Direct C-nitration of cyclic α,β-unsaturated oximes under the action of sodium nitrite and acetic acid in methanol

Article abstract of DOI:10.1023/A:1012785007135

Using a number of cyclic α,β-unsaturated oximes of the terpene series and some simplest model compounds as examples, unsaturated oximes bearing a hydrogen atom at the β-carbon atom were demonstrated to be converted into β-hydroxyiminonitroalkenes under the action of sodium nitrite and acetic acid in methanol. In the case of the introduction of an alkyl substituent at the terminal carbon atom of the diene C = C-C=NOH fragment, the reaction performed under the same conditions gave rise exclusively to conjugated ketone (a deoximation product).

Full text of DOI:10.1023/A:1012785007135

1410
Russian Chemical Bulletin, International Edition, Vol. 50, No. 8, pp. 1410—1418, August, 2001
Direct C-nitration of cyclic α,β-unsaturated oximes under the action
of sodium nitrite and acetic acid in methanol
A. M. Chibiryaev,a« A. Yu. Denisov,b D. V. Pyshnyi,b and A. V. Tkachevc
àNovosibirsk State University, Department of Natural Sciences,
2 ul. Pirogova, 630090 Novosibirsk, Russian Federation.
Fax: +7 (383 2) 34 4752. E-mail: chibirv@nioch.nsc.ru
bInstitute of Bioorganic Chemistry, Siberian Branch of the Russian Academy of Sciences,
8 prosp. Akad. Lavrent´eva, 630090 Novosibirsk, Russian Federation.
cN. N. Vorozhtsov Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences,
9 prosp. Akad. Lavrent´eva, 630090 Novosibirsk, Russian Federation.
Fax: +7 (383 2) 34 4752/34 4855. E-mail: atkachev@nioch.nsc.ru
Using a number of cyclic α,β-unsaturated oximes of the terpene series and some simplest
model compounds as examples, unsaturated oximes bearing a hydrogen atom at the β-carbon
atom were demonstrated to be converted into β-hydroxyiminonitroalkenes under the action of
sodium nitrite and acetic acid in methanol. In the case of the introduction of an alkyl
substituent at the terminal carbon atom of the diene C=C—C=NOH fragment, the reaction
performed under the same conditions gave rise exclusively to conjugated ketone (a deoximation
product).
Key words: α,β-unsaturated oximes, conjugated ketones, nitrosation, C-nitration,
deoximation, nitroalkenes, circular dichroism.
Recently, we have reported1 that oximes of a num-
Scheme 2
ber of cyclic α,β-unsaturated ketones were converted
under the action of sodium nitrite in acetic acid into
R2
R1
unsaturated nitroacetates (Scheme 1).
NOH
NaNO2—AcOH—MeOH
Scheme 1
R2
Me
R1
O2N
NOH
O
NOH
NaNO2—AcOH
or
R
31—62%
(R1 = H)
15—70%
O2N
OAc
O2N
R1 = H, R2 = Me; R1 = Me, R2 = H; R1 = R2 = Me
and/or
OAc
Reaction conditions: 4 h—7 days, ∼20 °C.
R
R
Reaction conditions: +5—10 °C, 2—4 h.
number of α,β-unsaturated oximes of the terpene series
and some structurally simpler model compounds under
the action of the NaNO2—AcOH system using metha-
nol as the solvent. Below are presented the results of
these investigations.
The use of methanol as the solvent with re-
tention of the above-mentioned nitrosating system
(NaNO2—AcOH) was found to have a dramatic effect
on the course of the reaction giving rise to different
products, predominantly, β-hydroxyiminonitroalkenes
(Scheme 2).
Results and Discussion
Since nitroalkenes are being extensively studied and
are used as precursors in the synthesis of some heterocy-
clic compounds, natural compounds, and drugs,2 we
carried out detailed investigation of conversions of a
We studied the behavior of oximes of (+)-car-2-en-
4-one (1), (–)-carvone (2), 2-methylcyclohex-2-en-1-
one (3), eucarvone (4), and pinocarvone (5) in the
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1342—1349, August, 2001.
1066-5285/01/5008-1410 $25.00 ©ꢀ2001 Plenum Publishing Corporation

Nitration of α,β-unsaturated oximes with NaNO2
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 8, August, 2001
1411
reactions with NaNO2 and AcOH in MeOH (Scheme 3).
The time required for complete conversion of the starting
oximes varied from 4 h to 7 days and can be represented
as the following sequence: t1 > t3 > t4 > t2 ≈ t5. In the
case of oxime 1, the degree of conversion was only 35%
although more than 10 equiv. of NaNO2 were used and
the reaction was carried out for 7 days. The reaction of
carvone oxime 2 afforded ketone of carvone (8) along
with the major product. After chromatography, the yield
of 8 was 10%.
In all cases, conjugated nitro oximes 6, 7, 9, 11, and
12 were obtained as the major reaction products
(Scheme 3). Their structures were established by spec-
tral methods. In the 1H NMR spectra of the products, a
signal for the olefinic proton at the β-carbon atom of
the HCβ=Cα—C=NOH fragment (in the case of the
starting oximes 1, 2, 3, and 5) and a signal for the
hydrogen atom at the terminal carbon atom of the
triene HCδ=Cγ—Cβ=Cα—C=NOH system (in the case
of oxime 4) disappear, while the remaining signals of
the starting compounds (including the signal of
HO—N=) persist. Detailed analysis of the 1H and
13C NMR spectra suggested that the carbon skeleton of
the initial oximes was retained in the reaction products.
The mass spectra and the data from elemental analysis
of the products are indicative of the introduction of the
nitro group into the molecules. The IR spectra of the
products have two intense absorption bands in the re-
gions of 1325—1341 and 1509—1538 cm–1, which are
characteristic of the conjugated nitro group.
Scheme 3
10
3
NOH
O2N
NOH
2
4
5
E
1
62%
6
9
7
8
The formation of β-nitroalkenes from α,β-unsatur-
ated oximes can occur through two essentially different
pathways shown in Scheme 4.
ꢀ
$
10
2
First, the formation of nitroalkenes can be con-
ceived as direct nitration, i.e., as the replacement of the
vinyl hydrogen atom at the β position with respect to
the oxime group, the latter remaining intact (path A).
This reaction pathway should afford products 6, 7, 9,
11, and 12. Second, the reactions of oximes in the
NaNO2—AcOH system are generally considered as
nitrosation because the product of addition of the
nitrosonium cation NO+ to the substrate is formed as
the primary reaction product. The addition of NO+ at
the terminal atom of the diene system (at the β position
with respect to the oxime group; path B in Scheme 4)
should give rise to the nitroso group at the secondary
carbon atom resulting in the appearance of the oxime
group due to the subsequent obligatory tautomeric con-
version. Taking into account that the NaNO2—AcOH
system, among other things, acts as an oxidizer and that
the formation of nitro compounds upon oxidation of
oximes is a well-known process, the conversion of the
oxime group into the nitro group could be the final
stage of the reaction according to path B.
NOH
O2N
NOH
O
3
1
6
E
+
4
5
7
8
9
% (31%)
& (10%)
7
2
OH
NOH
O2N
3
O2N
NOH
NOH
1
6
E
+
4
5
!
