Metal-Free 2,2,6,6-tetramethylpiperidin-1-yloxy radical (TEMPO) catalyzed aerobic oxidation of hydroxylamines and alkoxyamines to oximes and oxime ethers

Article abstract of DOI:10.1002/hlca.201200175

TEMPO-Mediated oxidation of hydroxylamines (=hydroxyamines) and alkoxyamines to the corresponding oxime derivatives is reported (TEMPO=2,2,6,6-tetramethylpiperidin-1-yloxy radical; Scheme 2). These environmentally benign oxidations proceed in good to excellent yields (Table 1). For alkoxyamines, oxidation to the corresponding oxime ethers can be performed by using dioxygen as a terminal oxidant in the presence of 5-10 mol-% of TEMPO or 4-substituted derivatives thereof as a catalyst (Scheme 3 and Table 2). Importantly, benzyl bromides can directly be transformed to oxime ethers via in situ alkoxyamine formation by a nucleophilic substitution followed by TEMPO-mediated oxidation (Scheme 4 and Table 3). Copyright

Full text of DOI:10.1002/hlca.201200175

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Helvetica Chimica Acta – Vol. 95 (2012)
Metal-Free 2,2,6,6-Tetramethylpiperidin-1-yloxy Radical (TEMPO)
Catalyzed Aerobic Oxidation of Hydroxylamines and Alkoxyamines to
Oximes and Oxime Ethers
by Sebastian Wertz and Armido Studer*
Organisch-Chemisches Institut, Westfꢀlische Wilhelms-Universitꢀt Mꢁnster, Corrensstr. 40,
DE-48149 Mꢁnster (phone: þ 49-251-8333291; fax: þ 49-251-8336523;
e-mail: studer@uni-muenster.de)
Dedicated to Prof. Dieter Seebach on the occasion of his 75th birthday
TEMPO-Mediated oxidation of hydroxylamines (¼ hydroxyamines) and alkoxyamines to the
corresponding oxime derivatives is reported (TEMPO ¼ 2,2,6,6-tetramethylpiperidin-1-yloxy radical;
Scheme 2). These environmentally benign oxidations proceed in good to excellent yields (Table 1). For
alkoxyamines, oxidation to the corresponding oxime ethers can be performed by using dioxygen as a
terminal oxidant in the presence of 5 – 10 mol-% of TEMPO or 4-substituted derivatives thereof as a
catalyst (Scheme 3 and Table 2). Importantly, benzyl bromides can directly be transformed to oxime
ethers via in situ alkoxyamine formation by a nucleophilic substitution followed by TEMPO-mediated
oxidation (Scheme 4 and Table 3).
Introduction. – As valuable intermediates in organic synthesis [1] as well as in
biosynthesis [2] and therapeutics [2][3], oximes and derivatives thereof have been
intensively investigated. Condensation of aldehydes and ketones with hydroxylamines
is the most commonly used synthetic route to oximes. Other methods for oxime
formation not discussed in detail herein are also known [4]. In biological systems,
formation of oximes as final metabolites in the degradation of biogenic amines is
reported to presumably occur via an alternative pathway, namely via the oxidation of
intermediately formed hydroxylamines (¼ hydroxyamines) [5]. This oxidative ap-
proacꢁh has found application mainly for the synthesis of nitrones
(R3ꢀ (ꢀ ꢂ )¼C(R1)R2) starting with N,N-disubstituted hydroxylamines [6] and is well
N
O
investigated for the generation of nitroso compounds from hydroxylamines which lack
an a-H-atom (for reviews, see [7]). Moreover, 2-iodoxybenzoic acid (IBX) as a
stoichiometric oxidant was successfully used for the oxidation of hydroxylamines and
alkoxyamines to their corresponding oxime derivatives [8]. Transformation of
hydroxylamines to oximes by reaction with dioxygen is known; however, only few
substrates seem to be oxidized under aerobic conditions in the absence of any catalyst
[9]. Problematic in this aerobic oxidation is the formation of diazene N-oxides of the
type 4 as by-products, which result from condensation of an intermediately formed
nitroso compound 2 with unreacted hydroxylamine 1 (Scheme 1) [10]. Low yields of
oximes 3 are achieved if tautomerization of 2 is slow as compared to condensation with
1 to give 4. An oxidation process that involves formation of 2 as an intermediate or
ꢂ 2012 Verlag Helvetica Chimica Acta AG, Zꢁrich

Helvetica Chimica Acta – Vol. 95 (2012)
1759
which adheres to conditions accelerating tautomerization of 2 or suppressing
condensation of 1 with 2 might offer an answer to that problem. Along this line, a
successful transition-metal-catalyzed aerobic oxidation of alkoxyamines to oxime
ethers was published in 2006 [11]. Herein we report our results on 2,2,6,6-
tetramethylpiperidin-1-yloxy (¼2,2,6,6-tetramethylpiperidine 1-oxyl; TEMPO) radical
mediated oxidation of hydroxylamines and alkoxyamines to oximes and oxime ethers.
Scheme 1. Oxidation of Hydroxylamines
Results and Discussion. – TEMPO and derivatives thereof have widely been used as
mild commercially available oxidants in organic synthesis (for recent reviews, see [12]).
In most of the cases, the N-oxoammonium salt, readily generated in situ from TEMPO
by the use of a co-oxidant, is the active reagent. Due to the low redox potential of
TEMPO as compared to its N-oxoammonium salt (E(TEMPOþ/TEMPO) ¼ 0.64 V vs.
SCE, see [13]), reports on TEMPO acting as a direct oxidizing reagent without the aid
of any transition metal are rare [14][15].
In line with our own investigation towards transition-metal-free TEMPO-mediated
oxidation processes [15], we found that commercially available N-benzylhydroxyl-
amine hydrochloride (1a · HCl) was cleanly and quantitatively transformed to the
corresponding oxime 3a within 30 min in the presence of 2.2 equiv. of 4-hydroxy-
TEMPO (4-OH-TEMPO) and 1.1 equiv. of Et3N in THF at room temperature. The
reaction worked equally well in a,a,a-trifluorotoluene (¼ benzotrifluoride, BTF) and
TEMPO as oxidant (Scheme 2 and Table 1, Entry 1). The fluorinated solvent better
dissolves dioxygen [16]; this fact will become an important issue for the aerobic
nitroxide-catalyzed oxidations which will be discussed below. To study the substrate
scope, we treated various hydroxylamines and alkoxyamines, i.e., 1b – 1l, with TEMPO,
4-OH-TEMPO, or 4-acetamido-TEMPO (4-AcNH-TEMPO; 2.2 equiv.) in BTF1).
Aliphatic hydroxylamines turned out to be less reactive. A longer reaction time at
higher temperature was necessary to reach full conversion. Oximes 3b and 3c were
isolated in moderate to good yields (Entries 2 and 3). a,a-Disubstituted hydroxyl-
amines 1d, 1e, the cyclic congener 1f, and the aliphatic N-cyclopentylhydroxylamine
(1g) were cleanly oxidized to the corresponding ketoximes in excellent yields
(Entries 4 – 7). Oxidation of the aliphatic N-(benzyloxy)hexanamine (1h) with
TEMPO gave oxime ether 3h in 94% yield (Entry 8). As compared to the hydroxyl-
1
)
The cheaper 4-AcNH-TEMPO could be used. As by-products, TEMPOH or 4-AcNH-TEMPOH
were formed in these reactions. In cases where TEMPOH is difficult to separate from the product
by column chromatography, we recommend to switch to 4-AcNH-TEMPO or 4-OH-TEMPO.

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Scheme 2. Nitroxide-Mediated Oxidation of Hydroxylamines and Alkoxyamines. For X and 3, see
Table 1.
Table 1. Nitroxide-Mediated Oxidation of Hydroxylamines and Alkoxyamines to Oximes and Oxime
Ethersa)
Entry
Substrate 1
1a · HCl
X
H
Product 3
Time [h]
0.5
Yield [%]b)
99
1c)d)
3a
3b
3c
3d
2
1b
1c
1d
H
H
H
4
6
2
74
42
95
3
4c)
5
1e
1f
H
H
3e
3f
0.5
0.5
98
76
6e)
7
1g
H
3g
1
99
8
9
1h
1i
H
3h
3i
12
12
12
12
94
86
99
94
AcNH
AcNH
H
10
11
1j
3j
1k
3k
12
1l
H
3l
12
96
a) According to Scheme 2 on a 0.5 mmol scale under Ar. b) Yield of isolated 3. c) Run at r.t. d) With
1.1 equiv. of Et3N. e) Product obtained as a single stereoisomer.

