Nitration-Oximization of Styrene Derivatives with tert-Butyl Nitrite: Synthesis of α-Nitrooximes

Article abstract of DOI:10.1002/cjoc.201600167

A highly efficient method for direct nitration-oximization of styrene derivatives using tert-butyl nitrite (t-BuONO) in DMSO was developed. The present method offers a convenient and practical approach for the synthesis of α-nitrooximes in moderate to high yields. The salient features entail mild reaction conditions, metal-free reagent, environmentally benign solvent and simple experimental procedure.

Full text of DOI:10.1002/cjoc.201600167

FULL PAPER
DOI: 10.1002/cjoc.201600167
Nitration-Oximization of Styrene Derivatives with
tert-Butyl Nitrite: Synthesis of α-Nitrooximes
Napasawan Chumnanvej, Praewpan Katrun, Manat Pohmakotr, Vichai Reutrakul,
Darunee Soorukram, and Chutima Kuhakarn*
Department of Chemistry and Center of Excellence for Innovation in Chemistry (PERCH-CIC), Faculty of Science,
Mahidol University, Rama VI Road, Bangkok 10400, Thailand
A highly efficient method for direct nitration-oximization of styrene derivatives using tert-butyl nitrite
(t-BuONO) in DMSO was developed. The present method offers a convenient and practical approach for the syn-
thesis of α-nitrooximes in moderate to high yields. The salient features entail mild reaction conditions, metal-free
reagent, environmentally benign solvent and simple experimental procedure.
Keywords α-nitrooximes, tert-butyl nitrite, nitration-oximization, styrenes
Introduction
practical aspect, metal-free syntheses are preferable, as
the reaction under metal-free conditions would be of
great importance to the pharmaceutical fields. Therefore,
a related set of transformations would be of particular
interest, if it can be carried out under metal-free condi-
tions without lowering the reaction efficiency. It is
worth to note here that limited works toward the realm
of α-nitrooxime synthesis were published.[10] During a
process of preparation this manuscript, a report on the
use of t-BuONO in a mixture of DMSO-water (2∶1,
V∶V), r.t., 12 h for α-nitrooxime synthesis of styrene
derivatives was disclosed by Tan and co-workers.[10e]
This prompts us to report our findings. We report herein
that a range of styrene derivatives, vinyl-substituted
heteroaromatics as well as 1-aryl-1,3-butadienes can
readily undergo nitration-oximization employing
t-BuONO in DMSO under an air atmosphere at room
temperature for 30 min to yield their corresponding
The development of environmentally friendly and
operationally simple synthetic methods for the construc-
tion of functionalized molecules receives continuous
attention in modern organic synthesis.[1] Therefore,
chemists aim to develop green and sustainable proce-
dures, such as heterogeneous catalysis,[2] metal-free
synthesis[3] or catalyst-free synthesis.[4] In particular,
metal-free synthetic protocols which avoid the utiliza-
tion of any metals have been extensively studied as the
alternatives to reactions mediated by toxic, expensive
and difficult to handle metallic reagents. Additionally,
the metal residue and environmental pollution are usu-
ally the important problem caused by metal-mediated
transformations. Vicinal diamines exist in many natu-
rally occurring and biologically active compounds and
exhibit as important building blocks and ligands in the
field of asymmetric synthesis.[5] Therefore, a number of
research efforts have been devoted to devise convenient
methods for vicinal diamine syntheses.[6] Among those,
direct diamination of alkenes is clearly a powerful route
to construct vicinal diamine scaffolds.[7] As a part of our
ongoing interest in the development of new methodolo-
gy towards difunctionalization of alkenes and alkynes,[8]
we recently disclosed OXONE® mediated α-nitrooximes
synthesis employing NaNO2 in aqueous acetonitrile
(Scheme 1).[9] The method while offering a direct
method for preparation of α-nitrooximes from styrene
derivatives had several limitations including require-
ment of excess quantities of reagents, poor results with
electron-releasing substituted styrene derivatives and
portion-wise addition of a reagent. Notably, from a
Scheme 1 Nitration-oximization of styrene derivatives
*
E-mail: Chutima.kon@mahidol.ac.th
Received March 17, 2016; accepted April 1, 2016; published online XXXX, 2016.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201600167 or from the author.
Chin. J. Chem. 2016, XX, 1—9
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1

Chumnanvej et al.
FULL PAPER
α-nitrooximes (Scheme 1). The method offers experi-
mental simplicity, practical and facile method, using
non-metallic reagents under mild and facile reaction
conditions.
215.0223, found 215.0213.
1-(3-Chlorophenyl)-2-nitroethanone oxime (2c):[9]
Yellow viscous oil (80.1 mg, 74% yield). 1H NMR (400
MHz, CDCl3, isomeric ratio 13.3∶1, minor isomer
marked *) δ: 9.53 (br s, 1H of major and minor isomers),
7.63 (t, J＝1.6 Hz, 1H of major and minor isomers),
7.48－7.34 (m, 3H of major and minor isomers), 5.62 (s,
1.86H), 5.39* (s, 0.14H); 13C NMR (100 MHz, CDCl3)
δ: 147.5 (C), 135.1 (C), 134.7 (C), 130.5 (CH), 130.3
(CH), 130.0* (CH), 128.5* (CH), 126.3 (CH), 126.2*
(CH), 124.3 (CH), 77.8* (CH2), 68.2 (CH2) (Some
peaks of the minor isomer could not be detected by 13C
NMR due to their low intensity); IR (KBr) ν: 3274 (O－
H), 1630 (C＝N), 1559 and 1373 (NO2) cm1; HRMS
(APCI-TOF) calcd for C8H7ClN2NaO3 [M ＋ Na] ＋
237.0043, found 237.0041.
Experimental
General
1H NMR spectra were recorded with a Bruker
DPX-300 (300 MHz) or a Bruker Ascend™ 400 (400
MHz) spectrometer in CDCl3 using tetramethylsilane as
an internal standard or in acetone-d6 using a residual
non-deuterated solvent peak as an internal standard. 13C
NMR spectra were recorded with a Bruker DPX-300
(75 MHz) or a Bruker Ascend™ 400 (100 MHz) spec-
trometer in CDCl3 or acetone-d6 using a residual non-
deuterated solvent peak as an internal standard. IR spec-
tra were recorded with a Perkin Elmer 683 GX FTIR
System spectrometer. High resolution mass spectra were
recorded with a Bruker micro TOF spectrometer. Melt-
ing points were recorded with a digital Electrothermal
Melting 9100 apparatus and uncorrected. Column
chromatography was performed using Merck silica gel
(Art 7734). Other common solvents (dichloromethane,
hexanes, ethyl acetate, and acetone) were distilled be-
fore use.
1-(2-Chlorophenyl)-2-nitroethanone oxime (2d):[9]
Yellow viscous oil (64.8 mg, 60% yield). 1H NMR (400
MHz, CDCl3, isomeric ratio 1.6∶1, minor isomer
marked *) δ: 9.50 (br s, 0.59H), 8.78* (br s, 0.35H),
7.53－7.34 (m, 4H of major and minor isomers), 5.60 (s,
1.24H), 5.42* (s, 0.76H); 13C NMR (100 MHz, CDCl3)
δ: 148.9 (C), 148.0* (C), 132.6 (C), 132.5* (C), 131.7
(CH), 131.5 (CH), 131.2* (CH), 130.7* (CH), 130.0
(CH), 129.8* (CH), 129.6 (C), 127.5 (CH), 127.1* (CH),
77.4* (CH2), 70.2 (CH2) (Some peaks of the minor iso-
mer could not be detected by 13C NMR due to their low
intensity); IR (neat) ν: 3272 (O－H), 1622 (C＝N),
General procedure for the synthesis of α-nitrooximes
tert-Butyl nitrite (103.1 mg, 0.12 mL, 1 mmol) was
added to a solution of the substrate (0.5 mmol) in dime-
thylsulfoxide (2.5 mL). The solution was stirred under
an air atmosphere at room temperature (32－35 ℃) for
30 min. Then the reaction solution was quenched by the
addition of water (5 mL) and was extracted with EtOAc
(15 mL×3). The combined organic layers were washed
with H2O (20 mL) and brine (20 mL), dried (anhydrous
MgSO4), filtered and vacuumed (aspirator). The residue
was purified by column chromatography (SiO2) using
acetone/hexanes as the eluent to afford the correspond-
ing product.
1558 and 1373 (NO2) cm1; HRMS (APCI-TOF) calcd
for C8H7ClN2NaO3 [M ＋ Na]
237.0042.
