Stereoselective (exo-specific) synthesis, dynamic 1H NMR and quantum chemical conformational and configurational analysis of norbornene-aziridine-E- imidoyl system

Article abstract of DOI:10.1007/s13738-011-0029-4

Stereoselective (exo-specific) synthesis, dynamic ¹H NMR and computational analysis of exo-N0-{3-azatricyclo[3.2.1.0.^2,4]oct-3-yl) mesithyloxy)methylene}-1-benzensulfunamide (3) were investigated. Aziridine nitrogen inversion gives rise to two sets of configurations where the N-substituent is Syn (S) or Anti (A) to C7 of the norbornyl ring. At lower temperature, the proton signals of aziridine exo-E-3 decoalesces to show two syn conformers and one anti conformer (exo-E-3^1S = exo-E-3^2S = exo-E-3^3A) with ratio of 60:20:20, respectively. Experimentally, the Gibbs free energy of activations [DG= (kcal/mol) ± 0.08] were calculated 11.96, 12.45 for 3 isomerizations. The standard Gibbs free energy (DG^o kcal/mol) 0.174, 0, 0.174, and 0.298 at 213 K and energy minimum 6.64, 4.77 and 1.78 were calculated for 3^1S = 3^2S, 3 ^2S = 3^3A, 3^1S = 3^3A isomerizations, respectively. The enthalpy (δH=, kcal/mol) and entropy (δS=, cal mol^-1 K^-1) of activation for the nitrogen inversion of aziridine of 3 were calculated 11.2 and-0.80, respectively.

Full text of DOI:10.1007/s13738-011-0029-4

J IRAN CHEM SOC (2012) 9:339–348
DOI 10.1007/s13738-011-0029-4
ORIGINAL PAPER
1
Stereoselective (exo-specific) synthesis, dynamic H NMR
and quantum chemical conformational and configurational
analysis of norbornene-aziridine-E-imidoyl system
•
Hossein A. Dabbagh Alireza Najafi Chermahini
Received: 7 January 2011 / Accepted: 15 June 2011 / Published online: 27 January 2012
Ó Iranian Chemical Society 2012
Abstract
1
Stereoselective (exo-specific) synthesis, dynamic H NMR
and computational analysis of exo-N0-{3-azatricy-
clo[3.2.1.0.2,4]oct-3-yl)mesithyloxy)methylene}-1-benzen-
sulfunamide (3) were investigated. Aziridine nitrogen
inversion gives rise to two sets of configurations where the
N-substituent is Syn (S) or Anti (A) to C7 of the norbornyl
ring. At lower temperature, the proton signals of aziridine
exo-E-3 decoalesces to show two syn conformers and one
anti conformer (exo-E-31S ꢀ exo-E-32S ꢀ exo-E-33A
with ratio of 60:20:20, respectively. Experimentally, the
)
Gibbs free energy of activations [DGà (kcal/mol)
0.08]
were calculated 11.96, 12.45 for 3 isomerizations. The
standard Gibbs free energy (DGo kcal/mol) 0.174, 0, 0.174,
and 0.298 at 213 K and energy minimum 6.64, 4.77 and
1.78 were calculated for 31S ꢀ 32S, 32S ꢀ 33A
,
31S ꢀ 33A isomerizations, respectively. The enthalpy
(DHà, kcal/mol) and entropy (DSà, cal mol-1 K-1) of
activation for the nitrogen inversion of aziridine of 3 were
calculated 11.2 and -0.80, respectively.
Keywords Aziridine ꢀ Ring inversion ꢀ
Dynamic NMR ꢀ HF
Electronic supplementary material The online version of this
article (doi:10.1007/s13738-011-0029-4) contains supplementary
material, which is available to authorized users.
H. A. Dabbagh (&) ꢀ A. Najafi Chermahini
Department of Chemistry,
Introduction
Isfahan University of Technology,
8415483111 Isfahan, Iran
e-mail: dabbagh@cc.iut.ac.ir
Aziridines are versatile intermediates for the synthesis of
nitrogen-containing compounds via ring-opening and ring-
123

340
J IRAN CHEM SOC (2012) 9:339–348
expansion reactions [1–8]. In addition, aziridines as highly
strained ring systems have been attracting considerable
attention. Ethylenimine and some of its simple derivatives
are commercial products in different fields of applied
chemistry. Observations of the toxic action of aziridines
have resulted in extensive investigations on the synthesis
and testing of aziridines for pharmacological activity, some
substances having reached advanced stages of evaluation
as cancer chemotherapeutic agents and a few being in
regular clinical use [9].
