Synthesis of 1-carbamatoalkyl-2-naphthols in Tween 20 aqueous micelles

Article abstract of DOI:10.3184/174751913X13647554585207

A facile and efficient procedure for the preparation of 1-carbamatoalkyl-2-naphthols by a one-pot multi-component reaction of 2-naphthol, aldehydes and carbamates is described. The procedure is carried out under neutral conditions at 75-80 °C in an aqueous medium catalysed by the non-ionic surfactant Tween A loading of 20. 5 wt% of the catalyst was optimal. After the reaction, the catalyst could be simply recovered and reused directly without any further treatment. Product yields were slightly decreased after six cycles. The effect of some common solvents other than water on the reaction was explored besides the water. The generality of this multi-component condensation reaction was evaluated with various aldehydes and carbamates under the optimised conditions.

Full text of DOI:10.3184/174751913X13647554585207

JOURNAL OF CHEMICAL RESEARCH 2013
RESEARCH PAPER 279
MAY, 279–281
Synthesis of 1-carbamatoalkyl-2-naphthols in Tween® 20 aqueous
micelles
Jin-ming Yang, Chen-njing Jiang, Hao Dong and Dong Fang*
Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, YanchengTeachers University,
Yancheng 224002, Jiangsu, P. R. China
A facile and efficient procedure for the preparation of 1-carbamatoalkyl-2-naphthols by a one-pot multi-component
reaction of 2-naphthol, aldehydes and carbamates is described. The procedure is carried out under neutral conditions
at 75–80 °C in an aqueous medium catalysed by the non-ionic surfactant Tween® A loading of 20. 5 wt% of the catalyst
was optimal. After the reaction, the catalyst could be simply recovered and reused directly without any further treat-
ment. Product yields were slightly decreased after six cycles. The effect of some common solvents other than water
on the reaction was explored besides the water. The generality of this multi-component condensation reaction was
evaluated with various aldehydes and carbamates under the optimised conditions.
Keywords: 1-carbamatoalkyl-2-naphthols, Tween®, 2-napthol, aldehydes, alkyl carbamates
Water is becoming a more attractive solvent for economic and
environmental reasons.1 It has attracted much attention in
organic synthesis because of its unique effects on reactions,
which cannot be achieved using organic solvents.2 Addition-
ally, procedures do not requiredrying of solvents, substrates
and reagents.
The poor solubility of organic reactants in water is the main
obstacle to using water as a reaction medium in many cases.
To solve the problem, surfactants have been applied as
emulsifiers, and complexing agents in aqueous reactions, or as
solubilisers for biological systems on an industrial scale.3,4 It
is known that surfactants solubilise nucleophilic reagents,
enhance the nucleophilicity of anions5 and improve rates of
reaction by increasing the interfacial area.
Carbamates show important of biological activity and are
Found:in drugs such as nucleoside antibiotics and HIV prote-
ase inhibitors.6 In particular, 1-carbamatoalkyl-2-naphthol
derivatives exhibit a broad spectrum of biological and
pharmaceutical activities.7 They can be prepared by the multi-
component reaction (MCR) of 2-naphthol, aldehydes and
carbamates.8 The condensation is catalysed by various homo-
geneous and heterogeneous Lewis or Brønsted acids including
SiO2-NaHSO4,9 SiO2–HClO4,10 SiO2–PPA,11 zwitterionic-type
molten salts,12 ionic liquids,13–14 [MeC(OH)2]+ClO4−,15 SiO2-
nanoparticles,16 magneticnanoparticles,17 andMg(OOCCF3)2.18
However, the search for new, environmentally friendly,
efficient and more general kinds of catalysts, including neutral
ones, to synthesise 1-carbamatoalkyl-2-naphthols is ongoing.
