Roomerature synthesis of hydroxylnaphthalene-1,4-dione derivative catalyzed by phenylphosphinic acid

Article abstract of DOI:10.1080/00397911.2013.853314

An efficient one-pot synthesis of hydroxylnaphthalene-1,4-dione derivatives is accomplished by a three-component reaction of 2-hydroxynaphthalene-1,4- dione, aromatic aldehydes, and amines in water under ambient temperature catalyzed by phenylphosphinic acid. This method has the advantages of good yield, mild reaction conditions, simple workup, environmental friendliness and cost efficiency.

Full text of DOI:10.1080/00397911.2013.853314

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Room-Temperature Synthesis
of Hydroxylnaphthalene-1,4-
dione Derivative Catalyzed by
Phenylphosphinic Acid
Di Liu a , Shixue Zhou a & Jun Gao a
a College of Chemical and Environmental Engineering , Shandong
University of Science and Technology , Qingdao , Shandong , China
Accepted author version posted online: 02 Dec 2013.Published
online: 28 Mar 2014.
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To cite this article: Di Liu , Shixue Zhou & Jun Gao (2014) Room-Temperature Synthesis of
Hydroxylnaphthalene-1,4-dione Derivative Catalyzed by Phenylphosphinic Acid, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
44:9, 1286-1290, DOI: 10.1080/00397911.2013.853314
To link to this article: http://dx.doi.org/10.1080/00397911.2013.853314
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Synthetic Communications®, 44: 1286–1290, 2014
Copyright © Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397911.2013.853314
ROOM-TEMPERATURE SYNTHESIS
OF HYDROXYLNAPHTHALENE-1,4-DIONE
DERIVATIVE CATALYZED BY PHENYLPHOSPHINIC ACID
Di Liu, Shixue Zhou, and Jun Gao
College of Chemical and Environmental Engineering, Shandong University
of Science and Technology, Qingdao, Shandong, China
GRAPHICAL ABSTRACT
Abstract An efficient one-pot synthesis of hydroxylnaphthalene-1,4-dione derivatives is
accomplished by a three-component reaction of 2-hydroxynaphthalene-1,4-dione, aromatic
aldehydes, and amines in water under ambient temperature catalyzed by phenylphosphinic
acid. This method has the advantages of good yield, mild reaction conditions, simple workup,
environmental friendliness and cost efficiency.
Keywords Aldehyde; ambient temperature; amine, 2-hydroxy-1,4-naphthoquinone;
phenylphosphinic acid; synthesis
INTRODUCTION
Mannich reaction is one of the most important carbon–carbon bond-forming
reactions in organic synthesis because of its atom-economy advantages and appli-
cation in biologically active molecule syntheses. β-Amino carbonyl compounds are
valuable synthetic intermediates for various pharmaceuticals and natural products[1–3]
that can be easily formed via a Mannich reaction.[4] Current research focuses on the
three-component Mannich reaction from aldehydes, cyclohexanone or acetophenone,
and amines that allows for a wide range of structural variations.
2-Hydroxy-1,4-naphthoquinone has been known for the past 4000 years, is
found in many natural products, and has been employed as a synthetic intermedi-
ate for the preparation of numerous heterocyclic compounds. Molecules contain-
ing the heterocyclic quinone group constitute one of the most important classes
Received July 18, 2013.
Address correspondance to Di Liu, College of Chemical and Environmental Engineering, Shandong
University of Science and Technology, 579 Qianwangang Road, Economic and Technical Development
Zone, Qingdao, Shandong, 266590, China. E-mail: Ld002037132@163.com
1286

