Synthesis of imidazolyl dithiocarbamates and their reactions with phenacyl bromides

Article abstract of DOI:10.1007/s11172-011-0138-3

The reactions of ethyl (5-carbamoyl-3H-imidazol-4-yl)dithiocarbamate with phenacyl bromides afford the S-alkylation products as a mixture of E/Z-isomers, which undergo cyclization to 5-(2-oxo-4-arylthiazol-3-yl)-1H-imidazole-4- carboxamides under the acti

Full text of DOI:10.1007/s11172-011-0138-3

Russian Chemical Bulletin, International Edition, Vol. 60, No. 5, pp. 882—888, May, 2011
882
Synthesis of imidazolyl dithiocarbamates and their reactions
with phenacyl bromides*
O. S. El´tsov, V. S. Mokrushin, M. V. Smirnova, and M. Z. Shafikov
Ural Federal University named after the first President of Russia B. N. Yeltsin,
19 ul. Mira, 620002 Ekaterinburg, Russian Federation.
Fax: +7 (343) 374 5483. Eꢀmail: olegꢀeltsov@yandex.ru
The reactions of ethyl (5ꢀcarbamoylꢀ3Hꢀimidazolꢀ4ꢀyl)dithiocarbamate with phenacyl
bromides afford the Sꢀalkylation products as a mixture of E/Zꢀisomers, which undergo cyclizaꢀ
tion to 5ꢀ(2ꢀoxoꢀ4ꢀarylthiazolꢀ3ꢀyl)ꢀ1Hꢀimidazoleꢀ4ꢀcarboxamides under the action of a base.
Key words: imidazolyldithiocarbamates, alkylation, intramolecular heterocyclization,
5ꢀ(2ꢀoxoꢀ4ꢀarylthiazolꢀ3ꢀyl)ꢀ1Hꢀimidazoleꢀ4ꢀcarboxamides.
Earlier, we have shown that 5ꢀaminoimidazole amides
which undergo subsequently heterocyclization without
1a,b afford Sꢀethyldithiocarbamates 3a,b in high yields
upon sequential treatment with carbon disulfide and ethyl
iodide without isolation of the intermediate imidazolylꢀ5ꢀ
dithiocarbamic acid salt 2 (Scheme 1). The latter transꢀ
form easily into the corresponding thioureas under the
action of amines and results in imidazo[1,5ꢀc][1,3,5]ꢀ
thiadiazines in the reactions with dimethyl acetylenediꢀ
carboxylate.1,2
their isolation.5
The present work is aimed at the synthesis and study of
the reactions of 1Hꢀimidazolꢀ4ꢀyldithiocarbamate 2a and
esters 3a,b with phenacyl bromides.
Results and Discussion
Performing the reaction of 5ꢀaminoimidazoles 1a,b
with carbon disulfide under mild conditions allowed isolaꢀ
tion of triethylammonium 5ꢀcarbamoylꢀ1Hꢀimidazolꢀ4ꢀ
yldithiocarbamate (2a) in a high yield (see Scheme 1),
whose alkylation with ethyl iodide resulted in Sꢀethyl
dithiocarbamate 3a. We synthesized also the analogous
methylamide derivative 3b, but without isolation of the
intermediate salt of imidazolyldithiocarbamic acid 2b.
The presence of several nucleophilic centers in the molꢀ
ecule of substrate 2a contemplates ambiguousness of the
reaction pathway with aromatic haloketones.
Scheme 1
In the reaction of triethylammonium 5ꢀimidazolylꢀ
dithiocarbamate 2a with bromoacetophenones, the forꢀ
mation of several products with close chromatographic
mobilities was observed, which made impossible the use of
chromatography for separation and purification of subꢀ
stances. In attempting to crystallize compounds, they deꢀ
composed.
The reactions of 5ꢀaminoimidazoles 1a,b with carꢀ
bon disulfide and aromatic haloketones as alkylating
agents were performed analogously to the reaction with
ethyl iodide.
R1 = H (a), Me (b)
It is known that the reaction of 5ꢀaminoꢀ4ꢀimidꢀ
azole(pyrazole)carboxamides with carbon disulfide results
in the mercaptopurine3 and pyrazolopyrimidine derivaꢀ
tives,4 respectively, or pyrazolyldithiocarbamic acids,
However, these reactions resulted in no alkylation
products or subsequent cyclization products; after diluꢀ
tion of the reaction mixture with water, the symmetric
1
aromatic disulfides 4a,b (according to the data from H,
* Dedicated to Academician V. N. Charushin on the occasion of
his 60th birthday.
13C NMR, and mass spectrometry and elemental analyꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 862—868, May, 2011.
