Features of the synthesis of thiobarbituric acid arylidene derivatives in the presence of triethylamine

Article abstract of DOI:10.1134/S1070363209110218

The synthesis of thiobarbituric acid arylidene derivatives proceeds in two steps, which include 5-(2-hydroxy-2-phenyl)ethyl derivative formation and dehydration. The triethylamine promotes increase in the negative charge on the 5th carbon atom (from -0.39

Full text of DOI:10.1134/S1070363209110218

ISSN 1070-3632, Russian Journal of General Chemistry, 2009, Vol. 79, No. 11, pp. 2412–2416. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © A.I. Rahimov, S.A. Avdeev, 2009, published in Zhurnal Obshchei Khimii, 2009, Vol. 79, No. 11, pp. 1890–1894.
Features of the Synthesis of Thiobarbituric Acid Arylidene
Derivatives in the Presence of Triethylamine
a
b
A. I. Rahimov and S. A. Avdeev
a
Volgograd State Technical University , pr. Lenina 28, Volgograd, 400131 Russia
e-mail: organic@vstu.ru
b
Institute of Chemical Problems of Ecology, Russian Academy of Natural Sciences, Volgograd, Russia
e-mail: rakhimov@sprint-v.com.ru
Received April 9, 2009
Abstract—The synthesis of thiobarbituric acid arylidene derivatives proceeds in two steps, which include 5-(2-
hydroxy-2-phenyl)ethyl derivative formation and dehydration. The triethylamine promotes increase in the
negative charge on the 5th carbon atom (from –0.399 to –0.638) and positive charge on the aldehyde CH=O
group carbon atom (from 0.288 to 0.300) in the transition state due to associative interaction (analysis by
quantum-chemical method AM1), and it also promotes dehydration by “pushing out” the hydroxy group. The
yield of thiobarbituric acid arylidene derivatives reaches 92–99%.
DOI: 10.1134/S1070363209110218
At the condensation of thiobarbituric acid with
aromatic aldehydes HCl is commonly used [1]. In that
case the reaction mechanism includes the protonation
of nucleophilic centers of the initial reagents.
reaction course most probably includes the following
transition state:
H
O
O
O
H
In this communication we show a possibility to
apply a base instead of an acid in the synthesis of
thiobarbituric acid arylidene derivatives. For this
purpose triethylamine was used. The reaction proceeds
according to the following scheme:
.
.........................
HN
C
R
H
H
S
N
H
O
N(C H )
2
5 3
O
As the reaction medium we used anhydrous
ethanol. Apparently, during the first step molecular
association occurs of ethanol with the carbonyl group
oxygen atom and with the hydrogen atom of methylene
group with the formation of the associate with the
structure shown in Figs. 1, 2.
O
C
H
HN
+
S
N
H
O
R
O
As
a
result of associative interaction of
thiobarbituric acid with ethanol increases the negative
charge on the 5th carbon atom [from –0.213 (Fig. 1) in
the parent molecule to –0.582 (Fig. 2) in the associate].
In the second step the remaining proton of the me-
thylene group associates with the triethylamine mole-
cule and simultaneously the carbon atom approaches
the electrophilic carbon atom of the carbonyl group of
benzaldehyde molecule with the formation of the
transition state shown in Fig. 3.
TEA
HN
_
H O
2
S
N
O
R
H
3 3 2
R = H (I), CH (II), OCH (III), F (IV), NO (V).
In contrast to the data reported in [1] the activation
of electrophilic centers by triethylamine can increase
the selectivity of the first stage of the process. The
2412

