Full text of DOI:10.14233/ajchem.2018.21192

Asian Journal of Chemistry; Vol. 30, No. 5 (2018), 1093-1098
A
SIAN
J
OURNAL OF HEMISTRY
C
https://doi.org/10.14233/ajchem.2018.21192
ZrO2 Nanoparticles-Supported Cu2(II)-β-Cyclodextrin Mediated Synthesis of
N-2 Substituted Tetrazoles by [2+3] Cycloaddition and Post Tetrazole Alkylation
1
2
3
YARABHALLY R. GIRISH , KOTHANAHALLY S. SHARATH KUMAR , KEREYAGALAHALLY H. NARASIMHAMURTHY ,
2
3,*
KANCHUGARAKOPPAL S. RANGAPPA and SHEENA SHASHIKANTH
1Deparment of Organic Chemistry, Indian Institute of Science, Bengaluru-560 012, India
2Deparment of Studies in Chemistry, University of Mysore, Manasagangotri, Mysuru-570 006, India
3Deparment of Studies in Organic Chemistry, University of Mysore, Manasagangotri, Mysuru-570 006, India
*Corresponding author: Fax: +91 821 518835; Tel: +91 821 2419668; E-mail: shashis1956@gmail.com
Received: 21 December 2017;
Accepted: 1 February 2018;
Published online: 29 March 2018;
AJC-18847
An efficient one-pot ZrO2 nanoparticles-supported Cu2(II)-β-cyclodextrin promoted [2+3] cycloaddition of benzonitriles and sodium
azide followed by post tetrazole alkylation using aralkyl esters for the synthesis of N-2-substituted tetrazoles has been presented. One-pot
operation, atom-economical, regioselectivity and good yields are the main advantages of this protocol. From the atom economy, it is clear
that, catalyst can be reused up to four times without any appreciable changes in catalytic activity
Keywords: ZrO2 Nanoparticles, [2+3] Cycloaddition, Alkylation, Tetrazoles, Benzonitriles.
The conventional method for the synthesis of N-alkyalted
tetrazoles is via [2+3] cycloaddition between an azide and
nitrile results in the formation of 5-substituted 1H-tetrazole
and followed by the subsequent treatment with base and alkyl
halides [21,22]. Several research groups have attempted for
the synthesis of 5-substituted 1H-tetrazole using various catalysts
such as TMSN3-TBAF [23], Zn/Al-hydrocalcite [24], Fe2O3
[25], Zn-hydroxyapatite [26], ionic liquid 1-N-butylimidazolium
tetrafluoroborate [27], FeCl3-SiO2 [28], Cu2O [29], CuFe2O4
nanoparticles [30],Amberlyst-15 [31], nano copper oxide [32],
AgNO3 [33] and ceric ammonium nitrate supported HY-zeolite
[34]. It is noteworthy to mention that none of the above mentioned
methods have reported the post tetrazole alkylation using esters
as an alkylating agent.
Roh et al. [35] reported one-pot regioselective vinylation
of tetrazoles using 1,2-dibromoethane and triethylamine at
reflux temperature (Scheme-I, eqn 1). Gyoung et al. [36] have
described improved reaction conditions for regiospecific
synthesis of 2-allylated-5-substituted tetrazoles via palladium-
catalyzed reaction of nitriles, allyl acetates and trimethylsilyl
azide. However, the above said methods require harsh reaction
conditions, use of toxic chemicals and long duration of time.
