Tautomerism and conformational isomerism of mercaptoacetylhydrazones of aliphatic and aromatic aldehydes

Article abstract of DOI:10.1134/S1070428009050030

Mercaptoacetylhydrazones of aliphatic and aromatic aldehydes exist in the solutions as tautomeric mixtures of open-chain and cyclic 1,3,4-thiadiazine forms. The linear hydrazone form consists of a set of isomers due to the configurational and conformation

Full text of DOI:10.1134/S1070428009050030

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 5, pp. 660−666. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © A.Yu.Ershov, I.V. Lagoda, S.I. Yakimovich, V,V. Pakal’nis, I.V. Zerova, A.V. Dobrodumov, V.V. Shamanina, 2009,
published in Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 5, pp. 678−684.
Tautomerism and Conformational Isomerism
of Mercaptoacetylhydrazones of Aliphatic
and Aromatic Aldehydes
A. Yu. Ershova, I. V. Lagodab, S. I. Yakimovichc, V. V. Pakal’nisc, I. V. Zerovac,
A. V. Dobrodumova, and V. V. Shamanina
aInstitute of Macromolecular Compounds, Russian Academy of Sciences, St. Petersburg, 199004 Russia
e-mail: ershov@hq.macro.ru
bResearch Test Center of Medical and Biological Protection of the State Research Testing Institute of Military
Medicine of the Defence Ministry of the Russian Federation, St. Petersburg, Russia
cSt. Petersburg State University, St. Petersburg, Russia
Received February 6, 2008
Abstract—– Mercaptoacetylhydrazones of aliphatic and aromatic aldehydes exist in the solutions as tautomeric
mixtures of open-chain and cyclic 1,3,4-thiadiazine forms. The linear hydrazone form consists of a set of isomers
due to the configurational and conformational isomerism. At growing bulk of the alkyl substituent at the C=N
bond of the aliphatic aldehydes derivatives decreases the fraction of the cyclic tautomer; therewith the logarithms
of the constants of the chain-ring tautomeric equilibrium correlate with the steric constants of the alkyl substituents.
In the series of the aromatic aldehydes mercaptoacetylhydrazones the linear tautomer prevails, and the equilibrium
position is insignificantlyt affected at variation of the electronic characteristics of the substituents in the aromatic
ring.
DOI: 10.1134/S1070428009050030
The condensation products of carbonyl compounds
with thioglycolic acid hydrazide attract attention as
potential tautomeric systems capable to exist either in
the linear mercaptoacetylhydrazone (A) or in cyclic 1,3,4-
thiadiazine (B) forms. The latter arises therough an
intramolecular nucleophilic addition of the SH group to
the C=N bond of the hydrazone fragment. We showed
formerly that methyl alkyl ketones mercaptoacetyl-
hydrazones were capable of the ring-chain tautomerism,
and the equilibrium position was governed by the steric
characteristics of the alkyl substituent [1, 2]. In extension
of this research we investigated the ability to ring-chain
Scheme.
RCH O + H2NNHCOCH2SH
Ia_In
II
H
R
N
R
H
N
H
R
N
R
H
N
H
N
N
O
H
N
O
H
N
H
O
N
H
O
O
NH
5
2
6
S
R
SH
SH
SH
SH
B
E,Z'-A
Z,Z'-A
Z,E'-A
E,E'-A
IIIa_IIIn
R = Me (a), Et (b), Pr (c), Bu (d), i-Pr (e), i-Bu (f); R = XC6H4, X = 4-NO2 (g), 3-NO2 (h), H (i), 4-Me (j), 4-OH (k), 4-MeO (l),
4-Me2N (m), 2-HO (n).
660

TAUTOMERISM AND CONFORMATIONAL ISOMERISM OF MERCAPTOACETYLHYDRAZONES
661
Table 1. Correlation of logarithms of the constants of
tautomeric equilibria QT of compounds IIIa–IIIf with the steric
constants of Taft ES, Palm ES°, and Charton õ along the
equation: log KT = A + B X ; (n = 6)
tautomerism of condensation products of aliphatic and
aromatic aldehydes with thioglycolic acid hydrazide (see
the scheme).
Compounds IIIa–IIIn were obtained in 40–85%
yields by short keeping at room temperature in a water-
alcoholic solution of equimolar amounts of the thioglycolic
acid hydrazide (II) and of the appropriate aldehyde (see
EXPERIMENTAL).
