Studies of the structure, amidicity, and reactivity of n-chlorohydroxamic esters and n-chloro-β,β-dialkylhydrazides: Anomeric amides with low resonance energies

Article abstract of DOI:10.1071/CH14270

Density functional calculations have been carried out to determine the properties of the title anomeric amides. At the B3LYP/6-31G(d) level, N-chloro-N-methoxyacetamide 8a is computed to be strongly pyramidal at nitrogen with a long amide bond that is unt

Full text of DOI:10.1071/CH14270

RESEARCH FRONT
CSIRO PUBLISHING
Aust. J. Chem. 2014, 67, 1344–1352
Full Paper
http://dx.doi.org/10.1071/CH14270
Studies of the Structure, Amidicity, and Reactivity of
N-Chlorohydroxamic Esters and N-Chloro-b,b-
dialkylhydrazides: Anomeric Amides with Low
Resonance Energies*
A B
,
A
A
Stephen A. Glover,
Adam A. Rosser, and Robert M. Spence
A
Chemistry, School of Science and Technology, University of New England, Armidale,
NSW 2351, Australia.
B
Corresponding author. Email: sglover@une.edu.au
Density functional calculations have been carried out to determine the properties of the title anomeric amides. At the
B3LYP/6-31G(d) level, N-chloro-N-methoxyacetamide 8a is computed to be strongly pyramidal at nitrogen with a long
amide bond that is untwisted. N-Chloro-N-dimethylaminoacetamide 9a is completely planar, but its amide bond is still
much longer than that in N,N-dimethylacetamide 4. This is a steric, rather than a resonance, effect. COSNAR and a trans-
amidation method calculate low resonance energies for both model amides, which is attributed to the combined
electronegativity of the heteroatoms at the amide nitrogen and the strong anomeric effect when there is a chlorine
substituent on nitrogen. When M06 and vB97X-D dispersion-corrected density functional methods are used with the
expanded 6-311þþG(d,p) basis set, the resonance energies of 8a (ꢀ34 kJ molꢀ1) and 9a (ꢀ49 kJ molꢀ1) are in line with
the gross electronegativity of the substituent atoms. Unlike other anomeric amides, 8a and 9a are not predicted to undergo
HERON reactivity.
Manuscript received: 29 April 2014.
Manuscript accepted: 19 May 2014.
Published online: 19 June 2014.
Introduction
In addition to crystal data, these altered properties are
supported by experimental and spectroscopic data as well as
theoretical studies.[1–3,6–12]
Anomeric amides, an unusual class of amides highlighted in
our research, bear two electronegative atoms on the amide
nitrogen. Amides 1a–d (Chart 1) all possess properties that are
a response to the electron demand of the atoms X and Y.[1–6]
The substituent atoms at nitrogen induce localization of the
nitrogen atom lone pair electrons in an sp3 hybrid orbital, which
results in loss of resonance stabilization through both the
increased ‘s’ character, as well as the reduced basicity of
the lone pair. Nonetheless, the lone pair still benefits from an,
albeit weakened, resonance interaction with the carbonyl
carbon as X-ray structural data for a variety of congeners
show relatively little twist about the N–CO bond.[6–9]
The reduced resonance is evident in much higher than
expected carbonyl stretch frequencies in their infrared spectra.
For instance, N,N-dialkoxyamides 1b (ONOsystems), N-acyloxy-
N-alkoxyamides 1c (ONOAc systems), and N-alkoxy-N-
aminoamides 1d (NNO systems) exhibit solution-state amide
carbonyl stretch frequencies in ranges of 1710–1720, 1718–
1750, and 1700–1744 cmꢀ1 respectively.[1–3,9,13] Crystal struc-
tures demonstrated strong pyramidality at nitrogens of ONO and
ONOAc systems with two oxygen atoms at nitrogen (Winkler–
Dunitz[14,15] pyramidalityof x ¼ 56–588and 60–618respectively).
OR1
O
O
R
X
Y
O
OMe
N
OMe
O
R
OMe
N
NMe2
O
Me
N
Me
N
N
(CH2)
n
O
Me
Me
R2
ꢀ 1, R1 ꢀ Bu, R2 ꢀ Me
ꢀ 2, R1 ꢀ Bu, R2 ꢀ Me
ꢀ 1, R1 ꢀ Me, R2 ꢀ H
ꢀ 2, R1 ꢀ Me, R2 ꢀ H
1a, X Cl, Y OR
1b, X OR, Y OR
1c, X OAc, Y OR
1d, X OR, Y NR2
1e, X Cl, Y NR2
3a R Me
3b R
2
4
5a
5b
5c
5d
,
,
,
,
n
n
n
n
H
Chart 1.
*This paper is dedicated to the memory of Professor Roger Brown, one of Australia’s most notable physical organic chemists and a true gentleman.
Journal compilation Ó CSIRO 2014
www.publish.csiro.au/journals/ajc

ONCl and NNCl Anomeric Amides
1345
The NNO amides studied to date are less pyramidal but nonethe-
less significantly puckeredat nitrogen (x ¼ 47–488).[8] In all cases,
the amide bonds are relatively untwisted but weakened resonance
Anomeric destabilization of the N–X bond by a lone pair on
Y plays a role in determining the ease of migration of X.[1,3,19]
When Y is nitrogen, the high-energy amino lone pair results in a
strong nN-s*NX interaction and a weakening of the N–X bond in
accord with the much lower activation energy (EA) for the
HERON reaction in NNO systems 1d relative to ONO systems
1b and 1c. However, computed migration transition states in all
HERON reactions demonstrate that residual RE is sacrificed, in
that the group X migrates in a plane orthogonal to the N—C(O)
plane, necessitating complete rotation of the nitrogen lone pair
away from conjugation and into that plane (Fig. 2). Clearly, this
loss of conjugation is a component of the overall activation
energy, and heteroatoms at nitrogen also impact on the HERON
activation barriers through their impact on the RE. The net
rearrangement energy (Erearr) is the difference between the
overall EA and the RE, and Erearr for N,N-dimethoxyacetamide
2 and N-methoxy-N-dimethylaminoacetamide 3a has been esti-
mated at 120 and 43 kJ molꢀ1 respectively.[18]
˚
is evidenced by long N—CO bond lengths (ONO, 1.41–1.42 A,
˚
ONOAc, 1.44 A, NNO, 1.41A) when compared with typical
˚
[7]
˚
˚
amides (average 1.359 A, median 1.353 A), and very low
barriers to amide isomerism. The barrier to rotation of several
N,N-dialkoxyamides could not be observed by NMR down
to ꢀ908C.[1] An nY—s*NX anomeric stabilization is evident from
alignment of a p-type lone pair on Y and the N–X s* orbital in
crystal structures of all three systems.