Continuing our work on clean MCRs,19 and considering the
importance of reactions in aqueous media, we wish to report
the behavior of Tween® 20, a non-ionic surfactant, as a neutral
catalyst in the synthesis of 1-carbamatoalkyl-2-naphthols by a
three-component condensation (Scheme 1). The effect of the
catalyst, solvent, and other conditions has been investigated.
The reaction is carried out for the first time under neutral
conditions.
Initially, to find the optimal conditions, benzaldehyde,
2-naphthol, and methyl carbamate were selected as the model
reactants under various conditions and loadings of the catalyst
(Table 1). No product was observed in the absence of a catalyst
after 2 H, even at 100 °C. It is noteworthy that the water-
catalyst system could be reused several times without an
appreciable decrease in yield and reaction rate. The reaction of
2-naphthol, benzaldehyde and methyl carbamate proceeded
smoothly in Tween® 20 aqueous media, and the optimal
loading of the catalyst was 5 wt %.
The model reaction was carried out in the presence of 5 wt%
catalyst in different solvents and under solvent-free conditions.
The results are summarised in Table 2. The yields of the reac-
tion in polar solvents such as H2O, EtOH, and CH3CN were
greater than in non-polar solvents and solvent-free conditions.
Of the polar solvents, water gave the best result in terms of
efficiency. The product could be separated from the aqueous
medium (water, catalyst, etc.) simply by filtration and the cata-
lyst contained in the water could be reused directly without
any treatment. Therefore removing water from products was
not a highly energy-consuming process. When the reaction
was completed, the catalyst could be reused at least six
times without appreciable decrease in yield. Any decrease in
Table 1 Optimisation of the condensation of benzaldehyde,
2-naphthol and methyl carbamatea
Entry
Catalytic
system
Loading
/wt%
T/°C
Time
/min
Yield
/%
1
2
3
4
5
6
catalyst free
Tween® 20
Tween® 20
Tween® 20
Tween® 20
Tween® 20
–
1
100
120
45
45
45
45
45
0
61
73
89
89
88
75–80
75–80
75–80
75–80
75–80
3
5
7
10
a Reaction conditions: naphthol (2 mmol), benzaldehyde
(2 mmol), methyl carbamate (2 mmol), catalyst (0.1 mmol),
aqueous media (4 mL).
Table 2 Effects of solvents on reaction of benzaldehyde,
2-naphthol and methyl carbamate
Entry
Solvents
Temperature /°C Time/min Yield/%
1
2
3
4
5
6
7
8
Solvent-free
H2O
100
120
45
45
45
45
45
45
45
23
89
34
46
26
25
31
42
75–80
Reflux
Reflux
Reflux
Reflux
Reflux
100
EtOH
CH3CN
CHCl3
CH2Cl2
Benzene
Toluene
Scheme 1 Synthesis of 1-carbamatoalkyl-2-naphthols.
* Correspondent. E-mail: fangdong106@sina.com

280 JOURNAL OF CHEMICAL RESEARCH 2013
yield might be due to loss of the catalyst in the recycling
procedures.
Lastly, we propose the following possible mechanism to
account for the reaction (Fig. 1). In the micelle neutral aqueous
micelles of Tween® 20, the hydrophobic moieties escape from
the water molecules that encircle the micelle core of the sur-
factant. The reactants are hydrophobic molecules in aqueous
media; they are activated by hydrogen bonding and migrate
into the hydrophobic core of the micellar droplets,20 where the
reactions take place more easily and solid products thus formed
immediately precipitate.
In conclusion, an efficient procedure for the preparation of
2-carbamatoalkyl-2-naphthols by the one-pot three-compo-
nent condensation reaction catalysed by Tween® 20 has been
established. The reaction can be carried out at 75–80 °C in an
aqueous medium. The methodology gives advantages such as
mild conditions, recyclability of the catalyst and easy work-up
and isolation of the products.
