Heterocycles from aroylacetic aldehydes and SH-containing hydrazides

Article abstract of DOI:10.1134/S1070428009020225

Condensation products of aroylacetic aldehydes with hydrazides of thioglycolic, 3-mercaptopropionic and 2-mercaptobenzoic acids exist in cyclic 1,3,4-thiadiazine, 1,3,4-thiadiazepine, or 1,3,4-benzothiadiazepine forms arising at the intramolecular additio

Full text of DOI:10.1134/S1070428009020225

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 2, pp. 285−291. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © V,V. Pakal’nis, I.V. Zerova, S.I. Yakimovich, A.Yu. Ershov, I.V. Lagoda, 2009, published in Zhurnal Organicheskoi
Khimii, 2009, Vol. 45, No. 2, pp. 295−300.
Heterocycles from Aroylacetic Aldehydes
and SH-Containing Hydrazides
V. V. Pakal’nisa, I. V. Zerovaa, S. I. Yakimovicha, A. Yu. Ershovb, and I. V. Lagodac
aSt. Petersburg State University, St. Petersburg,198504 Russia
e-mail: viktoriapakalnis@mail.ru
bInstitute of Macromolecular Compounds, Russian Academy of Sciences, St. Petersburg, Russia
cResearch Test Center of Medical and Biogical Protection of the State Research Testing Institute
of Military Medicine of the Defence Ministry of the Russian Federation, St. Petersburg, Russia
Received March 5, 2008
Abstract—Condensation products of aroylacetic aldehydes with hydrazides of thioglycolic, 3-mercaptopropionic
and 2-mercaptobenzoic acids exist in cyclic 1,3,4-thiadiazine, 1,3,4-thiadiazepine, or 1,3,4-benzothiadiazepine forms
arising at the intramolecular addition of the mercapto group to the C=N bond of the initially formed hydrazone
tautomer. The appearance of an alternative 5-hydroxy-2-pyrazoline form is favored by introduction of a strong
electron-acceptor substituent into the aromatic ring of the 1,3-ketoaldehyde or by going over to benzoylacetone
derivatives. In solutions the derivatives of aroylacetic aldehydes and of benzoylacetone show no tendency to
tautomeric transition into linear hydrazine or enhydrazine forms.
DOI:10.1134/S1070428009020225
The reaction of 1,3-ketoaldehydes with acylhydrazines
proceeding exclusively at the aldehyde function stops at
the stage preceding the 1-acylpyrazoles formation [1–
8]. The condensation products depending on the structure
of the 1,3-dicarbonyl and hydrazine components in the
crystalline state may have a hydrazone, conjugated
enhydrazine, or 5-hydroxy-2-pyrazoline structure. In solu-
tions they are involved in a number of prototropic and
ring-chain equilibria with various combination of the above
cited tautomers [7, 8].
amounts of reagents in anhydrous methanol at cooling
the reaction mixture with ice.
On completion of the reaction determined by TLC
monitoring the solvent was removed under a reduced
pressure, and the obtained crystalline product was analyz-
1
1
ed by H and 13C NMR spectroscopy. In the H NMR
spectra of the condensation products of aroylacetic
aldehydes Ia–Id recorded just after dissolution a single
set of resonance signals was observed (see EXPERI-
MENTAL). This finding indicated first of all the expected
100% regiodirectional reaction at the aldehyde function.
Inasmuch as the spectra were obtained directly after
dissolution of the samples when the possible tautomeric
and configurational transitions yet not occurred it was
presumable that the spectra registered the structure of
the derivatives of aroylacetic aldehydes in the crystals.
The comparison of these spectra with the spectral data
on the previously obtained condensation products of
1,3-ketoaldehydes with acylhydrazines [1–3, 5, 6] made
it possible to exclude with confidence the hydrazone (A)
form (since were absent a doublet proton signal from the
methylene group of the 1,3-dicarbonyl moiety in the region
4.0–4.2 ppm and the signal of SH proton in the region
2.2–2.8 ppm) and the enhydrazine (B) structure (since
In the present study we investigated the reactions of
aroylacetic aldehydes with hydrazides of thioglycolic,
3-mercaptopropionic, and 2-mercaptobenzoic acids
containing a nucleophilic SH function. Consequently the
condensation products of the cited hydrazides with the
aroylacetic aldehydes might exist not only in the
hydrazone (A), enhydrazine (B) or 5-hydroxy-2-pyrazo-
line (C) forms but also in six- or seven-membered cyclic
form D originating from the attack of the SH function on
the C=N bond (Scheme 1).
