Nucleic acid components and their analogues: A novel and efficient method for the synthesis of a new class of bipyridyl and biheterocyclic-nitrogen thioglycosides from pyridine-2(1H)-thiones

Article abstract of DOI:10.1081/NCN-120014820

A novel synthesis of a new class of bipyridyl and biheterocyclic-nitrogen thioglycosides utilizing the reactions of heterocyclic substituted pyridine-2(1H)-thiones and α-bromoglucose or α-bromogalactose tetraacetate as starting components is described.

Full text of DOI:10.1081/NCN-120014820

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NUCLEIC ACID COMPONENTS AND THEIR ANALOGUES:
A NOVEL AND EFFICIENT METHOD FOR THE SYNTHESIS
OF A NEW CLASS OF BIPYRIDYL AND BIHETEROCYCLIC-
NITRO GEN THIOGLYCOSIDES FROM PYRIDINE-2(1H)-
THIONES
Galal H. Elgemeie a , Mervat M. El-Enany b , Mohamed M. Ismail b & Eman K. Ahmed b
a Chemistry Department , Helwan University , Ain-Helwan, Helwan, Cairo, Egypt
b Department of Organic Chemistry , Cairo University , Cairo, Egypt
Published online: 31 Aug 2006.
To cite this article: Galal H. Elgemeie , Mervat M. El-Enany , Mohamed M. Ismail & Eman K. Ahmed (2002) NUCLEIC ACID
COMPONENTS AND THEIR ANALOGUES: A NOVEL AND EFFICIENT METHOD FOR THE SYNTHESIS OF A NEW CLASS OF BIPYRIDYL
AND BIHETEROCYCLIC-NITRO GEN THIOGLYCOSIDES FROM PYRIDINE-2(1H)-THIONES, Nucleosides, Nucleotides and Nucleic
Acids, 21:6-7, 477-493
To link to this article: http://dx.doi.org/10.1081/NCN-120014820
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MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS
Vol. 21, Nos. 6 & 7, pp. 477–493, 2002
NUCLEIC ACID COMPONENTS AND THEIR
ANALOGUES: A NOVEL AND EFFICIENT
METHOD FOR THE SYNTHESIS OF A NEW
CLASS OF BIPYRIDYL AND BIHETEROCYCLIC-
NITROGEN THIOGLYCOSIDES FROM
PYRIDINE-2(1H )-THIONES
Galal H. Elgemeie,1,* Mervat M. El-Enany,2 Mohamed M. Ismail,2
and Eman K. Ahmed2
1Chemistry Department, Faculty of Science, Helwan University,
Ain-Helwan, Helwan, Cairo, Egypt
2Department of Organic Chemistry, Faculty of Pharmacy,
Cairo University, Cairo, Egypt
ABSTRACT
A novel synthesis of a new class of bipyridyl and biheterocyclic-nitrogen
thioglycosides utilizing the reactions of heterocyclic substituted pyridine-
2(1H)-thiones and a-bromoglucose or a-bromogalactose tetraacetate as
starting components is described.
Key Words: Pyridine thioglycosides; Pyridine-2(1H)-thiones; Coupling
reactions; Biheterocyclic thioglycosides
*Corresponding author. Fax: 002 02 5870668; E-mail: rughe@rusys.eg.net or elgemei@
hotmail.com
477
DOI: 10.1081=NCN-120014820
Copyright # 2002 by Marcel Dekker, Inc.
1525-7770 (Print); 1532-2335 (Online)
www.dekker.com

478
ELGEMEIE ET AL.
Pyridinethione nucleosides were recently reported by us to exert inhibitory
effects on both DNA and RNA containing viruses.[1–5] On the basis of these
findings, it was of interest to prepare modified analogues to search for more
effective agents. This paper describes the synthesis of nonclassical bipyridyl
and biheterocyclic-nitrogen thioglycosides. As far as we know, these are the
first reported examples of biheterocyclic thioglycosides. The sequence of
reactions followed in the preparation of the designed compounds, is sum-
marized in the following schemes (Charts 1–4). Thus, it was found that
heating of cyclopentanone, cyclohexanone, cycloheptanone or cyclooctanone
with cyanothioacetamide and a catalytic amount of ammonium acetate=
acetic acid in benzene for 3 h with azeotropic removal of water gave the
corresponding cycloalkylidenecyanothioacetamides 1 in good yields. Com-
pounds 1 reacted with pyridylmethylenemalononitriles 2 in refluxing ethanol
containing catalytic amounts of piperidine for 2 h to give the bipyridyl
derivatives 5a^h. The structures of compounds 5 are established on the basis
of their elemental analyses and spectral data. Thus, 5c revealed a molecular
1
formula C15H13N3S (m=z ¼ 267). The H NMR spectrum of 5c showed a
broad scale at d 14.12 ppm assigned to the NH proton. The formation of 5
from 1 and 2 is assumed to proceed via addition of the active methylene
group of 1 to the olefenic bond of 2 to give the intermediate 3. This Michael
adduct 3 then cyclizes via malononitrile elimination to give the intermediate
dihydropyridine derivative 4, which is oxidized under the reaction conditions
to yield the fused pyridinethiones 5. The interesting course of the reac-
tion between the cycloalkylidene-cyanothioacetamides 1 and the pyridyl-
methylenemalononitriles 2 prompted us to investigate the reaction between
the pyridylmethylene(cyano)thioacetamides 6a,b and the cycloalkylidene-
malononitriles 7a^d under the same conditions. The obtained products were
shown to be the same as those resulting from the reaction of 1 with 2 by their
m.p.s and spectral data. The mechanism of the reaction of 6 with 7 is
assumed to proceed through the formation of the initial adduct 8, which lead
to intermediates 9 and subsequently to the products 5, as the same produced
by the reaction of 1 with 2. Compounds 5 could be coupled with different
classes of sugar halides to give a novel ring system of glycosides. Thus, it was
found that compounds 5a^h reacted with 2,3,4,6-tetra-O-acetyl-a-D-gluco-
and -galacto-pyranosyl bromides 13a,b in the presence of aqueous potassium
hydroxide to give the corresponding S-glucosides 15a^h and S-galactosides
15i^p, respectively. The structures of the reaction products 15 were estab-
lished on the basis of their elemental analyses and spectral data (MS, IR, UV,
1H NMR, 13C NMR). Thus, the analytical data for 15c revealed a molecular
formula C29H31N3O9S (m=z ¼ 597). The 1H NMR spectrum of 15c show the
anomeric proton as a doublet at d 6.15 ppm with a spin-spin coupling con-
stant of 11.28 Hz corresponding to a diaxial orientation of H-10 and H-20
protons and indicating the b-configuration. The other six protons of the
glucopyranosyl ring resonated in the d 3.99–5.53 ppm region. The remaining

NEW THIOGLYCOSIDES
479
Chart 1.

480
ELGEMEIE ET AL.
Chart 2.

NEW THIOGLYCOSIDES
481
Chart 3.