In order to evaluate the generality of this multi-component
condensation reaction, the reactions of various aldehydes and
carbamates in the presence of Tween® 20 were explored. As
Table 3 shows, this one-pot, three-component reaction was
completed within 30–60 min and the products were isolated in
moderate to good yields. It noteworthy that aromatic aldehydes
carrying either electron-donating or electron-withdrawing
substituents afforded similarly good yields of the correspond-
ing carbamatoalkyl naphthols. In addition, methyl, ethyl and
benzyl carbamates could also afford reasonable to good yields.
In case of aliphatic aldehydes, the corresponding product
(Table 3 entries 16–18) appeared not to be generated. This
observation is general for aliphatic aldehydes, and the reason
is being investigated. It is intended to extend the method to
reaction of thiocarbamates, ureas, etc.
The results obtained with α-naphthol, benzaldehyde, and
methyl carbamate under the optimised conditions were
compared with those from previous work reported in recent
years using other catalysts for this reaction. The data listed in
Table 4 show that Tween® 20 is a good catalyst for the synthe-
sis of carbamatoalkylnaphthols based on cost-effectiveness,
post-procedure, recyclability and yields.
Experimental
Melting points were measured on an X-6 melting point apparatus with
1
microscope. H NMR spectra were recorded on a Bruker DRX300
(300 MHz) spectrometer and 13C NMR spectra on Bruker DRX300
(75.5 MHz) spectrometer. Mass spectra were obtained with an
automated Fininigan TSQ Quantum Ultra AM (Thermal) LC/MS
spectrometer. Elemental analyses were recorded on a Perkin-Elmer C,
analyser. Tween® 20 (polyoxyethylene 20 sorbitan monolaurate,
C58H114O26; M 1227.5) and other chemicals (AR grade) were commer-
cially available from the Sinopharm Chemical Reagent Co., Ltd, and
were used directly without further treatment.
Table 3 Tween® 20-catalysed three-component reaction of
naphthol, carbamate and various aromatic aldehydesa
Entry
Ar
R
Time Yield/% M.p.
Lit. m.p.
/ °C Ref.
/min
/°C
Synthesis of 1-carbamatoalkyl-2-naphthols; general procedure
In a typical experiment (Scheme 1), β-naphthol (2 mmol), aldehyde
(2 mmol) and carbamate (2 mmol) were added to a round-bottomed
flask charged with a solution of 5 wt% Tween® 20 aqueous micelles
(4.0 mL) under stirring. The mixture was then vigorously stirred at
75–80 °C. After completion of the condensation (monitored by TLC),
1
2
C6H5
4-ClC6H4
2-ClC6H4
Me
Me
Me
45
45
89
90
88
86
92
91
79
78
89
93
92
90
91
87
90
–
220–222 222–22412
201–203 203–20512
3
45
214–216
–
4
2,4-Cl2C6H3 Me
2-NO2C6H4 Me
3-NO2C6H4 Me
4-CH3C6H4 Me
2-CH3C6H4 Me
60
194–196 194–19612
237–239 241–24212
247–249 253–25512
5
30
6
30
7
50
186–188
18817
8
60
229–231 230–23212
179–181 180–18212
Table 4 Comparison of our results with previously reported
methods
9
C6H5
PhCH2
50
10
11
12
13
14
15
16
17
18
2-NO2C6H4 PhCH2
3-NO2C6H4 PhCH2
2-ClC6H4 PhCH2
30
206–208
–
30
201–203 205–20712
166–168 163–16512
196–198 195–19613
Entry
Catalyst
Reaction conditions Time Yields
/min
/%Ref.
