Design and synthesis of naphthol derivative using three components system and its relation with physicochemical parameters log P and π

Article abstract of DOI:10.14233/ajchem.2013.13905

A naphthol derivative was synthesized using the three-component system (β-naphthol, benzaldehyde and N-(2-aminoethyl)-4-hydroxybenzamide) and characterized by spectral analyses. In order to characterize the structural and chemical requirements of naphthol derivative, some parameters such as log P and π were evaluated. The results showed an increase in the values of log P and π for the compound 4 in comparison with 1, 2 and 3. These data indicate a high degree of lipophilicity and steric impediment for compound 4 in comparison with 1, 2 and 3.

Full text of DOI:10.14233/ajchem.2013.13905

Asian Journal of Chemistry; Vol. 25, No. 6 (2013), 3421-3423
http://dx.doi.org/10.14233/ajchem.2013.13905
Design and Synthesis of Naphthol Derivative Using Three Components
System and Its Relation with Physicochemical Parameters log P and π
1,*
2
1
1
1
L.FIGUEROA-VALVERDE , F.DÍAZ-CEDILLO , E. GARCÍA-CERVERA , E. POOL GÓMEZ and JOHANY CORDOVA-VAZQUEZ
1Laboratory of Pharmaco-Chemistry, Faculty of Chemical Biological Sciences, University Autonomic of Campeche, Av. Agustín Melgar s/n,
Col., Buenavista C.P. 24039 Campeche Cam., México
2Escuela Nacional de Ciencias Biológicas del Instituto Politécnico Nacional, Prol. Carpio y Plan de Ayala s/n Col. Santo Tomas, D.F. C.P.
11340, México
*Corresponding author: E-mail: lauro_1999@yahoo.com
(Received: 14 April 2012;
Accepted: 24 December 2012)
AJC-12603
A naphthol derivative was synthesized using the three-component system (β-naphthol, benzaldehyde and N-(2-aminoethyl)-4-
hydroxybenzamide) and characterized by spectral analyses. In order to characterize the structural and chemical requirements of naphthol
derivative, some parameters such as log P and π were evaluated. The results showed an increase in the values of log P and π for the
compound 4 in comparison with 1, 2 and 3. These data indicate a high degree of lipophilicity and steric impediment for compound 4 in
comparison with 1, 2 and 3.
Key Words: Naphthol, Derivatives, Synthesis.
derivative was synthetized using the three-component system
[β-naphthol, benzaldehyde and N-(2-aminoethyl)-4-hydroxy-
benzamide].
INTRODUCTION
Aromatic-condensed derivatives are a important hetero-
cyclic compounds which induced several biological activities
such as antibacterial1,2 and as material in the production of
polyesters fibers and plastics3. There are several methods
reported for synthesis of aromatic-condensed derivatives, e.g.,
the synthesis of naphthyl ketone by the reaction of o-
alkynylbenzaldehydes with alkynes using AuCl3 as catalyst4.
In addition, other studies shown the synthesis of 1,3-disubsti-
tuted naphthalenes from the Baylis-Hillman acetates with the
help of manganese(III) acetate5. Other reports indicate the
tandem pummerer Diels-Alder sequence for the preparation
of α-thio substituted naphthalene derivatives6. Additionally,
other studies7 showed the synthesis of 1,8-diphenylnaphtalene
and 1-iodo-8-phenylnaphtalene by the reaction of lithium
diphenyl cuprate and aryl halides. Other studies by Ganapathy
and Viswanathan8 shown the synthesis of polysubstituted naph-
thalene derivatives through gallium trichloride catalyzed by
alkyne-aldehyde coupling. In addition, some carbamato-alkyl-
naphthol derivatives9 have been synthetized by condensation
of β-naphthol, aromatic aldehyde and methyl carbamate in
ionic liquid media.All these experimental results show several
procedures which are available for synthesis of naphthalene
derivatives. Nevertheless, expensive reagents and special
conditions are required. Therefore, in this study a naphthol
EXPERIMENTAL
N-(2-Aminoethyl)-4-hydroxybenzamide was prepared
according to reported method10. The other compounds evaluated
in this study were purchased from Sigma-Aldrich Co., Ltd.
The melting points for the different compounds were deter-
mined on an electrothermal (900 model). Infrared spectra was
recorded using KBr pellets on a Perkin Elmer Lambda 40 spec-
trometer. 1H and 13C NMR spectra were recorded on a varian
VXR-300/5 FT NMR spectrometer at 300 and 75.4 MHz in
CDCl3 using TMS as internal standard. EIMS spectra were
obtained with a Finnigan Trace GCPolaris Q. Spectrometer.
elementary analysis data were acquired from a Perkin-Elmer
Ser. II CHNS/0 2400 elemental analyzer.
4-Hydroxy-N-(2-{[(2-hydroxy-naphtalen-1-yl)-phenyl-
methyl]-amino}-ethyl)-benzamide (4): A solution of N-(2-
aminoethyl)-4-hydroxybenzamide (126 mg, 0.69 m mol),
β-naphthol (100 mg, 0.69 mmol), benzaldehyde (70 µL, 0.69
mmol) in 10 mL of ethanol was stirring for 48 h to room
temperature. The reaction mixture was evaporated to a smaller
volume.After the mixture was diluted with water and extracted
with chloroform. The organic phase was evaporated to dryness
under reduced pressure, the residue was purified by crystalli-

