Hypervalent iodine in synthesis. 75. A convenient synthesis of oxadiazoles by palladium-catalyzed carbonylation and cyclization of diaryliodonium salts and amidoximes

Article abstract of DOI:10.1081/SCC-120002699

3,5-Disubstituted-1,2,4-oxadiazoles were prepared in one-pot procedure in moderate yields via the palladium-catalyzed carbonylation of diaryliodonium salts with amidoximes under one atmosphere of carbon monoxide followed by intramolecular dehydrative cycl

Full text of DOI:10.1081/SCC-120002699

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HYPERVALENT IODINE IN SYNTHESIS. 75. A CONVENIENT
SYNTHESIS OF OXADIAZOLES BY PALLADIUM-
CATALYZED CARBONYLATION AND CYCLIZATION OF
DIARYLIODONIUM SALTS AND AMIDOXIMES
Tao Zhou a & Zhen-Chu Chen a
a Department of Chemistry, Zhejiang University, Xixi Campus, Hangzhou, 310028, P.R. China
Published online: 16 Aug 2006.
To cite this article: Tao Zhou & Zhen-Chu Chen (2002): HYPERVALENT IODINE IN SYNTHESIS. 75. A CONVENIENT SYNTHESIS
OF OXADIAZOLES BY PALLADIUM-CATALYZED CARBONYLATION AND CYCLIZATION OF DIARYLIODONIUM SALTS AND AMIDOXIMES,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:6, 887-891
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SYNTHETIC COMMUNICATIONS, 32(6), 887–891 (2002)
HYPERVALENT IODINE IN SYNTHESIS.
75. A CONVENIENT SYNTHESIS OF
OXADIAZOLES BY PALLADIUM-
CATALYZED CARBONYLATION AND
CYCLIZATION OF DIARYLIODONIUM
SALTS AND AMIDOXIMES
*
Tao Zhou and Zhen-Chu Chen
Department of Chemistry, Zhejiang University
(Xixi Campus), Hangzhou, 310028, P.R. China
ABSTRACT
3,5-Disubstituted-1,2,4-oxadiazoles were prepared in one-pot
procedure in moderate yields via the palladium-catalyzed
carbonylation of diaryliodonium salts with amidoximes
under one atmosphere of carbon monoxide followed by intra-
molecular dehydrative cyclization.
As part of our research interest in palladium-catalyzed reaction of
diaryliodonium salts,1 here we wish to report a convenient synthetic
method for 3,5-disubstituted-1,2,4-oxadiazoles by palladium-catalyzed
carbonylation and cyclyzation of diaryliodonium salts and amidoximes
(Scheme 1).
*Corresponding author.
887
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

888
ZHOU AND CHEN
Scheme 1.
We examined the reaction of diphenyliodonium tetrafluoroborate
and benzamidoxime under one atmosphere of carbon monoxide in the
presence of palladium catalyst at 95–100ꢀC in several alternative solvents
including DMF, DME, dioxane and diglyme and found that dioxane was
the most suitable solvent for this reaction. Diaryliodonium salt reacts with
amidoxime under one atmosphere of carbon monoxide in the presence of
palladium catalyst to form O-acylation product 3 which is subjected to a
rapid intramolecular cyclo-dehydration at about 100ꢀC in dioxane to give
oxadiazole 4 in moderate yields. Several diaryliodonium salts having
electron-donating or -withdrawing group (such as methyl, methoxy,
chloro, nitro and bromo) and amidoximes were tested, the reaction is appli-
cable for these substrates. The results are summarized in Table 1. All
1
products were characterized by satisfactory H NMR, IR and m.p. data.
In summary, we have described a convenient one-pot synthesis of
3,5-disubstituted-1,2,4-oxadiazoles by palladium-catalyzed carbonylation
and cyclization of diaryliodonium salts and amidoximes. With the simple
procedure and the mild reaction conditions, our method nicely complements
existing ones.2–9 Furthermore, the range of useful applications of palladium-
catalyzed reaction of diaryliodonium salts in organic synthesis has been
extended.
EXPERIMENTAL
Melting points were uncorrected. 1H NMR data were recorded on
PMK-60spectrometer using CC1 4 as the solvent or on Avance 400 spectro-
meter using CDC13 as the solvent with TMS as an internal standard. IR
spectra were determined on Vector 22 infrared spectrometer with KBr
pallet. MS spectrum was recorded on HP5859B mass spectrometer.
Elemental analysis was determined on EA1110.