HYDROXYLNAPHTHALENE DERIVATIVES
1287
Scheme 1. Synthesis of hydroxylnaphthalene-1,4-dione derivatives.
of compounds in organic chemistry because of their biological properties such as
antitumor, antibacterial, antifungal, and anti-inflammatory agents.[5–7] Thus, the
development of new and simple synthetic methods for the preparation of the com-
pounds containing napthoquinone fragments would be highly desirable.
Herein, we report a simple and efficient method for the preparation of hydrox-
ylnaphthalene-1,4-dione derivatives by a three-component variant Mannich reaction
of 2-hydroxynaphthalene-1,4-dione, aromatic aldehydes, and heterocyclic or carbo-
cyclic amines. A literature survey showed us that the reaction has been improved in
the presence of a catalyst. Dabiri et al. synthesized hydroxylnaphthalene-1,4-dione
derivatives using Lewis acid InCl3 as catalyst[8], and weak basic ionic liquids were also
reported for this reaction[9]. These methods show varying degrees of success as well as
limitations such as use of an excess of expensive reagents/catalysts, tedious workup
procedures, or harsh reaction conditions. Thus, the development of an alternative
procedure is in high demand.
Considering these reports, our program aimed at developing selective and sim-
ple methodologies for the preparation of hydroxylnaphthalene-1,4-dione derivatives.
In this artical, a simple and efficient route using Bronsted acid–polyphosphoric acid
(PPA) as catalyst under ambient temperature is developed (Scheme 1).
RESULTS AND DISCUSSION
Initially, based on the current report, two Lewis acids [FeCl3·6H2O,
(CH3COO)2Zn·2H2O] and two Bronsted acids (NaHSO4·H2O, C6H5PO2H2) were
chosen to catalyze the reaction of aniline, benzaldehyde, and 2-hydroxy-1,4-naphtho-
quinone in refluxing water to search for an effective catalyst. A summary of the exper-
iment optimization is provided in Table 1. As can be seen in Table 1, C6H5PO2H2 was
Table 1. Optimization of the reaction conditions for synthesis of 2-hydroxy-3-[phenyl
(phenylamino)methyl]naphthalene-1,4-dione
Entry
Catalyst (mol%)
Conditions
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
FeCl3·6H2O (15)
(CH3COO)2Zn·2H2O (15)
C6H5PO2H2 (15)
NaHSO4·H2O (15)
C6H5PO2H2 (20)
C6H5PO2H2 (25)
C6H5PO2H2 (20)
C6H5PO2H2 (20)
—
H2O (reflux)
H2O (reflux)
H2O (reflux)
H2O (reflux)
H2O (reflux)
H2O (reflux)
H2O (rt)
4
4
4
4
4
4
4
6
4
58.0
69.2
75.5
40.2
80.9
81.2
80.5
87.9
<15.0
H2O (rt)
H2O (rt)

1288
D. LIU, S. ZHOU, AND J. GAO
Table 2. Synthesis of 2-hydroxyl naphthalene-1,4-dione derivatives catalyzed by PPA
Entry
X
Y
Product
Time (h)
Yield (%)a
1
2
3
4
5
6
7
8
9
H
4-HO
4-NO2
H
4-HO
4-NO2
H
H
H
H
4-Me
4-Me
4-Me
4-F
4-F
H
4a
4b
4c
4d
4e
4f
4g
4h
4i
6
6.5
6
7.5
7.5
6.5
7.5
6
87.9
86.4
85.0
87.0
85.8
80.0
84.1
79.5
—
4-NO2
Lauraldehyde
6
aIsolated yield.
found to be the most efficient catalyst compared with other catalysts. The effect of the
amount of catalyst was examined in this reaction. The results showed that a 20% mol
amount of C6H5PO2H2 was sufficient to promote the reaction and larger amounts
of the catalyst did not lead to any significant changes in the reaction yield. Also we
studied the model reaction catalyzed by C6H5PO2H2 (20 mol%) at room temperature.
Surprisingly, nearly the same yield was obtained, which indicated the reaction could
be efficiently catalyzed by C6H5PO2H2 at ambient temperature. In addition, it should
be mentioned that the yield was very poor without catalyst under ambient condition
for this reaction (Table 1, entry 9).
With this optimized procedure in hand, we have extended the condensation
reaction of aldehydes and 2-hydroxy-1,4-naphthoquinone under similar condi-
tions, furnishing the respective 2-hydroxyl naphthalene-1, 4-diones. The optimized
results are summarized in Table 2. Good yields (79.5–87.9%) were obtained using
aromatic aldehydes and aromatic amines carrying electron-donating or electron-
withdrawing substituents. Finally, the feasibility of employing aliphatic aldehydes
for the synthesis of 2-hydroxy-1,4-naphthoquinone derivatives was also investi-
gated. The result showed that aliphatic aldehyde reacted poorly under the same
conditions.
To show the merit of the present work, we summarized the results for the syn-
thesis of 2-hydroxy-3-[phenyl(phenylamino)methyl]naphthalene-1,4-dione obtained
by other workers (Table 3). As shown in Table 3, although weak basic ionic liquids
have high catalytic activity, they are very expensive. Compared with our catalyst,
InCl3 exhibits similar catalytic performance, but the reaction condition is harsh. So
our method has the advantages of mild reaction conditions, low cost, and environ-
ment friendliness comparison with results in the literature.
Table 3. Comparison of the efficiencies of various catalysts used in the synthesis of
2-hydroxy-3-[phenyl(phenylamino)methyl]naphthalene-1,4-dione
Catalyst
Conditions/T/°C
Time
Yield (%)
Reference
InCl3
Ionic liquids
C6H5PO2H2
Water/refluxing
Solvent-free/rt
Water/rt
6 h
5–9 min
6 h
90
89–91
87.9
[8]
[9]
This work

