1H and13C NMR study of 5-substituted-4-(arylidene) amino-2,4-dihydro-3H-1,2,4-triazole-3-thiones and 6-aryl-3-(D-glucopentitol-1- yl)-7H-1,2,4-triazolo[3,4-b] [1,3,4]thiadiazines

Article abstract of DOI:10.1002/mrc.1829

Five 5-substituted-4-(arylidene)amino-2,4-dihydro-3H-1, 2,4-triazole-3-thiones (2a-2e) and seven 6-aryl-3-(D-glucopentitol-1-yl)-7H-1,2, 4-triazolo[3,4-b][l,3,4]thiadiazines (3a-3g) were synthesized. The complete ¹H and ¹³C NMR chemical shift assignments were analyzed on one-and two-dimensional NMR techniques, including DEPT, NOE-DIF, COSY, gHMBC, and gHSQC. Copyright

Full text of DOI:10.1002/mrc.1829

MAGNETIC RESONANCE IN CHEMISTRY
Magn. Reson. Chem. 2006; 44: 813–816
Published online 20 April 2006 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/mrc.1829
Spectral Assignments and Reference Data
1H and 13C NMR study of 5-substituted-4-
(arylidene)amino-2,4-dihydro-3H-1,2,4-
triazole-3-thiones and 6-aryl-3-(D-gluco-
pentitol-1-yl)-7H-1,2,4-triazolo[3,4-b]
[1,3,4]thiadiazines
Preparation of 6-aryl-3-(D-gluco-pentitol-1-yl)-7H-1,2,4-
triazolo[3,4-b][1,3,4]thiadiazines
The mixture of 4-amino-5-(D-gluco-pentitol-1-yl)-2,4-dihydro-3H-
1,2,4-triazole-3-thione (40 mmol), ω-bromoacetophenones (42 mmol),
ethanol (70 ml), and water (30 ml) was stirred and refluxed for 3 h.
The solution was cooled and then filtered. The precipitate was
washed with ether and dried. The crude material was recrystallized
from 70% ethanol solution giving the pure products (3a–3g) at a
yield of 60–88%.
Anjiang Zhang,∗ Lixue Zhang and Xinxiang Lei
NMR spectra
Department of Chemistry, Wenzhou University, Wenzhou 325035, China
1H NMR and 13C NMR spectra were recorded on a Bruker Avance-
300NMR spectrometerin DMSO-d6 solutionusing TMS asaninternal
reference and operating at 300.132 MHz for 1H and 74.475 MHz for
Received 12 January 2006; revised 25 February 2006; accepted 6 March 2006
Five 5-substituted-4-(arylidene)amino-2,4-dihydro-3H-1,
2,4-triazole-3-thiones (2a–2e) and seven 6-aryl-3-(D-gluco-
pentitol-1-yl)-7H-1,2,4-triazolo[3,4-b][1,3,4]thiadiazines
(3a–3g) were synthesized. The complete 1H and 13C
NMR chemical shift assignments were analyzed on one-
and two-dimensional NMR techniques, including DEPT,
NOE-DIF, COSY, gHMBC, and gHSQC. Copyright 
2006 John Wiley & Sons, Ltd.
Table 1. 1H NMR and 13C NMR data of compound 2a–2e (Solv:
DMSO-d6)
Position
υ
2a
2b
2c
2d
2e
2
3
5
7
υH 14.10
υc 161.75
υc 148.37
υc 163.96
13.93
161.84
147.99
166.88
9.04
13.88 13.86
161.41 161.38
150.18 149.72
161.63 165.02
13.93
161.47
150.97
162.93
9.84
KEYWORDS: 1H NMR; 13C NMR; tautomerism; 1,2,4-triazoles;
thiadiazines; synthesis
υH
9.65
10.02
9.38
8
9
υc 131.08
υc 130.13
118.78
130.34
7.55
131.03 118.60
130.18 130.38
131.15
129.19
7.96
INTRODUCTION
υH
7.78
7.85
7.66
In recent years, 2,4-dihydro-3H-1,2,4-triazole-3-thione, 1,2,4-triazolo
