Using any necessary reagents, show how you would accomplish the following syntheses.

(g)

The following drugs are synthesized using the methods in this chapter and in previous chapters. Devise a synthesis for each, starting with any compounds containing no more than six carbon atoms.

(a) Phenacetin, used with aspirin and caffeine in pain-relief medications.

The following drugs are synthesized using the methods in this chapter and in previous chapters. Devise a synthesis for each, starting with any compounds containing no more than six carbon atoms.

(b) Methamphetamine, once considered a safe diet pill, but now known to be addictive and destructive to brain tissue.

The following drugs are synthesized using the methods in this chapter and in previous chapters. Devise a synthesis for each, starting with any compounds containing no more than six carbon atoms.

(c) Dopamine, one of the neurotransmitters in the brain. Parkinson’s disease is thought to result from a dopamine deficiency.

Synthesize Novocaine from benzene and any other reagents of four carbons or fewer.

Synthesize from benzene. (Hint: All of these require diazonium ions.)

(a) 3-ethylbenzoic acid

Synthesize from benzene. (Hint: All of these require diazonium ions.)

(c) 2-methyl-5-hydroxybenzoic acid

Synthesize from benzene. (Hint: All of these require diazonium ions.)

(d) 4-methoxyaniline

Propose mechanisms for the following reactions.

(a)

Propose mechanisms for the following reactions.

(b)

The two most general amine syntheses are the reductive amination of carbonyl compounds and the reduction of amides. Show how these techniques can be used to accomplish the following syntheses.

(a) benzoic acid → benzylamine

The two most general amine syntheses are the reductive amination of carbonyl compounds and the reduction of amides. Show how these techniques can be used to accomplish the following syntheses.

(b) benzaldehyde → benzylamine

The two most general amine syntheses are the reductive amination of carbonyl compounds and the reduction of amides. Show how these techniques can be used to accomplish the following syntheses.

(c) pyrrolidine → N-ethylpyrrolidine

The two most general amine syntheses are the reductive amination of carbonyl compounds and the reduction of amides. Show how these techniques can be used to accomplish the following syntheses.

(d) cyclohexanone → N-cyclohexylpyrrolidine

Several additional amine syntheses are effectively limited to making primary amines. The reduction of azides and nitro compounds and the Gabriel synthesis leave the carbon chain unchanged. Formation and reduction of a nitrile adds one carbon atom. Show how these amine syntheses can be used for the following conversions.

(a) allyl bromide → allylamine 

Several additional amine syntheses are effectively limited to making primary amines. The reduction of azides and nitro compounds and the Gabriel synthesis leave the carbon chain unchanged. Formation and reduction of a nitrile adds one carbon atom. Show how these amine syntheses can be used for the following conversions.

(c) 1-bromo-3-phenylheptane → 3-phenylheptan-1-amine

Show how you can synthesize the following tertiary amine three different ways, each using a different secondary amine and adding the final substituent by

(a) reductive amination (3 ways).

Show how you can synthesize the following tertiary amine three different ways, each using a different secondary amine and adding the final substituent by (b) acylation–reduction (3 ways).

Show how you can synthesize the following compounds starting with benzene, toluene, and alcohols containing no more than four carbon atoms as your organic starting materials. Assume that para is the major product (and separable from ortho) in ortho, para mixtures.

(a) pentan-1-amine

Show how you can synthesize the following compounds starting with benzene, toluene, and alcohols containing no more than four carbon atoms as your organic starting materials. Assume that para is the major product (and separable from ortho) in ortho, para mixtures.

(b) N-methylbutan-1-amine

Show how you can synthesize the following compounds starting with benzene, toluene, and alcohols containing no more than four carbon atoms as your organic starting materials. Assume that para is the major product (and separable from ortho) in ortho, para mixtures.

(c) N-ethyl-N-propylbutan-2-amine

Show how you can synthesize the following compounds starting with benzene, toluene, and alcohols containing no more than four carbon atoms as your organic starting materials. Assume that para is the major product (and separable from ortho) in ortho, para mixtures.

(d) N-benzylpropan-1-amine

Show how you can synthesize the following compounds starting with benzene, toluene, and alcohols containing no more than four carbon atoms as your organic starting materials. Assume that para is the major product (and separable from ortho) in ortho, para mixtures.

(g) 4-isobutylaniline

Using any necessary reagents, show how you can accomplish the following multistep syntheses.

(b)

Using any necessary reagents, show how you can accomplish the following multistep syntheses.

(c)

Pyrrole undergoes electrophilic aromatic substitution more readily than benzene, and mild reagents and conditions are sufficient. These reactions normally occur at the 2-position rather than the 3-position, as shown in the following example.

a. Propose a mechanism for the acetylation of pyrrole just shown. You may begin with pyrrole and the acylium ion, CH3C≡O+. Be careful to draw all the resonance structures of the intermediate.

Pyrrole undergoes electrophilic aromatic substitution more readily than benzene, and mild reagents and conditions are sufficient. These reactions normally occur at the 2-position rather than the 3-position, as shown in the following example.

b. Explain why pyrrole reacts more readily than benzene, and also why substitution occurs primarily at the 2-position rather than the 3-position.

The following spectra for A and B correspond to two structural isomers. The NMR singlet at δ1.16 in spectrum A disappears when the sample is shaken with D₂O. The singlet at δ0.6 ppm in the spectrum of B disappears on shaking with D₂O. Propose structures for these isomers, and show how your structures correspond to the spectra. Show what cleavage is responsible for the base peak at m/z 44 in the mass spectrum of A and the prominent peak at m/z 58 in the mass spectrum of B.

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Guanidine (shown) is about as strong a base as hydroxide ion. Explain why guanidine is a much stronger base than most other amines.

Show why p-nitroaniline is a much weaker base (3 pK_b units weaker) than aniline.