β-Cyclodextrin-mediated highly efficient [2+3] cycloaddition reactions for the synthesis of 5-substituted 1H-tetrazoles

Article abstract of DOI:10.1039/c3nj00569k

A β-cyclodextrin-promoted [2+3] cycloaddition reaction between nitriles and sodium azide in the presence of ammonium chloride in DMF at 120 °C is reported, affording various 5-substituted 1H-tetrazoles in good to excellent yields in short reaction times. The presence of β-CD renders the formation of a precipitate-like gel in the reaction media when heated. No precipitation occurs in the absence of NaN₃ and NH₄Cl. The precipitation responses with other salts such as LiCl and NiCl₂ were weaker than with NH₄Cl. In the present paper the application of supramolecular aggregates is reported for the [2+3] cycloaddition reaction. β-Cyclodextrin can be recovered and reused without any significant loss of activity.

Full text of DOI:10.1039/c3nj00569k

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Graphical Abstract:
βꢀCD has been reported as an effective supramolecular catalyst for [2+3] cycloaddition reaction.

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βꢀCyclodextrin mediated highly efficient [2+3] cycloaddition reaction for
synthesis of 5ꢀsubstituted 1Hꢀ tetrazoles
a
a
b
b
a
Dipak R. Patil , Yogesh B. Wagh , Pravin G. Ingole , Kripal Singh , Dipak S. Dalal *
a
Department of Organic Chemistry, School of Chemical Science, North Maharashtra University, Jalgaon ꢀ 425
001, M. S., India.
b
Central Salt and Marine Chemicals Research Institute, Council of Scientific and Industrial Research (CSIR),
Bhavnagar ꢀ 364 021, Gujarat, India.
Fax +91ꢀ2572258403 Email: dsdalal2007@gmail.com
Abstract βꢀCyclodextrin promoted [2+3] cycloaddition reaction between nitriles and sodium
0
azide in presence of ammonium chloride in DMF at 120 C is reported affording various
5
ꢀsubstituted 1Hꢀtetrazoles in good to excellent yields in short reaction times. The presence
of βꢀCD renders the formation of precipitateꢀlike gel in reaction media under the thermal
effect. No precipitation occurs in absence of NaN as well as NH Cl. The precipitation
responses with other salts such as LiCl, NiCl were weaker than with NH Cl. In present paper
3
4
2
4
the application of supramolecular aggregates reported for the [2+3] cycloaddition reaction.
The βꢀcyclodextrin can be recovered and reused without significance loss of activity.
Keywords βꢀCyclodextrin (βꢀCD), [2+3]ꢀCycloaddition, 5ꢀSubstituted 1Hꢀtetrazoles.
Introduction
Tetrazoles are the class of heterocyclic compounds which has wide range of applications like
1
in coordination chemistry as ligands, in medicinal chemistry as isosteric replacement for
2
3
carboxylic acid in drug design, as precursors of different nitrogen containing heterocycles,
4
5
in material science as explosive and in information recording system. Tetrazoles have
similar acidities to those of carboxylic acids; they have been used in drugs as replacement for
the COOH unit when the carboxylic acid has unsatisfactory properties for human medicine. A
1

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simple example is the antiꢀarthritis drug indomethacin whose carboxylic acid group may be
6
replaced by tetrazole with no loss of activity. Tetrazole moieties has also been incorporated
7
into angiotensin II antagonist structures sartans (Losartan, Valsartan and BMSꢀ183920) (Fig.
1).
N
N
N
HN
N
N
N
N
HOOC
N
N
N
N
N
H
H
O
MeO
N
O
N
N
N
O
N
N
NH
HO
HO
N
O
Cl
Indomethacinꢀantiarthritis drug
Cl
Losartan
Valsartan
BMSꢀ183920
Fig. 1 Bioactive tetrazole moieties.
Conventional method for synthesis of 5ꢀsubstituted 1Hꢀtetrazole is via [2+3]
8
,9
cycloaddition between an azide and nitrile. Recently Sharpless and coꢀworkers reported a
“
click” chemistry approach for synthesis of tetrazoles by [2+3] cycloaddition of nitriles and
1
0,11,12
NaN
3
using stoicheometric amounts or 50 mol % of Zn(II) salts
but still requires
tedious time consuming steps such as removal of zinc salts from acidic products. Earlier
reported methods for synthesis of 5ꢀsustituted 1Hꢀ tetrazole suffer from drawback such as the
use of strong lewis acids or expensive and toxic metals. In order to overcome these
1
3,14
difficulties several new pathways have been developed such as use of metal complexes
as
1
5
16
17
18
a catalyst, use of TMSN
3
ꢀTBAF, FeCl
3
ꢀSiO
2
,
Zn/Alꢀhydrocalcite, Fe
2
O
3
,
Zn
1
9
20
21
22
Hydroxyapatite, Sb
2
O
3
, NaHSO
4
.SiO
2
or I
2
, Mesoporous ZnS nanospheres, Tungstates
2
3
24
as novel heterogeneous catalyst and CuFe O . The catalytic role of βꢀCD for the synthesis
2
4
of 5ꢀphenyl 1Hꢀtetrazole has been compared with various reported catalyst (Table 1).
However some of these methods still require long reaction times to achieve reasonable yields,
environmentally hazardous catalysts and tedious purification of products.
2

