5. Equatorial vs. axial substituents in cyclohexane. For G-cyclohexane, where G = -Me, -F, -OH, -NH2, -BH2, what are the relative energies of the two conformations? How do these compare with the experimentally determined A-values? What is the steric effect of lone-pairs on the heteroatoms?
16.
Do a complete conformational analysis of monoalkylcyclohexanes with R =
Me, Et, iPr, tBu. Calculate relative energies of axial vs. equatorial
conformations; be sure to include both of the completely staggered conformations
for Et and iPr, in both axial and equatorial conformations. Do the axial/equatorial
energy differences calculated for the series methyl, ethyl, isopropyl agree
with expectations? Discuss fully.
[Booth, H.; Everett, J. R. J. Chem. Soc., Perkin Trans 2
1980, 255;
Squillacote, M. E. J. Chem. Soc., Chem. Commun. 1986, 1406.]
20.
Do the complete conformational analysis of the 1,2,3,4- tetramethylcyclohexanes
(six isomers) plus an estimation of the 1,3- diaxial CH3/CH3
interaction.
[Mann, G.; Werner, H.; Miethe, D.; Mühlstädt, M. Tetrahedron 1972, 28, 1839.]
21. Do the complete
conformational analysis of the 1,2,4,5- tetramethylcyclohexanes (five isomers)
plus an estimation of the 1,3- diaxial CH3/CH3 interaction.
[Allinger, N. L.; Pamphilis, N. A. J. Org. Chem. 1971, 36, 3437.]
25. Do the conformational
analysis of all-trans-1,2,3,4,5,6- hexaalkylcyclohexanes. For R = CH3,
it is alleged that the all equatorial conformation is more stable than
the all axial, but that R = CH(CH3)2 exists preferentially
as the all axial structure. Calculate the geometries and energies of the
all equatorial and all axial conformations of R = methyl, ethyl, and isopropyl.
[Goren, Z.; Biali, S. E. J. Am. Chem. Soc. 1990,
112, 893;
Golan, O; Goren, Z.; Biali, S. E. Ibid. 1990, 112,
9300.]
103. (R)-(-)-a-Phellandrene
(shown to the right) can have its isopropyl group axial or equatorial;
for each of these situations, there are three staggered conformations for
rotation about the ring carbon to isopropyl carbon bond. Calculate the
energy of all six conformations as well as the "skew" angle for
the diene unit; compare your results with those in the cited article.
[Araki, S.; Sakakibara, K.; Hirota, M.; Nishio, M.; Tsuzuki, S.; Tanabe, K. Tetrahedron Lett. 1991, 32, 6587.]
111. In many cases,
the axial/equatorial energy difference for single substituents is additive
when two substituents are placed on a cyclohexane ring. Recent evidence
(see the cited reference) suggests that this may not hold for 1-alkyl-1-
arylcyclohexanes. You should calculate the axial/equatorial energy differences
for mono-methyl, -tert-butyl, and -phenyl cyclohexane (R1
= substituent, R2 = H) and for the various 1,1-disubstituted
compounds: R1 = methyl, R2 = t-butyl; R1
= methyl, R2 = phenyl; and R1 = t-butyl, R2
= phenyl. Determine if the single-substituent values are or are not additive;
discuss any discrepancies found.
[Juaristi, E. Introduction to Stereochemistry and Conformational Analysis; Wiley: New York, 1991; p 265.]
127. The set of
conformations (to the right) has been investigated by a version of MM.
Note that when R = H, the four structures are the same. When R = CH3,
the structures are different: 1 and 2 have an equatorial
methyl, but differ in whether the axial substituent from Ring A is CHR
(1) or CH2 (2); similarly, 3 and 4
have axial methyl, but differ in whether the axial substituent on ring
A is CHR (3) or CH2 (4). The cited reference has
several tables with all of the bond distances, angles, dihedral angles,
and energies. Your job is to do a complete MMX analysis of the parent compound
(R = H) and of the four mono-methyl conformations shown; discuss the factors
responsible for the relative energies of the conformations. [Note: this
problem is quite similar to the spiroacetal problem number 122.]
