Syntheses based on α-azidooximes: I. Reduction of α-azidooximes

Article abstract of DOI:10.1134/S1070428007080027

Convenient procedures were developed for selective and exhaustive reduction of α-azido-oximes that were easily prepared from aliphatic nitro compounds. Nitroalkanes were shown to be convenient precursors of β-functionalized amines (1,2-diamines, iminophos

Full text of DOI:10.1134/S1070428007080027

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 8, pp. 1106−1113. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © A.Yu. Sukhorukov, A.N. Semakin, A.V. Lesiv, Yu.A. Khomutova, S.L. Ioffe, 2007, published in Zhurnal Organicheskoi Khimii,
2007, Vol. 43, No. 8, pp. 1118−1124.
Dedicated to the Full Member of the Russian Academy of Sciences
V.A.Tartakovsky on occasion of his 75th birthday
Syntheses Based on α-Azidooximes: I. Reduction
of α-Azidooximes
A. Yu. Sukhorukov, A. N. Semakin, A. V. Lesiv, Yu. A. Khomutova, and S. L. Ioffe
Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, 119991 Russia
e-mail: iof@ioc.ac.ru
Received May 30 2007
Abstract—Convenient procedures were developed for selective and exhaustive reduction of α-azido-oximes
that were easily prepared from aliphatic nitro compounds. Nitroalkanes were shown to be convenient precursors
of β-functionalized amines (1,2-diamines, iminophosphonates, β azidohydroxyl-amines, α-aminooximes).
DOI: 10.1134/S1070428007080027
The silylation of aliphatic nitro compounds
significantly extends the opportunities of their application
to organic synthesis [1]. In particular, this strategy
provides a possibility to regard nitroalkanes as fairly
convenient precursors of various α-functionalized oxime.
Among several procedures developed for preparation of
these products the synthesis of poorly known α-azido-
oximes I is distinguished by efficiency, universatility,
and simplicity [2] (Scheme 1). In this event α-azido-
oximes I become promising reagents for preparation of
versatile polyfunctional compounds.
reducers and approaches, like the hydrogenation on
Raney nickel (Ni/Ra) [3] or on palladium on carbon [4],
lithium aluminum hydride [5], sodium in alcohol [6],
titanium(III) chloride [7], and many other. Interestingly,
the same reducers can be applied to the reduction of azido
group (see, e.g., [8–12]). Analysis of data from [3–12]
shows that oximes apparently easier react with hydride
reducers whereas in contrast azides are better reduced
by the catalytic hydrogenation. In general it may be
concluded that the exhaustive reduction of azido-
oximes I should not be a great problem but the selective
reduc-tion of azido or oximimino fragments is quite non-
trivial.
We report here on various aspects of selective and
exhaustive reduction of oximes I. The reduction of the
oximimino fragment was attempted using versatile
Some examples of exhaustive and selective reduction
of α-azidooximes and their derivatives were described
in [13, 14] but there was not shown a general pattern of
this considerably complex process.
Scheme 1.
NO2
NO(SiMe3)2
R
Using a fairly representative set of azidooximes Ia–
Ii that we had previously prepared from nitroalkanes [2]
we performed a systematic investigation of their reduc-
tion (see the table and Scheme 2).
R
SiMeX, Et3N
R'
R'
The complete reduction of oximes Ia–Ii → IIa–IIi is
advantageously performed by the catalytic hydrogena-
tion on Ni/Ra at elevated pressure and high temperature
in the presence of di-tert-butyl dicarbonate (Βoc2O)
necessary for protection of the arising amino groups
(Scheme 2, a). Special experiments carried out with
azidooxime Ic showed that the use of Pd/C instead of
N3
(1) SiMe3N3, Et3N
(2) MeOH
NOH
R'
R
I
X = Cl, Br, OTf.
1106

SYNTHESES BASED ON α-AZIDOOXIMES: I.
1107
Scheme 2.
Ni/Ra resulted in formation of complex reaction
mixtures. The lack of amino groups protection led to
a sharp decrease in the yield of target diamines II
apparently due to their decomposition on the catalyst.
The reaction performed under milder conditions resulted
in incomplete hydrogenation of initial oximes I.
NOH
R
_
N
+
Ph3P
R'
_
IVа IVi
d
e
Evidently first the azido group is reduced as has been
specially demonstrated by an example of azidooxime Ic:
Under milder conditions (Scheme 2, b) the prevailing
reaction product is the corresponding aminooxime IIIc.
N3
NHBoc
NOH
NOH
b
R'
R'
R'
The catalytic hydrogenation seems more preferable
than the application of chemical reducers (e.g., LiAlH4)
for the latter are capable of reducing also functional
groups (for instance, ester group) present in the initial
substrates.
R
R
_
_
Iа Ii
IIIа IIIi
c
е
a
NHBoc
N3
NHBoc
NHOH
g
The hydrogenation of substarate Ig shows that this
R'
reaction is characterized by low diastereoselectivity.
R
R
_
_
In order to perform the selective reduction of azido
group in azidooximes I we used the ability of the group
to form ylides with triphenylphosphine (I → IV,
Scheme 2, d). A mild hydrolysis of iminophosphonates
IV in most cases led to the formation of the aminooximes
III (Scheme 2, e). The reduction of alkylazides in this
manner was known [13, 16]. As a rule this reaction sequ-
ence was performed without isolation of the intermediate
iminophosphonates. However the isolation of ylides IV
increased the yield and simplified the purification of
target aminooximes III.*
Vа Vi
IIа IIi
R = R' = H (a); R = H, R' = Me (b); R' = H, R = Me, (c),
Ph (d), Bn (e), COOEt (f), R = COOMe, R' = Me (g);
R = H, R' = CH2OH (h), R = H, R' = (CH2)2COOMe (i).
(a) H2, Ni/Ra, 70 at H2, 80°C, Boc2O; (b) H2, Ni/Ra, 1 at
H2, 20°C, Boc2O; (c) H2, Ni/Ra, 50 at H2, 70°C, Boc2O;
(d) PPh3, Et2O, 20°C; (e) THF, H2O, then Boc2O; (f)
NaBH3CN/AcOH (or HCl); (g) H2, Ni/Ra, 10 at H2, 20°C,
Boc2O.
