Heterocyclic synthesis using nitrilimines: Part 9. Synthesis of new 1,3,4-thiadiazin-5-one derivatives

Article abstract of DOI:10.1515/znb-2008-0517

A series of new 3,5,6-thiadiaza-4-hexenoates (4a-k) were synthesized from the reaction of the corresponding hydrazonoyl halides 1 with ethyl mercaptoacetate (3). These compounds underwent intramolecular cyclization to 1,3,4-thiadiazin-5-one derivatives (5a-k) in the presence of MeONa or LiH. The structures of the synthesized compounds were confirmed by their elemental analyses and spectral data.

Full text of DOI:10.1515/znb-2008-0517

Heterocyclic Synthesis Using Nitrilimines: Part 9. Synthesis of New
1,3,4-Thiadiazin-5-one Derivatives
Hany M. Dalloula, El-Hossain A. R. Mohamedb, and Ali Z. El-Shorafaa
a Chemistry Department, Faculty of Science, Al-Aqsa University of Gaza, P. O. Box 4051, Gaza,
Palestine
b Chemistry Department, Faculty of Education, Ain Shams University, Cairo, Egypt
Reprint requests to Dr. H. M. Dalloul. E-mail: hanydallool@yahoo.com
Z. Naturforsch. 2008, 63b, 585 – 590; received December 10, 2007
A series of new 3,5,6-thiadiaza-4-hexenoates (4a – k) were synthesized from the reaction of the
corresponding hydrazonoyl halides 1 with ethyl mercaptoacetate (3). These compounds underwent
intramolecular cyclization to 1,3,4-thiadiazin-5-one derivatives (5a – k) in the presence of MeONa or
LiH. The structures of the synthesized compounds were confirmed by their elemental analyses and
spectral data.
Key words: Nitrilimines, Intramolecular Cyclization, Ethyl Mercapto-acetate,
1,3,4-Thiadiazin-5-ones
Introduction
hand, the reaction of the nitrilimines 2 with ethyl mer-
captoacetate (3) for 2 – 3 d at r. t. gave acyclic elec-
trophilic addition products (4a – k) (Scheme 1). Cy-
clization to the corresponding 1,3,4-thiadiazin-5-ones
5a – k did not occur. This behavior is similar to that
reported by Abuthaher et al. [11], where α-mercapto-
alkanoic acids and N-aryl acetohydrazonoyl chlorides
reacted to afford 4-arylhydrazono-5-oxo-3-thiahexan-
oic acids, which underwent cyclization to thiadiaz-
inone rings in the presence of dicyclohexylcarbod-
imide (DCC).
The acyclic adducts 4a – k were cyclized intramol-
ecularly to the corresponding 2,4-disubstituted 1,3,4-
thiadiazin-5-ones 5a – k by heating them with methan-
olic sodium methoxide or lithium hydride (Scheme 1).
The antimicrobial and antitumor activities of com-
pounds 5a – k are now under investigation at the Free
University of Berlin, Germany.
1,3,4-Thiadiazines and their derivatives represent a
class of heterocyclic compounds that have been asso-
ciated with several pharmacological [1, 2] and medic-
inal applications [3]. Some thiadiazinones described
in the literature exhibit spasmolytic effects and bio-
logical activities [4 – 8]. Different methods were used
to synthesize 1,3,4-thiadiazin-5-one derivatives, some
of which employed thiosemicarbazide [9], mercap-
toacetyl hydrazine [10], and 4-arylhydrazono-5-oxo-3-
thiahexanoic acid [11]. The other methods afforded the
fused 1,3,4-thiadiazin-5-ones through basic or thermal
cyclization of 4-amino-3-ethoxycarbonylmethylthio-
1,2,4-triazoles [12 – 15] or 4-amino-3-carboxymethyl-
thio-1,2,4-triazinon-5-ones[16]. In continuation of our
research line dealing with the construction of hete-
rocyclic systems by means of the nitrilimine cyclo-
condensation methodology [17, 18], we investigated
the reaction of C-substituted N-arylnitrilimines 2 with
ethyl mercaptoacetate (3) in an attempt to synthesize
new derivatives of 1,3,4-thiadiazin-5-ones5a – k in an-
ticipation of expected interesting biological activities.
Spectral data analysis
The characteristic data of compounds 4a – k are
given in detail in the Experimental Section. All com-
pounds gave satisfactory combustion analysis for the
proposed structures which were confirmed on the basis
of their spectroscopic data.