The reaction of aroylacetic aldehydes Ia–Ie with the
thioglycolic acid hydrazide (Scheme 2) occurred under
mild conditions: by mixing the solutions of equimolar
285

PIKAL’NIS et al.
286
Scheme 1.
NH2
XSH
H
Ar
HN
+
O
O
O
H
H
HN
HN
Ar
H
H
Ar
Ar
CHCOAr
S
N
HO
O
N
O
N
HSXCOHNHN
X
NHCOXSH
O
XSH
O
B
D
А
C
X = CH2, (CH2)2, o-C6H4
structure the signal from the carbon atom in the position
5 of the ring linked to oxygen and nitrogen atoms appeared
at the 92–97 ppm [3, 9, 10]. Obviously, the signal of the
corresponding carbon atom should be observed in this
region in the spectra of condensation products under
discussion produced from 1,3-ketoaldehydes Ia–Id and
thioglycolic acid hydrazide of they possessed the 5-hy-
droxy-2-pyrazoline structure C.
Scheme 2.
Ar
O
R
HN
HN
S
R
Ar
O
O
O
Iа_If
+
D, IIа_IId
We modeled the 1,3,4-thiadiazine form D by the
condensation product from propionic aldehyde with
thioglycolic acid hydrazide IV (Scheme 3).
H2N
O
R
NH
Ar
SH
N
N
Compound IV in the crystalline state has the cyclic
1,3,4-thiadiazine structure D, and in the DMSO-d6 solution
is a tautomeric mixture of hydrazone (A) and 1,3,4-
thiadiazine (D) forms, and the content of the latter is no
less than 90%.
HO
SH
O
C, IIIe, IIIf
In the 13C NMR spectrum of this compound taken in
DMSO-d6 the carbon atoms in positions 2 (linked to sulfur
and nitrogen atoms), 5 , and 6 of the ring appeared as
signals at δ 66.0, 172.8 and 28.8 ppm.
In the 13C NMR spectra of derivatives of aroylacetic
aldehydes IIa–IId a signal is observed in the region 60–
61 ppm. This is an ultimate confirmation of the 1,3,4-
thiadiazine structure D of compounds IIa–IId.
R = H,Ar = 4-XC6H4, X = MeO (a), Me (b), H (c), Br (d),
NO2 (e); R = CH3, Ar = C6H5 (f).
were absent the signals in the region 5.5–6.0 and 7.0–
7.5 ppm from the protons at the C=C bond and the signal
of SH proton in the region 2.2–2.8 ppm). The choice
between the cyclic forms C and D is somewhat more
difficult.Against the 5-hydroxy-2-pyrazoline structure C
testified the absence of signal of the proton at C=N bond
and the proton of the mercapto group. The appeared
signals were well consistent with the 1,3,4-thiadiazine
structure D (see EXPERIMENTAL).
Scheme 3.
H
The ultimate choice of the 1,3,4- thiadiazine structure
D was done with the help of the 13C NMR spectroscopy.
According to the 13C NMR spectra of the condensation
products obtained from 1,3-dikrtones and ketoaldehydes
with acylhydrazine possessing 5-hydroxy-2-pyrazoline
H
S
NH
NH
N
NHCOCH2SH
O
IV
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 2 2009

HETEROCYCLES FROM AROYLACETIC ALDEHYDES
287
1
The H and 13C NMR spectra of solutions of com-
At the use in the reaction with the chosen 1,3-dicar-
bonyl compounds of 3-mercaptopropionic acid hydrazide
we succeeded to isolate in the spectrally pure form only
derivatives of ketoaldehyde Ia and of benzoylacetone (If):
compounds Va and VIf (Scheme 4).
pounds IIa–IId do not change in time. It means that no
transition occur into the probable open-chain tautomeric
forms A and B or into the alternative cyclic 5-hydroxy-
2-pyrazoline structure C.
1
According to the H and 13C NMR spectra (see
The condensation product of ketoaldehyde Ie bearing
a 4-nitrophenyl substituent, compound IIIe, takes a spe-
cial place. The H NMR spectra of this compound
solutions in CDCl3 and DMSO-d6 also contain a single
set of resonance signals, but it corresponds to 5-hydroxy-
2-pyrazoline C.
EXPERIMENTAL) the condensation prodyct of 1,3-keto-
aldehyde Ia (compound Va) had the 1,3,4-thiadiazepine
structure D, and the derivative of 1,3-diketone If was
5-hydroxy-2-pyrazoline VIf.