482
ELGEMEIE ET AL.
Chart 4.

NEW THIOGLYCOSIDES
483
four acetoxy groups appeared as four singlets at d 1.80–2.03 ppm and the
four methylene protons of the agylcon resonated at d 1.65, 1.78, 2.15 and
3.02 ppm. The 13C NMR spectrum was characterized by a signal at dc 80.08
corresponding to the C-10 atom of the b-D-glucopyranose. The four signals
appearing at dc 169.01–170.08 ppm were due to the four acetoxy carbonyl
carbon atoms, while the four signals at dc 20.00–20.20 were attributed to the
acetate methyl carbons. The five methylene carbon atoms of the aglycone
resonated at dc 25.00, 26.05, 27.00, 28.30, 33.30 ppm. Another five signals at
dc 61.80, 68.00, 69.01, 73.20 and 75.00 were assigned to C-60, -40, -20, -30 and
-50, respectively. The IR spectrum of compound 15c was characterized by the
presence of acetoxy carbonyl groups at 1755 cmꢀ1. It could have been argued
that the coupling reaction of 5 with 13 happened on the nitrogen atom to give
the corresponding N-glycosides 14. However, the formation of the S-glyco-
sides 15 was proved using 13C NMR which revealed the absence of the thione
carbon at dc 178 ppm[6] and appearance of C-2 at dc 161 ppm,[7] nearly the
same value as the corresponding S-methyl derivatives 17. Also, the UV
spectra of compounds 15 proved that the reaction had led selectively to the
formation of S-glycosyl derivatives since the corresponding S-methyl deri-
vatives 17 gave the same UV absorption maxima. For example, the S-methyl
derivative 17c showed two maxima at 277 and 362 nm and its corresponding
glucosyl derivative also exhibited two maximum absorption bands at 272.2
and 317.6 nm. The protected nucleosides 15a^p were deblocked through
treatment with methanolic ammonia to give the free glycosides 16a^p after
chromatographic purification. TLC of compounds 16a^p showed that a
single unique compound was produced, and their structures were confirmed
by their elemental analysis and spectral data. The analytical data for com-
pound 16j revealed a molecular formula C20H21N3O5S (m=z ¼ 415). The IR
absorption spectrum of this compound showed a characteristic band at 3200–
3600 cmꢀ1 due to the hydroxy groups of the galactose moiety. The 1H NMR
spectrum of compound 16j revealed the presence of a doublet at d 5.62
0
0
(J1 –2 ¼ 10.75 Hz), indicating the presence of only the b-D galactopyranose.
The other six-galactose protons appeared as a multiplet at d 3.10–3.80 ppm,
while the four hydroxy protons of the galactose moiety resonated at d 4.55,
4.95 and 5.30 ppm (exchangeable by D2O). The 13C NMR spectrum was
characterized by a signal at dc 83.50 corresponding to the C-10 atom of b-D
galactopyranose. Another five signals at dc 60.00, 69.50, 69.10, 75.10, and
80.00 were assigned to C-60, -40, -20, -30, and -50 of the galactose part,
respectively. In order to explore the synthetic potential of this exchange
reaction for producing not readily accessible condensed pyridinethiones and
their corresponding nucleosides, we investigated this reaction with other
class of cycloalkylidene ring system. So, it was been found that tetra-
linylidenecyanothioacetamide 18b reacted with pyridylmethylidene-malono-
nitrile 2a,b in refluxing ethanol containing catalytic amounts of piperidine for
3 h to give the interesting phenanthridine analogues 20a,b. The formation of

484
ELGEMEIE ET AL.
20 from 18b and 2a,b is assumed to proceed via addition of the active
methylene group of 1 to the double bond of 2a,b, giving Michael inter-
mediates which then cyclize via malononitrile elimination and oxidation
under the reaction conditions to yield compounds 20. The obtained products
20 were shown to be the same as those resulted from the reaction of 18a with
6a,b by TLC, melting point and spectral data. The mechanism of the reaction
of 18a and 6a,b is assumed to proceed through Michael addition followed by
the exchange reaction between the cycloalkylidene group of 18a and the
pyridylmethylidene group of 6a,b, which leads to the intermediates 19 and
hence to the final product 20. The analytical data for compound 20a revealed
a molecular formula C19H13N3S (m=z ¼ 315). The IR spectrum showed a
1
broad band at 3250–3650 cmꢀ1 indicating the NH group. The H NMR of
20a also illustrated the presence of NH proton as a broad band at d
14.02 ppm. Compounds 20a,b were then reacted with 2,3,4,6-tetra-O-acetyl-
a-D-glycopyranosyl bromide 13a in the presence of aqueous potassium
hydroxide to give the corresponding glycosides 22a,b. The structures of the
reaction products 22a,b were established by their elemental analyses and
spectral data (MS, IR, UV, 1H NMR and 13C NMR). The analytical data for
1
22a revealed a molecular formula C33H32N3SO9 (m=z ¼ 645). The H NMR
spectrum showed the anomeric proton as a doublet at d 6.10 ppm with a
spin-spin coupling constant of 8.7 Hz, which corresponds to the diaxial
orientation of 10-H and 20-H protons, indicating the presence of only the
b-configuration. The other six protons of the glucopyranosyl ring resonated
in the d 3.95–5.45 ppm region, while the four acetoxy groups appeared as four
singlets at d 1.78–2.18 ppm. The formation of the S-glycosides 22 was proved
using the UV spectra, which gave the same UV absorption maxima as the
corresponding S-methyl derivatives 24. The S-methyl derivative 24a showed
two maxima at 280 and 360 nm and its glucosyl derivative 22a also exhibited
two absorption maxima at 271 and 355 nm. Moreover, the 13C NMR of 22a
revealed the absence of the thione carbon at dc 178 ppm[6] and the appearance
of the C-2 at dc 159 ppm,[7] the same value of the corresponding S-methyl
derivative 24a. Upon deprotection of compounds 22 with methanolic
ammonia the free nucleosides 23 were obtained in almost quantitative yields,
the structures of the latter were established on the basis of elemental analyses
and spectral data. The analytical data for compound 23a revealed a mole-
cular formula C25H24N3O5S (m=z ¼ 482). The IR absorption spectra of
this compound showed a characteristic band at 3200–3600 cmꢀ1 due to the
1
hydroxy groups of the glucose moiety. H NMR spectrum revealed the
0
0
presence of a doublet at d 5.69 (J1 –2 ¼ 9.8 Hz), indicating the presence of
only the b-D-glucopyranose. The other six-galactose protons appeared as a
multiplet at d 3.18–3.70 ppm, while the four hydroxy groups of glucose
moiety resonated at d 4.55, 5.14, 5.28 and 5.58 ppm (exchangeable by D2O).
13C NMR spectrum were characterized by a signal at dc 84.01 corresponding
to the C-10 atom of b-D-glucopyranose. Another five signals, at dc 60.00,

