A new synthesis of 4-cyano-1,3-dihydro-2-oxe-2h-5-(N1-tosyl)carboxamide: Reactive precursor for thiopurine analogues

Article abstract of DOI:10.1002/jhet.5570380420

N-[(5-Cyano-2-oxoimidazolidin-4-yl)-iminomethyl]-p-toluensulfonamide 3 was prepared in fairly good yield by the base catalyzed cyclisation of N-[(Z)-2-amino-1,2-dicycanovinylcarbamoyl]-p-toluenesulfonamide 2. The N-[(Z)-2-amino-1,2-dicycanovinyl carbamoyl]-p-toluenesulfonamide 2 was reacted readily with two molar amount of p-nitrobenzaldehyde at room temperature in the presence of base to give 7,8-dihydro-2-(4-nitrophenyl)-8-oxo-9-tosylpurine-6-carboxamide 8. Thiation of compounds 3 and 8 using Lawesson's reagent in tetrahydrofuran gave novel thioimidazoles 4, 5, and 6 and thiopurines 9, 10, and 11, which have been characterized spectroscopically.

Full text of DOI:10.1002/jhet.5570380420

Jul-Aug 2001
A New Synthesis of 4-Cyano-1,3-dihydro-2-oxo-2H-imidazole-5-
(N -tosyl)carboxamide : Reactive Precursor for Thiopurine Analogues
939
1
Abdel-Sattar S. Hamad* and Hamed. A. Y. Derbala
*Department of Chemistry, Faculty of Science, University of Ain Shams, Abbassia 11566, Cairo, Egypt
Received July 12, 2000
N-[(5-Cyano-2-oxoimidazolidin-4-yl)-iminomethyl]-p-toluensulfonamide 3 was prepared in fairly good
yield by the base catalyzed cyclisation of N-[(Z)-2-amino-1,2-dicycanovinylcarbamoyl]-p-toluenesulfon-
amide 2. The N-[(Z)-2-amino-1,2-dicycanovinyl carbamoyl]-p-toluenesulfonamide 2 was reacted readily
with two molar amount of p-nitrobenzaldehyde at room temperature in the presence of base to give 7,8-dihy-
dro-2-(4-nitrophenyl)-8-oxo-9-tosylpurine-6-carboxamide 8. Thiation of compounds 3 and 8 using
Lawesson's reagent in tetrahydrofuran gave novel thioimidazoles 4, 5, and 6 and thiopurines 9, 10, and 11,
which have been characterized spectroscopically.
J. Heterocyclic Chem., 38, 939 (2001).
Introduction.
Recently, we are concerned with the thiohydantoin
derivatives [10] used as potential hypolipidemic agents
[11], bearing imidazole-2-thione functional group and
responsible for biological activity. The reported biological
importance of thione compounds prompted us to try the
conversion of N-[(5-cyano-2-oxoimidazolidin-4-yl)-imi-
nomethyl]-p-toluensulfonamide 3 and 7,8-dihydro-2-(4-
nitrophenyl)-8-oxo-9-tosylpurine-6-carboxamide 8 into
the corresponding thione derivatives 4-6 and 9-11 respec-
tively, to search for active and less toxic compounds.
In the last decade diaminomaleonitrile 1 (DAMN) has
received much interest as a source of nitrogen heterocy-
cles. The reactions most widely used in those syntheses are
condensations with carbonyl compounds. One approach is
exemplified by the photochemical conversion of DAMN 1
into 4-amino-5-cyanoimidazole [1] resulting from the
trans isomer, diaminofumaronitrile [2]. No chemical reac-
tions of trans isomer, however, are known mainly because
it reverts to the cis isomer 1 under the influence of acid,
base, charcoal, light or heating [3]. Again many of the
chemical properties of these imidazoles are still unknown.
In this investigation DAMN 1 is used as cis-1,2-
diaminoethylene component.
We would like to report here a reaction pattern of
DAMN 1, in which 1 is used as a cis 1,2-diaminoethylene
component. This is demonstrated by the successive reac-
tion of 1 with isocyanate to give imidazole, this result is
inconsistent to the result described by Ohtsuka et al. [4] in
the base catalyzed cyclisation of N-[(Z)-2-amino-1,2-dicy-
canovinylcarbamoyl]-p-toluenesulfonamide 2.