1
The most significant was the presence in the 13C NMR
spectrum of the solution of compound Va in DMSO-d6
of a signal at δ 72.79 ppm belonging to the carbon atom
in the position 2 of the 1,3,4-thiadiazepine ring connected
to nitrogen and sulfur atoms. In the 13C NMR spectrum
of the solution of the derivative of 1,3-diketone (compound
VIf) was present a signal at δ 93.89 ppm. It can be
unambiguously assigned to the carbon atom in the position
5 of the 5-hydroxy-2-pyrazoline ring C linked to oxygen
and nitrogen atoms.
In full agreement with the 5-hydroxy-2-pyrazoline
13
structure the C NMR spectrum contains a signal at δ
95.56 ppm corresponding to the carbon atom in the
position 5 of the ring linked to oxygen and nitrogen atoms
[2, 3, 9], and lacks the signal in the region 60–61 ppm
characteristic as reasoned above of the 1,3,4- thiadiazine
structure D. The existence of compound IIIe in the
5-hydroxy-2-pyrazoline form C is due to the effect of
a strong electron-acceptor, nitro group, attached to the
aromatic ring. It favors the cyclization of the inter-
mediately formed hydrazone by addition of the NH group
to the C=O bond. In this compound we also did not
observe any tendency to the tautomer transitions; 1H and
13C NMR spectra of solutions registered immediately
after preparation and after long storage were identical.
Regretfully, we failed to obtain in a p;ausible form the
derivatives of the other 1,3-ketoaldehydes. Consequently
the problem remained unsolved of the effect of the
electronic properties of the substituent in the aromatic
ring on the direction of the intramolecular cyclization and
of the possibility of the existence of tautomeric equilibria.
The reaction of aroylacetic aldehydes Ia–Ie with
2-mercaptobenzoic acid hydrazide was carried out in
an aqueous-alcoholic medium at 50°C (Scheme 5).
We additionally prepared the condensation product of
benzoylacetone (If) with thioglycolic acid hydrazide IIIf.
According to the 1H and 13C NMR spectra (see EXPERI-
MENTAL) compound IIIf had the structure of 5-hy-
droxy-2-pyrazoline C.
1
The condensation products according to the H and
13C NMR spectra both in the crystalline state and in
solutions in DMSO-d6 have cyclic 1,3,4-benzothiadi-
azepine structure VIIa–VIIe and do not go over in the
The comparison of compounds IIc and IIIf shows
that the transition from a derivative of 1,3-ketoaldehyde
to a derivative of 1,3-diketone favors the formation of
5-hydroxy-2-pyrazoline tautomer C. This fact may be
understood as follows. In the 1,3,4-thiadiazine form D of
compound IIc at the chair conformation of the heterocycle
the hydrogen atom in the position 2 takes the axial orienta-
tion, and the rest of the 1,3-dicarbonyl component,
CH2COPh moiety, would be in a feasible equatorial
position. In a 1,3,4-thiadiazine form of the benzoylacetone
derivative IIIf either methyl group of the CH2COPh
fragment should be axially oriented. Therefore arise
unfavorable syn-axial interactions with one of the
hydrogens of the methylene group in the position 6 of the
heterocycle. This destabilization of the 1,3,4-thiadiazine
structure D prevents its successful competition with the
5-hydroxy-2- pyrazoline form C.
Scheme 4.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 2 2009

PIKAL’NIS et al.
288
EXPERIMENTAL
Scheme 5.
Ar
1H and 13C NMR spectra were registered on a spec-
trometer Bruker DPX-300 at operating frequencies
300.13 and 75.47 MHz respectively. The quantitative
composition of isomers and tautomers was determined
by integration of intensity of the corresponding signals in
the 1H NMR spectra. The measurements error was 3%.
The reaction progress was monitored and the purity of
compounds obtained was checke by TLC on Silufol UV-
254 plates, eluent chloroform.
