Oxidative phenylamination of 5-substituted 1-hydroxynaphthalenes to N-phenyl-1,4-naphthoquinone monoimines by air and light "on water"

Article abstract of DOI:10.3762/bjoc.10.255

A number of N-phenyl-1,4-naphthoquinone monoimines 6 - 10 were prepared by on-water oxidative phenylamination of 1,5-dihydroxynaphthalene (1 ) and 5-acetylamino-1-hydroxynaphthalene ( 5 ) with oxygen-substituted phenylamines under aerobic conditions and e

Full text of DOI:10.3762/bjoc.10.255

Oxidative phenylamination of 5-substituted 1-hydroxy-
naphthalenes to N-phenyl-1,4-naphthoquinone monoimines
by air and light “on water”
Julio Benites*1,2, Juan Meléndez1, Cynthia Estela1, David Ríos1, Luis Espinoza3,
Iván Brito4 and Jaime A. Valderrama1,2
Letter
Open Access
Address:
Beilstein J. Org. Chem. 2014, 10, 2448–2452.
1
Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla
21, Iquique, Chile, 2Instituto de Ciencias Exactas y Naturales
ICEN), Universidad Arturo Prat, Casilla 121, Iquique, Chile, 3Facultad
de Química, Universidad Técnica Federico Santa María, Casilla
10-V, Valparaíso, Chile and 4Departamento de Química, Facultad de
doi:10.3762/bjoc.10.255
1
(
Received: 27 July 2014
Accepted: 09 October 2014
Published: 22 October 2014
1
Ciencias Básicas Universidad de Antofagasta, Casilla 170,
Antofagasta, Chile
Associate Editor: M. Rueping
Email:
© 2014 Benites et al; licensee Beilstein-Institut.
License and terms: see end of document.
Julio Benites* - julio.benites@unap.cl
*
Corresponding author
Keywords:
,4-naphthoquinone monoimines; on water; oxidative coupling; rose
1
bengal; solar radiation
Abstract
A number of N-phenyl-1,4-naphthoquinone monoimines 6–10 were prepared by on-water oxidative phenylamination of 1,5-dihy-
droxynaphthalene (1) and 5-acetylamino-1-hydroxynaphthalene (5) with oxygen-substituted phenylamines under aerobic condi-
tions and either solar or green LED radiation, in the presence of rose bengal as singlet oxygen sensitizer. As compared to the
conventional oxidative phenylamination procedures, this novel synthetic method offers the advantage of aerobic conditions “on
water” instead of hazardous oxidant reagents currently employed in aqueous alcoholic media.
Introduction
The growing demand for the application of environmentally (2, juglone, Figure 1) by sensitized phothooxygenation of 1,5-
friendly technologies has led, in the last decades, to a great deal dihydroxynaphthalene (1, 1,5-DHN) [7] and the preparation of
of research effort to develop low-impact alternative synthetic 2-phenylamino-1,4-naphthoquinones by reaction of 1,4-
methods as well as to replace toxic and harmful solvents by naphthoquinones with phenylamines “on water” [8] represent
more environmentally benign ones [1-6]. In this context, the two valuable examples on the scope of green methodologies in
sunlight-induced synthesis of 5-hydroxy-1,4-naphthoquinone the field of quinone synthesis.
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Beilstein J. Org. Chem. 2014, 10, 2448–2452.
reactions outlined in Scheme 1. According to this sequence the
nascent juglone (2), generated by sensitized solar-induced
photooxygenation of 1,5-DHN (1), might undergo in situ
phenylamination followed by aerobic oxidation to give the
expected target aminojuglone 4a and/or 4b. In order to evaluate
the reactions involved in this hypothetical strategy, the solar
photosensitized photooxygenation of 1,5-DHN (1) and the
amination of juglone (2) with 4-hydroxyphenylamine on water
were examined separately. It is noteworthy that similar reac-
tions have been recently reported by using a one-flask proce-
dure where juglone 2 was first produced by photoinduced
Figure 1: Structures of compounds 1–3.
