MAGNETIC RESONANCE IN CHEMISTRY
Magn. Reson. Chem. 2001; 39: 411–413
Spectral Assignments and Reference Data
1H and 13C NMR study of
6-aryl-3-cinchopheny-1,2,4-triazolo[3,4-b]-
1,3,4-thiadiazoles
N2H4• H2O
CS2, KOH
COONHNH
N
COOH
N
2
abs C2H5OH
Ph
Ph
Xue-hui Liu,1 Hao Xu,2 Yi-ou Fang,1 Yu-xin Cui1∗ and
Peng-fei Xu3
(A)
(B)
N
N
1
National Key Laboratory of Natural and Biomimetic Drugs, Medical and
N
Health Analysis Center; Peking University, Beijing 100083, China
N
Ar−COOH
POCl3
2
S
Department of Chemistry, Peking University, Beijing 100871, China
Ph
N
N
N
3
Department of Chemistry, Lanzhou University, Lanzhou 730000, China
N
N
SH
Received 19 September 2000; Revised 2 January 2001; Accepted 22 January
2001
Ph
H N
2
R
(C)
(D)
Ten new 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives
were synthesized and their NMR spectra were analyzed
by 1D and 2D NMR techniques (gCOSY, gHMBC,
gHMQC). Copyright 2001 John Wiley & Sons, Ltd.
Scheme 2
and we used 45 pulses for the experiments. 13C NMR experiments
were performed under similar conditions on a Varian VXR-300
°
KEYWORDS: NMR; 1H NMR; 13C NMR; thiadiazoles
13
°
spectrometer, operating at 75.43 MHz for C. The 90 pulse was
°
19.6 µs and we used 30 pulses for the measurements. The gradient
INTRODUCTION
field strength for gCOSY experiments was 3.6 ð 10ꢀ4 T cmꢀ1. For
the gHMQC and gHMBC experiments we used 11.4 ð 10ꢀ4, and
5.7 ð 10ꢀ4 T cmꢀ1, respectively. The digital resolution for 13C NMR
at 75.43 MHz was better than 2.5 Hz, and that for 1H NMR at-
500 MHz was better than 0.5 Hz. For the 2D experiments we used
digital resolutions between 6 and 19 Hz. The concentration for
In recent years, 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives
have displayed unique properties both in chemical synthesis and
in chemical biology,1–3 as they possess broad-spectrum biological
activities such as antibacterial, hypotensive and CNS depressant
activities.4,5 Compounds 1–10 (Scheme 1) have been synthesized
utilizing cinchophen as the starting material. These compounds
were prepared by the reaction of cincophen (A) and ethanol in the
presence of sulfuric acid and then reaction with hydrazine hydrate
in absolute ethanol to give cincophen hydrazine (B), that yielded 4-
amino-5-cinchophenyl-3-thiohydroxy-1,2,4-triazole (C) on treatment
with CS2 and KOH. Reaction of C with various substituted benzoic
acids in the presence of POCl3 gave compounds 1–10 (Scheme 2)
compound 7 in TFA was 3.58 ð 10ꢀ2 mol lꢀ1
.
RESULTS AND DISCUSSION
NMR data for 1–10 are presented in Tables 1 and 2.
Assigning 1H NMR data
19
R
18
17
1
2
3
4
5
6
7
8
9
R = p-Cl
R = p-F
The 1H NMR spectra chemical shifts of 1–10 range from 7.72 to
9.62 ppm (excluding the methyl group in 4 and 7). Because of the
similarity in structures, assigning the spectra of 7 is described as an
example. The single peak at υ 9.63 is H-3. H-8 υ 9.43 appears at a
lower field than H-5 owing to the nitrogen atom’s electron-attracting
ability. H-7 and H-6 can be found with the aid of gCOSY. In each of
the 10 compounds, there is a triplet (1H) at υ 8.09 and a doublet (2H)
at υ 5.36. This means these three protons are on the unsubstituted
benzene ring. We therefore assigned H-26 to υ 8.09, H-25 to υ 7.98
and H-24 to υ 8.33 from their mutual spin–spin couplings. At higher
field, a triplet of H-21 at υ 7.72 couples with a doublet of H-20 at
υ 7.81 and a multiplet of H-22 at υ 8.00. Finally, H-18 yields a singlet
at υ 8.00.
13
S
15
N
20
21
14
R = p-I
12
N
22
R = p-CH3
R = m-F
R = m-Cl
R = m-CH3
R = o-Cl
R = p-Br
N
10
N
11
16
9
5
8
4
4a
8a
6
7
3
2
24
25
26
N
23
1
10 R = m-Br
Scheme 1
Assigning 13C NMR data
All the tertiary carbons can be distinguished with the help of gHMBC
and gHMQC experiments. The assignment of the 10 quaternary
carbons depends on gHMBC and analyzing the electron effects in
the molecules. We take 7 as an example again. C-8a at υ 141.57
correlates with H-8 at υ 9.43 and C-4a couples with H-5 at υ 8.73 and
H-3 at υ 9.63. In addition to coupling of C-23 at υ 131.83 with H-
2 and H-24, there are two carbons, υa 158.39, υ 144.47, that have
cross peaks with H-2 on HMBC. Because N-b1 was protonated
by TFA, the electron density at C-2 is lower than that at C-4.
Therefore, C-2 is at υ 158.34. On the substituted benzene ring, C-
19 couples with H-20 at υ 7.81 and H-18 at υ 8.00. C-14 and C-17
correlate with H-22 and H-14, H-18, respectively. Concerning the
other two carbons, C-12, which has electron-attracting nitrogen
and sulfur atoms around it, appears at a lower field than C-9 at
υ 139.43. The chemical shifts of other compounds can be assigned in
a similar way.
1H and 13C NMR data for 1–10, not previously reported, were
of interest to us. We report here the1H and 13C chemical shifts and
part of the Jꢀ1H, 1Hꢁ data. The assignments were based on gCOSY,
gHMQC and gHMBC experiments.
EXPERIMENTAL
All the 1H NMR and 2D NMR experiments were recorded at room
temperature on a Varian INOVA 500 spectrometer, operating at
499.89 MHz for 1H and 125.71 MHz for 13C. The 90 pulse was 8.6 µs
°
ŁCorrespondence to: Y. Cui, National Key Laboratory of Natural and
Biomimetic Drugs, Medical and Healthy Analysis Center, Peking University,
Beijing 100083, China. E-mail: yxcui@mail.bjmu.edu.cn
DOI: 10.1002/mrc.837
Copyright 2001 John Wiley & Sons, Ltd.
Liu, Xue-Hui