FEATURES OF THE SYNTHESIS OF THIOBARBITURIC ACID ARYLIDENE DERIVATIVES
2413
O –0.302
0.333
H
0
.168
–
0.357
H
0
.282
0
.305
O
H
O –0.365
C
1
.126A 0.167
–0.213
N –0.338
C
H
0
.380
0
.279
0
.133
0.305
H
H 0.347
C
C
C
N –0.338
N –0.320
C
C
–0.582
S –0.148
O –0.302
0
.178
H
0
.282
0.194
0
.353
H
C
–
1
E –1354.97 kcal mol
–
0.316
N –0.360
Fig. 1. Electronic structure of thiobarbituric acid.
S
O
–
0.144
H 0.270
E –2071.34 kcal mol
–
1
0
.317
Fig. 2. Electronic structure of thiobarbituric acid associate
with ethanol.
H
–
0.386
0
.280
O
H
O –0.410
–
0.362
O
0
.240
0
.356
O –0.252
H
S
O –0.627
C
H 0.305
.815A
0
.300
1
0
.275
N –0.289
C
C
C
0.233
–0.638
O –0.347
H
S
C
H 0.210
.575A
H 0.314
H 0.015
–0.008
0.228
3
C
C
C
–
0.064
0
.335
N –0.244
–0.399
C
2 5 3
N(C H )
H 0.183
H 0.076
N –0.325
O –0.425
0.176
0.371
C
0
.806
N –0.317
O –0.314
H 0.220
0.413
–
1
E –5412.93 kcal mol
H 0.263
E –3653.11 kcal mol
–
1
Fig. 3. Electronic structure of the transition state in the
reaction of thiobarbituric acid with benzaldehyde in the
presence of triethylamine.
Fig. 4. Electronic structure of the transition state in the
reaction of thiobarbituric acid with benzaldehyde in the
absence of triethylamine.
Triethylamine contributes to the proceeding of the
the electrophilic attack by the benzaldehyde molecule
on the nucleophilic center of the thiobarbituric acid.
This leads to a considerable decrease in the total energy.
condensation reaction (Figs. 3, 4) since it influences
the bond polarization C–H···N(C H ) and increases
2
5 3
substantially the negative charge on the 5th carbon
from –0.399 to –0.638) and also the positive charge
on the carbon atom of the benzaldehyde carbonyl
group (from 0.228 to 0.300), which undoubtedly favors
(
The influence of a substituent on the electronic
structure of transition state consists in the contribution
of the electron-donor CH O group to further bond
3
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 11 2009

2
414
RAHIMOV, AVDEEV
0
.317
H
–
0.386
O
O –0.302
O –0.410
0
.168
H
0
.282
0
.240
0
.305
0.356
H
O –0.627
C
H
S
H
0.305
1.815A
C
1
.126A
H 0.167
0
.300
N –0.338
C
–0.213
N –0.289
C
C
C
–0.638
0
.133
0.305
H 0.314
H 0.015
–0.008
C
C
–
0.064
0
.335
N –0.338
C
S –0.148
O –0.302
2 5 3
N(C H )
N –0.325
O –0.425
0
.282
0
.806
H
–
1
E –5787.33 kcal mol
H 0.220
E –5741.63 kcal mol
–
1
Fig. 5. Electronic structure of the transition state in the
reaction of thiobarbituric acid with p-methoxybenzal-
dehyde in the presence of triethylamine.
Fig. 6. Electronic structure of the transition state in the
reaction of thiobarbituric acid with p-nitrobenzaldehyde in
the presence of triethylamine.
polarization (charges on the 5th carbon atom of
thiobarbituric acid and on the carbon atom of CH=O
group become –0.645 and 0.305, respectively) favor-
ing the reaction progress. On the contrary, the introduc-
tion of a nitro group leads to the smaller charge on the
By quantum-chemical calculations using the
method AM1 [2] we calculated the electronic structure
of the formed aldol (Fig. 7).
Under the action of triethylamine the formed aldol
gives a complex (Fig. 8), which finally decomposes
affording the reaction product and water.
5
th carbon of thiobarbituric acid (–0.620) and to a sig-
nificant decrease in the charge on the C=O carbon atom.
Further the transition state is converted into the
anion with the negative charge on the of oxygen atom,
which under the action of medium forms aldol:
The influence of a substituent on the electronic
structure of the aldol–triethylamine complex is seen in
the fact that the electron-acceptor group NO to a
2
greater extent contributes to the release of water
H
molecule, since the interatomic distances C(CH )···H
and C–O increase to favor the reaction course (Fig. 9).
On the contrary, the introduction of methoxy group
2
O
O
H
H
O
O
H
HN
C
R
(
Fig. 10) results in a decrease in the bond lengths
C(CH )···H and C–O that to a considerable degree
2
S
N
H
N(C H )
2 5 3
hampers the splitting off of the water molecule and
thus decelerates the second step of the reaction.
_
O
O
HN
Thus, at the condensation of thiobarbituric acid
with aromatic aldehydes in the presence of triethyl-
amine in the first step the electron-donor substituents
in the para position of the aldehyde molecule promote
the reaction, while they hamper the second step of the
reaction. On the contrary, the electron-acceptor sub-
stituents in the para position of the aldehyde molecule
in the first step retard the reaction, while in the second
step they promote it.
_
_
C H OH
2
5
R
N(C H )
2
5 3
S
N
O
H
O
OH
O
HN
R
S
N
H
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 11 2009

