Reactions of 3-carene, limonene, and α-pinene nitrosochlorides with imidazole, benzotriazole, and indole

Article abstract of DOI:10.1007/s11172-012-0085-7

The reactions of terpene nitrosochlorides derived from 3-carene, α-pinene, and limonene, with simplest azaheterocycles (imidazole, benzotriazole, and indole) were studied. On the base of these transformations, preparative procedures to access chiral oxime

Full text of DOI:10.1007/s11172-012-0085-7

Russian Chemical Bulletin, International Edition, Vol. 61, No. 3, pp. 589—595, March, 2012
589
Reactions of 3ꢀcarene, limonene, and ꢀpinene nitrosochlorides
with imidazole, benzotriazole, and indole
S. N. Bizyaeva and A. V. Tkacheva,b
aN. N. Vorozhtsov Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences,
9 prosp. Akad. Lavrent´eva, 630090 Novosibirsk, Russian Federation
bDepartment of Natural Sciences, Novosibirsk State University,
2 ul. Pirogova, 630090 Novosibirsk, Russian Federation.
Fax: (383) 330 9752. Eꢀmail: atkachev@nioch.nsc.ru
The reactions of terpene nitrosochlorides derived from 3ꢀcarene, ꢀpinene, and limonene,
with simplest azaheterocycles (imidazole, benzotriazole, and indole) were studied. On the base of
these transformations, preparative procedures to access chiral oximes bearing azaheterocyclic
moieties in the ꢀposition to the oxime fragment, namely, ꢀ(1Hꢀimidazolꢀ1ꢀyl)ꢀ, ꢀ(1Hꢀbenzoꢀ
[d][1,2,3]triazolꢀ1ꢀyl)ꢀ, and ꢀ(1Hꢀindolꢀ3ꢀyl)ꢀsubstituted terpenic oximes, were developed.
Transformations of the studied monoterpene nitrosochlorides into ꢀsubstituted oximes proꢀ
ceeded stereoselectively to give in the moderate yields (30—60%) the only stereoisomer arising
from the attack of the heterocyclic anion from the less hindered side of the intermediate nitroso
olefin generated in situ from nitrosochloride.
Key words: monoterpenoids, 3ꢀcarene, ꢀpinene, limonene, ꢀaminoꢀoxime, imidazole,
benzotriazole, indole, nitroso olefin.
The reactions between amines and olefin nitrosoꢀ
chlorides (products of addition of NOCl to olefins) inꢀ
cluding a number of terpene nitrosochlorides1 are well
known giving rise to ꢀaminoꢀoximes, the novel chiral
chelating ligands.2 The promise of ꢀsubstituted oximes
as synthons for the design of complex chiral polycyclic
frameworks encourages further study of chemistry of nitroꢀ
sochlorides and development of synthetic procedures to
introduce various substituents into the ꢀposition to the
oxime fragment using nitrosochlorides as convenient highꢀ
ly reactive intermediates. We have previously shown that
nitrosochlorides react with the Cꢀnucleophiles giving chiral
malonates3 and some Sꢀnucleophiles.4 With the aim at
expanding the synthetic utility of nitrosochlorides, in the
present work we studied reactions (Scheme 1) of nitrosoꢀ
chlorides of natural monoterpenes, 3ꢀcarene (1), liꢀ
monene (6), and ꢀpinene (11), with simplest azaheteroꢀ
cycles (imidazole, benzotriazole, and indole).
When the reaction of monoterpene nitrosochlorides
with amines was carried out under "standard" conditions
(EtOH, excess of amine, heating),1 the satisfactory results
for primary and secondary amines (aliphatic and aromatꢀ
ic) were achieved, however for the studied heterocyclic
amines only trace amounts of the target substitution
products were found. In all cases, the major products
were ,ꢀunsaturated ketoximes, namely, 2ꢀcarenꢀ4ꢀone
(E)ꢀoxime,5—7 carvone (E)ꢀoxime,8 and a mixture of piꢀ
nocarvone (E)ꢀ and (Z)ꢀoximes9 formed in the reactions
of nitrosochlorides of 3ꢀcarene (1), limonene (6), and
ꢀpinene (11), respectively. These ketoximes are the reꢀ
sult of the extremely easy dehydrochlorination typical of
terpene nitrosochlorides. A detailed study of reaction of
monoterpene nitrosochlorides with imidazole, benzotriꢀ
azole, and indole under different conditions (different solꢀ
vents and temperature, in the presence of additional bases
and auxiliary agents) revealed the particular conditions
required for the smooth transformations of monoterpene
nitrosochlorides into ꢀsubstituted chiral ketoximes bearꢀ
ing azaheterocyclic fragment in the ꢀposition to the oxime
moiety (see Scheme 1).
Reproducible results and moderate yields of the target
products were achieved via optimization of the reaction
conditions. Thus, for the synthesis of ꢀ(1Hꢀimidazolꢀ1ꢀ
yl)ꢀsubstituted derivatives, the reaction can be carried out
in MeOH in the presence of NaOH at 30 C. Syntheses of
ꢀ(1Hꢀbenzo[d][1,2,3]triazolꢀ1ꢀyl)ꢀsubstituted derivatives
were performed in MeOH at a slightly higher temperaꢀ
ture (35 C) in the presence of anhydrous Mg(ClO4)2
and K2CO3 as a base. Addition of preliminary prepared
Nꢀindolyl manganese bromide (prepared from indole and
EtMgBr in diethyl ether at 15 C under inert atmosphere)
was necessary for the synthesis of ꢀ(1Hꢀindolꢀ3ꢀyl)ꢀsubꢀ
stituted oximes. In all cases, the corresponding ,ꢀunꢀ
saturated ketoximes mentioned above were the main side
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 587—593, March, 2012.
1066ꢀ5285/12/6103ꢀ589 © 2012 Springer Science+Business Media, Inc.

