The synthesis of 2-cyano-cyanothioformanilides from 2-(4-Chloro-5H-1,2,3- dithiazol-5-ylideneamino)benzonitriles using DBU

Article abstract of DOI:10.1055/s-0029-1217059

A series of 2-(4-chloro-5H-1,2,3-dithiazol-5-ylideneamino) benzonitriles were prepared from the reaction of 4,5-dichloro-1,2,3-dithiazolium chloride (Appel salt) and the corresponding anthranilonitriles. Reaction of the 1,2,3-dithiazolimines with DBU (3 e

Full text of DOI:10.1055/s-0029-1217059

PAPER
4167
The Synthesis of 2-Cyano-cyanothioformanilides from 2-(4-Chloro-5H-1,2,3-
dithiazol-5-ylideneamino)benzonitriles Using DBU
Synthesis of
2
o
n
p
othioforman
hilides ia S. Michaelidou, Panayiotis A. Koutentis*
Department of Chemistry, University of Cyprus, P.O. Box 20537, 1678 Nicosia, Cyprus
Fax +357(22)892809; E-mail: koutenti@ucy.ac.cy
Received 30 June 2009
While the use of triphenylphosphine (2 equiv) was report-
Abstract: A series of 2-(4-chloro-5H-1,2,3-dithiazol-5-ylideneam-
ino)benzonitriles were prepared from the reaction of 4,5-dichloro-
1,2,3-dithiazolium chloride (Appel salt) and the corresponding an-
thranilonitriles. Reaction of the 1,2,3-dithiazolimines with DBU (3
ed to give good yields of the cyanothioformanilides, it was
not possible to obtain 2-cyano-cyanothioformanilide (2a)
from the reaction of 2-(4-chloro-5H-1,2,3-dithiazol-5-
equiv) at –5 °C gave the corresponding 2-cyano-cyanothioforma- ylideneamino)benzonitrile (1a) despite the preparation of
the 4,5-dimethoxy analogue in high yield.24c Nevertheless
nilides in near quantitative yields. Treatment of 2-(4-chloro-5H-
1,2,3-dithiazol-5-ylideneamino)benzonitrile with DBU (4 equiv) at
Kim et al. successfully isolated 2-cyano-cyanothioform-
–5 to +20 °C gave 2-isothiocyanatobenzonitrile in 96% yield. The
anilide (2a) from the reaction of the dithiazolimine 1a
latter compound was also formed directly from 2-cyano-cyanothio-
with either NH2OH·HCl (4 equiv) in pyridine at ~20 °C
formanilide on treatment with DBU (1 equiv) in 95% yield. A ten-
for 4 h (27%)19 or as a by-product from reaction with
tative mechanism for the DBU-mediated dithiazole to
phosphoraneylidenes in low yield (8%).23 As part of our
cyanothioformanilide transformation is proposed and all com-
pounds were fully characterized.
ongoing investigations of 4,5-dichloro-1,2,3-dithiazolium
chloride (Appel salt)26 and our desire to study the chemis-
try of 2-cyano-cyanothioformanilides 2, we required an
efficient synthesis that tolerated a range of aryl substitu-
ents. Here, we describe the reaction of 2-(4-chloro-5H-
1,2,3-dithiazol-5-ylideneamino)benzonitriles 1 with 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU), which affords the
desired 2-cyano-cyanothioformanilides 2 in near quantita-
tive yields.
Key words: Appel salt, DBU, Cyanothioformanilide, isothiocyan-
ate
Cyanothioformanilides (thiooxanilonitriles) demonstrate
herbicidal activity,1 and have been used extensively for
the preparation of various heterocycles including pyr-
roles,2a,b imidazoles,3 oxazoles,4 1,3,4-thiadiazoles,5
quinazolines,6 and other fused heterocycles.7 Further-
more, cyanothioformanilides participate in Diels–Alder8
and ene-reactions,9 they can be N-aroylated10 and, upon
addition of water, hydrogen sulfide or hydroxylamine to
the nitrile, afford aminooxothioacetylanilines, amino-
thioxothioacetylanilines (N-aryldithioxamides)3d,11 or
amidinothioformylanilines,4c,12 respectively.
Treatment of 2-(4-chloro-5H-1,2,3-dithiazol-5-ylidene-
amino)benzonitrile (1a) with only DBU (3 equiv) in
dichloromethane at ca. –5 °C gave near quantitative con-
version of dithiazolimine 1a into 2-cyano-cyanothioform-
anilide (2a) and no sulfur formation could be observed by
TLC. The use of an additional equivalent of DBU led to
the clean formation of 2-isothiocyanatobenzonitrile (3),
which could also be formed directly from a pure sample
of 2-cyano-cyanothioformanilide (1a; Scheme 1). No re-
action occurred between the dithiazolimine 1a and three
equivalents of either pyridine, 1,4-diazabicyclo[2.2.2]oc-
Cyanothioformanilides are traditionally prepared by the
reaction of N-aryl isothiocyanates with cya-
nide,3j,4c,6a,7f,g,8c,13 or bis(dialkylamino)acetonitriles14 and
also via dethiohydration of N-aryldithiooxamides,13d,15
thionation–dethiohydration of N-arylthiooxalamides,15
and thionation–dehydration of aryloxalamides.15 More re-
cent methods involve treating 2-(4-chloro-5H-1,2,3-dithi-
azol-5-ylideneamino)benzenes with either the oxidizing
agent m-chloroperoxybenzoic acid (MCPBA),16 the re-
ducing agent sodium cyanoborohydride (NaBH3CN),17 or
with nucleophilic (thiophilic) reagents such as aqueous
sodium hydroxide,18 hydroxylamine,19 tert-butylamine,20
tryptamine,21 o-aminophenethylamine and o-phenylene-
diamine,22 triphenylphosphoraneylidenes,23 triphenyl-
phosphine in moist dichloromethane,24 and through the
use of ethylmagnesium bromide (1 equiv).24h,25
tane
(DABCO),
4-(N,N-dimethylamino)pyridine
(DMAP) or triethylamine in dichloromethane at ~20 °C.
The high-yielding formation of the isothiocyanate 3 is
worthy of note; since 1995, only four reports have ap-
peared on the conversion of 2-(4-chloro-5H-1,2,3-dithia-
iii
CN
S
N
Cl
i
ii
NCS
N
H
CN
S
N
CN
CN
S
1a
2a
3
SYNTHESIS 2009, No. 24, pp 4167–4174
Advanced online publication: 19.10.2009
DOI: 10.1055/s-0029-1217059; Art ID: T12909SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
9
Scheme 1 Reagents and conditions: (i) DBU (3 equiv), CH2Cl2,
–5 °C, 5 min, 93%; (ii) DBU (1 equiv), 20 °C, 0.5 h, 95%; (iii) DBU
(4 equiv), CH2Cl2, –5 to +20 °C, 0.5 h, 96%.

4168
S. S. Michaelidou, P. A. Koutentis
PAPER
zol-5-ylideneamino)benzenes into N-aryl isothiocyanates. Table 1 Reaction of Anthranilonitriles 4 with 4,5-Dichloro-1,2,3-
dithiazolium Chloride (5) Followed by Treatment with Pyridinea
These have involved the use of either MCPBA,16 ethyl-
magnesium bromide (2 equiv) in hot anhydrous THF un-
der an argon atmosphere,24f,h,25 or sodium hydride (2.2
equiv) in anhydrous THF at 67 °C for 18 hours.24h Fur-
thermore, only two methods have appeared on the conver-
sion of cyanothiofomanilides into N-aryl isothiocyanates
using either ethylmagnesium bromide (2 equiv) in hot, an-
hydrous THF under an argon atmosphere,24h,25 or in neat
2,6-lutidine using microwave irradiation.24h Despite this,
the conversion of the cyanothioformanilide 2a into
isothiocyanate 3 in the presence of DBU (1 equiv) was not
surprising. A quick screen of alternative 3° amine bases (1
equiv) in dichloromethane at ~20 °C showed that pyridine
was unreactive, whereas the use of DABCO or DMAP led
to incomplete conversion after two days, and that triethyl-
amine could effect the conversion slowly (10 h) to give
the isothiocyanate 3 in 65% yield. The unusual reactivity
of dithiazole towards DBU was, however, at first unclear.