' (44%)
ꢀꢁ* (10%)
10
2
NOH
NOH
3
1
E
4
7
40%
6
5
9
O2N
8
Hence, alternative structures 6a, 7a, 9a,* 11a, and
12a, which could be formed due to conversion through
path B, can be related to structures 6, 7, 9, 11, and 12,
respectively. Therefore, the unambiguous proof of struc-
tures 6, 7, 9, 11, and 12 will allow an understanding of
the mechanism of formation of nitroalkenes from unsat-
urated oximes.
In all starting oximes 1—5, the oxime group has the
E configuration. A comparison of the chemical shifts of
the signals for the atoms of the adjacent methylene
group in the 1H and 13C NMR spectra of the initial
oximes and the corresponding nitroolefins unambigu-
ꢀꢀ
O2N
"
10
NOH
NOH
2
1
3
E
7
4
54%
9
6
5
8
#*
ꢀ *
Reagents and conditions: i. NaNO2—AcOH—MeOH, ∼20 °C,
4 h—7 days.
* Hereinafter, the racemate is marked with an asterisk («).
* 9a ≡ 9.

1412
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 8, August, 2001
Chibiryaev et al.
Scheme 4
ON
O2N
NOH
NOH
NOH
HON
NO2
+
H
+[O]
–
)
*
–H
HON
NO2
O2N
NOH
%=
HON
H
HON
NO2
NO2
HON
NO2
NO2
HON
ꢀꢀ=
$=
ꢀ =
'= ≡ '
ously indicates that the oxime group in the nitration
products retains the E configuration. In the 13C NMR
spectrum of nitroalkene 12 prepared from pinocarvone
oxime (5), the signal at δC 149.68 corresponds to the
azomethine C(3) atom, which has the vicinal spin-spin
coupling constant with the hydrogen atom of the
HO—N=C(3) oxime group (3JC(3)—H = 8.1 Hz).
In addition, the H(10) atom has the spin-spin
coupling constants with the C(1) and C(3) atoms
that the shape of the circular dichroism curves (CD
curves) correlates with the syn/anti isomerism of the
oxime group.4—6
Since the oxime group in all compounds under
consideration has the E configuration, the shape of the
CD curves should be determined only by the absolute
configuration of these compounds. The CD curve of
oxime 1 has two extrema with opposite signs of the
Cotton effect, viz., the negative effect at λ = 227 nm
(3JH(10)—C(1) = 6.5 Hz; JH(10)—C(3) = 4.3 Hz) whose
(∆ε = –8.9 mol–1 L cm–1, π→π* transition) and the posi-
3
–1
values indicate that the H(10) atom is in the cis orienta-
tion with respect to the C(3) atom. The structure of
nitro derivative 6 prepared from oxime 1 was proved
analogously. In the 2D 13C—1H COSY NMR spectrum
of product 6 at the long-range spin-spin coupling con-
stants 2,3J (tuning to J = 10 Hz), the only cross-peak at
δC 152.44 (the signal for the azomethine C(4) atom)
was observed for the signal of HO—N= (δH 11.89). This
cross-peak, in turn, has cross-peaks with the H(5α) and
H(5β) atoms at δH 2.64 and δH 2.75, respectively. These
facts provide unambiguous support for structure 6 and
allows one to reject alternative structure 6a.
tive extremum at λ = 263 nm (∆ε = +8.7 mol–1 L cm
,
n→π* transition) (Fig. 1). A comparison of the CD
curves of oxime 1 and compound 6 clearly demon-
strates that the extrema are shifted bathochromically
(227 → 283 nm and 263 → 348 nm) on going from
unsaturated oxime to nitro oxime due to conjugation of
the diene system with the nitro group; in this case the
signs of both extrema are retained and the intensity of
dichroic absorption decreases. The Cotton effects in the
CD curve of (–)-carvone oxime (2) are opposite in sign
–1
–1
(λ = 222 nm with ∆ε = +4.1 mol
λ = 247 nm with ∆ε = –3.4 mol
L cm
and
L cm–1) to those
–1
For nitro compounds 7 and 9, the origin of the nitro
group cannot be inferred from the NMR spectral data.
Hence, we proved structure 7 based on the fact that the
corresponding product was prepared from optically ac-
tive carvone oxime (2).
It is known that the chiroptical properties of com-
pounds are determined by their spatial molecular struc-
tures. For α,β-unsaturated ketones, there are simple
correlations between the observed Cotton effect and the
three-dimensional molecular structure.3 However, no
analogous regularities have been revealed for oximes of
α,β-unsaturated ketones because of a small number of
the models studied. It can only be said with assurance
observed in the CD curve of oxime 1. On going from
oxime 2 to nitro oxime 7, only the bathochromic shift
of the extrema is observed (222 → 275 nm and
247 → 341 nm) with retention of the signs of the Cotton
effects. This is evidence for structure 7 because the signs
of the Cotton effects in the case of structure 7a would
be expected to be reversed on going from oxime to
nitro oxime.
A comparison of the 1H and 13C NMR spectra of
eucarvone oxime (4) and nitroolefin 11 demonstrated
that the chemical shifts of the C(7), H(7), C(10), and
H(10) atoms located in the vicinity of the oxime group
differ only slightly, which is indicative of retention of its

Nitration of α,β-unsaturated oximes with NaNO2
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 8, August, 2001
1413
–1
–1
∆ε/mol L cm
nitrosation, the trisubstituted double carbon—carbon
bond undergoes nitration. In this case, the oxime group
exerts an activating effect because the reactions does not
take place in its absence (in the case of the correspond-
ing olefinic hydrocarbons). The carbonyl group does not
exhibit such an effect, which was exemplified by the
reaction of carvone (8). Thus, ketone 8 did not react
with an eightfold excess of the NaNO2—AcOH mixture
in MeOH during 5 days (TLC and 1H NMR). In
addition, it should be noted that examples of nitration
of the C=C double bond under the action of sodium or
potassium nitrites have been reported in the litera-
ture;11—13 however, the latter reactions were carried out
under conditions of electrochemical oxidation,11 with
a
10
1
5
6
0
–5
250
300
350
400
λ/nm
–1
–1
∆ε/mol L cm
5
b
the use of ultrasonic activation, or by heating with the
0
12
addition of co-oxidizers, viz., Ce(NH4)2(NO3)6
or
2
iodine.13 In the case of nitrosation of α,β-unsaturated
oximes with NaNO2 and AcOH, no additional oxidizers
and ultrasonic activation are needed. The proposed
procedure for the synthesis of conjugated nitro oximes is
an alternative to the procedure, which has been devel-
oped previously14 for the synthesis of a nor derivative of
compound 9 based on oximation of the available
nitroolefin under the action of NaNO2 and alkyl nitrite
in DMSO.
7
–5
250
300
350
400
λ/nm
Fig. 1. Circular dichroism curves for oximes of α,β-unsaturated
terpenic ketones 1 (a) and 2 (b) and the corresponding β-nitro
derivatives of α,β-unsaturated ketoximes 6 (a) and 7 (b).
position in the molecule. Otherwise (for structure 11a),
substantial shifts of the signals for the C(7) and H(7)
atoms, and, particularly, for the C(10) and H(10) at-
oms, would be observed.
