First synthesis of double headed 1,2,4-triazino[5,6-b]indole acyclo C-nucleosides

Article abstract of DOI:10.1002/jccs.200500075

Heterocyclization of bis(2-oxo-indol-3-ylidene)-galactaric acid hydrazide (3) with a variety of one-nitrogen cyclizing agents gave the corresponding 1,4-bis{1,2,4-triazino[5,6-b]indol-3-yl}-galacto-tetritols 4-8. Acetylation of the latter double headed ac

Full text of DOI:10.1002/jccs.200500075

Journal of the Chinese Chemical Society, 2005, 52, 519-524
519
First Synthesis of Double Headed 1,2,4-Triazino[5,6-b]indole Acyclo
C-Nucleosides
Adel Z. Nasr
Chemistry Department, Faculty of Science, Cairo University, Faiyoum 63514, Egypt
Heterocyclization of bis(2-oxo-indol-3-ylidene)-galactaric acid hydrazide (3) with a variety of one-
nitrogen cyclizing agents gave the corresponding 1,4-bis{1,2,4-triazino[5,6-b]indol-3-yl}-galacto-tetritols
4-8. Acetylation of the latter double headed acyclo C-nucleosides with acetic anhydride in the presence of
pyridine at ambient temperature resulted in N- and O-acetylation to give the corresponding 1,2,3,4-tetra-O-
acetyl-1,4-bis{1,2,4-triazino[5,6-b]indol-3-yl}-galacto-tetritols 9-13 which were found to exist in centro-
symmetric zigzag conformations 20. The assigned structures were corroborated by 1H, 13C NMR as well as
mass spectra.
Keywords: Bis(2-oxo-indol-3-ylidene)-galactaric acid hydrazide; One-nitrogen cyclizing agents;
Heterocyclization; Double headed 1,2,4-triazino[5,6-b]indole acyclo C-nucleosides.
INTRODUCTION
The synthesis of 1,2,4-triazino[5,6-b]indoles has been
cations, and to the best of our knowledge, the incorporation
of a tetritolyl moiety to 1,2,4-triazino[5,6-b]indoles has not
been reviewed. Consequently, the goal in the present work is
to develop the first synthesis of the double headed 1,2,4-tri-
azino[5,6-b]indole acyclo C-nucleosides as a part of our stud-
ies on the synthesis of acyclo C-nucleosides.14,25,30-33
surveyed in three reviews.1-3 A large number of compounds
belonging to this ring system were extensively synthesized
from both research and medicinal chemistry points of view.
The incorporation of certain functional groups into the skel-
ton of this ring system may yield a compound with enhanced
biological activities. Thus, 3-hydrazino- and 3-thiosemicar-
bazido- derivatives of 1,2,4-triazino[5,6-b]indoles have been
found to possess antimicrobial,4-8 antiviral,9 antihyper-
tensive,9,10 blood-platelet aggregation inhibitory,10,11 and an-
algesic12 activities. In addition, 3-arylidene- and 3-alditol-1-
ylidenehydrazino-1,2,4-triazino[5,6-b]indoles showed anti-
tumor activity against P388 lymphocytic leukemia in mice13
and antibacterial activity.14,15
RESULTS AND DISCUSSION
Recently, we synthesized bis(2-oxo-indol-3-ylidene)-
galactaric acid hydrazide (3) by the condensation of 2,3-
dioxo-indole (1) with galactaric acid bis hydrazide (2) and
studied the heterocyclization of its tetra-O-acetate derivative
to the double headed 1,3,4-oxadiazino[5,6-b]indole acyclo
C-nucleoside.34 We report in the present investigation on the
utilization of compound 3 as double headed 1,2,4-triazino-
[5,6-b]indole acyclo C-nucleoside synthons. Thus, fusion of
compound 3 with ammonium acetate gave a product which
showed characteristic IR absorption due to overlapped OH
and NH at 3287 and C=N at 1628 cm-1 and lacked amide ab-
sorptions and was correctly analyzed for the molecular for-
mula C22H18N8O4. 1H NMR of the product revealed beside the
aromatic eight protons and the tetritolyl four CH protons,
signals due to six exchangeable protons: two NH protons
resonated as a singlet signal at d 12.25 and tetritolyl four OH
protons appeared as two doublet signals at d 5.80 and 5.07
ppm. The product was ascribed, therfore, the 1,4-bis{5H-
1,2,4-triazino[5,6-b]indol-3-yl}-galacto-tetritol structure
On the other hand, the chemistry of acyclo C-nucleo-
sides have been reviewed16-22 and valuable medicinal appli-
cations and biological activities have been found to be associ-
ated with acyclo C-nucleosides carrying various types of
heterocycles due to their ability to mimic isosteric N-nucleo-
sides. Various synthetic members of acyclo C-nucleosides
have been reported to be useful as antivirals,23 antibacte-
rials,24 antifungals,25 protein kinase inhibitors,26 lympho-
penia producers27 and diagnostic markers for cancer.28 More-
over, pharmaceutical applications including the treatment of
some metabolic diseases such as Parkinson’s disease29 have
been attributed to some acyclo C-nucleoside precursors. De-
spite all these highly desirable activities and medicinal appli-

520 J. Chin. Chem. Soc., Vol. 52, No. 3, 2005
Nasr
(8) (Scheme I).