Yields of products of azidooximes Ia–Ii transformation
The sequence I → IV → III is of a general character
and makes it possible to obtain quite different amino-
oximes III in moderate yields. Only azidooximes If and
Ig containing an ester group in the α-position with respect
to oximino fragment form an exception.
Yield, %
Azidooxime
II (a)
58
III (e)
57
IV (d)
87
V (f)a
–b (40)
30 (56)
65 (58)
Ia
Ib
Ic
50
64
72
46
90
71
Basically, aminoximes III can be used for catalytic
hydrogenation providing diamines II (Scheme 2, c) but
the one-stage hydrogenation of azidooximes I (proce-
dure a) appears more preferable.
75
65
42
85e
65
61
65
60
–
92
45
58 (79)
85 (65)
–d (– d)
21 (–d)
–b (–b)
Id
Ie
If
a
–
c
We already mentioned that hydride reducers reduced
the azido group slower than the C=N bond of the oximino
fragment. Therefore the use of weaker hydride reducer
and application of acid catalysis may result in a selective
reduction of the oximino fragment in azidooximes I.
Actually, with NaBH3CN a selective reduction of the C=N
bond became possible for the most of tested azidooximes
–
68 e
Ig
Ih
Ii
97
88
59g
79d
48 (38)
a The yield at the use of HCl instead ofAcOH is given in parentheses.
b Unidentified products.
c Only products of tarring.
d No reaction occurred.
e Diastereomers mixture, 1.2 : 1.
f
* Iminophosphonates can be used in the synthesis of Schiff’s bases
[17], pyrroles [18], and other compounds.
Unstable ylides.
g Compound IIIi has a structure
O
NOH.
.
HN
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 8 2007

SUKHORUKOV et al.
1108
I (see the table, Scheme 2, f).* Acetic and hydrochloric
acids are employed as activating acids since they
transform the oximino group into a more active iminium
cation A (Scheme 3).
Scheme 3.
OH
R
H
OH
R
H
OH
R
+
N
N
N
H+
NaBH3CN
As a result we obtained and characterized previously
unknown β-azidosubstituted hydroxylamines V.
A strong electronegative substituent, for instance, R =
CO2Alk (If and Ig) in the α-position to the oximino
fragment decreased the nucleophilicity of the nitrogen
in the oximino moiety thus hampering the formation of
the corresponding activated cations A. Therefore no good
results were obtained in reaction of NaBH3CN with
azidooximes If and Ig.
A
EXPERIMENTAL
NMR spectra were registered on a spectrometer
Bruker AM-300. Chemical shifts (1H and 13C) are
reported in the δ scale and are measured from the solvent
signals used as internal reference [22]. IR spectra were
recorded on a spectrophotometer Bruker Vector-22.
Elemental analyses were carried out in the microanalysis
laboratory of the Institute of Organic Chemistry and in
the analytical center of the Moscow Chemical Lycee.
Melting points were measured on a Koeffler heating block
and were reported without correction. TLC was
performed on plates purchased from Merck (silica gel
with QF-254 indicator). Spots were visualized under UV
irradiation and/or using ninhydrine solution in ethanol.
The preparative liquid chromatography was done on
columns packed with silica gel Merck Kieselgel 60A 230-
400 mesh.
Both acetic and hydrochloric acids can provoke side
processes. The former can acylate the arising
hydroxylamines to hydroxamic acids that are involved
into further reduction (see, e.g., [20]), the latter causes
a hydrolysis of the oximino fragment. Therefore the
yields of the target hydroxylamines V were not necessari-
ly high and depended on the structure of azidooximes I
subjected to reduction.
We demonstrated by an example of hydroxylamine
Vc that azidohydroxylamines can be hydrogenated to
yield the corresponding Βoc-protected diamines II
(Scheme 2, g). Although the conditions of the process
are milder than those of the direct exhaustive hydro-
genation of azidooximes I, the one-stage reaction I →
II is still as a rule preferable.
Initial α-azidooximes I were prepared by published
procedures [2]. The catalytic hydrogenation was carried
out in a steel pressure reactor (Pike instrument) equipped
with a magnetic stirrer.
The composition and structure of compounds II–IV
were confirmed by elemental analysis and NMR spec-
troscopy. The configuration of substituted oximes III
and IV was derived from the data of 1H and 13C NMR
spectra applying the rules described before (see, e.g.,
[21]). Azidohydroxylamines V could be isolated by
column chromatography without impurities (according
to NMR data). However we failed to obtain plausible
results of elemental analysis due to the instability of these
compounds. The structure of azidohydroxylamines was
Hydrogenation of α-azidooximes I into diamines
II. a. Raney nickel (about 0.05 g in methanol) was added
to a solution of an appropriate α-azidooxime I (1 mmol)
and 0.55 g (2.5 mmol) of Boc2O in 2.5 ml of methanol.
The mixture was hydrogenated at 80°C and 70 at of H2
for 3 h, then the catalyst was filtered off and the solvent
was distilled off in a vacuum. The reaction product was
subjected to column chromatograpy on silica gel (eluent
hexane–AcOEt, 10:1 → 3:1, for IIh 5:1 → 1:1).
tert-Butyl N-2-[(tert-butoxycarbonyl)amino]-
ethylcarbamate (IIa). mp 120–125°C, Rf 0.54 (hexane–
ethyl acetate, 1:1). 1H NMR spectrum (CDCl3), δ, ppm:
1.45 s (18H, H3C), 3.23 m (4H, H2C), 4.39 br.s (2H, HN).
13C NMR spectrum (CDCl3), δ, ppm: 28.3 (CH3), 41.1
(CH2), 79.4 (CCH3), 156.2 (C=O). All spectral data are
consistent with published results [23].
1
proved by H and 13C NMR spectra and also by their
conversion into substituted diamines II (by an example
of compound Vc). The presence of the azido and
hydroximino groups was additionally confirmed by IR
spectra. Thus we demonstrated that azidooximes prep-
ared in two stages from nitroalkanes were precursors of
β-functionalized amines (1,2-diamines, oximinophos-
phonates, β-azidohydroxylamines, α-aminooximes) and
hydroxylamines.
tert-Butyl N-2-[(tert-butoxycarbonyl)amino]-1-
methylethylcarbamate (IIb). mp 112–115°C (110°C
[15]), Rf 0.57 (hexane–ethyl acetate, 1:1). 1H NMR spec-
trum (CDCl3), δ, ppm: 1.13 d (3H, H3CCH, J 6.6 Hz),
*
NaBH3CN was successfully used for selective reduction of the
C=N bond [19].