＋
237.0043, found
1-(4-Fluorophenyl)-2-nitroethanone oxime (2e):[10d]
Yellow viscous oil (71.2 mg, 71% yield). 1H NMR (400
MHz, CDCl3, isomeric ratio 8.5∶1, minor isomer
marked *) δ: 9.67 (br s, 0.83H), 9.35* (br s, 0.10H),
7.59 (dd, J＝8.6, 4.6 Hz, 2H of major and minor iso-
mers), 7.11 (dd, J＝8.6, 4.6 Hz, 2H of major and minor
isomers), 5.62 (s, 1.79H), 5.40* (s, 0.21H); 13C NMR
(100 MHz, CDCl3) δ: 164.0 (d, J＝250.4 Hz, C), 163.4*
(d, J＝250.4 Hz, C), 147.8 (d, J＝12.5 Hz, C), 130.7 (d,
J＝8.6 Hz, 2×CH), 129.1 (d, J＝3.2 Hz, C), 128.3* (d,
J＝8.6 Hz, 2×CH), 116.3 (d, J＝21.8 Hz, 2×CH),
115.9* (d, J＝21.8 Hz, 2×CH), 78.0* (CH2), 68.6 (CH2)
(Some peaks of the minor isomer could not be detected
by 13C NMR due to their low intensity); IR (KBr) ν:
3279 (O－H), 1602 (C＝N), 1549 and 1376 (NO2) cm1;
HRMS (APCI-TOF) calcd for C8H7FN2NaO3 [M＋Na]＋
221.0338, found 221.0337.
1-(4-Bromophenyl)-2-nitroethanone oxime (2a):[9]
White solid (112.6 mg, 87% yield). m.p. 97－98 ℃
1
(CH2Cl2/hexanes); H NMR (400 MHz, acetone-d6) δ:
11.67 (s, 1H), 7.75 (d, J＝8.6 Hz, 2H), 7.63 (d, J＝8.6
Hz, 2H), 5.89 (s, 2H); 13C NMR (100 MHz, acetone-d6)
δ: 147.2 (C), 133.5 (C), 131.8 (2×CH), 127.9 (2×CH),
123.4 (C), 68.0 (CH2); IR (KBr) ν: 3232 (O－H), 1636
(C＝N), 1558 and 1375 (NO2) cm1; HRMS (APCI-
TOF) calcd for C8H8BrN2O3 [M＋H]＋ 258.9718, found
258.9719.
1-(3-Fluorophenyl)-2-nitroethanone oxime (2f):[9]
Yellow viscous oil (72.8 mg, 74% yield). 1H NMR (400
MHz, CDCl3, isomeric ratio 26.9∶1, minor isomer
marked *) δ: 9.28 (br s, 1H of major and minor isomers),
7.44－7.36 (m, 3H of major and minor isomers), 7.18－
7.13 (m, 1H of major and minor isomers), 5.63 (s,
1.88H), 5.40* (s, 0.07H); 13C NMR (100 MHz, CDCl3)
δ: 163.0 (d, J＝245.9 Hz, C), 147.6 (d, J＝2.4 Hz, C),
135.1 (d, J＝7.9 Hz, C), 130.7 (d, J＝8.3 Hz, CH),
130.4* (d, J＝8.3 Hz, CH), 123.7* (d, J＝3.0 Hz, CH),
1-(4-Chlorophenyl)-2-nitroethanone oxime (2b):[10d]
Yellow viscous oil (79.8 mg, 74% yield). 1H NMR (400
MHz, CDCl3) δ: 9.18 (br s, 1H), 7.56 (d, J＝8.5 Hz, 2H),
7.41 (d, J＝8.5 Hz, 2H), 5.63 (s, 2H); 13C NMR (100
MHz, CDCl3) δ: 147.7 (C), 136.7 (C), 131.4 (C), 129.4
(2×CH), 127.5 (2×CH), 68.2 (CH2); IR (KBr) ν: 3235
(O－H), 1596 (C＝N), 1562 and 1379 (NO2) cm1;
HRMS (APCI-TOF) calcd for C8H8ClN2O3 [M＋H]＋
2
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Chin. J. Chem. 2016, XX, 1—9

Nitration-Oximization of Styrene Derivatives with tert-Butyl Nitrite: Synthesis of α-Nitrooximes
121.9 (d, J＝3.0 Hz, CH), 117.5 (d, J＝21.2 Hz, CH),
115.9* (d, J＝23.3 Hz, CH), 113.3 (d, J＝23.3 Hz, CH),
77.9* (CH2), 68.2 (CH2) (Some peaks of the minor iso-
mer could not be detected by 13C NMR due to their low
intensity); IR (KBr) ν: 3274 (O－H), 1610 (C＝N),
3-(1-(Hydroxyimino)-2-nitroethyl)benzaldehyde
(2j):[9] Yellow solid (69.4 mg, 66% yield). m.p. 118－
1
119 ℃ (EtOAc/hexanes); H NMR (400 MHz, ace-
tone-d6) δ: 11.83 (s, 1H), 10.11 (s, 1H), 8.33 (s, 1H),
8.12 (d, J＝7.8 Hz, 1H), 8.01 (d, J＝7.8 Hz, 1H), 7.70 (t,
J＝7.8 Hz, 1H), 5.98 (s, 2H); 13C NMR (100 MHz, ac-
etone-d6) δ: 191.8 (CH), 147.3 (C), 137.2 (C), 135.4 (C),
131.5 (CH), 130.3 (CH), 129.6 (CH), 126.9 (CH), 68.1
(CH2) (Some peaks of the minor isomer could not be
detected by 13C NMR due to their low intensity); IR
(KBr) ν: 3203 (O－H), 1610 (C＝N), 1554 and 1381
(NO2) cm1; HRMS (ESI-TOF) calcd for C9H8N2NaO4
[M＋Na]＋ 231.0382, found 231.0375.
1558 and 1376 (NO2) cm1; HRMS (APCI-TOF) calcd
＋
for C8H7FN2NaO3 [M ＋ Na]
221.0338, found
221.0331.
1-(4-Nitrophenyl)-2-nitroethanone oxime (2g):[9]
Pale yellow solid (70.2 mg, 62% yield). m.p. 123－
1
124 ℃ (EtOAc/hexanes); H NMR (400 MHz, ace-
tone-d6, isomeric ratio 21.2∶1, minor isomer marked *)
δ: 12.15 (s, 1H of major and minor isomers), 8.31 (d,
J＝9.0 Hz, 2H of major and minor isomers), 8.08 (d,
J＝9.0 Hz, 2H of major and minor isomers), 5.98 (s,
1.91H), 5.78* (s, 0.09H); 13C NMR (100 MHz, ace-
tone-d6) δ: 148.4 (C), 146.8 (C), 140.4 (C), 130.0* (2×
CH), 127.1 (2×CH), 123.8 (2×CH), 123.3* (2×CH),
77.9* (CH2), 67.9 (CH2) (Some peaks of the minor iso-
mer could not be detected by 13C NMR due to their low
intensity); IR (KBr) ν: 3364 (O－H), 1599 (C＝N),
1567 and 1380 (NO2) cm1; HRMS (ESI-TOF) calcd for
C8H7N3NaO5 [M＋Na]＋ 248.0283, found 248.0282.
1-(3-Nitrophenyl)-2-nitroethanone oxime (2h):[9]
Pale yellow solid (74.0 mg, 66% yield). m.p. 98－
1-(4-(Chloromethyl)phenyl)-2-nitroethanone oxime
(2k):[9] Pale yellow solid (84.2 mg, 73% yield). m.p.
83－84 ℃ (CH2Cl2/hexanes); 1H NMR (400 MHz,
acetone-d6) δ: 11.43 (s, 1H), 7.64 (d, J＝8.4 Hz, 2H),
7.37 (d, J＝8.4 Hz, 2H), 5.71 (s, 2H), 4.57 (s, 2H); 13C
NMR (100 MHz, acetone-d6) δ: 147.3 (C), 139.3 (C),
134.2 (C), 129.0 (2×CH), 126.3 (2×CH), 68.1 (CH2),
45.4 (CH2); IR (KBr) ν: 3227 (O－H), 1605 (C＝N),
1574 and 1383 (NO2) cm1; HRMS (APCI-TOF) calcd
for C9H10ClN2O3 [M＋H]＋ 229.0380, found 229.0375.