We have been particularly interested in developing a
route to the hitherto unknown compound 2 as a precur-
sor in the synthesis of a range of new 1,2-dihydropurine
and purine derivatives. We now report the successful
synthesis of compound 2 as a precursor for the prepa-
ration of new 1,2-dihydropurines 7 and 6-carbamoyl-
purines 8.
It was reported that the angular 7H-1,2,3-triazolo[3,4-
i]purine analogues have been investigated recently for
their potential xanthine oxidase inhibitory activities [5].
Allopurinol is known to inhibit xanthine oxidase [6] and is
now widely employed in the treatment of gout and hyper-
uricemia resulting from uric acid [6-8]. No clinically effec-
tive xanthine oxidase inhibitors for the treatment of hyper-
uricemia have been developed since allopurinol was intro-
duced for clinical use in 1963 [6]. In addition, purine ana-
logues are useful as anticancer and antiviral agent [9].
Results and Discussion.
When DAMN 1 was allowed to react with tosyliso-
cyanate, compound 2 was produced. Cyclisation reaction
of compound 2 with a catalytic amount of 1,8-diazabicy-
clo[5.4.0]undec-7-ene in acetonitrile produced compound
3 in fairly high yield (93%). This result is inconsistent to
that obtained by Ohtsuka et al. for cyclisation of com-
pound 2 to the cytosine derivatives under the same reac-
tion conditions [4].
The infrared spectra of compound 2 showed a strong
-1
stretching vibration at 1645 cm due to the carboxamide ν
C=O. The characteristic feature of compound 2 is a strong
-1
C≡Ν stretching vibration at 2209 cm and a week cyano
-1
stretching vibration at 2255 cm as shown in Table 1. The
1
H NMR spectrum of compound 2 exhibit a broad singlet
signal for the acidic proton at δ 11.17 of (-CO-NHSO Ar),
2
singlet signals at δ 7.77 for the (-CO-NH-C-) and a broad
singlet signal having a shoulder at δ 7.38 ppm for the
(-C=CCNNH ) as illustrated in Table 1.
2
The infrared spectra of compound 3 showed the appear-
-1
ance of a strong stretching vibration at 1724 cm for ν
C=O in the imidazol-2-one ring characteristic of the five
membered ring and a week C≡N stretching vibration at
-1
1
2231 cm as shown in Table 1. The H NMR spectrum of
compound 3 exhibit a broad singlet signal at δ 11.51 for
two proton of (-NH-) and the two singlet signals having a
shoulder at δ 8.41-8.37 for two protons of (-NH) groups in
the imidazol-2-one ring.

940
A.-S. S. Hamad and H. A. Y. Derbala
Vol. 38
A possible mechanism for the formation of N-[(5-cyano-
result is inconsistent with that described by Testa et al. [18]
for thiation of compounds containing cis amino-cyano neigh-
boring group by using Lawesson's reagent.
2-oxoimidazolidin-4-yl)-iminomethyl]-p-toluensulfon-
amide 3 from the reaction of compound 2 with 1,8-diazabi-
cyclo[5.4.0]undec-7-ene (DBU), is hypothesized. The
mechanistic pathway for that reaction is attributed to Ernst
Schaumann et al [12] as illustrated in Scheme 2.
The infrared spectra of compound 4 showed the appear-
-1
ance of ν C=S in the imidazole-2-thione ring at 1158 cm
characteristic of the five member thiolactam ring and ν C=O
-1
The reaction of compound 3 with Lawesson's reagent
[13,14,15,16] was tried in tetrahydrofuran under a nitrogen
atmosphere, the corresponding thione-compound 4 was pro-
duced in 45% yield with the unexpected by-product of com-
pounds 5 and 6. The novel compounds 5 and 6 were obtained
after chromatographic separation as a yellow crystalline
material in (10%) and (15%) yield respectively (Scheme 1).
Spot tests [17] confirmed the presence of C=S groups. This
at 1629 cm characteristic of the amide group for com-
pound 4. In compound 5 appearance ν C=S at 1086-1158
cm in imidazole-2-thione ring characteristic of the five
member thiolactam ring and thioamide groups as shown in
-1
-1
Table 1. In compound 6, ν C=O at 1713 cm is observed
consistent with the imidazole-2-one ring and ν C=S at 1098-
-1
1170 cm characteristic of thioamide group and intense
-1
band in the 3200-3441 cm region for (ν NH) group.

