CHEM 344 Summer 2023 Final Exam (200 pts)
Name:
TA Name:
Exam Length = 120 min
DO NOT REMOVE ANY PAGES FROM THIS EXAM PACKET.
Directions for drawing molecules, reactions, and electron-pushing mechanisms:
Draw all lone pairs, bonds, arrows, formal charges, and stereochemistry explicitly in all molecular
structures.
Take care when drawing molecules and labeling them with NMR assignments that you do not change the
chemical formula. Examples for 2-methyl-2-butanol are shown below.
acceptable acceptable acceptable unacceptable unacceptable
Directions for all calculations:
Explicitly show all work on all calculations and include all important labels.
1
,1) The nitration of 4-methylaniline (p-toluidine) is carried out under two different sets of reaction
conditions, resulting in two different regioisomeric products (X and Y). Use the provided spectra and
structures to rationalize the different outcomes. (90 pts total)
Experimental procedure for synthesis of product X: In a 25 mL round bottom flask, 4-methylaniline (107
mg, 1.0 mmol) is dissolved in conc. H2SO4 (0.3 mL). The mixture is cooled in an ice-water bath and conc.
HNO3 (0.3 mL) is added drop-wise. Upon complete addition of HNO3, the reaction mixture is warmed to
room temperature and stirred for 15 min. The reaction mixture is poured into ice-cold aq. 40% NaOH
solution (~5 mL) and the yellow solid isolated by filtration and washed with ice-cold water (2 × 5 mL). The
crude product is recrystallized from 95% aq. ethanol solution. Purified product X is isolated by vacuum
filtration.
a) In the reaction to produce X, the nitration reagents are added directly to 4-methylaniline. Before an
EAS reaction can proceed, an acid-base reaction occurs between 4-methylaniline and the nitric/sulfuric
acid mixture. Provide a balanced chemical equation (not an electron-pushing mechanism) for the
reaction of 4-methylaniline with nitric acid. Use a pKa table to provide an estimate of the pKa of each
acid in the balanced chemical equation and indicate the dominant side of the equilibrium by using
appropriate reaction arrows. (6 pts)
b) The N-atom lone pair in 4-methylaniline (like other aniline derivatives) is less basic than typical N-
atom lone pairs on aliphatic amines. Draw an electron-pushing mechanism for the deprotonation of
each protonated amine shown below with hydroxide ion. Explain the reduced basicity of aniline relative
to cyclohexylamine using the pKa values provided for the two protonated species. (10 pts)
2
, c) The nitration of an aromatic molecule such as 4-methylaniline requires the generation of a strong
electrophile. Provide an electron-pushing mechanism depicting the generation of the appropriate
electrophile from nitric and sulfuric acids. (4 pts)
d) The mono-nitration of 4-methylaniline under acidic conditions occurs primarily from protonated 4-
methylaniline. Use the structures and B3LYP energies of the two arenium cation intermediates to draw
a potential energy surface (PES) for the rate-determining step of the nitration reaction. Clearly label
the relative energies (kcal/mol) of the two intermediates on the energy surface, identify and label the
feature(s) on the PES responsible for the observed regioselectivity, and clearly identify the pathway that
leads to the major product. (12 pts)
Intermediate A Intermediate B
-333774.28 kcal/mol -333768.53 kcal/mol
3
Name:
TA Name:
Exam Length = 120 min
DO NOT REMOVE ANY PAGES FROM THIS EXAM PACKET.
Directions for drawing molecules, reactions, and electron-pushing mechanisms:
Draw all lone pairs, bonds, arrows, formal charges, and stereochemistry explicitly in all molecular
structures.
Take care when drawing molecules and labeling them with NMR assignments that you do not change the
chemical formula. Examples for 2-methyl-2-butanol are shown below.
acceptable acceptable acceptable unacceptable unacceptable
Directions for all calculations:
Explicitly show all work on all calculations and include all important labels.
1
,1) The nitration of 4-methylaniline (p-toluidine) is carried out under two different sets of reaction
conditions, resulting in two different regioisomeric products (X and Y). Use the provided spectra and
structures to rationalize the different outcomes. (90 pts total)
Experimental procedure for synthesis of product X: In a 25 mL round bottom flask, 4-methylaniline (107
mg, 1.0 mmol) is dissolved in conc. H2SO4 (0.3 mL). The mixture is cooled in an ice-water bath and conc.
HNO3 (0.3 mL) is added drop-wise. Upon complete addition of HNO3, the reaction mixture is warmed to
room temperature and stirred for 15 min. The reaction mixture is poured into ice-cold aq. 40% NaOH
solution (~5 mL) and the yellow solid isolated by filtration and washed with ice-cold water (2 × 5 mL). The
crude product is recrystallized from 95% aq. ethanol solution. Purified product X is isolated by vacuum
filtration.
a) In the reaction to produce X, the nitration reagents are added directly to 4-methylaniline. Before an
EAS reaction can proceed, an acid-base reaction occurs between 4-methylaniline and the nitric/sulfuric
acid mixture. Provide a balanced chemical equation (not an electron-pushing mechanism) for the
reaction of 4-methylaniline with nitric acid. Use a pKa table to provide an estimate of the pKa of each
acid in the balanced chemical equation and indicate the dominant side of the equilibrium by using
appropriate reaction arrows. (6 pts)
b) The N-atom lone pair in 4-methylaniline (like other aniline derivatives) is less basic than typical N-
atom lone pairs on aliphatic amines. Draw an electron-pushing mechanism for the deprotonation of
each protonated amine shown below with hydroxide ion. Explain the reduced basicity of aniline relative
to cyclohexylamine using the pKa values provided for the two protonated species. (10 pts)
2
, c) The nitration of an aromatic molecule such as 4-methylaniline requires the generation of a strong
electrophile. Provide an electron-pushing mechanism depicting the generation of the appropriate
electrophile from nitric and sulfuric acids. (4 pts)
d) The mono-nitration of 4-methylaniline under acidic conditions occurs primarily from protonated 4-
methylaniline. Use the structures and B3LYP energies of the two arenium cation intermediates to draw
a potential energy surface (PES) for the rate-determining step of the nitration reaction. Clearly label
the relative energies (kcal/mol) of the two intermediates on the energy surface, identify and label the
feature(s) on the PES responsible for the observed regioselectivity, and clearly identify the pathway that
leads to the major product. (12 pts)
Intermediate A Intermediate B
-333774.28 kcal/mol -333768.53 kcal/mol
3
