Mendeleev Commun., 2019, 29, 94–95
The reactions of ureas 1a–c or thioureas 1d–g with paraform-
aldehyde and barbituric acid 2a or thiobarbituric acid 2b gave
the target barbiturils 3a,b or thiobarbiturils 3c–i in yields from
In conclusion, a general method for synthesizing hitherto
unknown (thio)barbiturils with a new substitution type has
been developed. For this purpose three-component one-stage
(Method 1) and two-stage one-pot (Method 2) procedures were
elaborated, with their preference being dictated by the nature
of certain reactants.
1
5 to 75% (see Scheme 2). Prolongation of these reactions did
not improve the yields. HCl-assisted three-component version in
water led to complex mixtures containing no target products 3.
Furthermore, we studied whether this reaction could be
performed in one-pot two-stage version with intermediate forma-
tion of urons (Scheme 3, Method 2). We found that the following
reactants were suitable fot this procedure: urea 1a, thioureas
Online Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi: 10.1016/j.mencom.2019.01.032.
1
d–f, and barbituric acid 2a; the products 3a,c–e were thus
obtained. At the first stage, condensation of (thio)ureas 1a,d–f
with (CH O) was performed (H O, concentrated hydrochloric
References
2
x
2
1 (a)A. N. Kravchenko,V.V. Baranov and G.A. Gazieva, Russ. Chem. Rev.,
2018, 87, 89; (b)Ya. A. Barsegyan, V. V. Baranov andA. N. Kravchenko,
Chem. Heterocycl. Compd., 2017, 53, 116 (Khim. Geterotsikl. Soedin.,
13
acid, reflux, 2 h). At the second stage, barbituric acid 2a was
reacted at 65°C. The yields of products 3a (55%) and 3e (27%)
were somewhat higher than those achieved in Method 1 (see
Scheme 2). Thiobarbituric acid 2b turned to be unsuitable in
Method 2 even when the reaction mixture was boiled. Also,
2
017, 53, 116); (c) Ya. A. Barsegyan, V. V. Baranov, A. N. Kravchenko,
Yu. A. Strelenko, L. V. Anikina, V. A. Karnoukhova and N. G. Kolotyrkina,
Synthesis, 2018, 50, 2099; (d) E. V. Ivanov, E. Yu. Lebedeva, S. G.
Petrovskaya, V. V. Baranov, A. N. Kravchenko and N. G. Ivanova, J. Mol.
Liq., 2017, 242, 160; (e) L. V. Anikina, Yu. B. Vikharev, V. V. Baranov,
O. R. Malyshev and A. N. Kravchenko, Mendeleev Commun., 2018,
28, 317; (f) V. V. Baranov, Yu. V. Nelyubina, A. N. Kravchenko, N. G.
Kolotyrkina and K. A. Biriukova, Tetrahedron Lett., 2015, 56, 6085;
(
thio)barbiturils 3 were not formed if AcOH was used instead
of HCl/H O system.
2
Apparently, Method 1 (see Scheme 2) is more general than
Method 2 (see Scheme 3) and allows one to obtain a series of
new barbiturils and their thio analogues. However, Method 2 is
preferrable for the preparation of compounds 3a and 3e.
(g) Y. Wu, L. Xu, Y. Shen, Y. Wang and Q. Wang, New J. Chem., 2017,
4
7
1, 6991; (h) Y. Shen, L. Zou and Q. Wang, New J. Chem., 2017, 41,
857; (i) Y. Wu, L. Xu, Y. Shen, Y. Wang, L. Zou, Q. Wang, X. Jiang,
J. Liu and H. Tian, Chem. Commun., 2017, 53, 4070; ( j) E. A. Bugnet,
T. D. Nixon, C. A. Kilner, R. Greatrex and T. P. Kee, Tetrahedron Lett.,
O
2
003, 44, 5491.
R1
HN
NH
2 M. M. Abelman, S. C. Smith and D. R. James, Tetrahedron Lett., 2003,
44, 4559.
