Chapter Questions
Name the following compounds, using (i) numbers and (ii) Greek letters.
Write structures for ( $a$ ) 2-benzoylthiophene, (b) 3-furansulfonic acid, (c) $\alpha, \beta^{\prime}$-dichloropyrrole.
Account for the aromaticity of furan, pyrrole and thiophene which are planar molecules with bond angles of $120^{\circ}$
Account for the following dipole moments: furan, 0.7 D (away from O); tetrahydrofuran, 1.7 D (toward $\mathrm{O}$ ).
Pyrroles, furans, and thiophenes are made by heating 1,4-dicarbonyl compounds with $\left(\mathrm{NH}_4\right)_2 \mathrm{CO}_3, \mathrm{P}_4 \mathrm{O}_{10}$, and $\mathrm{P}_2 \mathrm{~S}_5$, respectively. Which dicarbonyl compound is used to prepare (a) 3,4-dimethylfuran;(b) 2,5-dimethylthiophene; (c) 2,3-dimethylpyrrole?
Prepare pyrrole from succinic anhydride.
Identify compounds (A) through (D).
Dilantin (5,5-diphenylhydantoin), an anticonvulsant drug used in the treatment of epileptic seizures, is a pyrrole with the molecular formula $\mathrm{C}_{15} \mathrm{H}_{12} \mathrm{~N}_2 \mathrm{O}_2$. What is the structural formula for Dilantin?
(a) In terms of relative stability of the intermediate, explain why an electrophile ( $\mathrm{E}^{+}$) attacks the $\alpha$ rather than the $\beta$ position of pyrrole, furan, and thiophene. (b) Why are these heterocyclics more reactive than $\mathrm{C}_6 \mathrm{H}_6$ to $\mathrm{E}^{+}$-attack?
Explain why pyrrole is not basic.
Give the type of reaction and the structures and names of the products obtained from: (a) furfural,and concentrated aq. $\mathrm{KOH}$; (b) furan with (i) $\mathrm{CH}_3 \mathrm{CO}-\mathrm{ONO}_2$ (acetyl nitrate), (ii) $\left(\mathrm{CH}_3 \mathrm{C}\right.$ $\mathrm{H}_2 \mathrm{O}$; (c) pyrrole with (i) $\mathrm{SO}_3$ and pyridine, (ii) $\mathrm{CHCl}_3$ and $\mathrm{KOH}$, (iii) $\mathrm{PhN}_2^{+} \mathrm{Cl}^{-}$, (iv) $\mathrm{Br}_2$ an and (i) $\mathrm{H}_2 \mathrm{SO}_4$, (ii) $\left(\mathrm{CH}_3 \mathrm{CO}\right)_2 \mathrm{O}$ and $\mathrm{CH}_3 \mathrm{COONO}_2$, (iii) $\mathrm{Br}_2$ in benzene.
Write structures for the mononitration products of the following compounds and explain their formation: (a) 3-nitropyrrole, (b) 3-methoxythiophene, (c) 2-acetylthiophene, (d) 5-methyl-2-methoxy-thiophene, (e) 5-methylfuran-2-carboxylic acid.
Give the Diels-Alder product for the reaction of furan and maleic anhydride.
Give the products of reaction of pyrrole with $(a) \mathrm{I}_2$ in aqueous $\mathrm{KI} ;(b) \mathrm{CH}_3 \mathrm{CN}+\mathrm{HCl}$, followed by hydrolysis; (c) $\mathrm{CH}_3 \mathrm{MgI}$.
Write the structural formulas and give the names of the isomeric methylpyridines.
(a) Account for the aromaticity of pyridine, a planar structure with $120^{\circ}$ bond angles. (b) Is pyridine basic? Explain. (c) Explain why piperidine (azacyclohexane) is more basic than pyridine. (d) Write the equation for the rection of pyridine with $\mathrm{HCl}$.
Explain why pyridine (a) undergoes electrophilic substitution at the $\beta$ position, and $(b)$ is less reactive than benzene.
How do the ${ }^1 \mathrm{H}$ nmr spectra of pyridine and benzene differ?
Compare and explain the difference between pyridine and pyrrole with respect to reactivity toward electrophilic substitution.
Predict and account for the product obtained and conditions used in nitration of 2-aminopyridine.
Explain why ( $a$ ) pyridine and $\mathrm{NaNH}_2$ give $\alpha$-aminopyridine, $(b)$ 4-chloropyridine and $\mathrm{NaOMe}$ give 4-methoxypyridine, $(c)$ 3-chloropyridine and $\mathrm{NaOMe}$ give no reaction.
(a) Toward $\mathrm{H}_3 \mathrm{O}^{+}:$2,6-dimethylpyridine (2,6-lutidine) $>$pyridine(b) Toward the Lewis acid $\mathrm{BMe}_3$ : pyridine $>2,6$-lutidine
Pyridine $N$-oxide is converted to pyridine by $\mathrm{PCl}_5$ or by zinc and acid. Use this reaction for the synthesis of 4-bromopyridine from pyridine.