Results and Discussion
Recently we found that α-amino esters react readily
with nitrilimines, generated in situ from triethylamine
The electron impact (EI) mass spectra displayed the
and hydrazonoyl halides, yielding the corresponding correct molecular ions (M+·) in accordance with the
4,5-dihydro-1,2,4-triazin-5-ones [19, 20]. On the other suggested structures.
c
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586
H. M. Dalloul et al. · Heterocyclic Synthesis Using Nitrilimines: Part 9. New 1,3,4-Thiadiazin-5-one Derivatives
Entry
Ar
X
a
b
c
d
e
f
Ph
Cl
g
h
i
j
k
PhNH-
H
PhNH-
Cl
PhNH-
Br
PhNH-
F
PhNH-
Me
2-Furyl
Cl
2-Thienyl
Cl
2-Naphthyl
H
2-Naphthyl
Cl
2-Naphthyl
Me
Scheme 1. Synthetic pathway for the preparation of compounds 4a – k and 5a – k.
The IR spectra showed the strong absorption band posed structures, indicating the disappearance of ethyl
of NH of the ring in the region 3300 – 3200 cm−1
.
(CO2CH2CH3) and N–NH protons. Finally, also the
The carbonyl absorption of the ester group appeared 13C NMR data illustrated that compounds 5a – k have
in the region 1730 – 1710 cm−1, and the C–S stretch- the assigned cyclic structure by the absence of sig-
ing band appeared in the region 1230 – 1220 cm−1
.
nals for ethoxy carbons and the presence of the sig-
1
The H NMR spectra of compounds 4a – k showed nal at δ ≈ 159 ppm which is typical for a lactam
signals of the ethyl protons at δ = 1.3 – 1.1 ppm (t, group. Furthermore, the signal of the methylene car-
3H, CH3) and 4.2 – 4.1 ppm (q, 2H, OCH2), indicat- bon of the thioester moiety in the acyclic adducts 4a – k
ing clearly that the ethyl group of the ester was not (δ ≈ 34 ppm) is shifted upfield to δ ≈ 26 ppm in com-
lost, and that the compounds have the acyclic struc- pounds 5a – k, whereas the signal of the C=N carbon
ture. Also the N–NH proton appeared as a singlet at is recorded at δ ≈ 143 ppm.
δ = 10.4 – 10.3 ppm.
In conclusion, the results demonstrate that nitril-
imines 2 react in a two-step reaction with ethyl mer-
captoacetate to give the cyclic derivatives 5a – k.
The 13C NMR spectra illustrate that compounds
4a – k have the assigned acyclic structures. The car-
bonyl carbon of the ester group appeared at about δ =
170 ppm, and the signals of the CH2 and CH3 carbon Experimental Section
atoms of the ethoxy group appeared at about δ = 61
Melting points were determined using an electrothermal
melting temperature apparatus and are uncorrected. The IR
and 14 ppm, respectively. The methylene carbon of S–
CH2 appeared at about δ = 34 – 33 ppm, and the signal
at δ ≈ 141 ppm is attributed to the C=N carbon atom.
spectra were measured as KBr pellets using a Satellite 3000
1
Mid infrared spectrometer. H NMR and 13C NMR spectra
Structure elucidation of the obtained thiadiazin-
were recorded on a Bruker AM 300 MHz spectrometer at
ones 5a – k was achieved by analytical and spectral r. t. in [D6]DMSO solution using tetramethylsilane (TMS) as
internal reference. Electron impact (EI) mass spectra were
run on a Shimadzu GCMS-QP1000 EX spectrometer at
70 eV. Elemental analyses were performed at Cairo Univer-
sity, Egypt. The hydrazonoyl halides 1 were prepared accord-
ing to literature procedures [21 – 24], and ethyl mercapto-
acetate (3) was purchased from Avocado Research Chemi-
cals, England, and used without further purification.
data summarized in the Experimental Section. Their
mass spectra displayed the correct molecular ion peaks
[M]+ in accordance with the suggested structures and
showed the loss of an ethoxy group from the acyclic
adducts 4a – k via ethanol elimination. The IR spec-
tra of compounds 5a – k support the formation of the
cyclic structure by the absence of NH and C=O vi-
brations of the ester, and the appearance of a new ab-
sorption band for a lactam (C=O of the ring) in the
region 1680– 1670 cm−1. The 1H NMR spectra of
Synthesis of compounds 4a – k
General method: To a stirred solution of the appropriate
compounds 5a – k showed all the signals of the pro- hydrazonoyl halide 1 (5 mmol) and ethyl mercaptoacetate
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H. M. Dalloul et al. · Heterocyclic Synthesis Using Nitrilimines: Part 9. New 1,3,4-Thiadiazin-5-one Derivatives
587
(3) (10 mmol) in tetrahydrofuran (THF) (50 mL), triethy- Ethyl 6-(4-fluorophenyl)-4-phenylaminocarbonyl-3,5,6-
lamine (4 mL, 3 mmol) in THF (10 mL) was dropwise added thiadiaza-4-hexenoate (4d)
at r. t. Stirring was continued for 2 – 3 d, then the solvent was
M. p. 118 – 120 ◦C (ethanol). – Yield 81 %. – IR: ν =
3320, 3270 (N–H), 1720 (ester C=O), 1650 (amide C=O),
1616 (C=N), 1226 (C–S) cm−1. – 1H NMR: δ = 10.25
(s, 1H, N–H), 9.90 (s, 1H, PhN–H), 7.77 – 7.05 (m, 9H,
Ar-H), 4.10 – 3.98 (q, 2H, OCH2, J = 7 Hz), 3.86 (s, 2H,
SCH2), 1.21 – 1.10 (t, 3H, CH3, J = 7 Hz) ppm. – 13C NMR:
δ = 169.5 (ester C=O), 160.9 (amide C=O), 140.5 (C=N),
139.2 – 115.7 (Ar-C), 61.6 (OCH2), 33.9 (SCH2), 14.3
(CH3) ppm. – MS: m/z = 375 [M]+. – C18H18FN3O3S
(375.42): calcd. C 57.59, H 4.83, N 11.19; found C 57.37,
H 4.69, N 11.19.
