Novel Method for the Synthesis of Substituted Imidazothiazolones

Article abstract of DOI:10.1055/s-0035-1560657

A general and highly selective method for the synthesis of 4-substituted 3a,6a-diphenyltetrahydro-2H-imidazo[4,5-d][1,3]thiazole-2,5(3H)-diones has been developed through a new reaction of 1-substituted 5-hydroxy-4,5-diphenyl-1H-imidazol-2(5H)-ones with p

Full text of DOI:10.1055/s-0035-1560657

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© Georg Thieme Verlag Stuttgart · New York
2015, 26, 2521–2526
letter
2521
A. N. Kravchenko et al.
Letter
Synlett
Novel Method for the Synthesis of Substituted Imidazothiazolones
Angelina N. Kravchenkoa
Ph
H
Maria M. Antonovaa
Vladimir V. Baranov*a
Yulia V. Nelyubina*b
N
S
*
O
O
*
N
N
H
KSCN, AcOH
MeOH, reflux, 1 h
H
N
HNO3, MeCN
r.t., 5 min
Ph
Ph
Ph
Ph
R
N
N
O
O
8 examples, 53–92%
Ph
a N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of
Sciences, 47 Leninsky prosp., 119991 Moscow, Russian Federation
b A. N. Nesmeyanov Institute of Organoelement Compounds,
Russian Academy of Sciences, 28 Vavilova St., 119991 Moscow,
Russian Federation
*
OH
N
H
N
H
N
Ph
R
R
*
O
S
*
N
O
ase1313@mail.ru
unelya@xrlab.ineos.ac.ru
Ph
R
Received: 10.07.2015
Accepted after revision: 10.09.2015
Published online: 01.10.2015
Me
Me
N
H
H
H
N
N
COOEt
Ph
HOOC
N
S
O O
O
DOI: 10.1055/s-0035-1560657; Art ID: st-2015-b0531-l
N
H
N
N
S
H
Abstract A general and highly selective method for the synthesis of
4-substituted 3a,6a-diphenyltetrahydro-2H-imidazo[4,5-d][1,3]thi-
azole-2,5(3H)-diones has been developed through a new reaction of
1-substituted 5-hydroxy-4,5-diphenyl-1Н-imidazol-2(5Н)-оnes with po-
tassium thiocyanate in the presence of acetic acid in acetonitrile. De-
tails of supramolecular organization in the crystalline imidazothiazolo-
nes, as revealed by X-ray diffraction, are highlighted.
Me
Me
biotin
mebicar
leucogen
Bn
O
HOOC
HN
S
Me
S
N
N
Me
Key words cyclocondensations, potassium thiocyanate, heterocycles,
polycycles, imidazolоnes, imidazothiazoles
Ph
O
N
levimasole
COOH
benzylpenicillin
Figure 1 Representative examples of drugs containing imidazolidin-2-
one or thiazole moieties
Imidazolidin-2-one and thiazole moieties are present in
several heterocyclic molecules that exhibit various biologi-
cal and pharmacological activities (Figure 1). For instance,
biotin is found in all eukaryotic cells, where it acts as a co-
factor for carboxylase enzymes such as acetyl-coenzyme A
(CoA) carboxylase, pyruvate carboxylases, propionyl-CoA
carboxylase, and 3-methylcrotonyl-CoA carboxylases.1
Mebicar {1,3,4,6-tetramethyltetrahydroimidazo[4,5-d]-
imidazole-2,5(1H,3H)-dione} is used as a tranquilizer.2 Leu-
cogen is used to vaccinate cats against feline leukemia vi-
rus.3 Levimasole, an antihelminthic drug, is used as an im-
munomodulator in rheumatoid arthritis and as an adjuvant
therapy in the treatment of colorectal cancer and head-
and-neck cancer.4 Penicillin and other penicillin-like β-lac-
tams are among the most important antibiotics for both
humans and animals.5
substituted 2H-imidazo[4,5-d]thiazoles 1–4 (Figure 2) have
been reported,6 as no general approach to their synthesis
has been developed.
