Supplementary material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2004
N,O-diacylhydroxylamines – structures in crystals and
solutions
Jan Schraml,
a
Jan Sýkora,a Pavel Fiedler,b Jana Roithová,c Jaromír Mindl,a
Vratislav Blechta,a Ivana Císařovád and Otto Exner b
a
Institute of Chemical Process Fundamentals, Academy of Science of the
Czech Republic, Rozvojová 135, 165 02, Prague 6, Czech Republic, E-mail:
schraml@icpf.cas.cz;
b
Institute of Organic Chemistry and Biochemistry, Academy of Science of the
Czech Republic, Flemingovo 2, 166 10, Prague 6, Czech Republic;
c
J. Heyrovský Institute of Physical Chemistry, Academy of Science of the
Czech Republic, Dolejškova 3, 18223, Prague 8, Czech Republic;
d
Department of Chemistry, Charles University, Hlavova 8, 128 43 Prague 2,
Czech Republic
Supplementary Data
Structures in solid state
Results of X-ray structure analysis of low temperature data are summarized in
the ORTEP drawings of the molecules (Figures S1 – S4) showing also atom
labeling. The compounds 1 – 4 form three different types of supramolecular
structures (chains) despite that their molecules are tied together by the same
type of intermolecular hydrogen bonding in the crystal. It is always oxygen
O(1) from the CO-NH group which is proton acceptor in the hydrogen bond.

To whom correspondence should be addressed.
Oxygen O(6) from the O-CO group never participates in the hydrogen bonding
with NH hydrogen. The O(6) attracts hydrogen only from peripheral groups.
The hydrogen bond distances of HO are in the range 1.85 – 1.96 Å (Table
1).
In the structure of the first type (compound 2, Figure S5) the chain is
formed only by one of the conformers either with positive or negative torsion
angle τ. The chains built from conformers with the positive angles alternate
with the chains built from conformers with negative angles. Chains are
arranged along the crystal's Y-axis (Figure S6). Hydrogen NHOC bonding is
supported by a weaker interaction of CH3 hydrogen atoms with O(1) along this
direction, with the distance of 2.65(2) Å. Neighboring chains are hold together
by strong - stacking of aromatic units down in the (10-1) direction. The
aromatic units are parallel. Perpendicular distance between them is 3.40(1) Å.
An additional intermolecular interaction in the direction of the second base
diagonal (101) is provided by the interaction of O-CO group with CH3 group,
2.63(2) Å.
In the structure of the second type (1 and 3) the two conformers
regularly alternate in every chain (Figure S7); Hydrogen bonds are oriented
along the direction of internal diagonal (111) in the crystal packing of 1 (Figure
S8). In the direction of X-axis there are molecules connected through weaker
hydrogen bonds provided by OCOCH3OC-NH, with HO distance 2.52(5)
Å. Other significant intermolecular interactions, OCOCH3OC-NH take place
in the direction of Y-axis, OH distance 2.85(4) Å. Chains of 3, oriented in the
Y-axis direction, form layers in the X direction (Figure S9 – 10). Connections
inside the layer are provided by OCOHAr interactions, between layers by
2
OCOCH3OC-NH, with distances 2.66(2) and 2.69(3) Å, respectively. The
distance between the layers is about 3 Å. There is also remarkable CH
interaction of two adjacent aromatic rings in the (10-2) direction. The distance
CHAr plane is 2.83(2) Å.
The third type was found in 4 with only one conformer present (Figure
S11). Two adjacent molecules are mutually tilted by 180° and connected by
hydrogen bond along X-axis. Chain forming is additionally supported by weak
NHCOHAr interaction along this direction, with the OH distance 2.54(3) Å.
Chains are again arranged along the Z direction into layers (Figure S12). The
molecules are connected by interactions of both CO groups with aromatic
hydrogens inside one layer, the shortest OH distance is 2.45(2) Å. The two
planes defined by the aromatic units R and R' form an angle of 87°. Short
distances between parallel phenyl groups, 3.2 Å, indicate strong - stacking.
Further intermolecular interactions are provided also by CH interactions.
The published data1 on 5 - 7 fall well within this classification: in crystals of 6
chains of the first type are encountered similarly as chains of the second type
are found in crystals of 5 and 7. Of course, 8 is exceptional as its two different
NH groups and two CO groups can participate in the hydrogen bonding.
IR spectra of solutions
Since in the case of O-benzylhydroxamic acid, the population of the NH
tautomer increased in polar solvents2, we investigated the compounds 1  4
both in tetrachloromethane and acetonitrile.
