Substituted quinolinones, part 14: Synthesis of novel dispiro(heterocycle- N,2′-[1,3]dithietane-4′,3″-quinolinedione) derivatives under PTC conditions

Article abstract of DOI:10.1080/10426507.2010.496746

Chemical Equation Presented The four-membered spiro-heterocycles ethyl cyano(1-methyl-2,4-dioxospiro{1,3-quinoline-3,4′-[1,3]dithietane} -4′-ylidene)-acetate 2a, -malononitrile 2b, -acetylacetone 2c, and thiazetidine isomer 3 were prepared under phase transfer catalysis (PTC) conditions. The thermal treatment of dithietanes 2a-c led to the bis-quinolinyl sulfide 4. Some interesting nucleophilic additions followed by cyclization reactions were carried out with the dithietane 2a to give the corresponding novel dispiro derivatives 5-8, 10-13, and 15. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426507.2010.496746

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Substituted Quinolinones, Part 14:
Synthesis of Novel Dispiro(heterocycle-
N,2′-[1,3]dithietane-4′,3″-
quinolinedione) Derivatives Under PTC
Conditions
Mohamed Abass a & Ahmed Khodairy b
a Chemistry Department, Faculty of Education , Ain Shams
University , Cairo, Egypt
b Chemistry Department, Faculty of Science , Sohag University ,
Sohag, Egypt
Published online: 19 Feb 2011.
To cite this article: Mohamed Abass & Ahmed Khodairy (2011) Substituted Quinolinones, Part 14:
Synthesis of Novel Dispiro(heterocycle-N,2′-[1,3]dithietane-4′,3″-quinolinedione) Derivatives Under
PTC Conditions, Phosphorus, Sulfur, and Silicon and the Related Elements, 186:2, 287-297, DOI:
10.1080/10426507.2010.496746
To link to this article: http://dx.doi.org/10.1080/10426507.2010.496746
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Phosphorus, Sulfur, and Silicon, 186:287–297, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.496746
SUBSTITUTED QUINOLINONES, PART 14: SYNTHESIS OF
NOVEL DISPIRO(HETEROCYCLE-N,2ꢀ-[1,3]DITHIETANE-
4ꢀ,3ꢀꢀ-QUINOLINEDIONE) DERIVATIVES UNDER
PTC CONDITIONS
Mohamed Abass1 and Ahmed Khodairy2
1Chemistry Department, Faculty of Education, Ain Shams University, Cairo, Egypt
2Chemistry Department, Faculty of Science, Sohag University, Sohag, Egypt
GRAPHICAL ABSTRACT
Abstract The four-membered spiro-heterocycles ethyl cyano(1-methyl-2,4-dioxospiro{1,3-
quinoline-3,4ꢁ-[1,3]dithietane}-4ꢁ-ylidene)-acetate 2a, -malononitrile 2b, -acetylacetone 2c,
and thiazetidine isomer 3 were prepared under phase transfer catalysis (PTC) conditions.
The thermal treatment of dithietanes 2a–c led to the bis-quinolinyl sulfide 4. Some interesting
nucleophilic additions followed by cyclization reactions were carried out with the dithietane
2a to give the corresponding novel dispiro derivatives 5–8, 10–13, and 15.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.
Keywords Dispiro-heterocycles; 1,3-dithietane; phase transfer catalysis; quinolinone
INTRODUCTION
The heterocyclic synthetic utility of ketene-S,S-acetals1–3 as well as ketene-N,S-
acetals4 has attracted considerable attention. The ketene-S,S-acetals have been used as
starting materials for the synthesis of a wide variety of heterocycles.5–7 Geminal dihalo com-
pounds, such as 3,3-dichloroquinoline-2,4-diones, have revealed important activity towards
nucleophilic substitution with various N, S, and O-nucleophiles, leading to 3,3-disubstituted
Received 6 March 2010; accepted 25 May 2010.
Dedicated to the memory of the late Professor Ahmed K. El-Shafie.