Helvetica Chimica Acta – Vol. 95 (2012)
1761
amine oxidations, a longer reaction time was required in this case. However, in contrast
to the results obtained for the oxidation of aliphatic hydroxylamines (see Entries 2 and
3), the reaction with alkoxyamine 1h was high yielding. Encouraged by the clean
conversion of alkoxyamines 1h, we tested other substrates of this compound class. Thus
oxime ethers 3i – 3l were isolated in excellent yields from 1i – 1l (Entries 9 – 12). We did
not find any difference on the reaction outcome by switching from TEMPO to the less
expensive 4-AcNH-TEMPO or 4-OH-TEMPO.
Encouraged by the work of Han and co-workers on nitroxide-catalyzed aerobic
oxidation of cyclic acetals [14] and by our own results on aerobic TEMPO-catalyzed
homocouplings of arylboronic acids [17], we decided to develop a protocol that uses
catalytic amounts of a nitroxide in combination with dioxygen as the terminal oxidant.
For the catalytic protocol (Scheme 3, Method A), we used 5 mol-% of TEMPO under
an O2 atmosphere in BTF (24 h). To establish the catalytic activity of TEMPO, each
reaction was repeated in the absence of nitroxide under otherwise identical conditions
(Method B). Results are summarized in Table 2.
Scheme 3. Nitroxide-Catalyzed Aerobic Oxidation of Hydroxylamines and Alkoxyamines. For X and 3,
see Tables 2 and 1, resp.
Table 2. Nitroxide-Catalyzed Aerobic Oxidation of Hydroxylamines and Alkoxyaminesa)
Entry
Temp. [8]
X
Product 3
Yield [%]b)
Method A
Method B
1c)
2
3
4
5
6
7
8
9
10
11
12
13
r.t.
80
80
r.t.
r.t.
r.t.
80
80
80
80
80
80
80
OH
H
H
H
H
H
H
H
AcNH
H
3a
3b
3c
3d
3e
3f
3h
3i
3i
3j
3j
3k
3l
94
15d)
< 1d)
58
88
13d)
< 1d)
< 1
< 1
9
< 1
< 1
< 1
< 1
< 1
< 1
< 1
43d)
94
92
90
88
98
AcNH
H
H
94
91
85e)
a) According to Scheme 3 on a 0.5 mmol scale. b) Yield of isolated 3. c) With 1a · HCl and 1.1 equiv. of
Et3N. d) The corresponding diazene-N-oxide of type 4 was formed (see Scheme 1). e) 10 mol-% of
catalyst for 48 h.
For the reactive hydroxylamine 1a, we found that oxidation also occurred efficiently
with dioxygen at room temperature (Entry 1, Method B). Only little acceleration was
noted upon adding the nitroxide as a catalyst (Entry 1, Method A). The less reactive
aliphatic hydroxylamine 1b was oxidized to 3b in a low yield, and TEMPO did not

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Helvetica Chimica Acta – Vol. 95 (2012)
affect the reaction outcome (Entry 2). Hydroxylamine 1c did not react to 3c under
aerobic conditions neither in the absence nor in the presence of TEMPO (Entry 3).
Obviously, for less reactive substrates, a stoichiometric amount of TEMPO is required
for successful oxidation. Pleasingly, a catalytic effect of TEMPO was observed in the
formation of ketoxime 3d (58%; Entry 4); the oxidation was clean, and 3d was the only
detectable product in the oxidation of hydroxylamine 1d, the remaining starting
material (34%) being recovered. In the absence of TEMPO, 3d was not formed, clearly
documenting the catalytic activity of TEMPO for this reaction. A slightly lower yield
was achieved for the catalytic oxidation of 1e (Entry 5). The cyclic hydroxylamine 1f
was cleanly oxidized under aerobic conditions with TEMPO as a catalyst (94%;
Entry 6). In the absence of nitroxide, only low conversion towards the desired oxime 3f
(9%) was achieved. As for the nitroxide mediated oxidations discussed above,
alkoxyamines turned out to be excellent substrates for the catalytic process (Entries 7 –
13). The corresponding oxime ethers were isolated in good to excellent yields in the
presence of nitroxide catalyst. It should be noted that in the absence of the
organocatalyst, these alkoxyamines remained unreacted upon exposure to dioxygen
(Method B); full recovery of the starting materials was possible in all these cases. The
aliphatic alkoxyamine 1h was converted to the corresponding oxime ether 3h in very
good yield (92%; Entry 7). Alkoxyamines 1i and 1j were cleanly transformed to oxime
ethers 3i and 3j under TEMPO catalysis (Entries 8 and 10), and switching to 4-AcNH-
TEMPO gave similar results in both cases (Entries 9 and 11). The slightly enhanced
reactivity of the (benzyloxy)amine 1j as compared to the methoxyamine 1i was also
observed in the oxidation to oxime ethers with stoichiometric amounts of TEMPO (see
Table 1, Entries 9 and 10). While the cyclic alkoxyamine 1k gave cyclopentanone O-
benzyl oxime (3k) in a very good yield (91%) by TEMPO catalysis (Entry 12), a higher
nitroxide loading and prolonged reaction time were necessary to oxidize the sterically
more crowded alkoxyamine 3l (85% yield with 10 mol-% of TEMPO for 48 h,
Entry 13).
Finally, we decided to develop an oxime ether synthesis via a two-step one-pot
process starting with halides in which the alkoxyamine to be oxidized is generated in
situ by a nucleophilic substitution reaction with O-benzylhydroxylamine. A problem to
be solved was the competing overalkylation of the intermediately formed alkoxyamine.
As a test substrate we chose benzyl bromide. After intensive experimentation, we
found that the highest yield (79%) of oxime ether 3j was achieved with an excess of O-
benzylhydroxylamine (5.5 equiv.) and Et3N in the presence of 2.2 equiv. of TEMPO in
EtOH (Scheme 4 and Table 3, Entry 1). Transformation of benzyl chloride under the
same conditions provided 3j in significantly lower yield (43%), but aliphatic halides
were not converted to the targeted oxime ethers under these conditions. Therefore, all
further experiments were conducted with activated bromides. Benzyl bromides bearing
an electron-withdrawing or electron-donating substituent at the para-position were
readily oxidized to oxime ethers 3m – 3p in 57 – 84% yield (Entries 2 – 5). ortho- and
meta-Substituents were tolerated in that two-step process, and products 3q – 3v were
isolated in good to excellent yields (73 – 91%, Entries 6 – 11). Electronic effects at the
arene moiety did not influence the reaction outcome to a large extent. Allyl and
secondary benzyl bromides gave the desired oxime ethers 3w and 3x in moderate yields
(Entries 12 and 13). In these cases, formation of unidentified by-products was

Helvetica Chimica Acta – Vol. 95 (2012)
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Scheme 4. TEMPO-Mediated Oxidation of in situ Generated Alkoxyamines. For R1 and R2, see Table 3.
Table 3. TEMPO-Mediated Oxidation of in situ Generated Alkoxyaminesa)
Entry
R1
R2
Product
Yield [%]b)
1
2
3
4
5
6
7
8
9
10
11
12
13
14c)
H
H
H
H
H
H
H
H
H
H
H
H
Ph
3j
79
84
63
57
60
91
78
74
82
84
73
48
44
84
4-tBuꢀC6H4
4-MeꢀC6H4
4-MeOꢀC6H4
4-BrꢀC6H4
3-MeꢀC6H4
3-NO2ꢀC6H4
3-IꢀC6H4
2-MeꢀC6H4
2,4-Me2C6H3
2-BrꢀC6H4
(E)-PhCH ¼ CH
Ph
3m
3n
3o
3p
3q
3r
3s
3t
3u
3v
3w
3x
3y
Me
COOMe
Ph
a) According to Scheme 4 from the corresponding activated bromide on a 1 mmol scale. b) Yield of
isolated 3. c) MeOH as solvent.
observed. However, preparation of ketoxime ether 3y was achieved in 84% yield from
the corresponding doubly activated bromide in a good yield (Entry 14).
The exact mechanism for the TEMPO-mediated oxidation of hydroxylamines and
alkoxyamines to the corresponding oxime derivatives is not known. Due to the fact that
for some hydroxylamine oxidations, diazene-N-oxides 4 were isolated as by-products,
we currently assume that the oxidation of hydroxylamines occurs via nitroso
compounds. Nitroso compounds are probably generated via H-abstraction from OH
by TEMPO. This process should be thermodynamically feasible as the bond
dissociation energy (BDE) difference between hydroxylamine (NH2OH, ca. 81 –
82 kcal/mol for NH and 75 – 77 kcal/mol for OH) [18] which should be further lowered
by the introduction of substituents and TEMPOH (69 kcal/mol) [19] is rather small.
Renewed H-transfer to a second equivalent of TEMPO leads to the nitroso derivative
that eventually isomerizes to the oxime (Scheme 5, Eqn. 1). As nitroso compounds are
likely intermediates, we currently disregard disproportionation of two aminoxyl
radicals to give the oxime and the starting hydroxylamine [20], see also [15f]. Note that
this pathway can not be followed for the oxidation of alkoxyamines. For these
substrates, the reaction might proceed via H-transfer from either the a-CH next to the
N-atom or from NH to TEMPO (Eqn. 2). A second H-transfer from these
intermediately formed C- or N-centered radicals to TEMPO would directly lead to
oxime ethers.

