Indium(III) chloride: An efficient catalyst for the synthesis of amidoalkyl naphthols

Article abstract of DOI:10.1080/00397910903340702

Indium chloride was found to be a very efficient catalyst for the synthesis of amidoalkyl naphthols from β-naphthol, aromatic aldehydes, and acetamide/urea under solvent-free conditions using microwave irradiation.

Full text of DOI:10.1080/00397910903340702

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Indium(III) Chloride: An Efficient
Catalyst for the Synthesis of Amidoalkyl
Naphthols
Neelam L. Chavan a , Prajakta N. Naik a , Sandip K. Nayak b &
Radhika S. Kusurkar a
a Department of Chemistry, University of Pune, Pune, India
b Bio-organic Division, Bhabha Atomic Research Centre, Mumbai,
India
Version of record first published: 25 Aug 2010
To cite this article: Neelam L. Chavan, Prajakta N. Naik, Sandip K. Nayak & Radhika S. Kusurkar
(2010): Indium(III) Chloride: An Efficient Catalyst for the Synthesis of Amidoalkyl Naphthols, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
40:19, 2941-2947
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Synthetic Communications1, 40: 2941–2947, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903340702
INDIUM(III) CHLORIDE: AN EFFICIENT CATALYST FOR
THE SYNTHESIS OF AMIDOALKYL NAPHTHOLS
Neelam L. Chavan,1 Prajakta N. Naik,1 Sandip K. Nayak,2
and Radhika S. Kusurkar1
1Department of Chemistry, University of Pune, Pune, India
2Bio-organic Division, Bhabha Atomic Research Centre, Mumbai, India
Indium chloride was found to be a very efficient catalyst for the synthesis of amidoalkyl
naphthols from b-naphthol, aromatic aldehydes, and acetamide/urea under solvent-free
conditions using microwave irradiation.
Keywords: Acetamide; amidoalkyl naphthols; aromatic aldehyde; indium(III) chloride; b-naphthol; urea
INTRODUCTION
The development of multicomponent organic synthesis is a very popular area
of research in recent years and is acceptable from a ‘‘green chemistry’’ point of view.
The major advantages of multicomponent reactions are (i) the use of simple and
diverse precursors to construct complex molecules, (ii) a single purification step,
requiring less solvents, and (iii) better yields when compared to stepwise reactions.
Strecker[1] in 1850 first demonstrated the concept of multicomponent reactions,
and the same concept has been subsequently used in both liquid- and solid-phase
reactions to construct important structures for pharmaceutical research.
Aminonaphthols are valuable synthetic scaffolds because of their usefulness in
the synthesis of organic molecules that exhibit various biological activities including
antihypertensive, adrenoceptor blocking, and Ca2þ channel blocking activities.[2]
This class of compounds can be easily prepared by the reduction of the respective
amidonaphthols. Thus, synthesis of amidoalkyl naphthols has received renewed
interest, and several catalysts used so far are HClO4-SiO2,[3] molybdophosphoric
acid,[4] PPA-SiO2,[5] FeH(SO4)2,[6] Al(H2PO4)3,[7] Sr(OTf)3,[8] alumina–sulfuric
acid,[9] NaHSO4 ꢀ H2O,[10] FeCl3 ꢀ SiO2,[11] zirconyl(IV) chloride,[12] montmorillonite
K10 clay,[13] Ce(SO4)2,[14] iodine,[15] K5CoW12O4 ꢀ 3H2O,[16] p-toluenesulforic acid
(p-TSA),[17] sulfamic acid,[18] cation-exchanged resins,[19] and silica-sulfuric acid.[20]
Some of these methods suffer from drawbacks including involvement of strong acids,
long reaction time, toxic catalysts, and poor yields. Consequently, there is a need to
develop protocol for using nontoxic materials with greater yields. Recently, indium
Received July 23, 2009.
Address correspondence to Radhika S. Kusurkar, Department of Chemistry, University of Pune,
Pune 411 007, India. E-mail: rsk@chem.unipune.ac.in
2941