3
Our data collected in Table S1 do not reveal any bands attributable to the O-H
or C=N vibrations, hence the presence of 1B  4B in the amount of several
percent can be excluded.
IR measurements in tetrachloromethane and in acetonitrile differ not only in
the solvent polarity but also in the concentrations employed and so some
observed frequency shifts could be attributed to association. Both the amide I
and amide II frequencies are shifted markedly while the (C=O) frequencies
belonging to the ester-like carbonyl are unchanged. We assume that
association proceeds through a hydrogen bond of the NH hydrogen atom to
the O=CN oxygen as found here also in the solid state. The amide I
frequencies in dioxane3 at a concentration of 0.4 mol l-1 were less shifted than
in acetonitrile indicating less extensive association.
The IR absorption spectra of were recorded on a Bruker IFS 55 FT-IR
spectrometer in tetrachloromethane at a concentration c = 0.001 mol l-1 (d =
10 mm) and in acetonitrile at c = 0.1 mol l-1, except the less soluble compound
4 for which c = 0.05 mol l-1 (d = 0.103 mm for all compounds).
On the observed NMR line-widths
Processes responsible for line broadening (Table 4) obviously, do not affected
the line of O-C(O) carbon as its line-width does not change with substitution
on the two ends of the molecule.
The observed NH proton line-widths result from a combination of the
proton exchange, conformational exchange (see below) and quadrupolar
effects of the abundant
14N
nuclei. Even in the of dry solvent used (DMSO),
the NH proton exchange is so fast in 2 and 3 that it effectively decouples this
4
proton preventing observation of 1J(15N-1H) in
15N
NMR spectrum. Detailed
study of the exchange is not feasible as the available temperature range is
very narrow (the solutions freeze around 15 ºC, compounds decompose
around 50 ºC).
The change of substituent R‘, while it affects the
effect on the
13C
line-width of C(O)-N line. Both
15N
15N
and
line-width, has no
13C
line-widths in the
C(O)-N moiety are affected substantially when methyl group is replaced by
phenyl in the substituent R. In the case of the
13C
linewidth of C(O)-N carbon
a contribution from the scalar relaxation of the second kind 4 induced by the
14N
quadrupolar nucleus is possible. This mechanism, however, cannot
contribute to the
15N
line-width unless some associates/aggregates are
formed which bring the rare
abundant
14N
15N
nuclei into a close neighborhood of the
nuclei in solutions. One possible common cause of the
observed broadening of
15N
and
13C
lines is conformational exchange, i.e.,
rotation around C(O)-N and/or N-O bonds. While rotations around C(O)-N
bonds in amides were studied extensively (for a review of the older literature
see ref.5) we could locate only one preliminary report on such rotation in
hydroxylamine derivatives similar to 1 - 46. The authors found comparable
barriers to rotation about both the N-O and C-N bonds in the compounds of
the type R-C(O)-N(R'')-O-C(O)-R (R, R'' = C6H5, CH3, CH2C6H5). The amide
rotation barrier around the C-N bond was lowered supposedly by the inductive
effect of the O-acyl substituent. This barrier was found to be ΔG ‡ = 14.2 ± 0.1
kcal/mole in the compound R = R''= CH3 dissolved in chloroform. The two
methyl proton lines (Δδ = 0.15 ppm,) coalesce at -16 oC. In the compounds
studied here R'' = H it is reasonable to assume even lower barriers to
5
analogous rotation unless some complexes are formed either among solute
molecules or with the solvent.
In the absence of experimental data we had to resort to computational
modeling. Several local energy minima were found for the NH tautomers 1A
and 3A, differences were mainly in the conformations around the N-O, C-N
and O-C bonds (Table S2).
The favourable arrangement of the N-O-C-O fragment is syn-periplanar
(sp, conformers 1Aa – 1Ad and 3Aa – 3Ad) as it is preferred in esters and all
similar structures with the O=C-O grouping7. The anti-periplanar arrangement
(ap, 1Ae, 1Af, 3Ae and 3Af) leads to an increase in energy of more than 12
kJ/mol and, accordingly, only the sp conformers (N-O-C-O fragment) are
expected to be present in solution. Changes of conformations on other bonds,
namely C-N and N-O, lead to several minima which are close in energy.
