General method for the high yield preparation of 2-(4-X-phenylene)amine-1,4-naphthoquinones (X = ferrocenyl, OMe, Me, I, Cl, and NO2) from 2-methoxy-1,4-naphthoquinone and investigation of H+ and Mg2+ catalysts with DFT calculations

Article abstract of DOI:10.1016/j.molstruc.2008.03.028

A rapid and simple method for the high yield preparation of 2-(4-X-phenylene)amine-1,4-naphthoquinones from 2-methoxy-1,4-naphthoquinone, in boiling MeOH, using MgCl₂ and p-toluenesulfonic acid as catalysts is described. This methodology has been applied successfully to the synthesis of electron donor (4-OMe, 4-Me, 4-ferrocenyl) and electron withdrawing (4-I, 4-Cl, 4- and 3-NO₂) aniline derivatives. The effect of both H⁺ and Mg²⁺ as catalysts was investigated using DFT calculations carried out at the B3LYP/6-31G(d) level. The electronic properties of the novel 2-(4-ferrocenylphenylene)amine-1,4-naphthoquinone 3b were investigated and show that the ferrocenyl and the methoxy group have similar electron donor properties in 2-(4-methoxy)amine-1,4-naphthoquinone 3a.

Full text of DOI:10.1016/j.molstruc.2008.03.028

Journal of Molecular Structure 891 (2008) 228–232
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
General method for the high yield preparation of
2-(4-X-phenylene)amine-1,4-naphthoquinones (X = ferrocenyl, OMe, Me, I, Cl,
and NO2) from 2-methoxy-1,4-naphthoquinone and investigation of H+ and Mg2+
catalysts with DFT calculations
a
a
Acácio I. Francisco a, Maria D. Vargas a, , J. Walkimar de M. Carneiro , Maurício Lanznaster ,
*
José C. Torres b, Celso A. Camara c, Angelo C. Pinto d
a Instituto de Química, Universidade Federal Fluminense, Campus do Valonguinho, CEP 24020-141, Niterói, RJ, Brazil
b CEFET Química – Unidade Nilópolis, CEP: 26530-060, Nilópolis, RJ, Brazil
c Instituto de Química, Universidade Federal Rural de Pernambuco, Brazil
d Instituto de Química, Universidade Federal do Rio de Janeiro, 21949-900, Rio de Janeiro, RJ, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
A rapid and simple method for the high yield preparation of 2-(4-X-phenylene)amine-1,4-naphthoqui-
nones from 2-methoxy-1,4-naphthoquinone, in boiling MeOH, using MgCl2 and p-toluenesulfonic acid
as catalysts is described. This methodology has been applied successfully to the synthesis of electron
donor (4-OMe, 4-Me, 4-ferrocenyl) and electron withdrawing (4-I, 4-Cl, 4- and 3-NO2) aniline derivatives.
The effect of both H+ and Mg2+ as catalysts was investigated using DFT calculations carried out at the
B3LYP/6-31G(d) level. The electronic properties of the novel 2-(4-ferrocenylphenylene)amine-1,4-naph-
thoquinone 3b were investigated and show that the ferrocenyl and the methoxy group have similar elec-
tron donor properties in 2-(4-methoxy)amine-1,4-naphthoquinone 3a.
Received 19 December 2007
Received in revised form 13 March 2008
Accepted 20 March 2008
Available online 28 March 2008
Keywords:
1,4-Naphthoquinone
Ferrocenylphenyleneamine-1,4-
naphthoquinone
Ó 2008 Elsevier B.V. All rights reserved.
Nucleophilic substitution
DFT calculations
UV–vis spectra
1. Introduction
of 2-methoxy-1,4-naphthoquinone with amines in boiling ethanol
[27,28] or methanol [28] is the best route to 2-amino-1,4-naphtho-
The growing interest in 2-amino-1,4-naphthoquinones is due to
their wide range of pharmacological properties [1] including anti-
malarial [2–4], antibacterial [5], anticancer [6–9], larvicide [10],
molluscicide [11,12], herbicide [13–15], and fungicide [16].