H
Ar
O
O
O
H
Iа_Ie
HN
S
+
H2N
O
HN
NH SH
O
VIIа_VIIe
2-[2-(4-Methoxyphenyl)-2-oxoethyl]-1,3,4-thia-
diazin-5-one (IIa). A mixture of 0.318 g (3 mmol) of thio-
glycolic acid hydrazide and 0.534 g (3 mmol) of 1,3-keto-
aldehyde Ia in 5 ml of anhydrous methanol was kept at
20°C for 2 h. The solvent was removed under a reduced
pressure, the separated crystals were filtered off and
washed with methanol. Yield 0.591 g (74%), mp 150–
151°C. 1H NMR spectrum (DMSO-d6), δ, ppm: 3.12 d
(1H, C6HΒ, J 13.4 Hz), 3.16 d (1H, C6HA, J 13.4 Hz),
3.37 d.d (1H, HΒ, JAΒ 17.4, JΒX 8.7 Hz), 3.57 d.d (1H,
HA, JAΒ 17.4, JAX 5.1 Hz), 3.86 s (3H, OCH3), 4.84 br.s
other possible tautomeric forms (by comparison of spectra
registered just after dissolution of the samples and after
long storage).
Without detailed discussion of the spectral data we
would only like to note that in the 13C NMR spectra of
com-pounds VIIa–VIIe was found a signal in the
region 70 ppm. This signal can be duly assigned to the
carbon atom in the position 2 of the heterocycle. Note
for comparison the results of the study of acetone con-
densation with 2-mercaptobenzoic acid hydrazide [11].
This compound exists in solutions as a tautomeric mixture
of hydrazone and 1,3,4-benzothiadiazepine form. In its
13C NMR spectrum the signal of the carbon atom in the
position 2 of the cyclic tautomer appears at δ 77.6 ppm.
It should be stated that as soon as the structure of the
condensation product of 4-methoxybenzoylacetic alde-
hyde and 3-mercaptopropionic acid hydrazide (compound
Va) was established, the existence of the reaction
products of 1,3-aroylacetic aldehydes with 2-mer-
captobenzoic acid hydrazide in the form of 1,3,4-benzo-
thiadiazepines (compounds VIIa–VIIe) was expectable.
It is well known that the growing rigidity of the unit
connecting the electrophilic and nucleophilic sites in the
systems capable of the ring-chain tautomerism essentially
favors the formation of the cyclic tautomer [12–14].
(1H, H2), 5.85 br.s (1H, NH), 6.98 d (2H, Harom
,
J 8.7 Hz), 7.90 d (2H, Harom, J 8.7 Hz), 8.85 br.s (1H,
NHCO). 13C NMR spectrum (DMSO-d6), δ, ppm: 28.64
(C6), 45.14 (CH2), 56.08 (OCH3), 60.73 (C2), 114.45,
130.11, 130.99, 164.08 (Carom), 173.43 (C5), 195.66
(C=O). Found, %: C 54.22; H 5.26; N 10.38. C12H14N2O3S.
Calculated, %: C 54.12; H 5.30; N 10.52.
Likewise were obtained derivatives IIb–IId and IIIf,
IIIe.
2-[2-(4-Methylphenyl)-2-oxoethyl]-1,3,4-thia-
diazin-5-one (IIb). Yield 0.323 g (43%), mp 132°C.
1H NMR spectrum (DMSO-d6), δ, ppm: 2.42 s (3H,
CH3), 3.13 d (1H, C6HΒ, J 13.4 Hz), 3.17 d (1H, C6HA,
J 13.4 Hz), 3.40 d.d (1H, HΒ, JAΒ 17.4, JΒX 8.0 Hz),
3.52 d.d (1H, HA, JAΒ 17.4, JAX 5.1 Hz), 4.85 m (1H, H2),
5.86 br.s (1H, NH), 7.28 d (2H, Harom, J 8.0 Hz), 7.84 d
(2H, Harom, J 8.0 Hz), 8.84 br.s (1H, NHCO). 13C NMR
spectrum (DMSO-d6), δ, ppm: 22.03 (CH3), 28.49 (C6),
45.48 (CH2), 60.83 (C2), 128.91, 130.22, 134.63, 144.83
(Carom), 173.71 (C5), 197.51 (C=O). Found, %: C 57.49;
H 5.63; N 11.04. C12H14N2O2S. Calculated, %: C 57.58;
H 5.64; N 11.19.
It should be mentioned in conclusion that also the
thiobenzoylhydrazones of aroylacetic aldehydes have
a five-membered cyclic 1,3,4-thiadiazoline structure [15].
The cyclization occurs by the attack of the sulfur atom
of the SH function arising in transition of the hydrazone
form into the tautomeric azinoenthiol form.
Thus it can be stated that the condensation products
obtained from 1,3-ketoaldehydes and hydrazides posses-
sing an additional SH function (even in a latent form, like
in the condensation products with thiobenzoylhydrazine)
are prone to exist as five-, six-, and even seven-membered
heterocycles.
