A recyclable and highly effective sulfamic acid/EtOH catalytic system in synthesis and natural product chemistry of lignan compounds

Article abstract of DOI:10.14233/ajchem.2013.13071

The utilization of green chemistry techniques is dramatically reducing chemical waste and reaction times and has recently been proven in several organic syntheses and chemical transformations. To illustrate these advantages sulphamic acid is used as a nov

Full text of DOI:10.14233/ajchem.2013.13071

Asian Journal of Chemistry; Vol. 25, No. 2 (2013), 899-904
http://dx.doi.org/10.14233/ajchem.2013.13071
A Recyclable and Highly Effective Sulfamic Acid/EtOH Catalytic System in
Synthesis and Natural Product Chemistry of Lignan Compounds
*
Z. ALI , S. DEO and F. INAM
Department of Chemistry, Institute of Science, R.T. Road, Nagpur-440 001, India
*Corresponding author: E-mail: tanishqmc@rediffmail.com
(Received: 16 November 2011;
Accepted: 25 August 2012)
AJC-12006
The utilization of green chemistry techniques is dramatically reducing chemical waste and reaction times and has recently been proven in
several organic syntheses and chemical transformations. To illustrate these advantages sulphamic acid is used as a novel recyclable
heterogeneous catalyst in the cyclization of Perkin condensation product α-arylidine-β-benzoyl propionic acid to achieve biologically
potent 1-phenylnaphthalene system and pericarbonyl lactone lignans under two experimental conditions i.e., conventional and microwave
irradiation. The generality of this protocol has been demonstrated by synthesizing a variety of substituted 1-phenyl-naphthalene systems
in excellent yields, short reaction time and with good purity.
Key Words: Sulphamic acid/Ethanol system, Lignans, Cyclization, Recyclable system.
INTRODUCTION
EXPERIMENTAL
1-Phenylnaphthalene system attracted special attention of
organic chemists because these are biologically active with
potential applications as antiinflammatory1, antibacterial2,
antioxidant3, anticancer4 and CNS depressants5. 1-Phenyl-
naphthalenes are versatile moieties in that their pendant like
skeleton exists in a number of pharmaceuticals and natural
products. As a result of their importance from industrial,
biological and synthetic point of view, it is desirable to choose
an efficient and versatile protocol for their easy and clean
synthesis.
All the chemicals and reagents were of LR or AR grade
and procured from S.D. Fine Chem. Limited, (Mumbai),
LOBA Chemie, Mumbai, E. Merck (India ) Ltd. and used as
received. IR spectra were recorded on Perkin-Elmer FT spectro-
1
photometer in KBr disc. H NMR were recorded on Varian
300 MHz spectrophotometer in CDCl3 as a solvent and TMS
as an internal standard. Melting points were recorded on a
melting point apparatus with capillary tubes and are uncor-
rected. Analytical TLC was performed on glass slides coated
of silica gel G/UV-254 of 0.2 mm thickness. Elemental analysis
data were recorded using Thermo Finnegan FLASH EA 1112
CHN analyzer. For the microwave irradiation experiments
described below, a conventional (unmodified) house hold
microwave oven equipped with a turn able was used (LG Smart
Chef MS-255r operating at 2450 MHz having maximum
output of 800 W).
The catalytic activity of sulphamic acid (SA) has emerged
as a useful acid imparting high region and chemo selectivity
in various chemical transformations6-9. It is a dry, nonvolatile,
non hygroscopic, odorless and white crystalline solid Bronsted
acid with outstanding physical properties. It is inexpensive,
insoluble in common organic solvents, highly stable and its
zwitterionic property makes its recycling and reuse very conve-
nient10,11
.
Conversion of β-benzoyl propionic acid to α-arylidine-
β-benzoyl propionic acid: For the synthesis of 1-phenyl-
naphthalene system, β-benzoyl propionic acid was taken as a
starting moiety. Perkin condensation of β-benzoyl propionic
acid with aryl aldehyde yields butenolide12 which on cleavage
by methanolic solution of Na2CO3 leads to α-arylidine-β-
benzoyl propionic acid13 (Scheme-I). The system (4) thus
contains the required skeleton to prepare 1-phenylnaphthalene
system and pericarbonyl lactone lignans14,15 (Scheme-II).
We report herein a highly efficient procedure for the
synthesis of various substituted 1-phenylnaphthalene systems
and pericarbonyl lactones using sulphamic acid as an efficient
and versatile catalyst under both methods-conventional and
microwave irradiation.
By the use of microwave in combination with sulphamic
acid, the term "green chemistry" ideally disappears as all
chemistry becomes green.