tyl protons in addition to the aromatic eight protons and ana-
lyzed for the molecular formula C34H30N8O10. These data are
in agreement with both O-acetylation of the tetritolyl four
hydroxyl groups and N-acetylation of the two heteroaryl NH
protons of compound 8. The MS of the acetylation product
did not reveal its molecular ion peak, yet showed a fragment
at m/z 335 (15) resulting from C1-C2 bond cleavage of the
tetritolyl chain in addition to the fragments at m/z 241 (16),
Acetylation of compound 8 with acetic anhydride in the
presence of pyridine at ambient temperature gave a single
product which lacked OH and NH IR absorptions, in addition
to two NH and four OH 1H NMR proton signals of the parent
compound. It showed OAc, CON and C=N IR absorptions as
1
well as H NMR proton signals attributed to the tetra-O-
acetyl-tetritolyl chain protons (4CH and 4OAc), two N-ace-
Scheme I

First Synthesis of Double Headed C-Nucleosides
J. Chin. Chem. Soc., Vol. 52, No. 3, 2005 521
m/z 212 (17), m/z 186 (18) and m/z 158 (19) (Fig. 1). Frag-
ment 16 is indicative for the carbon-carbon linkage between
the tetritolyl chain and the base moiety of acyclic C-nucleo-
sides,35,36 while fragment 19 indicated that the acetylation
process was involved the pyrrole ring nitrogen rather than the
1,2,4-triazine ring N2 or N4 and, consequently, the acetyla-
tion product was assigned the 1,2,3,4-tetra-O-acetyl-1,4-bis-
{5-acetyl-1,2,4-triazino[5,6-b]indol-3-yl}-galacto-tetritol
structure (9). Our result of preference of acetylation of the
pyrrole ring nitrogen rather than the 1,2,4-triazine ring N2 or
N4 of the 5H-1,2,4-triazino[5,6-b]indole skeltons is in har-
mony with the previously reported results.32,37 13C NMR
spectrum of compound 9 showed each set of signals from the
respective carbon completely overlapped with each other;
thus, it revealed signals at d 20.06, 20.12 (4OCOOCH3),
24.09 (2NCOCH3), 66.99, 70.84 (tetritolyl 4 carbons), 110.20
(2C6), 117.11 (2C9a), 120.09 (2C7), 122.10 (2C9), 129.43
(2C8), 138.66 (2C5a), 140.80 (2C9b), 147.28 (2C4a), 160.39
(2C3), 162.91 (2NCOCH3), 169.36, 170.17 (4OOCH3). These
13C NMR data were assigned on the basis of comparing with
the data reported for 1,2,4-triazino[5,6-b]indoles5,14 and poly-
O-acetyl-3-alditol-1-ylidenehydrazino-1,2,4-triazino[5,6-
b]indoles.14
doublet signals at d 5.41 and 5.08 and tetritolyl four CH pro-
tons as two doublet signals at d 4.86 and 3.82 ppm. These
spectral results are consistent with the 1,4-bis{4-amino-
1,2,4-triazino[5,6-b]indol-3-yl}-galacto-tetritol structure 5.
The 13C NMR spectrum of 5 gave characteristic signals in ac-
cordance with the assigned structure (see experimental). The
MS of compound 5 showed its molecular ion peak (M+) at m/z
488 (0.58%). This very low intensity may be attributed to the
relative instability of 5 caused by the presence of sugar moi-
ety in its structure.38,39 The structure of compound 5 was also
supported by its easy reaction with p-nitro-benzaldehyde to
give the p-nitrobezylidene derivative 14. In a similar fashion
compound 3 underwent a condensative cyclization reaction
with phenylhydrazine or 1-methyl-1-phenylhydrazine to
give the double headed acyclo C-nucleosides 6 and 7, respec-
tively.
