Novel Mercaptopurine and Thioguanine Analogues: The Reaction of Dimethyl N-Cyanodithioiminocarbonate with Oxo- and Amino-diazoles

Article abstract of DOI:10.1081/SCC-120028352

A novel and efficient method for the synthesis of a new variety of methylsulfanyl derivatives of azoloazines and azoloazoles by the reaction of dimethyl N-cyanodithioiminocarbonate with diazoles containing oxo- and amino functions. The synthetic potential of the method is demonstrated.

Full text of DOI:10.1081/SCC-120028352

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Novel Mercaptopurine and Thioguanine
Analogues: The Reaction of Dimethyl
N‐Cyanodithioiminocarbonate with Oxo‐ and
Amino‐diazoles
Siham Y. Alqaradawi a & Galal H. Elgemeie b
a Chemistry Department, College of Science, Qatar University, Doha, Qatar
b Chemistry Department, Faculty of Science, Helwan University, Ain‐Helwan, Cairo,
Egypt
Published online: 20 Aug 2006.
To cite this article: Siham Y. Alqaradawi & Galal H. Elgemeie (2004) Novel Mercaptopurine and Thioguanine Analogues:
The Reaction of Dimethyl N‐Cyanodithioiminocarbonate with Oxo‐ and Amino‐diazoles, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 34:5, 805-815, DOI: 10.1081/
SCC-120028352
To link to this article: http://dx.doi.org/10.1081/SCC-120028352
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 5, pp. 805–815, 2004
Novel Mercaptopurine and Thioguanine
Analogues: The Reaction of Dimethyl
N-Cyanodithioiminocarbonate with
Oxo- and Amino-diazoles
Siham Y. Alqaradawi1 and Galal H. Elgemeie2,
*
1Chemistry Department, College of Science, Qatar University,
Doha, Qatar
2Chemistry Department, Faculty of Science, Helwan University,
Ain-Helwan, Cairo, Egypt
ABSTRACT
A novel and efficient method for the synthesis of a new variety of
methylsulfanyl derivatives of azoloazines and azoloazoles by the reaction
of dimethyl N-cyanodithioiminocarbonate with diazoles containing oxo-
and amino functions. The synthetic potential of the method is
demonstrated.
Key Words: Mercaptopurine; Thioguanine; 4-Aminoantipyrine;
Diazoles; Dimethyl N-cyanodithioiminocarbonate; Azoloazines;
Azoloazoles.
*
Correspondence: Galal H. Elgemeie, Chemistry Department, Faculty of Science,
Helwan University, Ain-Helwan, Cairo, Egypt; E-mail: elgemeie@hotmail.com.
805
DOI: 10.1081/SCC-120028352
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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During the course of our studies directed toward exploring the synthetic
potential of ketene dithioacetals for synthesizing new classes of novel
antimetabolites,[1,2] we have recently reported different successful approaches
for synthesis of purine analogues by the reaction of ketene dithioacetals with
active methylene functions.[3,4] In an extension of this work, the present paper
describes a novel and convenient method for the synthesis of fused imidazoles
and pyrazoles carrying a methylsulfanyl group. Derivatives of these ring
systems are interesting because they are sulfanylpurine analogues and as such
may have useful properties as antimetabolites in purine biochemical reactions.
Thus, it has been found that reaction of cyanamide I with carbon disulfide
in the presence of KOH followed by the alkylation with methyl iodide gives
the dimethyl N-cyanodithioiminocarbonate 2. Reaction of compound 2 with
2-thioxohydantoin derivatives 3a,b in refluxing ethanol containing a catalytic
amount of piperidine gives the corresponding 5-amino-7-(methylthio)-3-
thioxo-imidazo[1,5-c]imidazol-1-ones 5. The structures of 5 were established
and confirmed on the basis of their elemental analysis and spectral data (MS,
IR, 1H NMR, and 13C NMR). The formation of 5 from the reaction of 2 and
thioxohydantoins 3 is assumed to proceed via the intermediacy of acyclic
Michael adducts, which cyclize via CH3SH elimination and addition to the
cyano group to yield the final stable diazapentalene analogues 5. The course of
the reaction between 2 and 3 prompted us to investigate this reaction between
2-thioxohydantoin ketene dithioacetals 6 and cyanamide 1 under the same
conditions. The products obtained were shown to be the same as those
obtained from the reaction of 2 with 3 by their melting points and spectral data
to give the imidazo[1,5-c]imidazoles 5. The 2-thioxohydantoin ketene dithio-
acetals 6a,b were prepared by the reaction of 2-thioxohydantoin derivatives
3a,b with carbon disulfide in the presence of sodium ethoxide followed by
treatment with methyl iodide (Sch. 1). The behavior of dithioacetals 2 towards
pyrazolones was also investigated. Thus, it has been found that compound 2
react with 3-aryl-5-oxopyrazole 7 in refluxing ethanol containing catalytic
amounts of piperidine to yield the corresponding 4-(methylthio)pyrazolo[4,3-
e][1,3]oxazin-6-imine derivatives 9 in good yields. The structure of com-
pounds 9 was established on the basis of their elemental analysis and spectral
data (IR, 1H NMR, and MS). The formation of 9 from the reaction of 2 and 7 is
assumed to proceed via the initial Michael addition of the active methylene in
7 to the double bond of 2 to yield the intermediate 8. This Michael adduct then
cyclizes via CH3SH elimination followed by cyclization to the cyano group to
give the stable product 9. Compounds 9 could also be prepared by the reaction
of pyrazolone ketene ditlnoacetals 10 with cyanamide in refluxing ethanol
containing catalytic amounts of piperidine (Sch. 2). The reaction of dimethyl
N-cyanodithioiminocarbonate 2 with 4-amino-2,3-dimethyl-l-phenylpyrazo-
lin-5-one 11 in refluxing ethanol containing piperidine afforded the