1,4-Naphthoquinones substituted at C-2 can be obtained through
nucleophilic processes, either addition or substitution reactions
[17]. Direct addition of arylamines to 1,4-naphthoquinone [18,19]
or to 6(7)-alkyl-1,4-naphthoquinones [20,21] was shown to produce
the respective 2-arylamine-1,4-naphthoquinones in moderate to
low yields, especially with electron deficient systems, such as
nitroanilines, though the use of CeCl3ꢀ7H2O to catalyze the reaction
of 1,4-naphthoquinone with anilines has led to improved yields of
the products [22,23]. Substitution reaction of 2,3-dichloro-1,4-
naphthoquinone with arylamines in pyridine [24–26] has been
reported to lead to the desired 2-arylamine-1,4-naphthoquinones,
albeit in poor yields; in the presence of alcohols, the 2-arylamine-
3-chloroisobtainedinstead[25]. Althoughnucleophilicsubstitution
quinones, the reactions with substituted anilines give the desired
products in yields not higher than 60%, depending on the aniline
[27,28]. This work describes a rapid and simple method for the
high yield preparation of 2-(4-X-phenylene)amine-1,4-naphthoqui-
nones from 2-methoxy-1,4-naphthoquinone, using MgCl2 and
p-toluenesulfonic acid as catalysts. Electron donor (4-OMe, 4-Me,
4-ferrocenyl) and electron withdrawing (4-I, 4-Cl, 4- and 3-NO2)
aniline derivatives were obtained in good yields, and the novel
2-(4-ferrocenylphenylene)amine-1,4-naphthoquinone is described
herein. Furthermore the effect of both H+ and Mg2+ catalysts on the
reaction mechanism was investigated using DFT calculations carried
out at the B3LYP/6-31G(d) level.
2. Experimental
2.1. Instruments and methods
Melting points are uncorrected. The NMR spectra were recorded
on a Varian 300 MHz spectrometer. Chemical shifts are reported in
* Corresponding author. Tel.: +55 21 26292225; fax: +55 21 2629 2236.
E-mail address: mdvargas@vm.uff.br (M.D. Vargas).
0022-2860/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2008.03.028

A.I. Francisco et al. / Journal of Molecular Structure 891 (2008) 228–232
229
ppm relative to TMS as internal reference. IR spectra were recorded
on a FT-IR spectrum One (Perkin–Elmer) (KBr). UV–vis spectra
were obtained in a Diode Array 8452A (Hewlett Packard – HP)
spectrometer, in spectroscopic grade acetonitrile. Mass spectra
were obtained in a HR-ESI-MS performed in the positive mode
(UltrOTOF-Q system, version 1.10, Bruker Daltonics, MA, USA).
Cyclic voltammograms were obtained on an Epsilon – BAS poten-
tiostat-galvanostat from 1 ꢁ 10ꢂ3 mol/L solutions in dichlorometh-
ane containing 0.1 mol/L of TBAPF6 as supporting electrolyte, at
room temperature and under argon atmosphere. A standard three
component system was used: a carbon-glassy working electrode, a
platinum wire auxiliary electrode, and an Ag/AgCl reference elec-
trode for organic media. Ferrocene was used as an internal stan-
dard (E1/2 0.40 V vs NHE). Analytical thin-layer chromatography
was performed with precoated silica gel 60 F-254 plates
(0.25 mm thick) from Sorbent Technologies and visualized by UV
(254 nm). Purification by column chromatography was carried
out over Merck silica gel 60 (0.063–0.200 mm).
1 equiv. of 2a (Table 1, entry 5). The reactions were stopped after
5 h, when formation of the product was quantified.
2.2.2. General method for the preparation of 3b–3h
The syntheses of 3b–3h were carried out as described for 3a,
using 62 mg (0.32 mmol) of 1, 48 mmol of anilines 2b–2h in MeOH
(6 mL), under reflux, in the presence of the catalysts (5% cat1 + 5%
cat2) for varying periods of time (see Table 2). The reactions were
monitored by TLC (ethylacetate:hexane 3:7). The products were
purified as follows: column chromatography with ethyl acetate/
hexane 5% gave pure 3b (80%, Table 2, entry 2); filtration over silica
with ethyl acetate/hexane 5% and recrystallization from dichloro-
methane yielded pure 3d (85%) and 3e (75%) (entries 5 and 6);
products 3g and 3h (70 and 74%, respectively) were isolated free
from the respective anilines 2g and 2h by washing the crude solids
with cold methanol after elimination of cat1 and cat2, followed by
recrystallization from acetonitrile.