3422 Figueroa-Valverde et al.
Asian J. Chem.
O
H
zation from methanol: water (4:1) yielding 60 % of product,
O
m.p. 72-74 ºC; IR (KBr, νmax, cm-1): 3630, 3320, 1630 and
OH
1
H2N
1580; H NMR (300 MHz, CDCl3) δH: 3.02 (t, 2H, J = 6.5
NH
+
+
Hz), 3.53 (t, 2H, J = 6.5 Hz), 5.07 (s, 1H), 5.16 (broad), 6.82
(d, 2H), 6.96 (d, 2H), 7.06 (m, 1H), 7.11 (m, 2H), 7.20 (m,
1H), 7.42-7.54 (m, 3H), 7.57 (d, 2H), 7.68-7.75 (m, 2H)
ppm.13C NMR (74.5 MHz, CDCl3) δC: 40.13 (C-15), 53.35
(C-14), 54.43(C-12), 114.38 (C-9), 115.07(C-27, C-29),
121.18 (C-8), 123.47 (C-6), 126.62 (C-7), 126.76 (C-2), 127.25
(C-25), 127.38 (C-22), 128.03 (C-4), 128.94 (C-10), 128.95
(C-26, C-30), 129.52 (C-20, C-24), 129.82 (C-5), 130.07 (C-
21, C-23), 138.95 (C-19), 139.01 (C-3), 152.11 (C-1), 160.43
(C-28), 169.53 (C-17) ppm. EI-MS m/z: 412.72 (M+, 12),
231.19, 143.16, 121.11. Anal. calcd. (%) for: C26H24N2O3: C,
75.71; H, 5.86; N, 6.79; O, 11.64. Found (%): C, 75.68; H,
5.83.
OH
1
2
3
O
NH
NH
OH
OH
4
Fig. 1. Synthesis of 4-hydroxy-N-(2-{[(2-hydroxy-naphtalen-1-yl)-phenyl-
methyl]-amino}-ethyl)-benzamide (4) using the three-component
system[β-naphthol (1), benzaldehyde (2) and N-(2-aminoethyl)-4-
hydroxybenzamide (3)]
RESULTS AND DISCUSSION
TABLE-1
Many procedures for formation of naphthol derivatives
are available in the literature. Nevertheless, despite their wide
scope, these procedures suffer from several drawbacks; some
reagents are of limited stability and preparation can be dange-
rous11-13. Therefore, in this study we report a straight forward
route for synthesis of new naphthol derivative using the three-
component system [β-naphthol, benzaldehyde and N-(2-
aminoethyl)-4-hydroxybenzamide] in ethanol under reflux
(Fig. 1). The 1H NMR spectrum of 4 shows signals at 3.02 and
3.53 ppm for protons involved in the arm bound to amide and
amine groups; at 5.07 ppm for hydrogen of methylene which
is bound to both phenyl and naphthol groups. Other signal at
5.16 ppm for both amino and hydroxyl groups were found.
Finally, the spectrum contains several signals at 6.82-6.96,
7.11, 7.20 and 7.57 ppm for phenyl groups; at 7.06, 7.42-7.75
ppm for naphthol group. The 13C NMR spectrum contains
peaks at chemical shifts of 42.13 and 53.35 ppm for the carbons
of the methylenes involved in the arm bound to amide and
amine groups. A signal at 54.43 ppm for methylene bound to
phenyl group and naphthol group was found. In addition,
several signals at 114.38, 121.18-126.76, 128.03-128.94,
129.82 and 139.03-152.11 ppm for carbons involved in the
naphthol group; at 115.07, 127.25-127.38, 128.95-129.52,
130.07-138.98 and 160.43 ppm for carbons of phenyl groups;
169.53 ppm for amide group were found. In addition, the
presence of 4 was further confirmed from mass spectrum which
showed a molecular ion at m/z 412.72.
Analyses of physicochemical parameters: In order to
characterize the structural and chemical requirements of
naphthol derivative (4), some descriptors such as log P and π