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Scheme 1.
corresponding pyrazolone ketene N,S-acetal derivative 12. The structure of 12
was established on the basis of its elemental analysis and spectral data (IR, 1H
NMR, 13C NMR, and MS). Attempted cyclization of the compounds 12 in
boiling ethanolic hydrochloric acid resulted in the formation of a colorless
product, two possible isomeric structures, 13 and 14, for which were con-
sidered according to the molecular weight (by mass spectra) (Sch. 3). The 1H
NMR spectrum revealed an imine function (D2O exchangeable) and three
different methyl protons indicating that the methyl group at C-3 was not
involved in the cyclization. The pyrazolo[4,3-d]pyrimidine structure 14 was

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Alqaradawi and Elgemeie
Scheme 2.
therefore suggested for the reaction product and not the pyrazolo[4,3-
d]diazapine structure 13. As far as we know this is the first intramolecular
cyclization reaction of this type to be reported for pyrazolone ketene
S,N-acetals. In order to investigate further the scope of reactions of compound
2 with oxo- and amino-diazoles, we studied the reaction of dimethyl
N-cyanodithioiminocarbonate 2 with aminopyrazoles, thus, it has been found
that reaction of dimethyl N-cyanodithioiminocarbonate 2 with 5-aminopyra-
zoles 15 in refluxing ethanol containing catalytic amounts of piperidine gave
the corresponding 4-(methylthio)pyrazolo[1,5-a][1,3,5]-triazin-2-amines
18a–f in good yield. The structure of compounds 18 were established and
1
confirmed on the basis of their elemental analysis and spectral data (IR, H

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Scheme 3.
NMR, 13C NMR, and MS). The formation of 18 from the reaction of 2 and 15
is assumed to proceed via the intermediate 16, which cyclized to yield the end
products 18 (Sch. 4). Although, one may argue that the reaction of 2 with
5-aminopyrazoles 15 may involve the exocyclic pyrazole nitrogen leading to
the other possible 4-amino regioisomers. However, it is known that the
endocyclic ring nitrogen is the most nucleophilic center in the molecule and in
basic medium will initially add to the unsaturated bouble bond of 2.[5] In
summary, we have achieved a regiospecific synthesis of intersting mercapto-
purine and thioguanine analogues by the reaction of dimethyl N-cyano-
dithioiminocarbonate with diazoles containing amino- and oxo-functions.
EXPERIMENTAL
All melting points are uncorrected on a Gallenkamp melting point
apparatus. The IR spectra were recorded (KBr disk) on a Perkin Elmer 11650
FT-IR instrument. The 1H NMR spectra were measured on a Varian 400 MHz

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Alqaradawi and Elgemeie
Scheme 4.
spectrometer for solutions in (CD3)2 SO using Si(CH3)4 as an internal
standard. Mass spectra were recorded on a Varian MAT 112 spectrometer.
5-Amino-7-(methylthio)-3-thioxo-2,3-dihydro-1H-imidazo
[1,5-c]imidazol-1-ones (5a,b)
Method (a): General Procedure
A mixture of imidazolidines 3a,b (0.01 mol) and dimethyl N-cyano-
dithioiminocarbonate 2 (0.01 mol, 1.48 g) was boiled under reflux in ethanol
(30 mL) containing a catalytic amount of piperidine for 4 hr. The product
precipitated was collected and recrystallized from the appropriate solvent.

