Synthesis, theoretical investigation of 5-(4-dimethylaminobenzylidene) thiobarbituric acid

Article abstract of DOI:10.14233/ajchem.2013.12595

In this study, synthesis of 5-benzylidene thiobarbituric acid derivative has been described. The route of preparation involved the uses of thiobarbituric acid as starting material and treated with 4-dimethylaminobenzaldehyde compound to give required derivative. This compound was identified by spectroscopic methods; H NMR, FTIR and CHNS analysis and also by measuring its melting point. A theoretical investigation is performed using hybrid Beck model (B3LYP), ESP showed regular distribution of charge density of whole molecule when one of the two proton is removed from ?-carbon, the ESP for HOMO electron density is heavily localized on α negative carbon, reflect the reactivity of thiobarbituric molecule and show it as highly effective nucleophile when act into nucleophilic substitution reactions.

Full text of DOI:10.14233/ajchem.2013.12595

Asian Journal of Chemistry; Vol. 25, No. 6 (2013), 2953-2955
http://dx.doi.org/10.14233/ajchem.2013.12595
Synthesis and Theoretical Investigation of 5-(4-Dimethylaminobenzylidene)thiobarbituric Acid
1
2,*
AHMED H. MAGEED and KARRAR A.S. AL-AMEED
1Department of Chemistry, Faculty of Science, University of Kufa, Najaf, Iraq
2Department of Ecology, Faculty of Science, University of Kufa, Najaf, Iraq
*Corresponding author: E-mail: karrar.saeed@yahoo.com
(Received: 11 November 2011;
Accepted: 3 December 2012)
AJC-12494
In this study, synthesis of 5-benzylidene thiobarbituric acid derivative has been described. The route of preparation involved the uses of
thiobarbituric acid as starting material and treated with 4-dimethylaminobenzaldehyde compound to give required derivative. This
compound was identified by spectroscopic methods; H NMR, FTIR and CHNS analysis and also by measuring its melting point. A
theoretical investigation is performed using hybrid Beck model (B3LYP), ESP showed regular distribution of charge density of whole
molecule when one of the two proton is removed from α-carbon, the ESP for HOMO electron density is heavily localized on α negative
carbon, reflect the reactivity of thiobarbituric molecule and show it as highly effective nucleophile when act into nucleophilic substitution
reactions.
Key Words: Synthesis, 5-(4-Dimethylaminobenzylidene)thiobarbituric acid.
standard in DMSO-d6. Elemental analysis, E.A.G.E.R. -100,
Carlo Erba strumentazione, Italy.
INTRODUCTION
Active hydrogen compounds condense with aldehydes and
ketones kown as Knoevenagel condensations. These aldol-like
condensations usually catalyzed with weak bases. Iminium
ions are intermediates which from α,β-unsaturated compounds
having structures corresponding to these formed by mixed
aldol condensations followed by dehydration. These reactions
are catalyzed by amines or buffer systems containing an amine
and an acid are referred to as Knoevenagel condensations1.
Cross aldol-type condensation of thiobarbituric acid with aro-
matic aldehydes using acetic acid as a catalyst is available for
the preparation2. In this paper, we described a rapid and convenient
method for the synthesis of 5-arylidene thiobarbituric acids
under uncatalyzed conditions using water as the solvent. It is
interesting that the reaction easily occurs in water although
the mechanism involves a net dehydration to the alcoholic
intermediate obtained by nucleophilic attack of the active
methylene neighboring to the carbonyl groups3.
Synthesis of thiobarbituric acid: Thiobarbituric acid was
prepared according to the literature4.
Synthesis of 5-(4-dimethylaminobenzylidene)thiobar-
bituric acid (3a): A mixture of 4-dimethylaminobenzaldehyde
(10 mmol) and thiobarbituric acid (10 mmol) in water (40 mL)
was stirred at 95-100 ºC for 2 h. Then the solid was filtered
and washed subsequently with boiling water and finally with
ether and drying in vacuum. The residue was dissolved in warm
ethanol and recrystallized (76.92 % yield) as a red solid, m.p.
256 ºC; 1H NMR (DMSO-d6) δ: 2.6 [s, 6H, N(CH3)2], δ 6.1 (s,
1H, CH), δ 6.78-7.26 (m, 4H), δ 12.3 (s, 1H, NH); FTIR (KBr,
ν
max, cm-1) 3122 (NH), 3066 (CH), 1689 (C=O), 1647 (C=S),
1606 (C=C). Anal. calcd. for C13H13N3O2S: C, 56.71; H, 4.76;
N, 15.26; S, 11.65 Found: C, 58.37; H, 5.01; N, 15.57; S,
10.91.
Synthesis of 5-(4-hydroxy-2-methoxybenzylidene)-
thiobarbituric acid (3b): According to the preparation of
3a, 3b was prepared from thiobarbituric acid and 4-hydroxy-
2-methoxybenzylidene as a yellow solid, m.p. 223 ºC; FTIR
(KBr, νmax, cm-1) 3184 (NH), 3385 (OH),3066 (CH),1670
(C=O),1647 (C=S), 1606 (C=C).Anal. calcd. for C12H10N2O4S:
C, 51.79; H, 3.62; N, 10.07; S, 11.52 Found: C, 52.17; H,
3.51; N, 10.57; S, 11.89.
EXPERIMENTAL
Solvents and materials were obtained from Fluka
(Taufkirchen, Germany). Electro thermal 1A melting point
apparatus was used to measure the melting point of prepared
compound. Infrared spectra were recorded as KBr discs using
Fourier transform infrared spectrophotometer FTIR-8400s
1
Synthesis of 5-(4-bromobenzylidene)thiobarbituric
acid (3c): According to the preparation of 3a, 3c was prepared
SHIMADZU. H NMR spectra were recorded by Brukur,
Ultra Shield 300 MHz, Switzerland with TMS as internal

