Some observations on the base-catalyzed cyclocondensation of 2,6-Dihalobenzaldehydes, ethyl cyanoacetate, and thiourea

Article abstract of DOI:10.1080/00397910903098730

The reaction of 2,6-difluorobenzaldehyde, 2-chloro-6-fluorobenzaldehyde, or 2,6-dichlorobenzaldehyde and ethyl cyanoacetate and thiourea, in the presence of potassium carbonate, yielded a mixture of the cis-and trans-5,6-dihydro-2- thiouracil derivatives 4a-c. Compounds 4a-c, which were found to be resistant to atmospheric oxidation even at high temperatures, were successfully dehydrogenated to 5a-c via prolonged heating with chloranil in toluene. Meanwhile, oxidation of the dihydro derivative 4b by heating in dimethylsufphoxide for 10 min yielded the corresponding 2-thiouracil 5b in 73% yield, in addition to the disulfide derivative 7 as a minor product. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910903098730

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Some Observations on the Base-
Catalyzed Cyclocondensation of
2,6-Dihalobenzaldehydes, Ethyl
Cyanoacetate, and Thiourea
Mohamed A. Al-Omar a , Abdul-Rahman M. Al-Obaid a , Nasser R. El-
Brollosy a & Ali A. El-Emam a
a Department of Pharmaceutical Chemistry , College of Pharmacy,
King Saud University , Riyadh, Saudi Arabia
Published online: 23 Apr 2010.
To cite this article: Mohamed A. Al-Omar , Abdul-Rahman M. Al-Obaid , Nasser R. El-Brollosy
& Ali A. El-Emam (2010) Some Observations on the Base-Catalyzed Cyclocondensation of 2,6-
Dihalobenzaldehydes, Ethyl Cyanoacetate, and Thiourea, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 40:10, 1530-1538, DOI:
10.1080/00397910903098730
To link to this article: http://dx.doi.org/10.1080/00397910903098730
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Synthetic Communications1, 40: 1530–1538, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903098730
SOME OBSERVATIONS ON THE BASE-CATALYZED
CYCLOCONDENSATION OF
2,6-DIHALOBENZALDEHYDES, ETHYL
CYANOACETATE, AND THIOUREA
Mohamed A. Al-Omar, Abdul-Rahman M. Al-Obaid,
Nasser R. El-Brollosy, and Ali A. El-Emam
Department of Pharmaceutical Chemistry, College of Pharmacy,
King Saud University, Riyadh, Saudi Arabia
The reaction of 2,6-difluorobenzaldehyde, 2-chloro-6-fluorobenzaldehyde, or 2,6-
dichlorobenzaldehyde and ethyl cyanoacetate and thiourea, in the presence of potassium
carbonate, yielded a mixture of the cis- and trans-5,6-dihydro-2-thiouracil derivatives
4a–c. Compounds 4a–c, which were found to be resistant to atmospheric oxidation even
at high temperatures, were successfully dehydrogenated to 5a–c via prolonged heating with
chloranil in toluene. Meanwhile, oxidation of the dihydro derivative 4b by heating in
dimethylsufphoxide for 10 min yielded the corresponding 2-thiouracil 5b in 73% yield, in
addition to the disulfide derivative 7 as a minor product.
Keywords: Antimicrobial activity; cyclocondensation; 5,6-dihydro-2-thiouracils; 2-thiouracils
INTRODUCTION
A pyrimidine nucleus constitutes the active part of several biologically active
compounds. 2-Thiouracils have long been known for their antithyroid activity.[1,2]
In addition, potent antiviral activity was observed among several pyrimidine nonnu-
cleoside and pyrimidinethiol derivatives.[3–8] Moreover, marked antibacterial[9,10]
and antimycotic activity[11,12] was displayed by several 5-cyano-6-aryl-2-thiouracil
derivatives. The structure activity studies on several biologically active derivatives
revealed that the presence of 2,6-dihalophenyl substituents greatly improved the
antiviral activity.[5,13,14] In continuation of our interest in the chemical and pharma-
cological properties of pyrimidinethiols and their related derivatives,[15–20] we synthe-
sized new 5-cyano-6-(2,6-dihalophenyl)-2-thiouracils as potential chemotherapeutic
agents via the previously reported general procedure of Kambe et al.,[21] which
utilized the reaction of the corresponding aldehyde, ethyl cyanoacetate, and thiourea
in the presence of potassium carbonate in ethanol to yield the target derivatives.
