Studies on 4-thiazolidinones: Scope of the reactions of 3-aryl-2-thioxo-1,3-thiazolidin-4-ones with cyanide and cyanate ions

Article abstract of DOI:10.1002/hlca.200890159

Treatment of 3-aryl-2-thioxo-1,3-thiazolidin-4-ones 1 with CN^- and NCO^- effected the ring cleavage providing [(cyanocarbonothioyl) amino]benzenes 4 and arylisothiocyanates 5, respectively. Similar treatment of 5-(2-aryl-2-oxoethyl) derivatives 2 afforded 2,4-bis(2-aryl-2-oxoethylidene) cyclobutane-1,3-diones 6 along with each of the preceding products. Treatment of the respective (E,Z)-5-(2-aryl-2-oxoethylidene) analogues 3b and 3c with CN^- gave 4b and 4c and 2-(arylcarbonyl)-2-methoxy-4- oxopentanedinitriles 7b and 7c, in addition to 3,6-bis[2-(4-chlorophenyl)-1- methoxy-2-oxoethylidene]-1,4-dithiane-2,5-dione 8c, which has been generated from 3c. Reactions of 3c or 3d with NCO^- provided 5c or 5d, together with 8c or 8d as pure isomers. In the formation of the MeO products 7 and 8, the solvent (MeOH) has participated. Structures of these products are based on microanalytical and spectroscopic data. Rationalizations for the above transformations are given.

Full text of DOI:10.1002/hlca.200890159

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Studies on 4-Thiazolidinones: Scope of the Reactions of 3-Aryl-2-thioxo-1,3-
thiazolidin-4-ones with Cyanide and Cyanate Ions
by Mohamed T. Omar, Mohamed E. Shaban, Nadia K. El-Aasar*, and Khaled F. Saied
Department of Chemistry, Faculty of Science, Ain Shams University, Cairo, Egypt
(e-mail: nadia.alaasar@yahoo.com)
Treatment of 3-aryl-2-thioxo-1,3-thiazolidin-4-ones 1 with CNꢀ and NCOꢀ effected the ring cleavage
providing [(cyanocarbonothioyl)amino]benzenes 4 and arylisothiocyanates 5, respectively.Similar
treatment of 5-(2-aryl-2-oxoethyl) derivatives 2 afforded 2,4-bis(2-aryl-2-oxoethylidene)cyclobutane-
1,3-diones 6 along with each of the preceding products.Treatment of the respective ( E,Z)-5-(2-aryl-2-
oxoethylidene) analogues 3b and 3c with CNꢀ gave 4b and 4c and 2-(arylcarbonyl)-2-methoxy-4-
oxopentanedinitriles 7b and 7c, in addition to 3,6-bis[2-(4-chlorophenyl)-1-methoxy-2-oxoethylidene]-
1,4-dithiane-2,5-dione 8c, which has been generated from 3c.Reactions of 3c or 3d with NCOꢀ provided
5c or 5d, together with 8c or 8d as pure isomers.In the formation of the MeO products 7 and 8, the solvent
(MeOH) has participated.Structures of these products are based on microanalytical and spectroscopic
data.Rationalizations for the above transformations are given.
1. Introduction. – In continuation of our previous work [1][2] on 1,3-thiazolidin-4-
ones [3], we planned to use the ability of this ring system to cleave the 1,2- as well as the
3,4-bond with the aim of synthesizing [(cyanocarbonothioyl)amino]benzenes and
cyanato analogues.These are believed to be useful intermediates in heterocyclic
synthesis [4].The reactions were carried out in hot dioxane/MeOH solution with 22.
equiv.of cyanide and/or cyanate ions; they have not been studied until now.
2. Results and Discussion. – The starting 3-aryl-2-thioxo-1,3-thiazolidin-4-ones 1a –
1d and 2a were prepared according to previously reported methods [5][6].3-Aryl-5-(2-
aryl-2-oxoethyl)-2-thioxo-1,3-thiazolidin-4-ones 2b – 2d were synthesized from aroyl-
acrylic acids and aryldithiocarbamates according to Nagase [7], whilst (E,Z)-3-aryl-5-
(2-aryl-2-oxoethylidene)-2-thioxo-1,3-thiazolidin-4-ones 3a – 3d were obtained from
the corresponding 2a – 2d on treatment with Br2 in hot AcOH solution; a reaction first
reported by Nagase [7], and extensively studied by Omar et al. [1].
Structures of 2b – 2d and (E,Z)-3a – 3d were confirmed by microanalytical and
spectroscopic data.The 1H-NMR spectra of compounds 2 exhibited the pattern
consistent with the ꢀCHAꢀCHMHXꢀ moiety, which has collapsed into an olefinic
singlet in the spectra of the respective compounds 3.
The olefinic H-atom integration showed that 3a and 3b are pure isomers, whereas 3c
and 3d are (E)/(Z)-mixtures in which the (Z)-isomer constitutes 92 and 90%,
respectively.The configuration assignment of the ( Z)-isomer is based on the
assumption that the vinylic H-atoms in these isomers are more deshielded by the 4-
ꢀ 2008 Verlag Helvetica Chimica Acta AG, Zürich

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oxo group, as in azlactones [8] and 2-pyrazolin-5-ones [9], compared with the (E)-
counterparts.