[3,4-b][1,3,4]thiadiazine, and 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole
derivatives have received considerable attention as they possess
diverse biological activities such as antimicrobial, antibacterial,
herbicidal, antiviral, anthelmintic, and plant-growth regulating
properties.1–3 However, there was a controversy about the existing
structure of 2,4-dihydro-3H-1,2,4-triazole-3-thione (thione form),
which could exist as tautomer 3-mercapto-1,2,4-triazole (thiole
form) as assumed by chemists for many years. Furthermore,
almost all of the substituents at 3- and 6-position in 1,2,4-
triazolo[3,4-b][1,3,4] thiadiazines synthesized in the past were
alkyl or aryl, which led to their poor water solubility. Trying
to attach hydrophilic D-glucono residues at the 3-position in
thiadiazines was of interest. Prompted by these reasons, we report
here the synthesis of 5-substituted-4-(arylidene) amino-2,4-dihydro-
3H-1,2,4-triazole-3-thiones (2a–2e) and 6-aryl-3-(D-gluco-pentitol-1-
yl)-7H-1,2,4-triazolo[3,4-b][1,3,4]thiadiazines (3a–3g), and the total
assignments of 1H and 13C NMR chemical shifts of the title
compounds (Scheme 1).
(3J D 9.0 Hz)
111.47
6.73
(3J D 8.7 Hz)
130.37
7.63
10
υc 129.26
υH 7.56
129.24 111.47
7.59 6.78
11
12
υc 137.21
υc 112.80
υH
153.13
113.09
137.22 153.11
133.36 133.38
137.20
66.18
5.66
(3J D 5.4 Hz)
13
14
υc 156.13
υH
156.10
127.66 127.62
70.22
7.43
125.40 125.36
7.41 7.41
7.42
4.83
υc 115.94
115.96
6.87
(3J D 8.1 Hz)
132.11
7.33
70.52
υH
6.90
3.15
15
16
υc 132.36
υH 7.35
υc 118.87
υH 6.92
127.71 127.64
7.81 7.84
71.16
3.51
118.76
131.42 131.44
63.30
3.35
6.88
EXPERIMENTAL
(3J D 6.9 Hz)
131.03
7.36
3.51
Materials
17
18
19
20
υc 131.10
128.50 128.45
5-substituted-4-amino-2,4-dihydro-3H-1,2,4-triazole-3-thione (1)was
prepared by the method given in the literature.4–6 All other chemicals
and solvents used were of analytical reagent grade.
υH
υc
7.38
7.91
125.79 125.78
7.51 7.52
126.27 126.24
7.53 7.54
123.90 123.89
8.14 8.15
7.93
39.60
υH
υc
2.98
Preparation of 5-substituted-4-(arylidene)amino-2,4-dihydro-
3H-1,2,4-triazole-3-thiones
υH
υc
A round-bottomed flask was charged with 5-substituted-4-amino-
2,4-dihydro-3H-1,2,4-triazole-3-thione (1) (40 mmol), aryl aldehyde
(42 mmol), ethanol (70 ml), and water (30 ml); the mixture was
stirred and the pH of the solution was controlled at 4.5 by dilute
hydrochloric acid and refluxed for 3 h. The solution was then cooled
and filtered. The precipitate was washed with ether and then dried.
The crude material was recrystallized from ethanol solution giving
the pure products (2a–2e) at a yield of 68–75%.
υH
υc
21
22
131.01 131.12
28.19 28.26
υc
υH
υc
4.61
4.54
39.60
3.03
23
υH
ŁCorrespondence to: Anjiang Zhang, Department of Chemistry, Wenzhou
University, Wenzhou 325035, China. E-mail: ajzhang@wznc.zj.cn
OH
υH 10.03
9.98
Copyright  2006 John Wiley & Sons, Ltd.

