Electrochemical oxidation of substituted amide oximes and 4,5-dihydro-1,2,4-oxadiazoles

Article abstract of DOI:10.1246/bcsj.76.427

The electrooxidation of several substituted amide oximes to yield the corresponding nitriles, alcohols, and imidate was successfully carried out. The reaction products were dependent on the substituents. Additionally, 4,5-dihydro-1,2,4-oxadiazoles derived from amide oximes were electro-oxidized to afford 1,2,4-oxadiazoles in good yields.

Full text of DOI:10.1246/bcsj.76.427

c. Jpn.
Bull. Chem. Soc. Jpn., 76, 427–428 (2003)
427
e Chemical
ciety of Ja-
n
Short Articles
e Chemical
ciety of Ja-
n
and PhCO (1d, 1e, and 1f, respectively), mixtures of benzoni-
trile and corresponding alcohols (3d and 3e) were obtained,
while and in the case of 1f, methyl benzoate instead of the
alcohol was formed. On the other hand, in the case of R1 =
Me, R2 = H, and R3 = Ph (1g), imidate 4g was obtained as the
main product. As a note, 4g was produced previously by a
two-step photochemical reaction of an alkoxytungstencarbene
complex with azobenzene5 and an alkoxychromiumcarbene
complex with sulfilimines.6 However, this two-step method
was limited by a somewhat troublesome preparation of the
starting materials; in contrast, 4g could be obtained in reason-
able yields using readily available substrates in our electrooxi-
dation method. Although the detailed reaction mechanisms are
not clear, based on our observations that these oxidation reac-
tions were almost complete after the consumption of 1.2 F/mol
of electricity, it can be assumed that the electrooxidation of 1
to 2, 3, and 4 proceeded through one-electron transfer oxida-
tion.
In addition, as shown in Fig. 1, amide oxime readily reacted
with certain aldehydes to give 4,5-dihydro-1,2,4-oxadiazoles
(5).7 Although the electroreductions of 1,3,4-oxadiazoles have
been reported,8 the electrooxidative behavior of 5 was not ex-
amined. Typically, the compounds are oxidized using strong
oxidizing agents, such as potassium permanganate9 or sodium
hypochlorite,10 to yield the corresponding oxadiazoles (6).11
In our case, electrooxidation was successful in affording 6 in
72–85% isolated yields, as shown in Table 2. In every case,
the substrates were almost completely consumed after 2.2 F/
mol of electricity had been passed. The electrooxidation reac-
tion of 5 could also be carried out without any substituent
effects at the 3- and 5-positions under the conditions described
in the experimental section. In conclusion, although amide
oximes, unlike aldoximes, are relatively stable towards solvo-
lysis in the presence of strong acid or base catalysts, even at
Electrochemical Oxidation of
Substituted Amide Oximes and
4,5-Dihydro-1,2,4-Oxadiazoles
M. Okimoto et al.
03
7
8
SJA8
09-2673
2749
Mitsuhiro Okimoto* and Yukio Takahashi
Department of Applied Chemistry and Circumstance
Engineering, Kitami Institute of Technology, Koen-chyo 165,
Kitami 090-8507
(Received September 12, 2002)
02
02
The electrooxidation of several substituted amide
oximes to yield the corresponding nitriles, alcohols, and imi-
date was successfully carried out. The reaction products were
dependent on the substituents. Additionally, 4,5-dihydro-
1,2,4-oxadiazoles derived from amide oximes were electro-
oxidized to afford 1,2,4-oxadiazoles in good yields.
.3
0.2
We previously reported on the electrooxidations of various
nitrogen-containing organic compounds, such as enamines,1
hydrazones,2 and imines.3 As a continuation of this series of
studies, we carried out the direct electrooxidation of amide
oximes and its derivatives. Shono and co-workers have
reported4 on the indirect electrooxidation of aldoxime using
halide ion as the electron carrier in forming the corresponding
nitriles; however, to the best of our knowledge, the direct elec-
trooxidation of amide oxime (1) has not been reported to date.
In this study, we observed that the type of product formed from
1 was remarkably dependent on the substituents (R1, R2, and
R3; Table 1). In the cases of R2 = R3 = H and R1 = Ph,
PhCH2, and iso-C5H11 (1a, 1b, and 1c, respectively), the corre-
sponding nitriles (2a, 2b, and 2c) were isolated in good yields.
In the cases of R1 = Ph, R3 = H, and R2 = iso-C5H11, PhCH2,
Table 1. Electrochemical Oxidation of Amide Oximesa)
Fig. 1.
Table 2. Electrochemical Oxidation of 4,5-Dihydro-1,2,4-
oxadiazolesa)
Yieldb)/%
R1
R2
R3
2
3
4
1a Ph
H
H
H
H
H
H
H
H
H
Ph
85
70
80
(81)
(88)
(85)
R1
R2
Yieldb) of 6/%
1b PhCH2
1c iso-C5H11
1d Ph
1e Ph
1f Ph
5a
5b
5c
5d
5e
5f
iso-C5H11
Ph
Ph
Et
Et
iso-C3H7
n-C5H11
Et
72
78
82
80
81
85
84
iso-C5H11
PhCH2
PhCO
H
(75)
(78)
(58)c)
Ph
1g Me
72
p-ClC6H4
PhCH2
PhCH2
Et
iso-C3H7
a) 1.2–1.5 F/mol of electricity was passed. b) Values in
parenthesis were determined by GLC analysis. c) Yield of
methyl benzoate.
5g
a) 2.2 F/mol of electricity was passed. b) Isolated yield.

