Ionic liquid [NMP] +HSO4-: An efficient and recyclable catalyst for the synthesis of 1-amidoalkyl-2-naphthols and 1-carbamatoalkyl-2-naphthols under solvent-free conditions

Article abstract of DOI:10.1080/00397911.2010.522293

A simple and efficient protocol for the one-pot synthesis of 1-amidoalkyl-2-naphthols and novel 1-carbamatoalkyl-2-naphthols has been described under solvent-free conditions, using N-methyl-2-pyrrolidone hydrogen sulfate (NMP⁺HSO₄^-) as a reusable Brnsted acidic ionic liquid. This methodology has several advantages such as use of a halogen-free ionic liquid (NMP⁺HSO₄^-), excellent yields, short reaction time, easy workup procedure, and reusable catalyst.

Full text of DOI:10.1080/00397911.2010.522293

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Ionic Liquid : An Efficient and
Recyclable Catalyst for the Synthesis
of 1-Amidoalkyl-2-naphthols and 1-
Carbamatoalkyl-2-naphthols Under
Solvent-Free Conditions
Krishna M. Deshmukh a , Ziyauddin S. Qureshi a , Yogesh P. Patil a &
Bhalchandra M. Bhanage a
a Department of Chemistry, Institute of Chemical Technology,
Mumbai, India
Accepted author version posted online: 30 Jun 2011.
To cite this article: Krishna M. Deshmukh , Ziyauddin S. Qureshi , Yogesh P. Patil & Bhalchandra
M. Bhanage (2012): Ionic Liquid : An Efficient and Recyclable Catalyst for the Synthesis of 1-
Amidoalkyl-2-naphthols and 1-Carbamatoalkyl-2-naphthols Under Solvent-Free Conditions, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
42:1, 93-101
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Synthetic Communications1, 42: 93–101, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.522293
IONIC LIQUID [NMP]+HSO–4: AN EFFICIENT AND
RECYCLABLE CATALYST FOR THE SYNTHESIS
OF 1-AMIDOALKYL-2-NAPHTHOLS AND
1-CARBAMATOALKYL-2-NAPHTHOLS UNDER
SOLVENT-FREE CONDITIONS
Krishna M. Deshmukh, Ziyauddin S. Qureshi, Yogesh P. Patil,
and Bhalchandra M. Bhanage
Department of Chemistry, Institute of Chemical Technology, Mumbai, India
GRAPHICAL ABSTRACT
Abstract A simple and efficient protocol for the one-pot synthesis of 1-amidoalkyl-2-
naphthols and novel 1-carbamatoalkyl-2-naphthols has been described under solvent-free
conditions, using N-methyl-2-pyrrolidone hydrogen sulfate ðNMPþHSO4ꢀÞ as a reusable
Brønsted acidic ionic liquid. This methodology has several advantages such as use of a
halogen-free ionic liquid NMPþHSO4ꢀ, excellent yields, short reaction time, easy workup
procedure, and reusable catalyst.
Keywords Aldehyde; amides; ionic liquids; multicomponent reaction; solvent free
INTRODUCTION
The 1,3-amino oxygenated functional motifs are widely used in many natural
products, potent drugs, and HIV protease inhibitors.[1] Traditionally, these
Received February 21, 2010.
Address correspondence to Bhalchandra M. Bhanage, Department of Chemistry, Institute of
Chemical Technology, N. Parekh Marg, Matunga, Mumbai 400 019, India. E-mail: bhalchandra_
bhanage@yahoo.com
93