900 Ali et al.
Asian J. Chem.
Adopting the above described two alternative methods,
four different substituted 1-phenylnaphthoic acids (7a-7d)
were identified and characterized (Table-2).
Path-B
Conversion of α-arylidine β-benzoyl propionic acid (4) to
α-arylidine-β-methylene-β-benzoyl propionic acid (5)
To a solution of α-arylidine-β-benzoyl propionic acid in
10 % aq. NaOH solution was added 40 % formalin solution
and was left overnight. It was then cooled and dried with
anhydrous sodium sulphate. Ethanol is added to separate the
product. Evaporation of solvent gave a gummy solid which
was crystallized from ethanol/water to give α-arylidine-β-
methylene-β-benzoyl propionic acid. The IR spectra of (5)
showed broad peak at 1660 cm-1 for carboxyl and keto group.
Cyclization of α-arylidine-β-methylene-β-benzoyl propi-
onic acid (5) to 1-phenyl naphthalene lactone/pericarbonyl
lactone (8)
Conventional method:A mixture of 1 mmol of α-arylidine-
β-benzoyl propionic acid, 0.2 mmol (20 mmol %) sulphamic
acid and ethanol 10 mL was taken as a reaction solvent and
stir the mixture vigorously (using magnetic stirrer) by keeping
in reflux at 118-120 ºC for an appropriate time (Table-1). The
reaction was worked-up and purified as described above (Path-A).
Microwave irradiation:The reaction mixture as specified
above was taken in a dry 250 mL beaker. It was mixed properly
with the help of glass rod. An inverted funnel was placed over
the rim of the beaker and irradiated in a microwave oven at
800 W for 14-15 min while monitoring the reaction with the
help of TLC. After the completion of the reaction, immediate
temperature of the reaction mixture was taken out by the
thermometer, which is recorded as 75 ºC.The reaction was
worked-up and purified to give 1-phenyl-naphthalene lactone/
pericarbonyl lactone.Adopting the above described two alterna-
tive methods, four different substituted 1-phenyl naphthalene
lactones (8a-8d) were identified and characterized (Table-2).
Scheme-I
Path-A
Cyclization of α-arylidine-β-benzoyl propionic acid (4) to
1-phenylnaphthoic acid (7)
Conventional method:A mixture of 1 mmol of α-arylidine-
β-benzoyl propionic acid, 0.2 mmol (20 mmol %) sulphamic
acid and ethanol (taken in excess: 10 mL) was taken as a
reaction solvent in 250 mL round bottom flask. Stir the mixture
vigorously by keeping in reflux at 118-120 ºC for an appropriate
time as mentioned in Table-1. After completion of reaction as
indicated by TLC, the reaction mixture was cooled at room
temperature and diluted with diethyl ether [3 × 10 mL] to preci-
pitate sulphamic acid. Thus sulphamic acid could be separated
easily. The combined organic layers were dried over anhydrous
Na2SO4. The solvent was removed and the residue was column
chromatographed using petroleum ether:ethyl acetate (2:3) as
the eluent, to obtain pure compound.
Path-C
Conversation of α-arylidine-β-benzoyl propionic acid
(4) to methyl-α-arylidine-β-benzoyl propionic acid (6):
α-Arylidine-β-benzoyl propionic acid was converted to its
ester by CH2N2 to give methyl-α-arylidine-β-benzoyl propionic
acid having melting point of 96 ºC. Its IR spectra showed
absorption at 1680 cm-1.
Cyclization of methyl α-arylidine-β-benzoyl propionic acid
(6) to 1-phenyl naphthoate (9)
Conventional method:A mixture of 1 mmol of α-arylidine-
β-methylene-β-benzoyl propionic acid, 0.2 mmol (20 mmol %)
sulphamic acid and ethanol 10 mL was taken as a reaction
solvent and stir the mixture vigorously (using magnetic stirrer)
by keeping in reflux at 118-120 ºC for an appropriate time
(Table-1). The reaction was worked-up and purified (likewise
Path-A) to give 1-phenylnaphthoate.
Microwave irradiation:The reaction mixture as specified
above was taken in a dry 250 mL beaker. It was mixed properly
with the help of glass rod. An inverted funnel was placed over
the rim of the beaker and irradiated in a microwave oven at
800 W for 14-15 min while monitoring the reaction with the
help of TLC. After the completion of the reaction, immediate
temperature of the reaction mixture was taken out by the
thermometer, which is recorded as 75 ºC.The reaction was
worked-up and purified as described above under conventional
method.
Microwave irradiation:The reaction mixture as specified
above was taken in a dry 250 mL beaker. It was mixed properly
with the help of glass rod. An inverted funnel was placed over
the rim of the beaker and irradiated in a microwave oven at
800 W for 14-15 min while monitoring the reaction with the