X
A
B
r
sD
ES
1.09±0.04
0.82±0.08
0.983
0.057
ES°
1.17±0.06
1.96±0.09
0.67±0.09
0.964
0.989
0.083
0.047
1
The variation in time of the H NMR spectra of
υ
–1.68±0.13
compounds IIIa–IIIn suggests that they exist in the
crystalline state in the cyclic thiadiazine form B. For
instance, in the freshly prepared solution of compound
IIIa in DMSO-d6 a single set of peaks is observed cor-
responding just to B form. It is indicated by two signals
of NH groups protons at 5.77 and 9.00 ppm and by
a quartet at 4.48 ppm (H2), and the 13C NMR spectrum
of this form is characterized by the signal of sp3-hybridiz-
ed atom C2 at 63.8 ppm.
Gradually in the 1H NMR spectrum of compound IIIa
in DMSO-d6 signals appear corresponding to the stereo-
isomers of the linear acylhydrazone form A: three signals
of azomethine protons at 7.16, 7.32, and 7.49 ppm, and
also broadened signals of NH protons in the region
11.0 ppm. After some time the spectrum of compound
IIIa stopped to change indicating that the ring-chain
equlibrium was attained where alongside the cyclic
thiadiazine form B existed three stereoisomeric
modifications of the linear form A.
figurational isomer Z,E'-A and to the considerable
increase in the content in the solution of isomers E,E'-A
and Z',E'-A. Logs of the constants of the tautomeric
equilibria are in linear correlation with the steric constants
of Taft ES [6, 7] and Palm ES° [6]; the use of Charton
steric constants õ [8] improves the correlation (Table 1).
Thus the products of aliphatic aldehydes condensation
with thioglycolic acid hydrazide in the crystalline state
possess the structure 1,3,4-thiadiazine, and only in solution
in strongly polar solvents they partially transform into the
open-chain form; consequently, it is only tentatively
possible to use the name “mercaptoacetylhydrazone” for
such compounds.
Comparing the tautomeric behavior of aldehydes IIIa–
IIIf mercaptoacetylhydrazones with the previously studied
condensation products of thioglycolic acid hydrazide and
methyl alkyl ketones [2] it turns out that the aldehydes
derivatives tend to be present prevailingly in the cyclic
form, and for the methyl alkyl ketones mercaptoacetyl-
hydrazones the equilibrium is considerably shifted to linear
forms. This fact is apparently due to the possibility for
alkyl substituent in the position 2 of the chair conforma-
tion of the 1,3,4-thiadiazine ring to be equatorially oriented.
In the derivatives of methyl alkyl ketones the methyl or
alkyl group are forced to occupy the axial position and to
occur in a strong syn-axial interaction with a hydrogen
atom in the position 4 thus destabilizing the 1,3,4-thia-
diazine; therefore the open-chain tautomers successfully
compete with the cyclic form.
Four spatial structures are conceivable for the carbonyl
compounds acylhydrazones distinguished by the position
of substituents with respect to the C=N bond (geometric
Z,E-isomerism) and C–N bond of the amide fragment
(conformational Z',E'-isomerism) [3, 4]. The aldehydes
derivatives exist predominantly or totally in the Ε-con-
figuration with respect to the C=N bond.
The assignment of signals to geometric Z,E-isomers
can be made based on the deshielding effect of the
hydrazone fragment on the cis-located azomethine protons
observed in the 1H NMR spectra of acylhydrazones [5].
Owing to it the strongest downfield signal at 7.32 ppm in
the spectrum of compound IIIa should originate from
the E,E'-isomer, the weakest upfield signal at 7.16 ppm,
to the Z,E'-isomer, and the signal of intermediate intensity
at 7.49 ppm, to Ε,Z'-isomer.
Likewise appear the spectra of solutions in DMSO-
d6 of compounds IIIb–IIIf. Going to compounds IIIe
and IIIf containing bulky isopropyl and isobutyl groups
leads to the exclusion from the equilibrium of the con-
In aromatic aldehydes mercaptoacetylhydrazones the
ring-chain tautomeric equilibrium should shift to the open-
chain form A for the latter is stabilized by involving the
aromatic ring in the system of π-p-π-conjugation of the
acylhydrazone fragment [3, 4]. This assumption was
completely confirmed by the study of NMR spectra of
compounds IIIi–IIIn.
1
The H NMR spectrum of benzaldehyde mercapto-
acetylhydrazone IIIi registered just after dissolution in
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 5 2009

ERSHOV et al.
662
In the 1H and 13C NMR spectra of the compound IIIi
solution in DMSO-d6 gradually appeared signals cor-
responding to the cyclic 1,3,4-thiadiazine form B. The
typical signals of this form in the 1H NMR spectrum are
the peaks of protons H2 and NH at 5.45 and 6.20 ppm
respectively; diastereotopic protons H6 give rise to AΒ
system at 3.24 and 3.51 ppm (coupling constant 14.7 Hz),
the signal of the sp3-hybridized C2 atom appears in the
13C NMR spectrum at 65.5 ppm. Hence in the compound
IIIi solution in DMSO-d6 the ring-chain equilibrium was
established between E,E'- and E,Z'-stereoisomers of A
form and the cyclic 1,3,4-thiadiazine B form.