None of the alternative bases screened (pyridine, DAB-
CO, DMAP, and Et3N) under similar reaction conditions
(3 equiv base at ~20 °C in CH2Cl2) showed any reactivity.
CN
Cl
+S
Cl
R
CN
N
Cl
R
+
N
NH2
S
S
N
Cl–
S
4a–g
5
1a–g
4
R
Product
1a
Yield (%)
4a
4b
4c
4d
4e
4f
H
92
91
80
87
86
74
76
6-Me
5-O2N
4-Cl
1b
1c
1d
5-Cl
1e
4-MeO
1f
4g
4,5-(MeO)2
1g
a Reaction conditions: 4 (0.65 mmol), 5 (1 equiv), CH2Cl2, ~20 °C, 1
h then pyridine (2 equiv), ~20 °C, 2 h.
DBU and DBN are commonly used to effect base-induced
dehydrohalogenations and other eliminations to produce
carbon–carbon and carbon–heteroatom multiple bonds.27
As such, these bicyclic amidines are often referred to as
non-nucleophilic strong bases.28 Nevertheless, a careful
search of the literature revealed multiple reports of nu-
cleophilic behavior for both DBU and DBN, notably in re-
actions with either phosphorus29 or carbon30 electrophiles
to afford adducts sporting new nitrogen–phosphorus and
nitrogen–carbon bonds, respectively. On the basis that,
under identical conditions, DMAP failed to react with the
1,2,3-dithiazolimine 1a it can be qualitatively said that
DBU was a more powerful nucleophile, or at least more
thiophilic towards the 1,2,3-dithiazolimine 1a. Similar
differences between the reactivity of DMAP and DBU
have been reported.31 The enhanced nucleophilicity was
not altogether unsurprising considering the enamine-like
character of the bicyclic amidine.32
Table 2 Reaction of 2-(4-Chloro-5H-1,2,3-dithiazol-5-ylideneami-
no)benzonitriles 1 with DBU
CN
CN
R
S
DBU
N
Cl
R
N
H
CN
S
N
S
1a–g
2a–g
1
R
Temp
(°C)
Time
(min)
Product Yield
(%)
1a
1b
1c
1c
1d
1d
1e
1f
H
– 5
5
2a
2b
2c
2c
2d
2d
2e
2f
93
94
69
93
82
91
87
95
88
6-Me
5-O2N
5-O2N
4-Cl
– 5
5
– 5
10
45
15
35
15
15
15
–78 to 20
– 5
The facile conversion of 1,2,3-dithiazolimine 1a into 2-
cyano-cyanothioformanilide (2a) was extended to a wider
range of 2-(4-chloro-5H-1,2,3-dithiazol-5-ylideneami-
no)benzonitriles 1b–g, which were readily prepared from
the corresponding anthranilonitriles 4a–g and 4,5-dichlo-
ro-1,2,3-dithiazolium chloride 5 (Table 1).
4-Cl
–78 to 20
– 5
5-Cl
4-MeO
– 5
1g
4,5-(MeO)2 – 5
2g
In general, the reaction of the dithiazolimines 1 with DBU
(3 equiv) at ca. –5 °C rapidly gave the desired 2-cyano-cy-
anothioformanilides 2 in high yield (Table 2). In a couple
of examples where the yield was significantly lower than
90%, the reactions could be initiated at ca. –78 °C and, un-
der these conditions, the products were obtained in yields
>90%.
a Reaction conditions: 1 (0.40 mmol), DBU (3 equiv), anhyd CH2Cl2
(2 mL).
subsequent ring-opening can afford the disulfide 6. A sec-
ond equivalent of DBU could then abstract HCl to give the
neutral disulfide 7. Further nucleophilic attack by a third
equivalent of DBU could cleave the disulfide S–S bond to
ultimately give the cyanothioformanilide and the neutral
sulfane 8 (Scheme 2).
A tentative mechanistic rationale for the reaction can be
proposed as follows. Nucleophilic attack via the DBU
amidine nitrogen at the dithiazole S(2) ring sulfur and
Synthesis 2009, No. 24, 4167–4174 © Thieme Stuttgart · New York

PAPER
Synthesis of 2-Cyano-cyanothioformanilides
4169
ter the melting point. UV spectra were obtained using a Perkin–
Elmer Lambda-25 UV/Vis spectrophotometer; inflections are iden-
tified by the abbreviation ‘inf’. IR spectra were recorded on a Shi-
madzu FTIR-NIR Prestige-21 spectrometer with a Pike Miracle Ge
ATR accessory; strong (s), medium (m) and weak (w) peaks are ab-
CN
CN
N
Cl
N
CN
DBU
S
N
S
– DBU•HCl
S
S
N
1
breviated. H and 13C NMR spectra were recorded on a Bruker
Cl–
Avance 300 instrument (300 and 75 MHz, respectively). Deuterated
solvents were used for homonuclear lock and the signals are refer-
enced to the deuterated solvent peaks. Low resolution (EI) mass
spectra were recorded on a Shimadzu Q2010 GCMS with direct in-
let probe. 4,5-Dichloro-1,2,3-dithiazolium chloride 1 was prepared
according to the literature procedure.33
N
N+
N
6
CN
S
N
2-(4-Chloro-5H-1,2,3-dithiazol-5-ylideneamino)benzonitrile
(1a); Typical Procedure
N
N
CN
CN
_
S
CN
N
To a stirred solution of 4,5-dichloro-1,2,3-dithiazolium chloride (5;
352.4 mg, 1.69 mmol) in CH2Cl2 (4 mL) at ~20 °C and protected
with CaCl2 drying tube, was added 2-aminobenzonitrile (4a; 200
mg, 1.69 mmol). After 1 h, pyridine (273.4 mL, 3.38 mmol, 2 equiv)
was added dropwise, and the reaction mixture was stirred at ~20 °C
for an additional 2 h. The reaction mixture was adsorbed onto silica
and chromatography (hexane) gave S8 (traces). Further elution
(hexane–CH2Cl2, 8:2) gave 4-chloro-5H-1,2,3-dithiazole-5-thione
(9; 10 mg, 6%) and (hexane–CH2Cl2, 2:8) gave the title compound
1a.
S
N
H
S
N
N
N
N+
N
7
S
S
+
N
N
N
N
N
CN
H
Yield: 395 mg (92%); yellow crystals; mp 125–126 °C (Lit.21
128 °C) (cyclohexane–CH2Cl2).
CN
8
IR: 3088 (w), 3025 (w; ArCH), 2238 (m; C≡N), 1593 (s), 1562 (s),
Scheme 2
1479 (s), 1145 (s), 857 (s), 771 (s) cm–1.
1H NMR (300 MHz, CDCl3): d = 7.76–7.65 (m, 2 H, ArH), 7.35–
7.29 (m, 2 H, ArH).
13C NMR (75 MHz, CDCl3): d = 161.5, 153.2, 148.0, 134.4 (ArCH),
134.0 (ArCH), 126.3 (ArCH), 117.4 (ArCH), 116.3 (C≡N), 106.0
(CC≡N).
13C NMR (75 MHz, DEPT-135, DMSO-d6): d = 134.4 (ArCH),
134.0 (ArCH), 125.3 (ArCH), 117.4 (ArCH).
MS (EI): m/z (%) = 255 (35) [M+ + 2], 253 (84) [M+], 192 (99), 160
(12), 154 (18), 128 (11), 125 (10), 116 (4), 102 (71), 93 (13), 75
(53), 64 (100), 51 (31).
