Diisothiocyanates as heterodienophiles or dipolarophiles in the presence of α-thioxothioamides or mesoionic thiazoles

Article abstract of DOI:10.1002/hc.1093

Reactions of α-thioxothioamides (1) with diisothiocyanates were carried out in the hope of generating the N,N′-bis(1,3-thiazoline-2-thiones) (A). Although that purpose could not be achieved, we succeeded in preparing the monocycloadducts 7 from the phenylene-1,2-diisothiocyanate (4). The benzimidazole derivatives 8 and 9 were also characterized and a mechanism was assumed to account for this intramolecular process. On the other hand, the regioselective synthesis of the N,N′-biimidazole (13) containing the phenylene bridge was performed by the treatment of the 5-aminothiazolium chloride (2) with the diisothiocyanate (4) in a basic medium. The mesoionic derivative 13 probably arises from the monoimidazolium-4-thiolate (12) which was shown to react with the salt 2 under similar conditions to give the primary cycloadduct 14 as an intermediate towards the bis(imidazolium) (13).

Full text of DOI:10.1002/hc.1093

Heteroatom Chemistry
Volume 12, Number 7, 2001
Diisothiocyanates as Heterodienophiles or
Dipolarophiles in the Presence of
-Thioxothioamides or Mesoionic Thiazoles
Georges Morel and Evelyne Marchand
Synthe`se et Electrosynthe`se Organiques, UMR 6510, Universite´ de Rennes I, Campus de Beaulieu,
Avenue du General Leclerc, 35042 Rennes Cedex, France
Received 26 February 2001; revised 14 May 2001
␣ thioxothioamides (1) with aryl and methyl isoth-
ABSTRACT: Reactions of -thioxothioamides (1)
iocyanates afforded a range of 5-amino-2,3-dihydro-
with diisothiocyanates were carried out in the hope of
2-thioxothiazoles [2]. The process implied a regio-
generating the N,N0-bis(1,3-thiazoline-2-thiones) (A).
selective [4 + 2] cycloaddition to the C N bond
Although that purpose could not be achieved, we suc-
of the heterocumulene, followed by S-1 extrusion
ceeded in preparing the monocycloadducts 7 from
in the transient 3-thioxo-1,4,2-dithiazines (path a,
the phenylene-1,2-diisothiocyanate (4). The benzim-
Scheme 1). More recently, aryl and alkyl isothio-
idazole derivatives 8 and 9 were also characterized
cyanates were demonstrated to react in a basic
and a mechanism was assumed to account for this
medium with the 2-(phenylthio)-5-aminothiazolium
intramolecular process. On the other hand, the re-
chloride (2). A rapid and regioselective interconver-
gioselective synthesis of the N,N0-biimidazole (13)
sion of the mesoionic ring systems was observed, the
containing the phenylene bridge was performed by
starting azomethine yield 3 giving the corresponding
the treatment of the 5-aminothiazolium chloride (2)
5-(phenylthio)imidazolium-4-thiolates under very
with the diisothiocyanate (4) in a basic medium.
mild conditions [3]. Such a result was explained by a
The mesoionic derivative 13 probably arises from the
1,3-dipolar addition to the C N unsaturation of the
monoimidazolium-4-thiolate (12) which was shown
heteroallene, with subsequent t BuNCS elimination
to react with the salt 2 under similar conditions to
(path b, Scheme 1).
give the primary cycloadduct 14 as an intermediate
Considering the facility of these reactions, we
C
towards the bis(imidazolium) (13). 2001 John Wiley
& Sons, Inc. Heteroatom Chem 12:617–624, 2001
wondered whether it might be possible, under suit-
able conditions, to involve some diisothiocyanates
in similar procedures. If successful, double cycload-
ditions could provide useful and straightforward
routes to new N,N0-bis(1,3-thiazoline-2-thiones)
(A) and bis(imidazolium) salts (B) (Scheme 2).