DMSO-d6 contained two sets of resonances cor-
responding to two stereoisomers of the linear form A.
The major isomer present in 65% fraction in the initial
moment gives rise to the following signals: a singlet of
the azomethine proton at 8.01 ppm, a doublet of methyl-
ene protons at 3.59 ppm, a triplet of the proton of SH
group at 2.71 ppm, and a broadened singlet of NH group
at 11.44 ppm. The analogous signals of the minor
stereoisomer (35%) are observed at 8.18, 3.20, 2.89, and
11.52 ppm respectively. The 13C NMR spectrum also con-
firms the presence of two isomers of the linear form A.
The acylhydrazones of aromatic aldehydes are known
to exist prevailingly or completely in the Ε-configuration
[3, 9]. Consequently, the observed doubling of the signals
in the 1H and 13C NMR spectra of compound IIIi is not
caused by the configurational equilibrium with respect to
the C=N bond, but the presence of the conformational
Z',E'-isomers with different position of substituents
relative to the amide C–N bond.
Mercaptoacetylhydrazones of other aromatic
aldehydes IIIg–IIIn posses the hydrazone steructure A
in the crystals, and in DMSO-d6 solutions exist tautomeric
mixtures of open-chain and cyclic forms. The tautomeric
equilibrium in the series of aromatic aldehydes derivatives
is shifted to the open-chain tautomer A, and the fraction
of the thiadiazine tautomer does not exceed 5% excluding
any conclusions on the effect of the electronic properties
of the substituent in the aromatic ring.
The assignment of signals belonging to E,E'- and E,Z'-
isomers of linear form A was based on the known
difference in the chemical shifts of the carbon atoms in
the C=N and C=O bonds in the 13C NMR spectra of
conformational isomers of monocarbonyl compounds
acylhydrazones; the E'-isomer signals of these groups
were located in the region 145 and 170 ppm, whereas
those of Z'-isomer, at 150 and 160 ppm respectively [2,
9, 10]. In the 13C NMR spectrum of compound IIIi the
resonances of the carbon atoms of C=N and C=O bonds
of the prevailing isomer appeared at 143.7 and 170.2 ppm,
the corresponding signals of the minor stereoisomer were
observed at 147.6 and 164.8 ppm. In view of the above
the major isomer had E,E'-configuration, and the struc-
tural arrangement of the minor isomer was E,Z'.
By an example of compound IIIi we explored the
effect of solvent on the tautomeric equilibrium (Table 2).
In low-polar CDCl3 even trace amounts of the cyclic
form were not detected. In going to basic dipolar solvents
(DMSO-d6 and DMF-d7) the appearance of the thia-
diazine form B was favored. Its stabilization is due to the
possibility of hydrogen bonds formation between the NH
groups of the thiadiazine ring and the polar solvent
molecules.
The relative amounts of E,E'- and E,Z'-isomers of the
linear form A of aromatic aldehydes IIIi–IIIn mercapto-
acetylhydrazones was practically independent of the
electronic effect of the substituent in the aromatic ring.
Going over from CDCl3 to polar solvents as show the
data on the benzaldehyde derivative IIIi increased the
stability of more polar E,Z'-stereoisomer (Table 2).
Table 2. Tautomeric composition of compound IIIi in various
solvents registered 48 h after dissolution
Form A, %
The conformational composition of linear form A might
significantly change on introduction into the aromatic ring
of benzaldehyde of a substituent capable to form an
intramolecular hydrogen bond. For salicylaldehyde
mercaptoacetylhydrazone (IIIn) the prevailing isomer in
the solution became E,Z'-isomer. The stabilization of this
stereoisomer may be due to the formation of an additional
intramolecular hydrogen bond between OH and C=O
groups alongside the hydrogen bond between OH and
C=N possible in both conformers.
Solvent
Form B, %
E,E'-
91
E,Z'-
9
Chloroform-d1
Pyridine-d5
–
1
79
20
Acetone-d6
74
65
23
32
3
3
Acetonitrile-d3
DMSO-d6
DMF-d7
60
61
34
32
6
7
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TAUTOMERISM AND CONFORMATIONAL ISOMERISM OF MERCAPTOACETYLHYDRAZONES
663
HS
The data obtained provide certain possibility for
forecasting more complex tautomeric systems [16–18]
with the mercaptoacetylhydrazone fragment involving into
the equilibrium additional cyclic forms, for instance,
resulting from the condensation of the thioglycolic acid
hydrazide with 1,3-dioxo compounds and
monosaccharides that we plan for our further
investigations.