Here, we propose a novel highly selective method for
the synthesis of 4-substituted 3a,6a-diphenyltetrahydro-
2H-imidazo[4,5-d][1,3]thiazole-2,5(3H)-dione (imidazothi-
azolediones) through condensation of 1-substituted 5-hy-
droxy-4,5-diphenyl-1,5-dihydro-2H-imidazol-2-ones (im-
idazolоnes) with potassium thiocyanate in the presence of
acetic acid in methanol.
Our motivation for choosing these reactions arose from
our recent synthesis of imidazoxazoles 5a–c by simple
reactions of (4S*,5R*)-1,3-dialkyl-4,5-dihydroxy-4,5-di-
phenylimidazolidin-2-(thi)ones (6а,b and 7а) with potassi-
um thiocyanate and acetic acid (Scheme 1).7 The mecha-
nism of the formation of compounds 5a–c was reported in
our previous communication.7
Therefore, the synthesis of heterocycles containing
these two moieties in the same molecule is of both synthet-
ic and practical interest. However, only few examples of
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 2521–2526

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A. N. Kravchenko et al.
Letter
Synlett
Table 1 Synthesis of 1-Substituted Imidazolones 8a–ha
O2N
H
N
S
N
S
N
*
O
Ph
Ph
*
O
NH⋅HClO4
O
N
*
*
N
H
N
H
N
NO2
HO
O2N
NO2
NH2
NH
1a
1b
11
ii
O
t-Bu
Me
O
H
R1
Me
N
S
H
N
N
S
N
*
Ph
Ph
Ph
S
N
HNO3
N
10a–e
*
*
*
S
N
N
N
t-Bu
O
O
N
*
t-Bu
OH
Me
i
N
R2
N
O
Me
Me
Me
O
Me
Me
Ph
R2
O
2a
2b
9a–h
8a–h
Ph
Ph
Ac2O
N
Ph
Ph
H
N
S
N
S
iii
*
*
*
*
N
R1
S
O
O
N
N
H
N
N
H
Ph
Ph
NH
12a–c
NH
Ph
Ph
3
4
Entry R1 (compound 10 or 12) R2 (compound 8 or 9)
Yield (%) of 8
Figure 2 Some heterocycles containing the imidazolidine and thiazole
moieties
1
2
3
4
5
6
7
8
Me (10a)
Me (8a, 9a)
88
81
83
80
90
87
72
90
Et (10b)
Et (8b, 9b)
Pr (10c)
Pr (8c, 9c)
R
R
Ph
Ph
H
N
N
Bu (10d)
Bu (8d, 9d)
OH
OH
N
KSCN, AcOH
MeOH
*
*
*
X
X
S
Bn (10e)
Bn (8e, 9e)
*
N
N
O
(CH2)2OH (12a)
(CH2)3OH (12b)
(CH2)4OH (12c)
(CH2)2OAc (8f, 9f)
(CH2)3OAc (8g, 9g)
(CH2)4OAc (8h, 9h)
Ph
Ph
R
R
5a–c
6a,b,7a
6 X = S, R = Me (a), Et (b)
7 X = O, R = Me (a)
5 X = S, R = Me (a), Et (b)
X = O, R = Me (c)
a Reaction conditions: (i) HNO3, MeCN, r.t., 5 min; (ii) 11, ethylene glycol,
165 °C, 1 h; (iii) Ac2O, CHCl3, r.t., 24 h.
Scheme 1 Synthesis of the known imidazoxazole derivatives 5a–c. Re-
agents and conditions: KSCN, AcOH, MeOH, reflux, 1 h.
