On water: A practical and efficient synthesis of benzoheterocycle derivatives catalyzed by nanocrystalline copper(II) oxide

Article abstract of DOI:10.1080/00397910903007103

Recyclable CuO nanoparticles provide an efficient, economic, and novel method for the synthesis of quinoxaline, benzoxazine, and benzothiazine. This method provides a wide range of substrate applicability, avoids the use of organic solvents, and gives benzoheterocycles in satisfactory yields. Copyright Taylor & Francis Group, LLC.

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On Water: A Practical and Efficient
Synthesis of Benzoheterocycle
Derivatives Catalyzed by Nanocrystalline
Copper(II) Oxide
Sodeh Sadjadi a b , Rahim Hekmatshoar b , Seyed Javad Ahmadi a ,
Morteza Hosseinpour c & Mohammad Outokesh c
a Nuclear Fuel Cycle School, Nuclear Science and Technology
Research Institute, Tehran, Iran
b Department of Chemistry, School of Science, Alzahra University,
Vanak, Tehran, Iran
c Department of Energy Engineering, Sharif University of Technology,
Tehran, Iran
Version of record first published: 03 Feb 2010.
To cite this article: Sodeh Sadjadi , Rahim Hekmatshoar , Seyed Javad Ahmadi , Morteza Hosseinpour
& Mohammad Outokesh (2010): On Water: A Practical and Efficient Synthesis of Benzoheterocycle
Derivatives Catalyzed by Nanocrystalline Copper(II) Oxide, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 40:4, 607-614
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Synthetic Communications1, 40: 607–614, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903007103
ON WATER: A PRACTICAL AND EFFICIENT SYNTHESIS
OF BENZOHETEROCYCLE DERIVATIVES CATALYZED BY
NANOCRYSTALLINE COPPER(II) OXIDE
Sodeh Sadjadi,1,2 Rahim Hekmatshoar,2 Seyed Javad
Ahmadi,1 Morteza Hosseinpour,3 and Mohammad Outokesh3
1Nuclear Fuel Cycle School, Nuclear Science and Technology Research
Institute, Tehran, Iran
2Department of Chemistry, School of Science, Alzahra University,
Vanak, Tehran, Iran
3Department of Energy Engineering, Sharif University of Technology,
Tehran, Iran
Recyclable CuO nanoparticles provide an efficient, economic, and novel method for the
synthesis of quinoxaline, benzoxazine, and benzothiazine. This method provides a wide
range of substrate applicability, avoids the use of organic solvents, and gives benzohetero-
cycles in satisfactory yields.
Keywords: Benzothiazine; benzoxazine; CuO nanoparticles; quinoxaline; water
INTRODUCTION
1,4-Benzoxazin-3(4H)-one and 1,4-benzothiazin-3(4H)-one derivatives are an
interesting group of compounds, both pharmacologically and agriculturally. The
1,4-benzoxazin-3(4H)-one moiety can be found in molecules that exhibit plant resist-
ance factors against microbial diseases and insects and analgesic, antimicrobial and
potassium-channel modulating properties, whereas 1,4-benzothiazin-3(4H)-ones,
like semotiadil, are antihypertensive drugs, calcium antagonists, and highly potent
inhibitors of low density lipoprotein (LDL) oxidation.[1]
Quinoxaline not only has application as dyes[2] and building blocks in the syn-
thesis of organic semiconductors[3] but also serves as useful rigid subunits in macro-
cyclic receptors for molecular recognition[4] and chemically controllable switches.[5]
Nanocrystalline metal oxides find excellent applications as active adsorbents