2942
N. L. CHAVAN ET AL.
chloride has attracted much attention because it has emerged as an alternative safe,
economical, and air- and moisture-tolerant Lewis acid, which has been used in vari-
ous organic transformations.
Microwave irradiation (MW) has become an established tool in organic
synthesis because of the rate enhancements, greater yields, and often improved
selectivity as compared to conventional reaction conditions. In addition, solvent-free
MW processes are also clean and efficient, and moreover, reactions using either
organic or inorganic solid supports have received increased attention. There are
several advantages of performing synthesis in solvent-free media such as (i) short
reaction time, (ii) increased safety, (iii) economic advantages because of the absence
of solvent, and (iv) environmentally friendly reactions.[21] Herein, we report remark-
able catalytic activity of indium chloride in multicomponent synthesis of amidoalkyl
naphthols using microwave conditions.
RESULTS AND DISCUSSION
In a preliminary study, the reaction of b-naphthol (1 mmol), 4-nitro benzal-
dehyde (1 mmol), acetamide (1.2 mmol), and 10 mol% of indium chloride was carried
out, in which the corresponding amidoalkylnaphthols were obtained in 75% yield
after heating for 90 min. To enhance the rate of the reaction, the same reaction
was carried out under microwave irradiation. Gratifyingly, the reaction proceeded
smoothly to afford the corresponding amidoalkylnaphthol 4a in very high yield
(95%), which was characterized by both spectral and analytical data and also by
comparison with reported values. Upon irradiation in a microwave without InCl3,
no reaction occurred. During optimization of the catalyst loading in the reaction,
it was observed that 10 mol% of InCl3 is essential to get the greatest yield of the
product.
Having this in hand, the scope and limitation of the protocol were investigated.
Thus, a variety of aromatic aldehydes having electron-donating as well as
electron-withdrawing substituents were used, and in all the cases the corresponding
amidoalkylnaphthols were obtained in good yields (Scheme 1; Table 1, entries a–f).
More interestingly, reactions with urea in place of acetamide proceeded
smoothly to afford the corresponding hydrazides in excellent yields (Table 1, entries
g–l). All the products were characterized by spectroscopic methods. As expected, the
aldehydes with electron-withdrawing groups reacted faster than aldehydes having
electron-donating groups. We could successfully achieve the synthesis of products
4c, 4g, 4h, and 4j using indium chloride in very good yield for the first time.
Scheme 1. Indium chloride–catalyzed multicomponent reaction.

INDIUM(III) CHLORIDE: AN EFFICIENT CATALYST
2943
Table 1. Indium chloride–catalyzed reaction of b-naphthol, aldehydes, and acetamide or urea using
microwaves
Entry
Aldehydes (2)
Urea or amide (3)
Product (4)
Time (min) Yield (%)
a
NH2COCH3
3
95
b
c
NH2COCH3
NH2COCH3
8
7
88
92
d
e
f
NH2COCH3
NH2COCH3
NH2COCH3
10
5
89
94
90
8
g
NH2CONH2
6
93
h
i
NH2CONH2
NH2CONH2
NH2CONH2
10
13
11
85
87
j
89
(Continued )

2944
N. L. CHAVAN ET AL.
Table 1. Continued
Entry
Aldehydes (2)
Urea or amide (3)
Product (4)
Time (min) Yield (%)
k
NH2CONH2
NH2CONH2
8
91
96
l
10
It is known that amides undergo a-cleavage next to the carbonyl group in mass
spectrometry. The same was observed in the case of products 4g–l. Because of the
instability, the molecular ion peak was not observed in the mass spectrum. The
M-17 ion was observed as a peak at the greatest mass because of the loss of ammonia
molecule (Scheme 2).
Comparison of yield and time for the reaction using other catalysts under
microwave irradiation are shown in Table 2, which clearly indicates that use of
indium chloride under microwave conditions is an efficient method for the synthesis
of amidoalkyl naphthols.
Scheme 2. Genesis of M-17 ion observed in mass spectrum.
Table 2. Comparison of results for the synthesis of N-((2-hydroxynaphthalen-1-yl)(4-nitrophenyl)methyl)
acetamide using various catalysts[3,6,7,10] under microwave irradiation
Entry
Catalyst
Time (min)
Yield (%)
1
2
3
4
5
NaHSO4
Al(H2PO4)
FeHSO4
HClO4-SiO2
InCl3
3
3
89
66
96
91
95
5
12
3