According to the relative energies, the conformers 1Aa, 1Ab, 1Ac and
1Ad should be present in relative ratios 6.3:5.0:4.2:1. Their
15N
and
13C
NMR
calculated shifts are different (spanning 18 and 6 ppm, respectively). Since
only one line (though broad) is observed in both
15N
and
13C
NMR spectra of
1A, a fast conformer inter-conversion must occur. To check possibility of such
fast exchange, the potential energy curves for the rotations around the N-O
and C-N bonds were calculated (Figures S13a and S14a; note that the basis
set which was used for calculation of potential energy curves was smaller – 631G** - and thus the relative energies are slightly different). According to
Figure S13a there is no significant barrier to rotation around the N-O bond, so
the exchange between 1Aa and 1Ab conformers is fast. On the other hand,
the exchange between 1Aa/1Ab and 1Ac via the rotation around the C-N bond
6
(Figure S14a) is subject of substantially higher barrier: The height of the
barrier is 48.5 kJ/mol on the assumption that 1Aa changes to 1Ab in the
course of rotation (transition from one curve to the other), Hence
conformational change between 1Aa/1Ab and 1Ac is slower. The analogous
potential energy curves were calculated also for the molecule 3A (Figures
S13b and S14b) and they show similar features. The height of the barrier for
the inter-conversion of 3Aa to 3Ad is 36.8 kJ/mol. These results indicate that
an interplay of several stable conformers with different
15N
and
13C
chemical
shifts combined with suitably different exchange rates could account for the
observed linewidths in the spectra of all studied compounds. However, in view
of poor signal-to-noise ratio in
13C
15N
NMR spectra, quadrupolar broadening of
NMR signal of C(O)-N carbon, and possible inaccuracy of the calculated
shifts we have not attempted any optimization of the exchange rates to fit the
experimental spectra.
NMR Spectra –details of measurements
The 1H NMR spectra were measured using the spectral width of 8000 Hz and
acquisition time 4 s, FID data were zero filled to 128 K. The spectra were
referenced to the line of solvent (δ = 2.500 relative to TMS). The
13C
NMR
spectra were measured using the spectral width of 20000 – 30000 Hz. GARP
decoupling was applied both during acquisition (1 – 2 s) and relaxation delay
(2 - 5 s). Up to 3000 transients were accumulated. Zero filling to 128 K and a
mild line broadening were used in data processing. The spectra were
referenced to the line of the solvent (δ = 39.70 relative to TMS). The
13C-13C
couplings were determined by 1D INADEQUATE experiments8 performed on
7
samples of higher concentration.
15N
NMR spectra were measured using 90o
excitation pulses, 20 – 60 s relaxation delay, and 2s acquisition for the
spectral width of 30 kHz. Usually, 500 – 1000 transients yielded spectra with a
sufficient S/N ratio. The spectra were referenced externally to the
15N
NMR
line of nitromethane in 50% solution in the same solvent, no susceptibility
correction was applied.
The
13C
chemical shifts of the O-C(O) and N-C(O) carbon atoms differ
very little, the difference being smaller than the substituent effects. The lines
were assigned by recording the spectra measured without proton decoupling
when the line of carbon bearing the methyl group appeared as a quartet while
that to which phenyl group was attached appeared as a poorly resolved triplet.
In symmetrically substituted compounds 1 and 4 selective experiments of the
types
13C-{1HN}
and
13C-{1H C}
3
or
13C-{1HC
arom}
yielded unambiguous
assignments. Diluted solution data are assembled in Table S3.
8
Notes and references
1 S. Göttlicher and P. Ochsenreiter, Chem. Ber., 1974, 107, 398-413.
2 A. I. Artemenko, E. K. Anufriev, I. V. Tikunova and O. Exner, Zh. Prikl.
Spektroscop., 1980, 33, 131-135.
3 O. Exner and M. Horák, Collect. Czech. Chem. Commun., 1959, 24, 29923001.
4 A. Abragam, The Principles of Nuclear Magnetism, Oxford University Press,
London, 1961.
5 W. E. Stewart and T. H. I. Siddall, Chemical Reviews, 1970, 70, 517-551.
6 B. J. Price and I. O. Sutherland, Chem. Commun., 1967, 1070-1071.
7 O. Exner, in The Chemistry of Functional Groups. Supplement A3: The
chemistry of double-bonded functional groups, ed. S. Patai,
Interscience, New York, 1997, p. 261.
8 A. Bax, R. Freeman and S. P. Kempsell, J. Am. Chem. Soc., 1980, 102,
4849-4851.
9
Supplementary material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2004
Compd.
