Chapter 22: Problem 4
Draw structural formulas for the product of nitration of each compound. Where you predict ortho-para substitution, show both products.
Chapter 22: Problem 4
Draw structural formulas for the product of nitration of each compound. Where you predict ortho-para substitution, show both products.
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Get started for freeWrite a structural formula for the product from Friedel-Crafts alkylation or
acylation of benzene with each compound.
(a)
One potential synthesis of the anti-inflammatory and analgesic drug nabumetone is chloromethylation (Problem 22.48) of 2 -methoxynaphthalene followed by an acetoacetic ester synthesis (Section 19.6). (a) Account for the regioselectivity of chloromethylation at carbon 6 rather than at carbon 5 or 7 . (b) Show steps in the acetoacetic ester synthesis by which the synthesis of nabumetone is completed.
Diazepam, better known as Valium, is a central nervous system (CNS) sedative/ hypnotic. As a sedative, it diminishes activity and excitement and thereby has a calming effect. Back in 1976, based on the number of new and refilled prescriptions processed, diazepam was the most prescribed drug in the United States. Following is a retrosynthetic analysis for a synthesis of diazepam. Note that the formation of compound B involves a Friedel-Crafts acylation. In this reaction, it is necessary to protect the \(2^{\circ}\) amine by prior treatment with acetic anhydride. The acetyl-protecting group is then removed by treatment with aqueous \(\mathrm{NaOH}\) followed by careful acidification with \(\mathrm{HCl}\). (a) Given this retrosynthetic analysis, propose a synthesis for diazepam. (b) Is diazepam chiral? If so, how many of the possible stereoisomers are formed in this synthesis?
Arrange the compounds in each set in order of decreasing reactivity (fastest
to slowest) toward electrophilic aromatic substitution.
(a)
Starting with benzene, toluene, or phenol as the only sources of aromatic rings, show how to synthesize the following. Assume in all syntheses that mixtures of ortho-para products can be separated into the desired isomer. (a) 1-Bromo-3-nitrobenzene (b) 1-Bromo-4-nitrobenzene (c) \(2,4,6\)-Trinitrotoluene (TNT) (d) \(m\)-Chlorobenzoic acid (e) \(p\)-Chlorobenzoic acid (f) \(p\)-Dichlorobenzene (g) \(m\)-Nitrobenzenesulfonic acid
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