Vol. 25, No. 2 (2013)
Highly Effective Sulfamic Acid/EtOH Catalytic System in Synthesis of Lignan Compounds 901
Scheme-II

902 Ali et al.
Asian J. Chem.
TABLE-1
COMPARATIVE DATA ON CONVENTIONAL ACID AND GREEN ACID CATALYZED
SYNTHESIS OF 1-PHENYLNAPHTHALENE SYSTEMS
Time (min)
H2SO4 Green-sulphamic acid
Yield (%)
H2SO4 Green-sulphamic acid
m.p. (ºC)
Found Lit.
Entry Productsa
PPA
PPA
OB
60
60
60
60
60
60
60
60
60
60
60
60
CC
MS
90
88
90
88
90
88
90
89
90
89
88
89
MW
15
OB
85
84
78
82
82
83
78
84
80
83
82
83
CC
85
85
78
81
80
83
78
82
79
83
82
83
MS
93
93
85
89
95
88
86
92
92
90
91
91
MW
96
95
85
96
94
92
89
95
94
92
95
94
1
2
7a
7b
7c
7d
8a
8b
8c
8d
9a
9b
9c
9d
1440
1440
1440
1440
1440
1440
1440
1440
1440
1440
1440
1440
215-217
238-240
177-179
220-223
203-205
209-211
209-210
233-235
122-124
170-171
150-152
130-132
217-218 [12]
238-239 [12]
179-180 [12]
221-223 [12]
203-205 [12]
208-209 [12]
209-210 [14]
231-233 [14]
123-124 [14]
169-171 [14]
152-153 [14]
130-132 [14]
14.5
15
3
4
14.5
15
5
6
14.5
15
7
8
14
9
15
10
11
12
14.5
14.5
15
aYields refer to pure isolated products; OB = Oil bath; CC = Cold condition; MS = Magnetic stirrer; MW = Microwave.
TABLE-2
CHARACTERIZATION AND SPECTRAL ANALYSIS OF 1-PHENYLNAPHTHALENE SYSTEMS
Elemental analysis
(%): Obs. (calcd.)
Sr.
No.
1-Phenylnaphthalene system
m.f.
IR (cm–1)
NMR (δ)
C
H
C19H16O4
C19H12O4
C18H1404
74.75
(74.02)
5.24
(5.19)
1680
1680
1681
3.84 (s, 6H, 20 CH3), 7.2 (s, 1H, C8-H), 7.35(s, 1H, C5-
H), 7.43-7.85 (5H, Phenyl) & 8.45(s, 1H, C4-H)
1
2
3
7a (1-Phenyl -6,7-dimethoxy
naphthalene 3-carboxylic acid)
75.24
(75.00)
3.96
(3.94)
–
7b (1-Phenyl-6,7-methylenedioxy
naphthalene-3-carboxylic acid)
74.22
(73.46)
4.81
(4.46)
4.1(s, 10 CH3), 4.5(s, 1H, OH aromatic protons), 7.0
(s, 1H, C8-H), 7.0-8.8 (s, aromatic protons), 7.5(m, 5H,
Phenyl)
7c (1-Phenyl-6-methoxy,7-
hydroxy-naphthalene-3-
carboxylic acid)
C20H1605
C20H16O4
72.07
(71.42)
4.80
(4.80)
1683
1760
3.8-3.9-3.95 (s, 9H, 3 OCH3), 6.5-8.5 (m, aromatic
protons, 7.5(m, 5H, phenyl)
4
5
7d (1-Phenyl-6,7,8-trimethoxy
naphthalene-3-carboxylic acid)
75.04
(75.47)
5.39
(5.03)
3.86 & 4.06 (s, 6H, 2-OCH3)5.22 (s, 2H, Lactone