Imidazolones 8a–h were prepared from the correspond-
ing imidazolinones 9а–h in 72–90% yield by treatment with
nitric acid in acetonitrile (Table 1). Note that the melting
points and NMR spectra of compounds 8а and 8е are mark-
edly different from those reported earlier by Mobinikhaledi
and Amiri.8 The structure and homogeneity of the com-
pound 8а were confirmed by 1H and 13C NMR spectroscopy,
elemental analysis, and X-ray diffraction (Figure 3). We can
therefore confirm that compounds other than 8а and 8е
were obtained by Mobinikhaledi and Amiri.8
Imidazolinones 9a–e were prepared by using a simple
approach, starting from ureas 10а–e and benzoin (2-hy-
droxy-1,2-diphenylethanone; 11) (Table 1, entries 1–5).9
Compounds 9f–h were prepared from the corresponding
imidazole oxides 12а–с (entries 6–8).10
5-Hydroxy-1-methyl-4,5-diphenyl-1,5-dihydro-2H-im-
idazol-2-one (8а) was used as a model compound to devel-
op a procedure for the synthesis of imidazothiazole 13а.
Under the conditions used for the formation of imidazoxa-
zoles 5a–c,7 condensation of potassium thiocyanate with
imidazolone 8a in the presence of acetic acid gave the
imidazothiazole 13a in 35% yield (Table 2, entry 1). Methyl
Figure 3 General view of compounds 8a (left) and 8b (right); nonhy-
drogen atoms are shown as thermal ellipsoids at the 50% probability
level
ether 1411 proved to be the second and major product of
this reaction (entry 1); complete conversion of imidazolone
8a into imidazothiazole 13а occurred only after five hours
(entry 2). An attempt to synthesize imidazothiazole 13а
from 4,5-dihydroxy-1-methyl-4,5-diphenylimidazolidin-2-
one (15)11 and potassium thiocyanate under the same con-
ditions (AcOH, MeOH, reflux, 1 h) resulted in the formation
of imidazothiazole 13a and methyl ether 14 in 15% and 80%
yields, respectively (entry 3). However, conversion of the
compound 15 into imidazothiazole 13а was complete after
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 2521–2526

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A. N. Kravchenko et al.
Letter
Synlett
Table 2 Optimization of Reaction Conditions for the Synthesis of Imidazothiazole 13а
KSCN, AcOH
(b,c)
KSCN, AcOH
(b,c)
Ph
OMe
KSCN
AcOH
Ph
Ph
KSCN
AcOH
H
N
H
N
Ph
S
N
N
N
N
OH
OH
*
*
O
O
O
O
O
*
*
*
*
OH
(a)
(a)
N
N
N
H
Ph
Ph
Ph
Ph
Me
Me
Me
Me
8a
13a
14
15
KSCN, AcOH
(b,d)
Entry
Reactant
Conditions
Yield (%) of 13a
1
2
3
4
5
6
7
8
8a
8a
15
15
14
8a
15
14
(a) MeOH, reflux, 1 h
(b) MeOH, reflux, 5 h
(a) MeOH, reflux, 1 h
(b) MeOH, reflux, 5 h
(b) MeOH, reflux, 5 h
(c) MeCN, reflux, 1 h
(c) MeCN, reflux, 1 h
(d) MeCN, reflux, 2 h
35a
85
15b
87
89
92
92
90
a A 60% yield of 14 was also obtained.
b An 80% yield of 14 was also obtained.
five hours (entry 4); this can be explained by the initial for-
mation of methyl ether 14 as a first stage in the reaction of
imidazolone 8a or imidazolidinone 15 with potassium thio-
cyanate in the presence of acetic acid in methanol; ether 14
then reacts with further potassium thiocyanate in the pres-
ence of acetic acid to give imidazothiazole 13a. This hy-
pothesis was confirmed by preparing imidazothiazole 13а
in 89% yield by condensation of methyl ether 14 with potas-
sium thiocyanate in the presence of acetic acid under the
same conditions (entry 5).
and highly selective method for the preparation of previ-
ously inaccessible imidazothiazoles 13b–h in 53–88%
yields.