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Helvetica Chimica Acta – Vol. 95 (2012)
Scheme 5. Possible Mechanisms for TEMPO-Mediated Oxidation of Hydroxylamines and Alkoxy-
amines
Conclusions. – We presented a high-yielding TEMPO-mediated oxidation of
various hydroxylamines and alkoxyamines to the corresponding oximes and oxime
ethers. For alkoxyamines, reactions could be run with catalytic amounts of a nitroxide
with dioxygen as a terminal oxidant. In addition, a method for direct conversion of
benzyl bromides to oxime ethers via in situ formation of alkoxyamines was developed.
The project has been funded within the research cluster ꢃSusChemSysꢄ by the Ministerium fꢀr
Innovation, Wissenschaft und Forschung, NRW.
Experimental Part
1. General. All reactions involving moisture- and/or air-sensitive reagents and/or intermediates were
carried out in heat-gun-dried glassware under Ar and were performed by using standard Schlenk
techniques. A dioxygen atmosphere was provided by the balloon technique. Solvents and Et3N were
freshly distilled from appropriate drying reagents or stored over molecular sieve under Ar. O-
Benzylhydroxylamine was liberated from its hydrochloride salt by dissolving in sat. aq. NaHCO3 soln.
and extracting with CH2Cl2 (3ꢃ). All other chemicals were purchased from Sigma Aldrich, Fluka, Acros
Organics, ABCR, or Alfa Aesar and were used as received. TLC: silica gel 60 F254 plates (SiO2; Merck).
Flash chromatography (FC): silica gel 60 (SiO2, 40 – 63 mm; Merck) with Ar excess pressure of ca. 0.4 bar.
M.p.: SMP-10 apparatus (Stuart Scientific); uncorrected. IR Spectra: Digilab-FTS-4000 instrument
1
equipped with a Specac-MKII-Golden-Gate single reflection ATR system; in cmꢀ1. H- and 13C-NMR
Spectra: Bruker-DPX-300 spectrometer; in CDCl3 at 258; d in ppm rel. to solvent residual peak as
internal standard, J in Hz. HR-ESI-MS: Bruker MicroTof spectrometer; in m/z.
2. Hydroxylamines (¼ Hydroxyamines) or Alkoxyamines from the Corresponding Carbonyl
Compounds. Starting materials were prepared according to literature procedures starting from the
corresponding carbonyl compounds. Condensation with hydroxylamine hydrochloride (NH2OH · HCl)
or O-benzylhydroxylamine hydrochloride (NH2OBn · HCl) at r.t. [21] or under reflux conditions [22]
afforded the desired oxime or oxime ether which was subsequently reduced to the desired hydroxylamine
or alkoxyamine upon treatment with NaBH3CN [23] or BH3 · pyridine complex [24].
N-(3-Phenylpropyl)hydroxylamine (¼ N-Hydroxybenzenepropanamine; 1b) [25a]: According to
1
[21][24a] in 84% yield over two steps. Colorless solid. H-NMR (300 MHz, CDCl3): 7.34 – 7.14 (m, 5
arom. H); 5.19 (br. s, NH, OH); 2.97 (t, J ¼ 7.2, CH2N); 2.68 (t, J ¼ 7.7, CCH2); 1.88 (m, CH2CH2N).
13C-NMR (75 MHz, CDCl3): 141.8 (C); 128.5 (2 CH); 127.6 (CH); 125.9 (2 CH); 53.3 (CH2); 33.4 (CH2);
28.7 (CH2). HR-ESI-MS: 152.1072 ([M þ H]þ, C9H14NOþ; calc. 152.1070).
N-Hexylhydroxylamine (¼ N-Hydroxyhexan-1-amine; 1c) [25b]: According to [21][23] in 84% yield
over two steps. Colorless solid. 1H-NMR (300 MHz, CDCl3): 2.94 (t, J ¼ 7.1, CH2N); 1.49 – 1.43 (m,
CH2CH2N); 1.41 – 1.21 (m, CH2); 0.97 – 0.77 (m, Me). 13C-NMR (75 MHz, CDCl3): 54.0 (CH2); 31.7
(CH2); 27.0 (CH2); 26.8 (CH2); 22.6 (CH2); 14.0 (Me). HR-ESI-MS: 118.1230 ([M þ H]þ, C6H16NOþ;
calc. 118.1226).
N-Benzhydrylhydroxylamine (¼ N-Hydroxy-a-phenylbenzenemethanamine; 1d) [25c]: According to
1
[21][23] in 85% yield over two steps. Colorless solid. H-NMR (300 MHz, CDCl3): 7.47 – 7.16 (m, 10
arom. H); 5.58 (br. s, OH); 5.23 (s, CHN); 4.99 (br. s, NH). 13C-NMR (75 MHz, CDCl3): 140.7 (2 C);