814
Spectral Assignments and Reference Data
Scheme 1. Synthesis of 4-(arylidene)amino-2,4-dihydro-3H-1,2,4-triazole-3-thiones and 1,2,4-triazolo[3,4-b][1,3,4] thiadiazines derivatives.
1
13
13C. The H 90 pulse was 11 µs, and C 90 pulse was 7.8 µs.
The gradient field was 50 ð 10ꢀ4 T cmꢀ1. The gHMBC spectra
resulted from a 256 ð 1024 data matrix size with 16 scans per
t1, 200 µs delay for homospoil/gradient recovery (D16), 1 ms for
°
°
homospoil/gradient pulse (P16), and 5 : 3 : 4 gradient combination
using a pulse sequence optimized for 8 Hz. The gHSQC spectra were
measured with same D16 (200 µs) and P16 (1 ms) and a different 4 : 1
gradient combination.
Copyright  2006 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2006; 44: 813–816

815
Spectral Assignments and Reference Data
Table 2. 1H NMR and 13C NMR data of compound 3a–3g (Solv: DMSO-d6ꢀ
Position
υ
3a
3b
3c
3d
3e
3f
3g
3
6
7
υc
153.70
154.50
23.03
4.35
153.48
154.20
22.74
4.37
153.34
153.54
22.84
4.37
153.51
154.41
25.75
153.61
153.61
22.68
153.82
152.61
22.95
153.56
153.91
22.79
υc
υc
υH
υc
4.25
4.36
4.46
4.42
9
140.63
65.89
5.06
140.35
65.65
5.03
140.25
65.77
5.03
140.39
65.71
140.43
65.82
140.29
65.96
140.37
65.74
10
υc
υH
4.94
5.03
5.04
5.06
(3J D 8.7 Hz)
(3J D 8.1 Hz)
(3J D 8.3 Hz)
(3J D 8.4 Hz)
11
12
υc
70.22
4.40
70.38
4.38
70.37
4.39
70.26
70.36
70.43
70.40
υH
υc
4.32
4.38
4.41
4.41
70.82
3.12
70.45
3.14
70.41
3.13
70.39
70.44
70.43
70.47
υH
3.09
3.14
3.14
3.15
(3J D 7.8 Hz)
(3J D 8.4 Hz)
13
14
υc
71.44
3.53
71.33
3.52
71.30
3.52
71.25
71.28
71.29
3.53
71.34
3.53
υH
υc
3.50
3.51
63.56
63.40
63.40
63.35
63.39
63.45
63.43
υH
υc
3.36, 3.53
133.68
127.71
8.03
3.34, 3.52
130.76
127.53
7.94
3.35, 3.52
130.27
3.34, 3.50
132.54
129.64
3.34, 3.50
132.75
129.54
7.99
3.33, 3.53
139.58
128.98
8.28
3.34, 3.53
132.48
128.23
8.14
15
16
υc
130.15
υH
8.11
(3J D 8.1 Hz)
129.44
7.37
(4JHF D 5.4 Hz)
17
υc
129.04
7.57
115.96
127.90
7.87
131.91
7.79
123.93
8.39
127.01
7.88
υH
(3JHF
D
3JHH D 8.8 Hz)
(2JCF D 22.0 Hz)
(4J D 1.8 Hz)
(3J D 8.8 Hz)
18
19
20
υc
131.94
7.57
141.95
164.15
136.16
125.61
149.09
143.18
υH
υc
(1JCF D 250.5 Hz)
115.96
129.04
7.57
129.44
7.37
132.46
7.61
131.91
7.79
123.93
8.39
127.01
7.88
υH
υc
7.42
127.71
8.03
127.53
7.94
130.15
133.46
129.54
128.98
8.28
128.23
8.14
υH
8.11
7.70
7.99
(3J D 8.4 Hz)
(3J D 8.4 Hz)
21
υc
138.81
126.84
22(26)
υc
υH
7.78
(3J D 7.8 Hz)
23(25)
24
υc
129.05
υH
υc
7.57
126.84
υH
7.43
(3J D 7.2 Hz)
27
υc
20.98
2.40
υH
RESULTS AND DISCUSSION
Elucidation of the structure of
4-amino-2,4-dihydro-3H-1,2,4-triazole-3-thione
It had been assumed for many years that there were tautomers
for 2,4-dihydro-3H-1,2,4-triazole-3-thione derivatives, which were
exchanged by 3-mercapto-1,2,4-triazole (thiole form) in a state of
equilibrium (Scheme 2).7,8 However, so far there is no evidence
to indicate that thiole form could exist in room temperature.9 The
chemical shift and intensity integral of NH proton (υ > 13) of
4-amino-2,4-dihydro-3H-1,2,4-triazole-3-thione clarify thatthe thione
form is the unique structure in solution. In order to get information
Scheme 2. Structures of 2,4-dihydro-3H-1,2,4-triazole-3-thione and
3-mercapto-1,2,4-triazole.
Copyright  2006 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2006; 44: 813–816

816
Spectral Assignments and Reference Data
and 13C NMR chemical shifts were determined completely by the
same methods. Discriminating H-13 from H-14 and H-17 from H-20
for 2d was not easy and NOE difference spectra were applied. When
radiating at υ 4.54 (H-22, methylene proton), the signals at υ 7.42, and
υ 8.15 were increased by 5.7%, and 10.0% respectively, and thus the
signals of H-13 (υ 7.42), and H-20 (υ 8.15) were assigned.
of the exact structure in solid, a single-crystal X-ray diffraction
experiment was performed. The results showed that 4-amino-5-(D-
gluco-pentitol-1-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione in solid
also presented in the thione form.10 The situation is similar to that in
products (2a–2e). For example, H-2 (NH, υ 14.10) couples with C-5
(υ 148.37) via 3JCNNH on the gHMBC spectrum of 2a, which confirms
the thione structure. The 1H chemical shift and signal intensity of H-2
(NH) proton also verify the unique thione. Therefore, we come to
the conclusion that there is no tautomerism for 4-amino-2,4-dihydro-
3H-1,2,4-triazole-3- thione and its derivatives. Besides, H-2 (υ 14.10)
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correlates with C-3 (υ 161.75) via JHNC, hydroxy proton (υ 10.03)
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The complete assignments of 1H and 13C NMR data
In Scheme 1, the structures and numbering of the title compounds
are presented. Their 1H and 13C NMR chemical shifts are given in
Tables 1 and 2. For example, assigning the spectra of 2a is described
as follows. H-7 (υ 9.65), H-2 (υ 14.10), H-9 (υ 7.78), H-10 (υ 7.56),
and hydroxyl proton (υ 10.03) were assigned directly, and 1H signals
of H-14 ¾ H-17 were determined by the combination of COSY,
gHSQC, and gHMBC experiments. Six quaternary carbons were
observed by DEPT technique and assigned by gHMBC experiment,
the assignments were C-3 at υ 161.75, C-13 at υ 156.13, C-5 at υ 148.37,
C-11 at υ 137.21, C-8 at υ 131.08, and C-12 at υ 112.80. All the other 1H
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Copyright  2006 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2006; 44: 813–816