O
H
H
N
H
H
H
N
SH
N
O
N
O
H
O
E,E'-A
E,Z'-A
IIIn
EXPERIMENTAL
Compounds IIIi–IIIn are prone to oxidation giving
dimerization products IV. In reactions performed directly
in the NMR tubes in DMSO-d6 solution at room
temperature these products for the majority of compounds
were spectrally detected after 2–3 weeks. The products
of compounds IIIi–IIIn dimerization were obtained in
high yield by treating methanol solutions of aromatic
aldehydes mercaptoacetylhydrazones with 5% solution
1H and 13C NMR spectra were registered on a spec-
trometer Bruker AV-400 at operating frequencies 400
and 100 MHz respectively (internal reference HMDS).
The quantitative composition of isomeric and tautomeric
mixtures was determined from the integration of the
corresponding resonances in the 1H NMR spectra. The
reaction progress was monitored and the purity of
compounds obtained was checked by TLC on Silufol UV-
254 plates, eluent benzene–acetone, 4:1.
1
of hydrogen peroxide. In the H and 13C NMR spectra
of benzaldehyde thiobisacetylhydrazone (IVa) appeared
three sets of resonances corresponding to conformational
isomers E,E', E,Z', and Z,Z' (40, 45, and 15% respectively).
Aldehydes mercaptoacetylhydrazones IIIa–IIIn.
A mixture of 15 mmol of an aliphatic aldehyde Ia–If and
1.06 g (10 mmol) of thioglycolic acid hydrazide (II) in
50 ml of a mixture methanol–water, 1:4, or 9 mmol of
aromatic aldehyde Ig–In and 10 mmol of compound II
in 50 ml of methanol was kept at 25°C for 2 h. The
separated crystals were filtered off, washed with ether,
dried, and recrystallized from a mixture benzene–
petroleum ether, 1:4. Compound IIIa was purified by
column chromatography, eluent benzene–acetone, 4:1.
O
H
N
H
N
S
Ar
2
IV
Thus unlike the described [11–13] condensation
products of aldehydes with hydrazides of glycolic and
aminoacetic acids potentially able to undergo cyclization
into 1,3,4-oxydiazine or 1,3,4-triazine forms respectively,
mercaptoacetylhydrazones of aromatic and aliphatic
aldehydes are capcble of cyclization giving six-membered
1,3,4-thiadiazine ring. This is understandable taking into
account considerably greater nucleophilicity of sulfur in
the SH group involved into the cyclization compared to
the nucleophilicity of oxygen and nitrogen from OH and
NH groups in the hydrazones obtained by the use of the
hydrazides of glycolic and aminoacetic acids. The
tendency to intramolecular cyclization is common to the
mercaptoacetylhydrazones and to products we have
formerly investigated of the carbonyl compounds con-
densation with hydrazides of thiobenzoic and 2-mercapto-
benzoic acids where the intramolecular attack of the sulfur
atom on the C=N bond of the hydrazone fragment has
given 1,3,4-thiadiazoline [14] and 1,3,4-benzothiadiaze-
pine [10, 15] rings respectively.
Acetic aldehyde mercaptoacetylhydrazone (IIIa).
Yield 40%, viscous oily substance. 1H NMR spectrum
(DMSO-d6), δ, ppm, form A-E,E' (4%): 3.42 d
(CH2S, J 8.0 Hz), 7.32 br.s (HC=N), 11.02 br.s (NH);
form A-E,Z' (2%): 7.49 br.s (HC=N), 11.05 br.s (NH);
form A-Z,E' (1%): 7.16 br.s (HC=N), 11.12 br.s (NH);
form B (93%): 3.47, 3.55 (H6, JAB 15.5 Hz), 4.48 q (H2,
J 6.8 Hz, ), 5.77 d (H3, J 6.8 Hz), 9.00 br.s (H4). 13C
NMR spectrum (DMSO-d6), δ, ppm, form B: 20.8 (CH3),
28.4 (C6), 63.8 (C2), 172.7 (C5). Found, %: C 36.29;
H 6.05; N 21.23. C4H8N2OS. Calculated, %: C 36.35;
H 6.10; N 21.19.
Propionic aldehyde mercaptoacetylhydrazone
1
(IIIb). Yield 75%, mp 103–104°C. H NMR spectrum
(DMSO-d6), δ, ppm, form A-E,E' (6%): 1.01 t (CH3,
J 7.6 Hz), 2.21 m (CH2), 2.67 t (SH, J 7.1 Hz), 3.43 d
(CH2S, J 7.1 Hz), 7.34 t (HC=N, J 5.0 Hz), 11.01 br.s
(NH); form A-E,Z' (3%): 2.84 t (SH, J 7.8 Hz), 3.32 d
(CH2S, J 7.8 Hz), 7.47 t (HC=N, J 5.0 Hz), 11.07 br.s
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 5 2009

ERSHOV et al.