removed under vacuum, and the residual solid was washed
with water (100 mL). The solid products were collected and
recrystallized from an appropriate solvent to afford the de-
sired compounds. The following compounds were prepared
by this method.
Ethyl 6-phenyl-4-phenylaminocarbonyl-3,5,6-thiadiaza-4-
hexenoate (4a)
M. p. 113 – 115 ◦C (ethanol). – Yield 82 %. – IR: ν =
3320, 3270 (N–H), 1715 (ester C=O), 1650 (amide C=O),
1600 (C=N), 1225 (C–S) cm−1. – 1H NMR: δ = 10.33
(s, 1H, N–H), 9.93 (s, 1H, PhN–H), 7.76 – 7.02 (m, 10H,
Ar-H), 4.21 – 4.02 (q, 2H, OCH2, J = 7 Hz), 3.90 (s, 2H,
SCH2), 1.25 – 1.13 (t, 3H, CH3, J = 7 Hz) ppm. – 13C NMR:
δ = 169.9 (ester C=O), 159.9 (amide C=O), 140.0 (C=N),
139.9 – 119.3 (Ar-C), 61.3 (OCH2), 33.2 (SCH2), 13.8
(CH3) ppm. – MS: m/z = 357 [M]+. – C18H19N3O3S
(357.43): calcd. C 60.49, H 5.36, N 11.76; found C 60.27,
H 5.57, N 11.55.
Ethyl 6-(4-methylphenyl)-4-phenylaminocarbonyl-3,5,6-
thiadiaza-4-hexenoate (4e)
M. p. 129 – 130 ◦C (ethanol). – Yield 77 %. – IR: ν =
3320, 3270 (N–H), 1710 (ester C=O), 1650 (amide C=O),
1620 (C=N), 1229 (C–S) cm−1. – 1H NMR: δ = 10.36
(s, 1H, N–H), 9.90 (s, 1H, PhN–H), 7.78 – 7.00 (m, 9H,
Ar-H), 4.18 – 4.06 (q, 2H, OCH2, J = 7 Hz), 3.91 (s, 2H,
SCH2), 2.25 (s, 3H, CH3), 1.23 – 1.11 (t, 3H, CH3, J =
7 Hz) ppm. – 13C NMR: δ = 169.9 (ester C=O), 160.3
(amide C=O), 141.6 (C=N), 139.1 – 114.5 (Ar-C), 61.2
(OCH2), 33.7 (SCH2), 20.5 (CH3), 14.0 (CH3) ppm. – MS:
m/z = 371 [M]+. – C19H21N3O3S (371.46): calcd. C 61.44,
H 5.70, N 11.31; found C 65.18, H 5.67, N 11.18.
Ethyl 6-(4-chlorophenyl)-4-phenylaminocarbonyl-3,5,6-
thiadiaza-4-hexenoate (4b)
M. p. 136 – 138 ◦C (ethanol). – Yield 75 %. – IR: ν =
3320, 3270 (N–H), 1718 (ester C=O), 1655 (amide C=O),
1615 (C=N), 1226 (C–S) cm−1. – 1H NMR: δ = 10.30
(s, 1H, N–H), 9.93 (s, 1H, PhN–H), 7.80 – 7.10 (m, 9H,
Ar-H), 4.20 – 4.03 (q, 2H, OCH2, J = 7 Hz), 3.96 (s,
2H, SCH2), 1.27 – 1.11 (t, 3H, CH3, J = 7 Hz) ppm. –
13C NMR: δ = 169.9 (ester C=O), 160.2 (amide C=O),
140.0 (C=N), 139.9 – 119.8 (Ar-C), 61.3 (OCH2), 33.2
(SCH2), 13.8 (CH3) ppm. – MS: m/z = 391/393 [M]+. –
C18H18ClN3O3S (391.88): calcd. C 55.17, H 4.63, N 10.72;
found C 55.44, H 4.59, N 10.63.