3b: IR (KBr): mmax (cm-1) 3270 (NH), 1682 (C@O), 1621 (C@O),
1596 (C@C), 1123 and 992 (C@C Fc); 1H NMR (CDCl3, 300 MHz):
d 4.06 (s, 5H, Cp), 4.35 (dd, J = 2.28, 1.96 Hz, 2H), 4.65 (dd,
J = 2.28, 1.96 Hz, 2H), 6.48 (s, 1H), 7.22 (dd, J = 6.06, 2.04 Hz, 2H),
7.53 (dd, J = 6.06, 2.04 Hz, 2H), 7.69 (m, 1H), 7.79 (m, 1H), 8.13
(ddd, J = 7.55, 1.52, 0.49 Hz, 1H), 8.16 (ddd, J = 7.55, 1.52, 0.49 Hz,
1H); 13C NMR (CDCl3, 300 MHz) d 183.7, 182.1, 144.5, 137.0,
135.8, 135.7, 133.1, 132.5, 130.9, 127.4 (2C), 126.6, 126.2, 122.9
(2C), 103.8, 84.9, 70.0 (5C), 69.7 (2C), 66.8 (2C); HRMS found:
434.0838. Calcd for C26H19NO2Fe: 434.0858.
2.2. Chemicals
The starting 2-methoxy-1,4-naphthoquinone 1 [29] and 4-fer-
rocenylaniline 2b [30,31] were synthesized by literature proce-
dures. The substituted anilines (Sigma–Aldrich) were used as
received. Solvents were distilled before use. The identity of the
known products was established by comparison of their melting
points with literature values (Table 2) and 1H NMR spectra.
2.2.1. 2-[40-methoxyphenyl)amine-1,4-naphthalenedione (3a) [24]
2.3. Calculations
2-Methoxy-1,4-naphthoquinone
1 (62 mg; 0.32 mmol) in
MeOH (6 mL) was heated under reflux in the presence of
MgCl2ꢀ6H2O (3.3 mg, 0.05 equiv. = cat1) and p-toluenesulfonic acid
(2.7 mg; 0.05 equiv. = cat2) for 10 min. to dissolve most of 1, and 4-
methoxyaniline (51.4 mg, .48 mmol) was then added as a solid. The
reaction was kept under reflux for 5 h after which time no starting
material 1 was observed on the TLC plate (ethylacetate:hexane
3:7). The dark purple solid formed when the mixture was left to
cool down to room temperature was filtered off, washed with
water to eliminate cat1 and cat2, and dried under vacuum. Pure
3a was obtained after excess 2a was eliminated upon dissolving
the crude product in ethylacetate/hexane and filtering the solution
through silica (95%).
Density functional calculations were carried out using the
Gaussian03W molecular orbital package [32]. Geometries were
fully optimized using the B3LYP functional [33] with the stan-
dard 6-31G(d)basis set [34]. The nature of each stationary point
was characterized at the same level via calculation of the second
order force constant matrix. Transition states were identified by
the presence of one imaginary vibrational frequency. Solvent ef-
fects were estimated by single-point calculations on the gas-
phase optimized geometries by mean of the continuum solvation
model using the conductor-like polarizable continuum model
[35] (CPCM) at the same level. Methanol was selected as the sol-
vent since reactions were carried out in this medium. The
parameters in the solvation simulations were kept at the default
values.
