Problem Set 5
Chapter 6
Due: Monday, February 20, 2006
1. The inversion of configuration in an
SN2 reaction is often called a Walden inversion,
named after its discoverer, Paul Walden. In the cycle shown
above, the overall conversion of one enantiomer of malic
acid to the other one must require an inversion of
configuration. Similarly, the same is true of the chloro
acids. More generally, each interconversion of enantiomers
must require an odd number of inversions. The
PCl5 reaction requires a single inversion which
means that the Ag2O reaction involves an even
number of inversions of configuration, namely two in this
instance. (-)-Malic acid is of the
(S)-configuration. a) Show how malic acid, like any alcohol,
might react with PCl5 and then undergo inversion
to form a chloride. Remember that phosphoric acid is a
strong acid and its conjugate base and analogs thereof are
also good leaving groups. b) Silver oxide is an anhydrous form of
AgOH. The carboxylic acid group closest to the hydroxyl
group plays a role in the process. The reaction medium is
mildly alkaline. c) Draw these four enantiomers as Fischer
projections. (-)-Malic acid is of the
(S)-configuration. 2. In each of the following reactions one
equivalent of each reactant competes for one equivalent of
reagent (over the arrow) in an SN2 reaction. Only
half of the reactants can react because of the limited
amount of reagent (two equivalents would be required for
complete reaction). Draw the structure of the major product
in each example and explain why it is formed preferentially.
Provide mechanisms (curved arrow formalism). a) Does the formation of tosylate
C from alcohol B involve an inversion of
configuration? Explain. b) How might tosylate C be formed
from tosyl chloride 1? Provide a
mechanism.
3. A student needs a sample of
(S)-2-octanethiol (A). She locates a bottle of
(S)-(+)-octanol (B). Unaware of any procedure to
transmute oxygen into sulfur nor aware of any procedure that directly
substitutes sulfur for oxygen with retention of configuration, she
launches a plan of her own. She prepares the tosylate C of the
alcohol B. When the tosylate was mixed with excess anhydrous
NaI in acetone, iodide D was isolated within a short period of
time. Iodide D was allowed to react with excess
Na2S, which formed (S)-A with an optical
rotation of [α]D=
+29.6o.
c) Using Table 6.4, explain why iodides are
formed from tosylates and not vice versa.
d) Provide mechanisms and configurations to illustrate the sequence of reactions C --> D --> A.
e) What is the optical purity of the mercaptan A (Chapter 6 and pg. 351)?
f) When the formation of the iodide was allowed to
proceed for twice as long, the optical purity of the derived
mercaptan was even less than when the reaction was run for a shorter
period of time. Explain and illustrate. 5. Provide the unknown product of each
reaction or provide an explanation for the results (5b). In
all cases, provide mechanisms and a rationale.
4. (3S,6S)-6-Chloro-3-octanol (A) forms
optically inactive B (C8H16O) upon
exposure to aqueous NaOH. A stereoisomer of A, namely,
C also forms B under the same conditions. Two other
stereoisomers of A, namely D and E as a 50/50
mixture, form optically inactive F, a diastereoisomer of
B. What are the structures of A-F. Expalin and
illustrate with mechanisms.