664
7.39 d (HC=N, J 5.0 Hz), 11.03 br.s (NH); form B (83%):
0.97 d (CH3, J 6.5 Hz), 1.01 d (CH3, J 6.6 Hz), 1.93 m
(CH), 3.10, 3.17 (H6, JAB 13.5 Hz), 4.10 br.s (H2),
5.68 br.s (H3), 8.96 br.s (H4). 13C NMR spectrum
(DMSO-d6), δ, ppm, form B: 19.0 (CH3), 19.9 (CH3), 29.2
(C6), 33.1 (CH), 71.7 (C2), 173.6 (C5). Found, %: C 45.04;
H 7.51; N 17.54. C6H12N2OS. Calculated, %: C 44.97;
H 7.55; N 17.48.
(NH); form A-Z,E' (1%): 6.72 br.s (HC=N), 3.88 d
(CH2S, J 8.8 Hz), 11.14 br.s (NH); form B (90%):
0.90 t (CH3, J 7.5 Hz), 1.64 m (CH2), 3.12, 3.18 (H6,
JAB 14.3 Hz), 4.28 t (H2, J 6.4 Hz), 5.73 d (H3, J 6.4 Hz),
8.97 br.s (H4). 13C NMR spectrum (DMSO-d6), δ, ppm,
form B: 11.0 (CH3), 27.6 (CH2), 28.8 (C6), 66.0 (C2),
172.8 (C5). Found, %: C 40.98; H 6.92; N 19.21.
C5H10N2OS. Calculated, %: C 41.07; H 6.89; N 19.16.
Butyric aldehyde mercaptoacetylhydrazone
Isovaleric aldehyde mercaptoacetylhydrazone
(IIIf). Yield 60%, mp 90–91°C. H NMR spectrum
1
(IIIc). Yield 70%, mp 81–83OC. H NMR spectrum
1
(DMSO-d6), δ, ppm, form A-E,E' (6%): 1.02 t (CH3,
J 7.5 Hz), 2.16 m (2CH2), 2.67 t (SH, J 7.8 Hz), 3.43 d
(CH2S, J 7.8 Hz), 7.31 t (HC=N, J 4.7 Hz), 10.89 br.s
(NH); form A-E,Z' (4%): 2.73 t (SH, J 8.3 Hz), 3.35 d
(CH2S, J 8.3 Hz), 7.46 t (HC=N, J 6.0 Hz), 10.91 br.s
(NH); form A-Z,E' (1%): 3.89 d (CH2S, J 11.4 Hz),
6.73 t (HC=N, J 6.3 Hz), 11.15 br.s (NH); form B (88%):
0.91 t (CH3, J 7.5 Hz), 1.34 m (CH2), 1.61 m (CH2),
3.12, 3.19 (H6, JAB 13.5 Hz), 4.34 t (H2, J 6.8 Hz), 5.73 d
(H3, J 6.8 Hz), 8.96 br.s (H4). 13C NMR spectrum
(DMSO-d6), δ, ppm, form B: 13.7 (CH3), 19.3 (CH2),
27.5 (C6), 37.7 (CH2), 64.1 (C2), 172.4 (C5). Found, %:
C 45.04; H 7.50; N 17.53. C6H12N2OS. Calculated, %:
C 44.98; H 7.55; N 17.48.
(DMSO-d6), δ, ppm, form A-E,E' (18%): 0.92 d (2CH3,
J 6.7 Hz), 1.83 m (CH2), 2.18 m (CH), 2.65 t (SH,
J 7.2 Hz), 3.50 d (CH2S, J 7.2 Hz), 7.32 t (HC=N,
J 4.0 Hz), 11.00 br.s (NH); form A-E,Z' (15%): 0.92 d
(2CH3, J 6.7 Hz), 1.83 m (CH2), 2.18 m (CH), 2.84 t
(SH, J 7.8 Hz), 3.87 d (CH2S, J 7.8 Hz), 7.47 t (HC=N,
J 4.7 Hz), 11.10 br.s (NH); form B (67%): 0.88 d (CH3,
J 6.5 Hz), 0.90 d (CH3, J 6.5 Hz), 1.36 m (CH2), 1.79 m
(CH), 3.13, 3.20 (H6, JAB 13.6 Hz), 4.41 br.s (H2),
5.73 br.s (H3), 8.97 br.s (H4). 13C NMR spectrum
(DMSO-d6), δ, ppm, form A-E,E': 22.3 (2CH3), 26.1
(CH2S), 38.3 (CH), 40.6 (CH2), 147.1 (C=N), 170.1
(C=O); form A-E,Z': 22.3 (2CH3), 26.6 (CH2S), 38.3
(CH), 41.2 (CH2), 150.8 (C=N), 164.7 (C=O); form B:
21.5 (2CH3), 24.9 (CH), 28.1 (C6), 37.6 (CH2), 65.3 (C2),
173.0 (C5). Found, %: C 48.31; H 8.17; N 15.97.