Calculations employing the B3LYP/6–31G(d) level of
theory have been found to reproduce the structural proper-
ties of anomeric amides as well as their reduced resonance
energies.[9–12,16] We recently demonstrated that the residual
resonance energy (RE) in amides and lactams in general
can be determined isodesmically[17] and, using those methods,
models N,N-dimethoxyacetamide 2 and N-methoxy-N-dimethy-
laminoacetamide 3 retain only 36 kJ molꢀ1 and 51–52 kJ molꢀ1
of resonance respectively, approximately 47 and 67 % that of
Two anomeric amides 1a (ONCl) and 1e (NNCl) have
received less attention. However, ONCl systems show all of
the characteristics of other anomeric amides. A recent X-ray
structure of N-chloro-N-methoxy-4-nitrobenzamide 6 (Chart 2)
confirms a strongly pyramidal nitrogen (x ¼ 538), a twist angle
about the N—C(O) bond of only 138, a long N—C(O) bond of
N,N-dimethylacetamide 4 (76 kJ molꢀ1 [9,18]
)
Anomeric amides 1b–d have been shown to undergo
the unusual HERON reaction,y which is illustrated in Fig. 1
and involves an anomerically driven migration of an electro-
negative atom from nitrogen to the carbonyl carbon with
production of a stabilized nitrene.[16,19–26] Initially discovered
from spontaneous decomposition of N-alkoxy-N-aminoamides
1b,[2,21,22,24,27–30] it has subsequently been observed in the
thermal decomposition of N-acyloxy-N-alkoxyamides 1c at
elevated temperatures.[26] Acyclic N,N-dialkoxyamides
instead undergo homolysis at elevated temperatures to alkoxyl
and N-alkoxyamidyl radicals[13] but several cyclic forms of
N,N-dialkoxyamides 5a and 5b rearrange at room temperature
in reactions under stereoelectronic control.[16] Theoretical
activation barriers from B3LYP/6–31G(d) calculations are in
line with these observations. Computed barriers to rearrange-
ment of methoxyl in 2 and 3a are, respectively, 189 and
˚
1.41 A, and ideal anomeric alignment of the p-type lone pair on
oxygen with the N—Cl s* orbital.[6] Earlier B3LYP/6–31G(d)
calculations on formamide 8b predicted these properties.[10]
Infrared carbonyl stretch frequencies for a wide range of N-
alkoxy-N-chloroamides range from 1718 to 1744 cmꢀ1 and are
on average ,40 cmꢀ1 higher than their hydroxamic ester pre-
cursors.[1,3] From a dynamic NMR study on N-benzyloxy-N-
chlorobenzamide 7, DGz of 41.8 kJ molꢀ1 for rotation about the
O—N bond was determined but amide isomerism could not be
detected and must have an even lower barrier.[1] Corresponding
computed isomerization barriers in N-chloro-N-methoxyforma-
mide 8b were 44.3 and 29.3 kJ molꢀ1 [10]
.
In contrast to ONCl systems, the structural and spectroscopic
properties of NNCl systems 1e are thus far unknown. The
147 kJ molꢀ1 [16,18,19,22]
by ring opening and ring contraction respectively with com-
puted barriers of 108 and 139 kJ molꢀ1 [16]
.
Model lactams 5c and 5d rearrange
.
(a)
Y
(b)
R
C
R
O
N
X
O
O
Y
N
ꢂ
C
ꢁ
Y
HERON
O
C
R
N
ꢁ
N
Y
N
Y
X
R
X
X
Fig. 2. Theoretically derived transition state for the generalized HERON
reaction of an XNY amide. (a) Perspective drawing; (b) Newman projection
along the N–C bond.
Fig. 1. A generalized HERON reaction where X and Y are electronegative
atoms.
O
O
OMe
Cl
O
OCH2Ph
O
OMe
Cl
NMe2
Cl
O
NHMe
Cl
N
N
N
N
N
Cl
4-NO2C6H4
R
R
Me
Ph
6
7
8a R ꢀ Me
8b R ꢀ H
9a R ꢀ Me
9b R ꢀ H
10
Chart 2.
yHeteroatom rearrangements on nitrogen; first presented to the Second Heron Island Conference on Reactive Intermediates and Unusual Molecules, Heron
Island, Australia, 1994.

1346
S. A. Glover, A. A. Rosser, and R. M. Spence
Table 1. B3LYP/6–31G(d) optimized geometries for N-chloro-N-methoxyacetamide 8a, N-chloro-N-dimethylaminoacetamide 9a, and N-chloro-N-
methylaminoacetamide 10 together with data for 2 and 3a
C2
C1
C1
C1
N1
O1
C2
N2
N2
C2
O1
O1
N1
N1
O2
C3
Cl
Cl
Cl
8a
9a
10
t [8]A
x [8]B
y [8]C
Twist [8]D
˚
N1—C1 [A]
˚
C1—O1 [A]
˚
N1—O2 or N1—N2 [A]
˚
N1—Cl [A]
8a
9a
10
2E
ꢀ5.3
0
52.3
0
112.5
120.0
116.8
114.3
115.5
1.432
1.396
1.414
1.417
1.404
1.207
1.212
1.209
1.212
1.217
1.388
1.351
1.359
1.406E
1.387F
1.787
1.820
1.828
1.391E
1.43F
1
0
ꢀ7.8
8.5
35.1
48.1
41.8
6
67/84
10
3aF
5.4
AWinkler–Dunitz twist parameter.[14,15]
BWinkler–Dunitz pyramidality index.[14,15]
CAverage angle at nitrogen.
DTwist of O2 (in 8a) or N2 (in 9a and 10) lone pair axes from the N—Cl bonds; a measure of anomeric alignment.
EPreviously published data; N—O bonds in 2.[9]
F
[18]
˚
New data; N—N (1.387 A) and N—O (1.430 A) in 3a.
˚
conformers of N-chloro-N-dimethylaminoformamide 9b have
been calculated at the B3LYP/6–31G(d) level as part of our
initial investigations of anomeric amides and the nitrogen was
predicted to be strongly pyramidal (average angle at the amide
nitrogen of 1128) and to have a long N—C(O) bond
(a)
(b)
Cl
C
Cl
[10]
˚
(1.418 A). However, to our knowledge no stable N-amino-
N-chloroamides are known.
O
HERON reactions have not been observed for ONCl systems,
which are thermally stable at room temperature. HERON reac-
tions of NNCl systems would be expected to occur more readily
than in ONCl systems and HERON has been implicated in at
least one reaction between a hydrazide and tert-butyl hypochlo-
rite (see below).
O
C
N
N
Fig. 3. Space-filling models of (a) N-chloro-N-dimethylaminoacetamide
9a; (b) N-chloro-N-methylaminoacetamide 10.