1066ꢀ5285/11/6005ꢀ882 © 2011 Springer Science+Business Media, Inc.

Synthesis of imidazolyldithiocarbamates
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 5, May, 2011
883
sis) were isolated (Scheme 2). In addition, the starting
aminoimidazoles 1a,b were fixed chromatographically.
Further, we studied the reactions of ethyl imidꢀ
azolyldithiocarbamates 3a,b with bromoacetophenones.
When performing this reaction in DMF in the presence of
triethylamine, dialkylated imidazolyldithiocarbamates
5a—i were produced (Scheme 3, Tables 1 and 2).
Scheme 2
Scheme 3
4: R2 = Cl (a), NO2 (b)
1
The H NMR spectra of the isolated products 4a,b
contain no signals for the imidazole ring and its substituꢀ
ents and contain signals for the aromatic protons and СН2
group. The peak values of molecular ion and fragment
ions in the mass spectrum suggest also the formation of
disulfides 4a,b.
R1
H
H
R2
H
Cl
R1
H
Me
R2
NO2
H
R1
R2
a
b
d
e
g
h
Me OMe
Me NO2
c
H
OMe
f
Me
Cl
i
Me
Me
Table 1. Yields, melting points, data from elemental analysis, 1Н NMR spectroscopy and mass spectrometry of compounds 2a, 4a,b,
5a—i, and 6a—h
Comꢀ Yield M.p.
pound (%) /°С
Found
Calculated
Molecular
formula
1Н NMR, δ (J/Hz)
[M+],
m/z
(%)
N
C
H
2а
91
120 43.76 7.50 23.52 C11H21N5OS2
43.56 6.93 23.10
13.54, 11.02 (both s, 1 H each, NH); 7.19 (s, 1 H, CHIm);
7.10 (br.s, 2 H, CONH2); 3.06 (q, 6 H, CH2CH3,
J = 7.6); 1.18 (t, 9 H, CH2CH3, J = 7.6)
303
4a
4b
5a
70
75
75
141 51.90 3.40
51.76 3.26
—
С16H12O2S2Cl2
С16H12N2O6S2
7.98—7.59 (AA´BB´ system, 4 H, HAr);
4.41 (s, 2 H, CH2)
371
392
348
122 48.65 2.75 7.55
48.97 3.08 7.14
8.35—8.17 (AA´BB´ system, 4 H, HAr);
4.50 (s, 2 H, CH2)
188 52.20 4.55 16.15 С15H16N4O2S2
51.72 4.60 16.09
12.92, 12.76 (s, 1 H, NHIm); 8.02—7.60 (m, 5 H, HAr);
7.69, 7.28 (br.s, 2 H, CONH2); 7.32 (s, 1 H, CHIm);
4.86 (s, 2 H, CH2); 3.13, 3.08 (q, CH2CH3, 2 H, J = 7.0);
1.29, 1.23 (t, 3 H, CH2CH3, J = 7.0)
5b
81
231 46.83 4.25 14.21 С15H15ClN4O2S2 12.80, 12.66 (s, 1 H, NHIm); 8.03—7.36 (AA´BB´ system,
382
47.05 3.95 14.63
4 H, HAr, J = 8.5); 7.32 (s, 1 H, CHIm);
7.29, 6.99 (br.s, 2 H, CONH2); 4.79, 4.73 (s, 2 H,
CH2); 3.15, 3.08 (q, 2 H, CH2CH3, J = 7.2);
1.38, 1.34 (t, 3 H, CH2CH3, J = 7.2)
(to be continued)

884
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 5, May, 2011
El´tsov et al.
Table 1 (continued)
Comꢀ Yield M.p.