NEW THIOGLYCOSIDES
485
69.76, 71.86, 78.68 and 81.68, were assigned to C-60, -40, -20, -30, and -50 of the
glucose moiety, respectively.
In summary, we have achieved the synthesis of interesting nonclassical
bipyridyl and biheterocyclic-nitrogen thioglycosides by the reaction of sub-
stituted pyridinethiones with a-halosugars. These glycosides can be utilized as
an excellent starting material for the synthesis of other carbohydrate deri-
vatives and for biological evaluation studies.
EXPERIMENTAL
All evaporations were carried out under reduced pressure at 40ꢁC.
M.p.s are uncorrected. Aluminum sheets coated with silica gel F254 (Merck)
were used for TLC. Detection was effected by viewing under a short-
wavelength UV lamp. IR spectra were obtained (KBr disk) on a Pye Uni-
1
cam Spectra 1000. H NMR and 13C NMR spectra were measured on a
Wilmad 270 MHz or on a Varian 400 MHz spectrometer for solution in
CDCl3 or (CD3)2SO with SiMe4 as the internal standard. J values are given
in Hz. Mass spectra were recorded on a Varian MAT 112 spectrometer.
Analytical data were obtained from the Microanalytical Data Center at
Cairo University.
Cycloalkane Ring-Fused 6-Pyridyl-3-cyanopyridine-2-(1H )-thiones (5a–h)
General Procedure
To a mixture of 2a,b and 1a ^ d or 6a,b and 7a^d (0.01 mol of each) in
ethanol (50 mL), piperidine (1 mL) was added. The mixture was heated under
reflux for 2 h, and then set aside overnight. The resultant precipitate filtered
off and crystallized from the appropriate solvent.
5a: orange, from EtOH-DMF, m.p. 275ꢁC, yield 80%. IR: nmax=cmꢀ1
(KBr): 3240 (NH); 2225 (CN). C14H11N3S Calcd: C, 66.42; H, 4.35; N, 16.60,
S, 12.64%. Found: C, 66.23; H, 4.23; N, 16.34, S, 12.83%, 5b: orange, from
EtOH-DMF, m.p. 275ꢁC, yield 60%, IR: nmax=cmꢀ1 (KBr): 3240 (NH); 2225
(CN), C14H11N3S, Calcd: C, 66.42; H, 4.35; N, 16.60, S, 12.64%. Found: C,
66.23; H, 4.25; N, 16.38, S, 12.85%, 5c: yellow, from EtOH-DMF, m.p.
265ꢁC, yield 80%, IR: nmax=cmꢀ1 (KBr): 3330 (NH); 2225 (CN), 1H NMR: d
ppm: 1.60 (m, 2H, CH2); 1.65 (m, 2H, CH2); 2.10 (m, 2H, CH2); 2.80 (m, 2H,
CH2); 7.42 (d, 2H, pyridyl-H); 8.78 (d, 2H, pyridyl-H); 14.12 (br s, 1H, NH),
13C NMR: d ppm: 20.85 (CH2); 21.55 (CH2); 24.85 (CH2); 27.85 (CH2);
113.10 (C-5); 116.00 (CN); 119.85 (C-3); 123.00 (2CH, pyridyl-C); 142.30 (C-
40, pyridyl-C); 149.85 (2CH, pyridyl-C); 152.80 (C-4); 155.30 (C-6); 176.00
(C¼S) C15H13N3S (Mþ ¼ 267), Calcd: C, 67.40; H, 4.87; N, 15.73; S, 11.99%.
Found: C, 67.63; H, 4.64; N, 15.92; S, 11.70%, 5d: yellow, from EtOH-

486
ELGEMEIE ET AL.
DMF, m.p. 265ꢁC, yield 60%, IR: nmax=cmꢀ1 (KBr): 3330 (NH); 2225 (CN),
C15H13N3S, Calcd: C, 67.40; H, 4.87; N, 15.73; S, 11.99%. Found: C, 67.28;
H, 4.94; N, 15.95; S, 12.14%, 5e: yellow, from EtOH-DMF, m.p. 280ꢁC,
yield 80%, IR: nmax=cmꢀ1 (KBr): 3330 (NH); 2225 (CN), C16H15N3S, Calcd:
C, 68.32; H, 5.34; N, 14.95; S, 11.39%. Found: C, 68.12; H, 5.54; N, 14.72; S,
11.20%, 5f: yellow, from EtOH-DMF, m.p. 280ꢁC, yield 80%, IR:
n
max=cmꢀ1 (KBr): 3330 (NH); 2225 (CN), C16H15N3S, Calcd: C, 68.32; H,
5.34; N, 14.95; S, 11.39%. Found: C, 68.24; H, 5.65; N, 14.73; S, 11.57%, 5g:
yellow, from EtOH-DMF, m.p. 285ꢁC, yield 80%, IR: nmax=cmꢀ1 (KBr):
3400 (NH); 2225 (CN), C17H17N3S, Calcd: C, 69.15; H, 5.76; N, 14.23; S,
10.85%. Found: C, 69.35; H, 5.45; N, 14.41; S, 10.73%, 5h: yellow, from
EtOH-DMF, m.p. 220ꢁC, yield 60%, IR: nmax=cmꢀ1 (KBr): 3400 (NH); 2225
(CN), 1H NMR: d ppm: 1.20–1.55 (m, 6H, 36CH2); 1.65 (m, 2H, CH2); 2.28
(m, 2H, CH2); 2.88 (m, 2H, CH2); 7.55 (d, 1H, pyridyl-H); 7.87 (d, 1H,
pyridyl-H); 8.55 (d, 1H, pyridyl-H); 8.65 (d, 1H, pyridyl-H); 14.18 (br s, 1H,
NH), 13C NMR: d ppm: 24.00 (CH2); 25.5 (CH2); 26.8 (CH2); 27.8 (CH2);
29.85 (CH2); 31.2 (CH2); 114.60 (C-5); 115.50 (CN); 123.50 (CH, pyridyl-C);
124.20 (C-3); 132.30 (C-30, pyridyl-C); 135.00 (CH, pyridyl-C); 138.40 (CH,
pyridyl-C); 151.50 (CH, pyridyl-C); 155.80 (C-4); 156.70 (C-6); 176.70
(¼C¼S), C17H17N3S (Mþ ¼ 295), Calcd: C, 69.15; H, 5.76; N, 14.23; S,
10.85%. Found: C, 69.05; H, 5.58; N, 14.43; S, 10.96%.
2-(20,30,40,60-Tetra-o-acetyl-b-D-gluco- and galacto-pyranosylthio)-
4-pyridyl-pyridine-3-carbonitriles (15a–p)
General Procedures
To a solution of pyridine-2-(1H)-thiones 5a^h (0.01mol) in aqueous
potassium hydroxide [0.56 g, 0.01 mol, in distilled water (6 mL)] was added a
solution of 2,3,4,6-tetra-O-acetyl-a-D-gluco- or -galacto-pyranosyl bromide
12a,b (4.521 g, 0.011 mol) in acetone (30 mL). The reaction mixture was
stirred at room temperature until reaction judged complete by TLC (30 min
to 2 h). The mixture was evaporated under reduced pressure at 40ꢁC, and the
residue was washed with distilled water to remove the formed potassium
bromide. The product was dried, and crystallized from the appropriate
solvent.
15a: yellow, from EtOH, m. p. 195ꢁC, yield 60%, IR: nmax=cmꢀ1 (KBr):
2220 (CN); 1750 (C¼O), C28H29N3O9S, Calcd: C, 57.63; H, 4.97; N, 7.2; S,
5.49%. Found: C, 57.43; H, 4.75; N, 7.43; S, 5.62%, 15b: white, from EtOH,
1
m.p. 125ꢁC, yield 65%, IR: nmax=cmꢀ1 (KBr): 2220 (CN); 1750 (C¼O), H
NMR: d ppm: 1.58 (t, 2H, CH2); 1.7–2.2 (4 s, 12H, 46OAc); 2.56 (t, 2H,
CH2); 3.13 (t, 2H, CH2); 3.85–4.23 (m, 3H,060-H2, 50-H); 5.18–5.39 (m, 3H, 40-
H, 30-H, 20-H); 6.01 (d, J1 –2 10.2 Hz, 1H, 1 -H); 7.45 (m, 1H, pyridyl-H); 7.80
0
0