Helvetica Chimica Acta – Vol. 95 (2012)
1765
128.7 (4 CH); 127.7 (4 CH); 127.6 (2 CH); 70.8 (CH). HR-ESI-MS: 222.0884 ([M þ Na]þ,
C13H13NNaOþ; calc. 222.0889).
N-(1-Phenylpropyl)hydroxylamine (¼a-Ethyl-N-hydroxybenzenemethanamine; 1e) [25d]: Accord-
ing to [21][23] in 54% yield over two steps. Colorless solid. 1H-NMR (300 MHz, CDCl3): 7.39 – 7.23 (m, 5
arom. H); 4.71 (br. s, NH, OH); 3.87 (dd, J ¼ 8.5, 5.6, CHN); 1.96 – 1.51 (m, CH2); 0.83 (t, J ¼ 7.5, Me).
13C-NMR (75 MHz, CDCl3): 141.2 (C); 128.5 (2 CH); 127.8 (2 CH); 127.6 (CH); 68.7 (CH); 26.4 (CH2);
10.6 (Me). HR-ESI-MS: 152.1068 ([M þ H]þ, C9H14NOþ; calc. 152.1070).
N-(Chroman-4-yl)hydroxylamine (¼ 3,4-Dihydro-N-hydroxy-2H-1-benzopyran-4-amine; 1f): Ac-
cording to [21][23] in 88% yield over two steps. Colorless solid. M.p. 1288. IR (neat): 3258m, 3163m (br.),
2934m, 2888m, 1607m, 1581m, 1489s, 1452m, 1414m, 1314m, 1272m, 1250m, 1221s, 1179m, 1138m, 1118m,
1096m, 1055s, 1007s, 974m, 910s, 767s, 752s, 667m, 605m, 561m. 1H-NMR (300 MHz, CDCl3): 7.30 – 7.15
(m, 2 arom. H); 6.96 – 6.81 (m, 2 arom. H); 4.33 – 4.18 (m, CH2O); 4.15 – 4.06 (m, CHN); 2.27 – 2.19 (m,
1 H, CH2CH); 2.13 – 1.94 (m, 1 H, CH2CH). 13C-NMR (75 MHz, CDCl3): 155.7 (C); 130.3 (CH); 129.5
(CH); 120.3 (CH); 119.8 (C); 117.2 (CH); 62.0 (CH2); 54.9 (CH); 25.2 (CH2). HR-ESI-MS: 166.0864
([M þ H]þ, C9H12NOþ2 ; calc. 166.0863).
N-Cyclopentylhydroxylamine (¼ N-Hydroxycyclopentanamine; 1g) [25e]: According to [21][23] in
67% yield over two steps. Colorless solid. 1H-NMR (300 MHz, CDCl3): 4.69 (br. s, NH, OH); 3.39 – 3.26
(m, CHN); 1.64 – 1.12 (m, 4 CH2). 13C-NMR (75 MHz, CDCl3): 63.3 (CH); 30.4 (2 CH2); 24.7 (2 CH2).
HR-ESI-MS: 102.0902 ([M þ H]þ, C5H12NOþ; calc. 102.0913).
O-Benzyl-N-hexylhydroxylamine (¼ N-(Phenylmethoxy)hexan-1-amine; 1h): According to [22][23]
in 85% yield over two steps. Colorless oil. IR (neat): 3090w, 3065w, 3032w, 2929s (br.), 2857s (br.),
2363w, 2338w, 1496w, 1454m, 1363m, 1207w, 1059w, 1009m (br.), 961m (br.), 910w, 743m, 698s, 612w.
1H-NMR (300 MHz, CDCl3): 7.38 – 7.27 (m, 5 arom. H); 5.54 (br. s, NH); 4.71 (s, CH2O); 2.94 (t, J ¼ 7.0,
CH2N); 1.56 – 1.46 (m, CH2); 1.37 – 1.23 (m, 3 CH2); 0.96 – 0.83 (m, Me). 13C-NMR (75 MHz, CDCl3):
138.1 (C); 128.4 (2 CH); 128.4 (2 CH); 127.8 (CH); 76.2 (CH2); 52.3 (CH2); 31.7 (CH2); 27.3 (CH2); 26.9
(CH2); 22.6 (CH2); 14.0 (Me). HR-ESI-MS: 208.1686 ([M þ H]þ, C13H22NOþ; calc. 208.1696).
N-Benzyl-O-methylhydroxylamine (¼ N-Methoxybenzenemethanamine; 1i) [25f]: According to
1
[24b] in 91% yield. Colorless oil. H-NMR (300 MHz, CDCl3): 7.40 – 7.27 (m, 5 arom. H); 5.06 (br. s,
NH); 4.07 (s, CH2); 3.54 (s, Me). 13C-NMR (75 MHz, CDCl3): 137.6 (C); 128.8 (2 CH); 128.5 (CH); 127.5
(2 CH); 61.8 (CH2); 56.2 (Me). HR-ESI-MS: 138.0919 ([M þ H]þ, C8H12NOþ; calc. 138.0913).
N,O-Dibenzylhydroxylamine (¼ N-(Phenylmethoxy)benzenemethanamine; 1j) [8]: According to
[22][23] in 95% yield over two steps. Colorless oil. 1H-NMR (300 MHz, CDCl3): 7.41 – 7.25 (m, 10 arom.
H); 5.73 (br. s, NH); 4.67 (s, CH2O); 4.06 (s, CH2N). 13C-NMR (75 MHz, CDCl3): 137.9 (C); 137.7 (C);
129.0 (2 CH); 128.5 (2 CH); 128.4 (2 CH); 128.4 (CH); 127.8 (2 CH); 127.5 (CH); 76.3 (CH2); 56.6
(CH2). HR-ESI-MS: 214.1220 ([M þ H]þ, C14H16NOþ; calc. 214.1226).
O-Benzyl-N-cyclopentylhydroxylamine (¼ N-(Phenylmethoxy)cyclopentanamine; 1k): According to
[22][23] in 89% yield over two steps. Colorless oil. IR (neat): 3088w, 3064w, 3031w, 2956s (br.), 2910m
(br.), 2868m (br.), 1496w, 1453m, 1356m, 1207w, 1053m, 1027m, 986s, 910m, 737s, 697s. 1H-NMR
(300 MHz, CDCl3): 7.41 – 7.27 (m, 5 arom. H); 5.37 (br. s, NH); 4.73 (s, CH2O); 3.62 – 3.51 (m, CH);
1.82 – 1.41 (m, 4 CH2). 13C-NMR (75 MHz, CDCl3): 138.1 (C); 128.4 (2 CH); 128.3 (CH); 127.7 (2 CH);
76.5 (CH2); 61.9 (CH); 30.5 (2 CH2); 24.4 (2 CH2). HR-ESI-MS: 192.1388 ([M þ H]þ, C12H18NOþ; calc.
192.1383).
O-Benzyl-N-(1-phenylpropyl)hydroxylamine (¼a-Ethyl-N-(phenylmethoxy)benzenemethamine; 1l)
1
[25g]: According to [21][23] in 92% yield over two steps. Colorless oil. H-NMR (300 MHz, CDCl3):
7.39 – 7.19 (m, 10 arom. H); 5.69 (br. s, NH); 4.62 (d, J ¼ 11.4, 1 H, CH2O); 4.55 (d, J ¼ 11.4, 1 H, CH2O);
3.90 (dd, J ¼ 8.5, 5.6, CHN); 1.93 – 1.54 (m, MeCH2); 0.81 (t, J ¼ 7.5, Me). 13C-NMR (75 MHz, CDCl3):
141.7 (C); 137.9 (C); 128.5 (2 CH); 128.3 (2 CH); 127.9 (2 CH); 127.7 (2 CH); 127.4 (2 CH); 76.8 (CH2);
67.5 (CH); 26.7 (CH2); 10.6 (Me). HR-ESI-MS: 242.1537 ([M þ H]þ, C16H20NOþ; calc. 242.1539).
3. Nitroxide-Mediated Oxidation of Hydroxylamines or Alkoxyamines: General Procedure 1 (GP1).
TEMPO, 4-OH-TEMPO, or 4-AcNH-TEMPO (1.1 mmol, 2.2 equiv.) was added to a soln. of the
hydroxylamine or alkoxyamine (0.50 mmol, 1.0 equiv.; 0.2m) in BTF (2.5 ml). The mixture was stirred at
r.t. or 808 until complete conversion of starting material (TLC monitoring). After evaporation of the
solvent, the crude mixture was purified by FC to afford the desired oxime or oxime ether.