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Method (b): General Procedure
Imidazolidine ketene dithioacetals 6a,b (0.01 mol) and 3 drops of piperi-
dine were added to a stirred suspension of cyanamide 1 (0.01 mol, 0.4 g) in
ethanol (50 mL). The mixture was refluxed for 5 hr and then allowed to cool.
The solid precipitate was isolated by suction and recrystallized from the
appropriate solvent.
5a: Yellow; m.p. 268–2708C; from DMF; yield, 80%; nmax/cm21 (KBr)
3400–3300 (NH, NE2); 1710 (CO); 1H NMR (DMSO) d: 2.60 (s, 3H, SCH3);
8.55 (s, br, 2H, NH2), 10.96 (s, br, 1H, NH); m/z ¼ 214; calcd. for
C6H6N4OS2 (214): C, 33.64; H, 2.80; N, 26.17%; found: C, 33.4; H, 2.5; N,
26.0%. 5b: Yellow; m.p. 288–2908C, from ethanol–DMF; yield, 70%; nmax
/
cm21 (KBr) 3450–3300 (NH2); 1700 (CO); 1H NMR (DMSO) d: 2.50 (s, 3H,
SCH3); 7.19–7.89 (m, 5H, C6H5); 8.90 (s, br, 2H, NH2); 13C NMR: 19.31
(SCH3); 126.00–130.00 (phenyl-C); 133.50 (C-8); 138.22 (C-7), 145.62
(C-5); 155.61 (C-3); 170.54 (C-1); m/z 290; calcd. for C12H10N4OS2 (290):
C, 49.66%; H, 3.45%; N, 19.31%; found: C, 49.5%; H, 3.3%; N, 19.0%.
5-[Bis(methylthio)methylene]-2-thioxoirnidazolidin-4-ones
(6a,b)
General Procedure
A mixture of 2-thioxohydantoin derivatives 3a,b (0.01 mol) and sodium
ethoxide (0.02 mol, 1.36 g) in ethanol (30 mL) was boiled under reflux for
15 min. The solution was cooled and carbon disulphide (0.01 mol, 0.76 g) was
added followed by addition of methyl iodide (0.02 mol, 2.82 g). The solution
was stirred for 10 min at room temperature. The formed solid product was
filtered off and recrystallized from ethanol.
6a: Yellow; m.p. 2488C; from ethanol; yield, 77%; nmax/cm21 (KBr)
3417–3134 (NH), 1714 (CO); 1H NMR (DMSO) d: 2.40 (s, 3H, SCH3); 2.45
(s, 3H, SCH3); 11.76 (s, 1H, NH); 12.16 (s, 1H, NH); 13C NMR: 17.31 (SCH3);
17.77 (SCH3); 128.89 (C-6); 130.02 (C-5); 161.06 (C-2); 174.72 (C-4);
m/z ¼ 220; calcd. for C6H8N2OS3: C, 32.72%; H, 3.63%; N, 12.72% found:
C, 32.5; H, 3.7%; N, 12.7% 6b: Orange; m.p. 2028C; from ethanol; yield,
1
85%; nmax/cm21 (KBr) 3155, 3124 (NH), 1720 (CO); H NMR (DMSO) d:
2.05 (s, 3H, SCH3); 2.51 (s, 3H, SCH3); 7.32–7.52 (m, 5H, C6H5); 12.24
(s, 1H, NH); 13C NMR: 17.36 (SCH3); 17.97 (SCH3); 127.37-128.88 (Phenyl-
C); 131.99 (C-6); 133.48 (C-5); 159.12 (C-2); 174.31 (C-4); m/z ¼ 296;
calcd. for C12H12N2OS3: C, 48.64%; H, 4.05%; N, 9.46%; found: C, 48.8%;
H, 3.9%; N, 9.5%.