Treatment of 1a – d with KCN (Method i) and KOCN (Method i’) effected
heteroring cleavage, providing [(cyanocarbonothioyl)amino]benzenes 4a – d and
arylisothiocyanates 5a – d [10 – 12], respectively (Scheme 1).Compound 4 was obtained
in high yield, whereas 5 was obtained contaminated with ca.20% of 1.This could be
rationalized in terms of the reaction reversibility, since the thiolate ion B could react
with the produced 5 to reform 1.This assumption is supported by the synthesis of 1,3-
thiazolidine derivatives from isothiocyanates and mercaptoacetic acid or its esters [13].
Scheme 1. Reactions of 1a – 1d with KCN and KOCN
The structures of 4a and 4c were elucidated by comparison (m.p. and admixing
m.p.) with authentic samples [14][15], whilst those of 4b and 4d were confirmed by
microanalytical and spectroscopic data.
The 1H-NMR spectrum of 4b exhibited two singlets for the MeO group at 3.39 and
3.97 ppm; likewise, two doublets were displayed at 7.72 and 8.96 ppm for the aromatic
HꢀC(3), indicating the existence of two forms.The shielded signals originated from
the open form, whilst the deshielded signals are belonging to a form in which the NꢀH
undergoes a H-bond with the O-atom of the MeO group (Fig. 1).This is supported by
the highly deshielded d value of HꢀC(3) in the H-bonded form.Moreover, the H-bond
in N-aryl-2-methoxyaniline [16], as well as in 2-methoxyphenol [17], gives further
support to this interpretation.Integration of the two MeO singlets indicated that the H-
bonded form constitutes 76% of the mixture.The IR spectrum displayed the stretching
absorptions at 3280 and 2230 cmꢀ1 for NH and CN groups, respectively.The EI-MS
exhibits an abundant molecular ion peak and a base peak m/z 161 of the ion radical
Fig.1. H-Bonded form of 4b (76%; in CDCl3)

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[M ꢀ MeO]þ.The structures of compounds 5 were confirmed by matching m.p. with
authentic samples [10 – 12].
Similar treatment of 2a – 2d with CNꢀ (Method ii) or NCOꢀ (Method ii’) provided
in fair yield 2,4-bis(2-aryl-2-oxoethylidene)cyclobutane-1,3-diones 6a – 6d, along with
high yields of 4a – 4d and/or 5a – 5d, respectively.Formation of 6 is believed to proceed
via a [2 þ 2] head-to-tail cycloaddition, similar to disubstituted ketenes [18]
(Scheme 2).The structures of 6a – 6d, which do not contain N- or S-atoms, were
confirmed by microanalytical and spectroscopic data.The IR spectra showed two
˜n(C¼O) absorptions consistent with the aroyl and highly conjugated cyclic ketone
1
functions.In spite of the poor solubility of 6 in most of the solvents, the H-NMR
spectrum of 6b, which is slightly soluble in (D6)DMSO, is quite satisfactory for
structure confirmation; the spectrum displayed the expected aromatic multiplets and a
broad singlet for the olefinic H-atom.These compounds exist, most likely, as ( E)/(Z)-
mixtures, but ratios of these isomers could not be measured, as the olefinic H-atoms of
these isomers have the same chemical shift (Fig. 2).The EI-MS of 6a – 6d exhibited
intense molecular ion peaks, along with less abundant peaks consistent with [M ꢀ CO]þ
and [M ꢀ 2 CO]þ fragments.Moreover, all spectra displayed aroyl fragments as base
peaks, and low abundant peaks at exactly half of the m/z values that inferred with the
possibility of the retro [2 þ 2] reaction at high temperatures.
Scheme 2. Reactions of 2a – 2d with KCN and KOCN
Moreover, thiation of 6 was believed to afford soluble thione derivatives, which by
measuring their 13C-NMR spectra would further support the structure of 6.Therefore,
the reaction of 6a with Lawessonꢁs reagent [19] was carried out, providing the

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Fig.2. Configurations of (Z)-6b and (E)-6b
respective cyclobutane-1,3-dithione analogue 6’a (Scheme 2).Unfortunately, 6’a was
also insoluble in most of the solvents.The IR spectrum of 6’a showed a ˜n(C¼O)
absorption at 1735 cmꢀ1, whereas the ˜n(C¼O) absorption at 1696 cmꢀ1 of the parent 6a
has disappeared.The EI-MS showed that the thiation process has occurred only at the
two cyclic ketone groups, as it displayed a correct molecular ion peak m/z 376 (25%)
and the [4-MeC6H4CO]þ fragment m/z 119 (99%), besides the fragment m/z 344 for
ꢀ1
[M ꢀ S]þ as the base peak.Thus, the CO absorption at 1696 cm
is assigned to the
strained cyclobutanedione, whilst the one at 1735 cmꢀ1 is assigned to the conjugated
aroyl groups in 6a.Two factors could affect these unexpected data; the conjugation of
the ethylene bonds with the more electron-withdrawing dione ring rather than the aroyl
groups, and the possible intramolecular H-bond between the vinylic H-atoms and the
cyclic CO groups [20].