This reaction was also carried out as described above but: (i) in
the absence of both catalysts using 1 or 1.5 equiv. of 2a (Table 1,
entries 1 and 2, respectively); (ii) in the presence of 10% of each
catalyst (entries 3 and 4) and using both catalysts (5% each) using
Previous theoretical [36] and experimental [37] studies indi-
cate that the first solvation shell on a Mg2+ ion is well simulated
Table 2
Table 1
Reactions of 1 with 2a–h in MeOH (0.053 mol Lꢂ1), under reflux, in the presence of
the catalysts (5% cat1 = MgCl2 + 5% cat2 = 4-toluenesulfonic acid) to yield 3a–h
Reactions of 1 with 4-methoxyaniline 2a in MeOH (0.053 mol Lꢂ1), under reflux for
5 h, in the dark and in the absence or presence of cat1 (MgCl2), or/and cat2 (4-
toluenesulfonic acid) to yield 3a
Entry
Aniline
(R)
Time/h
Product
(R)
Aprox.
yield/%
mp/°C
O
O
O
1
2a (4-OCH3)
5
3a
95
150–152 (CH2Cl2)
Lit: 155–157 (CHCl3)a
227–229 (CH2Cl2)
205–206 (CH2Cl2)
Lit: 201 (CHCl3)a
182–184 (CH2Cl2)
Lit: 191a
H
N
OMe
+
2
3
2b (4-Fc)
2c (4-Me)
6
5
3b
3c
80
82
MeOH/Δ 5-8h
cat1 and/or cat2
2a
OMe
3a
1
O
4
2d (H)
6
3d
85
Entry
1:2a ratio
Catalyst
Yields (%)*
5
6
2e (4-I)
2f (4-Cl)
8
7
3e
3f
75
81
220–222 (CH2Cl2)
227 °C (CHCl3)
1
2
3
4
5
6
1:1
1:1.5
1:1
1:1
1:1
–
–
40
47
50
50
62
97
Lit: 230–232 (CH2Cl2)a
337–339 Lit: 339a
252–255 (CH2Cl2)
Lit: 258–260(MeCN)b
cat110%
cat210%
7
8
2g (4-NO2)
2h (3-NO2)
10
10
3g
3h
70
74
cat1 + cat2 10%
cat1 + cat2 10%
1:1.5
a
Ref. [24].
Ref. [22].
*
b
Isolated yields.

230
A.I. Francisco et al. / Journal of Molecular Structure 891 (2008) 228–232
by six water molecules. Following this observation we simulated
cat1 as a Mg2+ ion explicitly solvated by five water molecules
which, after coordination to the oxygen atom of the naphthoqui-
none, completes the coordination shell of the Mg2+ ion in an
approximately octahedral arrangement. For cat2 the situation is
somewhat more complex. Proton hydration, H+(H2O)n, has been
observed for several values of n, depending on the experimental
conditions [38]. We made several attempts to find the ideal num-
ber of water molecules able to solvate the proton bonded to the
naphthoquinone. Calculations seem to converge to a di-coordi-
nated proton, therefore bonded to only one water molecule.
When adding more water molecules to the first solvation shell
it moves away from the proton. Dihydrated proton has been ob-
served experimentally [39]. Based on these facts we decided to
simulate cat2 including only one water molecule in the first sol-
vation shell.
Fig. 1. Structure of 2-(4-ferrocenylphenylene)amine-1,4-naphthoquinone.
3. Results and discussion
3.1. Syntheses
As summarized in Table 1, the reaction of 2-methoxy-1,4-naph-
thoquinone 1 (0.053 mol Lꢂ1) with 4-methoxyaniline 2a in boiling
MeOH was investigated in the presence of either 10% MgCl2 (cat1),
or 10% p-toluenesulfonic acid (cat2), or both catalysts (5 + 5%). The
reactions were stopped after 5 h, when formation of the product
was quantified. In the absence of catalyst the reaction resulted in
poor yield of 3a (entry 1) that improved slightly upon using 50%
excess of 2a (entry 2). In the presence of cat1 or cat2 yield im-
proved after the same period of time (entries 3 and 4), however,
the two catalysts together led to best yield (97%), after 5 h, when
a 50% excess of 2a was used (entries 5 and 6).
The reactions of 1 with anilines 2b–i (Table 2) were then inves-
tigated in the 1:1.5 ratio, under the conditions described in entry 6
of Table 1. They were monitored by TLC and were stopped when 1
was no more visualized on the plate. Although the reaction with 2b
was carried out under argon, maximum conversion and yield of the
product (entry 2) was obtained after 6 h; heating for longer period
of time resulted in lower yield, possibly due to oxidation of the fer-
rocenylaniline 2b and/or the product 3b in the presence of cat2. As
expected anilines containing electron donor groups reacted fastest,
and those with electron withdrawing groups, slowest, also result-
ing in slightly lower yields of products.