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Table 1 Comparison for preparation of 5ꢀphenyl 1H tetrazole with various reported catalyst.
Entry
Catalyst
Time (h)
24
Yield (%)
Ref.
[10]
[15]
[16]
[17]
[18]
[19]
[20]
[24]
1
2
3
4
5
6
7
8
ZnBr (in H O)
76
86
79
84
81
78
86
82
2
2
TMSN
3
ꢀTBAF.3H
2
O
18
FeCl
Zn/Al hydrocalcite
Fe
Zn Hydroxyapatite
Sb
CuFe O4
3
ꢀSiO
2
12
12
2
O
3
36
12
2
O
3
08
12
2
Cyclodextrins are cyclic oligomers of Dꢀglucose and are named α, β and
2
5
γꢀ cyclodextrin for hexamer, heptamer and octamer respectively. They have toroidal cyclic
structure (Fig. 2) with secondary hydroxyl glucose Cꢀ2 and Cꢀ3 on their more open face and
26
the primary Cꢀ6 hydroxyl group on primary face. They catalyze reaction by supramolecular
catalysis involving the formation of hostꢀguest complexes by non covalent bonding
27
interactions. The internal cavity of cyclodextrin molecule is strongly hydrophobic in nature
and this particular characteristic of cyclodextrin molecule enables them to bind with wide
2
8
range of guest molecules. Cyclodextrin binds with substrate in its hydrophobic cavity and
catalyze reactions in selective manner. Supramolecular catalysis is the discipline chemistry
which involves all intermolecular interactions where covalent bonds are not established
29
between interacting species that is molecules, ions or radicals. Among various
cyclodextrins, βꢀCD as a catalyst is attractive since it is useful both from economic and
3
0
environment point of view, apart from being non toxic, metabolically safe and can also be
readily recovered and reused.
3

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Fig. 2 The chemical structure (A) and the toroidal shape (B) of βꢀcyclodextrin molecule.
Literature survey shows that some of the organic molecules bind with cyclodextrins
by supramolecular interactions in the nonꢀaqueous solvent like dimethyl sulfoxides (DMSO),
31
DMF, acetonitrile, etc. Hostꢀguest interactions of cyclodextrin with guest were efficiently
32, 33
employed in constructing the supramolecular gel.
The earlier expertise in the field of
3
4ꢀ37
biomimetic modeling of organic chemical reaction involving cyclodextrins,
continuation
38
of our work in the field of βꢀCD and the complex forming ability of βꢀCD by
supramolecular interaction in nonꢀaqueous solvent like DMF studied by Guang Yan Du et
39
al. prompted us to attempt the synthesis of 5ꢀsubstituted 1Hꢀtetrazoles.
Results and Discussion
In order to optimized the reaction condition and performance of βꢀCD as a catalyst for [2+3]
cycloaddition, the reaction between benzonitrile, NaN and NH Cl has been selected as a
3
4
model reaction for synthesis of 5ꢀ phenyl 1Hꢀtetrazole using different reaction parameters
Table 2). The NH Cl has been choose as it helps in situ formation of ammonium azide by its
reaction with NaN
(
4
4
0
3
4
in DMF. The reaction does not proceed in absence of NH Cl. The best
result was obtained for 2 mmol of βꢀCD (Table 2, entry 4) affording 89% of 5ꢀphenyl 1Hꢀ
tetrazole in 0.75 h. Further increase in amount of catalyst has no significant effect on the
yield as well as reaction time (Table 2, entry 5ꢀ8). The reaction in water (Table 2, entry 9)
4

