A new class of biheterocyclic thioglycosides from pyridine-2-(1H)-thiones

Article abstract of DOI:10.1081/NCN-120016511

A reported method for preparation of a new class of biheterocyclic thioglycosides via reaction of pyridinethiones with 2,3,4,6-tetra-O-acetyl-α-D-gluco- and galactopyranosyl bromides has been studied.

Full text of DOI:10.1081/NCN-120016511

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A NEW CLASS OF BIHETEROCYCLIC THIOGLYCOSIDES
FROM PYRIDINE-2-(1H)-THIONES
Galal H. Elgemeie a & Mona A. Ahmed a
a Chemistry Department, Helwan University, Ain-Helwan, Cairo, Egypt
Version of record first published: 31 Aug 2006.
To cite this article: Galal H. Elgemeie & Mona A. Ahmed (2002): A NEW CLASS OF BIHETEROCYCLIC THIOGLYCOSIDES FROM
PYRIDINE-2-(1H)-THIONES, Nucleosides, Nucleotides and Nucleic Acids, 21:11-12, 837-847
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NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS
Vol. 21, Nos. 11 & 12, pp. 837–847, 2002
A NEW CLASS OF BIHETEROCYCLIC
THIOGLYCOSIDES FROM PYRIDINE-
2-(1H )-THIONES
Galal H. Elgemeie* and Mona A. Ahmed
Chemistry Department, Faculty of Science, Helwan University,
Ain-Helwan, Cairo, Egypt
ABSTRACT
A reported method for preparation of a new class of biheterocyclic
thioglycosides via reaction of pyridinethiones with 2,3,4,6-tetra-O-acetyl-
a-D-gluco- and galactopyranosyl bromides has been studied.
INTRODUCTION
In recent years nucleoside analogues have occupied a significant
position in the search for effective antiviral agents, owing to the fact that
a large number of unnatural nucleoside derivatives have been shown to
inhibit infection caused by viruses.[1–3] The deazapyrimidine nucleosides
constitute a class of analogues with potential biological activity.[4] As a
part of our program directed towards the development of new, simple and
efficient procedures for synthesis of antimetabolites,[5,6] we have recently
described that pyridinethione nucleosides exerted inhibitory effects on
both DNA and RNA containing viruses.[7] On the basis of these findings,
*Corresponding author. Fax: 2 02 5870668; E-mail: rughe@rusys.eg.net
837
DOI: 10.1081=NCN-120016511
Copyright # 2002 by Marcel Dekker, Inc.
1525-7770 (Print); 1532-2335 (Online)
www.dekker.com

838
ELGEMEIE AND AHMED
it was of interest to prepare modified analogues to search for more effec-
tive agents.
RESULTS AND DISCUSSION
This paper describes the synthesis of nonclassical biheterocyclic glyco-
sides. The latter compounds will be considered as precursors of modified
glycosides. Thus, it has been found that heating of cyclopentanone, cyclo-
hexanone, 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 cycloalk-
ylidenecyanothioamides 1 in good yields. Compounds 1 react with quinoline-
4-ylidenemalononitrile 2 in refluxing ethanol containing catalytic amounts of
piperidine for 2 h to give the corresponding 6-quinolyl-pyridine-2(1H )-
thiones 5a–d. The structures of compounds 5 were established on the basis of
their elemental analysis and spectral data. Thus, structure 5c is supported by
1
its mass and H NMR spectra, the latter included a broad band at d 14.26
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 double bond of
2 to give the intermediate 3.This Michael adduct then cyclizes via mal-
ononitrile elimination to give the intermediate dihydropyridine derivative 4
which is oxidized under the reaction conditions to yield the condensed
6-quinolyl-pyridine-2-(1H)-thiones 5. We also investigated the reaction
between the cycloalkylidenemalononitrile 6 and the quinoline-4-ylidenecya-
nothioacetamide 7 under the same conditions. The products were identified
as the same as that obtained from the reaction of 1 and 2 by their m.p.s and
spectral data. The mechanism of the reaction of 6 and 7 is assumed to be
initiated by an exchange process between the cycloalkylidene group of 6 and
the quinolylidene group of 7 to give the intermediate 3 and hence to the
products 5 as produced by the reaction of 1 with 2. Similar mechanism for
other analogues was reported by us.[8] Compounds 5 can be coupled with
different classes of sugar halides to give a novel ring system of glycosides. As
far as we know, this is the first coupling reaction of this type to be reported
for this ring system. Thus, it has been found that compounds 5a–d reacted
with 2,3,4,6-tetra-O-acetyl-a-D-gluco- and galactopyranosyl bromides 10a,b
in the presence of aqueous potassium hydroxide to give the corresponding
S-glycosides 11a–h. The structures of the reaction products 11a–h were
established and confirmed for the reaction products on the basis of their
1
elemental analysis and spectral data (MS, IR, UV, H NMR, 13C NMR).