Table S1 IR bands in the spectra of compounds 1 – 4a
R
R’ solvent
1 Me Me
2 Me Ph
3 Ph Me
4 Ph Ph
a Meanings
CCl4
CH3CN
CCl4
CH3CN
CCl4
CH3CN
CCl4
CH3CN
ν(NH)
3357w,br,~3320w,br,sh
3278m,br
3350w,br,~3315w,br,sh
3275m,vbr
3396w,br,3345w,br, ~3302w,br,sh
3267m,vbr
~3400vw,br,sh, 3340w,br, 3306w,br
3262w,br
ν(CO)
Amide I
1791s
1740vs
1794vs
1715vs, 1692m,sh
1764s,1738vs
1725vs
1768vs
1716s,br
1790s, ~1770m,sh 1723vs,1701m,sh
1794vs
1697s,br
1761m,1749m
1716vs,br
1768s
1700m,br
Amide II
1443m,br
1487w,br
~1442m,br
~1490w,br
1435m,br
1505w,br, 1478m,br
1432m,br
1478w,br
of abbreviations used: br – broad, m – medium, s – strong, sh – shoulder, vbr – very broad, vs – very strong, w – weak.
Supplementary material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2004
Table S2 Selected geometrical parameters, relative electronic energies,
relative energies at 0 K and 15N and 13C NMR chemical shifts calculated
for several conformers of the compounds 1A, 1B, 3A, and 3B.a
Dihedral angles
O-C-N- C-N-OO
C
N-O-C-O
1Aa
1Ab
1Ac
1Ad
1Ae
1Af
1Ba
1Bb
1Bc
1Bd
-11.9
-11.8
163.6
15.0
-156.5
23.8
0.0
0.0
180.0
180.0
-79.7
-132.4
-140.8
-94.8
-123.5
-94.0
180.0
180.0
180.0
180.0
-8.3
1.0
2.7
-6.1
178.5
-178.4
180.0
0.0
0.0
180.0
3Aa
3Ab
3Ac
3Ad
3Ae
3Af
3Ba
3Bb
3Bc
3Bd
-6.8
-7.9
13.4
151.3
20.5
-160.5
0.0
0.0
177.7
180.0
-82.3
-130.3
-93.8
-130.2
-93.8
-114.7
180.0
180.0
-169.3
180.0
-8.5
1.1
-4.8
1.6
-178.2
180.0
180.0
0.0
3.0
180.0
a
Erel
Erel (0 K)
[kJ/mol]
[kJ/mol]
0/ 437.172086d
0.62
1.05
5.30
16.43
18.74
11.06
15.46
26.51
28.51
0/ 628.953421d
0.48
5.30
6.85
18.88
26.56
11.85
15.09
37.43
39.52
0/ 437.057445e
0.80
0.93
4.48
16.56
19.02
12.10
15.19
25.17
28.19
0/ 628.785322e
0.51
5.10
6.92
19.46
26.73
11.88
13.97
36.50
39.13
Chemical shifts  [ppm]
(N) b
(N-CO)c (O-CO)c
-217.0
-209.5
-198.7
-218.7
175.1
171.6
177.7
170.7
179.7
176.3
173.2
175.0
-80.8
-80.3
-75.8
-76.3
166.7
167.2
170.4
170.1
176.1
169.3
170.8
176.7
-217.8
-209.7
-217.8
-205.1
175.1
171.9
172.5
178.9
179.8
176.6
174.6
174.2
-78.1
-77.1
-81.0
-76.9
164.2
164.8
167.1
162.7
176.4
169.6
171.1
177.6
Energies are related to the most stable isomers of the given molecules (1Aa
and 3Aa, respectively). Total electronic energies as well as energies at 0 K in
Hartrees are given only for most stable isomers 1a and 3a, respectively.
b
Chemical shifts of nitrogen atoms are related to the calculated value for
nitromethane (-152.4).
c
Chemical shifts of carbon atoms are related to the
calculated value for TMS (184.0).
energy in Hartrees.
e
d
B3LYP/6-311+G(d,p) total electronic
B3LYP/6-311+G(d,p) energy at 0 K (includes zero point
vibrational energy) in Hartrees.
Supplementary material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2004
1 Me
2 Me
3 Ph
4 Ph
Me
Ph
Me
Ph
a Chemical
11.557
11.833
12.307
12.631
167.02
167.35
164.73
165.04
168.74
164.04
168.83
164.54
(13C-4 )
(13C-3,5)
(13C-2,6 )
(13Cα)
(1H3C)
(13C-4 )
(13C-3,5)
(13C-2,6 )
(13Cα)
(1H3C)
(13COO )
R'
(13CON )
R
(1H)
Compd.