Address correspondence to Ahmed Khodairy, Chemistry Department, Faculty of Science, Sohag University,
Postal Code 82524, Sohag, Egypt. E-mail: khodairy@yahoo.com
287

288
M. ABASS AND A. KHODAIRY
R1
O
N
O
N
R2
Cl
S
CS2 / R1-CH2-R2
K2CO3/ TBAB
S
Cl
O
O
60 oC/ 1 h
72-88 %
CH3
CH3
2a, R1 = CN, R2 = CO2Et
1
2b, R1 = R2 = CN
2c, R1 = R2 = COMe
PhNCS / CH2(CN)2
K2CO3/ TBAB
60 oC/ 1 h
84 %
DMSO
180 oC/ 0.5 h
75 %
CN
OH
O
OH
CN
S
S
N
O
N
N
N
OO
CH3
CH3
3
CH3
4
Scheme 1
quinolinediones and/or fused quinolines at face-c.8–11 The interesting structures and proper-
ties of 1,3-dithietanes and 1,3-thiazetanes12,13 prompted our attention to obtain novel spiro-
heterocyclic ring systems starting from ketene-S,S-acetals and 3,3-dichloroquinoline-2,4-
dione.14 Quinolinones are associated with important biological activities,15–17 and during
our recent investigation of new 3-substituted quinolinones, these compounds showed signif-
icant antiparasitic activity, especially towards bilharzias. In this article, we report Michael
reaction of a spiro[(4-methylidene[1,3]dithietane)-2,3ꢁ-quinolinedione] leading to dispiro-
dithietane derivatives as novel heterocyclic systems (Scheme 1). Since dithietanes are a
four-membered heterocyclic system, which is sensitive to nucleophilic and thermal treat-
ments,18 the application of phase transfer catalysis (PTC) conditions19–21 enabled carrying
out nucleophilic reactions, such as Michael addition, under mild conditions: temperature,
basic catalysis, and solvent.
RESULTS AND DISCUSSION
3,3-Dichloro-1-methylquinoline-2,4(1H,3H)-dione (1)14 is a geminal dichloro
derivative that was subjected to the reaction with a mixture of some active methylene
compounds, viz.; ethyl cyanoacetate, malononitrile, and acetylacetone and carbon
disulfide, using potassium carbonate as a catalyst in dioxane, under PTC conditions.
Tetrabutyl ammonium bromide (TBAB) was selected as a PT-catalyst where experimental
results showed the best yield percentage (72–88%) and purity of product in the presence

SUBSTITUTED QUINOLINONES, PART 14
289
Figure 1 MM2-optimized structure of the spiro compound 2a.
of TBAB. This reaction led to the formation of novel spiro[1,3-dithietane-2,3ꢁ-quinoline]
derivatives 2a–c.
Figure 1 shows MM2-minimized energy 3D-structure22 of the spiro compound 2a,
which reveals that the dithietane nucleus lies in a plane perpendicular to the quinolinedione
nucleus plane. As expected, the molecule of compound 2a assumed this configuration
to avoid repulsion between sulfur atoms of the dithietane ring and oxygen atoms of the
quinoline-2,4-dione system.
Similarly, treating the dichloro compound 1 with phenyl isothiocyanate under the
above conditions furnished spiro[quinoline-3,2ꢁ-[1,3]thiazetidin] 3 in 84% yield (Scheme
1). The structure of these four spiro four-membered 1,3-diaza-heterocyclic derivatives was
checked using IR, 1H NMR, and mass spectra. The experimental results revealed relative
thermal stability of these small heterocyclic systems. Interestingly, heating of any of the trio
2a–c in boiling DMSO (179–180◦C) led to breaking of the dithietane ring with coupling of
two molecules furnishing 4-hydroxy-3-[(4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinolin-
3-yl)sulfanyl]-1-methylquinolin-2(1H)one (3). The structure of the sulfide 4 was supported
via its mass fragmentation pattern (Figure S1, Supplemental Materials, available online).
Mass spectrum showed the molecular ion peak at m/e 380 (I, 24.7%) and the base peak
at m/e 175 (I, 100%), which is related to 4-hydroxy-1-methylquinolin-2(1H)-one cation
(Figure 2).
The reaction of the dithietane 2a with certain cyclic α-active methylene keto-
compounds, viz., cyclopentanone, cyclohexanone, cycloheptanone, tetralone, 4-hydroxy-
1-methylquinolin-2(1H)-one (9), cyanoacetamide, and cyanothioacetamide, in presence of
piperidine as a catalyst gave rise to seven innovative dispiro dithietane heterocyclic systems.