Thus, the analytical data for 11c revealed a molecular formula C34H35N3O9S
(m=z 661). H NMR spectroscopy was used to confirm this structure for the
1
product. The 1H NMR spectrum showed the anomeric proton as doublet at d
0
0
6.21 with a spin-spin coupling constant of (J1 ,2 ¼ 11.28 Hz) corresponding to

BIHETEROCYCLIC THIOGLYCOSIDES
839
a diaxial orientation of H-10 and H-20 protons indicating the b-configuration.
The other six protons of the glucopyranosyl ring resonated in the d 4.02–5.59
region. The four acetoxy groups appear as four singlets at d 1.96–2.05 and the
five methylene protons of the agylcon resonate at d 1.35, 1.66, 1.78 and 3.25.
13C NMR spectra were characterized by a signal at d 80.1 corresponding to
the C-10 atom of the b-D-glucopyranose. The four signals appearing at d
169.2–170.4 are due to the four acetoxy carbonyl carbon atoms, while the five
signals at d 22.2–22.3 are attributed to the acetate methyl carbons. The five
methylene carbon atoms of the aglycone resonated at d 21.9, 26.2, 27.6, 29.1,
32.8. Another five signals at d 61.7, 67.8, 69.1, 73.01 and 74.9 were assigned
to C-60, -40, -20, -30 and -50, respectively. The IR spectrum of compound 11c
was characterized by the presence of acetoxy carbonyl groups at 1752 cmꢀ 1
.
It may be argued that the coupling reaction of 5 with 10 happened on the
nitrogen atom to give the corresponding N-glycosides 12a–h. The formation
of the S-glycosides 11a–h was proven using 13C NMR which revealed the
absence of the thione carbon at d 178 and the appearance of the C-2 carbon
at d 161 of the same value of the corresponding S-methyl derivative 14a–
d.[9,10] Also, the UV spectra of compounds 11a–h proved that the reaction
had led selectively to the formation of S-glycosyl derivatives since the cor-
responding S-methyl derivatives 14a–d gave the same UV absoption maxima.
Thus, the S-methyl derivative of compound 5c shows three maxima at 216,
268 and 340 nm and its corresponding glucosyl derivative also exhibited three
maximum absorption bands at 224, 266 and 340 nm. The protected glycoside
11a–h were deblocked through treatment with methanolic ammonia to give
the free glycosides 13a–h after chromatographic purification. TLC of com-
pounds 13a–h showed that a single unique compound was produced, and
their structures were confirmed by their elemental analysis and spectral data.
Thus, the analytical data for compound 13d revealed a molecular formula
C27H29N3O5S (m=z 507). The IR absorption spectra of this compound
showed a characteristic band at 3600–3200 cmꢀ1 due to the hydroxy groups
1
of the glucose moiety. H NMR spectroscopy was used to confirm this
structure for the product. Thus, the 1H NMR spectra revealed the presence of
0
0
a doublet at d 5.63 (J1 –2 ¼ 10.75 Hz), indicating the presence of only the b-D-
glucopyranose. The other six-glucose protons appear as a multiplet at d 3.45–
3.70, while the four hydroxy groups of glucose moiety resonated at d 5.02,
5.21 and 5.55 (exchangeable by D2O). 13C NMR spectra were characterized
by a signal at d 84.01 corresponding to the C-10 atom of b-D glucopyranose.
