Reaction of 1-Alkyl(aryl)-5-alkyl(aryl)amino-2-oxo-2,3-dihydro-1H- imidazole-4-carbonitriles with Lawesson's reagent

Article abstract of DOI:10.1134/S1070363212070055

The reaction of substituted 2-oxo-2,3-dihydro-1H-imidazole-4-carbonitriles with Lawesson's reagent gave new compounds of the fused imidazo[4,5-d][1,3,2] diazaphosphinine system. Pleiades Publishing, Ltd., 2012.

Full text of DOI:10.1134/S1070363212070055

ISSN 1070-3632, Russian Journal of General Chemistry, 2012, Vol. 82, No. 7, pp. 1219–1223. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © S.A. Chumachenko, O.V. Shablykin, A.N. Vasilenko, V.S. Brovarets, 2012, published in Zhurnal Obshchei Khimii, 2012, Vol. 82,
No. 7, pp. 1100–1104.
Reaction of 1-Alkyl(aryl)-5-alkyl(aryl)amino-2-oxo-2,3-dihydro-
1H-imidazole-4-carbonitriles with Lawesson’s Reagent
S. A. Chumachenko, O. V. Shablykin, A. N. Vasilenko, and V. S. Brovarets
Institute of Bioorganic and Petroleum Chemistry, National Academy of Sciences of Ukraine,
ul. Murmanskaya 1, Kiev, 02660 Ukraine
e-mail: brovarets@bpci.kiev.ua
Received May 23, 2011
Abstract—The reaction of substituted 2-oxo-2,3-dihydro-1H-imidazole-4-carbonitriles with Lawesson’s reagent
gave new compounds of the fused imidazo[4,5-d][1,3,2]diazaphosphinine system.
DOI: 10.1134/S1070363212070055
We previously described a simple and convenient
procedure for the synthesis of 1-alkyl(aryl)-5-alkyl-
(aryl)amino-2-oxo-2,3-dihydro-1H-imidazole-4-carbo-
nitriles I [1] on the basis of accessible acrylonitrile
derivatives [2]. These compounds have already found
wide application in the syntheses of many other
heterocyclic systems [3–10]. In the present work we
studied the reaction of substituted imidazol-2-ones I
with Lawesson’s reagent (II) which is known as mild
and efficient sulfurizing agent. We found that heating
of compounds I and II in toluene over a period of 3 h
yields imidazodiazaphosphinines V rather than their
thio derivatives VI (Scheme 1).
It should be noted that even fourfold excess of
Lawesson’s reagent very slowly replaces the oxo group
in the imidazole fragment by thioxo. After prolonged
(~10 h) heating of the reaction mixture, we succeeded
in detecting only ~4% of thioxo analog VI by GC–MS.
Several examples of sulfurization of imidazolones and
their analogs with Lawesson’s reagent have been
reported [11–13]; on the other hand, in same cases the
Scheme 1.
H
N
H
N
P
S
C
CN
S
S
SH
S
N
N
toluene
+ R'
P
R'
O
O
P
Δ, 3 h
N
R
N
R
NH
R
R'
S
R
Ia_Ie
II
III
H
H
H
S
S
NH
N
N
N
NH
P
NH
P
S
P
S
S
S
O
S
O
N
R
N
R
N
R
N
R
N
R
N
R
R'
R'
R'
Va_Ve (35_58%)
VI
IV
I, V: R = PhCH2 (a), PhCH2CH2 (b), Ph (c),4-MeC6H4 (d), 4-MeOC6H4 (e); R' = 4-MeOC6H4.
1219

1220
CHUMACHENKO et al.
HMBC
NOESY
Fig. 1. Principal correlations (shown with arrows) and signal assignment (δ, δC, ppm) in the H and 13C NMR spectra of compound
1
Ia.
HMBC
NOESY
31P–13C and 31P–1H spin–spin interaction
1
Fig. 2. Principal correlations (shown with arrows) and signal assignment (δ, δC, ppm) in the H and 13C NMR spectra of compound
Va.
carbonyl group was resistant to that reagent [14–17].
The use of a more potent sulfurizing agent, phosphorus
pentasulfide, in the reaction with imidazolones I
resulted in the formation of a complex mixture of pro-
ducts which we failed to isolate and identify.
