Molecular structure of substituted phenylamine α-OMe- and α-OH-p-benzoquinone derivatives. Synthesis and correlation of spectroscopic, electrochemical, and theoretical parameters

Article abstract of DOI:10.1021/jo010302z

Thirteen C₆ para-substituted anilinebenzoquinones derived from perezone (PZ) (2-(1,5-dimethyl-4-hexenyl)-3-hydroxy-5-methyl-1,4-benzoquinone) were prepared to analyze the effect of the substituents on quinone electronic properties. The effect of a hydrogen bond between the α-hydroxy and carbonyl C₄-O₄ groups was determined in perezone derivatives by substituting electron-donor and electron-acceptor groups such as -OMe, -Me, -Br, and -CN and comparing the -OH (APZs) and -OMe (APZms) derivatives. Reduction potentials of these compounds were measured using cyclic voltammetry in anhydrous acetonitrile. The typical behavior of quinones, with or without α-phenolic protons, in an aprotic medium was not observed for APZs due to the presence of coupled, self-protonation reactions. The self-protonation process gives rise to an initial wave, corresponding to the irreversible reduction reaction of quinone (HQ) to hydroquinone (HQH₂), and to a second electron transfer, attributed to the reversible reduction of perezonate (Q^-) formed during the self-protonation process. This reaction is favored by the acidity of the α-OH located at the quinone ring. To control the coupled chemical reaction, we considered both methylation of the -OH group (APZms) and addition of a strong base, tetramethylammonium phenolate (Me₄N⁺C₆H₅O^-), to completely deprotonate the APZs. Methylation led to recovery of reversible, bi-electronic behavior (Q/Q^?- and Q^?-/Q^2-), indicating the nonacidic properties of the NH group. The addition of a strong base resulted in reduction of perezonate (Q^-) obtained from the acid-base reaction of APZs with Me₄N⁺C₆H₅O^- to produce the dianion radical (Q^?2-). Although the nitrogen atom interferes with direct conjugation between both rings by binding the quinone with the para-substituted ring, the UV-vis spectra of these compounds showed the existence of intramolecular electronic transfer from the respective aniline to the quinone moiety. ¹³C NMR chemical shifts of the quinone atoms provided additional evidence for this electron transfer. These findings were also supported by linear variation in cathodic peak potentials (E_pc) vs Hammett σ_p constants associated with the different electrochemical transformations: Q/Q^?-, Q^?-/Q^2- for APZms or HQ/HQH₂ and Q^-/Q^?2- for APZs. The electronic properties of model anilinebenzoquinones were determined at a B3LYP/6-31G(d,p) level of theory within the framework of the density functional theory. Our theoretical calculations predicted that all the compounds are floppy molecules with a low rotational C-N barrier, in which the degree of conjugation of the lone nitrogen pair with the quinone system depends on the magnitude of the electronic effect of the substituents of the aniline ring. Natural charges show that C₁ is more positive than C₄ although the LUMO orbital is located at C₄. Hence, if the natural charge distribution in the molecule controls the first electron addition, this should occur at carbon atom C₁. If the process is controlled by the LUMO orbitals, however, electron addition would first occur at C₄. For the APZms series susceptibility of the first reduction wave to the substitution effect (p_π = 147 mV) is lower than that of the second reduction wave (p_π = 156 mV). Thus, the first, one-electron transfer in the quinone system is controlled by the natural charge distribution of the molecule and therefore takes place at C₁.

Full text of DOI:10.1021/jo010302z

J . Org. Chem. 2001, 66, 8349-8363
8349
Molecu la r Str u ctu r e of Su bstitu ted P h en yla m in e r-OMe- a n d
r-OH-p-Ben zoqu in on e Der iva tives. Syn th esis a n d Cor r ela tion of
Sp ectr oscop ic, Electr och em ica l, a n d Th eor etica l P a r a m eter s
M. Aguilar-Mart´ınez,*,†,‡ J . A. Bautista-Mart´ınez,† N. Mac´ıas-Ruvalcaba,† I. Gonza´lez,§
E. Tovar,† T. Mar´ın del Alizal,| O. Collera,† and G. Cuevas†
Universidad Nacional Auto´noma de Me´xico, Instituto de Qu´ımica, Ciudad Universitaria,
04510 Me´xico D.F., Me´xico, Universidad Auto´noma Metropolitana-Iztapalapa, Departamento de Quı´mica,
Apartado postal 55-534, 09340 Me´xico D.F., Mexico, and Universidad la Salle, Escuela de Ciencias
Quı´micas, Benjamin Franklin 47, Hipo´dromo Condesa, 06140 Me´xico D.F., Mexico
marthaa@servidor.unam.mx
Received March 19, 2001
Thirteen C6 para-substituted anilinebenzoquinones derived from perezone (PZ) (2-(1,5-dimethyl-
4-hexenyl)-3-hydroxy-5-methyl-1,4-benzoquinone) were prepared to analyze the effect of the
substituents on quinone electronic properties. The effect of a hydrogen bond between the R-hydroxy
and carbonyl C4-O4 groups was determined in perezone derivatives by substituting electron-donor
and electron-acceptor groups such as -OMe, -Me, -Br, and -CN and comparing the -OH (APZs)
and -OMe (APZms) derivatives. Reduction potentials of these compounds were measured using
cyclic voltammetry in anhydrous acetonitrile. The typical behavior of quinones, with or without
R-phenolic protons, in an aprotic medium was not observed for APZs due to the presence of coupled,
self-protonation reactions. The self-protonation process gives rise to an initial wave, corresponding
to the irreversible reduction reaction of quinone (HQ) to hydroquinone (HQH2), and to a second
electron transfer, attributed to the reversible reduction of perezonate (Q-) formed during the self-
protonation process. This reaction is favored by the acidity of the R-OH located at the quinone
ring. To control the coupled chemical reaction, we considered both methylation of the -OH group
(APZms) and addition of a strong base, tetramethylammonium phenolate (Me4N+C6H5O-), to
completely deprotonate the APZs. Methylation led to recovery of reversible, bi-electronic behavior
(Q/Q•- and Q•-/Q2-), indicating the nonacidic properties of the NH group. The addition of a strong
base resulted in reduction of perezonate (Q-) obtained from the acid-base reaction of APZs with
Me4N+C6H5O- to produce the dianion radical (Q•2-). Although the nitrogen atom interferes with
direct conjugation between both rings by binding the quinone with the para-substituted ring, the
UV-vis spectra of these compounds showed the existence of intramolecular electronic transfer from
the respective aniline to the quinone moiety. 13C NMR chemical shifts of the quinone atoms provided
additional evidence for this electron transfer. These findings were also supported by linear variation
in cathodic peak potentials (Epc) vs Hammett σp constants associated with the different electro-
chemical transformations: Q/Q•-, Q•-/Q2- for APZms or HQ/HQH2 and Q-/Q•2- for APZs. The
electronic properties of model anilinebenzoquinones were determined at a B3LYP/6-31G(d,p) level
of theory within the framework of the density functional theory. Our theoretical calculations
predicted that all the compounds are floppy molecules with a low rotational C-N barrier, in which
the degree of conjugation of the lone nitrogen pair with the quinone system depends on the
magnitude of the electronic effect of the substituents of the aniline ring. Natural charges show
that C1 is more positive than C4 although the LUMO orbital is located at C4. Hence, if the natural
charge distribution in the molecule controls the first electron addition, this should occur at carbon
atom C1. If the process is controlled by the LUMO orbitals, however, electron addition would first
occur at C4. For the APZms series susceptibility of the first reduction wave to the substitution
effect (Fπ ) 147 mV) is lower than that of the second reduction wave (Fπ ) 156 mV). Thus, the first,
one-electron transfer in the quinone system is controlled by the natural charge distribution of the
molecule and therefore takes place at C1.
In tr od u ction
and photosynthesis.2 These compounds occur in other
natural contexts3 and as pollutants.3,4 Quinones form an
important class of toxic metabolites and, paradoxically,
Quinones are found in all respiring animal and plant
cells where they function primarily as components of the
electron transport chains involved in cellular respiration1
(1) Morton, R. A., Ed. Biochemistry of Quinones; Academic Press:
New York, NY, 1965.
† Universidad Nacional Auto´noma de Me´xico.
‡ On leave from Universidad Nacional Auto´noma de Me´xico, Fac-
ultad de Qu´ımica, Departamento de Fisicoqu´ımica, Ciudad Universi-
taria, 04510 Me´xico D.F., Me´xico.
(2) (a) Bentley, R.; Campbell, I. M. In Patai, S. Ed. The Chemistry
of Quinoid Compounds; J ohn Wiley & Sons: London, 1974; pp 683-
736. (b) Nohl, H.; J ordan, W.; Youngman, R. J . Adv. Free Radical Biol.
Med. 1986, 2, 211-279.
(3) Monks, T. J .; Hanzlik, R. P.; Cohen, G. M.; Ross, D.; Graham,
D. G. Toxicol. Appl. Pharmacol. 1992, 112, 2-16.
§ Universidad Auto´noma Metropolitana-Iztapalapa.
| Universidad la Salle.
10.1021/jo010302z CCC: $20.00 © 2001 American Chemical Society
Published on Web 11/08/2001

8350 J . Org. Chem., Vol. 66, No. 25, 2001
Aguilar-Mart´ınez et al.
can be either mutagenic and, therefore, potentially car-
cinogenic, or effective anticancer agents.5 Some quinones
possibly play a role in cellular defense since they ef-
fectively inhibit growth of bacteria,6 fungi,7 or parasites.8
A variety of biologically active, naturally occurring
quinones with such properties9 contain acidic hydrogens
in their structure, and many are more active than
quinones lacking acidic hydrogens. Such anticancer drugs
as adriamycin, daunorubicin, streptonigrim, lapachol,
and their analogues contain quinones with hydroxyl
groups.10 Methylation of either or both of the R-hydroxyl
groups of the quinone carbonyl groups in the anticancer
agent, daunomycin, results in a significant reduction in
antitumor effects.11 This could be due to greater difficulty
in semiquinone formation resulting from obstruction of
the hydroxyl groups by methylation.12,13
Some hydroxynaphthoquinones were found to have
higher trypanocidal activity than quinones lacking the
-OH group.14 Measurements of the corresponding meth-
oxy and acetoxyquinones11 indicate that internal hydro-
gen bonding in the R-hydroxyquinones contributes to
stabilization of the semiquinone, probably as a result of
increased delocalization due to exchange of the hydroxyl
hydrogen between the two neighboring oxygen atoms.
Hydroxyl-substituted derivatives of antineoplastic furan-
quinones capable of internal hydrogen bonding exhibit
the most positive E1/2 values and are generally more
active than unsubstituted counterparts.15
acidic groups17 or within a family of quinones with
R-hydroxiphenolic groups that lack electron-accepting or
-donating substituents.18,19,20 Several reports21,22 consider
the effect of the substituents on the electrochemical
properties of quinone families that have an R-phenolic
group. In such quinones, the intramolecular hydrogen
bonding stabilizes the semiquinone radical and two, one-
electron reversible reduction processes are maintained
despite the hydrogen bond presence.19,20 However, in
these molecules, the R-OH groups at the quinone rings
are more acidic than those of the phenolic group. Thus,
electrochemical behavior of the R-hydroxy quinones is
more irreversible than that of the phenolic quinones due
to the transfer of the hydrogen bonding proton during
electron addition.18,22,23
Since quinones containing more acidic protons, such
as the R-hydroxyquinones, display different electrochemi-
cal behavior17,23 than quinones without them, we were
interested in studying the effect of the substituents on
the electrochemical properties of a family of quinones
containing an R-hydroxy group in its structure, the
anilineperezones APZs, and comparing their behavior
with that of their methylated quinones (APZms, Table
1). Using these anilines allowed us to control modification
of the effect of the substituents on the redox potential of
the quinone system. In previous electrochemical reduc-
tion studies of a group of quinone molecules lacking acidic
hydrogen, the 2-[(R-phenyl)amine]-1,4-naphthalene-
diones in acetonitrile, we found that half-wave potential
values varied linearly with the electronic effect of the
substituents.24 We also observed that the nitrogen from
the aniline group softened the electronic effect of the
substituents.
Biological activity is closely related to the redox and
acid-base chemistry of the quinones, semiquinones, and
hydroquinones. The ability as electron donors or accep-
tors of the substituents present in quinones significantly
alters their acid-base properties. To understand how
quinones function in such varied and crucial biochemical
roles, it is important to evaluate the effect of the sub-
stituents on the electrochemical behavior of R-hydroxy-
quinones.
In addition to substituent effects, the redox and acid-
base equilibrium properties of quinones are also modified
by controlling media acidity. Control of pH is important
for those compounds where self-protonation can occur
since a more acid environment modifies the quantity of
quinone transformed to hydroquinone. Diminished qui-
none transformation occurs since some molecules are
involved in protonation of the electrochemical reduction
products, leaving a smaller number of molecules to
participate in the electron-transfer process.25 In this
work, the strong base, tetramethylammonium phenolate
The electrochemical behavior of different quinones is
extensively reviewed.16 The effects of quinone substitu-
ents have been described for molecules without functional
(4) (a) Fox, M. A.; Olive, S. Science 1979, 205, 582-583. (b) Pryor,
W. A.; Hales, B. J .; Premivic, P. I.; Church, D. F. Science 1982, 220,
425-427.
(5) Lin, A. J .; Cosby, L. A.; Sartorelli, A. C. Cancer Chemother. Rep.
Part 2 1974, 4, 23-25.
(6) Hoover, J . R. E.; Dag, A. R. J . Am. Chem. Soc. 1954, 76, 4148-
4152.
(16) (a) Chambers, J . Q. Electrochemistry of Quinones. In The
Chemistry of Quinonoid Compounds. Vol II; Patai, S., Rappoport, Z.,
Eds.; J ohn Wiley and Sons, Ltd.: New York, 1988; Chapter 12. (b)
Bard, A. J .; Faulkner, L. R. Electrochemical Methods. Fundamentals
and Applications; J ohn Wiley & Sons, Inc.: New York, 1980. (c) Evans,
D.; Laviron, E. J . Electroanal. Chem. 1986, 208, 357-372.
(17) (a) Glezer, V.; Turovska, B.; Stradins, J .; Freimanis, J . Elec-
trochim. Acta 1990, 35, 1933-1940. (b) Illescas, B.; Mart´ın, N.; Segura,
J . L.; Seoane, C.; Ort´ı, E.; Viruela, P. M.; Viruela, R. J . Org. Chem.
1995, 60, 5643-5650.
(18) Gonza´lez, F. J .; Aceves, J . M.; Miranda, R. And Gonza´lez, I. J .
Electroanal. Chem. 1991, 310, 293-303.
(19) Wightman, R. M.; Cockrell, J . R.; Murria, R. W.; Burnett, J .
N.; J ones, S. B. J . Am. Chem. Soc. 1976, 98, 2562-2570
(20) Piljac, I.; Murray, R. W. J . Elecetrochem. Soc. 1971, 118, 1758-
1764.
(21) Li, C.-Y.; Caspar, M. L.; Dixon, D. W. Electrochim. Acta 1980,
25, 1135-1142.
(22) Edwards, T. G.; Grinter, R. Trans. Faraday Soc. 1968, 69,
1070-1076.
(23) Ortiz, J . L.; Delgado, J .; Baeza, A.; Gonza´les, I.; Sanabria, R.;
Miranda, R. J . Electroanal. Chem. 1996, 411, 103-107.
(24) Aguilar-Mart´ınez, M.; Cuevas, G.; J´ıme´nez-Estrada, M.; Gonza´-
lez, I.; Lotina-Hessen, B.; Mac´ıas-Ruvalcaba, N. J . Org. Chem. 1999,
64, 3684-3694.
(25) Amatore, C.; Capobianco, G.; Farnia, G.; Sandona`, G.; Save´ant,
J . M.; Severin, M. G.; Vianello, E. J . Am. Chem. Soc. 1985, 107, 1815-
1824.
(7) (a) Rich, S. In Fungicides, An Advanced Treatise; Torgeson, D.
C., Ed.; Academic Press: New York, 1969. (b) Clark, N. G. Pestic. Sci.
1985, 16, 23-32.
(8) Howland, J . L. Biochim. Biophys. Acta 1963, 73, 665-667.
(9) (a) Inbaraj, J . J .; Gandhidasan, R.; Murugesan, R. Free Radical
Biol. Med. 1999, 26, 1072-1078. (b) Frigaard, N. U.; Tokita, S.;
Matsuura, K. Biochim. Biophys. Acta 1999, 1413, 108-116. (c) Rod-
r´ıguez Hahn, L.; Esquivel, B.; Sa´nchez, A. D.; Sa´nchez, C.; Ca´rdenas,
J .; Ramamoorthy, T. P. Rev. Latinoamer. Quim. 1989, 20, 105-113.
(d) Pezzuto, J . M.; Fong, H. H. S.; Farnsworth, N. R.; Che, C. T. J .
Nat. Prod. 1989, 52, 571-575. (e) Inbaraj, J . J .; Krishna, M. C.;
Gandhidasan, R.; Murugesan, R. Biochim. Biophys. Acta 1999, 1413,
462-470.
(10) Bachur, N. R.; Gordon, S. L.; Gee, M. V. Cancer Res. 1978,
1745-1750.
(11) Ashnagar, A.; Bruce, J . M.; Dutton, P. L.; Prince, R. C.Biochim.
Biophys. Acta 1984, 801, 351-359.
(12) Rao, G. M.; Lown, J . W.; Plambeck, J . A. J . Electrochem. Soc.
1978, 125, 534-539.
(13) Rao, G. M.; Lown, J . W.; Plambeck, J . A. J . Electrochem. Soc.
1978, 125, 540-543.
(14) Goulart, M. O. F.; Zani, C. L.; Tonholo, J .; Freitas, L. R.; de
Abreu, F. C.; Oliveira, A. B.; Raslan, D. S.; Starling, S.; Chiari. E.
Bioorg. Med. Chem. Lett. 1997, 7, 2043-2048.
(15) Crawford, P. W.; Carlos, E.; Ellegood, J . C.; Cheng, C. C.; Dong,
Q.; Liu, D. F.; Luo, Y. L. Electrochim. Acta 1996, 41, 2399-2403.