2-Nitro-1-(p-tolyl)ethanone oxime (2l):[10d] Yellow
1
viscous oil (77.0 mg, 79% yield). H NMR (400 MHz;
1
99 ℃ (CH2Cl2/hexanes); H NMR (400 MHz, ace-
CDCl3, isomeric ratio 18.2∶1, minor isomer marked *)
δ: 9.73 (br s, 1H of major and minor isomers), 7.50 (d,
J＝8.0 Hz, 2H of major and minor isomers), 7.23 (d,
J＝8.0 Hz, 2H of major and minor isomers), 5.63 (s,
1.82H), 5.40* (s, 0.10H), 2.37 (s, 3H of major and mi-
nor isomers); 13C NMR (100 MHz, CDCl3) δ: 148.3 (C),
140.7 (C), 130.2 (C), 129.8 (2×CH), 129.4* (2×CH),
128.3* (2×CH), 126.1 (2×CH), 78.2* (CH2), 68.5
(CH2), 21.5* (CH3), 21.3 (CH3) (Some peaks of the mi-
nor isomer could not be detected by 13C NMR due to
their low intensity); IR (KBr) ν: 3292 (O－H), 1611
(C＝N), 1546 and 1377 (NO2) cm1; HRMS (ESI-TOF)
calcd for C9H10N2NaO3 [M＋Na]＋ 217.0589, found
217.0595.
tone-d6, isomeric ratio 20.6∶1, minor isomer marked *)
δ: 12.09 (s, 1H of major and minor isomers), 8.62 (s, 1H
of major and minor isomers), 8.30 (dd, J＝8.0, 1.3 Hz,
1H of major and minor isomers), 8.22 (d, J＝8.0 Hz, 1H
of major and minor isomers), 7.76 (t, J＝8.0 Hz, 1H of
major and minor isomers), 6.00 (s, 1.85H), 5.82* (s,
0.09H); 13C NMR (100 MHz; acetone-d6) δ: 148.6 (C),
146.6 (C), 136.1 (C), 134.8* (CH), 132.0 (CH), 130.2
(CH), 129.8* (CH), 124.2* (CH), 124.0 (CH), 123.6*
(CH), 120.6 (CH), 77.9* (CH2), 67.9 (CH2) (Some
peaks of the minor isomer could not be detected by 13C
NMR due to their low intensity); IR (KBr) ν: 3314 (O－
H), 1575 (C＝N), 1533 and 1378 (NO2) cm1; HRMS
(ESI-TOF) calcd for C8H7N3NaO5 [M＋Na]＋ 248.0283,
found 248.0276.
Methyl-4-(1-(hydroxyimino)-2-nitroethyl)benzoate
(2i): Yellow viscous oil (73.5 mg, 60% yield). 1H NMR
(400 MHz, acetone-d6, isomeric ratio 27.6∶1, minor
isomer marked *) δ: 11.89 (br s, 1H of major and minor
isomers), 8.07 (d, J＝8.5 Hz, 2H of major and minor
isomers), 7.93 (d, J＝8.5 Hz, 2H of major and minor
isomers), 5.94 (s, 1.93H), 5.73* (s, 0.07H), 3.91 (s, 3H
of major and minor isomers); 13C NMR (100 MHz, ac-
etone-d6) δ: 165.9 (C), 147.3 (C), 138.5 (C), 130.9 (C),
129.6 (2×CH), 129.2* (2×CH), 128.8* (2×CH),
126.1 (2×CH), 68.0 (CH2), 51.7* (CH2) (Some peaks
of the minor isomer could not be detected by 13C NMR
due to their low intensity); IR (KBr) ν: 3399 (O－H),
1716 (C＝O), 1608 (C＝N), 1561 and 1380 (NO2) cm1;
MS m/z (%) relative intensity 238 (M＋, 3), 191 (8), 161
(90); HRMS (ESI-TOF) calcd for C10H10N2NaO5 [M＋
Na]＋ 261.0487, found 261.0488.
1-(4-Methoxyphenyl)-2-nitroethanone
oxime
(2m):[10d] Pale yellow solid (66.5 mg, 63% yield). m.p.
1
109－110 ℃ (CH2Cl2/hexanes); H NMR (400 MHz,
acetone-d6) δ: 11.30 (s, 1H), 7.73 (dd, J＝6.9, 2.0 Hz,
2H), 7.00 (dd, J＝6.9, 2.0 Hz, 2H), 5.85 (s, 2H), 3.84 (s,
3H); 13C NMR (100 MHz; acetone-d6) δ: 161.0 (C),
147.4 (C), 127.5 (2×CH), 126.7 (C), 114.0 (2×CH),
68.2 (CH2), 54.8 (CH3); IR (KBr) ν: 3229 (O－H), 1606
(C＝N), 1559 and 1380 (NO2) cm1; HRMS (ESI-TOF)
calcd for C9H11N2O4 [M ＋ H] ＋ 211.0719, found
211.0720.
1-(4-(tert-Butyl)phenyl)-2-nitroethanone
oxime
(2n):[9] Yellow solid (100.7 mg, 85% yield). m.p. 102－
103 ℃ (CH2Cl2/hexanes); 1H NMR (400 MHz, CDCl3,
isomeric ratio 14.4∶1, minor isomer marked *) δ: 9.66
(br s, 1H of major and minor isomers), 7.55 (d, J＝8.6
Hz, 2H of major and minor isomers), 7.45 (d, J＝8.6 Hz,
2H of major and minor isomers), 5.64 (s, 1.87H), 5.41*
(s, 0.13H), 1.32 (s, 9H of major and minor isomers); 13C
Chin. J. Chem. 2016, XX, 1—9
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Chumnanvej et al.
FULL PAPER
NMR (100 MHz, CDCl3) δ: 154.0 (C), 148.5 (C), 130.0
(C), 128.2* (2×CH), 126.1 (2×CH), 126.0 (2×CH),
125.7* (2×CH), 78.1* (CH2), 68.5 (CH2), 34.9 (C),
31.1 (3×CH3) (Some peaks of the minor isomer could
not be detected by 13C NMR due to their low intensity);
IR (KBr) ν: 3300 (O－H), 1608 (C＝N), 1558 and 1374
(NO2) cm1; HRMS (ESI-TOF) calcd for C12H16N2NaO3
[M＋Na]＋ 259.1059, found 259.1058.
(CH2), 24.7 (CH2); IR (KBr) ν: 3300 (O－H), 1598
(C＝N), 1547 and 1375 (NO2) cm1; HRMS (ESI-TOF)
calcd for C10H10N2NaO3 [M＋Na]＋ 229.0589, found
229.0584.
1-(Naphthalen-1-yl)-2-nitroethanone oxime (2s):[9]
Yellow viscous oil (69.7 mg, 60% yield); 1H NMR (400
MHz, CDCl3, isomeric ratio 1.4∶1, minor isomer
marked *) δ: 9.65 (br s, 0.58H), 8.89* (br s, 0.45H),
7.97－7.83 (m, 3H of major and minor isomers), 7.64－
7.33 (m, 4H of major and minor isomers), 5.59 (s,
1.16H), 5.42* (s, 0.84H); 13C NMR (100 MHz, CDCl3)
δ: 149.4* (C), 149.2 (C), 133.8 (C), 133.5* (C), 130.8*
(C), 130.7 (C), 130.6 (CH), 130.5* (CH), 130.3* (C),
129.4 (C), 128.8 (CH), 128.7* (CH), 127.4* (CH),
127.36 (CH), 127.1* (CH), 126.58 (CH), 126.57 (CH),
125.4* (CH), 125.20* (CH), 125.19 (CH), 125.1* (CH),
124.4 (CH), 78.9* (CH2) , 71.6 (CH2); IR (neat) ν: 3273
(O－H), 1592 (C＝N), 1558 and 1372 (NO2) cm1;
HRMS (ESI-TOF) calcd for C12H10N2NaO3 [M＋Na]＋
253.0589, found 253.0588.
4-(1-(Hydroxyimino)-2-nitroethyl)phenyl
acetate
(2o):[9] Yellow solid (96.6 mg, 81% yield). m.p. 114－
1
115 ℃ (EtOAc/hexanes); H NMR (400 MHz, ace-
tone-d6, isomeric ratio 13.3∶1, minor isomer marked *)
δ: 11.61 (s, 0.80H), 11.25* (s, 0.06H), 7.83 (d, J＝8.7
Hz, 2H of major and minor isomers), 7.22 (d, J＝8.7 Hz,
2H of major and minor isomers), 5.89 (s, 1.86H), 5.69*
(s, 0.14H), 2.28 (s, 3H of major and minor isomers); 13C
NMR (100 MHz, acetone-d6) δ: 168.8 (C), 152.1 (C),
147.2 (C), 131.8 (C), 129.9* (2×CH), 127.2 (2×CH),
122.1 (2×CH), 121.7* (2×CH), 78.4* (CH2), 68.2
(CH2), 20.1 (CH3) (Some peaks of the minor isomer
could not be detected by 13C NMR due to their low in-
tensity); IR (KBr) ν: 3278 (O－H), 1604 (C＝N), 1570
and 1369 (NO2) cm1; HRMS (ESI-TOF) calcd for
C10H10N2NaO5 [M＋Na]＋ 261.0487, found 261.0480.