Found
Calculated
Molecular
formula
1Н NMR, δ (J/Hz)
[M+],
m/z
(%)
N
pound (%)
/°С
C
H
5c
5d
71
59
219 51.05 4.65 14.55 С16H18N4O3S2
50.79 4.79 14.81
12.70, 12.65 (s, 1 H, NHIm); 7.97—6.99 (AA´BB´ system,
4 H, HAr, J = 9.0); 7.52, 7.44 (s, 1 H, CHIm);
7.34, 6.88 (br.s, 2 H, CONH2); 4.69, 4.67 (s, 2 H, CH2);
3.87 (s, 3 H, OCH3); 3.14, 3.05 (q, 2 H, CH2CH3,
J = 7.5); 1.35, 1.33 (t, 3 H, CH2CH3, J = 7.5)
378
393
242 45.99 4.05 17.33 С15H15N5O4S2
45.79 3.84 17.80
12.77, 12.65 (s, 1 H, NHIm); 8.40—8.32 (AA´BB´ system,
4 H, HAr, J = 9.0); 7.52, 7.43 (br.s, 1 H, CHIm);
7.23, 6.81 (br.s, 2 H, CONH2); 4.85 (s, 2 H, CH2);
3.06 (q, 2 H, CH2CH3, J = 7.5);
1.37 (t, 3 H, CH2CH3, J = 7.5)
5e
5f
55
70
65
171 53.20 5.34 15.20 С16H18N4O2S2
53.04 5.01 15.46
12.84, 12.68 (br.s, 1 H, NHIm); 8.02—7.62 (m, 5 H, Ph);
7.78, 7.24 (q, 1 H, NH, J = 4.6); 7.61, 7.41 (s, 1 H, CHIm);
4.77, 4.75 (s, 2 H, CH2); 3.14, 3.10 (q, 2 H, CH2CH3,
J = 7.2); 2.88, 2.68 (d, 3 H, NHCH3, J = 4.6);
1.35 (t, 3 H, CH2CH3, J = 7.2)
362
396
392
175 48.05 4.01 14.10 С16H17ClN4O2S2 12.51, 12.34 (br.s, 1 H, NHIm); 7.71—7.19 (AA´BB´
48.42 4.32 14.12
system, 4 H, HAr, J = 8.7); 7.43, 6.91 (q, 1 H, NH,
J = 4.3); 4.42, 4.40 (s, 2 H, CH2); 2.80, 2.70 (q, 2 H,
CH2CH3, J = 7.3); 2.54, 2.39 (d, 3 H, NHCH3, J = 4.3);
1.01 (t, 3 H, CH2CH3, J = 7.3)
5g
188 52.19 5.02 14.13 С17H20N4O3S2
52.04 5.14 14.27
12.84, 12.68 (br.s, 1 H, NHIm); 8.02—7.00 (AA´BB´
system, 4 H, HAr, J = 8.8); 7.78, 7.30 (q, 1 H, NH,
J = 4.5); 7.51, 7.42 (s, 1 H, CHIm); 4.70, 4.68 (s, 2 H,
CH2); 3.88 (s, 3 H, OCH3); 3.16, 3.10 (q, 2 H, CH2CH3,
J = 7.3); 2.88, 2.72 (d, 3 H, NHCH3, J = 4.5);
1.35 (t, 3 H, CH2CH3, J = 7.3)
5h
5i
51
40
183 47.50 4.01 17.00 С16H17N5O4S2
47.16 4.21 17.19
12.86, 12.70 (s, 1 H, NHIm); 8.35—8.24 (AA´BB´ system,
4 H, HAr, J = 8.5); 7.75, 7.23 (q, 1 H, NH, J = 5.5);
7.51, 7.42 (s, 1 H, CHIm); 4.84, 4.82 (s, 2 H, CH2);
3.14, 3.11 (q, 2 H, CH2CH3, J = 7.5); 2.87, 2.73
(d, 3 H, NHCH3, J = 5.5);
407
376
1.35 (t, 3 H, CH2CH3, J = 7.5)
168 53.98 5.21 14.97 С17H20N4O2S2
54.23 5.35 14.89
12.84, 12.68 (s, 1 H, NHIm); 7.93—7.31 (AA´BB´
system, 4 H, HAr, J = 9.5); 7.77, 7.26 (q, 1 H, NH,
J = 4.3); 7.51, 7.42 (s, 1 H, CHIm); 4.73 (br.s, 2 H,
CH2); 3.16, 3.12 (q, 2 H, CH2CH3, J = 7.3); 2.87, 2.69
(d, 3 H, NHCH3, J = 4.3); 2.43 (s, 3 H, CH3);
1.39 (t, 3 H, CH2CH3, J = 7. 3)
6a
6b
6c
6d
38
46
51
38
189 54.30 3.55 20.20 С13H10N4O2S
54.55 3.52 19.57
12.81 (s, 1 H, NHIm); 7.74 (m, 2 H, Ph); 7.58 (s, 1 H,
CHIm); 7.44—7.33 (m, 5 H, Ph, CONH2);
7.22 (s, 1 H, CH)
286
320
331
200 48.32 3.02 17.13 С13H9ClN4O2S 12.81 (s, 1 H, NHIm); 7.77—7.42 (AA´BB´ system,
48.67 2.83 17.47
4 H, HAr, J = 8.8); 7.57 (s, 1 H, CHIm); 7.34—7.31
(m, 3 H, CONH2, CH)
242 47.38 3.10 20.85 С13H9N5O4S
47.13 2.74 21.14
12.85 (s, 1 H, NHIm); 8.30—8.00 (AA´BB´ system, 4 H,
HAr, J = 8.8); 7.73 (s, 1 H, CHIm); 7.60 (s, 1 H, CH);
7.35, 7.32 (br.s, 2 H, CONH2)
177 55.80 4.32 18.35 С14H12N4O2S
56.00 4.03 18.65
12.85 (s, 1 H, NHIm); 7.76 (m, 2 H, Ph); 7.70 (q, 1 H, NH, 300
J = 4.3); 7.55 (s, 1 H, CHIm); 7.44 (m, 3 H, Ph);
7.24 (s, 1 H, CH); 2.95 (d, 3 H, NHCH3, J = 4.3)
(to be continued)

Synthesis of imidazolyldithiocarbamates
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 5, May, 2011
885
Table 1 (continued)
Comꢀ Yield M.p.
