The Journal of Organic Chemistry
Article
Scheme 1. Plausible Mechanism for Oxime Formation
7. (E)-4-Hydroxybenzaldehyde Oxime (4g).50,59 White solid; yield:
0.102 g, 92%; mp: 93−95 °C; 1H NMR (500 MHz, DMSO): δ 10.824
(s, 1), 9.737 (s, 1H), 7.986 (s, 1H), 7.396−7.379 (d, J = 8.55, 2H),
6.765−6.748 (d, J = 8.55, 2H); ESI-MS m/z 137 [M]+.
CONCLUSIONS
■
In summary, we have developed a rapid and selective protocol
for oxidation of various benzyl, alicyclic, and aliphatic amines to
corresponding oximes using m-CPBA at room temperature.
The oximes obtained from various benzyl amine derivatives
selectively give E-isomer, whereas aliphatic amines give a
mixture of E- and Z-isomers. The solvent used, ethyl acetate,
was found to be most promising which offered easy separation
of desired products from the reaction mixture.
8. (E)-2-Nitrobenzaldehyde Oxime (4h).60 White solid; yield: 0.099
g, 91%; mp: 99−100 °C; 1H NMR (500 MHz, CDCl3) δ 8.69 (s, 1H),
8.07 (d, J = 8.2 Hz, 1H), 7.94 (d, J = 7.8 Hz, 1H), 7.73 (s, 1H), 7.66 (t,
J = 7.6 Hz, 1H), 7.59−7.54 (m, 1H); ESI-MS m/z 166 [M]+.
9. (E)-3-Nitrobenzaldehyde Oxime (4i).50,61 White solid; yield:
1
0.097 g, 89%; mp: 120−122 °C; H NMR (500 MHz, CDCl3): δ
8.451−8.444 (t, J = 2, 1H), 8.256−8.233 (dd, J = 8.5, 2.5, 1H), 8.215
(s, 1H), 7.926−7.913 (dd, J = 8.0, 1.5, 1H), 7.736 (s, 1H), 7.603−
7.572 (t, J = 8, 7.5, 1H); ESI-MS m/z 166 [M]+.
EXPERIMENTAL SECTION
■
10. (E)-4-Nitrobenzaldehyde Oxime (4j).50,62 Light yellow solid;
yield: 0.10 g, 92%; mp: 126−128 °C; 1H NMR (500 MHz, DMSO): δ
11.84 (s, 1H), 8.31 (s, 1H), 8.28−8.23 (m, 2H), 7.88−7.83 (m, 2H);
ESI-MS m/z 166 [M]+.
Chemicals and Instruments. The m-CPBA used was “Synthesis
Grade” m-CPBA. The ethyl acetate used was AR grade “DRY” Ethyl
1
Acetate. The H NMR spectroscopic data were recorded on a 500
MHz, 400 MHz spectrometer with CDCl3 and DMSO-d6 as solvent,
and chemical shifts are expressed in δ ppm using TMS as an internal
standard. GC analysis were carried out using column-TR-1, 30mX0.25
mm, IDX0.25um film, FID detector and sample size 0.11 μL. All
melting points are uncorrected and are presented in Celsius.
General Procedure for the Oxidation of Benzylamine. An
oven-dried round-bottom flask was charged with 2 mL of ethyl acetate
and 100 μL of benzylamine (0.933 mmol, 1 equiv) at room
temperature. The above mixture was stirred for 2 to 3 min. To this
320 mg of m-CPBA (0.187 mmol, 2 equiv) was added under constant
stirring. The reaction mass was further stirred at room temperature,
and the progress of reaction was monitored by TLC. After completion,
the reaction was quenched by adding 3 mL of saturated sodium
bicarbonate solution. The product was extracted by adding an extra 5
mL of ethyl acetate and stirred for 15 min. The aqueous layer was
further extracted in ethyl acetate (3 × 5 mL). All organic layers were
combined and washed with water until neutral pH, dried over
anhydrous sodium sulfate, and concentrated to give crude product
which was further purified by column chromatography using a hexane/
ethyl acetate system.