Acetylation of the acyclo C-nucleosides 5-7 caused
acetylation of each of the tetritolyl chain hydroxyls of the
three startings as well as NH of the two amino and the two
phenylamino groups of 5 and 6, respectively. Each 1H NMR
spectrum of the resulting tetra-O-acetates 11-13 revealed
proton signals attributed to aromatic eight protons and the
tetra-O-acetyl-tetritolyl chain (4CH and 4OCOCH3). Com-
pound 11 showed in addition, two exchangeable NH protons
and two N-acetyl protons while each compound of 12 and 13
displayed aromatic ten protons and two methyl group protons
(two NAc for compound 12 and two NCH3 for compound 13).
The 13C NMR spectrum of 11 showed the expected signals of
its carbon skelton (see experimental).
Similarly, heterocyclization of compound 3 by heating
with methylamine afforded the corresponding 1,4-bis{4-
methyl-1,2,4-triazino[5,6-b]indol-3-yl}-galacto-tetritol (4)
which was further characterized with its tetra-O-acetate de-
rivative 10 obtained by acetylation with acetic anhydride in
the presence of pyridine at room temperature.
Subjecting compound 3 to hydrazinolysis by heating
with hydrazine hydrate afforded a product which revealed IR
absorptions characteristic of OH, NH2 and C=N. In addition
to eight aromatic proton signals, the 1H NMR of the product
displayed two exchangeable NH2 protons as a singlet signal
at d 5.86, tetritolyl four exchangeable OH protons as two
It is notable that the 1H NMR spectrum of each of the
five tetra-O-acetates 9-13 showed its tetritolyl protons as two
singlet signals with zero coupling constants confirming their
centerosymmetric zigzag conformations 20 (Fig. 2) which is
in agreement with the results obtained for other galacto-tetri-
tol-1,4-yl acyclo C-nucleoides.34,39-41
Fig. 1. Mass spectrum fragments of compound 9.

522 J. Chin. Chem. Soc., Vol. 52, No. 3, 2005
Nasr
EXPERIMENTAL
2H each, tetritolyl H), 5.07, 5.80 (2d, exchangeable, 2OH
each), 7.14-7.18, 7.48-7.52 (2m, 4H each, Ar-H), 12.25 (s, br,
exchangeable, 2NH). Anal. Calcd. for C22H18N8O4: C, 57.64;
H, 3.93; N, 24.45. Found: C, 57.58; H, 3.96; N, 24.61.
Melting points were determined on a MEL-TEMP II
melting point apparatus in open glass capillaries and are un-
corrected. The infrared spectra IR were recorded for potas-
sium bromide discs on a Pye-Unicam SP1025 spectropho-
tometer. NMR spectra were carried out at ambient tempera-
ture (~25 °C) with a Brucker AC-250 spectrometer or with a
Varian Gemini 200 spectrometer at 250 MHz using tetra-
methylsilane (TMS) as an internal standard. Mass spectra
(MS) were preformed on a Hewlett-Packard 5995 gas chro-
matography-mass spectrometer system or on a Shimadzu
GCMS-QP 1000 EX mass spectrometer. Homogeneity of the
products and follow up of the reactions were checked by as-
cending thin-layer chromatography TLC on plates precoated
with silica gel G (E. Merck; layer thickness 0.25 mm), used
without pretreatment. All ratios of the used solvent systems
were volume to volume V/V; the solvent systems used were:
(A) CHCl3/MeOH (1:2) and (B) CHCl3/MeOH (9:1); the dis-
tance of the solvent travel was 5 cm and the spots were visual-
ized by exposure to iodine vapour for a few minutes. Elemen-
tal microanalyses were performed at the Microanalytical
Unit, Cairo University, Cairo, Egypt.
1,4-Bis{4-substituted-1,2,4-triazino[5,6-b]indol-3-yl}-galacto-
tetritols (4-7)
A mixture of compound 3 (2 g, 4.03 mmol) and methyl-
amine or the appropriate hydrazine derivatives (hydrazine
hydrate, phenylhydrazine or 1-methyl-1-phenylhydrazine)
(30 mL) was heated at reflux for 6 h and then evaporated un-
der reduced presure. The obtained residue was crystallized
from H2O-EtOH. The following compounds were prepared.