Experimental
General
The dynamic NMR spectra were recorded by a BRUKER
AVANCE DRX500 spectrometer at Tarbiat Modarres
University. NMR samples were prepared in precision
5-mm tubes. All spectra are referenced to tetramethylsilane
at 0 ppm. The IR spectrums were recorded on a JASCO
FT/IR-680 PLUS spectrometer and mass spectra were
determined on a Uk Fisons Trio 1000 spectrometer. Melt-
ing points was taken by GALLENKAMP melting point
apparatus and are uncorrected. Potassium carbonate and
norbornene and solvents purchased from Merck, methyl
iodide purchased from Riedel–Dehaen. Cyanogen bromide
and 5-(mesithyloxy)-1H-tetrazole (1) was prepared by
method of Ref. [24]. Synthesis of N’-[azido(mesithyl-
oxy)methylen]-1-benzene sulfonamide (2) was reported
earlier [25].
Aziridines were predicted to exhibit high barriers to
amino nitrogen inversion. These compounds represent the
first class of compounds in which nitrogen inversion was
studied by dynamic 1H NMR technique [10–18]. The
magnitude of the nitrogen inversion barrier in aziridine
derivatives is sensitive to the electronic effect of substituent.
A typical example is the fact that invertomers of 1-chloro-2-
methylaziridine can be isolated [16]. However; it is dan-
gerous to conclude that electronegative groups on nitrogen
generally enhance the barrier to inversion. One report
compares barrier in N-substituted aziridines and a low
barrier for electron-withdrawing group such as 2,4-dini-
trobenzensulfenyl aziridine was reported [17]. In addition
when an acyl group is attached to N atom of aziridines this
compounds exhibit very low barriers to inversion. This
attributed to a very close planar ground state [18]. In our
Computational procedure
All semi-empirical and ab initio calculations were carried
out on a Pentium IV personal computer by means of
HyperChem-V6 or GAUSSIAN98W (GAUSSIANVIEW)
[26, 27]. The vibrational frequencies were computed for
the optimized geometries of isomers at same level of theory
to verify the nature of the stationary points found on the
potential energy surface. All the equilibrium isomers
without imaginary frequency correspond to the minimum
points on the potential surface. The AM1 and PM3 were
selected for calculations and the 3-21G* optimized geom-
etries were then taken for further optimization with 6-31G
(d) basis set. The calculated 1H NMR chemical shifts were
obtained by ACD/HNMR.
1
previous work, synthesis and dynamic H NMR study of
2-(tert-butoxymethyl)-1-[N’-(4-methylbenzenesulfonyl)(4-
methylphenoxy)imidoyl] aziridine was reported. The
dynamic behavior of this compound was attributed to
inversion of aziridine nitrogen [19–24, (and references there
31–33)].
Generally speaking, the energy required by molecules to
interact during a chemical reaction stem from the nature of
configurations and/or conformations. The geometry of
conformations and configuration of the transition state
and\or of the intermediate is documented to pre-establish
the selectivity of the chemical reactions and/or the ste-
reochemistry of the adducts [7]. Experimental and theo-
retical study of isomerization during the course of chemical
reaction helps to have a better understanding of the
chemistry of our environment. In other words, the purpose
of conformational–configurational analysis is to obtain a
description of the 3D structure of molecules at any stage of
the reaction. Such knowledge is required in order to
understand the interactions between biomolecules, e.g.
carbohydrates, DNA, RNA and proteins.
exo-N0-[3-azatricyclo[3.2.1.0.2,4]oct-3yl)-
mesithyloxy)methylene]-1-benzensulfun- amide (3)
In
a
flask N0-[azido(mesithyloxy)methylen]-1-benzene
sulfonamide (2) (0.34 g, 10 mmol) and norbornene (0.1 g,
11 mmol) dissolved in 50-ml dry THF and under dry
nitrogen kept at 40 °C for 3 h. Then the reaction mixture
brought to room temperature, the solvent evaporate at
reduced pressure to give a residue. The residue passes
through a silica gel column with cyclohexane-ethylacetate
(80:20) and recrystallized in chloroform-n-hexane system.
(0.28 g, 50%), mp = 126–128 °C. 1H-NMR (CDCl3
500 MHz) d0.75 (d, 1H, J = 10.0 Hz), 1.12 (d, 1H,
J = 10.0 Hz), 1.18 (d, 2H, J = 8.18 Hz), 1.45 (d, 2H,
J = 8.2 Hz), 1.98 (s, 6H), 2.25 (s, 3H), 2.37 (s, 3H), 2.95
(s, 2H), 6.80 (s, 2H), 7.19 (d, 2H, J = 8.0 Hz), 7.71 (d, 2H,
J = 8.0 Hz). 13C NMR (CDCl3-d6): 16.0, 20.7, 21.5, 25.3,
In the continuum of on going research on the chemistry
of tetrazoles and their derivatives, [24, 25, 28–32] herein,
we report the exo-selective synthesis, dynamic NMR,
quantum chemical conformational and configurational
analysis of an aziridine derivative of norbornene, 3, are
investigated.