It was found that use of classic base catalyzed reaction conditions (piperidine in dioxane)
or phase transfer catalyzed reaction conditions (potassium carbonate/TBAB in dioxane)
gave the same products and in nearly the same yields. In this article, we describe the con-
venient method using piperidine due to its simplicity in working up the products. Spectral
characterization of the products illustrated that a Michael-type addition took place between
the in situ–formed carbanion and activated exo-cyclic double bond of the dithietane 2a
followed by an intramolecular cyclocondensation leading to the dispiro pyrans 5–8, 10, and
the dispiro piperidines 11a,b (Schemes 2 and 3).

290
M. ABASS AND A. KHODAIRY
Figure 2
1
In general, as shown by IR and H NMR spectra of the products, it was noted that
in these cyclization reactions selectively, the carboxylate group is involved in an addition-
elimination (condensation) process, leading to a pyran or a piperidine ring, at the same
time the cyano-group remained away from the possible nucleophilic addition. This is just
an empirical result, but we have no explanation for this regioselective behavior.
When the dithietane 2a was treated with certain diaza-binucleophiles, such as guani-
dine hydrochloride, thiourea, and 4-amino-5-(trifluoromethyl)-4H-1,2,4-triazole-3-thiol
(14)23 under PTC conditions, some interesting dispiro diaza- and or triaza-heterocyclic

SUBSTITUTED QUINOLINONES, PART 14
291
O
O
O
NC
S
O
O
O
O
O
N
S
O
Piperidine/ dioxane
60 oC/ 4 h
CH3
5
42 %
O
NC
O
S
S
NC
S
Piperidine/ dioxane
60 oC/ 2 h
N
O
O
N
CO2C2H5
S
CH3
6
55 %
O
O
NC
CH3
2a
O
S
S
Piperidine/ dioxane
60 oC/ 2 h
N
O
CH3
7
48 %
O
O
NC
O
O
S
S
Piperidine/ dioxane
60 oC/ 4 h
N
O
CH3
8
71 %
Scheme 2
compounds were obtained. Comparison between use of traditional bases, such as piperi-
dine and PTC systems like potassium carbonate/TBAB to catalyze such addition-cyclization
reaction, clearly showed that PTC conditions are more suitable due to significant differ-
ence in yield percentage between the two methodologies. While use of piperidine as
catalyst led to yields that did not exceed 30%, this PTC reaction afforded the pyrim-
idine 12, 1,3-thiazinane 13, and 1,3,4-thiadiazepine 15 in excellent yields (72–85%)
(Scheme 4).
Again the IR spectra of the compounds 12, 13, and 15 revealed the presence of a
cyano group, showing that it was not included in the reaction course. At the same time, there
is no indication for an ethyl set of protons in the 1H NMR spectra of these three compounds,
providing clear evidence for its inclusion in the cyclization process. All structures were

292
M. ABASS AND A. KHODAIRY
CN
O
S
CO2C2H5
S
N
O
CH3
2a
X
OH
NC
NH2
Piperidine/dioxane
60 oC/ 4h
73 %
Piperidine/dioxane
60 oC/ 4h
67-84 %
N
O
CH3
9
O
O
O
NC
NC
NH
O
N
O
S
S
X
S
S
CN
N
O
O
N
O
CH3
CH3
CH3
11a, X = O
11b, X = S
10
Scheme 3
also supported by mass spectrometry along with satisfactory elemental analyses ( 0.4%)
for carbon, hydrogen, nitrogen, and sulfur.
CONCLUSIONS
Phase transfer catalyzed nucleophilic substitution of geminal dihalo compounds with
in situ–prepared ketene-S,S-acetals and/or ketene-N,S-acetals is an efficient methodology
to obtain spiro 1,3-dithietane compounds. Many dispiro heterocyclic compounds including
dithietane ring system can be prepared via a convenient method and in excellent yields using
piperidine as catalyst especially in the case of addition of α-active methylene keto com-
pounds to 2-methylidine-1,3-dithietanes. Potassium carbonate/TBAB in dioxane proved to
be the catalyst of choice when diaza-binucleophiles are reacted with activated exocyclic
double bond systems like 2-methylidine-1,3-dithietanes.