2-Nitro-1-phenylethanone oxime (2p):[11] Yellow
solid (66.3 mg, 73% yield). m.p. 95—96 ℃ (CH2Cl2/
hexanes, lit.[11] m.p. 95 ℃); 1H NMR (400 MHz, CDCl3)
δ: 9.31 (br s, 1H), 7.63－7.61 (m, 2H), 7.46－7.41 (m,
3H), 5.65 (s, 2H); 13C NMR (100 MHz, CDCl3) δ: 148.6
(C), 132.9 (C), 130.5 (CH), 129.1 (2×CH), 126.2 (2×
CH), 68.5 (CH2); IR (KBr) ν: 3222 (O－H), 1636 (C＝
N), 1559 and 1383 (NO2) cm1; HRMS (ESI-TOF)
calcd for C8H8N2NaO3 [M＋Na]＋ 203.0433, found
203.0434.
1-(Naphthalen-2-yl)-2-nitroethanone oxime (2t):
Yellow solid (60.1 mg, 52% yield). m.p. 115－116 ℃
1
(EtOAc/hexanes); H NMR (400 MHz, acetone-d6, iso-
meric ratio 32.3∶1, minor isomer marked *) δ: 11.67
(br s, 1H of major and minor isomers), 8.32 (d, J＝0.7
Hz, 1H), 8.04－7.92 (m, 4H of major and minor iso-
mers), 7.58－7.54 (m, 2H of major and minor isomers),
6.04 (s, 1.94H), 5.81* (s, 0.06H); 13C NMR (100 MHz,
acetone-d6) δ: 147.9 (C), 133.8 (C), 133.2 (C), 131.8 (C),
129.8* (CH), 129.5* (CH), 128.5 (CH), 128.4 (CH),
128.2* (CH), 127.9* (CH), 127.7 (CH), 127.4* (CH),
127.3* (CH), 127.0 (CH), 126.7 (CH), 126.5* (CH),
126.0 (CH), 123.1 (CH), 78.6* (CH2) , 68.0 (CH2)
(Some peaks of the minor isomer could not be detected
by 13C NMR due to their low intensity); IR (KBr) ν:
3262 (O－H), 1625 (C＝N), 1568 and 1383 (NO2) cm1;
MS m/z (%) relative intensity 230 (M＋, 49), 166 (100),
153 (65); HRMS (ESI-TOF) calcd for C12H10N2NaO3
[M＋Na]＋ 253.0589, found 253.0590.
2-Nitro-1-phenylpropan-1-one oxime (2q):[9] Yellow
solid (79.1 mg, 81% yield). m.p. 96 — 97 ℃
1
(EtOAc/hexanes); H NMR (400 MHz, acetone-d6, iso-
meric ratio 2.3∶1, minor isomer marked *) δ: 11.34 (s,
0.67H), 10.91* (s, 0.30H), 7.64—7.40 (m, 5H of major
and minor isomers), 6.12 (dd, J＝13.7, 6.9 Hz, 0.70H),
5.84* (dd, J＝13.7, 6.9 Hz, 0.30H), 1.87 (d, J＝6.8 Hz,
2.00H), 1.76* (d, J＝6.8 Hz, 1.00H); 13C NMR (100
MHz, acetone-d6) δ: 152.5 (C), 151.5* (C), 134.0 (C),
131.3* (C), 129.4 (CH), 129.2* (CH), 128.6 (2×CH),
128.3* (2×CH), 128.2* (2×CH), 126.6 (2×CH),
85.4* (CH), 77.5 (CH), 16.3* (CH3), 14.6 (CH3); IR
(KBr) ν: 3237 (O－H), 1648 (C＝N), 1546 and 1386
(NO2) cm1; HRMS (ESI-TOF) calcd for C9H10N2NaO3
[M＋Na]＋ 217.0589, found 217.0587.
1-(Benzo[b]thiophen-2-yl)-2-nitroethanone oxime
(2u): Yellow solid (74.8 mg, 63% yield). m.p. 152－
1
153 ℃ (EtOAc/hexanes); H NMR (400 MHz, ace-
tone-d6, isomeric ratio 2.9∶1, minor isomer marked *)
δ: 12.19* (br s, 0.21H), 11.74 (br s, 0.65H), 8.01－7.83
(m, 3H of major and minor isomers), 7.48－7.36 (m, 2H
of major and minor isomers), 5.96 (s, 1.48H), 5.89* (s,
0.52H); 13C NMR (100 MHz, acetone-d6) δ: 144.6 (C),
139.7 (C), 139.5 (C), 138.6 (C), 126.2* (CH), 126.0
(CH), 125.8* (CH), 124.8 (CH), 124.7* (CH), 124.4
(CH), 124.3 (CH), 122.2 (CH), 121.9* (CH), 77.3*
(CH2), 67.7 (CH2) (Some peaks of the minor isomer
could not be detected by 13C NMR due to their low in-
tensity); IR (KBr) ν: 3255 (O－H), 1623 (C＝N), 1560
and 1381 (NO2) cm1; MS m/z (%) relative intensity 236
2-Nitro-3,4-dihydronaphthalen-1(2H)-one
oxime
(2r):[12] Pale brown solid (67.7 mg, 70%). m.p. 138－
139 ℃ (CH2Cl2/hexanes, lit.[12] m.p. 140－142 ℃);
1H NMR (400 MHz, acetone-d6) δ: 11.41 (s, 1H), 8.00
(d, J＝7.7 Hz, 1H), 7.36－7.23 (m, 3H), 6.15 (dd, J＝
5.3, 4.2 Hz, 1H), 2.88－2.78 (m, 2H), 2.60－2.53 (m,
1H), 2.45－2.36 (m, 1H); 13C NMR (100 MHz, ace-
tone-d6) δ: 146.6 (C), 137.4 (C), 129.4 (CH), 129.3 (C),
128.7 (CH), 126.8 (CH), 123.9 (CH), 77.3 (CH), 27.7
(M＋, 21), 172 (16), 147 (100); HRMS (ESI-TOF) calcd
＋
for C10H8N2NaO3S [M ＋ Na]
259.0153, found
259.0152.
1-(Benzofuran-2-yl)-2-nitroethanone oxime (2v):
4
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© 2016 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2016, XX, 1—9

Nitration-Oximization of Styrene Derivatives with tert-Butyl Nitrite: Synthesis of α-Nitrooximes
Yellow solid (84.2 mg, 77% yield). m.p. 124－125 ℃
(EtOAc/hexanes); H NMR (400 MHz, acetone-d6, iso-
129.9 (CH), 128.4 (CH), 127.4 (CH), 127.2 (CH), 124.8
1
(C), 124.5 (C), 124.1 (CH), 120.8 (CH), 120.7 (CH),
115.0 (CH), 111.4 (CH), 111.3 (CH), 75.5 (CH2), 66.4
(CH2), 55.2 (CH3), 55.1 (CH3); IR (KBr) ν: 3276 (O－
H), 1618 (C＝N), 1560 and 1341 (NO2), 1249 (C－O)
cm1; MS m/z (%) relative intensity 236 (M＋, 1), 205
(55), 159 (100); HRMS (ESI-TOF) calcd for
C11H12N2NaO5 [M＋Na]＋ 259.0695, found 259.0690.
meric ratio 0.6∶1, minor isomer marked *) δ: 12.11
(br s, 1H of major and minor isomers), 7.97 (s, 1H of
major and minor isomers), 7.79 (d, J＝7.8 Hz, 0.6H),
7.70* (d, J＝7.8 Hz, 0.4H), 7.58－7.55 (m, 1H of major
and minor isomers), 7.47－7.39 (m, 1H of major and
minor isomers), 7.35－7.28 (m, 1H of major and minor
isomers), 5.89* (s, 0.77H), 5.79 (s, 1.23H); 13C NMR
(100 MHz, acetone-d6) δ: 155.2* (C), 153.2 (C), 150.6*
(C), 145.2 (C), 140.9* (C), 138.9 (C), 128.3 (C), 128.1*
(C), 126.8 (CH), 126.0* (CH), 123.7 (CH), 123.5* (CH),
122.6 (CH), 121.8* (CH), 113.9 (CH), 111.4 (CH),
111.3* (CH), 106.9* (CH), 75.2 (CH2), 67.5* (CH2); IR
(KBr) ν: 3286 (O－H), 1611 (C＝N), 1563 and 1375
(NO2) cm1; MS m/z (%) relative intensity 220 (M＋, 14),
131 (100), 115 (46); HRMS (ESI-TOF) calcd for
C10H8N2NaO4 [M＋Na]＋ 243.0382, found 243.0384.
