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through a planar or nearly planar transition state leading to an equivalent
pyramidal form, for example, in ammonia.
H N H H
N The inversion barrier (energy difference between pyramidal and planar
forms) is typically very small (24 kJ/mol for ammonia), meaning that the
process is hard to stop. Note, that unlike free and constrained rotation
discussed earlier (and pseudorotation to be discussed in the next section),
inversion will not normally lead to molecules with different energies.
However, inversion of molecules where the pyramidal center is bonded to
three different atoms or groups leads to a change in chirality at that center,
that is, to the other enantiomer. In most cases, the low barrier to inversion
means that a racemic mixture results. 25 Nitroamide: Two opposing factors compete to determine the equilibrium geometry of
nitroamide, O2N-NH2. One is the preference for the amino group to be pyramidal and
not planar and the second that delocalization of the lone pair on the amino group into
the nitro group is best accommodated by a planar geometry. Is nitroamide planar or non
planar? Use the B3LYP/6-31G* model to decide. Start from a non-planar structure. If it
is non-planar, what is the barrier to inversion? To answer, you need to determine the
geometry of planar nitroamide and calculate the energy difference between non-planar
and planar structures.
Inversion in Cyclic Amines: Pyramidal inversion at nitrogen that is part of a three or
four-membered ring might be expected to be more difficult that inversion of an acyclic
amine. This is because the transition state incorporates a planar nitrogen center (ideal
bond angles of 120o) which is more difficult to achieve if one of the angles is
constrained to ~60o or ~90o. Use the HF/6-31G* model to obtain geometries for
dimethylamine (to act as a reference), aziridine and azetidine and their respective
inversion transition states. H3 C N H H H N N
CH3 H2C H2 C
H2 Calculate inversion barriers (difference between pyramidal and planar forms) for the
three molecules. Is the barrier in aziridine significantly larger than that in
dimethylamine? Is the barrier in azetidine midway between those in dimethylamine and
aziridine, or is it much closer to one of them? Rationalize you result.
Pyramidal Inversion in Phosphine and Trifluorophosphine: Phosphine (PH3) is also
pyramidal and inverts via a planar transition state. Obtain both the equilibrium
geometry and transition state using the HF/6-31G* model. Is this barrier smaller, larger
or about the same as that for ammonia? Provide a rationale if it is markedly different.
Repeat your calculations for trifluorophosphine (PF3). Rationalize any significant
increase or decrease in inversion barrier relative to that for phosphine.
Pyramidal Inversion of Sulfoxides: The anti-ulcer drug esomeprazole (Nexium) is the
S enantiomer of an older unresolved drug. While both enantiomers are active, the R
enantiomer is metabolized faster than the S enantiomer (the pure S compound lasts
longer lasting than the racemic mixture). 26 Esomeprazole does not contain any chiral carbon centers, and the two enantiomers
differ only because of the fact that the sulfoxide group is pyramidal and not planar.
Were racemization to occur at room temperature (via inversion at sulfoxide), the pure S
enantiomer would not be any more effective than the racemate, and the “new”
compound would not provide additional market value. In order for racemization not to
happen, the inversion barrier needs to be >150 kJ/mol and preferable > 200 kJ/mol.
Estimate the barrier to racemization in espmeprazole using methyl vinyl sulfoxide as
model compounds. First obtain the “correct” equilibrium geometry (with a pyramidal
sulfoxide group), and then a geometry for the transition state (with a planar sulfoxide
group). For the latter, start with a planar structure (with Cs symmetry) to avoid having
to do transition-state search. Use the HF/6-31G* model.
What is the energy required for inversion in methyl vinyl sulfoxide? Do you results
suggest that racemization of esomeprazole via inversion is likely to occur at room
temperature? Elaborate. Pseudorotation
Pseudorotation exchanges equatorial and axial positions in fivecoordinate, trigonal-bipyramidal centers, for example, the five-coordinate
phosphorous center in phosphorous pentafluoride. equatorial F F axial
F axial Here, the process involves simultaneously decreasing (from 180o) the FPF
angle involving two axial fluorines and increasing (from 120o) the FPF angle
involving two of the equatorial fluorines. This leads to a structure in which
what were the two axial fluorines and two of the equatorial fluorines form
the base of a square-based pyramid. This is the transition state. Continuing
the motion returns to the stable trigonal-bipyramidal geometry but with axial
and equatorial fluorines exchanged. Repeated pseudorotation moves fully
scramble the fluorines.
F P F F F F P F
F F F HF/6-31G* calculations confirm that the transition...
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This note was uploaded on 02/22/2010 for the course CHEM N/A taught by Professor Head-gordon during the Spring '09 term at Berkeley.
- Spring '09