Synthesis of 5-aryl-1,3-dimethyl-7-selenoxopyrimidino[4,5-d]pyrimidine-2,4(1H,3H)-dione

Article abstract of DOI:10.3184/174751918X15265512038216

A one-pot method for the synthesis of six novel 5-aryl-1,3-dimethyl-7-selenoxopyrimidino[4,5-d]pyrimidine-2,4(1H,3H)-diones in excellent yields at room temperature has been achieved via reaction between potassium selenocyanate and an aroyl chloride follow

Full text of DOI:10.3184/174751918X15265512038216

2
64 RESEARCH PAPER
VOL. 42 MAY, 264–266
JOURNAL OF CHEMICAL RESEARCH 2018
Synthesis of 5-aryl-1,3-dimethyl-7-selenoxopyrimidino[4,5-d]pyrimidine-
2
,4(1H,3H)-dione
a
a
b
Sonia Singh , Mohammad H. Mosslemin * and Alireza Hassanabadi
a
Department of Chemistry, Yazd Branch, Islamic Azad University, Yazd, Iran
Department of Chemistry, Zahedan Branch, Islamic Azad University, Zahedan, Iran
b
A one-pot method for the synthesis of six novel 5-aryl-1,3-dimethyl-7-selenoxopyrimidino[4,5-d]pyrimidine-2,4(1H,3H)-diones in excellent
yields at room temperature has been achieved via reaction between potassium selenocyanate and an aroyl chloride followed by the
addition of 6-amino-N,N′-dimethyluracil.
Keywords: potassium selenocyanate, 6-amino-N,N′-dimethyluracil, acyl chlorides, pyrimidine-2,4-diones, three-component condensation
Owing to the importance of pyrimidine derivatives,
considerable attention has been devoted to their chemistry and
biological activity. In recent years, there has been increasing
and potassium selenocyanate (KSCN). We thought that a
synthesis of some seleno analogues of the 5-aryl-1,3-dimethyl-
7-thioxopyrimidino[4,5-d]pyrimidine-2,4(1H,3H)-diones that
we synthesised and reported in 2011 might be simply achieved
by a similar reaction in which 2-aminopyridine was replaced by
6-amino-N,N′-dimethyluracil.
So it proved, and a series of six 5-aryl-1,3-dimethyl-7-
selenoxopyrimidino[4,5-d]pyrimidine-2,4(1H,3H)-diones (4a–
f) were prepared in good yield by using a variety of substituted
benzoyl chlorides (2; Ar = various) in reaction with 6-amino-
N,N′-dimethyluracil (1) and KSCN (3) at room temperature
(Scheme 1). To avoid any ambiguity as to whether the acyl
chloride or the amine would add to KSCN (3), the acyl chloride
was reacted with KSCN for 10 min at room temperature before
the addition of the amine.
1
16
interest in their synthesis, and some methods allow access to a
2
–5
large number of multifunctionalised pyrimidine derivatives.
The current interest in selenium-containing organic compounds
6
–10
stems from their remarkable biological functions.
The first
synthesis of acyl isoselenocyanates, which were generated by
the reaction of acyl chlorides and potassium selenocyanate,
11
was described by Douglas. Recently, a few syntheses of
12–15
heterocycles from acyl isoselenocyanates have been reported.
Also, in 2011, a synthesis of functionalised pyrimido[4,5-d]
16
pyrimidines from acyl isothiocyanates was reported. Herein,
we describe a synthesis of some seleno analogues, namely
5
2
-aryl-1,3-dimethyl-7-selenoxopyrimidino[4,5-d]pyrimidine-
,4(1H,3H)-dione 4, by the reaction of acyl isoselenocyanates,
The structures of compounds 4a–f were deduced from
1
13
generated from acyl chlorides and potassium selenocyanate,
their elemental analyses and their IR, H NMR and C NMR
spectra. The mass spectra of compounds 4a–f are fairly similar
and display molecular ion peaks. For example, the mass
spectrum of the simplest 1-phenyl compound (4a) showed a
molecular ion peak at 347 confirming that it is a 1:1:1 adduct of
6-amino-N,N′-dimethyluracil, benzoyl chloride and potassium
selenocyanate. The IR spectrum of compound 4a also supports
the suggested structure with strong absorption bands observed
with 6-amino-N,N′-dimethyluracil in acetone using a reported
12
method.
Results and discussion
12
A recent report described the synthesis of a series of aryl
triazanaphthalene-selones by the reaction at room temperature
in solvent acetone between 2-aminopyridine, an acyl chloride
O
O
H C
CH3
O
3
N
N
N
H C
CH3
3
O
2
N
N
Acetone
+
+ KSeCN
3
HN
Ar
Cl
r. t., 12 h
H N
O
2
Se
Ar
1
4
a
a
4
a
Ar
Yield (%) m.p.(°C)
4
Ar
Yield (%) m.p.(°C)
d
C H
75
78
81
228-230
214-216
237-239
3-O N C H 71
2
251-253
262-264
6
5
6
4
b 4-ClC H
e 4-O N C H
2
6
73
6
4
4
c 4-BrC H
6
4
f 4-CH C H
82
205-207
3
6
4
*
Yields refer to the pure isolated products
Scheme 1
*
Correspondent. E-mail: mhmosslemin@gmail.com

JOURNAL OF CHEMICAL RESEARCH 2018 265
Scheme 2 Suggested mechanism for formation of compound 4.
−
1
at 3080, 1706, 1637 and 1227 cm , respectively, for the NH,
was collected by filtration and washed with cold water (20 mL) and
recrystallised from EtOH to afford the pure title compounds.
1
two carbonyl groups and C=Se. The 500 MHz H NMR
1
,3-Dimethyl-5-phenyl-7-selenoxopyrimidino[4,5-d]pyrimidine-
spectrum of 4a exhibited multiplets at δ 7.26–7.92 ppm for five
aromatic protons and two sharp lines (δ 3.42, and 3.44 ppm)
corresponding to the protons of the methyl groups. A singlet
signal was observed at δ = 10.94 ppm for the NH proton, which
disappeared after addition of a few drops of D O to the DMSO
solution of 4a. The C NMR spectrum of compound 4a showed
2
,4(1H,3H)-dione (4a): White powder; m.p. 228–230 °C; IR (KBr)
−1
1
(νmax cm ): 3080, 1706, 1637, 1549, 1443, 1227; H NMR: δ 3.42 and
3
.44 (6H, 2s, 2CH ), 7.26–7.92 (5H, m, 5CH aromatic), 10.94 (1H, s,
3
13
NH); C NMR: δ 28.6 and 31.4 (2CH ), 100.3, 127.6, 129.3, 129.5,
3
2
141.4, 143.7, 152.6, 165.1 and 170.4 (9C), 188.6 (C=Se); MS m/z (%):
13
3
47 (8). Anal. calcd for C H N O Se: C, 48.43; H, 3.48; N, 16.14;
14
12
4
2
1
2 distinct resonances in agreement with the proposed structure.
A tentative mechanism for this transformation is proposed
found: C, 48.55; H, 3.61; N, 16.26%.
-(4-Chlorophenyl)-1,3-dimethyl-7-selenoxopyrimidino[4,5-d]
pyrimidine-2,4(1H,3H)-dione (4b): White powder; m.p. 214–216 °C;
5
in Scheme 2. The reaction starts with formation of aroyl
isoselenocyanate 5, followed by addition of 6-amino-N,N′-
dimethyluracil 1 to generate 6, subsequent cyclisation of which
generates 7, which is converted into 4 by elimination of water
and a [1,3]-H shift.
