J. CHEM. RESEARCH (S), 1998 165
the structure. Thus, 1H NMR revealed a band at d 2.68
assignable to the SMe group and two broad singlets at
d 5.52 and 8.42 assignable to two amino groups. The 13C
NMR spectrum revealed a signal at d 18.93 assigned to the
SMe group and signals appeared at d 120.32, 122.90, 147.14,
149.17 and 160.96 corresponding to C-5, C-3, C-4, C-6 and
C-2, respectively. The formation of 5 from the reaction of 1
and cyanoacetohydrazide 2 is assumed to proceed via the
intermediacy of Michael adducts, which cyclized to yield the
®nal N-amino-2-pyridones . The reaction of ketene dithio-
acetals with Schi bases was also examined. Thus, when
1a,b were reacted with 1-cyanoacetyl-4-arylmethylidene-
semicarbazide 6 in the presence of KOH±1,4-dioxane, the 2-
pyridone-N-Schi bases 8 were obtained. The structures of 8
were established on the basis of elemental analysis and spec-
NH) (Found: C, 49.5; H, 3.0; N, 18.4%. C16H11N5S2O3 requires C,
49.9; H, 2.9; N, 18.2%).
N-Amino-4-methylsulfanyl-2-pyridone Derivatives 5a,bÐGeneral
Procedure.ÐA mixture of [bis(methylsulfanyl)methylene]malono-
nitriles 1a or ethyl 2-cyano-3,3-bis(methylsulfanyl)acrylate 1b
(0.01 mol), cyanoacetohydrazide 2 (0.01 mol), and potassium hy-
droxide (0.012 mol) in dry 1,4-dioxane (50 ml) was stirred at room
temperature for 24 h. The reaction mixture was acidi®ed with hydro-
chloric acid and the formed precipitate was collected by ®ltration,
dried and then recrystallized from the appropriate solvent.
1
5a: yield 40%, mp >300 8C (from MeOH), ꢀmax (KBr)/cm
3549, 3292 (NH2), 2216 (CN), 1734 (CO) (Found: C, 43.6; H, 3.3;
N, 31.5%. C8H7N5SO requires C, 43.4; H, 3.2; N, 31.6%).
1
5b: yield 35%; mp 150±151 8C (from MeOH); ꢀmax (KBr)/cm
3609, 3316 (OH, NH2), 2213 (CN), 1734 (CO) (Found: C, 43.4; H,
2.9; N, 25.0%. C8H6N4SO2 requires C, 43.2; H, 2.7; N, 25.5%).
1-(N-Substituted)arylmethylideneamino-4-methylsulfanyl-2-pyridone
Derivatives 8a±f. Method A.ÐA mixture of [bis(methylsulfanyl)-
methylene]malononitriles 1a or ethyl 2-cyano-3,3-bis(methyl-
sulfanyl)acrylate 1b (0.01 mol), 1-cyanoacetyl-4-arylidenesemicarba-
zide (0.01 mol), potassium hydroxide (0.012 mol) and 1,4-dioxane
(50 ml) were stirred at room temperature for 24 h. The reaction
mixture was acidi®ed with hydrochloric acid and the precipitate
formed was collected by ®ltration, dried and then recrystallized
from the appropriate solvent.
1
tral data (MS, H NMR, 13C NMR and IR). The analytical
data for 8c revealed a molecular formula C16H13N5SO
(M+=323). The 13C NMR showed a signal at d 18.15 due
to the SMe carbon and a signal at d 160.17 attributed to
a 2-pyridone carbonyl carbon. Compounds 4 and 8 can
also be prepared by the reaction of the corresponding N-
amino-2-pyridones 5 with substituted isothiocyanates and
aldehydes, respectively, in re¯uxing 1,4-dioxane for 2 h.
Compounds 8 reacted with hydrazine in re¯uxing ethanol to
give the corresponding pyrazolo[3,4-c]pyridines 9. The struc-
tures of each of the compounds 9 were established on the
basis of elemental analysis and spectral data.