(3E)-1-Nitro-4-phenylbut-3-en-2-one oxime (2w):
Orange solid (27.1 mg, 25% yield). m.p. 125－126 ℃
General procedure for oxidative hydrolysis of
α-nitrooximes 2
To a solution of α-nitrooxime 2 (0.5 mmol) in
CH2Cl2 (2 mL), NaNO2 (34.5 mg, 0.5 mmol), Amber-
lyst-15 (157.2 mg, 0.5 mmol) and H2O (1 mL) were
added at 0－5 ℃. The resulting mixture was slowly
warmed to room temperature (32－35 ℃). After 2 h,
the Amberlyst-15 was filtered off and washed with
CH2Cl2. The filtrate was extracted with CH2Cl2 (10 mL
×3). The combined CH2Cl2 extracts were washed with
H2O (10 mL), brine (10 mL), dried (anhydrous MgSO4),
filtered and vacuumed (aspirator). The crude residue
was purified by column chromatography (SiO2) using
EtOAc/hexanes as eluent to provide the corresponding
α-nitroketone product.
1
(EtOAc/hexanes); H NMR (400 MHz, acetone-d6, iso-
meric ratio 1∶1) δ: 11.41 (br s, 0.40H), 11.28 (br s,
0.46H), 7.64－7.57 (m, 2.31H), 7.45－7.32 (m, 3H)
7.23 (dd, J＝16.7, 10.8 Hz, 1H), 7.03 (d, J＝16.7 Hz,
0.45H), 5.75 (s, 0.94H), 5.62 (s, 1.06H); 13C NMR (100
MHz, acetone-d6) δ: 148.7 (C), 147.3 (C), 136.3 (C),
136.0 (C), 135.7 (C), 133.5 (C), 129.3 (CH), 128.9 (2×
CH), 128.8 (2×CH), 128.6 (CH), 127.4 (2×CH), 126.9
(2×CH), 123.7 (CH), 114.7 (CH), 75.3 (CH2), 66.3
(CH2); IR (KBr) ν: 3237 (O－H), 1625 (C＝N), 1556
and 1373 (NO2) cm1; MS m/z (%) relative intensity 206
1-(4-Bromophenyl)-2-nitroethanone (4a):[13] White
solid (97.4 mg, 80% yield). m.p. 139 － 140 ℃
1
(EtOAc/hexanes, lit.[13] m.p. 142－143 ℃); H NMR
(400 MHz, CDCl3) δ: 7.77－7.69 (m, 4H), 5.85 (s, 2H);
13C NMR (100 MHz, CDCl3) δ: 183.7 (C), 136.8 (C),
132.8 (2×CH), 129.6 (2×CH), 128.2 (C), 81.0 (CH2).
1-(4-(Chloromethyl)phenyl)-2-nitroethanone (4k):
Pale yellow solid (92.3 mg, 87% yield). m.p. 126－
(M＋, 6), 160 (58), 115 (100); HRMS (ESI-TOF) calcd
1
＋
127 ℃ (EtOAc/hexanes); H NMR (400 MHz, ace-
for C10H10N2NaO5 [M ＋ Na]
229.0589, found
tone-d6) δ: 8.05 (d, J＝8.3 Hz, 2H), 7.71 (d, J＝8.3 Hz,
2H), 6.41 (s, 2H), 4.84 (s, 2H); 13C NMR (100 MHz,
acetone-d6) δ: 187.1 (C), 144.7 (C), 133.6 (C), 129.3
(2×CH), 128.8 (2×CH), 82.2 (CH2), 44.8 (CH2); IR
(KBr) ν: 3031 (ArH), 1699 (C＝O), 1560 and 1387
(NO2) cm1; MS m/z (%) relative intensity 213 (M＋, 2),
178 (100), 161 (46); HRMS (ESI-TOF) calcd for
C9H8ClNO3 [M＋Na]＋ 236.0090, found 236.0081.
2-Nitro-1-(p-tolyl)ethanone (4l):[13] White solid
(69.9 mg, 77% yield). m.p. 137－138 ℃ (EtOAc/
hexanes, lit.[13] m.p. 139－140 ℃); 1H NMR (400 MHz,
CDCl3) δ: 7.78 (d, J＝8.2 Hz, 2H), 7.34 (d, J＝8.2 Hz,
2H), 5.88 (s, 2H), 2.46 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ: 185.3 (C), 146.5 (C), 135.9 (C), 130.0 (2×
CH), 128.4 (2×CH), 81.3 (CH2), 21.9 (CH3).
229.0586.
(3E)-4-(Benzo[d][1,3]dioxol-5-yl)-1-nitrobut-3-en-
2-one oxime (2x): Yellow liquid (12.2 mg, 28% yield).
1H NMR (400 MHz, acetone-d6, isomeric ratio 1∶1) δ:
11.26 (br s, 0.40H), 11.13 (br s, 0.50H), 7.40 (d, J＝16.8
Hz, 0.58H), 7.21－7.02 (m, 3H), 6.86 (t, J＝8.2 Hz,
1.48H), 6.05 (s, 1.20H), 6.04 (s, 0.81H), 5.70 (s, 0.88H),
5.57 (s, 1.12H); 13C NMR (100 MHz, acetone-d6) δ:
148.7 (C), 147.4 (C), 135.5 (CH), 133.3 (CH), 130.8 (C),
130.5 (C), 123.4 (CH), 122.6 (CH), 121.9 (CH), 113.0
(CH), 108.4 (CH), 108.3 (CH), 105.8 (CH), 105.5 (CH),
101.7 (CH2), 101.5 (CH2), 75.3 (CH2), 66.3 (CH2); IR
(KBr) ν: 3256 (O－H), 1624 (C＝N), 1559 and 1376
(NO2), 1257 (C－O) cm1; MS m/z (%) relative intensi-
ty 250 (M＋, 48), 204 (41), 187 (100); HRMS (ESI-TOF)
calcd for C11H10N2NaO5 [M＋Na]＋ 273.0487, found
273.0489.
2-Nitro-1-phenylethanone (4p):[13] Pale yellow solid
(70.2 mg, 85% yield). m.p. 101－102 ℃ (EtOAc/
hexanes, lit.[13] m.p. 103－105 ℃); 1H NMR (400 MHz,
CDCl3) δ: 7.88 (d, J＝7.8 Hz, 2H), 7.70 (t, J＝7.4 Hz,
1H), 7.55 (t, J＝7.8 Hz, 2H), 5.92 (s, 2H); 13C NMR
(100 MHz, CDCl3) δ: 185.9 (C), 135.4 (CH), 129.3 (2×
CH), 128.3 (2×CH), 126.9 (C), 81.4 (CH2).
(3E)-4-(2-Methoxyphenyl)-1-nitrobut-3-en-2-one
oxime (2y): Orange liquid (19.1 mg, 13% yield); H
1
NMR (400 MHz, acetone-d6, isomeric ratio 1∶1) δ:
11.33 (br s, 0.38H), 11.19 (br s, 0.47H), 7.67－7.59 (m,
1.52H), 7.44－7.31 (m, 2H) 7.09－6.97 (m, 2.46H),
5.75 (s, 0.89H), 5.61 (s, 1.11H), 3.90 and 3.97 (s, 3H);
13C NMR (100 MHz, acetone-d6) δ: 157.8 (C), 157.4
(C), 149.1 (C), 147.8 (C), 130.7 (CH), 130.4 (CH),
Results and Discussion
The generation of NO radical from tert-butyl nitrite
Chin. J. Chem. 2016, XX, 1—9
© 2016 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
5

Chumnanvej et al.
Table 1 Solvent and reagent optimizationa
FULL PAPER
(t-BuONO) and its conversion to the NO2 radical under
aerobic conditions has been well precedent in the litera-
ture.[14] Thus, we envisaged that tert-butyl nitrite, a safe
and easily handled non-metallic reagent capable of gen-
erating a NO radical, would trigger a one-pot nitra-
tion-oximization of olefins. In a preliminary set of ex-
periments employing 4-bromostyrene as a benchmark
substrate with t-BuONO in different solvents confirmed
the validity of our hypothesis, as the corresponding
α-nitrooxime derived from 4-bromostyrene was ob-
tained in variable yields depending on type of solvents
(Table 1). In the initial experiment, 4-bromostyrene was
allowed to react with t-BuONO (2 equiv.) in CH2Cl2 at
room temperature (32－35 ℃) for 30 min leading to
poor yields of α-nitrooxime 2a (9% yield) and nitroal-
kene 3a (E isomer, 3% yields) (Table 1, Entry 1). The
reactions did not proceed when acetone and methanol
(MeOH) were employed as the solvents; the 4-bromo-
styrene was untouched (TLC analysis) (Table 1, Entries
2－3). Nitroalkene 3a was obtained as a sole product
when ethyl acetate (EtOAc) was employed as the sol-
vent (Table 1, Entry 4). The reactions performed in tet-
rahydrofuran (THF), acetonitrile (CH3CN), N,N-dimeth-
ylformamide (DMF) and water (H2O) led to significant
improvement; 2a was isolated in moderate yields along
with the formation of nitroolefin 3a in all cases (Table 1,
Entries 5－8). It is worth also to mention here that ex-
cept DMSO where 2a was isolated as a single isomer,
all other solvents attempted in Table 1 yielded 2a as a
mixture of two isomers.[9,15] The Z isomer whose
methylnitro group is syn to the hydroxy group being
stabilized through the hydrogen bonding was believed
to be formed as a major isomer. In comparison with a
Yieldb/%
Entry
RONO
Solvent
2ac
3a
1
t-BuONO
t-BuONO
t-BuONO
t-BuONO
t-BuONO
t-BuONO
t-BuONO
t-BuONO
t-BuONO
t-BuONOd
t-BuONO
t-BuONO
i-AmONO
t-BuONO
CH2Cl2
Acetone
MeOH
EtOAc
THF
9
3
－
－
30
9
2
－
－
－
64
44
36
36
87
25
75
79
45
37
3
4
5
6
CH3CN
DMF
12
10
18
7
7
8
H2O
9
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
10
11e
12f
13
14g
0
14
4
5
－
a Reaction conditions: 1 (0.5 mmol) and RONO (2 equiv.) in sol-
vent (2.5 mL) under an air atmosphere at room temperature (32－
35 ℃) for 30 min. b Isolated yield. c Except DMSO, all other
solvents yielded 2a as a mixture of two isomers (E (minor) and Z
(major)). d t-BuONO (3 equiv.) was employed. e Reaction time: 60
min. f The reaction was performed at 100 ℃. g Employing de-
gassed DMSO and under an Ar atmosphere.