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3-Aryl-4-(methylthio)pyrazolo [4,3-e][1,3]oxazin-6(1H)-
imine (9a,b)
Method (a): General Procedure
A suspension of dimethyl N-cyanodithioiminocarbonate 2 (0.01 mol,
1.46 g) in ethanol (30 mL) was refluxed with 3-aryl-5-oxopyrazole 7a,b
(0.01 mol) and 3 drops of piperidine for 3 hr, the reaction mixture was left to
cool to room temperature and the crystals separated on cooling were filtered
off and crystallized from the appropriate solvent.
Method (b): General Procedure
Pyrazolin-5-one ketene dithioacetals 10a,b (0.01 mol) and 3 drops of
piperidine were added to a stirred suspension of cyanamide 1 (0.01 mol, 0.4 g)
in ethanol (50 mL). The mixture was refluxed for 5 hr and then allowed to cool.
The solid precipitate was isolated by suction and recrystallized from the
appropriate solvent.
9a: Yellow, m.p. 1888C (from EtOH), yield (85%). IR (KBr) nmax/cm21
1
3440–3360 (NH). H NMIR (DMSO) d: 2.71 (s, 3H, SCH3), 7.08 (s, br, 1H
imine NH). 7.15–7.94 (m, 5H, C6H5), 10.07 (s, br, IH, NH); Mþ 258,
C12H10N4OS. Calcd: C, 55.81%; H, 3.88%; N, 21.72%. Found: C, 55.6%; H,
3.5%; N, 21.5%. 9b: Yellow, m.p. 2318C (from DMF), yield (70%). IR (KBr)
nmax/cm21 3400, 3250 (NH). 1H NMR (DMSO) d: 2.45 (s, 3H, SCH3), 7.00
(s, br, 1H, imine NH). 7.20–7.99 (m, 411, C6H4), 9.89 (s, br, 1H, NH). 13C
NMR (DMSO): 17.00 (SCH3), 120.09–129.22 (phenyl carbons), 143.77
(C-8), 145.00 (C-3), 148.11 (C-4), 156.67 (C-7), 167.00 (C-6). C12H9FN4OS.
Calcd: C, 52.17%; H, 3.26%; N, 20.29%. Found: C, 52.0%; H, 3.3%; N,
20.2%.
5-Aryl-4[bis(methylthio)methylene]-2,4-dihydro-3H-pyrazol-
3-ones (10a,b)
General Procedure
A mixture of pyrazolin derivatives 7a,b (0.01 mol) and sodium ethoxide
(0.02 mol, 1.36 g) in ethanol (30 mL) was boiled under reflux for 15 min. The
solution was cooled and carbon disulphide (0.01 mol, 0.76 g) was added,
followed by addition of methyl iodide (0.02 mol, 2.82 g). The solution was
stirred for 10 min at room temperature. The formed solid product was filtered
off and recrystallized from the appropriate solvent. 10a: Yellow; m.p. 1508C;
from methanol; yield, 70%; nmax/cm21 (KBr); 3480–3670 (NH), 1690 (CO);