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 8 2007

SYNTHESES BASED ON α-AZIDOOXIMES: I.
1109
1.45 s (18H, H3C), 3.11 d.d (1H, H2C, J 7.4, 14.0 Hz),
3.19 d.d (1H, H2C, J 5.5, 14.0 Hz), 3.72 m (1H, HC,
J 6.6 Hz), 4.35 and 4.58 br.s (2H, HN). 13C NMR
spectrum (CDCl3), δ, ppm: 18.5 (H3CCH), 28.3 (CH3),
46.4 (H2C), 47.4 (HC), 79.3 (CCH3), 155.7 and 156.3
(C=O). All spectral data are consitent with published
results [15] .
(H3CCH), 28.1 (H3C), 48.3 and 48.5 (HCCH3), 52.0 and
52.1 (H3CO), 57.6 and 58.0 (HC), 79.4, 79.5, 79.9 and
80.0 (CCH3), 154.9, 155.0 and 155.4 (NC=O), 171.0 and
171.1 (C=O). Found, %: C 54.27; H 9.01; N 8.18.
C15H28N2O6. Calculated, %: C 54.20; H 8.49; N 8.43.
tert-Butyl N-2-[(tert-butoxycarbonyl)amino]-1-
(hydroxymethyl)ethyl]carbamate (IIh). mp 94–99°C,
Rf 0.29 (hexane–ethyl acetate, 1:1). 1H NMR spectrum
(CDCl3), δ, ppm: 1.46 s (18H, H3C), 3.16 br.s (1H, HO),
3.24 d.d (1H, H2CN, J 6.6, 14.7 Hz), 3.34 d.d (1H, H2CN,
J 7.4, 14.7 Hz), 3.50–3.77 m (3H, HC and H2C),
4.89 br.s, 5.02 br.s (2H, HN). 13C NMR spectrum
(CDCl3), δ, ppm: 28.3 (H3C), 40.9 (H2CN), 52.8 (HC),
62.2 (H2C), 79.6 and 80.1 (CCH3), 155.8 and 157.3
(C=O). Found, %: C 53.55; H 9.34; N 9.34. C13H26N2O5.
Calculated, %: C 53.78; H 9.03; N 9.65.
tert-Butyl N-2-[(tert-butoxycarbonyl)amino]-1-
phenylethylcarbamate (IId). mp 132–134°C, Rf 0.70
(hexane–ethyl acetate, 1:1). 1H NMR spectrum (CDCl3),
δ, ppm: 1.41 s, 1.45 s (18H, H3C), 3.42 m (2H, H2C),
4.71 m (1H, HC), 4.84 br.s, 5.43 br.s (2H, HN), 7.22–
7.41 m (5H, Harom). 13C NMR spectrum (CDCl3), δ, ppm:
28.2 (CH3), 45.7 (H2C), 55.9 (HC), 79.4 and 79.6 (CCH3),
126.3, 127.5 and 128.6 (Carom), 140.1 (Ci), 155.7 and
156.7 (C=O). Found, %: C 64.24; H 8.59; N 8.10.
C18H28N2O4. Calculated, %: C 64.24; H 8.39; N 8.33.
Methyl 4,5-bis[(tert-butoxycarbonyl)amino]-
pentanoate (IIi). mp 70–73°C {for (S)-enantiomer 113–
115°C [24]}, Rf 0.52 (hexane–ethyl acetate, 1:1).
1H NMR spectrum (CDCl3), δ, ppm: 1.44 s and 1.45 s
(18H, H3C), 1.67 m (1H, H2CCH2), 1.84 m (1H,
H2CCH2), 2.41 d.d (2H, H2CCH2, J 7.4, 7.6 Hz),
3.16 d.d (1H, H2C, J 6.6, 14.0 Hz), 3.23 d.d (1H, H2C,
J 5.2, 14.0 Hz), 3.63 m (1H, HC), 3.68 C (3H, H3CO),
4.41 br.s, 4.65 br.s (2H, HN). 13C (CDCl3), d, ppm:
27.9 and 30.6 (H2CCH2) 28.3 (H3C), 44.9 (H2C), 51.37
and 51.43 (HC and H3CO), 79.4 (CCH3), 155.9 and 156.3
(NC=O), 173.5 (C=O). All spectral data are consitent
with published results [24].
tert-Butyl N-1-benzyl-2-[(tert-butoxycarbonyl)-
amino]ethylcarbamate (IIe) mp 125–127°C, Rf 0.66
(hexane–ethyl acetate, 1:1). 1H NMR spectrum (CDCl3),
δ, ppm: 1.42 s and 1.45 s (18H, H3C), 2.74 d.d (1H, H2C,
J 7.3, 14.0 Hz), 2.86 d.d (1H, H2C, J 6.6, 14.0 Hz),
3.20 m (2H, H2CN), 3.88 m (1H, HC), 4.73 br.s,
5.30 br.s (2H, HN), 7.15–7.37 m (5H, Harom). 13C NMR
spectrum (CDCl3), δ, ppm: 28.2 (H3C), 39.0 (H2C), 44.0
(H2CN), 52.6 (HC), 79.4 and 79.5 (CCH3), 126.3, 128.3
and 129.1 (Carom), 137.4 (Ci), 156.0 and 156.7 (C=O).
Found, %: C 65.41; H 8.99; N 7.68. C19H30N2O4.
Calculated, %: C 65.12; H 8.63; N 7.68.
Ethyl 2,3-bis[(tert-butoxycarbonyl)amino]-
propionate (IIf). mp 113–114°C, Rf 0.62 (hexane–ethyl
acetate, 1:1). 1H NMR spectrum (CDCl3), δ, ppm: 1.30 t
(3H, H3CCH2, J 7.4 Hz), 1.45 s, 1.46 s (18H, H3C),
3.51 d.d (2H, H2C, J 5.2, 5.9 Hz), 4.22 q (2H, H2CO,
J 7.4 Hz), 4.32 d.t (1H, HC, J 5.9, 7.4 Hz), 4.78 br.s,
5.31 br.s (2H, HN). 13C NMR spectrum (CDCl3), d, ppm:
14.0 (H3C), 28.3 (H3CC), 42.7 (H2C), 54.5 (HC), 61.6
(H2CO), 79.7 and 80.1 (CCH3), 155.3 and 155.9 (NC=O),
170.6 (C=O). Found, %: C 53.98; H 8.18; N 8.20.