After having the optimized conditions in hands,
transformation of a collection of styrene substrates was
examined and the results were summarized in Table 2.
In most cases, the α-nitrooximes 2 were obtained as a
mixture of two isomers as evidenced by 1H NMR analy-
sis of the crude mixtures and analytically pure products
after chromatographic purification and in most cases the
corresponding nitroalkenes 3 were isolated in variable
yields. Notably, the nitration-oximization reactions em-
ploying t-BuONO in DMSO was superior to those em-
ploying NaNO2/OXONE® in aqueous acetonitrile[9] in
that the crude mixture was cleaner (TLC analysis) and
the α-nitrooxime products were easily isolated. Halo-
gen-substituted styrene derivatives yielded their corre-
sponding α-nitrooximes in moderate to good yields
(60%－87% yields) (Table 2, Entries 1－6). Styrene
derivatives bearing electron-withdrawing substituents
including NO2 and CO2Me groups and sensitive sub-
stituents including －CHO and －CH2Cl groups read-
ily underwent the reaction to give the corresponding
products in moderate yields (60%－73% yields, Table 2,
Entries 7 － 11). While a combination of NaNO2/
OXONE® in aqueous acetonitrile was found less effi-
cient, the use of t-BuONO in DMSO was found to be
well accommodated with electron-donating substituted
derivatives including 4-Me-, 4-MeO- and 4-t-Bu-sub-
1
closely related structure, the H NMR signals of the
methylene protons of the Z isomer resonate at a lower
field than those of the E isomer due to the deshielding
effect of the electronegative oxygen atom.[15] On this
basis, the ratios of the E and Z isomers of α-nitrooximes
2 could be assigned. Gratifyingly, the use of dimethyl
sulfoxide (DMSO) as the solvent led to the best yield of
2a (87% yield) along with 3a (7% yield) (Table 1, Entry
9). An increase in the stoichiometry of t-BuONO (from
2 equiv. to 3 equiv.) was found harmful to the reaction
efficiency; unidentifiable mixtures were observed (base-
line, TLC analysis) (Table 1, Entry 10). Prolonged reac-
tion time and an increasing reaction temperature (from
r.t. to 100 ℃) did not help to improve the results (Table
1, Entries 11－12). When t-BuONO was replaced by
isoamyl nitrite (i-AmONO), 2a was isolated in poorer
yield (45% yield) (Table 1, Entry 13). Finally, the reac-
tion performed in degassed DMSO and under an Ar at-
mosphere proved to be less efficient; 2a was obtained in
lower yield (37% yield) (Table 1, Entry 14). From the
results shown in Table 1, the optimum reaction condi-
tions could be identified and are to treat the substrate
with t-BuONO (2 equiv.) in DMSO at room temperature
for 30 min (Table 1, Entry 9).
6
www.cjc.wiley-vch.de
© 2016 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2016, XX, 1—9

Nitration-Oximization of Styrene Derivatives with tert-Butyl Nitrite: Synthesis of α-Nitrooximes
stituted styrenes; the corresponding products were ob-
tained in high yields (63%－85% yield) (Table 2, En-
tries 12－14). Significantly improved yields (60%－
81% yields) were also observed with the reactions of
4-acetoxystyrene, a simple styrene, β-methylstyrene,
1,2-dihydronaphthalene and 1-vinylnaphthalene (Table
2, Entries 15－19). While NaNO2/OXONE® in aqueous
acetonitrile led to complex and unidentifiable mixtures,
the reaction of 2-vinylnaphthalene with t-BuONO under
the standard reaction conditions provided α-nitrooxime
2t in 52% yield (Table 2, Entry 20). It is worth to note
that scaling up experiments (10 mmol scale) for the re-
actions of 4-bromostyrene and styrene were also inves-
tigated under the optimized conditions (Scheme 2).
α-Nitrooximes 2a and 2p were obtained in similar effi-
ciency in 82% and 72% yields, respectively.
Scheme 2 Scaling up reactions of 4-bromostyrene and styrene
Having demonstrated the synthetic utilities of the
present protocol to a collection of styrene derivatives
bearing electronically different substituents, the reac-
tions of vinyl-substituted heteroaromatic compounds,
aliphatic alkenes, electron deficient alkenes (α,β-unsat-
urated ester) and 1-aryl-1,3-butadienes were also evalu-
ated. The results are summarized in Table 3. 2-Vinyl-
benzothiophene and 2-vinylbenzofuran also gave the
corresponding products in 63% and 77% yields, respec-
tively (Table 3). Unfortunately, aliphatic alkenes
(1-octene and cyclohexene), 2- and 3-vinylpyridines and
n-butyl acrylate failed to provide the desired products;
only starting compounds were observed (1H NMR anal-
ysis). Finally, the reactions of 1-aryl-1,3-butadienes se-
lectively led to products 2w － 2y derived from a
1,2-addition at the terminal carbon of 1-aryl-1,3-buta-
dienes in low yields (13%－28% yields). Attempts to
improve the yield of 2w by performing the reaction at
prolonged reaction time (from 30 min. to 2 h), at higher
temperature (from r.t. to 100 ℃), or by increasing the
stoichiometry of t-BuONO (from 2 equiv. to 3 equiv.)
led to inferior results; extensive decomposition was ob-
served (TLC analysis).
Table 2 Nitration-oximization reaction of styrene derivativesa
Substrate
Ar
Product; yieldb/%
2 (isomer ratio)c
Entry
R
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
3
1
4-BrC6H4
2a; 87 (single isomer)
2b; 74 (single isomer)
2c; 74 (13.3∶1)
3a; 7
3b; 6
3c; 8
3d; 8
3e; 8
3f; 5
3g; 7
3h; 9
3i; 0
2
4-ClC6H4
3
3-ClC6H4
4
2-ClC6H4
2d; 60 (1.6∶1)
5
4-FC6H4
2e; 71 (8.5∶1)
6
3-FC6H4
2f; 74 (26.9∶1)
Table 3 Nitration-oximization reaction of 2-vinylbenzothio-
phene, 2-vinylbenzofuran and 1-aryl-1,3-butadienesa,b,c
7
4-NO2C6H4
3-NO2C6H4
4-(MeO2C)C6H4
3-OHCC6H4
4-(ClCH2)C6H4
4-MeC6H4
4-MeOC6H4
4-t-BuC6H4
4-AcOC6H4
C6H5
2g; 62 (21.2∶1)
8
2h; 66 (20.6∶1)
9
2i; 60 (27.6∶1)
10
11
12
13
14
15
16
17
2j; 66 (single isomer)
2k; 73 (single isomer)
2l; 79 (18.2∶1)
3j; 6
3k; 4
3l; 5
NOH
NO2
2m; 63 (single isomer)
2n; 85 (14.4∶1)
3m; 5
3n; 3
3o; 3
3p; 7
3q; 6
2w
25%d (1:1)
2o; 81 (13.3∶1)
2p; 73 (single isomer)
NOH
NO2
C6H5
CH3 2q; 81 (2.3∶1)
18
H
2r; 70 (single isomer)d
3r; 0
OMe
2y
19
20
1-Naphthyl
2-Naphthyl
H
H
2s; 60 (1.4∶1)
2t; 52 (32.3∶1)
3s; 3
3t; 0
13%e (1:1)
a Reaction conditions: 1 (0.5 mmol) and t-BuONO (2 equiv.) in
DMSO (2.5 mL), under an air atmosphere at room temperature
(32－35 ℃) for 30 min. b Isolated yield; in most cases their cor-
responding nitroalkenes (E isomers) were isolated in the range of
3%－9% yields. c The isomeric ratio (Z∶E ratio) was determined
by H NMR analysis. d 1H NMR spectrum of the crude mixture
exhibited a mixture of two isomers in a ratio of 10∶1.