To overcome these drawbacks we have developed an efficient
one-pot protocol for the regioselective synthesis of N-2-substi-
tuted tetrazoles via [2+3] cycloaddition using an ZrO2 nanopart-
icles supported Cu2(II)-β-cyclodextrin complex (without any
additives) followed by treatment with esters as an alkylating
INTRODUCTION
Tetrazoles are important class of five membered nitrogen
containing heterocycles which have considerable interest from
the past two decades. Tetrazole moieties have wide spread appli-
cations such as in bioisosteres replacement for carboxylic acid
group in drug industry [1], in coordination chemistry as ligands
[2], as energetic materials [3,4], in laser flash photolysis [5],
as effective adsorbents in clean energy application for adsorption
of CO2 by using microporous polymer with pending tetrazole
moieties [6], in fluorescent chemo sensor for detection of multiple
ions by bioimaging [7]. In addition tetrazole moiety is well explored
in biological field as AT1-receptor antagonists (Losartan) in
the regulation of blood pressure and fluid balance [8] as anti-
malarial and antiproliferative agents [9,10].
From past few years, several synthetic efforts have been
made for the synthesis of bioactive nitrogen containing hetero-
cycles and in that direction [11-15], we have been engaged in
investigating the synthesis of various heterocycles using different
catalysts [16,17]. Cu(II)-β-CD complex is well explored in the
literature for various reactions [18,19] and recently we have
reported ZrO2-Cu2(II)-β-CD catalyzed one-pot synthesis of
N-2-substituted 1,2,3-triazoles via azide-chalcone oxidative
cycloaddition and post-triazole alkylation [20]. To explore the
further scope of the newly synthesized catalyst, we have used
ZrO2-Cu2(II)-β-CD for the construction of N-2-alkylated tetrazoles
via [2+3] cycloaddition and post tetrazole alkylation.

1094 Girish et al.
Asian J. Chem.
N
N
2-Methyl-5-[4-(trifluoromethyl)phenyl]-2H-tetrazole
(3e) [22]: White solid; m.p. 112-115 ºC; (lit. 113-115 ºC) Rf =
0.47(hexane:EtOAc 8: 2); ATR-IR: 3054, 1832, 1756, 1543,
1468, 1354, 1130, 1125, 1021, 767 cm-1; 1H NMR (400 MHz,
CDCl3): δ 8.27-8.25 (d, J = 8.0Hz, 2H, ArH), 7.26-7.74 (d, J
= 8.0 Hz, 2H, ArH), 4.42 (s, 3H, N-Me); 13C NMR (100 MHz,
CDCl3): δ 164.03, 131.8, 130.6, 127.0, 125.8, 125.1, 39.5;
HRMS (ESI) m/z: Calculated for C8H7N4F3: 229.1782 (M+1)+;
Found: 229.0124 (M+1)+.
1. NaN3 (1.2 equiv.), DMF, 100 °C,
R2
CN
N
1-12 h, ZrO2-Cu2(II)-
2. RCOOR2, 12-48 h
β-CD (40 mol %)
N
R1
R1
Scheme-I: Strategy for the synthesis of 2,5-disubstituted tetrazoles
agent in DMF at 100 ºC. The main advantages of this protocol
are the simple starting materials, one pot operation, easy work-
up procedure and high regioselectivity.
5-(3-Bromophenyl)-2-methyl-2H-tetrazole (3f) [39]:
White solid; m.p. 121-123 ºC; (lit. 120-122 ºC); Rf = 0.5 (hexane:
EtOAc 8:2);ATR-IR: 3016, 1822, 1739, 1538, 1456, 1390, 1147,
1104, 1023, 789 cm-1; 1H NMR (400 MHz, CDCl3): δ 8.29 (s,
1H, ArH), 8.07-8.05 (d, J = 8.0Hz, 1H, ArH), 7.60-7.58 (d, J
= 8.0 Hz, 1H, ArH), 7.37-7.33 (t, J = 7.8Hz, 1H, ArH), 4.39
(s, 3H, N-Me); 13C NMR (100 MHz, CDCl3): δ 164.00, 133.2,
130.4, 129.7, 129.2, 125.2, 122.9, 39.5; HRMS (ESI) m/z:
Calculated for C8H7N4Br: 239.0760 (M+1)+, 241.0512 (M+3)+;
Found: 239.0652 (M+1)+, 241.0451 (M+3)+.