EXPERIMENTAL
Melting points were determined in open capillary tubes on a digital Stuart SMP3.
IR spectra were taken on a Perkin-Elmer FT-IR 1650 or Nicolet 710 FT-IR spectrometers,
using samples in KBr disks. 1H NMR spectra were recorded on Varian Gemini-200 NMR-
spectrometer (200 MHz), using DMSO-d6 or CDCl3 as solvents and TMS as internal
reference. Mass spectra were determined on a Carlo-Erba QMD-1000 instrument by direct

SUBSTITUTED QUINOLINONES, PART 14
293
O
NC
S
NH
NH
O
N
NH
N
H
NH2.HCl
H2N
S
K2CO3/ TBAB/ dioxane
O
60 oC/ 4 h
84 %
CH3
12
O
S
CN
CO2C2H5
NC
NH
O
S
O
S
S
NH
NH2
H2N
S
S
N
O
K2CO3/ TBAB/ dioxane
N
O
60 oC/ 4 h
72 %
CH3
CH3
2a
13
O
H
N
N
N
NC
S
CF3
O
N
F3C
SH
14
N
N
S
NH2
S
N
K2CO3/ TBAB/ dioxane
N
O
60 oC/ 4 h
85 %
CH3
15
Scheme 4
inlet, operating at 75 eV. Elemental microanalyses were performed on a Perkin Elmer
CHN-2400 Analyzer at the Microanalytical Center, Cairo University. All reactions were
monitored by TLC on 0.2-mm silica gel F-254 (Merck) plates, using UV light (λ =
254 nm) for detection.
3,3-Dichloro-1-methylquinoline-2,4(1H,3H)-dione (1)
This compound was obtained using the method described in the literature.14
General Procedure for the PTC-Synthesis of Dithietanes 2a–c
To a stirred mixture of anhydrous potassium carbonate (2.79 g, 20 mmol), TBAB
(0.1 g, 0.3 mmol), and an active methylene compound (5 mmol), viz., ethyl cyanoacetate
(0.55 mL), malononitrile (0.34 g), and acetylacetone (0.52 mL) in dry dioxane (30 mL),
carbon disulfide (0.31 mL, 5 mmol) diluted with dioxane (5 mL) was added dropwise
added. The mixture was then stirred at 60◦C for 0.5 h. A yellowish-orange precipitate was
obtained. Afterwards, a solution of compound 1 (1.22 g, 5 mmol) in dioxane (50 mL) was
added to the mixture, and the stirring was continued at 60◦C for 1 h. Then the mixture was

294
M. ABASS AND A. KHODAIRY
filtered off, and the filtrate was evaporated in vacuo. The residual solid that obtained was
crystallized to give the dithietanes 2a–c.
Ethyl
2-cyano-2-(1ꢀ-methyl-2ꢀ,4ꢀ-dioxo-2ꢀ,4ꢀ-dihydro-1ꢀH-spiro[[1,3]di-
thietane-2,3ꢀ-quinoline]-4-ylidene)acetate (2a). This compound was obtained
from ethyl cyanoacetate, yield 1.30 g (72%); mp 253–5◦C (dioxane); IR (νmax, cm−1):
1
2216 (C N), 1720 (C O), 1671–1642 (C O); H NMR (δ): 1.12–1.40 (t, J = 6.2 Hz,
3H, CO2CH2CH3), 3.80 (s, 3H, NCH3), 4.13–4.43 (q, J = 6.4 Hz, 2H, CO2CH2CH3),
7.40–7.90 (m, 4H, Harom); Mass (m/z, I%): M+· 360 (43%). Anal. calcd. for C16H12N2O4S2
(360.41): C, 53.32; H, 3.36; N, 7.77; S, 17.79%. Found: C, 53.60; H, 3.50; N, 7.90; S,
17.89%.