94
K. M. DESHMUKH ET AL.
Scheme 1. Synthesis of 1-amidoalkyl-2-naphthols and 1-carbamatoalkyl-2-naphthols.
compounds were synthesized by multicomponent condensation of aryl aldehydes,
2-naphthol, and acetonitrile or amide in the presence of Lewis or Brønsted acid
catalysts such as p-toluenesulfonic acid (p-TSA),[2] FeCl3 ꢁ SiO2,[3] cation exchange
resin,[4] and N-(4-sulfonic acid) butyl triethyl ammonium hydrogen sulfate ([TEB-
SA][HSO4].)[5] Shaterian et al. first investigated the synthesis of 1-carbamatoalkyl-2-
naphthol using a three-component reaction.[6] The previous methodologies have draw-
backs of long reaction time, moisture-sensitive catalysts, and poor catalyst reusability.
The use of ionic liquids has gained considerable interest in the context of green
synthesis and catalysis. They are emerging as most promising alternatives for a wide
variety of acid-catalyzed reactions as they have useful characteristics of both solid
acids and mineral liquid acids and they can be designed to replace customary mineral
liquid acids such as sulfuric acid and hydrochloric acid in chemical procedures.[7]
In continuation of our research on applications of ionic liquids in several
organic transformations,[8] herein we report a halogen-free Brønsted acidic ionic
liquid, N-methyl-2-pyrrolidone hydrogen sulfate ðNMPþHSO4ꢀÞ, as an efficient
and reusable catalyst for preparation of both 1-amidoalkyl-2-naphthols and
1-carbamatoalkyl-2-naphthols via a three-component reaction. The synthesis of
novel 1-carbamatoalkyl-2-naphthols is reported for the first time.
RESULTS AND DISCUSSION
The reaction conditions were optimized using condensation of 2-naphthol,
benzaldehyde, and acetamide as a model reaction under solvent-free conditions.
The reaction parameters such as different types of ionic liquids, effects of catalyst
loading (i.e., ionic liquid), and temperature on the reaction yield were optimized.
First, the influence of different types of Brønsted acidic ionic liquids was inves-
tigated. The ionic liquid, NMPþHSO4ꢀ, was found to be most effective in terms of
short reaction time with excellent yield (93%) of the desired product (Table 1, entry
4). The effect of catalyst loading on the reaction yield was also investigated, and
10 mol% of the catalyst was found to be effective giving good yield within 3 min.

IONIC LIQUID–CATALYZED REACTION
95
Table 1. Effects of various parameters on synthesis of 1-amidoalkyl-2-naphtholsa
Entry
Ionic liquid
Loading (mol%)
Temperature (ꢂC)
Time (min)
Yieldb (%)
Effects of various ionic liquids
1
2
3
4
5
6
C4MImþHSOꢀ4
C4MImþ p-TSA
HMImþ Tfaꢀ
NMPþHSOꢀ4
HMImþNOꢀ3
HMImþHSOꢀ4
10
10
10
10
10
10
125
125
125
125
125
125
18
12
42
3
78
80
75
93
71
84
50
10
Effects of ionic liquid loading
7
8
NMPþHSOꢀ4
NMPþHSOꢀ4
NMPþHSOꢀ4
NMPþHSOꢀ4
5
10
15
20
125
125
125
125
5
3
3
3
82
93
87
90
9
10
Effects of temperature
11
12
13
NMPþHSOꢀ4
NMPþHSOꢀ4
NMPþHSOꢀ4
10
10
10
60
80
20
7
83
86
87
110
7
aReactionꢀ conditions: 2-naphthol (2.5 mmol), benzaldehyde (2.5 mmol), acetamide (2.8 mmol),
NMPþHSO4 , temperature 125 ꢂC.
bIsolated yield.
(Table 1, entry 8). We have also tested the effects of temperature on the reaction
yield, for which we carried out the reaction at various temperatures (60, 80, 110,
and 125 ꢂC). It was observed that reaction at 125 ꢂC gives the best yield of the desired
product (Table 1, entry 4).
Using these optimized reaction conditions a wide range of 1-amidoalkyl-2-
naphthols were prepared (Table 2). It has been observed that the aromatic aldehydes
with activating group (-CH3) at the para position react faster than those with it at the
ortho position (Table 2, entries 2 and 3). Aromatic aldehydes with deactivating
groups (like -NO2, -Cl, -Br) require longer reaction time for completion of the reac-
tion (Table 2, entries 4–7, 9, and 14). Sterically hindered aromatic aldehydes such as
2-CH3, 2-NO2, 2-Cl, and 2-Br provide moderate to good yields of the desired pro-
duct in short reaction times (Table 2 entries 3, 5, 7, and 14). Further, we have also
varied the nucleophiles such as urea and benzamide (Table 2, entries 8–14).
Under these optimized reaction conditions, we explored the scope of ionic
liquid for the synthesis of 1-carbamatoalkyl-2-naphthols (Table 3). Aldehydes with
an electron donating group (-OCH3) react smoothly with urethane and phenyl car-
bamate to give a good yield of the product (Table 3, entries 2 and 4). On the other
hand, electron-withdrawing groups like (-NO2, -COOH) underwent the reaction at a
faster rate to yield the desired product (Table 3, entries 3, 5, and 6). Urethane shows
trends in reactivity similar to those of amides.
CONCLUSION
In conclusion, the synthesis of a wide range of 1-amidoalkyl-2-naphthols and
new 1-carbamato-alkyl-2-naphthol under mild operating conditions has been carried

