Massachusetts Institute of Technology

Organic Chemistry 5.12

February 7, 2011
Prof. Rick L. Danheiser
Problem Set #1

Due by Noon, Tuesday February 15

(1) For compounds with the molecular formula CH4N2

(a) Calculate the number of valence electrons
(b) Calculate the number of degrees of unsaturation
(c) Draw all reasonable Lewis structures, showing lone pair (unshared) electrons
and formal charges.
(d) Do stereoisomers exist for any of these Lewis structures? For the purposes of this problem,
assume that there is no inversion at sp3 nitrogen atoms.

(2) RDX ("cyclonite") is a powerful high explosive that was

used extensively in World War 2. Today it is widely used
as the main component of plastic explosives such as C-4 O O
N
and Semtex. Professor John Sheehan of MIT (who we
previously mentioned in connection with his development N
of the first synthesis of penicillin) was also involved in the
development of the method used to prepare RDX during O N N O
the Second World War while working in the laboratory of N N
Werner Bachmann. Shown to the right is a representation O O
of the structure of RDX. Calculate the number of valence
electrons and then complete this Lewis structure by filling
in all of the lone pair electrons and formal charges.

From J. Am. Chem. Soc. 1949, 71, 1842:

This material may not be reproduced or posted on an internet website without written permission of Professors Danheiser and Jamison.
(3) You may recognize the following molecules from our discussion of the "Top Ten Reasons Organic
Chemistry is Important to MIT Students". For each molecule, provide (a) its molecular formula, (b)
calculate the number of degrees of unsaturation (show your work), (c) identify all tetrahedral
carbon atoms that are stereogenic centers in the molecule and assign the configuration at each as R
or S, and (d) indicate whether the molecule is chiral or achiral. For the purposes of this problem,
assume that there is rapid inversion at sp3 nitrogen atoms (i.e., nitrogen atoms are not stereogenic
centers).
O
N H3CO
N
(a) (d) H

H3C N CH3 HO

2,6-dimethylpyrazine capsaicin

O CH3
(b)
CH3 N
isooctane N
(e)
O N N
O caffeine
CH3
CH3
(c)
(f) O
H H
S
N CH3
H
NH2 N CH3
O
muscone
penicillin O
HO

(4) For isooctane, muscone, and caffeine, indicate the hybridization and approximate bond angle at
each carbon atom.

(5) Identify all of the functional groups in the structure of penicillin above, ignoring the sulfur atom.

(6) Draw the structures of all of the reasonable molecules with the molecular formula C5H8. Do not
worry about conformational isomers differing by rotation about single bonds. Indicate which
molecules are chiral. This problem will provide you with lots of practice thinking about all of the
varieties of isomers we have studied in this unit. Don't give up too soon - there are over 30
different isomers associated with this formula!
(7) For each of the following pairs of structures, indicate whether or not they are expected to have the
same physical properties (e.g., boiling point, melting point, and density).

F Cl F Cl
(a) F F

F
F
NH2 NH2
Cl Cl

(b) (d) H3C H H3C H

H3C H H CH3

Br Br Br Br

H3C H H3C H
(c) F H
H3C H Cl H
(e) H3C H F CH3
Cl CH3
H3C H H Br

Br CH3

(8) Indinivar, trade name Crixovan, was one of the first protease inhibitors introduced for the treatment
of AIDS. This drug was invented by organic chemists at the Merck Pharmaceutical Company and
represented a huge advance in the treatment of people infected with HIV. Protease inhibitors act
by binding to and blocking the action of an enzyme (HIV protease) that cleaves viral polyproteins
into active proteins prior to the replication of the virus.

(a) How many tetrahedral carbon atoms

that are stereogenic centers are there in the
structure of indinivar? Label the
configuration of each as R or S. N OH
OH
H
(b) How many stereoisomers are possible N N
N
for this compound? For the purposes of this
problem, assume that there is rapid O
O N
inversion at sp3 nitrogen atoms (i.e., H
nitrogen atoms are not stereogenic centers).
(c) Draw the structures of two molecules
that are diastereomers of indinivar and label
each stereogenic center as R or S.
(d) Draw the structure of the enantiomer of
indinivar and label each stereogenic center
as R or S.
(9) Indicate whether each of the following molecules is chiral or achiral.

H3C
(a) e)

(b) H3C
(f) H
CH3
H

Br
(c)
(g) H
C C C
Br
H
O
(d) HO
CH3

(10) Carry out a conformational analysis of 2-methylpentane.

(a) Sighting along the C(2)-C(3) bond, draw Newman projections for the conformations of
minimum and maximum energy (there should be six conformations total).
(b) Calculate the relative energy of each conformation. In performing this calculation,
assume that interactions involving ethyl groups have the same magnitude as those involving
methyl groups. In other words, Me-H interactions have the same magnitude as Et-H,
Et-Me the same as Me-Me, etc.
(c) Construct a graph of energy vs. dihedral angle using the values determined in (b) above.
(d) Label conformations as anti, gauche, staggered, and eclipsed.
(e) What is the barrier to rotation about the C(2)-C(3) bond?

2
3
(11) Trans-cyclooctene (C8H14) is chiral! This surprising fact was verified in 1963 when Professor
Arthur C. Cope of MIT prepared trans-cyclooctene in optically active form (as one pure
enantiomer) for the first time. Explain how it is possible that this remarkable compound is chiral.
You may find it helpful to construct molecular models in thinking about this prolem.

Arthur C. Cope
1909-1966

From J. Am. Chem. Soc. 1963, 85, 3276:

(12) A challenging thought problem! Hemoglobin has the molecular formula

C2954H4516N780O806S12Fe4. It has been suggested that in a sample of hemoglobin (e.g., the
amount in one drop of blood, ca. 1017 hemoglobin molecules), in which all of the molecules
have the same conformation, nonetheless, no two molecules of hemoglobin are actually truly
identical. Suggest what is the basis for this surprising statement. Hint: if you are stumped,
consider what Frederick Soddy might say.