Another five signals, at d 60.1, 70.1, 72.1, 78.9 and 81.9 were assigned to
C-60, -40, -20, -30, and -50 of the glucose part, respectively.
In summary, we have achieved a regiospecific synthesis of interesting
biheterocyclic glycosides by the reaction of substituted pyridine-2-(1H )-
thiones with a halosugars. These glycosides can be utilized as an excellent
starting material for the synthesis of other carbohydrate derivatives and for
biological evaluation studies.

840
ELGEMEIE AND AHMED
Chart 1.
EXPERIMENTAL
All evaporations were carried out under reduced pressure at 40ꢁC.
M.p.s are uncorrected. Aluminun sheets coated with silica gel F254 (Merck)
were used for TLC. Detection was effected by viewing under a short-wave-
length UV lamp. IR spectra were obtained (KBr disk) on a Pye Unicam
1
spectra 1000. H NMR and 13C NMR spectra were measured on a Wilmad
270 MHz or on a Vairan 400 MHz spectrometer for solution in CDCl3 or
(CD3)2SO with SiMe4 as 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.

BIHETEROCYCLIC THIOGLYCOSIDES
841
Chart 2.

842
ELGEMEIE AND AHMED
Cycloalkylidenecyanothioacetamides 1a–d, quinoline-4-ylidenemalono-
nitrile 2, cycloalkylidenemalononitriles 6a–d and quinoline-4-ylidenecya-
nothioacetamide 7 were prepared following literature procedures.[8]
Cycloalkane Ring-Fused 6-(4-Quinolinyl)-3-cyanopyridine-2-(1H )-
thiones 5a–d
General Procedures
To a mixture of 1a–d and 2 or 6a–d and 7 (0.01 mol each) in ethanol
(50 mL), pipridine (1 mL) was added. The mixture was heated under reflux
for 2 h and then set aside overnight. The resultant precipitate was filtered off
and crystallized from the appropriate solvent.
5a: yellow, from EtOH; m.p: 238–240ꢁC; yield: (70%). IR: nmax=cmꢀ1
(KBr) 2222 (CN) 1H NMR: 2.00 (m, 2H, CH2); 2.31 (m, 2H, CH2); 3.03 (m,
2H, CH2); 7.83–7.90 (m, 4H, quinolyl-H); 8.16 (d, 2H, quinolyl-H); 14.62 (br,
1H, NH). 13C NMR: 22.3–32.5 (36CH2); 112.8 (C-5); 116.2 (CN); 121 (C-3);
121–132.8 (quinolyl-C); 152.8 (C-4); 155.3 (C-6); 176.1 (C¼S). Anal. Calcd
for C18H13N3S: C, 71.28; H, 4.29; N, 13.86; S, 10.7. Found: C, 71.5; H, 4.0;
N, 14.0; S, 10.9%.
5b: yellow, from EtOH; m.p: 265ꢁC; yield: (80%). IR: nmax=cmꢀ1 (KBr)
2220 (CN). H NMR: 1.62 (m, 2H, CH2); 1.83 (m, 2H, CH2); 2.78 (m, 2H
1
CH2); 3.07 (m, 2H, CH2); 7.82–7.89 (m, 4H, quinolyl-H); 8.17 (d, 2H, quinolyl-
H). 13C NMR: 21.1–33.4 (46CH2); 114.6 (C-5); 115.7 (CN), 120.8–
133.1 (quinolyl-C); 124 (C-3); 150.8 (C-4); 155 (C-6); 175.2 (C¼S). Anal.