2-(1ꢀ-Methyl-2ꢀ,4ꢀ-dioxo-2ꢀ,4ꢀ-dihydro-1ꢀH-spiro[[1,3]dithietane-2,3ꢀ-quin-
oline]-4-ylidene)malononitrile (2b). This compound was obtained from malonon-
itrile, yield 1.38 g (88%); mp > 300◦C (iso-propanol); IR (νmax, cm−1): 2299 (C N),
1
1665–1640 (C O), H NMR (δ): 3.80 (s, 3H, NCH3), 7.40–7.90 (m, 4H, Harom); Mass
(m/z, I%): M+· 313 (22.2%). Anal. calcd. for C14H7N3O2S2 (313.36): C, 53.66; H, 2.25;
N, 13.41; S, 20.46%. Found: C, 53.90; H, 2.41; N, 13.60; S, 20.58%.
4-(2,4-Dioxopentan-3-ylidene)-1ꢀ-methyl-1ꢀH-spiro[[1,3]dithietane-2,3ꢀ-
quinoline]-2ꢀ,4ꢀ-dione (2c). This compound was obtained from acetylacetone, yield
1.39 g (80%); mp 260–262◦C (ethanol); IR (νmax, cm−1): 1682 (C O), 1660–1643 (C O);
1H NMR (δ): 2.28 (s, 6H, COCH3), 3.78 (s, 3H, NCH3), 7.32–7.80 (m, 4H, Harom); Mass
(m/z, I%): M+·347 (36.5%). Anal. calcd. for C16H13NO4S2 (347.41): C, 55.32; H, 3.77; N,
4.03; S, 18.46%. Found C, 55.50; H, 3.50; N, 4.20; S, 18.20%.
2-(1-Methyl-2,4-dioxo-3ꢀ-phenyl-2,4-dihydro-1H-spiro[quinoline-3,2ꢀ-
[1,3]thiazetidine]-4ꢀ-ylidene)malononitrile (3)
To a stirred mixture of anhydrous potassium carbonate (2.79 g, 20 mmol), TBAB
(0.1 g, 0.3 mmol), and malononitrile (0.34 g, 5 mmol) in dry dioxane (30 mL), phenyl
isothiocyanate (0.66 mL, 5 mmol) in dioxane (5 mL) was added dropwise. The mixture
was then stirred at 60◦C for 0.5 h. A pale yellow precipitate was obtained. Afterward, a
solution of compound 1 (1.22 g, 5 mmol) in dioxane (50 mL) was added to the mixture,
and the stirring was continued at 60◦C for 1 h. Then, the mixture was filtered off, and the
filtrate was evaporated in vacuo. The residual solid that was obtained was crystallized from
DMF to give the thiazetidine 3. Yield 1.56 g (84%); mp 290–292◦C; IR (νmax, cm−1): 2197
(C N), 1660–1642 (C O); 1H NMR (δ): 3.80 (s, 3H, NCH3), 7.22–7.95 (m, 9H, Harom);
Mass (m/z, I%): M+· 372 (66.3%). Anal. calcd. for C20H12N4O2S (372.41): C, 64.51; H,
3.25; N, 15.04; S, 8.61%. Found: C, 64.76; H, 3.50; N, 15.21; S, 8.77%.
4-Hydroxy-3-[(4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinolin-3-yl)sul-
fanyl]-1-methylquinolin-2(1H)-one (4)
A solution of the dithietane 2a (1.08 g, 3 mmol) in DMSO (20 mL) was boiled under
reflux at ca. 180◦C for 0.5 h. Then, the mixture was left to cool to room temperature and
poured onto crushed ice. The precipitate so obtained was filtered and crystallized from
DMF, to give the sulfide 4. Yield 0.5 g (87%); mp >300◦C; IR (νmax, cm−1): 3440–2650
(H-bonded-OH), 1654–1642 (C O); 1H NMR (δ): 3.68 (s, 3H, NCH3), 3.72 (s, 3H, NCH3),
7.22–7.95 (m, 8H, Harom), 13.22–13.40 (b, 2H, 2 x OH; exchangeable with D2O); Mass

SUBSTITUTED QUINOLINONES, PART 14
295
(m/z, I%): M+· 380 (24.7%). Anal. calcd. for C20H16N2O4S (380.43): C, 63.15; H, 4.24;
N, 7.36; S, 8.43%. Found: C, 63.00; H, 3.90; N, 7.20; S, 8.30%.