In summary, we have achieved a regiospeci®c synthesis
of interesting N-substituted amino-4-methylsulfanyl-2-
pyridones and deazapurine analogues via the reaction of
ketene dithioacetals with semi- and thio-semicarbazide-
derivatives. The products obtained are currently under
biological evaluation studies.
Method B. To a solution of N-amino-2-pyridones 5 (0.01 mol)
in 1,4-dioxane (50 ml), aromatic aldehyde (0.01 mol) was added.
The resulting mixture was re¯uxed for 2 h and the solid product
collected by ®ltration and crystallized from the appropriate solvent.
1
8a: yield 51%; mp >300 8C (from 1,4-dioxane); ꢀmax (KBr)/cm
3425 (NH2), 2211 (CN), 1634 (CO) (Found: C, 52.7; H, 3.1; N,
20.2%. C15H10ClN5SO requires C, 52.4; H, 2.9; N, 20.4%).
8b: yield 83%; mp >300 (from 1,4-dioxane); ꢀmax (KBr)/cm
1
3446 (NH2), 2220 (CN), 1685 (CO) (Found: C, 59.0; H, 4.2; N,
21.5%. C16H13N5SO requires C, 59.4; H, 4.0; N, 21.7%).
1
8c: yield 76%; mp 285±287 8C (from MeOH); ꢀmax(KBr)/cm
3506±3345 (OH), 2209 (CN), 1654 (CO) (Found: C, 58.2; H, 3.3; N,
17.8%. C15H10N4SO2 requires C, 58.0; H, 3.2; N, 18.0%).
1
8d: yield 62%; mp 210±211 8C (from EtOH); ꢀmax/cm 3498,
3381 (NH2), 2206 (CN), 1687 (CO) (Found: C, 59.0; H, 3.9; N,
17.3%. C16H12N4SO2 requires C, 59.3; H, 3.7; N, 17.3%).
6-Amino-3-cyanopyrazolo[3,4-c]pyridin-2(1H)-one Derivatives 9a±d.
General Procedure.ÐA mixture of equivalent amounts of 5b,c,e,f
(0.01 mol) and hydrazine hydrate (0.01 mol) was heated in ethanol
(30 ml) for 4 h. The solid product formed was collected by ®ltration
and crystallized from the appropriate solvent.
Experimental
All melting points are uncorrected. IR spectra were obtained
(KBr) on a Pye Unicam instrument. 1H- and 13C-NMR spectra
were measured on a Varian 400 or Wilmad 270 MHz spectrometer
for (CD3)2SO solutions using SiMe4 as internal standard. Mass
1
9a: yield 53%; mp >300 8C (from DMF); ꢀmax (KBr)/cm 3479,
spectra were recorded on
a Varian MAT 112 spectrometer.
3315 (NH, NH2), 2210 (CN), 1655 (CO); dH (DMSO) 5.68 (s, br, 2
H, NH2), 6.87±7.89 (m, 4 H, C6H4), 8.12 (s, 1 H, ylidic CH), 8.28
(s, br, 2 H, NH2), 11.85 (s, br, 1 H, NH) (Found: C, 51.5; H, 2.9;
N, 30.2%. C14H10ClN7O requires C, 51.3; H, 3.1; N, 29.9%).
Analytical data were obtained from the Microanalytical Data
Centre at Cairo University.
N-(4-Methylsulfanyl-2-oxo-1-pyridyl)thiourea Derivatives 4a,b.
Method A.ÐA mixture of [bis(methylsulfanyl)methylene]malono-
nitriles 1a or ethyl 2-cyano-3,3-bis(methylsulfanyl)acrylate 1b
1
9b: yield 55%; mp >300 8C (from EtOH); ꢀmax (KBr)/cm
3600±3182 (NH, NH2), 2206 (CN), 1639 (CO) (Found: C, 58.2; H,
4.3; N, 32.2%. C15H13N7O requires C, 58.6; H, 4.2; N, 31.9%).
