Chlorination of oximes with aqueous H2O2/HCl system: Facile synthesis of gem-chloronitroso- and gem-chloronitroalkanes, gem-chloronitroso- and gem-chloronitrocycloalkanes

Article abstract of DOI:10.1055/s-2006-950304

Chlorination of cyclic and linear ketone oximes with aqueous H ₂O₂/HCl in a two-phase dichloromethane-water system selectively affords gem-chloronitroso compounds in yields of up to 94%. One-pot oxidation of the resulting gem-chloronitroso compounds with peracetic acid, prepared in situ, gives gem-chloronitroalkanes and cycloalkanes in yields of up to 82%. The advantages of the method are that it is facile and environmentally benign and does not require gaseous chlorine. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-950304

PAPER
3819
Chlorination of Oximes with Aqueous H2O2/HCl System: Facile Synthesis of
gem-Chloronitroso- and gem-Chloronitroalkanes, gem-Chloronitroso- and
gem-Chloronitrocycloalkanes
C
hlorination of Ox
l
imes
w
eith Aqueou 2
x
s
H
O
2/HClander O. Terent’ev,* Igor B. Krylov, Yuri N. Ogibin, Gennady I. Nikishin
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prosp., 119991 Moscow, Russia
Fax +7(495)1355328; E-mail: terentev@ioc.ac.ru
Received 5 June 2006
sized primarily from oximes by chlorination followed by
Abstract: Chlorination of cyclic and linear ketone oximes with
oxidation with an ozone-oxygen mixture,49 oxone,50 chlo-
aqueous H2O2/HCl in a two-phase dichloromethane–water system
rotriazines,51 or chloroperoxidases.52 The preparation of
gem-chloronitro compounds in low yields by the reactions
selectively affords gem-chloronitroso compounds in yields of up to
94%. One-pot oxidation of the resulting gem-chloronitroso com-
pounds with peracetic acid, prepared in situ, gives gem-chloro- of oximes with the H2O2/HCl synthesis was document-
ed.53 gem-Chloronitro compounds can also be synthesized
nitroalkanes and cycloalkanes in yields of up to 82%. The
advantages of the method are that it is facile and environmentally
benign and does not require gaseous chlorine.
by the reactions of nitro compounds with CCl4,54 by re-
ductive dehalogenation of gem-bromonitro compounds
followed by the reaction with NCS,55 by chlorination of
Key words: oximes, gem-chloronitroso compounds, gem-chloro-
nitro compounds, chlorination, oxidation, hydrogen peroxide
salts of nitro compounds,21 or by oxidation of gem-chlo-
ronitroso compounds with a tetrabutylammonium hydro-
sulfate/aqueous sodium hypochlorite system20 or
atmospheric oxygen under irradiation.47
Halogenation of organic compounds with an H2O2/HHal
system has received wide acceptance in the last decades.1–16
This system is most extensively used for halogenation of
arenes,1–3,7–14,16 alkenes,1,6 and ketones.4,5,15 The diversity
of halogenation and oxidation processes as a result of gen-
eration of several active molecules (HHalO, H2HalO+, and
Hal2) in the H2O2/HHal system17–19 allows the pathway
and selectivity of the reactions to be varied over a wide
range. The aqueous H2O2/HCl chlorination system is as
inexpensive as molecular chlorine and preferable from the
viewpoint of safety. In the present study, a new way of us-
ing the H2O2/HCl system for halogenation of organic
compounds is reported and exemplified by the synthesis
of gem-chloronitroso- and chloronitrohydrocarbons from
oximes.
In the present study, the synthesis of gem-chloronitroso
compounds was carried out in the two-phase aqueous
H2O2/HCl/CH2Cl2 system. An aqueous 34% HCl solution
was added to a solution of oxime 1, 3, or 5 in CH2Cl2, the
reaction mixture was warmed to 38–40 °C, and aqueous
37% H2O2 was added. The resulting two-phase system
contained a bright blue lower layer. Treatment of the latter
afforded gem-chloronitroso compounds (Scheme 1).