Received May 15, 2009.
Address correspondence to Ali A. El-Emam, Department of Pharmaceutical Chemistry, College of
Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. E-mail: elemam5@hotmail.com
1530

5-CYANO-2-THIOURACILS
1531
RESULTS AND DISCUSSION
The reaction of 2,6-difluorobenzaldehyde 1a, 2-chloro-6-fluorobenzaldehyde
1b, or 2,6-dichlorobenzaldehyde 1c with ethyl cyanoacetate 2 and thiourea 3, in
the presence of potassium carbonate, yielded an inseparable mixture of the cis-
and trans-5,6-dihydrothiouracil derivatives 4a–c rather than the expected 2-thioura-
cils 5a–c. Attempted two-step preparation of the target uracil derivatives 5a–c via the
reaction of the corresponding 2-cyano-3-(2,6-dihalophenyl)propenoates 6a–c with
thiourea, in ethanol, in the presence of potassium carbonate also yielded the
dihydrouracil derivatives 4a–c (Scheme 1). The structures of compounds (4a–c) were
1
based on their H NMR chemical shifts and coupling constant data,[22] in addition
to the 13C NMR and mass spectral data. The diastereomeric cis-trans ratio was
found to be dependent on the nature of the halogen. The cis-trans ratios in case of
2,6-difluorobenzaldehyde, 2-chloro-6-fluorobenzaldehyde, and 2,6-dichlorobenzal-
dehyde were found to be ca. 4:6, 2:8, and 0.8:9.2, respectively.
The NMR studies of 5,6-dihydrouracil derivatives afforded evidence for a
distorted half-chair conformation in which the NH-CO-NH-CO part of the molecule
is approximately planar.[23,24] In addition, the half-chair conformation of the
5,6-dihydrouracils has been confirmed by x-ray analysis.[25] The conformational
assignment of compounds 4a–c was mainly based on the coupling constant data
of the 1H, 5H, and 6H, which were in full agreement with previously reported
values.[23–25] In the cis conformers, the H-5 protons appeared as a doublet coupled
with the H-6 protons (JH5H6 ¼ 9.0–9.5 Hz), while the H-6 protons were shown as
doublet–doublet, indicating coupling with the H-5 and H-1 protons with coupling
constants JH5H6 ¼ 6.1–6.4 Hz and JH1H6 ¼ 4.2–4.5 Hz, respectively. In the trans con-
formers, the H-5 protons appeared as a downfield doublets coupled with the H-6
protons (JH5H6 ¼ 12.9–13.9 Hz), while the H-6 protons were shown as doublet
Scheme 1. Synthesis of compounds 4a–c.

1532
M. A. AL-OMAR ET AL.
indicating coupling with the H-5 protons with coupling constants JH5H6
12.9–13.0 Hz and no H6–H1 coupling was observed.
¼
The formation of the 2-thiouracils via one-pot condensation of aldehydes,
ethyl cyanoacetate, and thiourea in basic condition was described by Kambe
et al.[21] The reaction proceeds through the condensation of the appropriate aldehyde
A with ethyl cyanoacetate 2 to yield the intermediate 2-cyano-3-substituted-
propenoates B, which was subsequently cyclized by heating with thiourea to yield
the corresponding 5,6-dihydro-2-thiouracils C. Dehydrogenation of the dihydro-2-
thiouracils C was reported to occur through atmospheric oxidation (Scheme 2).
On the other hand, Garcia Navio et al.[26] reported the isolation of 5-cyano-6-
phenyl-5,6-dihydro-2-thiouracil under milder conditions through the reaction of
benzaldehyde, ethyl cyanoacetate, and thiourea, in ethanol, in the presence of
sodium ethoxide at room temperature. The oxidation of 5-cyano-6-phenyl-
5,6-dihydro-2-thiouracil was conducted by heating with 2,3-dichloro-5,6-dicyano-
p-benzoquinone (DDQ) in toluene. On thorough examination of experimental
procedures of these methods, it could be concluded that the oxidation of the
dihydro-2-thiouracils is dependent on the reaction temperature (thermal dehydro-
genation) rather than atmospheric oxidation. This finding is also supported by the
procedures adopted for purification of the reaction products, whereas the product
obtained by Kambe et al.[21] was crystallized from acetic acid (bp 117–118 ꢀC) and
the product of Garcia Navio et al.[26] was crystallized from ethanol (bp 78 ꢀC).