Reaction conditions: Substrate (0.5 mmol) and t-BuONO (2
a
equiv.) in DMSO (2.5 mL) under an air atmosphere at room tem-
perature (32－35 ℃) for 30 min. b Isolated yield. c The isomeric
ratio (Z∶E ratio)was determined by 1H NMR analysis. d Starting
materials underwent decomposition under the reaction conditions
and could not be recovered. e The starting diene was recovered
(60% yield).
1
Chin. J. Chem. 2016, XX, 1—9
© 2016 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
7

Chumnanvej et al.
Table 4 Hydrolysis of α-nitrooximea
FULL PAPER
On the basis of the precedent literature, we suggest-
ed that the present transformation proceeded through a
pathway involving the NO/NO2 radicals. To validate the
radical mechanism, the reaction of 4-bromostyrene un-
der the standard reaction conditions was carried out in
the presence of radical scavengers. Addition of TEMPO
(1 equiv.) or BHT (1 equiv.) ceased the reaction. Addi-
tionally, oxygen or air was found crucial for the reaction
to proceed since the reaction performed in degassed
DMSO and purged with Ar gas gave poor result (Table
1, Entry 14). A plausible mechanism of this one-pot ni-
tration-oximization of styrene derivatives is shown in
Scheme 3. A homolytic cleavage of the t-BuONO oc-
curs to generate tert-butoxy radical and nitric oxide (NO)
followed by the conversion of NO to NO2 radical under
aerobic conditions.[10e,14d-14g,16] Subsequently, the gener-
ated NO2 radical attacks styrene derivatives to generate
a more stable benzylic radical. Under high concentration
of t-BuONO, the benzylic radical can be rapidly trapped
with another molecule of NO generating C-nitroso de-
rivative which readily undergoes tautomerization, lead-
ing to the observed α-nitrooximes 2 which in most cases
were obtained as a mixture of two isomers (E and Z).
Alternatively, the benzylic radical can be oxidized fol-
lowed by deprotonation, yielding nitroalkenes 3 (E iso-
mer).
Substrate
Ar
Product; yieldb/%
Entry
R
4
1
2
3
4
4-BrC6H4
H
H
H
H
4a; 80
4k; 87
4l; 77
4p; 85
4-(ClCH2)C6H4
4-MeC6H4
C6H5
a Reaction conditions: 2 (0.5 mmol), NaNO2 (1 equiv.) and Am-
berlyst-15 (1 equiv.) in CH2Cl2/H2O (2∶1 mL) were stirred at
0 ℃ to room temperature (32－35 ℃) for 2 h. b Isolated yield.
tert-butyl nitrite in DMSO at room temperature. The
present work is superior to the previously reported
methods[10,14] as follows: (i) metal-free reagent, (ii) mild
reaction conditions, (iii) environmentally benign solvent
and (iv) simple experimental procedure and safe.
Therefore, the present protocol offers a general and
practical method for the synthesis of α-nitrooxime
compounds, although limited to those derived from sty-
rene derivatives. Additionally, the reaction can be scaled
up to 10 mmol scale and the prepared α-nitrooximes can
be readily converted to α-nitroketones in good yields.
Scheme 3 Plausible reaction mechanism
N
O
air
O
O
NO
NO2
O
+
nitric oxide
Acknowledgement
t-BuONO
We thank the Thailand Research Fund (No.
BRG5880012 and IRN58W0005), the Center of Excel-
lence for Innovation in Chemistry (PERCH-CIC), the
Office of the Higher Education Commission, Mahidol
University under the National Research Universities
Initiative, the Swedish Research Council through Swe-
dish Research Links Programme in collaboration with
Professor Pher G. Andersson, Stockholm University,
Sweden and CNRS-PICS Program through the
collaboration with Professor Fabien Gagosz, Ecole
Polytecnique, France for financial support.
t-BuONO
N
NO2
NO2
NO2
Ar
Ar
Ar
+ t-BuO
NO
C-nitroso
intermediate
Benzylic radical
- e-
- H+
NOH
NO2
NO2
Ar
Ar
nitroalkene 3
-nitrooxime 2
α-Nitrooxime compounds are synthetically useful
motifs in organic synthesis.[17] In this work, some of the
prepared α-nitrooxime compounds were readily con-
verted to α-nitroketones. Several reaction conditions
were attempted to convert an oxime moiety to the corre-
sponding keto group.[18] Gratifyingly, upon treatment of
α-nitrooximes 2 with NaNO2, Amberlyst-15 under O2
atmosphere, the respective α-nitroketones 4 were ob-
tained in good yields (77%－85% yields). The results
are summarized in Table 4.
References
[1] (a) Anastas, P. T.; Kirchhoff, M. M. Acc. Chem. Res. 2002, 35, 686;
(b) Trost, B. M. Acc. Chem. Res. 2002, 35, 695.
[2] (a) Mizuno, N.; Misono, M. Chem. Rev. 1998, 98, 199; (b) Akiyama,
R.; Kobayashi, S. Chem. Rev. 2009, 109, 594; (c) Ikegami, S.;
Hamamoto, H. Chem. Rev. 2009, 109, 583; (d) Climent, M.; Corma,
J. A.; Iborra, S. Chem. Rev. 2011, 111, 1072; (e) Guo, Z.; Liu, B.;
Zhang, Q.-H.; Deng, W.-P.; Wang, Y.; Yang, Y.-H. Chem. Soc. Rev.
2014, 43, 3480; (f) Zhang, Y.; Cui, X.-J.; Shi, F.; Deng, Y.-Q. Chem.
Rev. 2012, 112, 2467.
[3] (a) Cho, S. H.; Yoon, J.; Chang, S. J. Am. Chem. Soc. 2011, 133,
5996; (b) Xu, K.; Hu, Y.-B.; Zhang, S.; Zha, Z.-G.; Wang, Z.-Y.
Chem. Eur. J. 2012, 18, 9793; (c) Arancon, R. A. D.; Lin, C. S. K.;
Vargas, C.; Luque, R. Org. Biomol. Chem. 2014, 12, 10.
Conclusions
In summary, we have developed a practical and effi-
cient nitration-oximization of styrene derivatives using
[4] (a) Rao, C. B.; Chinnababu, B.; Venkateswarlu, Y. J. Org. Chem.
8
www.cjc.wiley-vch.de
© 2016 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2016, XX, 1—9

Nitration-Oximization of Styrene Derivatives with tert-Butyl Nitrite: Synthesis of α-Nitrooximes
2009, 74, 8856; (b) Zhou, L.; Tan, C.-K.; Zhou, J.; Yeung, Y.-Y. J.
Am. Chem. Soc. 2010, 132, 10245; (c) Kumar, A.; Kumar, M.; Gupta,
M. K. Green Chem. 2012, 14, 2677; (d) Gawande, M. B.; Bonifácio,
V. D. B.; Luque, R.; Brancoa, P. S.; Varma, R. S. Chem. Soc. Rev.
2013, 42, 5522; (e) Yang, Y.; Tang, L.; Zhang, S.; Guo, X.; Zha, Z.;
Wang, Z. Green Chem. 2014, 16, 4106.
Eur. J. Org. Chem. 2014, 7433.
[9] Chumnanvej, N.; Samakkanad, N.; Pohmakotr, M.; Reutrakul, V.;
Jaipetch, T.; Soorukram, D.; Kuhakarn, C. RSC Adv. 2014, 4, 59726.
[10] (a) Scheinbaum, M. L. J. Org. Chem. 1970, 35, 2790; (b) Uppu, R.
M.; Pryor, W. A. Anal. Biochem. 1996, 236, 242; (c) Grossi, L.;
Montevecchi, P. C.; Strazzari, S. Eur. J. Org. Chem. 2001, 741; (d)
Shaabani, A.; Bijanzadeh, H. R.; Karimi, A. R.; Teimouri, M. B.;
Soleimani, K. Can. J. Chem. 2008, 86, 248; (e) Cao, Q.; Liu, J.; Yu,
L.; Gui, Q.; Chen, X.; Tan, Z. Synth. Commun. 2015, 45, 2181.
[11] Duranti, E.; Balsamini, C.; Spadoni, G.; Lamberto, S. J. Org. Chem.
1988, 53, 2870.
[5] For reviews on 1,2-diamines, see: (a) Bennani, Y. L.; Hanessian, S.