We chose cyclododecanone oxime (1g) as a model com-
pound to examine the influence of the reaction conditions
on the synthesis of chloronitroso compounds. The chlori-
nation product of 1g, viz. 1-chloro-1-nitrosocyclodode-
cane (2g), is a stable and convenient compound. The
results of chlorination of oxime 1g and oximes 1c, 1d, 1h,
3a–c, and 5 are summarized in Table 1.
These compounds are of considerable interest as interme-
diates in organic synthesis. gem-Chloronitrosoalkanes
and cycloalkanes have found use in the synthesis of gem-
chloronitro compounds,20,21 dihalides,22,23 oxazines,24–36
and O-allylated oximes.37 gem-Chloronitroalkanes and
cycloalkanes are used in the synthesis of nitro com-
pounds,20,38,39 esters of a,b-unsaturated acids,40–42 and a-
nitroalkylphosphonates.43
The nature of the solvent and the phase composition of the
system are the key factors determining the yield of nitroso
compound 2g. The reactions were carried out with the use
of MeOH, THF, dioxane, AcOH (homogeneous systems,
runs 4–7), benzene, and CH2Cl2 (heterogeneous systems,
runs 1–3). After examination of different reaction condi-
tions for chlorination of oxime 1g, we succeeded in pre-
paring product 2g in high yield (85–94%) only with the
use of a heterogeneous system (runs 1–3). An increase in
the molar excess of H2O2 from 2.5 to 4 (runs 1 and 2, re-
spectively) leads to a slight decrease in the yield of 2g due
to the formation of a small amount of chloronitro com-
pound 9g. The yields of 2g are no more than 77% by chlo-
rination of oxime 1g in a homogeneous system (runs 4–7).
Presumably, different results of chlorination are attributed
to the fact that the reaction in heterogeneous systems
(Scheme 2) occurs in an organic solvent under the action
of molecular chlorine (Table 1, runs 1–3 and 8–14),
Procedures for the synthesis of gem-chloronitroso com-
pounds are based on chlorination of oximes with chlo-
rine,21,22,44–47 tert-butyl hypochlorite,36 and N-tert-butyl N-
chlorocyanamide.48 Since low-molecular-weight gem-
chloronitroso compounds are unstable, syntheses with the
use of these compounds are generally performed without
their isolation. gem-Chloronitro compounds are synthe-
SYNTHESIS 2006, No. 22, pp 3819–3824
x
x
.x
x
.
2
0
0
6
Advanced online publication: 09.10.2006
DOI: 10.1055/s-2006-950304; Art ID: P06706SS
© Georg Thieme Verlag Stuttgart · New York

3820
A. O. Terent’ev et al.
PAPER
NOH
NOH
R2
Cl
NO2
( )n
Cl
NO2
R2
i, ii
i, ii
R1
R1
( )n
3a–c
7b–c
R
a R1 = R2 = iPr
b R1 = R2 = Bu
R
i
9a–h
1a–h
c R1 = R2 = C5H11
Cl
R1
NO
R2
i
a (n = 0, R = H); b (n = 1, R = H);
c (n = 1, R = Me); d (n = 1, R = tBu);
e (n = 2, R = H); f (n = 3, R = H);
g (n = 7, R = H); h (n = 10, R = H)
Cl
NO
4a–c
( )n
R
2c,d,g,h
Cl
Cl
NO
NOH
i, ii
i
NO2
8
5
6
Scheme 1 Reagents and conditions: i. aq H2O2/HCl/CH2Cl2, 20 min, 38–40 °C; ii. aq H2O2–AcOH, 2–12 h, 25–30 °C.
Water H2O2 + HCl = HClO + H2O
phase HClO + HCl = Cl2 + H2O
Table 1 Chlorination of Oximes 1c, 1d, 1h, 1g, 3a–c, and 5 with the
Aqueous H2O2/HCl Systema
Run
Oxime
Solvent
H2O2/oxime Product
molar ratio
Yield
(%)b
Cl
NOH
OH
NO
Cl
N
Cl
CH2Cl2
phase
1
2
1g
1g
1g
1g
1g
1g
1g
1c
1d
1h
3a
3b
3c
5
CH2Cl2
CH2Cl2
benzene
MeOH
THF
2.5
4
2g
2g
2g
2g
2g
2g
2g
2c
2d
2h
94
85
84
trace
73
77
32
79
84
89
78
87
88
76
– HCl
Scheme 2
3
2.5
2.5
2.5
3
the presence of a smaller excess of H2O2 (run 14) because
the nitroso group in this compound is more prone to fur-
ther oxidation.
4c
5c
6c
7c
8
Under the condition optimized for chlorination of cy-
clododecanone oxime 1g, we performed chlorination of
oximes 1a,b,e containing five-to-seven-membered rings.
It was difficult to directly estimate the yield of chloroni-
troso compounds because of their lability. The fact that
oxidation of these oximes affords chloronitroso com-
pounds in high yields is indirectly evident from the yields
of chloronitro compounds 9a,b,e because the one-pot syn-
thesis of the latter proceeds through the formation of chlo-
ronitroso compounds.
dioxane
AcOH
3
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
2.5
2.5
2.5
2.5
2.5
2.5
2.1
9
10
11
12
13
14
4a
4b
As mentioned above, a simple increase in the excess of
hydrogen peroxide in run 2 (Table 1) did not lead to the
formation of chloronitrocyclododecane (2g) from oxime
with good selectivity. With the aim of developing a con-
venient procedure for the synthesis of chloronitro com-
pounds 7a–c, 8, and 9a–h, we examined oxidation of
oximes with peracetic acid prepared in situ (Scheme 1,
Table 2). The course of the reaction was monitored visu-
ally by observing the decrease in the intensity of the blue
color of the reaction mixture. After completion of the re-
actions, the solutions turned almost colorless.
4c
6
a For general reaction conditions, see experimental.
b The yields are given with respect to the isolated product.
c The reaction mixture was warmed at 45–50 °C.
whereas deoximation of oximes followed by chlorination
of the resulting ketones are the essential side processes in
homogeneous systems (runs 4–7).
In heterogeneous conditions with the use of CH2Cl2 as the
solvent, products 2c,d,h, 4a–c, and 6 were obtained in 76–
89% yields (runs 8–14). Compound 6 was synthesized in
According to this procedure, oxidative chlorination of
oximes was carried out in two steps. Initially, the reaction
with a fourfold molar excess of hydrogen peroxide afford-
Synthesis 2006, No. 22, 3819–3824 © Thieme Stuttgart · New York

PAPER
Chlorination of Oximes with Aqueous H2O2/HCl
3821
Table 2 Synthesis of gem-Chloronitroalkanes and gem-Chloronitrocycloalkanesa
Run
15
16
17
18
19
20
21
22
23
24
25
26
27
1h
Oxime
3a
3b
3c
5
1a
1b
1b
1c
1d
1e
1f
1g
Yield (%)
7a –c 7b 81 7c 82 8 82 9a 74 9b 79 9b 63d 9c 67 9d 73 9e 60 9f 48 9ge 81 9h 80
of chloronitro compoundsb
a For general reaction conditions, see experimental.
b The yields are given with respect to the isolated product.
c Compound 7a was not obtained.
d The HCO2H/H2O2 system was used as an oxidizing agent for the chloronitroso compound formed in situ.
e The synthesis was scaled with increasing amounts of the reagents by a factor of 10.
H2O2 solution and an aq 34% HCl solution of high purity grade were
used without additional purification.
ed predominantly chloronitroso compounds and small
amounts of chloronitro compounds. Then acetic acid and
a tenfold excess of hydrogen peroxide were added to the Oximes 1a–h, 3a–c, and 5 were prepared by the reaction of
NH2OH·HCl with the corresponding ketones.
bright blue reaction mixture and the mixture was stirred
1a, mp 56–57.5 °C (Lit.56 mp 57–58.5 °C); 1c, mp 35–37 °C (Lit.57
mp 36–37 °C); 1d, mp 86–88 °C (Lit.58 mp 87–89 °C); 1e, bp 70–
73 °C/1 Torr (Lit.59 bp 150–152 °C/20 Torr); 1f, mp 35–37 °C
(Lit.59 mp 35–37 °C); 1g, mp 133–135 °C (Lit.60 mp 133–134 °C);
1h, mp 76–78 °C (Lit.59 mp 76–77 °C); 3a, mp 31–33 °C (Lit.61 mp
34 °C); 3b, bp 110–112 °C/8 Torr) (Lit.62 bp 125 °C/15 Torr); 3c,
bp 132–134 °C/8 Torr) (Lit.63 bp 144.2 °C/12 Torr); 5, mp 163–
164.5 °C (Lit.64 mp 164.5–165.5 °C).
until it turned colorless.
Attempts to synthesize gem-chloronitro compound 7a
from diisopropylketone oxime 3a containing the sterically
hindered reaction center essentially failed (run 15). Chlo-
ronitro compounds 9e (run 24) and 9f (run 25) were pre-
pared in moderate yields (60% and 48%, respectively).
Apparently, this is attributed to low stability of intermedi-
ate chloronitroso compounds, which have no time to be
oxidized to nitro compounds and are consumed in com-
petitive side reactions. The yields of nitro compounds in
runs 16–23 and 26–27 are rather high (74–82%). The syn-
thesis of 1-chloro-1-nitrocyclohexane (9b) demonstrated
that the reaction with performic acid prepared in situ af-
fords the target product in lower yield (63%, run 21) than
the reaction with peracetic acid (79%, run 20).
The solvents CH2Cl2, MeOH, benzene, THF, dioxane, AcOH,
HCO2H, and petroleum ether (40–70) of high purity grade were
used without additional purification.
Chloronitroso Compounds; General Procedure
Oxime (0.5 g, 2.09–3.94 mmol) was dissolved in CH2Cl2 (MeOH,
benzene, THF, dioxane, or AcOH; 10 mL), a five-fold molar excess
of aq 34% HCl (1.125–2.11 g, 10.45–19.63 mmol) was added, and
the mixture was warmed to 38–40 °C (45–50 °C for MeOH, THF,
dioxane, or AcOH). Then aq 37% H2O2 solution (2.1–4-fold molar
excess) was added with stirring in 1 min. The mixture was stirred
for 20 min and cooled to 20 °C. Petroleum ether (50 mL) and H2O
(50 mL) were added. The lower layer was separated, and the upper
layer was washed with H2O (4 × 10 mL), dried (MgSO4), filtered
and concentrated. The target chloronitroso compounds were isolat-
ed by flash chromatography using petroleum ether as the eluent.
Nitroso and nitro compounds have low polarity and are
readily soluble in hexane in petroleum ether, due to which
these solvents are convenient both for isolation from the
reaction mixture and chromatography.
In conclusion, we found the conditions for the synthesis of
gem-chloronitrosoalkanes and chloronitrosocycloalkanes
by oxidation of linear alkanone and cycloalkanone oximes
with aqueous H2O/HCl. The two-phase dichloromethane–
water system is a mixture of choice for this purpose. The
one-pot synthesis of gem-chloronitroalkanes and chloron-
itrocycloalkanes was carried out by oxidation of the cor-
responding nitroso compounds with peracetic acid
prepared in situ. Depending on the structure of oximes,
1-Chloro-4-methyl-1-nitrosocyclohexane (2c)65
Blue oil; mixture of isomers; Rf = 0.59 (petroleum ether).
1H NMR (250.13 MHz, CDCl3): d = 0.91–1.10 (m, 3 H, CH3), 1.35–
1.93 (m, 7 H, CH, CH2), 2.49–2.77 (m, 2 H, CH2).
13C NMR (125 MHz, CDCl3): d = 20.4, 21.8 (CH3), 29.7, 30.9, 31.4,
32.0, 32.8, 34.3 (CH, CH2), 111.9, 118.8 (C).
chloronitro and chloronitroso compounds were synthe- 4-tert-Butyl-1-chloro-1-nitrosocyclohexane (2d)20
sized in 48–94% yields. The method is facile and environ-
mentally benign and affords the target products in high
yields.
Blue oil; mixture of isomers; Rf = 0.61 (petroleum ether).
1H NMR (250.13 MHz, CDCl3): d = 0.87, 0.94 (s, 9 H, t-C4H9),
1.26–2.09 (m, 7 H, CH, CH2), 2.48–2.82 (m, 2 H, CH2).
13C NMR (125 MHz, CDCl3): d = 22.4, 25.2, 27.4 (for both iso-
mers), 31.8, 32.4 (C), 33.3, 37.3 (CH2), 46.7, 46.8 (CH), 119.2,
109.5 (CCl).
The NMR spectra were recorded on Bruker DRX-500 (125 MHz for
13C), Bruker WM-250 (250.13 MHz for 1H and 62.9 MHz for 13C),
1
and Bruker AC-200 (200.13 MHz for H and 50.32 MHz for 13C)
1-Chloro-1-nitrosocyclododecane (2g)21
Blue crystals; mp 55.5–56.5 °C (CHCl3) (Lit.21 mp 53–55 °C);
Rf = 0.57 (petroleum ether).
1H NMR (200.13 MHz, CDCl3): d = 1.30–1.92 (m, 20 H, CH2),
2.29–2.52 (m, 2 H, CH2C).
spectrometers in CDCl3. The TLC analysis was carried out on chro-
matographic Silufol UV-254 plates. Column chromatography was
performed with the use of 63–200 mesh silica gel (Merck). Melting
points were determined on a Kofler hot stage and are uncorrected.
Ketones, hydroxylamine hydrochloride, and cyclohexanone oxime
(1b) were commercial reagents (Aldrich and Acros). An aq 37%
Synthesis 2006, No. 22, 3819–3824 © Thieme Stuttgart · New York

3822
A. O. Terent’ev et al.
PAPER
13C NMR (50.32 MHz, CDCl3): d = 20.2, 22.1, 22.6, 25.6, 26.2
(CH2), 32.6 (CH2C), 118.8 (C).
colorless. Petroleum ether (50 mL) and H2O (50 mL) were added,
the lower aqueous layer was separated, and the upper layer was
washed with H2O (4 × 10 mL), dried (MgSO4), and filtered. The fil-
trate was concentrated, and the target chloronitro compounds were
isolated by flash chromatography using petroleum ether as the elu-
ent.
Anal. Calcd for C12H22ClNO: C, 62.19; H, 9.57; N, 6.04. Found: C,
62.28; H, 9.53; N, 6.08.
1-Chloro-1-nitrosocyclopentadecane (2h)66
Blue oil; Rf = 0.63 (petroleum ether).
1H NMR (250.13 MHz, CDCl3): d = 1.25–1.70 (m, 24 H, CH2),
1.79–1.94 (m, 2 H, CH2C), 2.30–2.45 (m, 2 H, CH2C).
13C NMR (62.9 MHz, CDCl3): d = 22.4 26.4, 26.6, 26.7, 27.0, 27.5
(CH2), 35.4 (CH2C), 118.5 (C).
5-Chloro-5-nitrononane (7b)50
Colorless oil; Rf = 0.52 (petroleum ether).
1H NMR (250.13 MHz, CDCl3): d = 0.89 (t, J = 6.6 Hz, 6 H, CH3),
1.15–1.65 (m, 8 H, CH2), 2.09–2.43 (m, 4 H, CH2C).
13C NMR (62.9 MHz, CDCl3): d = 13.7 (CH3), 22.1 (CH2CH3), 26.2
(CH2CH2CH3), 41.8 (CH2C), 110.4 (C).
Anal. Calcd for C15H28ClNO: C, 65.79; H, 10.31; N, 5.11; Cl, 12.95.
Found: C, 65.84; H, 10.67; N, 5.22; Cl, 12.89.
6-Chloro-6-nitroundecane (7c)
Colorless oil; Rf = 0.54 (petroleum ether).
1H NMR (250.13 MHz, CDCl3): d = 0.89 (t, J = 6.6 Hz, 6 H, CH3),
1.15–1.63 (m, 8 H, CH2), 2.10–2.43 (m, 4 H, CH2C).
13C NMR (62.9 MHz, CDCl3): d = 13.7 (CH3), 22.2, 23.7, 31.0
(CH2), 42.0 (CH2C), 110.3 (C).
3-Chloro-2,4-dimethyl-3-nitrosopentane (4a)
Blue oil; Rf = 0.6 (petroleum ether).
1H NMR (250.13 MHz, CDCl3): d = 0.88 (d, J = 6.6 Hz, 6 H, CH3),
1.05 (d, J = 6.6 Hz, 6 H, CH3), 3.33 (m, 2 H, CH).
13C NMR (62.9 MHz, CDCl3): d = 16.7, 17.3 (CH2), 34.3 (CH2C),
120.7 (C).
Anal. Calcd for C11H22ClNO2: C, 56.04; H, 9.41; N, 5.94. Found: C,
56.28; H, 9.63; N, 5.81.
Anal. Calcd for C7H14ClNO: C, 51.38; H, 8.62; N, 8.56; Cl, 21.66.
Found: C, 51.29; H, 8.72; N, 8.45; Cl, 21.80.
2-Chloro-2-nitroadamantane (8)51
White crystals; mp 190–191 °C (CHCl3) (Lit.51 mp 192–193 °C);
Rf = 0.49 (petroleum ether).
5-Chloro-5-nitrosononane (4b)
Blue oil; Rf = 0.65 (petroleum ether).
1H NMR (250.13 MHz, CDCl3): d = 0.86 (t, J = 6.9 Hz, 6 H, CH3),
1.20–1.38 (m, 8 H, CH2), 2.18–2.34 (m, 2 H, CH2C), 2.53–2.67 (m,
2 H, CH2C).
13C NMR (62.9 MHz, CDCl3): d = 13.7 (CH3), 22.6 (CH2CH3), 25.3
(CH2CH2CH3), 37.3 (CH2C), 122.4 (C).
1H NMR (250.13 MHz, CDCl3): d = 1.70–2.82 (m, 14 H, CH2, CH).
13C NMR (62.9 MHz, CDCl3): d = 25.5, 25.9, 34.1, 34.8, 37.0, 37.4
(CH2, CH), 108.0 (C).
Anal. Calcd for C10H14ClNO2: C, 55.69; H, 6.54; N, 6.49. Found: C,
55.28; H, 6.53; N, 6.18.
Anal. Calcd for C9H18ClNO: C, 56.39; H, 9.46; N, 7.31; Cl, 18.49.
Found: C, 56.71; H, 9.63; N, 7.02; Cl, 18.21.
1-Chloro-1-nitrocyclopentane (9a)49
Colorless oil; Rf = 0.40 (petroleum ether).
1H NMR (200.13 MHz, CDCl3): d = 1.75–2.05 (m, 4 H, CH2), 2.25–
2.43 (m, 2 H, CH2C), 2.62–2.85 (m, 2 H, CH2C).
13C NMR (50.32 MHz, CDCl3): d = 23.1 (CH2), 42.1 (CH2C), 107.5
(C).
6-Chloro-6-nitrosoundecane (4c)65
Blue oil; Rf = 0.69 (petroleum ether).
1H NMR (250.13 MHz, CDCl3): d = 0.85 (t, J = 6.9 Hz, 6 H, CH3),
1.16–1.38 (m, 12 H, CH2), 2.15–2.35 (m, 2 H, CH2C), 2.50–2.66
(m, 2 H, CH2C).
13C NMR (62.9 MHz, CDCl3): d = 13.7 (CH3), 22.2, 22.8, 31.6
(CH2), 37.5 (CH2C), 122.1 (C).
1-Chloro-1-nitrocyclohexane (9b)52
Colorless oil; Rf = 0.39 (petroleum ether).
1H NMR (250.13 MHz, CDCl3): d = 1.49–1.85 (m, 6 H, CH2), 2.20–
2-Chloro-2-nitrosoadamantane (6)67
2.49 (m, 4 H, CH2C).
Blue crystals; mp 154–156 °C (CHCl3) (Lit.67 mp 161–163 °C);
Rf = 0.57 (petroleum ether).
13C NMR (62.9 MHz, CDCl3): d = 22.9, 23.9 (CH2), 38.2 (CH2C),
103.7 (C).
1H NMR (250.13 MHz, CDCl3): d = 1.69–2.12 (m, 5 H, CH2, CH),
2.22–2.51 (m, 9 H, CH2, CH).
13C NMR (62.9 MHz, CDCl3): d = 26.87, 26.94, 34.3, 34.5, 34.7,
37.0, 37.5, 44.8 (CH2, CH), 114.0 (C).
1-Chloro-4-methyl-1-nitrocyclohexane (9c)
Colorless oil; mixture of isomers Rf = 0.45 (petroleum ether).
1H NMR (250.13 MHz, CDCl3): d = 0.85–0.98 (m, 3 H, CH3), 1.32–
2.93 (m, 9 H, CH, CH2).
13C NMR (62.9 MHz, CDCl3): d = 20.7, 21.2 (CH3), 29.6, 30.7
(CH), 30.6, 31.4 (CH2), 37.7, 37.9 (CH2C), 101.4, 104.6 (C).
Anal. Calcd for C10H14ClNO: C, 60.15; H, 7.07; N, 7.01. Found: C,
60.25; H, 7.33; N, 6.88.
Chloronitro Compounds; General Procedure
Oxime (0.5 g, 2.09–5.05 mmol) was dissolved in CH2Cl2 (10 mL),
a five-fold molar excess of aq 34% HCl (1.125–2.71 g, 10.45–25.25
mmol) was added, and the mixture was warmed to 38–40 °C. Then
aq 37% H2O2 (four-fold molar excess) was added with stirring in 1
min, the mixture was stirred for 20 min, AcOH (HCO2H) (10 mL)
and a tenfold molar excess of aq 37% H2O2 (1.92–4.64 g, 20.9–50.5
mmol) were added, and the mixture was finally stirred at 25–30 °C
for 2–12 h. If the conversion of the nitroso compound was incom-
plete, a five-fold molar excess of aq 37% H2O2 (0.96–2.32 g, 10.45–
25.25 mmol) was added and the mixture was stirred until it turned
Anal. Calcd for C7H12ClNO2: C, 47.33; H, 6.81; N, 7.89; Cl, 19.96.
Found: C, 47.58; H, 6.55; N, 7.68; Cl, 19.62.
4-tert-Butyl-1-chloro-1-nitrocyclohexane (9d)68
Colorless oil; mixture of isomers; Rf = 0.47 (petroleum ether).
1H NMR (250.13 MHz, CDCl3): d = 0.82 (0.88) (s, 9 H, t-C4H9),
1.05–2.28 (m, 7 H, CH, CH2), 2.46–3.07 (m, 2 H, CH2).
13C NMR (62.9 MHz, CDCl3): d = 23.5, 24.9, 26.9, 27.0, 31.5, 32.2
(C), 38.4, 38.8 (CH2), 45.7, 46.3 (CH), 101.0, 104.8 (CCl).
Synthesis 2006, No. 22, 3819–3824 © Thieme Stuttgart · New York

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Chlorination of Oximes with Aqueous H2O2/HCl
3823
1-Chloro-1-nitrocycloheptane (9e)20
Colorless oil; Rf = 0.46 (petroleum ether).
(11) Vyas, P. V.; Bhatt, A. K.; Ramachandraiah, G.; Bedekar, A.
V. Tetrahedron Lett. 2003, 44, 4085.
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1996, 334.
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E. S. h. Russ. J. Org. Chem. 1993, 29, 1519; Zh. Org. Khim.
1993, 29, 1828.
1H NMR (250.13 MHz, CDCl3): d = 1.52–1.82 (m, 8 H, CH2), 2.32–
2.75 (m, 4 H, CH2C).
13C NMR (62.9 MHz, CDCl3): d = 22.7, 28.2 (CH2), 42.4 (CH2C),
108.6 (C).
(14) Hanson, J. R.; Opakunle, A.; Petit, P. J. Chem. Res., Synop.
1995, 457.
(15) Tillu, V. H.; Shinde, P. D.; Bedekar, A. V.; Wakharkar, R.
D. Synth. Commun. 2003, 33, 1399.
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B. Org. Process Res. Dev. 1999, 3, 10. (b) Mukhopadhyay,
S.; Ananthakrishnan, S.; Chandalia, S. B. Org. Process Res.
Dev. 1999, 3, 196. (c) Mukhopadhyay, S.;
Ananthakrishnan, S.; Chandalia, S. B. Org. Process Res.
Dev. 1999, 3, 451.
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64, 1191.
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York, 1990.
1-Chloro-1-nitrocyclooctane (9f)68
Colorless oil; Rf = 0.48 (petroleum ether).
1H NMR (250.13 MHz, CDCl3): d = 1.51–1.88 (m, 10 H, CH2),
2.20–2.81 (m, 4 H, CH2C).
13C NMR (62.9 MHz, CDCl3): d = 22.9, 24.4, 27.4 (CH2), 37.2
(CH2C), 108.5 (C).
1-Chloro-1-nitrocyclododecane (9g)21
White crystals; mp 48.5–49.5 °C (CHCl3) (Lit.21 mp 49.5–50.5 °C);
Rf = 0.52 (petroleum ether).
1H NMR (250.13 MHz, CDCl3): d = 1.15–1.62 (m, 18 H, CH2),
2.13–2.42 (m, 4 H, CH2C).
13C NMR (62.9 MHz, CDCl3): d = 20.6, 22.0, 22.3, 25.5 (CH2), 35.1
(CH2C), 106.4 (C).
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64.
1-Chloro-1-nitrocyclopentadecane (9h)
Colorless oil; Rf = 0.57 (petroleum ether).
1H NMR (250.13 MHz, CDCl3): d = 1.15–1.60 (m, 24 H, CH2),
2.14–2.51 (m, 4 H, CH2C).
13C NMR (62.9 MHz, CDCl3): d = 22.7, 26.5–26.8 (CH2), 38.5
(CH2C), 106.8 (C).
Anal. Calcd for C15H28ClNO2: C, 62.16; H, 9.74; N, 4.83; Cl, 12.23.
Found: C, 62.38; H, 9.43; N, 4.59; Cl, 12.01.
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Tetrahedron 1981, 37, 629.
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J. Synthesis 2000, 1719.
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Acknowledgment
This work is supported by the Program for Support of Leading Sci-
entific Schools of the Russian Federation (Grant NSh 5022.2006.3)
and the Russian Science Support Foundation.
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