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does not give the product because no formation of gel like precipitate occurs in presence of
water. Where as in DMFꢀH O (7:3) and DMSO, only partial formation of gel like precipitate
2
occurs affording only 47% (Table 2, entry 10) and 61% (Table 2, entry 11) of product
3 4
respectively. The increase in amount of NaN and NH Cl from 13 to 15 mmol was found to
be no effect on the yield (89%). The role of βꢀCD as a catalyst has been confirmed when
similar reaction was carried out in absence of catalyst (Table 2, entry 1) giving only 86% of
yield with longer reaction time of 8 h. It indicates that βꢀCD not only improves the yield of
product but also accelerate the rate of [2+3] cycloaddition reaction.
N
β-CD
N
N
C N
+
NaN3
R
N
H
R
NH Cl, DMF,
4
0
1
20 C
1
a-q
2
3
a-q
Scheme 1 A general scheme for synthesis of 5ꢀsubstituted 1Hꢀtetrazole
a
Table 2 Formation of 5ꢀphenyltetrazole using various reaction conditions.
b
Entry
Solvent
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
Water
DMFꢀH
βꢀCD (mmol)
ꢀ
0.5
1
2
3
4
5
10
2
Time (h.)
8
2.5
2
0.75
0.75
1
Yield (%)
1
2
3
4
5
6
7
8
9
86
80
88
89
89
88
87
89
ꢀ
1
1.25
15
12
10
2
O
2
47
(7:3)
1
1
DMSO
2
6
61
a
Reaction was carried out with benzonitrile (10 mmol), NaN
chloride (13 mmol), solvent (25 mL) and catalytic amount of Betaꢀcyclodextrin , Isolated
yield.
3
(13 mmol), ammonium
b
The significant presence of βꢀCD has great influence on reaction time as well as yield
(Table 3, entry 1). The reaction was also carried out in presence of salts like Li and Ni salts in
order to check their azide ion releasing capacity and its influence on precipitateꢀlike gel
5

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formation but affording only 67% and 46% of product respectively. The comparative study
for synthesis of 5ꢀphenyl 1Hꢀtetrazole with and without catalyst is shown in Fig. 3. The
novelty of reaction is that, the presence of βꢀCD leads to the formation of precipitation like
gel that makes the clear visible difference between active role of presence and absence of
catalyst for these reactions. Temperature plays an important role as surprisingly there were no
precipitations occurs at lower temperature and reaction does not proceed. The system is
multicomponent solution in which each of components is required for formation of
precipitation.
Fig. 3 Comparisons of reaction without and with βꢀCD
Where, A: Reaction without βꢀCD at zero time, B: Reaction with βꢀCD at zero time, C: Reaction without βꢀCD
after 0.25h, D: Reaction with βꢀCD after 0.25h, E: Reaction without βꢀCD after 0.75h, F: Reaction with βꢀCD
after 0.75h
A variety of structurally divergent nitriles possessing a wide range of functional
groups (Scheme 1) selected to understand the scope and generality of the βꢀCD promoted
[
2+3] cycloaddition reaction to form 5ꢀsubstituted 1Hꢀtetrazoles. The results obtained are
summarized in Table 3. For all nitriles, DMF used as a solvent and the reaction was
0
conducted at 120 C. In all cases the conversion was completed within 0.5 ꢀ 8 h with good to
excellent yields (Except Table 3, Entry 6). Further increase in reaction time has no significant
effect on yields. Aromatic nitriles containing both electron donating and electron
withdrawing groups underwent the conversion smoothly. The nitriles having electron
donating substituents require longer reaction time (Table 3, entry 6, 8, 10) as donating
substituent on aromatic ring decreases the electrophilic character of nitrile. The benzyl
6