Account for the fact that the $\mathrm{CH}_3$ 's of $\alpha$ - and $\gamma$-picolines (methylpyridines) are more acidic than the $\mathrm{CH}_3$ of toluene.
From picolines prepare (a) the vitamin niacin (3-pyridinecarboxylic acid), (b) the anti-tuberculosis drug isoniazide (4-pyridinecarboxylic acid hydrazide).
Name the following compounds:
(a) 1,3-diazine (pyrimidine); (b) 1,3-thiazole; (c) 1,4-diazine (pyrazine); (d) 1,2-oxazole; $(e$ ) imidazole.
Write the tautomeric structures of these pyrimidines.
(a) What makes imidazole (Prob. 20.30a) aromatic? (b) Explain why imidazole, unlike pyrrole, is basic. Which $\mathrm{N}$ is the basic site?
Which dicarboxylic acid is formed on oxidation of quinoline?The pyridine ring is more stable than the benzene ring [Problem 20.17(a)].
Quinoline is prepared by the Skraup reaction of aniline, glycerol and nitrobenzene. Suggest a mechanism involving Michael addition of aniline to an $\alpha, \beta$-unsaturated aldehyde, ring closure, and then dehydration and oxidation.
Give structures for the products of reaction of quinoline with (a) $\mathrm{HNO}_3, \mathrm{H}_2 \mathrm{SO}_4 ;(b) \mathrm{NaNH}_2 ;($ c $)$ PhLi.
Outline a mechanism for the Bischler-Napieralski synthesis of 1-methylisoquinoline from Nacetylphenylethylamine by reaction with strong acid and $\mathrm{P}_2 \mathrm{O}_5$, and then oxidation of the dihydroisoquinoline intermediate.
Supply systematic names for:
(a) 4-phenyl-1,2-oxazole, (b) 3-methyl-5-bromo-1,2,4-triazine-6-carboxylic acid, (c) 2,4-dimethyl-1,3-thiazole,(e) 1,2,3,4-thiatriazole, (e) 2,3-benzazole (indole).
Name the following compounds systematically:
(a) azole (pyrrole), (b) 1,3-thiazole, (c) 2H-oxirine, (d) 4H-oxirine (pyran), (e) 1,4-dithiazine, $(f)$ 1,3-diazine (pyrimidine).$2 H$ - and $4 H$ - are used in $(c)$ and $(d)$ to differentiate the position of the saturated $s p^3$ atom. Common names are given in parentheses.
Write structures for (a) oxirane, (b) 1,2-oxazole, (c) 1,4-diazine (pyrazine), (d) 1-thia-4-oxa-6azocine, (e) $3 H$-1,2,4-triazole, $(f)$ azepane.
How many thiophenyl-thiophenes (bithienyls) are possible?
Identify the compounds represented by Roman numerals.
(a) Quinoline $\stackrel{\mathrm{C}_6 \mathrm{H}_9 \mathrm{CO}_2 \mathrm{H}}{\longrightarrow} \mathrm{I} \stackrel{\mathrm{HNO}_3}{\longrightarrow}$ II $\stackrel{\mathrm{PCl}_3}{\longrightarrow}$ III(c) Furan (FuH) $\stackrel{\left(\mathrm{CH}_3 \mathrm{CO}_2\right)_2 \mathrm{O}}{\longrightarrow} \mathrm{I} \stackrel{\mathrm{NaOI}}{\longrightarrow}$ II $\stackrel{\text { fum. } \mathrm{H}_2 \mathrm{SO}_4}{\longrightarrow}$ III
Prepare (a) 3-aminopyridine from $\beta$-picoline, (b) 4-aminopyridine from pyridine, (c) 8-hydroxyquinoline from quinoline, $(d)$ 5-nitro-2-furoic acid from furfural, $(e)$ 2-pyridylacetic acid from pyridine.
(a) Explain why pyran [Problem 20.34(d)] is not aromatic. (b) What structural change would theoretically make it aromatic?
How can pyridine and piperidine be distinguished by infrared spectroscopy?
How can nmr spectroscopy distinguish among aniline, pyridine and piperidine?
From pyridine ( $\mathrm{PyH})$, 2-picoline (2-PyMe), and any reagent without the pyridine ring prepare ( $a$ ) 2-acetylpyridine, (b) 2-vinylpyridine, (c) 2-cyclopropylpyridine, (d) 2- $\mathrm{PyCH}_2 \mathrm{CH}_2 \mathrm{CH}_2 \mathrm{COOH}$, 2-PyC $(\mathrm{Me})=\mathrm{CHCH}_3,(f)$ 2-pyridinecarboxaldehyde. Any synthesized compound can be used in ensuing steps.
(a) Account for the aromaticity of $\alpha$ - and $\gamma$-pyridones. (b) Explain why $\alpha$-pyridone predominates over $\alpha$-pyridinol, especially in the solid state. (The same is true for the $\gamma$-tautomers.) (c) How can ir spectroscopy show which tautomer predominates?