1
Jul-Aug 2001
A New Synthesis of 4-Cyano-1,3-dihydro-2-oxo-2H-imidazole-5-(N -tosyl)carboxamide
941
1
pale orange solid identified as 7,8-dihydro-2-(4-nitro-
phenyl)-8-oxo-9-tosylpurine-6-carboxamide 8. Thus, it
proved impossible to obtain accurate spectroscopic analysis
data for compound 7. In this reaction the 7,8-dihydro-2-(4-
nitrophenyl)-8-oxo-9-tosylpurine-6-carboxamide 8 was
isolated and may arise from the 6-carbamoyl-1,2-dihydro-
purine 7 by loss of hydrogen under the reaction condition
and this due to the oxidation by p-nitrobenzaldehyde.
In the study of the thiation of 7,8-dihydro-2-(4-nitro-
phenyl)-8-oxo-9-tosylpurine-6-carboxamide 8 with
Lawesson's reagent, refluxing of compound 8 in tetrahydro-
furan produced the corresponding compounds 9, 10 and 11 in
low yield, 15, 12, 32% respectively. The infrared spectra of
compound 7 as shown in Table 1 showed the appearance of a
The H NMR spectra of compounds 4, 5 and 6 exhibited
four singlet signals at δ 8.34, 8.66, 10.14 and 10.86 ppm for
NH and NH groups always showed up as a singlet at δ
2
10.53-10.56 and this seems to be a typically feature of those
13
compounds as shown in Table 1. All bands in the C NMR
are sharp, with the signals for (C ) of the C=S group around
i
δ 185.3 as shown in Table 3. Compound 2 react with 2-fold
molar amount of p-nitrobenzaldehyde at room temperature
in dry acetonitrile solution in the presence of triethylamine
(3 mole equivalents), with the formation of a characteristic
orange spot on tlc for the 6-carbamoyl-1,2-dihydropurine 7
derivatives. These can be isolated as air unstable, orange
solids 7 as illustrated in Scheme 3 after chromatographic
separation. Compound 7 is very unstable both in solution
and in the solid state and its color gradually fades to give a
-1
strong stretching vibration at 1697 and 1636 cm for two

942
A.-S. S. Hamad and H. A. Y. Derbala
Vol. 38
ν C=O characteristic of the lactam ring and amide open chain.
ν C=O characteristic of the lactam ring and sharp intense
1
-1
The H NMR spectra, exhibited two doublet signals at δ 6.98
band at 1169 cm for the ν C=S characteristic of the
1
1
thioamide open chain. The H NMR spectrum, showing
and δ 8.81 typical of the N -H and C -H of a 6-carbamoyl-
2
7
two singlet signal at δ 11.45 and 10.61 for N -H and (-CS-
1,2-dihydropurine, clearly indicating the assigned structure.
The infrared spectra of compound 8 as shown in Table 1
showed the appearance of a strong stretching vibration at
NH ) of 6-thiocarbamoylpurine, that clearly indicated to
2
the assigned structure as shown in Table 1.
-1
1705 and 1680 cm for two ν C=O characteristic of lactam
1
ring and amide open chain [19]. The H NMR spectra of com-
EXPERIMENTAL
7
pound 8 exhibited a singlet signal at δ 11.45 typical of N -H
1
and two doublet signal at δ 8.29 and δ 8.37 for (4H) aromatic
H NMR spectra were recorded on Varian Plus 300 (300 MHz)
13
or Bruker XL 300 (300 MHz) instruments and the C NMR spec-
protons of 4-NO C H -R (p), at the same coupling constant J
2
6 4
tra (with DEPT 135) were measured on a Bruker WP80 or XL 300
instrument. Infrared spectra listed as recorded ‘neat’ refer to a thin
film of material on NaCl disks, and were taken on a Perkin Elmer
1600 FT-IR spectrometer. Melting points were measured on an
electrothermal digital melting point apparatus and are uncor-
= 8.7 Hz, which was clearly indicated to the assigned structure.