Z. Xu and Y. Tu, Chin. J. Org. Chem., 2015, 35, 1357.
4 J. L. Mokrosz, M. H. Paluchowska, E. Szneler and B. Dro z˙ d z˙ , Arch.
Pharm., 1989, 322, 231.
5 S. R. Jetti, D. Verma and S. Jain, J. Chem. Pharm. Res., 2012, 4, 2373.
P. Gupta, S. Gupta, A. Sachar, D. Kour, J. Singh and R. L. Sharma,
J. Heterocycl. Chem., 2010, 47, 324.
D. Prajapati, D. Bhuyan, M. Gohain and W. Hu, Mol. Divers., 2011,
O
X
NH
NH
O
O
i
ii
3
X
N
N
R1
R2
N
N
R1
R2
R2
a,d–f
X
6
1
Urons
3a,c–e
1
2
1
1
1
1
a, 3a X = O, R = R = Me (55%)
7
1
2
d, 3c X = S, R = R = Me (75%)
1
5, 257.
1
2
e, 3d X = S, R = R = Et (22%)
8
9
A. Shaabani, A. Bazgir and H. R. Bijanzadeh, Mol. Divers., 2004, 8, 141.
1
2
f, 3e X = S, R = Me, R = Et (27%)
1
0.1155/2013/392162.
Scheme 3 Reagents and conditions: i, (CH O) , H O, HCl, D, 2 h; ii, 2a,
2
x
2
1
1
1
0 A. Shaabani and A. Bazgir, Tetrahedron Lett., 2004, 45, 2575.
1 M. M. Amini, A. Shaabani and A. Bazgir, Catal. Commun., 2006, 7, 843.
2 G. Kaur, P. Gupta, K. Harjai and V. Singh, Drug Dev. Res., 2014, 75, 202.
6
5°C, 12 h.
8
,10-Dimethyl-2,4,8,10-tetraazaspiro[5.5]undecane-1,3,5,9-tetraone
13 H. Petersen, Synthesis, 1973, 5, 243.
3
a. White powder, yield 27% (Method 1), 55% (Method 2), mp 228–230 °C.
14 P. A. Belyakov, V. I. Kadentsev, A. O. Chizhov, N. G. Kolotyrkina, A. S.
Shashkov and V. P. Ananikov, Mendeleev Commun., 2010, 20, 125.
15 H. Valizadeh and L. Dinparast, Monatsh. Chem., 2012, 143, 251.
16 S. M. Abdul Hai, S. Perveen, R. A. Khan, K. M. Khan and N. Afza, Nat.
Prod. Res., 2003, 17, 351.
1
H NMR, d: 2.75 (s, 6H, 2Me), 3.56 (s, 4H, 2CH ), 11.28 (s, 2H, 2NH).
2
13
3
C NMR, d: 35.21 (Me), 49.52 (C), 51.97 (CH ), 150.22 (C =O), 156.11
2
9
1
5
+
(C =O), 169.81 (C =O+C =O). HRMS, m/z: 241.0934 [M+H] (calc. for
C H N O , m/z: 241.0931).
9
13
4
4
8
-Methyl-2,4,8,10-tetraazaspiro[5.5]undecane-1,3,5,9-tetraone 3b. Light
1
yellow powder, yield 61% (Method 1), mp 272–274°C. H NMR, d: 2.75
s, 3H, Me), 3.41 (d, 2H, C H , J 3.4 Hz), 3.54 (s, 2H, C H ), 6.50 (br. s,
11
3
7
(
1
(
(
2
2
10
2
4
13
H, N H), 11.26 (s, 2H, N H+N H). C NMR, d: 34.52 (Me), 46.26
7
11
3
9
C H ), 48.91 (C), 50.73 (C H ), 150.29 (C =O), 155.55 (C =O), 169.86
2
2
1
5
+
C =O+C =O). HRMS, m/z: 227.0785 [M+H] (calc. for C H N O ,
8
11
4
4
m/z: 227.0775).
For more details, see Online Supplementary Materials.
Received: 3rd July 2018; Com. 18/5627
–
95 –