−1
1
IR (KBr) (νmax cm ): 3090, 1715, 1637, 1564, 1442, 1227; H NMR: δ
3
3
.44 and 3.45 (6H, 2s, 2CH ), 7.48 (2H, d, J = 8 Hz, 2CH of C H Cl),
3 HH 6 4
3
13
7
.91 (2H, d, J = 8 Hz, 2CH of C H Cl), 11.35 (1H, s, NH); C NMR:
HH 6 4
δ 28.9 and 32.0 (2CH ), 100.5, 127.9, 131.4, 134.9, 136.8, 143.1, 152.2,
3
1
65.0 and 168.9 (9C), 190.1 (C=Se); MS m/z (%): 381 (5). Anal. calcd
Experimental
for C H ClN O Se: C, 44.06; H, 2.90; N, 14.68; found: C, 44.21; H,
1
4
11
4
2
Melting points were determined with an Electrothermal 9100
apparatus and are uncorrected. Elemental analyses for C and H were
performed using a Heraeus CHN-O-Rapid analyser. Mass spectra
were recorded on a FINNIGAN-MAT 8430 mass spectrometer
operating at an ionisation potential of 70 eV. IR spectra were recorded
on a Shimadzu IR-470 spectrometer. NMR spectra were obtained on a
3.02; N, 14.57%.
5-(4-Bromophenyl)-1,3-dimethyl-7-selenoxopyrimidino[4,5-d]
pyrimidine-2,4(1H,3H)-dione (4c): White powder; m.p. 237–239 °C;
IR (KBr) (νmax cm ): 3080, 1706, 1637, 1543, 1443, 1227; H NMR: δ
−1
1
3
3.44 and 3.46 (6H, 2s, 2CH ), 7.54 (2H, d, J = 8 Hz, 2CH of C H Br),
3
HH
6
4
3
13
7.85 (2H, d, J = 8Hz, 2CH of C H Br), 11.15 (1H, s, NH); C NMR:
HH
6
4
1
13
Brucker DRX 500 Avance spectrometer ( H NMR at 500 Hz, C NMR
δ 31.1 and 32.5 (2CH ), 100.5, 124.4, 131.1, 133.7, 136.6, 143.0, 152.1,
164.9 and 168.7 (9C), 189.7 (C=Se); MS m/z (%): 426 (3). Anal. calcd
3
at 125 Hz) in DMSO-d using TMS as an internal standard. Chemical
6
shifts (δ) are given in ppm. All of the chemicals used in this study were
purchased from Merck or Fluka (Buchs, Switzerland) and were used
without further purification.
for C H BrN O Se: C, 39.46; H, 2.60; N, 13.15; found: C, 39.59; H,
2.71; N, 13.31%.
14
11
4
2
1,3-Dimethyl-5-(3-nitrophenyl)-7-selenoxopyrimidino[4,5-d]
pyrimidine-2,4(1H,3H)-dione (4d): White powder; m.p. 251–253 °C;
CAUTION: All of the reactions involving selenium-containing
compounds should be carried out in a well-ventilated hood.
−1
IR (KBr) (ν cm ): 3093, 1711, 1634, 1575, 1530, 1440, 1368, 1228;
max
1
H NMR: δ 3.37 and 3.42 (6H, 2s, 2CH ), 7.96–8.24 (4H, m, 4CH
3
13
aromatic), 11.25 (1H, s, NH); C NMR: δ 29.4 and 31.9 (2CH ), 100.3,
3
Synthesis of 5-aryl-1,3-dimethyl-7-selenoxopyrimidino[4,5-d]pyrimidine-
121.7, 123.2, 130.5, 136.6, 143.1, 147.3, 148.5, 152.0, 164.7 and 168.3 (11C),
2
,4(1H,3H)-diones (4a–f); general procedure
1
89.4 (C=Se); MS m/z (%): 392 (10). Anal. calcd for C H N O Se: C,
14
11
5
4
An aroyl chloride (1 mmol) in dry acetone (3 mL) was added to a
solution of potassium selenocyanate (1 mmol) in dry acetone (3 mL).
The reaction mixture was stirred at room temperature for 10 min. Then
42.87; H, 2.83; N, 17.85; found: C, 43.01; H, 2.95; N, 18.00%.