Hence, the terminal hydrogen atom of the conju-
gated H(C=C—)nC=NOH system (n = 1 or 2) in
α,β-unsaturated cyclic oximes 1—5 is replaced by the
nitro group under the action of NaNO2 and AcOH in
MeOH with retention of the C=NOH function of the
starting oxime as exemplified by products 6, 7,
11, and 12.
To account for the formation of nitro oximes in
these reactions, mechanisms of two alternative types,
viz., radical and ionic, can be proposed (Scheme 5). In
the case of the ionic mechanism, the nucleophilic addi-
tion accompanied by the primary attack of the nitrite
anion at the terminal position of the conjugated system
(13 → 14) should be, apparently, excluded from consid-
–
eration because the nucleophilic addition of NO2 to
the C=C double bond under the condition used is
•
unlikely. According to the radical mechanism, the NO2
Using structurally simple oximes of acyclic α,β-un-
saturated ketones as examples, it has been shown many
times7—10 how the conditions of nitrosation (the change
of the nitrosating agent, the performance of the reaction
under an inert atmosphere or in the presence of atmo-
spheric oxygen, the use of other co-oxidizers or transi-
tion metal salts) influence the qualitative and quantita-
tive compositions of the conversion products. However,
in no case did the change of the solvent result in the
formation of the predominating product of the funda-
mentally different type starting from the same oxime.
The reaction described in the present study is the first
example of this kind. The change of the solvent (in
essence, the use of MeOH as a diluent instead of a large
excess of AcOH) gave rise to α,β-unsaturated β-nitro
oximes rather than to unsaturated nitroacetates. The
following facts were unexpected. First, the oxime group
of the initial molecule is retained in the final product in
spite of the facts that the reaction proceeds in the
presence of a large excess of the nitrosating agent and
that the reactions of oximes generally involve the attack
of the nitrosating species occurring primarily on the
C=N—OH group. Second, under the conditions of
radical acts as a nitrating species, which can be gener-
ated from the nitrite anion.15 This species attacks the
C=C bond at the terminal position of the heterodiene
system of the starting oxime 13. Then radical intermedi-
ate 16 is oxidized to carbocation 17 under the action of
the oxidizer (a nitrosating agent or atmospheric oxygen)
followed by deprotonation to form the final product 15.
An analogous mechanism for nitration of alkenes has
been proposed previously.12 In the cited study, cerium
ammonium nitrate was used as a co-oxidizer. It has
been demonstrated that the reaction in the absence of
the co-oxidizer proceeded much more slowly to give the
final nitroolefin in lower yield.
The addition of the electrophilic NO+ species
at the terminal carbon atom of the diene system
(C(3)-nitrosation) followed by oxidation of cation 18 to
nitro derivative 17 seems to be preferential. Within the
framework of this scheme, it can be assumed that
oxidation 18 → 17 proceeds much more rapidly than
prototropic rearrangement 18 → 19. Otherwise, the
formation of symmetrical cation 19 would be expected,
which, in the case of optically active starting com-
pounds (for example, oxime 2), would give rise to

1414
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 8, August, 2001
Chibiryaev et al.
Scheme 5
O2N
NOH
O2N
NOH
–
–
NO2
H
–
–H
ꢀ"
ꢀ#
–H+
O2N
O2N
NOH
NOH
NOH
•
+
•
H
H
NO2
[O]
ꢀ$
ꢀ%
ꢀ!
[O]
ON
NOH
HON
NOH
+
+
H
NO+
ꢀ&
ꢀ'
racemic nitro oxime. However, this is contradictory to
the observed optical activity of compound 7. The ap-
pearance of alcohol 10 among products of nitrosation16
of oxime 3 is an argument in favor of the formation of
intermediate cation 17. Thus, the nucleophilic addition
of a water molecule at the cationic center of intermedi-
ate 17 adopting the most stable conformation with the
pseudoequatorial nitro group, which proceeds as the
sterically most favorable antiparallel attack (Scheme 6),
should afford alcohol with the cis arrangement of the
nitro and hydroxy groups. This situation was proved
based on the NMR spectral data.
spin-spin coupling constant 3JH(3)—C(7) should be equal
to 6—8 Hz).
The conversion of oximes of α,β-unsaturated cyclic
ketones into conjugated nitro oximes discovered by us is
the reaction common to a series of structurally related
unsaturated oximes bearing substituents at the α posi-
Scheme 7
7
2
8
3
NOH
O
E, 70%
or
EE, 68%
1
6
4
5
Scheme 6
ꢁ
!
H
H
NOH
NOH
10
3
H2O
ꢀꢁ
–H+
3
2
O2N
O2N
4
5
E, 45%
or
EE, 40%
+
1
+OH2
6
7
7
NOH
O
H2O
ꢀ%
8
9
Analysis of the spin-spin coupling constants
ꢀ*
"*
3
3JH(3)—C(7) and JH(3)—H(4) for the H(3) atom in the
10
2
NMR spectra of compound 10 revealed the relative
arrangement of the substituents in the molecule.
The presence of the spin-spin coupling constant
3JH(3)—H(4) = 11.0 Hz is indicative of the axial position
of the H(3) atom. In the case of the axial arrangement
of the H(3) atom, the presence of the spin-spin cou-
pling constant 3JH(3)—C(7) = 2.2 Hz points to the equa-
torial position of the methyl group (in the case of
the axial arrangement of the methyl group, the
1
3
E, 53%
or
EE, 47%
7
4
9
6
NOH
O
5
8
*
#*
Reagents and conditions: i. NaNO2—AcOH—MeOH, ∼20 °C,
4—6 h; ii. NaNO2—AcOH, +5—10 °C, 1—3 h.

Nitration of α,β-unsaturated oximes with NaNO2
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 8, August, 2001
1415
(–)-Carvone (8) purchased from Fluka AG was used without
additional purification.
Synthesis of the starting oximes. (+)-(1S,6R)-Car-2-en-4-
tion and at least one vinyl hydrogen atom at the β
position. Nitrosation of cyclic oximes 20—22, which do
not contain the free β-vinyl hydrogen atom, with the
NaNO2—AcOH—MeOH system led to their oxidative
deoximation10,17—20 giving rise to the corresponding
ketones 23—25 (Scheme 7). In the latter case, the
reactions proceeded analogously to those in the
NaNO2—AcOH system, the yields of the reaction prod-
ucts being somewhat higher. The results obtained in the
reactions involving oximes 20—22 is the first example of
the conversion of α,β-unsaturated oximes under the
conditions of nitrosation yielding ketone as the major
conversion product. Previously, deoximation under the
conditions of nitrosation has been observed only as a
side process giving rise to carbonyl compounds as minor
products.9,10
one (E)-oxime (1) was prepared from (+)-3-carene according
to a known procedure21: m.p. 93—94 °C (from EtOAc); cf. lit.
data22: 94—95 °C; [α]578
+265 (c 2.37); cf. lit. data22:
24
[α]D +374 (EtOH). The 1H and 13C NMR spectra were
reported in Ref. 23.
(–)-(4R)-p-Mentha-1(6),8-dien-2-one (E)-oxime (2)
((–)-carvone oxime) was prepared from (–)-carvone (8) ac-
cording to a procedure reported previously24: m.p. 72—74 °C
(from MeCN); cf. lit. data25: 72 °C; [α]578 –48 (c 4.89).