Molecular Structure of Phenylamine p-Benzoquinone Derivatives
J . Org. Chem., Vol. 66, No. 25, 2001 8351
Ta ble 1. Str u ctu r e of (2-(1,5-Dim eth yl-4-h exen yl)-
3-h yd r oxy-5-m eth yl-6-[4′-(R2-p h en yl)a m in e]-1,4-
ben zoqu in on es (AP Zs) a n d Th eir 3-Meth oxy Der iva tives
(R1 ) Me) Syn th esized in Th is Wor k
F igu r e 1. Structures of (2-(1,5-dimethyl-4-hexenyl)-3-hy-
droxy-5-methyl-1,4-benzoquinone (PZ) and (2-(1,5-dimethyl-
4-hexenyl)-3-methoxy-5-methyl-1,4-benzoquinone (PZm).
compd
APZ
p-MeOAPZ
p-BrAPZ
p-MeAPZ
p-CNAPZ
p-MeCOAPZ
p-NO2APZ
APZm
p-MeOAPZm
p-BrAPZm
p-MeAPZm
p-CNAPZm
p-MeCOAPZm
p-NO2APZm
R1
R2
-H
-H
-H
-OCH3
-Br
-CH3
-CN
-COCH3
-NO2
-H
-OCH3
-Br
-CH3
-CN
-COCH3
-NO2
-H
-H
-H
-H
-H
-CH3
-CH3
-CH3
-CH3
-CH3
-CH3
-CH3
F igu r e 2. Synthesis of APZs and APZms.
This difference in yield may be due to the polarization
effect of the OH group on the quinone carbonyl through
a hydrogen bond that is susceptible to a Michael-type
addition at the C6 position. The derivatives obtained with
the first method varied in color from purple (substituents
with the methoxy group) to red (substituents with the
nitro group).
Sp ectr oscop y. In methanol, these quinones display
some common absorption bands that concur with our
interests, such as one in the 204-211 nm region assigned
to the intense benzene and quinone π-π* transition. In
the 313-361 nm region, there is a transfer band and a
very broad, low energy band at 449-543 nm due to the
n-π* transition of the carbonyl groups of the quinones.
Some quinones show specific absorptions originating from
the aniline substituents and will not be discussed in this
paper.
The λmax corresponding to the n-π* transition has
interesting shifts depending on the nature of the sub-
stituents. Electron-donor groups cause a change in
absorption at higher wavelengths for both hydroxylated
(R1 ) -OH) and methylated derivatives (R1 ) -OMe),
while electron-accepting groups cause the opposite effect.
The graph of 1/λmax for the n-π* transition for each series
of compounds vs the Hammett constant31 (σp) shows a
linear correlation for the methylated derivatives (eq 1),
but this linearity does not persist for the hydroxylated
compounds (eq 2).
(Me4N+C6H5O-), was added to avoid the self-protonation
reaction.
Electrochemical studies of compounds are generally
performed in aqueous solutions under conditions close
to physiological pH 7 to reproduce their native biological
activity. However, some biological electron-transfers oc-
cur in the lipid phase.26 Thus, it is important to determine
the electrochemical behavior of these compounds in
aprotic solvents in order to mimic the cells nonpolar
environment.11,15,27
We report the synthesis, characterization, X-ray analy-
sis, and electrochemical behavior of PZ and 2-(1,5-di-
methyl-4-hexenyl)-5-methyl-3-methoxy-1,4-benzoquinone
(PZm) (Figure 1) and their 6-(4′-R-phenyl)amine deriva-
tives APZs and APZms (Table 1) in acetonitrile and
present a theoretical analysis for a molecular model of
these quinones.
Resu lts a n d Discu ssion
Syn th esis. Perezone derivatives (Table 1) were pre-
pared by addition of the corresponding para-substituted
aniline in anhydrous THF to an equimolar solution of
PZ28,29 (1, Figure 2), under nitrogen atmosphere. Meth-
ylated derivatives (3, Figure 2) were obtained by adding
an anhydrous dimethyl sulfate solution in dry acetone
to the previously prepared perezone adducts30 (2, Figure
2). Yields were notably improved when the aniline was
introduced to the perezone first and then methylated
rather than performing the methylation first.
1/λmax (nm-1
1/λmax (nm-1
)
)
APZms ) 1.64 × 10-4σp + 1.9 × 10-3
(n ) 7, r ) 0.99) (1)
APZs ) 4.04 × 10-5σp + 1.9 × 10-3
(n ) 7, r ) 0.42) (2)
(26) Weiss, H.; Friedrich, T.; Hofhaus, G.; Preis, D. Eur. J . Biochem.
1991, 197, 563.
(27) (a) Li, C.-Y.; J enq, J . Electrochim. Acta 1991, 36, 269-276. (b)
Crawford, P. W.; Gross, J .; Lawson, K.; Cheng, C. C.; Dong, Q.; Liu,
D. F.; Luo, Y. L.; Szczepankiewicz, B. G.; Heathcock, C. H. J .
Electrochem. Soc. 1997, 144, 3710-3715. (c) J eziorek, D.; Ossowski,
T.; Liwo, A.; Dyl, D.; Nowacka, M.; WoY¨ nicki, W. J . Chem. Soc., Perkin
Trans. 2 1997, 229-236.
(28) Walls, F.; Salmo´n, M.; Padilla, J .; J oseph-Nathan, P.; Romo, J .
Bol. Inst. Quı´m. Univ. Nac. Auton. Mex. 1965, 17, 3-15.
(29) Ko¨gl, F.; Boer, A. G. Rec. Trav. Chim. Pays-Bas 1935, 54, 779-
794.
These data show that even if there is no direct
conjugation between the substituents at position 4′ on
(30) Rodr´ıguez-Herna´ndez, A.; Barrios, H.; Collera, O.; Enr´ıquez,
R. G.; Ortiz, B.; Sa´nchez Obrego´n, R.; Walls, F.; Yuste, F.; Reynolds,
W. F.; Yu, M. Nat. Prod. Lett. 1994, 4, 133-139.
(31) Ewing, D. F. in Chapman, N. B. Shorter Correlation Analysis
in Chemistry: Recent Advances; Plenum: New York, 1978; pp 357-
396 and references therein.

8352 J . Org. Chem., Vol. 66, No. 25, 2001
Aguilar-Mart´ınez et al.
Ta ble 2. Cor r ela tion betw een Ch em ica l Sh ifts (δ) w ith
th e Ha m m ett Con sta n t (σp ) of (2-(1,5-Dim eth yl-4-
h exen yl)-3-h yd r oxy-5-m eth yl-6-[4′-(R2-p h en yl)a m in e]-
1,4-ben zoqu in on es (AP Zs) a n d (2-(1,5-Dim eth yl-4-
h exen yl)-3-m eth oxy-5-m eth yl-6-[4′-(R2-p h en yl)a m in e]-
1,4-ben zoqu in on es (AP Zm s)
δ ) Fπσp + b
with n molecules in the correlation and r correlation coefficient
F igu r e 3. Dominant hybrids of APZs and APZms showing:
(a) donation of electrons from the nitrogen atom to the segment
C6-C5-C4-O4 and (b) donation of electrons from the oxygen
atom to the segment C3-C2-C1-O1.
APZs
APZms
carbon
Fπ
b
n
r
carbon
Fπ
b
n
r
C1
C2
C3
C4
0.31 182.80
5.41 126.74
-0.45 153.60
0.60 181.97
6
5
6
6
1a
C1
C2
C3
C4
C4
C5
C6
C7
C12
C13
C13
-0.52 184.95
1.33 131.70
-0.58 158.04
0.28 183.18
0.29 183.20
7.99 112.39
5.86 140.62
1.55 12.49
-0.21 124.51
0.25 131.46
0.29 131.45
7
6
7
5
7
6
6
7
6
6
7
0.97
0.99c
0.99
0.96d
0.90
0.99a
0.90e
0.98
0.98
0.99f
0.75
1a,b
1a
the aromatic ring and the quinone, the effects are
transmitted through the nitrogen atom connecting these
two moieties (Figure 3a). The σp values used in this study
correspond to the standard Hammett values.32
Loss of linearity for the hydroxylated derivatives is
more accentuated for electron-donor groups (-OMe,
-Me). The elimination of these points improves the
correlation (eq 3).
1a
C5
C6
C7
C12
C13
0.94 118.76
-0.41 143.06
1.06 11.82
-0.54 124.95
0.13 130.96
6
6
6
6
6
1a
1a
1a
1a
1a
a
b
Without the group -CN. Without the group -Me. c Without
1/λmax (nm-1
)
APZs ) 1.36 × 10-4σp + 1.9 × 10-3
the group -Br. Without the groups -CN and -H. e Without the
d
group -MeO. f Without the group -H.
(n ) 5, r ) 0.92) (3)
Sensitivity of the carbon atom of the quinone methyl
group (C7) to the effect of the substituent is interesting
since the carbon atom can only participate in this process
through hyperconjugation. In the APZm derivatives
This spectroscopic behavior is probably due to the
hydroxyl group polarizing the C4-O4 carbonyl intensify-
ing the methoxy and methyl groups donor properties.
This is not possible when R1 is a methyl group, as this
group is incapable of improving the acceptor properties
of the carbonyl. This effect then occurs because the
electron-donor capabilities of the -OMe and -Me groups
in the APZm series are saturated. The hydrogen bridge
modifies the donor properties of the substituents that
impact this correlation.
Nuclear magnetic resonance is very sensitive to the
electronic effect of the substituents.33 The Hammett
equation applies to many physical measurements includ-
ing infrared frequencies and NMR chemical shifts.31
Plotting the chemical shift (δ) values obtained for each
carbon atom of every compound (see the Experimental
Section) against the σp Hammett substituent32 constants
produced a linear correlation (Table 2), where the slope
is a measure of sensitivity of the chemical shift to
electronic substituent effects. For the APZ series, the
group that deviates from the linear correlation is -CN
in all cases and the -CN and -Me groups for the C2.
The same is described for each anomalous substituent
in the APZm derivatives. Because of their low steric
volume and the small polarization capabilities of some
groups, it is difficult to explain the origin of the effect on
the observed chemical shift in terms of special donor
properties or solvation.
1
(Table 1), in H NMR the methyl group at C5 varies its
chemical shift from 1.56 ppm (R2 ) -OMe) to 1.69 ppm
(R2 ) -NO2). However, there is no linear correlation
between this shift and the σp value. This effect is similar
for the APZ derivatives and suggests that when the
quinone ring is substituted by electron-donor groups, the
hydrogen atoms involved in the hyperconjugative inter-
action gain charge in the electron-transfer process.
In the APZ series, the C2 carbon is more sensitive to
the effect of the substituents than the same carbon on
the methylated derivatives. This can be observed by the
lower slope value for the methylated derivatives (Table
2). The positive slope implies that the electron-accepting
substituents produce a low field chemical shift. These
results demonstrate the greater donor capability of the
hydroxy group with respect to the methoxy group and
that this electron donation is favored when the ring
substituent is an electron-donor. The values in Table 2
show that C1 is less sensitive to the effect of the
substituent than C4.
The high field shift of C4 is likely due to compensation
of the low electronic density associated with the carbonyl
atom by the donor capability of the nitrogen atom. This
capability is decreased by electron-accepting substituents.
The effect is more remarkable for the APZ than APZm
series due to greater polarization of the carbonyl group
originated by the hydrogen bridge.
The carbonyl atom C1 in the APZm series behaves in
the opposite manner, where electron-accepting groups
produce the high field chemical shift. This effect has its
origin in the different acidic properties of the hydrogen
atom attached to nitrogen. The nitro group increases
hydrogen acidity and the strength of the N-H‚‚‚O
hydrogen bridge, diminishing electronic density of the
carbonyl atom. The reverse occurs for the methoxy group
at C3. The OH group at C3 of the APZ series attenuates
In the 13C NMR spectra, carbonyl groups of the quinoid
ring show marked sensitivity to the effect of the substit-
uents even if they are located up to nine bonds away from
the group that originates the perturbation (Table 2). As
expected, no substituent effect was observed on the
saturated carbons of the lateral chain. In contrast, the
carbons at positions 5 and 6 and the methyl on the qui-
none are the most sensitive to the effect of the substit-
uents. 34
(32) Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165-
195.
(33) (a) Derome, A. E. Modern NMR Techiques for Chemistry
Research; Pergamon Press: Oxford, 1987. (b) Sanders, J . K. M.; Hunter,
B. K. Modern NMR Spectroscopy. A Guide for Chemists; Oxford
University Press: Oxford, 1987.
(34) This numbering is in agreement with Scheme 1 in Table 1.