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Nitroxide-Catalyzed Aerobic Oxidation of Hydroxylamines or Alkoxyamines: General Procedure 2
(GP2). TEMPO, 4-OH-TEMPO, or 4-AcNH-TEMPO (5 – 10 mol-%) was added to a soln. of the
hydroxylamine or alkoxyamine (0.50 mmol, 1 equiv.; 0.2m) in BTF (2.5 ml). The mixture was vigorously
stirred under dioxygen (balloon technique) at r.t. or 808 for 24 – 48 h. Evaporation of the solvent followed
by FC afforded the desired oxime or oxime ether. Each experiment was repeated in the absence of any
nitroxide catalyst under otherwise identical conditions.
TEMPO-Mediated Oxidation of in situ Generated Alkoxyamines: General Procedure 3 (GP3). Et3N
(157 ml, 1.10 mmol, 1.1 equiv.) and the activated bromide (1.00 mmol, 1.0 equiv.; 0.25m) were added to a
soln. of TEMPO (344 mg, 2.20 mmol, 2.2 equiv.) and NH2OBn (570 ml, 5.50 mmol, 5.5 equiv.) in EtOH
(4 ml). The mixture was then heated to 808 over 30 min, and stirring was continued at 808 for an
additional 6 h. After evaporation of the solvent, the crude mixture was purified by FC to afford the
desired oxime ether.
Benzaldehyde Oxime (3a) [26a]: Preparation with a Stoichiometric Amount of 4-OH-TEMPO: Et3N
(0.70 ml, 1.1 mmol, 1.1 equiv.) was added to a soln. of 1a · HCl (160 mg, 1.00 mmol, 1.0 equiv.) in THF
(2.5 ml). After 5 min stirring at r.t., 4-OH-TEMPO (378 mg, 2.20 mmol, 2.2 equiv.) was added, and the
mixture was stirred for another 0.5 h at r.t. The precipitate was filtered off and the solvent evaporated. FC
(petroleum ether/tBuOMe 20 :1) afforded 3a (120 mg, 99%). Colorless solid. The experiment was
repeated under analogous conditions in BTF on a 0.5 mmol scale with TEMPO as the oxidant to give 3a
in 99% isolated yield.
Preparation with a Catalytic Amount of 4-OH-TEMPO in the Presence of O2. Et3N (0.35 ml,
0.55 mmol, 1.1 equiv.) was added to a soln. of 1a · HCl (80 mg, 0.50 mmol, 1.0 equiv.) in BTF (2.5 ml). 4-
OH-TEMPO (3.9 mg, 25 mmol, 5 mol-%) was added after 5 min stirring at r.t., and the mixture was
exposed to dioxygen (balloon technique). After 24 h stirring at r.t., the solvent was removed under
reduced pressure. FC (pentane/tBuOMe 20 :1) afforded 3a (57 mg, 94%). Colorless solid. The control
experiment under identical conditions without addition of nitroxide catalyst afforded 3a in 88% yield
(53 mg). 1H-NMR (300 MHz, CDCl3): 8.15 (s, CH); 8.08 (s, OH); 7.53 – 7.63 (m, 2 arom. H); 7.44 – 7.33
(m, 3 arom. H). 13C-NMR (75 MHz, CDCl3): 148.5 (CH); 130.1 (C); 128.1 (CH); 126.9 (2 CH); 125.1
(2 CH). HR-ESI-MS: 144.0417 ([M þ Na]þ, C7H7NNaOþ; calc. 144.0420).
Benzenepropanal Oxime (3b) ([25a] for (E)-isomer): According to GP1, with 1b (75 mg, 0.50 mmol,
1.0 equiv.) and TEMPO (173 mg, 1.10 mmol, 2.2 equiv.) for 4 h at 808. FC (petroleum ether/AcOEt
20 :1) afforded 3b (55 mg, 0.37 mmol, 74%). Colorless solid.
According to GP2, with 1b (75 mg, 0.50 mmol, 1 equiv.) and TEMPO (3.9 mg, 25 mmol, 5 mol-%) in
the presence of O2 for 24 h at 808. FC (pentane/AcOEt 20 :1) afforded 3b (11 mg, 15%). Colorless solid.
In the control experiment under identical conditions without addition of nitroxide catalyst, 13% (10 mg)
of 3b were isolated. 1H-NMR (300 MHz, CDCl3; (E)/(Z) mixtures were obtained; both stereoisomers):
7.47 (t, J ¼ 5.8, CHN, (E)-isomer); 7.37 – 7.15 (m, 10 arom. H); 6.76 (t, J ¼ 5.3, CHN, (Z)-isomer); 2.89 –
2.77 (m, 4 H, CH2); 2.77 – 2.64 (m, CH2, (Z)-isomer); 2.59 – 2.46 (m, CH2, (E)-isomer). 13C-NMR
(75 MHz, CDCl3; both stereoisomers): 151.6 (CH); 151.3 (CH); 140.6 (C); 140.6 (C); 128.5 (4 CH); 128.3
(2 CH); 128.2 (2 CH); 126.2 (2 CH); 32.8 (CH2); 31.9 (CH2); 31.2 (CH2); 26.4 (CH2). HR-ESI-MS:
172.0736 ([M þ Na]þ, C9H11NNaOþ; calc. 172.0733).
Hexanal Oxime (3c): According to GP1, with 1c (59 mg, 0.50 mmol, 1 equiv.) and TEMPO (173 mg,
1.10 mmol, 2.2 equiv.) for 6 h at 808. FC (pentane/AcOEt 20 :1) afforded 3c (24 mg, 42%, ca. 1:1 (E)/
(Z)-mixture). Colorless solid. M.p. 538. IR (neat): 3255m (br.), 3110m (br.), 2956s, 2928s, 2863m, 1661w,
1359m, 1380w, 1302w, 1047w, 981m, 924s, 727m, 600m. 1H-NMR (300 MHz, CDCl3; both stereoisomers):
7.89 (br. s, OH, 1st isomer); 7.53 (br. s, OH, 2nd isomer); 7.43 (t, J ¼ 6.1, CH, 2nd isomer); 6.72 (t, J ¼ 5.5,
CH, 1st isomer); 2.44 – 2.32 (m, CH2CH, 1st isomer); 2.26 – 2.13 (m, CH2CH, 2nd isomer); 1.58 – 1.43 (m,
4 H, CH2CH2CH); 1.42 – 1.23 (m, 8 H, MeCH2CH2); 1.01 – 0.91 (m, 6 H, Me). 13C-NMR (75 MHz,
CDCl3; both stereoisomers): 153.1 (CH); 152.4 (CH); 31.5 (CH2); 31.2 (CH2); 29.4 (CH2); 26.2 (CH2);
25.7 (CH2); 24.9 (CH2); 22.3 (2 CH2); 13.9 (2 Me). HR-ESI-MS: 138.0886 ([M þ Na]þ, C6H13NNaOþ;
calc. 138.0889).
Diphenylmethanone Oxime (3d) [21]: According to GP1, with 1d (100 mg, 501 mmol, 1.0 equiv.) and
TEMPO (172 mg, 1.10 mmol, 2.2 equiv.) for 2 h at r.t. FC (pentane/tBuOMe 20 :1) afforded 3d (94 mg,
95%). Colorless solid.

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According to GP2, with 1d (100 mg, 501 mmol, 1.0 equiv.) and TEMPO (3.9 mg, 25 mmol, 5 mol-%)
in the presence of O2 for 24 h at r.t. FC (pentane/tBuOMe 20 :1) afforded 3d (57 mg, 58%). Colorless
solid, beside 34% of recovered 1d. In the control experiment under identical conditions without addition
of nitroxide catalyst, 99% 1d was recovered. 3d: 1H-NMR (300 MHz, CDCl3): 7.73 (s, OH); 7.52 – 7.28 (m,
10 arom. H). 13C-NMR (75 MHz, CDCl3): 158.1 (C); 136.2 (C); 132.7 (C); 129.5 (CH); 129.2 (2 CH);
129.1 (CH); 128.3 (2 CH); 128.2 (2 CH); 127.9 (2 CH). HR-ESI-MS: 220.0732 ([M þ Na]þ,
C13H11NNaOþ; calc. 220.0733).
1-Phenylpropan-1-one Oxime (3e) [26b]: According to GP1, with 1e (76 mg, 0.50 mmol, 1.0 equiv.)
and TEMPO (172 mg, 1.10 mmol, 2.2 equiv.) for 0.5 h at 808. FC (pentane/AcOEt 20 :1) afforded 3e
(73 mg, 0.49 mmol, 98%). Colorless solid.
According to GP2, with 1e (119 mg, 788 mmol, 1 equiv.) and TEMPO (5.9 mg, 38 mmol, 5 mol-%) in
the presence of O2 for 24 at r.t. FC (pentane/AcOEt 20 :1) afforded 3e (50 g, 43%). Colorless solid. In
the control experiment under identical conditions without addition of nitroxide catalyst, 99% of 1e was
recovered. 3e: 1H-NMR (300, CDCl3): 8.07 (br. s, OH); 7.68 – 7.56 (m, 2 arom. H); 7.44 – 7.33 (m, 3 arom.
H); 2.82 (q, J ¼ 7.6, CH2); 1.18 (t, J ¼ 7.6, Me). 13C-NMR (75 MHz, CDCl3): 160.8 (C); 135.6 (C); 129.2
(CH); 128.7 (CH); 128.5 (CH); 127.8 (CH); 126.5 (CH); 19.8 (CH2); 10.9 (Me). HR-ESI-MS: 172.0726
([M þ Na]þ, C9H11NNaOþ; calc. 172.0733).
2,3-Dihydro-4H-1-benzopyran-4-one Oxime (3f) [26c]: According to GP1 with 1f (83 mg,
0.50 mmol, 1.0 equiv.) and TEMPO (172 mg, 1.10 mmol, 2.2 equiv.) for 0.5 h at 808. FC (petroleum
ether/AcOEt 20 :1) afforded 3f (62 mg, 76%). Colorless solid.
According to GP2, with 1f (83 mg, 0.50 mmol, 1 equiv.) and TEMPO (3.9 mg, 25 mmol, 5 mol-%) in
the presence of O2 for 24 h at r.t. FC (pentane/AcOEt 20 :1) afforded 3f (76 mg, 94%). Colorless solid.
The control experiment under identical conditions without addition of nitroxide catalyst yielded 9%
(7 mg, 43 mmol) of 3f, beside 77% of recovered 1f. 3f: 1H-NMR (300 MHz, CDCl3): 8.01 (br. s, OH); 7.83
(dd, J ¼ 7.9, 1.7, CHaromCO); 7.31 – 7.22 (m, CHCCN); 7.03 – 6.84 (m, 2 arom. H); 4.25 (t, J ¼ 6.2, CH2O);
2.99 (t, J ¼ 6.2, CH2CN). 13C-NMR (75 MHz, CDCl3): 156.8 (C); 150.0 (C); 131.3 (CH); 124.0 (CH);
121.5 (CH); 118.2 (C); 117.9 (CH); 65.0 (CH2); 23.6 (CH2). HR-ESI-MS: 186.0527 ([M þ Na]þ,
C9H9NNaOþ2 ; calc. 186.0525).
Cyclopentanone Oxime (3g) [26d]. According to GP1, with 1g (51 mg, 0.50 mmol, 1.0 equiv.) and
TEMPO (172 mg, 1.10 mmol, 2.2 equiv.) for 1 h at 808. FC (pentane/AcOEt 10 :1) afforded 3g (49 mg,
99%). Colorless solid. 1H-NMR (300 MHz, CDCl3): 7.92 (br. s, OH); 2.52 – 2.29 (m, 4 H, CH2CN); 1.84 –
1.66 (m, 2 CH2). 13C-NMR (75 MHz, CDCl3): 167.4 (C); 30.9 (CH2); 27.1 (CH2); 25.0 (CH2); 24.6 (CH2).
HR-ESI-MS: 122.0566 ([M þ Na]þ, C5H9NNaOþ; calc. 122.0576).
Hexanal O-(Phenylmethyl)oxime (3h): According to GP1, with 1h (104 mg, 507 mmol, 1.0 equiv.)
and TEMPO (172 mg, 1.10 mmol, 2.2 equiv.) for 12 h at 808. FC (pentane/AcOEt 100 :1) afforded 3h
(97 mg, 94%; ca. 2 :3 (E)/(Z)-mixture). Colorless oil.
According to GP2, with 1h (207 mg, 1.00 mmol, 1 equiv.) and TEMPO (7.8 mg, 50 mmol, 5 mol-%) in
the presence of O2 for 24 h at 808. FC (petroleum ether/AcOEt 100 :1) afforded 3h (189 mg, 92%; ca. 2 :3
(E)/(Z)-mixture). Colorless oil. In the control experiment under identical conditions without addition of
nitroxide catalyst, 99% of 1h was recovered. 3h: IR (neat): 3065w, 3033m, 2957s (br.), 2929s (br.), 2861s
(br.), 2360w, 2335w, 1497m, 1455m, 1367m, 1309w, 1209w, 1055s, 1014s, 916m, 879m, 837w, 736m, 697s.
1H-NMR (300 MHz, CDCl3; both stereoisomers): 7.45 (t, J ¼ 6.2, CH, major isomer); 7.40 – 7.26 (m, 10
arom. H); 6.68 (t, J ¼ 5.5, CH, minor isomer); 5.11 (s, CH2O, minor isomer); 5.06 (s, CH2O, major
isomer); 2.43 – 2.32 (m, CH2CH, minor isomer); 2.25 – 2.13 (m, CH2CH, major isomer); 1.54 – 1.41 (m,
4 H, CH2); 1.39 – 1.22 (m, 8 H, CH2); 0.97 – 0.82 (m, 6 H, Me). 13C-NMR (75 MHz, CDCl3; both
stereoisomers): 152.6 (CH); 151.7 (CH); 138.2 (C); 137.8 (C); 128.3 (2 CH); 128.2 (2 CH); 127.9 (2 CH);
127.8 (2 CH); 127.7 (2 CH); 75.7 (CH2); 75.5 (CH2); 31.5 (CH2); 31.3 (CH2); 29.5 (CH2); 26.4 (CH2); 25.9
(CH2); 25.8 (CH2); 22.3 (2 CH2); 13.9 (2 Me). HR-ESI-MS: 228.1359 ([M þ Na]þ, C13H19NNaOþ; calc.
228.1359).
Benzaldehyde O-Methyloxime (3i) [11]: According to GP1, with 1i (69 mg, 0.50 mmol, 1.0 equiv.)
and 4-OH-TEMPO (189 mg, 1.10 mmol, 2.2 equiv.) or 4-AcNH-TEMPO (234 mg, 1.10 mmol, 2.2 equiv.)
for 12 h at 808. FC (pentane/AcOEt 10 :1) afforded 3i (with 4-OH-TEMPO: 58 mg, 85%; with 4-AcNH-
TEMPO: 60 mg, 86%). Yellow oil.