On the other hand, when the methylidene derivatives 3b and 3c were reacted with
CNꢀ under the preceding conditions (Method iii, Scheme 3), they afforded 4b and 4c
and 2-aroyl-2-methoxy-4-oxopentanedinitriles 7b and 7c, along with 3,6-bis[2-(4-
chlorophenyl)-1-methoxy-2-oxoethylidene]-1,4-dithiane-2,5-dione (8c), in the case of
3c.
Furthermore, allowing 3c and 3d to react with KOCN (Method iii’) gave 5c and 5d,
respectively, in high yield, together with the dithianes 8c and 8d as minor products
(Scheme 3).Since the thiolate ion B’’ lacks a MeO group; participation of the solvent
(MeOH) was expected [21], providing 7, as well as 8 (Scheme 3).
The IR spectra of 7b and 7c showed the stretching absorptions of CꢀH, broad
CꢁN, and two different C¼O groups, as well as OꢀH, which supports its existence in
the enolic form.The 1H-NMR spectra exhibited a singlet at 3.90 ppm for MeO, and a
broad singlet, most likely a collapsed AB system, for ꢀCH2ꢀ attached to a chiral center
[22].The EI-MS exhibited correct molecular ion peaks, which showed elimination of
MeOH to give the base peak of 7c and an abundant peak in 7b.Moreover, the
13C-NMR spectrum of 7c is in accord with the structure, as it showed two resonances for
the two CN groups, whereas the high resonance for the C(3) was attributed to the
existence of 7c in the enolic form under the effect of the polar solvent (D6)DMSO
(Fig. 3).
1
The H-NMR spectra of 8 displayed a singlet for the two MeO groups at ca.
3.72 ppm, beside the expected pattern of the aromatic H-atoms. Displaying only one
singlet for the two MeO groups indicated that 8 could be assigned either the (3Z,6Z) or
(3E,6E) configuration.The EI-MS did not exhibit the molecular ion peaks, but an
[M ꢀ S]þ ion peak was displayed.The IR spectra of 8c and 8d showed two C¼O
absorptions, and the microanalytical data agreed with the given structure.

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Scheme 3. Reactions of 3b – 3d with KCN and KOCN
Fig.3. Carbon numbering of 7c in the enolic form, in (D6)DMSO
Moreover, formation of 5 could be also performed on treatment of 1, 2, and/or 3
with KCN, if the reaction mixtures were left at room temperature for 24 h before
working up.During this long time, the sluggish elimination of CN ꢀ took place affording
5 at the expense of 4.Syntheses of [(cyanocarbonothioyl)amino]benzenes and
arylisothiocyanates have been recently reported via different methods [14][23 – 25].
With the exception of 6, which was filtered off from the reaction mixture, all products
were separated by column chromatography.
A possible mechanism for all the above transformations is presented in Schemes 1 –
3: the nucleophilic anions Yꢀ (CNꢀ or CNOꢀ) attack the thiazolidine ring at C(2) or
C(4) to cleave it providing the anion A or the thiolate B, B’, or B’’.Protonation of A
gave [(cyanocarbonothioyl)amino]benzenes 4, whereas elimination of Yꢀ afforded the
arylisothiocyanates 5 at the expense of the hypothetically formed [(cyanatocarbono-
thioyl)amino]benzenes.Elimination of Y ꢀ from B’ (Scheme 2) afforded the mercapto-
ketene C, which in turn gave the cyclobutane-1,3-diones 6 via head-to-tail cyclo-
dimerization [18].The unsaturated thiolate B’’ (Scheme 3) added a molecule of MeOH

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and eliminated HSꢀ to give D or dimerized [26].The intermediate [ D] added a CNꢀ ion
which afforded 7 on protonation, whereas dehydrogenation [27][28] of the dimer gave 8.
3. Conclusions. – [(Cyanocarbonothioyl)amino]benzenes 4 and arylisothiocyanates
5 could be prepared in good yield via treatment of 2 and/or 3 with cyanide and cyanate
ions, respectively; nevertheless, compound 2 is preferred, since the counterpart product
6 is so easy to be separated by filtration.
Experimental Part
General.Light petroleum was referred to the fraction bp.. ¼ 60 – 808. 1a – 1d [5] and 2a [6] were
prepared according to previously reported methods.Recorded yields of 6 are obtained from heating of
2a – 2c with KOCN.Thin layer chromatography (TLC) was performed on Merck Kieselgel 60 F254
aluminum packed plates.Column chromatography (CC) was carried out with silica gel S (SiO2; 0.63 –
0.1 mm; Riedel-de-Haen; column dimensions: l ¼ 17 cm, ˘ ¼ 1.7 cm). M.p.: Stuart Scientific; uncorrect-
ed.IR Spectra: Perkin Elmer 1600 instrument in KBr.Unless otherwise stated, spectra of 1H-NMR
(200 MHz) and 13C-NMR (50 MHz, APT Technique) were measured in CDCl3 soln.on Varian Gemini
spectrometers; chemical shifts (d) are reported in ppm downfield relative to Me4Si.Mass Spectra:
Shimadzu GC-MS-QP 1000X instrument operating at 70 eV.