It is worthy of note that the sulfane sulfur could migrate
from N to C(6) and similar N–P to C(6)–P migrations
have been reported with DBU adducts.29i While isolation
of the anticipated sulfane 8 was not successful, the need
for three equivalents of DBU was confirmed, since the use
of less than this amount gave incomplete conversion of
the starting dithiazolimine. The absence of elemental sul-
fur from the reaction mixture tentatively added support to
the entrapment of the sulfur, possibly as the sulfane.
Treatment of 2-(4-chloro-5H-1,2,3-dithiazol-5-ylidene-
amino)benzonitriles 1a–g with DBU (3 equiv) in dichlo-
romethane at ambient or sub-ambient temperatures
provides a simple and high-yielding protocol for the prep-
aration of 2-cyano-cyanothioformamides 2a–g. In one
case, 2-(4-chloro-5H-1,2,3-dithiazol-5-ylideneamino)ben-
zonitrile (1a) was reacted with DBU (4 equiv) to afford 2-
isothiocyanatobenzonitrile (3) in high yield. These condi-
tions provide the most efficient route to this class of
cyanothioformanilides found to date.
UV/Vis (CH2Cl2): lmax (log e) = 231 (3.33), 268 (inf; 2.79), 302
(2.65), 379 (2.92), 398 (inf; 2.85), 423 nm (inf; 2.56); identical to
an authentic sample.
2-(4-Chloro-5H-1,2,3-dithiazol-5-ylideneamino)-6-methylben-
zonitrile (1b)
Similar treatment of 2-amino-6-methylbenzonitrile (4b; 200 mg,
1.52 mmol), 4,5-dichloro-1,2,3-dithiazolium chloride (5; 315.9 mg,
1.52 mmol) and pyridine (245.9 mL, 3.04 mmol, 2 equiv) in CH2Cl2
(4 mL) gave the title compound 1b.
Yield: 369.3 mg (91%); yellow cotton fibers; mp 109–110 °C (cy-
clohexane–EtOH).
CH2Cl2 was freshly distilled from CaH2 under argon. Reactions
were protected from atmospheric moisture by CaCl2 drying tubes.
Anhydrous Na2SO4 was used for drying organic extracts, and all
volatiles were removed under reduced pressure. All reaction mix-
tures and column eluents were monitored by thin-layer chromatog-
raphy using commercial glass-backed TLC plates (Merck Kieselgel
60 F254); the plates were observed under UV light at 254 and 365
nm. The technique of dry flash chromatography was used through-
out for all non-TLC-scale chromatographic separations using
Merck Silica Gel 60 (<0.063 mm). Melting points were determined
using a PolyTherm-A, Wagner & Munz, Koefler-Hotstage Micro-
scope apparatus. Solvents used for recrystallization are indicated af-
IR: 2232 (w; C≡N), 1601 (m), 1582 (s), 1461 (m), 1149 (s), 961 (s),
790 (s), 779 (s) cm–1.
1H NMR (300 MHz, CD2Cl2): d = 7.56 (dd, J = 7.8, 7.8 Hz, 1 H,
ArH-4), 7.20 (d, J = 7.8 Hz, 1 H, ArH-3 or 5), 7.16 (d, J = 8.1 Hz,
1 H, ArH-3 or 5), 2.57 (s, 3 H, CH3).
13C NMR (75 MHz, CD2Cl2): d = 161.6, 153.8, 148.35, 144.55,
134.1 (ArCH), 127.85 (ArCH), 115.75 (C≡N), 114.5 (ArCH), 107.1
(CC≡N), 20.8 (CH3).
13C NMR (75 MHz, DEPT-135, CD2Cl2): d = 134.1 (ArCH), 127.85
(ArCH), 114.5 (ArCH), 20.8 (CH3).
Synthesis 2009, No. 24, 4167–4174 © Thieme Stuttgart · New York

4170
S. S. Michaelidou, P. A. Koutentis
PAPER
MS (EI): m/z (%) = 269 (27) [M+ + 2], 267 (65) [M+], 206 (87), 174
(5), 168 (13), 142 (12), 116 (22), 115 (21), 102 (4), 89 (28), 76 (6),
70 (6), 64 (100), 51 (5).
5-Chloro-2-(4-chloro-5H-1,2,3-dithiazol-5-ylideneamino)ben-
zonitrile (1e)
Similar treatment of 2-amino-5-chlorobenzonitrile (4e; 200 mg,
1.31 mmol), 4,5-dichloro-1,2,3-dithiazolium chloride (5; 273.1 mg,
1.31 mmol) and pyridine (212 mL, 2.62 mmol, 2 equiv) in CH2Cl2
(4 mL) gave the title compound 1e.
UV/Vis (CH2Cl2): lmax (log e) = 232 (3.04), 271 (inf; 2.47), 378 nm
(2.63).
Anal. Calcd for C10H6ClN3S2: C, 44.9; H, 2.3; N, 15.7. Found: C,
44.9; H, 2.3; N, 15.7.
Yield: 323.3 mg (86%); yellow cotton fibers; mp 147–148 °C (cy-
clohexane–CH2Cl2).
2-(4-Chloro-5H-1,2,3-dithiazol-5-ylideneamino)-5-nitroben-
zonitrile (1c)
IR: 3071 (w; ArCH), 2237 (w; C≡N), 1568 (s), 1492 (s), 876 (s),
865 (s), 816 (s), 769 (s) cm–1.
Similar treatment of 2-amino-5-nitrobenzonitrile (4c; 200 mg, 1.36
mmol), 4,5-dichloro-1,2,3-dithiazolium chloride (5; 283.6 mg, 1.36
mmol) and pyridine (220 mL, 2.72 mmol, 2 equiv) in CH2Cl2 (4 mL)
gave the title compound 1c.
1H NMR (300 MHz, DMSO-d6): d = 8.09 (d, J = 2.4 Hz, 1 H, ArH-
6), 7.85 (dd, J = 8.8, 2.4 Hz, 1 H, ArH-4), 7.51 (d, J = 8.8 Hz, 1 H,
ArH-3).
13C NMR (75 MHz, DMSO-d6): d = 163.5, 152.0, 146.7, 135.3
(ArCH), 133.5 (ArCH), 129.9, 119.7 (ArCH), 115.4 (C≡N), 106.9
(CC≡N).
13C NMR (75 MHz, DEPT-135, DMSO-d6): d = 135.3 (ArCH),
133.5 (ArCH), 119.7 (ArCH).
MS (EI): m/z (%) = 291 (8) [M+ + 4], 289 (28) [M+ + 2], 287 (37)
[M+], 228 (21), 226 (47), 194 (9), 188 (7), 162 (9), 136 (12), 127 (7),
125 (6), 109 (5), 100 (31), 93 (8), 75 (10), 70 (8), 64 (100), 50 (8).
Yield: 324.2 mg (80%); red powder; mp 181–182 °C (EtOH).
IR: 3099 (w) and 3077 (w; ArCH), 2234 (w; C≡N), 1586 (m), 1569
(s), 1515 (s), 1345 (s), 914 (s), 873 (s), 796 (s) cm–1.
1H NMR (300 MHz, DMSO-d6): d = 8.83 (d, J = 2.5 Hz, 1 H, ArH-
6), 8.59 (dd, J = 9.0, 2.6 Hz, 1 H, ArH-4), 7.72 (d, J = 9.0 Hz, 1 H,
ArH-3).
13C NMR (75 MHz, DMSO-d6): d = 165.1, 158.2, 146.7, 144.1,
130.6 (ArCH), 130.1 (ArCH), 119.2 (ArCH), 115.0 (C≡N), 106.0
(CC≡N).
13C NMR (75 MHz, DEPT-135, DMSO-d6): d = 130.6 (ArCH),
130.1 (ArCH), 119.2 (ArCH).
MS (EI): m/z (%) = 300 (6) [M+ + 2], 298 (14) [M+], 237 (15), 205
(1), 175 (3), 157 (6), 127 (8), 125 (8), 115 (6), 100 (13), 93 (10), 88
(7), 75 (15), 70 (8), 64 (100), 50 (13).