Although the formation of 2-thiouracils seemed to be a thermal dehydrogena-
tion, the 5,6-dihydro-2-thiouracils 4a–c were resistant to thermal dehydrogenation
even with prolonged heating at 100 ꢀC up to 24 h. In addition, these derivatives were
stable to atmospheric oxidation. Meanwhile, the dehydrogenated derivatives 5a–c
were successfully obtained in fair yields by heating compounds 4a–c with tetra-
chloro-p-benzoquinone (chloranil) in toluene.[27] Because of the previously reported
oxidative properties of dimethylsulfoxide,[28,29] in addition to its high boiling point, it
Scheme 2. Proposed pathway for the formation of 2-thiouracils.

5-CYANO-2-THIOURACILS
1533
Scheme 3. Oxidation of compounds 4a–c with chloranil and DMSO.
was used in an attempt to oxidize compound 4b. Thus, heating compound 4b with
dimethylsulfoxide for 10 min resulted in the formation of the corresponding 2-
thiouracil 5b in good yield (73%), in addition to its disulfide derivative 7 as a minor
product (11%) (Scheme 3).
In conclusion to the present study, we believe that the base-catalyzed reaction
of aldehydes, ethyl cyanoacetate, and thiourea is not a general reaction for the prep-
aration of the corresponding 5-cyano-2-thiouracils. The reaction product depends
mainly on the nature of the aldehyde and the reaction conditions. The high stability
of the 6-(2,6-dihalophenyl)-5,6-dihydro-2-thiouracils to atmospheric and thermal
oxidation may be attributed to the steric hindrance around the C-6 resulting
from the bulky 2,6-dihalophenyl substituents in addition to possible intramolecular
hydrogen bonding between the halogen and 6-H hydrogen.
Compounds 4a–c, 5a–c, and 7 were tested for their in vitro antimicrobial
activity against a panel of standard pathogenic strains of the Institute of
Fermentation of Osaka (IFO), namely the Gram-positive bacteria Staphylococcus
aureus IFO 3060, Bacillus subtilis IFO 3007, and Micrococcus luteus IFO 3232, the
Gram-negative bacteria Escherichia coli IFO 3301 and Pseudomonas aeuroginosa
IFO 3448, and the yeast-like pathogenic fungus Candida albicans IFO 0583. The
screening was carried out using the agar disc-diffusion method.[30] None of the tested
compounds displayed significant activity relative to the broad-spectrum antibacterial
antibiotic ampicillin trihydrate and the antifungal drug clotrimazole.
EXPERIMENTAL
Melting points (ꢀC, uncorrected) were determined using a Fisher–Johns
melting-point apparatus. Infrared (IR) spectra were recorded in KBr disc using a

1534
M. A. AL-OMAR ET AL.
Jasco Fourier transform (FT)–IR 460 Plus spectrometer and expressed in wave
number (cmꢁ1). NMR spectra were obtained on a Bruker AC 500 Ultra Shield
1
NMR spectrometer at 500 MHz for H and 125 MHz for 13C; the chemical shifts
are expressed in d (ppm) downfield from tetramethylsilane (TMS). Electron-impact
mass spectra were recorded on a Shimadzu GC–MS-QP 5000 instrument. Elemental
analyses (C, H, N, S) were in full agreement with the proposed structures within
ꢂ0.4% of the theoretical values.
5-Cyano-6-(2,6-dihalophenyl)-5,6-dihydro-2-thiouracils (4a–c)
Method A
A mixture of the appropriate 2,6-dihalobenzaldehyde 1a–c (0.01 mol), ethyl
cyanoacetate 2 (1.13 g, 0.01 mol), thiourea 3 (0.76 g, 0.01 mol), and potassium car-
bonate (1.38 g, 0.01 mol), in ethanol (30 mL), was heated under reflux for 6 h. On
cooling, the separated precipitate was filtered, washed with ether, and dried. The
obtained solid was added to water (20 mL), and the mixture was heated at
80–90 ꢀC until a clear solution was obtained. After cooling, the solution was acidified
with acetic acid, and stirring was continued for 30 min. The deposited precipitate was
filtered, washed with cold water, dried, and crystallized from ethanol.