Calcd. for C19H15N3S: C, 71.92; H, 4.73; N, 13.24; S, 10.09. Found: C, 72.1;
H, 4.5; N, 12.9; S, 10.2%.
5c: yellow, from EtOH; m.p: 172ꢁC; yield: (75%). IR: nmax=cmꢀ1
(KBr) 2220 (CN). 1H NMR: 1.28 (m, 2H, CH2); 1.65 (m, 2H, CH2); 1.73 (m,
2H, CH2); 2.33 (m, 2H, CH2); 3.06 (m, 2H, CH2); 7.83–7.89 (m, 4H, quinolyl-
H); 8.15 (d, 2H, quinolyl-H); 14.26 (br, 1H, NH). 13C NMR: 24.8–31.9
(56CH2); 112.8 (C-3); 118.1 (CN); 120.1–131.4 (quinolyl-C); 153.1 (C-4);
158.3 (C-6); 176.2 (C¼S). MS: m=e ¼ 331. Anal. Calcd. for C20H17N3S: C,
72.50; H, 5.13; N, 12.68; S, 9.66. Found: C, 72.5; H, 5.0; N, 12.5; S, 9.3%.
5d: yellow, from EtOH; m.p: 190ꢁC; yield: (70%). IR: nmax=cmꢀ1
(KBr) 2215 (CN). 1H NMR: 1.11 (m, 2H, CH2); 1.43 (m, 2H, CH2); 1.81 (m,
2H, CH2); 2.20 (m, 2H, CH2); 2.76 (m, 2H, CH2); 2.99 (m, 2H, CH2); 7.00–
7.94 (m, 4H, quinolyl-H); 8.09 (d, 2H, quinolyl-H); 14.00 (br, 1H, NH). 13C
NMR: 22.5–30.2 (66CH2); 110.1 (C-3); 116.9 (CN); 120.8–130.5 (quinolyl-
C); 151.0 (C-4); 155.1 (C-6); 174.8 (C¼S). MS: m=e ¼ 345. Anal. Calcd. for

BIHETEROCYCLIC THIOGLYCOSIDES
843
C21H19N3S: C, 73.04; H, 5.51; N, 12.17; S, 9.27. Found: C, 72.9; H, 5.3; N,
12.2; S, 9.3%.
3-(20,30,40,60-Tetra-O-acetyl-b-D-gluco- and galactopyranosylthio)-1-
(4-quinolinyl)cycloalkeno[c]pyridine-4-carbonitriles 11a–h
General Procedures
To a solution of condensed 3-cyanopyridine-2-(1H )thione 5 (0.01 mol)
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-b-D-glucopyranosyl bromide
10a,b (4.52 g, 0.01 mol) in acetone (30 mL). The reaction mixture was stirred
at room temperature until the reaction was 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
potassium bromide formed. The product was dried, and crystallized from
the appropriate solvent.
11a: buff, from EtOH; m.p: 160ꢁC; yield: (65%). UV: nmax 218, 268,
316. IR: nmax=cmꢀ1 (KBr) 2222 (CN). Anal. Calcd. for (C32H31N3O9S): C,
60.66; H, 4.89; N, 6.63; S, 5.05. Found: C, 60.5; H, 4.6; N, 6.5; S, 4.9%.
11b: yellow, from EtOH; m.p: 140ꢁC; yield: (65%). UV: lmax 220, 262,
340 nm. IR: nmax=cmꢀ1 (KBr) 2223 (CN). MS: m=e ¼ 647. Anal. Calcd. for
C33H33N3SO9: C, 61.20; H, 5.10; N, 6.49; S, 4.94. Found: C, 61.5; H, 4.9; N,
6.5; S, 5.0%.