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According to GP2, with 1i (69 mg, 0.50 mmol, 1 equiv.) and TEMPO (3.9 mg, 26 mmol, 5 mol-%) or
4-AcNH-TEMPO (4.9 mg, 23 mmol, 5 mol-%) in the presence of O2 for 24 h at 808. FC (pentane/AcOEt
20 :1) afforded 3i (with TEMPO: 61 mg, 90%; with 4-AcNH-TEMPO: 59 mg, 88%). Yellow oil. In the
control experiment under identical conditions without addition of nitroxide catalyst, 99% of 1i was
1
recovered. 3i: H-NMR (300 MHz, CDCl3): 8.06 (s, CHN); 7.62 – 7.54 (m, 2 arom. H); 7.40 – 7.38 (m, 3
arom. H); 3.98 (s, Me). 13C-NMR (75 MHz, CDCl3): 148.6 (C); 132.1 (CH); 129.8 (CH); 128.7 (2 CH);
127.0 (2 CH); 62.0 (Me). HR-ESI-MS: 136.0765 ([M þ H]þ, C8H10NOþ; calc. 136.0757).
Benzaldehyde O-(Phenylmethyl)oxime (3j) [22]: According to GP1, with 1j (107 mg, 501 mmol,
1.0 equiv.) and 4-OH-TEMPO (189 mg, 1.10 mmol, 2.2 equiv.) or 4-AcNH-TEMPO (234 mg, 1.10 mmol,
2.2 equiv.) for 12 h at 808. FC (pentane/AcOEt 20 :1) afforded 3j (with 4-OH-TEMPO: 97 mg, 92%; with
4-AcNH-TEMPO: 104 mg, 99%). Colorless oil.
According to GP2, with 1j (107 mg, 501 mmol, 1 equiv.) and TEMPO (3.9 mg, 26 mmol, 5 mol-%) or
4-AcNH-TEMPO (4.9 mg, 25 mmol, 5 mol-%) in the presence of O2 for 24 h at 808. FC (pentane/AcOEt
20 :1) afforded 3j (with TEMPO: 103 mg, 98%; with 4-AcNH-TEMPO: 99 mg, 94%). Colorless oil. In
the control experiment under identical conditions without addition of nitroxide catalyst, 99% of 1j was
recovered.
According to GP3, with benzyl bromide (120 ml, 1.00 mmol, 1 equiv.). FC (pentane/tBuOMe 100 :1)
1
afforded 3j (167 mg, 79%). Colorless oil. H-NMR (300 MHz, CDCl3): 8.15 (s, CHN); 7.64 – 7.52 (m, 2
arom. H); 7.48 – 7.28 (m, 8 arom. H); 5.22 (s, CH2). 13C-NMR (75 MHz, CDCl3): 149.0 (CH); 137.6 (C);
132.3 (C); 129.8 (2 CH); 128.7 (2 CH); 128.4 (2 CH); 128.0 (2 CH); 127.1 (2 CH); 76.4 (CH2). HR-ESI-
MS: 234.0887 ([M þ Na]þ, C14H13NNaOþ; calc. 234.0889).
Cyclopentanone O-(Phenylmethyl)oxime (3k) [26e]: According to GP1, with 1k (96 mg, 0.50 mmol,
1.0 equiv.) and TEMPO (172 mg, 1.10 mmol, 2.2 equiv.) for 12 h at 808. FC (pentane/AcOEt 100 :1)
afforded 3k (89 mg, 94%). Colorless oil.
According to GP2, with 1k (191 mg, 1.00 mmol, 1 equiv.) and TEMPO (7.8 mg, 50 mmol, 5 mol-%) in
the presence of O2 for 24 h at 808. FC (pentane/AcOEt 100 :1) afforded 3k (172 mg, 91%). Colorless oil.
In the control experiment under identical conditions without addition of nitroxide catalyst, 99% of 1k
1
was recovered. 3k: H-NMR (300 MHz, CDCl3): 7.40 – 7.27 (m, 5 arom. H); 5.09 (s, CH2O); 2.52 – 2.32
(m, 2 CH2); 1.81 – 1.67 (m, 2 CH2). 13C-NMR (75 MHz, CDCl3): 167.1 (C); 138.4 (C); 128.3 (2 CH); 127.9
(2 CH); 127.6 (CH); 75.5 (CH2); 31.0 (CH2); 30.0 (CH2); 25.2 (CH2); 24.7 (CH2). HR-ESI-MS: 212.1052
([M þ Na]þ, C12H15NONaþ; calc. 212.1046).
1-Phenylpropan-1-one O-(Phenylmethyl)oxime (3l) [26f]: According to GP1, with 1l (121 mg,
501 mmol, 1.0 equiv.) and TEMPO (172 mg, 1.10 mmol, 2.2 equiv.) for 12 h at 808. FC (pentane/AcOEt
20 :1) afforded 3l (114 mg, 481 mmol, 96%). Colorless oil.
According to GP2, with 1l (121 mg, 501 mmol, 1 equiv.) and TEMPO (7.8 mg, 50 mmol, 10 mol-%) in
the presence of O2 for 48 h at 808. FC (pentane/AcOEt 50 :1) afforded 3l (102 mg, 85%). Colorless oil. In
the control experiment under identical conditions without addition of nitroxide catalyst, 99% of 1l was
recovered. 3l: 1H-NMR (300 MHz, CDCl3): 7.69 – 7.58 (m, 2 arom. H); 7.46 – 7.27 (m, 8 arom. H); 5.24 (s,
CH2O); 2.80 (q, J ¼ 7.6, CH2CN); 1.15 (t, J ¼ 7.6, Me). 13C-NMR (75 MHz, CDCl3): 160.0 (C); 138.3 (C);
135.7 (C); 129.0 (2 CH); 128.4 (2 CH); 128.3 (CH); 128.1 (2 CH); 127.7 (CH); 126.3 (2 CH); 76.2 (CH2);
20.3 (CH2); 11.1 (Me). HR-ESI-MS: 262.1197 ([M þ Na]þ, C16H17NNaOþ; calc. 262.1202).
4-(1,1-Dimethylethyl)benzaldehyde O-(Phenylmethyl)oxime (3m): According to GP3, with 4-tert-
butylbenzyl bromide (184 ml, 1.00 mmol, 1 equiv.). FC (pentane/tBuOMe 100 :1) afforded 3m (254 mg,
84%). Colorless solid. M.p. 278. IR (neat): 3069w, 3032w, 2969m (br.), 2904m, 2868m, 1611m, 1496m,
1454m, 1395w, 1364m, 1340m, 1269m, 1219m, 1107m, 1082m, 1038s, 1014s, 985s, 936s, 914s, 860m, 830s,
733s, 695s, 642m, 615m. 1H-NMR (300 MHz, CDCl3): 8.17 (s, CHN); 7.61 – 7.43 (m, 2 arom. H); 7.42 – 7.31
(m, 7 arom. H); 5.25 (s, CH2O); 1.36 (s, 3 Me). 13C-NMR (75 MHz, CDCl3): 152.0 (CH); 147.8 (C); 136.6
(C); 128.4 (C); 127.3 (2 CH); 127.2 (2 CH); 126.8 (CH); 125.8 (2 CH); 124.5 (2 CH); 75.2 (CH2); 33.7
(C); 30.1 (3 Me). HR-ESI-MS: 290.1511 ([M þ Na]þ, C18H21NNaOþ; calc. 290.1515). Anal. calc. for
C18H21NO: C 80.86, H 7.92, N 5.24, found: C 80.89, H 8.03, N 5.51.
4-Methylbenzaldehyde O-(Phenylmethyl)oxime (3n): According to GP3, with 4-methylbenzyl
bromide (185 mg, 1.00 mmol, 1 equiv.). FC (pentane/tBuOMe 100 :1) afforded 3n (142 mg, 63%).
Colorless oil. IR (neat): 3067w, 3031w, 2922m (br.), 2871w (br.), 1612m (br.), 1513m, 1497m, 1454m,