Chem. Rev. 1997, 97, 3161; (b) Lucet, D.; Gall, T. L.; Mioskowski,
C. Angew. Chem., Int. Ed. 1998, 37, 2580; (c) Viso, A.; de la Pradilla,
R. F.; García, A.; Flores, A. Chem. Rev. 2005, 105, 3167; (d) Bo-
gatcheva, E.; Hanrahan, C.; Nikonenko, B.; Samala, R.; Chen, P.;
Gearhart, J.; Barbosa, F.; Einck, L.; Nacy, C. A.; Protopopova, M. J.
Med. Chem. 2006, 49, 3045; (e) Kotti, S. R. S. S.; Timmons, C.; Li,
G. Chem. Biol. Drug Des. 2006, 67, 101; (f) Kizirian, J.-C. Chem.
Rev. 2008, 108, 140; (g) Grygorenko, O. O.; Radchenko, D. S.; Vo-
lochnyuk, D. M.; Tolmachev, A. A.; Komarov, I. V. Chem. Rev. 2011,
111, 5506.
[6] (a) Okada, A.; Shibuguchi, T.; Ohshima, T.; Masu, H.; Yamaguchi,
K.; Shibasaki, M. Angew. Chem., Int. Ed. 2005, 44, 4564; (b) Ura-
guchi, D.; Koshimoto, K.; Ooi, T. J. Am. Chem. Soc. 2008, 130,
10878; (c) Handa, S.; Gnanadesikan, V.; Matsunaga, S.; Shibasaki,
M. J. Am. Chem. Soc. 2010, 132, 4925; (d) Davis, T. A.; Johnston, J.
N. Chem. Sci. 2011, 2, 1076; (e) Olson, D. E.; Roberts, D. A.; Bois, J.
D. Org. Lett. 2012, 14, 6174; (f) Kano, T.; Sakamoto, R.; Akakura,
M.; Maruoka, K. J. Am. Chem. Soc. 2012, 134, 7516; (g) Liew, S. K.;
He, Z.; St Denis, J. D.; Yudin, A. K. J. Org. Chem. 2013, 78, 11637;
(h) Noble, A.; Anderson, J. C. Chem. Rev. 2013, 113, 2887.
[7] (a) de Figueiredo, R. M. Angew. Chem., Int. Ed. 2009, 48, 1190; (b)
Ramirez, T. A.; Zhao, B.; Shi, Y. Chem. Soc. Rev. 2012, 41, 931; (c)
Muñiz, K.; Martínez, C. J. Org. Chem. 2013, 78, 2168; (d) Bar, G. L.
J.; Lloyd-Jones, G. C.; Booker-Milburn, K. I. J. Am. Chem. Soc.
2005, 127, 7308; (e) Zhao, B.; Peng, X.; Zhu, Y.; Ramirez, T. A.;
Cornwall, R. G.; Shi, Y. J. Am. Chem. Soc. 2011, 133, 20890; (f)
Röben, C.; Souto, J. A.; González, Y.; Lishchynskyi, A.; Muñiz, K.
Angew. Chem., Int. Ed. 2011, 50, 9478; (g) Kim, H. J.; Cho, S. H.;
Chang, S. Org. Lett. 2012, 14, 1424; (h) Ingalls, E. L.; Sibbald, P. A.;
Kaminsky, W.; Michael, F. E. J. Am. Chem. Soc. 2013, 135, 8854; (i)
Cornwall, R. G.; Zhao, B.; Shi, Y. Org. Lett. 2013, 15, 796; (j) Turn-
penny, B. W.; Chemler, S. R. Chem. Sci. 2014, 5, 1786; (k) Zhang,
B.; Studer, A. Org. Lett. 2014, 16, 1790.
[8] (a) Katrun, P.; Chiampanichayakul, S.; Korworapan, K.; Pohmakotr,
M.; Reutrakul, V.; Jaipetch, T.; Kuhakarn, C. Eur. J. Org. Chem.
2010, 5633; (b) Samakkanad, N.; Katrun, P.; Techajaroonjit, T.;
Hlekhlai, S.; Pohmakotr, M.; Reutrakul, V.; Jaipetch, T.; Soorukram,
D.; Kuhakarn, C. Synthesis 2012, 44, 1693; (c) Muangkaew, C.;
Katrun, P.; Kanchanarugee, P.; Pohmakotr, M.; Reutrakul, V.;
Soorukram, D.; Jaipetch, T.; Kuhakarn, C. Tetrahedron 2013, 69,
8847; (d) Hlekhlai, S.; Samakkanad, N.; Sawangphon, T.; Pohma-
kotr, M.; Reutrakul, V.; Soorukram, D.; Jaipetch, T.; Kuhakarn, C.
[12] Kametani, T.; Sugahara, H.; Yagi, H. J. Chem. Soc. C 1966, 7, 717.
[13] Takamoto, M.; Kurouchi, H.; Otani, Y.; Ohwada, T. Synthesis 2009,
4129.
[14] (a) Koley, D.; Colon, O. C.; Savinov, S. N. Org. Lett. 2009, 11, 4172;
(b) Galliker, B.; Kissner, R.; Nauser, T.; Koppenol, W. H. Chem. Eur.
J. 2009, 15, 6161; (c) Wu, X. F.; Schranck, J.; Neumann, H.; Beller,
M. Chem. Commun. 2011, 47, 12462; (d) Taniguchi, T.; Yajima, A.;
Ishibashi, H. Adv. Synth. Catal. 2011, 353, 2643; (e) Taniguchi, T.;
Sugiura, Y.; Hatta, T.; Yajima, A.; Ishibashi, H. Chem. Commun.
2013, 49, 2198; (f) Kilpatrick, B.; Heller, M.; Arns, S. Chem. Com-
mun. 2013, 49, 514; (g) Maity, S.; Naveen, T.; Sharma, U.; Maiti, D.
Org. Lett. 2013, 15, 3384; (h) Manna, S.; Jana, S.; Saboo, T.; Maji,
A.; Maiti, D. Chem. Commun. 2013, 49, 5286; (i) Rokade, B. V.;
Prabhu, K. R. Org. Biomol. Chem. 2013, 11, 6713; (j) Shen, T.; Yuan,
Y.; Jiao, N. Chem. Commun. 2014, 50, 554; (k) Dutta, U.; Maity, S.;
Kancherla, R.; Maiti, D. Org. Lett. 2014, 16, 6302; (l) Hao, X.-H.;
Gao, P.; Song, X.-R.; Qiu, Y.-F.; Jin, D.-P.; Liu, X.-Y.; Liang, Y.-M.
Chem. Commun. 2015, 51, 6839.
[15] (a) Baji, H.; Flammang, M.; Kimny, T.; Gasquez, F.; Compagnon, P.
L.; Delcourt, A. Eur. J. Med. Chem.1995, 30, 617; (b) Balsamo, A.;
Breschi, M. C.; Chiellini, G.; Favero, L.; Macchia, M.; Martinelli, A.;
Martini, C.; Rossello, A.; Scatizzi, R. Eur. J. Med. Chem. 1995, 30,
743; (c) Karakurt, A.; Alagöz, M. A.; Sayoǧlu, B.; Çaliş, Ü.; Dalkara,
S. Eur. J. Med. Chem. 2012, 57, 275.
[16] (a) Grossi, L. Chem. Eur. J. 2005, 11, 5419; (b) He, X.; Shen, Z.; Mo,
W.; Sun, N.; Hu, B.; Hu, X. Adv. Synth. Catal. 2009, 351, 89; (c)
Galliker, B.; Kissner, R.; Nauser, T.; Koppenol, W. H. Chem. Eur. J.
2009, 15, 6161.
[17] (a) Curini, M.; Epifano, F.; Carla, M.; Rosati, O.; Ballini, R.; Bosica,
G. Tetrahedron Lett. 2000, 41, 8817; (b) Ovchinnikov, I. V.;
Finogenov, A. O.; Epishina, M. A.; Kulikov, A. S.; Strelenko, Yu. A.;
Makhova, N. N. Russian Chem. Bull. 2009, 58, 2137; (c) Zhao, J.-Q.;
Zhou, M.-Q.; Zuo, J.; Xu, X.-Y.; Zhang, X.-M.; Yuan, W.-C. Tetra-
hedron 2015, 71, 1560.
[18] (a) Krishnaveni, N. S.; Surendra, K.; Nageswar, Y. V. D.; Rao, K. R.
Synthesis 2003, 1968; (b) Ganguly, N. C.; Nayek, S.; Barik, S. K.
Synth. Commun. 2009, 39, 4053; (c) Quan, N.; Shi, X.-X.; Nie, L.-D.;
Dong, J.; Zhu, R.-H. Synlett 2011, 1028.
(Pan, B.; Qin, X.)
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9