Compounds of class A are excellent precursors, by
intramolecular coupling, for the formation of N,N0-
bridged dithiadiazafulvalenes [4] which have been
proved to be powerful electron -donors in conduct-
ing charge transfer salts [5]. The 1,10-polymethylene
biimidazolium dications of class B have also re-
ceived much attention in recent years [6]. Some
of these salts exhibit interesting pharmacological
INTRODUCTION
Isothiocyanates are important and versatile agents
in organic chemistry which have been widely utilized
for the synthesis of heterocyclic compounds [1]. In
particular, we previously reported that treatment of
Correspondence to: Georges Morel; e-mail: Georges.Morel@
univ-rennes1.fr
c
2001 John Wiley & Sons, Inc.
617

618 Morel and Marchand
SCHEME 1
SCHEME 2
activities [7]. The N,N0-bridged diquaternary salts of
2,20-biimidazole [8,9] and the N,N0-annulated 2,20-
unsubstituted bis(imidazolium) species [8] have gen-
erated considerable interest for their ability to pro-
vide highly air sensitive 2,20-diimidazolinylidenes
(tetraazafulvalenes).
To our knowledge, the use of diisothiocyanates
for Diels Alder and dipolar cycloadditions was
unprecedented in the literature. As representative
models, we chose to investigate the behavior of
the readily available phenylene-1,2-diisothiocyanate
(4) [10] and ethylene diisothiocyanate (5) [11].
Compounds 4 and 5 (Scheme 3) are highly re-
active heterocumulenes which undergo facile in-
tramolecular reactions in the presence of nu-
cleophiles [12,13]. For example, the thiadiazino
bis(benzimidazole) (6) was rapidly obtained from
the phenylene diisothiocyanate (4), according to
a complex cyclodimerization/CS2 elimination se-
quence [10,12]. The present article describes our tri-
als to employ the reagents 4 and 5 in the procedures
outlined in Scheme 2.
SCHEME 3
cycloadducts 7 and 8 accompanied by smaller
quantities of a hydrolyzed derivative 9 (Table
1, Scheme 4). Their relative proportions were found
to be markedly dependent on the nature of the sub-
stituent R1. Despite the use of a great excess of di-
isothiocyanate (4), large amounts of starting dithio-
carbonyl compound 1 were recovered because 4 was
rapidly converted into the pentacyclic derivative 6
which precipitated from the solution. Obtaining the
adducts 7 and 8 in acceptable yields required either a
second addition of 4 during the course of the reaction
(entries 2, 5 and 7) or the use of an initial threefold
RESULTS AND DISCUSSION
Reactions of -Thioxothioamides (1) with
Diisothiocyanates
1H NMR analyses of crude mixtures obtained from
substrates 1 and 4 indicated the formation of two

Diisothiocyanates as Heterodienophiles or Dipolarophiles in the Presence of ␣-Thioxothioamides or Mesoionic Thiazoles 619
TABLE 1 Reactions of -Thioxothioamides (1) with Phenylene-1,2-diisothiocyanate (4)
Compounds’ Ratiob
Reactions Conditionsa
4 mol. eq. (time, h)
Isolated Products
(yield, %)c
Entry
Thioamide
1
7
8
9
1
2
3
4
5
6
7
8
1a
1a
1a
1b
1b
1c
1c
1c
1.5 (18)
1.5 (18) then 0.5 (24)
3 (17)
2 (6)
2 (6) then 3 (24)
2 (6)
58
50
45
58
35
40
17
18
5
6
7
21
28
47
67
70
29
30
46
21
34
11
6
8
14
2
–
3
2
10
7
–
7a (4); 8a (20); 9a (8)
7a (4); 8a (38)
–
7b (23); 8b (25); 9b (5)
–
2 (6) then 2 (16)
3 (17)
7c (62); 9c (7)
7c (63); 9c (5)
5
aThe reactions were performed in refluxing acetonitrile, starting from a 0.5 M solution of thioamide and a large excess of diisothiocyanate. For
entries 2, 5, and 7, an additional quantity of compound 4 was poured into the reaction mixture, according to the specified conditions.
bDistributions were estimated on the basis on the 1H NMR spectra of crude mixtures.
cYields represent purified products after flash chromatography and/or crystallization.
SCHEME 4
excess of 4 (entries 3 and 8). Attempts to prepare
related cycloadducts by treatment of thioamide 1c
with ethylene diisothiocyanate (5) were unsuccess-
ful, the heterodiene 1c being essentially recovered,
even after a prolonged heating in acetonitrile.