C15H28N2O6. Calculated, %: C 54.20; H 8.49; N 8.43.
Preparation of phosphinylides (IV). d. Triphenyl-
phosphine (0.26 g, 1 mmol) was added to a solution of
an appropriate α-azidooxime I (1 mmol) in 3.0 ml of
anhydrous ethyl ether. The mixture was vigorously stirred
for 6 h at room temperature, the separated colorless
precipitate was filtered off and dried in a vacuum. Yields
are given in the table.
2-[(Triphenylphosphoranylidene)amino]-
acetaldoxime (IVa). mp 120–125°C (decomp.). Mixture
of isomers E and Z, 1.4:1. E-isomer. 1H NMR spectrum
(DMSO-d6), δ, ppm: 3.67 d.d (2H, H2C, J 5.8, 19.8 Hz),
7.24 t (1H, HCN, J 5.8 Hz), 7.48–7.72 m (15Harom),
10.22 br.s (1H, HO). 13C NMR spectrum (DMSO-d6), δ,
ppm: 44.0 (H2C), 128.6 d (Cm, J 11.6 Hz), 131.5 (Cp),
131.9 d (Co, J 9.1 Hz), 151.8 d (C=N, J 17.6 Hz). Z-iso-
Methyl 2,3-bis[(tert-butoxycarbonyl)amino]-
butanoate (IIg). Oily substance, Rf 0.62 (hexane–ethyl
1
acetate, 1:1). Diastereomers mixture 1.2:1. H NMR
spectrum (CDCl3), δ, ppm: 1.11 d, 1.18 d (3H, H3CCH,
J 6.6 Hz), 1.42 s, 1.45 s (18H, H3C), 3.74 s (3H, H3CO),
4.12 m (1H, HCCH3), 4.25 d.d 4.43 d.d (1H, HC, J 4.2,
8.3 and J 3.8, 8.3 Hz), 4.65 br.s, 4.85 br.s, 5.29 br.s (2H,
HN). 13C NMR spectrum (CDCl3), δ, ppm: 16.5 and 18.1
1
mer. H NMR spectrum (DMSO-d6), δ, ppm: 3.85 d.d
(2H, H2C, J 3.7, 17.7 Hz), 6.71 t (1H, HCN, J 3.7 Hz),
7.48–7.72 m (15Harom), 10.42 br.s (1H, HO). 13C NMR
spectrum (DMSO-d6), δ, ppm: 40.6 (H2C), 128.6 d (Cm,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 8 2007

SUKHORUKOV et al.
1110
J 11.6 Hz), 131.5 (Cp), 131.9 d (HCo, J 9.1 Hz), 155.3 d
(C=N, J 18.7 Hz). Found, %: C 71.64; H 5.70; N 8.35.
C20H19N2OP. Calculated, %: C 71.84; H 5.73; N 8.38.
4.48 d.q (1H, HC, J 6.6, 19.5 Hz), 7.50–7.75 m (15H,
Harom), 10.1 br.s (1H, HO). 13C NMR spectrum (DMSO-
d6), δ, ppm: 22.6 d (H3C, J 9.0 Hz), 48.6 (HC), 51.7
(H3CO), 129.1 d (Cm, J 12.6 Hz), 132.2 d (Co, J 9.0 Hz),
132.6 d (Cp, J 3.6 Hz), 155.0 d (C=N, J 9.0 Hz), 164.2
(C=O).
E-2-[(Triphenylphosphoranylidene)amino]-
propanaloxime (IVb). mp 146–154°C (decomp.).
1H NMR spectrum (DMSO-d6), δ, ppm: 1.11 d (3H, H3C,
J 6.6 Hz), 3.76 d.d.q (1H, HCN, J 6.6, 6.6, 20.6 Hz),
7.13 d (1H, HC, J 6.6 Hz), 7.47–7.66 m (15Harom),
10.0 br.s (1H, HO). 13C NMR spectrum (DMSO-d6), δ,
ppm: 25.1 d (H3C, J 14.0 Hz), 49.2 (HC), 128.4 d (Cm,
J 11.5 Hz), 131.3 (Cp), 132.0 d (Co, J 8.7 Hz), 155.5 d
(C=N, J 11.3 Hz). Found, %: C 72.72; H 6.14; N 7.56.
C21H21N2OP. Calculated, %: C 72.40; H 6.08; N 8.04.
E-Oxime of 1-hydroxy-3-[(triphenylphosphoranyl-
idene)amino]acetone (IVh). mp 102–109°C (decomp.).
1H NMR spectrum (DMSO-d6), δ, ppm: 3.31 br.s (1H,
HOC), 3.80 d (2H, H2CN, J 17.0 Hz), 4.44 s (2H, H2C),
7.50–7.81 m (15H, Harom), 10.3 br.s (1H, HO). 13C NMR
spectrum (DMSO-d6), δ, ppm: 46.6 (H2CN), 58.2 (H2C),
128.6 d (Cm, J 12.6 Hz), 131.6 (Cp), 132.1 d (Co,
J 9.0 Hz), 159.6 d (C=N, J 18.0 Hz). Found, %: C 68.87;
H 5.63, N 7.24. C21H21N2O2P. Calculated, %: C 69.22;
H 5.81; N 7.69.
E-Oxime of 2-[(triphenylphosphoranylidene)-
amino]acetone (IVc). mp 139–141°C (decomp.).
1H NMR spectrum (DMSO-d6), δ, ppm: 1.76 s (3H, H3C),
3.60 d (2H, H2C, J 18.3 Hz), 7.50–7.65 m (15H, Harom),
10.0 br.s (1H, HO). 13C NMR spectrum (DMSO-d6), δ,
ppm: 11.7 (H3C), 48.9 d (H2C, J 3.6 Hz), 128.67 d (Cm,
J 12.6 Hz), 131.6 d (Cp, J 3.6 Hz), 132.1 d (Co, J 9.0
Hz), 157.9 d (C=N, J 19.8 Hz). Found, %: C 72.30;
H 6.08; N 8.12. C21H21N2OP. Calculated, %: C 72.40;
H 6.08; N 8.04.
Preparation of α-aminooximes III. e. To a disper-
sion of 1 mmol of ylide IV in 5.6 ml of THF was added
0.054 ml (3 mmol) of water, and the mixture was kept at
room temperature for 24 h. Then 0.22 g (1 mmol) of
Boc2O was added, and the mixture was kept for another
24 h. The solution was evaporated in a vacuum, and the
residue was subjected to chromatography on silica gel
(eluent hexane–AcOEt, 10:1 → 3:1). Yields are given in
the table.
E-Oxime of 2-[(triphenylphosphoranylidene)-
amino]acetophenone (IVd). mp 139–143°C (decomp.).
1H NMR spectrum (DMSO-d6), δ, ppm: 4.24 d (2H, H2C,
J 18.3 Hz), 7.22–7.40 m (5H, Harom), 7.42–7.66 m (15H,
HCPPh3), 10.39 br.s (1H, HO). 13C NMR spectrum
(DMSO-d6), δ, ppm: 49.0 (H2C), 126.6, 127.9 and 128.7
(Carom), 128.7 d (Cm, J 10.8 Hz), 131.6 (Cp), 132.1 d (Co,
J 9.0 Hz), 136.6 (CC=N), 157.5 d (C=N, J 16.2 Hz).
Found, %: C 76.18; H 5.88; N 6.64. C26H23N2OP.
Calculated, %: C 76.08; H 5.65; N 6.83.
1,1-Dimethylethyl (2E)-2-(hydroximino)ethyl-
carbamate (IIIa). mp 74–80°C, Rf 0.46 (hexane–ethyl-
acetate, 1:1). 1H NMR spectrum (CDCl3), δ, ppm: 1.44 s
(9H, H3C), 3.89 m (2H, H2C), 5.08 br.s (1H, HN), 7.43 t
(1H, HC, J 4.4 Hz), 8.74 br.s (1H, HO). 13C NMR
spectrum (CDCl3), δ, ppm: 28.3 (H3C), 39.7 (H2C), 80.0
(CCH3), 147.6 (HC), 156.0 (C=O). All spectral data are
consitent with published results [25].
tert-Butyl N-[2-(hydroximino)-1-methylethyl]-
carbamate (IIIb). mp 65–70°C, Rf 0.54 (hexane–ethyl
acetate, 1:1) Mixture of isomers E and Z, 3.5:1. E-isomer.
1H NMR spectrum (CDCl3), δ, ppm: 1.31 d (3H, H3CCH,
J 6.6 Hz), 1.46 s (9H, H3C), 4.41 m (1H, HC), 4.81 br.s
(1H, HN), 7.42 d (1H, HCN, J 3.7 Hz), 7.78 br.s (1H,
HO). 13C NMR spectrum (CDCl3), δ, ppm: 19.2
(H3CCH), 28.4 (H3C), 46.0 (HC), 80.0 (CCH3), 151.6
(C=O and C=N). Z-isomer. 1H NMR spectrum (CDCl3),
δ, ppm: 1.31 d (3H, H3CCH, J 6.6 Hz), 1.46 C (9H, H3C),
4.41 m (1H, HC), 5.53 br.s (1H, HN), 6.69 d (1H, HCN,
J 3.7 Hz), 7.99 br.s (1H, HO). 13C NMR spectrum
(CDCl3), δ, ppm: 17.4 (H3CCH), 28.4 (H3C), 43.1 (HC),
80.0 (CCH3), 151.6 (C=O and C=N). Found, %: C 51.41;
H 8.90; N 14.41. C8H16N2O3. Calculated, %: C 51.05;
H 8.57; N 14.88.
E-Oxime of 1-[(triphenylphosphoranylidene)-
amino]-3-phenylacetone (IVe). mp 84–92°C (decomp.).
1H NMR spectrum (DMSO-d6), δ, ppm: 3.55 d (2H,
H2CN, J 16.0 Hz), 3.77 s (2H, H2C), 7.05–7.33 m (5H,
Harom), 7.50–7.65 m (15H, HCPPh3), 10.38 br.s (1H, HO).
13C NMR spectrum (DMSO-d6), δ, ppm: 30.5 (H2C), 46.8
(H2CN), 125.7, 128.1 and 128.9 (Carom), 128.7 d (Cm,
J 12.6 Hz), 131.5 (Cp), 132.1 d (Co, J 9.0 Hz), 137.9
(CCH2), 159.5 d (C=N, J 21.5 Hz). Found, %: C 76.02;
H 5.73; N 6.41. C27H25N2OP. Calculated, %: C 76.40;
H 5.94; N 6.60.
Z-Methyl 2-(hydroximino)-3-[(triphenylphos-
phoranylidene)amino]butanoate (IVg). Unstable at
1
room temperature. H NMR spectrum (DMSO-d6), δ,
ppm: 1.23 t (3H, H3C, J 6.6 Hz), 3.64 s (3H, H3CO),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 8 2007

SYNTHESES BASED ON α-AZIDOOXIMES: I.
1111
2-(Hydroximino)-1,1-dimethylethylpropyl-
carbamate (IIIc). mp 86–88°C, Rf 0.55 (hexane–ethyl-
acetate, 1:1) Mixture of isomers E and Z, 10:1. E-isomer.
1H NMR spectrum (CDCl3), δ, ppm: 1.44 s (9H, H3C),
1.87 s (3H, H3CCN), 3.84 d (2H, H2C, J 5.9 Hz),
5.20 br.s (1H, HN), 8.99 br.s (1H, HO). 13C NMR
spectrum (CDCl3), δ, ppm: 12.2 (H3CCN), 28.4 (H3C),
44.4 (H2C), 79.9 (CCH3), 155.1 and 156.0 (C=O and
13C NMR spectrum (CDCl3), δ, ppm: 28.3 (H3C), 35.6
(H2CN), 61.8 (H2C), 80.6 (CCH3), 156.8 and 157.7 (C=O
and C=N). Z-isomer. 1H NMR spectrum (CDCl3), δ, ppm:
1.45 s (9H, H3C), 3.86 br.s (1H, HO), 3.98 d (2H, H2CN,
J 6.6 Hz), 4.48 s (2H, H2C), 5.26 br.s (1H, HN), 8.62 br.s
(1H, HON). 13C NMR spectrum (CDCl3), δ, ppm: 28.3
(H3C), 40.3 (H2CN), 56.6 (H2C), 80.6 (CCH3), 156.9 and
159.0 (C=O and C=N). Found, %: C 47.11; H 7.76;
N 14.03. C8H16N2O4. Calculated, %: C 47.05; H 7.90;
N 13.72.
1
C=N). Z-isomer. H NMR spectrum (CDCl3), δ, ppm:
1.44 s (9H, H3C), 1.87 s (3H, H3CCN), 4.04 d (1H, H2C,
J 5.2 Hz), 5.73 br.s (1H, HN), 9.74 br.s (1H, HO).
13C NMR spectrum (CDCl3), δ, ppm: 18.0 (H3CCN), 28.4
(H3C), 38.3 (H2C), 79.9 (CCH3), 155.1 and 156.0 (C=O
and C=N). Found, %: C 51.03; H 8.50; N 14.90.
C8H16N2O3. Calculated, %: C 51.05; H 8.57; N 14.88.
Tetrahydro-2,5-pyridinedione 5-oxime (IIIi). To
a solution of 0.19 g (1 mmol) of azidooxime Ii in 3 ml of
ether was added at stirring 0.26 g (1 mmol) of triphenyl-
phosphine. The reaction mixture was kept at room
temperature for 6 h and then it was evaporated in
a vacuum.The residue consisted of an unstable ylide IVi
as a mixture of E- and Z-isomers in a ratio 1.1:1.
1H NMR spectrum (CDCl3), δ, ppm: 2.29–2.80 m (4H,
H2CH2CCO and H2CH2CCO), 3.61 s, 3.63 s (3H,
H3COCO), 3.81 d (2H, H2CCN, Ε-isomer, J 19.0 Hz),
4.00 d (2H, H2CCN, Z-isomer, J 13.8 Hz), 6.37 br.s (1H,
HON), 7.40–7.73 m (15Harom).
tert-Butyl N-[(2E)-2-(hydroximino)-2-phenyl-
ethyl]carbamate (IIId). mp 94–97°C, Rf 0.54 (hexane–
ethyl acetate, 1:1). 1H NMR spectrum (CDCl3), δ, ppm:
1.44 s (9H, H3C), 4.44 d (2H, H2C, J 5.9 Hz), 5.37 br.s
(1H, HN), 7.40 m, 7.73 m (5H, Harom), 9.80 br.s (1H,
HO). 13C NMR spectrum (CDCl3), δ, ppm: 28.4 (H3C),
36.6 (H2C), 79.9 (CCH3), 126.9, 128.7 and 129.6 (Carom),
134.2 (Ci), 155.9 and 157.3 (C=N and C=O). Found, %:
C 62.46; H 7.55; N 11.16. C13H18N2O3. Calculated, %:
C 62.38; H 7.25; N 11.19.
Ylide IVi obtained was dissolved in a mixture of
4.0 ml of THF and 0.043 ml (2.4 mmol) of water, and
the solution was kept at room temperature for 24 h. The
separated colorless precipitate was filtered off and dried
in a vacuum. Yield of compound IIIi 0.06 g (47% cal-
culated on initial azidooxime Ii). mp 169–172°C
2-(Hydroximino)-1,1-dimethylethyl-3-phenyl-
propylcarbamate (IIIe). mp 75–80°C, Rf 0.53 (hexane–
ethyl acetate, 1:1). Mixture of isomers E and Z, 3.75:1.
1
E-isomer. H NMR spectrum (CDCl3), δ, ppm: 1.43 C
1
(decomp.). Mixture of isomers E and Z, 1:1. H NMR
(9H, H3C), 3.74 C (2H, H2C), 3.85 d (2H, H2CN,
J 5.2 Hz), 5.00 br.s (1H, HN), 7.18–7.36 m (5H, Harom),
8.00 br.s (1H, HO). 13C NMR spectrum (CDCl3), δ, ppm:
28.4 (H3C), 32.6 (H2C), 43.0 (H2CN), 79.8 (CCH3),
126.8, 128.7 and 129.1 (Harom), 135.9 (Ci), 155.0 and
spectrum (CDCl3), δ, ppm: 2.31 m and 2.55 m (4H,
H2CCO and H2CC=N), 3.76 s (2H, H2CNH, E-isomer),
3.98 s (2H, H2CNH, Z-isomer), 7.51 s and 7.75 s (1H,
HN), 10.69 s and 10.74 s (1H, HO). 13C NMR spectrum
(CDCl3), δ, ppm: 21.2 (H2CC=N, E-isomer), 25.6
(H2CC=N, Z-isomer), 29.5 (H2CCO, E-isomer), 30.5
(H2CCO, Z-isomer), 39.8 (H2CNH, Z-isomer), 43.0
(H2CNH, E-isomer), 151.9 and 153.1 (C=N), 171.6 and
172.6 (C=O). Found, %: C 46.82; H 6.31; N 21.62.
C5H8N2O2. Calculated, %: C 46.87; H 6.29; N 21.68.
1
155.1 (C=N and C=O). Z-isomer. H NMR spectrum
(CDCl3), δ, ppm: 1.45 C (9H, H3C), 3.58 C (2H, H2C),
3.99 d (2H, H2CN, J 6.6 Hz), 5.62 br.s (1H, HN), 7.18–
7.36 m (5H, Harom), 9.59 br.s (1H, HO). 13C NMR
spectrum (CDCl3), δ, ppm: 28.4 (H3C), 37.3 (H2C), 39.0
(H2CN), 79.8 (CCH3), 126.9, 129.0 and 129.1 (Carom),
135.9 (Ci), 156.0 and 156.1 (C=O and C=N). Found, %:
C 63.61; H 7.92; N 10.73. C14H20N2O3. Calculated, %:
C 63.62; H 7.63; N 10.60.
Synthesis of azidohydroxylamines Vb–Ve, Vg, and
Vi. f.Adispersion of NaBH3CN (0.19 g, 3 mmol) in acetic
acid (2.2 ml) was added at stirring to a solution of
azidooxime I (1 mmol) in acetic acid (2.2 ml). The
reaction mixture was stirred at room temperature for 2 h
and then poured into a mixture of ethyl acetate (100 ml)
and saturated solution of Na2CO3 (100 ml). The water
phase was treated with ethyl acetate (2×50 ml), the
combined organic solutions were washed with a saturated
sodium chloride solution (50 ml) and dried with Na2SO4.
tert-Butyl N-[3-hydroxy-2-(hydroximino)propyl]-
carbamate (IIIh). Oily substance, Rf 0.32 (hexane–ethyl
acetate, 1:1). Mixture of isomers E and Z, 1:1. E-isomer.
1H NMR spectrum (CDCl3), δ, ppm: 1.45 s (9H, H3C),
3.86 br.s (1H, HO), 4.07 d (2H, H2CN, J 6.6 Hz), 4.22 s
(2H, H2C), 5.26 br.s (1H, HN), 8.62 br.s (1H, HON).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 8 2007

SUKHORUKOV et al.
1112
The solution was evaporated in a vacuum, the residue
was subjected to chromatography on silica gel.
1-[3-Azido-2-(hydroxylamino)propyl]benzene
(Ve). Oily substance, Rf 0.48 (hexane–ethyl acetate, 1:1).
IR spectrum (KBr), ν, cm–1: 3420 (OH, NH), 3255 (OH,
NH), 2925, 2103 (N3), 1603, 1496, 1454, 1286, 1077,
745, 700, 533. 1H NMR spectrum (CDCl3), δ, ppm: 2.73
d.d (1H, H2C, J 7.2, 13.8 Hz), 2.88 d.d (1H, H2C, J 7.2,
13.8 Hz), 3.21 d.d.d.d (1H, HC, J 7.2, 7.2, 5.9 and
4.3 Hz), 3.44 d.d (1H, H2CN, J 5.9, 12.5 Hz), 3.55 d.d
(1H, H2CN, J 4.3, 12.5 Hz), 6.75 br.s (2H, HN and HO),
7.14–7.40 m (5Harom). 13C NMR spectrum (CDCl3), δ,
ppm: 35.4 (H2C), 51.2 (H2CN), 62.1 (HC), 126.9, 128.9
and 129.3 (Carom), 137.4 (Ci).
Synthesis of azidohydroxylamines Va–Ve and Vi.
To a solution of 1 mmol of azidooxime I in 2 ml of
dichloromethane was added 0.10 g (1.6 mmol) of
NaBH3CN and then a mixture of 0.2 ml of concn. HCl
and 1.2 ml of MeOH. The reaction mixture was stirred
at room temperature for 2 h and then poured into
a mixture of ethyl acetate (50 ml) and saturated solution
of Na2CO3 (50 ml). The water phase was treated with
ethyl acetate (2×30 ml), the combined organic solutions
were washed with a saturated sodium chloride solution
(50 ml) and dried with Na2SO4. The solution was
evaporated in a vacuum, the residue was subjected to
chromatography on silica gel.
Methyl 3-azido-2-(hydroxylamino)butyrate (Vg).
Oily substance, Rf 0.37 (hexane–ethyl acetate, 1:1).
Mixture of diastereomers, 1:1.1. IR spectrum (KBr), ν,
cm–1: 3450 (OH, NH), 3258 (OH, NH), 2962, 2103 (N3),
1-Azido-2-(hydroxylamino)ethane (Va). Oily
substance, Rf 0.17 (hexane–ethyl acetate, 1:1). IR
spectrum (KBr), ν, cm–1: 3410 (OH, NH), 3262 (OH,
1
1714 (CO), 1440, 1269, 1212, 1059, 852. H NMR
spectrum (CDCl3), δ, ppm: 1.36 d and 1.37 d (3H, H3C,
J 6.6, 7.2 Hz), 3.61 d and 3.69 d (1H, HCNO, J 6.6,
5.3 Hz), 3.82 s (3H, H3CO), 3.88 2 m (1H, HC),
6.02 br.s (2H, HN and HO). 13C NMR spectrum (CDCl3),
δ, ppm: 16.0 and 16.7 (H3C), 52.5 and 52.6 (H3CO), 56.1
and 56.3 (HC), 68.4 and 68.9 (HCNO), 166.2 and 166.4
(C=O).
1
NH), 2103 (N3), 1442, 1253, 1070, 949. H NMR
spectrum (CDCl3), δ, ppm: 3.07 t and 3.56 t (4H, 2H2C,
J 5.2 Hz), 6.05 br.s (2H, HN and HO). 13C NMR spectrum
(CDCl3), δ, ppm: 48.3 and 52.1 (2CH2).
2-Azido-1-(hydroxylamino)propane (Vb). Oily
substance, Rf 0.26 (hexane–ethyl acetate, 1:1). IR
spectrum (KBr), ν, cm–1: 3400 (OH, NH), 3258 (OH,
NH), 2929, 2104 (N3), 1448, 1377, 1280, 1101, 1014,
Methyl 5-azido-4-(hydroxylamino)pentanoate
(Vi). Oily substance, Rf 0.34 (hexane–ethyl acetate, 1:1).
IR spectrum (KBr), ν, cm–1: 3450 (OH, NH), 3264 (OH,
NH), 2953, 2105 (N3), 1734 (CO), 1439, 1274, 1203,
1
963, 814. H NMR spectrum (CDCl3), δ, ppm: 1.29 d
(3H, H3C, J 6.6 Hz), 2.80 d.d (1H, H2C, J 9.2, 13.2 Hz),
2.99 d.d (1H, H2C, J 3.6, 13.2 Hz), 3.91 m (1H, HC),
5.89 br.s (2H, HN and HO). 13C NMR spectrum (CDCl3),
δ, ppm: 16.9 (H3C), 54.5 and 58.1 (HC and H2C).
1
1175, 1064, 883, 653. H NMR spectrum (CDCl3), δ,
ppm: 1.71 d.t (1H, H2CCNO, J 5.3, 7.2 Hz), 1.83 d.t
(1H, H2CCNO, J 7.2, 7.2 Hz), 2.41 t (2H, H2CCO, J 7.2,
7.2 Hz), 2.88 t.t (1H, HC, J 7.2, 5.3 Hz), 3.48 d.d (2H,
H2CN, J 7.2, 10.5 Hz), 3.66 s (3H, H3CO), 6.11 br.s (2H,
HN and HO). 13C NMR spectrum (CDCl3), δ, ppm: 24.0
(H2CCNO), 30.7 (H2CCO), 51.6 and 51.9 (H2CN and
H3CO), 60.1 (HC), 174.2 (C=O).
1-Azido-2-(hydroxylamino)propane (Vc). Oily
substance, Rf 0.27 (hexane–ethyl acetate, 1:1). IR
spectrum (KBr), ν, cm–1: 3390 (OH, NH), 3251 (OH,
NH), 2921, 2105 (N3), 1439, 1372, 1261, 1170, 1058,
1
943, 880. H NMR spectrum (CDCl3), δ, ppm: 1.11 d
Hydrogenation of azidohydroxylamine Vc. g.
Raney nickel (about 0.05 g in methanol) was added to
a solution of 0.10 g (0.86 mmol) of azidohydroxylamine
Vc and 0.38 g (1.72 mmol) of ΒoC2O in 3 ml of MeOH.
The mixture was hydrogenated at room temperature and
10 at of H2 for 2 h, , then the catalyst was filtered off and
the solvent was distilled off in a vacuum. The reaction
product was subjected to column chromatograpy on silica
gel (eluent hexane–AcOEt, 10:1 → 3:1). Yield of com-
pound IIc 0.90 g (43%).
(3H, H3C, J 6.6 Hz), 3.14 m (1H, HC), 3.40 d.d (1H,
H2C, J 6.6, 11.8 Hz), 3.50 d.d (1H, H2C, J 4.6, 11.8 Hz),
6.30 br.s (2H, HN and HO). 13C NMR spectrum (CDCl3),
δ, ppm: 15.1 (H3C), 53.2 and 56.2 (HC and H2C).
1-[2-Azido-1-(hydroxylamino)ethyl]benzene (Vd).
Oily substance, Rf 0.50 (hexane– ethyl acetate, 1:1). IR
spectrum (KBr), ν, cm–1: 3418 (OH, NH), 3250 (OH,
NH), 2927, 2104 (N3), 1489, 1450, 1218, 1036, 730, 529.
1H (CDCl3), δ, ppm: 3.69 d (2H, H2C, J 6.6 Hz), 4.13 t
(1H, HC, J 6.6 Hz), 7.04 br.s (2H, HN and HO), 728–
7.42 m (5Harom). 13C NMR spectrum (CDCl3), δ, ppm:
52.9 (H2C), 65.2 (HC), 127.8, 128.7 and 128.9 (Carom),
137.2 (Ci).
REFERENCES
1.Tartakovskii, V.A., Ioffe, S.L., Dil’man, A.D., and Tish-
kov, A.A., Izv. Akad. Nauk, Ser. Khim., 2001, p. 1850.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 8 2007

SYNTHESES BASED ON α-AZIDOOXIMES: I.
1113
2.Sukhorukov, A.Yu., Bliznets, I.V., Lesiv, A.V., Khomuto-
va, Y.A., and Ioffe, S.L., Synthesis, 2005, p. 1077.
3.Baker, W.R. and Condon, S.L. J. Org. Chem., 1993, vol. 58,
p. 3277.
4.Davey, D.D. and Lumma, W. C., J. Org. Chem., 1989,
vol. 54, 3211.
5.Lee-Ruff, E., Wan, W.-Q., and Jiang, J.-L., J. Org. Chem.,
1989, vol. 54, 3292.
6.Rausser, R., Weber, L., Hershberg, E.B., and Oliveto, E.P.,
J. Org. Chem., 1966, vol. 31, 1342.
7.Timms, G.H. and Wildsmith, E., Tetrahedron Lett., 1971,
vol. 12, 195.
8.Evans, D. A. and Ellman, J.A., J. Am. Chem. Soc., 1989,
vol. 111, p. 1063.
9.Murahashi, S., Taniguchi, Y., Imada, Y., and Tanigawa, Y.,
J. Org. Chem., 1989, vol. 54, p. 3292.
10. Boyer, J.H. and Canter, F.C., Chem. Rev., 1954, 54, p. 1.
11. Fukuyama, T. and Chen, X., J. Am. Chem. Soc., 1994,
vol. 116, p. 3125.
14. Shatzmiller, S. and Bercovici, S., Lieb. Ann., 1992, p. 1005.
15. Enders, D. and Wiedermann, J., Synthesis, 1996, p. 1443.
16. Shiozaki, M., Arai, M., Kobayashi, Y., Kasuya, A.,
Miyamoto, S., Furukawa, Y., Takayama, T., and Haruya-
ma, H., J. Org. Chem., 1994, vol. 59, p. 4450.
17. Barluenga, J., Ferrero, M., and Palacios, F., J. Chem. Soc.,
Perkin Trans. I, 1990, p. 2193.
18. Nitta, M., Soeda, H., and Iino, Y., Bull. Chem. Soc. Jpn.,
1990, vol. 63, p. 932.
19. Keck, G.E., Wager, T.T., and McHardy, S.F., Tetrahedron,
1999, vol. 55, p. 11755.
20. Gribble, G.W., Leiby, R.W., and Sheehan, M.N., Synthesis,
1977, p. 856.
21. Lesiv, A.V., Ioffe, S.L., Strelenko, Yu.A., and Tartakov-
sky, V.A., Helv. Chim. Acta, 2002, vol. 85, p. 3489.
22. Gottlieb, H.E., Kotlyar, V., and Nudelman, A., J. Org.
Chem., 1997, vol. 62, p. 7512.
23. Spivak, D. and Shea, K.J., J. Org. Chem., 1999, vol. 64,
p. 4627.
12. Stanovnic, B., Tisler, M., Polanc, S., and Gracner, M.,
Synthesis, 1978, p. 65.
24. Bellis, E., Markidis, T., and Kokotos, G., Synthesis, 2002,
p. 1359.
13. Heathcock, C.H. and Smith, S.C., J. Org. Chem., 1994,
vol. 59, p. 6828.
25. White, J.D. and Hansen, J.D., J. Org. Chem., 2005, vol. 70,
p. 1963.
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