pound (%) /°С
Found
Calculated
Molecular
formula
1Н NMR, δ (J/Hz)
[M+],
m/z
(%)
N
C
H
6e
6f
45
65
59
68
165 50.10 3.65 16.82 С14H11ClN4O2S 12.86 (s, 1 H, NHIm); 7.79—7.44 (AA´BB´ system, 4 H,
334
345
316
300
50.23 3.31 16.74
HAr, J = 8.8); 7.67 (q, 1 H, NH, J = 4.7); 7.55 (s, 1 H,
CHIm); 7.33 (s, 1 H, CH); 2.95 (d, 3 H, NHCH3, J = 4.7)
250 49.01 3.03 20.01 С14H11N5O4S
48.70 3.21 20.29
12.90 (s, 1 H, NHIm); 8.31—8.02 (AA´BB´ system, 4 H,
HAr, J = 8.8); 7.74 (s, 1 H, CHIm); 7.65 (q, 1 H, NH,
J = 5.0); 7.57 (s, 1 H, CH); 2.96 (d, 3 H, NHCH3, J = 5.0)
6g
6h
205 53.02 3.56 18.08 С14H12N4O3S
53.16 3.82 17.71
12.92 (s, 1 H, NHIm); 7.75 (s, 1 H, CHIm); 7.65—7.27
(AA´BB´ system, 4 H, HAr, J = 8.3); 7.49, 7.36 (s, 2 H,
CONH2); 7.18 (s, 1 H, CH); 3.80 (s, 3 H, OCH3)
215 55.86 4.00 18.90 С14H12N4O2S
56.00 4.03 18.65
12.92 (s, 1 H, NHIm); 7.75 (s, 1 H, CHIm); 7.69—7.01
(AA´BB´ system, 4 H, HAr, J = 9.5); 7.49, 7.38
(s, 2 H, CONH2); 7.12 (s, 1 H, CH); 3.33 (s, 3 H, CH3)
Table 2. 13C NMR spectral data for compounds 4a,b, 5a—i, and 6a—h
Compound
13C NMR, δ
4a
4b
5a
193.00 (CO); 138.84, 133.68, 130.33, 128.53 (all CAr); 95.77 (CH2)
193.98 (CO); 150.40, 140.22, 130.06, 124.01 (all CAr); 44.50 (CH2)
193.81 (CO); 164.12 (CS); 163.33 (CONH2); 145.05 (C(5)); 135.78 (Ci); 134.19 (C(2)); 130.12, 128.89,
128.86 (Co, Cp, Cm); 115.91 (C(4)); 39.90 (CH2); 26.91 (CH2CH3); 14.47 (CH2CH3)
192.74 (CO); 163.87 (CS); 160.67 (CONH2); 145.05 (C(5)); 135.69 (C(2)); 134.74 (Cp); 134.19 (Cm);
128.63 (Co); 120.28 (Ci); 115.91 (C(4)); 39.90 (CH2); 26.91 (CH2CH3); 14.67 (CH2CH3)
191.25 (CO); 163.69 (CS); 160.24 (CONH2); 145.15 (C(5)); 138.19 (Ci); 135.37 (Cp); 134.03 (C(2));
123.89 (Co, Cm); 115.48 (C(4)); 55.35 (OCH3); 39.19 (CH2); 26.47 (CH2CH3); 14.30 (CH2CH3)
192.17 (CO); 160.54 (CS); 160.63 (CONH2); 144.9 (C(5)); 140.18 (Ci); 130.71 (C(2)); 129.63, 125.98,
123.80 (Cm, Co, Cp); 95.80 (C(4)); 39.99 (CH2CH3); 26.72 (CH2CH3); 14.36 (CH2CH3)
194.06 (CO); 163.87 (CS); 159.62 (CONH2); 144.79 (C(5)); 135.53 (Ci); 134.19 (C(2)); 133.22 (Cp);
128.89, 127.58 (Co, Cm); 115.91 (C(4)); 39.90 (CH2CH3); 26.91 (CH2CH3); 25.31 (CH3)
193.05 (CO); 163.60 (CS); 159.62 (CONH2); 144.80 (C(5)); 138.97 (Ci); 134.47 (Cp); 130.48 (C(2));
128.85 (Co, Cm); 116.18 (C(4)); 39.90 (CH2CH3); 26.91 (CH2CH3); 25.31 (CH3)
192.20 (CO); 164.12 (CS); 159.62 (CONH2); 145.05 (C(5)); 144.19 (Cp); 131.28 (C(2)); 128.37 (Ci);
127.60, 124.62 (Co, Cm); 115.91 (C(4)); 55.79 (OCH3); 39.62 (CH2CH3); 26.91 (CH2CH3); 25.06 (CH3)
