Letters in Organic Chemistry, 2012, 9, 273-275
273
One-Pot Synthesis of Amidoalkyl Naphthols Using POCl3/Na2B4O7 as a
Heterogeneous Catalyst
Hadi Jafari*,a and Hassan Moghanianb
aDepartment of Chemistry, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran
bDepartment of Chemistry, Dezful Branch, Islamic Azad University, Dezful, Iran
Received August 24, 2011: Revised February 01, 2012: Accepted February 01, 2012
Abstract: A convenient and efficient procedure for the synthesis of 1-amidoalkyl-2-naphthols by condensation of β-
naphthol, aldehydes and amid/urea in the presence of POCl3/ Na2B4O7 is described. This method offers several advantages
including low cost and easy availability of the catalyst, environmentally friendly procedure and easy work-up under
solvent-free conditions.
Keywords: 1-Amidoalkyl-2-naphthols, borax, multicomponent reactions, POCl3.
INTRODUCTION
supported catalyst, we wish to report the synthesis of 1-
amidoalkyl-2-naphthols by condensation of aryl
4
The multicomponent reactions (MCRs) [1] are attracting
the interest of organic chemists and other researchers due to
their significant potential for converting more than two
adducts directly into respective products in quantitative
yields in a one-pot reaction as compared to conventional
strategies used in multi-step synthesis of various biologically
active organic compounds. MCRs are particularly useful to
generate diverse chemical libraries of ‘druglike’ molecules
for biological screening [2, 3]. One of these MCRs is the
preparation of amidoalkyl naphthols. 1-amidoalkyl-2-
naphthols and their derivatives have attracted considerable
interest in recent years due to biologically important
antibacterial, natural products and potent drugs including a
number of nucleoside antibiotics and HIV protease
inhibitors, such as ritonavir and lipinavir [4, 5].
aldehydes,2-naphthol and amide/urea in the presence of
POCl3/ Na2B4O7 at 120 °C under solvent-free conditions
(Scheme 1).
RESULTS AND DISCUSSION
To study the feasibility of the BPO catalyzed in this
reaction, the reaction of benzaldehyde (10 mmol) 2, β -
naphthol (10 mmol) 1 and acetamide (12 mmol) 3 was
selected as a model under solvent-free conditions. We first
studied the model reaction catalyzed by 0.1 g BPO at
different temperatures. The reaction rate was increased as the
reaction temperature was raised. When it was carried out at
120 ˚C, the maximum yield was obtained in a short reaction
period. Next, to evaluate the effect of catalyst concentration,
the model reaction was carried out in the presence of
different amounts of catalyst (0.05, 0.08, 0.1 and 0.12 g) at
120 ˚C. The result showed, that for the model reaction 0.1 g
of catalyst was sufficient to achieve a fairly high yield (Table
1).
The preparation of 1-amidoalkyl-2-naphthols can be
carried out by multi-component condensation of aryl
aldehydes, 2-naphthol amide/urea in the presence of catalysts
such as PPA-SiO2, Iodine, K5CoW12O40.3H2O, cation-
exchange resins, HClO4-SiO2, Ce(SO4)2, Yb(OTF)3 and
Indium(III) Chloride [6-8]. However, many of these
methodologies suffer from the drawback of green chemistry
and have been associated with several shortcomings such as
long reaction times, expensive reagents and low product
yields. Therefore, to overcome these limitations, the search
for a new, easily available catalyst with high catalytic
activity for the preparation of amidoalkyl naphthols is
strongly desirable.
With the optimized condition established above, we then
attempted to extend the process to β-naphthol, various types
of aromatic aldehydes and different amides including
acetamide, urea and benzamide under solvent-free conditions
at 120 °C. The results have been summarized in Table 2. In
all cases, 1-amidoalkyl-2-naphthols 4 were obtained in high
to excellent yields without formation of any side products
such as di-benzoxanthenes, which are normally observed
under the influence of strong acids. Although as it can be
seen from the results of Table 2, this reaction is affected by
electronic and steric factors. Aldehydes with electron-
withdrawing groups, give higher yields than aldehydes with
electron-donating groups. Aliphatic aldehyde like
propionaldehyde was also examined, but the yields were low
as compared to aromatic aldehyde (Table 2, entry 15).
The use of catalysts and reagents on solid supports has
been developed because such reagents not only simplify
purification processes but also help to prevent the release of
reaction residue into the environment [9]. In continuation of
our interest in the use of POCl3/Na2B4O7 (BPO) [10, 11] as a
*Address correspondence to this author at the Department of Chemistry,
Sanandaj Branch, Islamic Azad University, Sanandaj, Iran;
Tel: +98-8314274512; Fax: +98-8314274559; E-mail: hjs292@yahoo.com
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