Molecular Structure of Phenylamine p-Benzoquinone Derivatives
J . Org. Chem., Vol. 66, No. 25, 2001 8353
F igu r e 4. Hydrogen bondings showing the electronic com-
munication between the enone segments.
this effect by direct conjugation and the balance of both
influences produces a similar trend for C4.
Carbons C2 and C5 in both series experience low field
chemical shifts when effective donor groups are substi-
tuted by groups with poor donor character. This shift is
associated to charge depletion and agrees with the reso-
nant structures shown in Figure 3. On the other hand, a
similar resonant structure explains the high field chemi-
cal shift of the 13C NMR signals of C3 and C6 in both
series originated by the oxygen atom attached to C3.
The results of both UV-vis and 13C NMR spectra
indicate that two resonant forms are relevant in the
stabilization of the hydroxylated derivatives. One of these
is generated by donation of the nitrogen atom to the
quinone ring and the other by donation of the oxygen
atom (of the hydroxyl group) to the quinone connected
by the hydrogen bridge (Figures 3a and 3b, respectively).
Substituents that increase the electron-donor capacity of
the nitrogen atom (electron-donor substituents) favor
participation of the oxygen atom.
F igu r e 5. Typical cyclic voltammograms obtained with a
glassy carbon electrode (7 mm2), scan rate 100 mVs-1 in 0.1
M Et4NBF4/acetonitrile in the presence of the corresponding
quinone 1 mM: (a) p-MeAPZm and (b) p-MeAPZ. The cathodic
(Ic, IIc and I′c, II′c) and anodic (Ia, IIa and I′a, II′a) peaks are
indicated.
APZm series which proceeded in two, one-electron dif-
fusion stages, waves I and II (mechanism EE):
APZm + e - a APZm•-
APZm•- + e - a APZm2-
(4)
(5)
The same behavior was observed within the sweep
potential range of 50-1000 mVs-1. At scan rates above
1000 mVs-1, however, small distortions were detected in
the cyclic voltammograms confounding determination of
the corresponding electrochemical parameters. In our
discussion of the results, we therefore dealt only with
data obtained between 100 and 1000 mVs-1. The half-
wave potential values, E1/2, for both waves were evaluated
from the voltammograms obtained at a sweep rate of 100
mVs-1, where E1/2 ) (Epa + Epc)/2 and Epa and Epc
correspond to the anodic and cathodic peak potentials for
each wave. However, for comparative purposes with the
APZ series, where determination of E1/2 was not possible,
In the 13C NMR spectra, the C4 carbon shifts to a
higher field than the C1 carbon. The ∆δ varies depending
on electronic properties of the substituents and on donor
properties of the -OH group compared to the -OMe
group. These effects are likely due to the overall lower
donor capacity of the -OMe group decreasing the protec-
tive effect at C1. On the other hand, the amino group has
a protective effect at C4 that increases through participa-
tion of a hydrogen bonding OH‚‚‚O3-C3 to polarize the
carbonyl fragment and facilitate the nN f π* electronic
interaction.
The resonant forms described in Figure 3 are based
on these experimental observations and allow us to
establish that the hydrogen bond serves as electronic
communication between the enone segments in the
quinone (Figure 4). Structure b in Figure 4 represents
one extreme of this effect.
Greater sensitivity is observed in the unsaturated
carbons on the side chain of the PZ. In both series (R1 )
-OH, R1 ) -OMe), the sign of Fπ differs with the more
substituted carbon atom having a positive sign (Table 2).
Such sensitivity can only be explained in terms of an
interaction of the charge transference complex between
the double bond and the quinoid ring in solution. The
explanation for this observation will be pursued in a
subsequent study.
Electr och em istr y. The redox potentials of the aniline-
perezones APZs and APZms determined in this work
were measured by cyclic voltammetry at 25 °C controlled
temperature using a glassy carbon electrode in aceto-
nitrile solvent and tetraethylammonium tetrafluoro-
borate as the supporting electrolyte. The voltammograms
were recorded in the potential range from 250 to -2500
mV vs Fc/Fc+.
we used the cathodic peak potential for peak I (EpcI)
values at 100 mV s-1 for APZms and APZs. In all APZms,
the cathodic peak current (ipc) vs the square root of the
sweep rate (v1/2), produced a linear relationship with zero
intercept for both peaks indicating the lack of detectable
chemical kinetic complications.26 Consistent voltammetric
function (ipcv-1/2c-1) with the logarithm of the sweep rate
confirmed this behavior. The ipcv-1/2c-1 values are re-
ported in Table 3. Voltammetric function values were
standardized for concentration and reported as ipcv-1/2c-1
,
where c is the concentration of compound in mol/cm3. The
degree of reversibility for both electron transfers is
indicated by the relationship ipa/ipc, which is close to 1,
the value that describes reversible systems (Table 3).16b
The values of ∆Ep) (Epa - Epc) also approach the
theoretical value of 60 mV reported for one-electron,
reversible systems. The EpcI values (Table 3) for the first
one-electron transfer, corresponding to the formation of
the radical-anion (eq 4), are in the potential range of
-1096 to -1223 mV. For the second one-electron trans-
fer, the EpcII values leading to the formation of the
corresponding dianion (eq 5) fall within the range of
-1594 to -1731 mV (Table 3). The variation in peak
potential indicates the influence of the substituent on the
redox properties of APZm.
Electr och em ica l Beh a vior of AP Zm Der iva tives.
Figure 5a shows the typical electrochemical behavior of

8354 J . Org. Chem., Vol. 66, No. 25, 2001
Aguilar-Mart´ınez et al.
Ta ble 3. Electr och em ica l P a r a m eter sa of th e (2-(1,5-Dim eth yl-4-h exen yl)-3-h yd r oxy-5-m eth yl-1,4-ben zoqu in on e a n d Its
6-[4′-(R2-p h en yl)a m in e] a n d 3-Meth oxy-6-[4′-(R2-p h en yl)a m in e] Der iva tives
ipcv-1/2c-1
(AV-1/2 s1/2 mol-1 cm3)
ipa/ipc
wave II
∆Ep (mV)
Epc (mV)
wave II
or II′
wave I
wave II
wave I
or I′
wave I
wave II
wave I
or I′
b
compd
PZm
σp
or I′
or II′
or II′
or I′
or II′
34.1
44.3
51.6
62.5
31.3
48.3
48.0
25.4
31.6
45.6
48.9
16.7
1.03
1.16
0.84
0.81
0.80
1.02
0.48
0.21
0.25
0.44
0.27
0.61
1.06
1.05
0.94
1.01
1.18
1.15
1.12
1.09
1.07
0.86
1.20
0.23
68
60
69
70
69
79
65
73
63
72
-1113
-1223
-1216
-1197
-1165
-1096
-926
-1096
-1062
-1015
-1011
-925
-1635
p-MeOAPZm
p-MeAPZm
APZm
p-BrAPZm
p-CNAPZm
PZ
p-MeOAPZ
p-MeAPZ
APZ
p-BrAPZ
p-CNAPZ
-0.27
-0.17
0.00
0.23
0.66
-1731
-1762
-1714
-1646
35.6
76
62
71
-1594
c
315
494
437
478
449
317
-1720 (-1654)d
-1900 (-1840)d
-1910 (-1891)d
-1808 (-1823)d
-1882 (-1777)d
-1745 (-1679)d
c
c
c
c
c
-0.27
-0.17
0.00
0.23
0.66
39.9e
113
101
75
146
162
c
27.8e
33.1e
c
Measured by cyclic voltammetry (mV vs Fc/Fc+), 0.1 M Et4NBF4/acetonitrile with glassy carbon electrode (7 mm2). The standard
a
b
Hammett values were taken from ref 32. c The values varied with the scan rate potential. Epc values obtained after addition of
d
Me4N+C6H5O- to corresponding APZs are given in parentheses. e These values correspond to the independent behavior of voltamperom-
metric function with respect to the scan rate potential.
The ratio of current function of the second peak to the
first reduction peak was lower than expected for a simple
EE reaction. This suggests a reaction after the first
reduction step, e.g., the disproportionation of the radical
anion (APZ•-) as shown in eq 6. Such a phenomenon has
been observed in other two-step electrochemical processes
as described theoretically by Lehman and Evans.35,36
Equation 6 associates a very small equilibrium constant
(K) and also a very small forward constant kinetic rate
(kf), especially in aprotic conditions where APZm2- is
present.35,36 The voltammetric behavior presents no
kinetic complications, however, the current function is
associated with the voltammetric peaks obtained for
APZm. Nevertheless, we report the voltammetric param-
eters for the APZ series as peak I′ and peak II′ in Table
3. The results show that the value of the current function
ipcv-1/2c-1 is not constant with the scan rate potential for
all APZs. Moreover, the values obtained for most of the
APZs were less than for the corresponding APZms (Table
3). As the size and shape of the APZm and APZ deriva-
tives are very similar, the decrease in current function
can not be attributed to a change in diffusion coefficient.
The ∆Ep values (EpaI′ - EpcI′) for peak I′c (Table 3) are in
the range of 315-494 mV, much higher than the value
of 60 mV reported for the simple, one-electron systems.16b
This large ∆Ep value merely indicates irreversibility in
the system due to kinetics or coupled chemical reactions.
The ratio of ipa/ipc, for peak I′c confirms the presence of
chemical reactions coupled to electron-transfer and,
accordingly, the values of the half-wave potential could
not be calculated. Only the cathodic peak potentials for
these compounds (Epc), obtained at 100 mVs-1 for both
waves, are described in Table 3.
Electrochemical behaviors similar to that displayed by
APZs (Figure 5b and Table 3) have been observed in
electrochemical reduction of quinones in electrolytic
media containing proton donors18 as well as in quinones
with acidic protons in their structure (HQ).17 For the
latter type of molecules that have functional groups with
acidic characteristics, such as the -OH group at position
C3 of the perezone, reduction of the quinone (HQ) has
been described as occurring via the reactions shown in
eqs 7-10.
36
sensitive to this phenomenon.35,
kf
kb
2APZ•-
{
} APZm + APZm2- K )
(6)
kf
kb
Electr och em ica l Beh a vior of AP Z Der iva tives.
Figure 5b shows the typical electrochemical behavior of
APZ. The same behavior was observed for all its deriva-
tives within the sweep potential range of 100-1000
mVs-1. Voltammograms for all the compounds studied
are very different from the typical behavior observed for
quinone reduction in aprotic media (Figure 5a)16 indicat-
ing that an additional effect must be operating on the
electrode process in the APZ derivatives. Since the only
structural difference between the compounds is the
replacement of the -OMe group with an -OH group at
the C3 position (Figure 1, Table 1), the proton in the -OH
group must be responsible for the altered electrochemical
behavior. It is important to recall that quinones contain-
ing phenolic groups (i.e., 1,8-dihydroxyanthraquinone19
and 1-hydroxy-9,10-anthraquinone20) maintain the typi-
cal electrochemical behavior of quinones despite intra-
molecular hydrogen bonding. Thus, the APZ series dif-
ference in electrochemical behavior is due to elevated
acidity of the -OH group in these molecules since the
-OH group is located on the quinone ring. The electro-
chemical reactions associated with each voltammetric
peak in the APZ cases, certainly differ from those
Since in these experiments no donor proton was
present, the acidic hydrogen of the -OH in the APZ
molecule (HQ) acts as an inner proton donor in a typical
self-protonation reaction.
HQ + 1e- a HQ•-
HQ•- + HQ a HQH• + Q-
HQH• + 1e- a HQH-
(7)
(8)
(9)
HQH- + HQ a HQH2 + Q-
(10)
(35) Evans, D. H.; Lehmann, M. W. Acta Chim. Scand. 1999, 53,
765-774.
(36) Lehmann, M. W.; Evans, D. H. Anal. Chem. 1999, 71, 1947-
HQ + 2/3 e- a 1/3 HQH2 + 2/3 Q-
(11)
1950