In this paper, we explore the theoretical properties of
model ONCl system N-chloro-N-methoxyacetamide 8a, and
NNCl systems N-chloro-N-dimethylaminoacetamide 9a and
N-chloro-N-methylaminoacetamide 10 to establish their stab-
ility and REs as well as the potential for HERON reactivity in
ONCl and NNCl systems.
amide nitrogen is completely sp2 hybridized and it represents the
first anomeric amide that is not predicted to become pyramidal
in response to the electron demand of the heteroatoms. NNO
systems are less pyramidal than ONO systems but in 3a, the
amide nitrogen is still computed to be quite pyramidal (x ¼ 428)
and the average angle at nitrogen in the formamide 3b was
predicted to be 1168.[12,18] NNCl systems should exhibit appre-
ciable pyramidality, even with the lower electronegativity of
chlorine. However, although sp2 hybridization shortens adjacent
bonds, the N—C(O) bond in 9a is in fact quite long when
Results and Discussion
The lowest-energy structures of N-chloro-N-methoxyacetamide
8a, N-chloro-N-dimethylaminoacetamide 9a, and N-chloro-N-
methylaminoacetamide 10, together with important geometrical
parameters, are shown in Table 1.
˚
compared with N,N-dimethylacetamide 4 (1.378 A at B3LYP/
6–31G(d)) in which the amide nitrogen is similarly planar.[17]
The driving force for the lack of pyramidality at the amide
nitrogen in 9a becomes clear on inspecting space-filling models
of 9a and of the B3LYP/6–31G(d) optimized structure of 10
(Fig. 3). Steric congestion in 9a, which is relieved in the
methylamino analogue 10, enforces planarity in 9a. The electro-
negativity of the –NHMe group in 10 would not be expected to
differ greatly from –NMe2 in 9a, and on replacement of one
methyl by sterically less-demanding hydrogen, the nitrogen
becomes reasonably pyramidal (x ¼ 358). The N—C(O) bond
also lengthens in line with that of the methoxy analogue 8a.
The computed structure around nitrogen for 8a closely
matches the X-ray structure of 6 and the degree of pyramidality
at nitrogen is akin to that computed for other anomeric amides
with similar electron demand at nitrogen such as N,N-dimethox-
yacetamide 2, for which x ¼ 488.[9] The characteristic N—C(O)
˚
bond is longer than that for 2 (1.417 A), which would imply even
less amide character relative to 2. From the twist angle, the
anomeric alignment in 8a is nearly optimal and indicates an
nO—s*NCl conformational stabilization in the ground state.
The theoretical structure of N-chloro-N-dimethylaminoace-
tamide 9a is, at first inspection, quite anomalous in that the

ONCl and NNCl Anomeric Amides
1347
In both NNCl systems, the amino nitrogen lone pair axis lies
very close to the plane containing the N—Cl bond, in support of
an nN—s*NCl anomeric interaction.
Unequivocal support for reduced amidicity in both 8a and 9a
can be derived from isodesmic calculations of the RE in each
case. As in previous papers,[9,16–18] we have established RE by
two independent methods: carbonyl substitution nitrogen atom
replacement (COSNAR)[31,32] and a trans-amidation process.[17]
Table 2. B3LYP/6-31G(d)-derived COSNAR and trans-amidation
data for N-chloro-N-methoxyacetamide 8a, N-chloro-N-dimethylami-
noacetamide 9a, and N-chloro-N-methylaminoacetamide 10 from Eqns
1–4 and acetyl chloride–methoxynitrene complex energies in Fig. 5
Structure
Energy [kJ molꢀ1 A
]
N-Chloro-N-methoxyacetamide 8a
DECOSNAR for 8aB
ꢀ29.60 [38 %]
69.91
DEReact for 8aC
DEInductive for 8aD
RE for 8aE
23.41
Y
Y
O
O
Y
Y
ΔECOSNAR
Cl Y ꢀ OMe, NMe2
N
N
ꢁ
ꢁ
ꢀ29.47 [39 %]
Cl
Cl
Cl
H3C
H3C
H3C
H3C
N-Chloro-N-dimethylaminoacetamide 9a
DECOSNAR for 9aB
11
12
13
14
ꢀ28.73 [38 %]
64.54
DEReact for 9aC
ð1Þ
DEInductive for 9aD
17.60
RE for 9aE
ꢀ29.04 [37 %]
The COSNAR process, represented by Eqn 1, gives the
energy stabilization when ketone 11 and amine 12, in the same
skeletal matrix, generate the amide 13 and hydrocarbon 14. For
N,N-dimethylacetamide 4, the stabilization is ꢀ77.5 kJ molꢀ1
and amidicity is given as a percentage of this value.[17]
N-Chloro-N-methylaminoacetamide 10
DECOSNAR for 10B
ꢀ32.56 [42 %]
66.57
DEReact for 10C
DEInductive for 10D
23.18
RE for 10E
ꢀ32.58 [43 %]
173.3 (166.3)F
165.0 (158.4)F
Complex Fig. 5 anti (i136 cmꢀ1
)
CH3
Complex Fig. 5 syn (i178 cmꢀ1
)
O
CH3
CH3
Y
O
Y
N
N
ΔEreact
ꢁ
N
N
ꢁ
H3C
CH3
H3C
H3C
Cl
H3C
Cl
AAmidicities in square parentheses.
BFrom Eqn 1.
Y ꢀ OMe, NMe2
4
12
13
15
CFrom Eqn 2.
ð2Þ
DFrom Eqn 3.
EFrom Eqn 4.
The alternative method, which gives very similar REs but, in
FRelative to the energy of 8a; ZPE and enthalpy-corrected values in
addition, sheds light on the effect of inductive substituents at
nitrogen, first determines the change in stability of an amide
relative to 4 through Eqn 2. However, electronegative substi-
tuents at nitrogen further destabilize the carbonyl of an amide
through their b-inductive effect, and this can be determined
isodesmically from Eqn 3 where the amides are fully twisted and
are obtained as transition states by B3LYP/6–31G(d). As the
total destabilization due to loss of resonance, DEreact, includes
DEinductive, the destabilization due to loss of RE is obtained as
the difference between these two energies. In this approach, the
maximum possible loss of resonance is ꢀ76.0 kJ molꢀ1 (deter-
mined from the destabilization in 1-aza-2-adamantanone,
which, like Kirby’s trimethylated derivative,[33,34] is fully
twisted[17]) and the residual RE is given by Eqn 4.
parentheses.