HYPERVALENT IODINE IN SYNTHESIS. 75
889
Table 1. Preparation of 3,5-Disubstituted-1,2,4-oxadiazoles
Entry
Ar
R
Product
Yield (%)*
1
2
3
4
5
6
7
8
9
10
11
12
13
Ph
p-Tol
Ph
Ph
Ph
Ph
Ph
Ph
4a
4b
4c
4d
4e
4f
4g
4h
4i
72
71
64
62
56
78
52
61
70
65
53
58
42
p-ClC6H4
p-CH3OC6H4
p-BrC6H4
m-NO2C6H4
Ph
p-CH3OC6H4
p-CH3OC6H4
p-CH3OC6H4
p-CH3OC6H4
p-ClC6H4
p-Tol
p-CH3OC6H4
p-ClC6H4
Ph
p-Tol
Ph
4j
4k
4l
p-ClC6H4
PhCH2
4m
*Isolated yield based on diaryliodonium salt.
General procedure for preparation of 3,5-disubstituted oxadiazoles.
A mixture of diaryliodonium salt 1 (1 mmol), amidoxime 2 (2 mmol), K2CO3
(2.5 mmol), PdC12(PPh3)2 (5 mol%) and dioxane (8 ml) was stirred under
CO atmosphere (1 atm) at 95–100ꢀC for 4–5 h. After cooling, the reaction
mixture was diluted with saturated NH4Cl aqueous (20ml), and extracted
with diethyl ether (3 ꢁ 15 ml). The combined organic layer was washed with
brine, dried over anhydrous sodium sulfate. After the removal of solvent
under vacuum, the residue was chromatographed on silica gel plate using
c-hexane/ethyl acetate (8:1) as a developer to give pure product 4.
Physical and Spectroscopic Data
3,5-Diphenyl-1,2,4-oxadiazole 4a. M.p. 105–107ꢀC (lit10 107–108ꢀC).
1H NMR (60MHz, CCl 4) dH 7.3–7.65 (m, 6H), 7.95–8.30(m, 4H). IR
1609, 1563, 1493, 1446, 1365, 1272, 1181, 1133, 1070, 1024, 972, 720, 795,
727, 688 cmꢂ1
.
5-(4-Methylphenyl)-3-phenyl-1,2,4-oxadiazole 4b. M.p. 114–116ꢀC
(lit10 117–118ꢀC). H NMR (60MHz, CCl ) dH 2.67 (s, 3H), 7.0–7.4 (m,
1
4
5H), 7.85–8.3 (m, 4H). IR 1611, 1561, 1495, 1452, 1371, 1262, 1177, 1032,
905, 839, 748, 716, 687 cmꢂ1
.
5-(4-Chlorophenyl)-3-phenyl-1,2,4-oxadiazole 4c. M.p. 122–124ꢀC (lit10
126ꢀC). H NMR (60MHz, CCl ) dH 7.1–7.55 (m, 5H), 7.8–8.4 (m, 4H).
1
4