Table S3 Chemical shifts ( in ppm) and coupling constant (J in Hz) of R-C(O)-NH-O-C(O)-R' measured in 10mM DMSO
solutionsa
C(O)-NH-O-C(O)
unit R
unit R'
1.856 19.52
2.135 18.31
1.950 19.47
127.09 129.30 129.62 134.50
131.26 128.82 127.54 132.45 2.229 18.31
b
b
b
b
b
b
b
131.37 129.70 129.39 134.63
127.04 127.61 128.92 132.59b
shifts in  scale relative to external tetramethylsilane. Cα denotes either methyl carbon (R, R’ = Me) or C-1 carbon of the
phenyl ring (R, R’ = Ph).b Tentative assignment only.
O1
O4
C7
N3
C2
C8
C5
H31
O6
Figure S1. ORTEP drawing of 1.
O1
C10
C9
C7
O4
N3
C8
C2
C11
C5
C12
H31
C13
O6
Figure S2. ORTEP drawing of 2.
C9
O1
C8
O6
C7
C10
C13
C2
N3
C5
C12
O4
C11
H31
Figure S3. ORTEP drawing of 3.
C9
C15
C8
O1
O6
C14
C7
C16
C2
C10
N3
C5
C13
C17
C11 C12
O4
H31
Figure S4. ORTEP drawing of 4.
13
C18
Figure S5. Schematic view of the molecular packing in 2. Molecules with the
positive C(2)-N(3)-O(4)-C(5) torsion angle are green, negative are red. Green and
black dashed lines present hydrogen bonds and CH3···O interactions, respectively.
14
Z
X
Y 0
Figure S6. Crystal packing of 2 (PLUTO). Dashed lines presents
intermolecular CH3···O interactions.
15
Figure S7. Schematic view of the molecular packing in 1. Molecules
with the positive C(2)-N(3)-O(4)-C(5) torsion angle are green,
negative are red. Green and black dashed lines present hydrogen
bonds and CH3···O interactions, respectively.
16
Z
X
0
Y
Figure S8. Crystal packing of 1 (ORTEP). Dashed lines presents
intermolecular CH3···O interactions.
17
Figure S9. Schematic view of the molecular packing in 3. Molecules
with the positive C(2)-N(3)-O(4)-C(5) torsion angle are green, negative
are red.
18
Y
Z
0X
Figure S10. Crystal packing of 3 (PLUTO). Dashed and dotted lines
presents intermolecular CH···Ar and CH3···OC interactions,
respectively.
19
Figure S11. Schematic view of the molecular packing in 4. Only
molecules with the negative value of C(2)-N(3)-O(4)-C(5) torsion angle
are present in this structure. Green and black dashed lines present
hydrogen bonds and ArH···O interactions, respectively.
20
Y
0
Z
X
Figure S12. Crystal packing of 4 (ORTEP). Dashed lines
represent hydrogen bonding.
21
Erel 70
[kJ/mol] 60
a
The arrangement of O-C-N-O
in optimized structures:
syn-periplanar
anti-periplanar
50
40
30
20
10
1c
0
1a
0
1b
100
200
300
0
dihedral angle C-N-O-C [ ]
Erel
[kJ/mol] 70
b
60
The arrangement of O-C-N-O
in optimized structures:
syn-periplanar
anti-periplanar
50
40
30
20
10
0
0
100
200
300
0
dihedral angle C-N-O-C [ ]
Figure S13. Potential energy curves of 1A (a) and 3A (b) along the dihedral
angle C-N-O-C. The positions of three lowest lying minima of 1 are symbolically
depicted.
22
Erel 80
[kJ/mol] 70
a
The arrangement of C-N-O-C
in optimized structures:
syn-clinal
anti-clinal
60
50
40
30
20
10
1b
0
1a
0
1c
100
200
300
0
dihedral angle O-C-N-O [ ]
Erel
[kJ/mol] 80
The arrangement of C-N-O-C
in optimized structures:
syn-clinal
anti-clinal
b
70
60
50
40
30
20
10
0
0
100
200
300
0
dihedral angle O-C-N-O [ ]
Figure S14. Potential energy curves of 1A (a) and 3A (b) along the dihedral
angle O-C-N-O. The positions of three lowest lying minima of 1A are marke
23