UV/Vis (CH2Cl2): lmax (log e) = 430 (inf; 2.39), 383 (2.78), 313
(2.39), 247 (2.96), 229 nm (3.03).
Anal. Calcd for C9H3Cl2N3S2: C, 37.5; H, 1.05; N, 14.6. Found: C,
37.6; H, 1.1; N, 14.7.
2-(4-Chloro-5H-1,2,3-dithiazol-5-ylideneamino)-4-methoxy-
benzonitrile (1f)
Similar treatment of 2-amino-4-methoxybenzonitrile (4f; 200 mg,
1.35 mmol), 4,5-dichloro-1,2,3-dithiazolium chloride (5; 281.8 mg,
1.35 mmol) and pyridine (218 mL, 2.70 mmol, 2 equiv) in CH2Cl2
(4 mL) gave the title compound 1f.
UV/Vis (CH2Cl2): lmax (log e) = 490 (2.83), 305 (2.77), 265 (2.81),
231 nm (3.07).
Anal. Calcd for C9H3Cl2N4O2S2: C, 36.2; H, 1.0; N, 18.8. Found: C,
36.2; H, 1.0; N, 18.6.
Yield: 282.7 mg (74%); orange needles; mp 163–164 °C (cyclohex-
ane–CH2Cl2).
4-Chloro-2-(4-chloro-5H-1,2,3-dithiazol-5-ylideneamino)ben-
zonitrile (1d)
Similar treatment of 2-amino-4-chlorobenzonitrile (4d; 200 mg,
1.31 mmol), 4,5-dichloro-1,2,3-dithiazolium chloride (5; 273.1 mg,
1.31 mmol) and pyridine (212 mL, 2.62 mmol, 2 equiv) in CH2Cl2
(4 mL) gave the title compound 1d.
IR: 2965 (w) and 2835 (w; CH3), 2221 (s; C≡N), 1589 (s), 1495 (s),
1249 (s), 1095 (s), 1022 (s), 871 (s), 821 (s), 756 (s) cm–1.
1H NMR (300 MHz, CDCl3): d = 7.66 (d, J = 8.7 Hz, 1 H, ArH-6),
6.81 (dd, J = 8.7, 2.4 Hz, 1 H, ArH-5), 6.75 (d, J = 2.4 Hz, 1 H, ArH-
3), 3.88 (s, 3 H, CH3).
Yield: 327.1 mg (87%); yellow powder; mp 177–178 °C (cyclohex-
ane–CH2Cl2).
13C NMR (75 MHz, DMSO-d6): d = 164.3, 163.6, 156.0, 146.3,
135.7 (ArCH), 116.9 (C≡N), 112.4 (ArCH), 103.4 (ArCH), 95.7
(CC≡N), 56.1 (CH3).
13C NMR (75 MHz, DEPT-135, DMSO-d6): d = 135.7 (ArCH),
112.4 (ArCH), 103.3 (ArCH), 56.1 (CH3).
MS (EI): m/z (%) = 285 (19) [M+ + 2], 283 (47) [M+], 222 (42), 190
(4), 184 (7), 158 (100), 147 (11), 128 (24), 117 (15), 115 (19), 102
(15), 93 (8), 89 (18), 76 (11), 64 (55), 50 (7).
IR: 3069 (w; ArCH), 2237 (m; C≡N), 1587 (s), 1552 (s), 1148 (s),
919 (s), 875 (s), 858 (s), 832 (s), 799 (s), 753 (s) cm–1.
1H NMR (300 MHz, DMSO-d6): d = 7.98 (d, J = 8.4 Hz, 1 H, ArH-
6), 7.60 (d, J = 1.9 Hz, 1 H, ArH-3), 7.47 (dd, J = 8.4, 2.0 Hz, 1 H,
ArH-5).
13C NMR (75 MHz, DMSO-d6): d = 164.7, 155.0, 146.3, 139.8,
135.8 (ArCH), 126.3 (ArCH), 118.3 (ArCH), 115.9 (C≡N), 103.3
(CC≡N).
13C NMR (75 MHz, DEPT-135, DMSO-d6): d = 135.8 (ArCH),
126.3 (ArCH), 118.3 (ArCH).
MS (EI): m/z (%) = 291 (5) [M+ + 4], 289 (26) [M+ + 2], 287 (35)
[M+], 228 (36), 226 (76), 194 (5), 188 (6), 162 (6), 136 (10), 127 (9),
125 (7), 100 (30), 93 (10), 84 (8), 75 (13), 64 (100), 50 (9).
UV/Vis (CH2Cl2): lmax (log e) = 234 (3.30), 256 (inf; 3.17), 272
(inf; 2.88), 302 (2.53), 367 (2.75), 411 nm (inf; 2.51).
Anal. Calcd for C10H5ClN3OS2: C, 42.3; H, 2.1; N, 14.8. Found: C,
42.4; H, 2.0; N, 14.8.
2-(4-Chloro-5H-1,2,3-dithiazol-5-ylideneamino)-4,5-dimeth-
oxybenzonitrile (1g)
Similar treatment of 2-amino-4,5-dimethoxybenzonitrile (4g; 200
mg, 1.12 mmol), 4,5-dichloro-1,2,3-dithiazolium chloride (5; 233.5
mg, 1.12 mmol) and pyridine (181 mL, 2.24 mmol, 2 equiv) in
CH2Cl2 (4 mL) gave the title compound 1g.
UV/Vis (CH2Cl2): lmax (log e) = 233 (3.25), 272 (inf; 2.76), 337 nm
(2.78).
Anal. Calcd for C9H3Cl2N3S2: C, 37.5; H, 1.05; N, 14.6. Found: C,
37.6; H, 1.1; N, 14.7.
Yield: 266.4 mg (76%); orange crystals; mp 156–157 °C (cyclohex-
ane–EtOH).
Synthesis 2009, No. 24, 4167–4174 © Thieme Stuttgart · New York

PAPER
Synthesis of 2-Cyano-cyanothioformanilides
4171
IR: 3002 (w; ArCH), 2961 (w), 2829 (w; CH3), 2224 (m, C≡N),
13C NMR (75 MHz, DEPT-135, DMSO-d6): d = 133.85 (ArCH),
130.0 (ArCH), 124.6 (ArCH), 20.0 (CH3).
1591 (s), 1498 (s), 1281 (s), 1222 (s), 1103 (s), 902 (s), 763 (s) cm–1.
1H NMR (300 MHz, CDCl3): d = 7.12 (s, 1 H, ArH-6), 6.81 (s, 1 H,
ArH-3), 3.93 (s, 3 H, CH3O), 3.93 (s, 3 H, CH3O).
13C NMR (75 MHz, DMSO-d6): d = 162.6, 153.9, 148.8, 146.6,
146.5, 117.0 (C≡N), 115.0 (ArCH), 101.55 (ArCH), 95.1 (CC≡N),
56.3 (CH3O), 56.2 (CH3O).
MS (EI): m/z (%) = 201 (56) [M+], 200 (31), 186 (14), 174 (100),
168 (15), 149 (14), 142 (17), 131 (6), 116 (87), 104 (16), 89 (43), 77
(25), 70 (24), 63 (25), 51 (15).
UV/Vis (CH2Cl2): lmax (log e) = 226 (3.71), 255 (inf; 3.38), 337 nm
(3.65).
13C NMR (75 MHz, DEPT-135, DMSO-d6): d = 115.0 (ArCH),
101.6 (ArCH), 56.3 (CH3O), 56.2 (CH3O).
Anal. Calcd for C10H7N3S: C, 59.7; H, 3.5; N, 20.9. Found: C, 59.7;
H, 3.5; N, 20.9.
MS (EI): m/z (%) = 315 (26) [M+ + 2], 313 (63) [M+], 300 (7), 298
(16), 220 (11), 214 (6), 205 (8), 188 (100), 177 (9), 173 (20), 162
(8), 145 (18), 134 (8), 119 (11), 117 (22), 104 (15), 102 (16), 90
(20), 83 (8), 76 (21), 70 (7), 64 (33), 51 (7).