Synthesis of 3-Aryl-5-(2-aryl-2-oxoethyl)-2-thioxo-1,3-thiazolidin-4-ones 2b – 2d.Ammonium (2-
methoxyphenyl)carbamodithioate (2.3 g, 10.75 mmol), 2.15 g ammonium (4-methylphenyl)carbamodi-
thioate (10.75 mmol), or 2.4 g ammonium (4-chlorophenyl)carbamodithioate (10.75 mmol) was added
portionwise to a stirred soln.of 17.6 g 4-oxo-4-phenylbut-2-enoic acid (10 mmol), 21.g 4-(4-
chlorophenyl)-4-oxobut-2-enoic acid (10 mmol), or 2.54 g 4-(4-bromophenyl)-4-oxobut-2-enoic acid
(10 mmol) [29] in EtOH (10 ml) and stirred at r.t. for 30 min. Then, the mixture was acidified with conc.
HCl (3 ml), boiled for 5 min, and left to cool.The precipitated solid was filtered off, washed with H 2O, air
dried, and the crude product was recrystallized from the proper solvent to give the product.
3-(2-Methoxyphenyl)-5-(2-oxo-2-phenylethyl)-2-thioxo-1,3-thiazolidin-4-one (2b). 3.0 g (84%). M.p.
153 – 1558 (toluene/MeOH).IR (KBr): 3050 (aryl-H), 2930, 2850 (alkyl-H), 1740, 1685 (C ¼O), 1240
(C¼S), 750, 690 (d5-H). 1H-NMR: 3.64 (dd, JMX ¼ 19.6, JAX ¼ 11.8, 1 HX); 3.83 (s, MeO); 4.21 (dd, JMX
¼
19.6, JAM ¼ 3.0, 1 HM); 4.77 (dd, JAX ¼ 11.6, JAM ¼ 3.0, 1 HA); 7.10 (t, J ¼ 8.0, HꢀC(5), 1 Hanisyl); 7.12 (d,
J ¼ 9.0, HꢀC(3), 1 Hanisyl); 7.23 (d, J ¼ 7.8, HꢀC(6), 1 Hanisyl); 7.40 – 7.70 (m, 4 Harom); 7.99 (d, J ¼ 8.2,
2 Harom).EI-MS: 357 (4, Mþ), 252 (91, [M ꢀ PhCO]þ), 159 (90, [M ꢀ MeOC6H4 ꢀ NCS2H]þ), 105 (100
[PhCO]þ), 77 (86, Phþ).Anal.calc.for C 18H15NO3S2: C 60.49, H 4.23, N, 3.92; found: C 60.51, H 4.18, N
3.89.
5-[2-(4-Chlorophenyl)-2-oxoethyl]-3-(4-methylphenyl)-2-thioxo-1,3-thiazolidin-4-one (2c).29. g
(77%).Mp..169 – 171 8 (toluene).IR (KBr): 3060, 3030 (aryl-H), 2950, 2920, 2850 (alkyl-H), 1735,
1680 (C¼O), 1230 (C¼S), 820 (d2-H). 1H-NMR: 2.38 (s, Me); 3.76 (dd, JMX ¼ 18.8, JAX ¼ 8.0, 1 HX); 4.06
(dd, JAM ¼ 3.0, JMX ¼ 18.8, 1 HM); 5.02 (dd, JAX ¼ 8.0, JAM ¼ 3.0, 1 HA); 7.21, 7.37 (2d, J ¼ 8.2, 2 Harom); 7.65,
8.03 (2d, J ¼ 8.4, 2 Harom).EI-MS: 375 (18, Mþ), 236 (100, [M ꢀ 4-ClC6H4CO]þ), 149 (27, [4-
MeC6H4NCS]þ), 139 (51, [4-ClC6H4CO]þ), 111 (38, [4-ClC6H4]þ).Anal.calc.for C 18H14ClNO2S2: C
57.52, H 3.79, N 3.73; found: C 57.61, H 3.73, N 3.75.
5-[2-(4-Bromophenyl)-2-oxoethyl]-3-(4-chlorophenyl)-2-thioxo-1,3-thiazolidin-4-one (2d).37. g
(84%).Mp. .168 – 170 8 (toluene/MeOH).IR (KBr): 3050 (aryl-H), 2950, 2920, 2860 (alkyl-H), 1735,
1
1685 (C¼O), 1235 (C¼S), 810 (d2-H). H-NMR: 3.76 (dd, JMX ¼ 18.8, JAX ¼ 8.0, 1 HX); 4.06 (dd, JMX
¼
18.8, JAM ¼ 3.0, 1 HM); 4.80 (dd, JAX ¼ 8.0, JAM ¼ 3.0, 1 HA); 7.18, 7.49 (2d, J ¼ 8.6, 2 Harom); 7.69, 7.91
(2d, J ¼ 8.6, 2 Harom).EI-MS: 439 (26, Mþ), 256 (100, [M ꢀ 4-BrC6H4CO]þ), 183 (49, [4-BrC6H4CO]þ),
155 (31, [4-BrC6H4]þ).Anal.calc.for C 17H11BrClNO2S2: C 46.35, H 2.52, N 3.18; found: C 46.33, H 2.44,
N 3.12.