1,4-Bis{4-methyl-1,2,4-triazino[5,6-b]indol-3-yl}-galacto-
tetritol (4)
Yellow crystals, yield: 61%; m.p.: 232-235 °C; TLC
(A), Rf: 0.60; IR (KBr) nmax: 3315 (br, OH), 1602 (C=N) cm-1;
1H NMR [DMSO-d6]: d = 3.49 (s, 6H, 2CH3), 3.91, 4.55 (2d,
2H each, tetritolyl H), 5.17, 5.75 (2d, exchangeable, 2OH
each), 7.13-7.16, 7.48-7.51 (2m, 4H each, Ar-H). Anal.
Calcd. for C24H22N8O4: C, 59.26; H, 4.53; N, 23.05. Found:
C, 59.09; H, 4.63; N, 23.21.
1,4-Bis{5H-1,2,4-triazino[5,6-b]indol-3-yl}-galacto-tetritol
(8)
1,4-Bis{4-amino-1,2,4-triazino[5,6-b]indol-3-yl}-galacto-
tetritol (5)
Compound 3 (2 g, 4.03 mmol) was successively mixed
with anhydrous ammonium acetate (0.62 g, 8.06 mmol), and
the mixture was heated in a fusion tube provided with an air
condenser at 170 °C for 2 h. The obtained mass was triturated
with water and crystallized from H2O-EtOH to give com-
pound 8 as yellow crystals; yield: 66%; m.p.: 218-220 °C/
dec.; TLC (A), Rf: 0.61; IR (KBr) nmax: 3287 (br, OH + NH),
1628 (C=N) cm-1; 1H NMR [DMSO-d6]: d = 3.70, 4.53 (2d,
Yellowish white crystals, yield: 69%; m.p.: 220-222
°C/dec.; TLC (A), Rf: 0.59; IR (KBr) nmax: 3280 (br, OH +
NH2), 1643 (C=N) cm-1; 1H NMR [DMSO-d6]: d = 3.82, 4.86
(2d, 2H each, tetritolyl H), 5.08, 5.41 (2d, exchangeable,
2OH each), 5.86 (s, br, exchangeable, 2NH2) 7.49-7.52,
7.78-7.84 (2m, 4H each, Ar-H); 13C NMR (DMSO-d6]: d =
70.93, 71.23 (tetritolyl 4 carbons), 110.84 (2C6), 118.17
(2C9a), 119.13 (2C7), 122.31 (2C9), 128.71 (2C8), 137.31
(2C5a), 140.41 (2C9b), 147.93 (2C4a), 159.31 (2C3); MS
m/z (relative intensity) 488 (M+, 0.58), 198 (41.05), 169
(100). Anal. Calcd. for C22H20N10O4: C, 54.10; H, 4.10; N,
28.69. Found: C, 54.26; H, 4.07; N, 28.77.
1,4-Bis{4-phenylamino-1,2,4-triazino[5,6-b]indol-3-yl}-
galacto-tetritol (6)
Yellowish white crystals, yield: 64%; m.p.: 258-260
°C/dec.; TLC (A), Rf: 0.58; IR (KBr) nmax: 3362 (OH), 3317
(NH), 1630 (C=N) cm-1; 1H NMR [DMSO-d6]: d = 3.89, 4.70
(2d, 2H each, tetritolyl H), 5.17, 5.94 (2d, exchangeable,
2OH each), 7.12-7.14 (m, 4H, Ar-H), 7.49-7.58 (m, 10H, Ar-
H), 7.94-7.96 (m, 4H, Ar-H), 9.09 (s, exchangeable, 2NH).
Anal. Calcd. for C34H28N10O4: C, 63.75; H, 4.38; N, 21.88.
Fig. 2. Conformations of compounds 9-13.

First Synthesis of Double Headed C-Nucleosides
J. Chin. Chem. Soc., Vol. 52, No. 3, 2005 523
Found: C, 63.88; H, 4.27; N, 21.69.
(2C4a), 160.39 (2C3), 162.91 (2NCOCH3), 169.36, 170.17
(4OOCCH3); MS m/z (relative intensity) 355 (33.70), 241
(9.20), 212 (4.10), 186 (2.07), 169 (100), 158 (9.92). Anal.
