Structures of N, N-dialkoxyamides: Pyramidal anomeric amides with low amidicity

Article abstract of DOI:10.1021/jo201856u

The first X-ray structures of two anomeric N,N-dialkoxyamides (2 and 3) have been obtained, which confirm that they are highly pyramidalized at nitrogen and have long N - CO bonds, a characteristic of other anomeric amides and a consequence of drastically

Full text of DOI:10.1021/jo201856u

Article
pubs.acs.org/joc
Structures of N,N-Dialkoxyamides: Pyramidal Anomeric Amides with
Low Amidicity
Stephen A. Glover,*,† Jonathan M. White,‡ Adam A. Rosser,† and Katherine M. Digianantonio†
†Department of Chemistry, School of Science and Technology, University of New England, Armidale, NSW 2351, Australia
‡School of Chemistry and Bio-21 Institute, University of Melbourne, Parkville, Vic 3010, Australia
S
* Supporting Information
ABSTRACT: The first X-ray structures of two anomeric N,N-dialkoxyamides (2 and 3) have
been obtained, which confirm that they are highly pyramidalized at nitrogen and have long
N−CO bonds, a characteristic of other anomeric amides and a consequence of drastically
reduced amidicity. The crystals also demonstrate chirality at the amide nitrogen in the solid
state. The structures are well-predicted by density functional calculations using N,N-dimethoxyacetamide as a model. The
amidicity of N,N-dimethoxyacetamide has been estimated by two independent methods, COSNAR and a new transamidation
method, which give almost identical resonance stabilization energies of −8.6 kcal mol−1 and only 47% that of N,N-
dimethylacetamide computed at the same level. The total destabilization is composed of a resonance and an inductive
contribution, which we have evaluated separately. The electronegative oxygens at nitrogen are responsible for localization of the
nitrogen lone pair on the amide nitrogen, a factor that contributes to a loss of resonance over and above the impact of
pyramidalization at nitrogen, as well as the fact that N,N-dimethoxyacetamide is predicted to protonate on the carbonyl oxygen in
preference to nitrogen.
Scheme 1
INTRODUCTION
■
Anomeric amides (1a−f) are defined as amides that are
substituted at nitrogen with two electronegative atoms.1 This
configuration at nitrogen radically alters the amide character-
istics since the electronegative requirements of the heteroatoms
are best satisfied if the nitrogen assumes sp3 hybridization in
which the nitrogen lone pair becomes localized in a hybrid
orbital. The reduced p-character results in vastly reduced amide
resonance. In addition, by analogy with bis-heteroatom-
substituted carbon, such amides usually exhibit ground-state
anomeric effects through the amide nitrogen, which influence
their conformation and reactivity. With a good leaving group at
nitrogen (1a and 1b), nY−σ*NX overlap weakens the N−X
bond and they can undergo both SN1 and SN2 reactions at the
amide nitrogen.2−10 With weaker leaving groups (1d or with 1b
in nonpolar solvents), the anomeric effect drives the unusual
HERON reaction11 in which anomeric destabilization results in
migration of a substituent, X, from nitrogen to the carbonyl
carbon with attendant formation of a Y-atom-stabilized nitrene
(Scheme 1).9,12−18
Spectroscopic, theoretical, and structural evidence has been
presented for a range of such amides (1a−f).1,9,17 Notably,
theoretical calculations on model structures predict a high
degree of pyramidality at nitrogen (Winkler−Dunitz pyrami-
dality indices19,20 vary from χ = 32° for 1e to 58° for 1b), long
C−N bonds that range between 1.40 Å for 1d and 1.43 Å for
1a, but relatively small twist angles about the C−N bond
(τ ranges between 2 and 9°),17 and these predictions are borne
out by structural properties where these are available and by
spectroscopic data.1,9,17,21,22 While there is a significant
lengthening of the C−N bond in anomeric amides, theoretical
and structural data predict relatively small changes in the
carbonyl bond lengths. However, this is well-known for many
amides in which amide resonance is reduced by twisting about
the amide bond23−28 and reflects the contemporary view that
amide resonance is best described as a HOMO−LUMO
interaction between the lone pair on nitrogen and carbonyl
antibonding orbital, which has its major contributor on carbon
rather than oxygen (Figure 1a).29 Reduction in amide
resonance therefore impacts more upon the N−C bond than
the CO bond. The contribution of resonance form II to the
hybrid (Figure 1b) is small. However, all anomeric amides
exhibit relatively high carbonyl stretch frequencies in their
infrared spectra (typically 1710−1770 cm−1), and force
constants appear to be more sensitive to the presence of
electronegative substituents at nitrogen. While anomeric amides
Received: September 10, 2011
Published: October 20, 2011
© 2011 American Chemical Society
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were low-melting solids. 2 could be crystallized as colorless
prisms by solvent displacement at low temperature using
ethylacetate/hexane, while 3 crystallized as colorless needles
directly from cold methanol at 10 °C. Both exhibited relatively
high carbonyl stretch frequencies at 1708 (1) and 1709 cm−1
(2) in their chloroform IR spectra and some 20 wave numbers
higher than their hydroxamic acid precursors. Their 13C NMR
carbonyl resonance frequencies were at 172 and 174 ppm,
respectively, and at similar shifts to the analogous N-acyloxyl
substrates, 1b.1,9,17
Figure 1. (a) Frontier orbital interaction and (b) resonance in simple
amides.