2-(2-Oxo-2-phenylethyl)-1,3,4-thiadiazin-5-one
(IIc).Yield 0.262 g (37%), mp 159–160°C. 1H NMR spec-
trum (DMSO-d6), δ, ppm: 3.11 d (2H, C6HΒ, J 13.4 Hz),
3.15 d (1H, C6HA, J 13.4 Hz), 3.39 d.d (1H, HΒ, JAΒ 17.4,
JΒX 8.1 Hz), 3.51 d.d (1H, HA, JAΒ 17.4, JAX 5.1 Hz),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 2 2009

HETEROCYCLES FROM AROYLACETIC ALDEHYDES
289
1
4.82 m (1H, H2), 5.73 br.s (1H, NH), 7.30–7.49 m (5H,
arom), 9.03 br.s (1H, NHCO). 13C NMR spectrum
(DMSO-d6), δ, ppm: 28.50 (C6), 45.32 (CH2), 60.72 (C2),
126.02, 128.24, 131.40, 137.58 (Carom), 173.54 (C5),
196.83 (C=O). Found, %: C 55.79; H 5.15; N 11.80.
C11H12N2O2S. Calculated, %: C 55.92; H 5.12; N 11.86.
1.095 g (75%), mp 103–104°C. H NMR spectrum
(DMSO-d6), δ, ppm, ΕΕ' (6%): 2.67 t (1H, SH, J 7.1 Hz),
3.43 d (2H, CH2SH, J 7.1 Hz), 7.34 t (1H, HC=N,
J 5.0 Hz), 11.01 br.s (1H, NH); EZ2 (3%): 2.84 t (1H,
SH, J 7.8 Hz), 3.32 d (2H, CH2SH, J 7.8 Hz), 7.47 t (1H,
HC=N, J 5.0 Hz), 11.07 br.s (1H, NH); ZE2 (<3%):
3.88 d (2H, CH2SH, J 8.8 Hz), 6.72 br.s (1H, HC=N),
11.14 br.s (1H, NH); D (90%): 3.12 d (1H, HΒ,
JAΒ 14.3 Hz), 3.18 d (1H, HA, JAΒ 14.3 Hz), 4.28 br.s
(1H, H2), 5.73 br.s (1H, NH), 8.97 br.s (1H, NHCO).
13C NMR spectrum (DMSO-d6), δ, ppm, D: 11.00 (CH3),
27.61 (CH2), 28.82 (C6), 66.00 (C2), 172.81 (C5). Found,
%: C 40.98; H 6.92; N 19.21. C5H10N2OS. Calculated,
%: C 41.07; H 6.89; N 19.16.
H
2-[2-(4-Bromophenyl)-2-oxoethyl]-1,3,4-thia-
diazin-5-one (IId). Yield 0.548 g (58%), mp 133–134°C.
1H NMR spectrum (DMSO-d6), δ, ppm: 3.11 d (1H,
C6HΒ, J 13.8 Hz), 3.17 d (1H, C6HA, JAΒ 13.8 Hz),
3.43 d.d (1H, HΒ, JAΒ 17.4, JΒX 8.0 Hz), 3.53 d.d (1H,
HA, JAΒ 17.4, JAX 5.1 Hz), 4.85 m (1H, H2), 5.86 br.s (1H,
NH), 7.66 d (2H, Harom, J 8.0 Hz), 7.88 d (2H, Harom
,
J 8.0 Hz), 8.83 br.s (1H, NHCO). 13C NMR spectrum
(DMSO-d6), δ, ppm: 28.48 (C6), 45.59 (CH2), 60.60 (C2),
128.53, 130.84, 132.44, 132.77 (Carom), 173.66 (C5),
197.32 (C=O). Found, %: C 41.98; H 3.47; N 8.78.
C11H11BrN2O2S. Calculated, %: C 41.92; H 3.52; N 8.89.
2-[2-(4-Methoxyphenyl)-2-oxoethyl]-1,3,4-thia-
diazepin-5-one (Va). A mixture of 0.236 g (2 mmol) of
3-mercaptopropionic acid hydrazide and 0.356 g (2 mmol)
of 1,3-ketoaldehyde Ia in 6 ml of anhydrous methanol
was kept at 20°C for 2 h. The solvent was removed at
a reduced pressure. Yield 0.180 g (32%), oily substance.