Calcd. for C34H30N8O10: C, 57.47; H, 4.23; N, 15.78. Found:
C, 57.60; H, 4.12; N, 15.90.
1,4-Bis{4-(methylphenyl)amino-1,2,4-triazino[5,6-b]indol-
3-yl}-galacto-tetritol (7)
Yellowish white crystals, yield: 60%; m.p.: 272-275
°C/dec.; TLC (A), Rf: 0.57; IR (KBr) nmax: 3251 (br, OH),
1
1637 (C=N) cm-1. H NMR [DMSO-d6]: d = 3.79 (s, 6H,
1,2,3,4-Tetra-O-acetyl-1,4-bis{4-methyl-1,2,4-triazino[5,6-
b]indol-3-yl}-galacto-tetritol (10)
2CH3), 3.95, 4.79 (2d, 2H each, tetritolyl H), 5.05, 5.44 (2d,
exchangeable, 2OH each), 7.09-7.52 (m, 10H, Ar-H), 7.78-
7.82, 8.08-8.10 (2m, 4H each, Ar-H). Anal. Calcd. for
C36H32N10O4: C, 64.67; H, 4.79; N, 20.96. Found: C, 64.63;
H, 4.81; N, 21.01.
Pale yellow crystals, yield: 79%; m.p.: 240 °C; TLC
(B), Rf: 0.63; IR (KBr) nmax: 1747 (OAc), 1626 (C=N) cm-1.
1H NMR [DMSO-d6]: d = 2.17, 2.25 (2s, 6H each, OAc), 3.68
(s, 6H, NCH3), 5.08, 5.59 (2s, 2H each, tetritolyl H), 7.49-
7.52, 7.74-7.77 (2m, 4H each, Ar-H). Anal. Calcd. for
C32H30N8O8: C, 58.72; H, 4.59; N, 17.13. Found: C, 58.59; H,
4.63; N, 17.18.
1,4-Bis{4-(p-nitrobenzylideneamino)-1,2,4-triazino[5,6-b]-
indol-3-yl}galacto-tetritol (14)
A suspension of compound 5 (1 g, 2.05 mmol) in etha-
nol (30 mL) was treated with a solution of p-nitrobenzalde-
hyde (0.62, 4.11 mmol) in ethanol (20 mL) containing 2 drops
of CH3COOH. The mixture was heated at reflux for 1 h and
the product was filtered, washed with hot EtOH and crystal-
lized from H2O-EtOH to give compound 14 as pale yellow
crystals; yield: 71%; m.p.: 287-290 °C/dec.; TLC (A), Rf:
1,2,3,4-Tetra-O-acetyl-1,4-bis{4-acetamido-1,2,4-triazino-
[5,6-b]indol-3-yl}-galacto-tetritol (11)
Colorless crystals, yield: 78%; m.p.: 258 °C; TLC (B),
Rf: 0.61; IR (KBr) nmax: 3218 (NH), 1751 (OAc), 1678 (CON),
1
1624 (C=N) cm-1. H NMR [DMSO-d6]: d = 1.98, 2.04 (2s,
6H each, OAc), 2.98 (s, 6H, 2NAc), 5.09, 5.49 (2s, 2H each,
alditolyl H), 7.49-7.52, 7.75-7.77 (2m, 4H each, Ar-H), 8.26
(s, br, exchangeable 2NH); 13C NMR (DMSO-d6]: d = 20.10,
20.71 (4OCOOCH3), 24.13 (2NCOCH3), 68.14, 68.08 (tetri-
tolyl 4 carbons), 110.73 (2C6), 117.53 (2C9a), 119.99 (2C7),
122.04 (2C9), 129.01 (2C8), 138.39 (2C5a), 140.31 (2C9b),
147.61 (2C4a), 159.47 (2C3), 163.41 (2NCOCH3), 169.71,
170.34 (4OOCCH3). Anal. Calcd. for C34H32N10O10: C,
55.14; H, 4.32; N, 18.92. Found: C, 55.24; H, 4.22; N, 19.01.
1
0.56; IR (KBr) nmax: 3296 (br, OH), 1635 (C=N) cm-1; H
NMR [DMSO-d6]: d = 3.81, 4.79 (2d, 2H each, tetritolyl H),
5.17, 5.82 (2d, exchangeable, 2OH each), 7.33-7.38, 5.48-
5.57 (2m, 8H each, Ar-H), Anal. Calcd. for C36H26N10O8: C,
59.50; H, 3.58; N, 19.28. Found: C, 59.58; H, 3.55; N, 19.33.