96
K. M. DESHMUKH ET AL.
Table 2. NMPþHSOꢀ4 -catalyzed synthesis of 1-amidoalkyl-2-naphthola
Entry
Aldehyde
Nucleophiles
CH3CONH2
Product
Time (min) Yieldb (%) Mp (ꢂC)[Ref.]
1c
3
15
4
93, 92, 90 244–245[3]
2
CH3CONH2
82
85
206–208[3]
3
CH3CONH2
215–216[3]
4
5
6
CH3CONH2
CH3CONH2
CH3CONH2
7
16
8
94
92
92
222–223[3]
214–216[3]
246–247[3]
203–204[3]
7
8
CH3CONH2
22
18
68
90
NH2CONH2
171–173[4]
(Continued )

IONIC LIQUID–CATALYZED REACTION
97
Table 2. Continued
Entry
Aldehyde
Nucleophiles
NH2CONH2
Product
Time (min) Yieldb (%) Mp (ꢂC)[Ref.]
9
9
93
169–170[4]
10
NH2CONH2
8
81
194–196[4]
11
12
PhCONH2
PhCONH2
5
91
76
231–233[4]
19
178–180[4]
13
PhCONH2
7
95
216–218[4]
14
PhCONH2
9
80
224–226[4]
aReaction conditions: 2-naphthol (2.5 mmol), aldehyde (2.5 mmol), nucleophile (2.8 mmol),
NMPþHSOꢀ4 (10 mol%), temperature 125 ꢂC.
bIsolated yield.
cRecyclability.
out using NMPþHSOꢀ4 as a reusable and moisture-stable Brønsted acidic ionic
liquid in an efficient manner. The system tolerates a wide range of functional groups,
affording the desired products with good to excellent yields.

98
K. M. DESHMUKH ET AL.
Table 3. NMPþHSOꢀ4 -catalyzed synthesis of 1-carbamatoalkyl-2-naphthola
Time
(min)
Yieldb
(%)
Mp
(ꢂC)
Entry
Aldehyde
Nucleophiles
Product
1
6
90
195–196
202–204
2
14
79
3
9
93
215–217
4
5
6
20
60
85
82
180–182
9
178–179
7
183–185
aReaction conditions: 2-naphthol (2.5 mmol), aldehyde (2.5 mmol), nucleophile (2.8 mmol),
NMPþHSOꢀ4 (10 mol%), temperature (125 ꢂC).
bIsolated yield.