590
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 3, March, 2012
Bizyaev and Tkachev
Scheme 1
i. Imidazole, NaOH, MeOH, 15 h, 30 C; ii. Benzotriazole, Mg(ClO4)2, K2CO3, MeOH, 10 h, 35 C; iii. Indole, EtMgBr, Et2O, 10 h,
15 C, under nitrogen.

Reactions of terpene nitrosochlorides
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 3, March, 2012
591
Table 1. 1H NMR spectra of (+)ꢀ3ꢀcarene derivatives 3, 4, and 5
H Atom
H (J/Hz)
3 (CDCl3)
4 (CCl4—CDCl3)
5 (CDCl3)
1
0.71 (ddd, J = 9.1, J = 9.1,
J = 5.7)
1.09 (ddd, J = 9.3, J = 9.3,
J = 5.3)
0.83 (ddd, J = 9.5, J = 8.6,
J = 5.5)
2 (proꢀS)
2 (proꢀR)
5 (proꢀR)
5 (proꢀS)
6
2.76 (dd, J = 16.1, J = 9.1)
1.67 (dd, J = 16.1, J = 5.7)
2.25 (dd, J = 19.0, J = 8.8)
2.90 (dd, J = 19.0, J = 2.1)
0.63 (ddd, J = 9.1, J = 8.8,
J = 2.1)
3.72 (dd, J = 9.3, J = 15.3)
1.81 (dd, J = 5.0, J = 15.2)
1.86 (dd, J = 18.7, J = 8.9)
3.15 (d, J = 18.7)
0.47 (ddd, J = 0.8, J = 9.0,
J = 9.0)
2.80 (dd, J = 15.0, J = 9.5)
1.61 (dd, J = 15.0, J = 5.5)
2.14 (dd, J = 18.5, J = 9.0)
3.02 (dd, J = 18.5, J = 0.5)
0.57 (ddd, J = 9.0, J = 8.6,
J = 0.5)
8
0.85 (s)
0.91 (s)
0.92 (s)
9
0.97 (s)
0.95 (s)
0.97 (s)
10
1.50 (s)
1.66 (s)
1.52 (s)
=NOH
NH
ArH
10.9 (br, W1/2 = 500)
9.90 (br.s)
9.80 (br.s)
8.06 (br.s)
7.10 (dd, J = 8.0, J = 7.5);
7.11 (d, J = 2.5); 7.18 (dd,
J = 8.0, J = 7.5); 7.34 (d,
J = 8.0); 7.80 (d, J = 8.0)
6.95 (dd, J = 1.4, J = 1.4);
7.06 (dd, J = 1.4, J = 1.0);
7.66 (dd, J = 1.4, J = 1.0)
7.28 (dd, J = 8.2, J = 7.0);
7.33 (dd, J = 8.3, J = 7.0);
7.48 (ddd, J = 8.2, J = 1.0,
J = 1.0); 8.05 (ddd, J = 8.2,
J = 1.0, J = 1.0)
products. The target products were purified by column
chromatography on silica gel (for imidazole and benzoꢀ
triazole derivatives) or aluminum oxide (for indole deꢀ
rivatives).
a diastereomer mixture; the diastereomers can be separatꢀ
ed by preparative column chromatography. In the case of
the reaction of ꢀpinene with benzotriazole, formation of
the unusual product arising from alkylation of the N(2)
All heterocyclic monoterpene derivatives are colorless
crystalline compounds isolated in the pure state and fully
characterized by physicochemical and spectroscopic methꢀ
ods. The spatial structure of compounds synthesized were