exhibit greatly reduced amide resonance, the carbonyls are not
ketonic as the 13C NMR carbonyl resonances are some 30 ppm
upfield of ketones and aldehydes and are more typical of esters
or acid chlorides.1,17 The triad of electronegative atoms
adjacent to the carbonyl destabilizes the polar resonance form
III (Figure 1b), and the best resonance representation of an
anomeric amide is I in Figure 1b.
Anomeric amides 1 exhibit very different spectroscopic
properties to those of amides with one heteroatom at nitrogen.
For instance, the hydroxamic ester precursors to 1a−d exhibit
much lower carbonyl stretch frequencies (typically between
1650 and 1690 cm−1), and unlike 1a−d, many exhibit line
broadening in their NMR spectra on account of high barriers to
E−Z isomerization.1,9,17,30−32
X-ray structures of both N,N-dialkoxyamides are illustrated in
Figure 2, and selected data are presented in Table 1.
While theoretical, spectroscopic, and structural data for
ONCl, ONOAc, and ONN systems have been reported, the
properties of dialkoxyamides (1c) are less well-known. The
spectroscopic properties of a limited number have been
reported to date,1,17,33 and the only crystallographic data
available are for two urea analogues, N,N-dimethoxyurea (4a)
and, very recently, its N′-4-nitrophenyl analogue (4b)34,35 both
of which possess a highly pyramidal dimethoxylated nitrogen
attached by a long N−C bond but, on account of the
competing α-amino group, are not fully representative of a pure
anomeric amide.
In this paper, we report the first crystal structures of two
N,N-dialkoxyamides and demonstrate that they exhibit all the
hallmarks of true anomeric amides. In addition, we have
determined computationally the extent of amide resonance in
the model N,N-dimethoxyacetamide and show that N,N-
dialkoxyamides are likely to have amidicity <50% that of
N,N-dimethylacetamide.
Figure 2. X-ray structures of (a) N-ethoxy-N-methoxy-4-nitro-
benzamide 2 and (b) N-methoxy-N-(4-nitrobenzyloxy)benzamide 3.