Molecular Structure of Phenylamine p-Benzoquinone Derivatives
J . Org. Chem., Vol. 66, No. 25, 2001 8355
According to reactions 7-10, we conclude that the first
reduction wave (I′c) observed in the cyclic voltammograms
of the APZ (HQ) derivatives (Figure 5b) corresponds to
the overall reaction 11 in which the quinone is reduced
through 2/3 of an electron to produce the corresponding
hydroquinone HQH2 and the perezonate Q-. In these
reactions, part of HQ is used for the redox reactions (eqs
7 and 9) and another part for the protonation reactions
(eqs 8 and 10). This effect diminishes the quantity of
quinone transformed to hydroquinone. The decrease in
current function value (Table 3, peak I′c) and reduction
current observed for the first cathodic wave of the APZs
compared to that corresponding to the APZms (Figure
5a,b) substantiates these effects. The cathodic peak
potential for the first wave (peak I′c) from the APZs is
less negative than the corresponding value from the
APZms (peak Ic), as seen in Table 3 (i.e., EpcI′ for APZ is
104 mV higher than EpcI for APZm). A lower charge
density occurs in the APZs system due to formation of a
hydrogen bridge between the -OH group and the adja-
cent carbonyl group C4-O4 (Figure 4a) stabilizing the
anion-radical of the APZ. This effect is also observed for
R-phenolic quinones, however, the direct proton transfer
to the anion-radical (equation 8) is absent. APZs thus
have less negative reduction potentials than the corre-
sponding APZms.
F igu r e 6. Typical cyclic voltammograms for 1 mM p-MeOAPZ
in 0.1 M Et4BNF4/acetonitrile obtained with a glassy carbon
electrode (7 mm2), at 100 mVs-1 scan rate: (a) in the ab-
sence of Me4N+C6H5O- and (b) in the presence of 2 mM
Me4N+C6H5O-.
Me4N+C6H5O- is a sufficiently strong base to deprotonate
the -OH group on the APZ (HQ) derivatives (eq 13) and
generate perezonate (Q-).
HQ + C6H5O- a C6H5OH + Q-
(13)
Previous studies on this type of molecules22,25 only
investigated the electroreduction process that occurred
in the first wave. In a recent work37 and in the present
study, the process corresponding to the second wave (II′c),
was evaluated as well.
Intermediates formed in the sequence of reactions
7-10 suggest that, at the negative potentials of the
second wave (-1720 to -1910 mV), the only species that
can exist on the electrode interface is perezonate (Q-)
formed in the self-protonation reactions (eqs 8 and 10).
We therefore proposed that the second reduction process
observed in the APZs corresponds to reduction of this
intermediate.
Perezonate is responsible for the cathodic peak (II′c)
observed at potentials in the range of -1654 to -1891
mV (Table 3). Unlike the behavior observed in aprotic
medium (Figure 6a), in the presence of Me4N+C6H5O-,
the perezonate reduction peak is an irreversible process
(Figure 6b). In the voltammograms (Figure 6a) of the APZ
series, sometimes a small peak precedes peak I′c, prob-
ably due to an adsorption process. The current associated
with this pre-peak shows more significant variation with
the scan rate than that of peak I′c confirming the
adsorption processes involved in the pre-peak. Analysis
of the reversible behavior of the perezonate peak and the
adsorption process mentioned above require a more
detailed electrochemical study which is beyond the scope
of this work.
Q- + 1e- a Q•2-
(12)
To test if the second reduction process of the APZ series
(Figure 5b) corresponded to reaction 12, a strong base
was used to generate perezonate Q- in the solution. Pilaj
and Murray also added a strong base to the hydroxy-
quinone solution to analyze the electrochemical behavior
corresponding to the conjugated base of this quinone20
In our experiments, cyclic voltammetry was carried out
in electrolytic media containing 2 mM of tetramethyl-
ammonium phenolate (Me4N+C6H5O-) (Figure 6b). Under
these conditions, the first wave (peak I′c) corresponding
to the reduction of APZ, disappeared and the second wave
became broad and irreversible. Regardless of the quantity
of Me4N+C6H5O- added to the solution, a small quantity
of APZ remained in solution, as detected by a small pre-
peak observed in Figure 6b. A previous study showed that
the cathodic peak associated with APZ reduction presents
a negative shift and a decrease of its associated current
when the phenolate concentration was increased.38 This
behavior provides further compelling evidence that
Su bstitu tion Effects. The cyclic voltammogram of PZ
was similar to that of APZ, both complicated by the
presence of chemical reactions caused by self-protonation.
The aniline substituent at the C6 position in APZ made
the electroreduction process more difficult compared with
that of PZ (Table 3) since the electron-donor ability of
the nitrogen atom increases the electronic density in the
quinone system. This effect also caused the hydrogen of
the hydroxyl group in APZ to be less acidic than in PZ.
The introduction of 4′-para substituents on the aniline
ring in APZm produced significant negative and positive
shifts in the peak potential associated with the first
reduction process depending on the electronic effect of
the substituent. As observed in similar systems,24 even
when the substituent is not directly conjugated with the
quinone group, the substitution effect of the aniline
system on electrochemical reduction of the quinone is
evident. Methoxy and methyl electron-donor groups on
the APZm made reduction of the quinone more difficult
than for APZm (Table 3), while with the electron-
accepting groups the opposite effect was observed.
In the APZ series, the substituents also displayed
electronic effects according to their σp Hammett constants
(37) Ferraz, P. A. L.; de Abreu, F. C.; Pinto, A. V.; Glezer, V.;
Tonholo, J .; Goulart, M. O. F. J . Electroanal. Chem. 2001, 507, 275-
286.
(38) J . A. Bautista-Mart´ınez, M. Sc. Thesis, UNAM Facultad de
Qu´ımica, Mexico, 2000.

8356 J . Org. Chem., Vol. 66, No. 25, 2001
Aguilar-Mart´ınez et al.
despite the fact that the electrochemical reaction associ-
ated at the first reduction process is different for APZ
and APZm (see reactions 11 and 4, respectively). The
magnitude of this effect was less for APZm than for APZ.
Reduction of perezonate (wave II′c, Figure 6b) formed
during the reaction of APZs and Me4N+C6H5O- also was
influenced by the substituents. Electron-donor substit-
uents caused EpcII′ values (shown in parentheses in Table
3) to shift toward more negative potentials than the
corresponding unsubstituted APZ. The opposite effect
was observed for the electron-accepting substituents.
Ha m m ett-Zu m a n Con text. For a better understand-
ing of the electroreduction mechanism, the electronic
effects of different substituents R2 (Table 1) in the Epc
potentials were studied using the Hammett-Zuman
equation (eq 14)39 and Hammett σp constants.32
F igu r e 7. Dominant hybrids of ABQs and ABQms (model
compounds for APZs and APZms) according to the electronic
properties of the substituents: (a) effect of the electron-
accepting groups; (b) effect of the electron-donor groups at the
aniline moiety.
A relationship between ∆Ep for quinones with and
without -OH in their structures has been described
previously.21,36
The reduction of anilineperezonates (eq 12) was
evaluated by analyzing the cathodic peaks (peak II′c,
∆Epc ) ERpc - EHpc ) Fπσp
(14)
5O-
EpcAPZ-C H ) obtained in the cyclic voltammogram of
6
APZs (HQ) in the presence of Me4N+C6H5O- (eq 18). The
Where EHpc is the reduction potential of the unsubsti-
tuted parent compound, EpRc is the reduction potential of
the substituted compound and Fπ is the reaction constant.
The two reaction series, APZs (HQ) and APZms, were
evaluated. The corresponding relationships for the trans-
formation of HQ to HQH2 (eq 11) in APZs and of APZm
to APZm•- (eq 4) in the APZms in aprotic medium are
described in the following equations (eqs 15 and 16,
respectively):
Fπ value illustrates that Q•2- is highly unstable due to
the increased charge density in the system, and the
dianion-radical formed in the electroreduction process of
perezonate (eq 12) is very sensitive to the effect of the
substituents. The electron-accepting substituents thereby
help to stabilize the charge excess in the system.21,36
∆Epc (mV)APZ-C H -) 204σp - 0.0026
O
6
5
(n ) 5, r ) 0.90) (18)
∆Epc (mV)APZ ) 171σp - 0.0218 (n ) 5, r ) 0.95)
(15)
Th eor etica l Ca lcu la tion s. To interpret our experi-
mental observations, we performed a full geometry
optimization of model p-benzoquinones, substituted by
a p-substituted-aniline group at position 6 and by hy-
droxy or methoxy groups at position 3, ABQ and ABQm,
respectively (Figure 7). Models are useful here due to the
large number of conformers associated with the rotation
of the side chain. Recently, we found evidence of a
conformer where the isolated double bond interacts with
the quinone ring. Computational requirements increase
rapidly with respect to the number of electrons taken into
account. A full explanation of the model design is
discussed below. The studies were performed within the
framework of density functional theory40 with the B3LYP
hybrid functional, using a double ê split valence basis
set as implemented in Gaussian 94 (G94) programs.41
Relevant geometric data are included in Table S1 of the
Supporting Information. Table S2 (Supporting Informa-
tion) shows the Wiberg bond indexes (WBI), calculated
with the natural bond orbital program (NBO)42 at a
B3LYP/6-31G(d,p) level of theory, as well as the densities
∆Epc (mV)APZm ) 147σp - 0.0005 (n ) 5, r ) 0.98)
(16)
In the APZs system, the relationship between the
values of the EpcI′ and the Fπ-constant characterizes not
only the stage of heterogeneous electron-transfer but also
the subsequent homogeneous chemical reaction con-
nected with the radical-anion protonation (eqs 7-10).
However, in the case of APZms, reversibility of the first
stage mentioned above precludes subsequent chemical
reactions (eq 4).
Sensitivity of the reaction to the electronic effect of the
substituents, characterized by positive values of the Fπ-
constant (the slope in eqs 15 and 16), indicates that there
is an important substituent effect for both series. The
reaction is facilitated by low electronic density on the
electro active group, and the electron-accepting ability
of these APZms and APZs follows a linear relationship
to the electronic perturbation of the substituents. How-
ever, the APZs are more susceptible to the electron-donor
substituent effect than the APZms. As mentioned above,
the -OH in the APZs polarizes the carbonyl C4-O4
(Figure 4) causing the substituent, R2, to have greater
electron-donor and electron-accepting properties than the
APZm series.
2
of the relevant critical points (F) and the Laplacians (∇ F)
(39) Zuman, P. Collect. Czech. Chem. Comun. 1962, 27, 2035-
2057.
(40) Malkin, V. G.; Malkina, O. L.; Eriksson, L. A.; Salahub, D. R.
In Modern Density Functional Theory. A tool for Chemistry; Seminario,
J . M., Politzer, P., Eds.; Elsevier: Amsterdam, 1995.
(41) Frisch, M. J .; Trucks, G. W.; Schlegel, H. B.; Gill, P. M. W.;
J ohnson, B. G.; Robb, M. A.; Cheeseman, J . R.; Keith, T.; Peterson, G.
A.; Montgomery, J . A.; Raghavachar, K.; Al-Laham, M. A.; Zakrzewski,
V. G.; Ortiz, J . V.; Foresman, J . B.; Cioslowski, J .; Stefanov, B. B.;
Nanayakkara, A.; Challacombe, M.; Peng, C. Y.; Ayala, P. Y.; Chen,
W.; Wong, M. W.; Andres, J . L.; Replogle, E. S.; Gomper, R.; Martin,
R. L.; Fox, D. J .; Binkley, J . S.; Defrees, D. J .; Baker, J .; Stewart, J .
P.; Head-Gordon, M.; Gonzalez, C.; Pople, A. Gaussian 94, Revision
E2; Gaussian, Inc.: Pittsburgh, PA, 1995.
A correlation between the reduction potentials and
Hammett’s σp-constants has also been established in the
case of the second electron transfer in APZms. The value
of the Fπ-constant (eq 17) indicates that the reduction of
APZm•- to APZm2- is also sensitive to the substituents’
effects.
(42) Glendening, E. D.; Badenhoop, J . K.; Reed, A. E.; Carpenter,
J . E.; Weinhold, F. NBO 3.1; Theoretical Chemistry Institute, Uni-
versity of Wisconsin: Madison, WI, 1994.
∆Epc (mV)APZ ) 156σp - 0.003 (n ) 5, r ) 0.84)
(17)

Molecular Structure of Phenylamine p-Benzoquinone Derivatives
J . Org. Chem., Vol. 66, No. 25, 2001 8357
angles are: C1′-N-C6-C5 (31.5°) and C6′-C1′-N-C6
(42°) with respect to the quinone plane. This rotation is
due to the greater steric repulsion of the methyl group
than of the hydrogen atom located at C5, and methyl
group dominance over the hydrogen bond stabilizing
contribution.
Evaluation of the APZ crystal revealed several impor-
tant structural characteristics. The bond distance is
greater for C4-O4 than for C1-O1 as supported by
theoretical calculations at the B3LYP/6-31G(d,p) level of
theory for the model p-benzoquinones used in this study
(see below). The quinone ring is slightly distorted from
planarity with the C5-C6-C1-C2 dihedral angle equal
to 5.5°. This distortion is possibly the result of steric
strain. Two different intramolecular hydrogen bonds
were determined. The C4-O4‚‚‚H-O3 bond is stronger
than C1-O1‚‚‚H-N, as expected, and bond distances are
2.079 and 2.224 Å, respectively. The O4‚‚‚H(O3) bond
favors electron donation from the aniline group and
explains the bond length pattern. The nitrogen atom is
pyramidalized with the angle between the H-N-C6 and
C1′-C6-H planes equal to 30.4°. In planar nitrogen, this
angle would be 0°. The bond length pattern in the N-C6-
C5-C4-O4 segment supports the existence of the reso-
nance hybrids suggested in Figure 7.
F igu r e 8. Dependence between the C6-N-C1-C6′ dihedral
angle and energy of the ABQm molecule.
and ellipticities (ꢀ) determined using the AIM program.43
Table S3 includes the natural charges and Table S4
(Supporting Information) the total and HOMO-LUMO
energies. We determined the critical bond point densities
of the compounds studied here according to the topologi-
cal theory of atoms in molecules.44
The ABQ derivatives (Figure 7, R1 ) H) are flat, and
analysis of the normal vibrational modes establishes
correspondence to minimal points on the potential surface
since all the frequencies are positive. We thus expect that
the methoxylated derivatives are also flat as they experi-
ence the stabilizing effect provided by complete conjuga-
tion of the system. However, total planarity results in
proximity of the hydrogen atoms at positions 5 and 6’ to
produce steric repulsion. Complete optimization of the
geometry of the ABQm from flat structures permits
isolation of stationary points whose geometries are
described in Table S1 (Supporting Information). Analysis
of the normal modes of vibration, however, establishes
that the flat arrangements correspond to transition states
associated with rotation around the C1′-N bond (Figure
7). We evaluated the effect of rotation of this bond on
the energy of the system. For R2 ) H (ABQ), the value of
the energy was determined every 10 degrees of the
dihedral angle C6-N-C1-C6′ obtaining the profile shown
in Figure 8. At this potential, two maximal points, one
corresponding to the flat molecule located at 0.7 kcal/
mol with respect to the minimal located at 27.9° and the
other located at 90°, are observed. The absolute minimum
corresponds to the point where the dihedral angle is
27.9°. The geometric properties of this compound are
described in table S1. As expected, at the latter point
(90°) the conjugation is broken reinforcing the importance
of the hydrogen bridge as a stabilizing contribution
present on the ABQ series and absent on ABQm. The
final geometry is the result of a fine balance between the
hydrogen bridge and the repulsion between hydrogen
atoms at positions 5 and 6′ (Figure 7). A difference of
only 0.7 kcal/mol suggests a molecule with free rotation
at that region and, thus, its description by only one group
of coordinates is impossible and the molecule corresponds
to the type denominated as fluxional. The planar struc-
ture of ABQ is very different from the structure of the
parent APZ, in which, according to the X-ray structure
shown in Figure S1 and tables S4-S8 (Supporting Infor-
mation), the aniline ring is rotated and the dihedral
The molecular geometry is attributable to the equilib-
rium between the steric destabilizing and the stabilizing
electronic delocalization contributions. Since the elec-
tronic effects are maximized in a planar system, in our
molecular ABQ models we substituted the methyl group
with a hydrogen atom allowing a highly conjugated,
planar molecular frame. For the ABQms, we analyzed
planar structures located at only 0.7 kcal/mol with
respect the minimum in the molecule in order to main-
tain constant the full electronic delocalization. Energy
of 0.7 kcal/mol is less than that of the zero point energy
correction. Two different hydrogen bridges are observed
in the model derivatives of APZs (Figure 9). The O4-H(O)
bond distance is less than that of O1-H(N). The Wiberg
bond index and the electronic density at critical bond
point (Table S2, Supporting Information) are greater for
the hydrogen bridge formed by the oxygen than by the
nitrogen atom. In both cases, the Laplacians are positive,
indicating the high ionic character of the interaction. The
hydrogen bridge O4‚‚‚H(O) is sensitive to the effect of the
substituents. Thus, the O4-H(O) distance of the ABQ
series increases gradually from 1.880 Å when R2 ) -OMe
to 1.914 when R2 ) -CN. For the nitro group, the
distance increases only to 1.915 Å. The N-H bridge does
not show a definite trend in bond distance or in electronic
density of the critical bond point (Tables S1 and S2). The
bonding strength of O-H, therefore, is decreased by
electron-accepting groups and increased by the electron-
donor groups. This is evidence of the participation of the
resonant forms shown in Figure 7.
Theoretical calculations establish that the nitrogen
atom joining the quinone to the phenyl-substituted group
hinders direct conjugation between these groups, inter-
acting with one or the other, depending on the substitu-
ent. Electron-donor groups favor interaction with the
quinoid ring (Figure 7b), while electron-accepting groups
favor interaction with the aromatic ring (Figure 7a). The
pattern of bond lengths in the segment C1′-N-C6-C5-
C4-O4 shows that for the hydroxylated derivatives, as
the attractant character of the substituent increases, the
(43) Biegler-Koenig, F. W.; Bader, R. F. W.; Tang, T. H. J . Comput.
Chem. 1982, 2, 317-328.
(44) (a) Bader, R. F. W. Atoms in MoleculessA Quantum Theory;
Clarendon Press. Oxford, 1990. (b) Bader, R. F. W. Acc. Chem. Res.
1985, 18, 9-15. (c) Bader, R. F. W. Chem. Rev. 1991, 91, 893-928.