The N-methylamino variant, 10, has slightly greater resonance
than that of 9a and here the nitrogen is distinctly pyramidal
(x ¼ 358; Table 2). The computed structure of 9a in which the
nitrogen is completely sp2 hybridized with zero twist clearly
plays no role in promoting amide resonance, which must be
reduced owing to localization of the amide nitrogen atom lone
pair. Furthermore, resonance cannot account for the planarity in
9a. B3LYP/6–31G(d) predicts the amide resonance in this NNCl
system to be some 20 kJ molꢀ1 lower than that computed for the
NNO model 3a (,50 kJ molꢀ1).[18] The combined Pauling
electronegativities of oxygen with chlorine (6.5) and nitrogen
with chlorine (6) are less than that of two oxygen atoms (7), yet
the dampening of amide resonance at the B3LYP/6–31G(d)
level of theory is similarly marked in the systems with lower
overall electronegativity at nitrogen.
ΔEinductive
N
Me
N
N
Me
Me
N
Me
Y
Cl
Me
Me
Me
Me
ꢁ
ꢁ
Y
Cl
Y ꢀ OMe, NMe2
O
O
4
12
13
15
One possible contributor to this anomaly could be the
enhanced anomeric effect in these systems. nY—s*NX anome-
ric interactions are favoured by Y atoms to the left and X atoms
to the right of the p-block because the lone pair on Y, nY, and
the N–X antibonding orbital, s*N–X, become closer in energy,
resulting in a stronger orbital interaction. Furthermore, s*NX
becomes lower proceeding down the halogen group
(Fig. 4a).[1,3,35,36] The anomeric interactions in 8a, 9a, and 10
(Fig. 4b) are likely to be stronger than those in 2 or 3a on
account of the lower-energy s*NCl orbital when compared with
s*NO. The attendant charge separation and lengthening of the
N—Cl bond in 8a, 9a, and 10 (Fig. 4c) when compared with a
weaker nO—s*NO interaction in 3 warrant a more rigorous
methodology.
ð3Þ
Residual RE ¼ ꢀ76:0 þ ðDEreact ꢀ DEinductiveÞ kJ molꢀ1 ð4Þ
Based on B3LYP/6–31G(d) energies for all structures
(Table S1 in the Supplementary Material), DECOSNAR, DEreact
,
DEinductive, and REs have been computed for 8a, 9a, and 10
(Table 2). For N-chloro-N-methoxyacetamide 8a, the COSNAR
and trans-amidation REs are virtually identical and lower than
that computed for N,N-dimethoxyacetamide 2 (36 kJ molꢀ1),
indicating only ,38 % retention of the level of resonance in N,
N-dimethylacetamide 4. The pyramidality is very similar in 2
(x ¼ 488) and 8a, but 8a is less twisted than 2 (t ¼ 8.5) (Table 1).
After incorporation of the b-inductive destabilizing effect
of chlorine and nitrogen, the trans-amidation and COSNAR
methods give very similar stabilization for each of 9a and 10.
Although the geometries and energies of a diverse range
of amides and lactams in general are adequately and cost-
effectively dealt with at the B3LYP/6–31G(d) level,[17] the

1348
S. A. Glover, A. A. Rosser, and R. M. Spence
(a)
E
(b)
(c)
O
O
σ∗
σ∗
R
N
δꢁ
N—O
N—Cl
C
Y
R
N
Y
nY
σ∗
—
N
Cl
Cl
ꢂCl
nN
nO
δ
Fig. 4. (a) Energetics of anomeric effects; (b) anomeric overlap with an N—Cl bond; (c) polarization through
nY-s*NCl anomeric interaction; Y is N and O.
Table 3. Geometries of N-chloro-N-methoxyacetamide 8a, N-chloro-N-dimethylaminoacetamide 9a and N-chloro-N-methylaminoacetamide 10 at
the B3LYP/6–31111G(d,p), M06/6–31111G(d,p), and vB97X-D/6–31111G(d,p) levels of density functional theory (DFT)
8a
9a
10
B3LYP
M06
vB97X-D
B3LYP
M06
vB97X-D
B3LYP
M06
vB97X-D
˚
N—Cl [A]
˚
N—O or N—N [A]
˚
N—CO [A]
˚
C—O [A]
1.783
1.385
1.430
1.202
87.1
1.746
1.368
1.418
1.197
89.1
1.743
1.372
1.419
1.198
89.7
1.821
1.349
1.394
1.208
60/60
120.0
0
1.776
1.347
1.391
1.201
60/60
120.0
0
1.764
1.354
1.388
1.204
60/60
120.0
0
1.821
1.357
1.410
1.205
59/71
117.43
31.6
1.775
1.352
1.400
1.200
61/70
118.3
25.6
1.760
1.361
1.398
1.203
65/58
118.4
25.1
CONCl or CNNCl [8]
y [8]A
x [8]B
t [8]C
113.0
50.73
4.8
114.1
47.3
113.7
48.6
5.3
4.5
0
0
0
6.2
5.26
4.45
AAverage angle at nitrogen.
BWinkler–Dunitz pyramidality index.[14,15]
CWinkler–Dunitz twist parameter.[14,15]
potential for partial charge separation described above would
suggest that a density functional theory (DFT) method with
dispersion corrections, together with a much-expanded basis set,
with both extended polarization and with diffuse functions, might
be more reliable. To test this, the structures, COSNAR REs, and
amidicities of N-chloro-N-methoxyacetamide 8a, N-chloro-N-
dimethylaminoacetamide 9a, and N-chloro-N-methylaminoace-
tamide 10 were computed at the B3LYP/6–311þþG(d,p), M06/
6–311þþG(d,p), and vB97X-D/6–311þþG(d,p) levels of
theory. Both the M06[37] and vB97X-D functionals[38] are
designed to correct empirically for dispersion.[39] From Table 3,
the geometries of the M06- and vB97X-D-derived structures for
8a, 9a, and 10 were similar to those from B3LYP in most
respects. All the bond lengths were slightly shorter than those
obtained using B3LYP/6–311þþG(d,p) and B3LYP/6–31G(d)
methods but by all three methods, the nitrogens were predicted to
be strongly pyramidal in 8a (x close to 508) while twist angles
were small and nearly identical (t close to 58). Like B3LYP/
6–31G(d), all three methods predicted 9a to be completely planar
with zero twist (x, t ¼ 0) and for 10, all three methods predicted
reasonably pyramidal nitrogens with limited twist. For all
three anomeric amides, the N—C(O) bond lengths by B3LYP/
6–311þþG(d,p), M06/6–311þþG(d,p), and vB97X-D/
6–311þþG(d,p) methods were much longer than N,N-dimethy-
Table 4. COSNAR energies (from Eqn 1) and amidicities for N-chloro-
N-methoxyacetamide 8a, N-chloro-N-dimethylaminoacetamide 9a, N-
chloro-N-methylaminoacetamide 10, and N,N-dimethylacetamide 4
obtained at B3LYP/6–31111G(d,p), M06/6–31111G(d,p), and
vB97X-D/6–31111G(d,p) levels of density functional theory (DFT)
DFT method
B3LYP
M06
vB97X-D
DECOSNAR 8a [kJ molꢀ1
DECOSNAR 9a [kJ molꢀ1
DECOSNAR 10 [kJ molꢀ1
]
]
]
ꢀ27.2
ꢀ28.6
ꢀ29.4
ꢀ75.9
35.8
ꢀ34.4
ꢀ48.7
ꢀ46.0
ꢀ75.9
45.4
ꢀ33.9
ꢀ48.5
ꢀ45.0
ꢀ77.1
44.0
DECOSNAR 4 [kJ molꢀ1
Amidicity 8a [%]
Amidicity 9a [%]
Amidicity 10 [%]
]
37.7
64.2
62.9
38.8
60.6
58.4
from DECOSNAR for 4 (Table 4) are very similar and almost
the same as the B3LYP/6–31G(d) value (ꢀ77.5 kJ molꢀ1).[17]
Dispersion contributions are clearly unimportant in the treat-
ment of this N,N-dialkylamide. However, the values for
8a, where the DFT incorporated dispersion corrections, are
,7 kJ molꢀ1 higher than the B3LYP/6–311þþG(d,p) value,
which suggests an improvement when dispersion is taken into
account. Nonetheless, N-chloro-N-methoxyacetamide 8a still
retains only ,45 % of the resonance in 4. This discrepancy
between B3LYP and dispersion-corrected DFT methods is
measurably greater for N-chloro-N-dimethylaminoacetamide
9a and N-chloro-N-methylaminoacetamide 10, where reson-
ance is computed to be ,60 % that of N,N-dimethylacetamide
4 and substantially higher than that predicted from B3LYP/
6–311þþG(d,p), which was identical to the B3LYP/6–31G(d)
value (29 kJ molꢀ1). Furthermore, the RE parity for 8a and 9a at
˚
lacetamide 4 at those levels (1.374, 1.372, and 1.369 A respec-
tively). Anomeric interactions were optimized in all cases as
evidenced by CONCl dihedral angles close to 908 in 8a, and
CNNCl dihedrals of 608 in 9a and close to 608 in 10.