HYDROXYLNAPHTHALENE DERIVATIVES
1289
Scheme 2. Proposed reaction mechanism for the synthesis of hydroxyl naphthalene-1,4-dione derivatives
catalyzed by PPA.
Although the detailed mechanism of the reaction remains to be fully clarified,
a reasonable possibility is proposed in Scheme 2 according to the mechanism of
Mannich reaction.
EXPERIMENTAL
All reagents were of analytical grade and purchased from Sinopharm Chemical
Reagent Co., Ltd., and were used without further purification.
General Procedure for the Synthesis of Hydroxylnaphthalene-1,4-
dione Derivatives
A mixture of aldehyde (5 mmol), amine (5 mmol), 2-hydroxynaphthalene-1,4-
dione (5 mmol), and PPA (1 mmol) was stirred under ambient conditions in water
(5 mL) for the specific time. The reaction was monitored by thin-layer chromatogra-
phy (TLC). After completion, the reaction mixture was filtered, and the precipitate
was purified by recrystallization in aqueous EtOH (60 %, v) to afford the product.
All the products are known compounds. The desired pure products were char-
1
acterized by analytical and spectral data (including infrared spectrum (IR), H and
13C nuclear magnetic resonance (NMR), elemental analyses, melting point) and by
comparison of their physical and spectral data with those of known compounds.[4,5]
2-Hydroxy-3-[phenyl(phenylamino)methyl]naphthalene-1,4-dione (4a)
Orangepowder;mp:142–145°C;IR(KBr,cm–1):3431,3319,1660,1639;1HNMR
(300 MHz, DMSO-d6): δ=6.00 (s, 1H, CH), 7.26–8.09 (m, 14H, ArH and NH), 9.27
(s, 1H, OH); 13C NMR (75 MHz, DMSO-d6): δ=37.4, 113.5, 123.9, 126.0, 126.6,
128.5, 129.7, 130.4, 132.8 133.2, 133.7, 135.1, 138.1, 146.2, 156.9, 157.7, 181.9, 184.2.
Anal. calcd. for C23H17NO3: C, 77.73; H, 4.82; N, 3.94. Found: C, 77.66; H, 4.72; N,
3.87.

1290
D. LIU, S. ZHOU, AND J. GAO
CONCLUSION
A simple and efficient method for the synthesis of 2-hydroxy-1,4-naphthoqui-
none derivatives using PPA as catalyst in water under room temperature has been
developed, which affords good yield in mild reaction conditions with a simple proce-
dure that is environmentally friendly and utilizes an inexpensive catalyst.
FUNDING
The authors are thankful to Shandong University of Science and Technology for
thepartialsupportof thisresearchandforthefinancialsupportof theNationalNatural
Science Foundation of China (Grant No. 21306106), Specialized Research Fund for
the Doctoral Program of Higher Education of China (Grant No. 20123718120012),
and China Postdoctoral Science Foundation (Grant No. 2013M541941).
SUPPLEMENTAL MATERIAL
Supplemental data for this article can be accessed on the publisher’s website.
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