1H NMR spectrum (CDCl3), δ, ppm: 2.68 m (2H, C6H2),
2.95 m (2H, C7H2), 3.23 d.d (1H, HΒ, JAΒ 18.2,
JΒX 4.4 Hz), 3.49 d.d (1H, HA, JAΒ 18.2, JAX 5.8 Hz),
3.85 s (3H, OCH3), 5.59 m (2H, H2, NH), 6.93 d (2H,
1-[5-Hydroxy-5-(4-nitrophenyl)-4,5-dihydro-1H-
pyrazol-1-yl]-2-sulfanylethan-1-one (IIIe). Yield
0.177 g (21%), mp 124°C. 1H NMR spectrum (CDCl3),
δ, ppm: 2.15 d.d (1H, SH, J 8.7, J 8.0 Hz), 3.03 d (1H,
C4HΒ, JAΒ 19.6 Hz), 3.43 d (1H, C4HA, JAΒ 19.6 Hz),
3.54 d.d (1H, HΒ, JAΒ 13.8, JΒX 8.0 Hz), 3.70 d.d (1H,
HA, JAΒ 13.8, JAX 8.7 Hz), 5.0–6.0 br (1H, OH), 7.06 s
H
arom, J 8.7 Hz), 7.64 d (2H, Harom, J 8.7 Hz), 7.84 br.s
1
(1H, NHCO). H NMR spectrum (DMSO-d6), δ, ppm:
2.61 m (2H, C6H2), 2.92 m (2H, C7H2), 3.14 d.d (1H,
HΒ, JAΒ 18.5, JΒX 3.9 Hz), 3.34 d.d (1H, HA, JAΒ 18.5, JAX
4.2 Hz), 3.80 s (3H, OCH3), 5.48 br.s (1H, H2), 5.72 br.s
(1H, H3), 7.59 d (2H, Harom, J 8.7 Hz), 8.23 d (2H, Harom
,
13
J 8.7 Hz). C NMR spectrum (CDCl3), δ, ppm: 26.82
(CH2SH), 43.30 (C4), 93.56 (C5), 124.52, 127.97, 136.35,
149.20 (Carom), 144.23 (C3), 168.71 (C=O). Found, %:
C 46.92; H 3.95; N 14.79. C11H11N3O4S. Calculated, %:
C 46.97; H 3.94; N 14.94.
(1H, NH), 7.01 d (2H, Harom, J 8.7 Hz), 7.65 d (2H, Harom
,
J 8.7 Hz), 9.30 br.s (1H, NHCO). 13C NMR spectrum
(CDCl3), δ, ppm: 20.68 (C7), 38.86 (C6), 44.96 (CH2),
55.79 (OCH3), 72.79 (C2), 114.55, 127.34, 128.67, 162.00
(Carom), 171.46 (C5), 195.23 (C=O). Found, %: C 55.76;
H 5.68; N 9.86. C13H16N2O3S. Calculated, %: C 55.70;
H 5.75; N 9.99.
1-(5-Hydroxy-3-methyl-5-phenyl-4,5-dihydro-
1H-pyrazol-1-yl)-2-sulfanylethan-1-one (IIIf). Yield
1
0.308 g (41%), mp 84–85°C. H NMR spectrum
(DMSO-d6), δ, ppm: 2.02 s (3H, CH3), 2.70 d.d (1H,
SH, J 7.3 Hz), 3.00 d (1H, C4HΒ, JAΒ 18.3 Hz), 3.13 d
(1H, C4HA, JAΒ 18.3 Hz), 3.45 d.d (1H, HΒ, JAΒ 14.2,
JΒX 7.3 Hz), 3.58 d.d (1H, HA, JAΒ 14.2, JAX 7.3 Hz),
6.85 (1H, OH), 7.33–7.38 m (5Harom). 13C NMR spectrum
(CDCl3), δ, ppm: 16.49 (CH3), 27.45 (CH2SH), 54.95
(C4), 93.89 (C5), 124.33, 126.03, 128.49, 129.10 (Carom),
143.51 (C3), 169.48 (C=O). Found, %: C 57.46; H 5.58;
N 11.20. C12H14N2O2S. Calculated, %: C 57.58; H 5.64;
N 11.19.
1-(5-Hydroxy-3-methyl-5-phenyl-4,5-dihydro-
1H-pyrazol-1-yl)-3-sulfanylpropan-1-one (VIf) was
similarly obtained. Yield 0.100 g (19%), mp 49–50°C.
