Catalyst-free three-component synthesis of hydroxyalkyltriazolylmethylidene barbiturates

Article abstract of DOI:10.1016/j.mencom.2019.11.017

5-[(5-Hydroxyalkyl-1H-1,2,3-triazol-4-yl)methylidene]barbiturates were eco-friendly synthesized in up to 89% yields by one-pot three-component processing (no catalyst, H₂O–EtOH, room temperature, 38 h) of 4-hydroxyalkynals, trimethylsilylazide

Full text of DOI:10.1016/j.mencom.2019.11.017

Mendeleev
Communications
Mendeleev Commun., 2019, 29, 655–657
Catalyst-free three-component synthesis of
hydroxyalkyltriazolylmethylidene barbiturates
a
a
b
a
Maria M. Demina, Alevtina S. Medvedeva, Tran D. Vu, Lyudmila I. Larina,
a
a
Inessa V. Mitroshina and Olesya A. Shemyakina*
a
b
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences,
64033 Irkutsk, Russian Federation. Fax: +7 3952 419 346; e-mail: shemyakina@irioch.irk.ru
Irkutsk National Research Technical University, 664074 Irkutsk, Russian Federation
6
DOI: 10.1016/j.mencom.2019.11.017
R3
O
5
-[(5-Hydroxyalkyl-1H-1,2,3-triazol-4-yl)methylidene]barbi-
R2
O
O
R1
5 oC, 38 h HO
O
+
H O / EtOH
R2
N
N
2
turates were eco-friendly synthesized in up to 89% yields by
one-pot three-component processing (no catalyst, H O–EtOH,
room temperature, 38 h) of 4-hydroxyalkynals, trimethylsilyl
azide and barbituric acids.
R1
Me3SiN3 +
O
N
N
R3 2
OH
R3
2
R3
O
N
N
O
H
N
R1, R2 = Alk; R + R2 = (CH2)5; R3 = H, Me
1
8 examples
One of the most important challenges for chemists is a search for
efficient, economicalandeco-friendlyprocessesinorganic synthesis.
Multicomponent reactions allow one to synthesize the target
hydroxyalkyl-containing 5-(1H-1,2,3-triazol-4-ylmethylidene)-
barbiturates. Our experiments revealed thatthereactionproceeded
under mild conditions (without catalyst, H O–EtOH, 20–25°C,
2
1
compounds in a single operation from three or more reactants.
38 h) to assemble new functionalized heterocyclic hybrids 3a-h
†
This rational strategy combines both the economic and environ-
mental aspects of organic chemistry for practical applications.
Considerable efforts have been directed to the development of
multi-component procedures for the construction of various
in 72–89% yields (Scheme 1). It is important that all the products
R1
R2
R2
O
ꢇ
Me SiN
O
ꢇ
2
R1
ꢀO
heterocycles due to their significant therapeutic potential.
ꢀ
2O ꢍ EtOꢀ
Additionally, the molecular hybridization based on the
combination of two bioactive parts may afford new compounds
which can be more efficient, economical and safe as compared to
Oꢀ
ꢀ
N
ꢀ
N
o
2
ꢆ Cꢁ ꢇꢈ h
N
1
a−d
A
1
2
3
a R ꢂ R ꢂ Me
the parent ones.
1
2
b R ꢂ Meꢁ R ꢂ Et
Among N-heterocycles, barbituric acid derivatives occupy an
important place in pharmacology as quick-acting agents for urgent
1
2
c R ꢂ Meꢁ R ꢂ Pr
1
2
d R ꢃ R ꢂ ꢄCꢀ ꢅ
2
ꢆ
4
anesthesia, relieving seizures and preventing epileptic seizures,
5
6
and possessing antimicrobial, antioxidant, selective cell adhesion
