Synthesis of 3-[(4-chloro-phenyl) oxiranyl]thiophen-2-yl-propanone and their reactions with some nucleophilles for antiviral evaluations

Article abstract of DOI:10.1080/10426500701564225

Compounds 2, 3, 4, 7, 10, 11, 12 and 13 were formed via the reactions of [3-(4-chlorophenyl)oxiranyl]thiophen-2-yl-propanone with hydrazine derivatives, hydroxyl-amine hydrochloride, thiourea, thiosemicarbazide, carbon disulfide, phenyl isothiocyanate, me

Full text of DOI:10.1080/10426500701564225

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Phosphorus, Sulfur, and Silicon
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Synthesis of 3-[(4-Chloro-
phenyl) oxiranyl]thiophen-2-yl-
propanone and Their Reactions
with Some Nucleophilles for
Antiviral Evaluations
H. H. Sayed a & M. A. Ali b
a Photochemistry Department , National Research
Centre , Dokki, Cairo, Egypt
b Virology Laboratory , National Research Centre ,
Dokki, Cairo, Egypt
Published online: 20 Feb 2008.
To cite this article: H. H. Sayed & M. A. Ali (2007) Synthesis of 3-[(4-Chloro-phenyl)
oxiranyl]thiophen-2-yl-propanone and Their Reactions with Some Nucleophilles for
Antiviral Evaluations, Phosphorus, Sulfur, and Silicon and the Related Elements, 183:1,
156-167, DOI: 10.1080/10426500701564225
To link to this article: http://dx.doi.org/10.1080/10426500701564225
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Phosphorus, Sulfur, and Silicon, 183:156–167, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701564225
Synthesis of 3-[(4-Chloro-phenyl)
oxiranyl]thiophen-2-yl-propanone and Their Reactions
with Some Nucleophilles for Antiviral Evaluations
H. H. Sayed1 and M. A. Ali2
1Photochemistry Department, National Research Centre, Dokki,
Cairo, Egypt
2Virology Laboratory, National Research Centre, Dokki, Cairo, Egypt
Compounds 2, 3, 4, 7, 10, 11, 12 and 13 were formed via the reactions
of [3-(4-chlorophenyl)oxiranyl]thiophen-2-yl-propanone with hydrazine deriva-
tives, hydroxyl-amine hydrochloride, thiourea, thiosemicarbazide, carbon disulfide,
phenyl isothiocyanate, methyl isothiocyanate and phosphorus pentasulfide, respec-
tively. Pyrimidine derivative 4 was in turn used as precursor for preparation of
thiazolopyrimidines 5 and 6. Pyrazolothioamide 7 was treated with D-glucose and
arbinose to afford the corresponding hydrazones 8 and 9.
Keywords Dithiole; HSV-1; oxathiolane; oxazine; oxazole; pyrazole; pyrimidine
INTRODUCTION
Pyrazoles, oxazoles, pyrimidines, thiazolopyrimidines, oxazines, oxathi-
oles and dithioles are of current interest by versatile biological
activities. Pyrazoles moieties possesses analgesic, antipyretic and
hyperglycemic.1−3 Oxazoles moieties have antidepressant,4 antibiotic,5
and antimicrobial properties.6 Pyrimidines and thiazolopyrimidines
possess tyrosine kinas inhibitor,7,8 analgesic, anticonvulsant, and an-
tiparkinsonian agent properties.9 On the other hand, oxathiolanes have
antitumor,10 plant growth regulator,11 herbicides,12 and ectoparasiti-
cides properties,13 while oxazines have antitumor14 and anticonvulsant
attributes.15 This information stimulated us to obtain new compounds
to possess notable chemical and biological activities.
RESULTS AND DISCUSSION
[3-(4-Chlorophenyl)oxiranyl]thiophen-2-yl-propanone (1) was prepared
according to our previously work16−18 from arylidenethiophene-2-yl-
Address correspondence to H. H. Sayed, Photochemistry Department, National Re-
search Centre, Dokki, Cairo 12622, Egypt. E-mail: hayamsayed@yahoo.com
156