Table 1. Selected Structural Properties of N-Ethoxy-N-
methoxy-4-nitrobenzamide 2, N-Methoxy-N-(4-
nitrobenzyloxy)benzamide 3, and B3LYP/6-31G(d) Minimum
Energy Structure for N,N-Dimethoxyacetamide 5 (Figure 4a)
RESULTS AND DISCUSSION
■
A limited number of N,N-dialkoxyamides have been synthe-
sized by solvolysis of N-alkoxy-N-chloroamides in aqueous
alcohol1,13 or by the reaction of N,N-dialkoxyamines with acyl
halides or isocyanates.36 Following the recent discovery that
hydroxamic esters can be readily oxidized to N-acyl-N-
alkoxynitrenium ions by hypervalent iodine reagents,37−42 we
have found that, upon oxidation of hydroxamic esters in the
presence of alcohols, either as solvents or as reagents in
acetonitrile, N,N-dialkoxyamides can be made in synthetically
useful yields and with short reaction times. We recently
reported the synthesis, spectroscopic properties, and radical
decomposition reactions of a number of congeners.33
While almost all N,N-dialkoxyamides made to date are oils at
room temperature, we found that N-ethoxy-N-methoxy-4-
nitrobenzamide (2) and N-methoxy-N-(4-nitrobenzyloxy)-
benzamide (3), which were synthesized directly from N-
ethoxy-4-nitrobenzamide and N-(4-nitrobenzyloxy)benzamide
in methanol with phenyliodine[III]bistrifluoroacetate (PIFA),
parameter
rC(7/1)O(1) (Å)
2
3
5
1.206(3)
1.409(4)
1.393(3)
1.418(3)
1.211(2)
1.421(2)
1.402(2)
1.408(2)
1.212
1.417
1.391
1.406
rC(7/1)N(1) (Å)
rN(1)O(2) (Å)
rN(1)O(3) (Å)
C(7/1)−N(1)−O(2) (°)
O(3)−N(1)−O(2) (°)
O(3)−N(1)−C(7/1) (°)
111.7
111.5
114.2
109.4
110.1
110.4
6.7
109.4
113.7
111.5
13.9
111.9
116.9
114.3
8.5
a
⟨β⟩ (°)
b
τ (°)
c
χN (°)
58.3
55.6
48.1
66.6
83.8
C(8/2)−O(2)−N(1)−O(3) (°)
C(10/15/3)−O(3)−N(1)−O(2) (°)
−114.1
95.9
−101.6
−63.8
a
b
⟨β⟩ = Σ(β)/3. Angle subtended by the axes of the nitrogen lone pair
c
and the carbonyl carbon 2pz orbital. Amide distortion parameters
defined in accordance with Winkler−Dunitz.19,20
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Both amides exhibit a high degree of pyramidality at
nitrogen. The Winkler−Dunitz pyramidality indices, χN, are
58 and 56° for 1 and 2, respectively.19,20 Though highly
pyramidalized at nitrogen, they are less pyramidal than N-
acyloxy-N-alkoxyamides, which have χN of 65°.17,22 The N−C
bonds are typical of bis-oxo-substituted amides and much
longer than those for primary, secondary, and tertiary amides
(average bond length 1.359 Å with median 1.353 Å22). The
bonds are slightly shorter than the corresponding bonds in
N-acyloxy-N-alkoxyamides (1b), where crystallographic evi-
dence gives the N−C bond length at 1.44 Å.9,17,22 In keeping
with previous findings for twisted23−28,43 and anomeric
amides,17,21,22 the carbonyls undergo relatively little contrac-
tion.
Like other anomeric amides, there is relatively little twist
about the N−C bonds (τ = 7 and 14° for 1 and 2, respectively)
and the nitrogen lone pair is in reasonably good alignment with
the neighboring carbon 2pz orbital. In common with all
structures of anomeric amides, there appears to be a
conformational preference enabling some overlap with the
carbonyl carbon 2pz orbital. This general feature of anomeric
amides is rational. Though the lone pair on nitrogen is
contracted on account of electron demand of both nitrogen
substituents, alignment with the carbonyl is still a stabilizing
influence, albeit much more weakly than in conventional
primary, secondary, or tertiary amides. However, low-temper-
ature NMR studies failed to detect isomerization processes
down to −90 °C in support of a low E/Z isomerization barrier.1
In N-methoxy-N-(4-nitrobenzyloxy)benzamide 3, the me-
thoxyl group is endo to the nitrogen pyramid while both alkoxyl
alkyl groups in N-ethoxy-N-methoxy-4-nitrobenzamide 2 are
exo. On account of the similar electron demand of the nitrogen
substituents, anomeric effects are expected to be weaker in
these systems than in N-acyloxy-N-alkoxyamides (1b) or N-
alkoxy-N-chloroamides (1a).1,9,17 In both structures, the
conformation at the nitrogen appears to be dictated by two
anomeric effects. However, one anomeric effect is stronger than
the other in both structures, based on orbital overlap
considerations. Thus in compound 2, the CH3−O−N−OCH2
dihedral angle is 96° and the CH2−O−N−OCH3 is −114°,
while in compound 3, the CH3−O−N−OCH2 dihedral angle is
−64° and the CH2−O−N−OCH3 is 102° The N−O bond
distances would appear to be dictated by other geometrical
factors in addition to the anomeric effect; the N−O bonds syn
to the carbonyl oxygen are shorter in each structure.