Products 3b–c were isolated impure with the respective ani-
lines and the purification strategy in each case depended on the
aniline (see Section 2). The identity of 3a and 3d–h was confirmed
by NMR spectroscopy and melting points. To our knowledge these
are the best yields of these compounds reported so far.
Fig. 2. Cyclic voltamograms of 1 mmol/L of 3a and 3b in 0.1 mol/L TBAPF6/CH2Cl2
solutions obtained at 0.1 V/s with a glassy carbon working electrode. E1/2 (Fc/F-
c+) = 0.55 V vs Ag/AgCl (organic).
Table 3
Voltametric data (V) of 3b and 3a
Compound
E1/2(1)
E1/2(2)
E1/2(3)
E1/2(1)ꢂE1/2(2)
3ba
3aa
3ab
ꢂ1.26
ꢂ1.26
ꢂ1.24
ꢂ1.67
ꢂ1.69
ꢂ1.81
0.05
–
–
0.41
0.43
0.57
a
Data obtained in CH2Cl2.
Obtained in MeCN [42].
b
to the consecutive one-electron transfer to the naphthoquinone
moiety, generating the semiquinone radical (QÅꢂ) and the hydro-
quinone anion (Q2ꢂ): Q + 1eꢂ ¢ QÅꢂ + 1eꢂ ¢ Q2ꢂ. In CH2Cl2, the
first one electron reduction occurs at the same potential for 3a
and 3b, which is only 0.02 V more negative than the value found
for 3a in MeCN [42]. For the second process, the effect of the sol-
vent is more pronounced since in CH2Cl2 and in MeCN 3a has,
respectively, 0.02 and 0.14 V more negative potentials than 3b.
The effect of different solvents on the electrochemistry of quinones
has been discussed in the literature [43]. Based on the DE1/2 values
in Table 3 it seems reasonable to say that CH2Cl2 destabilizes the
semiquinone species in 3a with respect to disproportionation,
when compared with MeCN. A third process is also present in
the CV of 3b, which is assigned to the one electron oxidation of
the ferrocenyl group: Fc ¢ Fc+ + 1eꢂ. Interestingly the half wave
potential for the ferrocenyl group in 3b is only 0.05 V more positive
3.2. Characterization of 2(ferrocenylamine)-1,4-naphthoquinone 3b
Reddish-purple compound 3b (see Fig. 1) is the first example of
a 2(ferrocenylamine)-1,4-naphthoquinone, although naphthoqui-
nones containing the Fc group have been reported previously
[40,41]. HRMS, infrared and NMR data are consistent with the com-
position and structure of 3b (see Section 2).
The electronic properties of naphthoquinone 3b were investi-
gated and compared to those of 3a. The redox behavior of com-
pound 3b was evaluated by cyclic voltammetry (CV) at room
temperature in DCM/TBAPF6 and compared with that of 3a [42].
The CVs, depicted in Fig. 2, were obtained in the potential range
from +1.3 to ꢂ2.1 V vs Fc/Fc+. Voltammetric data are presented in
Table 3.
Two quasi-reversible pairs of waves were observed for 3a and
3b in the negative region of the CV. These processes are attributed

A.I. Francisco et al. / Journal of Molecular Structure 891 (2008) 228–232
231
than the Fc/Fc+ couple used as the reference potential. Finally, an
irreversible wave was also observed in the CVs of 3a and 3b at
Epa ꢃ +1.1 V vs Fc/Fc+, and is tentatively assigned to the oxidation
of the aniline group.