1H NMR spectrum (CDCl3), δ, ppm: 2.01 t (1H, SH,
J 8.0 Hz), 2.07 s (3H, CH3), 2.80 m (2H, CH2CO), 2.94
d (1H, HΒ, JAΒ 18.9 Hz), 3.05 m (2H, CH2SH), 3.29 d
(1H, HA, JAΒ 18.9 Hz), 5.4-6.7 br.s (1H, OH), 7.35–
7.40 m (5H, Harom). 1H NMR spectrum (DMSO-d6), δ,
ppm: 2.01 s (3H, CH3), 2.29 t (1H, SH, J 7.3 Hz), 2.75 m
(2H, CH2CO), 3.01 m (2H, CH2SH), 3.25 d (1H, HΒ,
2-Ethyl-1,3,4-thiadiazin-5-one (IVa). A mixture of
1.06 g (10 mmol) of thioglycolic acid hydrazide and
0.580 g (10 mmol) of propionic aldehyde in 50 ml of
methanol was kept at 25°C for 2 h. The separated crystals
were filtered off, washed with ether, and dried. Yield
J
AΒ 18.2 Hz), 3.49 d (1H, HA, JAΒ 18.2 Hz), 6.71 s (1H,
OH), 7.32–7.45 m (4H, Harom). 13C NMR spectrum NMR
spectrum (CDCl3), δ, ppm: 16.46 (CH3), 19.94 (CH2SH),
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290
38.82 (CH2CO), 54.66 (C4), 93.98 (C5), 124.31, 128.47,
129.11, 129.18 (Carom), 155.17 (C3), 170.83 (C=O).
Found, %: C 58.91; H 6.09; N 10.69. C13H16N2O2S.
Calculated, %: C 59.07; H 6.10; N 10.60.
(C5), 196.92 (C=O). Found, %: C 64.51; H 4.70; N 9.34.
C16H14N2O2S. Calculated, %: C 64.41; H 4.73; N 9.39.
2-[2-(4-Bromophenyl)-2-oxoethyl]-3,4-dihydro-
1,3,4-benzothiadiazepin-5(2H)-one (VIId). Yield
1
0.462 g (49%), mp 172–173°C. H NMR spectrum
2-[2-(4-Methoxyphenyl)-2-oxoethyl]-3,4-di-
hydro-1,3,4-benzothiadiazepin-5(2H)-one (VIIa). To
a solution of 0.445 g (2.5 mmol) of 1,3-ketoaldehyde Ia
in 5 ml of ethanol was added dropwise at stirring a solution
of 0.420 g (2.5 mmol) of 2-mercaptobenzoic acid
hydrazide in 15 ml of water maintaining the temperature
of the reaction mixture at ~50°C. The precipitated crystals
were filtered off, recrystallized from ethanol, and dried.
(DMSO-d6), δ, ppm: 3.39 d.d (1H, HΒ, JAΒ 16.4,
JΒX 5.1 Hz), 3.57 d.d (1H, HA, JAΒ 16.4, JAX 4.2 Hz),
5.08 br.s (1H, H2), 5.95 br.s (1H, NH), 7.46–7.61 m (4H,
Harom), 7.77 d (2H, Harom, J 8.7 Hz), 7.88 d (2H, Harom
,
J 8.7 Hz), 9.51 br.s (1H, NHCO). 13C NMR spectrum
(DMSO-d6), δ, ppm: 43.48 (CH2), 69.07 (C2), 128.47,
129.44, 130.93, 131.13, 131.92, 132.44, 132.74, 134.36,
136.27, 141.12 (Carom), 173.91 (C5), 196.64 (C=O).
Found, %: C 50.87; H 3.47; N 7.49. C16H13BrN2O2S.
Calculated, %: C 50.94; H 3.47; N 7.43.
1
Yield 0.460 g (56%), mp 157–158°C. H NMR spec-
trum (DMSO-d6), δ, ppm: 3.28 d.d (1H, HΒ, JAΒ 16.7,
JΒX 5.8 Hz), 3.50 br.d (1H, HA, JAΒ 16.7 Hz), 3.89 s (3H,
CH3), 5.21 br.t (1H, H2, J 5.8 Hz), 5.95 br.s (1H, NH),
6.95 d (2H, Harom, J 8.7 Hz), 7.42–7.65 m (4H, Harom),
7.93 d (2H, Harom, J 8.7 Hz), 9.50 br.s (1H, NHCO).
13C NMR spectrum (DMSO-d6), δ, ppm: 43.09 (CH2),
56.45 (OCH3), 69.42 (C2), 114.85, 127.44, 129.39, 130.25,
131.12, 131.29, 131.91, 134.36, 141.13, 164.23 (Carom),
173.93 (C5), 195.63 (C=O). Found, %: C 62.24; H 4.98;
N 8.46. C17H16N2O3S. Calculated, %: C 62.18; H 4.91;
N 8.53.