Figure 3. Crystal packing for (a) N-ethoxy-N-methoxy-4-nitro-
benzamide 2 and (b) N-methoxy-N-(4-nitrobenzyloxy)benzamide 3.
relatively unchanged carbonyl at 1.21 Å. The methoxyl syn to
carbonyl was endo relative to the nitrogen pyramid, though the
exo/exo structure analogous to N-ethoxy-N-methoxy-4-nitro-
benzamide was only 1 kcal mol−1 higher in energy. Anomeric
effects were computed to be weaker in N,N-dimethoxyforma-
mide relative to N-chloro-N-methoxyformamide or N-chloro-
N-dimethylaminoformamide and N-dimethylamino-N-methox-
yacetamide.48 A theoretical amide rotational barrier of some
12 kcal mol−1 was reported. This level of theory successfully
predicts structural properties, barriers to conformational
change, as well as the activation energies for reactions of a
range of anomeric amides.8−10,14,16−18,30,48,49
The structure of N,N-dimethoxyacetamide has been
computed at the same level in this study and is depicted in
Figure 4a with selected data given in Table 1. Its properties are
very similar to those computed for the formamide, and
predicted properties of N,N-dimethoxyacetamide correspond
well to the crystallographic data for 2 and 3. In the lowest
energy conformer, the methoxyl group syn to the carbonyl is
endo to the nitrogen pyramid and this form is 1.8 kcal mol−1
lower in energy than the exo/exo structure. The amide nitrogen
in the most stable conformer has a χN of 48° and angle, τ, of
only 8°. The N−C bond length of 1.42 Å is long when
compared to N,N-dimethylacetamide computed at the B3LYP/
6-31G(d) level (1.38 Å), while the carbonyl bond length
of 1.21 Å was similar to the computed length in
Both molecules are chiral at nitrogen, but in solution,
enantiomers can interconvert by inversion at nitrogen. While
acyclic pyramidal N,N-dialkoxyamines are known to have high
nitrogen inversion barriers and are configurationally stable,44−47
in anomeric amides, inversion at nitrogen is a low-energy
process on account of the fact that the planar inversion
transition state is stabilized by resonance delocalization of the
nitrogen lone pair.1,17,30,48 However, chiral amide nitrogens are
clearly evident in the unit cells in both crystals, which comprise
two pairs of enantiomers (Figure 3a,b).
In an earlier paper, we reported in detail theoretical
properties of N,N-dimethoxyformamide.30 B3LYP/6-31G(d)
calculations predicted a long N−C bond of 1.396 Å and a
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Figure 4. (a) B3LYP/6-31G(d) optimized geometry and (b) HOMO of the lowest energy conformer of N,N-dimethoxyacetamide.
N,N-dimethylacetamide (1.23 Å). In the theoretical structure,
the C(3)−O(3)−N(1)−O(2) twist angle is close to 90°, and the
nO −σ*NO anomeric interaction appears to be favored over
(3)
(2)
the alternative overlap.
The N−C bonds in 2 and 3, though much longer than those
of N,N-dialkylamides, are shorter than that found in the 1-aza-
2-adamantanone 6, Kirby’s most twisted amide, which has a
N−C bond length of 1.455 Å.26,50−52 This, together with the
low twist angle in N,N-dimethoxyacetamide suggests that these
highly pyramidalized amides might still possess a degree of
amide resonance. We have computed the residual amide
resonance in N,N-dimethoxyacetamide by two independent
isodesmic methods: by COSNAR53−55 and by a transamidation
method we have developed. COSNAR measures directly the
resonance stabilization when a carbonyl and an amino nitrogen
are proximate in the same scaffold. Thus, for N,N-
dimethoxyacetamide, 5, eq 1 applies.The transamidation
energies for the optimized geometries of 7, 9 and various amides
and amines used in eqs 1−4. Since isodesmic reactions were
used, ΔECOSNAR, ΔEreact, and ΔEinductive were calculated without
incorporation of zero-point energies (ZPE) or thermodynamic
quantities, which largely cancel. The residual resonance
stabilization computed by COSNAR (from eq 1) is −8.59
kcal mol−1. By our method, ΔEreact for 1-aza-2-adamantanone
from eq 2 yields a maximum destabilization due to complete
loss of resonance of 18.17 kcal mol−1. For N,N-dimethox-
yacetamide 5, ΔEreact is computed from eq 3 to be 13.87 kcal
mol−1, the sum of destabilization due to both loss of resonance
as well as the inductive influence of dimethoxyl substitution.