8358 J . Org. Chem., Vol. 66, No. 25, 2001
Aguilar-Mart´ınez et al.
F igu r e 9. Bond and ring critical points in the density of 6-[4′-(R2-phenyl)amine]-3-hydroxy-1,4-benzoquinones. R2) -OMe (a),
-CH3 (b), -H (c), -F (d), -CF3 (e), -CN (f). Values correspond to the density of bond critical points.
distances N-C1′, C5-C6, and C4-O4 tend to decrease,
while the C6-N and C5-C4 distances tend to increase.
In contrast, the segment O3-C3-C2-C1-O1 does not
change with substituent variation. The C6-N-C1′ angle
remains constant regardless of the nature of the sub-
stituent since the H5-H6′ repulsion dominates. In the
case of the -NO2 group, the H5-H6′ repulsion increases
noticeably due to shortening of the N-C1′ bond, justifying
the loss of molecular planarity.
Insensitivity of the segment O3-C3-C2-C1-O1 to
substituent effects is unexpected since the electron-donor
groups that favor participation of the nitrogen atoms in
the delocalization of the quinone should increase the
interaction of the O3 proton with O4, favoring participa-
tion of the resonant form (b) shown in Figure 4. We
conclude that for an isolated molecule in the vapor phase
at 0 K, there is no participation of the resonating form
4b, since the average O1-C1 distance is 1.233 Å and this
distance is insensitive to the effect of the substituents.
In comparison, the O4-C4 distance varies from 1.242 to
1.237 Å when the -OMe group is changed for the -NO2
group.
electronic delocalization is not influenced by the total
molecular energy and the electronic density on the
conjugated system tends to increase for the C6-C5, C5-
C4 bonds. Electronic density is practically constant for
the C4-O bond while on the C4-C3, C3-C2, C1-C2 bonds,
it shows a decrease of F. This can not be explained in
terms of electronic delocalization (π) but rather in terms
of the inductive effect and stresses. To compare the ABQ
with ABQm series for determining the effect of the
hydrogen bridge, these bonds need to be kept flat.
Analysis of the Wiberg bond indexes and the electronic
density of the critical points and their Laplacians (Table
S2, Supporting Information) leads us to hypothesize that
the electronic delocalization is greater in the hydrox-
ylated than in the methoxylated derivatives. The C1′-
N-C6-C5-C4-O4 segment produces a pattern of bond
order and electronic density that agrees with the reso-
nant forms described in Figure 7. In addition, the
nitrogen atom of the aniline interacts with the aromatic
ring when it is substituted with electron-accepting groups
and with the quinoid ring when the substituents are
electron-donors.
The C-CdO valence angles of the two carbonyl groups
on the quinone tend to be approximately 6° smaller on
the side forming the hydrogen bond than on the side
where no such bonds form. The C3-O3 bond displays
similar behavior. In contrast, on the methylated deriva-
tives the O4-C4 distance is notably less than the C1-O1
distance. This may be due to the absence of the hydrogen
bridge that produces polarization of the carbonyl group
and facilitates the resonant form (a) in Figure 4. In
addition, the patterns of bonding lengths for the C1′-N-
C6-C5-C4-O4 and O3-C3-C2-C1-O1 segments decrease
in intensity for the same para substituent between the
-OH and -OMe series.
Table S9 (Supporting Information) shows the effect of
rotation around the dihedral angle C6-N2-C1′-C6′ on the
density of the relevant critical points of ABQm. The
density of the molecule’s critical points on the minimal
energy conformation (27.94°) does not change substan-
tially with respect to the flat structure and does not
change the previous arguments. In addition, as the
dihedral angle of interest increases, the C6-N bond
becomes stronger because the nitrogen decreases its
delocalization effect on the aromatic ring and thus,
increases the possibility of interacting with the quinone.
The N-C1′ bond shows the opposite trend when its angle
reaches 90°, conjugation decreases notably. Variation of
Besides the hydrogen bridges already described, the
study of molecular topology through the bond and ring
critical points revealed an unexpected H5-H6′ bonding
path (Figure 9). This unexpected critical point corre-
sponds to an interaction line between the attractors of
steric origin and corresponds to the dihydrogen interac-
tion (so-called dihydrogen-bridge).45 Such interactions
have been described by Cioslowski46 and the interaction
distance (H5-H6′) found for the compounds studied here
agrees with those previously reported.24 The interaction
is observed in the model molecules used in those studies
because it considered a proton at the C5 position, however
APZs and APZms have a methyl group in that position
and thus, the H5-H6′ interaction does not exist.
2
The Laplacians ∇ F are very sensitive to electronic
delocalization. Behavior of the carbonyl group in the
compounds studied allowed us to efficiently differentiate
between the two quinone carbonyl groups. For the -OH
series, the Laplacians of the critical points of the C-O
bonds indicate an increased ionic character (positive
Laplacians values, Table S2, Supporting Information)
(45) Alkorta, I.; Rozas, I.; Elguero, J . Chem. Soc. Rev. 1998, 27, 163-
170.
(46) (a) Cioslowski, J .; Mixon, S. T.; Edwards, W. D. J . Am. Chem.
Soc. 1991, 113, 1083-1085. (b) Cioslowski, J .; Mixon, S. T. J . Am.
Chem. Soc. 1992, 114, 4382-4387.

Molecular Structure of Phenylamine p-Benzoquinone Derivatives
J . Org. Chem., Vol. 66, No. 25, 2001 8359
Ta ble 4. En er gy of th e F r on tier Or bita ls a n d Th eir Neigh bor s for 6-[4′-(R2-p h en yl)a m in e]-3-h yd r oxy-1,4-ben zoqu in on es
(ABQs) a n d 6-[4′-(R2-p h en yl)a m in e]-3-m eth oxy-1,4-ben zoqu in on es (ABQm s) (En er gy in Ha r tr ees)
compd
EHOMO - 1
EHOMO
ELUMO
ELUMO + 1
η
Etotal
p-MeOABQ
p-MeABQ
ABQ
-0.24949
-0.2556
-0.20773
-0.21656
-0.22158
-0.22241
-0.23365
-0.23793
-0.24324
-0.19756
-0.20610
-0.21104
-0.21195
-0.22392
-0.22848
-0.23416
-0.10642
-0.10933
-0.11165
-0.11377
-0.12086
-0.12645
-0.12867
-0.09898
-0.10148
-0.10349
-0.10564
-0.11243
-0.11782
-0.12024
-0.02086
-0.01916
-0.01945
-0.03081
-0.03941
-0.05785
-0.09241
-0.01293
-0.01152
-0.01225
-0.02274
-0.03243
-0.05101
-0.08584
0.05066
0.05362
0.05497
0.05432
0.05640
0.05574
0.05729
0.04929
0.05231
0.05375
0.05316
0.05575
0.05560
0.05696
-857.65195
-782.44815
-743.12730
-842.35738
-1080.16221
-835.36797
-794.62737
-896.94255
-821.73910
-782.41852
-881.64866
-1119.45424
-874.66038
-956.91991
-0.25908
-0.26027
-0.26798
-0.27123
-0.27442
-0.24673
-0.24967
-0.25189
-0.25405
-0.26105
-0.26623
-0.26764
p-FABQ
p- CF3ABQ
p-CNABQ
p- NO2ABQ
p-MeOABQm
p-MeABQm
ABQm
p-FABQm
p- CF3ABQm
p-CNABQm
p- NO2ABQm
Ta ble 5. P a r a m eter s of th e HOMO a n d LUMO Or bita l
En er gies vs σp Ha m m ett Con sta n t P lots of
6-[4′-(R2-p h en yl)a m in e]-3-h yd r oxy-1,4-ben zoqu in on es
(ABQs) a n d 6-[4′-(R2-p h en yl)a m in e]-
with the C1-O1 group being more electrophilic than C4-
O4 (natural charges in Table S3, Supporting Information).
For isolated molecules in gas phase, C4 is more electro-
philic in the -OMe than in -OH series, as shown in 13C
NMR observations. For the ABQ series, on the other
hand, the hydrogen bridge O1-H(N) polarizes the C1-
O1 group, but the donating oxygen at C3 makes the
carbonyl group at C4 more susceptible to the addition of
an electron, protecting C1 from electronic addition and
increasing the strength of the hydrogen bridge. The
opposite is observed for the methoxy series, where the
donor capabilities of the oxygen atom at C3 are dimin-
ished. The Laplacians of the critical points in both cases
support participation of the resonant forms shown in
Figure 7.
3-m eth oxy-1,4-ben zoqu in on es (ABQm s)
Ex(Hartrees) )Fπσ + b
with n molecules in the correlation and r correlation coefficient
Ex
series
Fπ
b
n
r
EHOMO
ELUMO
EHOMO
ELUMO
ABQms
ABQms
ABQs
-0.0305
-0.0194
-0.0293
-0.0203
-0.2090
-0.1041
-0.2195
-0.1121
7
7
7
7
0.98
0.98
0.97
0.98
ABQs
here. This demonstrates that overall hardness properties
do not provide adequate reactivity indexes.48
Con clu sion s
Table 4 includes the energies of the frontier molecular
orbitals as well as the absolute hardness (η), defined as
(ELUMO - EHOMO)/2. For all compounds, the NBO analysis
established that the HOMO orbital corresponds to the
lone pair of one of the heteroatoms (mainly of the
substituents on the aromatic ring) and the LUMO
corresponds to the Rydberg orbital of sp type located at
C4. Interestingly, the LUMO at C4 permits better interac-
tion with the nitrogen lone pair making the charge-
transfer associated with this interaction possible. Natural
charges (Table S3, Supporting Information) show that
C1 is more positive than C4, in agreement with an
electronic transfer process activated by the N atom, and
is more positive in the -OMe series than in the -OH
series as shown in spectroscopic observations (see 13C
NMR chemical shifts). If the process is controlled by
natural charge, the more sensitive carbonyl group would
be C1-O1 and reduction would be easier in the methoxy
than in the hydroxy series.47 It is reasonable to locate
the LUMO orbital at C4 since it is closer in energy to the
nitrogen lone pair allowing an efficient and dominant nN
f π* stereoelectronic interaction.
A linear relationship occurs between the HOMO and
LUMO orbital energies of these molecules and the
experimental σp Hammett parameter (Table 5).
Absolute hardness (η) described in Table 4 is a reactiv-
ity index. For the same substituent in the phenyl ring,
this value is greater for the ABQ with respect to the
ABQm series and for nitro with respect to methoxy
derivatives. These results contradict experimental ob-
servations since larger values of η imply more stable
molecules, which is not the case for the molecules studied
We synthesized 13 novel derivatives of perezone that,
with the exception of APZ and PZm, have not been
previously reported (Table 1). PZ and APZs (HQ), which
have an acidic hydrogen at the C3 position, displayed very
different electrochemical behavior than that of typical
quinones. For the compounds containing acidic hydro-
gens, the cyclic voltammograms produced two waves. The
first of these corresponded to the irreversible reduction
from HQ to HQH2, and the second to a one-electron
transfer due to the reversible reduction from perezonate
(Q-) formed during the self-protonation reaction to Q•2-
.
In basic media (Me4N+C6H5O-), the cyclic voltammogram
of APZs (HQ) showed only the wave corresponding to the
Q- to Q•2- reduction, confirming that the second wave in
aprotic media is due to this reduction process. Following
the methylation reaction of APZs, the presence of the two
characteristic, one-electron charge-transfer waves was
observed for APZm.
APZs and APZms are quinones-NH-substituted phen-
yls, in which the amine group located between the
quinone and the substituted aryl groups interferes with
the direct transmission of the substituent effect on the
quinone system. We observed a linear variation of 1/λmax
for nN f π* and 13C chemical shifts of the unsaturated
carbons of perezone derivatives as a function of σp. This
variation indicates a direct influence of the donor-
acceptor properties of the substituent in the aniline ring
on the electronic properties of the quinone ring. Our
analysis of the effect of the substituents on the cathodic
peak potentials (Epc) demonstrated that this effect is
(48) (a) Perez, P.; Toro-Labbe, A.; Contreras, R. J . Phys. Chem. A.
2000, 104, 5882-5887. (b) Fuentealba, P.; Perez, P.; Contreras, R. J .
Chem. Phys. 2000, 113. 2544-2551.
(47) J ensen, F. Introduction to Computational Chemistry; Wiley:
New York, 1999; pp 347-348.