NMR spectra of the 2-(dimethylamino)-thiazolo[3,2-
a]benzimidazoles (8) display resonances at 141
ppm for C-2, 124 ppm for C-3, and 152 ppm for
C-9a. The last two values compare favorably with
shifts for carbon atoms C-3 and C-7a of imidazo[2,1-
b]thiazole derivatives [14]. Hydrolysis was shown by
appearance of a typical IR band in the C O re-
Structure assignments were based on elemental
analyses and standard spectroscopic methods (see
1
1
the Experimental section for H and 13C NMR data
gion (1635 cm ) while a singlet at approximately
and mass fragmention patterns). Significantly, the
presence of an NCS function in the 2-thioxothiazoles
(7) was indicated in both their 13C NMR (141 ppm,
7.60 ppm was observed in the 1H NMR spectra. The
aromatic structure 9 seems to exist only as the single
tautomeric form owing to the lack of an NH ab-
sorption peak and the lack of a low-field resonance
1
singlet) and IR spectra (2000 cm , broad). The 13C

620 Morel and Marchand
thioxo carbon. Additional evidence for structure 9a
is found in the easy methylation to afford the 2-
(methylthio)benzimidazole (10a).
Cycloaddition of the Mesoionic Compound 3
with Diisothiocyanates
The thiazolium chloride 2 underwent a fast reac-
tion with the phenylene-1,2-diisothiocyanate (4) at
room temperature in the presence of triethylamine.
In addition to the side-compound 6, two mesoionic
species could be isolated in yields which were highly
dependent upon the amount of the reagent 4 that
was employed. The use of diisothiocyanate 4 in a
threefold excess resulted in the formation of 12 in
excellent yield (isolated 68%) and 13 in only trace
amount. Formation of the bis(imidazolium) adduct
13 as the major product required a smaller excess of
the substrate 4 (1.2 mol. eq.). Cycloadducts 12 and
13 were thereby obtained in 26% and 28% yields,
respectively. We have verified that the monoimida-
zole (12) readily reacts with the salt 2 under similar
conditions to provide the N,N0-biimidazole (13) in
good yield (66%). This result is rationalized through
the tandem [3 + 2] cycloaddition/cycloreversion se-
quence displayed in Scheme 5. The primary adduct
14 occurs as an unstable intermediate which could
The overall sequence of reactions is summarized
in Scheme 4. Formation of cycloadduct 7 appears
to be totally regioselective and takes place accord-
ing to the aforementioned ring contraction path a
(Scheme 1). The isothiocyanate 7 is surprisingly un-
reactive towards the conjugated heterodiene 1, no
compound of class A being detected in the crude
medium in spite of the continued presence of 1 (cf.
Table 1). Further treatment of 7 in refluxing MeCN
failed also to furnish the fused benzimidazole 8 and
gave back starting material. This fact suggests the
participation of the -iminothioamide intermediate
11 in the generation of 8, via elimination of CS2
from the corresponding 2-thioxo-1,3-thiazetidine as
previously described [2]. Intramolecular [4 + 2] cy-
cloaddition of the compound 11 to the C S bond
of the heterocumulene moiety is followed by a sul-
fur extrusion to afford 8. Separation of products by
column chromatography on silica gel induces a par-
tial hydrolysis to form the 2-mercaptobenzimidazole
(9).
Imidazothiazoles have been mentioned over
many years in the literature on account of their nu-
merous biological activities [14,15]. However, the 2-
(dimethylamino)-thiazolo[3,2-a]benzimidazoles (8)
are new compounds. Similar fused heteropental-
enes having a phenylazo substituent at the 2-position
have generally been prepared by the addition of
2-mercaptobenzimidazole to hydrazonoyl halides
[16].
1
only be observed by H NMR spectroscopy of the
crude mixture, before extrusion of tert-butyl isothio-
cyanate (cf. Experimental section).
The mesoionic heterocycles 12 and 13 were char-
acterized by their NMR spectral data and mass spec-
tra. Assignment of the regiochemistry of their for-
mation is based upon analogy to closely related
imidazolium-4-thiolates (path b, Scheme 1) with par-
ticular regard to the chemical shifts for the three en-
docyclic carbons [3]. As anticipated, alkylation of 12
SCHEME 5

Diisothiocyanates as Heterodienophiles or Dipolarophiles in the Presence of ␣-Thioxothioamides or Mesoionic Thiazoles 621
and 13 works very well with iodomethane at room
temperature to afford the stable mono and N,N0-
biimidazolium salts 15 and 16 (Scheme 6).
solution, unless otherwise indicated (internal
standard Me4Si).