CH2), 7.16 (s, 1H, C8- H), 7.37(s, 1H, C5 - H) 7.6 (br, s,
5H.phenyl) & 8.36 (s, 1H, C4 -H)
8a (1-Phenyl-6,7-dimethoxy
naphthalene lactone)
C19H12O4
C20H1604
C21H1905
75.01
(75.12)
3.87
(3.94)
1762
1761
1762
5.23, (s, 2H lactone CH2), 6.10(s, 2H, O-CH2O-) 7.13-
7.4, (d, 6H, aromatic), 8.28(s, 1H, C4-H)
6
7
8
8b (1-Phenyl-6,7-methylenedioxy
naphthalene lactone)
75.02
(75.00)
5.01
(5.08)
3.83, (s, 3H, 10CH3), 5.20 (s, 2H, lactone CH2), 7.04-
7.30(m, 7H, 1H, OH aromatic), 8.25 (s, 1H, C4 -H )
8c (1-Phenyl-6-methoxy-7-
hydroxy-naphthalene lactone)
71.48
(71.79)
5.70
(5.41)
3.90, 4.01, 4.25(s, 9H, 3-OCH3 ), 5.30 (s, 2H,
lactoneCH2), 7.1- 7.7 (m, 6H, aromatic), 8.4(s, 1H, C4 -
H)
8d (1-Phenyl-6,7,8-trimethoxy
naphthalene lactone)
C20H18O4
C21H14O4
74.14
(74.52)
5.52
(5.88)
1720
1720
3.85, 3.96, 4.03 (s, 9H, CO2, CH3, OCH3), 7.24 &7.30
(s, sh) C3-H & C8-H), 7.85 (s, sh, phenyl), 7.9 (d, J =
2H2, 1H, C4-H), 8.47(d, J = 2H2, C2 -H)
4.02 (s, 3H, OCH3), 5.94 (s, 2H, OCH2O-), 7.32&7.38
(5(sh)2H, C5-H & C8-H), 7.60 (s, sh, phenyl), 8.04 (d,
J = 2H2, 1H, 2H) and 8.86 (d, J = 2H2, 1H, C4 - H)
–
9
9a (1-Phenyl-3-carbomethoxy-
6,7-dimethoxy naphthoate)
76.19
(76.36)
4.12
(4.24)
10
9b (1-Phenyl-3-carbomethoxy-
6,7-methylenedioxy naphthoate)
C19H18O4
C21H22O5
73.38
(73.54)
5.68
(5.80)
1720
1720
11
12
9c (1-Phenyl-6-methoxy-7-
hydroxy-naphthoate)
71.02
(71.18)
6.05
(6.21)
–
9d (1-Phenyl-3-carbomethoxy-
6,7,8-trimethoxy naphthoate)
help of TLC. After the completion of the reaction, immediate
temperature of the reaction mixture was taken out by the
thermometer, which is recorded as 75 ºC.The reaction was
worked -up and purified to give 1-phenyl-naphthoate. Adopting
the above described two alternative methods, four different
substituted 1-phenylnaphthoates (9a-9d) were identified and
characterized (Table-2).
RESULTS AND DISCUSSION
To prepare 1-phenylnaphthalene system and pericarbonyl
lactone lignans, β-benzoyl propionic acid16 was used which
has two reactive methylene groups and a carboxylic functional
group which could lead to the basic skeleton of lignans. The
carboxyl group would yield part of furan ring and the oxo