428 Bull. Chem. Soc. Jpn., 76, No. 2 (2003)
© 2003 The Chemical Society of Japan
hPa. IR (neat) 2986, 2943, 1580, 1497, 1456, 887, 733, 696 cm−1
.
elevated temperatures, they readily underwent electrooxidation
to yield nitriles, alcohols, and imidate under very mild condi-
tions. Moreover, 4,5-dihydro-1,2,4-oxadiazoles that were ob-
tained by a simple condensation reaction between an amide
oxime and an aldehyde were electrooxidized to afford the cor-
responding 1,2,4-oxadiazoles in good yields.
1H NMR (CDCl3) δ 1.28 (t, 3H, J = 7 Hz), 2.78 (t, 2H, J = 8 Hz),
4.00 (s, 2H), 7.0–7.6 (m, 5H). 13C NMR (CDCl3) δ 10.6 (CH3),
20.2 (CH2), 32.3 (CH2), 127.0 (CH), 128.6 (CH), 129.0 (CH),
135.7 (C), 169.3 (C), 180.7 (C). MS m/z (rel intensity) 188 (M+,
28), 173 (40), 132 (100), 131 (25), 103 (25), 91 (25), 77 (18), 57
(17), 29 (20). HRMS m/z Found: 188.0911 (M+), Calcd for
C11H12ON2: 188.0950.
Experimental
3-Benzyl-5-isopropyl-1,2,4-oxadiazole (6g).
Bp 114–115
Amide oximes 1a–c were prepared by reactions between hy-
droxylamine and the corresponding nitriles.12 1d–f were prepared
by the reaction of benzamide oxime with alkyl halide.13a 1g was
synthesized by the reaction of acetamide oxime hydrochloride
with aniline.13b 4,5-dihydro-1,2,4-oxadiazoles 5 were prepared by
refluxing the corresponding amide oximes and aldehydes in
EtOH.7 Preparative-scale electrooxidation was carried out in a tall
50- or 100-mL beaker equipped with a fine frit cup as the cathode
compartment, a cylindrical platinum net anode (diameter, 33 mm;
height, 40 mm), and a nickel coil cathode. The electrooxidation of
amide oxime 1 was carried out in MeOH (80 mL) containing 1 (20
mmol) and KOH (20 mmol) under a constant current (0.4 A). The
electrooxidation of 4,5-dihydro-1,2,4-oxadiazoles 5 was carried
out in MeOH (40 mL) containing 5 (5 mmol) and NaOAc (10
mmol) under a constant current (0.3 A). In both cases, the anolyte
was stirred using a magnetic stir bar, and the temperature of the
solution was maintained at ca. 15 °C. After completion of the
electrooxidation, treatment of the reaction mixture was achieved
as follows. The anolyte was concentrated in vacuo at ca. 30 °C to
approximately one-fifth of its original volume. The resulting resi-
due was treated with water (50 mL), then extracted with ether (3
× 50 mL). The ethereal extracts were combined, and dried over
anhydrous magnesium sulfate. After removal of the solvent, the
residue was purified either by distillation in vacuo or by recrystal-
lization from MeOH.