890
ZHOU AND CHEN
IR 1630, 1598, 1553, 1506, 1467, 1440, 1332, 1125, 1088, 1012, 895, 780,
695 cmꢂ1
.
5-(4-Methoxyphenyl)-3-phenyl-1,2,4-oxadiazole 4d. M.p. 95–97ꢀC (lit11
97–98ꢀC). H NMR (60MHz, CCl ) dH 3.8 (s, 3H), 6.87–7.10(m), 7.3–7.6
1
4
(m, total 5H), 8.0–8.3 (m, 4H). IR 1614, 1503, 1472, 1442, 1421, 1370, 1262,
1180, 1137, 1024, 906, 832, 749, 711, 688 cmꢂ1
.
5-(4-Bromophenyl)-3-phenyl-1,2,4-oxadiazole 4e. M.p. 112–114ꢀC (lit11
113–114ꢀC). H NMR (400 MHz, CDCl3) dH 7.52 (m, 3H), 7.71 (d, 2H),
1
8.09 (d, 2H), 8.16 (m, 2H). IR 1605, 1554, 1484, 1445, 1362, 1272, 1134,
1011, 970, 913, 834, 743, 708, 690 cmꢂ1
.
5-(3-Nitrophenyl)-phenyl-1,2,4-oxadiazole 4f. M.p. 150–152ꢀC (lit12
152–153ꢀC). H NMR (400 MHz, CDCl3) dH 7.54 (m, 3H), 7.80(m, 1H),
1
8.19 (m, 2H), 8.48 (m, 1H), 8.55 (m, 1H), 9.09 (m, 1H). IR 1620, 1525, 1443,
1352, 1270, 1145, 1072, 918, 818, 720, 686 cmꢂ1
.
3-(4-Methoxyphenyl)-5-phenyl-1,2,4-oxadiazole 4g. M.p. 96–98ꢀC (lit8
97–98ꢀC). 1H NMR (400 MHz, CDCl3) dH 3.89 (s, 3H), 7.02 (m, 2H),
7.54–7.61 (m, 3H), 8.11 (m, 2H), 8.21 (m, 2H). IR 1599, 1555, 1469, 1331,
1294, 1178, 1149, 1125, 760, 693 cmꢂ1
.
3-(4-Methoxyphenyl)-5-(4-methylphenyl)-1,2,4-oxadiazole 4h. M.p.
108–110ꢀC (lit13 111.5–112ꢀC). H NMR (400 MHz, CDCl3) dH 2.45 (m,
1
3H), 3.88 (s, 3H), 7.01 (d, 2H), 7.35 (d, 2H), 8.10 (m, 4H). IR 1612, 1561,
1504, 1423, 1358, 1254, 1171, 1033, 839, 760 cmꢂ1
.
3,5-bis(4-Methoxyphenyl)-1,2,4-oxadiazole 4i. M.p. 130–132ꢀC (lit14
132ꢀC). H NMR (400 MHz, CDCl3) dH 3.86 (s, 6H), 6.95 (d, 4H), 7.59
1
(d, 4H). IR 1601, 1558, 1482, 1415, 1355, 1272, 1171, 1025, 825 cmꢂ1
.
5-(4-Chlorophenyl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole 4j. M.p.
138–139ꢀC. 1H NMR (400 MHz, CDCl3) dH 3.88 (s, 3H), 7.02 (d, 2H), 7.53
(d, 2H), 8.10 (d, 2H), 8.15 (d, 2H). IR 1609, 1558, 1490, 1420, 1369, 1253,
1174, 1094, 1032, 837, 759 cmꢂ1. MS m/z 288 (Mþþ 2, 33.23), 286 (Mþ, 100),
149 (93.50), 139 (25.55), 111 (15.75), 106 (39.61). Anal. Calcd. for
C15H11ClN2O2: C, 62.83; H, 3.87; N, 9.77. Found: C, 62.72; H, 3.87; N, 9.84.
3-(4-Chlorophenyl)-5-phenyl-1,2,4-oxadiazole 4k. M.p. 108–110ꢀC)
(lit15 108–109ꢀC). H NMR (400 MHz, CDCl3) dH 7.50(m, 2H), 7.56 (m,
1
2H), 7.61 (m, 1H), 8.13 (m, 2H), 8.21 (m, 2H). IR 1604, 1557, 1490, 1410,
.
1362, 1275, 1136, 1090, 1014, 966, 836, 741 cmꢂ1
3-(4-Chlorophenyl)-5-(4-methylphenyl)-1,2,4-oxadiazole
4l.
M.p.
126–128ꢀC (lit16 129.5–130ꢀC). H NMR (400 MHz, CDCl3) dH 2.46 (s,
1
3H), 7.35 (m, 2H), 7.49 (m, 2H), 8.10(m, 4H). IR 1592, 1562, 1501, 1411,
1363, 1274, 1136, 1091, 1014, 839, 754 cmꢂ1
.
5-Phenyl-3-phenylmethyl-1,2,4-oxadiazole 4m. M.p. 82–84ꢀC (lit17
81–82ꢀC). 1H NMR (60MHz, CCl 4) dH 4.0(s, 2H), 7.–07.6 (m, 8H),
7.9–8.25 (m, 2H). IR 1608, 1561, 1451, 1363, 730, 712, 692 cmꢂ1
.

HYPERVALENT IODINE IN SYNTHESIS. 75
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Received in the Netherlands April 12, 2001