2015 CH 420 Take Home Quiz 3 March 24

CH 420, Take-Home Quiz 3
Spring 2015
Name__________________________________
Section
11:30 am
1:30 pm
Only answers recorded in the boxes will be graded. For full credit, please ensure you draw all structures
accurately, indicating the appropriate regiochemistry, stereochemistry, and/or formal charges.
1) Assign the appropriate pKa value to each molecule below as 5, 9, 19, 25 or 30.
2) Draw an arrow to clearly indicate the most acidic site in each of the following compounds.
3) Which of the following carboxylic acids has the lowest pKa?
a.
b.
c.
d.
3-nitrobenzoic acid
4-nitrobenzoic acid
3-methoxybenzoic acid
4-methoxybenzoic acid
4) Cassava root is extensively cultivated and consumed in tropical and subtropical regions, though it must
be properly prepared to avoid toxicity due to breakdown of cyanogenic glucosides such as linamarin.
Enzymatic hydrolysis of linamarin releases glucose and a cyanohydrin. The cyanohydrin further breaks
down to two components, one of which is toxic (the same molecules are the precursors for cyanohydrin
formation). Complete the following scheme.
5) Histamine is synthesized in vivo via decarboxylation of the amino acid histadine. The reaction is
mediated by pyridoxyl phosphate (PLP), in which an imine (Schiff base) is first formed between histidine
and PLP. Decarboxylation occurs, followed by rearomatization of the pyridine ring. Subsequent imine
cleavage affords histamine and regenerates PLP.
N
HN
O
O
P
HO - O
O
PLP
H
N
CO2
O
OH
NH3
N
N
H
histidine
N
O
P
HO - O
O
O
OH
CO2
N
H
N
H
N
N
HN
HN
N
H+
N
O
P
HO - O
O
OH
N
H
NH2
histamine
N
O
P
HO - O
O
OH
O
O
P
HO - O
O
N+
H
PLP
OH
N
H
a. In the boxes above, clearly draw arrows to show the flow of all electrons.
b.
Indicate the general type of reaction (e.g. oxidation, reduction, hydration, dehydration, hydrolysis,
condensation, decarboxylation, rearrangement) that occurs for:
6) Indicate “yes” or “no”
whether each of the
compounds at right can
undergo racemization in
aqueous base or aqueous
acid.
Racemization can involve deprotonation to a sp2 hybridized carbanion followed by reprotonation on
either face or keto-enol tautomerization under acidic conditions.
7) Celebrex® is a non-steroidal
anti-inflammatory drug (NSAID)
that selectively inhibits
cyclooxygenase 2 (COX2). It is
synthesized by two successive
condensation reactions
followed by tautomerization to
the aromatic pyrazole ring.
Note the regioselectivity (one
could “flip” either substrate horizontally to see the other theoretical product). In the boxes above, draw
an arrow to the more nucleophilic nitrogen atom in the hydrazine substrate. In addition, circle the most
electrophilic carbonyl in the 1,3-diketone substrate.
8) The Wittig reaction is a powerful method of
preparing exocyclic olefins. Indicate the
appropriate reagent for transforming camphor
to its methylene derivative.
9) What byproduct is formed in Wittig reactions? Note this high molecular
weight compound is often difficult to remove from the desired olefination
product.
10) Acetals and ketals are often used as protecting groups in organic synthesis. Draw the ketal hydrolysis
products in the following reaction.
11) Circle which one of the following compounds undergoes decarboxylation upon heating.
12) By which mechanism does the base-catalyzed dehydration of a β-hydroxyketone proceed?
a.
b.
c.
d.
E1
E2
E1cB
None of
the above
13) Which cyclic anhydride will
react with cyclohexylamine to
afford the following amide?
14) Outline a 2-3 step synthesis of
phenylacetic acid from benzyl bromide.
There is more than one possible answer,
though indicate only one route.
Br
15) Indicate the most appropriate reaction conditions for the following transformations.
COOH
16) Complete the following schemes. Where more than one product is formed, indicate all products.
17) Circle which one of the following compounds preferentially exists in the enol tautomer.
18) Sodium valproate(Depakote®) is used for the treatment of epileptic seizures, bipolar disorder, migraine
headaches, and schizophrenia. Outline a synthesis of this drug from diethyl malonate. Specify the
appropriate equivalents of reagents.