The REs of N,N-dimethylacetamide 4, used as calibration for
the amidicities of 8a, 9a, and 10, necessitated computation of
DECOSNAR (from Eqn 1) by the three different DFT methods for
N,N-dimethylacetamide 4 along with 8a, 9a and 10. The REs

ONCl and NNCl Anomeric Amides
1349
Clꢂ
O
C
O
C
O
C
ꢁ
ButOCl
NMe2
NMe2
NMe2
Elimination
Path (ii)
N
Ph
Ph
Ph
NH
N
Benzene
Cl
16
17
18
Path (i) HERON
16
O
C
PhCO
ꢂ
N
ꢁ
NMe2
16
ꢁ
N
NMe2
Ph
Cl
PhCO
19
20
21
Scheme 1.
(a)
(b)
Cl
Cl
2.662 Å
2.552 Å
N
1.257 Å
N
1.247 Å
1.941 Å
45.5ꢃ
48.6ꢃ
1.988 Å
O
O
2.303 Å
O
1.181 Å
2.219 Å
C
C
O
1.185 Å
Anti
Syn
Fig. 5. Methoxynitrene–acetyl chloride complexes from 8a with oxygens (a) anti, and (b) syn relative to the N—C—Cl plane.
O
C
on treatment with tert-butyl hypochlorite according to
Scheme 1. The intermediate 17 could undergo HERON reac-
tion to form benzoyl chloride 19 and 1,1-dimethyldiazene 21.
Alternatively, elimination of chloride could give 18. Both 18
and 19 could be responsible for N,N-bisacyl substitution in 20
by rapid reaction with unreacted hydrazide.
O
C
ꢂ
Cl
ꢁ
N
Y
Y
ꢁ
Me
Me
N
Cl
22a Y ꢀ OMe
22b Y ꢀ NMe2
Scheme 2.
Both 8a and 9a could also undergo elimination reactions to
form respectively the N-acetyl-N-methoxynitrenium ion 22a
and N-acetyl-N-dimethylaminonitrenium ion 22b (Scheme 2).
Both processes would be driven by the anomeric effect at the
amide nitrogen, which, as outlined, is strongly favoured with
geminal chlorine. B3LYP/6–31G(d) calculations shed some
light on these experimental possibilities.
A HERON transition state search with 8a using geometries
similar to that in Fig. 2 generates two structures with oxygens
syn and anti (Fig. 5), each with one imaginary frequency, and
their energies relative to the ground state including thermal
correction are given in Table 2. The structures exhibit very long
N—C(O) and N—Cl bonds, and a short Cl—CO separation that
is not much greater than the length of the Cl—CO bond in acetyl
B3LYP is no longer observed with M06 and v97X-D, which
predicted nearly identical REs that are significantly higher than
those for 8a and in line with the lower overall electronegativity
of nitrogen and chlorine. 10 has slightly less resonance than the
dimethyl analogue 9a but the results again show that the
planarity in 9a is a steric rather than an electronic factor. These
results would indicate the necessity for inclusion of dispersion
corrections in treatments of molecules where anomeric interac-
tions are likely to have a pronounced influence.
The REs of ONCl and NNCl systems are still low when
compared with normal amides, and because this energy is
sacrificed in HERON reactions, both systems might be suscep-
tible to HERON rearrangements. However, the overall EA for
HERON reactions has not only a component equivalent to the
RE but also a rearrangement component, Erearr, which, if
substantial, can be rate-limiting.[18]
Many N-alkoxy-N-chloroamides 1a have been synthesized
in our laboratory as precursors to N-alkoxynitrenium ions[40–42]
and a wide range of biologically active mutagens, N-acyloxy-
N-alkoxyamides 1c.[1–3,23,27,43–53] Despite their very low REs,
to date HERON reactions of 1a have not been observed. The
HERON reaction of N-chloro-N-aminoamides 1e could be
inferred from the quantitative conversion of b,b-dimethyl-
benzhydrazide 16 to 1,1-dibenzoyl-2,2-dimethylhydrazine 20
˚
chloride optimized at the same level (1.835 A). The lowest
,
energy difference relative to ground state 8a is 158 kJ molꢀ1
which places these just below the energy of the products, acetyl
chloride and methoxynitrene, and each structure can best be
regarded as a complex between the two. Gas-phase separated
acetyl chloride and methoxynitrene are higher than ground state
8a by 168 kJ molꢀ1. They do not represent HERON transition
states, as from either structure a small contraction of the N–Cl
separation resulted in a different complex between chloride and
N-acetyl-N-methoxynitrenium ion 22a. This is clear from anal-
ysis of charge separation and geometry in Fig. 6a where the
chlorine bond is long, is orthogonal to the N—C(O) plane, and
bears a charge of ꢀ0.3 as opposed to its þ0.1 charge in the

1350
S. A. Glover, A. A. Rosser, and R. M. Spence
(a)
(b)
Cl (ꢂ0.26)
Cl (ꢂ0.31)
Dihedral OCNCl ꢀ ꢂ86ꢃ
98ꢃ
2.103 Å
Dihedral OCNCl ꢀ ꢂ101ꢃ
2.382 Å
1.319 Å
N
93ꢃ
1.317 Å
1.477 Å
N
1.495 Å
C
N
O
O
C
1.202 Å
O
1.202 Å
Fig. 6. (a) Optimized structure from contraction of the N—Cl bond in Fig. 6a; (b) structure of 22b from HERON transition state
search on 9a.