inhibitory and DNA cleavage activities. Some of them exhibit
O
O
7
8
9
Rꢇ
nonlinear optical properties and are employed as ligands in
Rꢇ
Rꢇ
O
coordination chemistry.10 The important barbituric acid deriva-
tives are the 5-ylidene ones.
R1
N
O
R2
N
2
aꢁb
O
ꢀ
O
In parallel, 1,2,3-triazoles are of great interest as pharmaceuti-
−ꢀ2O
N
Rꢇ
cals,11 agrochemicals, corrosion inhibitors, dyes and
12
13
14
O
N
N
ꢇ
2
2
a R ꢂ ꢀ
15
ꢀ
photostabilizers. The most important access to them is the ‘click’-
synthesis based on 1,3-dipolar cycloaddition of alkynes and
ꢇ
b R ꢂ Me
3
a−h
1
6
azides.
1
2
ꢇ
a R ꢂ R ꢂ Meꢁ R ꢂ ꢀ ꢄꢈ2ꢉꢅ
The integration of 1,2,3-triazole and barbiturate heterocyclic
rings in the same molecule may lead to new hybrid compounds
with potential biological activities.
1
2
ꢇ
b R ꢂ Meꢁ R ꢂ Etꢁ R ꢂ ꢀ ꢄꢈꢊꢉꢅ
1
2
ꢇ
c R ꢂ Meꢁ R ꢂ Prꢁ R ꢂ ꢀ ꢄꢈꢋꢉꢅ
1
2
ꢇ
d R ꢃ R ꢂ ꢄCꢀ ꢅ ꢁ R ꢂ ꢀ ꢄꢋꢇꢉꢅ
2
ꢆ
Early, we showed that available 4-hydroxyalkynals 117 bearing
sterically unhindered aldehyde group and the activated triple
bond can be efficiently used in the metal-free synthesis of
N-unsubstituted 1,2,3-triazolecarbaldehydes.18 Also, 1H-1,2,3-tri-
azolylmethylidenepyrimidines and -1,3-dioxanes were prepared
from element-substituted propynals, trimethylsilyl azide and
heterocyclic CH-acids.19
1
2
ꢇ
e R ꢂ R ꢂ R ꢂ Me ꢄꢈ9ꢉꢅ
1
ꢇ
2
f R ꢂ R ꢂ Meꢁ R ꢂ Et ꢄꢈꢇꢉꢅ
1
ꢇ
2
g R ꢂ R ꢂ Meꢁ R ꢂ Pr ꢄꢈꢌꢉꢅ
1
2
ꢇ
h R ꢃ R ꢂ ꢄCꢀ ꢅ ꢁ R ꢂ Me ꢄꢋ2ꢉꢅ
2
ꢆ
Scheme 1
In continuation of our search for new polyfunctional N-un-
substituted 1,2,3-triazoles, we report herein on the results of three-
component reaction of 4-hydroxyalkynals 1, trimethylsilyl azide
and barbituric acids 2 in aqueous medium with a goal to synthesize
†
-Hydroxyalkynals 1 were prepared according to published methods.17,21
General procedure for the synthesis of compounds 3a-h. A 10 ml round
4
bottom flask was charged with water (2 ml) and 4-hydroxyalkynal 1
(1 mmol), trimethylsilyl azide (0.138 g, 1.2 mmol) was then added, and the
©
2019 Mendeleev Communications. Published by ELSEVIER B.V.
–
655 –
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.

Mendeleev Commun., 2019, 29, 655–657
are easily isolated by sequential washing the crude precipitate
Online Supplementary Materials
with ethyl acetate and methanol. The isolated yields of the
products are not quantitative due to probable losses during
purification and the insignificant polymerization of hydroxy
alkynals 1. The steric hindrance slightly affects the yields of
products. Products 3d,h bearing hydroxycyclohexyl substituent
were isolated in 72–73% yield. Compounds 3a–h turned to be
poorly soluble in most organic solvents.
Supplementary data associated with this article can be found
in the online version at doi: 10.1016/j.mencom.2019.11.017.
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656 –

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2
Received: 21st May 2019; Com. 19/5931
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