HRMS: Centre Re´gional de Mesures Physiques de
l’Ouest; Varian MAT 311 instrument, electron im-
pact mode using a potential of 70 eV, except for
compounds 12, 13, 15 and 16: MS/MS ZabSpec
TOF Micromass spectrometer, ionization mode
positive LSIMS with Cs+, matrix mNBA.With
the exception of molecular-ion peaks, only mass-
spectral fragments with relative intensities of 10%
or more are reported.
Treatment of salt 2 with triethylamine and
ethylene diisothiocyanate (5) (1.6 mol. eq.) in THF
solution at room temperature gave only one isolable
product whose mass spectral data and elemental
analysis indicated a molecular formula C19H17N3S3.
This adduct was deduced to be mesoionic monoim-
idazole (17) in full accord with the NMR and IR
spectroscopic studies. The reaction failed to gener-
ate any detectable quantities of the bis(imidazolium)
compound.
IR spectra: Perkin-Elmer 1420 spectrophotometer,
suspensions in nujol.
In conclusion, we have demonstrated for the first
time the ability of phenylene-1,2-diisothiocyanate
(4) to undergo hetero Diels Alder and 1,3-dipolar
cycloaddition reactions in the context of a reaction
with a suitable heterodiene and dipole. The two het-
erocumulene moities successively react with mes-
oionic thiazole (3) to give the expected N,N0-biimida-
zolium species 13 under satisfactory conditions.
Unfortunately, only one isothiocyanate function be-
haves as an active dienophile towards -thioxothioa-
mides (1) and attempts to construct bis(thiazoline-
thiones) of type A were unsuccessful. However, our
results provide a new contribution for the synthesis
of thiazolo[3,2-a]benzimidazoles.
Elemental analyses: Analytical laboratory, CNRS.
Acetonitrile and tetrahydrofuran (THF) were
freshly distilled from P2O5 and NaH, respectively.
Na2SO4 was used to dry organic layers after ex-
tractions.
Starting Materials
We previously described the procedures for prepar-
ing the -thioxothioamides (1) [17] and salt (2)
[18]. Hull has reported on the formation of the
phenylene-1,2-diisothiocyanate (4) by the fission of
benzimidazole under the action of thiophosgene
and base [10]. The yellow crystalline thiadiazino
bis(benzimidazole) (6) was clearly identified on
the basis of elemental analysis and NMR evidences
[10]. The ethylene diisothiocyanate (5) was synthe-
sized using a slight modification to a literature
method [11], i.e., on the decomposition, at room
temperature, of the carbethoxy ethylene bis(dithio-
carbamate) on alumina-dispersed potassium fluo-
ride as solid support in CH2Cl2. Although the so-
lution of 5 might be stored (refrigerator) for long
periods without alteration, evaporation under re-
duced pressure gave an oil which rapidly polymer-
ized on standing under usual conditions.
EXPERIMENTAL
General
NMR spectra: Bruker ARX 200 spectrometer (200
MHz for 1H and 50.3 MHz for 13C) in CDCl3
Reactions of -Thioxothioamides (1) with the
Phenylene Diisothiocyanate (4)
An excess of diisothiocyanate (see Table 1) was added
to a solution of thioamide (5 mmol) in CH3CN
(10 ml), and the mixture was maintained at reflux
temperature for the time indicated in this Table.
The side-product 6 precipitated in large quantities
from the reaction medium and was filtered off. The
solvent was removed in vacuo, and the residual
1
substance was analyzed by H NMR spectroscopy
in order to monitor the progress and distribution
of the reaction. Trituration with diethyl ether gave
the crystalline 2-thioxothiazoles (7a–c) which were
SCHEME 6

622 Morel and Marchand
collected by filtration. The filtrate was purified by a
flash chromatography on Merck 60 silica gel. The
column was first eluted with CH2Cl2/CCl4 (2:1) to
recover the starting heterodiene 1 and remaining
parts of 7. Other products of Table 1 were iso-
lated with diethyl ether as eluent and recrystal-
lized from CH2Cl2/petroleum ether (compounds 8)
or diethyl ether/petroleum ether (compounds 9, un-
precise melting points).