1,3-Dimethyl-5-(4-nitrophenyl)-7-selenoxopyrimidino[4,5-d]
pyrimidine-2,4(1H,3H)-dione (4e): White powder; m.p. 262–264 °C;
−1
6
-amino-N,N′-dimethyluracil (1 mmol) in dry acetone (4 mL) was added
IR (KBr) (ν cm ): 3090, 1708, 1631, 1571, 1533, 1442, 1373, 1226;
max
1
3
to the mixture. The resulting mixture was stirred at room temperature
for periods of up to 12 h. The progress of the reaction was monitored
by TLC. After completion of the reaction, the resulting precipitate
H NMR: δ 3.40 and 3.45 (6H, 2s, 2CH ), 8.08 (2H, d, J = 8 Hz,
3
HH
3
2CH of C H NO ), 8.14 (2H, d, J = 8Hz, 2CH of C H NO ), 11.20
6
4
2
HH
6
4
2
13
(1H, s, NH); C NMR: δ 29.5 and 32.2 (2CH ), 100.5, 123.0, 130.4,
3

2
66 JOURNAL OF CHEMICAL RESEARCH 2018
1
43.0, 147.1, 148.2, 152.1, 164.9 and 168.1 (9C), 188.9 (C=Se); MS m/z
3
4
M. Dabiri, H. Arvin-Nezhad, H.R. Khavasi and A. Bazgir, Tetrahedron,
007, 63, 1770.
S. Samai, G. Chandra Nandi, S. Chowdhury and M. Shankar Singh,
Tetrahedron, 2011, 67, 5935.
P. Molina, M.J. Vilaplana and J. Pérez, Tetrahedron, 1990, 46, 7855.
T. Wirth, Organoselenium chemistry: synthesis and reactions. Wiley-
VCH, Weinheim, 2012.
2
(%): 392 (7). Anal. calcd for C H N O Se: C, 42.87; H, 2.83; N, 17.85;
14
11
5
4
found: C, 42.98; H, 2.96; N, 18.03%.
,3-Dimethyl-5-(p-tolyl)-7-selenoxopyrimidino[4,5-d]pyrimidine-
,4(1H,3H)-dione (4f): White powder; m.p. 205–207 °C; IR (KBr)
1
5
6
2
−1
1
(νmax cm ): 3076, 1704, 1628, 1524, 1436, 1223; H NMR: δ 2.34, 3.35
and 3.41 (9H, 3s, 3CH ), 7.42–7.83 (4H, m, 4CH aromatic), 11.16 (1H,
7
8
M.O. Sydnes and M. Isobe, Monatsh. Chem., 2015, 146, 351.
A.C. Razus, L. Birzan, A. Hanganu, M. Cristea, E.-M. Ungureanu, M.-L.
Soare and G.-O. Buica, Monatsh. Chem., 2014, 145, 1999.
M.D. Rvović, V.M. Divac, N.Ž. Janković and Z.M. Bugarčić, Monatsh.
Chem., 2013, 144, 1227.
N. Filipović, N. Polović, B. Rašković, S. Misirlić-Denčić, M. Dulović, M.
Savić, M. Nikšić, D. Mitić, K. Andelković and T. Todorović, Monatsh.
Chem., 2014, 145, 1089.
3
13
s, NH); C NMR: δ 20.4, 29.2 and 31.7 (3CH ), 100.2, 126.5, 127.6,
3
131.2, 136.5, 148.3, 159.1, 164.2 and 168.3 (9C), 190.1 (C=Se); MS m/z
9
(
%): 361 (14). Anal. calcd for C H N O Se: C, 49.87; H, 3.91; N, 15.51;
15
14
4
2
found: C, 50.01; H, 4.05; N, 15.66%.
10
Received 8 April 2018; accepted 29 April 2018
Paper 1805366
https://doi.org/10.3184/174751918X15265512038216
Published online: 4 June 2018
1
1
I.B. Douglas, J. Am. Chem. Soc., 1937, 59, 740.
I. Yavari and S. Mosaferi, Monatsh Chem., 2017, 148, 963.
R. Zhiani, J. Chem. Res., 2017, 41, 452.
12
13
14
R. Zhiani, J. Chem. Res., 2017, 41, 455.
15
S. Singh, M.H. Mosslemin and A. Hassanabadi, J. Chem. Res., 2018, 42,
References
145.
1
2
A.R. Katritzky, Adv. Heterocycl. Chem., 1984, 36, 1.
C.O. Kappe, Molecules, 1998, 3, 1.
16 R. Mohebat, M.H. Mosslemin, A. Dehghan-Darehshiri and A. Hassanabadi,
J. Sulfur. Chem., 2011, 32, 557.