C7H14N2OS. Calculated, %: C 48.25; H 8.10; N 16.08.
Valeric aldehyde mercaptoacetylhydrazone
1
(IIId). Yield 65%, mp 63–65°C. H NMR spectrum
(DMSO-d6), δ, ppm, form A-E,E' (8%): 0.94 t (CH3,
J 7.4 Hz), 1.53 m (2CH2), 2.11 m (CH2), 2.67 t (SH,
J 7.1 Hz), 3.40 d (CH2S, J 7.1 Hz), 7.44 t (HC=N,
J 3.1 Hz), 11.01 br.s (NH); form A-E,Z' (4%): 0.94 t
(CH3, J 7.4 Hz), 1.53 m (2CH2), 2.11 m (CH2), 2.85 t
(SH, J 7.6 Hz), 3.32 d (CH2S, J 8.3 Hz), 7.47 t (HC=N,
J 3.1 Hz), 11.08 br.s (NH); form A-Z,E' (1%): 3.89 d
(CH2S, J 11.4 Hz), 7.30 t (HC=N, J 6.0 Hz), 11.13 br.s
(NH); form B (86%): 0.89 t (CH3, J 7.5 Hz), 1.43 m
(2CH2), 1.73 m (CH2), 3.13, 3.19 (H6, JAB 14.3 Hz),
4.33 t (H2, J 6.8 Hz), 5.73 d (H3, J 6.8 Hz), 8.97 br.s
(H4). 13C NMR spectrum (DMSO-d6), δ, ppm, form B:
13.8 (CH3), 22.1 (CH2), 27.6 (CH2), 28.3 (C6), 35.4
(CH2), 64.4 (C2), 172.6 (C5). Found, %: C 48.21; H 8.06;
N 16.13. C7H14N2OS. Calculated, %: C 48.25; H 8.10;
N 16.08.
4-Nitrobenzoic aldehyde mercaptoacetyl-
hydrazone (IIIg). Yield 55%, mp 187–190°C. 1
H NMR
spectrum (DMSO-d6), δ, ppm, form A-E,E' (56%):
2.82 t (SH, J 7.7 Hz), 3.65 d (CH2S, J 7.7 Hz), 7.94–
8.27 m (Ar), 8.10 s (HC=N), 11.74 br.s (NH); form A-
E,Z' (43%): 2.98 t (SH, J 8.6 Hz), 3.25 d (CH2S,
J 8.6 Hz), 8.17 s (HC=N), 11.82 br.s (NH); form B (2%):
5.78 d (H2, J 8.0 Hz), 6.38 d (H3, J 8.0 Hz), 9.21 br.s
(H5). Found, %: C 45.22; H 3.84; N 17.52. C9H9N3O3S.
Calculated, %: C 45.18; H 3.79; N 17.56.
3-Nitrobenzoic aldehyde mercaptoacetyl-
1
hydrazone (IIIh). Yield 65%, mp 166–168°C. H NMR
spectrum (DMSO-d6), δ, ppm, form A-E,E' (57%):
2.82 t (SH, J 8.0 Hz), 3.64 d (CH2S, J 8.0 Hz), 7.79–
8.34 m (Ar), 8.10 s (HC=N), 11.68 br.s (NH); form A-
E,Z' (39%): 2.98 t (SH, J 8.4 Hz), 3.25 d (CH2S,
J 8.4 Hz), 8.12 s (HC=N), 11.72 br.s (NH); form B (2%):
3.31, 3.57 (H6, JAB 13.3 Hz), 5.79 d (H2, J 7.3 Hz),
6.42 d (H3, J 7.3 Hz), 9.22 br.s (H5). Found, %: C 45.13;
H 3.72; N 17.60. C9H9N3O3S. Calculated, %: C 45.18;
H 3.79; N 17.56.
Isobutyric aldehyde mercaptoacetylhydrazone
1
(IIIe). Yield 80%, mp 142–144°C. H NMR spectrum
(DMSO-d6), δ, ppm, form A-E,E' (10%): 1.12 d (2CH3,
J 6.7 Hz), 2.34 t (SH, J 7.5 Hz), 2.56 m (CH), 3.43 d
(CH2S, J 7.5 Hz), 7.26 d (HC=N, J 4.0 Hz), 10.98 br.s
(NH); form A-E,Z' (7%): 1.12 d (2CH3, J 6.7 Hz), 2.41 t
(SH, J 8.0 Hz), 2.56 m (CH), 3.34 d (CH2S, J 8.0 Hz),
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TAUTOMERISM AND CONFORMATIONAL ISOMERISM OF MERCAPTOACETYLHYDRAZONES
665
Benzoic aldehyde mercaptoacetylhydrazone
(IIIi). Yield 85%, mp 111–113°C. H NMR spectrum
(CH2S, J 8.2 Hz), 3.79 s (CH3O), 8.12 s (HC=N), 11.41
br.s (NH); form B (4%): 3.22, 3.52 (H6, JAB 13.1 Hz),
5.50 d (H2, J 8.5 Hz), 6.11 d (H3, J 8.5 Hz), 9.14 br.s
(H5). 13C NMR spectrum (DMSO-d6), δ, ppm, form
E,E': 24.8 (CH2S), 55.4 (CH3O), 114.4–160.8 (Ar), 143.4
(C=N), 171.4 (C=O); form E,Z': 26.4 (CH2S), 55.2
(CH3O), 147.0 (C=N), 166.2 (C=O). Found, %: C 53.53;
H 5.39; N 12.49. C10H12N2O2S. Calculated, %: C 53.55;
H 5.39; N 12.49.