11c: yellow, from EtOH; m.p: 119ꢁC; yield: (65%). UV: lmax 224, 266,
340 nm. IR: nmax=cmꢀ1 (KBr) 2224 (CN). 1H NMR: 1.35 (m, 2H, CH2); 1.66
(m, 2H, CH2); 1.78 (m, 2H, CH2); 1.96–2.05 (4s, 12H, 46CH3CO); 2.32 (m,
2H, CH2); 3.25 (m, 2H, CH2); 4.02 (m, 2H, H-60,600); 4.15 (m, 1H, H-50); 5.03
(m, 1H, H-40); 5.16 (d, 1H, H-30); 5.59 (t, 1H, H-20); 6.21 (d, J1 ,2 , 11.28 Hz,
1H, H-10); 7.84–7.89 (m, 4H, quinolyl-H); 8.17 (d, 2H, quinolyl-H) 13C
NMR: 21.9 (46CH3); 22.2–32.4 (46CH2); 61.7 (C-60); 67.8 (C-40); 69.1 (C-
20); 73.0 (C-30); 74.9 (C-50); 80.1 (C-10); 105 (C-3); 114 (CN); 121–134.1
(quinolyl-C); 131.1 (C-5); 149.8 (C-4); 152.4 (C-6); 155 (CꢀS); 169.2–170.4
(46CO). MS: m=e ¼ 661. Anal. Calcd. for C34H35N3O9S: C, 61.72; H, 5.29;
N, 6.35; S, 4.84. Found: C, 61.6; H, 5.2; N, 6.1; S, 4.7%.
0
0
11d: yellow, from EtOH; m.p: 178ꢁC; yield: (65%). UV: lmax 220, 264,
340 nm. IR: nmax=cmꢀ1 (KBr) 2226 (CN). Anal. Calcd. for C35H37N3SO9: C,
62.22; H, 5.48; N, 6.20; S, 4.74. Found: C, 62.5; H, 5.5; N, 5.9; S, 4.8%.

844
ELGEMEIE AND AHMED
11e: yellow, from EtOH; m.p: 120ꢁC; yield: (80%). IR: nmax=cmꢀ1
(KBr) 2222 (CN). Anal. Calcd. for C32H31N3SO9: C, 60.66; H, 4.89; N, 6.63;
S, 5.05. Found: C, 60.5; H, 4.6; N, 6.3; S, 4.9%.
11f: yellow, from EtOH; m.p: 117ꢁC; yield: (75%). IR: nmax=cmꢀ1
(KBr) 2222 (CN). H NMR: 1.62 (m, 2H, CH2); 1.78 (m, 2H, CH2); 2.05–
1
2.08 (4s, 12H, 46CH3CO); 2.71 (m, 2H, CH2); 2.83 (m, 2H, CH2); 3.98 (m,
2H, H-60,600); 4.18 (m, 1H, H-50); 5.19 (m, 1H, H-40); 5.24 (d, 1H, H-30); 5.59
0
(t, 1H, H-20); 6.21 (d, J1 ,2 , 9.9 Hz, 1H, H-1 ); 7.84–7.89 (m, 4H, quinolyl-H);
8.30 (d, 2H, quinolyl-H). 13C NMR: 21.2 (46CH3); 24.8–27.11 (46CH2);
61.7 (C-60); 67.8 (C-40); 69.1 (C-20); 74.9 (C-30); 76.2 (C-50); 80.1 (C-10); 105
(C-3); 114 (CN); 121–134.1 (quinolyl-C); 131.1 (C-5); 149.8 (C-4); 152.4 (C-
6); 155 (C–S); 169.2–170.4 (46CO). MS: m=e ¼ 647. Anal. Calcd for
C33H33N3SO9: C, 61.20; H, 5.10; N, 6.49; S, 4.94. Found: C, 61.0; H, 5.0; N,
7.1; S, 5.1%.
0
0
11g: yellow, from EtOH; m.p: 118ꢁC; yield: (70%) IR: nmax=cmꢀ1(KBr)
2222 (CN). Anal. Calcd. for C34H35N3SO9: C, 61.72; H, 5.29; N, 6.35; S, 4.84.
Found: C, 61.6; H, 5.1; N, 6.1; S, 4.6%.