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1H NMR (DMSO) d: 2.55 (s, 3H, SCH3); 2.62 (s, 3H, SCH3); 7.11–7.82
(m, 5H, C6H5); 11.00 (s, 1H, NH); 13C NMR: 16.00 (SCH3); 18.43 (SCH3);
120.56–129.00 (phenyl-C), 130.48 (C-6); 138.00 (C-4); 158.68 (C-5); 177.00
(C-3); m/z ¼ 264; calcd. for C12H12N2OS2: C, 54.55%; H, 4.55%; N, 10.61%.
found: C, 54.3%; H, 4.5%; N, 10.3% 10b: Buff; m.p. 1898C; from ethanol;
yield, 70%; nmax/cm21 (KBr) 3380, 3200 (NH), 1700 (CO); 1H NMR
(DMSO) d: 2.44 (s, 3H, SCH3); 2.58 (s, 3H, SCH3); 7.05–7.78 (m, 4H, C6H4);
12.00 (s, 1H, NH); 13C NMR: 17.00 (SCH3); 19.12 (SCH3); 120.11–129.34
(Phenyl-C); 132.78 (C-6); 137.00 (C-4); 157.00 (C-5); 170.00 (C-3); calcd. for
C12H11FN2OS2: C, 51.06%; H, 3.90%; N, 9.93%. Found: C, 51.0%; H, 3.9%;
N, 9.5%.
Methyl N-cyano-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-
Dihydro-1H-pyrazol-4-yl)imidothiocarbamate (12)
General Procedure
A mixture of ketene dithioacetal 2 (0.01 mol, 1.46 g) and 4-amino-
antipyrine 11 (0.01 mol, 2.03 g) was refluxed in ethanol containing piperidine
(3 drops) for 30 min. The formed solid product was collected and recrystal-
lized from ethanol. Yellow crystals, (from ethanol), m.p. 2208C (yield 85%);
1
nmax/cm21 (KBr) 3440, 3380 (NH), 2220 (CN), 1680 cm21 (CO); H NMR
(DMSO) d: 2.28 (s, 3H, CH3), 2.48 (s, 3H, SCH3), 2.99 (s, 3H, N–CH3), 7.12–
7.90 (m, 5H, C6H5), 9.22 (s, 1H, NH); 13C NMR: 11.99 (CH3), 16.50 (SCH3),
32.12 (N–CH3), 109.00 (CN), 121.00–128.32 (phenyl-C), 131.60 (C-5),
148.78 (C-4), 163.00 (C-6), 175.73 (C-3); m/z 301; calcd. for C14H15N5OS:
C, 55.5%, H, 4.6%, N, 23.2%. Found: C, 55.81%, H, 4.98%, N, 23.26%.
7-Imino-1,7a-dimethyl-5-(methylthio)-2-phenyl-1,2,7,7a-
tetrahydro-3H-pyrazolo[4,3-d]pyrimidin-3-one (14)
General Procedure
A solution of each of 12 (0.01 mol, 3.01 g) in ethanol (30 mL) was treated
with concentrated hydrochloric acid (1 mL). The reaction mixture was heated
under reflux for 30 min and then evaporated under reduced pressure. The
resulting solid product was collected by filtration and recrystallized from
ethanol. Colorless crystals, (from ethanol), m.p. 260–628C (yield 50%);
1
nmax/cm2 1 (KBr) 3400, 3430 (NH), 1700 (CO); H NMR (DMSO) d: 2.26
(s, 3H, CH3), 2.40 (s, 3H, SCH3), 2.95 (s, 3H, N–CH3), 5.13 (s, 1H, 55NH),

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7.08–7.59 (m, 5H, C6H5); m/z ¼ 301; 13NMR: 17.00 (CH3), 19.13 (SCH3),
31.67 (N–CH3), 109.00 (C-7a), 121.22–129.00 (Phenyl-C), 145.17 (C-4a),
157,56 (C-5), 163.98 (C-7), 175.88 (C-3); calcd. for C14H15N5OS: C, 55.81%,
H, 4.98%, N, 23.26%. Found: C, 55.6%; H, 4.7%; N, 23.2%.
4-(Methylthio)pyrazolo[1,5-a][1,3,5]triazin-2-amine (18a–f)
General Procedure
A suspension of dimethyl N-cyanodithioiminocarbonate 2 (0.01 mol,
1.46 g) in ethanol (30 mL) was refluxed with 5-aminopyrazoles 15a–f
(0.01 mol) and 3 drops of piperidine for 3 hr, the reaction mixture was left to
cool to room temperature. The crystals separated on cooling were filtered off,
and recrystallized from the appropriate solvent. 18a: Yellow, m.p. 277–798C,
(from EtOH), yield (80%). IR (KBr) nmax/cm21 3400, 3300 (NH2). 1H NMR
(DMSO) d: 2.28 (s, 3H, CH3), 2.55 (s, 3H, SCH3), 7.10–7.92 (m, 5H, C6H5),
8.10 (s, 2H, NH2). 13C NMR (DMSO): 13.00 (CH3), 17.32 (SCH3), 113.55
(C-9), 120.45–129.84 (Phenyl-C), 147.22 (C-8), 154.97 (C-7), 156.73 (C-4),
160.99 (C-2). (m/z ¼ 271); calcd. for C13H13N5S: C, 57.56%; H, 4.80%, N,
25.83%; found: C, 57.5%; H, 4.6%; N, 25.5%. 18b: Yellow, m.p. 207–098C
(from DMF), yield (80%). IR (KBr) nmax/cm21 3480, 3300 (NH2). 1H NMR
(DMSO) d: 2.55 (s, 3H, SCH3), 7.11–7.92 (m, 5H, C6H5), 8.50 (s, br, 2H,
NH2). 13C NMR (DMSO): 18.00 (SCH3), 115.00 (C-9), 121.67–130.45
(Phenyl-C), 146.00 (C-8), 153.11 (C-7), 158.56 (C-4), 163.28 (C-2). Calcd. for
C12H10BrN5S: C, 42.86%; H, 2.98%; N, 20.83%. Found: C, 42.8%; H, 3.0%;
N, 21.0%. 18c: Brown, m.p. . 3008C (from EtOH), yield (80%). IR (KBr)
nmax/cm21 3400 (NH2). C13H10N6S, calcd: C, 55.32%; H, 3.55%; N, 29.79%;
found: C, 55.0%; H, 3.5%; N, 29.5%. 18d: Yellow, m.p. . 278–2808C (from
1
DMF), yield (70%). IR (KBr) nmax/cm21 3420 (NH, NH2); 1685 (CO). H
NMR (DMSO) d: 2.58 (s, 3H, SCH3), 7.19–7.65 (m, 4H, C6H5), 8.21 (s, 2H,
NH2), 9.28 (s, 1H, NH). 13C NMR (DMSO): 14.54 (SCH3), 121.00 (C-9),
122.78–130.14 (Phenyl-C), 150.00 (C-8), 157.61 (C-4), 158.15 (C-2), 171.12
(C-7). (m/z ¼ 301); calcd. for C12H11N7SO: C, 47.84%; H, 3.65%; N,
32.56%; found: C, 47.6%; H, 3.5%; N, 32.5%. 18e: Yellow, m.p. . 3008C
(from DMF), yield (70%). IR (KBr) nmax/cm21 3480, 3400 (NH, NH2), 1690
1
(CO). H NMR (DMSO) d: 2.50 (s, 3H, SCH3), 7.18–7.90 (m, 4H, C6H4),
8.50 (s, br, 2H, NH2), 9.40 (s, br, 1H, NH). 13C NMR (DMSO): 13.00 (SCH3),
117.00 (C-9), 123.78–128.00 (Phenyl-C), 150.28 (C-8), 155.00 (C-4), 158.00
(C-2), 172.37 (C-7). Calcd. for C12H10ClN7OS: C, 42.92%; H, 2.98%; N,
29.21%. Found: C, 42.6%; H, 3.2%; N, 29.0%. 18f: Orange, m.p. 288–908C
(from DMF), yield (90%). IR (KBr) nmax/cm21 3400, 3360 (NH, NH2); 1690