FEATURES OF THE SYNTHESIS OF THIOBARBITURIC ACID ARYLIDENE DERIVATIVES
2415
–
0.271
–0.359
0
.220
H
O
O
0.207
0
.179
H
O –0.316
0.194
H
0
.280
0.280
H
–0.403
0
.308
0.361
H
H
O
N –0.345–
0.146
N –0.33 2– 0.240
0.400
0.351
0.112
0
.096
R
0
.133
0.306
H
H
0
.225
0
.177
N
N
S
O
–0.301
S
0.179
O
–
0.340
–0.337
–
–0.302
–
0.162
–
0.309
H 0.281
E –2934.05 kcal mol
H 0.280
N(C H )
2
5 3
–
1
–1
E –4871.32 kcal mol
Fig. 7. Electronic structure of aldol obtained in the first
stage of the reaction of thiobarbituric acid with benzaldehyde.
Fig. 8. Electronic structure of the transition state of the
complex aldol−triethylamine (R=H).
–
0.382
–0.304
O
O
0
.197
0.207
H
H
0
.200
0.197
0.282
0
.280
–
0.404
0
.361
H
0.348
N–0.33 –5 0.218
0.134
H
–0.405
H
O
H
O
N–0.33–6
0.264
0.082
R
R
0.444
0
.146
0
.359
0.368
H 0.142
H 0.189
O
–0.357
N
–0.331
O
–0.353
S
0.217
N
–0.335
S
–
0.156
–
–
N(C
0.181
–0.310
N(C H )
2 5 3
H0.275
H0.282
2
H
5
)
3
–
1
–1
E –5156.61 kcal mol
Fig. 9. Electronic structure of the transition state of the
complex aldol−triethylamine (R=OCH ).
E –5046.69 kcal mol
Fig. 10. Electronic structure of the transition state of the
complex aldol−triethylamine (R=NO ).
3
2
EXPERIMENTAL
5-(4-Methylbenzylidene)-2-thioxodihydropyrimi-
1
dine-4,6(1H,5H)-dione (II) was obtained analogously
from 5 g (34.7 mmol) of thiobarbituric acid, 4.1 ml
The H NMR spectra were registered on a Varian
Mercury 300 MHz instrument, internal reference
(
34.7 mmol) of p-methylbenzaldehyde, and 2.4 ml of
HMDS, solvent DMSO-d . Melting point were deter-
mined in accordance with the procedure [3].
6
1
triethylamine. Yield 8.0 g (94%), mp >300°C. H
NMR spectrum, δ, ppm: 2,8 s (3H, CH ), 5.99 s (1H,
3
5
-Benzylidene-2-thioxodihydropyrimidine-4,6-
1H,5H)-dione (I). To a boiling suspension of 6 g
41.6 mmol) of thiobarbituric acid in 50 ml of
C=CH), 6.94–7.39 m (4H, Harom), 11.5 s (1H, NH),
(
(
1
1.8 s (1H, NH). Found, %: N 11.04. C H N O S.
12 10 2 2
Calculated, %: N 11.37.
anhydrous ethanol was poured 2.9 ml (20.8 mmol) of
triethylamine and 4.25 ml (41.6 mmol) of freshly
distilled benzaldehyde, and the mixture was refluxed at
stirring for 15 min. Then the reaction mixture was
cooled, the solid phase was washed with water and
5-(4-Methoxybenzylidene)-2-thioxodihydropyrimi-
dine-4,6(1H,5H)-dione (III) was obtained analo-
gously from 5 g (34.7 mmol) of thiobarbituric acid, 4.2
ml (34.7 mmol) of p-methoxybenzaldehyde, and 2.4
1
alcohol, and dried. Yield 9.6 g (99%), mp 271–272°C
ml of triethylamine. Yield 8.8 g (97%), mp >300°C. H
1
(
decomp.). H NMR spectrum, δ, ppm: 5.95 s (1H,
NMR spectrum, δ, ppm: 3.8 s (3H, CH ), 5.96 s (1H,
3
C=CH), 6.96–7.36 m (5H, Harom), 11.5 s (1H, NH),
C=CH), 6.91–7.24 m (4H, Harom), 11.6 s (1H, NH),
11.8 s (1H, NH). Found, %: N 10.34. C H N O S.
1
1.8 s (1H, NH). Found, %: N 11.54. C H N O S.
11 8 2 2
12 10
2
3
Calculated, %: N 12.06.
Calculated, %: N 10.68.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 11 2009