ground-state structure 8a. The complexes do not lie on a
HERON reaction coordinate. In the gas phase, the enforced
adoption of a typical HERON transition-state geometry, similar
to that in Fig. 2, results in collapse to acetyl chloride and
methoxynitrene. ONCl systems would not be expected to
undergo HERON reactions in accord with the experimental
findings. In solution, particularly, ONCl systems would be
expected to dissociate to nitrenium and chloride ions according
to Scheme 2.
No transition state could be found for the HERON reaction of
9a. All approximations to transition states similar to that in
Fig. 2 resulted in a complex between chloride and N-acetyl-N-
dimethylaminonitrenium ion 22b. An exemplary structure is
shown in Fig. 6b. Here, too, the chlorine is orthogonal to the
N—C(O) plane and bears substantial negative charge relative to
the ground state structure of 9a where chlorine bears þ0.2
charge. Strong anomeric destabilization of the N—Cl bond
coupled with formation of a strongly resonance-stabilized nitre-
nium ion would favour this reaction over a HERON, particularly
in solution. The most probable route to 1,1-dibenzoyl-2,2-
dimethylhydrazine 20 in Scheme 1 is pathway (ii).
anomeric delocalization into the low-lying N—Cl s* orbital in
8a and particularly in 9a. With higher-energy s*NO orbitals, such
as in 2 and 3, the B3LYP/6–31G(d) method probably performs
adequately. However, the origin of resonance dampening in
anomeric amides warrants further theoretical investigation.
Although the structures of ONCl and NNCl systems are
likely to possess lowered REs, a component of activation
energies for HERON reactions, neither N-chloro-N-methoxya-
cetamide nor N-chloro-N-dimethylaminoacetamide will rear-
range concertedly to acetyl chloride and nitrenes. Instead, they
are predicted to undergo preferential elimination of chloride,
which would suggest that ONCl and NNCl systems would
produce stabilized nitrenium ions, particularly in polar solvents.
Experimental
Materials and Methods
Melting points were determined on a Reichert microscopic hot
stage and are uncorrected. Infrared spectra were recorded on a
Perkin Elmer 1725X Fourier-transform (FT) instrument.
300 MHz 1H NMR spectra were recorded on a Bruker AC-300P
FT spectrometer with a 5-mm probe operating at 300.13 MHz.
Conclusion
Computational Methods
N-Chloro-N-methoxyacetamide is computed to have the typical
properties of anomeric amides, namely a strongly pyramidal
nitrogen and long N—C(O) bond as well as correct orbital
alignment for an nO—s*NCl interaction. N-chloro-N-dimethyla-
minoacetamide 9a has a most unusual structure, being planar at
nitrogen, yet with reduced resonance with the carbonyl. The
planarity is not borne out of a requirement to optimize the reso-
nance interaction, but rather it derives from steric inhibition to
pyramidalization at nitrogen because in 10, where steric com-
pression is relaxed, the nitrogen becomes puckered as expected.
The combination of nitrogen with chlorine at the amide nitrogen
results in similarly low REs whether the nitrogen is planar or not
and this must be attributed to the electronic influence of the
electronegative atoms. Although at the B3LYP/6–31G(d) level,
the RE in these NNCl systems, with total electronegativity at
nitrogen less than in the ONCl model 8a, is approximately the
sameas thatcalculatedfor 8a, with DFT methods thatincorporate
dispersion corrections such as M06 and vB97X-D and an
expanded 6–311þþG(d,p) basis set, the NNCl model has greater
resonance than the ONCl model, which in turn has slightly more
intrinsic resonance than computed at B3LYP/6–31G(d). The
difference probably lies in the very much better treatment of the
Energies and geometries for fully optimized ground states of
models of all structures in Tables 1–4 and associated structures
utilized in Eqns 1–3, as well as complexes depicted in Figs 5 and
6, were computed by DFT based on Becke’s three-parameter
functional B3LYP,[54,55] the dispersion-corrected functionals
M06 of Zhao and Truhlar[37] and vB97X-D of Chai and Head-
Gordon[38] with split-valence basis sets[56,57] at the B3LYP/6–
31G(d), B3LYP/6–311þþG(d,p), M06/6–311þþG(d,p), and
vB97X-D/6–311þþG(d,p) levels using MacSpartan 10[58] and
Gaussian 03.[59] B3LYP/6–31G(d) has been shown to perform
well in determinations of structure and properties of a wide
range of amides, lactams, and anomeric amides.[9,10,12,16–19,22]
Energies of model structures in isodesmic Eqns 1, 2, and 3 were
computed without ZPE and thermal corrections because these
largely cancel. For 8a and the complexes (Fig. 5a, b) ZPE and
vibrational corrections required full frequency calculations. The
complexes possessed one imaginary frequency. Lowest-energy
twisted amides used in Eqn 3 were obtained by transition
state searches starting with twisted forms. The most stable
twisted forms of N,N-dimethylacetamide 4, N-chloro-N-
methoxyacetamide 8a, N-chloro-N-dimethylaminoacetamide
9a, and N-chloro-N-methylaminoacetamide 10 had the lone

ONCl and NNCl Anomeric Amides
1351
pairs respectively anti, syn, anti, and syn to the carbonyl. In the
cases of 8a and 10, these conformations needed to be con-
strained to keep the lone pair in the N—C(O) plane. In addition,
optimized structures of the corresponding amines 12 (Y ¼ OMe
and NHMe) used in Eqn 3 were not global minima but were
obtained with the lone pair and 2-methyl anti for consistent
steric impact. Geometries for all structures computed at B3LYP/
6-31G* level are provided as Supplementary Material.
[5] V. G. Shtamburg, O. V. Shishkin, R. I. Zubatyuk, S. V. Kravchenko,
A.V. Tsygankov,V. V.Shtamburg,V.B.Distanov,R.G.Kostyanovsky,
Mendeleev Commun. 2007, 17, 178. doi:10.1016/J.MENCOM.
2007.05.016
[6] V. G. Shtamburg, A. T. Tsygankov, O. V. Shishkin, R. I. Zubatyuk,
B. V. Uspensky, V. V. Shtamburg, A. V. Mazepa, R. G. Kostyanovsky,
Mendeleev Commun. 2012, 22, 164. doi:10.1016/J.MENCOM.2012.