193.26 (CO); 163.60 (CS); 159.89 (CONH2); 150.61 (C(5)); 142.79 (Cp); 140.55 (Ci); 129.69 (C(2));
125.55, 124.12 (Co, Cm); 116.18 (C(4)); 39.90 (CH2CH3); 26.91 (CH2CH3); 25.31 (CH3)
193.84 (C(9)); 164.23 (C(7)); 163.59 (C(6)); 145.85 (C(5)); 135.80 (Ci); 134.19 (C(2)); 130.22 (Cp);
128.89, 128.86 (Co, Cm); 115.91 (C(4)); 39.90 (CH2CH3); 26.91 (CH2CH3); 14.47 (CH3)
164.46 (C(2´)); 161.22 (CONH2); 146.69 (C(4´)); 143.76 (C(5)); 134.32 (C(2)); 130.42, 129.34, 125.05
(Co, Cm, Cp); 127.45 (Ci); 115.45 (C(4)); 102.35 (C(5´))
164.26 (C(2´)); 161.22 (CONH2); 145.17 (C(4´)); 143.43 (C(5)); 134.54 (C(2)); 134.11 (Cp); 129.55,
126.95 (Cm, Co); 126.90 (Ci); 115.45 (C(4)); 102.87 (C(5´))
163.33 (C(2´)); 160.95 (CONH2); 147.18 (C(4´)); 144.53 (C(5)); 142.67 (Cp); 134.72 (C(2));
133.39 (Ci); 125.72, 124.12 (Cm, Co); 115.12 (C(4)); 106.38 (C(5´))
164.12 (C(2´)); 159.89 (CONHCH3); 146.11 (C(4´)); 142.40 (C(5)); 129.42 (C(2)); 130.55, 129.50,
124.66 (Co, Cm, Cp); 127.83 (Ci); 115.12 (C(4)); 101.08 (C(5´)); 25.85 (CH3)
164.21 (C(2´)); 158.14 (CONHCH3); 148.00 (C(4´)); 144.33 (C(5)); 140.52 (Cp); 135.40 (C(2));
133.37 (Ci); 123.12, 121.88 (Cm, Co); 115.03 (C(4)); 103.15 (C(5´)); 25.75 (CH3)
163.60 (C(2´)); 160.16 (CONHCH3); 147.70 (C(4´)); 144.53 (C(5)); 142.14 (Cp); 134.47 (C(2));
133.39 (Ci); 125.72 (Cm); 124.12 (Co); 115.66 (C(4)); 106.65 (C(5´)); 25.31 (CH3)
163.92 (C(2´)); 160.59 (CONHCH3); 145.95 (C(4´)); 143.03 (Cp); 138.85 (Ci); 129.66, 125.06 (Co, Cm);
115.03 (C(4)); 99.57 (C(5´)); 55.32 (OCH3)
5b
5c
5d
5e
5f
5g
5h
5i
6a
6b
6c
6d
6e
6f
6g
6h
164.53 (C(2´)); 160.95 (CONH2); 146.11 (C(4´)); 140.04 (Cp); 125.91, 124.66 (Co, Cm); 120.54 (Ci);
115.17 (C(4)); 98.29 (C(5´)); 20.60 (CH3)

886
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 5, May, 2011
El´tsov et al.
It should be noted that, due to the presence of the
absence of the proposed cross peaks between the signals
for the carbon atom bound to the aromatic substituent and
two heterocyclic CH protons (of the imidazole and thiaꢀ
diazepine rings) for the condensed imidazothiadiazepines 7
are the most informative data.
The peak values of molecular ions in the mass specꢀ
tra of compounds 6a—f corresponds to the calculated
ones. One can note an identical type of fragmentation:
four most intensive fragment ions caused by destruction
of the thiazolidine ring are distinguished in all mass specꢀ
tra with the exception of nitro derivatives (Scheme 5,
Table 3).