were calculated. log P describes the logarithmic octanol-
water partition coefficient; therefore, it represents the lipophilic
effects of a molecule that includes the sum of the lipophilic
contributions of the parent molecule and its substituents14. The
difference between the substituted and unsubstituted log P
values is conditioned by the π value for a particular substi-
tuent15. In this work, log P and π parameters were calculated
by the method reported by Leo14 and Mannhold and
Waterbeemd16. The results (Tables 1-4) showed an increase in
both log P and π values of compound 4 with respect to 1, 2
PHYSICOCHEMICAL PARAMETERS
log Kow AND π OF β-NAPHTHOL (1)
Compound
log Kow fragment
Aromatic carbon
-OH [hydroxy, aromatic attach]
Contributions
2.9400
-0.4802
0.2290
2.6888
-0.4820
Equation constant
1
log Kow
π
TABLE-2
PHYSICOCHEMICAL PARAMETERS
log Kow AND π OF BENZALDEHYDE (2)
log Kow fragment
Aromatic carbon
-OH [aldehyde, aromatic attach]
Compound
Contributions
1.7640
-0.2828
0.2290
1.7102
-0.2828
Equation constant
2
log Kow
π
TABLE-3
PHYSICOCHEMICAL PARAMETERS log Kow AND π OF
N-(2-AMINOETHYL)-4-HYDROXYBENZAMIDE (3)
Compound
log Kow fragment
-CH2 [aliphatic carbon]
-NH2 [aliphatic attach]
-NH- [aliphatic attach]
Aromatic carbon
-OH [hydroxy, aromatic attach]
-C(=O)N [aromatic attach]
Equation constant
log Kow
Contributions
0.9822
-1.4148
-1.4962
1.7640
-0.4802
0.1599
0.2290
-0.2561
1.1381
3
π
and 3. These results showed that both aliphatic carbon (-CH)
and aromatic carbon involved in chemical structure of 4 contri-
bute to the highlipophilicity in comparison with compounds
1, 2 and 3. These data indicate a high steric impediment and
different conformationalpreferences and internal rotation of 4
in comparison with 1, 2 and 3. These data are supported by
studies of Bryantsev and coworkers17, who showed that confor-
mational differences between several chemical functional
groups have important consequences.

Vol. 25, No. 6 (2013)
Design and Synthesis of Naphthol Derivative Using Three Components System 3423
TABLE-4
REFERENCES
PHYSICOCHEMICAL PARAMETERS log Kow
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AND π OF NAPHTHOL DERIVATIVE (4)
Compound
log Kow fragment
-CH2 [aliphatic carbon]
-NH2 [aliphatic attach]
-NH- [aliphatic attach]
Aromatic carbon
Contributions
0.9822
0.3614
-2.9924
6.4680
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-C(=O)N [aromatic attach]
Equation constant
log Kow
0.9604
4
(2002).
0.1599
0.2290
4.2477
1.5577
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π
Conclusion
In this study, we report an easy methodology for synthesize
a naphthol derivative using the three-component system
(β-naphthol, benzaldehyde and N-(2-aminoethyl)-4-hydroxy-
benzamide). In addition, other results indicate a high degree
of lipophilicity and a steric impediment of compound 4 in
comparison with 1, 2 and 3.
17. S. Bryantsev and P. Hay, J. Phys. Chem. A, 110, 4678 (2006).