[Varnali, T. J. Molec. Struct. 1992, 268, 181.]
129. Consider the
conformational equilibrium between equatorial (1) and axial (2)
adamantylcyclohexane. In the cited reference, it is alleged that the normal
balance (equatorial more stable) can be reversed by having large U-shaped
groups which can destabilize the equatorial more than the axial. The article
offers a 50- carbon molecule (see 4 in the reference) as an example.
In this MMX problem, see if much smaller molecules (such as 3 with
R = H or CH3 or C(CH3)3) can also be examples;
use your imagination - try other crowded molecules, along the lines suggested
in the paper.
[Biali, S. E. J. Org. Chem. 1992, 57, 2979.]
130.
Those who do Problem 16 on the axial/equatorial energy
differences for the series R = Me, Et, iPr, tBu will find the "surprising"
result that the first three are essentially the same (1.78, 1.82, and 1.72
kcal/mol, respectively) and that the fourth is very large (5.00 kcal/mol).
In the cited reference, it is stated "Even though CF3 is
thought of as a small group, it is significantly larger than CH3
..." The present MMX Problem is to calculate the axial/equatorial
energy differences for the perfluoroalkyl groups ranging from R = CF3
to C(CF3)3, and to compare the answers with those
for the non-fluorinated alkyl groups (available on request). Be sure to
do calculations on two different staggered conformations for both C2F5
and C3F7 in both their axial and equatorial conformations.
[Allen, A. D.; Krishnamurti, R.; Prakash, G. K. S.; Tidwell, T. T. J. Am. Chem. Soc. 1990, 112, 1291.]
131. An assumption
in conformational analysis is that axial/equatorial energy differences
for a single substituent can be applied to molecules in which that same
substituent competes with others (the principle of additivity). Using MMX,
calculate the relative conformational energies of the chair conformations
of cis-1,4-disubstituted cyclohexanes having "symmetrical" groups
of very different size (R = CH3 and R' = t-Bu; R = CF3
and R' = C(CF3)3) and of quite similar size (R =
CH3 and R' = CF3; R = t-Bu and R' = C(CF3)3.
Compare the results with those obtained based on simple additivity arguments
and discuss any differences; the MMX equatorial preferences (in kcal/mol)
for single substituents [Problems 16 and 130]
are: CH3 1.78; t-Bu 5.00; CF3 2.87; C(CF3)3
6.28.
132. Do exactly the
same as in Problem 131, but now for the cis-1,2-disubstituted cyclohexanes
in which steric interactions between the substituents (in addition to between
each substituent and the ring) should become significant. Do the same set
of R and R' substituents; use the same equatorial preferences for a single
substituent as given above.
150. Highly hindered
compounds, like those to the right, have interesting conformational properties.
For these two systems with R = CH3 or R = C(CH3)3
and with the resulting ethyl or neopentyl group either equatorial or axial,
it is alleged that the preferred conformation about the RCH2-CHR2
or RCH2-NR2 bond is nearly eclipsed; furthermore,
it is further alleged that the arrangement of atoms is non-alternating
(i.e., one dihedral angle near 0·, a second one positive, and a
third one negative - see the Newman projection). Do MMX calculations of
the structure and energy of all eight molecules; discuss the nature of
the preferred conformation about the key bond.
[Anderson, J. E. J. Chem. Soc., Perkin Trans. 2 1992, 1343.]
183. The methyl-substituted
bicyclic system to the right serves as a model for rings A and B of a steroidal
system. Do MMX calculations of the various octalins: the compounds having
a double bond at position a or b or c for both the
cis-fused and trans-fused systems; for the cis-fused
systems, of course, there will be two equilibrating conformations at equilibrium.
Discuss the factors that lead to different energy values for these various
isomers; compare your results with the experimental data for the corresponding
enol acetates.
[Thompson, H. W.; Gaglani, K. D. J. Chem. Soc., Perkin Trans. 2 1993, 967.]
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