Ethyl 4-benzoyl-6-(4-chlorophenyl)-3,5,6-thiadiaza-4-
hexenoate (4f)
◦
M. p. 136 – 138 C (methanol). – Yield 72 %. – IR: ν =
3316 (N–H), 1705 (ester C=O), 1645 (C=O), 1605 (C=N),
1232 (C–S) cm−1. – 1H NMR: δ = 10.35 (s, 1H, N–H),
8.05 – 7.07 (m, 9H, Ar-H), 4.25 – 4.14 (q, 2H, OCH2, J =
7 Hz), 3.89 (s, 2H, SCH2), 1.33 – 1.23 (t, 3H, CH3, J =
7 Hz) ppm. – 13C NMR: δ = 187.50 (C=O), 169.2 (ester
C=O), 141.7 (C=N), 136.9 – 115.5 (Ar-C), 61.9 (OCH2),
33.4 (SCH2), 14.1 (CH3) ppm. – MS: m/z = 376/378 [M]+. –
C18H17ClN2O3S (376.86): calcd. C 57.37, H 4.55, N 7.43;
found C 57.25, H 4.65, N 7.32.
Ethyl 6-(4-bromophenyl)-4-phenylaminocarbonyl-3,5,6-
thiadiaza-4-hexenoate (4c)
M. p. 150 – 152 ◦C (ethanol). – Yield 75 %. – IR: ν =
3320, 3270 (N–H), 1715 (ester C=O), 1650 (amide C=O),
1612 (C=N), 1225 (C–S) cm−1. – 1H NMR: δ = 10.36
(s, 1H, N–H), 9.95 (s, 1H, PhN–H), 7.78 – 7.06 (m, 9H,
Ethyl 6-(4-chlorophenyl)-4-(2-furoyl)-3,5,6-thiadiaza-4-
hexenoate (4g)
◦
M. p. 144 – 146 C (methanol). – Yield 78 %. – IR: ν =
Ar-H), 4.13 – 4.01 (q, 2H, OCH2, J = 7 Hz), 3.89 (s, 3333 (N–H), 1725 (ester C=O), 1665 (C=O), 1620 (C=N),
2H, SCH2), 1.25 – 1.13 (t, 3H, CH3, J = 7 Hz) ppm. – 1230 (C–S) cm−1. – 1H NMR: δ = 10.41 (s, 1H, N–H),
13C NMR: δ = 169.8 (ester C=O), 160.9 (amide C=O), 8.20 – 7.16 (m, 7H, Ar-H), 4.28 – 4.19 (q, 2H, OCH2, J =
140.5 (C=N), 139.8 – 118.4 (Ar-C), 61.1 (OCH2), 33.4 7 Hz), 3.90 (s, 2H, SCH2), 1.29 – 1.18 (t, 3H, CH3, J =
(SCH2), 13.8 (CH3) ppm. – MS: m/z = 436/438 [M]+. – 7 Hz) ppm. – 13C NMR: δ = 173.6 (C=O), 169.5 (ester
C18H18BrN3O3S (436.33): calcd. C 49.55, H 4.16, N 9.63; C=O), 141.4 (C=N), 139.9 – 119.8 (Ar-C), 62.1 (OCH2),
found C 49.71, H 3.95, N 9.56.
33.4 (SCH2), 14.1 (CH3) ppm. – MS: m/z = 366/368 [M]+. –
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H. M. Dalloul et al. · Heterocyclic Synthesis Using Nitrilimines: Part 9. New 1,3,4-Thiadiazin-5-one Derivatives
C16H15ClN2O4S (366.83): calcd. C 52.39, H 4.12, N 7.64; m/z = 406 [M]+. – C23H22N2O3S (406.51): calcd. C 97.96,
found C 52.50, H 4.00, N 7.73.
H 5.46, N 6.89; found C 68.05, H 5.35, N 6.95.
Ethyl 6-(4-chlorophenyl)-4-(2-thenoyl)-3,5,6-thiadiaza-4-
hexenoate (4h)
Cyclization of compounds 4a – k
Method A: Compounds 4a – k (5 mmol) were added to a
methanolic solution of sodium methoxide – prepared from
sodium metal (0.12 g, 5 mmol) and methanol (20 mL) – un-
der stirring at r. t. The resulting solution was refluxed for 2 –
3 h. After cooling the solvent was removed under reduced
pressure, and the residue was washed with water. The solid
was collected and recrystallized from ethanol to give the de-
sired cyclic compounds 5a – k.