2
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RAHIMOV, AVDEEV
5
-(4-Fluorobenzylidene)pyrimidine-4,6(1H,5H)-
ppm: 6.01 s (1H, C=CH), 6.84–7.44 m (2H, Harom),
8.02–8.12 m (2H, CHarom.–CNO2–CHarom.), 11.54 s (1H,
NH), 11.63 s (1H, NH). Found, %: N 15.02.
C H N O S. Calculated, %: N 15.16.
dione (IV) was obtained analogously from 5 g
34.7 mmol) of thiobarbituric acid, 3.7 ml (34.7 mmol)
of p-fluorobenzaldehyde, and 2.4 ml of triethylamine.
(
1
1
7
3
4
1
Yield 8.0 g (92%), mp >300°C. H NMR spectrum, δ,
ppm: 5.90 s (1H, C=CH), 6.92–7.44 m (4H, Harom),
REFERENCES
1
1.6 s (1H, NH), 11.8 s (1H, NH). Found, %: N 11.01.
1
2
3
.
Medien, H.A.A and Zahran, A.A., Phosphorus, Sulfur
and Silicon, 2003, vol. 178, p. 1069.
Schmidt, M.W., Baldridge, K.K., and Boatz, J.A.,
J. Comput. Chem., 1993, vol. 14, p.1347.
Stepin, B.D., Tekhnika laboratornogo eksperimenta v
khimii (Technique of Laboratory Experiment in
Chenistry), Moscow: Khimiya, 1999, p. 600.
C H FN O S. Calculated, %: N 11.19.
11
7
2
2
5
-(4-Nitrobenzylidene)pyrimidine-4,6(1H,5H)-
dione (V) was obtained analogously from 5 g
34.7 mmol) of thiobarbituric acid, 5.2 g (34.7 mmol)
.
.
(
of p-nitrobenzaldehyde, and 2.4 ml of triethylamine.
Yield 9.0 g (94%), mp >300°C. H NMR spectrum, δ,
1
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 11 2009