Vol. 25, No. 2 (2013)
Highly Effective Sulfamic Acid/EtOH Catalytic System in Synthesis of Lignan Compounds 903
R1
COOR
R1
R2
R1
R2
COOR
COOR
R2
C
- HOH
O
C
R3
HO
R3
R3
Scheme-III
group could be reduced. β-Benzoyl propionic acid with aryl
aldehydes underwent Perkin condensation at α-methylene to
give α-arylidine-β-benzoyl propionic acid (Scheme-I). This
condensation reaction is restricted to aldehydes having hydroxyl,
methoxy or methylenedioxy groups at para positions only17.
Further cyclization of Perkin condensation product-α-arylidine-
β-benzoyl propionic acid using sulphamic acid gives 1-phenyl-
naphthalene system and pericarbonyl lactone lignans under
two experimental conditions-conventional and microwave
(Scheme-II).
have been plagued by a number of serious disadvantages. Now
we have found an analogous cyclization reaction which can
be conveniently performed under neutral and mild conditions
in the presence of catalytic amount of sulphamic acid under
the cooperative effect of microwave radiation and a novel
conventional refluxing/stirring method.
When compared to other acid catalysts, the use of
sulphamic acid facilitated the smooth conduct of the cycli-
zation reactions. The work out of the product was very simple
and better yields were recorded. As expected, the alternative
microwave-assisted method was found to be more convenient
over that of conventional, in terms of considerable reduction
in reaction time, improved yields and facile nature of reaction.
In this method the use of 20 mol % of the catalyst was
quite sufficient to promote the reaction; higher amount of the
catalyst did not improve the yield. The use of sub-stoichio-
metric quantity of sulphamic acid indicated its true catalytic
nature and also gave an advantage over other classical Bronsted
acids. Recovery of catalyst was very easy so that the sulphamic
acid could be recycled upto three cycles without significant
loss in its activity (Table-3).
To extend the scope of reaction and to generalize the
procedure, we carried out the reaction of β-benzoyl propionic
acid with a series of aryl aldehydes (veratraldehyde, pipernol,
vanillin, 3,4,5-trimethoxy-benzaldehyde) to obtain the corres-
ponding 1-phenylnaphthalene systems 7a-d, 8a-d and 9a-d
by adopting the above described two alternative methods. All
the cyclized products have been characterized by their IR, 1H
NMR spectral values and elemental analysis (Table-2).
The synthesis of (4) to (7) and (6) to (9) takes place
involving keto-enol tautomerism followed by removal of H and
OH. While in system (5) (α-arylidine-β-methylene-β-benzoyl
propionic acid) there is hyper-conjugation at CH2 and cyclization
take place by keto-enol tautomerism. The aromatic atmosphere
spread is more on S-cis butadiene than S-trans orientation.
Though the S-trans is more stable, here S-cis has more chance
to exit. Hence the facile cyclization via keto-enol tautomeri-
zation which in turn existed due to hyper conjugation which
is possible due to methylene group. All these intermediate
structures drive the reaction towards aryl lactonization via
cyclization by removal of H and OH and simultaneous tauto-
merism at the COOH and positive CH2 positive centre which
leads to the formation of pericarbonyl lactone.
TABLE-3
RECYCLABILITY OF SULPHAMIC ACID
IN THE CYCLIZATION REACTIONS
Yield (%) 7a
Yield (%) 8a
Yield (%) 9a
Cycle
No.
Conv.
MW
96
Conv.
MW
94
Conv.
MW
94
Fresh
93
92
90
88
95
94
92
91
92
91
90
88
1
2
3
95
93
92
94
91
91
92
90
88
aIsolated yield.
The literature survey disclose plethora of cyclizing
reagents such as H2SO4, polyphosphoric acid18, CH3COOH/
HCl19,20, lead tetra acetate21 for the synthesis of 1-phenylnaph-
thalene system. However, processes involving conventional
acids are inherently associated with problems such as high
toxicity, corrosion, catalyst waste, difficulty in separation and
recovery. Replacement of these conventional acids by solid
catalyst is desirable to achieve effective catalyst handling,
product purification and to decrease waste production.
Also the above conventional cyclization reactions have
been done using traditional heat transfer equipments such as
oil-bath, sand bath and heating jackets. These heating techni-
ques are however, rather slow and a temperature gradient can
develop. Therefore it is seen that above cyclization reactions
Conclusion
In summary, we have developed a simple and general
method for the synthesis of 1-phenylnaphthalene system and
pericarbonyl lactone lignans by using sulphamic acid as a
recyclable heterogeneous catalyst under the cooperative effect
of microwave radiation and a novel conventional method. The
procedure is convenient and highly efficient since the titled
compounds are produced in good to excellent yields after shot
reaction times. Moreover, sulphamic acid showed high thermal
stability and can be recovered and reused for at least three
consecutive cycles without significant loss of its activity. Conse-
quently, our method can be as a viable alternative to the
presently existing procedures.

904 Ali et al.
Asian J. Chem.
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