Synthesis of (Z)- and (E,Z)-3-Aryl-5-(2-aryl-2-oxoethylidene)-2-thioxo-1,3-thiazolidin-4-ones 3a –
3d.A soln.of 05. ml Br
(3.0 mmol) in 5 ml AcOH was added to a soln. of (10 mmol) of each of 2a,
2

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2b, 2c, or 2d in hot AcOH (50 ml).The mixture was gently warmed until HBr gas evolution ceased ( ca.
5 min).The precipitated solid was filtered off, washed with H 2O, air dried and crystallized from the
proper solvent to give (Z)-3a, (Z)-3b, (E,Z)-3c, and (E,Z)-3d.CC of ( E,Z)-3c and (E,Z)-3d over SiO2,
eluting with light petroleum/CHCl3 (4 :1 v/v) gave (Z)-3c and (Z)-3d, resp.
(5Z)-5-[2-(4-Methylphenyl)-2-oxoethylidene]-3-phenyl-2-thioxo-1,3-thiazolidin-4-one (3a).30. g
(88.4%) as yellow needles. M.p. 255 – 2578 (toluene).IR (KBr): 3045 (aryl-H), 2950 (alkyl-H), 1726
(br.), 1683 (C¼O), 1238 (C¼S), 820 (d2-H), 750, 700 (d5-H). 1H-NMR ((D6)DMSO): 2.46 (s, Me); 7. 28 (d,
J ¼ 8.0, 2 HPh); 7.50 – 7.63 (m, 3 HPh); 7.36, 8.02 (2d, J ¼ 8.0, 2 Harom); 8.01 (s, ¼CH).EI-MS: 339 (44, Mþ),
204 (19, [M ꢀ 4-CH3C6H4NCS]þ), 119 (100, [4-MeC6H4CO]þ), 91 (31, [C7H7]þ), 77 (11, Phþ).Anal.calc.
for C18H13NO2S2: C 63.70, H 3.86, N 4.13; found: C 63.45, H 3.70, N 3.72.
(5Z)-3-(2-Methoxyphenyl)-5-(2-oxo-2-phenylethylidene)-2-thioxo-1,3-thiazolidin-4-one (3b).28. g
(74.7%) as orange flakes. M.p. 237 – 2398 (toluene).IR (KBr): 3040 (aryl-H), 2950 (alkyl-H), 1725
(br.), 1685 (C¼O), 1240 (C¼S), 840 (d2-H), 750, 698 (d5-H). 1H-NMR ((D6)DMSO): 3.77 (s, MeO); 7.14
(t, J ¼ 8.0, HꢀC(5), 1 Hanisyl); 7.27 (d, J ¼ 8.40, 1 HꢀC(3), 1 Hanisyl); 7.40 (d, J ¼ 9.20, HꢀC(6), 1 Hanisyl);
7.56 (t, J ¼ 8.0, HꢀC(4), 1 Hanisyl); 7.63 (t, 2 HPh); 7.76 (t, J ¼ 7.1, 1 H Ph); 8.23 (d, J ¼ 7.10, 2 HPh); 8.17 (s,
¼CH).Anal.calc.for C 18H13NO3S2: C 60.83, H 3.69, N 3.94; found: C 60.80, H 3.67, N 3.98.
(5E,5Z)-5-[2-(4-Chlorophenyl)-2-oxoethylidene]-3-(4-methylphenyl)-2-thioxo-1,3-thiazolidin-4-one
(3c). 2.8 g (74.8%) as orange needles. M.p. 260 – 2628 (toluene/dioxane).IR (KBr): 3050 (aryl-H), 2950
(alkyl-H), 1725 (br.), 1680 (C¼O), 1225 (C¼S), 840 (d2-H). 1H-NMR ((D6)DMSO): for the (Z)-isomer
(92%): 2.39 (s, Me); 7.36, 7.32 (two central peaks, 4 Harom); 7.96, 8.28 (2d, J ¼ 8.4, 2 Harom); 8.14 (s, ¼CH);
for the (E)-isomer (8%): 2.28 (s, Me); 7.18, 7.28 (two central peaks, 4 Harom); 7.82, 8.42 (2d, J ¼ 8.8,
2 Harom); 8.01 (s, ¼CH).Anal.calc.for C 18H12ClNO2S2: C 57.83, H 3.24, N 3.75; found: C 57.92, H 3.19, N
3.80.