5-(5-Bromo-2-fluorophenyl)-2-methyl-2H-tetrazole (3g):
Pale yellow needles; m.p. 85-87 ºC; Rf = 0.5 (hexane:EtOAc
8:2);ATR-IR: 3042, 1820, 1734, 1543, 1456, 1392, 1154, 1102,
1012, 743 cm-1; 1H NMR (400 MHz, CDCl3): δ 8.04-8.01 (dd,
J = 8.8 Hz, 1H, ArH), 7.74-7.71 (m, 1H, ArH), 7.53-7.49 (m,
1H, ArH, F coupling), 4.41 (s, 3H, N-Me); 13C NMR (100
MHZ, CDCl3): δ 163.2, 133.7, 132.0, 129.5, 129.1, 125.7,
122.8, 40.1; HRMS (ESI) m/z:Calculated for C8H6N4BrF:
257.0664 (M+1)+, 259.0534 (M+3)+; Found: 257.0521 (M+1)+,
259.0454 (M+3)+.
5-(3-Chloro-4-fluorophenyl)-2-methyl-2H-tetrazole (3h):
Pink solid; m.p. 85-88 ºC; Rf = 0.4 (hexane:EtOAc 8: 2);ATR-
IR: 3026, 1823, 1745, 1542, 1465, 1391, 1117, 1104, 1021, 852
cm-1; 1H NMR (400 MHz, CDCl3): δ 8.17-8.16 (d, J = 2.0 Hz,
1H, ArH), 8.07-8.04 (d, J = 10.4 Hz, 1H, ArH), 7.29-7.24 (t, 1H,
ArH), 4.39 (s, 3H, N-Me); 13C NMR (100 MHz, CDCl3): δ164.2,
159.7, 139.0, 129.0, 126.18, 126.2, 125.0, 120.0, 39.5; HRMS
(ESI) m/z: Calculated for C8H6N4ClF: 213.6124 (M+1)+, 215.4124
(M+3)+; Found: 213.0154 (M+1)+, 215.0361 (M+3)+.
2-Methyl-5-(p-tolyl)-2H-tetrazole (3i) [37]:White solid;
m.p. 104-105 ºC; (lit 104-105 ºC); Rf = 0.6 (hexane:EtOAc 8: 2);
ATR-IR: 3036, 1853, 1725, 1532, 1467, 1392, 1123, 119, 1028,
778 cm-1; 1H NMR (400 MHz, CDCl3): δ 8.01-7.99 (d, J = 8.0
Hz, 2H,ArH), 7.63-7.62 (d, J = 8.4 Hz, 2H, ArH), 4.37 (s, 3H,
N-Me), 2.40 (s, 3H, P-Me); HRMS (ESI) m/z: Calculated for
C9H10N4: 175.2070 (M+1)+; Found: 175.0325 (M+1)+.
2-[5-(3-Bromophenyl)-2H-tetrazol-2-yl]ethyl 3-bromo-
benzoate (3j): Pale green solid; m.p. 75-77 ºC; Rf = 0.5 (hexane:
EtOAc 8: 2); ATR-IR: 3034, 1834, 1726, 1547, 1437, 1352,
1120, 1109, 1054, 762 cm-1; 1H NMR (400 MHz, CDCl3): δ 8.30
(s, 1H, ArH), 8.09-8.07 (d, J = 7.6 Hz, 1H, ArH), 7.76-7.73 (t,
J = 8.8 Hz, 1H,ArH), 7.64-7.59 (m, 2H,ArH), 7.38-7.32 (m, 3H,
ArH), 5.08-5.05 (t, 2H, CH2), 4.93-4.90 (t, 2H, CH2); 13C NMR
(100 MHz, CDCl3): δ 165.2, 164.2, 134.4, 133.3, 133.0, 131.6,
131.5, 130.7, 130.4, 129.8, 129.0, 127.2, 125.3, 122.95, 122.94,
62.0, 51.8 ; HRMS (ESI) m/z: Calculated for C16H12N4O2Br2:
451.9307 (M+1)+, 453.0652 (M+3)+, 455.0546 (M+5)+; Found:
451.0194 (M+1)+, 453.0204 (M+3)+, 455.0258 (M+5)+.