The 2-mercaptobenzimidazole (9a) (0.68 g,
2 mmol) was alkylated by iodomethane (0.43 g,
3 mmol) in dry CH2Cl2 (20 ml) containing triethy-
lamine (0.4 g, 4 mmol). The mixture was stirred at
room temperature for 10 min, washed with H2O and
concentrated to yield the 2-(methylthio) derivative
(10a) as a viscous product (0.65 g, 1.8 mmol).
2-(Dimethylamino)-3-(4-methoxyphenyl)-thiazo-
lo[3,2-a]benzimidazole (8a). m.p. 126 C. 1H NMR
2.65 (s, 6H), 3.89 (s, 3H), 6.80–7.20 (m, 3H), 7.06
(d, 2H, J = 8.8 Hz), 7.47 (d, 2H, J = 8.8 Hz), 7.70 (d,
1H, J = 8 Hz). 13C NMR 46.4 (NCH3), 55.3 (OCH3),
111.5, 114.2, 118.7, 120.1, 120.6, 122.7, 130.4,
131.4, 147.2, 160.5 (arom. C), 124.2 (t, 3 J = 3 Hz,
C-3), 140.5 (m, C-2), 152.3 (s, C-9a). MS calcd. for
C18H17N3OS m/z 323.1092 [M]+, found 323.1086;
m/z (rel. int.): 323 (100), 267 (70), 224 (10). Anal.
calcd.: C, 66.87; H, 5.26; N, 13.00; S, 9.90. Found: C,
66.94; H, 5.20; N, 13.11; S, 10.13.
3-(4-Chlorophenyl)-2-(dimethylamino)-thiazolo
[3,2-a]benzimidazole (8b). m.p. 130 C dec. 1H NMR
2.65 (s, 6H), 6.85–7.30 (m, 3H), 7.51 (s, 4H), 7.79
(d, 1H, J = 8 Hz). 13C NMR 46.3 (NCH3), 111.3,
118.9, 120.4, 122.9, 127.0, 129.1, 130.2, 131.3, 135.6,
147.1 (arom. C), 123.1 (br, C-3), 141.6 (m, C-2), 152.3
(s, C-9a). Anal. calcd. for C17H14ClN3S: C, 62.29; H,
4.27; N, 12.82; S, 9.77. Found: C, 62.08; H, 4.18;
N, 12.65; S, 10.11.
2,3-Dihydro-5-(dimethylamino)-3-(2-isothiocya-
natophenyl)-4-(4-methoxyphenyl)-2-thioxothiazole
(7a). m.p. 185 C (CH2Cl2/petroleum ether). IR 2000
1
1
cm . H NMR 2.60 (s, 6H), 3.72 (s, 3H), 6.74 (d,
2H, J = 8.9 Hz), 7.09 (d, 2H, J = 8.9 Hz), 7.00–7.30
(m, 4H). 13C NMR 45.5 (NCH3), 55.1 (OCH3), 113.7,
121.4, 125.5, 127.5, 130.3, 130.6, 130.8, 131.5, 135.8,
159.7 (arom. C), 131.9 (t, 3 J = 3.4 Hz, C-4), 140.9
(s, NCS), 141.8 (m, C-5), 184.8 (s, C-2). Anal. calcd.
for C19H17N3OS3: C, 57.14; H, 4.26; N, 10.53. Found:
C, 56.81; H, 4.12; N, 10.39.
N-[(Dimethylcarbamoyl) (4-methoxyphenyl)me-
thyl]-2-mercaptobenzimidazole (9a). m.p. 120 C
1
1
dec. IR 1635 cm . H NMR 3.13 (s, 3H), 3.14 (s,
3H), 3.77 (s, 3H), 6.90 (m, 6H), 7.30 (d, 2H, J = 8.7
Hz), 7.60 (s, 1H), 11.60 (br, 1H). 13C NMR 35.3,
36.5 (NCH3), 54.3 (OCH3), 58.6 (dt, 1 J = 137 Hz, 3 J =
4.3 Hz, CH), 108.9, 111.9, 113.4, 121.5, 121.8, 124.2,
128.7, 129.5, 131.4, 158.8 (arom. C), 167.4 (m, CO),
167.4 (screened, C-2). MS calcd. for C18H19N3O2S
m/z 341.1198 [M]+, found 341.1179; m/z (rel. int.):
341 (20), 296 (100), 273 (10), 167 (90). Anal. calcd.:
C, 63.34; H, 5.57; N, 12.32; S, 9.38. Found: C, 63.21;
H, 5.52; N, 12.25; S, 9.56.