19
13C NMR (CDCl3), δ: 17.65 (q, C(10)); 20.67 (q, C(9));
27.22 (t, C(6)); 30.25 (t, C(4)); 40.12 (d, C(5)); 110.05
(t, C(8)); 130.12 (d, C(3)); 132.63 (s, C(2)); 147.41 (s, C(7));
156.14 (s, C(1)).
2-Methylcyclohex-2-en-1-one (E)-oxime (3) was prepared
from 1-methylcyclohexene according to a known procedure21:
m.p. 63—64 °C (from MeCN); cf. lit. data21: 63—64 °C.
1H NMR (CDCl3—CCl4), δ: 1.73 (tt, 2 H, H2C(5), J
=
1
Experimental
J2 = 6.5 Hz); 1.81 (dt, 3 H, C(2)Me, J1 = J2 = 1.5 Hz); 2.15
(m, 2 H, H2C(4)); 2.58 (t, 2 H, H2C(6), J = 6.5 Hz); 5.97 (tq,
1 H, H(3), J1 = 5.0 Hz, J2 = 1.5 Hz); 9.20 (br.s, 1 H, HON=).
13C NMR (CDCl3—CCl4), δ: 18.11 (q, C(7)); 21.37 (t, C(5));
22.51 (t, C(6)); 25.25 (t, C(4)); 130.80 (s, C(2)); 132.80
(d, C(3)); 155.68 (s, C(1)).
The UV spectra were recorded on a Specord M-40 spectro-
–4
photometer in 95% EtOH (c = 1•10
mol L–1). The IR
spectra were measured on a Bruker Vector-22 instrument in
KBr pellets (unless otherwise indicated) with the concentration
of 0.25%. The mass spectra were obtained on a Finnigan
MAT 8200 spectrometer (50—100 °C, EI, 70 eV). The 1H
and 13C NMR spectra were recorded on Bruker AC-200
(200.13 MHz for 1H and 50.32 MHz for 13C) and Bruker
AM-400 (400.13 MHz for 1H and 100.61 MHz for 13C) spec-
2,6,6-Trimethylcyclohepta-2,4-dien-1-one (E)-oxime (4)
(eucarvone oxime) was prepared from eucarvone26 according to
a known procedure24: m.p. 105—107 °C (from MeCN); cf. lit.
data27: 105—106.5 °C. 1H NMR (CDCl3), δ: 1.11 (both s,
3 H each, H3C(8), H3C(9)); 2.01 (s, 3 H, C(2)Me); 2.77 (s,
2 H, H2C(7)); 5.57 (dd, 1 H, H(4), J1 = 11.5 Hz, J2 = 6.5 Hz);
5.60 (d, 1 H, H(5), J = 11.5 Hz); 5.91 (d, 1 H, H(3),
J = 6.5 Hz); 10.20 (br.s, 1 H, HO—N=). 13C NMR (CDCl3),
δ: 21.87 (q, C(10)); 27.90 (q, C(8), C(9)); 35.07 (s, C(6));
35.65 (t, C(7)); 121.50 (d, C(4)); 127.37 (d, C(5)); 135.37
(s, C(2)); 144.66 (d, C(3)); 157.67 (s, C(1)).
(±)-6,6-Dimethyl-2-methylenebicyclo[3.1.1]heptan-3-one
(E)-oxime (5) (pinocarvone oxime) was prepared from α-pinene
according to a known procedure21: m.p. 131—133 °C (from
light petroleum); cf. lit. data21: 132—134 °C (from hexane).
The 1H and 13C NMR spectra were reported in Ref. 23.
–1
trometers for solutions with concentrations of 70—100 mg mL
at 25—27 °C. The signals of the solvent, viz., chloroform-d
(δC = 76.90, δH = 7.24) or dimethyl sulfoxide-d6 (δC = 39.50,
δH = 2.50), were used as the internal standard. The assignment
of the signals was made using the 13C NMR spectra recorded
with the J modulation (proton-noise-decoupled spectra, the
opposite phases for the signals of the atoms with the odd and
even numbers of the attached protons, tuning to the constant
J = 135 Hz) and based on the data of the 2D COSY spectra:
(1)ꢀ homonuclear 1H—1H correlation, (2)ꢀ heteronuclear
13C—1H correlation at the direct spin-spin coupling constants
(J = 135 Hz), and (3)ꢀheteronuclear 13C—1H correlation at the
long-range spin-spin coupling constants (J = 10 Hz).
Microanalyses were performed on Hewlett Packard 185 and
Carlo Erba 1106 analyzers. The optical rotation was measured
on a Polamat A polarimeter in CHCl3. The circular dichroism
spectra of compounds 1, 2, 6, and 7 were recorded on a
JASCO 600 spectropolarimeter (JASCO, Japan) in MeOH
2,3-Dimethylcyclohex-2-en-1-one (E)-oxime (20) was pre-
26
pared from ketone 23ꢀ
according to a known procedure24:
m.p. 102—104ꢀ°C (from MeCN). UV (EtOH), λmax/nm (ε):
204 (8500), 238 (31500). IR (film), ν/cm–1: 760, 819, 860, 904,
925 (=N—OH); 1428, 1611 (C=N); 1630 (C=C). IR (CHCl3),
1
ν/cm–1: 3275 and 3587 (OH). H NMR (CDCl3—CCl4), δ:
1.69 (tt, 2 H, H(5), J1 = J2 = 6.5 Hz); 1.79 (br.s, 3 H,
C(3)Me); 1.82 (s, 3 H, C(2)Me); 2.12 (br.t, 2 H, H2C(4),
J = 6.5 Hz); 2.56 (t, 2 H, H2C(6), J = 6.5 Hz); 9.37 (br.s, 1 H,
=NOH, W1/2 = 10 Hz). 13C NMR (CDCl3—CCl4), δ: 12.40
(q, C(7)); 20.72 (q, C(8)); 20.94 (t, C(5)); 22.35 (t, C(6));
32.14 (t, C(4)); 124.36 (s, C(2)); 139.63 (s, C(3)); 157.08
(s, C(1)). MS, m/z (Irel (%)): 139 [M]+ (100), 122 (57),
106 (19), 95 (25), 94 (15), 93 (37), 81 (36), 80 (16), 79 (34), 77
(18), 67 (23), 55 (15), 53 (20), 41 (31), 39 (20). Found (%):
C, 68.9; H, 9.5; N, 10.1. C8H13NO. Calculated (%): C, 69.03;
H, 9.41; N, 10.06.
–4
(c = 10 mol L–1) with the optical path of 1 cm.
The melting points were determined on a Kofler stage.
Thin-layer chromatography was carried out on Silufol plates
with a fixed SiO2 layer. The spots were visualized by spraying
with ethanolic solutions of vanilline (2 g of vanilline + 5 mL of
concentrated H2SO4 in 150 mL of 95% EtOH) or iron(III)
chloride (3 g of FeCl3•6H2O in 150 mL of 95% EtOH)
followed by heating. Preparative column chromatography was
carried out on KSK silica gel (particle size 0.140—0.315 mm)
activated at 140 °C for 6—7 h.