for gases and destruction of hazardous chemicals.[6] They are also gaining tremen-
dous importance because of their distinct catalytic activities for various organic
transformations. Recently, researchers have reported various[7–10] organic transfor-
mations using different nanocrystalline metal oxides. These high reactivities are
Received February 28, 2009.
Address correspondence to Rahim Hekmatshoar, Department of Chemistry, School of Science,
Alzahra University, Vanak, Tehran, Iran. E-mail: rhekmatus@yahoo.com
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S. SADJADI ET AL.
due to the high surface areas combined with unusually reactive morphologies.
Copper oxide nanoparticles have been of considerable interest because of the role
of CuO in catalyts, gas sensors, and semiconductors.[11,12] CuO nanoparticles were
found to be effective catalysts for CO and NO oxidation as well as for the oxidation
of volatile organic chemicals, such as methanol.[13] Very recently, Kantam et al.
reported the asymmetric hydrosilylation reaction of prochiral ketones with excellent
enantioselectivity,[14] synthesis of propargylamines via three-component coupling of
aldehydes, amines, and alkynes,[15] and direct asymmetric aldol reactions[16] cata-
lyzed by nanocrystalline copper oxide.
Among methods to prepare nanoparticles, supercritical hydrothermal synthesis
is a unique technique to synthesize metal oxide and hydroxide nanocrystals from an
aqueous solution of metal salts, in which the size, morphology, and crystal structure
are controllable.[17] Supercritical water hydrothermal synthesis offers a relatively
simple route that is inherently scalable and chemically much more benign than
current technology. This method relies on the high reaction rate of hydrothermal
synthesis above the critical temperature of water and lower solubility for the formed
metal oxide,[18] which causes an extremely high degree of supersaturation of the
metal oxide and thus allows nanoparticle formation.[19]
As a part of our ongoing research on the synthesis and catalytic applications of
metal oxide nanoparticles, we first attempted synthesis of copper oxide nanoparticles
by a batchwise supercritical hydrothermal method. Advantages of this method are
shorter reaction time (<2 h) and possibility of performing it in a single step. After
preparation of CuO nanoparticles and characterization by x-ray diffraction
(XRD) and transition electron microscopy (TEM) techniques, the nanoparticles
were employed as a recyclable catalyst for an efficient synthesis of benzoheterocycle
(Scheme 1).
The XRD pattern of nano-sized is shown in Fig. 1. All diffraction peaks of
x-rays are indexed to the monoclinic crystal system of CuO. No characteristic peaks
are observed for other possible impurities, such as Cu(OH)2, Cu2O, or
Cu(OH)3NO3. Average size of the obtained CuO particles shown in Fig. 2 is
5 nm. The mean value of surface area of CuO catalyst was 32.457 m2=g from
BET analysis.
We began our study of the reaction shown in Scheme 1 by optimizing the reac-
tion conditions for the preparation of 3a; the reaction was carried out in water at rt
for 30 min. To our delight, at rt the reaction proceeded smoothly, and the product
was furnished in 94% yield after workup and simple isolation from water. A
Scheme 1. An efficient synthesis of benzoheterocycles.