8360 J . Org. Chem., Vol. 66, No. 25, 2001
Aguilar-Mart´ınez et al.
solution with CHCl3. In the last case the solvent spectra was
subtracted. Elemental analyses were performed by Galbraith
Laboratories, Inc. Melting points are not corrected.
transmitted through the amine group. For the Fπ con-
stants in the first reduction wave, the APZs showed
greater sensitivity to the effect of the substituent than
for the same wave in the APZm series (Fπ ) 171 and Fπ
) 147, respectively). This observation is explained by the
fact that in the APZs, the -OH group at C3 polarizes the
bond C4-O4 facilitating delocalization of the nitrogen lone
pair into the quinone system. This substantiates our
theoretical calculations that showed the pattern of bond-
ing lengths of C1′-N-C6-C5-C4-O4 and O3-C3-C2-
C1-O1 segments decreasing in intensity for the same
p-substituent from the -OH to the -OMe series. Accord-
ing to Figure 7, displacement of the unshared nitrogen
electrons mainly modifies the electronic density of the
C1′-N-C6-C5-C4-O4 segment and has less effect on the
electronic density of the C1-O1 bond, as demonstrated
by the Topological Theory of Atoms in Molecules indexes.
For the APZms system, greater susceptibility of the
second wave to the substitution effect (Fπ ) 156 mV)
indicates that this wave corresponds to the reduction of
carbonyl C4-O4. Natural charges show that C1 is more
positive than C4; nevertheless, the LUMO orbital is
located at C4. Thus, the electrochemical transfer in which
the quinone takes part is controlled by the natural charge
distribution of the quinones rather than by their orbital
energies, since the first wave belongs to the reduction of
the carbonyl, C1-O1.
Gen er a l P r oced u r e (I) for th e P r ep a r a tion of Su bsti-
tu ted 2-(1,5-Dim eth yl-4-h exen yl)-3-h yd r oxy-5-m eth yl-6-
[4′-(R2-p h en yl)a m in e]-1,4-ben zoqu in on es (AP Zs). A 2.01
mmol portion of the substituted aniline (dissolved in 20 mL of
anhydrous THF) was added dropwise via cannula with stirring
to the solution of perezone (500 mg, 2.01 mmol) in 25 mL of
anhydrous THF in a dry apparatus under N2 atmosphere. A
deep blue solution was obtained. The reaction mixture was
refluxed for 12 h. After cooling, 10 mL of 2 N HCl was added,
and the solvent was removed in a vacuum. The residue was
dissolved in CH2Cl2 (50 mL), and the organic phase washed
with water and brine and then dried. After the CH2Cl2 was
evaporated, the residue was subjected to column chromatog-
raphy (silica gel, n-hexane-ethyl acetate 9:1) yielding the
desired product.
2-(1,5-Dim eth yl-4-h exen yl)-3-h yd r oxy-5-m eth yl-6-[(4′-
m eth oxyp h en yl)a m in e]-1,4-ben zoqu in on e (p-MeOAP Z).
A 0.247 g portion of 4-methoxyaniline under general procedure
I yielded 0.70 g (97%) of the product: mp 125-127 °C; IR
(CHCl3, cm-1) 851, 929, 984, 1020, 1114, 1163; UV-vis (MeOH,
nm) 543, 290, 257, 209; 1H NMR (CDCl3) δ 1.2 (d, 3H, J ) 7.0
Hz, H8), 1.57 (s, 3H, H14), 1.55 (s, 3H, H7), 1.6 (m, 1H, H10),
1.65 (d, 3H, J ) 1 Hz, H15), 1.8 (m, 1H, H10), 1.9 (m, 2H, H11),
3.05 (dq, 1H, J ) 7.0, 9.0 Hz, H9), 3.93 (s, 3H, R2), 5.05 (ts,
1H, J ) 1.5, 7.0 Hz, H12), 6.95 (d, 2H, J ) 9.0 Hz, H2′,6′), 7.3 (s,
1H, OH), 7.6 (broad, 1H, NH), 7.97 (d, 2H, J ) 9.0 Hz, H3′,5′);
13C NMR (CDCl3) δ 182.72 (C1), 181.81 (C4), 153.72 (C3), 143.17
(C6), 139.84 (C4′), 131.33 (C1′), 130.93 (C13), 125.28 (C2), 125.10
(C12), 123.71 (C3′,5′), 118.5 (C5), 112.68 (C2′,6′), 54.15 (R2), 34.45
(C10), 29.4 (C9), 26.8 (C11), 26.27 (C15), 18.4 (C8), 17.99 (C14),
11.54 (C7); MS m/z 369, 326, 312, 300, 298, 288, 287, 286, 272,
260, 258, 229, 131, 123, 91. Anal. Calcd for C22H27O4N: C,
71.54, H, 7.31; N, 3.79. Found: C, 71.55; H, 7.19; N, 3.97.
2-(1,5-Dimethyl)-4-hexenyl)-3-hydroxy-6-[(4′-methylphen-
yl)a m in e]-1,4-ben zoqu in on e (p-MeAP Z). According to gen-
eral procedure I, 0.215 g (2 mmol) of p-toluidine yielded 0.639
g (90%) of the desired product: mp 117-118 °C; IR (CHCl3,
cm-1) 928, 1020, 1058, 1092, 1112, 1175, 1293, 1313, 1337,
1378, 1401, 1456, 1494, 1516, 1585, 1618, 1641, 1701, 1717,
2011, 2045, 2859, 2928, 2961, 3050, 3313; UV-vis (MeOH, nm)
LUMO energy values calculated for the different APZs
and APZms studied here predict that reduction facility
will follow the order p-NO2> p-CN> p-CF3> p-F> p-H>
p-Me> p-MeO. The reduction order agrees with the Epc
potentials (Table 3) obtained by cyclic voltammetry for
the reduction of APZs and APZms in aprotic media. A
good linear relationship between the ELUMO and the
corresponding EpcI for APZm/APZm•- reduction (eq 19)
was observed.
EpcI (mV)APZms )-6714ELUMO (Hartree) - 1946
(n ) 4, r ) 0.98) (19)
1
510, 315, 231; H NMR (CDCl3) δ 1.23 (d, 3H, J ) 7 Hz, H8),
1.51 (s, 3H, H7), 1.58 (s, 3H, H14), 1.6 (m, 1H, H10), 1.66 (d,
3H, J ) 1.5 Hz, H15), 1.8 (m, 1H, H10), 1.91 (m, 2H, H11), 2.42
(s, 3H, R2), 3.06 (dq, 1H, J ) 7, 8.5 Hz, H9), 5.1 (ts, 1H, J )
1.5, 7.0 Hz, H12), 6.95 (d, 2H, J ) 8.0 Hz, H2′,6′), 7.26 (d, 2H, J
) 8 Hz, H3′,5′), 7.7 (s, 1H, OH), 8.1 (broad, 1H, NH); 13C NMR
(CDCl3) δ 182.75 (C1), 181.87 (C4), 153.67 (C3), 143.13 (C6),
135.76 (C16), 132.86 (C19), 130.94 (C13), 128.07 (C3′,5′), 125.82
(C2), 125.04 (C12), 121.58 (C2′,6′), 118.6 (C5), 34.39 (C10), 29.4
(C9), 26.7 (C11), 26.3 (C15), 19.59 (R2), 18.4 (C8), 17.96 (C14),
11.64 (C7); MS m/z 353, 354, 272, 271, 270, 245, 244, 242, 198,
83. Anal. Calcd for C22H27O3N; C, 74.78; H, 7.64; N, 396.
Found: C, 74.56; H, 7.82; N, 3.97.
The correlation was not so straightforward for the
APZs (HQ) (eq 20) since in this system, in addition to
the electron transfer, self-protonation reaction is taking
place in the electrochemical process.
EpcI′ (mV)APZs ) -3422ELUMO(Hartree) -1434
(n ) 4, r ) 0.60) (20)
Exp er im en ta l Section
2-(1,5-Dimethyl-4-hexenyl)-3-hydroxy-5-methyl-6-phenyl-
a m in e-1,4-ben zoqu in on e (AP Z). According to general pro-
cedure I, 0.187 g (2 mmol) of aniline yielded 0.644 g (95%) of
the desired product: mp 132-133 °C; IR (CHCl3, cm-1) 1083,
1245, 1296, 1316, 1337, 1377, 1402, 1449, 1506, 1585, 1643,
2867, 2929, 2967, 3312; UV-vis (MeOH, nm) 535, 337, 260,
Syn th esis. All reactions were carried out under inert
nitrogen atmosphere. THF was distilled in an N2 atmosphere
prior to use over sodium-benzophenone ketyl and successively
over LiAlH4. Chromatographic purifications were carried out
on silica gel columns(Merck, 230-400 mesh) at medium
pressure using n-hexane-ethyl acetate (9:1) as eluent. PZ was
isolated from Perezia cuernavacana roots as described by
1
207; H NMR (CDCl3) δ 1.2 (d, 3H, J ) 7 Hz, H8), 1.5 (s, 6H,
H7, H14) 1.6 (m, 1H, H10), 1.69 (d, 3H, J ) 1.5 Hz, H15), 1.8 (m,
1H, H10), 1.9 (m, 2H, H11), 3.05 (dq, 1H, J ) 7, 8.5 Hz, H9),
4.75 (s, 1H, H16), 5.1 (ts, 1H, J ) 1.5, 7.0 Hz, H12), 7.0 (d, 2H,
J ) 7.5 Hz, H2′,6′), 7.21 (t, 1H, R2) 7.35 (d, 2H, J ) 7.5 Hz,
Walls,27 as golden-yellow leaflets, mp 104-106 °C, [R]20 -17
D
1
(Et2O). All other materials were purchased commercially. H
and 13C NMR spectra (500 and 75 MHz, respectively) were
recorded in CDCl3 and used TMS as a reference. Signal
multiplicity is described as follows: d, doublet; t, triplet; dq,
doublet of quintets; ts, triplet of septets; m: multiplet. Mo-
lecular numbering is given in Table 1. Mass spectra and high-
resolution mass spectra (HRMS) were performed by electron
impact with beam energy of 70 eV. IR spectra were recorded
in different media: directly as a film, in KBr pellets or in
H
3′,5′), 7.6 (broad, 1H, NH); 13C NMR (CDCl3) δ 182.8 (C1),
181.97 (C4), 153.6 (C3), 143.06 (C6), 138.51 (C4′), 130.97 (C13
)
127.61 (C3′,5′), 126.74 (C2), 124.95 (C12), 121.26 (C2′,6′), 122.94
(C1′), 118.76 (C5), 34.27 (C10), 29.7 (C9), 26.52 (C11), 26.35 (C15),
18.4 (C8), 17.9 (C14), 11.82(C7); MS m/z 339, 296, 282, 257, 230,
228, 180, 130, 109, 77, 69, 67, 55, 41. Anal. Calcd for
C21H25O3N; C, 74.33; H, 7.37; N, 4.12. Found: C, 74.10; H, 7.58;
N, 4.02.