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nitriles (Table 3, entry 11, 12, 13) require longer reaction times than benzonitriles because of
absence of conjugated electron withdrawing aromatic ring in benzyl nitrile. The ortho
substituted nitriles render lower yields (Table 3, entry 2, 6) due to the steric hindrance. The
longer reaction time of 8 h was required with 76% yield for 2, 2ꢀdiphenylacetonitrile (Table
3, entry 14), this might be steric hindrance of two phenyl rings. The 93% of yield was
obtained for ethylcyano acetate (Table 3, entry 17) within very short reaction time of 0.5 h
without affecting ester functionality. The βꢀCD was chosen as catalyst since it is inexpensive,
biodegradable and easily accessible. All synthesized compounds have been characterized by
1
13
its physical constant, FTIR, H NMR, C NMR and mass spectroscopy and compared with
literature data.
a
Table 3 βꢀCD catalyzed synthesis of 5ꢀsubstituted 1H tetrazoles.
b
Entry
1
Substrate
Product
3a
Time (h.)
0.75
Yield (%)
c
CN
89, 87
2
3
CN
3b
3c
2
1
76
93
Cl
CN
Cl
4
5
6
CN
3d
3e
3f
1.25
1.75
92
95
Cl
Br
CN
d
d
CN
CH3
16, 48
43 , 45
7

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7
CN
3g
2
90
CH3
8
9
CN
3h
3i
4
1
7
88
83
85
H C
3
CN
O N
2
1
0
CN
3j
H CO
3
1
1
2
CN
3k
3l
6
93
92
1
CN
1.5
H CO
3
1
3
4
CN
3m
3n
3.5
8
84
76
Cl
1
CN
1
5
6
3o
3p
1.25
1.25
80
84
N
CN
1
CN
N
1
7
O
3q
0.5
93
CN
H CH CO
3
2
a
3
Reaction was carried out with nitrile (10 mmol), NaN (13 mmol), ammonium chloride (13
0
b
c
mmol) and Beta cyclodextrin (2 mmol) in 25 mL of DMF at 120 C , Isolated yield, Yield
after third recycle of catalyst, Reaction not proceed to completion.
d
1
a
Table 4 500 MHz H chemical shift of βꢀCD protons in free and complex state in DMFꢀd6.
8

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OHꢀ2
OHꢀ3
OHꢀ6
Hꢀ1
Hꢀ2
Hꢀ3
Hꢀ4
Hꢀ5
Hꢀ6ab
βꢀCD
5.906
5.816
5.792
4.683
4.634
4.955
4.957
3.464
3.459
3.819
b
3.491
3.486
3.764
3.771
3.834
3.841
Complex 5.871
a
b
Chemical shifts expressed in ppm, Reading not occurs due to spectral overlap.
1
Evidence for the association of nitrile and cyclodextrin in DMF is provided by H
1
NMR spectroscopy. As the reaction medium is DMF, the H NMR of pure βꢀCD and βꢀCD:
pꢀchlorobenzonitrile complex were undertaken in DMFꢀd6 and the results obtained shown in
Table 4. Protons involved in hydrogen bonds are much more deshielded than “free” protons.
In pure βꢀCD the OHꢀ2, OHꢀ3 and OHꢀ6 show downfield shift because of solventꢀ
cyclodextrin association due to hydrogen bonding as DMF itself act as hydrogen acceptor.
However on addition of nitrile guest, the upfield shift in hydroxyl OHꢀ2, OHꢀ3 and OHꢀ6
protons occurs. This indicates that the association of cyclodextrin with solvent decreases and
on the other hand its association with guest molecule may occurs. Though our expectation for
the Hꢀ3 and Hꢀ5 proton of cyclodextrin in complex was upfield shift but actually in our
results we got upfield shift in Hꢀ2 and Hꢀ4 protons of cyclodextrin. Some loss of resolution in
the spectral lines of the NMR spectra can be observed, due to the complexation effects with
the βꢀCD molecule.
The catalytic activity of βꢀCD for these [2+3] cycloaddition reaction is established by
the fact that a long reaction time and comparatively lower yield of product was observed
(Table 2, entry 1) when similar reaction was carried out in absence of βꢀCD which do not
afford formation of precipitation. The presence of cyclodextrin in reaction medium may
prevent sublimation of ammonium azide that prepared in situ by reaction of sodium azide and
4
0
ammonium chloride and thus overall increasing the rate of reaction. The formation of
4
1
precipitation occurs due to the supramolecular aggregates by cyclodextrin. It is tough to
design the actual mechanism for reaction under the influence of such supramolecular
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aggregates. The high performance has been shown by beta cyclodextrin due to
1
supramolecular interactions with guest molecule (Prove by H NMR). The nitriles get
activated by hydrogen bonding with cyclodextrin and thus facilitate the attack of azide ion.
The presence of cyclodextrin and formation of precipitate like gel under the thermal effect
may allow the intimate contact of nitrile and azide in cavity for [2+3] cycloaddition. When
similar reaction was performed in open carbohydrate moiety like glucose or dextrose,
reaction does not complete even up to longer reaction time leading to blackish material
indicating the essential role of cyclodextrin.
The catalyst reusability was studied three times including use of fresh catalyst for
synthesis of 5ꢀphenyl 1Hꢀtetrazole. The catalyst was almost quantitatively recovered and no
significant loss in yields was observed (Fig. 4). The mass of recovered cyclodextrin has taken
+
which shows characteristics peak of (M+H) ion indicates that no reaction occurs on
cyclodextrin itself. The FTIR of fresh βꢀCD and recovered from reaction also studied (Fig. 5)
and no change found in functional group as well as fingerprint region indicating no reaction
occurs with βꢀCD.
100
89%
89%
87%
87%
8
6
4
2
0
0
0
0
0
Fresh
First
Second
Third
Fig. 4 Catalyst (βꢀcyclodextrin) recyclability data.
1
0