Compound 4a. Yield: 2.24 g (84%), mp: 215–217 ꢀC. IR, (cmꢁ1): 3238 (NH),
1
=
3082 (Ar-CH), 2909 (CH), 2228 (CN), 1710 (C O). H NMR (DMSO-d6): d 5.03 (d,
0.6 H, H-5, JH5H6 ¼ 13.0 Hz, trans), 5.42 (d, 0.4 H, H-5, JH5H6 ¼ 9.0 Hz, cis), 5.58 (dd,
0.4 H, H-6, JH5H6 ¼ 6.1 Hz, JH6H1 ¼ 4.3 Hz, cis), 5.71 (d, 0.6 H, H-6,
JH5H6 ¼ 13.0 Hz, trans), 7.20–7.60 (m, 3H, Ar-H), 10.21 (s, 0.4 H, 3-H, cis), 10.28
(s, 0.6 H, 3-H, trans). 11.74 (s, 0.6 H, 1-H, trans), 11.92 (s, 0.4 H, 1-H, cis). 13C
NMR: d 39.80 (C-6, cis), 39.97 (C-6, trans), 45.84 (C-5, cis), 47.06 (C-5, trans),
112.71 (CN, cis), 112.91 (CN, trans), 111.09, 132.88, 160.20, 160.49 (Ar-C), 161.80
=
=
=
=
(C O, cis), 162.43 (C O, trans), 178.28 (C S, cis), 178.84 (C S, trans). MS
(C11H7F2N3OS), m=z (rel. int.): 268 (Mþ þ 1, 37), 267 (Mþ, 99), 184 (55), 142 (100).
Compound 4b. Yield: 2.21 g (78%), mp 238–240 ꢀC. IR, (cmꢁ1): 3238 (NH),
1
=
3082 (Ar-CH), 2909 (CH), 2228 (CN), 1710 (C O). H NMR (DMSO-d6): d 5.05 (d,
0.8 H, H-5, JH5H6 ¼ 12.9 Hz, trans), 5.47 (d, 0.2 H, H-5, JH5H6 ¼ 9.4 Hz, cis), 5.71
(dd, 0.2 H, H-6, JH5H6 ¼ 6.4 Hz, JH6H1 ¼ 4.2 Hz, cis), 5.81 (d, 0.8 H, H-6,
JH5H6 ¼ 12.9 Hz, trans), 7.32–7.53 (m, 3H, Ar-H), 10.11 (s, 0.2 H, 3-H, cis), 10.22
(s, 0.8 H, 3-H, trans). 11.68 (s, 0.8 H, 1-H, trans), 11.87 (s, 0.2 H, 1-H, cis). 13C
NMR: d 36.14 (C-5, cis), 37.65 (C-5, trans), 49.51 (C-6, cis), 50.26 (C-6, trans),
113.27 (CN, cis), 114.23 (CN, trans), 115.74, 120.26, 126.48, 132.27, 134.69, 159.07
=
=
=
=
(Ar-C), 159.77 (C O, trans), 160.38 (C O, cis), 177.81 (C S, cis), 178.28 (C S,
trans). MS (C11H7ClFN3OS), m=z (rel. int.): 285 (Mþ þ 2, 37), 284 (Mþ þ 1, 15)
283 (Mþ, 95), 202 (18), 200 (49), 160 (38), 158 (100).
Compound 4c. Yield: 2.28 g (76%), mp 212–214 ꢀC. IR, (cmꢁ1): 3239 (NH),
5
6
1
=
3079 (Ar-CH), 2902 (C H, C H), 2222 (CN), 1712 (C O). H NMR (DMSO-d6): d
5.18 (d, 0.92 H, H-5, JH5H6 ¼ 13.9 Hz, trans), 5.61 (d, 0.08 H, H-5, JH5H6 ¼ 9.5 Hz,
cis), 5.85 (dd, 0.08 H, H-6, JH5H6 ¼ 6.3 Hz, JH6H1 ¼ 4.5 Hz, cis), 6.08 (d, 0.92H,

5-CYANO-2-THIOURACILS
1535
H-6, JH5H6 ¼ 13.0 Hz, trans), 7.47–7.57 (m, 3H, Ar-H), 10.17 (s, 0.08 H, 3-H, cis),
10.20 (s, 0.92 H, 3-H, trans), 11.71 (s, 0.92 H, 1-H, trans), 11.86 (s, 0.08 H, 1-H,
cis). 13C NMR: d 5.08 (C-5, cis), 36.65 (C-5, trans), 51.55 (C-6, cis), 52.73 (C-6,
trans), 114.50 (CN, trans), 115.0 (CN, cis), 129.48, 130.82, 132.31, 135.98 (Ar-C),
=
=
=
=
159.41 (C O, cis), 159.91 (C O, trans), 177.81 (C S, cis), 178.16 (C S, trans).