NEW THIOGLYCOSIDES
487
(m, 1 H, pyridyl-H); 8.47 (d, 1H, pyridyl-H); 8.72 (d, 1H, pyridyl-H),
C28H29N3O9S, Calcd: C, 57.63; H, 4.97; N, 7.2; S, 5.49%, Found: C, 57.80;
H, 4.70; N, 7.00; S, 5.6%. 15c: yellow, from EtOH, m.p. 215ꢁC, yield 60%.
1
IR: nmax=cmꢀ1 (KBr): 2200 (CN); 1720 (C¼O), UV: lmax: 317.6, 272.2; H
NMR: d ppm: 1.65 (m, 2H, CH2); 1.78 (m, 2H, CH2); 1.90–2.03 (4s, 12H,
46OAc); 2.15 (t, 2H, CH2); 3.02 (t, 2H, CH2); 3.99–4.20 (m, 3H, 60-H2, 50-
H); 4.98–5.22 (m, 2H, 40-H, 30-H); 5.53 (t, 1H, 20-H); 6.15 (d, J1 ꢀ 2 11.28 Hz
1H, 10-H); 7.47 (d, 2H, pyridyl-H); 8.79 (d, 2H, pyridyl-H), 13C NMR: d
ppm: 20–20.10 (46CH3); 21.10 (CH2); 25.5 (CH2); 27.8 (CH2); 33.30 (CH2);
61.80 (CH2, C-60); 68.00 (CH, C-40); 69.01 (CH, C-20); 73.20 (CH, C-30); 75.00
(CH, C-50); 80.50 (CH, C-10); 103.50 (C-5); 114.50 (CN); 123.40 (2CH, pyr-
idyl-C); 127.06 (C-3); 129.08 (C-400, pyridyl-C); 150.00 (2CH, pyridyl-C);
151.50 (C-4); 154.00 (C-6); 162 (¼C-S); 169.01–170.08 (46C¼O),
C29H31N3O9S (Mþ ¼ 597) Calcd: C, 58.29; H, 5.19; N, 7.03; S, 5.36%.
Found: C, 58.03; H, 5.42; N, 6.93; S, 5.34%, 15d: white, from EtOH, m.p.
135ꢁC, yield 70%, IR: nmax=cmꢀ1 (KBr): 2225 (CN); 1720 (C¼O), 1H NMR:
d ppm: 1.64 (m, 2H, CH2); 1.85 (m, 2H, CH2); 1.95–2.18 (4 s, 12H, 46OAc);
2.46 (m, 2H, CH2); 3.00 (m, 2H, CH2); 4.05 (m, 2H, 60-H2); 4.20 (t, 1H, 50-H);
0
0
5.05 (m, 1H, 40-H); 5.20 (m, 1H, 30-H); 5.50 (t, 1H, 20-H); 6.10 (d, J1 ꢀ 2
0
0
10.5 Hz, 1H, 10-H); 7.60 (t, 1H, pyridyl-H); 7.90 (t, 1H, pyridyl-H); 8.60 (t,
1H, pyridyl-H); 8.70 (d, 1H, pyridyl-H), 13C NMR: d ppm: 20.00–20.10
(46CH3); 20.20 (CH2); 26.20 (CH2); 29.8 (CH2); 33.50 (CH2); 61.30 (CH2,
C-60); 67.50 (CH, C-40); 68.50 (CH, C-20); 73.00 (CH, C-30); 75.00 (CH, C-50);
80.10 (CH, C-10); 105.50 (C-5); 114.50 (CN); 123.20 (CH, pyridyl-C); 129.00
(C-3); 131.00 (C-400 pyridyl-C); 136.00 (CH, pyridyl-C); 146.70 (CH, pyridyl-
C); 150.10 (CH, pyridyl-C); 151.20 (C-4); 152.10 (C-6); 161.02 ( ¼ C-S-);
169.01–170.08 (46C¼O), C29H31N3O9S (Mþ ¼ 598), Calcd: C, 58.29; H,
5.19; N, 7.03; S, 5.36%. Found: C, 58.05; H, 5.14; N, 6.95; S, 5.40%, 15e:
yellow, from EtOH, m.p. 203ꢁC, yield 60%, IR: nmax=cmꢀ1 (KBr): 2222
1
(CN); 1750 (C¼O), UV: lmax: 315.6, 271.2, H NMR: d ppm: 1.56 (m, 2H,
CH2); 1.75 (m, 2H, CH2); 1.95–2.15 (4s, 12H, 46OAc); 2.45 (m, 4H, CH2);
3.16 (m, 4H, 2CH2); 4.00 (m, 2H, 60-H2); 4.15 (m, 1H, 50-H); 5.05 (m, 1H, 40-
0
H); 5.15 (m, 1H, 30-H); 5.5 (t, 1H, 20-H); 6.20 (d, J1 ꢀ 2 9.9 Hz, 1H, 1 -H); 7.45
(m, 2H, pyridyl-H); 8.78 (d, 2H, pyridyl-H), 13C NMR: d ppm: 20.10
(46CH3); 24.30 (CH2); 26.20 (CH2); 29.00 (CH2); 32.8 (CH2), 39.40 (CH2);
61.5 (CH2, C-60); 66.50 (CH, C-40); 67.30 (CH, C-20); 73.00 (CH, C-30); 75.00
(CH, C-50); 80.10 (CH, C-10); 104.00 (C-5); 114.50 (CN); 124.10 (2CH, pyr-
idyl-C); 124.10 (C-3); 132.00 (C-400, pyridyl-C); 144.10 (C-4); 150.00 (2 CH,
pyridyl-C); 150.02 (C-6) 154.04 (¼C-S-); 168.10–170.10 (46C¼O),
C30H33N3O9S, Calcd: C, 58.91; H, 5.44; N, 6.87, S 5.24%. Found: C, 60.12,
H, 5.34; N, 6.62, S, 5.18%, 15f: white, from EtOH, m.p. 135ꢁC, yield 70%,
IR: nmax=cmꢀ1 (KBr): 2222 (CN); 1750 (C¼O), UV: lmax: 317.6, 273.2,
C30H33N3O9S, Calcd: C, 58.91; H, 5.44; N, 6.87, S, 5.24%, Found: C, 60.23,
H, 5.53; N, 6.92, S 5.12%, 15g: yellow, from EtOH, m.p. 155ꢁC, yield 60%,
0
0