05.019
[7] A.-M. E. Gillson, S. A. Glover, D. J. Tucker, P. Turner, Org. Biomol.
Chem. 2003, 1, 3430. doi:10.1039/B306098P
[8] S. A. Glover, G. Mo, A. Rauk, D. Tucker, P. Turner, J. Chem. Soc.,
Perkin Trans. 2 1999, 2053. doi:10.1039/A904575I
[9] S. A. Glover, J. M. White, A. A. Rosser, K. M. Digianantonio, J. Org.
Chem. 2011, 76, 9757. doi:10.1021/JO201856U
[10] A. Rauk, S. A. Glover, J. Org. Chem. 1996, 61, 2337. doi:10.1021/
JO9521817
[11] S. A. Glover, A. Rauk, J. Chem. Soc., Perkin Trans. 2 2002, 1740.
doi:10.1039/B204232K
[12] S. A. Glover, A. Rauk, J. Org. Chem. 1999, 64, 2340. doi:10.1021/
JO982048P
[13] K. M. Digianantonio, S. A. Glover, J. P. Johns, A. A. Rosser, Org.
Biomol. Chem. 2011, 9, 4116. doi:10.1039/C1OB00008J
[14] F. K. Winkler, J. D. Dunitz, J. Mol. Biol. 1971, 59, 169. doi:10.1016/
0022-2836(71)90419-0
b,b-Dimethylbenzydrazide 16
An ice-cold solution of benzoyl chloride (10 g, 71 mmol) in
diethyl ether (60 mL)was added dropwise to a stirred solution of
1,1-dimethylhydrazine (7.0 g, 119 mmol) in diethyl ether
(30 mL). After 1 h, the solution was washed with 10 % sodium
hydroxide (40 mL) and water. The ether layer was separated,
dried over sodium sulfate, and concentrated to a light-yellow
solid. Crystallization from benzene/petroleum spirit afforded 16
(7.2 g, 63 %). Mp 102–1048C (lit. mp 106–1078C[60]).
n
2.8 (s, 6H), 7.2–7.4 (m, 3H), 7.7–8.0 (d, 2H).
max(CHCl3)/cmꢀ1 3350 (br), 1690. dH (CDCl3, 300 MHz)
1,1-Dibenzoyl-2,2-dimethylhydrazine 20
[15] J. D. Dunitz, X-Ray Analysis and Structure of Organic Molecules
1979 (Cornell University Press: London).
To dry benzene (60 mL) was added b,b-dimethylbenzhydrazide
(1 g, 3.7 mmol) and the reaction vessel shielded from light. tert-
Butyl hypochlorite (0.66 g, 2.46 mmol) in benzene was added
dropwise. After standing for 12 h, the solution was concentrated
to afford a near-quantitative yield of 1,1-dibenzoyl-2,2-
dimethylhydrazine (0.87 g). Crystallization from ethanol affor-
ded colourless crystals. Mp 154.58C (lit. mp 152–1538[60]).
[16] S. A. Glover, A. A. Rosser, A. Taherpour, B. W. Greatrex, Aust.
J. Chem. 2014, 67, 507. doi:10.1071/CH13557
[17] S. A. Glover, A. A. Rosser, J. Org. Chem. 2012, 77, 5492. doi:10.1021/
JO300347K
[18] S. A. Glover, A. A. Rosser, J. Phys. Org. Chem. 2014. doi:10.1002/
POC.3322
n
max(CHCl3)/cmꢀ1 1700. dH (CDCl3, 300 MHz) 3.0 (s, 6H), 7.3–
[19] S. A. Glover, A. Rauk, J. M. Buccigross, J. J. Campbell,
G. P. Hammond, G. Mo, L. E. Andrews, A.-M. E. Gillson, Can.
J. Chem. 2005, 83, 1492. doi:10.1139/V05-150
7.8 (m, 10H). m/z (EI) 268 (10), 105 (100) 77(54) and 51 (10 %).
Anal. calc. for C16H16N2O: C 71.84, H, 6.01, N 10.43. Found:
C 71.63, H, 6.21, N 10.39 %.
[20] J. M. Buccigross, S. A. Glover, J. Chem. Soc., Perkin Trans. 2 1995,
595. doi:10.1039/P29950000595
Supplementary Material
[21] J. M. Buccigross, S. A. Glover, G. P. Hammond, Aust. J. Chem. 1995,
48, 353.
[22] S. A. Glover, G. Mo, A. Rauk, Tetrahedron 1999, 55, 3413.
doi:10.1016/S0040-4020(98)01151-X
[23] S. A. Glover, G. Mo, J. Chem. Soc., Perkin Trans. 2 2002, 1728.
doi:10.1039/B111250N
[24] J. J. Campbell, S. A. Glover, J. Chem. Res. (M) 1999, 8, 2075.
[25] S. A. Glover, in Merck Index Fourteenth Edition (Ed.
M. J. O’Neil) 2006, p. ONR-43 (Merck & Co., Inc.: Whitehouse
Station, NJ).
The following material is available on the Journal’s website:
1. Table S1. Full version of Table 2 incorporating B3LYP/
6-31G(d) energies for N-chloro-N-methoxyacetamide 8a,
N-chloro-N-dimethylaminoacetamide 9a, and N-chloro-N-
methylaminoacetamide 10, for relevant COSNAR and trans-
amidation structures in Eqns 1–3 and for complexes in Fig. 5.
2. Table S2. Full version of Table 4 incorporating DFT energies
and COSNAR data for N-chloro-N-methoxyacetamide 8a,
N-chloro-N-dimethylaminoacetamide 9a,N-chloro-N-methyla-
minoacetamide 10, and N,N-dimethylacetamide 4 at B3LYP,
M06 and vB97X-D with the 6-311þþG(d,p) basis set.
3. Geometries (xyz format) of all ground-state structures and
complexes in Table 2
[26] J. P. Johns, A. van Losenoord, C. Mary, P. Garcia, D. S. Pankhurst,
A. A. Rosser, S. A. Glover, Aust. J. Chem. 2010, 63, 1717. doi:10.1071/
CH10350
[27] K. L. Cavanagh, S. A. Glover, H. L. Price, R. R. Schumacher, Aust.
J. Chem. 2009, 62, 700. doi:10.1071/CH09166
[28] M. V. De Almeida, D. H. R. Barton, I. Bytheway, J. A. Ferriera,
M. B. Hall, W. Liu, D. K. Taylor, L. Thomson, J. Am. Chem. Soc. 1995,
117, 4870. doi:10.1021/JA00122A018
4. Complete ref. [59].
[29] L. M. Thomson, M. B. Hall, J. Phys. Chem. A 2000, 104, 6247.
doi:10.1021/JP000623Z
[30] N. Zhang, R. Yang, D. Zhang-Negrerie, Y. Du, K. Zhao, J. Org. Chem.
