Scratch Paper – Page A

Midterm Exam 1
Chem 3B, Spring 2019
Monday, March 4, 2018
7:00 – 9:00 pm
You have 120 minutes to complete this exam.

Please provide all answers in the space provided. Work drawn

in the margins may not be picked up by the scanner and
therefore will not be graded.

Point values are listed within each question. The exam is worth
200 points total.

This Page is Scratch Paper

Please tear this cover page and the next page (amino acid chart) off at the start of the exam. They will not be
collected, scanned, or graded, so make sure your answers are copied into the appropriate location on your exam.

Chemistry 3B Spring 2019 Midterm Exam #1

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Chemistry 3B Spring 2019 Midterm Exam #1

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Chemistry 3B Spring 2019 Midterm Exam #1

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Chemistry 3B Spring 2019 Midterm Exam #1

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1. Nitriles
A. Complete the acid-base reaction scheme and Keq calculation shown below. (10 pt)
B. Write the names of the functional groups for the base, conjugate base, and conjugate acid. (6 pt)

C. Describe the structure-basicity relationship that is illustrated by the reaction scheme above (an answer
based on pKa data is not sufficient.) (3 pt)

D. Draw a curved arrow mechanism for the reaction below. Your mechanism must account for all products
shown and include the major resonance contributor of each intermediate (where relevant). (10 pt)

Chemistry 3B Spring 2019 Midterm Exam #1

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E. Draw a curved arrow mechanism for the reaction below. Your mechanism must account for all products
shown and include the major resonance contributor of each intermediate (where relevant). (10 pt)

F. Fill in the missing reagents and structures in the following multistep synthesis schemes. Assume that only
one major product forms in each reaction. Do not include side products. Do not combine multiple reaction
steps in a single box (no numbered steps within a box) (12 pt)

G. Predict all organic product(s) from the following reactions. (8 pt)

Chemistry 3B Spring 2019 Midterm Exam #1

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2. Peptide Synthesis
A. Fill in the missing reagents and structures in the following synthesis scheme. Do not combine multiple
reaction steps in a single box (no numbered steps within a box). (8 pt)
B. Name the peptide product using 3-letter codes. (6 pt)

HO O O O

H2 N HN 1. H2 N
NH O
O F3 C OH
O O Cy O O
N C N
Cy O 2. O
NaOH
N O (excess) N O
H H
+ H2 N H2 N
O NH NH2
H
O N O O
O O O
O NH2 Gln-Lys

(name using 3-letter codes)

C. Fill in one multiple-choice circle per row to indicate the hybridization of each lone pair. (6 pt)

D. Choose which pH corresponds to the protonation state of the structure on the left, and complete the
drawing on the right to show the predominant protonation state at pH = 7. (6 pt)

H2N
H3N
O
O
O
N O O
H pH = 7 HN O
H2N
NH2
H2N
O NH3
protonation state at O
pH = 1 protonation state at pH = 7
pH = 12 (complete the drawing)

Chemistry 3B Spring 2019 Midterm Exam #1

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3. Valinomycin, pictured below, is an antibiotic produced by the bacteria Streptomyces fulvissimus.
A. Write names of the two types of carbonyl-containing functional groups present in Valinomycin. (4 pt)

B. If valinomycin is heated at high temperature with excess aqueous acid, a total of four different hydrolysis
products are formed.
i. Predict the organic products of Reaction X, including stereochemistry. (10 pt)
ii. For each product, choose if it is an amino acid or not. If it is, name it with a 3-letter code (including
stereochemistry). Leave the name box blank for structure(s) that are not amino acids. (4 pt)

C. If valinomycin is heated at moderate temperature with catalytic aqueous acid (instead of high
temperature and excess acid), a different set of products is expected (Reaction Y). On the valinomycin
structure below, label all reactive electrophilic sites with an “E”. Circle each labelled atom. Leave
blank all sites that will not react under these conditions. (4 pt)

Chemistry 3B Spring 2019 Midterm Exam #1

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D. Phospholipids (phosphoglycerides) are the major component of lipid bilayer membranes. Draw a
“phosphatidylethanolamine” in the predominant protonation state expected at neutral pH. (8 pt)
i. The phospholipid should be derived from two “monounsaturated” fatty acids
ii. The phospholipid “head group” derived from the hydroxyl of ethanolamine (the structure of
ethanolamine is provided at the left below)