ΔEinductive from eq 4 measures the additional destabilization of
N,N-bis-oxa-substitution in the fully twisted amide 15 at 4.27
kcal mol−1, and the residual resonance stabilization in N,N-
dimethoxyacetamide given by eq 5 is thus −8.58 kcal mol−1 and
essentially identical to the COSNAR stabilization energy.
(5)
method computes the total destabilization of an amide relative
to dimethylacetamide 10 and the maximum possible loss of
resonance can be estimated isodesmically from eq 2 for fully
The resonance stabilization in N,N-dialkoxyacetamide is
therefore likely to be about 47% that of N,N-dimethylaceta-
mide. With this reduction in resonance, the barriers to rotation
away from the ground state in N,N-dialkoxyamides are likely to
be below the normal detection limits of NMR spectroscopy.
This represents the first estimation of amidicity in an
anomeric amide. The loss of resonance in untwisted N,N-
dimethylacetamide due to complete pyramidalization at
nitrogen and localization of the lone pair in an sp3 rather
than a 2pz orbital is estimated to be about 6.5 kcal mol−1 from
the difference in energies between pyramidal 10 (χN = 60°,
τ = 0°) and planar 10 (χN = 0°, τ = 0°) (Table 2). Since the
degree of twist in N,N-dimethoxyacetamide 5 is relatively small,
the loss of a further 3−4 kcal mol−1 worth of resonance
interaction over and above the loss attributable to sp3
hybridization at nitrogen can be accounted for by localization
of the lone pair on nitrogen. As a consequence of the combined
electronegativity of both oxygens, the sp3 hybrid lone pair
orbital must be lowered in energy, resulting in a much greater
reduction in π overlap with the carbonyl carbon.
twisted 1-aza-2-adamantanone 13. The total destabilization of
N,N-dimethoxyacetamide 5 relative to N,N-dimethylacetamide
10 can be determined from eq 3. However, this energy is
composed of a resonance and an inductive destabilization, since
in the product N,N-dimethoxyacetamide 5, the polar carbonyl
is further destabilized by the inductive effect of two oxygen
substituents. We estimated this inductive contribution from the
difference between ΔEreact of 1-aza-2-adamantanone 13 and its
hypothetical N,N-dioxo analogue 15 or from the isodesmic
reaction in eq 4. After correction for the inductive
destabilization, the residual resonance stabilization can be esti-
mated from eqs 2, 3, and 4. Table 2 gives B3LYP/6-31G(d)
The HOMO of 5 is shown in Figure 4b and clearly has a N
sp3 lone pair, as well as some O 2py character, and protonation
could occur at both atoms. In keeping with this lowering in
energy of the lone pair on nitrogen, computed proton affinities
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Table 2. B3LYP/6-31G(d) Energies of Minimum Energy Conformations of 5, 7−15, Reaction Energies from Equations 1−5
and Proton Affinities of N,N-Dimethoxyacetamide 5 and N,N-Dimethylacetamide 10
structure
energy (au)
energy (kcal mol−1
)
a
N,N-dimethoxyacetamide 5
−438.150456 (−438.001676)
−422.190691
1,1-dimethoxypropanone 7
N,N-dimethoxyethylamine 8
−364.131007
1,1-dimethoxypropane 9
−348.184927
−287.830189 (−287.690489)
−287.819817
a
N,N-dimethylacetamide 10 (χN = τ = 0°)
N,N-dimethylacetamide 10 (χN = 60°, τ = 0°)
1-azaadamantane 11
−406.744846
N,N-dimethylethylamine 12
−213.788638
1-aza-2-adamantanone 13
−480.757454
2,6-dioxo-1-azaadamantane 14
−478.462685
2′,6′-dioxo-1-aza-2-adamantanone 15
−552.468467
−438.498605 (−438.336389)
−438.482551(−438.320598)
−288.189375(−288.037134)
−288.170972(−288.017956)
−0.013685
a
5 COH+
a
5 NH+
10 COH+
10 NH+
a
a
eq 1
−8.59
18.17
13.87
4.27
eq 2
0.028957
eq 3
0.022102
eq 4
0.006812
eq 5
−0.013667
0.010372
−8.58
6.51
pyramidal 10 − planar 10
PA−5 COH+
PA−5 NH+
PA−10 COH+
PA−10 NH+
a
a
0.348149 (0.334713)
218.46 (210.03)
a
a
0.332095 (0.318922)
208.39 (200.12)
a
ab
,
0.359178 (0.346644)
225.38 (217.52)
213.84 (205.49)
a
a
0.340776 (0.327467)
a
b
56
ZPE and enthalpy corrected values in parentheses. Experimental proton affinity at oxygen is 217 kcal mol−1
.