Molecular Structure of Phenylamine p-Benzoquinone Derivatives
J . Org. Chem., Vol. 66, No. 25, 2001 8361
2-(1,5-Dim eth yl-4-h exen yl)-3-h yd r oxy-5-m eth yl-6-[(4′-
br om oph en yl)am in e]-1,4-ben zoqu in on e (p-Br AP Z). A 0.346
g portion of 4-bromoaniline yielded 0.773 g (92%) of the desired
product: mp 127-128 °C; IR (film, cm-1) 816, 850, 933, 1011,
1071, 1092, 1172, 1247, 1286, 1306, 1335, 1377, 1396, 1453,
1502, 1581, 1603, 1641, 1700, 1743, 2858, 2875, 2927, 2966,
3316; UV-vis (MeOH, nm) 521, 345; 1H NMR (CDCl3) δ 1.21
(d, 3H, J ) 7.0 Hz, H8), 1.55 (s, 3H, H14), 1.59 (s, 3H, H7), 1.6
(m, 1H, H10), 1.67 (d, 3H, J ) 1.5 Hz, H15), 1.87 (m, 1H, H10),
1.95 (m, 2H, H11), 3.05 (dq, 1H, J ) 7.0, 8.5 Hz, H9), 5.09 (ts,
1H, J ) 1.5, 7.0 Hz, H12), 6.95 (d, 2H, J ) 8.75 Hz, H2′,6′), 7.45
(d, 2H, J ) 8.75 Hz, H3′,5′), 7.7 (broad, 1H, NH), 7.73 (s, 1H,
OH); 13C NMR (CDCl3) δ 182.87 (C1), 182.11 (C4), 153.49 (C3),
142.96 (C6), 138.6 (C4′), 130.99 (C13), 131.55 (C3′,5′); 127.98 (C2),
124.82 (C12), 123.31 (C2′,6′), 118.98 (C5), 116.40 (C1′), 34.12 (C10),
248, 247, 177, 166, 165, 146, 106. Anal. Calcd for C21H24O5N2;
C, 65.62; H, 6.25; N, 364. Found: C, 65.70; H, 6.19; N, 3.92.
Gen er a l P r oced u r e (II) for th e Syn th esis of Su bsti-
tu ted 2-(1,5-Dim eth yl-4-h exen yl)-3-m eth oxy-5-m eth yl-6-
[4′-(R2-p h en yl)a m in e]-1,4-ben zoqu in on es (AP Zm s). A 4 g
portion of sodium carbonate and 1.5 mmol of recently distilled
dimethyl sulfate (1.5 mmol, 0.189 g) were added to a solution
of 1.0 mmol of APZs in 25 mL of anhydrous acetone in a dry
flask. The reaction mixture was refluxed for 12 h. After the
mixture was cooled, 10 mL of 2 N KOH was added and the
solvent was removed in a vacuum. The residue was dissolved
in ethyl acetate (50 mL), and the organic phase was washed
with water and brine and then dried over Na2SO4. After the
solvent was evaporated, the residue was subjected to column
chromatography (silica gel, n-hexane-ethyl acetate 9:1) yield-
ing the desired product.
29.4 (C9), 26.42 (C15), 26.29 (C11), 18.3 (C8), 17.82 (C14), 12.07
(C7); MS m/z 417, 418, 419, 421, 360, 338, 336, 335, 309, 257,
180, 149, 334, 308. Anal. Calcd for C21H24O3N; C, 60.28; H,
5.74; N, 3.34; Br, 19.13. Found: C, 60.51; H, 5.47; N, 3.33; Br,
19.27.
2-(1,5-Dimethyl-4-hexenyl)-3-methoxy-5-methyl-1,4-benzo-
qu in on e (P Zm ). A 0.248 g portion of PZ under general
procedure II yielded 0.236 g (90%) of the desired product as a
yellow oil:21 IR (CHCl3, cm-1) 2965, 2928, 2856, 1655, 1636,
1599, 1449, 1377, 1273, 1057, 926, 889; UV-vis (MeOH, nm)
2-(1,5-Dimethyl-4-hexenyl)-3-hydroxy-7-[(4′-acetylphenyl)-
a m in e]-1,4-ben zoqu in on e (p-MeCOAP Z). A 0.304 g portion
of 4-aminoacetophenone yielded 0.690 g (90%) of the desired
product: mp 115-116 °C; UV-vis (MeOH, nm) 522, 316, 204;
1H NMR (CDCl3) δ 1.2 (d, 3H, J ) 7.0 Hz, H8), 1.5 (s, 3H, H7),
1.55 (s, 3H, H14), 1.6 (m, 1H, H10), 1.65 (d, 3H, J ) 1.0 Hz,
1
373, 262.5, 207; H NMR (CDCl3) δ 1.18 (d, 3H, J ) 7.0 Hz,
H8), 1.54 (s, 3H, H15), 1.59 (m, 1H, H10), 1.65 (d, 3H, J ) 1.5
Hz, H14), 1.75 (m, 1H, H10), 1.89 (m, 2H, H11), 2.01 (s, 3H, H7),
3.09 (dq, 1H, J ) 7.0, 8.5 Hz, H9), 3.95 (s, 3H, OMe), 5.06 (ts,
1H, J ) 1.5, 7.02 Hz, H12), 6.47 (q, 1H, H6); MS m/z 262, 247,
219, 205, 180, 165, 161, 137, 109, 91, 69, 55, 41, 28, 18, 17.
Anal. Calcd for C16H22O3: C, 73.28; H, 8.45. Found: C, 73.14;
H, 8.62.
H
15), 1.8 (m, 1H, H10), 1.9 (m, 2H, H11), 2.74 (s, 1H, R2), 3.05
(dq, 1H, J ) 8.7, 7.2 Hz, H9), 5.1 (ts, 1H, J ) 1.2, 7.2 Hz, H12),
6.9 (d, 2H, J ) 8.6 Hz, H3′,5′), 7.4 (broad, 1H, NH), 7.5 (d, 2H,
J ) 8.6 Hz, H2′,6′), 7.8 (s, 1H, OH); 13C NMR (CDCl3) δ 195.79
(R2), 182.96 (C1), 182.27 (C4), 153.37 (C3), 142.85 (C6), 138.5
(C4′), 131.16 (C1′), 131.03 (C13), 129.44 (C2), 128.79 (C3′,5′), 124.68
(C12), 119.23 (C5), 119.22 (C2′,6′), 33.95 (C10), 29.4 (C9), 26.5 (C15),
26.01 (C11), 18.3 (C8), 17.73 (C14), 12.35 (C7); MS m/z 381, 339,
324, 310, 300, 299, 273, 229, 226, 191, 158, 113, 111, 272, 257,
157, 135. Anal. Calcd for C24H27O4N; C, 72.44; H, 7.08; N, 3.67.
Found: C, 72.54; H, 7.08; N, 3.64.
2-(1,5-Dim eth yl-4-h exen yl)-3-m eth oxy-5-m eth yl-6-[(4′-
m eth oxyph en yl)am in o]-1,4-ben zoqu in on e (p-MeOAP Zm ).
A 0.370 g portion of the methoxy derivative (PZm) reacted
according to general procedure II. After column purification,
0.345 g (90% yield) of deep blue oil was obtained: IR (CHCl3,
cm-1) 3335, 2936, 2842, 1643, 1593, 1512, 1462, 1339, 1270,
1200, 1115; UV-vis (MeOH, nm) 543, 290, 257, 209; 1H NMR
(CDCl3) δ 1.2 (d, 3H, J ) 7.0 Hz, H8), 1.50 (S, 3H, H15), 1.56
(s, 3H, H7), 1.60 (m, 1H, H10), 1.66 (d, 3H, J ) 1.0 J z, H14),
1.77 (m, 1H, H10), 1.92 (m, 2H, H11), 3.11 (dq, 1H, J ) 7.0, 9.0
Hz, H9), 3.81 (s, 3H, R2), 4.04 (s, 3H, OMe), 5.09 (ts, 1H, J )
1.5, 7.0 Hz, H12), 6.85 (d, 2H, J ) 9 Hz, H2′,6′), 6.94 (d, 2H, J )
9.0 Hz, H3′,5′), 7.23 (broad, 1H, NH); 13C NMR (CDCl3) δ 185.01
(C1), 183.07 (C4), 158.22 (C3), 156.93 (C6), 141.16 (C4′), 132.64
(C1′), 131.44 (C2), 131.22 (C13), 125.02 (C3′,5′), 125.57 (C12), 114.0
(C2′,6′), 110.26 (C5), 61.40 (OMe), 55.46 (R2) 34.65 (C10), 29.60
(C9), 26.78 (C11), 25.66 (C14), 18.88 (C8), 17.65 (C15), 11.84 (C7);
MS m/z 383, 368, 352, 340, 301, 273, 248, 233, 205, 193, 167,
166, 149, 123, 108, 77, 69, 41, 39. A FAB+ ion mass spectrum
showed M+ peak at 383.2101 (calcd parent peak 383.2097) for
2-(1,5-Dim eth yl-4-h exen yl)-3-h yd r oxy-5-m eth yl-6-[(4′-
cya n op h en yl)a m in e]-1,4-b en zoq u in on e (p -CNAP Z). A
0.237 g portion of 4-aminobenzonitrile yielded 0.622 g (85%)
of the desired product: mp 93-95 °C; IR (KBr, cm-1) 3336,
3280, 2966, 2926, 2862, 2224, 1638, 1597, 1572, 1510, 1484,
1374, 1317, 1284, 1172, 1113, 1091, 828, 763, 697, 627, 550;
1
UV-vis (MeOH, nm) 513, 354, 281, 209; H NMR (CDCl3) δ
1.22 (d, 3H, J ) 7.0 Hz, H8), 1.55 (s, 3H, H14), 1.58 (m, 1H,
H
10), 1.63 (s, 3H, H7), 1.65 (d, 3H, J ) 1.2 Hz, H15), 1.8 (m,
1H, H10), 1.92 (m, 2H, H11), 3.07 (dq, 1H, J ) 7.2, 8.7 Hz, H9),
5.08 (ts, 1H, J ) 1.2, 7.2 Hz, H12), 6.98 (d, 2H, J ) 8.6 Hz,
H2′,6′), 7.63 (d, 2H, J ) 8.6 Hz, H3′,5′), 7.75 (broad, 1H, NH),
7.8 (s, 1H, OH); 13C NMR (CDCl3) δ 183.45 (C1), 182.49 (C4),
152.91 (C3), 141.10 (C6), 143.16 (C4′), 131.47 (C2, C13), 133.04
(C3′,5′), 124.33 (C12), 121.63 (C2′,6′), 120.21 (C5), 118.58 (R2),
111.85 (C1′), 34.07 (C10), 29.64 (C9), 26.59 (C11), 25.67 (C15),
18.26 (C8), 17.61 (C14), 13.21 (C7); MS m/z 364, 335, 322, 321,
307, 282, 253, 239, 180, 117, 155, 109. Anal. Calcd for
C
23H29O4N: C, 72.06; H, 7.57; O, 16.71; N, 3.66. Anal. Calcd
for C23H29O4N: C, 72.06; H, 7.57; N, 3.66. Found: C, 71.98;
H, 7.48; N, 3.60.
2-(1,5-Dim eth yl-4-h exen yl)-3-m eth oxy-5-m eth yl-6-[(4′-
m eth ylph en yl)am in e]-1,4-ben zoqu in on e (p-MeAP Zm ). Ac-
cording to general procedure II, 0.350 g of p-MeAPZ yielded
0.338 g (92%) of a deep blue oil: IR (film, cm-1) 3324, 2960,
2926, 2858, 1644, 1594, 1517, 1492, 1451, 1376, 1315, 1289,
1262, 1119, 1098, 1062; UV-vis (MeOH, nm) 535, 260, 210;
1H NMR (CDCl3) δ 1.18 (d, 3H, J ) 7.0 Hz, H8), 1.53 (s, 3H,
H7), 1.56 (s, 3H, H15), 1.6 (m, 1H, H10), 1.66 (d, 3H, J ) 1.5
Hz, H14), 1.76 (m, 1H, H10), 1.91 (m, 2H, H11), 2.33 (s, 3H, R2),
3.12 (dq, 1H, J ) 7.0, 8.5 Hz, H9), 4.04 (s, 3H, OMe), 5.08 (ts,
1H, J ) 1.5, 7.0 Hz, H12), 6.86 (d, 2H, J ) 8.0 Hz, H2′,6′), 7.11
(d, 2H, J ) 8.0 Hz, H3′,5′), 7.23 (broad, 1H, NH); 13C NMR
(CDCl3) δ 185.04 (C1), 183.14 (C4), 158.1 (C3), 140.70 (C6),
134.11 (C4′), 129.32 (C3′,5′), 131.41 (C2, C13), 124.52 (C12), 122.83
(C2′,6′), 137 (C1′), 111.35 (C5), 61.38 (OMe), 34.65 (C10), 29.61
(C9), 26.78 (C11), 25.67 (C14), 20.84 (R2) 18.9, (C8), 17.67 (C15),
12.35 (C7); MS m/z 367, 352, 336, 324, 298, 285, 270, 257, 242,
226, 183, 181, 180, 149, 144, 118. A FAB+ ion mass spectrum
showed M+ peak at 368.2224 (calcd parent peak 368.2226) for
C23H29O3N: C, 75.2; H, 7.9; 0, 13.08; N, 3.82. Anal. Calcd for
C23H29O3N; C, 75.20; H, 7.90; N, 3.81. Found: C, 75.13; H, 7.87;
N, 3.76.
C
22H24N2O3; C, 72.53; H, 6.59; N, 7.69. Found: C, 72.40; H,
6.53; N, 7.60.
2-(1,5-Dim eth yl-4-h exen yl)-3-h yd r oxy-5-m eth yl-6-[(4′-
n itr oph en yl)am in e]-1,4-ben zoqu in on e (p-NO2AP Z). A 0.277
g portion of 4-nitroaniline yielded 0.310 g (40%) of the desired
product: mp 132-135 °C; IR (CHCl3, cm-1) 832, 852, 922,
1013, 1058, 1091, 1113, 1178, 1262, 1279, 1303, 1341, 1378,
1398, 1453, 1507, 1591, 1619, 1643, 1711, 1723, 2857, 2929,
2965, 3326; UV-vis (MeOH, nm) 501, 368, 273, 205; 1H NMR
(CDCl3) δ 1.21 (d, 3H, J ) 7.0 Hz, H8), 1.54 (s, 3H, H14), 1.6
(m, 1H, H10), 1.65 (s, 3H, H7), 1.65 (d, 4H, J ) 1.0 Hz, H15),
1.8 (m, 1H, H10), 1.9 (m, 2H, H11), 3.05 (dq, 1H, J ) 7.0, 8.5
Hz, H9), 5.09 (ts, 1H, J ) 1.5, 7.0 Hz, H12), 6.95 (d, 2H, J )
9.0 Hz, H2′,6′), 7.6 (broad, 1H, NH), 7.7 (s, 1H, OH), 8.18 (d,
2H, J ) 9 Hz, H3′,5′); 13C NMR (CDCl3) δ 183.05 (C1), 182.44
(C4), 153.25 (C3), 142.74 (C6), 141.5 (C19), 137.77 (C1′), 131.06
(C13), 130.96 (C2), 124.53 (C12), 124.2 (C3′,5′), 119.5 (C5), 118.29
(C2′,6′), 33.76 (C10), 29.5 (C4′), 26.59 (C15), 25.72 (C11), 18.4 (C8),
17.63 (C14), 12.65 (C7); MS m/z 384, 341, 327, 303, 302, 249,