—С=N bond, products 5 form as a mixture of E/Zꢀisoꢀ
1
mers, which is evidenced by the Н NMR spectral data
where all signals are either broadened or appear as a douꢀ
ble set of signals (in a ration of 1 : 2). Compared to the
1H NMR spectra of the starting ethyl thioesters 3a,b, the
1H NMR spectra of compounds 5a—i display the signals
for the СН2 groups and aromatic protons in the absence of
the downfield signals for the NH group.
Taking into account the possibility of intramolecular
cyclization involving the electrophilic carbonyl carbon
atom and one of the nucleophilic centers in the molecules
of imidazolyldithiocarbamates 5a,b,d,e,f,h, we treated
them with triethylamine in DMF at 60 °С.
Scheme 5
1
Based on the data from Н, 13С NMR, and mass
spectrometry of isolated individual compounds, it was esꢀ
tablished that either imidazolylthiazolines 6a—f or conꢀ
densed sevenꢀmembered imidazothiadiazines 7a—f can
form as a result of heterocyclization (Scheme 4).
Scheme 4
R1 R2
R1
H
Me
R2
NO2
H
R1
Me
Me NO2
R2
Cl
a
b
H
H
H
Cl
c
d
e
f
Table 3. Peaks of the main fragment ions in the mass spectra of
compounds 6a—h
However, the compounds 6 and 7 have identical moꢀ
lecular formulas, molecular weights, and the number of
proton and carbon atoms with a lowꢀinformative multiꢀ
Comꢀ
pound
m/z (Irel (%))
M1
M2
M3
M4
1
plicity in the Н and 13С NMR spectra, which makes
difficult to assign the structures of isolated compounds by
the aboveꢀmentioned methods.
6a
6b
6c
6d
6e
6f
269 (44.87)
303 (19.86)
314 (61.63)
269 (12.42)
303 (12.35)
314 (25.89)
299 (4.40)
283 (8.52)
134 (47.22)
168 (23.07)
179 (8.73)
134 (40.06)
168 (36.20)
179 (12.08)
168 (11.31)
152 (14.33)
105 (100)
139 (100)
150 (65.30) 0000—
105 (100)
139 (100)
150 (86.16) 0000—
077 (53.47)
111 (34.46)
To establish exactly the structures of compound obꢀ
tained, the HMBC spectra were recorded, which allowed
us unambiguously to make choice in favor of imidazolylꢀ
thiazolidines 6a—f. The presence of the cross peaks beꢀ
tween the C(2) atom of the imidazole ring and the NH
proton, which is typical of compounds 6, as well as the
077 (36.54)
111 (28.78)
6g
6h
135 (100)
116 (89.63) 091 (7.89)
107 (6.78)

Synthesis of imidazolyldithiocarbamates
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 5, May, 2011
887
Scheme 6
Note that cyclization found proceeded only in the case
where the aromatic ring is unsubstituted or contains elecꢀ
tronꢀwithdrawing substituents (R2 = Cl, NO2). In the case
where the substituent R2 is electronꢀdonating (R2 = OMe,
Me), the reaction did not proceed under the analogous
conditions. Application of more severe conditions (temꢀ
perature increase, use of stronger bases) resulted in resiniꢀ
fication of the reaction mixture.
ical parameters, as well as compounds 6g,h. Consequentꢀ
ly, the formation of the thiazole ring was observed in the
case of both electronꢀwithdrawing and electronꢀdonating
substituents in the aromatic ring (Scheme 7).
Scheme 7
Such a behavior can be explained by the mechanism
proposed for the synthesis of products 6a—f (Scheme 6).
At the first step, the electron lone pair of the nitrogen
atom of the dithiocarbamate fragment, which is most likely
activated by triethylamine, attacks the positively charged
carbon atom of the carbonyl group to form the thiazole
ring. The readiness of this reaction depends on the nature
of the substituent in the paraꢀposition of the phenyl ring.
When the substituent is electronꢀdonating (methyl or
methoxy) group, the positive charge is insufficitent for the
closure of a novel ring.
In the case when the phenyl ring is unsubstituted (R2 = H)
or substituted with electronꢀwithdrawing groups (R = Cl,
NO2), the positive charge on the carbon atom increases,
which promotes the reaction. The addition of the hydrꢀ
oxyl group to a new ring is possible only where there is
a charge in the structure. This causes subsequent eliminaꢀ
tion of the Sꢀethyl fragment and proton, which form leavꢀ
ing ethanethiol.