General Procedure for the Synthesis of Compounds 5–8, 10, and 11a,b
To a mixture of the dithietane 2a (1.08 g, 3 mmol) and the proper active methylene
compound (3 mmol), viz., cyclopentanone (0.3 mL), cyclohexanone (0.35 mL), cyclohep-
tanone (0.4 mL), α-tetralone (0.42 mL), 4-hydroxy-1-methylquinolin-2(1H)-one (9) (0.53
g), cyanoacetamide (0.26 g), cyanothioacetamide (0.31 g) in dioxane (20 mL), or piperidine
(0.2 mL) was added. Then, the mixture was heated at 60◦C for 2–4 h. After that, the reac-
tion mixture was treated with icy dilute acetic acid (20 mL, 20%) to give solid precipitates,
which were collected by filtration, washed with cold water, dried, and crystallized to give
the dispiro compounds 5–8, 10, and 11a,b.
Dispiro[(3-cyano-2-oxo-2,3,4,5,6,7-hexahydrocyclopenta[b]pyran)-4,2ꢀ-(1,
3-dithietane)-4ꢀ-3”-(1”-methylquinoline-2”,4”(1”H,3”H)-dione)] (5). This com-
pound was obtained from cyclopentanone, yield 0.5 g (42%); mp 277–278◦C (ethanol); IR
(νmax, cm−1): 2210 (C N), 1682 (C O), 1668–1640 (C O); 1H NMR (δ): 1.61–2.03 (m,
6H, 3 x CH2), 3.60 (s, 3H, NCH3), 3.96 (s, 1H, Hpyran), 7.09–7.81 (m, 9H, Harom); Mass
(m/z, I%): M+· 398 (24.3%). Anal. calcd. for C19H14N2O4S2 (398.46): C, 57.27; H, 3.54;
N, 7.03; S, 16.09%. Found C, 57.30; H, 3.30; N, 7.20; S, 16.20%.
Dispiro[(3-cyano-2-oxo-3,4,5,6,7,8-hexahydro-2H-chromene)-4,2ꢀ -(1,3-
dithietane)-4ꢀ-3”-(1”-methylquinoline-2”,4”(1”H,3”H)-dione)] (6). This com-
pound was obtained from cyclohexanone, yield 0.68 g (55%), mp 256–258◦C (dioxane);
IR (νmax, cm−1): 2220 (C N), 1680 (C O), 1660–1632 (C O), 1H NMR (δ):1.40– 1.80
(m, 8H, 4 x CH2), 3.68 (s, 3H, NCH3), 3.88 (s, 1H, Hpyran), 7.56–8.13 (m, 4H, Harom);
Mass (m/z, I%): M+· 412 (20.2%). Anal. calcd. for C20H16N2O4S2 (412.49): C, 58.24; H,
3.91; N, 6.79; S, 15.55%. Found: C, 58.40; H, 3.60; N, 6.90; S, 15.70%.
Dispiro[(3-cyano-2-oxo-2,3,4,5,6,7,8,9-octahydrocyclohepta[b]pyran)-4,
2ꢀ-(1,3-dithietane)-4ꢀ-3”-(1”-methylquinoline-2”,4”(1”H,3”H)-dione)] (7). This
compound was obtained from cycloheptanone, yield 0.61 g (48%), mp 246–248 −C
1
(ethanol); IR (νmax, cm−1): 2222 (C N), 1683 (C O), 1656–1634 (C O); H NMR(δ):
1.23–1.96 (m, 10H, 5 x CH2), 3.70 (s, 3H, NCH3), 3.86 (s, 1H, Hpyran), 7.60–8.10 (m, 4H,
Harom); Mass (m/z, I%): M+· 426 (64.7%). Anal. calcd. for C21H18N2O4S2 (426.52): C,
59.14; H, 4.25; N, 6.57; S, 15.04%. Found: C, 59.10; H, 4.20; N, 6.60; S, 15.16%.