MS (C11H7Cl2N3OS), m=z (rel. int.): 303 (Mþ þ 4, 15), 301 (Mþ þ 2, 70), 299 (Mþ,
99), 266 (25), 264 (64), 174 (100).
Method B
A solution of the appropriate 2,6-dihalobenzaldehyde 1a–c (0.01 mol), ethyl
cyanoacetate 2 (1.13 g, 0.01 mol), and triethylamine (0.5 mL), in ethanol (15 mL),
was stirred at room temperature for 6 h and allowed to stand overnight. The sepa-
rated crystalline solid was filtered, washed with cold ethanol (5 mL), and dried to yield
the corresponding 2-cyano-3-(2,6-dihalophenyl)propenoates 6a–c in 90–94% yield.
A mixture of the appropriate compound 6a–c, thiourea 3 (0.76 g, 0.01 mol),
and potassium carbonate (1.38 g, 0.01 mol), in ethanol (20 mL), was heated under
reflux for 6 h. On cooling, the separated precipitate was filtered and dried. The
obtained solid was added to water (20 mL), and the mixture was heated at
80–90 ꢀC until a clear solution was obtained. After cooling, the solution was acidified
with acetic acid, and stirring was continued for 30 min. The deposited precipitate was
filtered, washed with cold water, dried, and crystallized from ethanol.
Compound 6a. Mp: 60–62 ꢀC. IR, (cmꢁ1): 3086 (Ar-CH), 3026 (CH C),
=
1
2909, 2850 (CH3, CH2), 2218 (CN), 1717 (C O), 1210 (C-O). H NMR (CDCl3):
=
d 1.42 (t, 3H, CH3, J ¼ 7.5 Hz), 4.41 (q, 2H, CH2, J ¼ 7.5 Hz), 7.05–7.54 (m, 3H,
Ar-H), 8.29 (s, 1H, CH¼). 13C NMR: d 13.90 (CH3), 63.34 (CH2), 113.73 (CN),
=
110.56 (¼C), 111.81, 112.26, 133.88, 161.56 (Ar-C), 159.64 (CH¼), 161.21 (C O).
MS (C12H9F2NO2), m=z (rel. int.): 237 (Mþ, 26), 218 (34), 192 (46), 166 (100), 164
(28), 127 (47).
Compound 6b. Mp: 71–73 ꢀC. IR, (cmꢁ1): 3103 (Ar-CH), 3022 (CH C),
=
1
2911, 2850 (CH3, CH2), 2220 (CN), 1723 (C O), 1221 (C-O). H NMR (CDCl3):
=
d 1.42 (t, 3H, CH3, J ¼ 7.5 Hz), 4.41 (q, 2H, CH2, J ¼ 7.5 Hz), 7.16–7.47 (m, 3H,
Ar-H), 8.30 (s, 1H, CH¼). 13C NMR: d 13.80 (CH3), 63.16 (CH2), 115.33 (CN),
112.62 (¼C), 120.02, 125.78, 132.99, 133.07, 135.27, 158.99þ(Ar-C), 160.99 (CH¼),
þ
=
161.03 (C O). MS (C12H9ClFNO2), m=z (rel. int.): 255 (M þ 2, 8), 253 (M , 21),
218 (55), 190 (100).
Compound 6c. Mp: 68–70 ꢀC. IR, (cmꢁ1): 3101 (Ar-CH), 3035 (CH C),
=
1
=
2981, 2880 (CH3, CH2), 2226 (CN), 1722 (C O). H NMR (CDCl3): d 1.40 (t,
3H, CH3, J ¼ 7.5 Hz), 4.38 (q, 2H, CH2, J ¼ 7.5 Hz), 7.23–7.56 (m, 3H, Ar-H),
8.28 (s, 1H, CH¼). 13C NMR: d 13.72 (CH3), 61.22 (CH2), 113.25 (CN), 110.88
=
(¼C), 125.40, 129.52, 133.42, 135.27 (Ar-C), 159.82 (CH¼), 160.01 (C O). MS
(C12H9Cl2NO2), m=z (rel. int.): 273 (Mþ þ 4, 1), 271 (Mþ þ 2, 4), 269 (Mþ, 13),
224 (65), 126 (33), 124 (100).