50
C6H5
4-ClC6H4
3-NO2C6H4
CH3CH2
n-C3H7
Et
Et
Et
Me
Me
Me
50
1
2
3
4
5
6
7
8
SiO2-NaHSO4
SiO2-HClO4
Neat/ 100 °C
Neat/ 85 °C
Neat/ 100 °C
Neat/ 80 °C
Neat/ 90 °C
3.5 818
45
210–212
–
909
30
222–224 215–21713
5
6
120
2
SiO2-PPA
9010
120
120
120
–
–
–
–
–
–
Zwitterionic salt
Acid ionic liquids
8011
–
8712
n-C4H9
–
[MeC(OH)2]+ClO4− Neat/ 80 °C or EtOAc/rt 27
8514
a Reaction conditions: naphthol (2 mmol), benzaldehyde
(2 mmol), carbamate (2 mmol), catalyst (5 wt. %, 4.0 mL
aqueous micelles).
Mg(OOCCF3)2
Neat/ 100 °C
H2O /75–80 °C
21
45
8517
Tween® 20
89this work
Fig. 1 Suggested mechanism for the formation of 1-carbamatoalkyl naphthol.

JOURNAL OF CHEMICAL RESEARCH 2013 281
the precipitate was filtered off to give the corresponding products. The
crude products were recrystallised from ethanol:H2O (2:1) to afford
pure 1-carbamatoalkyl-2-naphthols. The products obtained were
identified by 1H NMR, and physical data (m.p.) compared with those
reported in the literature (Table 3). The filtrate containing the catalyst
could be reused directly for the next run without any treatment.
Selected spectroscopic data for new compounds are given below.
Methyl[(2-hydroxynaphthalen-1-yl)(2-chlorophenyl)methyl]carba-
mate (Table 3, entry 3): White solid, mp 214-216 °C; 1H NMR (300 MHz,
DMSO-d6), δ 9.96 (s, 1H, OH), 8.04 (d, J = 8.1 Hz, 1H, NH), 7.86 (d,
J = 7.2 Hz, 1H, ArH), 7.77–7.26 (m, 8H, ArH), 7.16 (d, J = 8.4 Hz,
1H, ArH), 6.91 (d, J = 7.8 Hz, 1H, CH), 3.54 (s, 3H, OCH3). 13C NMR
(DMSO-d6, 125 MHz) δ 156.5, 153.9, 139.7, 133.0, 132.9, 130.3,
129.9, 129.7, 129.0, 128.8, 128.7, 126.9, 126.7, 123.3, 122.7, 118.9,
117.4, 51.9, 50.1. LC-MS m/z (%): 340 ([M-H]–, 100 {for35Cl}). Anal.
Calcd for C19H16ClNO3: C, 66.77; H, 4.72; N, 4.10. Found: C, 66.89;
H, 4.63; N, 4.04%.
We express our sincere thanks to the Ministry of Science and
Technology of the P. R. China (11C26213201395), Jiangsu
Provincial Department of Education (JHB2011-52), and the
Key Laboratory of Organic Synthesis of Jiangsu Province
(KJS1112) for financial assistance.
Received 6 January 2013; accepted 22 February 2013
Paper 1301709 doi: 10.3184/174751913X13647554585207
Published online: 15 May 2013
References
1
2
3
4
5
D. Dallinger and C.O. Kappe, Chem. Rev., 2007, 107, 2563.
S. Tiwari and A. Kumar, Angew. Chem. Int. Ed., 2006, 45, 4824.
A.J. Yu, Y.J. Wu and B.L. Cheng, Adv. Synth. Catal., 2009, 351, 767
M.N. Jones, Int. J. Pharm., 1999, 177, 137.
V.M. Torres, M. Posa, B. Srdjenovic and A.L. Simplicio, Colloids. Surf.,
2011, 82, 46.
Benzyl[(2-hydroxynaphthalen-1-yl)(2-nitrophenyl)methyl]carba-
1
6
7
S. Knapp, Chem. Rev., 1995, 95, 1859.
mate (Table 3, entry 10): White solid, m.p. 206–208 °C; H NMR
T. Dingermann, D. Steinhilber and G. Folkers, Molecular biology in
medicinal chemistry, Wiley-VCH: Weinheim, 2004.