INDIUM(III) CHLORIDE: AN EFFICIENT CATALYST
2945
CONCLUSION
In summary, we have demonstrated for the first time that indium chloride
showed good catalytic activity for three-component condensation of b-naphthol,
aromatic aldehydes, and acetamide or urea to furnish amidoalkyl naphthols under
solvent-free microwave conditions.
EXPERIMENTAL
NMR spectra were recorded on a 300-MHz Varian Mercury instrument as d
values in CDCl3 and dimethylsulfoxide (DMSO-d6) with reference to tetramethylsi-
lane (TMS) as internal standard. Fourier transform–infrared (FT-IR) spectra were
recorded on a Shimadzu 8400 instrument. Mass spectra were recorded on a
Shimadzu QP 5050 instrument. Elemental analyses were recorded on a Flash E. A.
1112 Thermo Fischer machine. A Domestic microwave oven (LG, 800 W) was used
for microwave irradiation.
General Procedure for the Synthesis of Amidoalkyl Naphthols
InCl3 (0.1 mmol, 10 mol%) was added to a mixture of 2-naphthol (1 mmol),
aldehydes (1 mmol), and acetamide or urea (1.2 mmol). The mixture was irradiated
in a domestic microwave oven at 800 W, and the progress of the reaction was
followed by thin-layer chromatography (TLC). After completion of the reaction,
the mixture was cooled to room temperature, and the residue was purified by column
chromatography to afford the pure compound. The products were characterized by
their spectral and analytical data and compared with those of the known
compounds.
Selected Data
Compound 4c. Yield: 92%, mp 205–206 ꢁC. IR (KBr, nmax): 3365, 3140 (br),
1626, 1510 cmꢂ1. 1H NMR (DMSO-d6): d 1.98 (s, 3H), 5.93 (d, 2H, J ¼ 4.4), 6.63 (d,
1H, J ¼ 7.7), 6.76 (m, 2H), 7.05 (d, 1H, J ¼ 7.9), 7.23 (m, 2H), 7.37 (bs, 1H), 7.79 (m,
2H), 7.88 (bs, 1H), 8.45 (d, 1H, J ¼ 8.2), 10.0 (bs, 1H). 13C NMR (DMSO-d6): 22.72,
47.69, 100.69, 106.59, 106.76, 107.75, 118.38, 118.69, 119.03, 122.26, 123.09, 126.21,
128.27, 128.38, 129.06, 132.05, 136.41, 145.32, 146.93, 152.84 and 168.98. MS
(GCMS): m=z 335. Anal. calcd. for C20H17N2O4: C, 71.63; H, 5.11; N, 4.18. Found:
C, 71.58; H, 5.05; N, 4.10.
Compound 4g. Yield: 93%, mp 161–162 ꢁC, IR (KBr, nmax): 3468, 3356 (br),
1668, 1602, 1512, 1415 cmꢂ1. 1H NMR (DMSO-d6): d 5.91 (s, 2H), 6.97(s, 2H), 7.19
(d, 1H, J ¼ 8.5), 7.28 (t, 1H, J ¼ 7.1), 7.38 (m, 3H), 7.80 (m, 3H), 8.12 (d, 2H,
J ¼ 8.8 Hz), 10.08 (s, 1H). 13C NMR (DMSO-d6): 48.01, 118.33, 119.12, 122.55,
123.16, 126.84, 128.30, 128.68, 129.53, 131.98, 145.73, 152.90 and 158.44. MS
(GCMS): m=z 320 (Mþ ꢂ 17). Anal. calcd. for C18H15N3O4: C, 64.09; H, 4.48; N,
12.46. Found: C, 63.91; H, 4.44; N, 12.42.

2946
N. L. CHAVAN ET AL.
Compound 4h. Yield: 85%, mp 223–224 ꢁC, IR (KBr, nmax): 3267, 3147 (br),
1718, 1606, 1512, 1402 cmꢂ1. 1H NMR (DMSO-d6): d 5.95 (d, 1H, J ¼ 2.4), 6.68 (m,
3H), 7.07 (m, 3H), 7.24 (d, 1H, J ¼ 8.8), 7.36–7.39 (m, 3H), 7.63 (d, 1H, J ¼ 8.2), 7.81
(m, 3H), 8.59 (bs, 1H). 13C NMR (DMSO-d6): 53.34, 114.43, 115.49, 116.80, 123.12,
124.95, 127.19, 128.19, 128.53, 128.87, 129.94, 130.36, 133.39, 147.22, 149.38 and
157.06. MS (GCMS): m=z 291(Mþ – 17). Anal. calcd. for C18H16N2O3: C, 70.12;
H, 5.23; N, 9.09. Found: C, 70.03; H, 5.19; N, 9.04.
Compound 4j. Yield: 89%, mp 183–185 ꢁC, IR (KBr, nmax): 3248, 3147 (br),
1
1749, 1627, 1487, 1228 cmꢂ1. H NMR (DMSO-d6): d 2.07 (s, 2H), 5.93 (d, 2H,
J ¼ 6.8), 6.09 (d, 1H, J ¼ 2.7), 6.69 (d, 1H, J ¼ 7.9), 6.81 (m, 2H), 7.08–7.16 (m,
1H), 7.33 (d, 1H, J ¼ 8.8), 7.42–7.49 (m, 2H), 7.76 (d, 1H, J ¼ 7.7), 7.94 (m, 2H),
8.77 (s, 1H). 13C NMR (DMSO-d6): 53.44, 101.11, 107.21, 108.36, 113.82, 116.70,
120.21, 122.96, 124.96, 127.23, 128.46, 128.72, 130.08, 130.24, 136.62, 146.72,
147.18, 147.40 and 149.14. MS (GCMS): m=z 319 (Mþ – 17). Anal. calcd. for
C19H16N2O4: C, 67.85; H, 4.79; N, 8.33. Found: C, 67.76; H, 4.70; N, 8.27.
ACKNOWLEDGMENTS
We are grateful to Mr. B. S. Kalshetti for IR spectra, Mrs. J. P. Choudhary for
NMR spectra, and Mr. D. S. Shishupal for GCMS. N. L. C. is thankful to Bhabha
Atomic Research Centre (BARC) for the award of a fellowship.
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