Table 3 Synthesis of Imidazothiazoles 13b–ha
KSCN
Ph
H
Ph
N
N
N
S
AcOH
*
O
O
O
OH
*
*
MeCN
N
N
H
reflux, 1 h
Ph
Ph
R
R
To optimize the procedure for the synthesis of imidazo-
thiazole 13а, acetonitrile was chosen as a solvent instead of
methanol. The duration of the reactions of the compounds
8а and 15 with potassium thiocyanate in the presence of
acetic acid was reduced from five hours to one hour, and
the yield of imidazothiazole 13а increased from 85–87% to
92% (Table 2; compare entries 2 and 4 with entries 6 and 7).
The reactivity of methyl ether 14 under similar conditions
was lower; the reactions of the compound 14 in acetonitrile
took two hours (entry 8). Our experiments showed that the
similar results were obtained using the imidazolone 8a and
dihydroxyimidazolidinone 15.
13b–h
8b–h
Entry
R
Yield (%)
1
2
3
4
5
6
7
Et
Pr
74
88
80
85
53
57
79
Bu
Bn
(CH2)2OAc
(CH2)3OAc
(CH2)4OAc
a Reagents and conditions: MeCN, reflux, 1 h.
With the optimized conditions in hand, we examined
reactions of various imidazolones 8b–h with potassium
thiocyanate in the presence of acetic acid in acetonitrile
(Table 3, entries 1–7).12 A detailed investigation of these
condensations confirmed that we have developed a new
We propose the following mechanism for the formation
of imidazothiazole 13a (Scheme 2). The first step in the re-
action of imidazolone 8а, 14, or 15 with potassium thiocya-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 2521–2526

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A. N. Kravchenko et al.
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Synlett
nate in the presence of acetic acid is the formation of a cat-
ion 16, which reacts with a thiocyanate anion as an N-nu-
cleophile to give adduct 17. Hydrolysis of the
isothiocyanate fragment gives adduct 18, which undergoes
intramolecular cyclization to form imidazothiazole 13a. De-
hydration of the compound 15 might proceed directly, with
the formation of the cation 16, or via the intermediate 8a or
14, depending on the nature of the solvent.
ecules are assembled with O–H···O hydrogen bonds [O···O
2.6706(16)–2.701(2) Å, OHO 164(1)–175(1)°] to form hy-
drogen-bonded tetramers around the –4 axis.
The homogeneity of the compound 8a was confirmed
by powder X-ray diffraction (Table S1 and Figure S1, see
Supporting Information). The structures of the imidazothi-
azoles 13a–h were confirmed by X-ray diffraction studies
on compounds 13c and 13d (Figure 4), which have similar
molecular geometries and supramolecular organizations in
their crystals. In both cases, the thiazole and imidazole
moieties have an envelope conformation in which the devi-
ation of atoms C(3) and C(1) is 0.35(1)–0.39(1) Å. The angle
between the mean planes of the heterocycles and the tor-
sion angle C(5)C(1)C(3)C(11) characterizing the mutual dis-
position of the phenyl substituents are within the narrow
ranges 107.2(1)–109.7(1)° and 23.02(19)–30.27(19)°, re-
spectively. Note that the imidazothiazole 13c crystallizes
with four independent molecules in an asymmetric part of
the unit cell. If these molecules are overlapped, the hetero-
cyclic moieties coincide nicely, but the alkyl chains do not;
the relevant pseudo-torsion angle С(3)N(3)C(18)C(19) for
one of these is 41.22(1)° versus 60.65(1)–61.68(1)° for the
others. In crystals of 13c and 13d, similar hydrogen-bonded
chains are formed through N–H···O hydrogen bonds [N···O
2.766(2)–3.009(2) Å, NHO 148(1)–178(1)°]; the corre-
sponding features in 13c involve all four of its independent
molecules. In these chains (Figure 5), the imidazothiazole
molecules are either related by an inversion center (13d) or
arranged in a ‘head-to-tail’ mode (13c); in the latter case,
the symmetry-equivalent species from the neighboring
chains form dimers through weak C–H···O contacts, result-
ing in centrosymmetric crystal structures (space group P-
1).