(Table 2) predict that protonation of N,N-dimethoxyacetamide
would still be more favorable at the carbonyl oxygen, rather
than on nitrogen, by some 10 kcal mol−1. This contrasts
markedly with highly twisted N,N-dialkylamides with low
amidicity where PAs indicate that localization of the lone pair
results in a more basic nitrogen than oxygen lone pair.54,55 The
PAs of both the carbonyl oxygen and the nitrogen of 5 are
significantly lower than those computed for N,N-dimethylace-
tamide (10) at B3LYP/6-31G(d), which with enthalpy
corrections predicts a PA at oxygen close to the experimental
value of 217 kcal mol−1.54−57
In this regard, a comparison with N-acylaziridines is
supportive. In these, the nitrogen is also pyramidal on account
of the three-membered ring, and the lone pair is conjugaed with
the carbonyl.43,58 However, in contrast with N,N-dimethox-
yacetamide, the lone pair is not subject to electronegative
tightening and calculations on N-formylaziridine at both the
MP2/6-31G(d,g)59 and more recently at the MP2/6-311+
+G(d,g) level43 predicted a small preference for protonation at
nitrogen (by 2 kcal mol−1 in the gas phase and 5 kcal mol−1 in
water,59 and 1 kcal mol−1 in the gas phase43). The resonance
stabilization in N-formylaziridine has also been estimated to be
some 15 kcal mol−1 at HF/3-21G(d) level,58 and we calculate it
to be 14 kcal mol−1 by the same method at B3LYP/6-31G(d).60
The reversal of proton affinities in N,N-dimethoxyacetamide, as
well as its lower resonance stabilization, is entirely consistent
with the electron demand of the alkoxyl oxygen atoms.
which is highly pyramidalized like that of the other bis-
heteroatom-substituted amides. Evidence for radically reduced
resonance can be found in a substantial lengthening of the N−
CO bond, but in keeping with previous findings for amides with
impaired resonance, the carbonyl bond length is little affected.
The lone pair, while largely aligned with the carbonyl carbon
2pz orbital, undergoes very limited delocalization on account of
its localization on nitrogen, a consequence of the electron
demand of the two oxyl substituents. The crystal packing
exhibits enantiomerism due to chirality at the nitrogen, a
property that cannot be detected in solution studies of these or
other chiral anomeric amides.
Density functional theory reproduces the structural proper-
ties observed in the crystalline forms of amides 2 and 3. In
addition, the model N,N-dimethoxyacetamide 5 is computed to
have less than half the resonance of planar N,N-dimethylace-
tamide. Pyramidalization at nitrogen cannot alone account for
this loss of resonance, which is also impaired by localization of
the lone pair on nitrogen due to the electronegativity of the
methoxyl substituents. Computed PAs of the carbonyl oxygen
and nitrogen accord with this localization. Protonation on the
carbonyl oxygen of 5 is preferable to the reaction at nitrogen.
The correspondence between COSNAR and our trans-
amidation method for computing residual amide resonance is
reproduced with other similar systems, and we will shortly
demonstrate that the resonance in this unusual class of amides,
as well as in mono-heteroatom-substituted amides, varies
largely in line with the total electronegativity of substituents
at the amide nitrogen. We have found that these two
approaches to determining amidicity (relative to N,N-
dimethylacetamide [100%] and 1-aza-2-adamantanone [0%])
are more reliable than the heat of hydrogenation method
CONCLUSION
■
The structures of two N,N-dialkoxyamides have been obtained
that demonstrate they are true anomeric amides. The nitrogen
lone pair resides in an sp3 hybrid orbital on the nitrogen atom,
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recently published by Csizmadia and co-workers,61−63 partic-
ularly when strained lactams are involved.
(7) Glover, S. A.; Mo, G. J. Chem. Soc., Perkin Trans. 2 2002, 1728−
1739.
(8) Cavanagh, K. L.; Glover, S. A.; Price, H. L.; Schumacher, R. R.