2-(Cyanothioformamido)-5-nitrobenzonitrile (2c)
Similarly, treatment of 2-(4-chloro-5H-1,2,3-dithiazol-5-ylidene-
amino)-5-nitrobenzo-nitrile (1c; 100 mg, 0.34 mmol) cooled to ca.
–78 °C with DBU gave, after chromatography (CH2Cl2–tert-butyl
methyl ether, 50:50), the title compound 2c.
UV/Vis (CH2Cl2): lmax (log e) = 350 (inf; 2.59), 379 (inf; 2.68), 398
(2.72), 418 (inf; 2.69), 443 nm (inf; 2.48).
Yield: 74.9 mg (95%); red powder; mp >300 °C (pentane–CH2Cl2).
Anal. Calcd for C11H8ClN3O2S2: C, 42.1; H, 2.6; N, 13.4. Found: C,
42.3; H, 2.6; N, 13.3.
IR: 3611 (w), 3399 (w; NH), 3053 (w; ArCH), 2236 (w; C≡N), 1597
(m), 1483 (s), 1443 (s), 1346 (s), 1261 (m), 1177 (m), 843 (m), 733
(m) cm–1.
1H NMR (300 MHz, DMSO-d6): d = 8.58 (d, J = 2.7 Hz, 1 H, ArH-
6), 8.33 (dd, J = 2.7, 9.0 Hz, 1 H, ArH-4), 7.64 (d, J = 9.0 Hz, 1 H,
ArH-3); NH missing.
13C NMR (75 MHz, DMSO-d6): d = 162.7, 160.75, 141.5, 128.85
(ArCH), 128.0 (ArCH), 122.85 (ArCH), 117.7 (C≡N), 116.1 (C≡N),
105.7 (CC≡N).
13C NMR (75 MHz, DEPT-135, DMSO-d6): d = 128.9 (ArCH),
128.0 (ArCH), 122.85 (ArCH).
2-(Cyanothioformamido)benzonitrile (2a); Typical Procedure
To a stirred solution of 2-(4-chloro-5H-1,2,3-dithiazol-5-ylidene-
amino)benzonitrile (1a; 100 mg, 0.39 mmol) in distilled CH2Cl2 (2
mL) cooled to ca. –5 °C and protected with a CaCl2 drying tube, was
added in one portion, DBU (175 mL, 1.17 mmol, 3 equiv). After 5
min at ca. –5 °C, no starting material remained (TLC) and the reac-
tion mixture was adsorbed onto silica. Chromatography (CH2Cl2)
gave the title compound 2a.
Yield: 67.8 mg (93%); orange powder; mp 100–101 °C (Lit.19 104–
105 °C) (pentane–CH2Cl2).
MS (EI): m/z (%) = 232 (19) [M+], 205 (100), 199 (8), 186 (6), 175
(36), 159 (37), 147 (24), 132 (14), 115 (26), 99 (7), 94 (14), 88 (17),
75 (21), 70 (16), 64 (21), 57 (14), 50 (13).
IR: 3113 (w) and 3036 (w; ArCH), 2241 (m; C≡N), 1547 (m), 1477
(m), 1450 (m), 1364 (s), 1115 (m), 752 (s) cm–1.
1H NMR (300 MHz, CDCl3): d = 9.79 (br s, 1 H, NH), 8.23 (d, J =
7.8 Hz, 1 H, ArH), 7.81 (d, J = 7.8 Hz, 1 H, ArH), 7.73 (dd, J = 8.0,
7.95 Hz, 1 H, ArH), 7.50 (dd, J = 7.1, 7.1 Hz, 1 H, ArH).
13C NMR (75 MHz, CDCl3): d = 164.6 (C=S), 138.3 (ArC-2), 134.0
(ArCH), 133.8 (ArCH), 128.6 (ArCH), 125.9 (ArCH), 115.5 (C≡N),
113.0 (C≡N), 107.8 (ArC-1, CC≡N).
13C NMR (75 MHz, DEPT-135, CDCl3): d = 134.0 (ArCH), 133.8
(ArCH), 128.6 (ArCH), 125.9 (ArCH).
MS (EI): m/z (%) = 187 (100) [M+], 186 (91), 160 (19), 135 (37),
UV/Vis (CH2Cl2): lmax (log e) = 228 (3.10), 254 (2.97), 283 (2.75),
332 (2.79), 348 nm (2.85).
Anal. Calcd for C9H4N4O2S: C, 46.55; H, 1.7; N, 24.1. Found: C,
46.5; H, 1.8; N, 24.1.
4-Chloro-2-(cyanothioformamido)benzonitrile (2d)
Similarly, treatment of 4-chloro-2-(4-chloro-5H-1,2,3-dithiazol-5-
ylideneamino)benzonitrile (1d; 100 mg, 0.35 mmol) cooled to ca.
–78 °C with DBU gave, after chromatography (CH2Cl2) the title
compound 2d.
117 (3), 108 (9), 102 (33), 70 (24), 61 (3), 51 (2).
Yield: 69.6 mg (90%); yellow powder; mp 85–86 °C (pentane–
CH2Cl2).
UV/Vis (CH2Cl2): lmax (log e) = 228 (3.60), 250 (3.45), 333 nm
(3.57); identical to an authentic sample.
IR: 3568 (w), 3374 (m; NH), 3096 (w; ArCH), 2232 (m) and 2216
(w; C≡N), 1632 (m), 1580 (m), 1474 (s), 1456 (s), 1366 (m), 1059
(m), 812 (s) cm–1.
1H NMR (300 MHz, CD2Cl2): d = 8.19 (br s, 1 H, NH), 7.75–7.72
(m, 2 H, ArH-3 and 6), 7.59 (dd, J = 2.1, 8.7 Hz, 1 H, ArH-5).
13C NMR (75 MHz, DMSO-d6): d = 162.4 (C=S), 154.6 (ArC),
137.4 (ArC), 134.2 (ArCH), 123.4 (ArCH), 122.3 (ArCH), 117.6
(C≡N), 117.1 (C≡N), 104.7 (CC≡N).
13C NMR (75 MHz, DEPT-135, DMSO-d6): d = 134.2 (ArCH),
123.4 (ArCH), 122.3 (ArCH).
2-(Cyanothioformamido)-6-methylbenzonitrile (2b)
Similarly, treatment of 2-(4-chloro-5H-1,2,3-dithiazol-5-ylidene-
amino)-6-methylbenzonitrile (1b; 100 mg, 0.37 mmol) cooled to ca.
–5 °C with DBU gave, after chromatography (CH2Cl2) the title
compound 2b.
Yield: 71.4 mg (96%); yellow cotton fibers; mp 128–129 °C (cyclo-
hexane–EtOH).
IR: 3229 (w), 3146 (w), 2986 (w), 2239 (m; C≡N), 1566 (m), 1474
(s), 1373 (s), 1179 (m), 1117 (m), 789 (s) cm–1.
1H NMR (300 MHz, CD2Cl2): d = 9.75 (br s, 1 H, NH), 7.90 (d, J =
8.1 Hz, 1 H, ArH-3 or 5), 7.63–7.55 (m, 1 H, ArH-4), 7.43–7.36 (m,
1 H, ArH-3 or 5), 2.61 (s, 3 H, CH3).
13C NMR (75 MHz, DMSO-d6): d = 165.4 (C=S), 143.5 (ArC),
139.3 (ArC), 133.9 (ArCH), 130.0 (ArCH), 124.6 (ArCH), 114.8
(C≡N), 113.5 (C≡N), 109.7 (ArC-1, CC≡N), 20.0 (CH3).
MS (EI): m/z (%) = 223 (13) [M+ + 2], 221 (34) [M+], 196 (39), 194
(100), 190 (5), 188 (17), 186 (9), 169 (9), 159 (10), 136 (22), 124
(5), 100 (30), 88 (8), 75 (19), 70 (24), 63 (7), 50 (13).