Oxiranyl Thiophenpropanone
157
propanone.19−20 The structure of compound 1 was confirmed with
spectral data. The IR spectrum showed a band at (ν, cm−1) 1693
(C O), and the1H NMR showed signals at (δ, ppm) 3.70 (d, 1H, oxi-
ranyl ring proton) and 3.90 (d, 1H, other oxiranyl ring proton). The
MS gave a molecular ion peak at m/z 264. Compound 1 reacted with
different amines, hydrazine hydrate, phenylhydrazine, hydroxylamine
hydrochloride, thiourea, and thiosemicarbazide via Micheal addition to
afford 2a,b, 3, 4, and 7, respectively (Schemes 1 and 2). The spectral
data of these compounds assigned their structures (cf. Experimental
Section). The IR spectrum of 2a, as an example, showed bands at (ν,
cm−1) 3100–3125 (NH), 3320–3380 (OH), and the absence of a (C O)
band. Its1H NMR spectrum showed signals at (δ, ppm) 3.85 (d, 1H,
C4 H), 4.00 (d, 1H, C5 H), 9.4 (s, 1H, NH, D2O exchangeable) and 10.2
(s, 1H, OH, D2O exchangeable). Its MS spectrum gave the molecular ion
peak at m/z 278. The IR spectra of isoxazole 3 showed bands at (ν, cm−1
)
3325–3390 (OH) and the absence of a (C O) band. Its1H NMR spec-
trum showed signals at (δ, ppm): 3.80 (d, 1H, C4 H), 4.6 (d, 1H, C5 H)
and 10.35 (s, 1H, OH, D2O exchangeable). Its MS spectrum gave the
molecular ion peak at m/z 279. When compound 1 reacted with thiourea
in the presence of an alkaline medium it afforded thioxopyrimidinone
derivative 4 (Scheme 1). The spectral data of this compound assigned
its structures. Its IR spectrum showed bands at (ν, cm−1) 3115–3180
(2NH) and 1700 (C O) band. Its1H NMR spectrum showed signals at (δ,
ppm) 5.6 (s, 2H, pyrimidine-H), 9.8 (s, 1H, NH, D2O exchangeable) and
11.0 (s, 1H, NH, D2O exchangeable). Its MS spectrum gave the molecu-
lar ion peak at m/z 322. It also was proven chemically via reaction with
chloroacetic acid to afford the thiazolopyrimidine-3,6-dione derivative
5. Its IR spectrum showed bands at (ν, cm−1) 1698 (C O) and 1705
(C O). Its1H NMR spectrum showed signals at (δ, ppm): 3.40 (s, 2H,
C2 H) (cf. Experimental). When the latter compound condensed with
p-chlorobenzaldhyde, it afforded compound 6 which could be prepared
directly via a one pot reaction by treating compound 4 with chloroacetic
acid and p-chlorobenzaldhyde. The spectral data of compounds 5 and 6
assigned their structures (cf. Experimental Section).
When compound 1 reacted with thiosemicarbazide, it afforded pyra-
zole carbothioamide derivative 7 (Scheme 2). The spectral data of this
compound assigned its structure (cf. Experimental Section). The 1H
NMR spectrum showed signal at (δ, ppm) 4.00, characteristic for pyra-
zole ring. Also compound 7 was confirmed chemically via condensation
with monosaccharides namely arbinose and D-glucose, to give the corre-
sponding hydrazones 8 and 9 (Scheme 2). The IR spectrum of 8 showed
bands at (ν, cm−1) 3320–3380 (OH groups) and the absence of NH2.
Its1H NMR spectrum showed signals at (δ, ppm) 3.30–3.63 (m, 11H,
6-CH-glucose +5OH, D2O exchangeable), 3.8 (d, 1H, C4 H), 4.1 (s, 1H,

158
H. H. Sayed and M. A. Ali
SCHEME 1
C5 H), 7.0–7.3 (m, 7H, A H), 7.8 (d, 1H, hydrazone), and 10.3 (s, 1H,
OH, D2O exchangeable). On the other hand, compound 1 reacted with
CS2 via a [3+2] cycloaddition to afford the 1,3-oxathiolane derivative 10.
The structure of the latter compound was confirmed from the spectral

Oxiranyl Thiophenpropanone
159
SCHEME 2
data since the IR spectrum showed a band at (ν, cm−1) 1695 (C O) and
its 1H NMR spectrum showed signals at (δ, ppm) 4.2 (d, 1H, oxathiolane-
H) and 4.8 (d, 1H, oxathiolane-H). Its MS spectrum gave the molecular
ion peak at m/z 340. Compound 1 reacted with isothiocyanates via a