488
ELGEMEIE ET AL.
IR: nmax=cmꢀ1 (KBr): 2225 (CN); 1720 (C¼O), UV: lmax: 314.6, 269.8,
Calcd: C, 59.52; H, 5.60; N, 6.72, S, 5.12%. Found: C, 59.42, H, 5.54; N,
6.60, S, 5.30%, 15h: white, from EtOH, m.p. 125ꢁC, yield 65%. IR:
1
n
max=cmꢀ1 (KBr): 2225 (CN); 1720 (C¼O), H NMR: d ppm: 0.84 (m, 2H,
CH2); 1.37 (m, 2H, CH2); 1.73–1.83 (m, 2H, CH2); 1.95–2.15 (4s, 12H,
46OAc); 2.56 (m, 2H, CH2); 3.12 (m, 2H, CH2); 3.46 (m, 2H, CH2); 3.95–
4.25 (m, 3H, 60-H2, 50-H); 4.98–5.24 (m, 2H, 40-H, 30-H); 5.61 (t, 1H, 20-H);
6.20 (d, J1 -2 10.0 Hz, 1H, 10-H); 7.57 (m, 1H, pyridyl-H); 7.89 (m, 1H,
pyridyl-H); 8.64 (d, 1H, pyridyl-HH); 8.75 (d, 1H, pyridyl-H), C31H35N3O9S,
Calcd: C, 59.52; H, 5.60; N, 6.72, S, 5.12%. Found: C, 59.34, H, 5.42; N,
6.85, S, 5.23%, 15i: white, from EtOH, m.p. 185ꢁC, yield 80%, IR:
0
0
n
max=cmꢀ1 (KBr): 2220 (CN); 1750 (C¼O), C28H29N3O9S, Calcd: C, 57.63;
H, 4.97; N, 7.2; S, 5.49%. Found: C, 57.83; H, 4.74; N, 7.43; S, 5.20%, 15j:
white, from EtOH, m.p. 125ꢁC, yield 60%, IR: nmax=cmꢀ1 (KBr): 2220 (CN);
1750 (C¼O), C28H29N3O9S, Calcd: C, 57.63; H, 4.97; N, 7.2; S, 5.49%.
Found: C, 57.72; H, 4.69; N, 7.32; S, 5.65%, 15k: yellow, from EtOH, m.p.
195ꢁC, yield 60%, IR: nmax=cmꢀ1 (KBr): 2200 (CN); 1720 (C¼O),
C29H31N3O9S, Calcd: C, 58.29; H, 5.19; N, 7.03; S, 5.36%. Found: C, 58.43;
H, 5.44; N, 6.80; S, 5.30%, 15l: white, from EtOH, m.p. 125ꢁC, yield 75%,
IR: nmax=cmꢀ1 (KBr): 2225 (CN); 1720 (C¼O), C29H31N3O9S, Calcd: C,
58.29; H, 5.19; N, 7.03; S, 5.36%. Found: C, 58.15; H, 5.36; N, 6.87; S,
5.42%, 15m: yellow, from EtOH, m.p. 207ꢁC, yield 75%, IR: nmax=cmꢀ1
(KBr): 2222 (CN); 1750 (C¼O), C30H33N3O9S, Calcd: C, 58.91; H, 5.44; N,
6.87, S, 5.24%. Found: C, 58.85, H, 5.34; N, 7.15, S, 5.18%, 15n: white, from
EtOH, m.p. 135ꢁC, yield 60%, IR: nmax=cmꢀ1 (KBr): 2222 (CN); 1750
(C¼O), C30H33N3O9S, Calcd: C, 58.91; H, 5.44; N, 6.87, S, 5.24%. Found: C,
60.25, H, 5.53; N, 6.90, S, 5.10% .15o: buff, from EtOH, m.p. 204ꢁC, yield
80%, IR: nmax=cmꢀ1 (KBr): 2225 (CN); 1720 (C¼O), C31H35N3O9S, Calcd:
C, 59.52; H, 5.60; N, 6.72, S, 5.12%. Found: C, 59.55, H, 5.43; N, 6.50, S
5.30%. 15p: white, from EtOH, m.p. 125ꢁC, yield 65%, IR: nmax=cmꢀ1
(KBr): 2225 (CN); 1720 (C¼O), C31H35N3O9S, Calcd: C, 59.52; H, 5.60; N,
6.72, S, 5.12%. Found: C, 59.45, H, 5.43; N, 6.82, S, 5.00%.
2-(b-D-gluco- and galacto-pyranosylthio)-6-pyridyl-pyridine-
3-carbonitriles (16a–p)
General Procedure
Dry gaseous ammonia was passed through a solution of a protected
nucleoside 15a^p (0.5 gm) in dry methanol (20 mL) at 0ꢁC for 0.5 h, then the
mixture was stirred at 0ꢁC until reaction was judged to be complete by TLC
(2–6 h). The mixture was evaporated at 40ꢁC to a solid residue, which was

