26. Amines

Rank the following substituted anilines from most basic to least basic:

Draw the product formed when pyridine reacts with ethyl bromide

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.

Basicity depends on availability of an electron pair to bond a proton. Correlate structural effects in these amines with their basicities.

(c) The pK_b of this compound is −2.3, making it not only a stronger base than a typical aniline, but even stronger than hydroxide ion. Explain its remarkable basicity.

Within each structure, rank the indicated nitrogens by increasing basicity.

(f)

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.

Within each structure, rank the indicated nitrogens by increasing basicity.

(c)

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.

Addition of one equivalent of ammonia to 1-bromoheptane gives a mixture of heptan-1-amine, some dialkylamine, some trialkylamine, and even some tetraalkylammonium bromide.

(a) Give a mechanism to show how this reaction takes place, as far as the dialkylamine. 

(b) How would you modify the procedure to get an acceptable yield of heptan-1-amine?

In each pair of compounds, select the stronger base, and explain your choice.

(a) HOCH₂CH₂NH₂ or CH₃CH₂NH₂

(b) PhNH₂ or PhCH₂NH₂

What is the major product of the following reactions?

c.

In Section 10.12, we saw that S-adenosylmethionine (SAM) methylates the nitrogen atom of noradrenaline to form adrenaline, a more potent hormone. If SAM methylates an OH group attached to the benzene ring instead, it completely destroys noradrenaline's activity.

b. Which reaction is more apt to occur, methylation on nitrogen or methylation on oxygen?

Which of the following compounds are capable of being resolved into enantiomers?

(d) 1,2,2-trimethylaziridine

(e)

(f)

Rank the amines in each set in order of increasing basicity.

(d)

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