Aust. J. Chem. 2009, 62, 700−710.
EXPERIMENTAL SECTION
■
(9) Glover, S. A. In Advances in Physical Organic Chemistry; Richard,
J., Ed.; Elsevier: London, 2008; Vol. 42, pp 35−123.
(10) Glover, S. A.; Adams, M. Aust. J. Chem. 2011, 64, 443−453.
(11) Heteroatom Rearrangements On Nitrogen.
Synthetic Details. The synthesis of N-ethoxy-N-methoxy-4-nitro-
benzamide 2 and N-methoxy-N-(4-nitrobenzyloxy)benzamide 3 by
PIFA oxidation of N-ethoxy-4-nitrobenzamide and N-(4-
nitrobenzyloxy)benzamide in methanol together with their character-
ization has recently been reported.33
X-ray Crystallography. Intensity data were collected with an
Oxford Diffraction SuperNova CCD diffractometer using Mo Kα
radiation (graphite crystal monochromator λ = 0.7107); the
temperature during data collection was maintained at 130.0(1) K
using an Oxford Cryosystems cooling device.
The structures were solved by direct methods and difference
Fourier synthesis.64 Thermal ellipsoid plots were generated using the
program ORTEP-365 integrated within the WINGX66 suite of
programs
Crystal Data for 2: C15H14N2O5, M = 302.28, T = 130.0(1) K, λ =
0.7107, monoclinic, space group P21/c, a = 10.9575(3), b =
17.3679(5), c = 7.9564(2) Å, β = 108.867(3)o, V = 1432.82(7) Å3,
Z = 4, Dc = 1.401 mg M−3 μ(Mo Kα) 0.107 mm−1, F(000) = 632,
crystal size 0.6 × 0.3 × 0.1 mm; 7060 reflections measured, 2522
independent reflections (Rint = 0.0221); the final R was 0.0348 [I >
2σ(I)], and wR(F2) was 0.0863 (all data).
Crystal Data for 3: C10H12N2O5, M = 240.22, T = 130.0(1) K, λ =
0.7107, orthorhombic, space group Pca21, a =12.2038(7), b =
4.1403(3), c = 22.3872(16) Å, V = 1131.17(13) Å3, Z = 4, Dc =
1.411 mg M−3 μ(Mo Kα) 0.115 mm−1, F(000) = 504, crystal size
0.6 × 0.5 × 0.4 mm; 3203 reflections measured, 1854 independent
reflections (Rint = 0.0321); the final R was 0.0490 [I > 2σ(I)], and
wR(F2) was 0.1268 (all data).
Computational Details. B3LYP/6-31G(d) calculations were
carried out using SPARTAN 08.67 Energies of global minima of
structures 5 and 7−15 for use in isodesmic eqs 1−4 were computed
directly without ZPE and enthalpy corrections. B3LYP/6-31G(d)
energies for N,N-dimethoxyacetamide 5 and planar N,N-dimethylace-
tamide 10 and their carbonyl oxygen- and nitrogen-protonated
structures for determination of proton affinities were computed
together with enthalpy corrections using frequency calculations.
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ASSOCIATED CONTENT
■
(29) Wiberg, K. B. In The Amide Linkage. Selected Structural Aspects in
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S
* Supporting Information
Geometries and energies of minimum energy structures listed
in Table 2. Calculation of the B3LYP/6-31G(d) resonance
energy for N-formylaziridine using the method of Greenberg
and co-workers.58 CIF’s for crystal structures of N-ethoxy-N-
methoxy-4-nitrobenzamide 2 and N-methoxy-N-(4-
nitrobenzyloxy)benzamide 3. This material is available free of
charge via the Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
■
(34) Shtamburg, V. G.; Shishkin, O. V.; Zubatyuk, R. I.; Kravchenko,
S. V.; Tsygankov, A. V.; Shtamburg, V. V.; Distanov, V. B.;
Kostyanovsky, R. G. Mendeleev Commun. 2007, 17, 178−180.
(35) Shtamburg, V. G.; Tsygankov, A. V.; Gerasimenko, M. V.;
Shishkin, O. V.; Zubatyuk, R. I.; Mazepa, A. V.; Kostyanovsky, R. G.
Mendeleev Commun. 2011, 21, 50−52.
Corresponding Author
*E-mail: sglover@une.edu.au.
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