11h: yellow, from EtOH; m.p: 238–240ꢁC; yield: (62%). IR: nmax=cmꢀ1
(KBr) 2222 (CN). Anal. Calcd. for C35H37N3SO: C, 62.22; H, 5.48; N, 6.20; S;
4.74. Found: C, 62.1; H, 5.6; N, 5.9; S, 4.5%.
3-(b-D-Gluco- and galactopyranosylthio)-1-
(4-quinolinyl)cycloalkeno[c]pyridine-4-carbonitriles 13a–h
General Procedures
Dry gaseous ammonia was passed through a solution of protected
glycoside 11a–h (0.5 g) in dry methanol (20 mL) at 0ꢁC for ca 0.5 h. Then the
mixture was stirred at 0ꢁC until reaction was judged complete (2–6 h). The
mixture was evaporated at 40ꢁC to give a solid residue, which was crystallized
from the appropriate solvent.
13a: brown, from MeOH; m.p: 211ꢁC; yield: (60%). UV: lmax 217,
272, 340 nm. IR: nmax=cmꢀ1 (KBr) 3375 (OH); 2219 (CN). Anal. Calcd. for
C24H23N3O5S: C, 61.39; H, 4.94; N, 9.03; S, 6.88. Found: C, 61.2; H, 5.0; N,
8.7; S, 6.6%.
13b: yellow, from EtOH; m.p: 158ꢁC; yield: (80%). UV: lmax 220, 266,
340 nm. IR: nmax=cmꢀ1 (KBr) 3397 (OH); 2222 (CN). 1H NMR: 1.55 (m, 2H,
CH2); 1.78 (m, 2H, CH2); 2.78 (m, 2H, CH2); 2.97 (m, 2H, CH2); 3.29 (m, 2H,
H-60,600); 3.34 (m, 1H, H-50); 3.42 (m, 1H, H-40); 3.50 (m, 1H, H-30); 3.69 (m,

BIHETEROCYCLIC THIOGLYCOSIDES
845
1H, H-20), 4.49 (t, 1H, 20-OH); 5.06 (t, 1H, 30-OH); 5.24 (t, 1H, 40-OH); 5.58
0
(d, 1H, 60-OH); 5.63 (d, J1 ,2 , 10.4 Hz, 1H, H-1 ); 7.79–7.88 (m, 4H, quinolyl-
H); 8.16 (d, 2H, quinolyl-H). 13C NMR: 21.7 (46CH3); 22.5–33.2 (46CH2);
61.7 (C-60); 66.1 (C-40); 73.2 (C-20); 78.9 (C-30); 81.2 (C-50); 82.1 (C-60); 104
(C-5); 114 (CN); 122–134.2 (quinolyl-C); 132.0 (C-3); 159.1 (C-4); 154.0 (C-
6); 168 (CꢀS). Anal. Calcd. for C25H25N3O5S: C, 62.63; H, 5.21; N, 8.76; S,
6.68%. Found: C, 62.5; H, 5.0; N, 8.4; S, 6.5%.
0
0
13c: yellow, from MeOH; m.p: 218ꢁC; yield: (60%). UV: lmax 220,
270, 316 nm. IR: nmax=cmꢀ1 (KBr) 3387 (OH); 2221 (CN). 1H NMR: 1.34 (s,
2H, CH2); 1.65 (s, 2H, CH2); 1.72 (s, 2H, CH2); 2.29 (m, 2H, CH2); 3.15 (m,
2H, CH2); 3.25 (m, 2H, H-60,600); 3.34 (m, 1H, H-50); 3.40 (m, 1H, H-40); 3.51
(t, 1H, H-30); 3.68 (t, 1H, H-20); 4.47 (t, 1H, 20-OH); 5.05 (t, 1H, 30-OH); 5.22
0
(t, 1H, 40-OH); 5.56 (d, 1H, 60-OH); 5.65 (d, J1 ,2 , 9.8 Hz, 1H, 1 -H); 7.81–7.88
(m, 4H, quinolyl-H); 8.17 (d, 2H, quinolyl-H). 13C NMR: 25.1–38.1
(46CH2); 61.2 (C-60); 69.9 (C-40); 74.1 (C-20); 80.1 (C-30); 82.2 (C-50); 84.5
(C-10); 106.1 (C-5); 115 (CN), 121.1–130.2 (quinolyl-C), 132.0 (C-3), 151.9 (C-
4), 155.8 (C-6); 168 (CꢀS). MS: m=e ¼ 493. Anal. Calcd. for C26H27N3O5S:
C, 63.28; H, 5.47; N, 8.51; S, 6.40. Found: C, 63.0; H, 5.5; N, 8.2; S, 6.2%.