IONIC LIQUID–CATALYZED REACTION
99
EXPERIMENTAL
Preparation and Characterization of NMPþHSO4ꢀ
NMPþHSOꢀ4 was prepared by using a reported procedure.[8] Brønsted acidity
of ionic liquid was determined using pyridine as a probe molecule by monitoring the
band range of 1350–1600 cmꢀ1 arising from its ring vibration modes.[9] The infrared
(IR) spectrum of pyridine shows a band at 1480 cmꢀ1. However, a slight shift was
observed in wave number after mixing pyridine with ionic liquid. The spectrum of
ionic liquids shows a band at 1550 cmꢀ1, indicating the presence of Brønsted acid
sites due to the formation of pyridinium ions.
General Procedure for Synthesis of 1-Amidoalkyl-2-naphthols and
1-Carbamatoalkyl-2-naphthols
NMPþHSOꢀ4 (10 mol %) was added to a mixture of 2-naphthol (2.5 mmol),
aldehyde (2.5 mmol), and acetamide=urea=urethane (2.8 mmol). The reaction mix-
ture was stirred at 125 ꢂC in a preheated oil bath for the appropriate time
(Tables 1 and 2). The progress of the reaction was monitored by thin-layar chroma-
tography (TLC). After completion of the reaction, the whole reaction mixture was
added in water. The resulting precipitate was filtered off, and the residue was recrys-
tallized from EtOH (20%).
Recyclability of Catalyst
To develop a greener and more economical protocol, a recycling experiment
was conducted for applications on a larger scale (20 mmol). After completion of
the reaction, the reaction mixture was added in water. The resulting white precipitate
was filtered off, and the catalyst was recovered from the filtrate. The recovered cata-
lyst was dried under vacuum using a rotavapor for 10 h and then charged for the next
run. The catalyst was successfully recycled up to three times (Table 2, entry 1).
Physical and Spectral Data of Selected Compounds
Ethyl [(2-hydroxynaphthalen-1-yl)(phenyl)methyl]carbamate (Table 2,
Entry 1). FT-IR (KBr): 3423, 3023, 2918, 1676, 1168, 941, 812, 740 cmꢀ1 1H
.
NMR (300 MHz, DMSO) d ¼ 1.04 (t, J ¼ 7 Hz, 3 H), 4 (q, J ¼ 5.4 Hz, 2 H), 6.82
(d, J ¼ 8.9 Hz, 1 H), 7.38 (d, J ¼ 7.7 Hz, 1 H), 7.54 (d, J ¼ 9.5 Hz, 1 H), 7.15–7.38
(m, 7 H), 7.73–7.8 (m, 2 H), 7.78 (d, J ¼ 7.9 Hz, 1 H), 10.1 (S, 1 H). 13C NMR
(75.43 MHz, DMSO) 156.1, 152.91, 142.44, 132.04, 129.25, 128.54, 128.34, 128.07,
126.55, 126.33, 125.98, 122.91, 122.5, 118.9, 118.5, 60.11, 50.32, 14.59. LC-MS
(ESI) m=z: 344 ([Mþ Na]þ).
Ethyl [(2-hydroxynaphthalen-1-yl)(4-methoxyphenyl)methyl]carbamate
(Table 2, Entry 2). FT-IR (KBr): 3417, 2956, 1673, 1510, 1176, 1041, 938, 749 cmꢀ1
.
1H NMR (300 MHz, DMSO) d ¼ 1.14 (3 H, t, J ¼ 7.33 Hz), 3.39 (s, 3 H), 4.01
(q, J ¼ 3.66 Hz, 2 H), 6.79 (m, 3 H), 7.13 (d, J ¼ 8.43 Hz, 1 H), 7.24 (m, 4 H), 7.38
(t, J ¼ 7.69 Hz, 1 H), 7.74–7.81 (m, 2 H), 7.91 (d, J ¼ 8.06 Hz, 1 H), 10.1 (S, 1 H).

