Ring-chain tautomerism of 2-mercaptobenzoylhydrazones of aromatic aldehydes

Article abstract of DOI:10.1007/s10593-010-0638-3

It has been shown by ¹H NMR spectroscopy that 2-mercaptobenzoylhydrazones of aromatic aldehydes 2-HSC₆H ₄CONHN=CHC₆H₄X (X = 4-NO₂, 3-NO ₂, 4-Br, H, 4-Me, 4-MeO, 4-Me₂N

Full text of DOI:10.1007/s10593-010-0638-3

Chemistry of Heterocyclic Compounds, Vol. 46, No. 9, 2010
RING-CHAIN TAUTOMERISM OF
2-MERCAPTOBENZOYLHYDRAZONES
OF AROMATIC ALDEHYDES
1
1
1
2
B. V. Chernitsa , A. Yu. Ershov *, V. A. Doroshenko , S. I. Yakimovich ,
3
2
2
1
I. V. Lagoda , I. V. Zerova , V. V. Pakal'nis , and V. V. Shamanin
1
It has been shown by H NMR spectroscopy that 2-mercaptobenzoylhydrazones of aromatic aldehydes
2
-HSC H CONHN=CHC H X (X = 4-NO , 3-NO , 4-Br, H, 4-Me, 4-MeO, 4-Me N) exist in DMSO-d
6 4 6 4 2 2 2 6
solution as tautomeric mixtures of linear and cyclic benzo-1,3,4-thiadiazepine forms. The linear
hydrazone form is represented by (E,Z')-conformational isomers, differing in the disposition relative to
the amide C–N bond. It was shown that the logarithm of the tautomeric equilibrium constant KT
correlates with the σ-constants of the substituents in the aromatic nucleus.
Keywords: benzo-1,3,4-thiadiazepines, 2-mercaptobenzoylhydrazones, ring-chain tautomerism, Hammett
equation.
It was shown previously that 2-mercaptobenzoylhydrazones of aliphatic aldehydes exist in solution as
tautomeric mixtures of linear and cyclic benzo-1,3,4-thiadiazepine forms. The position of the equilibrium was
determined by the effective volume of the terminal alkyl substituent [1].
The aim of the present work, being a continuation of the previous investigations, was to study the
structure of the products of condensation of 2-mercaptobenzoic acid hydrazide with a series of aromatic
aldehydes, and also the effect of the electronic properties of a substituent in the aromatic ring of the aldehyde
component on the position of the tautomeric equilibrium.
Compounds 2a-g were obtained in 65-90% yield after briefly maintaining equimolar quantities of
o
2
-mercaptobenzoic acid hydrazide 1 and the appropriate aromatic aldehyde in methanol solution at 25 C
(
Table 1 and EXPERIMENTAL).
_
*
______
To whom correspondence should be addressed, e-mail: ershov305@mail.ru.
1
Institute of Macromolecular Compounds, Russian Academy of Sciences, Saint-Petersburg 199004, Russia.
Saint-Petersburg State University, Saint-Petersburg 198504, Russia; e-mail: viktoriapakalnis@mail.ru
Scientific Research Test Center (Medical and Biological Defence), Federal Research Test Institute of Military
2
3
Medicine, Defence Ministry of Russian Federation, Saint-Petersburg 195043, Russia; e-mail: lagodai@peterstar.ru.
_
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1404-1409, September, 2010.
Original article submitted January 21, 2010
009-3122/10/4609-1133©2010 Springer Science+Business Media, Inc.
0
1133