Ethyl 2-[5-(5-bromo-2-fluorophenyl)-2H-tetrazol-2-
yl]acetate (3k): White solid; m.p. 78-80 ºC; Rf = 0.6 (hexane:
EXPERIMENTAL
General procedure for synthesis of N-2-substituted 1,2,
3,4-tetrazoles:Aromatic benzonitriles (1 mmol), sodium azide
(1.2 mmol), 40 mol % of ZrO2-Cu2(II)-β-CD (50 mg, 0.036
mmol) and 3 mL DMF were taken in a round bottom flask
equipped with stirrer. The reaction mixture was agitated at 100
ºC for 1-12 h, then ester (1 mmol) was added to the mixture
and the reaction continued at 100 ºC for 12-48 h. The reaction
mixture was diluted with water (4 mL) and extracted with
ethyl acetate (6 × 10 mL). The combined organic phases were
washed with brine (4 × 10 mL), dried over anhydrous Na2SO4
and concentrated in vacuum. The residue was subjected to column
chromatography with hexane/EtOAc as eluent to get the desired
product.
5-(4-Chlorophenyl)-2-methyl-2H-tetrazole (3a) [37]:
White solid; m.p. 106-108 ºC (lit. 107-108 ºC); Rf = 0.4 (hexane:
EtOAc 8:2); ATR-IR: 2968, 1727, 1606, 1448, 1439, 1415,
1163, 1114, 1048, 704 cm-1; 1H NMR (400 MHz, CDCl3): δ
8.08-8.06 (d, J = 8.8 Hz, 2H, ArH), 7.47-7.45 (d, J = 8.4Hz,
2H, ArH), 4.39 (s, 3H, N-Me); 13C NMR (100 MHz, CDCl3):
δ 164.3, 136.3, 129.18, 129.15, 128.0, 125.8, 39.4; HRMS (ESI)
m/z: Calculated for C8H7N4Cl: 194.6220 (M+1)+, 197.0330
(M+3)+; Found: 195.0924 (M+1)+, 197.0908 (M+3)+.
5-(3,5-Dichlorophenyl)-2-methyl-2H-tetrazole (3b):White
solid; m.p. 78-80 ºC; Rf = 0.5 (hexane: EtOAc 8:2); ATR-IR:
3028, 1856, 1742, 1512, 1447, 1386, 1106, 1100, 1029, 852 cm-1;
1H NMR (400 MHz, CDCl3): δ 8.03 (s, 2H, ArH), 7.44 (s, 1H,
ArH), 4.41 (s, 3H, N-Me); 13C NMR (100 MHz, CDCl3): δ163.5,
135.6, 130.17, 130.12, 130.07, 125.2, 125.1, 39.6; HRMS (ESI)
m/z: Calculated for C8H6N4Cl2: 229.9940 (M+1)+, 231.0630
(M+3)+, 233.0630 (M+5)+; Found: 229.0557 (M+1)+, 231.0542
(M+3)+, 233.0480 (M+5)+.
5-(4-Bromophenyl)-2-methyl-2H-tetrazole (3c) [38]:
White solid; m.p. 123-125 ºC; (lit. 124-126 ºC); Rf = 0.4 (hexane:
EtOAc 8:2); ATR-IR: 3042, 1826, 1732, 1542, 1467, 1387,
1140, 1105, 1032, 785 cm-1; 1H NMR (400 MHz, CDCl3): δ
8.01-7.99 (d, J = 8.4 Hz, 2H, ArH), 7.47-7.45 (d, J = 8.8Hz,
2H, ArH), 4.39 (s, 3H, N-Me); 13C NMR (100 MHz, CDCl3):
δ 165.2, 132.1, 128.2, 126.3, 124.6, 39.5; HRMS (ESI) m/z:
Calculated for C8H7N4Br: 239.0760 (M+1)+, 241.0326 (M+3)+;
Found: 239.0652 (M+1)+, 241.0523 (M+3)+.
