Chapter 16

Which compound in each of the following pairs would you expect to be more reactive toward addition of a common nucleophilic agent such as hydroxide ion to the carbonyl bond? Indicate your reasoning. a. 2-propanone and \(1,1,1\) -trichloro-2-propanone b. 2,2 -dimethylpropanal and 2 -propanone c. methyl 2-oxopropanoate and methyl 3-oxobutanoate d. 2 -propanone and 2,3 -butanedione e. 2 -oxopropanenitrile and 2 -propanone f. ketene \(\left(\mathrm{CH}_{2}=\mathrm{C}=\mathrm{O}\right)\) and cyclobutanone g. bicyclo[2.1.1]-5-hexanone and cyclobutanone

Assuming that you had ready access to ultraviolet, infrared, NMR, and mass spectrometers, which spectral technique would you select to differentiate as unambiguously as possible between the following pairs of compounds? Give your reasoning in enough detail to show that you understand how well each technique is capable of distinguishing between the members of each pair (D = hydrogen of mass 2) a. 2 -butanone and 2 -butanone- \(\mathrm{D}_{3}\) b. 3 -cyclohexenone and 2 -cyclohexenone c. 4 -penten- 2 -one and 4,4 -dichloro-1-pentene d. propanal and 2 -butanone e. 3 -hexanone \(-6-D_{3}\) and 3 -hexanone- \(1-D_{3}\)

Write equations to show the steps involved in the following carbonyl-addition reactions: (a) base-catalyzed addition of ethanol to ethanal to form the corresponding hemiacetal, 1 -ethoxyethanol; (b) formation of 1 -ethoxyethanol from ethanol and ethanal, but under conditions of acid catalysis; (c) formation of 1,1 -diethoxyethane from 1 -ethoxyethane and ethanol with an acid catalyst; and (d) formation of diethyl carbonate \(\left(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{O}\right)_{2} \mathrm{C}=\mathrm{O}\) from ethanol and carbonyl dichloride.

One possible way of carrying out the cyanohydrin reaction would be to dispense with hydrogen cyanide and just use the carbonyl compound and sodium cyanide. Would the equilibrium constant for cyanohydrin formation be more favorable, or less favorable, with 2 -propanone and sodium cyanide in water compared to 2 -propanone and hydrogen cyanide in water? Give your reasoning.

Explain what factors would operate to make the equilibrium constant for cyanohydrin formation 1000 times greater for cyclohexanone than for cyclopentanone. Why? What would you expect for cyclobutanone relative to cyclopentanone? Why?

a. Phosphorus ylides can be prepared by heating triphenylphosphine, \(\left(\mathrm{C}_{6} \mathrm{H}_{5}\right)_{3} \mathrm{P}\), with a primary alkyl halide, \(\mathrm{RCH}_{2} \mathrm{X}\), in a solvent such as benzene. The initial product then is mixed with an equivalent quantity of a very strong base, such as phenyllithium in ether. Write equations for the reactions and probable mechanisms involved, using ethyl bromide as the alkyl halide. b. Using the phosphorus ylide prepared according to Part a, draw structures for the products you would expect it to form with 2-pentanone.

The equilibrium constants for hydration are especially large for methanal, trichloroethanal, cyclopropanone, and compounds with the grouping \(-\mathrm{COCOCO}-\). Explain.

Sodium hydrogen sulfite addition products are decomposed to the parent carbonyl compounds when treated with mild acid or mild alkali. Write equations for the reactions involved and explain why the substances are unstable both in acid and base.

Explain how sodium hydrogen sulfite might be used to separate cyclohexanone (bp \(156^{\circ}\) ) from cyclohexanol (bp \(161^{\circ}\) ).

Write a reasonable mechanism for the polymerization of methanal in water solution under the influence of a basic catalyst. Would you expect base catalysis to produce any 1,3,5-trioxacyclohexane? Why?

Work out reasonable mechanisms for the reactions of phosphorus pentachloride and sulfur tetrafluoride with carbonyl groups. Both phosphorus and sulfur can accommodate five (or more) bonded atoms, and the structure of phosphorus pentachloride in the solid state is \(\left[\mathrm{PCl}_{4}^{+}\right]\left[\mathrm{PCl}_{6}^{-}\right]\).

Show how you could prepare the following substances from the indicated starting materials: a. 4-methylcyclohexanone from 4 -methylenecyclohexanone b. 4 -(hydroxymethyl)cyclohexanone from 4 -oxocyclohexanecarboxylic acid c. 4 -hydroxybutanoic acid from 4 -oxobutanoic acid d. \(2,2,2\) -trichloroethanol from \(2,2,2\) -trichloroethanal

Assume that an equimolar mixture of methanal and 2,2 -dimethylpropanal (each undergoes the Cannizzaro reaction by itself) is heated with sodium hydroxide solution. Write equations for the various possible combinations of Cannizzaro reactions which may occur. Would you expect methanal used in excess to reduce, or oxidize, 2,2 dimethylpropanal? Give your reasoning.