C H X
6
4
N
N
H
XC H4
6
H
O
NHNH2
O
H
N
XC H CH=O
N H
HS
6
4
SH
O
SH
E,E')-A
(
E,Z')-A
1
(
O
H
N
NH
S
C H X
6
4
B
a–g
2
2
2 2 2
a X = 4-NO , b X = 3-NO , c X = 4-Br, d X = H, e X = 4-Me, f X = 4-MeO, g X = 4-Me N
TABLE 1. Physicochemical Characteristics of Compounds 2a-g and 3a-g
Found, %
Com-
pound
Empirical
formula
——————
Calculated, %
mp, °C
Yield, %
С
H
N
2
2
2
2
2
2
2
3
3
3
3
3
3
3
а
b
c
d
e
f
C
C
C
C
C
C
C
C
C
C
C
C
C
C
14
14
14
14
15
15
16
28
28
28
28
30
30
32
H
H
H
H
H
H
H
H
H
11
11
N
N
3
3
O
3
3
2
S
55.87
3.60
3.68
3.73
3.68
3.27
3.31
4.67
4.72
5.28
5.22
4.86
4.93
5.67
5.72
3.41
3.36
3.30
3.36
2.96
3.02
4.29
4.34
4.91
4.86
4.64
4.59
5.36
5.40
13.89
13.95
14.04
13.95
8.41
8.36
11.02
10.93
10.30
10.36
9.82
9.78
13.98
14.04
13.92
13.99
14.04
13.99
8.43
8.38
11.05
10.97
10.38
10.40
9.77
9.82
14.12
14.08
207-209
206-208
189-191
161-163
174-176
166-168
170-172
80
85
70
75
85
80
65
90
90
80
85
90
80
75
5
5.80
O
S
55.76
5.80
5
11BrN
OS
50.21
0.16
5
12
14
14
17
20
20
N
N
N
N
N
N
2
2
2
3
6
6
OS
OS
65.67
5.60
6
66.58
6.64
6
O
2
S
63.01
2.92
6
g
a
b
c
d
e
f
OS
64.24
4.19
6
O
O
6
6
S
S
2
2
55.93
5.99
258-260
257-258 [2]
261-263
263-264 [2]
234-236
220-222
237-240
5
56.04
5.99
5
H20Br
2
N
4
O
2
S
2
50.28
0.31
5
H
H
H
H
22
26
26
32
N
N
N
N
4
4
4
6
O
O
O
O
2
2
4
2
S
S
S
S
2
65.91
5.86
6
2
2
2
66.94
6.89
6
63.07
3.14
254-256
252-253 [2]
239-240
241-243 [2]
6
g
64.35
4.40
6
1
In the H NMR spectra of solutions in DMSO-d of all the synthesized compounds there were signals
6
corresponding both to the linear A and to the cyclic benzo-1,3,4-thiadiazepine B tautomeric forms. The signals
of the linear tautomer were doubled in the spectra.
1
The observed doubling of the signals of the linear form A in the H NMR spectra of compounds 2a-g
must be linked with the presence of conformational (E',Z')-isomers, differing in the disposition of substituents
relative to the amide C–N bond. An (E,Z')-structure must therefore be attributed to the main isomer and an
1
134