11. (E)-4-Fluorobenzaldehyde Oxime (4k).50,63 White solid; yield:
1
0.098 g, 88%; mp: 87−88 °C; H NMR (500 MHz, CDCl3): δ 8.127
(s, 1H), 7.856 (s, 1H), 7.589−7.560 (dd, J = 5.4, 5.5, 2H), 7.106−
7.072 (t, J = 8.7, 8.65, 2H); ESI-MS m/z 139 [M]+.
12. (E)-4-Chlorobenzaldehyde Oxime (4l).50,54 White solid; yield:
1
0.10 g, 91%; mp: 108−110 °C; H NMR (500 MHz, CDCl3): δ 8.12
(s, 1H), 8.03 (s, 1H), 7.534−7.525 (d, J = 8.4, 2H), 7.385−7.359 (d, J
= 8.55, 2H); ESI-MS m/z 155 [M]+.
13. (E)-Acetophenone Oxime (4m).64,65 White solid; yield: 0.103 g,
1
92%; mp: 58 °C; H NMR (500 MHz, CDCl3): δ 8.984 (s, 1H),
7.650−7.630 (q, 2H); 7.408−7.393 (q, 3H), 2.319 (s, 3H); ESI-MS
m/z 135 [M]+.
14. (E)-1-Naphthaldehyde Oxime (4n).50,66 White solid; yield:
0.096 g, 88%; mp: 94−96 °C; 1H NMR (500 MHz, DMSO): δ 11.51
(s, 1H), 8.80 (s, 1H), 8.68 (d, J = 8.45 Hz, 1H), 7.95 (t, J = 7.5, 7.65
Hz, 2H), 7.81 (d, J = 6.6 Hz, 1H), 7.63−7.49 (m, 3H); ESI-MS m/z
171 [M]+.
15. (E)-Benzo[d][1,3]dioxole-5-carbaldehyde Oxime (4o).67 White
1
Spectral Data for the Representative Compounds. 1. (E)-
Benzaldehyde Oxime (4a).50,51 White solid; yield: 0.105 g, 93%; mp:
32−33 °C; 1H NMR (500 MHz, CDCl3): δ 8.78 (s, 1H), 8.19 (s, 1H),
7.61−7.59 (m, 2H), 7.42−7.43 (m, 3H); ESI-MS m/z 121 [M]+.
2. (E)-2-Methoxybenzaldehyde Oxime (4b).52,53 White solid; yield:
0.101 g, 92%; mp: 88−90 °C; 1H NMR (400 MHz, DMSO): δ 11.19
(s, 1H), 8.29 (s, 1H), 7.65 (dd, J = 7.7, 1.4 Hz, 1H), 7.41−7.31 (m,
1H), 7.06 (d, J = 8.4 Hz, 1H), 6.95 (t, J = 7.5 Hz, 1H), 3.82 (s, 3H);
ESI-MS m/z 151 [M]+.
solid; yield: 0.097 g, 89%; mp: 104−105 °C; H NMR (500 MHz,
CDCl3) δ 8.04 (s, 1H), 7.27 (d, J = 1.4 Hz, 1H), 7.17 (d, J = 1.3 Hz,
1H), 6.96 (d, J = 8.0 Hz, 1H), 6.81 (d, J = 8.0 Hz, 1H), 6.00 (d, J = 1.4
Hz, 2H) ; ESI-MS m/z 165 [M]+.
16. Cyclohexanone Oxime (4p).42,68 White solid; yield: 0.103 g,
1
90%; mp: 106−108 °C; H NMR (500 MHz, CDCl3): δ 8.546 (s,
1H), 2.522−2.497 (t, 2H), 2.228−2.203 (t, J = 6.0, 2H), 1.699−1.584
(m, J = 6.05, 6H); ESI-MS m/z 113 [M]+.