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(b)
(a)
4000
3500
3000
2500
2000
1500
1000
500
-1
cm
Fig. 5 FTIR of (a) Fresh βꢀCD (b) Recovered βꢀCD
Conclusions
In conclusion, we herein report βꢀCD as an efficient and environmentally benign catalyst for
2+3] cycloaddition of azide with wide varieties of nitriles in DMF to form 5ꢀsubstituted 1Hꢀ
[
tetrazoles. We have investigated the advantages of βꢀCD to form precipitation with
multicomponent system in DMF for the enhancement of [2+3] cycloaddition reaction. The
benefits of this catalytic system are: good yields of product, short reaction time, inexpensive
and nontoxicity of catalyst, simple and clean workup of desire product without column
chromatography, easy recovery and reuse of catalyst.
Experimental
General Remarks
3 4
All nitriles, NaN and NH Cl were purchased from S. D. Fine and Spectrochem. βꢀCD was
purchased from Aldrich. Infrared (IR) spectra were obtained with IR Affinity ModelꢀI
1
13
spectroscopy (Shimadzu) using KBr pelleting. Both H NMR and C NMR were recorded on
a Bruker Avanceꢀ II spectrophotometer operating at 200 MHz and 500 MHz. The mass
spectra were recorded under ESI mode on Waters Micromass equipment (model QꢀTOF
micro).
General process for preparation of 5ꢀsubstituted 1Hꢀ tetrazole
1
1

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βꢀCyclodextrin (2.26 g, 2 mmol) was dissolved in DMF (25 mL) at room temperature by
stirring until a clear solution was formed. Then benzonitrile (Table 3, entry 1, 1.03 g, 10
mmol) added and allows stirring at room temperature for 0.25 h followed by the addition of
NaN
3
4
(0.845 g, 13 mmol) and NH Cl (0.695 g, 13 mmol). The reaction mixture was
0
constantly stirred at 120 C for 0.75 h. Then reaction mixture was allowed to cool at room
temperature, acidify carefully to pH 5 with 5M HCl. The organic material was extracted
twice with ethyl acetate; the combined organic phase was washed with water, dried over
2 4
anhydrous Na SO and concentrated under reduced pressure. The resulting product, although
evident as single compound by TLC was purified by simple recrystalization in aqueous
ethanol giving pure 5ꢀphenyl 1Hꢀtetrazole (1.30 g, 89%),
Catalyst Recovery and Reuse
To the aqueous layer, acetone (5 mL) added dropwise with stirring at room temperature
0
giving white turbid solution of precipitated βꢀCD which was cooled to 5 C to recover
cyclodextrin by filtration, dried and reused.
Spectral data of selected compounds
0
42
ꢀ1
1
3
a. M. P. 218 C , IR (KBr) cm = 2459ꢀ3213, 1564, 1608, 727, H NMR (200 MHz,
13
DMSOꢀd
6
): δ = 7.62 ꢀ 7.65 (m, 3H, aromatic), 8.07 – 8.09 (m, 2H, aromatic), C NMR (500
MHz, DMSOꢀd
6
): δ = 155.62, 131.31, 129.45, 126.96, 124.05, m/z = 147 (M+1).
0
24
ꢀ1
1
3
c. M. P. 139ꢀ140 C , IR (KBr) cm = 3226ꢀ3460, 1577, 1556, 775, H NMR (200 MHz,
13
DMSOꢀd
6
6
): δ = 7.65 – 8.08 (m, 4H, aromatic), C NMR (500 MHz, DMSOꢀd ): δ = 154.87,
+
1
34.03, 131.48, 131.05, 126.55, 126.28, 125.63, m/z = 181 (M+1) .
0
42
ꢀ1
1
3
e. M. P. 267ꢀ268 C , IR (KBr) cm = 2482ꢀ3118, 1604, 829, 744, H NMR (200 MHz,
1
3
DMSOꢀd
6
): δ = 8.00 (d, 2H, J = 8.6 Hz, aromatic), 7.84 (d, 2H, J = 8.6 Hz, aromatic), C
+
NMR (500 MHz, DMSOꢀd
6
): δ = 155.67, 132.51, 128.90, 124.76, 123.48, m/z = 224 (M+1) .
1
2