4-(4-Chlorophenyl)-2,3-dihydro-5-(dimethylamino)-
3-(2-isothiocyanatophenyl)-2-thioxothiazole (7b).
m.p. 189 C (CH2Cl2/petroleum ether). 1H NMR ␦
2.61 (s, 6H), 7.11 (d, 2H, J = 8.5Hz), 7.21 (d, 2H,
J = 8.5 Hz), 7.30 (m, 4H). 13C NMR 45.4 (NCH3),
125.7, 127.6, 127.7, 128.7, 130.5, 130.6, 130.8, 131.4,
135.0, 135.4 (arom. C), 130.5 (screened, C-4), 141.0
(s, NCS), 142.5 (m, C-5), 185.1 (s, C-2). Anal. calcd.
for C18H14ClN3S3: C, 53.53; H, 3.47; Cl, 8.79; N, 10.40;
S, 23.79. Found: C, 53.15; H, 3.37; Cl, 8.81; N, 10.30;
S, 23.88.
N-[(4-Chlorophenyl) (dimethylcarbamoyl) methyl]-
2-mercaptobenzimidazole (9b). m.p. 125 C dec. IR
1
1630 cm . 1H NMR 3.13 (s, 3H), 3.14 (s, 3H), 6.97
(m, 4H), 7.31 (m, 4H), 7.61 (s, 1H), 11.70 (br, 1H). 13
C
NMR 36.4, 37.6 (NCH3), 59.1 (d, 1 J = 137 Hz, CH),
110.1, 112.7, 122.8, 123.1, 129.2, 129.7, 130.5, 132.0,
134.7 (arom. C), 167.8 (m, CO), 168.5 (t, J = 4.6 Hz,
C-2). MS calcd. for C17H16ClN3O m/z 345.0703 [M]+,
found 345.0705; m/z (rel. int.): 345 (20), 300 (100),
273 (20), 271 (15), 168 (35).
2,3-Dihydro-5-(dimethylamino)-3-(2-isothiocya-
natophenyl)-4-(4-nitrophenyl)-2-thioxothiazole (7c).
1
m.p. 183 C (CH2Cl2/diethyl ether). IR 2005 cm .
1H NMR 2.64 (s, 6H), 7.10–7.45 (m, 6H), 8.09 (d,
2H, J = 8.9 Hz). 13C NMR
45.4 (NCH3), 123.5,
126.0, 127.9, 130.5, 130.8, 135.0, 135.6, 147.3 (arom.
3
N-[(Dimethylcarbamoyl) (4-nitrophenyl) methyl]-
C), 128.7 (t, J = 3.7 Hz, C-4), 141.2 (s, NCS), 144.0
1
2-mercaptobenzimidazole (9c). m.p. 180 C dec. H
(m, C-5), 185.2 (s, C-2). MS calcd. for C18H14N4O2S3
+
.
NMR 3.13 (s, 3H), 3.15 (s, 3H), 7.04 (m, 4H), 7.49
(d, 2H, J = 8.6 Hz), 7.67 (s, 1H), 8.19 (d, 2H, J = 8.6
Hz), 11.70 (br, 1H). 13C NMR 36.7, 37.7 (NCH3),
59.0 (dt, 1 J = 136 Hz, 3 J = 3.6 Hz, CH), 110.3, 112.2,
m/z 414.0279 [M] , found 414.0267; m/z (rel. int.):
414 (100), 356 (70), 310 (10), 282 (12). Anal. calcd.:
C, 52.17; H, 3.38; N, 13.52; S, 23.18. Found: C, 52.18;
H, 3.22; N, 13.42; S, 23.24.

Diisothiocyanates as Heterodienophiles or Dipolarophiles in the Presence of ␣-Thioxothioamides or Mesoionic Thiazoles 623
123.2, 123.6, 124.0, 129.2, 130.5, 131.6, 141.2, 147.8
(arom. C), 167.2 (m, CO), 168.8 (t, J = 5.4 Hz, C-2).
MS calcd. for C17H16N4O3S m/z 356.0943 [M]+, found
356.0935.
cloadduct 14 was decomposed into the biimidazole
13 and tert-butyl isothiocyanate ( 1.42 s) by stand-
ing in CDCl3 solution at room temperature. After
complete degradation, the bis(mesoinic imidazole)
13 was isolated in the usual way (1.34 g, 2 mmol).