The infrared spectra of compound 9 showed the appearance
-1
of a strong stretching vibration at 1596 cm for ν C=O char-
-1
acteristic of the amide open chain and at 1188 cm for the ν
C=S characteristic of the thiolactam ring as shown in Table 1.
rected. The R value reported for TLC analysis was determined on
f
1
The H NMR spectra exhibited two singlet signals at δ 11.35
Macherey-Nagel 0.25 mm layer fluorescent UV
plates with
254
7
and 10.6 typical of the N -H and (-CS-NH ) of 7,8-dihydro-2-
the indicated solvent system. M-H-W Laboratories (Phoenix, AZ)
performed elemental analyses at University of Minho, Braga,
Portugal and Cairo University, Egypt.
2
(4-nitrophenyl)-8-thioxo-9-tosylpurine-6-carboxamide 9. The
infrared spectra of 10 appearance of a strong stretching vibra-
-1
tion at 1170 and 1232 cm for two ν C=S, characteristic of the
N-[(Z)-2-Amino-1,2-dicycanovinylcarbamoyl]-p-toluenesulfon-
amide (2).
thiolactam ring and thioamide open chain as shown in (Table
1
1). H NMR spectrum showed two singlet signals at δ 11.84
To a suspension of diaminomaleonitrile 1 (0.68 g, 6.3 mmoles)
in acetonitrile (5 mL) under nitrogen atmosphere at 0°, toluene-
sulfonylisocyanate (1 mL) was added and the whole was stirred
for 15 minutes and then at room temperature for 10 minutes. The
solid product was collected by filtration, washed with acetonitrile
and then ether to give 1.45 g of white powder in 75% yield.
7
and 10.58 typical of N -H and (-CS-NH ) of 7,8-dihydro-2-(4-
2
nitrophenyl)-8-thioxo-9-tosylpurine-6-thiocarboxamide 10.
The infrared spectra of 7,8-dihydro-2-(4-nitrophenyl)-8-
oxo-9-tosylpurine-6-thiocarboxamide 11 showed the
appearance of a strong stretching vibration at 1705 for
Table 1
1
Infrared and H NMR spectral Data for Compounds 2-11
1
Compound
IR
H NMR [deuteriodimethyl sulfoxide]
2
3393, 3201, 2255, 2209, 1645,
1611, 1511, 1457
δ = 2.4 (s, 3H, -CH ), 7.38 (s, 2H, -NH ), 7.41 (d, 2H, J = 7.8 Hz, Ar-H), 7.77 (brs,
3
2
1H, -NHCO), 7.79 (d, 2H, J = 7.8 Hz, Ar-H), 11.17 (brs, 1H, CONHTos) ppm
3
4
5
3285, 3070, 2231, 1724, 1663,
1621, 1557
3441, 3334, 3299, 3200, 1713, 1629,
1596, 1568.5, 1543, 1170, 1158
3442, 3334, 3200, 1629, 1596, 1568,
1543,1086, 1158
δ = 2.36 (s, 3H, -CH ), 7.36 (d, 2H, J = 8.7 Hz, Ar), 7.79 (d, 2H,
3
J = 8.7 Hz, Ar), 8.41-8.37 (brs, 2H, -NH), 11.51 (brs, 2H, NH) ppm
δ = 2.36 (s, 3H, -CH ), 7.37 (d, 2H, J = 8.4 Hz, Ar), 7.8 (d, 2H, J = 8.4 Hz, Ar),
3
8.34 (s, 1H, -NH), 10.14 (s, 1H, -NH), 10.95 (s, 1H, NH) ppm
δ = 2.36 (s, 3H, -CH ), 7.37 (d, 2H, J = 8.7 Hz, Ar), 7.8 (d, 2H, J = 8.7 Hz, Ar), 8.34 (s,
3
1H, -NH), 8.67 (s, 1H, -NH), 10.14 (s, 1H, CONHTos), 10.56 (brs, 2H, NH ),
2
11.95 (brs, 1H, NH) ppm
6
7
3441, 3334, 3299, 3200, 1713, 1629,
1596, 1568.5, 1543, 1098, 1170
δ = 2.36 (s, 3H, -CH ), 7.37 (d, 2H, J = 8.4 Hz, Ar), 7.8 (d, 2H, J = 8.4 Hz, Ar), 8.35
3
(s, 1H, -NH), 8.68 (s, 1H, NH), 10.12 (s, 1H, CONHTos), 10.57 (s, 2H, NH ),
2
11.97 (s, 1H, NH) ppm
3446, 3290, 1697, 1636, 1568
3450, 3158, 1694, 1597
δ = 2.32 (s, 3H, -CH ), 6.98 (brs, 2H, CONH ), 7.25 (d, 2H, J = 8.4 Hz, Ar-H), 7.84
3
2
(d, 2H, J = 8.4 Hz, Ar-H), 8.29 (d, 2H, J = 8.7 Hz, NO -C H -H), 8.36 (d, 2H, J = 8.7 Hz,
2
6 5
NO -C H -H), 9.71 (brs, 1H, NH), 11.35 (brs, 1H, NH) ppm.