(0.01 mol),
4-substituted
cyanoacetythiosemicarbazide
3a,b
(0.01 mol), potassium hydroxide (0.012 mol) and dry 1,4-dioxane
(50 ml) were stirred at room temperature for 24 h. The reaction
mixture was acidi®ed with hydrochloric acid and the formed precipi-
tate was collected by ®ltration, dried and then crystallized from the
appropriate solvent.
1
9c: yield 54%; mp >300 8C (from 1,4-dioxane); ꢀmax (KBr)/cm
3450, 3350 (OH, NH, NH2), 2205 (CN), 1702 (CO) (Found: C,
57.4; H, 3.5; N, 28.3%. C14H10N6O2 requires C, 57.1; H, 3.4; N,
28.6%).
1
9d: yield 54%; mp >300 8C (from MeOH); ꢀmax (KBr)/cm
Method B.ÐTo a solution of N-amino-2-pyridones 5 (0.01 mol)
in 1,4-dioxane (50 ml), phenyl isothiocyanate or benzoyl isothio-
cyanate (0.01 mol) was added. The resulting mixture was re¯uxed
for 2 h and the solid product collected by ®ltration and crystallized
from the appropriate solvent.
3451, 3352 (OH, NH, NH2), 2205 (CN), 1703 (CO) (Found: C,
58.0; H, 4.0; N, 27.5%. C15H12N6O2 requires C, 58.4; H, 3.9; N,
27.3%).
1
4a: yield 52%, mp 280±282 8C (from EtOH); ꢀmax (KBr)/cm
Received, 18th March 1997; Accepted, 13th August 1997
Paper E/7/01889D
3391 (NH, NH2), 2217 (CN), 1655 (CO) (Found: C, 50.3; H, 3.6;
N, 23.5%. C15H12N6S2O requires C, 50.7; H, 3.4; N, 23.6%).
4b: yield 52%, mp 242±244 8C (from 1,4-dioxane); ꢀmax (KBr)/
1
References
cm 3600, 3380, 3320±3100 (OH, NH), 2212 (CN), 1655 (CO)
(Found: C, 50.7; H, 3.0; N, 19.4%. C15H11N5S2O2 requires C, 50.4;
H, 3.1; N, 19.6%).
4c: yield 53%, mp >300 8C (from EtOH); ꢀmax (KBr)/cm 3312,
1 G. H. Elgemeie and B. A. Hussain, Tetrahedron, 1994, 50, 199.
2 G. H. Elgemeie, A. M. Attia, D. S. Farag and S. M. Sherif,
J. Chem. Soc., Perkin Trans. 1, 1994, 1285.
1
3280 (NH, NH2, 2211 (CN), 1650 (CO); dH (DMSO) 2.69 (s, 3 H,
SMe), 6.92 (m, 2 H, NH2), 7.19±7.77 (m, 5 H, Ph), 9.60 (s, br, 1 H,
NH), 10.53 (s, br, 1 H, NH) (Found: C, 49.7; H, 3.2; N, 21.9%.
C16H13N6S2O2 requires C, 50.0; H, 3.0; N, 21.6%).
4d: yield 55%, mp 290±293 8C (from MeOH); ꢀmax (KBr)/cm
3454, 3350 (OH, NH), 2213 (CN), 1634 (CO). 2.82 (s, 3 H, SMe),
7.18±7.81 (m, 5 H, Ph), 11.35 (s, br, 1 H, NH), 13.50 (s, br, 1 H,
3 G. H. Elgemeie, S. E. El-Ezbawy, H. A. Ali and A. K. Mansour,
Bull. Chem. Soc. Jpn, 1994, 67, 738.
4 T. Tsukamoto, W. H. Haile, J. J. McGuire and J. K. Coward,
J. Med. Chem., 1996, 39, 2536.
5 K. Peseke, J. Q. Suarez, F. Napoies and M. Basilia, Ger. (East)
DD 294 943 (Cl. C07D 487/04) (Chem. Abstr., 1992, 116, 128960
u).
1