(+)-3-Carene with [α]57820 +16.0 (d420 0.863) and α-pinene
(±)-p-Mentha-1,8-dien-3-one (E)-oxime (21) (isopipe-
ritenone oxime) was prepared from 2428 according to a proce-
dure reported previously24: m.p. 141—143 °C (from MeCN).
UV (EtOH), λmax/nm (ε): 205 (7000), 242 (19000). IR (film),
20
20
with [α]578 +20.4 (d4 0.856) were prepared by rectification
of turpentine obtained from Scotch pine (Pinus silvestris). To
prepare oximes by nitrosochlorination—dehydrochlorination,21
(+)-3-carene and α-pinene were converted into nitrosochlorides.
Due to the low optical purity of α-pinene, the corresponding
crystalline nitrosochloride was obtained as a racemate.
ν/cm–1: 771, 875, 900 (=CH2); 937 (N—O); 1150, 1220, 1245,
–1
1375, 1430, 1644 (C=C); 3087 (=C—H). IR (CHCl3), ν/cm
:
3275 and 3600 (OH). 1H NMR (CDCl3—CCl4), δ: 1.40 (s, 3 H,

1416
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 8, August, 2001
Chibiryaev et al.
C(7)Me); 1.70—2.05 (m, 2 H, H(5a), H(5b)); 1.90 (dd, 3 H,
C(3)Me, J1 = J2 = 1.5 Hz); 2.12 (br.t, 2 H, H(4a), H(4b),
J = 5.8 Hz); 3.02 (dd, 1 H, H(6), J1 = 8.2 Hz, J2 = 4.5 Hz);
4.73 (s, 2 H, H(8a), H(8b)); 6.61 (q, 1 H, H(2), J = 1.5 Hz);
9.72 (br.s, 1 H, HON=). 13C NMR (CDCl3—CCl4)*, δ: 20.01
(q, C(9)); 24.01 (q, C(10)); 26.79*** (t, C(5)); 29.53*** (t, C(4));
45.19 (d, C(6)); 112.82 (t, C(8)); 113.07 (d, C(2)); 144.45
(s, C(7)); 148.80 (s, C(3)); 153.90 (s, C(1)). MS, m/z (Irel (%)):
165 [M]+ (99), 164 (62), 151 (100), 150 (14), 149 (84), 147
(25), 136 (46), 133 (35), 132 (38), 131 (22), 119 (15), 118 (18),
117 (16), 108 (26), 107 (23), 106 (22), 105 (20), 94 (20), 93
(22), 91 (38), 81 (21), 80 (16), 79 (35), 77 (27), 68 (14), 67
(25), 65 (17), 55 (19). Found (%): C, 72.9; H, 9.1; N, 8.6.
C10H15NO. Calculated (%): C, 72.69; H, 9.15; N, 8.48.
(±)-2,6,6-Trimethylbicyclo[3.1.1]hept-2-en-4-one (22)
oxime (verbenone oxime) was prepared from racemic verbenone
(25)24 synthesized from α-pinene as a mixture of the E and
Z isomers in a ratio of 3 : 2, m.p. 121—123 °C (from MeCN);
cf. lit. data29: 119—120 °C (from naphtha).
yellow oil with a characteristic carvone odor was obtained in a
yield of 0.46 g. The 1H and 13C NMR and IR spectral data are
identical with the corresponding characteristics of the starting
ketone.
(+)-1S,6R-2-Nitrocar-2-en-4-one (E)-oxime (6). The re-
action of oxime 1 (400 mg, 2.4 mmol) with NaNO2 (2.00 g,
29.0 mmol) and AcOH (2 mL) in MeOH (50 mL) was carried
out according to procedure A for 7 days. Chromatography
afforded product 6 (112 mg, 62% with respect to the consumed
oxime) and the starting compound 1 (259 mg). M.p. of com-
pound 6 was 131—133 °C (from a hexane—EtOAc mixture).
16
[α]578 +364 (c 2.44). UV (EtOH), λmax/nm (ε): 211 (7900),
236 (9500), 323 (3600). IR (KBr), ν/cm–1: 784, 970 (=N—OH);
990, 1417, 1338 and 1538 (NO2); 1616 (C=C). IR (CHCl3),
1
ν/cm–1: 3280 and 3568 (OH). H NMR (DMSO-d6), δ: 0.80
(s, 3 H, H3C(8)); 1.17 (s, 3 H, H3C(9)); 1.40 (dd, 1 H, H(6),
J1 = 8.8 Hz, J2 = 8.4 Hz); 1.74 (d, 1 H, H(1), J = 8.8 Hz);
2.00 (s, 3 H, H3C(10)); 2.64 (dd, 1 H, H(5β), J1 = 20.0 Hz,
J2 = 8.4 Hz); 2.75 (d, 1 H, H(5α), J = 20.0 Hz); 11.89 (s, 1 H,
HO—N=). 13C NMR (DMSO-d6), δ: 12.05 (q, C(10)); 13.36
(q, C(8)); 17.54 (t, C(5)); 20.53 (d, C(6)); 23.68 (d, C(1)),
23.95 (s, C(7)); 26.24 (q, C(9)); 127.36 (s, C(3)); 148.96
(s, C(4)); 152.44 (s, C(2)). MS, m/z (Irel (%)): 210 [M]+ (29),
168 (100), 151 (27), 121 (17), 120 (17), 106 (19), 105 (18), 104
(18), 93 (24), 92 (19), 91 (29), 79 (21), 78 (21), 77 (37), 65
(19), 53 (19), 43 (19), 41 (50), 39 (22). Found (%): C, 57.3;
H, 6.9; N, 13.4. C10H14N2O3. Calculated (%): C, 57.13; H, 6.71;
N, 13.32.
(–)-(4R)-p-Mentha-6-nitro-1(6),8-dien-2-one (E)-oxime
(7). The reaction of oxime 2 (0.66 g, 4.0 mmol) with NaNO2
(1.10 g, 16.0 mmol) and AcOH (1.5 mL) in MeOH (10 mL)
was carried out according to procedure A for 4 h (according to
the 1H NMR spectral data, the ratio 7 : 8 in the crude product
was 2 : 1). After chromatography, product 7 (0.26 g, 31%) and
E isomer. 1H NMR (CDCl3—CCl4), δ: 1.02 (s, 3 H,
H3C(8)); 1.40 (s, 3 H, H3C(9)); 1.68 (d, 1 H, H(7
α
),
Me, J1 = J2 = 1.5 Hz); 2.21
(m, 1 H, H(1)); 2.70 (m, 2 H, H(5), H(7 )); 6.44 (dq, 1 H,
J = 8.2 Hz); 1.90 (dd, 3 H, C(2
)
β
H(3), J1 = J2 = 1.5 Hz); 9.72 (br.s, 1 H, HON=). 13C NMR
(CDCl3—CCl4), δ: 21.95 (q, C(8)); 23.55 (q, C(10)); 26.24
(q, C(9)); 37.32 (t, C(7)); 47.81 (s, C(6)); 48.13 (d, C(5)); 49.35
(d, C(1)); 110.23 (d, C(3)); 157.01 (s, C(2)); 158.60 (s, C(4)).