1
,4-Naphthoquinones possessing a substituted amino group in photooxygenation of 1,5-DHN (1) in CH2Cl2/MeOH and then
the 2-position have been the subject of study for many years in the same flask, the arylamination of 2 to the respective
due to their use in a variety of medical and biological applica- aminoquinones was accomplished [14].
tions. A well-documented procedure to prepare 2-amino-1,4-
naphthoquinone derivatives is based on the reaction of amines The on-water photooxygenation of 1,5-DHN (1) was carried
with 1,4-naphthoquinone [9]. This atom-economical method to out for 5 h in round-bottom flasks, under the presence of
construct aminoquinones occurs through an addition–oxidation 1.6 mmol % of rose bengal (RB) as singlet oxygen sensitizer,
reaction sequence [10]. In a previous work we described that by using sunlight (Canchones Experimental Center in Iquique/
2
-(4-hydroxyphenyl)amino-1,4-naphthoquinone (3), prepared Chile, latitude 20°26´43.80´´ S, 990 m above sea level) and
by acid-induced amination of 1,4-naphthoquinone with green LEDs as photochemical sources. Meanwhile, a gently
-hydroxyphenylamine in ethanol, strongly inhibit the prolifera- stream of air was bubbled through the solutions. Under these
4
tion of cancer cells [11,12]. These stimulating results were conditions juglone (2) was isolated in 81% (sunlight) and 55%
obtained by using prostate (DU-145), bladder (T24) and breast (LEDs) yields. On the other hand, the reaction of juglone (2)
(
MCF-7) cancer cells. These results and our continuous interest with 4-hydroxyphenylamine, performed in water suspension at
in the synthesis of aminoquinones for antiproliferative evalua- room temperature, gives rise compounds 4a and 4b in 45% and
tion [11-13], prompt us to explore a straightforward access to 16% yields, respectively. The structures of compounds 4a and
potential antiproliferative aminojuglone-analogues of com- 4b were fully established on the basis of their nuclear magnetic
pound 3. The study led us to discover a potential and green resonance (1H NMR, 13C NMR, 2D NMR) and high resolution
route for the preparation of N-phenyl-1,4-naphthoquinone mass spectrometry (HRMS). The position of the nitrogen
monoimines by on-water oxidative coupling reaction of substituent in these aminoquinones was determined by means of
1
-hydroxynaphthalene derivatives with oxygen-substituted HMBC experiments.
phenylamines under solar light or green LEDs radiation, rose
bengal as singlet oxygen sensitizer and aerobic conditions.
Encouraged by these results, the preparation of aminojuglones
a and 4b was attempted by employing the hypothetical one pot
procedure outlined in Scheme 1. A suspension of equimolar
4
Results and Discussion
Our goal was to develop a simple method for the preparation of amounts of 1,5-DHN (1) and 4-hydroxyphenylamine in water
phenylaminojuglone analogues of compound 3 via a green one- was irradiated by sunlight for 5 h, in the presence of RB. Work-
pot procedure “on water”, based on the hypothetical sequence up of the reaction mixture afforded a dark brown solid com-
Scheme 1: Hypothetical one-pot synthesis of compound 4a and/or 4b.
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Beilstein J. Org. Chem. 2014, 10, 2448–2452.
pound, which was fully characterized as 5-hydroxy-4-((4- N-phenyl-1,4-naphthoquinone-4-imines. A mechanism
hydroxyphenyl)imino)naphthalene-1(4H)-one (6, 98% yield). involving radical cation intermediates is supported by the rather
Under similar conditions, but using green LEDs light radiation, high product yields resulting from the reaction of 1,5-DHN (1)
compound 6 was isolated in 80% yield.
with electron-donor substituted phenylamines.
The structure of 6 was established by means of 1D and 2D Given the totally green and high yield access to compound 6
NMR and by X-ray crystallographic studies (Figure 2 and from 1,5-DHN (1) and 4-hydroxyphenylamine, we decided to
Table S1 in Supporting Information File 1). This unexpected study the reaction scope to include 5-acetylamino-1-hydroxy-
but interesting result indicates that on-water oxidative amina- naphthalene (5) as a 1-hydroxynaphthalene substrate and
tion reaction of 1,5-DHN (1) with 4-hydroxyphenylamine to phenylamines containing electron-donor and acceptor
produce compound 6 is more favorable than the photooxygena- substituents such as: 4-methoxyphenylamine, 2,5-dimethoxy-
tion reaction to give juglone (2).
phenylamine, 3,4,5-trimethoxyphenylamine and 4-nitrophenyl-
amine. The results obtained under standard conditions using
sunlight and green LEDs are outlined in Scheme 2. Since no
reaction was observed in the assay with 4-nitrophenylamine it
may be concluded that the oxidative arylamination of 1,5-DHN
(
1) is favorable with arylamines containing electron-donor
substituents.