2954 Mageed et al.
Asian J. Chem.
from thiobarbituric acid and 4-bromobenzylidene as a white
solid, m.p. 198 ºC; 1H NMR (DMSO-d6); δ 6.5 (s, 1H, CH), δ
6.78-7.26 (m, 4H), δ 12.1 (s,1H, NH); FTIR (KBr, νmax, cm-1)
3223 (NH), 3070 (CH), 1688 (C=O),1649 (C=S), 1600 (C=C).
Anal. calcd. for C11H7BrN2O2S: C, 42.46; H, 2.27; N, 9.00; S,
10.31 Found: C, 42.67; H, 2.54; N, 9.38; S, 9.98.
program package. The theoretical investigation are performed
by using one of more effective hybrid Beck6 model [B3LYP/
6-31G(d)] model chemistry in calculation the optimized
structures, the difference density plots were prepared using
Gauss view software.
TABLE-1
SYNTHESIS OF 5-BENZYLIDENETHIOBARBITURIC
ACID DERIVATIVES
Synthesis of 5-(2-bromobenzylidene)thiobarbituric
acid (3d): According to the preparation of 3a, 3d was prepared
from thiobarbituric acid and 2-bromobenzylidene as a white
solid, m.p. 203 ºC; FTIR (KBr, νmax, cm-1) 3223 (NH), 3070
(CH), 1653 (C=O), 1638 (C=S), 1598 (C=C). Anal. calcd. for
C11H7BrN2O2S: C, 42.46; H, 2.27; N, 9.00; S, 10.31 Found: C,
42.78; H, 2.59; N, 9.28; S, 10.12.
Compound
Ph
Yields (%)
76.92
p-N(CH3)2
o-OCH3, p-OH
p-Br
3a
3b
3c
3d
3e
3f
74.56
85.78
o-Br
83.45
Synthesis of 5-(3-methoxybenzylidene)thiobarbituric
acid (3e): According to the preparation of 3a, 3e was prepared
from thiobarbituric acid and 3-methoxybenzylidene as a
yellow solid, m.p. 204 ºC; FTIR (KBr, νmax, cm-1): 3211 (NH),
3066 (CH), 1680 (C=O), 1647 (C=S), 1606 (C=C).Anal. calcd.
for C12H10N2O3S: C, 54.95; H, 3.84; N, 10.68; S, 12.23 Found:
C, 54.37; H, 3.61; N, 10.58; S, 12.52.
m-OCH3
o-OH
77.87
53.54
Fig. 1 shows how the p-electron resonance is spreading
and distributed around larger regions on six member ring of
thiobarbitic acid anion(III) where the corresponding free
radical(II) and neutral(I) molecules the electron no localization
region is aggregate on one side, so the negative charge add to
molecular system more stability than the parent molecule, then
attend to be favourite to remove the first acidic hydrogen from
α-carbon.
Synthesis of 5-(2-hydroxybenzylidene)thiobarbituric
acid (3f): According to the preparation of 3a, 3f was prepared
from thiobarbituric acid and 2-hydroxybenzylidene as a yellow
solid, m.p. 243 ºC; FTIR (KBr, νmax, cm-1) 3345 (OH), 3219
(NH), 3065 (CH), 1675 (C=O), 1649 (C=S), 1606 (C=C).Anal.
calcd. for C11H8N2O3S: C, 53.22; H, 3.25; N, 11.28; S, 12.92
Found: C, 53.67; H, 3.60; N, 10.98; S, 12.72.
(I)
(II)
(III)
RESULTS AND DISCUSSION
The present investigation involved the application of
thiobarbituric acid as starting material which was readily
accessible from diethylmalonate and thiourea as shown on
(Scheme-I).
Fig. 1. Show the optimized structures of (thiobarbituric acid) molecule in
different (I) the neutral molecules and (II) and (III) free radical and
negative ones calculated by DFT methods [B3LYP/6-31G(d) ] level
theory
O
S
O
O
NH
NH
EtONa
H2N
S
NH2
110 oC , 7h
EtO
Fig. 2 shows a representation of electrostatic potential of
total electron density to thiobarbituric acid molecule, the red
region corresponding the high electron density locations, ESP
surface confirm the regular distribution of charge density of
whole molecules when one of the two proton are removed
from α-carbon atom.
OEt
thiourea
diethyl malonate
O
thiobarbituric acid
Scheme-I: Synthesis of thiobarbituric acid
In this paper, we describe a rapid and convenient method
for the synthesis of 5-arylidene thiobarbituric acids under
uncatalyzed conditions using water as the solvent (Scheme-
II).
O
O
H
NH
NH
H2O
C
NH
S
95-100 o
C
O
O
N
H
S
O
2
3
1
Scheme-II: Synthesis of 5-(4-dimethylaminobenzylidene)thiobarbituric acid
The electronic structure of (thiobarbituric acid) and 5-(4-
dimethylaminobe-nzylidene) thiobarbituric acid was calcu-
lated by density functional theory using the Gaussian095
Fig. 2. Electrostatic potential surface for total electron density of
(thiobarbituric acid) anion calculated by DFT methods [B3LYP/6-
31G (d)] level theory