123

J IRAN CHEM SOC (2012) 9:339–348
341
Ar
O
O
O
O
Tol
N
Ar
H
Tol
N
O
N
S
N
N
O
S
O
S
i
N
iii
ii
ArOCN
Me
ArOH
O
N
N
N3
1
2
iv
ArO
ArO
N
O
O
Me
Ar =
S
Favored structure
Unfavored struture
N
Me
N
H
H
Scheme 3 Resonance structures of aziridine
O
Ar
reaction is reported to pass trough a 1,2,3-triazoline inter-
mediate ([3 ? 2]-cycloaddition) below room temperature
without azide decomposition [33]. This intermediate is
stable at low temperature or in the dark, but under the light
or above room temperature spontaneously releases N2 to
produce aziridine. In one instance, 1,2,3-triazoline was
isolated from the reaction of phenyl azide with norbornene
[33]. In present study, the direction of addition of azide to
norbornene is totally diastereoselective (exo-specific) with
no trace of endo-adduct or formation of 1,2,3-triazoline
intermediate, Schemes 1 and 5.
3
Other conformers
Scheme 1 Reagents and conditions: (i) BrCN, (C2H5)3N, acetone;
(ii) NaN3, acetone-H2O, reflux; (iii) TsCl, (C2H5)3N, acetone, RT;
(iv) norbornene, THF, 40 °C
28.3, 36.1, 43.0, 127.0, 128.9, 129.4, 135.6, 139.6, 142.4,
146.8, 161.2. IR (KBr): 2995, 2966, 1556, 1383, 1201,
1053, 817 cm-1.MS m/z 424 (M?):360, 343, 319, 269,
227, 155, 91. Anal. Calcd. for C24H28N2O3S: C 69.70, H,
6.65, N, 6.65. Found: C, 70.1; H, 6.7; N, 6.9.
Result and discussion
Interconversion mechanisms
Synthesis
There are five important motions (Schemes 2, 3, 4, 5)
under consideration for exo-E-3. First, aziridines exhibit
nitrogen inversion which is sensitive to the electronic effect
of substituent [10–16]. Aziridine nitrogen inversion gives
rise to two sets of configurations where the N-substituent is
syn (S) or anti (A) to C7 of the norbornyl ring. Second,
there are rotations about nitrogen–sulfur of imidoylsulfonyl
moiety (–SO2–N = C). Third, rotation about oxygen of
aryloxy and carbon of imidoyl moiety (ArO–C =
NSO2Ar). Next, there are rotations about nitrogen of azi-
ridine and carbon of imidoyl moiety (–N–C = NSO2Ar).
Finally, another important motion is the E/Z isomerization
about nitrogen (C = N) of imine group.
Tetrazoles 5-(mesithyloxy)-1H-tetrazole (1), was synthe-
sized by reaction of its parent phenol with cyanogen
bromide and then addition of sodium azide in water–
acetone (1:1) mixture under refluxed temperature. The
N0-[azido(mesithyloxy)methylen]-1-benzene sulfonamide 2
was synthesized by reaction of tosyl chloride with tetra-
zoles 1. The electron-withdrawing group such as tosyl or
cyanide cause stability of imidoyl azide and produce
nitrenes that have good selectivity [24, 25, 28–32].
Aziridne exo-E-3 was prepared by the reaction of imidoyl
azide 2 with norbornene (Scheme 1). All compounds were
characterized by spectroscopic and physical methods.
In this investigation, the results of variable temperature
NMR study of compounds exo-E-3 are consistent with the
nitrogen inversion of aziridine ring and conformational
interconversions (pathway c, Scheme 2). We did not
observe E/Z isomerization, rotation about nitrogen of
aziridine–carbon of imidoyl moiety (N–C = NSO2Ar) nor
rotation about the nitrogen–sulfur of imidoylsulfonyl
moiety (–O2S—N = C). The former two require higher
and the latter rotation requires lower temperature.
Stereoselectivity
The mechanism of aziridine formation from organic azides
generally occurs by thermal decomposition of imidoyl
azide and production of imidoylnitrene [24, 28–30].