unambiguously established by comparison of their 1H and
13C NMR spectral data (Tables 1—6) with those of the
corresponding ꢀhetarylꢀsubstituted monooximes, derivꢀ
atives of 3ꢀcarene, limonene, and ꢀpinene prepared by
the reaction of nitrosochlorides with amines.10,11 The folꢀ
lowing conclusions were drawn: (i) the new asymmetric
atom C(3) of 3ꢀcarene derivatives 3, 4, and 5 has Sꢀconꢀ
figuration; (ii) the new asymmetric atom C(1) of derivaꢀ
tives of a paraꢀmenthane series 8, 9, and 10 has Sꢀconfigꢀ
uration; (iii) the new asymmetric atom C(2) of pinane
derivatives 13, 14, and 15 has Rꢀconfiguration; (iv) the
oxime group of all synthesized ꢀsubstituted oximes 3—15
has Eꢀconfiguration.
Table 2. 13C NMR spectra of (+)ꢀ3ꢀcarene derivatives 3, 4, and 5
C

C (JC—H/Hz)
Atom
3 (CDCl3) 4 (CCl4—CDCl3)
5 (CDCl3)
1
2
17.66 (J = 159.8)
32.95 (2 C—H,
J = 128.6)
018.57
033.89
19.40 (J = 158.8)
33.61 (2 C—H,
J = 128.3)
3
4
5
58.58
158.15
17.74 (J = 133.2,
J = 127.5)
063.40
159.57
018.87
39.95
165.63
18.89 (J = 132.5,
J = 126.3)
6
7
8
18.75 (J = 161.5)
17.74
14.48 (3 C—H,
J = 125.0)
019.43
019.39
014.95
20.06 (J = 161.1)
19.03
14.63 (3 C—H,
J = 126.0)
This configuration of the molecules is in agreement
with the generally accepted mechanistic description of the
reaction between nitrosochlorides and nucleophiles as
a twoꢀstep elimination—addition process, namely, transꢀ
formation of the studied monoterpene nitrosochlorides into
ꢀsubstituted oximes proceeds stereoselectively to give the
only stereoisomer, the structure of the latter corresponded
to the attack of the azaheterocyclic anion from the less
hindered side of the intermediate nitroso olefin generated
from nitrosochloride under reaction conditions.1 The only
exception is the limonene indole derivative, which is
9
27.68 (3 C—H,
J = 125.7)
27.23 (3 C—H,
J = 128.8)
117.00 (d, J = 188.0, 110.76 (d); 111.08 (d, J = 155.1);
J = 16.0, J = 3.5); 120.12 (d); 119.37 (d, J = 157.5);
128.52 (d, J = 189.0, 123.59 (d); 119.93 (d, J = 160.0);
J = 9.9, J = 9.9); 127.13 (d); 120.04 (s);
135.48 (d, J = 207.9, 132.48 (s); 121.59 (d, J = 160.0);
027.85
024.38
27.97 (3 C—H,
J = 125.5)
26.26 (3 C—H,
J = 128.0)
10
Ar
J = 10.0, J = 7.0)
146.34 (s) 121.70 (d, J = 182.5);
126.12 (s); 136.60 (s)