1
(DMSO-d6), δ, ppm, form A-E,E' (60%): 2.71 t (SH,
J 7.8 Hz), 3.59 d (CH2S, J 7.8 Hz), 7.42–7.67 m (Ar),
8.10 s (HC=N), 11.44 br.s (NH); form A-E,Z' (34%):
2.89 t (SH, J 8.1 Hz), 3.20 d (CH2S, J 8.1 Hz), 8.18 s
(HC=N), 11.52 br.s (NH); form B (6%): 3.24, 3.51 (H6,
JAB 14.7 Hz), 5.54 s (H2), 6.20 br.s (H3), 9.13 br.s (H5).
13C NMR spectrum (DMSO-d6), δ, ppm, form E,E': 24.7
(CH2S), 127.7–134.2 (Ar), 143.7 (C=N), 170.2 (C=O);
form E,Z': 26.3 (CH2S), 147.6 (C=N), 164.8 (C=O); form
B: 27.2 (C6), 65.6 (C2), 172.8 (C5). Found, %: C 55.63;
H 5.23; N 14.38. C9H10N2OS. Calculated, %: C 55.65;
H 5.19; N 14.42.
4-Dimethylaminobenzoic aldehyde mercapto-
acetylhydrazone (IIIm). Yield 65%, mp 112–115°C.
1H NMR spectrum (DMSO-d6), δ, ppm, form A-E,E'
(68%): 2.71 t (SH, J 8.0 Hz), 2.92 s (2CH3N), 3.55 d
(CH2S, J 8.0 Hz), 6.68–7.46 m (Ar), 8.09 s (HC=N),
11.28 br.s (NH); form A-E,Z' (30%): 2.77 t (SH,
J 8.5 Hz), 2.96 s (2CH3N), 3.16 d (CH2S, J 8.5 Hz),
8.12 s (HC=N), 11.36 br.s (NH); form B (2%): 5.50 br.s
(H2), 8.98 br.s (H5). Found, %: C 55.72; H 6.41; N 17.67.
C11H15N3OS. Calculated, %: C 55.67; H 6.37; N 17.71.
4-Methylbenzoic aldehyde mercaptoacetyl-
hydrazone (IIIj). Yield 60%, mp 143–145OC. 1
H NMR
spectrum (DMSO-d6), δ, ppm, form A-E,E' (60%):
2.32 s (CH3), 2.75 t (SH, J 7.6 Hz), 3.58 d (CH2S,
J 7.6 Hz), 7.23–7.56 m (Ar), 7.97 s (HC=N), 11.39 br.s
(NH); form A-E,Z' (35%): 2.30 s (CH3), 2.93 t (SH,
J 8.0 Hz), 3.21 d (CH2S, J 8.0 Hz), 8.14 s (HC=N),
11.47 br.s (NH); form B (5%): 2.28 s (CH3), 3.23, 3.54
(H6, JAB 13.3 Hz), 5.51 d (H2, J 8.4 Hz), 6.14 d (H3,
J 8.4 Hz), 9.15 br.s (H5). 13C NMR spectrum (DMSO-
d6), δ, ppm, form E,E': 21.1 (CH3), 24.7 (CH2S), 126.8–
131.5 (Ar), 143.5 (C=N), 171.2 (C=O); form E,Z': 21.0
(CH3), 26.3 (CH2S), 146.9 (C=N), 166.1 (C=O). form
B: 26.9 (C6), 64.8 (C2), 173.0 (C5). Found, %: C 57.71;
H 5.77; N 13.49. C10H12N2OS. Calculated, %: C 57.67;
H 5.81; N 13.45.
