Amines

Synthesize each compound from benzene. Use a diazonium salt as one of the synthetic intermediates.

Rank the following compounds in order of increasing basicity and explain the order you choose.

Draw the product Y of the following reaction sequence. Y was an intermediate in the remarkable synthesis of cyclooctatetraene by Wilstatter in 1911.

Devise a synthesis of each compound from the given starting material(s). Albuterol is a bronchodilator and proparacaine is a local anesthetic.

a.

b.

Heating compound X with aqueous formaldehyde forms Y \(\left( {{{\bf{C}}_{{\bf{17}}}}{{\bf{H}}_{{\bf{23}}}}{\bf{NO}}} \right)\),which has been converted to a mixture of lupinine and epilupinine, alkaloids isolated from lupin, a perennial ornamental plant commonly seen on the roadside in parts of Alaska (Section 25.10). Identify Y and explain how it is formed.

Question: Label the stereogenic centers in each compound.

a.

b.

Question: Name each amine.

a.

b.

c.

d.

e.

f.

Question: Draw a structure corresponding to each name.

a. 2,4-dimethylhexan-3-amine

b. N-methylpentan-1-amine

c. N-isopropyl-p-nitroaniline

d. N-methylpiperidine

e. N,N-dimethylethanaminef. 2-aminocyclohexanoneg. N-methylanilineh. m-ethylaniline

Question: Arrange the compounds in order of increasing boiling point.

Question: What is the structure of an unknown compound with molecular formula C₆H₁₅N  that gives the following ¹H NMR absorptions: 0.9 (singlet, 1 H), 1.10 (triplet, 3 H), 1.15 (singlet, 9 H), and 2.6 (quartet, 2 H) ppm?

Question: LSD (a hallucinogen) and codeine (a narcotic) are structurally more complex derivatives of 2-phenylethanamine. Identify the atoms of 2-phenylethanamine in each of the following compounds.

a.

b.

Question: Draw the product of each reaction.

a.

b.

Question: What alkyl halide is needed to prepare each 1° amine by a Gabriel synthesis?

a.

b.

c.

Question: Which amines cannot be prepared by a Gabriel synthesis? Explain your choices.

a.

b.

c.

d.

Question: What nitro compound, nitrile, and amide are reduced to each compound?

a.

b.

c.

What amine is formed by reduction of each amide?

a.

b.

c.

Which amines cannot be prepared by reduction of an amide?

a.

b.

c.

d.

Question: Draw the product of each reaction.

a.

b.

c.

d.

Question: Enalapril, a drug used to treat hypertension, is prepared from compounds D and E by reductive amination. What is the structure of enalapril?

Question: a. Explain why phentermine $\left[{\mathrm{phCH}}_2\mathrm{C}{\left({\mathrm{CH}}_3\right)}_2{\mathrm{NH}}_2\right]$  can't be made by a reductive amination reaction.

b. Give a systematic name for phentermine, one of the components of the banned diet drug fen–phen.

Question: What starting materials are needed to prepare each drug using reductive amination? Give all possible pairs of compounds when more than one route is possible.

a.

b.

Question: Draw the products of each acid–base reaction. Indicate whether equilibrium favors the reactants or products.

a.

b.

c.

Question: Write out steps to show how each of the following pairs of compounds can be separated by an extraction procedure.

a.   

and

b.

and

Question: Which compound in each pair is more basic:

a. ${\left({\mathrm{CH}}_3\right)}_2\mathrm{NH} \mathrm{and} {\mathrm{NH}}_3$ 

b. ${\mathrm{CH}}_3{\mathrm{CH}}_2{\mathrm{NH}}_2 \mathrm{and} {\mathrm{ClCH}}_2{\mathrm{CH}}_2{\mathrm{NH}}_2$ ?

Question: Rank the compounds in each group in order of increasing basicity.

a.

b.

Question: Rank the following compounds in order of increasing basicity

Question: Which nitrogen atom in each compound is more basic?

a.

b.

Question: Which N atom in each compound is more basic? What product is formed when each compound is treated with HCl?

a.

b.

Question: Draw the products formed when each carbonyl compound reacts with the following amines:

1. CH₃CH₂CH₂NH₂

2.(CH₃CH₂)₂NH

a.

b.

c.

Question: Devise a synthesis of each compound from aniline (C₆H₅NH₂₎

a.

b.

Question: Draw the product formed by treating each compound with excess CH₃I , followed by Ag₂O , and then heat.

a.

b.

c.

Question: Draw the product formed by treating each compound with excess CH₃I , followed by Ag₂O, and then heat.

a.

b.

c.

Question: Draw the major product formed in each reaction.

a.

b.

c.

d.

Question: Draw the product formed when each compound is treated with NaNO₂ and HCl.

a.

b.

c.

d.

Question: Draw the product formed in each reaction.

a.

b.

c.

d.

Question: Devise a synthesis of each compound from benzene.

a. 

b.

c.

d.

Question: Draw the product formed when C6H5N2+Cl– reacts with each compound.

a.

b.

c.

Question: What starting materials are needed to synthesize each azo compound?

a.

b.

Question: (a) What two components are needed to prepare para red by azo coupling? (b) What two components are needed to prepare alizarine yellow R?

Question: Give a systematic or common name for each compound.

Question: Which compound is the stronger base?

Question: Varenicline (trade name Chantix) is a drug used to help smokers quit their habit. 

(a) Which N atom in varenicline is most basic? Explain your choice. 

(b) What product is formed when varenicline is treated with HCl?

Question: Give a systematic or common name for each compound.

a.

b.

c.

d.

e.

f.

g.

h.

Question: Draw the structure that corresponds to each name. 

1. N-isobutylcyclopentanamine 
2. tri-tert-butylamine 
3. N, N-diisopropylaniline 
4. N-methyl pyrrole
5. N-methylcyclopentanamine
6. 3-methylhexan-2-amine
7. 2-sec-butylpiperidine
8. (S)-heptan-2-amine

Question: How many stereogenic centers are present in the following tetraalkylammonium salt? Draw all possible stereoisomers.

Rank the compounds in each group in order of increasing basicity.

(a)

(b)

Decide which N atom in each molecule is most basic and draw the product formed when each compound is treated with $C{H}_{3}C{O}_{2}H$ . Zolpidem (trade name Ambien) is used to treat insomnia, whereas aripiprazole (trade name Abilify) is used to treat depression, schizophrenia, and bipolar disorders.

(a)

(b)

Explain why pyrimidine is less basic than pyridine

Rank the nitrogen atoms in each compound in order of increasing basicity. Isoniazid is a drug used to treat tuberculosis, whereas histamine causes the runny nose and watery eyes associated with allergies. 

Explain why m-nitroaniline is a stronger base than p-nitroaniline