References
[1] S. A. Glover, Tetrahedron 1998, 54, 7229. doi:10.1016/S0040-4020
(98)00197-5
2013, 78, 8705. doi:10.1021/JO401435V
[31] A. Greenberg, D. T. Moore, T. D. DuBois, J. Am. Chem. Soc. 1996,
118, 8658. doi:10.1021/JA960294H
[32] A. Greenberg, in The Amide Linkage. Structural Significance in
Chemistry, Biochemistry and Materials Science (Eds A. Greenberg,
C. M. Breneman, J. F. Liebman) 2003, pp. 47–83 (John Wiley & Sons,
Inc.: New York, NY).
[2] S. A. Glover, in Advances in Physical Organic Chemistry (Ed.
J. Richard) 2008, Vol. 42, pp. 35–123 (Elsevier: London).
[3] S. A. Glover, in The Chemistry of Hydroxylamines, Oximes and
Hydroxamic Acids, Part 2 (Eds Z. Rappoport, J. F. Liebman) 2009,
pp. 839–923 (Wiley: Chichester).
[4] V. G. Shtamburg, O. V. Shishkin, R. I. Zubatyuk, S. V. Kravchenko,
A. V. Tsygankov, A. V. Mazepa, E. A. Klots, R. G. Kostyanovsky,
Mendeleev Commun. 2006, 16, 323. doi:10.1070/MC2006V016N06
ABEH002382
[33] A. J. Kirby, I. V. Komarov, P. D. Wothers, N. Feeder, Angew. Chem.
Int. Ed. 1998, 37, 785. doi:10.1002/(SICI)1521-3773(19980403)
37:6,785::AID-ANIE785.3.0.CO;2-J

1352
S. A. Glover, A. A. Rosser, and R. M. Spence
[34] A. J. Kirby, I. V. Komarov, N. Feeder, J. Chem. Soc., Perkin Trans. 2
2001, 522. doi:10.1039/B008270H
[47] S. A. Glover, G. P. Hammond, A. M. Bonin, J. Org. Chem. 1998, 63,
9684. doi:10.1021/JO980863Z
[35] N. D. Epiotis, W. R. Cherry, S. Shaik, Y. L. Yates, F. Bernardi,
Structural Theory of Organic Chemistry, 1977 (Springer-Verlag:
Berlin).
[48] J. J. Campbell, S. A. Glover, J. Chem. Res. (S) 1999, 8, 474.
doi:10.1039/A903555I
[49] A. M. Bonin, T. M. Banks, J. J. Campbell, S. A. Glover,
G. P. Hammond, A. S. Prakash, C. A. Rowbottom, Mutat. Res. 2001,
494, 115. doi:10.1016/S1383-5718(01)00189-9
[50] L. E. Andrews, T. M. Banks, A. M. Bonin, S. F. Clay, A.-M. E. Gillson,
S. A. Glover, Aust. J. Chem. 2004, 57, 377. doi:10.1071/CH03276
[51] T. M. Banks, A. M. Bonin, S. A. Glover, A. S. Prakash, Org. Biomol.
Chem. 2003, 1, 2238. doi:10.1039/B301618H
[36] E. L. Eliel, S. H. Wilen, L. N. Mander, Stereochemistry of Organic
Compounds 1994 (John Wiley & Sons, Inc.: New York, NY).
[37] Y. Zhao, D. G. Truhlar, Theor. Chem. Acc. 2008, 120, 215.
doi:10.1007/S00214-007-0310-X
[38] J.-D. Chai, M. Head-Gordon, Phys. Chem. Chem. Phys. 2008,
10, 6615. doi:10.1039/B810189B
[39] S. Grimme, WIREs Comput. Mol. Sci. 2011, 1, 211. doi:10.1002/
WCMS.30
[52] L. E. Andrews, A. M. Bonin, L. E. Fransson, A.-M. E. Gillson,
S. A. Glover, Mutat. Res. 2006, 605, 51. doi:10.1016/J.MRGENTOX.
2006.02.003
[53] S. A. Glover, R. R. Schumacher, A. M. Bonin, L. E. Fransson, Mutat.
Res. 2011, 722, 32. doi:10.1016/J.MRGENTOX.2011.02.007
[54] A. D. Becke, J. Chem. Phys. 1993, 98, 5648. doi:10.1063/1.464913
[55] P. J. Stephens, F. J. Devlin, C. F. Chabalowski, M. J. Frisch, J. Phys.
Chem. 1994, 98, 11623. doi:10.1021/J100096A001
[56] R. Ditchfield, W. J. Hehre, J. A. Pople, J. Chem. Phys. 1971, 54, 724.
doi:10.1063/1.1674902
[57] W. J. Hehre, L. Radom, P. R. Schleyer, J. A. Pople, Ab Initio Molecular
Orbital Theory 1986 (John Wiley & Sons: New York, NY).
[58] Spartan10 for Macintosh 2010. 1.1.0 2010 (Wavefunction
Inc.: Irvine, CA).
[40] S. A. Glover, A. Goosen, C. W. McCleland, J. L. Schoonraad, J. Chem.
Soc., Perkin Trans. 1 1984, 2255. doi:10.1039/P19840002255
[41] S. A. Glover, A. Goosen, C. W. McCleland, J. L. Schoonraad,
Tetrahedron 1987, 43, 2577. doi:10.1016/S0040-4020(01)81665-3
[42] S. A. Glover, C. A. Rowbottom, A. P. Scott, J. L. Schoonraad,
Tetrahedron 1990, 46, 7247. doi:10.1016/S0040-4020(01)87905-9
[43] R. G. Gerdes, S. A. Glover, J. F. Ten Have, C. A. Rowbottom,
Tetrahedron Lett. 1989, 30, 2649. doi:10.1016/S0040-4039(00)
99089-0
[44] J. J. Campbell, S. A. Glover, C. A. Rowbottom, Tetrahedron Lett.
1990, 31, 5377. doi:10.1016/S0040-4039(00)98076-6
[45] J. J. Campbell, S. A. Glover, G. P. Hammond, C. A. Rowbottom,
J. Chem. Soc., Perkin Trans.
2
1991, 2067. doi:10.1039/
[59] M. J. Frisch et al., Gaussian 03, Revision E.01 2005 (Gaussian,
Inc.: Wallingford, CT).
P29910002067
[46] A. M. Bonin, S. A. Glover, G. P. Hammond, J. Chem. Soc., Perkin
Trans. 2 1994, 1173. doi:10.1039/P29940001173
[60] R. L. Hinman, J. Am. Chem. Soc. 1956, 78, 1645. doi:10.1021/
JA01589A040