I. Szatmári and F. Fülöp, Tetrahedron, 2013, 69, 1255.
H.R. Shaterian, A. Hosseinian and M. Ghashang, Tetrahedron Lett., 2008,
49, 5804.
(300 MHz, DMSO-d6), δ 10.16 (s, 1H, OH), 8.08 (d, J = 7.9 Hz, 1H,
NH), 7.94 (d, J = 8.1 Hz, 1H, ArH), 7.79 (d, J = 8.0 Hz, 1H, ArH),
7.74 (t, J = 7.3 Hz, 2H, ArH), 7.62–7.26 (m, 11H, ArH), 7.08 (d,
J = 8.5 Hz, 1H, CH), 5.12 (d, J = 12.3 Hz, 1H, CH2), 5.06 (d, J =
12.3 Hz, 1H, CH2). 13C NMR (DMSO-d6, 125 MHz) δ 156.3, 154.1,
149.0, 137.5, 136.8, 133.3, 132.5, 130.4, 129.7, 129.4, 128.9, 128.7,
128.5, 128.2, 128.1, 127.8, 127.2, 127.0, 124.5, 123.0, 122.9, 118.8,
116.3, 65.9, 48.3. LC-MS m/z (%): 427 ([M-H]–, 100). Anal. Calcd for
C25H20N2O5: C, 70.09; H, 4.71; N, 6.54. Found: C, 70.21; H, 4.60; N,
6.46%.
8
9
10 H.R. Shaterian, A. Hosseinian and M. Ghashang, Synth. Commun., 2009,
39, 2560.
11 H.R. Shaterian, A. Hosseinian and M. Ghashang, Chin. J. Chem., 2009, 27,
821.
12 D. Kundu, A. Majee and A. Hajra, Catal. Commun., 2010, 11, 1157.
13 N. Tavakoli-Hoseini, M.M. Heravi, F.F. Bamoharran and A. Davoodnia,
Bull. Korean Chem. Soc., 2011, 32, 787.
14 K.M. Deshmukh, Z.S. Qureshi, Y.P. Patil and B.M. Bhanage, Synth.
Commun., 2012, 42, 93.
Ethyl[(2-hydroxynaphthalen-1-yl)(4-chlorophenyl)methyl]carba-
1
mate (Table 3, entry 14): White solid, m.p. 210–212 °C; H NMR
15 F. Tamaddon and J.M. Bistgani, Synlett., 2011, 2947.
16 M.M. Heravi, N. Tavakoli-Hoseini and F.F. Bamoharram, Green Chem.
Lett. Rev., 2010, 3, 263.
17 H. Yarahmadi and H.R. Shaterian, J. Chem. Res., 2012, 36, 52.
18 M.R.M. Shafiee, R. Moloudi and M. Ghashang, J. Chem. Res., 2011, 35,
622.
19 D. Fang, J.M. Yang and C.M. Jiao, Catal. Sci. Technol., 2011, 1, 243.
20 A.A. Jafari, F. Moradgholi and F. Tamaddon, Eur. J. Org. Chem., 2009,
1249.
(300 MHz, DMSO-d6), δ 10.15 (s, 1H, OH), 7.93 (d, J = 8.3 Hz, 1H,
NH), 7.80–7.22 (m, 10H, ArH), 6.87 (d, J = 8.1 Hz, 1H, CH), 4.05
(m, 2H, CH2), 1.17 (t, J = 6.9 Hz, 3H, CH3). 13C NMR (DMSO-d6,
125 MHz) δ 156.5, 153.3, 141.9, 132.3, 131.4, 129.9, 129.0, 128.7,
128.4, 128.2, 127.4, 127.1, 123.6, 123.0, 118.8, 60.7, 50.2, 14.9.
LC-MS m/z (%): 354 ([M-H]–, 100 {for 35Cl}). Anal. Calcd for
C20H18ClNO3: C, 67.51; H, 5.10; N, 3.94. Found: C, 67.70; H, 5.01; N,
3.79%.