8362 J . Org. Chem., Vol. 66, No. 25, 2001
Aguilar-Mart´ınez et al.
2-(1,5-Dim eth yl-4-h exen yl)-3-m eth oxy-6-p h en yla m in e-
1,4-ben zoqu in on e (AP Zm ). A 0.340 g portion of APZ reacted
according to general procedure II. After column purification,
0.30 g (85% yield) of deep blue oil was obtained: IR (CHCl3,
cm-1) 3339, 2966, 2934, 2858, 1645, 1589, 1506, 1449, 1377,
1315, 1173, 1097, 1061, 1022, 941, 895; UV-vis 526, 321, 261,
(s, 3H, OMe), 5.07 (ts, 1H, J ) 1.2, 7.2 Hz, H12), 6.88 (d, 2H,
J ) 8.6 Hz, H2′,6′), 7.27 (broad, 1H, NH), 7.59 (d, 2H, J ) 8.6
Hz, H3′,5′); 13C NMR (CDCl3) δ 184.58 (C1), 183.35 (C4), 157.64
(C3), 144.03 (C6), 138.84 (C4′), 133.13 (C3′,5′), 132.6 (C2), 131.62
(C13), 124.37 (C12), 120.21 (C2′,6′), 118.85 (R2), 117.74 (C1′),
105.71 (C5), 61.41 (OMe), 34.62 (C10), 29.73 (C9), 26.75 (C11),
25.66 (C14), 18.81 (C8), 17.66 (C15), 13.48 (C7); MS m/z 378, 347,
335, 309, 296, 268, 253, 251, 209, 183, 178, 155, 119, 109, 102,
69. A FAB+ ion mass spectrum showed M+ peak at 378.1958
(calcd parent peak 378.1943) for C23H26O3N2: C, 73.02; H, 6.88;
O, 12.70; N, 7.40. Anal. Calcd for C23H26O3N; C, 73.02; H.6.88;
N, 7.40. Found: C, 72.94; H 6.63; N, 7.35.
1
207; H NMR (CDCl3) δ 1.21 (d, 3H, J ) 7.0 Hz, H8), 1.55 (s,
6H, H7, H15), 1.6 (m, 1H, H10), 1.66 (d, 3H, J ) 1.5 Hz, H14),
1.76 (m, 1H, H10), 1.92 (m, 2H, H11), 3.12 (dq, 1H, J ) 7.0, 8.5
Hz, H9), 4.04 (s, 3H, OMe), 5.08 (ts, 1H, J ) 1.5, 7.0 Hz, H12),
6.95 (d, 2H, J ) 7.5 Hz, H2′,6′), 7.1 (t, 1H, R2), 7.28 (broad, 1H,
NH), 7.3 (d, 2H, J ) 7.5 Hz, H3′,5′); 13C NMR (CDCl3) δ 185.04
(C1), 183.29 (C4), 158.04 (C3), 140.46 (C6), 139.70 (C4′), 128.81
(C3′,5′), 131.65 (C2, C13), 124.54 (C12), 122.45 (C2′,6′), 124.14 (C1′),
112.51 (C5), 61.40 (OMe), 34.67 (C10), 29.65 (C9), 26.79 (C11),
25.67 (C14), 18.89 (C8), 17.67 (C15), 12.61 (C7); MS m/z 353, 338,
310, 306, 284, 271, 243, 228, 226, 198, 184, 166, 158, 130, 109,
93, 77, 69, 41, 39, 27, 15. A FAB+ ion mass spectrum showed
M+ peak at 354.2061 (calcd parent peak 354.2069) for
C22H28O3N: C, 74.79; H, 7.65; O, 13.60; N, 3.96. Anal. Calcd
for C22H27O3N; C, 74.85; H, 7.65; N, 3.97. Found: C, 74.78; H,
7.60; N, 3.85.
2-(1,5-Dim eth yl-4-h exen yl)-3-m eth oxy-5-m eth yl-6-[(4′-
n itr op h en yl)a m in e]-1,4-ben zoqu in on e (p-NO2AP Zm ). Ac-
cording to general procedure II, 0.380 g of p-NO2APZ yielded
0.260 g (65%) of a deep red oil: IR (CHCl3, cm-1) 3339, 2963,
2934, 2856, 1645, 1591, 1506, 1452, 1377, 1339, 1304, 1113,
1
1009; UV-vis (MeOH, nm) 491, 348, 274, 230, 210; H NMR
(CDCl3) δ 1.21 (d, 3H, J ) 7.0 Hz, H8), 1.55 (s, 3H, H15), 1.69
(s, 3H, H7), 1.61 (m, 1H, H10), 1.65 (d, 3H, J ) 1.0 Hz, H14),
1.75 (m, 1H, H10), 1.92 (m, 2H, H11), 3.14 (dq, 1H, J ) 7, 8.5
Hz, H9), 4.06 (s, 3H, OMe), 5.07 (ts, 1H, J ) 1.5 7.0 Hz, H12),
6.88 (d, 2H, J ) 9.0 Hz, H2′,6′), 7.38 (broad, 1H, NH), 8.02 (d,
2H, J ) 9.0 Hz, H3′,5′); 13C NMR (CDCl3) δ 184.51 (C1), 183.36
(C4), 157.61 (C3), 145.93 (C6), 142.44 (C4′), 125.14 (C3′,5′), 132.76
(C2), 131.66 (C13), 124.35 (C12), 119.23 (C2′,6′), 138.71 (C1′),
118.84 (C5), 61.42 (OMe), 34.61 (C10), 29.75 (C9), 26.75 (C11),
25.66 (C14), 18.80 (C8), 17.66 (C15), 13.60 (C7); MS m/z 398, 383,
355, 316, 301, 288, 262, 248, 227, 180, 179, 165, 109. A FAB+
ion mass spectrum showed M+ + 1 peak at 399.1939 (calcd
parent peak 399.1920) for C22H26O5N2: C, 66.33; H, 6.53; O,
20.1; N, 7.04. Anal. Calcd for C22H26O5N2: C, 66.33; H, 6.53;
N, 7.04. Found: C, 66.15; H, 6.48; N, 6.93.
2-(1,5-Dim eth yl-4-h exen yl)-3-m eth oxy-5-m eth yl-6-[(4′-
br om op h en yl)a m in e]-1,4-ben zoqu in on e (p-Br AP Zm ). Ac-
cording to general procedure II, 0.420 g of p-BrAPZ yielded
0.300 g (71%) of a blue oil: IR (film, cm-1) 3337, 2963, 2932,
2856, 1643, 1599, 1500, 1454, 1377, 1299, 1261, 1097, 1013;
1
UV-vis (MeOH, nm) 520, 328, 268, 208; H NMR (CDCl3) δ
1.2 (d, 3H, J ) 7.0 Hz, H8), 1.55 (s, 3H, H15), 1.56 (s, 3H, H7),
1.6 (m, 1H, H10), 1.65 (d, 3H, J ) 1.5 Hz, H14), 1.76 (m, 1H,
H
10), 1.91 (m, 2H, H11), 3.12 (dq, 1H, J ) 7.0, 8.5 Hz, H9), 4.04
(s, 3H, OMe), 5.08 (ts, 1H, J ) 1.5, 7.0 Hz, H12), 6.9 (d, 2H, J
) 8.75 Hz, H2′,6′), 7.18 (broad, 1H, NH), 7.42 (d, 2H, J ) 8.75
Hz, H3′,5′); 13C NMR (CDCl3) δ 184.82 (C1), 183.28 (C4), 157.93
(C3), 140.08 (C6), 138.9 (C4′), 131.85 (C3′,5′), 131.53 (C2, C13),
124.47 (C12), 123.60 (C2′,6′), 116.7 (C1′), 113.41 (C5), 61.41 (OMe),
34.64 (C10), 29.0 (C9), 26.7 (C11), 25.66 (C14), 18.85 (C8), 17.66
(C15), 12.82 (C7); MS m/z 433, 431, 401, 388, 351, 349, 321,
306, 279, 256, 227, 226, 210, 167, 149, 130, 109, 93.69. A FAB+
ion mass spectrum showed M+ peak at 433.1264 (calcd parent
peak 433.1253) for C22H26O3NBr: C, 61.11; H, 6.02; O, 11.11;
N, 3.24; Br, 18.52. Anal. Calcd for C22H26O3NBr; C, 61.11; H,
6.02; N, 3.24. Found: C, 60.98; H, 5.98; N, 3.19.
X-r a y P r oced u r e. Suitable crystals of APZ were grown by
slow evaporation from a n-hexane/ethyl acetate solution at
room temperature. A summary of data collection and refine-
ment conditions are given in Figure S1 (Supporting Informa-
tion). Intensities were collected on a Siemens P4/PC diffrac-
trometer using a ω-scan, with Mo KR radiation. The structures
were solved by direct methods and refined by a full-matrix
least-squares procedure.49
Hydrogen atoms were included at idealized geometric posi-
tions and forced to ride on the carbon parent atom. Only
hydrogen atoms related to hydrogen bonds were refined. See
the Supporting Information for details.
Electr och em ica l P r oced u r e. Solven t a n d Su p p or tin g
Electr olyte. Acetonitrile (AN) (Aldrich) was dried overnight
with CaCl2 (Merck) and purified by distillation on P2O5 (Merck)
under vacuum. Traces of water in the solvent were eliminated
by contact with a 3 Å molecular sieve (Merck) in the dark.
The absence of the characteristic -OH bands in the IR spectra
confirmed the completed elimination of water traces. Tetra-
ethylammonium tetrafluoroborate (Et4NBF4) (Fluka) was dried
under vacuum at 60 °C.
E lect r od es, Ap p a r a t u s, a n d In st r u m en t a t ion . Cyclic
voltammetry measurements were carried out in a conventional
three-electrode cell. A polished glassy 7 mm2 area carbon-disk
electrode was used as a working electrode. Prior to measure-
ments, this electrode was cleaned and polished with 0.05 µm
alumina (Buehler), wiped with a tissue, and sonicated in
distilled water for 2-4 min. A platinum wire served as the
counter electrode. The reference electrode was an aqueous
saturated calomel electrode (SCE), isolated from the main cell
body by a Luggin tube filled with 0.1 M Et4NBF4/acetonitrile.
Peak potentials were measured at controlled temperature
(25 °C) in acetonitrile solutions using 0.1 M Et4NBF4 as the
supporting electrolyte. APZs and APZms solutions (1.0 mM)
were used. At lower concentrations of the electroactive species
the current capacitive precluded acceptable evaluation of
current peaks. Me4N+C6H5O- was prepared with equimolar
2-(1,5-Dim eth yl-4-h exen yl)-3-m eth oxy-5-m eth yl-6-[(4′-
a cetylp h en yl)a m in e]-1,4-ben zoqu in on e (p-MeCOAP Zm ).
A 0.380 g portion of the p-MeCOAPZ reacted according to
general procedure II. After column purification, 0.328 g (83%
yield) of blue oil was obtained: IR (film, cm-1) 3318, 2961,
2927, 2856, 1676, 1645, 1593, 1517, 1492, 1449, 1412, 1358,
1309, 1259, 1177, 1121, 1097, 1062, 1013, 957, 829, 760; UV-
vis (MeOH, nm) 510, 313, 225.5, 207; 1H NMR (CDCl3) δ 1.21
(d, 3H, J ) 7.0 Hz, H8), 1.55 (s, 3H, H15), 1.65 (s, 3H, H7), 1.6
(m, 1H, H10), 1.65 (d, 3H, J ) 1.0 Hz, H14), 1.76 (m, 1H, H10),
1.92 (m, 2H, H11), 3.13 (dq, 1H, J ) 8.7, 7.2 Hz, H9), 2.5 (s,
1H, R2), 4.06 (s, 3H, OMe) 5.07 (ts, 1H, J ) 1.2, 7.2 Hz, H12),
6.89 (d, 2H, J ) 8.6 Hz, H2′,6′), 7.93 (d, 2H, J ) 8.6 Hz, H3′,5′),
7.36 (broad, 1H, NH); 13C NMR (CDCl3) δ 199.56 (R2), 184.74
(C1), 183.36 (C4), 157.71 (C3), 144.23 (C6), 139.27 (C4′), 131.93
(C1′), 132.32 (C2) 131.56 (C13), 129.56 (C3′,5′), 124.40 (C12), 119.99
(C2′,6′), 116.54 (C5), 61.41 (OMe), 34.65 (C10), 29.73 (C9), 26.78
(C11), 26.38 (R2), 25.69 (C14), 18.85 (C8), 17.68 (C15), 13.41 (C7);
MS m/z 395, 364, 352, 313, 285, 270, 256, 228, 197, 180, 167,
149, 109, 83. A FAB+ ion mass spectrum showed M+ peak at
396.2191, (calcd parent peak 396.2175) for C24H29O4N: C,
72.91; H, 7.34; O, 162.2; N, 3.54. Anal. Calcd for C24H29O4N;
C, 72.91; H, 7.34; N, 3.54. Found: C, 72.81; H, 7.29; N, 3.50.
2-(1,5-Dim eth yl-4-h exen yl)-3-m eth oxy-5-m eth yl-6-[(4′-
cya n op h en yl)a m in e]-1,4-ben zoqu in on e (p-CNAP Zm ). Ac-
cording to general procedure II, 0.360 g of p-CNAPZ yielded
0.320 g (85%) of blue oil: IR (CHCl3, cm-1) 3339, 2967, 2931,
2855, 2228, 1644, 1597, 1514, 1492, 1458, 1363, 1315, 1121;
1
UV-vis (MeOH, nm) 503.5, 283.5, 208.0; H NMR (CDCl3) δ
(49) (a) Altomare, G.; Cascarano, C.; Giacovazzo, A.; Guagliardi, M.
C.; Burla, G.; Polidori, M.; Camalli, J . J . Appl. Crystallogr. 1994, 27,
435. (b) Sheldrick, G. M. SHELLXL93. Program for Refinement of
Crystal Structures. University of Go¨ttingen, Germany, 1993.
1.2 (d, 3H, J ) 7.0 Hz, H8), 1.55 (s, 3H, H15), 1.57 (s, 3H, H7),
1.61 (m, 1H, H10), 1.65 (d, 3H, J ) 1.2 Hz, H14), 1.75 (m, 1H,
H
10), 1.9 (m, 2H, H11), 3.13 (dq, 1H, J ) 7.2, 8.7 Hz, H9), 4.05

Molecular Structure of Phenylamine p-Benzoquinone Derivatives
quantities of phenol and 0.1 tetramethylammonium
J . Org. Chem., Vol. 66, No. 25, 2001 8363
M
The orbital basis set, 6-31G(d,p), was used to add polariza-
tion functions to heavy atoms and hydrogens. Natural bond
orbital analyses (NBO) were carried out with version 3.1,
which is included in G94. Densities computed at B3LYP/6-
31G(d,p) level from the G94 output were used with the
AIMPAC33 set of programs to calculate the properties of critical
hydroxide. For cyclic voltammetric experiments, 2 mM
Me4N+C6H5O- was added to the electrolytic medium. Voltam-
metric curves were recorded using a BAS 100B/W Electro-
chemical Analyzer of Bioanalytical Systems interfaced with a
Gateway 2000 personal computer. Measurements were made
over a potential range between 250 and -2500 mV with a
sweep rate of 50-9000 mVs-1. Prior to the experiments,
solutions were purged with nitrogen, which was presaturated
with the appropriate solvent containing 3 Å sieves. All
potentials were determined under the same conditions to
obtain a consistent data set. To establish a reference system
with the experimental conditions of our particular system, the
redox potentials reported in this paper refer to the ferrocene/
ferrocinium (Fc/Fc+) pair, as recommended by IUPAC.50 In this
case, the potential for the ferrocene/ferrocinium (Fc/Fc+) redox
pair, determined by voltamperometric studies, was 412 mV
vs SCE.
Com p u ta tion a l Meth od s. Full geometry optimization
(without symmetry constraints) on the model structures of
perezone derivatives was performed at the B3LYP/6-31G(d,p)
level with the Gaussian 94 Program (G94).31 The Becke3LYP
hybrid functional defines the exchange function as a linear
combination of Hartree-Fock, local, and gradient-corrected
terms.51 The exchange function is combined with a local and
gradient-corrected correlation function.
2
points (cps) in the charge density (F), Laplacians (∇ F), and
ellipticities (ꢀ).
Ack n ow led gm en t. We are grateful to the Direccio´n
General de Servicios de Co´mputo Acade´mico, Univer-
sidad Nacional Auto´noma de Me´xico, DGSCA, UNAM,
and to the Escuela de Ciencias Qu´ımicas, Universidad
La Salle, for their computational support as well as for
the generous gift of supercomputer CPU time. We also
thank the Consejo Nacional de Ciencia y Tecnolog´ıa
(CONACyT) for financial support given as Grant Nos.
32420-E and 28016-E and fellowships to N.M.-R., J .A.B.-
M., E.T., and T.M.A. N.M.-R. and J .A.B.-M. are also
grateful to DGEP for a complementary fellowship. We
are grateful to Sylvain Bernes for the X-ray structure
determination, to Luis Velasco and Francisco Pe´rez
Flores for the mass spectral determination, and Ma. del
Rocio Patin˜o and to Isabel Chavez for technical support.
The correlation function used was C*EcLYP + (1 - c) -
*EcVWN, where LYP is the correlation functional of Lee, Yang
and Parr,52 and includes both local and nonlocal terms, and
VWN is the Vosko, Wilk, and Nusair 1980 correlation func-
tional fitting the RPA solution to the uniform gas, often
referred to as local spin density (LSD) correlation.53 VWN was
used to provide the excess of the local correlation, required
since LYP contains a local term essentially equivalent to
VWN.42,54
Su p p or tin g In for m a tion Ava ila ble: Tables of the crystal
data and structure refinement information, bond lengths and
bond angles, atomic and hydrogen coordinates, and isotropic
and anisotropic displacement coordinates for APZ. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O010302Z
(50) Gritzner, G.; Ku¨ta, J . Pure Appl. Chem. 1984, 4, 462-466.
(51) (a) Stephens, P. J .; Devlin, F. J .; Chabalowski, C. F.; Frisch,
M. J . J . Phys. Chem. 1994, 98, 11623-11627. (b) Becke, A. D. J . Chem.
Phys. 1993, 98, 1372-1377, 5648-5652.
(52) (a) Lee, C.; Yang, W.; Parr, R. G.; Phys. Rev. 1988, B37, 785-
789. (b) Miehlich, B.; Savin, A.; Stoll, H.; Preuss, H. Chem. Phys. Lett.
1989, 157, 200-206.
(53) Vosko, S. H.; Wilk, L.; Nusair, M. Can. J . Phys. 1980, 58, 1200-
1211.
(54) (a) Becke, A. D. J . Chem. Phys. 1988, 88, 1053-1062. (b) Becke,
A. D. Phys. Rev. A. 1988, 38, 3098-3100.