17. Cyclopentanone Oxime (4q).42,68 White solid; yield: 0.104 g,
3. (E)-3-Methoxybenzaldehyde Oxime (4c).52,54 White solid; yield:
0.104 g, 94%; mp: 39−40 °C; 1H NMR (400 MHz, DMSO): δ 11.16
(s, 1H), 8.10 (s, 1H), 7.25 (t, J = 7.5 Hz, 1H), 7.13 (d, J = 8.6 Hz,
2H), 6.87 (d, J = 7.5 Hz, 1H), 3.73 (s, 3H); ESI-MS m/z 151 [M]+.
4. (E)-4-Methoxybenzaldehyde Oxime (4d).50,55 White solid; yield:
1
89%; mp: 56−58 °C; H NMR (500 MHz, CDCl3) δ 7.62 (s, broad,
1H), 2.46 (t, J = 7.0 Hz, 2H), 2.37 (t, J = 6.9 Hz, 2H), 1.77 (dq, J =
11.3, 6.4 Hz, 4H); ESI-MS m/z 99 [M]+.
18. 1-Butyraldehyde Oxime (4s).69 Pale yellow liquid; yield: 0.093
1
g, 78%; bp:149−151 °C; H NMR (500 MHz, CDCl3) δ 4.27 (t, J =
1
0.10 g, 92%; mp: 63−64 °C; H NMR (400 MHz, DMSO): δ 10.93
7.2 Hz, 1H), 1.92−1.81 (q, 2H), 1.47−1.35 (m, 2H), 0.96 (t, J = 7.4
(s, 1H), 8.05 (s, 1H), 7.50 (d, J = 8.8 Hz, 2H), 6.93 (d, J = 8.8 Hz,
Hz, 3H); ESI-MS m/z 87 [M]+.
2H), 3.75 (s, 3H); ESI-MS m/z 151 [M]+.
19. 2-Butyraldehyde Oxime (4t).68 Yellow liquid; yield: 0.094 g,
5. (E)-4-(tert-Butyl)Benzaldehyde Oxime (4e).56 White solid; yield:
0.1 g, 92%; mp 105−106 °C; 1H NMR (500 MHz, CDCl3) δ 8.14 (s,
1H), 7.72 (s, broad, 1H), 7.55−7.49 (m, 2H), 7.42 (dd, J = 8.3, 1.5 Hz,
2H), 1.34 (d, J = 1.7 Hz, 9H); ESI-MS m/z 177 [M]+.
1
79%; bp: 150−152 °C; H NMR (500 MHz, CDCl3) δ 8.84 (s, 1H),
2.41−2.33 (m, 2H), 1.97 (s, 3H), 1.11−1.08 (m, 3H); ESI-MS m/z 87
[M]+.
20. 1-Octanal Oxime (4u).70 White solid; yield: 0.09 g, 81%; mp:
6. (E)-3,4-Dimethoxybenzaldehyde Oxime (4f).57,58 White solid;
1
1
58−60 °C; H NMR (500 MHz, CDCl3) δ 4.26 (t, J = 7.3 Hz, 1H),
yield: 0.102 g, 94%; mp 91−92 °C; H NMR (500 MHz, CDCl3) δ
1.87 (dd, J = 14.4, 6.8 Hz, 2H), 1.42−1.22 (m, 10H), 0.88 (t, J = 6.2
8.08 (s, 1H), 7.45 (s, 1H), 7.23 (s, 1H), 7.03 (d, J = 7.5 Hz, 1H), 6.86
(d, J = 7.2 Hz, 1H), 3.91 (s, 6H); ESI-MS m/z 181 [M]+.
Hz, 3H) ; ESI-MS m/z 142 [M-H]+.
D
J. Org. Chem. XXXX, XXX, XXX−XXX