Va–Ve are likely to be formed via phosphorylation of
the nitrogen atom to give derivative III and its sub-
sequent cyclization as a result of addition of the HS frag-
ment at the cyano group. Intermediates IV thus formed
undergo fast rearrangement into final products V.
Compounds Va–Ve are new representatives of al-
ready known imidazodiazaphosphinine system [18, 19].
By analogy with the data of [20], where the formation
of diazaphosphinine ring from β-aminonitrile fragment
and Lawesson’s reagent was described, compounds
The structure of Va–Ve was confirmed by their
elemental compositions and mass, IR, and NMR
spectra. In the IR spectra of Va–Ve, as well as in the
spectra of initial compounds Ia–Ie, we observed strong
carbonyl absorption in the region 1715–1724 cm–1.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 7 2012

REACTION OF 1-ALKYL(ARYL)-5-ALKYL(ARYL)AMINO-2-OXO-2,3-DIHYDRO-...
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Table 1. Correlations found in the COSY, NOESY, HSQC, and HMBC spectra of compound Iaa
1H, δ, ppm
13C, δС, ppm
1H, δ, ppm
COSY
7.36
NOESY
7.36, 4.87
7.23, 7.27
7.36
HSQC
127.62
129.12
128.00
42.96
46.55
–
HMBC
7.23
7.36
7.27
4.87
4.41
7.24
7.17
7.32
7.28
128.00, 127.62, 42.96
129.12, 137.28
127.62
7.23, 7.27
7.36
–
7.23, 7.24
7.24, 7.17
4.41, 4.87
7.32, 4.41
7.17, 7.28
7.32
137.28, 127.62, 150.61, 144.06
139.15, 127.53, 144.06
68.57
7.24
4.41
7.32
127.53
128.93
127.75
127.53, 127.75, 46.55
128.93, 139.15
7.17, 7.28
7.32
127.53
a
For signal assignment, see Fig. 1.
Table 2. Correlations found in the COSY, NOESY, HSQC, and HMBC spectra of compound Vaa
1H, δ, ppm
13C, δС, ppm
1H, δ, ppm
COSY
–
NOESY
HSQC
–
HMBC
10.74
11.31
5.13
4.73
5.49
4.86
7.14
6.84
3.79
7.23
7.29
7.28
7.16
7.33
7.40
–
–
116.80, 131.45, 151.42
–
–
116.80
4.73
5.13
4.86
5.49
6.84
7.14
–
4.73, 7.16
44.89
44.89
50.39
50.39
131.11
114.87
55.52
129.30
127.52
128.42
127.86
129.09
128.40
151.42, 136.18, 131.45, 127.86
5.13, 7.16, 7.23
4.86, 7.23
5.49, 7.16, 7.23
6.84
151.42, 136.18, 127.86
–
–
131.11, 162.66
114.87, 125.35
114.87
7.14
6.84
7.29
7.23, 7.28
7.29
7.33
7.16, 7.40
7.33
7.29, 4.86, 4.73
7.23, 7.28
7.29
129.30, 50.39, 128.42
127.52
129.30
7.33, 4.86, 4.73
7.16, 7.40
7.33
127.86, 128.40, 44.89
129.09
127.86
a
For signal assignment, see Fig. 2.
Their 13C NMR spectra characteristically displayed a
signal at δc 150.73–151.42 ppm (cf. δC 150.61 for Ia;
Figs. 1, 2; see Experimental). These findings indicate
that the imidazolone fragment does not change during
the transformation. The formation of diazaphosphinine
ring follows from the 1H NMR spectra. The N3H signal
in the spectra of Va–Ve is split due to coupling with
the phosphorus nucleus (2JHP = 14.0–15.0 Hz), and
protons in the methylene group on N1 in compounds
Va and Vb appear as multiplets due to additional
coupling with the phosphorus nucleus. However, the
formation of imidazodiazaphosphinine system was
unambiguously proved by two-dimensional homo- and
heteronuclear (NOESY, COSY, HSQC, HMBC) NMR
experiments performed for compounds Ia and Va. The
1
principal correlations and assignments of H and 13C
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 7 2012

1222
CHUMACHENKO et al.