160
H. H. Sayed and M. A. Ali
[4+2] cycloaddition to afford the 1,3-oxazinethione derivatives 11a,b
and not the 1,3 oxazole derivative. The IR spectrum of compound 11a
revealed the absence of C O band and 1H NMR spectrum showed sig-
nals at (δ, ppm) 4.6 (d, 1H, oxazine-H), 6.5 (d, 1H, oxazine-H) and 6.7–
7.3 (m, 12H, Ar H). Its MS spectrum gave the molecular ion peak at
m/z 383. (cf. Experimental Section) (Scheme 2). Thiation of compound
1 with phosphorus pentasulfide in dry pyridine afforded [1,3]dithiole
derivative 12. The structure of compound 12 was confirmed from the
spectral data. The IR spectrum showed the absence of a C O band.
The1H NMR spectrum showed signals at (δ, ppm) 4.9 (s, 1H, dithiol-H),
6.4 (s, 1H, dithiol-H) and 7.0–7.3 (m, 7H, Ar H). Its MS spectrum gave
the molecular ion peak at m/z 296.
Antiviral Screening
Preparation of Synthetic/Compounds for Bioassay
Tested compounds were dissolved as 100 mg each in 1 ml of 10%
DMSO in water. The final concentration was 100 µg/µl (Stock solution).
The dissolved stock solutions were sterilized by addition of 50 µg/ml
antibiotic-antimycotic mixture (10,000 U penicillin G sodium, 10,000 µg
streptomycin sulfates, and 250 µg amphotericin B, PAA Laboratories
GmbH, Austria).
Cell Culture. African green monkey, kidney-derived cells (Vero), and
human hepatoma cell line (HepG2) were used. The cells were propa-
gated in Dulbeccos’ Minimal essential medium; DMEM supplemented
with 10% Foetal bovine serum, and 1% antibiotic-antimycotic mixture.
The pH was adjusted at 7.20–7.40 by 7.50% sodium bicarbonate solu-
tion. The mixture was sterilized by filtration through 0.2 µm pore size
nitrocellulose membrane.
Viruses. Herpes Simplex Virus type-1 and Hepatitis A Virus (MBB
strain) were obtained from Environmental Virology Lab., Department
of Water Pollution Research, National Research Centre, Cairo, Egypt.
Cytotoxicity Assay. Cytotoxicity was assayed for both dimethyl sul-
foxide (DMSO) and the tested compounds. Serial dilutions were pre-
pared and inoculated on Vero cells grown in 96 well tissue culture plates.
The maximum tolerated concentration (MTC) for each compound was
determined by both cell morphology and cell viability by staining with
tryban blue dye.
Plaque Reduction Assay. A 6-well plate was cultivated with cell cul-
ture (105cell/ml) and incubated for 2 days at 37◦C. HAV was diluted to
give 104PFU/ml final concentrations for each virus and mixed with the

Oxiranyl Thiophenpropanone
161
tested compound at the previous concentration and incubated overnight
at 4◦C. Growth medium was removed from the multiwell plate, and
virus-compound mixture was inoculated (100 µl /well). After 1 h contact
time, the inoculum was aspirated, and 3 ml of MEM with 1% agarose
was overlaid the cell sheets. The plates were left to solidify and incu-
bated at 37◦C until the development of virus plaques. Cell sheets were
fixed in 10% formalin solution for 2 h and stained with crystal violet
stain. Control virus and cells were treated identically without chemical
compound. Virus plaques were counted, and the percentage of reduction
was calculated.21
Plaque infectivity assay was carried out to test compounds 2a,b, 3,
4, 5, 6 7, 8, 9, 10, 11a,b, and 12 for antiviral activity. The test was per-
formed to include the three possibilities for antiviral activity: virucidal
effect, virus adsorption, and an effect on virus replication for HSV-1.
It was observed that, compounds 2a, 4, 7, 8, and 9 revealed the high-
est anti-HSV-1 activity in comparison with Acyclovir as a control (Fig-
ure 1). In general, compounds 8 and 9 showed the highest effect on
HSV-1 than the other tested compounds, where their antiviral activity
increased from 60%, 64% at concentration of 20 µg/105 cells to 86%,
88% at concentration of 40 µg/105 cells, respectively. Compounds 5, 6,
10, 11a,b, and 12 didn’t show any activity against HSV-1.
FIGURE 1 Effect of novel derivatives on HSV-1.