Table 5
B3LYP/6-31G(d) absolute (a.u.) and relative (kcal molꢂ1) energies for relevant species
Species
Energy
Gas-phase
Methanol
The UV–vis spectrum of reddish-purple 3b exhibits two
absorption bands (Table 4). This spectrum is dominated by the
transitions of the naphthoquinone; the UV–vis spectrum of light
yellow 4-ferrocenylaniline in CH2Cl2 shows two relatively weak
absorption bands assigned to p–p* and d–d transitions, the ex-
pected band due to the Fe(d)–p* transition [44] being obscured
by the solvent. The spectrum of 3b is similar to those of a number
of other 2-arylamino-1,4-naphthoquinones [45] that show an in-
tense absorption band at about 240–272 nm (logemax = 4.32–
4.65), attributed to benzene and quinone p–p electron transitions,
a band in the visible region centered between 375 and 480 nm
(logemax = 3.67–3.78), which has been assigned to n–p transition
of the carbonyl groups in the quinone, besides specific absorption
bands originated from the substituents [42]. It has been shown
that the kmax value of the band in the visible region is modified
by the substituent in the aniline ring, electron donor groups shift-
ing the band to longer wavelengths and groups, to shorter wave-
lengths, compared with 1,4-naphthoquinone [42,45]. The
presence of the ferrocenyl group in 3b resulted in an appreciable
shift of the n–p* band to longer wavelength [k2/EtOH: 495 nm
(3.59); k2/CH2Cl2: 497 (3.80)] compared with 3a (R = OMe) [k2/
EtOH: 485 (3.43) and k2/CH2Cl2: 489 (3.54)]. Although this data
tends to suggest that the ferrocenyl group acts as a better elec-
tron donor than the OMe, the electrochemistry data of both ferr-
ocenyl and methoxy derivatives 3b and 3a are very similar (see
above) thus indicating that the donor capability of the two groups
is approximately the same.
IC.cat1
TS.cat1
AC.cat1
IC.cat2
TS.cat2
AC.cat2
ꢂ1519.15652 (0.0)
ꢂ1519.41241 (0.0)
ꢂ1519.12870 (17.5) ꢂ1519.38388 (17.9)
ꢂ1519.13143 (15.7) ꢂ1519.38500 (17.2)
ꢂ1014.06306 (0.0)
ꢂ1014.14174 (0.0)
ꢂ1014.04438 (11.7) ꢂ1014.12715 (9.2)
ꢂ1014.04923 (8.7)
ꢂ287.60176
ꢂ1014.13305 (5.5)
ꢂ287.61371
Aniline
Aniline(H+)
ꢂ287.95585
ꢂ288.05940
2-Methoxy-1,4-naphthoquinone
ꢂ649.64273
ꢂ649.65768
2-Methoxy-1,4-naphthoquinone(H+)
ꢂ649.99650
ꢂ650.08492
Relative energies are given in parenthesis.
ferred by 7.8 (gas) and 4.6 (solvent) kcal molꢂ1. We therefore
concluded that it was reasonable to simulate the interactions
of the two catalysts with oxygen 4.
The reaction mechanism consists of nucleophilic attack of the
aniline on carbon 2 of the naphthoquinone, which has its electro-
philicity increased by the presence of the catalyst attached to oxy-
gen 4. Therefore, three structures were simulated with each
catalyst: (i) the initial van der Waals type complex containing
the catalyst (IC.cat1 and IC.cat2) bonded to oxygen 4 and the ani-
line close to C2; (ii) these complexes may evolve to the respective
transition states (TS.cat1 and TS.cat2) and (iii) finally to the acti-
vated complexes (AC.cat1 and AC.cat2) in which the aniline nitro-
gen is bonded to C2 (see Fig. 3 for a representation of these three
stages for cat1). Taking the initial complexes as references, the rel-
ative energies of the TS, corresponding to the activation energies,
are higher for TS.cat1 [17.4 (gas-phase) and 17.9 (metha-
nol) kcal molꢂ1] than for TS.cat2 [11.7 (gas-phase) and 9.2 (metha-
3.3. Theoretical calculations
nol) kcal molꢂ1
]
(Table 5), the activation energy for the
The effect of both H+ and Mg2+ catalysts on the reaction mech-
anism was investigated. As a first step we calculated the proton
affinity of naphthoquinone 1 and aniline 2d. The relative proton
affinity was calculated considering the two reactions:
uncatalyzed process being much higher (about 38 kcal molꢂ1).