MeOH
– H2O
Ph
H
H
H
H
Ph
Ph
N
N
N
N
N
MeCN
MeOH
OH
OH
*
*
O
O
O
*
OMe
*
OH
– H2O
– 2 H2O
N
Ph
Ph
Ph
8a
Me
Me
Me
15
14
– 2H2O
Ph
H
N
H
H
O
– MeOH
– H2O
N
Ph
Me
16
NCS
S
Ph
C
N
N
H2O
O
*
N
Ph
17
Me
Ph
H
Ph
NH
N
N
N
S
*
O
O
O
*
*
N
N
H
O
Ph
HS
Ph
Me
Me
13a
18
Scheme 2 Proposed mechanisms for the formation of imidazothiazole
13a
The structures of imidazolones 8а–h and imidazothi-
azoles 13a–h were confirmed by 1H and 13C NMR spectros-
copy, and by X-ray diffraction studies on compounds 8a,b
and 13c,d (Figures 3 and 4). The X-ray diffraction results
(CCDC 1011396–1011397 and 1011495–1011496; Table
S1; see Supporting Information) showed that compounds
8a and 8b (Figure 3) are isostructural and that they crystal-
lize in a noncentrosymmetric space group (P-421 c); their
molecular geometries and supramolecular patterns are
very similar. In both cases, the imidazolone ring is planar
within 0.01 Å. The angle between its mean plane and that
of the phenyl substituent at the atom C(5) is 9.4(1)–
11.9(1)°, and the torsion angle C(6)C(4)C(5)C(12) character-
izing the mutual disposition of the two phenyl substituents
is 63.4(3)–68.70(18)°. In the crystals, the imidazolone mol-
Figure 4 General view of compounds 13c (left) and 13d (right); non-
hydrogen atoms are shown as thermal ellipsoids at the 50% probability
level
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A. N. Kravchenko et al.
Letter
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(3) Langhammer, S.; Fiebig, U.; Kurth, R.; Denner, J. Intervirology
2011, 54, 78.
(4) (a) Hess, C.; Ritke, N.; Broecker, S.; Madea, B.; Musshoff, F. Anal.
Bioanal. Chem. 2013, 405, 4077. (b) Hess, C.; Ritke, N.; Sydow, K.;
Mehling, L.-M.; Ruehs, H.; Madea, B.; Musshoff, F. Drug Test.
Anal. 2014, 6, 1049.
(5) (a) Moulin, G.; Cavalié, P.; Pellanne, I.; Chevance, A.; Laval, A.;
Millemann, Y.; Colin, P.; Chauvin, C. J. Antimicrob. Chemother.
2008, 62, 617. (b) Peterson, J. W.; Petrasky, L. J.; Seymour, M. D.;
Burkhart, R. S.; Schuiling, A. B. Chemosphere 2012, 87, 911.
(6) (a) Petersen, H. Synthesis 1973, 243. (b) Duspara, P. A.; Matta, C.
F.; Jenkins, S. I.; Harrison, P. H. M. Org. Lett. 2001, 3, 495.
(c) Schantl, J. G.; Lagoja, I. M. Heterocycles 1998, 48, 929.
(7) Baranov, V. V.; Kravchenko, A. N.; Nelyubina, Yu. V. Mendeleev
Commun. 2014, 24, 105.
(8) Mobinikhaledi, A.; Amiri, A. K. J. Chem. Sci. (Berlin, Ger.) 2013,
125, 1055.
(9) Baranov, V. V.; Antonova, M. M.; Nelyubina, Yu. V.; Kolotyrkina,
N. G.; Zanin, I. E.; Kravchenko, A. N. Mendeleev Commun. 2014,
24, 173.