Method B: To a stirred solution of compounds 4a – k
(5 mmol) in dry THF (30 mL) was carefully added lithium
hydride (0.08 g, 10 mmol) at r. t. The resulting reaction mix-
ture was refluxed for 30 min. After cooling excess lithium
hydride was destroyed with some drops of glacial acetic acid.
The solvent was evaporated under reduced pressure and the
◦
M. p. 155 – 157 C (methanol). – Yield 75 %. – IR: ν =
3330 (N–H), 1725 (ester C=O), 1660 (C=O), 1622 (C=N),
1232 (C–S) cm−1. – 1H NMR: δ = 10.44 (s, 1H, N–H),
8.25 – 7.20 (m, 7H, Ar-H), 4.30 – 4.20 (q, 2H, OCH2, J =
7 Hz), 3.91 (s, 2H, SCH2), 1.30 – 1.19 (t, 3H, CH3, J =
7 Hz) ppm. – 13C NMR: δ = 174.5 (C=O), 169.6 (ester
C=O), 141.3 (C=N), 139.9 – 119.8 (Ar-C), 62.3 (OCH2),
33.6 (SCH2), 14.3 (CH3) ppm. – MS: m/z = 382/384 [M+]. –
C16H15ClN2O3S (382.89): calcd. C 50.19, H 3.95, N 7.32;
found C 50.98, H 4.11, N 7.41.
Ethyl 4-(2-naphthoyl)-6-phenyl-3,5,6-thiadiaza-4-hexenoate
(4i)
◦
M. p. 173 – 175 C (methanol). – Yield 78 %. – IR: ν = product extracted three times with chloroform. The com-
bined organic extracts were dried over anhydrous magnesium
sulfate, and the solvent was removed under reduced pressure.
3314 (N–H), 1711 (ester C=O), 1647 (C=O), 1605 (C=N),
1222 (C–S) cm−1. – 1H NMR: δ = 10.38 (s, 1H, N–H),
8.75 – 7.13 (m, 11H, Ar-H), 4.31 – 4.20 (q, 2H, OCH2, J = The resulting solid product was collected and recrystallized
7 Hz), 3.89 (s, 2H, SCH2), 1.32 – 1.21 (t, 3H, CH3, J = from ethanol to give compounds 5a – k that were identical
7 Hz) ppm. – 13C NMR: δ = 187.2 (C=O), 169.2 (ester
with the ones prepared by method A.
C=O), 141.9 (C=N), 140.6 – 115.4 (Ar-C), 62.0 (OCH2),
33.2 (SCH2), 14.6 (CH3) ppm. – MS: m/z = 392 [M]+. –
C22H20N2O3S (392.48): calcd. C 67.33, H 5.14, N 7.14;
found C 67.20, H 5.26, N 7.23.
4-Phenyl-2-phenylaminocarbonyl-6H-1,3,4-thiadiazin-5-
one (5a)
M. p. 151 – 153 ◦C (ethanol). – Yield 70 %. – IR: ν =
3273 (N–H), 1678 (lactam C=O), 1652 (amide C=O), 1590
(C=N) cm−1. – 1H NMR: δ = 10.32 (s, 1H, PhN–H), 7.77 –
7.13 (m, 10H, Ar-H), 3.90 (s, 2H, CH2) ppm. – 13C NMR:
δ = 159.4 (lactam C=O), 158.2 (amide C=O), 143.4 (C=N),
138.7 – 115.6 (Ar-C), 26.0 (CH2) ppm. – MS: m/z = 311
[M]+. – C16H13N3O2S (311.36): calcd. C 61.72, H 4.21,
N 13.50; found C 61.55, H 4.10, N 13.65.
Ethyl 6-(4-chlorophenyl)-4-(2-naphthoyl)-3,5,6-thiadiaza-
4-hexenoate (4j)
◦
M. p. 168 – 170 C (methanol). – Yield 72 %. – IR: ν =
3305 (N–H), 1707 (ester C=O), 1640 (C=O), 1600 (C=N),
1220 (C–S) cm−1. – 1H NMR: δ = 10.40 (s, 1H, N–H),
8.72 – 7.10 (m, 11H, Ar-H), 4.32 – 4.22 (q, 2H, OCH2, J =
7 Hz), 3.92 (s, 2H, SCH2), 1.31 – 1.19 (t, 3H, CH3, J =
7 Hz) ppm. – 13C NMR: δ = 187.0 (C=O), 169.4 (ester
C=O), 141.9 (C=N), 140.2 – 116.5 (Ar-C), 61.3 (OCH2),
33.5 (SCH2), 14.6 (CH3) ppm. – MS: m/z = 426/428 [M]+. –
C22H19ClN2O3S (426.93): calcd. C 61.89, H 4.49, N 6.56;
found C 62.05, H 4.37, N 6.50.
