11 • Additional Problems
11 • Additional Problems
From what alkyl bromide was the following alkyl acetate made by SN2 reaction? Write the reaction, showing all stereochemistry.
Assign R or S configuration to the following molecule, write the product you would expect from SN2 reaction with NaCN, and assign R or S configuration to the product (green = Cl):
Draw the structure and assign Z or E stereochemistry to the product you expect from E2 reaction of the following molecule with NaOH (green = Cl):
We saw in Section 8.7 that bromohydrins are converted into epoxides when treated with base. Propose a mechanism, using curved arrows to show the electron flow.
The following tertiary alkyl bromide does not undergo a nucleophilic substitution reaction by either SN1 or SN2 mechanisms. Explain.
Metabolism of S-adenosylhomocysteine (Section 11.6) involves the following sequence. Propose a mechanism for the second step.
One step in the urea cycle for ridding the body of ammonia is the conversion of argininosuccinate to the amino acid arginine plus fumarate. Propose a mechanism for the reaction, and show the structure of arginine.
Methyl esters (RCO2CH3) undergo a cleavage reaction to yield carboxylate ions plus iodomethane on heating with LiI in dimethylformamide:
The following evidence has been obtained: (1) The reaction occurs much faster in DMF than in ethanol. (2) The corresponding ethyl ester (RCO2CH2CH3) cleaves approximately 10 times more slowly than the methyl ester. Propose a mechanism for the reaction. What other kinds of experimental evidence could you gather to support your hypothesis?
SN2 reactions take place with inversion of configuration, and SN1 reactions take place with racemization. The following substitution reaction, however, occurs with complete retention of configuration. Propose a mechanism. (Hint: two inversions = retention.)
Propose a mechanism for the following reaction, an important step in the laboratory synthesis of proteins:
Nucleophilic Substitution Reactions
The following Walden cycle has been carried out: Explain the results, and indicate where inversion occurs.
1-Chloro-1,2-diphenylethane can undergo E2 elimination to give either cis- or trans-1,2-diphenylethylene (stilbene). Draw Newman projections of the reactive conformations leading to both possible products, and suggest a reason why the trans alkene is the major product.
Predict the major alkene product of the following E1 reaction:
Reaction of the following S tosylate with cyanide ion yields a nitrile product that also has S stereochemistry. Explain.
Ethers can often be prepared by SN2 reaction of alkoxide ions, RO–, with alkyl halides. Suppose you wanted to prepare cyclohexyl methyl ether. Which of the following two possible routes would you choose? Explain.
How can you explain the fact that trans-1-bromo-2-methylcyclohexane yields the non-Zaitsev elimination product 3-methylcyclohexene on treatment with base?
Predict the product(s) of the following reaction, indicating stereochemistry where necessary:
Alkynes can be made by dehydrohalogenation of vinylic halides in a reaction that is essentially an E2 process. In studying the stereochemistry of this elimination, it was found that (Z)-2-chloro-2-butenedioic acid reacts 50 times as fast as the corresponding E isomer. What conclusion can you draw about the stereochemistry of eliminations in vinylic halides? How does this result compare with eliminations of alkyl halides?
(S)-2-Butanol slowly racemizes on standing in dilute sulfuric acid. Explain.
Reaction of HBr with (R)-3-methyl-3-hexanol leads to racemic 3-bromo-3-methylhexane. Explain.
Treatment of 1-bromo-2-deuterio-2-phenylethane with strong base leads to a mixture of deuterated and nondeuterated phenylethylenes in an approximately 7 : 1 ratio. Explain.
Although anti periplanar geometry is preferred for E2 reactions, it isn’t absolutely necessary. The following deuterated bromo compound reacts with strong base to yield an undeuterated alkene. A syn elimination has occurred. Make a molecular model of the reactant, and explain the result.
When a primary alcohol is treated with p-toluenesulfonyl chloride at room temperature in the presence of an organic base such as pyridine, a tosylate is formed. When the same reaction is carried out at higher temperature, an alkyl chloride is often formed. Explain.
The amino acid methionine is formed by a methylation reaction of homocysteine with N-methyltetrahydrofolate. The stereochemistry of the reaction has been probed by carrying out the transformation using a donor with a “chiral methyl group,” which contains protium (H), deuterium (D), and tritium (T) isotopes of hydrogen. Does the methylation reaction occur with inversion or retention of configuration?
Amines are converted into alkenes by a two-step process called the Hofmann elimination. SN2 reaction of the amine with an excess of CH3I in the first step yields an intermediate that undergoes E2 reaction when treated with silver oxide as base. Pentylamine, for example, yields 1-pentene. Propose a structure for the intermediate, and explain why it readily undergoes elimination.
The antipsychotic drug flupentixol is prepared by the following scheme: