The chemistry of N,N-bis(siloxy)enamines. Part 8. A general method for the preparation of α-azido oximes from aliphatic nitro compounds

Article abstract of DOI:10.1055/s-2005-861836

A new strategy for the synthesis of α-azido oximes from aliphatic nitro compounds via interaction of N,N-bis(silyloxy)enamines with trimethylsilylazide was realized to give the target products with good yields.

Full text of DOI:10.1055/s-2005-861836

PAPER
1077
The Chemistry of N,N-Bis(siloxy)enamines. Part 8.1 A General Method for the
Preparation of a-Azido Oximes from Aliphatic Nitro Compounds
P
reparationof
a
-A
l
zido O
e
ximes from
x
Aliphatic
N
e
itro Compo
y
unds Yu. Sukhorokov, Igor V. Bliznets, Alexey V. Lesiv,* Yulija A. Khomutova, Yuriy A. Strelenko,
Sema L. Ioffe*
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991, Moscow, Leninsky prosp. 47, Russian Federation
Fax +7(95)1355328; E-mail: iof@ioc.ac.ru
Received 14 December 2004
In this context elaboration of a convenient procedure for
Abstract: A new strategy for the synthesis of a-azido oximes from
the preparation of azido oximes 2 from available BENA 1
aliphatic nitro compounds via interaction of N,N-bis(silyl-
seems to be the most interesting approach (Scheme 1).
oxy)enamines with trimethylsilylazide was realized to give the tar-
get products with good yields.
Optimal reaction conditions are presented in Table 1. Ni-
Key words: aliphatic nitro compounds, azidotrimethylsilane, N,N- troso acetals 1 reacted within 24 hours at ambient temper-
bis(siloxy)enamines, a-azido oximes
ature with an excess of Me3SiN3 in dichloromethane in the
presence of catalytic amount of triethylamine to give tri-
methylsilyl derivatives 3. The latter underwent desilyla-
tion in an excess of methanol furnishing target azido
oximes 2 in good yields (see Table 1).19
The reactivity of aliphatic nitro compounds (ANC) can be
significantly increased by the silylation of the nitro
group.2 Among a variety of intermediates involved in this
process N,N-bis(siloxy)enamines (BENA; 1) have
emerged as the most interesting compounds, especially
since the recent advent of convenient procedures for their
preparation.3,4
The procedure presented in Scheme 1 has a wide scope;
terminal and internal BENA, as well as BENA bearing
functional groups, can be involved in this reaction.
The formation of a-nitroso olefins as key intermediates
and the contribution of chain-type processes in the inter-
action of BENA with various nucleophiles were discussed
in our earlier paper.10 Presumably, a similar interpretation
can be applied for the coupling of 1 with Me3SiN3.
The unique ability of BENA, to interact at the b-position
with some electrophiles5,6 as well as with various nucleo-
philes,7–13 can be used for the functionalization of the b-
carbon atom of readily available initial ANC. Earlier, we
developed this novel strategy for the synthesis of various
a-functionalized1,7–10,13 or modified11,12 oximes from the
simplest ANC.
In the present case the a-silyloxy oximes 4 were observed
as by-products (Scheme 2), which is similar to coupling
reactions of BENA with other nucleophiles.10 Compounds
4 result from the well known rearrangement of BENA
(see for example3,4).
Here we present the application of this approach for the
synthesis of poorly investigated a-azido oximes 2.
In order to minimize the amount of 4 and achieve maxi-
mum yields of target oximes 2 the coupling conditions of
model BENA 1b (reagents ratio, solvent, use of Et3N)
were extensively varied (see Table 2).
As indicated in Table 2, some impurities present in
Me3SiN3, (HMPA or HN3, entries 8–10) connected with
the specific method used for its preparation, gave rise to
an increase in the yield of by-product 4.
Scheme 1
To date no general procedure for the production of com-
pounds 2 is available and only a few examples of their
preparation have been reported, with a-hydroxyoximes14
or a-acyloxyoximes15 serving as precursors. On the other
hand, azido oximes 2 could be considered as very suitable
initial compounds for the synthesis of dinitriles,16 1,2-di-
amines,17 and amino oximes.18
Scheme 2
The same effect was observed in the absence of Et3N or by
decreasing the ratio Me3SiN3:1. Interestingly, an induc-
tion period for the coupling reaction was found under
these conditions.
SYNTHESIS 2005, No. 7, pp 1077–1082
x
x
.
x
x
.2
0
0
5
Advanced online publication: 21.02.2005
DOI: 10.1055/s-2005-861836; Art ID: P14804SS
© Georg Thieme Verlag Stuttgart · New York
Therefore, the optimal procedure for the preparation of
oximes 4 requires a large excess of Me3SiN3 (see Table 1).