UV/Vis (CH2Cl2): lmax (log e) = 230 (3.05), 259 (inf; 2.84), 264
(inf; 2.80), 327 (2.61), 340 (2.62), 380 nm (inf; 2.23).
Anal. Calcd for C9H4ClN3S: C, 48.8; H, 1.8; N, 19.0. Found: C,
48.9; H, 1.9; N, 19.0.
Synthesis 2009, No. 24, 4167–4174 © Thieme Stuttgart · New York

4172
S. S. Michaelidou, P. A. Koutentis
PAPER
5-Chloro-2-(cyanothioformamido)benzonitrile (2e)
Similarly, treatment of 2-(4-chloro-5H-1,2,3-dithiazol-5-ylidene-
amino)-5-chlorobenzonitrile (1e; 100 mg, 0.35 mmol) cooled to ca.
–5 °C with DBU gave, after chromatography (CH2Cl2), the title
compound 2e.
IR: 3198 (w), 3103 (w; NH), 2230 (m; C≡N), 1516 (s), 1354 (s),
1271 (s), 1236 (s), 993 (s), 866 (s), 779 (s) cm–1.
1H NMR (300 MHz, CD2Cl2): d = 7.83 (s, 1 H, ArH-3), 7.16 (s, 1 H,
ArH-5), 3.97 (s, 3 H, CH3O), 3.96 (3 H, CH3O); NH missing.
13C NMR (75 MHz, DMSO-d6): d = 165.3 (C=S), 153.0 (ArC),
148.4 (ArC), 133.5 (ArC), 116.1 (C≡N), 114.6 (ArCH), 113.5
(C≡N), 110.4 (ArCH), 100.5 (CC≡N), 56.3 (CH3O), 56.2 (CH3O).
Yield: 89.4 mg (89%); dark-red crystals; mp 131–132 °C (cyclo-
hexane).
IR: 3271 (m; NH), 3082 (w; ArCH), 2228 (w; C≡N), 1587 (m),
1468 (m), 1406 (m), 1302 (s), 1236 (s), 1163 (s), 1076 (s), 841 (s)
cm–1.
1H NMR (300 MHz, DMSO-d6): d = 8.18 (s, 1 H, ArH-6), 7.90 (dd,
J = 1.5, 7.5 Hz, 1 H, ArH-4), 7.68 (d, J = 8.7 Hz, 1 H, ArH-3); NH
missing.
13C NMR (75 MHz, DMSO-d6): d = 165.4 (C=S), 138.9 (ArC),
134.6 (ArCH), 133.3 (ArCH), 132.9 (ArC), 128.9 (ArCH), 114.7
(C≡N), 113.7 (C≡N), 110.9 (CC≡N).
13C NMR (75 MHz, DEPT-135, DMSO-d6): d = 134.6 (ArCH),
133.3 (ArCH), 128.9 (ArCH).
13C NMR (75 MHz, DEPT-135, DMSO-d6): d = 114.65 (ArCH),
110.4 (ArCH), 56.3 (CH3O), 56.2 (CH3O).
MS (EI): m/z (%) = 247 (100) [M+], 232 (7), 220 (50), 214 (15), 205
(27), 195 (35), 180 (21), 177 (28), 162 (13), 150 (10), 134 (13), 119
(17), 104 (13), 90 (7), 83 (7), 76 (15), 70 (23), 50 (11).
UV/Vis (CH2Cl2): lmax (log e) = 230 (3.56), 265 (3.48), 277 (inf;
3.51), 287 (3.56), 331 (inf; 3.07), 346 (3.11), 375 (3.16), 395 nm
(inf; 3.07).
Anal. Calcd for C11H9N3O2S: C, 53.4; H, 3.7; N, 17.0. Found: C,
53.4; H, 3.8; N, 16.9.
MS (EI): m/z (%) = 223 (37) [M+ + 2], 221 (82) [M+], 196 (37), 194
(100), 190 (18), 188 (53), 171 (18), 169 (48), 151 (7), 136 (37), 124
(15), 100 (38), 84 (34), 75 (29), 70 (25), 56 (45).
2-Isothiocyanatobenzonitrile (3) from 2-(Cyanothioformami-
do)benzonitrile (2a)
To a stirred solution of 2-(cyanothioformamido)benzonitrile (2a;
100 mg, 0.53 mmol) in distilled CH2Cl2 (2 mL) at ~20 °C and pro-
tected with a CaCl2 drying tube, was added dropwise, DBU (79.3
mL, 0.53 mmol, 1 equiv). The mixture was then allowed to stir at
~20 °C, until no starting material remained (TLC). The reaction
mixture was adsorbed onto silica and purified by chromatography
(CH2Cl2–tert-butyl methyl ether, 9:1) to give the title compound 3.
UV/Vis (CH2Cl2): lmax (log e) = 232 (4.10), 274 (3.43), 346 nm
(3.50).
Anal. Calcd for C9H4ClN3S: C, 48.8; H, 1.8; N, 19.0. Found: C,
48.8; H, 1.8; N, 18.8.
2-(Cyanothioformamido)-4-methoxybenzonitrile (2f)
Similarly, treatment of 2-(4-chloro-5H-1,2,3-dithiazol-5-ylidene-
amino)-4-methoxybenzonitrile (1f; 100 mg, 0.35 mmol) cooled to
ca. 0 °C with DBU gave, after chromatography (CH2Cl2), the title
compound 2f.
Yield: 81.4 mg (96%); colorless needles; mp 66–67 °C (Lit.24h
64 °C) (cyclohexane).
IR: 2232m (C≡N), 1624 (m), 1597 (m), 1493 (s), 1377 (m), 1319
(s), 1099 (m), 752 (s).
Yield: 73.7 mg (97%); yellow powder; mp 116–117 °C (cyclohex-
ane).
1H NMR (300 MHz, CDCl3): d = 8.26 (d, J = 7.8 Hz, 1 H, ArH),
7.80 (d, J = 7.8 Hz, 1 H, ArH), 7.73 (dd, J = 7.8, 7.8 Hz, 1 H, ArH),
7.50 (dd, J = 7.35, 7.35 Hz, 1 H, ArH).
MS (EI): m/z (%) = 161 (12) [M+ + 1], 160 (100) [M+], 133 (7), 116
(11), 102 (41), 91 (4), 76 (36) [C6H4], 75 (25), 70 (8), 64 (10), 51
(17), 50 (12), 44 (75), 43 (10); identical to an authentic sample.
IR: 3205 (w) and 3183 (w; NH), 3038 (w; ArCH), 2236 (m; C≡N),
1614 (s), 1549 (m), 1487 (m), 1449 (m), 1364 (s), 1252 (s), 817 (s)
cm–1.
1H NMR (300 MHz, CD2Cl2): d = 9.80 (br s, 1 H, NH), 7.80 (br s,
1 H, ArH-3), 7.71 (d, J = 8.7 Hz, 1 H, Ar H-6), 7.05–6.95 (m, 1 H,
ArH-5), 3.88 (s, 3 H, CH3O).
13C NMR (75 MHz, DMSO-d6): d = 164.9, 163.3, 142.2 (ArC),
135.1 (ArCH), 116.3 (C≡N), 114.3 (ArCH), 113.9 (C≡N), 112.6
(ArCH), 100.5 (CC≡N), 56.1 (CH3O).
13C NMR (75 MHz, DEPT-135, DMSO-d6): d = 135.1 (ArCH),
114.3 (ArCH), 112.6 (ArCH), 56.1 (CH3).