NEW THIOGLYCOSIDES
489
purified by chromatography or by crystallization from the appropriate
solvent.
16a: white, from MeOH, m.p. 245ꢁC, yield 55%, IR: nmax=cmꢀ1 (KBr):
3000–3600 (OH); 2225 (CN), 1H NMR: d ppm: 2.41–2.51 (m, 2H, CH2); 2.68
(m, 2H, CH2); 2.78 (m, 2H, CH2), 3.18–3.66 (m, 6H, 60-H2, 5-H0, 4-H0, 30-H);
4.51 (t, 1H, H-20); 5.11–5.23 (m, 2H, 30-OH, 40-OH); 5.50 (m, 1H, 60-OH);
0
0
0
5.73 (d, J1 ꢀ 2 10.1 Hz, H, 1 -H); 8.33 (d, 2H, pyridyl-H); 8.80 (d, 2H, pyridyl-
H), C20H21N3O5S, Calcd: C, 57.83; H, 5.06; N, 10.12; S, 7.72%. Found: C,
57.60; H, 4.90; N, 10.30; S, 7.80%, 16b: yellow, from MeOH, m.p. 245ꢁC,
yield 60%, IR:
n
max=cmꢀ1 (KBr): 3050–3600 (OH); 2225 (CN),
C20H21N3O5S, Calcd: C, 57.83; H, 5.06; N, 10.12; S, 7.72%. Found: C, 57.74;
H, 4.82; N, 10.00; S, 7.83%, 16c: white, from MeOH, m.p. 235ꢁC, yield 65%,
IR: nmax=cmꢀ1 (KBr): 3200–3600 (OH); 2225 (CN), UV: lmax: 322.2, 276.2,
1H NMR: d ppm: 1.26 (m, 4H, 2CH2); 1.73 (m, 2H, CH2); 1.82 (m, 2H, CH2),
2.02–2.34 (m, 2H, CH2), 3.39–3.99 (m, 6H, 60-H2, 50-H, 40-H, 30-H, 20-H);;
4.16 (t, 2H, 20-OH, 30-OH); 5.17 (m, 1H, 40-OH); 5.55 (m, 1H, 60-OH); 6.15
(d, J1 , ꢀ 2 9.7 Hz, H, 10-H); 7.42 (t, 2H, pyridyl-H); 8.79 (d, 2H, pyridyl-H),
C21H23N3O5S, Calcd: C, 58.74; H, 5.36; N, 9.79; S, 7.46%. Found: C, 58.62;
H, 5.63; N, 10.00; S, 7.62%, 16d: white, from MeOH, m.p. 175ꢁC, yield 70%,
IR: nmax=cmꢀ1 (KBr): 3200–3600 (OH); 2225 (CN), C21H23N3O5S, Calcd: C,
58.74; H, 5.36; N, 9.79; S, 7.46%. Found: C, 58.80; H, 5.40; N, 10.00; S,
7.30%, 16e: white, from MeOH, m.p. 225ꢁC, yield 60%, IR: nmax=cmꢀ1
(KBr): 3200–3600 (OH); 2225 (CN), UV: lmax: 324.6, 276.2, C22H25N3O5S,
Calcd: C, 59.59; H, 5.64; N, 9.48; S, 7.22%. Found: C, 59.80; H, 5.40; N,
9.20; S, 7.30%, 16f: white, from MeOH, m.p. 170ꢁC, yield 80%, IR:
0
0
n
max=cmꢀ1 (KBr): 3200–3600 (OH); 2225 (CN), UV: lmax: 324.6, 275.2,
C22H25N3O5S, Calcd: C, 59.59; H, 5.64; N, 9.48; S, 7.22%. Found: C, 59.70;
H, 5.40; N, 9.30; S, 7.00%, 16g: white, from MeOH, m.p. 211ꢁC, yield 70%,
IR: nmax=cmꢀ1 (KBr): 3200–3600 (OH); 2225 (CN),1H NMR: d ppm: 1.26
(m, 6H, 3CH2); 1.73 (m, 4H, 2CH2); 3.04 (m, 2H, CH2); 3.14–3.64 (m, 6H, 60-
H2, 50-H, 40-H, 30-H, 20-H); 4.48 (t, 1H, 20-OH); 5.05 (m, 1H, 30-OH); 5.25 (m,
1H, 40-OH); 5.63 (d, J1 -2 10.3 Hz, 1H, 10-H); 7.46 (t, 2H, pyridyl-H); 8.78 (d,
2H, pyridyl-H), C23H27N3O5S, Calcd: C, 60.39; H, 5.90; N, 9.19; S, 7.02%.
Found: C, 60.40; H, 5.60; N, 9.30; S, 7.00%, 16h: white, from MeOH, m.p.
185ꢁC, yield 75%, IR: nmax=cmꢀ1 (KBr): 3200–3600 (OH); 2225 (CN),
C23H27N3O5S, Calcd: C, 60.39; H, 5.90; N, 9.19; S, 7.02%. Found: C, 60.50;
H, 5.80; N, 9.30; S, 7.20%, 16i: white, from MeOH, m.p. 174ꢁC, yield 77%,
IR: nmax=cmꢀ1 (KBr): 3050–3550 (OH); 2225 (CN), C20H21N3O5S, Calcd: C,
57.83; H, 5.06; N, 10.12; S, 7.72%. Found: C, 57.60; H, 5.20; N, 10.20; S,
7.80%, 16j: yellow, from MeOH, m.p. 245ꢁC, yield 80%. IR: nmax=cmꢀ1
(KBr): 3050–3600 (OH); 2225 (CN), 1H NMR: d ppm: 2.06 (t, 2H, CH2); 2.80
(m, 2H, CH2); 3.00 (m, 2H, CH2); 3.1–3.80 (m, 6H, 60-H2, 50-H, 40-H, 30-H,
20-H); 4.55 (t, 2H, 20-OH, 30-OH); 4.95 (m, 1H, 40-OH); 5.35 (m, 1H, 60-OH);
0
0
5.62 (d, J1 -2 10.75 Hz, 1H, 10-H); 7.64 (t, 1H, pyridyl-H); 8.02 (m, 1H,
0
0