Z isomer. 1H NMR (CDCl3—CCl4), δ: 0.99 (s, 3 H,
H3C(8)); 1.43 (s, 3 H, H3C(9)); 1.58 (d, 1 H, H(7
J = 8.7 Hz); 1.85 (dd, 3 H, C(2)Me, J1 = J2 = 1.5 Hz); 2.20
(m, 1 H, H(1)); 2.56 (m, 1 H, H(7 )); 3.60 (ddd, 1 H, H(5),
α
),
β
J1 = J2 = 5.5 Hz, J3 = 1.5 Hz); 5.78 (dq, 1 H, H(3),
J1 = J2 = 1.5 Hz); 9.72 (br.s, 1 H, HON=). 13C NMR
(CDCl3—CCl4), δ: 22.32 (q, C(8)); 23.05 (q, C(10)); 26.18
(q, C(9)); 36.03 (t, C(7)); 41.46 (d, C(5)); 47.01 (s, C(6)); 49.17
(d, C(1)); 116.11 (d, C(3)); 152.89 (s, C(2)); 160.94 (s, C(4)).
Nitration of α,β-unsaturated oximes in methanol (general
procedure A). Powdered NaNO2 was added portionwise with
stirring to a solution of oxime in a mixture of MeOH and
AcOH at ∼20 °C. After the starting compound was consumed
(TLC control), the mixture was diluted with water (2—3-fold
by volume) and an excess of AcOH was neutralized with a 25%
aqueous solution of NH3 to pH 9—10 and extracted three times
with CH2Cl2. The combined organic extracts were washed
successively with water and a saturated aqueous solution of
NaCl and dried with anhydrous MgSO4. The solvent was
removed in vacuo and the residue was chromatographed on
SiO2 (gradient elution with the Et2O—light petroleum system).
Deoximation of α,β-unsaturated oximes in acetic acid (gen-
eral procedure B). Powdered NaNO2 was added portionwise
with stirring to a solution of oxime in glacial AcOH at +5—10 °C.
After the starting compound was consumed (TLC control), the
mixture was diluted with water and extracted with Et2O. The
combined organic extracts were washed successively with a
0.5 M aqueous solution of Na2CO3 and a saturated aqueous
solution of NaCl and dried with anhydrous MgSO4. The sol-
vent was removed in vacuo and the residue was chromatographed
on SiO2 (gradient elution with the Et2O—light petroleum
system).
carvone (8) (60 mg, 10%) were isolated. M.p. 120—122 °C
21
(from a toluene—hexane mixture). [α]578
–214 (c 3.75).
UV (EtOH), λmax/nm (ε): 206 (6800), 228 (9800), 303 (4900).
IR (CHCl3), ν/cm–1: 900 (=CH2); 965 (N—O); 1341 and
1510 (NO2); 1438, 1646 (C=C); 3093 (=CH2); 3300 and 3575
1
(OH). H NMR (CDCl3—CCl4), δ: 1.79 (dd, 3 H, C(7)Me,
J1 = 1.2 Hz, J2 = 0.8 Hz); 2.05 (dd, 3 H, C(2)Me, J1 = 2.2 Hz,
J2 = 1.2 Hz); 2.16 (dd, 1 H, H(6a), J1 = 16.7 Hz, J2 = 11.7 Hz);
2.48 (m, 1 H, H(5)); 2.68 (dq, 1 H, H(4a), J1 = 10.2 Hz,
J2 = 2.2 Hz); 2.82 (ddd, 1 H, H(4b), J1 = 16.7 Hz, J2 = 4.8 Hz,
J3 = 1.2 Hz); 3.20 (ddd, 1 H, H(6b), J1 = 16.7 Hz, J2 = 3.7 Hz,
J3 = 1.5 Hz); 4.82 (dq, 1 H, H(8a), J1 = J2 = 0.8 Hz); 4.87
(dq, 1 H, H(8b), J1 = 1.2 Hz, J2 = 0.8 Hz); 9.11 (br.s, 1 H,
HO—N=). 13C NMR (CDCl3—CCl4), δ: 12.47 (q, C(10));
20.64 (q, C(9)); 26.75 (t, C(6)); 31.65 (t, C(4)); 38.74 (d, C(5));
111.56 (t, C(8)); 129.80 (s, C(2)); 145.27 (s, C(7)); 151.11
(s, C(1)), 155.48 (s, C(3)). MS, m/z (Irel (%)): 146 (32), 132
(33), 131 (21), 130 (20), 120 (25), 118 (26), 106 (24), 105 (25),
93 (25), 91 (53), 79 (40), 78 (24), 77 (53), 67 (37), 65 (35), 53
(100), 52 (27), 51 (33), 43 (34), 41 (68). Found (%): C, 57.2;
H, 6.6; N, 13.2. C10H14N2O3. Calculated (%): C, 57.13; H, 6.71;
N, 13.32.
2-Methyl-3-nitrocyclohex-2-en-1-one (E)-oxime (9). The
reaction of oxime 3 (5.40 g, 43.1 mmol) with NaNO2 (11.90 g,
172.4 mmol) and AcOH (15 mL) in MeOH (100 mL) was
carried out according to procedure A for 24 h. After standard
treatment and removal of the solvent, a residue was obtained in
a yield of 6.31 g. The residue was crystallized from a hex-
ane—EtOAc mixture to obtain nitro oxime 9 (2.13 g). The
mother liquor was chromatographed and an additional amount
of product 9 (1.21 g, the total yield was 44%) along with
hydroxynitro-substituted oxime 10 (1.42 g, 10%) were ob-
The reaction of carvone (8) (0.50 g, 3.3 mmol) with
NaNO2 (1.88 g, 27.2 mmol) and AcOH (3 mL) in MeOH
(10 mL) was carried out according to procedure A for 3 days.
After standard treatment and removal of the solvent, a pale-
* Hereinafter, the assignments marked with asterisks (***) may
be reverse.

Nitration of α,β-unsaturated oximes with NaNO2
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 8, August, 2001
1417
tained. M.p. 138—138.5 °C (from an EtOAc—hexane mixture,
sublimation at 90 °C). UV (EtOH), λmax/nm (ε): 207 (4700),
226 (7800), 301 (3900). IR (KBr), ν/cm–1: 771, 875, 978
(N—O), 1017, 1325, and 1513 (NO2); 1618 (C=N); 1698
(C=C). IR (CHCl3), ν/cm–1: 3300 and 3575 (OH). 1H NMR,
(CDCl3—CCl4), δ: 1.87 (tt, 2 H, H2C(5), J1 = J2 = 6.5 Hz);
2.05 (t, 3 H, C(2)Me, J = 2.0 Hz); 2.64 (d, 2 H, H2C(6),
J = 6.5 Hz); 2.70 (dq, 2 H, H2C(4), J1 = 6.5 Hz, J2 = 2.0 Hz);
8.85 (s, 1 H, HO—N=). 13C NMR (CDCl3—CCl4), δ: 12.50
(q, C(7)); 19.88 (t, C(5)); 21.67 (t, C(6)); 26.78 (t, C(4));
130.35 (s, C(2)); 151.64 (s, C(1)); 155.60 (s, C(3)). MS,
m/z (Irel (%)): 170 [M]+ (76), 153 (100), 106 (22), 95 (62), 94
(29), 80 (32), 79 (49), 78 (23), 77 (67), 68 (24), 67 (49), 66
(21), 65 (34), 55 (24), 54 (44), 53 (57), 52 (28), 51 (31), 43
(49), 42 (21), 41 (81), 39 (58). Found (%): C, 49.5; H, 6.2;
N, 16.5. C7H10N2O3. Calculated (%): C, 49.41; H, 5.92;
N, 16.46.