4-(4-Chlorophenyl)-2-phenylaminocarbonyl-6H-1,3,4-
thiadiazin-5-one (5b)
M. p. 170 – 172 ◦C (ethanol). – Yield 68 %. – IR: ν =
3273 (N–H), 1678 (lactam C=O), 1652 (amide C=O), 1596
(C=N) cm−1. – 1H NMR: δ = 10.34 (s, 1H, PhN–H), 7.77 –
7.18 (m, 9H, Ar-H), 3.91 (s, 2H, CH2) ppm. – 13C NMR:
δ = 159.9 (lactam C=O), 158.5 (amide C=O), 143.1 (C=N),
138.9 – 115.9 (Ar-C), 26.0 (CH2) ppm. – MS: m/z = 345/347
[M]+. – C16H12ClN3O2S (345.81): calcd. C 55.57, H 3.50,
N 12.15; found C 55.42, H 3.61, N 12.08.
Ethyl 6-(4-methylphenyl)-4-(2-naphthoyl)-3,5,6-thiadiaza-4-
hexenoate (4k)
◦
M. p. 143 – 145 C (methanol). – Yield 74 %. – IR: ν =
3310 (N–H), 1718 (ester C=O), 1645 (C=O), 1610 (C=N),
1227 (C–S) cm−1. – 1H NMR: δ = 10.39 (s, 1H, N–H),
8.75 – 7.11 (m, 11H, Ar-H), 4.30 – 4.21 (q, 2H, OCH2, J =
7 Hz), 3.88 (s, 2H, SCH2), 2.27 (s, 3 H, CH3), 1.28 – 1.14 (t,
3H, CH3, J = 7 Hz) ppm. – 13C NMR: δ = 187.2 (C=O),
169.0 (ester C=O), 141.8 (C=N), 139.8 – 116.1 (Ar-C), 62.3
4-(4-Bromophenyl)-2-phenylaminocarbonyl-6H-1,3,4-thia-
diazin-5-one (5c)
M. p. 180 – 182 ◦C (ethanol). – Yield 75 %. – IR: ν =
(OCH2), 33.5 (SCH2), 20.7 (CH3), 14.5 (CH3) ppm. – MS: 3272 (N–H), 1675 (lactam C=O), 1652 (amide C=O), 1598
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H. M. Dalloul et al. · Heterocyclic Synthesis Using Nitrilimines: Part 9. New 1,3,4-Thiadiazin-5-one Derivatives
589
(C=N) cm−1. – 1H NMR: δ = 10.33 (s, 1H, PhN–H), 7.78 – 4-(4-Chlorophenyl)-2-(2-thenoyl)-6H-1,3,4-thiadiazin-5-
7.14 (m, 9H, Ar-H), 3.92 (s, 2H, CH2) ppm. – 13C NMR: one (5h)
δ = 159.5 (lactam C=O), 158.4 (amide C=O), 143.3 (C=N),
M. p. 184 – 186 ◦C (ethanol). – Yield 72 %. – IR: ν =
1681 (lactam C=O), 1656 (C=O), 1602 (C=N), 1205
(C–S) cm−1. – 1H NMR: δ = 8.28 – 7.20 (m, 10H, Ar-H),
3.88 (s, 2H, CH2) ppm. – 13C NMR: δ = 173.6 (C=O), 159.0
(lactam C=O), 143.7 (C=N), 141.3 – 115.4 (Ar-C), 26.2
(CH2) ppm. – MS: m/z = 336/338 [M]+. – C14H9ClN2O2S2
(336.82): calcd. C 49.92, H 2.69, N 8.32; found C 50.15,
H 2.58, N 8.26.
139.9 – 120.0 (Ar-C), 26.1 (CH2) ppm. – MS: m/z = 390/392
[M]+. – C16H12BrN3O2S (390.26): calcd. C 49.24, H 3.10,
N 10.77; found C 49.35, H 2.98, N 10.86.
4-(4-Fluorophenyl)-2-phenylaminocarbonyl-6H-1,3,4-thia-
diazin-5-one (5d)
M. p. 190 – 192 ◦C (ethanol). – Yield 70 %. – IR: ν =
3273 (N–H), 1678 (lactam C=O), 1652 (amide C=O), 1594
(C=N) cm−1. – 1H NMR: δ = 10.36 (s, 1H, PhN–H), 7.60 –
7.13 (m, 9H, Ar-H), 3.91 (s, 2H, CH2) ppm. – 13C NMR:
δ = 159.8 (lactam C=O), 158.5 (amide C=O), 141.6 (C=N),
139.0 – 115.2 (Ar-C), 26.0 (CH2) ppm. – MS: m/z = 329
[M]+. – C16H12FN3O2S (329.36): calcd. C 58.35, H 3.67,
N 12.76; found C 58.15, H 3.80, N 12.83.