signals are shown in Figs. 1 and 2, and their complete
list is presented in Tables 1 and 2, respectively. The
presence of the following cross peaks in the HMBC
spectrum of Va (Fig. 2) casts no doubts on the assumed
structure (δ, δC, ppm): N5H (10.74)–C4a (116.80), N3H
(11.31)–C4a (116.80), N7CH2 (5.13, 4.73)–C6 (151.42),
N7CH2 (5.13, 4.73)–C7a (131.45), N5H (10.74)–C7a
(131.45). The information obtained from the two-
dimensional spectra is supplemented by the 31P–13C
spin–spin coupling constants: (S)C4 J = 7.0 Hz; C4a,
J = 8.7 Hz; C7a, J 5.0 Hz.
diazaphosphinin-6-one 2-sulfides Va–Ve (general
procedure). Compound Ia–Ie, 10 mmol, was dispersed
in 50 ml of toluene, 7 mmol of Lawesson’s reagent
was added, and the mixture was heated for 3 h under
reflux. The mixture was cooled, the solvent was re-
moved under reduced pressure, the residue was treated
with 10 ml of ethyl acetate, and the precipitate was
filtered off, washed first with ethyl acetate (2×10 ml)
and then with diethyl ether (20 ml), and recrystallized
from ethyl acetate.
1,7-Dibenzyl-2-(4-methoxyphenyl)-4-thioxo-
1,2,3,4,5,7-hexahydro-6H-imidazo[4,5-d][1,3,2λ5]-
diazaphosphinin-6-one 2-sulfide (Va). Yield 55%,
mp 127–129°C. IR spectrum, ν, cm–1: 1722 (C=O),
EXPERIMENTAL
The IR spectra were recorded in KBr on a Bruker
1
3226 (NH). The H and 13C NMR data are given in
1
Vertex 70 spectrometer. The H, 13C, and 31P NMR
Table 2. 31P NMR spectrum: δP 58.5 ppm. Found, %: C
59.14; H 4.72; N 11.17; P 6.00; S 12.84. m/z 505, 507
[M]+. C25H23N4O2PS2. Calculated, %: C 59.27; H 4.58;
N 11.06; P 6.11; S 12.66. M 506.
spectra were measured on a Bruker Avance DRX-500
instrument at 500.07, 125.76, and 202.43 MHz,
respectively, from solutions in DMSO-d6; the chemical
shifts are given relative to tetramethylsilane (1H, 13C,
internal reference) or 85% phosphoric acid (external
reference). The mass spectra were run on an Agilent
1100 Series high-performance liquid chromatograph
(diode array) coupled with an Agilent LC\MSD SL
mass-selective detector [4.6×15-mm Zorbax SB-C18
column, grain size 1.8 μm, PN 821975–932; liquid
phases: acetonitrile–water (95:5 + 0.1% of trifluoro-
acetic acid (A), 0.1% aqueous trifluoroacetic acid (B);
flow rate 3 ml/min; injection volume 1 μl; UV
detectors, λ 215, 254, 285 nm; atmospheric pressure
chemical ionization, amu range 80–1000]. The melting
points were determined on a Fisher–Johns melting
point apparatus.
2-(4-Methoxyphenyl)-4-thioxo-1,7-bis(2-phenyl-
ethyl)-1,2,3,4,5,7-hexahydro-6H-imidazo[4,5-d]-
[1,3,2λ5]diazaphosphinin-6-one 2-sulfide (Vb). Yield
38%, mp 185–187°C. IR spectrum, ν, cm–1: 1719
1
(C=O), 3269 (NH). H NMR spectrum, δ, ppm: 2.61–
2.64 m (1H, CH2), 2.90–2.93 m (1H, CH2), 2.97 m
(2H, CH2), 3.71 m (1H, CH2), 3.77 s (3H, CH3), 3.88–
3.94 m (1H, CH2), 4.02 m (1H, CH2), 4.45 m (1H,
CH2), 6.86 m (2H, Harom), 7.03–7.29 m (10H, Harom),
7.60 m (2H, Harom), 10.51 s (1H, NH), 11.09 d (1H,
2
NH, JHP = 15.0 Hz). 13C NMR spectrum, δC, ppm:
34.09, 36.41, 43.06, 49.01, 55.96, 114.89, 115.01,
116.28, 116.35, 125.12, 126.22, 126.96, 127.10,
128.81, 128.94, 129.00, 129.08, 131.51, 131.63,
131.72, 131.76, 137.94, 137.96, 150.97, 162.95,
162.98, 179.63, 179.73. 31P NMR spectrum: δP 56.3
ppm. Found, %: C 60.48; H 5.01; N 10.62; P 5.89;
S.78. m/z 533, 535 [M]+. C27H27N4O2PS2. Calculated,
%: C 60.66; H 5.09; N 10.48; P 5.79; S.99. M 534.
