and RNA, hydroxyl groups are normally converted to triphenylmethyl (trityl) ethers to protect the hydroxyl group from reaction with other reagents. (a) Why are triphenylmethyl ethers so readily hydrolyzed by aqueous acid? (b) How might the structure of the triphenylmethyl group be modified to increase or decrease its acid sensitivity?

Use the roadmap you made for Problem 20.55 and update it to contain the reactions in the Key Reactions section of this chapter. Because of their highly specific nature, do not use reactions 1, 2, and 7 on your roadmap.

Using ethylbenzene as the only aromatic starting material, show how to synthesize the following compounds. In addition to ethylbenzene, use any other necessary organic or inorganic chemicals. Any compound already synthesized in one part of this problem may then be used to make any other compound in the problem.

Show how to convert 1-phenylpropane into the following compounds. In addition to this starting material, use any necessary inorganic reagents. Any compound syn- thesized in one part of this problem may be used to make any other compound in the problem.

Carbinoxamine is a histamine antagonist, specifically, an H1-antagonist. The maleic acid salt of the levorotatory isomer is sold as the prescription drug Rotoxamine. (a) Propose a synthesis of carbinoxamine. (Note: Aryl bromides form Grignard reagents much more readily than do aryl chlorides.) (b) Is carbinoxamine chiral? If so, how many stereoisomers are possible? Which of the possible stereoisomers are formed in this synthesis?

Cromolyn sodium, developed in the 1960s, has been used to prevent allergic reac- tions primarily affecting the lungs, as, for example, exercise-induced emphysema. It is thought to block the release of histamine, which prevents the sequence of events leading to swelling, itching, and constriction of bronchial tubes. Cromolyn sodium is synthesized in the following series of steps. Treatment of one mole of epichlorohydrin (Section 11.10) with two moles of 2,6-dihydroxyacetophenone in the presence of base gives I. Treatment of I with two moles of diethyl oxalate in the presence of sodium ethoxide gives a diester II. Saponification of the diester with aqueous NaOH gives cromolyn sodium.

The following stereospecific synthesis is part of the scheme used by E. J. Corey of Har- vard University in the synthesis of erythronolide B, the precursor of the erythromycin antibiotics. In this remarkably simple set of reactions, the relative configurations of five chiral centers are established. (a) Propose a mechanism for the conversion of 2,4,6-trimethylphenol to compound A. (b) Account for the stereoselectivity and regioselectivity of the three steps in the con- version of compound C to compound F. (c) Is compound F produced in this synthesis as a single enantiomer or as a racemic mixture? Explain.

Following is an outline of one of the first syntheses of the antidepressant fluoxetine (Prozac). (a) Propose a reagent for the conversion of A to B. (b) Propose a reagent for the conversion of B to C. (c) Propose a reagent for the conversion of C to D. (d) Propose a mechanism for the conversion of E to F. The reagent used in this synthe- sis is ethyl chloroformate. The other product of this conversion is chloromethane, CH3Cl. Your mechanism should show how the CH3Cl is formed. (e) Propose a reagent or reagents to bring about the conversion of F to fluoxetine. Note that the bracketed intermediate formed in this step is an N-substituted carbamic acid. Such compounds are unstable and break down to carbon dioxide and an amine. (f) Is fluoxetine chiral? If so, which of the possible stereoisomers are formed in this synthesis?

A finding that opened a route to b-blockers was the discovery that b-blocking activ- ity is retained if an oxygen atom is interposed between the aromatic ring and the side chain. To see this difference, compare the structures of labetalol (Problem 22.57) and propranolol. Thus, alkylation of phenoxide ions can be used as a way to introduce this side chain. The first of this new class of drugs was propranolol. (a) Show how propanolol can be synthesized from 1-naphthol, epichlorohydrin (Section 11.10), and isopropylamine. (b) Is propranolol chiral? If so, which of the possible stereoisomers are formed in this synthesis?

Side effects of propranolol (Problem 21.58) include disturbances of the central nervous system (CNS), such as fatigue, sleep disturbances (including insomnia and nightmares), and depression. Pharmaceutical companies wondered if this drug could be redesigned to eliminate or at least reduce these side effects. Propranolol, it was reasoned, enters the CNS by passive diffusion because of the lipidlike character of its naphthalene ring. The challenge, then, was to design a more hydrophilic drug that does not cross the blood-brain barrier but still retains a b-adrenergic antagonist property. A product of this research is atenolol, a potent b-adrenergic blocker that is hydrophilic enough that it crosses the blood-brain barrier to only a very limited extent. Atenolol is now one of the most widely used b-blockers. (a) Given this retrosynthetic analysis, propose a synthesis for atenolol from the three named starting materials. (b) Note that the amide functional group is best made by amination of the ester. Why was this route chosen rather than conversion of the carboxylic acid to its acid chloride and then treatment of the acid chloride with ammonia? (c) Is atenolol chiral? If so, which of the possible stereoisomers are formed in this synthesis?

Following is an outline of a synthesis of the bronchodilator carbuterol, a beta-2 adrener- gic blocker with high selectivity for airway smooth muscle receptors. (a) Propose reagents to bring about each step. (b) Why is it necessary to add the benzyl group, PhCH2 , as a blocking group in Step 1? (c) Suggest a structural relationship between carbuterol and ephedrine. (d) Is carbuterol chiral? If so, which of the possible stereoisomers are formed in this synthesis?

Following is a synthesis for albuterol (Proventil), currently one of the most widely used inhalation bronchodilators. (a) Propose a mechanism for conversion of 4-hydroxybenzaldehyde 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 trimethylsulfo- nium iodide as producing a sulfur equivalent of a Wittig reagent. (d) Propose reagents and experimental conditions for the conversion of C to D. (e) Propose reagents and experimental conditions for the conversion of D to albuterol. (f) Is albuterol chiral? If so, which of the possible stereoisomers are formed in this synthesis?

Estrogens are female sex hormones, the most potent of which is b-estradiol.

Following is a synthesis for toremifene, a nonsteroidal estrogen antagonist whose struc- ture is closely related to that of tamoxifen. (a) This synthesis makes use of two blocking groups, the benzyl (Bn) group and the tetrahydropyranyl (THP) group. Draw a structural formula of each group and describe the experimental conditions under which it is attached and removed. (b) Discuss the chemical logic behind the use of each blocking group in this synthesis. (c) Propose a mechanism for the conversion of D to E. (d) Propose a mechanism for the conversion of F to toremifene. (e) Is toremifene chiral? If so, which of the possible stereoisomers are formed in this synthesis?