SYNTHESIS OF BENZOHETEROCYCLE DERIVATIVES
609
Figure 1. Transmission electron micrographs of CuO nanoparticles.
Figure 2. XRD pattern of CuO nanoparticles.
summary of the optimization experiment is provided in Table 1. In addition to
MeCN, CH2Cl2, and EtOH were also tested as the reaction solvents. In these cases,
product 3a was formed in slightly lower yield (Table 1).
Table 1. Synthesis of 3a with CuO nanoparticles at different reaction conditions
Entry
1
T (ꢀC)
Solvent
Yield (%)
RT
Water
Water
CH2Cl2
EtOH
94
94
81
86
79
Reflux
Reflux
Reflux
Reflux
2
3
4
MeCN
aReaction condition: aromatic amine 1a (1 mmol), dialkyl acetylenedicarboxylate
2a (1 mmol), and catalyst (0.003 mmol).

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S. SADJADI ET AL.
Figure 3. IR spectra of CuO: (a) newly prepared and (b) used three times.
To demonstrate the efficiency and the applicability of the present method, we
performed the reaction with dimeyhyl acetylenedicarboxylate (DMAD) or diethyl
acetylenedicarboxylate (DEAD) with 2-amino-phenol and 2-amino-benzenethiol in
water at 50ꢀC and in the presence of CuO nanoparticles.
All the reactions proceeded to completion at the time indicated in Table 2, and
the yield data are for the isolated products. As shown in Table 2, we can see a series
of 1 reacted with 2 to give the corresponding products 3 in good yields.
The efficiency of bulk CuO catalyst was also studied for this reaction, but the
model reaction did not go to completion in the presence of this catalyst even after
long reaction times (2 h).
The increased catalytic activity of nano-CuO over commercially available bulk
CuO may be attributed to the higher surface area of nano-CuO than bulk CuO as
well as the higher surface concentration of the reactive sites. As seen with other metal
oxides, once they are made into nanoparticles, their reactivity is greatly enhanced.
This is thought to be due to the morphological differences, whereas larger crystallites
have only a small percentage of the reactive sites on the surface. Smaller crystallites
will possess a much higher surface concentration of such sites.[19]
The nano-CuO catalyst could be reused for four cycles without loss of activity
and selectivity. Infrared (IR) spectra of fresh and used nano-CuO catalyst confirmed
the fact that the structure and morphology of the catalyst remained the same during
the course of the reaction (Fig. 3).
In summary, there is no doubt that CuO nanoparticles are an effective catalyst
and provide a new and useful method to synthesize benzoheterocycle derivatives.
The catalysts show environmentally friendly character and can be easily prepared,
stored, and recycled without obvious loss of activity. Because of water-resistant
and oil-resistant character of CuO nanoparticles, the catalysts can also be reused
more conveniently. Therefore, a simple workup procedure, mild reaction conditions,
and good yields make our methodology a valid contribution to the existing processes
in the field of benzoheterocycle derivatives.

SYNTHESIS OF BENZOHETEROCYCLE DERIVATIVES
613
EXPERIMENTAL
Preparation of the CuO-Nanoparticle Catalyst
Copper(II) nitrate trihydrate (Merck A. G.) was used as the precursor
for synthesis of copper oxide nanoparticles. Preparation of CuO was implemented
in a stainless steel (316 Lit) autoclave that is able to endure working temperature
and pressure of 550ꢀC and 610 atm, respectively. Hydrothermal synthesis of
0.05 mol dmÀ3 Cu(NO3)2 during 2 h was carried out at 500ꢀC to accelerate the
hydrolysis reactions and thus shorten the fabrication period. To maintain the safety
margin, the 200-cm3 stainless steel autoclave was loaded with only 60–80 cm3 of the
solution. After removing it from the furnace, the autoclave was quenched by cold
water, and CuO nanoparticles were recovered from discharged solution by high-
speed centrifugation at 14,000 rpm for 60 min. Purification of the produced nano-
particles was performed by conducting centrifugation and decantation of washed
samples with water three times and then drying at ambient temperature.
Physical Measurements
Size and morphology of the obtained nanoparticles were observed by TEM
(LEO 912AB) (Fig. 2). Crystal structure of the prepared CuO nanoparticles and final
microspheres was analyzed by using Cu Ka radiation (Philips PW 1800) (Fig. 1). The
surface area of the CuO nanoparticles were determined by the nitrogen adsorption
BET method (Quantachrome Instruments, Nova 2000e).
Catalytic Reactions
The substituted aromatic amine (1 mmol) was dissolved in water (5 mL), and
dialkyl acetylenedicarboxylate (1 mmol) and catalyst (0.003 mmol) were added.
The reaction mixture was stirred at room temperature and monitored by thin-layer
chromatography (TLC).
Upon completion of the reaction, the reaction mixture was allowed to cool to
room temperature, and the solution was filtered to isolate the solid product. The
solid product was diluted with chloroform, and the catalyst was removed by simple
filtration (the catalyst is not soluble in chloroform). After evaporation of solvent,
more purification was obtained by column chromatography (eluted with 2:3
EtOAc–petroleum ether).
All the products obtained were characterized by spectroscopic methods such as
1
IR and H NMR, for unknown compounds (13C NMR and analytical data), and
also by comparison with the reported spectral data and melting point.[2]
ACKNOWLEDGMENTS
The authors are thankful to Alzahra Research Council and School of Energy
Engineering, Sharif University of Technology, for the partial financial support.

614
S. SADJADI ET AL.
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