(5E,5Z)-5-[2-(4-Bromophenyl)-2-oxoethylidene]-3-(4-chlorophenyl)-2-thioxo-1,3-thiazolidin-4-one
(3d). 3.4 g (77.5%) as orange clusters. M.p. 274 – 2768 (dioxane).IR (KBr): 3050 (aryl-H), 1725 (br.),
1
1685(C¼O), 1225 (C¼S), 840 (d2-H). H-NMR ((D6)DMSO): for the (Z)-isomer (90%) 7.50, 7.67 (2d,
J ¼ 8.4, 2 Harom); 7.84, 8.21 (2d, J ¼ 8.1, 2 Harom); 8.15 (s, ¼ CH); for the (E)-isomer (10%): 7.43, 7.60 (2d,
J ¼ 9.0, 2 Harom); 7.90, 8.27 (2d, J ¼ 9.0, 2 Harom); 8.08 (s, ¼CH).Anal.calc.for C 17H9BrClNO2S2: C 46.54,
H 2.07, N 3.19; found: C 46.70, H 2.25, N 3.40.
Reactions of 1, 2, and 3 with KCN and KOCN. General Procedure. A mixture of 1a – 1d, 2a – 2d, or
3b – 3d (1 mmol) and KCN or KOCN (2.2 equiv.) in dioxane (25 ml) was heated to 908 for 25 min.During
this time, 30 ml of MeOH was added in five portions till the red color first formed faded away.The
mixtures were worked up as mentioned below.
Reactions of 1a – d.The mixture obtained from 1 on treatment with KCN (Method i) or KOCN
(Method i’) was concentrated, poured into H2O (50 ml), acidified with conc.HCl (1 ml), and extracted
with CHCl3 (100 ml).The dried extract was evaporated, the residue was chromatographed over SiO 2 with
light petroleum/AcOEt (9 :1 v/v) to give the [(cyanocarbonothioyl)amino]benzenes 4a – 4d and/or with
light petroleum to afford arylisothiocyanates 5a – 5d [10 – 12] (TLC monitored separation).
Reactions of 2a – 2d.The insoluble creamy product 6, which precipitated from the mixtures of 2a – 2d
with KCN (Method ii) and/or KOCN (Method ii’), was filtered off, washed with H2O, and then with
MeOH.The dried product was recrystallized from nitrobenzene to afford the respective 2,4-bis(2-aryl-2-
oxoethylidene)cyclobutane-1,3-diones 6a – 6d.The mother liquors were concentrated, poured into H 2O
(50 ml), and worked up as previously mentioned to give 4a – 4d and 5a – 5d, which were matched TLC
and IR with authentic samples [10 – 12].
Reactions of 3b – 3d.The dark brown mixtures obtained by reacting 3b or 3c with KCN (Method iii)
and 3c or 3d with KOCN (Method iii’) were concentrated, poured into H2O (50 ml), and extracted with
100 ml toluene.The org.extract was dried (anh.CaCl 2) and evaporated.The residue was chromato-
graphed over SiO2 with light petroleum to give 5, then with light petroleum/CHCl3 (4 :1 v/v) to afford the
dithianedione 8c or 8d.The original aq.soln.was acidified with conc.HCl (1 ml) and then extracted with
CHCl3 (100 ml).The extract was dried (anh.CaCl 2) and evaporated.The residue was chromatographed
over SiO2 with light petroleum/CHCl3 (4 :1 v/v) to afford the [(cyanocarbonothioyl)amino]benzenes 4,
and then with light petroleum/CHCl3 (7:3 v/v) to give the pentanedinitriles 7b and 7c (TLC monitored
separation).

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Helvetica Chimica Acta – Vol.91 (2008)
[(Cyanocarbonothioyl)amino]benzene (4a).01. 3 g (83%, Method i), 0.14 g (87%, Method ii).Pale
yellow needles.Mp. .80 8 (light petroleum), in agreement with m.p. and IR of an authentic sample [15].
1-[(Cyanocarbonothioyl)amino]-2-methoxybenzene (4b).01.8 g (92%,
Method i), 0.18 g (92%,
Method ii), 0.16 g (82%, Method iii).Orange needles.Mp. .93 – 95 8 (light petroleum).IR (KBr): 3280
1
(NH), 3020 (aryl-H), 2230w (CN), 1120 (C¼S), 750 (d5-H). H-NMR: for the H-bonded form (Fig. 1;
76%): 3.97 (s, MeO); 6.99 (d, J ¼ 8.0, 1 HꢀC(6), 1 Hanisyl); 7.05 (t, J ¼ 8.0, 1 HꢀC(4), 1 Hanisyl); 7.31 (t, J ¼
8.0, HꢀC(5), 1 Hanisyl); 8.96 (d, J ¼ 8.2, HꢀC(3), 1 Hanisyl); 9.80 (br. s, NH); for the non-H-bonded, open
form (24%): 3.39 (s, MeO); 6.99 (d, J ¼ 8.0, 1 HꢀC(6), 1 Hanisyl); 7.06 (t, J ¼ 8.0, 1 HꢀC(4), 1 Hanisyl); 7.34
(t, J ¼ 8.0, HꢀC(5), 1 Hanisyl); 7.72 (d, J ¼ 8.2, HꢀC(3), 1 Hanisyl); 9.80 (br. s, NH).EI-MS: 192 (37, Mþ),
165 (14, [M ꢀ HCN]þ), 161 (100, [M ꢀ MeO]þ), 107 (21, [M ꢀ NHCSCN]þ).Anal.calc.for C 9H8N2OS:
C 56.23, H 4.19, N 14.57; found: C 56.23, H 4.09, N 14.59.