490
ELGEMEIE ET AL.
pyridyl-H); 8.7 (m, 2H, pyridyl-H), 13C NMR: d ppm: 22.02–33.01 (3CH2);
60.00 (CH2, 60-H2); 69.50 (CH, C-40); 69.10 (CH, C-20); 75.10 (CH, C-30);
80.00 (CH, C-50); 83.50 (CH, C-10); 103.3 (C-5); 115.03 (CN); 123.01 (CH,
pyridyl-C); 126.50 (C-3); 127.01 (C-500, pyridyl-C); 147.01 (C-4); 148.00 (CH,
pyridyl-C); 151.01 (CH, pyridyl-C); 160.00 (C-6); 168 (¼C-S), C20H21N3O5S,
Calcd: C, 57.83; H, 5.06; N, 10.12; S, 7.72%. Found: C, 57.70; H, 4.80; N,
10.00; S, 7.80%, 15k: white, from MeOH, m.p. 235ꢁC, yield 50%. IR:
n
max=cmꢀ1 (KBr): 3200–3600 (OH); 2225 (CN), C21H23N3O5S, Calcd: C,
58.74; H, 5.36; N, 9.79; S, 7.46%. Found: C, 58.60; H, 5.60; N, 10.00; S,
7.60%, 16l: white, from MeOH, m.p. 175ꢁC, yield 65%, IR: nmax=cmꢀ1
(KBr): 3200–3600 (OH); 2225 (CN), C21H23N3O5S, Calcd: C, 58.74; H, 5.36;
N, 9.79; S, 7.46%. Found: C, 58.80; H, 5.40; N, 10.00; S, 7.30, 16m: white,
from MeOH, m.p. 225ꢁC, yield 60%, IR: nmax=cmꢀ1 (KBr): 3200–3600 (OH);
2225 (CN), C22H25N3O5S, Calcd: C, 59.59; H, 5.64; N, 9.48; S, 7.22%.
Found: C, 59.80; H, 5.40; N, 9.20; S, 7.30%, 16n: white, from MeOH, m.p.
1
170ꢁC, yield 75%. IR: nmax=cmꢀ1 (KBr): 3200–3600 (OH); 2225 (CN), H
NMR: d ppm: 1.50–1.90 (m, 6H, 3 CH2); 3.01 (m, 4H, 2CH2); 3.21–3.80 (m,
6H, 60-H2, 50-H, 40-H, 30-H, 20-H); 4.50 (t, 2H, 20-OH, 30-OH); 4.95 (t, 1H, 40-
OH); 5.35 (d, 1H, 60-OH); 5.67 (d, J1 ꢀ 2 9.8 Hz, 1H, 10-H); 7.64 (t, 1H,
pyridyl-H); 7.83 (m, 1H, pyridyl-H); 8.55 (m, 1H, pyridyl-H); 8.72 (m, 1H,
pyridyl-H), 13C NMR: d ppm: 22.02 (CH2), 27.6 (CH2), 33.01 (CH2); 60.00
(CH2, 60-H2); 69.10 (CH, C-40); 69.20 (CH, C-20); 75.50 (CH, C-30); 80.00
(CH, C-50); 89.01 (CH, C-10); 103.50 (C-5); 115.50 (CN); 123.10 (CH, pyridyl-
C); 131.50 (C-3); 132.50 (C-500, pyridyl-C); 139.001 (C-3); 139.50 (CH, pyr-
idyl-C); 150.01 (CH, pyridyl-C); 156 (C-6); 167.50 (¼C-S), C22H25N3O5S,
Calcd: C, 59.59; H, 5.64; N, 9.48; S, 7.22%. Found: C, 59.70; H, 5.40; N,
9.30; S, 7.00, 16o: white, from MeOH, m.p. 211ꢁC, yield 70%, IR: nmax=cmꢀ1
(KBr): 3200–3600 (OH); 2225 (CN), 1H NMR: d ppm: 1.35 (m, 8H, 4 CH2);
1.76 (m, 2H, CH2); 3.23–3.574 (m, 6H, 60-H2, 50-H, 40-H, 30-H, 20-H); 4.46 (t,
1H, 20-OH); 5.03 (m, 1H, 30-OH); 5.25 (m, 1H, 40-OH); 5.60 (d, 1H, 60-OH);
0
0
5.69 (d, J1 -2 9.9 Hz, 1H, 10-H); 7.46 (t, 2H, pyridyl-H); 8.78 (d, 2H, pyridyl-
H), C23H27N3O5S, Calcd: C, 60.39; H, 5.90; N, 9.19; S, 7.02%. Found: C,
60.40; H, 5.60; N, 9.30; S, 7.00%, 16p: white, from MeOH, m.p. 185ꢁC, yield
80%, IR: nmax=cmꢀ1 (KBr): 3200–3600 (OH); 2225 (CN), C23H27N3O5S,
Calcd: C, 60.39; H, 5.90; N, 9.19; S, 7.02%. Found: C, 60.50; H, 5.80; N,
9.30; S, 7.20%.
0
0
4-Cyano-1-pyridyl-7,8-dihydrobenzo[f]isoquinoline-3(2H )-thiones (20a,b)
The above procedure for preparation of compounds 5 were followed.
20a: red, from EtOH=DMF, m.p. 275ꢁC, yield 80%, IR: nmax=cmꢀ1
1
(KBr): 3250–3750 (NH); 2225 (CN), H NMR: d ppm: 2.31–2.40 (m, 2H,
CH2); 2.58 (m, 2H, CH2); 7.32–7.68 (m, 4H, phenyl); 8.13 (d, 2H, pyridyl-H);

NEW THIOGLYCOSIDES
491
8.78 (t, 2H, pyridyl-H); 14.2 (bs, 1H, NH), C19H13N3S (Mþ ¼ 315), Calcd: C,
72.38; H, 4.13; N, 13.33; S, 10.15%. Found: C, 72.60; H, 4.00; N, 13.20; S,
10.10%, 20b: orange, from EtOH=DMF, m.p. 280ꢁC, yield 80%, IR:
1
n
max=cmꢀ1 (KBr): 3250–3750 (NH); 2225 (CN), H NMR: d ppm: 2.37
(m, 2H, CH2); 2.75 (m, 2H, CH2); 7.36–7.60 (m, 4H, phenyl); 7.96 (d, 1H,
pyridyl-H); 8.12 (d, 1H, pyridyl-H); 8 .70 (d, 1H, pyridyl-H); 8.76 (d, 1H,
pyridyl-H); 14.20 (s, bs, 1H, NH), C19H13N3S (Mþ ¼ 315), Calcd: C, 72.38;
H, 4.13; N, 13.33; S, 10.15%. Found: C, 72.50; H, 4.30; N, 13.10; S, 10.00%.
4-Cyano-1-pyridyl-3-(20,30,40,60-tetra-o-acetyl-b-d-glucopyranosylthio)-
7,8-dihydrobenzo[f]isoquinolines (22a,b)
The above procedure for preparation of compounds 15 were followed.
22a: white, from EtOH, m.p. 190ꢁC, yield 80%, IR: nmax=cmꢀ1 (KBr):
2220 (CN); 1750 (C¼O), UV: lmax: 355.0, 271.2 ,1H NMR: d ppm: 1.78–2.18
(4 s 12H, 4CH3); 2.67 (m, 2H, CH2); 2.85 (m, 2H, CH2); 3.95 (t, 1H, 60-H2);
4.17 (t, 1H, 50-H); 5.18–5.45 (m, 3H, 40-H, 30-H, 20-H); 6.1 (d, J1 -2 8.7 Hz, 1H,
10-H); 7.24–7.48 (m, 4H, phenyl-H); 8.26–8.31 (m, 2H, pyridyl-H); 8.87 (d,
2H, pyridyl-H), 13C NMR: d ppm: 20.20–20.40 (46CH3); 24.60 (CH2), 25.8
(CH2), 26.5 (CH2), 27.11 (CH2); 62.05 (CH2, C-60); 68.16 (C-40); 68.70 (C-20);
74.07 (C-30); 76.30 (C-50); 81.07 (C-10); 105.60 (C-5); 114.80 (CN); 123.14–
157.55 (aromatic-C, pyridyl-C), 169.4–170.00 (4 C¼O), C33H32N3O9S (Mþ ¼
646) Calcd: C, 61.40; H, 4.96; N, 6.51; S, 4.96%. Found: C, 61.23; H, 4.64; N,
0
0
6.51; S, 4.75%, 21b: white, from EtOH, m.p. 219ꢁC, yield 80%, IR:
1
n
max=cmꢀ1 (KBr): 2220 (CN); 1750 (C¼O), H NMR d ppm: 1.62–2.08 (s,
12H, 4 CH3); 2.70–2.83 (m, 4H, 2 CH2); 3.90 (m, 2H, 60-H2); 4.17 (t, 1H, 50-
H); 5.14–5.45 (m, 3H, 40-H, 30-H, 20-H) 6.1 (d, J1 -2 9.8 Hz, 1H, 10-H); 7.24–
7.48 (m, 4H, phenyl); 7.69 (d, 1H, pyridyl-H); 8.30 (d, 1H, pyridyl-H); 8.58 (s,
1H, pyridyl-C); 8.87 (d, 1H, pyridyl-H), C33H32N3O9S, Calcd: C, 61.40; H,
4.96; N, 6.51; S, 4. 96%. Found: C, 61.50; H, 4.75; N, 6.33; S, 4.80%.
0
0
3-(b-D-glucopyranosylthio)-4-cyano-1-pyridyl-7,8-dihydro-benzo[f]-iso-
quinolines (23a,b)
The above procedure for preparation of compounds 16 were followed.
23a: white, from MeOH, m.p. 260ꢁC, yield 70%, IR: nmax=cmꢀ1 (KBr):
3200–3600 (OH); 2225 (CN), UV: lmax: 363.6, 275.2, 1H NMR: d ppm: 2.52–
2.65 (m, 2H, CH2); 2.83 (t, 2H, CH2); 3.18–3.70 (m, 6H, 60-H2, 50-H, 40-H, 30-
H, 20-H); 4.55 (d, 1H, 20-OH); 5.14 (d, 1H, 30-OH); 5.28 (d, 1H, 40-OH); 5.28
(d, 1H, 60-OH); 5.69 (d, J1 -2 9.8 Hz 1H, 10-H); 7.20–7.68 (m, 4H, phenyl-H);
8.30 (d, 2H, pyridyl-H); 8.82 (d, 2H, pyridyl-H), 13C NMR: d ppm: 24.40
(CH2); 26.7 (CH2); 60 (CH, C-60); 69.76 (CH, C-40); 71.86 (CH, C-20); 78.68
(C-30); 81.68 (C-50); 84.01(C-10); 104.49 (C-b); 115.16 (CN); 123.45–158.40
(aromatic-C, pyridyl-C), C25H24N3O5S, Calcd: C, 62.24; H, 4.98; N, 8.71; S,
0
0