(±)-cis-2-Hydroxy-2-methyl-3-nitrocyclohexan-1-one
(E)-oxime (10), m.p. 99—102 °C (from MeCN). IR (KBr),
ν/cm–1: 704, 739, 848, 902, 946 (N—O); 1369 and 1555 (NO2);
1380, 1429, 1440, 1664 (C=C). IR (CHCl3), ν/cm–1: 3562 and
3666 (OH). 1H NMR (DMSO-d6), δ: 1.31 (ddddd, 1 H,
Hax(5), J1 = J2 = J3 = 12.0 Hz, J4 = J5 = 4.0 Hz); 1.36 (s, 3 H,
C(2)Me); 1.79 (ddd, 1 H, Heq(5), J1 = 12.0 Hz, J2 = 5.0 Hz,
J3 = 4.0 Hz); 1.84 (dddd, 1 H, Heq(4), J1 = 12.0 Hz, J2 = J3 =
J4 = 4.0 Hz); 1.95 (ddd, 1 H, Hpseudo-ax(6), J1 = 14.0 Hz,
J2 = 12.0 Hz, J3 = 5.0 Hz); 2.38 (dddd, 1 H, Hax(4), J1 =
J2 = 12.0 Hz, J3 = 11.0 Hz, J4 = 4.0 Hz); 2.91 (ddd, 1 H,
Hpseudo-eq(6), J1 = 14.0 Hz, J2 = J3 = 4.0 Hz); 4.54 (dd, 1 H,
H(3), J1 = 11.0 Hz, J2 = 4.0 Hz); 5.47 (s, 1 H, HO); 10.87 (s,
1 H, HO—N=). 13C NMR (DMSO-d6), δ: 17.41 (t, C(5));
18.63*** (t, C(4)); 20.79 (q, C(7)); 23.16*** (t, C(6)); 69.93
(s, C(2)); 90.08 (d, C(3)); 156.07 (s, C(1)). MS, m/z (Irel (%)):
170 [M+ – H2O] (7), 125 (9), 124 (55), 99 (8), 98 (13), 83
(17), 82 (24), 79 (9), 71 (9), 55 (26), 54 (12), 53 (9), 43 (100),
41 (17). Found (%): C, 44.8; H, 6.5; N, 14.9. C7H12N2O4.
Calculated (%): C, 44.68; H, 6.43; N, 14.89.
2,6,6-Trimethyl-5-nitrocyclohepta-2,4-dien-1-one
(E)-oxime (11). The reaction of oxime 4 (0.50 g, 3.0 mmol)
with NaNO2 (1.25 g, 18.1 mmol) and AcOH (3 mL) in MeOH
(15 mL) was carried out according to procedure A for 6 h. After
chromatography, product 11 was isolated in a yield of 253 mg
(40%), m.p. 148—150 °C (from CCl4). UV (EtOH), λmax/nm (ε):
211 (8800), 265 (5200), 294 (6900), 365 (6700). IR (CHCl3),
ν/cm–1: 962 and 971 (=N—OH); 1457, 1335, and 1515 (NO2);
1588 (C=C); 3282 and 3592 (OH). 1H NMR, (CDCl3—CCl4),
δ: 1.35 (both s, 3 H each, H3C(8), H3C(9)); 2.09 (d, 3 H,
C(2)Me, J = 1.3 Hz); 2.90 (s, 2 H, H2C(7)); 5.99 (dq, 1 H,
H(3), J1 = 9.0 Hz, J2 = 1.3 Hz); 6.63 (d, 1 H, H(4), J = 9.0 Hz);
9.42 (br.s, 1 H, HO—N=). 13C NMR (CDCl3—CCl4), δ: 21.44
(q, C(10)); 25.36 (q, C(8), C(9)); 36.29 (t, C(7)); 37.33 (s, C(6));
122.51 (d, C(3)); 123.28 (d, C(4)); 144.13 (s, C(2)); 156.47
(s, C(5)); 161.10 (s, C(1)). MS, m/z (Irel (%)): 210 [M]+ (98),
164 (100), 146 (30), 132 (66), 131 (68), 130 (30), 120 (26), 117
(30), 106 (30), 105 (30), 104 (29), 103 (33), 91 (57), 79 (30),
78 (26), 77 (60), 67 (25), 65 (40), 53 (49), 51 (33), 45 (34), 43
(45), 41 (66), 39 (66). Found (%): C, 57.3; H, 6.7; N, 13.3.
C10H14N2O3. Calculated (%): C, 57.13; H, 6.71; N, 13.32.
(±)-6,6-Dimethyl-2-methylene-(10E)-nitrobicyc-
lo[3.1.1]heptan-3-one (E)-oxime (12) ((10E)-nitropinocarvone
oxime). The reaction of oxime 5 (500 mg, 3.02 mmol) with
NaNO2 (1.04 g, 15.1 mmol) and AcOH (1.7 mL) in MeOH
(15 mL) was carried out according to procedure A for 4.5 h.
After chromatography, nitro oxime 12 was isolated as a yellow
viscous oil (343 mg, 1.63 mmol, 54%), which crystallized upon
storage. M.p. 69—71 °C (from a hexane—toluene mixture).
UV (EtOH), λmax/nm (ε): 208 (5400), 231 (6700), 312 (7200).
IR (CHCl3), ν/cm–1: 968 (=N—OH); 1341 and 1509 (NO2);
1645 (C=C); 3112 (=CH); 3288 and 3577 (OH). 1H NMR
(CDCl3), δ: 0.82 (s, 3 H, H3C(8)); 1.21 (d, 1 H, H(7α),
J = 11.0 Hz); 1.39 (s, 3 H, H3C(9)); 2.18 (dddd, 1 H, H(5),
J1 = J2 = 5.5 Hz, J3 = 3.5 Hz, J4 = 2.5 Hz); 2.60 (dddd, 1 H,
H(7β), J1 = 11.0 Hz, J2 = J3 = 5.5 Hz, J4 = 2.5 Hz); 2.72
(ddd, 1 H, H(4α), J1 = 19.0 Hz, J2 = J3 = 2.5 Hz); 2.91 (dd,
1 H, H(4β), J1 = 19.0 Hz, J2 = 3.5 Hz); 3.99 (dd, 1 H, H(1),
J1 = J2 = 5.5 Hz); 7.69 (s, 1 H, H(10)); 9.20 (br.s, 1 H,
HON=). 13C NMR (DMSO-d6), δ: 21.13 (q, C(8)); 26.08
(q, C(9)); 29.11*** (t, C(4)); 29.22*** (t, C(7)); 36.92 (d, C(5));
3
41.36 (s, C(6)); 43.16 (d, C(1), JC(1)—H(10) = 6.5 Hz);
3
130.49 (d, C(10), JC(10)—H(1) = 3.1 Hz); 149.67 (s, C(3),
3JC(3)—HON = 8.1 Hz, 3JC(3)—H(10) = 4.3 Hz); 150.32 (s, C(2),
2JC(2)—H(10) = 2.4). MS, m/z (Irel (%)): 167 (18), 152 (21), 148
(17), 146 (28), 136 (28), 134 (20), 132 (35), 131 (18), 122 (32),
121 (19), 120 (65), 119 (17), 106 (21), 105 (26), 104 (17), 94
(21), 93 (41), 92 (41), 91 (36), 81 (16), 80 (20), 79 (31), 78
(22), 77 (50), 69 (38), 68 (17), 67 (34), 66 (18), 65 (37), 55
(24), 53 (33), 52 (21), 51 (23), 43 (66), 41 (100), 39 (51).