1-[(Cyanocarbonothioyl)amino]-4-methylbenzene (4c).01.6 g (91%,
Method i), 0.16 g (91%,
Method ii), 0.15 g (87%, Method iii).Orange needles.Mp. .131 8 (light petroleum/CHCl3), in agreement
with m.p. and IR of an authentic sample [14].
1-Chloro-4-[(cyanocarbonothioyl)amino]benzene (4d).01.8 g (93%,
Method i), 0.19 g (96%,
Method ii).Yellow needles.Mp..116 – 118 8 (CHCl3/light petroleum).IR (KBr): 3260, 3050 (aryl-H),
2200w (CN), 1090 (C¼S), 825 (d2-H). 1H-NMR ((D6)DMSO): 7.57, 7.95 (2d, J ¼ 9.0, 2 Harom); 13.55 (br. s,
NH).Anal.calc.for C 8H5N2S: C 48.85, H 2.54, N 14.25; found: C 48.83, H 2.57, N 14.29.
Phenyl Isothiocyanate (5a).00. 5 g (32%, Method i’), 0.13 g (93%, Method ii’) [11].
2-Methoxyphenyl Isothiocyanate (5b).00. 6 g (35%, Method i’), 0.15 g (91%, Method ii’) [10].
4-Methylphenyl Isothiocyanate (5c).00. 5 g (32%, Method i’), 0.15 g (93%, Method ii’), 0.14 g (91%,
Method iii’) [11].
4-Chlorophenyl Isothiocyanate (5d).0.06 g (35%, Method i’), 0.16 g (95%, Method ii’), 0.15 g (90%,
Method iii’) [12].
2,4-Bis[2-(4-methylphenyl)-2-oxoethylidene]cyclobutane-1,3-dione (6a).01.2 g (42%).Mp..
> 3608.
IR (KBr): 3080 (aryl-H), 1735, 1696 (C¼O), 1595 (C¼C), 810 (d2-H).EI-MS: 344 (80, Mþ), 316 (8, [M ꢀ
CO]þ), 288 (48, [M ꢀ 2 CO]þ), 172 (6, [M ꢀ 4-MeC6H4COCH¼C¼CO]þ), 119 (100, [4-MeC6H4CO]þ),
91 (8, [4-MeC6H4]þ).Anal.calc.for C 22H16O4: C 76.73, H 4.68; found: C 76.71, H 4.58.
2,4-Bis(2-oxo-2-phenylethylidene)cyclobutane-1,3-dione (6b). 0.10 g (40%). M.p. > 3608.IR (KBr):
3080 (aryl-H), 1738, 1695 (C¼O), 1595 (C¼C), 740, 680 (d5-H). 1H-NMR ((D6)DMSO): 7.42 (br. s, 2 H,
¼CH); 7.61 – 7.45 (m, 6 Harom); 7.96 – 8.01 (m, 4 Harom).EI-MS: 316 (80, Mþ), 288 (10, [M ꢀ CO]þ), 260
(8, [M ꢀ 2 CO]þ), 158 (5, [PhCOCH¼C¼CO]þ), 105 (100, [PhCO]þ), 77 (77, Phþ).Anal.calc.for
C20H12O4: C 75.94, H 3.82; found: C 75.94, H 3.82.
2,4-Bis[2-(4-chlorophenyl)-2-oxoethylidene]cyclobutane-1,3-dione (6c).01.4 g (42%).Mp..
> 3608.
IR (KBr): 3090 (aryl-H), 1715, 1685 (br., C¼O), 1595 (C¼C), 810 (d2-H).EI-MS: 384 (69, Mþ), 356 (4,
[M ꢀ CO]þ), 328 (29, [M ꢀ 2 CO]þ), 192 (5.9, [4-ClC6H4COCH¼C¼CO]þ), 139 (100, [4-ClC6H4CO]þ),
111 (60, [4-ClC6H4]þ).Anal.calc.for C 20H10Cl2O4: C 62.36, H 2.62; found: C 62.44, H 2.68.
2,4-Bis[2-(4-bromophenyl)-2-oxoethylidene]cyclobutane-1,3-dione (6d). 0.18 g (43%). M.p. > 3608.
IR (KBr): 3050, 1715 (br.), 1678 (C¼O), 1595 (C¼C), 810.EI-MS: 472 (40, Mþ), 444 (3, [M ꢀ CO]þ),
416 (3, M ꢀ 2 CO]þ), 236 (2, [4-BrC6H4COCH¼C¼CO]þ), 183 (100, [4-BrC6H4CO]þ), 155 (80, [4-
BrC6H4]þ).Anal.calc.for C 20H10Br2O4: C 50.63, H 4.19; found: C 50.54, H 2.11.
2-Methoxy-4-oxo-2-(phenylcarbonyl)pentanedinitrile (7b). 0.035 g (15%). M.p. 169 – 1718 (toluene).