162
H. H. Sayed and M. A. Ali
EXPERIMENTAL
All melting points were uncorrected and were measured using an Elec-
trothermal IA 9100 apparatus. Analytical data were performed by Vario
El Mentar apparatus, organic microanalysis section, National Research
Centre, Cairo, Egypt. Their results were found to be in agreement with
the calculated values ( 0.3). The IR spectra (KBr) were recorded on
1
a Pye Unicam Sp-1000 spectrophotometer. H NMR spectra were de-
1
termined on a Varian H-Gemini 200 in DMSO-d6, and the chemical
shifts were expressed in ppm relative to TMS as internal reference.
Mass spectra were run at 70 eV on GC MSQR 1000Ex.
[3-(4-Chlorophenyl)oxiranyl]thiophen-yl-propanone (1)
Hydrogen peroxide (9 ml, 36%) was added dropwise to a mixture of 3-
(4-chlorophenyl)-1-thiophen-2-ylpropenone (2.48 g, 10 mmol) in acetone
(30 ml), and methanol (10 ml) containing NaOH (1 g) at 10–15◦C with
stirring for 2 h. The solid substance was filtered off, washed with water
and crystallized from methanol. White needle crystals were obtained
to give compound 1 (80%); m.p. 119–120◦C. IR spectrum (KBr, ν, cm−1):
1693 (C O);1H NMR spectrum (CDCl3, δ ppm): 3.70 (d, 1H, oxiranyl
ring proton), 3.90 (d, 1H, other oxiranyl rang proton) and 6.90–7.55
(m, 7H, Ar H); MS, m/z (%): 264 (M+, 70). Analysis for C13H9ClO2S
(264.73): required C, 58.98; H, 3.43; Cl, 13.39; S, 12.11; found C, 58.90;
H, 3.42; Cl, 13.36; S, 12.09.
5-(4-Chlorophenyl)-3-thiophen-2-yl-4,5-dihydro-1H-pyrazol-
4-ol (2a)
A mixture of compound 1 (1.32 g, 5 mmol) and hydrazine hydrate
(0.4 ml, 10 mmol) was refluxed in 25 ml of absolute ethanol for 3 h. The
solid substance was filtered off and crystallized from ethanol, to give
compound 2a as yellow crystals (70%); m.p. 133–134◦C. IR spectrum
(KBr, ν, cm−1): 3100–3125 (NH), 3320–3380 (OH);1H NMR spectrum
(CDCl3, δ ppm): 3.85 (d, 1H, C4-H), 4.00 (d, 1H, C5-H) and 7.0–7.35
(m, 7H, Ar-H), 9.4 (s, 1H, NH of pyrazole, D2O exchangeable), 10.2 (s,
1H, OH, D2O exchangeable); MS, m/z (%): 278 (M+, 25). Analysis for
C13H11ClN2OS (278.76): required C, 56.01; H, 3.98; Cl, 12.72; N, 10.05;
S, 12.11; found C, 56.30; H, 3.96; Cl, 12.52; N, 10.00; S, 12.39.
5-(4-Chlorophenyl)-1-phenyl-3-thiophen-2-yl-4,5-dihydro-1H-
pyrazol-4-ol (2b)
A mixture of compound 1 (1.32 g, 5 mmol) and phenyl hydrazine (1.06
ml, 10 mmol) was refluxed in 30 ml of absolute ethanol for 2 h. The