°C/5.3 hPa. IR (neat) 2978, 2937, 1576, 1498, 1456, 891, 727, 696
1
cm−1. H NMR (CDCl3) δ 1.24 (d, 6H, J = 7 Hz), 2.8–3.4 (m,
1H), 4.00 (s, 2H), 7.0–7.6 (m, 5H). 13C NMR (CDCl3) δ 20.0
(CH3), 27.4 (CH), 32.3 (CH2), 126.9 (CH), 128.6 (CH), 129.0
(CH), 135.8 (C), 169.2 (C), 183.8 (C), 168.3 (C). MS m/z (rel
intensity) 202 (M+, 21), 132 (100), 117 (20), 103 (21), 91 (26), 77
(16), 43 (39). HRMS m/z Found: 202.1115 (M+), Calcd for
C12H14ON2: 202.1106.
References
1
T. Chiba, M. Okimoto, H. Nagai, and Y. Takata, J. Org.
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2
a) T. Chiba, M. Okimoto, H. Nagai, and Y. Takata, J. Org.
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a) F. Tiemann, Ber. Dtsch. Chem. Ges., 22, 2419 (1889). b)
3-Isopentyl-5-ethyl-1,2,4-oxadiazole (6a). Bp 110–111 °C/
44 hPa. IR (neat) 2959, 2872, 1583, 891 cm−1. 1H NMR (CDCl3)
δ 0.95 (d, 6H, J = 7Hz), 1.39 (t, 3H, J = 7Hz), 1.4–1.8 (m, 3H),
2.71 (t, 2H, J = 7 Hz), 2.89 (q, 2H, J = 7 Hz). 13C NMR (CDCl3)
δ 10.8 (CH3), 20.2 (CH2), 22.3 (CH3), 24.1 (CH2), 27.8 (CH), 36.0
(CH2), 170.7 (C), 180.2 (C). MS m/z (rel intensity): 168 (M+), 125
(24), 113 (49), 112 (100), 97 (31), 57 (57), 41 (38), 29 (45).
HRMS m/z Found: 168.1262 (M+), Calcd for C9H16N2O:
168.1263.
7
8
9
D. Vorlander, Ber. Dtsch. Chem. Ges., 24, 803 (1891).
10 T. Nꢀ Gando, C. Malavaud, and J. Barrans, C. R. Acad. Sci.,
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11 a) L. C. Behr, “The Chemistry of Heterocyclic Com-
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A. R. Katritzky and A. J. Boulton, “Advances in Heterocyclic
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(1976) Vol. 20, p. 65.
12 F. Tiemann and P. Kruger, Ber. Dtsch. Chem. Ges., 17,
1693(1884).
13 These substrates were synthesized according to the method
described in “Beilsteins Handbuch der Organischen Chemie 4 th
ed”. a) Vol. 9, 307 (1942), b) Vol. 12, 243 (1943).
3-Phenyl-5-pentyl-1,2,4-oxadiazole (6d). Bp 138–139 °C/
5.3 hPa. IR (neat) 2959, 1595, 1572, 1447, 1364, 907, 721, 694
cm−1. 1H NMR (CDCl3) δ 0.90 (t, 3H, J = 7 Hz), 1.1–1.5 (m, 4H),
1.6–2.1 (m, 2H), 2.89 (t, 2H, J = 7 Hz), 7.3–7.6 (m, 2H). 13C
NMR (CDCl3) δ 13.8 (CH3), 22.2 (CH2), 26.4 (CH2), 26.6 (CH2),
31.2 (CH2), 127.2 (C), 127.4 (CH), 128.8 (CH), 131.0 (CH), 168.3
(C), 180.0 (C). MS m/z (rel intensity) 216 (M+, 34), 173 (40), 160
(74), 119 (100), 118 (78), 103 (53), 91 (37). HRMS m/z Found:
216.1270 (M+), Calcd for C13H16N2O: 216.1263.
3-Benzyl-5-ethyl-1,2,4-oxadiazole (6f). Bp 112–113 °C/5.3