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numerous other derivatives, we decided to study it in more
detail.
ꢀ
Two stereocenters are involved (Figure 1): the C2 N3
bond, which leads to E or Z geometries, and the N4 atom,
which enables synclinal or anticlinal (sc or ac) C2-N3-N4-C5
torsional angles (ꢁ 608 or ꢁ1208, respectively). This leads to
a potential energy surface with eight wells, which is reduced to
four when R’ = R’’, labeled E-ac, E-sc, Z-ac, and Z-sc.
Hydrazides are often observed as a mixture of two con-
formers[2,12,17–19] attributed to E/Z isomerism, although the
puzzling appearance of two very different free N3-H stretch
frequencies (3424 and 3303 cmꢀ1) in the IR spectra remains
unexplained.[19] To better understand this observation and
gain deeper insight into the interactions which shape hydra-
zides, a comprehensive conformational analysis was carried
out on three model compounds through a combination of
solution and conformer-selective gas-phase IR spectral anal-
ysis of the NH stretch region with high-level quantum
chemistry calculations of the isolated species.
First, N’,N’-dimethylacetohydrazide (NDMA) was stud-
ied since it is one of the simplest hydrazides which bears only
one NH moiety; thus if several transitions appear in the
spectral region of the NH stretch, a conformational mixture is
implicated. The FTIR spectrum in chloroform indeed shows
three transitions (Figure 2): a weak band at 3430 cmꢀ1 and two
intense bands at 3301 and 3334 cmꢀ1. To conclude that these
result from three conformations is not straightforward,
however. While the first transition is consistent with an NH
group not engaged in a hydrogen bond, the 3300–3350 cmꢀ1
range, where the intense doublet lies, is more typical of NH
groups engaged in strong hydrogen bonds.[20] It therefore
needs to be ascertained whether self-association of NDMA
through hydrogen bonding is responsible for this doublet, and
if not, why monomers would lead to such unusually red-
shifted transitions for nonbonded NH groups.
Figure 2. IR spectra of the three hydrazides recorded in solution (FTIR,
10 mm, in CHCl3) and in the gas phase (IR/R2PI-UV). The intensities
correspond to absorbance in solution (IA, ꢂ10ꢀ3) or depletion in the
gas phase (ID, %).
In this respect, obtaining IR spectra of isolated monomers
in the gas phase is of primary interest. To this end, IR/UV
double-resonance spectroscopy, a mass-resolved conformer-
selective technique,[21] is particularly suitable to record
separately the IR spectrum of each conformer of a conforma-
tional mixture, provided the system possesses a near-UV
chromophore (see the Supporting information). N’,N’-
dimethyl-2-phenylacetohydrazide (NDMPA) and N-(isoindo-
lin-2-yl)acetamide (NIA) were designed for such studies.
Figure 2 presents both their solution and gas-phase IR
spectra. First, their spectra in solution comprise three bands
resembling the pattern already described for NDMA. This
gives a first indication that the
vation for isolated molecules in a vacuum proves that the free
N3-H group is intrinsically able to reach a transition range
normally reserved for strongly hydrogen-bonded NH
groups.[20] Transitions of conformer B appear in the usual
range for a free NH group[20,22] (3456 and 3466 cmꢀ1
respectively).
,
To understand these observations, quantum chemistry
calculations on the isolated molecules were conducted on the
four conformers expected for NDMA, NDMPA, and NIA. In
the case of the latter two, the theoretical results can be
directly compared to gas-phase data. Energetics and NH
stretch frequencies are presented in Table 1. A first point is
aromatic ring has little interference
on the hydrazide function of these
systems. Gas-phase experiments
reveal that monomers have two
conformers, A and B, with A dom-
inating the UV spectrum (see the
Supporting information). For both
NDMPA and NIA, A is character-
ized by a narrow band in the 3300–
Table 1: Energetics and scaled harmonic frequency of the NH stretch.
NDMA
NDMPA
NIA
DG(300 K)[a]
n(NH)[b]
DG(300 K)[b]
n(NH)[b]
DG(300 K)[a]
n(NH)[b]
E-ac
Z-sc
Z-ac
E-sc
0
5
11
25
3306
3444
3283
3406
0
3
8
29
3294
3440
3305
3404
0
3
10
21
3303
3436
3285
3400
[a] In kJmolꢀ1. Electronic energies were calculated at the QCISD(T)/TZVPP level on MP2/TZVPP-
optimized geometries; thermodynamic corrections at 300 K were calculated at the RI-B97D/TZVPP level
on geometries optimized at the same level. [b] In cmꢀ1. A scaling function determined for amide groups
3350 cmꢀ1
range
(3320
and
3330 cmꢀ1, respectively). This obser- was used (see the Supporting Information).
2
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 1 – 5
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