Compounds 12 and 13 were quantitatively alky-
lated by iodomethane in dry CH2Cl2 during 10 min.
The solvent was removed under reduced pressure
and the residual syrup was triturated with di-
ethyl ether to give a yellowish insoluble material.
The methiodides 15 and 16 are stable amorphous
hemisolids (undefined melting points).
N-[(Dimethylcarbamoyl) (4-methoxyphenyl) me-
thyl]-2-(methylthio)benzimidazole (10a). Crude oily
1
product. IR 1650 cm . 1H NMR ␦ 2.69 (s, 3H), 2.80
(s, 3H), 2.94 (s, 3H), 3.65 (s, 3H), 6.32 (s, 1H), 6.75–
7.10 (m, 6H), 7.54 (d, 1H, J = 7.9 Hz). 13C NMR
14.2 (SCH3), 35.1, 36.0 (NCH3), 54.2 (OCH3), 58.6 (dt,
1 J = 134 Hz, 3 J = 3.9 Hz, CH), 110.7, 113.3, 117.0,
120.7, 121.0, 124.4, 128.5, 135.0, 142.7, 158.8 (arom.
3
C), 151.4 (qd, J = 4.2 Hz, C-2), 166.3 (m, CO). MS
3-(2-Isothiocyanatophenyl)-1-methyl-2-phenyl-5-
calcd. for C19H21N3O2S m/z 355.1354 [M]+, found
355.1354; m/z (rel. int.): 355 (40), 283 (90), 235 (20),
192 (30), 164 (100).
(phenylthio)imidazolium-4-thiolate (12). m.p. 160–
1
165 C (CH2Cl2/diethyl ether). IR 2040 cm . 1H NMR
␦ 3.69 (s, 3H), 7.15–7.60 (m, 14H). 13C NMR ␦ 34.2
(NCH3), 122.9, 126.3, 126.5, 127.7, 127.8, 129.3,
129.5, 129.7, 130.9, 131.3, 131.8, 132.6, 135.5 (arom.
Reactions of the Thiazolium Chloride 2 with
Diisothiocyanates
3
C), 118.2 (q, J = 3.1 Hz, C-5), 139.4 (s, NCS), 141.4
(m, C-2), 161.4 (s, C-4). MS calcd. for C23H18N3S3
m/z 432.0663 [M + H]+, found 432.0662.
In a general procedure, triethylamine (1.5 g,
15 mmol) was added dropwise to a suspension of
salt 2 (1.95 g, 5 mmol) and diisothiocyanate in dry
THF (25 ml). Quantities of the dipolarophile were
the following: 2.88 g, 15 mmol or 1.15 g, 6 mmol for
phenylene-1,2-diisothiocyanate (4); 1.15 g, 8 mmol
for ethylene diisothiocyanate (5) (see the discussion
before). A blood red color appeared immediately but
disappeared very rapidly. The reaction medium was
stirred at room temperature for 2 h in the case of 4
and for 6 h in that of 5. A mixture of triethylam-
monium chloride and imidazolium-4-thiolate (12)
or (17) was collected by filtration and successively
washed with H2O and diethyl ether to give the crude
monocycloadduct as the insoluble part (12: 1.45 g,
3.4 mmol or 0.56 g, 1.3 mmol according to the
excess of 4; 17: 0.46 g, 1.2 mmol). Diethyl ether
(10 mL) was poured into the filtrate in order to pre-
cipitate the remaining adduct 12 in admixture with
the side-product 6. Concentration of the last filtrate
and trituration with diethyl ether gave the yellow
crystalline biimidazole 13 (0.47 g, 0.7 mmol).
1,2-Bis[1-methyl-2-phenyl-5-(phenylthio)-4-thio-
late-imidazolium-3-yl]phenyl (13). m.p. 240–245 C
(CH2Cl2/diethyl ether). 1H NMR
3.55 (s, 6H),
6.75–7.90 (m, 24H). 13C NMR 34.5 (NCH3), 124.9,
125.5, 126.4, 128.5, 129.3, 130.8, 131.0, 131.7, 133.2,
3
136.4 (arom. C), 116.1 (q, J = 3 Hz, C-5), 143.5 (m,
C-2), 158.3 (s, C-4). MS calcd. for C38H30N4S4 m/z
670.1353 [M]+, found 670.1369; m/z (rel. int.): 670
(100), 593 (14), 444 (10), 373 (57), 307 (39).