Bearing in mind that the formation of the quinone monoimines
6
–10 under the above experimental conditions requires aerial
oxidation reactions, most likely mediated by oxygen species
such as singlet oxygen [20], we examined the effect of histidine,
a well-known singlet oxygen scavenger [21], on the formation
of iminoquinone 6 from 1,5-DHN (1) and 4-hydroxyphenyl-
amine. When the experiments were performed under standard
conditions by using sunlight or green LEDs in the presence of
histidine, compound 6 was obtained in 69 and 62% yield, res-
pectively. By comparing these results to that observed in the
absence of histidine, it may be suggested that singlet oxygen is
involved in the oxidative coupling reaction to produce com-
pound 6. In addition, experiments on the oxidative coupling
reaction of 1,5-DHN (1) with oxygen-substituted phenylamines
were performed in the absence of RB under in-door daylight
illumination. The results are outlined in Scheme 3 and showed
lower yields as compared to that obtained by using RB. Taking
into account all the experiments we have done, it may be
concluded that singlet oxygen is involved in the oxidative
Figure 2: Structure of compound 6 determined by single crystal X-ray
diffractometry.
The N-phenylquinone imines are considered as an important amination reaction, albeit with partial contribution to the aerial
class of compounds because of their properties as dyes for oxidation processes.
optical devices [15], antioxidants [16], anticancer agents [17]
and precursors of liquid crystalline materials [18]. With regard Conclusion
to the synthesis of N-phenyl-1,4-naphthoquinone monoimines, In summary, we have developed a green procedure for the syn-
Bukhtoyarova et al. [19], has described their preparation by thesis of N-phenyl-1,4-naphthoquinone monoimines, in
reaction of 1,5-DHN (1) with phenylamines using oxidants such moderate to excellent yields, from 5-substituted 1-hydroxy-
as K3Fe(CN)6, HIO3 and NaIO4 in aqueous alcohol. According naphthalenes and oxygen-substituted phenylamines using air,
to these authors, the oxidative phenylamination mechanism sunlight or green LEDs, rose bengal as sensitizer “on water”.
involves a radical cation intermediate generated by an electron This method offers operational simplicity, mild conditions and
transfer process from the phenylamine to the oxidant. Further environmental friendliness as the features of this protocol.
electrophilic substitution at the 4-position of compound 1 fol- Further investigations to expand the scope and potential of this
lowed by oxidation of the aminonaphthol intermediate, yield the methodology are under way in our laboratory.
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Beilstein J. Org. Chem. 2014, 10, 2448–2452.
Scheme 2: Evaluation of the substrate scope using RB as oxygen (1O2) sensitizer “on water”.
Scheme 3: Evaluation of the oxidative coupling in the absence of RB, on water.
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Beilstein J. Org. Chem. 2014, 10, 2448–2452.
18.Zharkova, G. M.; Streltsov, S. A.; Khachaturyan, V. M.; Éktova, L. V.;
Supporting Information
Bukhtoyarova, A. D.; Gerasimova, T. N. J. Struct. Chem. 1997, 38,
678–681. doi:10.1007/BF02762753
Supporting Information File 1
1
9.Bukhtoyarova, A. D.; Ektova, L. V.; Alekseev, S. N.; Beregovaya, I. V.
Russ. J. Org. Chem. 2003, 39, 1309–1315.
Experimental procedures, characterization data, copies of
the NMR spectra of compounds 4a, 9, 10 and X-ray view
of compound 6.
doi:10.1023/B:RUJO.0000010219.20915.5f
20.DeRosa, M. C.; Crutchley, R. J. Coord. Chem. Rev. 2002, 233–234,
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51–371. doi:10.1016/S0010-8545(02)00034-6
1.Hartman, P. E.; Hartman, Z.; Ault, K. T. Photochem. Photobiol. 1990,
1, 59–66. doi:10.1111/j.1751-1097.1990.tb01684.x
[http://www.beilstein-journals.org/bjoc/content/
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supplementary/1860-5397-10-255-S1.pdf]
5
Acknowledgements
License and Terms
The authors thank Pilar Diaz, for her excellent technical assis-
tance. This work was supported by Fondo Nacional de Ciencia
y Tecnología (Grant No. 1120050).
This is an Open Access article under the terms of the
Creative Commons Attribution License
(
http://creativecommons.org/licenses/by/2.0), which
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