2-(2-Naphthoyl)-4-phenyl-6H-1,3,4-thiadiazin-5-one (5i)
M. p. 203 – 205 ◦C (ethanol). – Yield 71 %. – IR: ν =
1677 (lactam C=O), 1640 (C=O), 1608 (C=N), 1212
(C–S) cm−1. – 1H NMR: δ = 8.55 – 7.03 (m, 10H, Ar-H),
3.86 (s, 2H, CH2) ppm. – 13C NMR: δ = 185.9 (C=O),
158.5 (lactam C=O), 144.3 (C=N), 139.6 – 115.2 (Ar-C),
26.4 (CH2) ppm. – MS: m/z = 346 [M]+. – C20H14N42O2S
(346.41): calcd. C 69.35, H 4.07, N 8.09; found C 69.43,
H 3.90, N 7.95.
4-(4-Methylphenyl)-2-phenylaminocarbonyl-6H-1,3,4-thia-
diazin-5-one (5e)
M. p. 195 – 197 ◦C (ethanol). – Yield 68 %. – IR: ν =
3272 (N–H), 1675 (lactam C=O), 1652 (amide C=O), 1598
(C=N) cm−1. – 1H NMR: δ = 10.02 (s, 1H, PhN–H),
7.87 – 7.14 (m, 9H, Ar-H), 3.92 (s, 2H, CH2), 2.37 (s,
2H, CH3) ppm. – 13C NMR: δ = 159.2 (lactam C=O),
158.1 (amide C=O), 142.2 (C=N), 139.7 – 114.9 (Ar-C),
26.0 (CH2), 20.9 (CH3) ppm. – MS: m/z = 325 [M]+. –
C17H15N3O2S (325.39): calcd. C 62.75, H 4.65, N 12.91;
found: C 62.90, H 4.52, N 13.05.
4-(4-Chlorophenyl)-2-(2-naphthoyl)-6H-1,3,4-thiadiazin-5-
one (5j)
M. p. 193 – 195 ◦C (ethanol). – Yield 67 %. – IR: ν =
1671 (lactam C=O), 1635 (C=O), 1599 (C=N), 1209
(C–S) cm−1. – 1H NMR: δ = 8.45 – 7.10 (m, 10H, Ar-H),
3.84 (s, 2H, CH2) ppm. – 13C NMR: δ = 185.5 (C=O), 158.8
(lactam C=O), 143.8 (C=N), 139.4 – 125.5 (Ar-C), 26.2
(CH2) ppm. – MS: m/z = 380/382 [M]+. – C20H13ClN2O2S
(380.86): calcd. C 63.07, H 3.44, N 7.36; found C 62.85,
H 3.53, N 7.22.
2-Benzoyl-4-(4-chlorophenyl)-6H-1,3,4-thiadiazin-5-one
(5f)
M. p. 153 – 155 ◦C (ethanol). – Yield 71 %. – IR: ν =
1680 (lactam C=O), 1645 (C=O), 1605 (C=N), 1208
(C–S) cm−1. – 1H NMR: δ = 8.1 – 7.15 (m, 10H, Ar-H), 3.86
(s, 2H, CH2) ppm. – 13C NMR: δ = 186.5 (C=O), 158.9
(lactam C=O), 143.5 (C=N), 139.2 – 115.1 (Ar-C), 26.3
(CH2) ppm. – MS: m/z = 330/332 [M]+. – C16H11ClN2O2S
(330.80): calcd. C 58.10, H 3.35, N 8.47; found C 57.90,
H 3.15, N 8.53.
4-(4-Methylphenyl)-2-(2-naphthoyl)-6H-1,3,4-thiadiazin-5-
one (5k)
M. p. 210 – 212 ◦C (ethanol). – Yield 65 %. – IR: ν =
1675 (lactam C=O), 1637 (C=O), 1607 (C=N), 1210
(C–S) cm−1. – 1H NMR: δ = 8.50 – 7.15 (m, 10H, Ar-H),
3.87 (s, 2H, CH2), 2.37 (s, 3H, CH3) ppm. – 13C NMR: δ =
185.6 (C=O), 158.6 (lactam C=O), 144.0 (C=N), 139.1 –
114.6 (Ar-C), 26.3 (CH2), 20.7 (CH3) ppm. – MS: m/z =
360 [M]+. – C21H16N2O2S (360.44): calcd. C 69.98, H 4.47,
N 7.77; found C 67.12, H 4.38, N 7.70.