3-(2-Isothiocyanatophenyl)-1-methyl-4-(methyl-
thio)-2-phenyl-5-(phenylthio)imidazolium iodide (15).
1H NMR ␦ 2.48 (s, 3H), 3.77 (s, 3H), 7.28–7.88 (m,
13H), 8.56 (dd, 1 J = 7.8 and 1.4 Hz, 1H). 13C NMR ␦
20.0 (SCH3), 35.5 (NCH3), 121.2, 125.7, 128.3, 128.5,
129.4, 129.7, 129.9, 130.1, 130.2, 131.1, 131.2, 131.6,
132.4, 132.8 (arom. C), 133.0 (q, 3 J = 3.3 Hz, C-5),
137.2 (q, 3 J = 4.4 Hz, C-4), 141.0 (s, NCS), 148.9 (m,
C-2). MS calcd. for C24H20N3S3 m/z 446.0819 [M-I]+,
Found 446.0815.
The reaction of the monoimidazole 12 (1.3 g,
3 mmol) with the salt 2 (1.56 g, 4 mmol) and triethy-
lamine (1 g, 10 mmol) was also performed in THF
(30 mL) at room temperature for 12 h. As previously
described, the workup procedure consists of filtra-
tion, washing with H2O, then diethyl ether, to afford
1,2-Bis[1-methyl-4-(methylthio)-2-phenyl-5-(phe-
nylthio)imidazolium-3-yl]phenyl diiodide (16). 1H
NMR (CDCl3+CF3CO2H) ␦ 2.08 (s, 6H), 3.85 (s, 6H),
7.20–8.10 (m, 24H). 13C NMR (CDCl3 + CF3CO2H) ␦
20.0 (SCH3), 37.2 (NCH3), 120.1, 128.6, 129.6, 130.2,
130.3, 130.7, 132.3, 133.2, 133.6 (arom. C), 133.2 (q,
1
a yellowish solid material. The H NMR analysis of
this crude product showed the primary cycloadduct
14 as the strongly dominant compound [ 1.08 (s,
9H), 2.35 (s, 3H), 3.62 (s, 3H), 6.95–7.70 (m, 24H)]
and only small amounts of biimidazole 13. The cy-
3
3 J = 3 Hz, C-5), 138.7 (q, J = 5 Hz, C-4), 147.6 (m,
C-2). MS calcd. for C40H36N4S4I m/z 827.0868 [M-I]+,
Found 827.0868.

624 Morel and Marchand
E. F. Gazz Chim Ital 1994, 124, 445; (b) Cabildo, P.;
Claramunt, R.; Lavandera, J. L.; Sanz, D.; Elguero,
J.; Enjalbal, C.; Aubagnac, J. L. J Heterocycl Chem
1997, 34, 367; (c) Diez-Barra, E.; Dotor, J.; de la Hoz,
A.; Foces-Foces, C.; Enjalbal, C.; Aubagnac, J. L.;
Claramunt, R. M.; Elguero, J. Tetrahedron 1997, 53,
7689 and references therein.
3-(2-Isothiocyanatoethyl)-1-methyl-2-phenyl-5-
(phenylthio)imidazolium-4-thiolate
(17). m.p.
1
1
186 C (CH2Cl2/petroleum ether). IR 2050 cm . H
NMR ␦ 3.52 (s, 3H), 4.36 (m, 4H), 7.15–7.70 (m,
10H). 13C NMR ␦ 34.0 (NCH3), 43.4, 45.4 (NCH2),
123.5, 126.9, 127.7, 129.8, 130.4, 130.5, 132.7, 135.9
(arom. C), 118.5 (q, J = 3.1 Hz, C-5), 133.4 (br, NCS),
142.7 (m, C-2), 157.9 (t, 3 J = 3.7 Hz, C-4). MS calcd.
for C19H17N3S3 m/z 383.0585 [M]+, found 383.0586;
m/z (rel. int.): 383 (15), 324 (10), 309 (100), 102 (80).
Anal. calcd.: C, 59.53; H, 4.44; N, 10.97; S, 25.06.
Found: C, 59.41; H, 4.38; N, 10.75; S, 25.19.
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