1536
M. A. AL-OMAR ET AL.
5-Cyano-6-(2,6-dihalophenyl)-2-thiouracils (5a–c)
Chloranil (1.0 g) was added to a suspension of compound 4a, 4b, or 4c
(0.01 mol), in dry toluene (15 mL), and the mixture was heated under reflux with stir-
ring for 6 h. The solvent was then evaporated in vacuo, and the residue was washed
with ether and chromatographed with chloroform=petroleum ether (3:1) to yield
compounds 5a–c.
Compound 5a. Yield: 1.75 g (66%), mp 238–240 ꢀC. IR, (cmꢁ1): 3228 (NH),
1
=
3105 (Ar-CH), 2228 (CN), 1719 (C O). H NMR (DMSO-d6): d 6.95–7.21 (m, 3H,
Ar-H), 12.95 (s, 2H, NH). 13C NMR: d 98.20 (C-5), 114.05 (CN), 110.53, 113.25,
=
=
133.72, 156.60 (Ar-C), 158.75 (C O), 166.78 (C-6), 176.28 (C S). MS
(C11H5F2N3O2), m=z (rel. int.): 266 (Mþ þ 1, 13), 265 (Mþ, 100), 127 (87).
Compound 5b. Yield: 1.46 g (52%), mp 255–257 ꢀC. IR, (cmꢁ1): 3226 (NH),
1
=
3096 (Ar-CH), 2225 (CN), 1722 (C O). H NMR (DMSO-d6): d 6.92–7.06 (m, 3H,
Ar-H), 13.02 (s, 2H, NH). 13C NMR: d 95.42 (C-5), 114.23 (CN), 112.45, 122.85,
=
=
126.75, 133.27, 135.65, 157.06 (Ar-C), 158.25 (C O), 168.70 (C-6), 176.64 (C S).
MS (C11H5ClFN3O2), m=z (rel. int.): 283 (Mþ þ 2, 38), 282 (Mþ þ 1, 21), 281
(Mþ, 100), 145 (11), 143 (36).
Compound 5c. Yield: 1.01 g (34%), mp 263–265 ꢀC. IR, (cmꢁ1): 3224 (NH),
1
=
3102 (Ar-CH), 2224 (CN), 1720 (C O). H NMR (DMSO-d6): d 7.12–7.31 (m, 3H,
Ar-H), 13.01 (s, 2H, NH). 13C NMR: d 95.89 (C-5), 112.54 (CN), 125.44, 129.30,
=
=
131.70, 135.01 (Ar-C), 155.88 (C O), 164.20 (C-6), 174.85 (C S). MS (C11H5
Cl2N3O2), m=z (rel. int.): 301 (Mþ þ 4, 11), 299 (Mþ þ 2, 24), 298 (Mþ þ 1, 9), 297
(Mþ, 100), 248 (82), 161 (13), 161 (47).
Oxidation of 4b with Dimethylsulfoxide
A solution of compound 4b (2.83 g, 0.01 mol) in dimethylsulfoxide (8 mL) was
heated under reflux for 10 min and allowed to cool to room temperature. Water
(10 mL) was added to the clear solution, and the mixture was stirred for 10 min.
The separated amorphous solid was filtered, washed with water, dried, and chroma-
tographed on a silica-gel column with chloroform to yield 2.06 g of compound 5b
(73%) and 0.31 g of the disulfide 7 (11%).
Compound 7. Mp: >300 ꢀC. IR, (cmꢁ1): 3342 (NH), 3093 (Ar-CH), 2222
1
=
(CN), 1726 (C O). H NMR (DMSO-d6): d 6.98–7.44 (m, 6H, Ar-H), 11.54 (s,
2H, NH). 13C NMR: d 100.10 (C-5), 115.31 (CN), 109.98, 121.50, 124.22, 130.25,
=
=
135.18, 158.62 (Ar-C), 157.41 (C O), 164.26 (C-6), 179.45 (C S). MS (C22H8
Cl2F2N6O2S2), m=z (rel. int.): 564 (Mþ þ 4, 4), 562 (Mþ þ 2, 9), 560 (Mþ, 14), 282
(24), 280 (100), 145 (9), 143 (40).
ACKNOWLEDGMENTS
The financial support of the Research Center of the College of Pharmacy, King
Saud University (Project C.P.R.C. 174), is greatly appreciated. The authors are

5-CYANO-2-THIOURACILS
1537
greatly indebted to Dr. Elsayed E. Habib, Department of Microbiology, University
of Mansoura, Egypt, for performing the antimicrobial screening.
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therapy, X: Antithyroid compounds: Synthesis of 5- and 6-substituted 2-thiouracils from
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