2-[2-(4-Nitrophenyl)-2-oxoethyl]-3,4-dihydro-
1,3,4-benzothiadiazepin-5(2H)-one (VIIe). Yield
1
0.318 g (37%), mp 187–188°C. H NMR spectrum
(DMSO-d6), δ, ppm: 3.41 d.d (1H, HΒ, JAΒ 16.7,
JΒX 5.0 Hz), 3.60 br.d (1H, HA, JAΒ 16.7 Hz), 5.10 br.s
(1H, H2), 5.98 br.s (1H, NH), 7.40–7.63 m (4H, Harom),
8.17 d (2H, Harom, J 8.0 Hz), 8.37 d (2H, Harom, J 8.0 Hz),
9.52 br.s (1H, NHCO). 13C NMR spectrum (DMSO-
d6), δ, ppm: 44.12 (CH2), 70.03 (C2), 124.71, 128.49,
128.67, 130.49, 131.22, 133.60, 141.02, 130.72, 138.72,
146.13 (Carom), 173.82 (C5), 197.58 (C=O). Found, %:
C 55.79; H 3.80; N 12.34. C16H13N3O4S. Calculated, %:
C 55.97; H 3.82; N 12.24.
Likewise were obtained derivatives VIIb–VIIe.
2-[2-(4-Methylphenyl)-2-oxoethyl]-3,4-dihydro-
1,3,4-benzothiadiazepin-5(2H)-one (VIIb). Yield
1
0.367 g (47%), mp 166–168°C. H NMR spectrum
(DMSO-d6), δ, ppm: 2.45 s (3H, CH3), 3.31 d.d (1H, HΒ,
REFERENCES
J
AΒ 16.7, JΒX 5.1 Hz), 3.54 br.d (1H, HA, JAΒ 16.7 Hz),
5.12 br.s (1H, H2), 5.94 br.s (1H, NH), 7.27 d (2H, Harom
J 8.0 Hz), 7.40–7.65 m (4H, Harom), 7.84 d (2H, Harom
,
,
1. Yakimovich, S.I. and Nikolaev, V.N., Zh. Org. Khim.,
1983, vol. 19, p. 880.
2. Yakimovich, S.I., Nikolaev, V.N., and Kutsenko, E.Yu.,
Zh. Org. Khim., 1983, vol. 19, p. 2333.
3. Yakimovich, S.I., Nikolaev, V.N., and Blokhtina, S.A.,
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4. Rateb, L., Nached, M.A., and Iskauder, M.F. Z.
Naturforsch., 1978, vol. 336, p. 1527.
J 8.0 Hz), 9.51 br.s (1H, NHCO). 13C NMR spectrum
(DMSO-d6), δ, ppm: 22.12 (CH3), 43.49 (CH2), 70.13
(C2), 127.89, 129.01, 130.25, 130.36, 130.74, 131.42,
133.53, 134.76, 141.10, 144.77 (Carom), 173.64 (C5),
197.54 (C=O). Found, %: C 65.31; H 5.11; N 8.99.
C17H16N2O2S. Calculated, %: C 65.36; H 5.16; N 8.97.
2-(2-Oxo-2-phenylethyl)-3,4-dihydro-1,3,4-
benzothiadiazepin-5(2H)-one (VIIc). Yield 0.239 g
(32%), mp 181–182°C. 1H NMR spectrum (DMSO-d6),
δ, ppm: 3.38 d.d (1H, HΒ, JAΒ 16.4, JΒX 5.0 Hz), 3.56 d.d
(1H, HA, JAΒ 16.4, JAX 4.2 Hz), 5.11 br.s (1H, H2), 5.96
br.s (1H, NH), 7.30–7.64 m (9H, Harom), 9.50 br.s (1H,
NHCO). 13C NMR spectrum (DMSO-d6), δ, ppm: 44.08
(CH2), 70.10 (C2), 125.92, 128.28, 128.32, 130.40, 130.65,
131.39, 131.45, 133.57, 137.54, 140.84 (Carom), 173.15
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9. Yakimovich, S.I., Zerova, I.V., Zelenin, K.N., and
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 2 2009

HETEROCYCLES FROM AROYLACETIC ALDEHYDES
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na, N.V., Alekseev, V.V., and Khrustalev, V.A., Zh. Org.
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