Found (%): C, 56.9; H, 6.7; N, 13.2. C10H14N2O3. Calcu-
lated (%): C, 57.13; H, 6.71; N, 13.32.
2,3-Dimethylcyclohex-2-en-1-one (23). The reaction of
oxime 20 (120 mg, 0.86 mmol) with NaNO2 (238 mg,
3.44 mmol) and AcOH (0.5 mL) in MeOH (5 mL) was carried
out according to procedure A for 5 h. After chromatography,
ketone 23 was isolated as a pale-yellow oil (75 mg, 0.60 mmol,
1
70%). The H NMR spectrum is identical with that of ketone
23 used for the synthesis of oxime 20.
The reaction of oxime 20 (120 mg, 0.86 mmol) with
NaNO2 (180 mg, 2.60 mmol) in AcOH (2 mL) was carried out
according to procedure B for 2 h. After chromatography, ketone
23 was isolated as a pale-yellow oil (73 mg, 0.58 mmol, 68%).
(±)-p-Mentha-1,8-dien-3-one (24) (isopiperitenone). The
reaction of oxime 21 (190 mg, 1.15 mmol) with NaNO2
(318 mg, 4.60 mmol) and AcOH (0.5 mL) in MeOH (5 mL)
was carried out according to procedure A for 6 h. After chroma-
tography, ketone 24 was isolated as a pale-yellow oil (78 mg,
0.52 mmol, 45%).
The reaction of oxime 21 (190 mg, 1.15 mmol) with
NaNO2 (164 mg, 2.37 mmol) in AcOH (3 mL) was carried out
according to procedure B for 3 h. After chromatography,
ketone 24 was isolated as a pale-yellow oil (69 mg, 0.46 mmol,
1
40%). H NMR (CDCl3), δ: 1.70 (br.s, 3 H, C(7)Me); 1.92
(ddd, 3 H, C(3)Me, J1 = 1.5 Hz, J2 = 1.0 Hz, J3 = 0.9 Hz);
1.95—2.20 (m, 2 H, H(5α), H(5β)); 2.29 (m, 2 H, H(4α),
H(4β)); 2.88 (ddd, 1 H, H(6), J1 = 10.0 Hz, J2 = 5.3 Hz,
J3 = 0.9 Hz); 4.69 (ddq, 1 H, H(8a), J1 = 1.5 Hz, J2 = 1.0 Hz,
J3 = 0.9 Hz); 4.88 (dq, 1 H, H(8b), J1 = J2 = 1.5 Hz); 5.82
(ddq, 1 H, H(2), J1 = J2 = J3 = 1.5 Hz). 13C NMR (CDCl3),
δ: 20.74 (q, C(9)); 24.05 (q, C(10)); 27.65*** (t, C(5)); 30.31***
(t, C(4)); 53.65 (d, C(6)); 113.41 (t, C(8)); 126.94 (d, C(2));
143.07 (s, C(7)); 160.41 (s, C(3)); 198.35 (s, C(1)).
(±)-2,6,6-Trimethylbicyclo[3.1.1]hept-2-en-4-one (25)
(verbenone). The reaction of oxime 22 (150 mg, 0.90 mmol)
with NaNO2 (235 mg, 3.60 mmol) and AcOH (0.5 mL) in
MeOH (5 mL) was carried out according to procedure A for
4 h. Chromatography afforded ketone 25 as a pale-yellow oil
(72 mg, 0.48 mmol, 53%).
The reaction of oxime 22 (150 mg, 0.90 mmol) with
NaNO2 (130 mg, 1.99 mmol) in AcOH (3 mL) was carried out
according to procedure B for 1 h. Chromatography afforded
ketone 25 as a pale-yellow oil (64 mg, 0.43 mmol, 47%).
1H NMR (CDCl3), δ: 0.90 (s, 3 H, H3C(8)); 1.39 (s, 3 H,
H3C(9)); 1.91 (d, 3 H, C(2)Me, J = 1.8 Hz); 1.96 (d, 1 H,

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Russ.Chem.Bull., Int.Ed., Vol. 50, No. 8, August, 2001
Chibiryaev et al.
H(7α), J = 9.2 Hz); 2.35 (ddd, 1 H, H(1), J1 = J2 = 5.5 Hz,
J3 = 1.8 Hz); 2.55 (ddd, 1 H, H(5), J1 = J2 = 5.5 Hz,
10. J. F. Hansen and P. J. Georgiou, J. Heterocycl. Chem.,
1994, 31, 1487.
J3 = 1.8 Hz); 2.70 (ddd, 1 H, H(7β), J1 = 9.2 Hz, J2
=
11. A. Kunai, Ya. Yanagi, and K. Sasaki, Tetrahedron Lett.,
1983, 24, 4443.
12. J. R. Hwu, K.-L. Chen, and S. Ananthan, J. Chem. Soc.,
Chem. Commun., 1994, 12, 1425.
13. D. Ghosh and D. E. Nichols, Synthesis, 1996, 2, 195.
14. E. J. Corey and H. Estreicher, J. Am. Chem. Soc., 1978,
100, 6294.
15. D. E. G. Shuker, in Nitrosamines: Toxicology and Microbiol-
ogy, Ed. M. J. Hill, Ellis Horwood, Chichester, 1988, 49.
16. V. N. Yandovskii, I. I. Ryabinkin, and I. V. Tselinskii,
Zh. Org. Khim., 1980, 16, 2084 [J. Org. Chem. USSR, 1980,
16 (Engl. Transl.)].
17. J. P. Freeman, Chem. Rev., 1973, 73, 283.
18. S. Adamopoulos, A. J. Boulton, R. Tadayoni, and G. A.
Webb, J. Chem. Soc., Perkin Trans. 1, 1987, 2073.
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37, 4223.
J3 = 5.5 Hz); 5.61 (ddq, 1 H, H(3), J1 = J2 = J3 = 1.8 Hz).
13C NMR (CDCl3), δ: 21.73 (q, C(8)); 23.21 (q, C(10)); 26.28
(q, C(9)); 40.51 (t, C(7)); 49.46 (d, C(1)); 53.68 (s, C(6)); 57.32
(d, C(5)); 120.86 (d, C(3)); 169.86 (s, C(2)); 203.58 (s, C(4)).
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 98-03-
32910), the International Association for the Promotion
of Cooperation with Scientists from the Newly Inde-
pendent States of the Former Soviet Union (INTAS,
Grant 97-0217), and the Presidium of the Siberian
Branch of the Russian Academy of Sciences (Grant for
Young Scientists, 2000).
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Received April 17, 2001