2
6 5
8
δ = 2.27 (s, 3H, -CH ), 7.25 (d, 2H, J = 8.4 Hz, Ar-H), 7.83 (d, 2H, J = 8.4 Hz, Ar-H), 8.29
3
(d, 2H, J = 8.7 Hz, NO -C H -H), 8.37 (d, 2H, J = 8.7 Hz, NO -C H -H), 8.82 (brs, 1H,
2
6
5
2
6 5
NH), 9.25 (brs, 1H, NH), 11.45 (s, 1H, NH) ppm
δ = 2.32 (s, 3H, -CH ), 7.43 (d, 2H, J = 8.4 Hz, Ar-H), 7.8 (d, 2H, J = 8.4 Hz, Ar-H),
9
3495, 3244, 1596, 1532, 1344,
1188, 1087
3
8.33 (d, 2H, J = 8.7 Hz, NO -C H -H), 8.38 (d, 2H, J = 8.7 Hz, NO -C H -H),
2
6
5
2
6 5
10.58 (s, 1H, NH), 11.84 (s, 1H, NH) ppm
δ = 2.32 (s, 3H, -CH ), 7.25 (s, 2H, NH ), 7.40 (d, 2H, J = 8.1 Hz, Ar-H), 7.98 (d, 2H,
10
11
3495, 3244, 1596, 1532, 1344,
1232, 1170
3
2
J = 8.1 Hz, Ar-H), 8.33 (d, 2H, J = 8.7 Hz, NO -C H -H), 8.38 (d, 2H, J = 8.7 Hz,
2
6 5
NO -C H -H), 9.27 (s, 1H, NH) ppm
2
6 5
3495, 3244, 1705, 1596, 1532, 1344,
1169, 1087
δ = 2.32 (s, 3H, -CH ), 7.25 (s, 2H, NH ), 7.43 (d, 2H, J = 8.4 Hz, Ar-H), 7.8
3 2
(d, 2H, J = 8.4 Hz, Ar-H), 8.33 (d, 2H, J = 8.7 Hz, NO -C H -H), 8.38 (d, 2H, J = 8.7 Hz,
2
6 5
NO -C H -H), 11.45 (s, 1H, NH) ppm
2
6 5

1
Jul-Aug 2001
A New Synthesis of 4-Cyano-1,3-dihydro-2-oxo-2H-imidazole-5-(N -tosyl)carboxamide
943
Table 2
Physical and Elemental Analytical Data for Compounds 2-11
Compound
Melting Point
mp(decompd)
Yield%
Molecular Formula
Elemental Analysis [Calcd/found]
C
H
N
S
2
3
4
5
6
7
8
9
10
11
>300
75%
91%
45%
10%
16%
C
C
C
C
C
C
C
C
C
C
H
N SO
N SO
N S O
N S O
47.21/47.12
47.21/47.21
42.47/42.42
40.56/40.40
42.47/42.42
50.00/50.05
50.22/50.18
46.91/47.09
46.91/47.09
48.51/48.46
3.60/3.61
3.60/3.72
3.83/3.81
3.66/3.96
3.83/3.61
3.50/3.55
3.08/3.15
2.88/3.01
2.88/3.01
2.97/3.15
22.95/22.89
22.95/22.82
20.64/20.74
19.71/19.63
20.64/20.47
18.42/18.48
18.50/18.62
17.28/17.11
17.28/17.11
17.87/17.81
10.49/10.56
10.49/10.59
18.88/18.75
27.04/27.15
18.88/18.05
7.01/7.02
12 11 5
3
3
262-263
280-282
>300
H
12 11 5
H
12 13 5 2 3
H
12 13 5 3 2
>300
H
N S O
12 11 5 2 3
195-198
205-207
215-217
212-215
222-555
H N SO
19 16 6
6
6
72%
81%
25%
32%
H
N SO
N S O
N S O
N S O
7.04/7.32
19 14 6
H
19.75/19.43
19.75/19.43
13.61/13.62
19 14 6 2 5
H
19 14 6 3 4
H
19 14 6 2 5
Table 3
C Chemical Shifts in Deuteriodimethyl Sulfoxide for N-[(Z)-2-Amino-1,2-dicycanovinylcarbamoyl]-p-toluenesulfonamide 2
13
Compound
C1'
C≡N
C≡N
C2'
C=O
C2, C6
127.5
C3, C5
129.5
C -1
C -4
CH
3
i
i
2
106.1