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0
42
ꢀ1
1
3
h. M. P. 250 C , IR (KBr) cm = 2476ꢀ3082, 1614, 823, H NMR (200 MHz, DMSOꢀ
d6): δ = 7.93 (d, 2H, J = 8 Hz, aromatic), 7.42 (d, 2H, J = 8 Hz, aromatic), 3.60 (brs, 1H), 2.39
1
3
(
6
s, 3H), C NMR (500 MHz, DMSOꢀd ): δ = 155.17, 141.32, 129.96, 126.87, 121.15, 21.02,
+
m/z = 161 (M+1) .
0
43
ꢀ1
1
3
i. M. P. 218ꢀ220 C , IR (KBr) cm = 3236ꢀ3444, 1533, 1340, 854, H NMR (200 MHz,
1
3
DMSOꢀd
6
): δ = 8.45 (d, 2H, aromatic), 8.31 (d, 2H, aromatic), C NMR (500 MHz, DMSOꢀ
+
d ): δ = 155.53, 148.74, 130.62, 128.24, 124.62, m/z = 192 (M+1) .
6
0
43
ꢀ1
1
3
j. M. P. 232ꢀ233 C , IR (KBr) cm = 2414ꢀ3145, 1614, 1502, 1182, 1056, 835, H
NMR (200 MHz, DMSOꢀd ): δ = 7.99 (d, 2H, J = 8.8 Hz, aromatic), 7.17 (d, 2H, J = 8.8 Hz,
6
1
3
aromatic), 3.85 (s, 3H), C NMR (500 MHz, DMSOꢀd
6
): δ = 161.44, 154.88, 128.65, 116.31,
+
1
14.86, 55.46, m/z = 176 (M ).
0
42
ꢀ1
1
3
k. M. P. 121ꢀ123 C , IR (KBr) cm = 2601ꢀ3101, 1548, 1531, 734, H NMR (200 MHz,
1
3
DMSOꢀd
6
): δ = 7.28 ꢀ 7.34 (m, 5H, aromatic), 4.29 (s, 2H), 3.76 (brs, 1H), C NMR (500
+
MHz, DMSOꢀd ): δ = 155.31, 135.90, 128.75, 128.65, 127.05, 28.86, m/z = 161 (M+1) .
6
0
ꢀ1
1
3
l. M. P. 162ꢀ164 C, IR (KBr) cm = 2468ꢀ3107, 1612, 1514, 1247, 1178, 825, H NMR
(
200 MHz, DMSOꢀd ): δ = 7.22 (d, 2H, J = 8.6 Hz, aromatic), 6.92 (d, 2H, J = 8.6 Hz,
6
1
3
aromatic), 4.24 (s, 2H), 3.74 (s, 3H), C NMR (500 MHz, DMSOꢀd
6
): δ = 158.28, 155.60,
+
1
29.76, 127.71, 114.13, 55.08, 28.01, m/z = 190 (M ).
0
42
ꢀ1
1
3
n. M. P. 165ꢀ166 C , IR (KBr) cm = 2455ꢀ3103, 1566, 1496, 725, H NMR (200 MHz,
1
3
DMSOꢀd
6
): δ = 7.20 – 7.40 (m, 10H, aromatic), 5.98 (s, 1H), C NMR (500 MHz, DMSOꢀ
+
d
6
): δ = 158.10, 140.00, 128.75, 128.40, 127.27, 45.73, m/z = 236 (M ).
0
44
ꢀ1
1
3
p. M. P. 256ꢀ258 C , IR (KBr) cm = 2970ꢀ3267, 1633, 1531, H NMR (200 MHz,
1
3
DMSOꢀd
6
): δ = 8.84 (d, 2H, aromatic), 8.04 (d, 2H, aromatic), 6.09 (bs, 1H), C NMR (500
+
MHz, DMSOꢀd
6
): δ = 155.33, 150.24, 133.19, 120.97, m/z = 148 (M+1) .
1
3