Vol. 25, No. 6 (2013)
Synthesis and Theoretical Investigation of 5-(4-Dimethylaminobenzylidene)thiobarbituric Acid 2955
The highest occupied molecular orbital (HOMO) (Fig. 3)
show electron density are heavily localized on α-negative
carbon atom, reflect the reactivity of thiobarbituric acid mole-
cule, and show it as highly effective nucleophile when act onto
nucleophilic substitution reactions.
Conclusion
A simple synthetic route for 5-(4-dimethylamino-
benzylidene)thiobarbituric acid by the condensation reaction
of 4-dimethylaminobenzaldehyde with thiobarbituric acid in
water without catalyst is described.
ACKNOWLEDGEMENTS
The authors thank Central Laboratory in Kufa University
for the research facilities.
REFERENCES
1. N. Tavakoli-Hoseini, M.M. Heravi and F.F. Bamoharram, Asian J. Chem.,
22, 7208 (2010).
2. A.I.D. Yachkov, B.A. Ivin, N.A. Smorygo and E.G. Sochilin, Zh. Org.
Khim., 12, 1115 (1976).
3. B.Q. Yang, J. Lu and M. Tian, Chinese Chem. Lett., 14, 1240 (2003).
4. M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb,
J.R. Cheeseman, G. Scalmani,V. Barone, B. Mennucci, G.A. Petersson,
H. Nakatsuji, M. Caricato, X. Li, H.P. Hratchian,A.F. Izmaylov, J. Bloino,
G. Zheng, J.L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda,
J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T.
Vreven, J.A. Montgomery, Jr. J.E. Peralta, F. Ogliaro, M. Bearpark,
J.J. Heyd, E. Brothers, K.N. Kudin, V.N. Staroverov, R. Kobayashi, J.
Normand, K. Raghavachari, A. Rendell, J.C. Burant, S.S. Iyengar, J.
Tomasi, M. Cossi, N. Rega, J.M. Millam, M. Klene, J.E. Knox, J.B.
Cross, V. Bakken, C.Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann,
O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, R.L. Martin,
K. Morokuma, V.G. Zakrzewski, G.A. Voth, P. Salvador, J.J.
Dannenberg, S. Dapprich, A.D. Daniels, O. Farkas, J.B. Foresman, J.V.
Ortiz, J. Cioslowski and D.J. Fox, Gaussian, Inc., Wallingford CT (2009).
5. A.D. Becke, J. Chem. Phys., 98, 1372 (1993).
Fig. 3. Electrostatic potential surface of HOMO electron density for
molecules calculated by DFT methods [B3LYP/6-31G(d)] level
theory for (thiobarbituric acid) anion
The electrostatic potential (Fig. 4) show of total electron
density of product compound, is clear that molecular system
have high dipole moment and that make the molecules is polar
one, because the highly density localized on lone pairs region
of oxygen and sulfur atoms (red colour) in one side where the
electron defiecent is clear (blue colour) on another side of
molecule, this polarity make 5-(4-dimethylaminobenzylidene)
thiobarbituric acid molecule tend to be soluble in polar solvent.
6. N.T. Fan, Examples of Organic Synthesis, Beijing University of Science
and Technology Press, Beijing,, p. 215 (1995).
Fig. 4. Electrostatic potential surface for total electron density of 5-(4-
dimethylaminobenzylidene)thiobarbituric acid molecule calculated
by DFT methods [B3LYP/6-31G(d)] level theory