Helvetica Chimica Acta – Vol. 95 (2012)
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1366m, 1341w, 1311w, 1249w, 1210m, 1178w, 1109w, 1082w, 1038s, 1017s, 958m, 938s, 914m, 856m, 814s,
776m, 734m, 697s, 623m. 1H-NMR (300 MHz, CDCl3): 8.13 (s, CHN); 7.55 – 7.29 (m, 7 arom. H); 7.23 –
7.14 (m, 2 arom. H); 5.22 (s, CH2O); 2.37 (s, Me). 13C-NMR (75 MHz, CDCl3): 149.1 (CH); 140.0 (C);
137.7 (C); 129.5 (2 CH); 129.4 (2 CH); 128.4 (C); 128.4 (CH); 127.9 (2 CH); 127.1 (2 CH); 76.3 (CH2);
21.4 (Me). HR-ESI-MS: 248.1046 ([M þ Na]þ, C15H15NNaOþ; calc. 248.1046).
4-Methoxybenzaldehyde O-(Phenylmethyl)oxime (3o) [26g]: According to GP3, with 4-methoxy-
benzyl bromide (201 mg, 1.00 mmol, 1 equiv.). FC (pentane/tBuOMe 100 :1) afforded 3o (138 mg, 57%).
1
Colorless oil. H-NMR (300 MHz, CDCl3): 8.10 (s, CHN); 7.55 – 7.50 (m, 2 arom. H); 7.45 – 7.29 (m, 5
arom. H); 6.92 – 6.87 (m, 2 arom. H); 5.19 (s, CH2); 3.83 (s, Me). 13C-NMR (75 MHz, CDCl3): 161.0
(CH); 148.7 (C); 137.7 (C); 133.0 (2 CH); 128.6 (2 CH); 128.5 (2 CH); 128.4 (CH); 124.9 (C); 114.2
(2 CH); 76.2 (CH2); 55.3 (Me). HR-ESI-MS: 264.0991 ([M þ Na]þ, C15H15NNaO2þ ; calc. 264.0995).
4-Bromobenzaldehyde O-(Phenylmethyl)oxime (3p): According to GP3, with 4-bromobenzyl
bromide (249 mg, 1.00 mmol, 1 equiv.). FC (pentane/tBuOMe 100 :1) afforded 3p (172 mg, 601 mmol,
60%). Colorless solid. M.p. 588. IR (neat): 3064w, 3032w, 2930w (br.), 2875w (br.), 1606w, 1590m, 1487s,
1454m, 1398m, 1366w, 1342w, 1301w, 1210m, 1070m, 1036m, 1009s, 986m, 948s, 918m, 849m, 819s, 734m,
1
698s, 632w, 609m. H-NMR (300 MHz, CDCl3): 8.08 (s, CH); 7.58 – 7.29 (m, 9 arom. H); 5.22 (s, CH2).
13C-NMR (75 MHz, CDCl3): 147.9 (CH); 137.4 (C); 131.9 (2 CH); 131.2 (C); 128.5 (2 CH); 128.5 (2 CH);
128.4 (2 CH); 128.1 (CH); 124.0 (CH); 76.6 (CH2). HR-ESI-MS: 290.0177 ([M þ H]þ, C14H13BrNOþ;
calc. 290.0175).
3-Methylbenzaldehyde O-(Phenylmethyl)oxime (3q): According to GP3, with 3-methylbenzyl
bromide (137 ml, 1.00 mmol, 1 equiv.). FC (pentane/tBuOMe 100 :1) afforded 3q (205 mg, 91%).
Colorless oil. IR (neat): 3063w, 3032w, 2921w, 2870w, 1950w, 1880w, 1605w, 1580w, 1496w, 1454m, 1366m,
1339m, 1249m, 1249w, 1209w, 1159m, 1082m, 1038m, 1025m, 985m, 945s, 913m, 782s, 733s, 692s, 650m,
1
606m. H-NMR (300 MHz, CDCl3): 8.13 (s, CHN); 7.51 – 7.14 (m, 9 arom. H); 5.23 (s, CH2O); 2.37 (s,
Me). 13C-NMR (75 MHz, CDCl3): 149.3 (CH); 138.4 (C); 137.6 (C); 132.2 (C); 130.7 (2 CH); 128.6
(2 CH); 128.4 (CH); 128.4 (CH); 127.9 (CH); 127.5 (CH); 124.5 (CH); 76.4 (CH2); 21.3 (Me). HR-ESI-
MS: 226.1227 ([M þ H]þ, C15H16NOþ; calc. 226.1226).
3-Nitrobenzaldehyde O-(Phenylmethyl)oxime (3r): According to GP3, with 3-nitrobenzyl bromide
(216 mg, 1.00 mmol, 1 equiv.). FC (pentane/tBuOMe 100 :1) afforded 3r (200 mg, 78%). Colorless solid.
M.p. 368. IR (neat): 3092w, 3033w, 2928w (br.), 2875w (br.), 1737w, 1611w, 1528s, 1454m, 1352s, 1212m,
1
1081m, 1018m, 950m, 920m, 829w, 807w, 735s, 697m, 677m, 642w. H-NMR (300 MHz, CDCl3): 8.46 –
8.40 (m, CCHCNO2); 8.26 – 8.15 (m, 1 arom. H); 8.18 (s, CH); 7.92 – 7.87 (m, 1 arom. H); 7.54 (t, J ¼
8.0, CHCHCNO2); 7.47 – 7.30 (m, 5 arom. H); 5.26 (s, CH2). 13C-NMR (75 MHz, CDCl3): 148.6 (CH);
146.6 (C); 137.0 (C); 134.2 (C); 132.5 (CH); 129.7 (CH); 128.5 (2 CH); 128.5 (2 CH); 128.2 (CH); 124.2
(CH); 121.8 (CH); 77.0 (CH2). HR-ESI-MS: 279.0745 ([M þ Na]þ, C14H12N2NaO3þ ; calc. 279.0740).
3-Iodobenzaldehyde O-(Phenylmethyl)oxime (3s): According to GP3, with 3-iodobenzyl bromide
(297 mg, 1.00 mmol, 1 equiv.). FC (pentane/tBuOMe 100 :1) afforded 3s (248 mg, 74%). Colorless oil. IR
(neat): 4050w, 3061w, 3031w, 2926w (br.), 2875w, 1875w, 1588w, 1556m, 1496w, 1467w, 1454m, 1418w,
1366w, 1336w, 1249w, 1206m, 1016s, 994s, 941s, 941s, 918s, 872m, 782m, 733m, 684s, 641w, 609m. 1H-NMR
(300 MHz, CDCl3): 8.03 (s, CH); 7.96 (m, CCHCI); 7.72 – 7.66 (m, 1 arom. H); 7.54 – 7.49 (m, 1 arom. H);
7.45 – 7.29 (m, 5 arom. H); 7.10 (t, J ¼ 7.8, CHCHCI); 5.22 (s, CH2). 13C-NMR (75 MHz, CDCl3): 147.4
(CH); 138.6 (CH); 137.3 (C); 135.6 (CH); 134.4 (C); 130.3 (CH); 128.5 (2 CH); 128.4 (2 CH); 128.1
(CH); 126.4 (CH); 94.5 (C); 76.7 (CH2). HR-ESI-MS: 338.0039 ([M þ H]þ, C14H13INOþ; calc.
338.0036).
2-Methylbenzaldehyde O-(Phenylmethyl)oxime (3t): According to GP3, with 2-methylbenzyl
bromide (134 ml, 1.00 mmol, 1 equiv.). FC (pentane/tBuOMe 100 :1) afforded 3t (92 mg, 82%). Colorless
oil. IR (neat): 3067s, 3031s, 2924s, 2871s, 2362s, 2336s, 1610s, 1496s, 1454m, 1366m, 1292s, 1226s, 1209s,
1082s, 1016s, 984s, 936s, 915s, 858m, 783m, 752s, 696s, 640m, 612m. 1H-NMR (300 MHz, CDCl3): 8.32 (s,
CHN); 7.65 – 7.57 (m, 1 arom. H); 7.38 – 7.04 (m, 8 arom. H); 5.14 (s, CH2); 2.31 (s, Me). 13C-NMR
(75 MHz, CDCl3): 148.1 (CH); 137.6 (C); 136.8 (C); 130.8 (2 CH); 130.5 (C); 129.6 (2 CH); 128.5 (CH);
128.5 (CH); 128.0 (CH); 127.0 (CH); 126.1 (CH); 76.4 (CH2); 19.9 (Me). HR-ESI-MS: 248.1037 ([M þ
Na]þ, C15H15NNaOþ; calc. 248.1046).