Oxiranyl Thiophenpropanone
163
reaction mixture was cooled. The solid substance was filtered off and
crystallized from dioxane to give compound 2b ( 85%); m.p. 197–198◦C.
IR spectrum (KBr, ν, cm−1): 3330–3390 (OH);1H NMR spectrum (CDCl3,
δ ppm): 3.85 (d, 1H, C4-H), 4.00 (d, 1H, C5-H) and 7.1–7.4 (m, 7H,
Ar-H), 10.35 (s, 1H, OH, D2O exchangeable); MS, m/z (%): 354 (M+,
50). Analysis for C19H15ClN2OS (354.85): required C, 64.31; H, 4.26;
Cl, 9.99; N, 7.89; S, 9.04; found C, 64.13; H, 4.22; Cl, 10.12; N, 7.70;
S, 9.00.
5-(4-Chlorophenyl)-3-thiophen-2-yl-4,5-dihydroisoxazol-4-
ol (3)
A mixture of compound 1 (1.32 g, 5 mmol), hydroxylamine hydrochloride
(0.35 g, 5 mmol) was stirred under reflux in ethanolic sodium hydroxide
(0.5 g, 30 ml) for 2 h. The reaction mixture was cooled and poured into
water (100 ml).The solid substance was filtered off and crystallized from
methanol to give compound 3 ( 60%); m.p. 143–144◦C. IR spectrum (KBr,
ν, cm−1): 3325–3390 (OH);1H NMR spectrum (CDCl3, δ ppm): 3.80 (d,
1H, C4-H), 4.6 (d, 1H, C5-H) and 7.10–7.38 (m, 7H, Ar-H), 10.35 (s,
1H, OH, D2O exchangeable); MS, m/z (%): 279 (M+, 30). Analysis for
C13H10ClNO2S (279.74): required C, 55.82; H, 3.60; Cl, 12.67; N, 5.01;
S, 11.46; found C, 55.60; H, 3.55; Cl, 12.45; N, 4.88; S, 11.33.
4-(4-Chlorophenyl)-6-thiophen-2-yl-2-thioxotetrahydro-
pyrimidin-5-one (4)
A mixture of compound 1 (1.32 g, 5 mmol), thiourea (0.76 g, 10 mmol)
was refluxed in ethanolic sodium hydroxide (1 g, 30 ml) for 3 h. The
reaction mixture was cooled and poured into water (100 ml), extracted
with benzene (50 ml), then dried with (anhydrous Na2SO4). The in-
organic was filtered off, and the mother liquor was concentrated under
reduced pressure, and yellowish white crystals were obtained which re-
crystallized from dioxane to give compound 4 ( 60%); m.p. 206–207◦C.
IR spectrum (KBr, ν, cm−1): 3115–3180 (2NH), 1700 (C O);1H NMR
spectrum (CDCl3, δ ppm): 5.6 (s, 2H, pyrimidine-H), 6.6–7.2 (m, 7H,
Ar-H), 9.8 (s, 1H, NH, D2O exchangeable), 11.0 (s, 1H, NH, D2O ex-
changeable); MS, m/z (%): 322 (M+, 9). Analysis for C14H11ClN2OS2
(322.83): required C, 52.09; H, 3.43; Cl, 10.98; N, 8.68; S, 19.87; found
C, 51.89; H, 3.44; Cl, 11.12; N, 8.70; S, 20.00.
5-(4-Chlorophenyl)-7-thiophen-2-yl-7H-thiazolo[3,2-a]
pyrimidine-3,6-dione (5)
A mixture of compounds 4 (1.61 g, 5 mmol) with chloroacetic acid (0.96 g,
10 mmol) and anhydrous sodium acetate (3 g) was refluxed in glacial

164
H. H. Sayed and M. A. Ali
acetic acid (30 ml)/ acetic anhydride (10 ml) for 3 h. The reaction mixture
was cooled and poured gradually with stirring into cold water (100 ml).
The formed solid was filtered off and recrystallized from ethanol to
give compound 5 (55%); m.p. 167–168◦C. IR spectrum (KBr, ν, cm−1):
1696 (C O), 1705 (C O);1H NMR spectrum (CDCl3, δ ppm): 3.40 (s,
2H, thiazole-H), 5.7 (s, 2H, pyrimidine-H), 7.0–7.4 (m, 7H, Ar-H); MS,
m/z (%): 362 (M+, 7.5). Analysis for C16H11ClN2O2S (362.86): required
C, 52.96; H, 3.06; Cl, 9.77; N, 7.72; S, 17.67; found C, 52.70; H, 3.00; Cl,
9.99; N, 7.92; S, 17.55.
2-(4-Chlorobenzylidene)-5-(4-chloro-phenyl)-7-thiophen-2-yl-
7H-thiazolo[3,2-a]pyrimidine-3,6-dione (6)
Method A
A mixture of compounds 5 (1.81 g, 5 mmol), 4-chlorobenzaldehyde
(0.7 g, 5 mmol) and anhydrous sodium acetate (3 g) was refluxed in
glacial acetic acid (30 ml) / acetic anhydride (10 ml) mixture for 3 h.
The reaction mixture was cooled and poured gradually with stirring into
cold water (100 ml). The formed solid was filtered off and recrystallized
from acetic acid to give compound 6 (65%); m.p. 227–228◦C. IR spectrum
(KBr, ν, cm−1): 1692 (C O), 1710 (C O); 1H NMR spectrum (DMSO-d6,
δ ppm): 5.8 (s, 2H, pyrimidine-H), 7.0–7.3 (m, 11H, Ar-H), 7.8 (s, 1H,
benzylic-H).
Method B
A mixture of compounds 4 (1.61 g, 5 mmol), chloroacetic acid (0.96 g,
10 mole), 4-chloro benzaldehyde (0.7 g, 5 mmol) and anhydrous sodium
acetate (3 g) was refluxed in glacial acetic acid (30 ml)/acetic anhydride
(10 ml) mixture for 3 h. The reaction mixture was cooled and poured
gradually with stirring into cold water (100 ml). The formed solid was
filtered off and recrystallized from acetic acid to give compound identical
in all aspects with an authentic sample (m.p., mixed m.p., and tlc).
5-(4-Chlorophenyl)-4-hydroxy-3-thiophen-2-yl-4,5-
dihydropyrazol-1-Thiocarboxilic Acid Amide (7)
A mixture of compound 1 (1.32 g, 5 mmol) and thiosemicarbazide (0.46
ml, 5 mmol) was refluxed in 25 ml of absolute ethanol for 2 h. The
solid substance was filtered off and crystallized from ethanol to give
compound 7 as orange crystals ( 80%); m.p. 194–195◦C. IR spectrum
(KBr, ν, cm−1): 3110–3190 (NH2), 3340–3395 (OH);1H NMR spectrum
(CDCl3, δ ppm): 3.77 (d, 1H, C4-H), 4.15 (d, 1H, C5-H), 4.8 (br, 2H,
NH2, D2O exchangeable), 7.0–7.65 (m, 7H, Ar-H), 10.0 (s, 1H, OH, D2O