5-(4-Fluorophenyl)-2-methyl-2H-tetrazole (3d) [37]:
White solid; m.p. 88-89 ºC; (lit. 88-89 ºC); Rf = 0.52 (hexane:
EtOAc 8: 2); ATR-IR: 3067, 1834, 1726, 1535, 1432, 1356,
1128, 1117, 1037, 792 cm-1; 1H NMR (400 MHz, CDCl3): δ8.14-
8.11 (m, 2H, ArH), 7.26-7.15 (m, 2H, ArH), 4.39 (s, 3H, N-Me);
13C NMR (100 MHz, CDCl3): δ 165.2, 162.7, 128.8, 128.7,
123.6, 123.5, 116.1, 115.8, 39.4; HRMS (ESI) m/z: Calculated
for C8H7N4F: 179.0688 (M+1)+; Found: 179.0521 (M+1)+.

Vol. 30, No. 5 (2018)
ZrO2 Nanoparticles-Supported Cu2(II)-β-Cyclodextrin Mediated Synthesis of N-2 Substituted Tetrazoles 1095
N
EtOAc 8:2);ATR-IR: 3046, 1829, 1754, 1532, 1456, 1392, 1128,
1100, 1037, 765 cm-1 ; 1H NMR (400 MHz, CDCl3): δ 7.52 (s,
1H, ArH),7.48-7.46 (d, J = 8.8 Hz, 1H, ArH), 6.46-6.43 (d, J
= 8.8 Hz, 1H, ArH), 4.27-4.26 (q, 2H, CH3), 3.96-3.95 (d, 2H,
CH2), 1.32-1.25 (t, 3H, CH3); 13C NMR (100 MHz, CDCl3): δ
169.2, 148.1, 137.1, 134.7, 116.0, 112.4, 108.3, 98.2, 61.8,
44.9, 14.1; HRMS (ESI) m/z: Calculated for C11H10N4O2BrF:
329.1294 (M+1)+, 331.0664 (M+3)+; Found: 329.0452 (M+1)+,
331.0564 (M+3)+.
N
CN
1. NaN3 (1.2 equiv.), DMF, 100 °C,
1 h, catalyst (40 mol %)
N
N
2. 2-Br-C6H4COOCH3 (2a), 12-48 h
Br
1d
Br
3g
Scheme-II: Strategies for the synthesis of 2,5-disubstituted tetrazoles
Then the reaction was screened using DMSO as solvent which
gave a moderate yield of 78 % (entry13, Table-1).
2-[5-(4-(Bromomethyl)phenyl)-2H-tetrazol-2-yl]ethyl
2-bromobenzoate (3l): Pale yellow liquid; Rf = 0.5 (hexane:
EtOAc 8:2);ATR-IR: 3034, 1824, 1721, 1534, 1454, 1397, 1127,
1107, 1028, 745 cm-1 ; 1H NMR (400 MHz, CDCl3): δ 8.17-8.15
(d, J = 8.0 Hz, 2H, ArH), 7.75-7.72 (t, J = 9.6 Hz, 1H, ArH),
7.63-7.61 (t, J = 8.8 Hz, 1H, ArH), 7.45-7.43 (d, J = 8.0 Hz,
2H,ArH), 7.33-7.27 (q, 2H,ArH), 5.08-5.05 (t, 2H, CH2), 4.93-
4.90 (t, 2H, CH2), 4.41 (s, 2H, CH2); 13C NMR (100 MHz, CDCl3):
δ 165.2, 164.9, 137.6, 134.4, 133.0, 131.6, 130.8, 130.7, 128.7,
128.5, 127.2, 127.1, 127.0, 121.8, 62.1, 54.3, 51.7; HRMS
(ESI) m/z: Calculated for C17H14N4O2Br2: 465.1330 (M+1)+,
467.3312 (M+3)+, 469.4261 (M+5)+; Found: 465.1298 (M+1)+,
467.3902 (M+3)+, 469.4869 (M+5)+.