Page 15 of 17
New Journal of Chemistry
View Article Online
DOI: 10.1039/C3NJ00569K
0
43
ꢀ1
1
3
q. M. P. 130 C , IR (KBr) cm = 2461ꢀ3471, 1747, 1568, H NMR (200 MHz, DMSOꢀ
1
3
d ): δ = 4.17 (s, 2H), 4.14 (q, 2H, J = 2 Hz), 1.20 (t, 3H, J = 2 Hz), C NMR (200 MHz,
6
+
DMSOꢀd
Acknowledgement
The authors are thankful to University Grants Commission, New Delhi, India for
6
): δ = 167.78, 150.55, 61.29, 29.53, 13.99, m/z = 157 (M+1) .
fellowship award and Department of Science and Technology, New Delhi, India for financial
support of this work.
References
1
2
3
4
R. Huisgen, J. Sauer, H. J. Sturn, J. H. Markgraf, Chem. Ber., 1960, 93, 2106.
R. J. Herr, Bioorg. Med. Chem., 2002, 10, 3379.
D. J. Moderhack, Pract. Chem./Chem-Ztg., 1988, 340, 687.
M. Kiskey, D. E. Chavez, D. C. Noud, S. F. Son, H. L. Berghout, C. A. Bome, Proc. Int.
Pyrotech. Semin., 2000, 27, 3.
5
6
G. I. Koldobskii, V. A. Ostrovskii, Usp. Khim., 1994, 63, 847.
J. Clayden, N. Greeves, S. Warren, P. Wothers Organic Chemistry Oxford University
Press 2008.
7
(a) R. R. Wexler, W. J. Greenlee and et al., J. Med. Chem., 1996, 39, 625. (b) B. Schmidt,
B. Schieffer, J. Med. Chem., 2003, 46, 2261.
8 J. V. Dunica, M. E. Pierce, J. B. Santella III, J. Org. Chem., 1991, 56, 2395.
9 D. P. Kurran, S. Hadida, S. Y. Kim, Tetrahedron, 1999, 55, 8997.
10 P. Z. Demko, K. B. Sharpless, J. Org. Chem., 2001, 66, 7945.
11 F. Himo, P. Z. Demko, L. Nood leman, K. B. Sharpless, J. Am. Chem. Soc., 2002, 124,
1
2210.
2 F. Himo, P. Z. Demko, L. Nood leman, K. B. Sharpless, J. Am. Chem. Soc., 2003, 125,
983.
1
9
1
4