Reaction of imidoylnitrene with double bond produces
aziridine. In the case of strained olefins such as norbornene,
Scheme 2 Rotations of S–N of
N-sulfonylimine, C–O and C–N
of imidoyl moeity
Tol
S
O
O
Tol
N
O
O
O
O
Tol
N
Tol
N
S
S
S
a
Tol
a
N
b
c
O
O
N
c
S
OAr
b
O
O
Ar
Ar
O
O
N
O
N
ArO
N
Ar
123

342
J IRAN CHEM SOC (2012) 9:339–348
Scheme 4 E/Z isomerisation
and anti/syn-aziridines
interconversion
O
O
O
Ar
O
O
N
S
Me
S
Me
N
N
N
H
O
H
O
S
N
N
O
Ar
Ar
O
Me
H
H
H
H
E/Z isomerization
Anti and Syn- Aziridine nitrogen inversion
Me
Me
H
Me
O
Flag pole
protons
H
N
Me
H
H
S O
N
H
O
O
S
O
a
Me
Me
C
H
H
N
H
H
Me
b
O
S
H
1S,4S
H
1S,2S
K3
N
K3
O
H
O
N
Me
O
N
a
Me
Me
b
H
H
H
H
H
2S,3A
H
4S,5A
K3
K3
exo-E-34S
exo-E-31S
exo-E-32S
Me
Me
Me
Me
1S,5A
1S,3A
K3
K3
3A,5A
K3
Me
H
H
O
Me
S
O
H
O
H
H
C
N
O
Me
H
H
N
N
N
H
Me
S
H
H
H
O
O
Me
H
exo-E-35A
exo-E-33A
Me
Superscripts = S (Syn), A (anti)
Scheme 5 Designation of potential aziridine isomers from 3
Recently, Bharatam and coworkers studied S–N interac-
tions in sulfonamides. They found a rotation barrier
0.5–5.7 kcal/mol for rotation about S–N bond in N-sulfo-
nylimines. In addition, they reported rotation barrier
1.66 kcal/mol about the S–N bond in MeSO2–NO [34–36].
Dabbagh, Modarresi-Alam and coworkers reported a very
high-energy barrier (%24 kcal/mol) for the E/Z intercon-
version for the aziridines conjugated with an imidoyl
group. Other examples of the E/Z isomerization is reported
with high-energy barrier (14–24 kcal/mol) [19–24, 29, 30].
We ruled out the rotation about C–N of nitrogen of
aziridine and carbon of imidoyl moiety (–N–C = NSO2Ar)
on the basis of the following facts. (1) The protons of the
ortho of tosyl did not show considerable shift and/or appear
as three signals (three isomers) at lower temperature.
(2) Rotation about the C–N bond should alter the chemical
shifts of the ortho protons of tosyl. (3) The chemical shift
of aziridine protons i (at C2 and C3) of 32S closely
resemble that from 31S. (4) The computer-generated mini-
mum for the highest-energy conformer (by applying rota-
tion about the C–N bond of N–C = NSO2Ar of exo-E-31S
or about C–O bond of N = C–OAr) predicts the energy
barrier is three times higher for the rotations about C–N
bond, Fig. 1. (5) Rotations must be restricted for the rates
K31S,4S K31S,5A K33A,5A K34S,5A (Scheme 5) and require
higher temperatures to investigate the dynamics by NMR.
1
Dynamic H NMR and coalescence temperature
measurements
1
At room temperature, the H NMR spectra, recorded in
1
chloroform-d, for compounds 3, Figs. 2 and 3. H NMR
spectra were then recorded for compounds 3 by systemat-
ically lowering the probe temperature until the maximum
123

J IRAN CHEM SOC (2012) 9:339–348
343
Fig. 1 Computer-generated minimum for the highest-energy conformers of exo-E-31S; using GAUSSIAN98W (GAUSSVIEW), PM3 method.
(Left) rotation about C–N bond of N–C=NSO2Ar. (Right) Rotation about C–O bond of N=C–OAr
separation was observed between split signals or until the
solubility limit was reached. The norbornene (flag pole
protons) aliphatic (aziridine protons) and aromatic proton
regions were particularly interesting and will be hereafter
described for compound 3.
of 60, 20 and 20, respectively, Fig. 2a. Protons of ortho
position of tosyl group (Hl) appear as a doublet with the
J = 8.0 Hz decoalesced to two signals at 7.915 ppm
(J = 8.0 Hz) and 7.695 ppm (J = 8.0 Hz) with ratio of
80:20, respectively, Fig. 2b.
As depicted in Fig. 2, at room temperature, flag pole
protons of norbornene of exo-E-3 appear as a doublet at
1.120 ppm (Hb) and 0.750 ppm (Ha) with both have
J = 10 Hz. The enantiotopic aziridine protons appear as a
singlet (Hi) at 2.95 ppm. Those signals of norbornene pro-
tons that appear as a doublet at 1.190 ppm (J = 8.20 Hz),
1.440 ppm (J = 8.20 Hz) and as singlet at 2.370 ppm did
not split with decreasing temperature and could reasonably
be assigned to Hc, Hd and Hh protons, respectively. The
aromatic protons appear as singlet at 6.80 ppm and as two
doublets at 7.19 ppm (Hk) J = 8.0 Hz and 7.75 ppm (Hl)
with J = 8.0 Hz. The former two signals did not split with
decreasing temperature and could reasonably be assigned to
mesithyloxy protons (Hj) and meta protons (Hk) of tosyl
group, respectively. At lower temperature, flag pole protons
of norbornene (Ha and Hb) shift to higher field and deco-
alesced to two signals at 0.80 and 0.60 ppm, respectively.