100
K. M. DESHMUKH ET AL.
13C NMR (75.43 MHz, DMSO) 157.91, 156.04, 152.79, 134.32, 132.03, 129.19,
128.58, 128.40, 127.28, 126.56, 122.96, 122.56, 119.04, 118.55, 113.55, 60.11, 55.01,
50.06, 14.63. LC-MS (ESI) m=z: 374 ([Mþ Na]þ).
Ethyl [(2-hydroxynaphthalen-1-yl)(3-nitrophenyl)methyl]carbamate
(Table 2, Entry 3). FT-IR (KBr): 3390, 3269, 3076, 2917, 2851, 1676, 1519, 1242,
1
1042, 806 cmꢀ1. H NMR (300 MHz, DMSO) d ¼ 1.16 (t, J ¼ 6.48 Hz, 3 H), 3.38
(q, J ¼ 6.4 Hz, 2 H), 6.92 (d, J ¼ 7.5 Hz, 1 H), 7.18–8.09 (m, 11 H), 10.2 (S, 1 H).
13C NMR (75.43 MHz, DMSO) 156.24, 153.12, 147.74, 145.05, 132.8, 131.88,
129.88, 129.68, 128.66, 128.32, 126.86, 122.67, 121.47, 120.47, 118.42, 117.9, 60.31,
49.92, 14.55. LC-MS (ESI) m=z: 389 ([Mþ Na]þ).
Phenyl [(2-hydroxynaphthalen-1-yl)(4-methoxy-phenyl)methyl]carbamate
(Table 2, Entry 4). FT-IR (KBr): 3317, 3004, 1695, 1510, 1334, 1246, 1037, 942,
1
836, 749 cmꢀ1. H NMR (300 MHz, DMSO) d ¼ 3.68 (S, 3 H), 6.74 (d, J ¼ 8.79 Hz,
2 H), 6.89–6.96 (m, 3 H), 7.09–7.22 (m, 7 H), 7.65–7.73 (m, 3 H), 8.85 (d, J ¼ 8.06 Hz,
2 H), 9.6 (S, 1 H). 13C NMR (75.43 MHz, DMSO) 157.99, 154.21, 152.86, 151.02,
133.7, 131.96, 129.29, 129.19, 128.52, 128.4, 128.15, 127.33, 126.42, 124.98, 123.08,
122.47, 121.74, 118.43, 113.57, 54.98, 50.12. LC-MS (ESI) m=z: 422 ([Mþ Na]þ).
Phenyl [(2-hydroxynaphthalen-1-yl)(3-nitro-phenyl)methyl]carbamate
(Table 2, Entry 5). FT-IR (KBr): 3313, 3076, 1700, 1597, 1346, 1230, 1034,
1
842 cmꢀ1. H NMR (300 MHz, DMSO) d ¼ 6.99 (d, J ¼ 6.59 Hz, 1 H), 7.14–7.4 (m,
8 H), 7.54 (d, J ¼ 8.06 Hz, 2 H), 7.8–7.9 (m, 3 H), 8.18 (d, J ¼ 8.43 Hz, 1 H), 8.52 (S,
1 H), 10.2 (S,1 H). 13C NMR (75.43 MHz, DMSO) 154.61, 153.28, 150.98, 150.21,
146.15, 131.94, 130.09, 129.29, 128.7, 128.43, 127.26, 126.83, 125.17, 123.42,
122.91, 122.69, 121.82, 118.37, 117.49, 50.4. LC-MS (ESI) m=z: 437 ([Mþ Na]þ).
Phenyl [(2-hydroxynaphthalen-1-yl)(4-carboxy-phenyl)methyl]carba-
mate (Table 2, Entry 6). FT-IR (KBr): 3417, 3296, 2967, 1679, 1604, 1516, 1250,
1
815 cmꢀ1. H NMR (300 MHz, DMSO) d ¼ 6.99 (d, J ¼ 7.69 Hz, 1 H), 7.14–7.19
(m, 3 H), 7.22–7.31 (m, 2 H), 7.34–7.44 (m, 5 H), 7.8–7.91 (m, 5 H), 8.4 (S, 1 H),
10.2 (S, 1 H), 12.8 (S, 1 H). 13C NMR (75.43 MHz, DMSO, TMS) 167.19, 154.55,
153.16, 151.04, 147.24, 132.02, 129.8, 129.35, 129.29, 129.04, 128.65, 128.46, 126.66,
126.21, 125.13, 123.15, 122.63, 121.85, 118.4, 118.01, 50.48. LC-MS (ESI) m=z: 438
([Mþ Na]þ).
ACKNOWLEDGMENT
The financial assistance from the Indira Gandhi Centre for Atomic Research
(IGCAR), Kalpakkam, India, is gratefully acknowledged.
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