113.7
117.0
129.7
149.8
137.0
144.0
21.0
Table 3
13
C Chemical Shifts in Deuteriodimethyl Sulfoxide for N-[5-Cyano-2-oxoimidazolidin-4-yl)-iminomethyl]-p-toluenesulfonamide (3)
Compound
C-5
C≡N
C-4
C=NH
150.93
C=O
C2',C6'
126.2
C3', C5'
129.3
C -1'
C -4'
CH
3
i
i
3
98.0
110.8
126.5
151.5
139.13
142.65
21.0
Recrystallization from ethanol gave colorless powder as shown
in Table 2.
acetonitrile to give 3 as a cream-white solid. Recrystallization
from ethanol gave colorless powder, mp 262-263°, yield 91%
(0.32 g) as shown in Table 2.
N-[5-Cyano-2-oxoimidazolidin-4-yl)-iminomethyl]-p-toluene-
sulfonamide (3).
Reaction of the N-[5-Cyano-2-oxoimidazolidin-4-yl)-imi-
nomethyl]-p-toluenesulfonamide (3) with Lawesson’s reagent.
To a suspension of compound 2 (0.35 g, 1.14 mmoles) in ace-
tonitrile (2 mL) under nitrogen atmosphere at 0°, 1,8-
Diazabicyclo[5.4.0] undec-7-ene (43 µL, 0.043 g, 0.285 mmole)
was added, and then stirred at room temperature for two hours.
The solid product was collected by filtration and washed with
A mixture of N-[5-cyano-2-oxoimidazolidin-4-yl)-imi-
nomethyl]-p-toluenesulfonamide (3) (0.37 g, 1.23 mmoles) and
Lawesson’s reagent (0.25 g, 0.616 mmole) was dissolved in
tetrahydrofuran (15 ml). The reaction mixture was refluxed for

944
A.-S. S. Hamad and H. A. Y. Derbala
Vol. 38
Table 3
13
1
C Chemical Shifts in Deuteriodimethyl Sulfoxide for 1,3-Dihydro-2-thioxo-4-(N -tosyl)amidino-2H-imidazole-5-carboxamide 4
Compound
C-5
C=S
C−4
C=NH
150.6
C=O
C2', C6'
126.5
C3',C5'
129.4
C -1'
C -4'
CH
3
i
i
4
126.0
185.2
132.0
153.7
138.4
143.0
21.0
6-10 hours, under nitrogen atmosphere. Evaporation, filteration
and successive washing with diethyl ether gave the products 4, 5
and 6 which were isolated by dry chromatography (ethanol/
dichloromethane; 2:8), in the yields 45%, 10% and 15% respec-
tively, as shown in Table 2.
then filtered off, washed with diethylether to give the correspond-
ing thione-compounds 9, 10 and 11 which were isolated by dry
chromatography (ethanol/dichloromethane; 2:8), in yields 81%,
25% and 32% respectively as shown in Table 2.
REFERENCES AND NOTES
7,8-Dihydro-2-(4-nitrophenyl)-8-oxo-9-tosylpurine-6-carbox-
amide (8).
*
Tel./Fax; (00)202-4831836 e-mail; hamad@asunet.
shams.eun.eg
[1] J. P. Ferris and F. R. Antonucci, J. Am. Chem. Soc., 96, 2010
(1974).