Aziridine protons (Hi) decoalesced to three signals at 2.650,
2.720 and 3.30 ppm, with the ratio of 60:20:20, respectively.
Protons of ortho-methyl group of mesithyl (He) appearing as
a singlet (at room temperature) at 1.850 ppm also deco-
alesced to three signals at 1.82, 1.89 and 2.0 ppm with ratio
Percent populations of each isomer were measured by
integrating the respective aziridine protons or ortho-methyl
of mesithyloxy signals on spectra recorded at the temper-
ature providing the highest Dm between the major and the
minor signal. Consequently, the major exo-isomer popu-
lation resulted within 80% as obtained for both compound
3. Compounds 3 provided three values 60, 20 and 20%.
The dynamic NMR of compound investigated here, the
coalescence of the aziridine signal was observable within a
temperature between 213 and 325 K, corresponding to a
nitrogen interconversion of aziridines exo-E-31S ꢀ exo-
E-33A, and conformational interconversion exo-E-31S
ꢀ
exo-E-32S with the DGà values of 11.96 and 12.45 kcal/
mol, respectively, as evaluated from standard equations,
Table 1, Scheme 5 [10–15].
The rate constants, k, for the interconversion of the
imidoyl aziridines at the coalescence temperature (Tc) were
calculated from equation ðk ¼ pDv=XÞ and X can be
ꢀ
obtained by numerical solving of equation X6 ꢁ 6X4
h
i
2
12 ꢁ 27ðDpÞ X2 ꢁ 8 ¼ 0Þ that Dp is the population dif-
ference between two sites, when two sites have equal
123

344
J IRAN CHEM SOC (2012) 9:339–348
Fig. 2 a Part of the variable
1
temperature H NMR
a
a
h
b
H
H
O
O
N
(expanded) of aziridine
of exo-3 measured in CDCl3.
b Part of the variable
l
S
H
k
N
H
c
1
l
H
O
g
temperature H NMR
of aromatic region
f
H
H
i
e
H
H
H
k
h
d
e
of the exo-3 measured in CDCl3.
c Experimental (left column)
and simulated (right column)
1H NMR spectra for aziridine Ci
protons of compound 3 at
different temperatures
j
j
exo-3
b
123

J IRAN CHEM SOC (2012) 9:339–348
345
is a good indication that congestion imposed on aziridine
by norbornene, aryl group and electron withdrawing imi-
doyl group does not effect the energy barrier for the
nitrogen inversion.
TS
The questions raised here are these, why? (1) Aziridine
protons (Hi) of exo-3 appeared as three signals at 2.650,
2.720 and 3.30 ppm at lower temperature, with the ratio of
60:20:20, respectively, Fig. 2a. (2) Protons of ortho-methyl
group of mesithyl of exo-3 at 1.850 appeared as three
signals at 1.82, 1.89 and 2.0 ppm at lower temperature,
with ratio of 60, 20 and 20, respectively, Fig. 2a. (3) Flag
pole protons of norbornene (Ha and Hb) at 1.120 and
0.780 ppm of exo-E-3 shift to higher field and appeared
(why not three signals) at 0.80 and 0.60 ppm at lower
temperature, respectively, Fig. 2a. (4) Protons of ortho
position of tosyl group of exo-E-3 at 7.20 ppm appeared as
two major signals (why not three signals) at 7.915 and
7.695 ppm with ratio of 80:20, respectively, Fig. 2b.
Reaction is 100% diastereoselective (exo-specific) pro-
ducing exo-3 isomer without any trace of endo-3 isomer.
The following explanations justify the raised questions
for 3. At reduced temperature, aziridine protons signals
(Hi) and protons of ortho-methyl group of mesithyloxy of
exo-E-3 appeared as three signals (ortho protons of tosyl
group did not) corresponding to the major conformation–
configuration exo-E-31S (60%), the minor conformation
exo-E-32S (20%) and the minor configuration exo-E-33A
(20%). The former two isomer shift to higher field (by the
imine of the imidoyl moiety) and the latter shift to lower
field. At reduced temperature, flag pole protons of nor-
bornene (Ha and Hb) of exo-E-3 shift to higher field (by the
imine of the imidoyl moiety) and appeared as two signals
with close chemical shifts (at 0.60 and 0.80 ppm) which
corresponds the exo-E-31S and exo-E-32S (80%). The exo-
E-33A (20%) shift to lower field at 1.230 and 1.590 ppm,
respectively, Fig. 2a. Conversely, protons of ortho position
of tosyl group of exo-E-31S overlapping the exo-E-32S
(80%) shift to lower field and protons of exo-E-33A (20%)
shift to higher field, Fig. 2b. Interestingly, the computer-
generated minimum geometry of 3 predicted that tosyl
group in 33A appear at the opposite location in compare to
the tosyl group of 31S, Figs. 2 and 4.