1078
A. Yu. Sukhorokov et al.
PAPER
Table 1 Optimal Conditions for 1 and Me3SiN3 Interaction and Yields of Target Products
Entry
1–3
R1
R2
Ratio of
Yield of 3 (%)
Yieldb of 2 (%)
Me3SiN:1
Crude Producta Pure Product E/Z
Pure Product
E/Z
3:4
6:1
3:1
2:1
5:4
5:1
3:2
13:1
10:1
1
2
3
4
5
6
7
8
9
a
b
c
d
e
f
H
H
2
5
5
3
2
2
2
2
2
89
84
87
82
–
13:10
Only E
16:1
3:1
79
87
80
85
92
95
91
87
93
Me
H
95
H
Me
H
90
(CH2)2CO2Me
94
c
CH2OSiMe3
H
98
–
3:5
Ph
H
ca.100
ca. 100
91
93
91
–
2:1
g
h
i
Bn
H
4:1
CO2Et
CO2Me
H
14:1
12:1
Me
96
–
a Determined by NMR spectroscopy with internal standard (toluene or nitromethane).
b Based on starting BENA 1.
c R1 = CH2OH for product 2e.
NMR spectra were recorded on Bruker AM-300 instrument (1H:
300.13 MHz, 13C: 75.47 MHz, 29Si: 59.63 MHz) referenced to a re-
sidual solvent peak or internal standard (TMS). Chemical shifts are
reported in ppm (d); multiplicities are indicated by s (singlet), d
(doublet), t (triplet), q (quartet), m (multiplet) and br (broad). The
INEPT pulse sequence was used for 29Si signal observation. Ele-
mental analyses were performed by the Analytical Center of the
Moscow Chemical Lyceum. MP’s were determined on a Koffler
melting point apparatus (uncorrected). Analytical thin-layer chro-
matography was performed on Merck silica gel plates with QF-254
indicator. Visualization was accomplished with UV light or with
ninhydrine in ethanol.
This allows one to simplify substantially the purification
of derivatives 2 and 3. Although an application of equimo-
lar amount of Me3SiN3 results only in a slight decrease of
yield of target oximes 2, the presence of large quantities
of by-product 4 necessitates more complicated techniques
for the purification of target compounds (for instance, col-
umn chromatography instead of filtration through silica
gel).
The structure of oximes 2 and derivatives 3 was con-
firmed by 1H and 13C NMR spectroscopic data, as well as
by elemental analysis of oximes 2. For a few oximes 2 the
azido group was identified by 14N NMR and IR spectros-
copy. To determine the configuration of the oximino
All solvents for chromatography and extractions were technical
grade and distilled from the indicated drying agents: petroleum
ether (60–70 °C) and EtOAc (K2CO3). Column chromatography
group the same rules we formulated previously were ap- was performed using Merck Kieselgel 60 230–400-mesh silica gel.
plied.10
The following chemicals were purchased from the indicated sourc-
es: chlorotrimethylsilane (Aldrich), bromotrimethylsilane (Fluka),
2-nitro-1-propanol (Acros), sodium azide (Acros). The following
In conclusion, a novel two-step strategy for the synthesis
of a-azido oximes from available ANC was developed
compounds were prepared by literature methods: (2-nitro-propyl)-
(Scheme 3).20
benzene,21 BENA 1a–d,3 1f,22 and 1i,j.4
Azidotrimethylsilane
Chlorotrimethylsilane (23.0 mL, 180 mmol) was added dropwise to
a stirred solution of NaN3 (12.4 g, 190 mmol) in HMPA (25 mL).
The reaction mixture was stirred at 20 °C for 2 h after which time
the azidotrimethylsilane (21.0 mL) was distilled from the mixture.
Yield: 87%; bp 52 °C/144 mmHg.23
Scheme 3
2-[N,N-Bis(trimethylsilyloxy)]amino-3-trimethylsilyloxyprop-
1-ene (1e)
Further efforts will be directed towards the use of oximes
2 as starting materials for the synthesis of various poly-
functional compounds and intermediates.
A solution of bromotrimethylsilane (2.64 mL, 20 mmol) in CH2Cl2
(5 mL) was added dropwise to a solution of 2-nitro-1-propanol
(0.53 g, 5 mmol) and Et3N (4.17 mL, 30 mmol) in CH2Cl2 (5 mL)
at 20 °C. The reaction mixture was maintained at this temperature
with occasional stirring for 72 h. The mixture was then diluted with
petroleum ether (50 mL) and poured into water (20 mL). The organ-
ic phase was washed with aq NaHSO4 [2 g in H2O (20 mL)], H2O
(2 × 10 mL), and brine (2 × 10 mL). Activated carbon was added,
All reactions were performed in oven-dried (150 °C) glassware un-
der an inert atmosphere of dry Ar. The following reaction solvents
and reagents were distilled from the indicated drying agents: Et3N
(CaH2), CH2Cl2 (CaH2), hexane (Na), HMPA (CaH2), MeOH (Mg).
Synthesis 2005, No. 7, 1077–1082 © Thieme Stuttgart · New York

PAPER
Preparation of a-Azido Oximes from Aliphatic Nitro Compounds
1079
h at 0 °C the temperature was allowed to rise to 20 °C. The reaction
mixture was maintained at this temperature with occasional stirring
for 72 h. The mixture was then diluted with petroleum ether (30 mL)
and poured into water (10 mL). The organic phase was washed with
aq NaHSO4 [0.5 g in H2O (10 mL)], water (2 × 10 mL), and brine
(2 × 10 mL). Activated carbon was added, the organic phase was
dried (Na2SO4), and concentrated in vacuum to afford 1g as a clean
colorless oil.
Table 2 The Optimization of Interaction BENA 1b with Me3SiN3
Entry Ratio
Me3SiN3:1
Procedurea
Yieldb (%)
3b
4
1
1
20 °C, without solvent,
48 h
73
18
2
2
5
1
2
3
5
5
5
5
20 °C, without solvent,
48 h
79
10
3
Yield: 0.81 (87%).
1H NMR (CDCl3): d = 0.24 (s, 18 H, SiMe3), 3.68 (s, 2 H, CH2Ph),
4.38 (s, 1 H, CH2), 5.11 (s, 1 H, CH2), 7.2–7.4 (m, 5 H, Ph).
13C NMR (CDCl3): d = 0.8 (SiMe3), 33.8 (CH2Ph), 105.4 (CH2),
126.0, 128.2, 129.6 (Ph), 139.3 (ipso-Ph), 159.6 (CN).
29Si NMR (CDCl3): d = 24.05.
3
20 °C, without solvent,
48 h
88
4
20–40 °C,c CH2Cl2, Et3N
(5%), 6 h
86
12
9
5
20–40 °C,c CH2Cl2, Et3N
(5%), 6 h
87
Anal. Calcd for C15H27NO2Si2: C, 58.20; H, 8.79; N, 4.52. Found:
C, 58.61; H, 8.91; N, 4.40.
6
20–40 °C,c CH2Cl2, Et3N
(5%), 6 h
90
5
Derivatives 3a–i; General Procedure (Table 1)
A solution of BENA 1a–i (10 mmol) in CH2Cl2 (10 mL) was added
to a stirred solution of Me3SiN3 and Et3N (0.7 mL, 0.5 mmol) at 20
°C. (The addition of BENA is an exothermic reaction; on a larger
scale BENA was added at such a rate so as to maintain a gentle re-
flux.) The reaction mixture was maintained at 20 °C for 24 h with
occasional shaking. The CH2Cl2 was evaporated in vacuum, toluene
(1.07 mL, 10 mmol) or nitromethane (0.54 mL, 10 mmol) was add-
ed to the residue and the yield of 3 was determined by NMR. Pure
samples of 3a–c and 3f,g were obtained by vacuum distillation or
column chromatography.
7
20–40 °C,c CH2Cl2, Et3N
(5%), 6 h
95
–
8
20–40 °C,c CH2Cl2, H2O
(10%), 24 h
43
41
28
20
–
9
20–40 °C,c CH2Cl2, Et3N
(5%), H2O (10%), 24 h
67
10
20–40 °C,c CH2Cl2, Et3N
(5%), HMPA (5%), 24 h
71
Azido-acetaldehyde O-(Trimethylsilyl)oxime (3a)
Bp 89–92 °C/36 mmHg.
11
12
13
0
0
5
NaN3, Et2O, 1 h
NaN3, DMF, 1 h
ca. 10
E-Oxime
ca. 10 ca. 10
1H NMR (CDCl3): d = 0.23 (s, 9 H, SiMe3), 3.88 (d, J = 5.9 Hz, 2
H, CH2), 7.57 (t, J = 5.9 Hz, 1 H, CH).
20 °C,d without solvent,
48 h
61
12
13C NMR (CDCl3): d = –0.9 (SiMe3), 49.0 (CH2), 148.8 (CH).
29Si NMR (CDCl3): d = 27.31.
14
5
20–40 °C,c CH2Cl2, Et3N
(5%), 6 h
88
–
Z-Oxime
a For entries 1–12: 1 mmol of 1b; for entries 13 and 14: 100 mmol of
1b.
1H NMR (CDCl3): d = 0.23 (s, 9 H, SiMe3), 4.19 (d, J = 4.4 Hz, 2
H, CH2), 6.97 (t, J = 4.4 Hz, 1 H, CH).
b By 1H NMR spectroscopy with toluene as the internal standard.
c A short increase of temperature during BENA addition is possible.
d An inductive period after BENA addition, followed by a spontane-
ous increase of temperature.
13C NMR (CDCl3): d = –0.9 (SiMe3), 45.8 (CH2), 150.2 (CH).
29Si NMR (CDCl3): d = 27.53.
1-Azido-propan-2-one O-(Trimethylsilyl)oxime (3b)
Bp 68–70 °C/9 mmHg.
the organic phase was dried (Na2SO4), and concentrated in vacuum
to afford 1e as a clean colorless oil.
E-Oxime
1H NMR (CDCl3): d = 0.23 (s, 9 H, SiMe3), 1.95 (s, 3 H, Me), 3.83
Yield: 1.28 g (80%).
(s, 2 H, CH2).
1H NMR (CDCl3): d = 0.15 (s, 9 H, COSiMe3), 0.20 (s, 18 H,
SiMe3) 4.43 (s, 2 H, CH2O), 4.94 (s, 1 H, CH2), 5.08 (s, 1 H, CH2).
13C NMR (CDCl3): d = –0.9 (SiMe3), 12.7 (Me), 54.4 (CH2), 156.5
(C=N).
13C NMR (CDCl3): d = –0.6 (COSiMe3), 0.0 (SiMe3), 58.3 (CH2O),
102.0 (CH2), 158.7 (CN).
29Si NMR (CDCl3): d = 25.64.
2-Azido-propionaldehyde O-(Trimethylsilyl)oxime (3c)
Bp 87–89 °C/27 mmHg.
29Si NMR (CDCl3): d = 20.10 (COSi), 24.60 (NOSi).
Anal. Calcd for C12H31NO3Si3: C, 44.81; H, 9.71; N, 4.35. Found:
C, 44.98; H, 9.77; N, 4.54.
E-Oxime
1H NMR (CDCl3): d = 0.21 (s, 9 H, SiMe3), 1.34 (d, J = 6.6 Hz, 3
H, Me), 4.14 (m, J = 6.6 Hz, 1 H, CH), 7.40 (d, J = 6.6 Hz, 1 H,
HC=N).
2-[N,N-Bis(trimethylsilyloxy)]amino-3-phenylprop-1-ene (1g)
Bromotrimethylsilane (0.91 mL, 6.9 mmol) was added dropwise to
a solution of (2-nitropropyl)benzene (0.50 g, 3 mmol) and Et3N
(1.05 mL, 7.5 mmol) in CH2Cl2 (10 mL) at 0 °C. After stirring for 1
13C NMR (CDCl3): d = –1.0 (SiMe3), 17.7 (Me), 55.9 (CH), 153.2
(C=N).
Synthesis 2005, No. 7, 1077–1082 © Thieme Stuttgart · New York

1080
A. Yu. Sukhorokov et al.
PAPER
29Si NMR (CDCl3): d = 27.05.
13C NMR (CDCl3): d = –0.9 (SiMe3), 32.3 (CH2Ph), 52.0 (CH2),
126.5, 128.5, 128.8 and 135.6 (Ph), 157.8 (C=N).
Z-Oxime
1H NMR (CDCl3): d = 0.21 (s, 9 H, SiMe3), 1.27 (d, J = 6.6 Hz, 3
H, Me), 4.89 (m, J = 6.6 Hz, 1 H, CH), 6.80 (d, J = 6.6 Hz, 1 H,
HC=N).
Z-Oxime
1H NMR (CDCl3): d = 0.23 (s, 9 H, SiMe3), 3.44 (s, 2 H, CH2Ph),
4.83 (s, 2 H, CH2), 7.0–7.2 (m, 5 H, Ph).
13C NMR (CDCl3): d = –0.9 (SiMe3), 17.2 (Me), 51.3 (CH), 154.1
(C=N).
13C NMR (CDCl3): d = –0.9 (Me3Si), 38.6 (CH2Ph), 45.5 (CH2),
126.7, 128.6, 128.8 and 135.6 (Ph), 158.1 (C=N).
29Si NMR (CDCl3): d = 27.26.
3-Azido-2-(trimethylsilyl)oxyiminopropionic Acid Ethyl Ester
(3h)
5-Azido-4-(trimethylsilyl)oxyiminopentanoic Acid Methyl Es-
Compound 3h was detected in the reaction mixture by NMR spec-
troscopy.
ter (3d)
Compound 3d was detected in the reaction mixture by NMR spec-
troscopy.
E-Oxime
1H NMR (CDCl3): d = 0.39 (s, 9 H, SiMe3), 1.39 (t, J = 7.3 Hz, 3 H,
Me), 4.26 (s, 2 H, CH2), 4.38 (q, J = 7.3 Hz, 2 H, CH2O).
13C NMR (CDCl3): d = –0.9 (SiMe3), 14.1 (Me), 42.5 (CH2), 62.0
(CH2O), 151.9 (C=N), 162.9 (C=O).
E-Oxime
1H NMR (CDCl3): d = 0.28 (s, 9 H, SiMe3), 2.6 (m, 4 H, CH2CH2),
3.72 (s, 3 H, Me), 3.93 (s, 2 H, CH2).
13C NMR (CDCl3): d = –1.0 (SiMe3), 22.6 (CH2CN), 29.8
(CH2CO), 51.4 (Me), 53.6 (CH2), 158.6 (C=N), 172.6 (C=O).
Z-Oxime
1H NMR (CDCl3): d = 0.39 (s, 9 H, SiMe3), 1.39 (t, J = 7.3 Hz, 3 H,
Me), 4.08 (s, 2 H, CH2), 4.38 (q, J = 7.3 Hz, 2 H, CH2O).
Z-Oxime
1H NMR (CDCl3): d = 0.28 (s, 9 H, SiMe3), 2.6 (m, 4 H, CH2CH2),
3.72 (s, 3 H, Me), 4.17 (s, 2 H, CH2).
13C NMR (CDCl3): d = –0.9 (SiMe3), 14.1 (Me), 46.1 (CH2), 61.7
(CH2O), 151.9 (C=N), 162.9 (C=O).
13C NMR (CDCl3): d = –1.0 (SiMe3), 27.5 (CH2CN), 30.0
(CH2CO), 47.0 (CH2), 51.3 (Me), 157.5 (C=N), 172.6 (C=O).
3-Azido-2-(trimethylsilyl)oxyiminobutyric Acid Methyl Ester
(3i)
1-Azido-3-hydroxypropan-2-one O-(Trimethylsilyl)oxime (3e)
Compound 3e was detected in the reaction mixture by NMR spec-
troscopy.
Compound 3i was detected in the reaction mixture by NMR spec-
troscopy.
E-Oxime
E-Oxime
1H NMR (CDCl3): d = 0.17 (s, 9 H, SiMe3), 1.42 (d, J = 7.3 Hz, 3
H, Me), 3.68 (s, 3 H, OMe), 4.86 (q, J = 7.3 Hz, 1 H, CH).
1H NMR (CDCl3): d = 0.12 (s, 9 H, COSiMe3), 0.26 (s, 9 H, SiMe3),
4.13 (s, 2 H, CH2N), 4.36 (s, 2 H, CH2).
13C NMR (CDCl3): d = –1.1 (SiMe3), 15.5 (Me), 50.4 (OMe), 52.0
(CH), 155.0 (C=N), 162.7 (C=O).
13C NMR (CDCl3): d = –0.7 and –0.6 (SiMe3), 44.1 (CH2N), 62.1
(CH2), 160.5 (C=N).
Z-Oxime
Z-Oxime
1H NMR (CDCl3): d = 0.39 (s, 9 H, SiMe3), 1.30 (d, J = 7.3 Hz, 3
H, Me), 3.68 (s, 3 H, OMe), 4.22 (q, J = 7.3 Hz, 1 H, CH).
1H NMR (CDCl3): d = 0.12 (s, 9 H, COSiMe3), 0.26 (s, 9 H, SiMe3),
3.95 (s, 2 H, CH2N), 4.53 (s, 2 H, CH2).
13C NMR (CDCl3): d = –1.3 (SiMe3), 16.8 (Me), 50.4 (OMe), 56.5
(CH), 154.6 (C=N), 162.7 (C=O).
13C NMR (CDCl3): d = –0.7 and –0.5 (SiMe3), 49.7 (CH2N), 57.3
(CH2), 158.2 (C=N).
Desilylation of Pure 3a–c,f,g; General Procedure
2-Azido-1-phenylethanone O-(Trimethylsilyl)oxime (3f)
Oil; Rf 0.80 (silica gel, hexane–EtOAc, 1:1).
Pure compound 3a–c,f,g (1 mmol) was added to a stirred solution
of MeOH (5 mL). The reaction mixture was maintained at 20 °C
with occasional shaking for 24 h. The solvent was evaporated in
vacuum to give analytically pure products 2.
E-Oxime
1H NMR (CDCl3): d = 0.24 (s, 9 H, SiMe3), 4.31 (s, 2 H, CH2), 7.2
and 7.5 (2 m, 5 H, Ph).
Desilylation of Crude Products 3a-i; General Procedure
Crude derivative 3a–i (1 mmol) was added dropwise to a stirred so-
lution of MeOH (5 mL). The reaction mixture was maintained at 20
°C with occasional shaking for 24 h. The solvents were evaporated
in vacuum and the residue was subjected to column chromatogra-
phy on silica gel (for yields of 2 see Table 1).
13C NMR (CDCl3): d = –0.7 (SiMe3), 53.08 (CH2), 126.1, 128.4 and
129.5 (Ph), 133.2 (ipso-Ph), 155.8 (CN).
Z-Oxime
1H NMR (CDCl3): d = 0.24 (s, 9 H, SiMe3), 4.58 (s, 2 H, CH2), 7.2
and 7.5 (2 m, 5 H, Ph).
Azido-acetaldehyde Oxime14 (2a)
Oil; Rf 0.49 (silica gel, hexane–EtOAc, 1:1).
13C NMR (CDCl3): d = –0.7 (SiMe3), 43.8 (CH2), 126.8, 128.4 and
129.5 (Ph), 134.6 (ipso-Ph), 157.2 (CN).
E-Oxime
1-Azido-3-phenylpropan-2-one O-(Trimethylsilyl)oxime (3g)
Oil; Rf 0.75 (silica gel, hexane–EtOAc, 1:1).
1H NMR (CDCl3): d = 3.88 (d, J = 5.9 Hz, 2 H, CH2), 7.45 (t,
J = 5.9 Hz, 1 H, CH), 9.33 (br, 1 H, OH).
13C NMR (CDCl3): d = 48.9 (CH2), 146.1 (CH).
E-Oxime
1H NMR (CDCl3): d = 0.13 (s, 9 H, SiMe3), 3.57 and 3.64 (2 s, 4 H,
CH2Ph and CH2), 7.0–7.2 (m, 5 H, Ph).
Synthesis 2005, No. 7, 1077–1082 © Thieme Stuttgart · New York

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Preparation of a-Azido Oximes from Aliphatic Nitro Compounds
1081
Z-Oxime
13C NMR (CDCl3): d = 27.2 (CH2CN), 30.4 (CH2CO), 46.8 (CH2),
1H NMR (CDCl3): d = 4.16 (d, J = 4.4 Hz, 2 H, CH2), 6.81 (t,
J = 4.4 Hz, 1 H, CH), 9.33 (br, 1 H, OH).
51.9 (Me), 154.6 (C=N), 173.2 (C=O).
Anal. Calcd for C6H10N4O3: C, 38.71; H, 5.41; N, 30.09. Found: C,
38.92; H, 5.58; N, 30.24.
13C NMR (CDCl3): d = 45.4 (CH2), 147.3 (CH).
Anal. Calcd for C2H4N4O: C, 24.00; H, 4.03; N, 55.98. Found: C,
24.26; H, 3.95; N, 55.96.
1-Azido-3-hydroxypropan-2-one Oxime (2e)
Oil; Rf 0.33 (silica gel, hexane–EtOAc, 1:1).
1-Azidopropan-2-one Oxime (2b)
Oil; Rf 0.54 (silica gel, hexane–EtOAc, 1:1).
E-Oxime
1H NMR (CDCl3): d = 3.2 (br, 1 H, OH), 4.28 and 4.31 (2 s, 4 H,
CH2N and CH2), 9.0 (br, 1 H, NOH).
13C NMR (CDCl3): d = 45.3 (CH2N), 61.5 (CH2), 155.0 (C=N).
IR (KBr): 3384, 2921, 2105 (N3), 1634 (C=NO), 1438, 1371, 1258,
1170, 1051, 933, 882 cm–1.
14N NMR (CDCl3): d = –313 (Dn1/2 ca.500 Hz, N2–N), –167 (Dn1/2
ca.250 Hz, N–N2), –134.1 (Dn1/2 ca.100 Hz, N–N–N), –30 (Dn1/2
ca.1000 Hz, NOH).
Z-Oxime
1H NMR (CDCl3): d = 3.2 (br, 1 H, OH), 4.05 (s, 2 H, CH2N), 4.56
(s, 2 H, CH2), 9.0 (br, 1 H, NOH).
Anal. Calcd for C3H6N4O: C, 31.58; H, 5.30; N, 49.10. Found: C,
31.63; H, 5.37; N, 49.33.
13C NMR (CDCl3): d = 50.5 (CH2N), 57.2 (CH2), 156.7 (C=N).
Anal. Calcd for C3H6N4O2: C, 27.69; H, 4.65; N, 43.06. Found: C,
27.89; H, 4.68; N, 43.13.
E-Oxime
1H NMR (CDCl3): d = 1.94 (s, 3 H, Me), 3.85 (s, 2 H, CH2), 9.66
(br, 1 H, OH).
2-Azido-1-phenylethanone Oxime (2f)
Oil, Rf 0.71 (silica gel, hexane–EtOAc, 1:1).
13C NMR (CDCl3): d = 12.2 (Me), 54.2 (CH2), 153.8 (C=N).
Z-Oxime
E-Oxime
1H NMR (CDCl3): d = 2.03 (s, 3 H, Me), 4.15 (s, 2 H, CH2), 9.66
1H NMR (CDCl3): d = 4.21 (s, 2 H, CH2), 7.4 and 7.6 (2 m, 5 H, Ph),
(br, 1 H, OH).
9.8 (br, 1 H, OH).
13C NMR (CDCl3): d = 53.8 (CH2), 126.4, 128.8 and 129.9 (Ph),
133.6 (ipso-Ph), 153.9 (C=N).
13C NMR (CDCl3): d = 17.7 (Me), 47.5 (CH2), 154.4 (C=N).
2-Azidopropionaldehyde Oxime (2c)
Oil; Rf 0.52 (silica gel, hexane–EtOAc, 1:1).
Z-Oxime
1H NMR (CDCl3): d = 4.48 (s, 2 H, CH2), 7.2 and 7.6 (2 m, 5 H, Ph),
IR (KBr): 3420, 2985, 2936, 2113 (N3), 1632 (C=NO), 1454, 1379,
1247, 1047, 955 cm–1.
9.8 (br, 1 H, OH).
13C NMR (CDCl3): d = 43.7 (CH2), 126.4, 128.1 and 128.5 (Ph),
134.1 (ipso-Ph), 155.1 (C=N).
14N NMR (CDCl3): d = –300 (Dn1/2 ca.500 Hz, N2–N), –164 (Dn1/2
ca.250 Hz, N–N2), –135.7 (Dn1/2 ca.100 Hz, N–N–N), –20 (Dn1/2
ca.1000 Hz, NOH).