0
0
13d: yellow, from MeOH; m.p: 210ꢁC; yield: (60%). UV: lmax 220;
1
268; 340 nm. IR: nmax=cmꢀ1 (KBr) 3600–3200 (OH); 2221 (CN). H NMR:
1.22 (s, 2H, CH2); 1.33 (m, 2H, CH2); 1.79 (m, 2H, CH2); 2.29 (m, 2H, CH2);
2.73 (s, 2H, CH2); 2.88 (s, 2H, CH2); 3.45–3.70 (m, 6H, H-60,600, 50, 40, 30, 20-
H); 4.46 (t, 1H, 20-OH); 5.02 (t, 1H, 30-OH); 5.21 (d, 1H, 40-OH); 5.55 (d, 1H,
0
60-OH); 5.63 (d, J1 ,2 , 10.75 Hz, 1H, 1 -H); 7.79–7.88 (m, 4H, quinolyl-H);
8.15(d, 2H, quinolyl-H) 13C NMR: 24.8–35.1 (56CH2); 60.1 (C-60); 70.1 (C-
40); 72.1 (C-20); 78.9 (C-30); 81.9 (C-50); 84.0 (C-10); 115 (CN); 121.1–130.2
(quinolyl-C), 132.0 (C-5), 149.8 (C-4), 156.0 (C-6); 169 (CꢀS). MS:
m=e ¼ 507. Anal. Calcd. for C27H29N3O5S: C, 63.90; H, 5.71; N, 8.28; S, 6.31.
Found: C, 64.0; H, 5.5; N, 7.9; S, 5.9%.
0
0
13e: yellow, from EtOH; m.p: 158ꢁC; yield: (80%). IR: nmax=cmꢀ1
(KBr) 2222 (CN). Anal. Calcd. for C24H23N3O5S: C, 60.66; H, 4.89; N, 6.63;
S, 5.05. Found: C, 60.4; H, 5.1; N, 6.5; S, 5.1%.
13f: yellow, from EtOH; m.p: 169ꢁC; yield: (70%). IR: nmax=cmꢀ1
1
(KBr) 3480–3333 (OH); 2221 (CN). H NMR: 2.51 (m, 2H, CH2); 2.65 (m,
2H, CH2); 2.86 (m, 2H, CH2); 3.31 (m, 2H, CH2); 3.97 (m, 2H, H-60,600); 3.42
(m, 1H, H-50); 4.55 (m, 1H, H-40); 5.12 (m, 1H, H-30); 5.12 (m, 1H, H-20); 5.48
(t, 1H, 20-OH); 5.58 (t, 1H,030-OH); 5.68 (t, 1H, 40-OH); 5.69 (d, 1H, 60-OH);
0
0
5.72 (d, J1 ,2 , 9.9 Hz, 1H, 1 -H); 7.55–7.55 (m, 4H, quinolyl-H); 8.35 (d, 2H,
13
quinolyl-H). C NMR: 24.8–35.1 (56CH2); 60.1 (C-60); 70.1 (C-40); 72.1
(C-20); 78.9 (C-30); 81.9 (C-50); 84.0 (C-10); 115 (CN); 121.1–130.2 (quinolyl-C),

846
ELGEMEIE AND AHMED
132.0 (C-5), 149.8 (C-4), 156.0 (C-6); 169 (C–S). Anal. Calcd. for
C25H25N3O5S: C, 61.1; H, 5.09; N, 8.55; S, 6.52. Found: C, 61.4; H, 5.1; N,
8.5; S, 6.2%.