Oxiranyl Thiophenpropanone
165
exchangeable); MS, m/z (%): 237 (M+, 12). Analysis for C14H12ClN3OS2
(337.85): required C, 49.77; H, 3.58; Cl, 10.49; N, 12.44; S, 18.98; found
C, 49.47; H, 3.55; Cl, 10.52; N, 12.50; S, 19.20.
5-(4-Chlorophenyl)-4-hydroxy-3-thiophen-2-yl-4,5-
dihydropyrazol-1-thiocarboxilic Acid
(2,3,4,5,6-Pentahydroxyhexylidene)amide (8)
To a solution of D-glucose (0.83 g, 5 mmol) in water (0.5 ml), compound
7 (1.63 g, 5 mmol) in absolute ethanol (30 ml) and few drops of acetic
acid was added. The mixture was stirred at 50◦C for 4 h. The product
that separated out on cooling was filtered off and washed with water,
followed by ethanol and dried to give compound 8 ( 40%); m.p. 163–
164◦C. IR spectrum (KBr, ν, cm−1): 3320–3380 (OH groups);1H NMR
spectrum (CDCl3, δ ppm): 3.30–3.63 (m, 11H, 6-CH-glucose +5OH, D2O
exchangeable), 3.8 (d, 1H, C4-H), 4.1 (s, 1H, C5-H), 7.0–7.3 (m, 7H, Ar-
H), 7.8 (d, 1H, hydrazone), 10.3 (s, 1H, OH, D2O exchangeable). Analysis
for C20H22ClN3O6S2 (499.06): required C, 48.04; H, 4.44; Cl, 7.09; N,
8.40; S, 12.83; found C, 48.34; H, 4.50; Cl, 7.00; N, 8.10; S, 12.53.
5-(4-Chlorophenyl)-4-hydroxy-3-thiophen-2-yl-4,5-
dihydropyrazol-1-thiocarboxilic Acid
(2,3,4,5-Tetrahydroxypentylidene)amide (9)
To a solution of arabinose (0.74 g, 5 mmol) in water (0.5 ml), compound
8 (1.63 g, 5 mmol) in absolute ethanol (30 ml) and few drops of acetic
acid was added. The mixture was stirred at 50◦C for 5 h. The product
that separated out on cooling was filtered off and washed with water,
followed by ethanol and dried to give compound 9 (45%); m.p. 163–
164◦C. IR spectrum (KBr, ν, cm−1): 3280–3350 (OH groups);1H NMR
spectrum (DMSO-d6, δ ppm): 3.35–3.68 (m, 9H, 5-CH-arabinose+4OH,
D2O exchangeable), 3.8 (d, 1H, C4-H), 4.0 (d, 1H, C5-H) and 7.1–7.4 (m,
7H, Ar-H), 7.9 (s, 1H, hydrazone), 10.4 (s, 1H, OH, D2O exchangeable).
Analysis for C19H20ClN3O5S2 (469.96): required C, 48.56; H, 4.29; Cl,
7.54; N, 8.94; S, 13.65; found C, 48.30; H, 4.32; Cl, 7.60; N, 9.00; S, 13.35.
4-(4-Chlorophenyl)-2-thioxo[1,3]oxathiolane-5-yl]thiophen-2-
yl methanone (10)
A mixture of compound 1 (1.32 g, 5 mmol) and CS2 (5 ml) was stirred
in absolute ethanol containing H2O2 (36%) as a catalyst (1 ml), and
then refluxed for 2 h. After cooling the product was filtered off and
crystallized from ethanol to give compound 10 (70%); m.p. 183–184◦C.