4-(4-Chlorophenyl)-2-(2-furoyl)-6H-1,3,4-thiadiazin-5-one
(5g)
M. p. 173 – 175 ◦C (ethanol). – Yield 73 %. – IR: ν =
1682 (lactam C=O), 1660 (C=O), 1600 (C=N), 1207
(C–S) cm−1. – 1H NMR: δ = 8.20 – 7.13 (m, 10H, Ar-H),
3.90 (s, 2H, CH2) ppm. – 13C NMR: δ = 172.8 (C=O), 159.1
(lactam C=O), 143.9 (C=N), 141.7 – 115.5 (Ar-C), 26.3
(CH2) ppm. – MS: m/z = 320/322 [M]+. – C14H9ClN2O3S
(320.76): calcd. C 52.42, H 2.83, N 8.73; found C 52.33,
H 3.00, N 8.90.
Acknowledgements
We wish to thank Dr. H. Z. El-Shorafa, Free Univer-
sity of Berlin, Germany, for obtaining some NMR spectra
and the Ministry of Higher Education for partially financial
support.
Unauthenticated
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590
H. M. Dalloul et al. · Heterocyclic Synthesis Using Nitrilimines: Part 9. New 1,3,4-Thiadiazin-5-one Derivatives
[1] P. Langer, D. Kowollik, Eur. J. Biochem. 1968, 6, 344.
[2] N. Demirbas, A. Demirbas, S. Karaoglu, E. Celik,
Arkivoc 2005, (i), 75.
[3] C. L. Zircle, C. Kaiser in Medicinal Chemistry, (Ed.: A.
Burger), Wiley-Interscience, New York 1970, pp. 1410.
[4] W. Hanefeld, M. Schlitzer, Arch. Pharm. 1993, 326,
249.
[14] P. Vainilavicius, R. Smicius, V. Takobkiene, S. Tumke-
vicius, Monatsh. Chem. 2001, 132, 825.
[15] S. M. Desenko, E. S. Gladkov, P. V. Nedeko, E. I. Mi-
hedkiva, International Conference Chemistry of Nitro-
gen Containing Heterocycles, C. NH-2003, p. 913.
[16] R. M. Abdel-Rahman, Pak. J. Sci. Ind. Res. 1987, 30,
490.
[5] R. Soliman, M. Gaber, M. S. Abouzeit-H, F. M. Shara-
bi, J. Pharm. Sci. 1980, 70, 94.
[6] Y. Matsubara, M. Yoshihara, T. Nakanura, S. Yamada,
T. Maeshima, Phosphorus and Sulfur 1983, 16, 89;
Chem. Pharm. Bull. 1984, 32, 1590.
[7] T. Jira, A. Stelzer, W.-D. Pfeifer, C. Schopplich, S. Si-
etzert, M. Kindermann, Pharmazie 1997, 52, 831 and
refs. cited therein.
[8] J. Mohan, Indian J. Chem. 2005, 44B, 628.
[9] W. Reeve, E. R. Barron, J. Org. Chem. 1975, 40, 1917.
[10] A. Yu. Ershov, M. V. Mokeev, E. V. Beloborodova,
A. V. Gribavov, Arkivoc 2002, (i), 49.
[11] B. A. Thaher, H.-H. Otto, Monatsh. Chem. 2002, 133,
1011.
[17] L. Garanti, A. Sala, G. Zecchi, Synthesis 1975, 666;
J. Org. Chem. 1977, 42, 1389.
[18] L. Bruche, L. Garanti, G. Zecchi, J. Chem. Soc., Perkin
Trans. I 1984, 2535; ibid. 1994, 433.
[19] A. M. Awadallah, A. R. Ferwanah, E. A. El-Sawi,
H. M. Dalloul, Heterocycl. Commun. 2002, 8, 369.
[20] H. M. Dalloul, unpublished results.
[21] P. Frohberg, G. Drutkowski, C. Wagner, Eur. J. Org.
Chem. 2002, 1654.
[22] A. M. Farag, H. M. Hassaneen, I. M. Abbas, A. S.
Shawali, M. S. Algharib, Phosphorus and Sulfur 1988,
39, 243.
[23] A. S. Shawali, A. O. Abdelhamid, Bull. Chem. Soc.
Jap. 1976, 49, 321.
[12] M. M. Ghorab, A. M. El-Sharief, Y. A. Ammar, Sh. I.
Mohamed, IL Farmaco 2000, 55, 354.
[13] A. M. El-Sharief, M. M. Ghorab, M. S. El-Gaby, Sh. I.
Mohamed, Y. A. Ammar, Heteroatom Chem. 2002, 13,
316.
[24] A. S. Shawali, H. M. Hassaneen, A. A. Fahmy, N. M.
Abunada, Phosphorus, Sulfur and Silicon, 1990, 53,
259.
Unauthenticated
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