(10) (a) Antonova, M. M.; Baranov, V. V.; Nelyubina, Yu. V.;
Kravchenko, A. N. Chem. Heterocycl. Compd. (Hoboken, NJ U. S.)
2014, 50, 503. (b) Jasiński, M.; Mlostoń, G.; Mucha, P.; Linden,
A.; Heimgartner, H. Helv. Chim. Acta 2007, 90, 1765.
(11) Biltz, H. Justus Liebigs Ann. Chem. 1909, 368, 156.
Figure 5 Hydrogen-bonded chains in crystals of 13с (top) and 13d
(bottom)
(12) 1-Substituted
5-Hydroxy-4,5-diphenyl-1,5-dihydro-2H-
imidazol-2-ones 8a–h; General Procedure
63% aq HNO3 (5 mL) was added dropwise to a suspension of the
appropriate imidazolone 9a–h (4 mmol) in MeCN (25 mL). The
reaction was monitored by the dissolution of the precipitated
9a–h and by the change in color of the solution. The mixture
was then extracted with 1:1 CHCl3/H2O, the CHCl3 layer was
evaporated, and the product was washed with Et2O.
In summary, we have developed a general method for
the synthesis of 1-substituted 5-hydroxy-4,5-diphenyl-1Н-
imidazol-2(5Н)-ones through the reaction of 1-substituted
5-hydroxy-1Н-imidazol-2(5Н)-ones with potassium thio-
cyanate in the presence of acetic acid. The desired com-
pounds were obtained in good to excellent yields from easi-
ly available starting materials. Further investigations on ex-
tending this approach to other imidazoline derivatives, as
well as studies on their pharmacological applications, are
currently in progress.
5-Hydroxy-1-methyl-4,5-diphenyl-1,5-dihydro-2H-imidazol-
2-one (8a)
White powder; yield: 0.94 g (88%); mp 222–224 °С. 1H NMR
(300 MHz, DMSO-d6): δ = 2.55 (s, 3 H, Me), 7.25–7.48 (m, 7 H,
Ph), 7.52–7.56 (m, 1 H, Ph), 7.75 (s, 1 H, OH), 8.01–8.04 (m, 2 H,
Ph). 13C NMR (75 MHz, DMSO-d6): δ = 23.82 (Me), 92.61
[С(Ph)OH], 125.18, 128.75, 128.83, 129.05, 129.60, 133.35,
136.61 (Ph), 163.44 (C=O), 186.39 (C=N). MS: m/z (%) = 266 (6)
[M+], 250 (61), 180 (13), 163 (56), 135 (53), 134 (56), 118 (100).
Anal. Calcd for C16H14N2O2: C, 72.16; H, 5.30; N, 10.52. Found: C,
72.07; H, 5.34; N 10.47.
Acknowledgment
This work was supported by grants 14-03-00556 and 14-03-31676
from the Russian Foundation for Basic Research.
1-Ethyl-5-hydroxy-4,5-diphenyl-1,5-dihydro-2H-imidazol-2-
one (8b)
White powder; yield: 0.91 g (81%); mp 214–216 °С. 1H NMR
(300 MHz, DMSO-d6): δ = 0.88 (t, J = 7.1 Hz, 3 H, Me), 2.87–3.04
(m, 1 H, СH2), 3.13–3.30 (m, 1 H, CH2), 7.25–7.50 (m, 7 H, Ph),
7.53–7.57 (m, 1 H, Ph), 7.73 (s, 1 H, OH), 7.99–8.02 (m, 2 H, Ph).