1-Alkyl(aryl)-5-alkyl(aryl)amino-2-oxo-2,3-dihydro-
1H-imidazole-4-carbonitriles Ia–Id were reported
previusly [1].
1-(4-Methoxyphenyl)-5-(4-methoxyphenylamino)-
2-oxo-2,3-dihydro-1H-imidazole-4-carbonitrile (Ie)
was synthesized as described in [1] for compounds Ia–
Id. Yield 72%, mp 205–207°C (from benzene). IR
spectrum, ν, cm–1: 1711 (C=O), 2209 (CN), 3264–3325
2-(4-Methoxyphenyl)-4-thioxo-1,7-diphenyl-
1,2,3,4,5,7-hexahydro-6H-imidazo[4,5-d][1,3,2λ5]-
diazaphosphinin-6-one 2-sulfide (Vc). Yield 35%,
mp 155–157°C. IR spectrum, ν, cm–1: 1715 (C=O,
band with a shoulder), 3125 (NH). 1H NMR spectrum,
δ, ppm: 3.84 s (3H, CH3), 6.89 m (2H, Harom), 7.01 m
(5H, Harom), 7.17 m (5H, Harom), 7.81 m (2H, Harom),
10.96 s (1H, NH), 11.25 br.s (1H, NH). 13C NMR
spectrum, δC, ppm: 56.05, 114.99, 115.11, 115.40,
115.46, 123.54, 124.64, 127.75, 127.84, 128.58,
128.73, 128.92, 129.15, 131.07, 132.43, 132.56,
132.68, 136.45, 150.73, 163.29, 163.31, 179.26. 31P
1
(NH). H NMR spectrum, δ, ppm: 3.69 s (3H, CH3),
3.77 s (3H, CH3), 6.79 d and 6.92 d (2H each, Harom
,
3JHH = 8.5 Hz), 7.00 d and 7.28 d (2H each, C6H4, 3JHH
=
8.5 Hz), 7.91 s (1H, NH), 10.61 s (1H, NH). Found, %:
C 64.11; H 4.61; N 16.78. m/z 335, 337 [M]+.
C18H16N4O3. Calculated, %: C 64.28; H 4.79; N 16.66.
M 336.
1,7-Dialkyl(diaryl)-4-thioxo-2-(4-methoxyphenyl)-
1,2,3,4,5,7-hexahydro-6H-imidazo[4,5-d][1,3,2λ5]-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 7 2012

REACTION OF 1-ALKYL(ARYL)-5-ALKYL(ARYL)AMINO-2-OXO-2,3-DIHYDRO-...
1223
3. Brovarets, V.S., Pil’o, S.G., Chernega, A.N.,
Romanenko, E.A., and Drach, B.S., Russ. J. Gen.
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4. Pil’o, S.G., Brovarets, V.S., Vinogradova, T.K.,
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2004, vol. 15, no. 6, p. 454.
6. Popil’nichenko, S.V., Brovarets, V.S., Chernega, A.N.,
Poltorak, D.V., and Drach, B.S., Heteroatom Chem.,
2006, vol. 17, no. 4, p. 411.
NMR spectrum: δP 56.4 ppm. Found, %: C 57.65; N
3.87; N 11.84; P 6.62; S 13.55. m/z 477, 479 [M]+.
S23N19N4O2PS2. Calculated, %: C 57.73; N 4.00; N
11.71; P 6.47; S 13.40. M 478.