492
ELGEMEIE ET AL.
6.64%. Found: C, 62.50; H, 4.60; N, 8.91; S, 6.85%, 23b: white, from MeOH,
m. p. 250ꢁC, yield 75%, IR: nmax=cmꢀ1 (KBr): 3200–3600 (OH); 2225 (CN),
C25H24N3O5S, Calcd: C, 62.24; H, 4.98; N, 8.71; S, 6.64%. Found: C, 62.50;
H, 4.60; N, 8.91; S, 6.85%.
2-Methylthio-6-pyridyl-3-cyano-pyridine-2-(1H)-thiones (17a-h) and 4-
Cyano-1-pyridyl-3-(methylthio)-7,8-dihydrobenzo[f] isoquinolines (24a,b)
General Procedure
A solution of compounds 5a^h and 20a,b (0.01 mol), methyl iodide
(0.01 mol) and NaOH (0.01 mol), water (16 mL) and ethanol (20 mL) was
stirred at 60ꢁC, and a white solid began to precipitate almost immediately.
Stirring was continued for 30 min and the mixture was allowed to cool, the
solid was collected, washed with water, dried and recrystalized from ethanol.
17a: white, from EtOH, m.p. 215ꢁC, yield 80%, C15H13N3S, Calcd: C,
67.40; H, 4.87; N, 15.73; S, 11.9%. Found: C, 67.67; H, 4.66; N, 15.82; S,
11.78%, 17b: white, from EtOH, m.p. 202ꢁC, yield 80%, IR: nmax=cmꢀ1
(KBr): 2220 (CN), C15H13N3S, Calcd: C, 67.40; H, 4.87; N, 15.73; S, 11.9%.
Found: C, 67.67; H, 4.66; N, 15.82; S, 11.78%, 17c: white, from EtOH, m.p.
300ꢁC, yield 80%, IR: nmax=cmꢀ1 (KBr): 2220 (CN). UV: lmax: 362, 277,
C16H15N3S, Calcd: C, 68.32; H, 5.34; N, 14.95; S, 11.39%. Found: C, 68.25;
H, 5.58; N, 14.60; S, 10.96%, 17d: white, from EtOH, m.p. 201, yield 80%,
IR: nmax=cmꢀ1 (KBr): 2220 (CN), C16H15N3S, Calcd: C, 68.32; H, 5.34; N,
14.95; S, 11.39%. Found: C, 68.25; H, 5.58; N, 14.60; S, 10.96%, 17e: white,
from EtOH, m.p. 219ꢁC, yield 80%, IR: nmax=cmꢀ1 (KBr): 2225 (CN), UV:
l
max: 328.6, 278.2,1H NMR: d ppm: 1.53 (m, 2H, CH2); 1.70 (m, 2H, CH2);
1.81 (m, 2H, CH2); 2.46 (m, 2H, CH2); 2.61 (s, 3H, CH3); 3.16 (m, 2H, CH2);
7.55 (d, 2H, pyridyl-H); 8.76 (d, 2H, pyridyl-H), 13C NMR: d ppm: 12.93
(CH3); 25.33–31.37 (5CH2); 108.07 (C-5); 118.92 (CN); 123.32 (2CH, pyridyl-
C); 128.01 (C-3); 131.19 (C-400); 143.70 (C-4); 149.58 (2CH, pyridyl-C);
154.09 (C-6); 161.70 (¼C-S-), C17H17N3S (Mþ ¼ 295), Calcd: C, 69.15; H,
5.76; N, 14.23; S, 10.85%. Found: C, 68.87; H, 5.66; N, 14.52; S, 10.78%, 17f:
white, from EtOH, m.p. 203ꢁC, yield 80%, IR: nmax=cmꢀ1 (KBr): 2225 (CN),
UV: lmax: 330.6, 280.2, C17H17N3S, Calcd: C, 69.15; H, 5.76; N, 14.23; S,
10.85%. Found: C, 68.97; H, 5.59; N, 14.00; S, 10.75%, 17g: white, from
EtOH, m.p. 197ꢁC, yield 85%, C18H19N3S, Calcd: C, 69.90; H, 6.14; N,
13.59; S, 10.35%. Found: C, 69.55; H, 5.88; N, 13.91; S, 10.66%, 17h: white,
from EtOH, m.p. 201ꢁC, yield 80%, C18H19N3S, Calcd: C, 69.90; H, 6.14; N,
13.59; S, 10.35%, Found: C, 69.75; H, 5.78; N, 13.40; S, 10.45%, 24a: white,
from EtOH, m.p. 201ꢁC, yield 70%, IR: nmax=cmꢀ1 (KBr): 2225, UV: lmax
:
360.6, 281.2,1H NMR: d ppm: 2.58 (m, 2H, CH2); 2.61 (s, 3H, CH3); 2.86 (m,
2H, CH2); 7.33–7.52 (m, 4H, phenyl-H); 8.34 (d, 2H, pyridyl-H); 8.79 (d, 2H,
pyridyl-H), 13C NMR: d ppm: 13.23 (CH3); 24.28 (CH2); 26.64 (CH2);
104.094–154.29 (aromatic-C, CN, pyridyl-C); 159.0 (¼C-S-), C20H15N3S

NEW THIOGLYCOSIDES
493
(Mþ ¼ 329), Calcd: C, 69.95; H, 6.10; N, 14.23; S, 10.85%. Found: C, 69.25;
H, 5.68; N, 14.40; S, 10.96%, 24b: white, from EtOH, m.p. 230ꢁC, yield 80%,
IR: nmax=cmꢀ1 (KBr): 2225 (CN), C20H15N3S, Calcd: C, 69.95; H, 6.10; N,
14.23; S, 10.85%. Found: C, 69.25; H, 5.68; N, 14.40; S, 10.96%.
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Received April 25, 2001
Accepted June 12, 2002