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Helvetica Chimica Acta – Vol. 95 (2012)
2,4-Dimethylbenzaldehyde O-(Phenylmethyl)oxime (3u): According to GP3, with 2,4-dimethylben-
zyl bromide (199 mg, 1.00 mmol, 1 equiv.). FC (pentane/tBuOMe 100 :1) afforded 3u (202 mg, 84%).
Colorless oil. IR (neat): 3031w, 2921m, 2869w, 1616m, 1497m, 1454m, 1366m, 1342w, 1248w, 1209w,
1082w, 1035s, 1017s, 984s, 941s, 818s, 734m, 697s, 626m. 1H-NMR (300 MHz, CDCl3): 8.40 (s, CHN); 7.61
(d, J ¼ 7.7, 1 arom. H); 7.52 – 7.28 (m, 5 arom. H); 7.08 – 6.97 (m, 2 arom. H); 5.23 (s, CH2); 2.38 (s, 1 Me);
2.33 (s, 1 Me). 13C-NMR (75 MHz, CDCl3): 148.1 (CH); 139.7 (C); 137.7 (C); 136.7 (C); 131.6 (C); 128.5
(2 CH); 128.5 (CH); 127.9 (CH); 127.6 (CH); 127.0 (CH); 126.9 (2 CH); 76.3 (CH2); 21.3 (Me); 19.8
(Me). HR-ESI-MS: 262.1198 ([M þ Na]þ, C16H17NNaOþ; calc. 262.1202).
2-Bromobenzaldehyde O-(Phenylmethyl)oxime (3v) [26h]: According to GP3, with 2-bromobenzyl
bromide (249 mg, 1.00 mmol, 1 equiv.). FC (pentane/tBuOMe 100 :1) afforded 3v (206 mg, 73%).
1
Colorless oil. H-NMR (300 MHz, CDCl3): 8.54 (s, CHN); 7.91 – 7.85 (m, 1 arom. H); 7.58 – 7.53 (m, 1
arom. H); 7.47 – 7.17 (m, 7 arom. H); 5.24 (s, CH2). 13C-NMR (75 MHz, CDCl3): 148.4 (CH); 137.3 (C);
133.1 (C); 131.6 (CH); 131.0 (CH); 128.5 (CH); 128.4 (2 CH); 128.1 (CH); 127.6 (2 CH); 127.5 (CH);
123.9 (C); 76.7 (CH2). HR-ESI-MS: 312.0005 ([M þ Na]þ, C14H12BrNNaOþ; calc. 311.9994).
3-Phenylprop-2-enal O-(Phenylmethyl)oxime (3w) [26i]: According to GP3, with cinnamyl bromide
(197 mg, 1.00 mmol, 1 equiv.). FC (pentane/tBuOMe 100 :1) afforded 3w (114 mg, 48%; ca. 2.5 :1 (E)/
1
(Z)-mixture). Colorless solid. H-NMR (300 MHz, CDCl3; both stereoisomers): 7.95 (dd, J ¼ 8.0, 1.1,
CHN, (E)-isomer); 7.52 – 7.28 (m, CHN, (Z)-isomer, and 20 arom. H); 6.91 – 6.74 (m, 4 H, CHCH); 5.22
(s, CH2, (Z)-isomer); 5.17 (s, CH2, (E)-isomer). 13C-NMR (75 MHz, CDCl3; both stereoisomers): 151.1
(CH); 148.5 (CH); 140.1 (C); 138.6 (C); 137.9 (C); 137.5 (C); 136.1 (CH); 135.9 (CH); 129.3 (2 CH);
128.8 (2 CH); 128.5 (2 CH); 128.3 (2 CH); 128.1 (2 CH); 128.0 (2 CH); 127.9 (4 CH); 127.5 (2 CH); 126.9
(2 CH); 122.0 (CH); 116.5 (CH); 76.3 (CH2); 76.3 (CH2). HR-ESI-MS: 260.1042d ([M þ Na]þ,
C16H15NNaOþ; calc. 260.1046).
1-Phenylethanone O-(Phenylmethyl)oxime (3x) [26j]: According to GP3, with (1-bromoethyl)ben-
zene (137 ml, 1.00 mmol, 1 equiv.). FC (pentane/tBuOMe 100 :1) afforded 3x (99 mg, 44%). Colorless oil.
1H-NMR (300 MHz, CDCl3): 7.69 – 7.64 (m, 2 arom. H); 7.47 – 7.30 (m, 8 arom. H); 5.27 (s, CH2); 2.28 (s,
Me). 13C-NMR (75 MHz, CDCl3): 155.0 (C); 138.1 (C); 136.7 (C); 129.0 (CH); 128.4 (CH); 128.1
(2 CH); 128.0 (2 CH); 127.8 (2 CH); 126.1 (2 CH); 76.2 (CH2); 12.9 (Me). HR-ESI-MS: 248.1040 ([M þ
Na]þ, C15H15NNaOþ; calc. 248.1046).
Methyl 2-[(Benzyloxy)imino]-2-phenylacetate (¼ Methyl a-[(Phenylmethoxy)imino]benzeneace-
tate; 3y): According to GP3, with methyl a-bromophenylacetate (158 ml, 1.00 mmol, 1 equiv.) in MeOH
(4 ml). FC (pentane/tBuOMe 20 :1) afforded 3y (226 mg, 84%). Colorless oil. IR (neat): 3065w, 3032w,
2953w, 1739s, 1604w, 1497m, 1454m, 1446m, 1434m, 1366m, 1333m, 1311m, 1220s, 1183m, 1038w, 1057m,
1006s, 999s, 951m, 919m, 878m, 840m, 769m, 751m, 734m, 689s, 654m. 1H-NMR (300 MHz, CDCl3):
7.63 – 7.52 (m, 2 arom. H); 7.45 – 7.29 (m, 8 arom. H); 5.29 (s, CH2); 3.95 (s, Me). 13C-NMR (75 MHz,
CDCl3): 164.0 (C); 151.0 (C); 137.3 (C); 130.3 (CH); 130.1 (C); 128.7 (2 CH); 128.3 (2 CH); 127.8 (CH);
127.8 (2 CH); 126.3 (2 CH); 77.0 (CH2); 52.3 (Me). HR-ESI-MS: 292.0946 ([M þ Na]þ, C16H15NNaO3þ ;
calc. 292.0944).
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Received April 5, 2012