32S
‡
ΔG
11.96
4.47
33A
6.64
31S
1.78
Fig. 3 Computational (HF/6-31G*) minimum relative energy
diagram for exo-31S, exo-32S, exo-33A. Experimental free energy of
activation (àGD, kcal/mol) are depicted with dashed lines
population this equation will equivalent to Gutowski-Holm
pffiffi
ꢀ
Á
equation k ¼ pDv= 2 [10–15]. Assuming the transmis-
sion coefficient, k, to be unity, the free energy of activation,
à
z
(DG ) was calculated from Eyring equation (DG ¼
RTc½lnTc ꢁ lnKc þ 23:76ꢂ) [10–15]. Using the equation:
ꢀ
ꢁ
Á
ꢀ
DGo ¼ ꢁRTLnKeq ¼ ꢁRT ln 31S 32S and ꢁRTLn 32S=
ꢀ
Á
33AÞ; ꢁRTLn 31S=33A , free energies (DGo, T = 213 °K)
are obtained 0.174, 0, 0.174, and 0.298 for isomerizations
of 31S ꢀ 32S, 32S ꢀ 33A and 31S ꢀ 33A, respectively.
The inversion barriers of aziridines depend on both
steric and electronic effects. The Gibbs free energy of
activation for aziridine of exo-3 and exo-3 inversion is
slightly lower than an aziridine with electron-withdrawing
groups. Because it is known that sp2-hybridized amines
show low basicity and the hybridization of the aziridine
nitrogen atom is nearly sp2, it follows that the availability
of the lone pair on nitrogen is low, rendering the nitrogen
atom slightly pyramidal and hence, resulting in low barrier
to inversion of nitrogen in this system. This can be
attributed to conjugation of nitrogen lone pair and imidoyl
moiety. In addition, the presence of bulky phenolic groups
cause increase in ground and activation state energy. This
1
Table 1 Dynamic H NMR data for interconversion of aziridens at coalescence temperature of 253 K (-20 °C)
Compound no
d ppm
Pop%
Major
Tsb
Dt (Hz)
k (s-1
)
DG (kcal/mol)à
Major
Minor
Minor
31S,2S ꢀ 33A
7.92
2.64
7.69
2.72
80a
60
20
20
213
213
110
40
248
11.96 0.08c
12.45
31S ꢀ 32S
85.5
a
80% population is a sum of 60% for major isomer 31 and 20% for one of the minor conformer 32
Temperature at which the maximum separation Dm is observed
The errors are estimated at 0.08 kcal/mol
b
c
123

346
J IRAN CHEM SOC (2012) 9:339–348
Fig. 4 Computer-generated minimum conformations and configura-
tions for compounds exo-E-31S (top), exo-E-32S (center) and exo-E-
33A (bottom) (detectable by NMR at lower temperature) using
GAUSSIAN98W (GAUSSVIEW) at HF/6-31G* level
c
Conformations 31S and 33A are less congested by the strain
than 32S, respectively. Therefore, the lower preference for
the 32S conformation must arise from steric hindrance
interactions between the norbornene and mesithyloxy group.
In our investigation, the highly congested endo-3 confor-
mation was not observed at the temperatures of 213–325 K.
Attempts to calculate the structures with minimum energy
for those compounds failed using all methods of calculation
(AM1, PM3, 3-21G*, 6-31G* at HF or B3LYP levels).
Simulation was done using WINDNMR3 to give rate
constants k for 31S,2S ꢀ 33A and 31S ꢀ 32S at the cor-
responding temperature. From the rate constants k3, DHà
and DSà were extracted by plotting ln(k/T) versus (1/T). For
compound 3, DHà = 11.20 kcal mol-1 and DSà = 0.80
cal mol-1 K-1
.