(E,E')-structural disposition to the minor isomer. The existence of an (E,Z)-configuration of isomer relative to
the C=N bond was not considered by us since aldoacylhydrazones exist exist primarily or completely in the
(E)-configuration relative to this bond [3-5].
Assignment of the signals of the (E,E')- and (E,Z')-isomers of the linear form A was based on the known
difference in position of the signals of the azomethine protons of the conformational (E',Z')-isomers in the
1
H NMR spectra. The signals of the (E')-isomer of this group are disposed at lower field than the analogous
1
signals of the (Z')-isomer (Table 2). An opposite value of both signals in the H NMR spectra is observed for the
protons of the NHCO groups of the (E',Z')-conformers [6]. Taking into consideration the above-indicated it may
be confirmed that the main isomer has the (E,Z')-structure, and the minor isomer the (E,E')-spatial disposition.
The existence of the cyclic form B in DMSO-d solution may be judged by the doublet signals of the
6
H-2 and NHCO protons at 5.8 and 9.6 ppm respectively and also by the doublet-doublet signals of the NH group
proton at 6.2 ppm, which is caused by a spin-spin interaction with the protons in positions 2 and 4 of the seven-
membered benzo-1,3,4-thiadiazepine heterocycle.
The introduction of an electron-withdrawing substituent into the aromatic ring of the aldehyde component
leads to a displacement of the ring-chain equilibrium A↔B to the side of the cyclic benzo-1,3,4-thiadiazepine form
(
Table 2), and a linear correlation is then observed between the logarithms of the tautomeric equilibrium
+
constants K and the Hammett σ-constant [7, 8]. The use of the σ -constant of Brown [8] improves the
T
correlation (Table 3).
1
TABLE 2. H NMR Spectra of Compounds 2a-g
Com-
Tautomeric
Chemical shifts, δ, ppm (J, Hz)
HС=N, s or H-2, d NH
K
Т
= [B]/[A]*
pound composition, %
2
2
2
2
2
2
2
а
b
c
d
e
f
(E,E')-A (6)
8.38
12.30 (br. s)
12.18 (br. s)
0.754
(
E,Z')-A (51)
B (43)
8.45
5.92 (J = 6.2)
6.41 (dd, J = 6.2, J = 2.5),
.70 (d, J = 2.5)
9
(E,E')-A (6)
8.31
12.27 (br. s)
0.695
0.587
0.408
0.370
0.205
0.075
(
E,Z')-A (53)
B (41)
8.48
12.17 (br. s)
5.95 (J = 6.6)
6.43 (dd, J = 6.6, J = 2.7),
9
.71 (d, J = 2.7)
(E,E')-A (9)
8.10
12.08 (br. s)
(
E,Z')-A (54)
B (37)
8.33
11.95 (br. s)
5.74 (J = 6.8)
6.26 (dd, J = 6.8, J = 3.0),
9
.62 (d, J = 3.0)
(E,E')-A (10)
8.13
12.02 (br. s)
(
E,Z')-A (61)
B (29)
8.36
11.88 (br. s)
5.73 (J = 6.6)
6.21 (dd, J = 6.6, J = 2.7),
9
.61 (d, J = 2.7)
(E,E')-A (10)
8.09
11.95 (br. s)
(
E,Z')-A (63)
B (27)
8.10
11.81 (br. s)
5.68 (J = 6.8)
6.16 (dd, J = 6.8, J = 2.9),
9
.59 (d, J = 2.9)
(E,E')-A (11)
8.06
11.88 (br. s)
(
E,Z')-A (72)
B (17)
8.29
11.75 (br. s)
5.67 (J = 7.0)
6.14 (dd, J = 7.0, J = 2.7),
9
.57 (d, J = 2.7)
g
(E,E')-A (13)
7.98
11.58 (br. s)
(
E,Z')-A (80)
B (7)
8.20
11.71 (br. s)
5.61 (J = 7.0)
6.05 (dd, J = 7.0, J = 3.9),
9
.55 (d, J = 3.9)
_
*
______
[A] is the total content of forms (E,E')-A and (E,Z')-A.
1
135