General procedure for acetylation of the acyclo C-nu-
cleosides 4-8
A mixture of the appropriate compound 4-8 (2 g, 3.00-
4.37 mmol), pyridine (10 mL) and acetic anhydride (30 mL)
was stirred at room temperature for 48 h. The mixture was
evaporated under reduced pressure and the product was crys-
tallized from CHCl3-EtOH. The folloiwng compounds were
prepared.
1,2,3,4-Tetra-O-acetyl-1,4-bis{4-(acetylphenyl)amino-
1,2,4-triazino[5,6-b]indol-3-yl}-galacto-tetritol (12)
Colorless crystals, yield: 71%; m.p.: 262 °C; TLC (B),
Rf: 0.58; IR (KBr) nmax: 1754 (OAc), 1675 (NCO), 1595 (C=N)
cm-1. 1H NMR [DMSO-d6]: d = 1.91, 2.19 (2s, 6H each, OAc),
2.59 (2s, 6H, NCOCH3), 5.21, 5.79 (2s, 2H each, alditolyl H),
6.94-6.99 (m, 4H, Ar-H), 7.13-7.17 (m, 10H, Ar-H), 7.48-
7.51 (m, 4H, Ar-H). Anal. Calcd. for C46H40N10O10: C, 61.88;
H, 4.48; N, 15.70. Found: C, 61.97; H, 4.36; N, 15.83.
1,2,3,4-Tetra-O-acetyl-1,4-bis{5-acetyl-1,2,4-triazino[5,6-
b]indol-3-yl}-galacto-tetritol (9)
Pale yellow crystals, yield: 81%; m.p.: 202 °C; TLC
(B), Rf: 0.62; IR (KBr) nmax: 1749 (OAc), 1696 (CON), 1611
1
(C=N) cm-1. H NMR [DMSO-d6]: d = 1.91, 2.05 (2s, 6H
1,2,3,4-Tetra-O-acetyl-1,4-bis{4-(methylphenyl)amino-
1,2,4-triazino[5,6-b]indol-3-yl}-galacto-tetritol (13)
Colorless crystals, yield: 72%; m.p.: 233 °C; TLC (B),
each, OAc), 2.79 (s, 6H, NCOCH3), 5.76, 5.92 (2s, 2H each,
tetritolyl H), 7.40, 7.49 (2t, 2H each, Ar-H), 7.80, 8.09 (2d,
2H each, Ar-H); 13C NMR (DMSO-d6]: d = 20.06, 20.12
(4OCOOCH3), 24.09 (2NCOCH3), 66.99, 70.84 (tetritolyl 4
carbons), 110.20 (2C6), 117.11 (2C9a), 120.09 (2C7), 122.10
(2C9), 129.43 (2C8), 138.66 (2C5a), 140.80 (2C9b), 147.28
Rf: 0.60; IR (KBr) nmax: 1754 (OAc), 1615 (C=N) cm-1. H
1
NMR [DMSO-d6]: d = 1.97, 2.19 (2s, 6H each, OAc), 3.73 (s,
6H, NCH3), 5.23, 5.56 (2s, 2H each, alditolyl H), 7.12-7.46
(m, 4H, Ar-H), 7.49-7.58 (m, 10H, Ar-H), 7.94-7.99 (m, 4H,

524 J. Chin. Chem. Soc., Vol. 52, No. 3, 2005
Nasr
Ed.; Academic Press: New York, 1998, 70, 163.
Ar-H), Anal. Calcd. for C44H40N10O8: C, 63.16; H, 4.79; N,
16.75. Found: C, 63.22; H, 4.81; N, 16.84.
20. El Ashry, E. S. H.; El Kilany, Y. In Advances in Heterocyclic
Chemistry; Katritzky, A. R. Ed.; Academic Press: New York,
1996, 67, 391.
21. El Ashry, E. S. H.; El Kilany, Y. In Advances in Heterocyclic
Chemistry; Katritzky, A. R. Ed.; Academic Press: New York,
1997, 68, 1.
Received June 23, 2004.
22. El Ashry, E. S. H.; El Kilany, Y. In Advances in Heterocyclic
Chemistry; Katritzky, A. R. Ed.; Academic Press: New York,
1998, 69, 129.
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