[2] T. H. Koch and R. M. Rodehorst., ibid., 96, 6707 (1974).
A mixture of compound 2 (1.22 g, 4 mmoles) and 4-nitrobenz-
aldehyde (1.21 g, 8 mmoles) in ethanol (10 ml) was stirred at 0°
then triethylamine (3 equivalents) was added dropwise and then
keep stirring at room temperature for 26 hours to isolate 1,2-dihy-
dropurine 7. The reaction mixture was continued stirred for two
days later to provide 8 as yellow solid. Compound 8 can be
obtained from the reaction of DAMN 1 with tosylisocyanate and
4-nitrobenxaldehyde in ethanol as one pot reaction after stirring
three days at room temperature. Recrystallization from ethanol
gave yellow crystalline, mp 205-207°, yield 72%, as illustrated in
Table 2. Spectral data characteristics were identical with those of
the authentic sample in all aspects.
[3] E. Ciganek, W. J. Linn, and O. W. Webster in "The Chemistry
of the Cyano Group" Z. Rappoport, Ed., Interscience, New York. NY,
1970, pp 508.
[4] Y. Ohtsuka, J. Org. Chem.., 43, 3231 (1978).
[5] T. Nagamatsu, Y. Watanabe, K. Endo and S. Imaizumi, PCT
Int. Appl. WO., 26, 208 (1996); (Chem. Abstr., 125, 247848j (1996).
[6] G. B. Elion, S. Callahan, H. Nathan, S. Bieber, R. W. Rundles
and G. H. Hitchings, Biochem. Pharmacol., 12, 85 (1963).
[7] R. W. Rundles, J. B. Wyngaarden, G. H. Hitchings, G. B.
Elion and H. R. Silberman, Trans. Assoc. Am. Physicians, 76, 126 (1963).
[8] T. F. Yu and A. B. Gutman, Am. J. Med., 37, 885 (1964).
[9a] M. R. Harden, C. A. Parkin and P. G. Wyatt, Tetrahedron
Lett., 29, 701 (1988); [b] M. R. Harden and R. L. Jarvest, J. Chem. Soc.,
Perkin Trans 1, 1705 (1990).
[10] A-S. S. Hamad and M. E. Azab, Phosphorus, Sulfur and
Silicon, (2000) in press.
[11] T. J. Ellsworth, J. Med. Chem., 29, 5, 855 (1986).
[12] E. Schaumann and S. Grabley, Chem. Ber., 113, 934 (1980).
[13] S. L. Baxter and J. S. Bradshaw, J. Org. Chem., 46, 83
(1981).
[14] S. P. Raucher, Tetrahedron Lett., 21, 4061 (1980).
[15] R. Shaban, J. B. Rasmussen and S. Lawesson, Bull. Soc.
Chim. Belg., 90, 75 (1981).
[16] A-S. S. Hamad, A. I. Hashem, A. F. El-kafrawy and M.M.
Saad, Phosphorus, Sulfur and Silicon, 159, 157-169 (2000).
[17a] Feigl "Spot Tests in Organic Analysis" Sixth Edition, 1934;
[b] F. Feigl, Mikrochemie, 1, 15 (1934).
[18] M. G. Testa, G. Perrini, U. Chiacchio and A. Corsaro,
Phosphorus, Sulfur and Silicon, 86, 75 (1994).
[19] M. J. Alves, O. K. Al-Duaij, B. L. Booth, A. Carvalho, P. R.
Eastwood and M. F. J. R. P. Proenca. J. Chem. Soc. Perkin Trans. I, 3571
(1994).
13
Figure. C Chemical shifts in deuteriodimethyl sulfoxide for 7,8-dihy-
dro-2-(4-nitrophenyl)-8-oxo-9-tosylpurine-6-carboxamide (8).
Reaction of the 7,8-Dihydro-2-(4-nitrophenyl)-8-oxo-9-
tosylpurine-6-carboxamide (8) with Lawesson’s reagent.
A mixture of compound 8 (100 mg, 0.15 mmole) and
Lawesson’s reagent (60 mg, 0.15 mmole) was dissolved in
tetrahydrofuran 10 ml. The reaction mixture was refluxed for 5-7
hours, under nitrogen atmosphere. Evaporation of the solvent and