New Journal of Chemistry
Page 16 of 17
View Article Online
DOI: 10.1039/C3NJ00569K
1
1
1
3 L. Bosch, J. Vilarrasa, Angew. Chem., 2007, 119, 4000.
4 L. Bosch, J. Vilarrasa, Angew. Chem. Int. Ed., 2007, 46, 3926.
5 D. Amantini, R. Beleggia, F. Fringuelli, F. Pizzo, L. Vaccoro, J. Org. Chem., 2004, 69,
896.
6 M. Nasrollahzadeh, Y. Bayat, D. Habibi, S. Moshaee, Tetrahedron Lett., 2009, 50, 4435.
2
1
1
1
1
2
2
2
2
7 M. L. Kantam, K. B. S. Kumar, K. P. Raja, J. Mol. Catal. A: Chem., 2006, 247, 186.
8 G. Qi, Y. Dai, Chinese Chem. Lett., 2010, 21, 1029.
9 M. L. Kantam, V. Balasubrahmanyam, K. B. S. Kumar, Synth. Commun., 2006, 36, 1809.
0 G. Venkateshwarlu, K. C. Rajanna, P. K. Saiprakash, Synth. Commun., 2009, 39, 426.
1 B. Das, C. R. Reddy, D. N. Kumar, M. Krishnaiah, R. Narender, Synlett, 2010, 3, 391.
2 L. Long, B. Li, W. Liu, L. Jiang, Z. Xu, G. Yin, Chem. Commun., 2010, 46, 448.
3 H. Jinghui, Li. Baojun, C. Fasheng, Xu. Zheng, Y. Gui, J. Mol. Catal. A: Chem., 2009,
3
04, 135.
2
2
2
2
2
2
3
4 B. Sreedhar, A. S. Kumar, D. Yada, Tetrahedron Lett., 2011, 52, 3565.
5 J. Szeijtli, Cyclodextrin Technology, Kluwer Academic Publishers, Dordrecht, 1998
6 Y. Cao, X. Xiao, R. Li, Q. Guo, J. Mol. Struct., 2003, 660, 73.
7 R. Villalonga, R. Cao, A. Fragoso, Chem. Rev., 2007, 107, 3088.
8 F. Hapiot, S. Tilloy, E. Monflier, Chem. Rev., 2005, 106, 767.
9 J. Szeijtli, Chem. Rev., 1998, 98, 1743.
0 J. HengꢀBing, S. DongꢀPo, S. Ming, L. Zhong, W. LeꢀFu, Tetrahedron Lett., 2005, 46,
2
517.
3
1 (a) B. Siegel, R. Breslow , J. Am. Chem. Soc., 1975, 97, 6869; (b) C. E. Feliciano, E.
Quinones, J. Photochem. Photobiol A, 1999, 23, 120; (c) S. Panja, P. R. Bangal, S.
Chakravorty, Chem. Phys. Lett., 2000, 329, 377; (d) S. Sen, D. Sukul, P. Dutta, K.
Bhattacharyya, J. Phys. Chem. A, 2001, 105, 10635; (e) P. Walla, V. B. Arion, U. H.
1
5

Page 17 of 17
New Journal of Chemistry
View Article Online
DOI: 10.1039/C3NJ00569K
Brinker, J. Org. Chem., 2006, 71, 3274.
3
3
3
2 W. Zhao, Y. Y. Li, T. Sun, H. Yan, A. Hao, F. Xin, H. Zhang, W. An, L. Kong, Y. Li,
Colloids Surf. A, 2011, 374, 115.
3 L. Kong, F. Xin, W. Zhao, H. Zhang, Z. Li, Y. Li, Y. Hou, S. Li, A. Hao, Colloids Surf.
A, 2011, 392, 156.
4 S. N. Murthy, B. Madhav, A. V. Kumar, K. RamaRao, Y. V. D. Nageswar, Tetrahedron ,
2
009, 65, 5251.
3
5 K. Kanagaraj, K. Pitchumani, Tetrahedron Lett., 2010, 51, 3312.
6 V. P. Kumar, V. P. Reddy, R. Shridhar, B. Srinivas, M. Narender, K. RamaRao, J. Org.
Chem., 2008, 73, 1646.
3
3
7 A. Kumar, V. D. Tripathi, P. Kumar, Green Chem., 2011, 13, 51.
8 D. R. Patil, P. G. Ingole, K. Singh, D. S. Dalal, J. Incl. Phenom. Macrocycl. Chem.,
3
2
012, DOI 10.1007/s10847ꢀ012ꢀ0203ꢀz.
39 G. Y. Du, J. Shen, T. Sun, H. Y. Sun, C. C. Shi, A. Y. Hao, Colloids Surf. A:
Physciochemical and Engineering Aspects, 2012, 414, 120.
4
4
4
0 W. G. Finnegan, R. A. Henry, R. Lofquist, J. Am. Chem. Soc., 1958, 80, 3908.
1 Y. Li and et al. J. Phys. Chem. B., 2010, 114, 10321.
2 B. Gutmann, J. P. Roduit, D. Roberge, O. Kappe, Angew. Chem. Int. Ed., 2010, 49,
7101.
4
3 T. Jin, F. Kitahara, S. Kamijo, Y. Yamamoto, Tetrahedron Lett., 2008, 49, 2824.
4 A. N. Chermahini, A. Teimouri, F. Momenbeik, A. Zarei, Z. Dalirnasab, A. Ghaedi, M.
Roosta, J. Heterocycl. Chem., 2010, 47, 913.
4
1
6