Dispiro[(3-cyano-2-oxo-3,4,5,6-tetrahydro-2H-benzo[h]chromene)-4,2ꢀ-
(1,3-dithietane)-4ꢀ-3”-(1”-methylquinoline-2”,4”(1”H,3”H)-dione)]
(8). This
compound was obtained from tetralone, yield 0.98 g (71%), mp 295–296◦C (iso-propanol);
IR (νmax, cm−1): 2212 (C N), 1688 (C O), 1656–1635 (C O); 1H NMR(δ): 2.23–2.48
(m, 4H, 2 x CH2), 3.64 (s, 3H, NCH3), 3.89 (s, 1H, Hpyran), 7.20–8.18 (m, 8H, Harom);
Mass (m/z, I%): M+· 460 (27.8%). Anal. calcd. for C24H16N2O4S2 (460.53): C, 62.59; H,
3.50; N, 6.08; S, 13.92%. Found: C, 62.40; H, 3.50; N, 6.10; S, 13.80%.
Dispiro[(2,4-dioxo-1-methyl-1,2,3,4-tetrahydroquinoline)-3,2ꢀ-(1,3-dithie-
tane)-4ꢀ,4”-(6”-methyl-2”,5”-dioxo-3”,4”,5”,6”-tetrahydro-2”H-pyrano[3,2-c]
quinoline-3”-carbonitrile)] (10). This compound was obtained from 4-hydroxy-1-
methylquinolin-2(1H)-one (9), yield 1.07 g (73%), mp >300◦C (DMF); IR (νmax, cm−1):
2203 (C N), 1640 (C O); 1H NMR (δ): 3.64 (s, 3H, NCH3), 3.70 (s, 3H, NCH3), 3.89 (s,
1H, Hpyran), 7.20–8.08 (m, 8H, Harom); Mass (m/z, I%): M+· 489 (33.5%). Anal. calcd. for

296
M. ABASS AND A. KHODAIRY
C24H15N3O5S2 (489.53): 58.89; H, 3.09; N, 8.58; S, 13.10%. Found: C, 58.80; H, 3.00; N,
8.70; S, 12.90%.
Dispiro[(3,5-dicyano-2,6-dioxopiperidine)-4,2ꢀ-(1,3-dithietane)-4ꢀ-3”-(1”-
methyl-quinoline-2”,4”(1”H,3”H)-dione)] (11a). This compound was obtained
from cyanoacetamide, yield 0.8 (67%), mp >300◦C (DMF); IR (νmax, cm−1): 3230–3205
1
(NH), 2203, 2198 (C N), 1680 (C O) 1652–1646 (C O); H NMR (δ): 3.28 (s, 1H,
Hpiperidine), 3.39 (s, 1H, Hpiperidine), 3.66 (s, 3H, NCH3), 7.18–7.89 (m, 4H, Harom), 11.40
(s, 1H, NH, exchangeable with D2O); Mass (m/z, I%): M+· 398 (14.6%). Anal. calcd. For
C17H10N4O4S2 (398.42): C, 51.25; H, 2.53; N, 14.06; S, 16.10%. Found: C, 51.30; H,
2.30; N, 14.20; S, 15.80%.
Dispiro[(3,5-dicyano-2-oxo-6-thioxopiperidine)-4,2ꢀ-(1,3-dithietane)-4ꢀ-
3”-(1”-methyl-quinoline-2”,4”(1”H,3”H)-dione)] (11b). This compound was
obtained from cyanothioacetamide, yield 1.04 (84%), m.p. 278–279◦C (DMF); IR (νmax
,
cm−1): 3434–3235 (br, NH), 2220 (C N), 2192 (C N), 1681 (C O), 1650–1640 (C O);
1H NMR (δ): 3.25 (s, 1H, Hpiperidine), 3.33 (s, 1H, Hpiperidine), 3.60 (s, 3H, NCH3), 7.08–7.80
(m, 4H, Harom), 11.30 (s, 1H, NH, exchangeable with D2O); Mass (m/z, I%): M+· 414
(8.2%). Anal. calcd. for C17H10N4O3S3 (414.49): C, 49.26; H, 2.43; N, 13.52; S, 23.21%.
Found: C, C, 49.50; H, 2.50; N, 13.40; S, 23.40%.