13g: yellow, from EtOH; m.p: 155ꢁC; yield: (65%). IR: nmax=cmꢀ1
(KBr) 2222 (CN). Anal. Calcd. for C26H27N3O5S: C, 63.28; H, 5.74; N, 8.51;
S, 6.40. Found: C, 62.9; H, 5.5; N, 8.3; S, 6.0%.
13h: yellow, from EtOH; m.p: 150ꢁC; yield: (70%). IR.: nmax=cmꢀ1
(KBr) 2222 (CN). Anal. Calcd. for C27H29N3O5S: C, 63.90; H, 5.71; N, 8.28;
S, 6.3. Found: C, 64.1; H, 5.5; N, 7.9; S, 5.9%.
3-(Methylthio)-1-(4-quinolinyl)-cycloalkeno[c]pyridine-4-carbonitriles
14a–d
General Procedures
To a solution of condenced 3-cyanopyridine-2(1H) thione 5 (0.01 mol)
in ethanol (30 mL) was added aqueous potassium hydroxide [0.56 g
(0.01 mol) in distilled water (1 mL)]. The reaction mixture was stirred at room
temperature until the reaction mixture was judged complete (30 min to 3 h). A
solution of methyl iodide (0.01 mol) was added and the reaction mixture was
heated at reflux for 3 h. The mixture was left to cool at room temperature and
the resultant precipitate was filtered off and crystallized from the appropriate
solvent.
14a: yellow, from EtOH; m.p: <300ꢁC; yield: (60%). IR: nmax=cmꢀ1
(KBr) 2221 (CN). MS: m=e ¼ 331. Anal. Calcd. for C19H15N3S: C, 71.92; H,
4.73; N, 13.24; S, 10.09. Found: C, 71.7; H, 4.5; N, 13.6; S, 9.7%.
14b: buff, from EtOH; m.p: <300ꢁC; yield: (70%). UV: lmax 216, 267,
348 nm. IR: nmax=cmꢀ1 (KBr) 2220 (CN). 1H NMR: 2.51 (m, 2H, CH2); 2.58
(m, 4H, 2CH2); 2.63 (s, 3H, SCH3); 2.83 (m, 2H, CH2); 7.33–7.52 (m, 4H,
quinolyl-H); 8.34–8.37 (d, 2H, quinolyl-H). 13C NMR: 13.23 (26CH2); 24.25
(SCH3); 26.64 (26CH2); 104.1 (C-3); 115.27 (CN); 125.42–132.67 (quinolyl-
C); 142.7 (C-5); 145.5 (C-4); 154.2 (C-6); 160.93 (C-2). MS: m=e ¼ 331. Anal.
Calcd. for C20H17N3S: C, 72.50; H, 5.13; N, 12.68; S, 9.66. Found: C, 72.1;
H, 5.4; N, 12.9; S, 10.0%.
14c: yellow, from EtOH; m.p: 260–262ꢁC; yield: (60%). UV: lmax 216,
268, 340 nm. IR: nmax=cmꢀ 1 (KBr) 2220 (CN). Anal. Calcd. for C21H19N3S:
C, 73.04; H, 5.50; N, 12.17; S, 9.27. Found: C, 73.2; H, 5.5; N, 12.6; S, 9.5%.

BIHETEROCYCLIC THIOGLYCOSIDES
847
14d: yellow, from EtOH; m.p: 240–242ꢁC; yield: (63%). IR:
max=cmꢀ1 (KBr) 2220 (CN). Anal. Calcd. for C22H21N3S: C, 73.53; H, 5.84;
N, 11.69; S, 8.91. Found: C, 73.2; H, 5.5; N, 11.4; S, 8.7%.
n
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Received November 7, 2000
Accepted August 27, 2002