Anal. Calcd for C8H8N4O: C, 54.54; H, 4.58; N, 31.80. Found: C,
54.21; H, 4.65; N, 31.57.
Anal. Calcd for C3H6N4O: C, 31.58; H, 5.30; N, 49.10. Found: C,
31.79; H, 5.30; N, 49.22.
1-Azido-3-phenylpropan-2-one Oxime (2g)
Oil; Rf 0.64 (silica gel, hexane–EtOAc, 1:1).
E-Oxime
1H NMR (CDCl3): d = 1.40 (d, J = 6.6, 3 H, Me), 4.18 (m, J = 6.6
Hz, 1 H, CH), 7.37 (d, J = 6.6 Hz, 1 H, HC=N), 8.4 (br, 1 H, OH).
E-Oxime
1H NMR (CDCl3): d = 3.84 and 3.89 (2 s, 4 H, CH2, CH2N), 7.2–7.4
13C NMR (CDCl3): d = 17.7 (Me), 55.8 (CH), 150.0 (C=N).
(m, 5 H, Ph), 9.7 (br, 1 H, OH).
13C NMR (CDCl3): d = 32.2 (CH2), 52.2 (CH2N), 127.0, 128.8 and
129.2 (Ph), 135.3 (ipso-Ph), 155.3 (C=N).
Z-Oxime
1H NMR (CDCl3): d = 1.34 (d, J = 6.6, 3 H, Me), 4.88 (m, J = 6.6
Hz, 1 H, CH), 6.71 (d, J = 6.6 Hz, 1 H, HC=N), 8.4 (br, 1 H, OH).
Z-Oxime
13C NMR (CDCl3): d = 17.0 (Me), 51.2 (CH2), 150.8 (C=N).
1H NMR (CDCl3): d = 3.71 (s, 2 H, CH2), 4.17 (s, 2 H, CH2N), 7.2–
7.4 (m, 5 H, Ph), 9.7 (br, 1 H, OH).
5-Azido-4-hydroxyiminopentanoic Acid Methyl Ester (2d)
Oil; Rf 0.55 (silica gel, hexane–EtOAc, 1:1).
13C NMR (CDCl3): d = 38.4 (CH2), 45.8 (CH2N), 127.1, 128.8 and
129.1 (Ph), 135.5 (ipso-Ph), 156.1 (C=N).
E-Oxime
Anal. Calcd for C9H10N4O: C, 56.83; H, 5.30; N, 29.46. Found: C,
56.72; H, 5.35; N, 29.18.
1H NMR (CDCl3): d = 2.64 (s, 4 H, CH2CH2), 3.65 (s, 3 H, Me),
3.92 (s, 2 H, CH2), 8.9 (br, 1 H, OH).
13C NMR (CDCl3): d = 22.2 (CH2CN), 29.5 (CH2CO), 51.9 (Me),
53.4 (CH2), 155.1 (C=N), 173.2 (C=O).
3-Azido-2-hydroxyiminopropionic Acid Ethyl Ester (2h)
Mp 70–71 °C; Rf 0.50 (silica gel, hexane–EtOAc, 1:1).
E-Oxime
Z-Oxime
1H NMR (CDCl3): d = 1.37 (t, J = 7.3 Hz, 3 H, Me), 4.25 (s, 2 H,
CH2), 4.33 (q, J = 7.3 Hz, 2 H, CH2O), 9.8 (br, 1 H, OH).
1H NMR (CDCl3): d = 2.58 and 2.62 (2 m, 4 H, CH2CH2), 3.65 (s,
3 H, Me), 4.17 (s, 2 H, CH2), 8.9 (br, 1 H, OH).
13C NMR (CDCl3): d = 14.0 (Me), 41.9 (CH2), 62.6 (CH2O), 147.0
(C=N), 162.5 (C=O).
Synthesis 2005, No. 7, 1077–1082 © Thieme Stuttgart · New York

1082
A. Yu. Sukhorokov et al.
PAPER
Z-Oxime
(4) Dilman, A. D.; Tishkov, A. A.; Lyapkalo, I. M.; Ioffe, S. L.;
Kachala, V. V.; Strelenko, Yu. A.; Tartakovsky, V. A. J.
Chem. Soc., Perkin Trans. 1 2000, 2926.
1H NMR (CDCl3): d = 1.37 (t, J = 7.3 Hz, 3 H, Me), 4.12 (s, 2 H,
CH2), 4.33 (q, J = 7.3 Hz, 2 H, CH2O), 9.8 (br, 1 H, OH).
(5) Dilman, A. D.; Lyapkalo, I. M.; Ioffe, S. L.; Strelenko, Yu.
A.; Tartakovsky, V. A. J. Org. Chem. 2000, 65, 8826.
(6) Ustinov, A. V.; Dilman, A. D.; Ioffe, S. L.; Strelenko, Yu.
A.; Smit, W. A.; Tartakovsky, V. A. Mendeleev Commun.
2003, 74.
13C NMR (CDCl3): d = 14.0 (Me), 50.6 (CH2), 62.6 (CH2O), 147.0
(C=N), 162.5 (C=O).