General Procedure for the PTC Synthesis of Compounds 12, 13, and 15
To a stirred mixture of anhydrous potassium carbonate (2.79 g, 20 mmol), TBAB
(0.1 g, 0.3 mmol), and the proper binucleophile (5 mmol), viz., guanidine hydrochloride
(0.49 g), thiourea (0.39 g), and 4-amino-5-(trifluoromethyl)-4H-1,2,4-triazole-3-thiol (14)
(0.92 g) in dry dioxane (50 mL), a solution of the dithietane 2a (1.8 g, 5 mmol) in dioxane
(50 mL) was added, and the stirring was continued at 60◦C for 4 h. Then the mixture was
cooled in an ice bath overnight. The mixture was then filtered, and the precipitate that was
obtained was washed several times with water to remove water-soluble salts. The residual
solid product was crystallized to give the dispiro compounds 12, 13, and 15. The filtrate of
the reaction mixture was evaporated in vacuo, and the solid so obtained was crystallized to
give an additional amount of the same product.
Dispiro[(5-cyano-2-imino-4-oxohexahydropyrimidine)-4,2ꢀ -(1,3-dithie-
tane)-4ꢀ-3”-(1”-methylquinoline-2”,4”(1”H,3”H)-dione)] (12). This compound
was obtained from guanidine hydrochloride, yield 1.57 (84%), mp 287–289◦C (dioxane);
IR (νmax, cm−1): 3430, 3324 (N–H), 3150 (N–H), 2210 (C N), 1662 (C O), 1646–1632
1
(C O). H NMR (δ): 3.70 (s, 3H, NCH3), 4.20 (s, 1H, Hpyrimidine), 7.23–7.90 (m, 4H,
Harom), 8.40 (b, 1H, NH, exchangeable with D2O), 9.00 (b, 1H, NH, exchangeable with
D2O), 10.40 (b, 1H, NH, exchangeable with D2O); Mass (m/z, I%): M+· 373 (16.2%).
Anal. calcd. for C15H11N5O3S2 (373.41) requires C, 48.25; H, 2.97; N, 18.75; S, 17.17%.
Found: C, 48.30; H, 2.70; N, 18.60; S, 17.00%.
Dispiro[(5-cyano-2-imino-4-oxo-1,3-thiazinane)-6,2ꢀ-(1,3-dithietane)-4ꢀ-
3”-(1”-methylquinoline-2”,4”(1”H,3”H)-dione)] (13). This compound was ob-
tained from cyanothioacetamide, yield 1.4 g (72%), mp 244–246◦C (DMF); IR (νmax
,
1
cm−1): 3480–3240 (N–H), 2220 (C N), 1664 (C O), 1653–1627 (C O); H NMR (δ):
3.67 (s, 3H, NCH3), 3.98 (s, 1H, Hthiazinane), 7.25–8.13 (m, 4H, Harom), 9.80 (b, 1H, NH,
exchangeable with D2O), 11.60 (b, 1H, NH, exchangeable with D2O); Mass (m/z, I%):

SUBSTITUTED QUINOLINONES, PART 14
297
M+· 390 (10.6%). Anal. calcd. for C15H10N4O3S3 (390.46): C, 46.14; H, 2.58; N, 14.35;
S, 24.64%. Found: C, 46.00; H, 2.60; N, 14.20; S, 24.40%.
Dispiro[(2,4-dioxo1-methyl-1,2,3,4-tetrahydroquinoline)-3,2ꢀ-(1,3-dithie-
tane)-4ꢀ-8”-(6”-oxo-3”-(trifluoromethyl)-5”,6”,7”,8”-tetrahydro[1,2,4]triazolo[3,
4-b]-[1,3,4]thiadiazepine-7”-carbonitrile)] (15). This compound was obtained from
4-amino-5-(trifluoromethyl)-4H-1,2,4-triazole-3-thiol (14), yield 2.11 g (85%), m.p.
198–200◦C (ethanol); IR(νmax, cm−1): 3430–3172 (N–H), 2200 (C N), 1678 (C O),
1654–1636 (C O). 1H NMR (δ): 3.72 (s, 3H, NCH3), 4.00 (s, 1H, Hthiadiazepine), 7.28–8.05
(m, 4H, Harom), 12.50 (s, 1H, NH, exchangeable with D2O); Mass (m/z, I%): M+· 498
(8.4%). Anal. calcd. for C17H9N6F3O3S3 (498.49): C, 40.96; H, 1.82; N, 16.86; S, 19.30%.
Found: C, 40.80; H, 2.00; N, 16.50; S, 19.10%.
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