2-(4-Methoxyphenyl)-1,7-bis(4-methylphenyl)-4-
thioxo-1,2,3,4,5,7-hexahydro-6H-imidazo[4,5-d]-
[1,3,2λ5]diazaphosphinin-6-one 2-sulfide (Vd). Yield
43%, mp 148–150°C. IR spectrum, ν, cm–1: 1724
1
(C=O), 3192 (NH). H NMR spectrum, δ, ppm: 2.14 s
(3H, CH3), 2.21 s (3H, CH3), 3.84 s (3H, CH3), 6.71 d
3
(2H, Harom, JHH = 7.5 Hz), 6.83 m (4H, Harom), 6.67 d
3
(2H, Harom, JHH = 7.5 Hz), 7.14 m (2H, Harom), 7.78 m
7. Shablykin, O.V., Brovarets, V.S., and Drach, B.S., Russ.
(2H, Harom), 10.80 s (1H, NH), 11.10 d (1H, NH, 2JHP
=
J. Gen. Chem., 2007, vol. 77, no. 5, p. 936.
14.5 Hz). 13C NMR spectrum, δC, ppm: 21.25, 21.54,
56.04, 114.94, 115.07, 115.11, 121.14, 121.43, 123.75,
124.84, 125.80, 127.77, 128.69, 129.38, 129.51,
129.94, 131.66, 131.71, 132.53, 132.64, 137.34,
137.83, 138.26, 150.87, 163.25, 163.28, 178.90,
178.96. 31P NMR spectrum: δP 56.5 ppm. Found, %: C
59.09; H 4.49; N 11.15; P 6.02; S 12.78. m/z 505, 507
[M]+. C25H23N4O2PS2. Calculated, %: C 59.27; H 4.58;
N 11.06; P 6.11; S 12.66. M 506.
8. Shablykin, O.V., Gakh, A.A., Brovarets, V.S., Rusa-
nov, E.B., and Drach, B.S., Heteroatom Chem., 2008,
vol. 19, no. 5, p. 506.
9. Kozachenko, A.P., Shablykin, O.V., Rusanov, E.B.,
Vasilenko, A.N., and Brovarets, V.S., Russ. J. Gen.
Chem., 2009, vol. 79, no. 5, p. 996.
10. Kozachenko, A.P., Shablykin, O.V., Vasilenko, A.N.,
and Brovarets, V.S., Russ. J. Gen. Chem., 2010, vol. 80,
no. 1, p. 127.
11. Costi, R., Di Santo, R., Artico, M., and Massa, S., J.
1,2,7-Tris(4-methoxyphenyl)-4-thioxo-1,2,3,4,5,7-
hexahydro-6H-imidazo[4,5-d][1,3,2λ5]diazaphos-
phinin-6-one 2-sulfide (Ve). Yield 58%, mp 230–232°
C (decomp.). IR spectrum, ν, cm–1: 1721 (C=O), 3065
Heterocycl. Chem., 2002, vol. 39, no. 1, p. 81.
12. Zhang, P., Terefenko, E., Kern, J., Fensome, A.,
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1
(NH). H NMR spectrum, δ, ppm: 3.64 s (3H, CH3),
3.69 s (3H, CH3), 3.84 s (3H, CH3), 6.60 d (2H, Harom
,
3JHH = 7.5 Hz), 6.74 m (4H, Harom), 6.86 d (2H, Harom
,
3JHH = 7.5 Hz), 7.15 m (2H, Harom), 7.78 m (2H, Harom),
2
10.83 s (1H, NH), 11.12 d (1H, NH, JHP = 14.0 Hz).
13C NMR spectrum, δC, ppm: 55.77, 55.87, 55.99,
114.18, 114.36, 114.43, 114.49, 114.86, 114.99,
115.15, 123.74, 124.84, 125.11, 126.55, 128.72,
129.44, 130.29, 130.33, 132.37, 132.55, 132.66,
151.00, 158.73, 159.30, 159.66, 163.19, 163.21,
178.35, 178.41. 31P NMR spectrum: δP 56.9 ppm.
Found, %: C 55.65; H 4.49; N 10.27; P 5.61; S 12.09.
m/z 537, 539 [M]+. C25H23N4O4PS2. Calculated, %: C
55.75; H 4.30; N 10.40; P 5.75; S 11.91. M 538.
14. Schaefer, P., Klintz, R., Hamprecht, G., Heistracher, E.,
Westphalen, K.O., Gerber, M., and Walter, H., US
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Silicon Relat. Elem., 2006, vol. 181, no. 11, p. 2519.
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Bioorg. Chem., 1978, vol. 7, no. 4, p. 421.
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