A. Rivera et al. / Tetrahedron Letters 49 (2008) 2154–2158
2155
involved in the reaction pathway; (3) to gain a better
understanding of the overall reaction mechanism; (4) to
determine some preliminary evidence of the kinetic
reaction.
1
The H NMR spectra of the crude reaction mixtures
(Fig. 1a–c) showed that both the starting aminal TATD
(2) and TATU (1) were present. In addition, a close inspec-
tion also revealed the presence of species with low intensity
signals, which can be attributed to intermediates or colla-
teral products. The downfield signal appearing as a singlet
at d 4.45 was assigned at the aminalic protons of urotro-
pine (3) by comparison with the spectrum of a mixture of
purified samples of 1, 2, and 3 (Fig. 1d), which showed
well-separated signals between 2.25 and 4.50 ppm. This
spectrum had five singlets, two of which were attributable
to ethylenic protons of 1 and 2 (d 3.01 and 3.03, respec-
tively), while others were attributable to aminalic protons
at 3.75 for 2, 4.04 for 1, and 4.45 for 3. The one-proton
doublet at d 3.62 and 4.31 with geminal coupling of
13.5 Hz was attributed to aminalic protons of 1. The split-
ting pattern, coupling constants, and NMR ratios of the
signal protons at d: 4.15 (J = 10.2 Hz), 3.84 (J =
13.1 Hz), 3.36 (J = 12.7), and 3.18 (J = 10.4 Hz)
(Fig. 2a), with an intensity ratio of 1:2:2:1, can indeed be
attributed to one of the secondary products (intermediate
or collateral products). These resonances were clearly
a
Selective TOCSY on 3.84 ppm
Selective COSY on 2.72 ppm
b
c
4.50
4.25
4.00
3.75
3.50
3.25
3.00
2.75
2.50
2.25
ppm (t1)
Fig. 2. TOCSY-selective experiments for 4.
differentiated as two AB-systems with a typical coupling
constant of geminal protons.
Based on the chemical shifts, we suggested the presence
of CH2-aminalic groups in its structure (4). To isolate the
spin systems from the spectrum of reaction mixture, 1D
TOCSY experiments were performed.4 Irradiation of the
signal at 3.84 ppm produced enhancements at 3.36 and
3.18 ppm (Fig. 2b). The appearance of signal at 3.36 ppm
as a doublet of doublets (J = 12.7 and 2.1 Hz) indicated
the presence of long-range NMR coupling constants. The
homonuclear small coupling constant value, which is
4
attributed to a JHH coupling constant between W-posi-
tioned hydrogen atoms in bicyclic compounds,5 suggested
that compound 4 had a bicyclic structure. Aside from these
resonances, the NMR ratio of the signal proton at
2.71 ppm (Fig. 2a) and its typical signal patterns of parti-
cular –CH2CH2– ring moieties indicated that this resonance
can be assigned to an ethylene bridge in a bicyclic system.
In fact, a COSY irradiation6 of this signal resulted in a
signal enhancement at ꢀ2.92 ppm (Fig. 2c) that overlapped
with another major resonance at 2.97 ppm, all of which
vindicated the presence of an ethane-bridge. Again, com-
a
b
c
1
parison of the H NMR spectra of 4 with those of the
known compounds 3-oxa-1,5-diazabicyclo[3.2.1]-octane
(5)5a and 3,30-ethane-1,2-diylbis-1,3,5-triazabicyclo[3.2.1]-
octane (6)5b (Table 1) showed very similar d and J values
suggesting that compound 4 had the bicyclo[3.2.1]octane
nucleus. Based on these data, compound 4 was identified
as 1,3,5-triazabicyclo[3.2.1]-octane (TABO, 4). Besides
urotropine, TATU, and TATD, the GC–MS analysis of
this solution confirms the formation of 4. TABO (4) had
in its EIMS the molecular ion peak at m/z 113 correct
for the formula C5H11N3, and the fragmentation pattern
was consistent with the speculative fragmentation course.
To the best of our knowledge, although its structure was
claimed in a patent,7 its NMR data are unprecedented.
We also focused on the strong peaks at 3.96 and
2.97 ppm, with approximate intensities, 2.61; 7.12
(Fig. 2a). In principle, these signal protons did not show
d
4.25
ppm (t1)
4.00
3.75
3.50
3.25
3.00
2.75
2.50
2.25
Fig. 1. 1H NMR spectra of a reaction mixture of 2 (1.41 M) and NH4F
(4.50 M) in a D2O at (a) t = 0 s, (b) t = 20 min 17 s, and (c) t = 440 min.
(d) 1H NMR spectrum of a mixture of 1 (0.09 M), 2 (0.09 M), and 3
(0.01 M) in D2O.