Mendeleev Commun., 2011, 21, 122–124
1,3,4,5-tetrahydro-2,4-dioxo-2H-pyrano[2,3-d]pyrimidine-6-carbo-
nitrile 3d was carefully studied (Table 1).
Cathode: ROH + e
R2
RO– + 1/2 H2
The current density 5 mA cm–2 (I = 25 mA, electrodes surface
5 cm2) was found to be the optimum and provided the highest
yield (81%) of the product 3d in ethanol at 78°C. Raising of
current density up to 10 mA cm–2 (I = 50 mA) results in a slight
decrease of the yield, what may be caused by acceleration of
undesired direct electrochemical processes leading to oligomeri-
zation of the reactants. The low yield and insufficient conver-
sion of starting compounds were observed when electrolysis was
carried out at 20°C.
R2
N
O
N
O
O
O
+ RO–
+ ROH
In solution:
N
N
R2
R2
O
O
2
C6H4R1
Among alcohols tested, EtOH is preferable in view of easy isola-
tion of reaction products by simple filtration after electrolysis.
Under the optimal conditions thus found (current density
5 mA cm–2, 0.1 F mol–1 passed, EtOH as a solvent, 78°C), the
electrolysis of aldehydes 1a–h, barbituric acids 2a,b and malono-
nitrile in ethanol at 78°C in an undivided cell gives rise to cor-
responding pyrano[2,3-d]pyrimidines 3a–j in 71–81% substance
yields and 710–810% current yields in ~30 min reaction period
(Scheme 1).†
H
O
1
R2
N
2
RO–
+
O
O
The beginning of new
catalytic cycle
N
R2
O
O
C6H4R1
CN
R2
O
C6H4R1
N
Taking into consideration the above results and the data on
the mechanisms of electrocatalytic chain cyclizations of tetra-
cyanocyclopropanes19 and mechanism of the electrocatalytic chain
transformation of aldehydes and C–H acids,15–18,20 the following
mechanism for the electrocatalytic chain transformation of alde-
hydes 1, barbituric acids 2 and malononitrile into pyrano[2,3-d]-
pyrimidines 3 is proposed (Scheme 2). As the initiation step of
the catalytic cycle, deprotonation of an alcohol at the cathode
leads to formation of alkoxide anion. Its subsequent reaction
in solution with barbituric acid 2 gives rise to barbituric acid
anion. Then Knoevenagel condensation of aldehyde 1 with bar-
bituric acid anion takes place in the solution with the elimination
of hydroxide anion and formation of the corresponding 5-benzyl-
idenepyrimidine-2,4,6(1H,3H,5H)-trione 4.21 The subsequent
hydroxide-promoted Michael addition of malononitrile to elec-
tron-deficient Knoevenagel adduct 4 followed by intramolecular
cyclization results in corresponding pyrano[2,3-d]pyrimidine 3
with regeneration of alkoxide anion at the last step, which con-
tinues the catalytic chain process by the interaction with the next
molecule of barbituric acid. Thus, the generation of even single
alkoxide anion at the cathode is theoretically sufficient for total
conversion of equimolar quantities of aldehyde, barbituric acid
and malononitrile into corresponding pyrano[2,3-d]pyrimidine
system.
R2
N
O
O
N
O
NH2
R2
O
N
O
R2
3
– HO–
ROH
O
O
C6H4R1
C6H4R1
CN
R2
O
R2
O
N
N
N
O
N
O
N
R2
R2
4
CN
CN
O
HO–
C6H4R1
O
C6H4R1
CN
R2
O
R2
O
CN
N
N
CN
CN
N
O
N
O
R2
R2
In conclusion, the simple electrocatalytic system can produce,
under neutral and mild conditions, a fast (~30 min) and selective
multicomponent transformation of aldehydes, barbituric acids and
malononitrile into 7-amino-1,3-dialkyl-5-aryl-2,4-dioxo-1,3,4,5-
tetrahydro-2H-pyrano[2,3-d]pyrimidine-6-carbonitriles in 70–80%
substance yields and 700–800% current yields. This novel electro-
catalytic chain process opens an efficient and convenient way to
Scheme 2
cyanofunctionalized pyrano[2,3-d]pyrimidines – the promising
compounds for the different biomedical applications. The proce-
dure requires simple equipment and an undivided cell; it is easily
carried out and is valuable from the viewpoint of environmentally
benign diversity-oriented large-scale processes. This efficient
electrocatalytic protocol represents novel synthetic concept for
multicomponent reactions strategy and allows one to combine
the synthetic virtues of conventional MCR with ecological benefits
and convenience of facile electrocatalytic procedure proposed;
therefore, makes the MCR strategy a step closer to a notion of
‘ideal synthesis’.22
†
General procedure. A solution of benzaldehyde 1 (5 mmol), N,N'-di-
alkylbarbituric acid 2 (5 mmol), malononitrile (0.33 g, 5 mmol) and sodium
bromide (0.05 g, 0.5 mmol) in ethanol (20 ml) was electrolyzed in an
undivided cell equipped with a magnetic stirrer, reflux condenser, a graphite
anode and an iron cathode at 78°C under a constant current density of
5 mA cm–2 (I = 25 mA, electrodes square 5 cm2) until the catalytic quantity
of 0.1 F mol–1 of electricity was passed. After the electrolysis was finished,
the solution was filtered to isolate the solid product 3, which was then
twice rinsed with an ice-cold ethanol/water solution (9:1, 5 ml), and dried
under reduced pressure. For 3i,j, after the electrolysis was finished, the
solution was evaporated to dryness, the residue was then rinsed with an
ice-cold ethanol/water solution (9:1, 3 ml) and filtered to isolate the solid
product 3, which was washed with ice-cold ethanol/water solution (9:1,
3 ml), diethyl ether (5 ml) and dried under reduced pressure.
This work was supported by the Presidential Scholarship
Program for State Support of Leading Science Schools of the
Russian Federation (project no. 4945.2010.3).
Online Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.mencom.2011.04.002.
For characteristics of 3a–j, see Online Supplementary Materials.
– 123 –
Elinson, Michail N.