2-Isothiocyanatobenzonitrile (3) from 2-(4-Chloro-5H-1,2,3-
dithiazol-5-ylideneamino)benzonitrile (1a)
To a stirred solution of 2-(4-chloro-5H-1,2,3-dithiazol-5-ylidene-
amino)benzonitrile (1a; 100 mg, 0.39 mmol) in distilled CH2Cl2 (2
mL) cooled to ca. –5 °C and protected with a CaCl2 drying tube, was
added in one portion, DBU (233 mL, 1.56 mmol, 4 equiv). The mix-
ture was then allowed to warm to ~20 °C, until no starting material
remained (TLC). The reaction mixture was adsorbed onto silica and
purified by chromatography (CH2Cl2–tert-butyl methyl ether, 9:1)
gave the title compound 3.
MS (EI): m/z (%) = 217 (100) [M+], 201 (7), 190 (42), 186 (26), 184
(21), 175 (6), 165 (23), 160 (11), 147 (15), 132 (16), 120 (11), 117
(15), 102 (12), 89 (14), 77 (20), 70 (21), 63 (17), 50 (9).
Yield: 59.3 mg (95%); colorless needles; mp 66–67 °C (Lit.24h
64 °C) (cyclohexane); identical to that described above.
UV/Vis (CH2Cl2): lmax (log e) = 217 (inf; 2.99), 229 (3.21), 250
(3.22), 272 (inf; 2.88), 337 nm (2.95).
Anal. Calcd for C10H7N3OS: C, 55.3; H, 3.3; N, 19.3. Found: C,
55.3; H, 3.3; N, 19.3.
Acknowledgment
The authors wish to thank the Cyprus Research Promotion Founda-
tion [Grant No. TEXNOLOPA/QEPIS/0308(BE)/08] and the fol-
lowing organizations in Cyprus for generous donations of
chemicals and glassware: the State General Laboratory, the Agri-
cultural Research Institute and the Ministry of Agriculture. Further-
more, we thank the A.G. Leventis Foundation for helping to
establish the NMR facility in the University of Cyprus.
2-(Cyanothioformamido)-4,5-dimethoxybenzonitrile (2g)
Similarly, treatment of 2-(4-chloro-5H-1,2,3-dithiazol-5-ylidene-
amino)-4,5-dimethoxybenzonitrile (1g; 100 mg, 0.32 mmol) cooled
to ca. –5 °C with DBU gave, after chromatography (CH2Cl2), the ti-
tle compound 2g.
Yield: 73.7 mg (88%); orange crystals; mp 145–146 °C (cyclohex-
ane–EtOH).
Synthesis 2009, No. 24, 4167–4174 © Thieme Stuttgart · New York

PAPER
Synthesis of 2-Cyano-cyanothioformanilides
4173
(13) (a) Gonda, J.; Kristian, P. Coll. Czech. Chem. Commun.
1988, 53, 1761. (b) Walter, W.; Hell, P.-M. Liebigs Ann.
1969, 727, 22. (c) Walter, W.; Bode, K.-D. Liebigs Ann.
1966, 698, 131. (d) Reissert, A.; Brüggemann, K. Chem.
Ber. 1924, 57, 981.
(14) Kantlehner, W.; Haug, E.; Isak, H.; Schulz, W.; Hippich, S.;
Baur, R.; Hagen, H. Chem. Ber. 1982, 115, 1721.
(15) Reissert, A. Chem. Ber. 1904, 37, 3708.
References
(1) Olin, J. F. US Patent 3287102, 1966.
(2) (a) El-Sharief, A. M. Sh.; Ammar, Y. A.; Mohamed, Y. A.;
El-Gaby, M. S. A. Phosphorus, Sulfur Silicon Relat. Elem.
1999, 148, 117. (b) Elagamey, A. A.; El-Taweel, F. M. A.;
El-Enein, R. A. N. A. Phosphorus, Sulfur Silicon Relat.
Elem. 2006, 181, 2155.
(3) (a) Singer, M. S. US Patent 3655689, 1972. (b) Huang, L.;
Graves, M. D. J. Heterocycl. Chem. 1987, 24, 1781. (c) El-
Sharief, A. M. Sh.; Ammar, Y. A.; Zahran, M. A.; Sabet, H.
Kh. Phosphorus, Sulfur Silicon Relat. Elem. 2004, 179, 267.
(d) Ketcham, R.; Schumann, E. J. Org. Chem. 1980, 45,
3748. (e) Kinzel, P.; Wilhelm, M. Ger Offen. 3000130,
1981. (f) Kinzel, P. Ger Offen. 3437853, 1986. (g) Ammar,
Y. A.; El-Sharief, A. M. Sh.; Ali, M. M.; Mohamed, Y. A.;
Mohamed, Sh. I. Phosphorus, Sulfur Silicon Relat. Elem.
2000, 166, 173. (h) El-Sharief, A. M. Sh.; Ammar, Y. A.;
Mohamed, Y. A.; Ali, M. M.; El-Gaby, M. S. A.; Ali, A. S.
Phosphorus, Sulfur Silicon Relat. Elem. 2001, 173, 39.
(i) El-Sharief, A. M. Sh.; Ammar, Y. A.; El-Gaby, M. S. A.;
Zahran, M. A.; Khames, A. A. Afinidad 2003, 60, 47.
(j) El-Gaby, M. S. A.; El-Sharief, A. M. Sh.; Atalla, A. A.;
El-Adasy, A. A. A. M. J. Chin. Chem. Soc. (Taipei) 2004,
51, 327. (k) Kobayashi-Matsunaga, Y.; Ishii, T.;
Hamaguchi, T.; Osada, H.; Sato, M. Lett. Drug Des.
Discovery 2005, 2, 224.
(4) (a) Ketcham, R. Synthesis 1980, 11, 869. (b) El-Sharief, A.
M. Sh.; Ammar, Y. A.; Mohamed, Y. A.; El-Gaby, M. S. A.
Phosphorus, Sulfur Silicon Relat. Elem. 1999, 148, 215.
(c) El-Sharief, A. M. Sh.; Ammar, Y. A.; Zahran, M. A.;
Sabet, H. Kh. J. Chem. Res., Synop. 2003, 162.
(16) Besson, T.; Rees, C. W. J. Chem. Soc., Perkin Trans. 1 1995,
1659.
(17) Lee, H.; Kim, K. Bull. Korean Chem. Soc. 1992, 13, 107.
(18) English, R. F.; Rakitin, O. A.; Rees, C. W.; Vlasova, O. G.
J. Chem. Soc., Perkin Trans. 1 1997, 201.
(19) Chang, Y.-G.; Kim, K. Heterocycles 1999, 51, 2653.
(20) Lee, H.-S.; Chang, Y.-G.; Kim, K. J. Heterocycl. Chem.
1998, 35, 659.
(21) Mohanta, P. K.; Kim, K. Tetrahedron Lett. 2002, 43, 3993.
(22) Pereira, M.-F.; Thiéry, V.; Besson, T. Tetrahedron 2007, 63,
847.
(23) Lee, H.-S.; Kim, K. Tetrahedron Lett. 1996, 37, 869.
(24) (a) Besson, T.; Emayan, K.; Rees, C. W. J. Chem. Soc.,
Chem. Commun. 1995, 1419. (b) Besson, T.; Emayan, K.;
Rees, C. W. J. Chem. Soc., Perkin Trans. 1 1995, 2097.
(c) Cottenceau, G.; Besson, T.; Gautier, V.; Rees, C. W.;
Pons, A.-M. Bioorg. Med. Chem. Lett. 1996, 6, 529.
(d) Besson, T.; Rees, C. W.; Cottenceau, G.; Pons, A.-M.
Bioorg. Med. Chem. Lett. 1996, 6, 2343. (e) Le, V.-D.;
Rees, C. W.; Sivadasan, S. Tetrahedron Lett. 2000, 41,
9407. (f) Besson, T.; Guillard, J.; Rees, C. W. J. Chem. Soc.,
Perkin Trans. 1 2000, 563. (g) Le, V.-D.; Rees, C. W.;
Sivadasan, S. J. Chem. Soc., Perkin Trans. 1 2002, 1543.
(h) Besson, T.; Guillard, J.; Rees, C. W.; Thiéry, V. J. Chem.
Soc., Perkin Trans. 1 1998, 889.
