JOURNAL OF CHEMICAL RESEARCH 2016 571
Table 3 Synthesis of 1-substituted-1H-1,2,3,4-tetrazoles catalysed by HNTf2a
m.p./°C
Entry
R
Product
Time/h
Yield/%b
Found
65–66
91–93
152–154
155–157
100–102
68–70
Lit.
1
2
3
4
5
6
7
8
C6H5
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
3
3.5
3
3.5
3
3.5
3
3
3.5
3
3
3.5
3
92
90
87
90
95
87
91
92
85
87
89
87
94
91
84
64–6510
93–9421
153–15521
157–15810
101–10214
68–6914
77–7914
4-MeC6H4
2-MeC6H4
4-ClC6H4
3-NO2C6H4
3-MeOC6H4
3-BrC6H4
4-MeCOC6H4
2-ClC6H4
3-HOC6H4
2,4-Cl2C6H3
2-Me-5-ClC6H3
2-pyridyl
76–78
146–148
127–129
166–168
146–148
55–56
126–128
59–60
142–143
148–15021
129–13121
168–17014
14610
54–5510
129–13010
57–5810
14315
9
10
11
12
13
14
15
C6H5CH2
CH3(CH2)3
4
5
aAll reactions were conducted in the presence of 5 mol% of HNTf2 in glycerol at room temperature.
bIsolated yield.
All the products are known compounds and the spectral data and
melting points were in agreement with those reported in the literature.
Selected spectral data for 2c and 2d is given below.
To expand the efficiency and generality of this methodology,
additional reactions of triethyl orthoformate and NaN3 with a
variety of amines (aromatic, heteroaromatic, and aliphatic)
were next attempted in the presence of 5 mol% of HNTf2 in
glycerol at room temperature. The results are summarised in
Table 3. Aromatic amines including both electron-donating and
electron-withdrawing groups on the aromatic ring provided
the corresponding products in excellent yields. Interestingly,
electron-donating or electron-withdrawing at para-, ortho-
or meta-position does not have significant influence on the
product yield (Table 3, entries 2–12). The heterocyclic based
1-substituted tetrazole was also formed with high yield
(Table 3, entry 13). Aliphatic amines such as benzylamine
and butylamine furnished the corresponding products in good
yields, but longer reaction times were required (Table 3, entries
1-(2-Methylphenyl)-1H-tetrazole (2c): White solid; m.p. 152–154 °C
(lit.21 153–155 °C); IR (νmax, cm–1) KBr: 3011, 2868, 1661, 1594, 1483
1
1179, 1166, 1093; H NMR (CDCl3, 400 MHz) δ 2.33 (s, 3H, CH3),
7.02–7.09 (m, 2H, ArH), 7.20–7.25 (t, J = 7.6 Hz, 2H, ArH), 8.16 (s,
1H, tetrazole); 13C NMR (CDCl3, 100 MHz) δ 17.9, 117.8, 123.6, 127.1,
128.5, 130.2, 144.6, 147.9; Anal. calcd for C8H8N4: C, 59.98; H, 5.03; N,
34.98; found: C, 60.13; H, 5.11; N, 34.86%.
1-(4-Chlorolphenyl)-1H-1,2,3,4-tetrazole (2d): White solid;
m.p. 155–157 °C (lit.10 157–158 °C); IR (νmax, cm–1) KBr: 3052, 2915,
2850, 1498, 1385, 1201, 992, 833; 1H NMR (CDCl3, 400 MHz) δ 7.53
(d, J = 8.6 Hz, 2H, ArH), 7.75 (d, J = 8.6 Hz, 2H, ArH), 8.41 (s, 1H,
tetrazole); 13C NMR (CDCl3, 100 MHz) δ 122.9, 123.8, 129.5, 136.1,
150.9; Anal. calcd for C7H5ClN4: C, 46.55; H, 2.79; N, 31.03; found: C,
46.41; H, 2.63; N, 31.16%.
14 and 15).
In conclusion, glycerol was found to be an effective
and environmentally benign medium for the synthesis of
1-substituted-1H-1,2,3,4-tetrazoles from amines, triethyl
orthoformate and sodium azide catalysed by HNTf2. The
advantages of this protocol include the use of a metal-free and
commercially available catalyst, ease of experimentation (room
temperature) and green solvent.
The authors gratefully acknowledge the financial support
provided by State Key Laboratory of Explosion Science and
Technology (No. KFJJ12-13M), Shaanxi Key Laboratory for
Phytochemistry (14JS006) and Baoji University of Arts and
Sciences (No. ZK14008).
Received 18 May 2016; accepted 14 July 2016
Published online: 1 September 2016
Experimental
Melting points were determined on an XT4A electrothermal apparatus
equipped with a microscope and are uncorrected. NMR spectra were
recorded on a Bruker Avance 400 spectrometer in DMSO-d6. IR
spectra were recorded on a Nicolet FTIR-750 spectrometer. Elemental
analyses were performed on a Perkin Elmer 240-C instrument. All
solvents were dried by standard procedures.
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