Benzenecarbaldehyde (benzaldehyde, \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{CHO}\) ) is oxidized to benzenecarboxylic acid (benzoic acid, \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{CO}_{2} \mathrm{H}\) ) by acid permanganate. The rate of the oxidation is proportional to the concentrations of \(\mathrm{H}^{\oplus}\), aldehyde, and \(\mathrm{MnO}_{4}^{-}\). The reaction is much slower with \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{CDO}\) than with \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{CHO} .\) When the reaction is carried wout in \(\mathrm{H}_{2} 18 \mathrm{O}\) with \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{CHO}\) and \(\mathrm{MnO}_{4}^{-}\), the product is \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{CO}_{2} \mathrm{H}\). With \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{CHO}, \mathrm{H}_{2} \mathrm{O}\), and \(\mathrm{Mn}^{18} \mathrm{O}_{4}^{-}\), the \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{CO}_{2} \mathrm{H}\) contains \({ }^{18} \mathrm{O}\). Write a mechanism for the reaction that is consistent with all the above facts. (Notice that the \(\mathrm{C}_{6} \mathrm{H}_{5}\) group is not involved.) Give your reasoning.

An elegant modification of the two-step procedure to prepare ketones from alkenes by hydroxylation and oxidative cleavage of the diol formed uses a small amount of potassium permanganate (or osmium tetroxide, \(\mathrm{OsO}_{4}\) ) as the catalyst and sodium periodate as the oxidizing agent: Explain how the reaction sequence could operate to enable \(\mathrm{KMnO}_{4}\) (or \(\mathrm{OsO}_{4}\) ) to function overall as a catalyst rather than as a reagent.

Explain how resonance can be used to account for the fact that the \(\Delta H^{0}\) for reduction of \(\mathrm{CH}_{3} \mathrm{CO}_{2} \mathrm{H}\) to \(\mathrm{CH}_{3} \mathrm{CHO}\) is about \(18 \mathrm{kcal} \mathrm{mol}^{-1}\) more positive than calculated from bond energies, whereas \(\Delta H^{0}\) for the corresponding reduction of \(\mathrm{CH}_{3} \mathrm{COCl}\) to \(\mathrm{CH}_{3} \mathrm{CHO}\) is about as expected from bond energies. Would you expect \(\Delta H^{0}\) for reduction of \(\mathrm{CH}_{3} \mathrm{CONH}_{2}\) to be as expected from the pertinent bond energies? Why?

Predict the products to be expected from acid-catalyzed rearrangement of 1,2 -propanediol and 2 -methyl-2,3butanediol.

How could one dehydrate 2,3 -dimethyl-2,3-butanediol to 2,3 -dimethyl-1,3-butadiene without forming excessive amounts of 3,3 -dimethyl-2-butanone in the process?

Strong acid converts 1,1 -diphenyl-1,2-ethanediol first to diphenylethanal and then more slowly to 1,2 diphenylethanone (benzyl phenyl ketone). Explain how and why kinetic and equilibrium control may be expected in this case to give different products.

a. Show the steps and reaction conditions by which 2 -methyl- 1,3 -butadiene can be converted to 3 -methylcyclopentanone by an alkylborane, \(\mathrm{RBH}_{2}\), when \(\mathrm{R}\) is a large alkyl group. b. Suggest a route to each of the following compounds from the indicated starting materials: (1) 2-methyl-4-heptanone from propene and 2 -methylpropene, and (2) octanedial from 1,5-hexadiene.

Write a mechanism for the oxidation of sodium methanoate (formate) to carbon dioxide by potassium permanganate which is consistent with the following facts: (a) \(v=k\left[\mathrm{HCO}_{2}^{-}\right]\left[\mathrm{MnO}_{4}^{-}\right]\) (b) the \(\mathrm{CO}_{2}\), has no \({ }^{18} \mathrm{O}\) in it if oxidized with \(\mathrm{Mn}^{18} \mathrm{O}_{4}^{-}\) (c) \(\mathrm{DCO}_{2}^{-}\) is oxidized at one seventh the rate of \(\mathrm{HCO}_{2}^{-}\) Compare your mechanism with that generally accepted for the Cannizzaro reaction.

Propanone reacts with trichloromethane in the presence of potassium hydroxide to give \(1,1,1\) -trichloro-2methyl-2-propanol. What is likely to be the mechanism of this reaction? What further evidence could be gained to establish the mechanism? (If you do not see a possible answer, refer to Section \(14-7 \mathrm{~B}\) for helpful information.)