(5) Mahran, A. M.; Hassan, N. A. Arch. Pharm. Res. 2006, 29,
46.
(25) Besson, T.; Guillard, J.; Rees, C. W.; Thérisod, M. J. Chem.
Soc., Chem. Commun. 1997, 881.
(26) Christoforou, I. C.; Koutentis, P. A.; Michaelidou, S. S.
ARKIVOC 2006, (vii), 207.
(6) (a) Deck, L. M.; Papadopoulos, E. P.; Smith, K. A. J.
Heterocycl. Chem. 2003, 40, 885. (b) El-Sharief, A. M. S.;
Ammar, Y. A.; Mohamed, Y. A.; El-Gaby, M. S. A.
Heteroat. Chem. 2002, 13, 291. (c) Besson, T.; Rees, C. W.
J. Chem. Soc., Perkin Trans. 1 1996, 2857.
(27) Oediger, H.; Möller, F.; Eiter, K. Synthesis 1972, 591.
(28) Cowley, A. H. Acc. Chem. Res. 1984, 17, 386.
(29) (a) Fujii, M.; Ozaki, K.; Sekine, M.; Hata, T. Tetrahedron
1987, 43, 3395. (b) Reed, R.; Réau, R.; Dahan, F.; Bertrand,
G. Angew. Chem. Int. Ed. 1993, 32, 399. (c) Lesnikowski,
Z. J.; Zabawska, D.; Jaworska-Maslanka, M. M.; Schinazi,
R. F.; Stec, W. J. New J. Chem. 1994, 18, 1197. (d) Dyer,
P.; Guerret, O.; Dahan, F.; Baceiredo, A.; Bertrand, G.
J. Chem. Soc., Chem. Commun. 1995, 2339. (e) Bouhadir,
G.; Reed, R. W.; Réau, R.; Bertrand, G. Heteroat. Chem.
1995, 6, 371. (f) Karsch, H. H.; Rupprich, T.; Heckle, M.
Chem. Ber. 1995, 128, 959. (g) Merckling, F. A.; Rüedi, P.
Tetrahedron Lett. 1996, 37, 2217. (h) Kers, A.; Stawiński,
J.; Dembkowski, L.; Kraszewski, A. Tetrahedron 1997, 53,
12691. (i) Kers, A.; Kers, I.; Bollmark, M.; Stawinski, J.
Acta Chem. Scand. 1998, 52, 1405. (j) Kers, A.; Kers, I.;
Stawinski, J. J. Chem. Soc., Perkin Trans. 2 1999, 2071.
(k) Blättner, M.; Nieger, M.; Ruban, A.; Schoeller, W. W.;
Niecke, E. Angew. Chem. Int. Ed. 2000, 39, 2768.
(l) Ionkin, A. S.; Marshall, W. J. Heteroat. Chem. 2003, 14,
197. (m) Dąbkowski, W.; Tworowska, I.; Kazimierczak, Ł.;
Michalski, J. Pol. J. Chem. 2005, 79, 467.
(7) (a) Kattak, I.; Ketcham, R.; Schaumann, E.; Adiwidjaja, G.
J. Org. Chem. 1985, 50, 3431. (b) El-Sharief, A. M. Sh.;
Hussein, A. M.; Atalla, A. A.; El-Gaby, M. S. A.; Hassan, A.
A. Phosphorus, Sulfur Silicon Relat. Elem. 2000, 160, 141.
(c) El-Sharief, A. M. Sh.; Hussein, A. M.; El-Gaby, M. S. A.;
Atalla, A. A.; Ahmed, A. A. Phosphorus, Sulfur Silicon
Relat. Elem. 2001, 170, 47. (d) El-Sharief, A. M. Sh.;
Mahmoud, F. F.; Taha, N. M.; Ahmed, E. M. Phosphorus,
Sulfur Silicon Relat. Elem. 2005, 180, 573. (e) El-Sharief,
A. M. Sh.; El-Gaby, M. S. A.; Atalla, A. A.; El-Adasy, A.-
B. A. A. M. Afinidad 2003, 60, 475. (f) El-Sharief, A. M.
S.; El-Gaby, M. S. A.; Atalla, A. A.; El-Adasy, A.-B. A. A.
M. Heteroat. Chem. 2005, 16, 218. (g) El-Sharief, A. M. S.;
Al-Amri, A. M.; Al-Raqa, S. Y. J. Sulfur Chem. 2006, 27,
245.
(8) (a) Friedrich, K.; Zamkanei, M. Tetrahedron Lett. 1977, 18,
2139. (b) Friedrich, K.; Zamkanei, M. Chem. Ber. 1979,
112, 1867. (c) Friedrich, J. D. J. Org. Chem. 1987, 52, 2442.
(9) Friedrich, K.; Zamkanei, M. Chem. Ber. 1979, 112, 1916.
(10) Friedrich, K.; Zamkanei, M. Chem. Ber. 1979, 112, 1873.
(11) Grabenko, A. D.; Danchenko, M. N.; Pel’kis, P. S. J. Org.
Chem. USSR (Engl. Transl.) 1972, 8, 532.
(30) (a) Richter, R. Chem. Ber. 1968, 101, 3002. (b) House, H.
O.; DeTar, M. B.; VanDerveer, D. J. Org. Chem. 1979, 44,
3793. (c) McCoy, L. L.; Mal, D. J. Org. Chem. 1981, 46,
1016. (d) Alder, R. W.; Sessions, R. B. Tetrahedron Lett.
1982, 23, 1121. (e) Juneja, T. R.; Garg, D. K.; Schäfer, W.
Tetrahedron 1982, 38, 551. (f) Forlani, L.; Sintoni, M.;
Todesco, P. E. J. Chem. Res., Synop. 1986, 344.
(12) El-Gaby, M. S. A.; Ammar, Y. A.; El-Sharief, A. M. Sh.;
Zahran, M. A.; Khames, A. A. Heteroat. Chem. 2002, 13,
611.
(g) Collina, G.; Forlani, L. J. Phys. Org. Chem. 1988, 1,
Synthesis 2009, No. 24, 4167–4174 © Thieme Stuttgart · New York

4174
S. S. Michaelidou, P. A. Koutentis
PAPER
351. (h) Forlani, L.; Cimarelli, C. J. Phys. Org. Chem. 1989,
2, 653. (i) Reid, J. G.; Runge, J. M. R. Tetrahedron Lett.
1990, 31, 1093. (j) Reisch, J.; Iding, M.; von Bassewitz, I.
Monatsh. Chem. 1993, 124, 1225. (k) Schenk, W. A.;
Urban, P.; Dombrowski, E. Chem. Ber. 1993, 126, 679.
(l) Chambers, R. D.; Roche, A. J.; Batsanov, A. S.; Howard,
J. A. K. J. Chem. Soc., Chem. Commun. 1994, 2055.
(m) Lammers, H.; Cohen-Fernandes, P.; Habraken, C. L.
Tetrahedron 1994, 50, 865. (n) Ma, L.; Dolphin, D.
Tetrahedron 1996, 52, 849. (o) Johnson, M. G.; Foglesong,
R. J. Tetrahedron Lett. 1997, 38, 7003. (p) Lönnqvist, J.-E.
S.; Jalander, L. F. J. Chem. Res., Miniprint 1999, 0430.
(31) Sekine, M.; Kume, A.; Hata, T. Tetrahedron Lett. 1981, 22,
3617.
(32) (a) Bard, R. R.; Strauss, M. J. J. Am. Chem. Soc. 1975, 97,
3789. (b) Miller, J.; Miyata, Y.; Sakazaki, E.; de Santos, T.
W. J. Chem. Res., Synop. 1986, 396.
(33) (a) Appel, R.; Janssen, H.; Siray, M.; Knoch, F. Chem. Ber.
1985, 118, 1632. (b) Koutentis, P. A. Molecules 2005, 10,
346.
Synthesis 2009, No. 24, 4167–4174 © Thieme Stuttgart · New York