IR (KBr): 3450, 3260, 3200 (OꢀH), 3040 (aryl-H), 2910 (alkyl-H), 2220 (CN), 1710, 1685 (C¼O), 760,
690. 1H-NMR: 3.90 (s, MeO); 5.77 (br. s, CH2CO); 7.38 – 7.49 (m, 3 Harom); 7.89 (d, J ¼ 7.8, 2 H arom).EI-
MS: 242 (55, Mþ), 210 (87, [M ꢀ MeOH]þ), 105 (100, [PhCO]þ), 77 (77, [Ph]þ).Anal.calc.for
C13H10N2O3: C 64.46, H 4.16, N 11.56; found: C 64.32, H 4.20, N 11.49.
2-[(4-Chlorophenyl)carbonyl]-2-methoxy-4-oxopentanedinitrile (7c).00. 4 g (15%).Mp. .194 – 196
8
(toluene).IR (KBr): 3500, 3300, 3200 (O ꢀH), 3100 (aryl-H), 2950 (alkyl-H), 2215 (CN), 1710, 1680
1
(C¼O), 820. H-NMR: 3.90 (s, MeO); 5.79 (br. s, CH2CO); 7.42, 7.82 (2d, J ¼ 7.2, 2 H arom). 13C-NMR
((D6)DMSO): 50.4 (C(7)); 85.6 (C(3)); 90.8 (C(4)); 113.6 (C(1)); 125.1 (C(10), C(12)); 125.6 (C(6));
128.9 (C(9), C(13)); 133.6 (C(11)); 147.3 (C(8)); 161.1 (C(2)); 161.8 (C(5)). EI-MS: 276 (75.9, Mþ), 244
(100, [M ꢀ MeOH]þ), 139 (82, [4-ClC6H4CO]þ), 111 (63, [4-ClC6H4]þ).Anal.calc.for C 13H9ClN2O3: C
56.44, H 3.28, N 10.12; found: C 56.63, H 3.42, N 10.30.

Helvetica Chimica Acta – Vol.91 (2008)
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3,6-Bis[2-(4-chlorophenyl)-1-methoxy-2-oxoethylidene]-1,4-dithiane-2,5-dione (8c).00.8 g (30%).
M.p. 212 – 2148 (CHCl3/light petroleum).IR (KBr): 3100 (aryl-H), 2950 (alkyl-H), 1725, 1680 (C ¼O),
810. 1H-NMR: 3.72 (s, MeO); 7.41, 7.68 (2d, J ¼ 8.6, 4 Harom).EI-MS: 476 (13, [ M ꢀ S]þ), 365 (23, [M ꢀ
S ꢀ 4-ClC6H4]þ), 333 (20, [M ꢀ S ꢀ 4-ClC6H4ꢀMeOH]þ), 139 (100, [4-ClC6H4CO]þ).Anal.calc.for
C22H14Cl2O6S2: C 51.88, H 2.77, S 13.12; found: C 52.0, H 2.76, S 13.12.
3,6-Bis[2-(4-bromophenyl)-1-methoxy-2-oxoethylidene]-1,4-dithiane-2,5-dione (8d).00.9 g (30%).
M.p. 239 – 2408 (CHCl3/light petroleum).IR (KBr): 3100 (aryl-H), 2950 (alkyl-H), 1725, 1680 (C ¼O),
810. 1H-NMR: 3.72 (s, MeO); 7.61, 7.59 (two central peaks, 4 Harom).EI-MS: 564 (13, [ M ꢀ S]þ), 409 (38,
[M ꢀ S ꢀ 4-BrC6H4]þ), 377 (32, [M ꢀ S ꢀ 4-BrC6H4ꢀMeOH]þ), 183 (100, [4-BrC6H4CO]þ).Anal.calc.
for C22H14Br2O6S2: C 44.17, H 2.36, S 10.72; found: C 44.23, H 2.61, S 11.3.
Reaction of 6a with Lawessonꢀs Reagent. A mixture of 6a (0.35 g, 1 mmol) and Lawessonꢁs reagent
(0.82 g, 0.2 mmol) was refluxed in dry xylene (50 ml) for 30 min. The mixture was filtered while hot and
washed with H2O (25 ml).The org.layer was separated, dried (CaCl 2), concentrated, and left to cool.
The crude product was filtered off, dried, recrystallized and treated with charcoal before filtration to
afford 6’a.
2,2’-(2,4-Dithioxocyclobutane-1,3-diylidene)bis[(4-methylphenyl)ethan-1-one] (6’a).03.0 g (85%)
deep violet crystals.Mp.. > 3008 (nitrobenzene).IR (KBr): 3050 (aryl-H), 1735 (aroyl C ¼O), 1182
(C¼S), 809.EI-MS: 376 (25, Mþ), 361 (33, [M ꢀ Me]þ), 360 (66, [M ꢀ CH4]þ), 344 (100, [M ꢀ S]þ), 332
(38, [M ꢀ CS]þ), 119 (99, [4-MeC6H4CO]þ), 91 (83, [C7H7]þ).Anal.calc.for C 22H16S2O2: C 70.18, H
4.28, S 17.07; found: C 70.07, H 4.23, S 16.99.
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Received March 5, 2008