The rate constants k3 (see Fig. 2c) have been determined
using line shape analysis at each temperature. The simu-
lation involves two independent rate constants, the inter-
conversion of aziridine 31S,2S ꢀ 33A (k31,2,3) and the
rotation between the two conformers 31S ꢀ 32S (k31,2),
Table 1. Excellent simulations conclude that this process is
negligibly slow in this system. This is reasonable, since this
process requires that the larger groups (Tosyl, mesithyl) to
by pass each other and/or the norbornene system. The
barriers separating the 31S and 32S have been calculated
using the Eyring equation, Table 1 and Figs. 2c and 3. The
31S conformation–configuration is less congested by strain
than conformation 32S and configuration 33A. Therefore, the
preference for the 31S conformation–configuration must
arise from minimum repulsion between the two attached
groups. The 32S, 33A isomers allow interactions between the
two attached groups and the norbornene. In this study, the
population of the 3 is dependent on aryloxy substituents.
To our knowledge, there is no published paper to
directly determine the magnitude parallel-coalescence of
configurational–conformational interconversions thus far.
We have found, through molecular modeling and experi-
mental studies, that exo-norbornene-aziridine-E-imidoyl
systems interconvert configurationally and conformation-
ally at the same coalescence temperature (253 K).
The conformational equilibrium between the 31S and the
32S in the 3 molecular system (Figs. 2, 4) was measured by
low-temperature NMR spectroscopy by taking advantage
of slow rate of inversion of the aziridine nitrogen and the
slow rotation of C19–O20 bonds of imidoyl group in
compound 3. At around 253 K, the rate of inversion of the
aziridine and the rotation around the C19–O20 bonds of
imidoyl group in compound 3 becomes sufficiently slow
123

J IRAN CHEM SOC (2012) 9:339–348
347
Table 2 Computer-generated minimum for isomers of aziridines 3
Compound no.
Relative energy (kcal/mol)
AM1a
PM3a
AM1b
PM3b
3-21G*b
6-31G*b
Exo-31S
Exo-32S
Exo-33A
a
0
0
0
0
0
0
2.64
1.80
3.06
0.18
2.33
2.04
5.13
0.29
4.43
0.18
6.64
1.87
Calculated by HyperChem V.6, HF/level
b
Calculated by GAUSSIAN98W, HF/level
Acknowledgments We would like to thank Isfahan University of
Technology (IUT) for the financial support (Research Council Grant).
that the proton signals (aziridine and ortho-methyl of
mesithyloxy) for the conformations–configurations
3
appeared as three singlets for 31S, 32S and 33S, Fig. 2. Thus,
the 31S/32S and 31S/33A ratios determined at low tempera-
ture provide a measure of the interactions between the
attached aryl group and/or the norbornene group, Fig. 2.
This model system probes the interaction of two attached
aryl of imidoyl group in E-configuration, rather than the
Z orientation and favoring exo-configuration rather than
endo configurations according to molecular modeling
studies using computational methods.
References
1. H.M. Osborn, J. Sweeney, Tetrahedron Asymmetr. 8, 1693
(1997)
2. D. Tanner, Angew. Chem. Int. Ed. Engl. 33, 599 (1994)
3. W. McCoull, F.A. Davis, Synthesis 1347 (2000)
4. J.B. Sweeney, Chem. Soc. Rev. 31, 247 (2002)
5. X.E. Hu, Tetrahedron 60, 2701 (2004)
6. P. Davoli, A. Forni, I. Morettii, F. Prati, G. Torre, Tetrahedron
57, 1801 (2001)
7. N. De Kimpe, D. De Smaele, Z. Sakonyi, J. Org. Chem. 62,
2448–2452 (1997)
Theoretical calculations
8. O. Kitagawa, S. Miyaji, Y. Yamada, H. Fujiwara, T. Taguchi,
J. Org. Chem. 68, 3184 (2003)
All AM1, PM3 and ab initio calculations were performed
in gas phase using either HyperChem-V6 or the Gaussian
98 [26, 27]. Starting geometries were initially obtained
through a conformational search at the AM1 and PM3
levels. The most stable conformers were completely opti-
mized at the HF/3-21G* and HF/6-31G*levels, Table 1.
Computer-generated minimum structures of three major
isomers of 3 are depicted on Fig. 4 (Scheme 5). All
methods predicted the exo-E-31S is the most stable isomer
and exo-E-33A with intermediate stability and exo-E-32S as
the most unstable isomer, Table 2 and Figs. 3, 4.