Anal. Calcd for C5H8N4O3: C, 34.89; H, 4.68; N, 32.55. Found: C,
34.69; H, 4.64; N, 32.20.
(7) Makarenkova, L. M.; Bliznets, I. V.; Ioffe, S. L.; Strelenko,
Yu. A.; Tartakovsky, V. A. Russ. Chem. Bull. 2000, 49,
1261.
3-Azido-2-hydroxyiminobutyric Acid Methyl Ester (2i)
Oil; Rf 0.48 (silica gel, hexane–EtOAc, 1:1).
(8) Feger, H.; Simchen, G. Liebigs Ann. Chem. 1986, 1456.
(9) Ioffe, S. L.; Makarenkova, L. M.; Strelenko, Yu. A.;
Bliznets, I. V.; Tartakovsky, V. A. Russ. Chem. Bull. 1998,
47, 1989.
(10) Lesiv, A. V.; Strelenko, Yu. A.; Ioffe, S. L.; Tartakovsky, V.
A. Helv. Chim. Acta 2002, 85, 3489.
E-Oxime
1H NMR (CDCl3): d = 1.55 (d, J = 7.3 Hz, 3 H, Me), 3.85 (s, 3 H,
OMe), 4.92 (q, J = 7.3 Hz, 1 H, CH), 10.1 (br, 1 H, OH).
13C NMR (CDCl3): d = 15.6 (Me), 50.2 (OMe), 52.8 (CH), 150.3
(C=N), 162.4 (C=O).
(11) Ustinov, A. V.; Dilman, A. D.; Ioffe, S. L.; Belyakov, P. A.;
Strelenko, Yu. A. Russ. Chem. Bull. 2002, 51, 1455.
(12) Dilman, A. D.; Lyapkalo, I. M.; Ioffe, S. L.; Strelenko, Yu.
A.; Tartakovsky, V. A. Synthesis 1999, 1767.
(13) Lesiv, A. V.; Ioffe, S. L.; Strelenko, Yu. A.; Bliznets, I. V.;
Tartakovsky, V. A. Mendeleev Commun. 2002, 99.
(14) Forster, M. O.; Fierz, H. E. J. Chem. Soc. 1908, 93, 72.
(15) Smiatacz, M.; Myszka, H. Carbohydr. Res. 1990, 196, 167;
and references cited therein.
Z-Oxime
1H NMR (CDCl3): d = 1.47 (d, J = 7.3 Hz, 3 H, Me), 3.85 (s, 3 H,
OMe), 4.35 (q, J = 7.3 Hz, 1 H, CH), 10.1 (br, 1 H, OH).
13C NMR (CDCl3): d = 16.8 (Me), 50.2 (OMe), 56.6 (CH), 150.3
(C=N), 162.4 (C=O).
Anal. Calcd for C5H8N4O3: C, 34.89; H, 4.68; N, 32.55. Found: C,
34.53; H, 4.55; N, 32.27.
(16) Takashi, T. T.; Satoh, J. Y.; Nomura, K. J. Chem. Soc.,
Perkin Trans. 1 1986, 909; and references cited therein.
(17) Shatzmiller, S.; Bercovici, S. Liebigs Ann. Chem. 1992,
1005.
(18) Heathcock, C. H.; Smith, S. C. J. Org. Chem. 1994, 59,
6828; and references cited therein.
(19) The derivatives 3 can be purified via rectification in vacuo or
after filtration through silica gel. The treatment of thus
purified intermediates 3 with methanol gave rise to azido
oximes 2 in quantitative yields without any purification.
(20) The attempts to preparate oximes 2 from ANC without
isolation of BENA 1 failed.
Acknowledgment
This work was performed at the Scientific Educational Center for
young chemists and supported by RFBR (grants ## 03-03-32777,
03-03-04001), Deutsche Forschungsgemeinschaft (grant MA 673/
19), Federal Program ‘Integration’ (project # B0062), and Scientific
School (1442.2003.3).
References
(1) For part 7, see: Lesiv, A. V.; Ioffe, S. L.; Strelenko, Yu. A.;
Danilenko, V. M. Russ. Chem. Bull. 2004, 53, 2137.
(2) Tartakovsky, V. A.; Ioffe, S. L.; Dilman, A. D.; Tishkov, A.
A. Russ. Chem. Bull. 2001, 50, 1936.
(21) Bhattacharjya, A.; Mukhopadhyay, R.; Pakrashi, S. C.
Synthesis 1985, 886.
(22) Dilman, A. D.; Ioffe, S. L.; Mayr, H. J. Org. Chem. 2001, 66,
3196.
(3) Dilman, A. D.; Tishkov, A. A.; Lyapkalo, I. M.; Ioffe, S. L.;
(23) Birkofer, L.; Wegner, P. Org. Synth. 1970, 50, 107.
Strelenko, Yu. A.; Tartakovsky, V. A. Synthesis 1998, 181.
Synthesis 2005, No. 7, 1077–1082 © Thieme Stuttgart · New York