2-Hydroxybenzoic aldehyde mercaptoacetyl-
hydrazone (IIIn). Yield 70%, mp 183–184°C. 1
H NMR
spectrum (DMSO-d6), δ, ppm, form A-E,E' (40%):
2.68 t (SH, J 7.6 Hz), 3.59 d (CH2S, J 7.6 Hz), 6.85–
7.48 m (Ar), 8.30 s (HC=N), 10.07 br.s (OH), 11.07 br.s
(NH); form A-E,Z' (56%): 2.87 t (SH, J 8.1 Hz), 3.21 d
(CH2S, J 8.1 Hz), 8.37 s (HC=N), 10.07 br.s (OH),
11.38 br.s (NH); form B (4%): 3.16, 3.49 (H6,
J
AB 13.2 Hz), 5.68 d (H2, J 7.1 Hz), 6.10 d (H3, J 7.1 Hz),
9.13 br.s (H5). 13C NMR spectrum (DMSO-d6), δ, ppm,
form E,E': 24.9 (CH2S), 116.4–157.5 (Ar), 143.6 (C=N),
171.0 (C=O); form E,Z': 26.1 (CH2S), 147.7 (C=N),
166.1 (C=O). Found, %: C 51.37; H 4.84; N 13.27.
C9H10N2O2S. Calculated, %: C 51.41; H 4.79; N 13.32.
4-Hydroxybenzoic aldehyde mercaptoacetyl-
hydrazone (IIIk). Yield 75%, mp 104–106°C. 1
H NMR
spectrum (DMSO-d6), δ, ppm, form A-E,E' (67%):
2.70 t (SH, J 7.5 Hz), 3.56 d (CH2S, J 7.5 Hz), 6.80–
7.49 m (Ar), 7.90 s (HC=N), 9.90 br.s (OH), 11.41 br.s
(NH); form A-E,Z' (30%): 2.88 t (SH, J 8.2 Hz), 3.18 d
(CH2S, J 8.2 Hz), 8.07 s (HC=N), 9.90 br.s (OH),
11.44 br.s (NH); form B (3%): 5.42 C (H2), 9.09 br.s
(H5). 13C NMR spectrum (DMSO-d6), δ, ppm, form
E,E': 24.8 (CH2S), 115.8–159.6 (Ar), 143.9 (C=N), 171.3
(C=O); form E,Z': 26.4 (CH2S), 147.4 (C=N), 166.1
(C=O). Found, %: C 51.46; H 4.73; N 13.38.
C9H10N2O2S. Calculated, %: C 51.41; H 4.79; N 13.32.
Benzaldehyde 2,2'-thiobisacetylhydrazone. To
a solution of 0.45 g (5 mmol) of compound IIIa in 5 ml of
methanol was added 0.5 ml of 5% solution of H2O2, and
the mixture was kept at 25°C for 2 h. The separated
crystals were filtered off, washed with ether, and dried.
Yield 85%, mp 182–184°C. 1H NMR spectrum (DMSO-
d6), δ, ppm, form E,E' (40%): 4.05 s (CH2S), 7.14–
7.46 m (Ar), 7.99 s (HC=N), 11.56 br.s (NH); form E,Z'
(45%): 3.63 C (CH2S), 4.08 s (CH2S), 7.99 s (HC=N),
8.21 s (HC=N), 11.56 br.s (NH), 11.62 br.s (NH); form
Z,Z' (15%): 3.67 s (CH2S), 8.22 s (HC=N), 11.64 br.s
(NH). 13C NMR spectrum (DMSO-d6), δ, ppm, form
E,E': 40.6 (CH2), 127.9–134.6 (Ar), 143.9 (C=N), 170.1
(C=O); form E,Z': 41.3 (CH2S), 147.8 (C=N), 164.9
(C=O); form Z,Z': 41.5 (CH2S), 147.3 (C=N), 165.4
4-Methoxybenzoic aldehyde mercaptoacetyl-
hydrazone (IIIl). Yield 60%, mp 119–121°C. 1
H NMR
spectrum (DMSO-d6), δ, ppm, form A-E,E' (63%):
2.75 t (SH, J 7.5 Hz), 3.59 d (CH2S, J 7.5 Hz), 3.83 s
(CH3O), 7.03–7.80 m (Ar), 7.95 s (HC=N), 11.32 br.s
(NH); form A-E,Z' (33%): 2.92 t (SH, J 8.2 Hz), 3.20 d
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 5 2009

ERSHOV et al.
666
9. Zelenin, K.N., Oleinik, S.V., Alekseev, V.V., and Pote-
khin,A.A., Zh. Obshch. Khim., 2001, vol. 71, p. 1182.
10. Ershov,A.Yu., Lagoda, I.V., Mokeev, M.V.,Yakimovich, S.I.,
Zerova, I.V., Pakal’nis, V.V., and Shamanin, V.V., Khim.
Geterotsikl. Soed., 2008, p. 460.
(C=O). Found, %: C 56.02; H 4.73; N 14.47;
C18H18N4O2S2. Calculated, %: C 55.94; H 4.69; N 14.50.
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