9. A. Padwa, A.D.Woolhouse, in Comprehensive Heterocyclic
Chemistry Small and Large Rings, vol. 7, ed. by W. Lwowski
(Pergamon Press, Ltd., Oxford, 1984), pp. 47–93
10. M. Oki, Application of Dynamic NMR Spectroscopy to Organic
Chemistry, Chapter 8 (VCH Publishers, 1985)
11. J. Sandstrom, Dynamic NMR Spectroscopy (Academic Press,
London, 1982)
12. H.J. Reich, in Win-DNMR: Dynamic NMR Spectra for Windows.
J. Chem. Educ. Softw. (1996–2003)
13. H. Gunnter, NMR Spectroscopy, 2nd edn (Wiley, New York,
1995)
14. A. Contini, D. Nava, P. Trimarco, J. Org. Chem. 71, 159 (2006)
15. B.W. Gung, X. Xue, H.J. Reich, J. Org. Chem. 70, 3641 (2005)
16. S.J. Brois, J. Am. Chem. Soc. 90, 508 (1968)
17. F.A.L. Anet, R.D. Trepka, D.J. Cram, J. Am. Chem. Soc. 89, 357
(1967)
18. F.A.L. Anet, J.M. Osyany, J. Am. Chem. Soc. 89, 1352 (1967)
19. H.A. Dabbagh, A.R. Modarresi-Alam, J. Chem. Res. (S.) 190
(2000)
Such results were quite consistent with nitrogen inter-
conversion of aziridine barriers measured in solution for
different aziridines, which are in the range reported in the
literature [31, 32].
20. P.J. Garratt, T.R. Wrigglesworth, Tetrahedron 50, 12219 (1994)
21. M. Raban, E. Carlson, J. Am. Chem. Soc. 93, 685 (1971)
22. M. Rabann, F.B. Jones, J. Am. Chem. Soc. 93, 2692 (1971)
23. H.O. Kalinowski, H. Kessler, Top. Stereochem. 7, 295 (1973)
24. H.A. Dabbagh, S. Gaelee, J. Org. Chem. 61, 3439 (1996)
25. H.A. Dabbagh, W. Lwowski, J. Org. Chem. 54, 3952 (1989)
26. M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A.
Robb, J.R. Cheeseman, V.G. Zakrzewski, J.A. Montgomery Jr,
R.E. Stratmann, J.C. Burant, S. Dapprich, J.M. Millam, A.D.
Daniels, K.N. Kudin, M.C. Strain, O. Farkas, J. Tomasi, V. Barone,
M. Cossi, R. Cammi, B. Mennucci, C. Pomelli, C. Adamo, S.
Clifford, J. Ochterski, G.A. Petersson, P.Y. Ayala, Q. Cui, K.
Morokuma, D.K. Malick, A.D. Rabuck, K. Raghavachari, J.B.
Foresman, J. Cioslowski, J.V. Ortiz, A.G. Baboul, B.B. Stefanov,
Conclusions
The thorough study of the conformational–configurational
interconversions of exo-norbornene-aziridine-E-imidoyl
systems in solution was possible through a combination of
theoretical and experimental techniques, where one method
filled in the gaps of the other. We could reasonably con-
clude that the exo conformational equilibrium observable
in solution was between the 31S and 32S forms, and the exo
configurational equilibrium between 31S and 33A
.
123

348
J IRAN CHEM SOC (2012) 9:339–348
G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. Gomperts, R.L.
Martin, D.J. Fox, T. Keith, M.A. Al-Laham, C.Y. Peng, A. Nana-
yakkara, C. Gonzalez, M. Challacombe, P.M.W. Gill, B. Johnson,
W. Chen, M.W. Wong, J.L. Andres, M. Head-Gordon, E.S. Repl-
ogle, J.A. Pople, GAUSSIAN98 GAUSSIAN98, Revision A.7
(Gaussian, Pittsburgh, PA, 1998)
29. H.A. Dabbagh, A. Najafi Chermahini, A.R. Modarresi-Alam,
Bull. Korean Chem. Soc. 26, 1229 (2005)
30. A. Subbaraj, O. Subba Rao, W. Lwowski, J. Org. Chem. 54, 3945
(1989)
31. H.A. Dabbagh, W. Lwowski, J. Org. Chem. 65, 7284 (2000)
32. H.A. Dabbagh, R. Karimzadeh, Molecules 7, 189 (2002)
33. J.W. Wijnen, R.A. Steiner, J.B.F.N. Engberts, Tetrahedron Lett.
36, 5389 (1995)
34. P.V. Bharatam, A.A. Gupta, D. Kuar, Tetrahedron 58, 1759
(2002)
27. A. Frisch, A.B. Nielsen, A.J. Holder, Gauss View User Manual,
Gaussian.C. Young Computational Chemistry, A Practical Guide
for Applying Techniques to Real-World Problems (Electronics)
(John Wiley and Sons, Inc., New York, 2001)
28. A.R. Modarresi-Alam, H. Kekha, F. Khamooshi, H.A. Dabbagh,
Tetrahedron 60, 1525 (2004)
35. P.V. Bharatam, P. Senthilkumar, Tetrahedron 60, 4801 (2004)
36. P.V. Bharatam, A. Kaur, Tetrahedron 58, 10335 (2002)
123