TABLE 3. Correlation of the Logarithms of the Tautomeric Equilibrium
+
Constants K with Constants of Hammett σ and Brown σ According to the
T
Equation: logK = A+B·X
T
X
A
B
r
s
D
n
σ
σ
-0.520 ± 0.043
-0.406 ± 0.028
0.614 ± 0.081
0.423 ± 0.034
0.959
0.987
0.112
0.064
7
6
+
1
TABLE 4. H NMR Spectra of Compounds 3a-g
Chemical shifts, δ, ppm
Com-
pound
HC=N (s)
NH (2Н, br. s)
Ar (m)
3
3
3
3
3
3
3
a
b
c
d
e
f
8.50
8.52
8.38
8.41
8.36
8.34
8.25
12.37
12.34
12.14
12.07
12.00
11.93
11.77
7.26-8.50 (16H)
7.26-8.28 (16H)
7.24-7.76 (16H)
7.32-.75 (18H)
2.28 (6Н, s, 2СН
3.81 (6Н, s, 2СН
3.04 (6Н, s, 2СН
3
3
3
); 7.13-7.74 (16H)
O); 7.02-7.71 (16H)
N); 6.75-7.72 (16H)
g
The same regularity is explained by the fact that the electron-withdrawing substituents strengthen the
electrophilicity of the oxygen atom towards the C=N bond, addition of the SH function to which leads to the
formation of benzo-1,3,4-thiadiazepine tautomer B. The conformational equilibria within the linear tautomer are
sensitive to a lesser extent to the nature of the substituent in the aromatic ring. Probably in both linear forms
(E,E')-A and (E,Z')-A identical systems of conjugation occur, reacting in the same way to the change of
electronic parameters of the substituent.
Compounds 2a-g are inclined to oxidize with the formation of dimeric products 3a-g having linear bis-
1
hydrazone structures. This process, judging by a survey of the H NMR spectra with time, begins 3-5 h after
dissolving compounds 2a-g in DMSO-d and is complete after several days with the quantitative formation of
6
dimers 3a-g.
Compounds 3a-g may also be obtained in high yield on treating methanolic solutions of 2-mercapto-
benzoylhydrazones 2a-g with 5% H O solution (EXPERIMENTAL). One set of resonance signals was
2
2
1
observed in the H NMR spectra of compounds 3a-g belonging to the conformational (E,Z')-isomer relative to
the amide C–N bond (Table 4).
H
H
2
a–g
N
S
S
N
H
H
O
O
N
N
XC H
C H X
6
4
6
4
3
a–g
3
a X = 4-NO
2
, b X = 3-NO
2
, c X = 4-Br, d X = H, e X = 4-Me, f X = 4-MeO,
g X = 4-Me
2
N
Unlike the condensation products of aromatic aldehydes with hydrazides of 2-hydroxy- and 2-amino-
benzoic acid known in the literature [9, 10], 2-mercaptobenzoylhydrazones display an inclination towards
cyclization with the formation of a seven-membered benzo-1,3,4-thiadiazepine ring. This is a natural reflection
1
136

of the significantly larger nucleophilicity of the sulfur atom in comparison with oxygen and nitrogen atoms of
OH and NH functions in hydrazones obtained on using hydrazides of 2-hydroxy- and 2-aminobenzoic acids. In
this respect 2-mercaptobenzoylhydrazones 2a-g are close to the condensation products of aromatic aldehydes
with hydrazides of thiobenzoic and thioglycolic acids investigated by us previously, for which intramolecular
attack by the sulfur atom at the C=N bond of the hydrazone fragment leads to the formation of 1,3,4-thia-
diazoline [11] and 1,3,4-thiadiazine [12] rings respectively.
EXPERIMENTAL
1
The H NMR spectra were taken on a Bruker AV 400 (400 MHz) spectrometer in DMSO-d , internal
6
standard was HMDS. The quantitative content of the tautomeric forms was determined by integrating the
1
appropriate signals in the H NMR spectra, error of measurement was ± 1%. A check on the progress of
reactions and the purity of the obtained compounds was effected by TLC on Silufol UV-254 plates in the system
benzene–acetone, 4:1.
The hydrazide of 2-mercaptobenzoic acid 1 was obtained by the known procedure of [2].
2
-Mercaptobenzoylhydrazones of Aromatic Aldehydes 2a-g. A mixture of carbonyl compound
(
2
10 mmol) and 2-mercaptobenzoic acid hydrazide 1 (1.68 g, 10 mmol) in methanol (50 ml) was maintained at
o
5 C for 2 h. The precipitated crystals were filtered off, washed with ether, and dried.
,2'-Dithiobenzoylhydrazones of Aromatic Aldehydes 3a-g. A 5% solution of H O (0.5 ml) was
2
2
2
o
added to a solution of compound 2a-g (5 mmol) in methanol (5 ml) and the mixture maintained at 25 C for 2 h.
The precipitated crystals were filtered off, washed with ether, and dried.
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