The relative energies of the activated complexes follow those of
the corresponding transition states, that of AC.cat1 being higher
than that of AC.cat2. For the uncatalyzed reaction no activated
complex was found.
Aniline þ Hþ ! AnilineðHþÞ and
Naphthoquinone þ Hþ ! NaphthoquinoneðHþÞ
We tried several pathways for the combined action of cat1 and
cat2, involving simultaneous interaction of both catalysts with the
naphthoquinone 1, however interaction of any catalyst with car-
bonyl oxygen 1 resulted in significant lowering of the electrophilic-
ity of C2, therefore increasing the activation energy for the process.
When considering the most favorable site for protonation of
naphthoquinone (carbonyl oxygen 4) the calculations showed
that protonation of the aniline and of the naphthoquinone are
competitive processes, with the gas-phase protonation of the
aniline being only 0.2 kcal molꢂ1 more favorable (ZPVE not in-
cluded) (Table 5). Based on this result we turned our attention
to the interaction between the catalysts [H+(H2O) and
Mg2+(H2O)5] and the naphthoquinone. Two sites for interaction
of the catalysts with the naphthoquinone were investigated,
4. Conclusions
In the presence of a Lewis or/and a Brönsted acid (MgCl2, cat1,
and p-toluenesulfonic acid, cat2) 2-methoxy-1,4-naphthoquinone
1
reacts with para-substituted anilines to give 2-(pheny-
the carbonyl oxygens
1 and 4. It was found that in the
lene)amine-1,4-naphthoquinones containing both electron donor
(4-OMe, 4-Me, 4-ferrocenyl) and electron withdrawing (4-I, 4-Cl,
4- and 3-NO2) groups. In the absence of a catalyst the reaction
leads to poor yields. In the presence of cat1 or cat2 yield improved
considerably, however, the two catalysts together led to the best
yield (97%). B3LYP/6-31G(d) calculations showed that either cat1
or cat2 considerably increases the electrophilicity of carbon C2,
therefore leading to reactions with much lower activation energy
than in the case of the uncatalyzed reaction. Attempts to find a
pathway involving simultaneous action of both catalysts does not
lead to any satisfactory result, mainly because attachment of any
catalyst to the C1 carbonyl considerably decreases the electrophi-
licity of carbon C2. We are thus led to conclude that the increase
in reaction rate observed when both catalysts act together is not
the result of a synergetic effect of the catalyst.
Mg2+(H2O)5 case, these two sites are equivalent, whereas in the
case of H+(H2O), protonation of the carbonyl oxygen 4 is pre-
Table 4
UV–vis spectra of compounds 3a, 3b, and 2b
Compound
[kmax (nm) (logemax), e in L molꢂ1 cmꢂ1
]
3ba
3aa
2bc
k1: 266 (4.37); k2: 495 (3.59)
k1: 257 (4.24); kb: 349 (2.97); k2: 485 (3.43); k2: 480 (3.67) [44]
k1: 326 (2.13); k2: 446 (2.17)
a
In EtOH.
b
Originated from the presence of the OMe substituent [45].
In CH2Cl2 as 2b is poorly soluble in EtOH.
c

232
A.I. Francisco et al. / Journal of Molecular Structure 891 (2008) 228–232
0
Fig. 3. Simulated structures of: (a) the initial van der Waals type complex, (b) the transition state, and (c) the activated complex containing cat1. The C2-N distance (AÅ) is
indicated in each case.
[21] J.M. Miguel Del Corral, M.A. Castro, M. Gordaliza, M.L. Martín, A.A.
Acknowledgements
Gualberto, A.M. Gamito, C. Cuevas, A. San Feliciano, Bioorg. Med. Chem.
13 (2006) 2812.
The authors thank the Brazilian agencies ‘Conselho Nacional de
Desenvolvimento Científico e Tecnológico’ (CNPq), ‘Fundacßão de
Amparo à Pesquisa do Estado do Rio de Janeiro’ (FAPERJ), and Pro-
nex-FAPERJ for financial support. The authors gratefully acknowl-
edge Prof. A. Neves (Departamento de Química – UFSC) for the
electrochemistry facilities and Prof. N. P. Lopes (FCRP-USP) for
the HRMS.
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