To prove the aboveꢀgiven cyclization pathway, the
trisubstituted thiourea 8 was chosen as the starting subꢀ
strate.1,2 It was assumed that the presence of the pyrroliꢀ
dine fragment would considerably activate the electron
lone pair of the nitrogen atom, which, in turn, would faꢀ
cilitate heterocyclization and the formation of the thiazole
ring. In this case, the nature of the substituent in the aroꢀ
matic ring will not influence the course of the reaction.
The reactions of imidazolylthiourea 8 with phenacyl
bromides afforded compounds identical to the earlier synꢀ
thesized imidazolylthiazolines 6b,с by their physicochemꢀ
6: R = Cl (b), NO2 (c), OMe (g), Me (h)
Thus, we found that alkylation of ethyl imidazolylꢀ
dithiocarbamates 3a,b with aromatic haloketones resulted
in the dialkylated imidazolyldithiocarbamates 5a—i as
a mixture of E/Zꢀisomers, which can undergo intramolecꢀ
ular cyclization in the presence of base to form imidꢀ
azolylthiazolidines 6a—f. The latter are produced only in
the presence of electronꢀwithdrawing substituents in the
aromatic ring. The analogous compounds can be obtained
from the substituted imidazolylthiourea 8 by the reactions
with bromoacetophenones containing both electronꢀwithꢀ
drawing and electronꢀdonating substituents in the aroꢀ
matic ring.
Experimental
1
Н and 13С NMR spectra were obtained on a Bruker
AVANCE II 400 (400.00 and 100.00 MHz, respectively) instruꢀ
ment in DMSOꢀd6 using Me4Si as the internal standard. Mass
spectra were recorded on a Varian МAТꢀ311A instrument

888
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 5, May, 2011
El´tsov et al.
(EI, the energy of ionizing electrons is 70 eV). IR spectra were
recorded on a Bruker Alpha FTꢀIR spectrometer with an ATR
adapter (ZnSe crystal). TLC was performed on Silufol UVꢀ254
plates in the chloroform—ethanol (3 : 1) system, compounds on
TLC were visualized using UV light or iodine vapor.
Triethylammonium (5ꢀcarbamoylꢀ3Hꢀimidazolꢀ4ꢀyl)dithioꢀ
carbamate (2a). To a solution of 5ꢀaminoimidazole 1a (2.83 mmol)
in DMF (3 mL) and Et3N (0.83 mL, 0.60 g, 5.95 mmol), carbon
disulfide (0.2 mL, 0.25 g, 3.34 mmol) was added and the reaction
mixture was kept for 24 h with stirring at room temperature. The
mixture was diluted with chloroform (10 mL). The precipitate
that formed was filtered off and purified by recrystallization from
ethanol.
Ethyl (5ꢀcarbamoylꢀ3Hꢀimidazolꢀ4ꢀyl)dithiocarbamate (3a).
To a solution of dithiocarbamate 2a (0.495 mmol) in DMF
(1 mL), ethyl iodide (0.1 g, 0.641 mmol) was added and the reacꢀ
tion mixture was kept for 5 h at room temperature. The mixture
was diluted with chloroform (25 mL). The precipitate that formed
was filtered off and purified by recrystallization from ethanol.
Bis(4ꢀchlorophenacyl) disulfide (4a), bis(4ꢀnitrophenacyl) diꢀ
sulfide (4b) (general procedure). To a solution of 5ꢀaminoimidꢀ
azole 1a,b (1.23 mmol) in DMF (1 mL) and Et3N (0.4 mL),
carbon disulfide (0.11 mL) was added and the reaction was kept
for 24 h with stirring at room temperature. Bromoacetophenone
(0.302 g, 1.29 mmol) was added. The mixture was kept for addiꢀ
tional 1—2 h at room temperature and diluted with ice water
(25 mL). The precipitate that formed was filtered off and puriꢀ
fied by recrystallization from ethanol.
Et3N (0.14 mL) was added and the reaction mixture was kept for
2 h with stirring at room temperature. The mixture was diluted
with water (15 mL). The precipitate that formed was filtered off
and purified by recrystallization from ethanol.