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1
(CO). H NMR (DMSO) d: 2.60 (s, 3H, SCH3), 7.10–7.90 (m, 4H, C6H4),
8.20 (s, br, 2H, NH2), 9.49 (s, br, 1H, NH). 13C NMR (DMSO): 15.00 (SCH3),
117.00 (C-9), 125.29–129.99 (Phenyl-C), 145.78 (C-8), 157.73 (C-4), 160.17
(C-2), 169.95 (C-7). Calcd. for C13H13N7SO: C, 49.52%; H, 4.13%; N,
31.11%. Found: C, 49.2%; H, 4.4%; N, 31.2%.
REFERENCES
1. Elgemeie, G.E.H.; Elghandour, A.H.; Elzanate, A.M.; Masoud, W.A.
Novel N-substituted amino-4-methylsulfanyl-2-pyridones and deazapurine
analogues from ketene dithioacetals. J. Chem. Research (S) 1998,
164–165.
2. Elgemeie, G.H.; Ali, H.A.; Elghandour, A.H.; Abd-Elaziz, G.W. Synthesis
of novel derivatives of 4-methylthio-N-aryl-2-pyridone and deazapurine
analogues: the reaction of ketene dithioacetals with substituted acetani-
lides. Phosphurs, Sulfur and Silicon 2000, 164, 189–197.
3. Elgemeie, G.H.; Elghandour, A.H.; Elzanate, A.M.; Ahmed, S.A. Syn-
thesis of some novel a-cyanoketene S,S-acetals and their use in hetero-
cyclic synthesis. J. Chem. Soc. Perkin Trans. 1 1997, 3285–3289.
4. Elgemeie, G.H.; Ali, H.A.; Elzanate, A.M. The reaction of cyanoketene
dithioacetals with imidazolidiones: a synthesis of methylsulfanylpyr-
rolo[1,2-c]imidazolones. J. Chem. Research (S) 1996, 340–341.
5. Elgemeie, G.H.; El-Ezbawy, S.R.; Ali, H.A.; Mansour, A.K. Novel
synthesis of mercaptopurine and pentaaza-as-indacene analogues: reaction
of [bis(methylthio)methylene]malononitrile and ethyl 2-cyano-3,3-bis-
(methylthio)acrylate with 5-aminopyrazoles. Bull. Chem. Soc. Japan 1994,
67, 738–748.
Received in the USA September 3, 2003

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