O
ethanolamine
"phospho" monounsaturated
O
protonation O
O
OH states at O O
H2 N pH = 7 H3 N P O
ethanolamine O "glyceride"

phosphatidylethanolamine derived from monounsaturated fatty acids at pH 7

E. Valinomycin acts as a transporter of potassium ions through lipid bilayer membranes.1 The valinomycin-
potassium complex travels through the non-polar middle of the lipid bilayer. Illustrate this transport
ability by adding the following items to the drawing below and clearly labelling the interactions. (6 pt)
i. A potassium ion participating in at least three favorable interactions with valinomycin
ii. A phospholipid favorably interacting with valinomycin to explain travel through the non-polar middle
of the lipid bilayer membrane. (You can choose to abbreviate any non-interacting parts of the
phospholipid.)

H
N O
O
O O NH
O O
R HN
O
phospholipid O O
O K
O O

NH
HN O O
O
O
O
O
favorable NH
non-polar (ID-
ID)
interaction(s)

(Add a potassium ion and an abbreviated phospholipid to this drawing)

(label the interactions)

1
Urry D.W. (1985) Chemical basis of ion transport specificity in biological membranes. In: Biomimetic and Bioorganic Chemistry.
Topics in Current Chemistry, vol 128. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-15136-2_7
Chemistry 3B Spring 2019 Midterm Exam #1
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4. Synthesis and use of “Boc Anhydride” (Di-tert-butyl dicarbonate)2
A. Add curved arrows to Reaction A. (4 pt)

O Reaction A O
C (add curved arrows)
O 0 °C O O
O

B. Reaction A is favorable, but becomes less favorable at higher temperatures. Explain why. (6 pt)

C. Draw a curved arrow mechanism for Reaction B. (10 pt)

D. Provide two different explanations (picture(s) and a few words) for why Reaction B is favorable. The
first explanation should use the ideas of “carbonyl resonance stabilization” and “electrophilicity”, and
the second should use the idea of “nucleophile basicity vs. leaving group basicity”. (8 pt)

2
Org. Synth. 1977, 57, 45
Chemistry 3B Spring 2019 Midterm Exam #1
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E. Draw a curved arrow mechanism for Reaction C, using the tertiary amine as a catalytic nucleophile that
starts by attacking the central carbonyl. (10 pt)
(Note: there is more than one possible reasonable mechanism. You only need to draw one of them.)

F. Use mostly structure drawing(s) and a few words to explain why a secondary amine could not be used
instead of the tertiary amine as a catalyst in Reaction C. (3 pt)

G. Circle and label functional groups in the starting structure for Reaction D to explain why the common
name of this reactant is “Boc Anhydride” (4 pt)
H. Predict all products of the following selective reaction (Reaction D). Make sure that the equation is
balanced. Include stereochemistry. (6 pt)
anhydride
Boc Boc
NH2 H
O O N O
OH
Reaction D CO2
O O O + N O
N
O
O
(1 equiv)
(circle and label to explain
names "Boc" and "Anhydride") (balanced equation products)

Chemistry 3B Spring 2019 Midterm Exam #1

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5. Carboxylic Acid Reductase Enzymes
Carboxylic acid reductases (CARs) are enzymes that catalyze the reaction shown below. They have two
different active sites, one for each reaction in the sequence below. The intermediate in the reaction scheme
below is covalently attached to the enzyme and rotates to move from one active site to the next.3

A. Name the functional groups in the reaction scheme below (below each structure). (8 pt)
B. Classify each reaction in the sequence (below each reaction arrow). (4 pt)

C. The first reaction in the sequence above uses adenosine triphosphate (ATP) as a reactant and has an acyl-
AMP intermediate. Select the multiple choice options to balance the equation, and draw the acyl-AMP
intermediate. (6 pt)

D. The second reaction in the sequence uses NADPH as a reactant and has an alkoxide intermediate. Draw the
structure of NADP+, select the multiple choice options to balance the equation, and draw a curved arrow
mechanism for the reaction. (10 pt)

3
Winkler, M. Carboxylic acid reductase enzymes (CARs). Curr. Opin. Chem. Biol. 43, 23–29 (2018).
Chemistry 3B Spring 2019 Midterm Exam #1