Furthermore, diverse nitriles possessing wide range of
functional groups were used to investigate the substrate toler-
ance under the given reaction condition and the results obtained
are summarized in Table-2. Nitriles bearing chloro, dichloro,
bromo, fluoro, trifluoro methyl, alkyl bromo and methyl groups
at different position on the benzene ring underwent reaction
smoothly to produce desired product in good yield within 12-
48 h (entry 1-9, Table-3). Since halogens having α-hydrogen
atoms are very good leaving group, when we used 2-chloroethyl-
3-bromobenzoate and ethylbromoacetate (entry 10-12, Table-
2) for alkylation, triazole anion undergoes substitution at α-
carbon of the halogens instead of α-carbon of the ester leading
to the formation of highly substituted tetrazole derivatives.
With the optimized reaction conditions in hand, we explored
the generality and scope of the protocol by keeping nitrile
component as common and used various substituted alkyl/
aralkyl esters for alkylation. The reaction of tetrazole anion
with an methyl ester containing bromine atom at the O-position
of the aryl group proceeded smoothly and regioselectively
produced the corresponding N-2-methylated tetrazole with an
excellent yield (entry 3, Table-3). Inspired by this, we went on
to examine different alkyl esters like ethyl, isopropyl, t-butyl,
n-butyl and isoamyl groups, unfortunately none of the groups
promoted the reaction (entries 4-8, Table-3).
RESULTS AND DISCUSSION
Initially, we have selected 3-bromobenzonitrile (1d) as a
model substrate to screen the reaction using different catalysts
such as CuO, α-Fe3O4, ZrO2-β-CD, ZrO2-Cu2(II)-β-CD, CuFe2O4,
sulfated ZrO2, ZnO and β-cyclodextrin (Scheme-II, Table-1).
Among all the catalysts, ZrO2-Cu2-β-CD was found to be better
for cyclization and only catalyst to effect the post tetrazole
alkylation. Then the reaction was screened using ZrO2-Cu2(II)-
β-CD as a catalyst by varying solvent, temperature and mol %
of catalyst. Initially 40 mol % of ZrO2-Cu2(II)-β-CD in DMF
at 110 ºC gave only 84 % of yield even after 18 h (entry 9,
Table-1).A decrease in temperature to 100 ºC resulted in increase
of product yield up to 86 % (entry 10, Table-1). Later with
optimal temperature and catalyst load, we have screened the
reaction in shorter time 16 h and noticed the increase in product
yield of 88 % (entry 11, Table-1). A decrease in catalyst load
percentage doesn't improve the product yield (entry 12, Table-1).
Conclusion
An efficient ZrO2 nanoparticles-supported Cu2(II)-β-cyclo-
dextrin complex catalyzed protocol for regioselective synthesis
of N-2-substituted tetrazoles in moderate to excellent yields
starting from aromatic benzonitrilesand sodium azide via [2+3]
cycloaddition and post-tetrazole alkylation using different aryl-
TABLE-1
EFFECT OF CATALYST AND SOLVENT ON THE REACTION
Entrya
1
2
3
4
5
6
7
8
Catalyst
Temp. (°C)
125
Mol (%)
–
Solvent
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
Time (h)
24
Yield (%)
–
CuO
–
–
–
–
–
–
–
–
84
86
110
110
110
110
110
110
110
110
40
40
40
40
40
40
40
40
10
20
1:30
12
24
14
1:45
18
α-Fe3O4
ZrO2-β-CD
CuFe2O4
Sulfated ZrO2
ZnO
β-CD
9
ZrO2-Cu2(II)-β-CD
ZrO2-Cu2(II)-β-CD
ZrO2-Cu2(II)-β-CD
ZrO2-Cu2(II)-β-CD
ZrO2-Cu2(II)-β-CD
10
11
12
13
100
40
18
100
100
100
40
30
40
DMF
DMF
DMSO
16
16
16
88
80
78
aReaction condition 3-bromo benzonitrile 1d (1 mmol), NaN3 (1.2 mmol), 40 mol % of ZrO2-Cu(II)-β-CD (50 mg) in DMF (3 mL) at 100 °C in air
for 1 h first, then 2-Br-C6H4COOCH3 (1 mmol), was added to mixture and the reaction continued for 12-48 h.