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H. H. Sayed and M. A. Ali
IR spectrum (KBr, ν, cm−1): 1695 (C O);1H NMR spectrum (DMSO-d6,
δ ppm): 4.2 (d, 1H, oxathiolane-H), 4.8 (d, 1H, oxathiolane-H) and 6.9–
7.4 (m, 7H, Ar-H); MS, m/z (%): 340 (M+, 10). Analysis for C14H9ClO2S3
(340.87): required C, 49.33; H, 2.66; Cl, 10.40; S, 28.22; found C, 49.60;
H, 2.60; Cl, 10.60; S, 28.50.
4-(4-Chlorophenyl)-3-phenyl-6-thiophen-2-yl-3,4-dihydro
[1,3]oxazine-2-thione (11a)
A mixture of compound 1 (1.32 g, 5 mmol) and phenyl isothiocyanate
(0.67 ml, 5 mmol) was refluxed in dry pyridine for 6 h. After cooling the
reaction mixture was poured gradually with stirring into cold water
(100 ml). The solid substance was filtered off and recrystallized from
1
benzene to give compound 11a (50%); m.p. 204–205◦C. H NMR spec-
trum (DMSO-d6, δ ppm): 4.6 (d, 1H, oxazine-H), 6.5 (d, 1H, oxazine-H)
and 6.7–7.3 (m, 12H, Ar-H); MS, m/z (%): 383 (M+, 8). Analysis for
C20H14ClNOS2 (383.92): required C, 62.57; H, 3.68; Cl, 9.23; N, 3.65; S,
16.70; found C, 62.72; H, 3.80; Cl, 9.00; N, 3.80; S, 17.00.
4-(4-Chlorophenyl)-3-phenyl-6-thiophen-2-yl-3,4-dihydro
[1,3]oxazine-2-thione (11b)
A mixture of compound 1 (1.32 g, 5 mmol) and methyl isothiocyanate
(0.37 ml, 5 mmol) was refluxed in dry pyridine for 6 h. After cooling the
reaction mixture was poured gradually with stirring into cold water
(100 ml). The solid substance was filtered off and recrystallized from
benzene to give compound 11a ( 55%); m.p. 188–189◦C. 1H NMR spec-
trum (CDCl3, δ ppm): 2.5 (s, 3H, CH3), 4.7 (d 1H, CH-Ar), 6.8 (d, 1H,
C CH) and 7.0–7.25 (m, 7H, Ar-H). MS, m/z (%): 321 (M+, 7.8). Analy-
sis for C15H12ClNOS2 (321.85): required C, 55.98; H, 3.76; Cl, 11.02; N,
4.35; S, 19.93; found C, 56.20; H, 3.80; Cl, 11.00; N, 4.50; S, 20.00.
2-(4-Chlorophenyl)-4-thiophen-2-yl[1,3]dithiol (12)
A mixture of compound 1 (1.32 g, 5 mmol) and P2S5(1.11 g, 5 mmol)
was refluxed in dry benzene for 3 h. The reaction mixture was filtered
off and the filtrate was concentrated under reduced pressure. The solid
substance was recrystallized from methanol to give compound 12 (50%);
m.p 143–144◦C. 1H NMR spectrum (CDCl3, δ ppm): 4.9 (s, 1H, dithiol-
H), 6.4 (s, 1H, dithiol-H) and 7.0–7.3 (m, 7H, Ar-H); MS, m/z (%): 296
(M+, 8). Analysis for C13H9ClS3 (295.89): required C, 52.60; H, 3.06; Cl,
11.94; S, 32.41; found C, 52.30; H, 3.00; Cl, 12.20; S, 32.63.

Oxiranyl Thiophenpropanone
167
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