13C NMR (50 MHz, DMSO-d6): δ = 13.79 (Me), 33.58 (CH2), 92.81
[С(Ph)OH], 125.20, 128.75, 128.82, 128.97, 129.65, 133.32,
137.32 (Ph), 163.38 (C=O), 186.07 (C=N). MS: m/z (%) = 280 (13)
[M+], 252 (3), 208 (4), 177 (50), 165 (8), 148 (75), 134 (35), 105
(75), 91 (7), 77 (100). Anal. Calcd for C17H16N2O2: C, 72.84; H,
5.75; N, 9.99. Found: C, 72.79; H, 5.78; N, 10.06.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1560657.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
ortioInfgrmoaitn
References and Notes
(1) Ahmed, R.; Spikings, E.; Zhou, S.; Thompsett, A.; Zhang, T.
J. Immunol. Methods 2014, 406, 143.
(2) (a) Kamburg, R. US 20080227838, 2008; Chem. Abstr. 2008, 149,
347537 (b) Ryzhkina, I. S.; Kiseleva, Y. V.; Mishina, O. A.;
Timosheva, A. P.; Sergeeva, S. Y.; Kravchenko, A. N.; Konovalov,
A. I. Mendeleev Commun. 2013, 23, 262.
4-Substituted
3a,6a-Diphenyltetrahydro-2H-imidazo[4,5-
d][1,3]thiazole-2,5(3H)-diones 13a–h; General Procedure
AcOH (3.00 mL) was added to a solution of the appropriate
imidazolone 8a–h (4 mmol) and KSCN (0.44 g, 4.5 mmol) in
MeCN (17 mL) at r.t., and the mixture was refluxed for 1 h. The
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 2521–2526

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A. N. Kravchenko et al.
Letter
Synlett
mixture was allowed to cool to r.t. and kept for 24 h to give a
precipitate.
(3aR*,6aR*)-4-Methyl-3a,6a-diphenyltetrahydro-2H-imid-
azo[4,5-d][1,3]thiazole-2,5(3H)-dione (13a)
(3aR*,6aR*)-4-Ethyl-3a,6a-diphenyltetrahydro-2H-imid-
azo[4,5-d][1,3]thiazole-2,5(3H)-dione (13b)
White powder; yield: 1.22 g (74%); mp 235–237 °С. 1H NMR
(300 MHz, DMSO-d6): δ = 1.12 (t, J = 7.0 Hz, 3 H, Me), 2.71–2.91
(m, 1 H, CH2), 3.31–3.50 (m, 1 H, CH2), 6.90–7.01 (m, 2 H, Ph),
7.02–7.19 (m, 6 H, Ph), 7.20–7.31 (m, 2 H, Ph), 8.20 [s, 1 H,
NH(NCO)], 9.65 [s, 1 H, NH(SCO)]. 13C NMR (75 MHz, DMSO-d6):
δ = 14.80 (Me), 35.15 (CH2), 83.81, 87.80 [(Ph)–C–C–(Ph)],
126.95, 127.47, 127.51, 127.84, 128.14, 128.65 (Ph), 133.87,
137.49 [C(Ph)], 158.42 [(N)C=O], 172.27 [(S)C=O]. HRMS: m/z [M
+ H]+ calcd for C18H18N3O2S: 340.1114; found: 340.1110.
White powder; yield: 1.20 g (92%); mp >300 °С. 1H NMR (300
MHz, DMSO-d6): δ = 2.64 (s, 3 H, Me), 6.85–6.98 (m, 2 H, Ph),
7.01–7.17 (m, 6 H, Ph), 7.18–7.28 (m, 2 H, Ph), 8.35 [s, 1 H,
NH(NCO)], 9.72 [s, 1 H, NH(SCO)]. 13C NMR (75 MHz, DMSO-d6):
δ = 25.73 (Me), 83.19, 87.52 [(Ph)–C–C–(Ph)], 126.93, 127.49,
127.57, 128.07, 128.18, 128.71 (Ph), 132.92, 137.51 [C(Ph)],
158.38 [(N)C=O], 171.91 [(S)C=O]. HRMS: m/z [M + H]+ calcd for
C17H16N3O2S: 326.0958; found: 326.0958.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 2521–2526