1096 Girish et al.
Asian J. Chem.
TABLE-2
SUBSTRATE SCOPE OF DIFFERENT BENZONITRILES AND ESTERS
N
N
1. NaN3, (1.2 equiv), DMF, 100°C, 1-12 h
CN
R2
N
ZrO2-Cu2(II)-β-CD (40 mol %)
N
2. RCOOR2(2(a-c)), 12-48 h
R1
1(a-j)
R1
3(a-l)
Entry
1
Substrate
Ester
Product
Time (h)
24
Yielda,b (%) [Ref.]
90 [[3377]]
O
N
N
CN
CN
N
N
O
Cl
Cl
Cl
Br
2a
3a
1a
N
N
O
O
N
Cl
N
2
30
85
Cl
1b
Br
2a
Cl
3b
3c
O
O
N
N
CN
CN
CN
N
N
3
4
5
16
48
48
94 [[3388]]
65 [[3377]]
82 [[2222]]
Br
F
Br
Br
2a
1c
1d
1e
O
O
N
N
N
N
F
Br
2a
3d
N
O
O
N
N
N
F3C
F3C
Br
2a
3e
N
N
CN
O
O
N
N
6
7
15
24
87 [[3399]]
50
Br
2a
Br
Br
1f
3f
N
O
O
N
Br
CN
F
N
Br
N
F
Br
2a
1g
3g
N
N
CN
O
O
N
N
8
48
40
F
F
Cl
1h
Br
2a
Cl
3h

Vol. 30, No. 5 (2018)
ZrO2 Nanoparticles-Supported Cu2(II)-β-Cyclodextrin Mediated Synthesis of N-2 Substituted Tetrazoles 1097
O
N
N
CN
N
O
N
9
12
16
50 [3377]]
Br
2a
1i
3i
Br
O
CN
O
N
N
O
Cl
N
O
N
10
60
Br
2b
Br
Br
1f
3j
O
N
O
N
O
Br
CN
N
Br
Br
11
N
32
70
O
F
F
2c
1g
3k
Br
O
O
O
N
N
CN
Cl
N
O
12
24
60
N
Br
Br
2b
1j
Br
3l
aIsolated yields; b Literature reported compounds.
TABLE-3
examined up to four cycles without appreciableloss of catalytic
activity (Table-4). Hence, the present method proved to be an
economical and very much useful in the synthesis of bioactive
tetrazole derivatives.
N-ALKYLATION USING DIFFERENT ESTERS
N
N
1. NaN3 (1.2 equiv), DMF, 100°C, 1hr
catalyst (40 mol%)
CN
N
N
2. RCOOR2 (2(a-c)), 12-48 hrs
ACKNOWLEDGEMENTS
Br
1d
Br
3(a-i)
Three of the authors (YRG, KHN& KSS) are grateful to
UGC, RFSMS, Government of India for Research fellowship.
Entry
R
R2
Yield (%)
Product
1
2
3
4
5
6
7
8
CH3
C6H5
CH2CH3
CH3
CH3
CH2CH3
Isopropyl
t-Butyl
n-Butyl
Isoamyl
–
56
88
Trace
–
–
–
–
–
3g
3g
–
–
–
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