5ꢀ[2ꢀOxoꢀ4ꢀphenylthiazolꢀ3ꢀyl]ꢀ1Hꢀimidazoleꢀ4ꢀcarboxꢀ
amide (6a), 5ꢀ[2ꢀoxoꢀ4ꢀ(4ꢀchlorophenyl)thiazolꢀ3ꢀyl]ꢀ1Hꢀimidꢀ
azoleꢀ4ꢀcarboxamide (6b), 5ꢀ[4ꢀ(4ꢀnitrophenyl)ꢀ2ꢀoxothiazolꢀ3ꢀ
yl]ꢀ1Hꢀimidazoleꢀ4ꢀcarboxamide (6c), 5ꢀ[2ꢀoxoꢀ4ꢀphenylthiazolꢀ
3ꢀyl]ꢀ1Hꢀimidazoleꢀ4ꢀ(Nꢀmethyl)carboxamide (6d), 5ꢀ[2ꢀoxoꢀ4ꢀ
(4ꢀchlorophenyl)thiazolꢀ3ꢀyl]ꢀ1Hꢀimidazoleꢀ4ꢀ(Nꢀmethyl)carbꢀ
oxamide (6e), 5ꢀ[4ꢀ(4ꢀnitrophenyl)ꢀ2ꢀoxothiazolꢀ3ꢀyl]ꢀ1Hꢀimidꢀ
azoleꢀ4ꢀ(Nꢀmethyl)carboxamide (6f), 5ꢀ[4ꢀ(4ꢀmethoxyphenyl)ꢀ2ꢀ
oxothiazolꢀ3ꢀyl]ꢀ1Hꢀimidazoleꢀ4ꢀcarboxamide (6g), 5ꢀ[2ꢀoxoꢀ4ꢀ
(pꢀtolyl)thiazolꢀ3ꢀyl]ꢀ1Hꢀimidazoleꢀ4ꢀcarboxamide (6h) (general
procedure A). To a solution of imidazolylthiazoline 5a,b,d,e,f,h
(0.28 mmol) in DMF (1 mL), Et3N (0.2 mL) was added and the
reaction mixture was kept for 5 (6c,f), 10 (6b,e), or 12 h (6a,d) at
60 °С. In the case of compounds 6c,f, the mixture was diluted
with water (20 mL). The precipitate that formed was filtered off.
In the case of compounds 6a,b,d,e, the reaction mixture was
concentrated and the products were purified by recrystallization
from an ethanol—acetonitrile (1 : 3) mixture.
Synthesis of compounds 6b,c,g,h (general procedure B).
A solution of compound 8 (0.42 mmol) and haloketone
(0.44 mmol) in acetonitrile (10 mL) was refluxed for 2 h. The
precipitate that formed was filtered off and recrystallized from
ethanol.
5ꢀ{[Ethylsulfanyl(phenacylsulfanyl)methylidene]amino}ꢀ1Hꢀ
imidazoleꢀ4ꢀcarboxamide (5a), 5ꢀ{[ethylsulfanylꢀ(4ꢀchlorophenꢀ
acylsulfanyl)methylidene]amino}ꢀ1Hꢀimidazoleꢀ4ꢀcarboxamide
(5b), 5ꢀ{[ethylsulfanylꢀ(4ꢀmethoxyphenacylsulfanyl)methylidene]ꢀ
amino}ꢀ1Hꢀimidazoleꢀ4ꢀcarboxamide (5c), 5ꢀ{[ethylsulfanylꢀ(4ꢀ
nitrophenacylsulfanyl)methylidene]amino}ꢀ1Hꢀimidazoleꢀ4ꢀcarꢀ
boxamide (5d), 5ꢀ{[ethylsulfanyl(phenacylsulfanyl)methylidene]ꢀ
amino}ꢀ1Hꢀimidazoleꢀ4ꢀ(Nꢀmethyl)carboxamide (5e), 5ꢀ{[ethylꢀ
sulfanylꢀ(4ꢀchlorophenacylsulfanyl)methylidene]amino}ꢀ1Hꢀimidꢀ
azoleꢀ4ꢀ(Nꢀmethyl)carboxamide (5f), 5ꢀ{[ethylsulfanylꢀ(4ꢀmethꢀ
oxyphenacylsulfanyl)methylidene]amino}ꢀ1Hꢀimidazoleꢀ4ꢀ(Nꢀ
methyl)carboxamide (5g), 5ꢀ{[ethylsulfanylꢀ(4ꢀnitrophenacylꢀ
sulfanyl)methylidene]amino}ꢀ1Hꢀimidazoleꢀ4ꢀ(Nꢀmethyl)carboxꢀ
amide (5h), 5ꢀ{[ethylsulfanylꢀ(4ꢀmethylphenacylsulfanyl)methylꢀ
idene]amino}ꢀ1Hꢀimidazoleꢀ4ꢀ(Nꢀmethyl)carboxamide (5i) (genꢀ
eral procedure). To a solution of ethyl dithiocarbamate 3a,b
(0.65 mmol) and haloketone (0.68 mmol) in DMF (1.5 mL),
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Received February 3, 2011;
in revised form March 30, 2011