June 1998
SYNTHESIS
913
Table 5. Summary of Analytical Dataa
Product
mp (°C)
Found
mp (°C)
Reported
1H NMR (DMSO-d6)
d, J (Hz)
IR (KBr)
–1
n (cm )
2
146–148
145–14617
1.95–2.35 (m, 2H), 2.96 (t, 2H, J = 7.7), 3.64 3331, 2762, 1736, 1684, 1537, 1319, 1275,
s, 3H), 4.16 (m, 1H), 5.04 (s, 2H), 7.36 (s, 1236, 1024, 756
H), 7.88 (d, 1H, J = 8.1)
(
5
4
9
151–153
215.5–216
153–154
151–152
245.5–246
144.5–145
201.5–202
263–263.5
201–202
225–226
237–238
99–100
146–1493
2.29 (s, 3H), 6.97 (d, 4H, J = 8.2), 7.12 (d, 2980, 2831, 2608, 1603, 1485, 1448, 1398,
2
H, J = 8.1), 7.53–7.69 (m, 4H)
1159, 1009, 910, 826, 756
217–21814
157–15814
152–152.514
250–250.514
143–14415
199–20016
268–2705
7.61–8.06 (m, 5H)
2689, 2546, 1609, 1564, 1485, 1165, 1057,
9
93, 791, 725, 704, 689
11
2.49 (s, 3H), 7.38–7.70 (m, 4H)
2.41 (s, 3H), 7.40–7.88 (m, 4H)
2.40 (s, 3H), 7.42–7.95 (m, 4H)
3.36 (br s, 2H), 6.67–7.73 (m, 4H)
6.74–7.26 (m, 4H)
2716, 2550, 1607, 1560, 1489, 1161, 1060,
91, 783, 746
9
1
1
1
1
2
2
2
2
3
3
5
7
9
1
3
5
7
1
3
2714, 2611, 1568, 1487, 1151, 1061, 1040,
04, 741, 689
8
2768, 2543, 1614, 1570, 1504, 1165, 1055,
91, 824, 744, 505
9
3385, 2997, 2785, 1616, 1553, 1492, 1464,
97, 750, 698, 669
9
3366, 3221, 2706, 1593, 1566, 1495, 1474,
157, 1065, 1038, 744, 679
1
5.79 (br s, 2H), 6.68–7.70 (m, 4H)
3485, 3387, 2735, 1622, 1607, 1512, 1408,
317, 1196, 1058, 839
1
3.37 (br s, 3H), 6.75 (dd, 1H, J = 8.5, 2.0), 3481, 3348, 2781, 1626, 1566, 1491, 1454,
6.97 (d, 1H, J = 2.0), 7.73 (d, 1H, J = 8.8)
1263, 1254, 1059, 910, 750
221–22218
233–24119
100.5–10114
92.5–93.514
7.00–8.02 (m, 4H)
3274, 2964, 1616, 1546, 1489, 1466, 1361,
1
298, 1070, 837, 812, 748
6.95–7.88 (m, 4H)
3429, 2711, 1614, 1601, 1516, 1416, 1281,
182, 1082, 845, 752, 523
1
3.04 (t, 2H, J = 4.2), 3.19 (t, 2H, J = 4.2),
3010, 2604, 1570, 1454, 1109, 1051, 993,
758, 719, 698
7
.17–7.30 (m, 5H)
3
90–91
1.98–2.05 (m, 2H), 2.65 (t, 2H, J = 4.0), 2.89 2866, 2623, 1570, 1497, 1454, 1421, 1256,
t, 2H, J = 4.0), 7.19–7.33 (m, 5H) 1107, 1049, 991, 746, 700
(
a
Elemental analysis C ± 0.37, H ± 0.37, N ± 0.29 except 27 C ± 0.59 and 2 N ± 0.43.
hexane, the reaction barely proceeded, probably due to the Commercially available reagents and solvents were used. Compound
1
was synthesized according to the published method.17 All HPLC
extremely low solubilities of the nitrile and the amine salt
to these solvents. The reaction in other aliphatic solvents
proceeded, but the yields are lower than for an aromatic
hydrocarbon.
analysis was performed with a UV detector (detection, 220 nm light),
a flow rate of 1.0 mL/min and using a Nucleosil 5C-18 (4.5 ´
1
50 mm) of column (eluent: MeCN/H O/H PO 2:8:0.001) except for
2 3 4
4
(with a UV detector (detection; 254 nm light), a flow rate of 1.0 mL/
min and using a Inertsil ODS (6 ´ 150 mm) of column [eluent:
Finally, we examined the effect of the acid on the reaction.
Amine salt was prepared by addition of an acid (HCl,
MeCN/H PO (1 mM) 65:35]. HPLC analysis were recorded by using
3
4
a SHIMADZU SPD-10A UV-VIS detector, a SHIMADZU LC-10A
HOAc, and H SO ) to a solution of triethylamine in tolu- LIQUID CHROMATOGRAPH, and a SHIMADZU C-R6A CHRO-
2
4
1
ene. To the resulting mixture, 8 and NaN were added for MATOPAC. H NMR spectra were obtained on a JEOL JNM-GX400
3
(400MHz) FT-NMR spectrometer, chemical shifts are reported rela-
the synthesis of 9. As shown in Table 4, 9 was obtained in
high yield, with only little decrease in yield during the re-
action with acetic acid.
tive to TMS. IR spectra were recorded on a Shimadzu 8200 PC spec-
trophotometer. Elemental analyses were performed with a Perkin–
Elmer CHNS/O Analyzer 2400. Mps were obtained on a Mettler
melting point apparatus FP61, and are uncorrected.
In conclusion, the novel method for the synthesis of tetra-
zole compounds we found is facile, inexpensive, safe, and
applicable to a variety of 5-substituted tetrazoles.