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Bizyaev and Tkachev
Table 3. 1H NMR spectra (CDCl3) of (+)ꢀlimonene derivatives 8, 9, 10a, and 10b
H Atom
H (J/Hz)*
8
9
10a
10b
3 (proꢀR)
3 (proꢀS)
4
1.47 (dd, J = 14.3,
J = 13.1)
1.24 (dd, J = 13.1,
J = 13.1)
1.66 (dd, J = 13.3,
J = 12.9)
3.42 (ddd, J = 13.3,
J = 3.3, J = 1.3)
2.17 (m, W1/2 = 25)
2.25 (dd, J = 11.0,
J = 11.0)
2.99 (d.m, J = 11.0)
3.52 (ddd, J = 14.0,
J = 3.5, J = 1.8)
2.09 (dddd, J = 12.3,
J = 12.3, J = 3.3,
J = 3.3)
3.51 (ddd, J = 13.5,
J = 2.8, J = 1.5)
2.22 (dddd, J = 12.4,
J = 12.4, J = 3.5,
J = 3.5)
[2.28]
5 (proꢀR)
5 (proꢀS)
6 (proꢀS)
[1.46]
[1.80—1.90]
[1.80—1.90]
[1.78]
[1.78]
2.67 (m)
[1.83] or [1.75]
[1.75] or [1.83]
[1.75]
1.75 (d.m, J = 13.8)
2.59 (ddd, J = 14.9,
J = 3.3, J = 3.3)
1.88 (ddd, J = 14.9,
J = 13.6, J = 3.7)
4.61 (br.s)
3.58 (ddd, J = 14.5,
J = 3.3, J = 3.3)
1.98 (ddd, J = 13.5,
J = 13.5, J = 4.4)
4.57 (br.s)
6 (proꢀR)
[1.78]
2.41 (ddd, J = 14.1,
J = 11.5, J = 3.5)
4.85 (br.s)
4.87 (br.s)
1.81 (br.s)
8 (Ha)
8 (Hb)
9
4.62 (br.s)
4.65 (br.s)
1.64 (br.s)
4.67 (br.s)
1.62 (br.s)
4.63 (br.s)
1.59 (br.s)
10
1.54 (s)
1.72 (s)
1.57 (s)
1.57 (s)
=NOH
NH
11.9 (br)
9.61 (s)
9.24 (br)
8.03 (br.s)
8.5 (br)
8.01 (br.s)
ArH
6.93 (dd, J = 1.1,
J = 1.1); 7.08 (dd,
J = 1.1, J = 1.1);
7.61 (dd, J = 1.1,
J = 1.1)
7.32 (dd, J = 8.2,
J = 7.0); 7.38 (dd,
J = 8.2, J = 7.0);
7.59 (d, J = 8.2);
8.08 (d, J = 8.2)
7.02 (d, J = 2.5);
7.10 (ddd, J = 8.1,
J = 7.1, J = 1.1);
7.18 (ddd, J = 8.1,
J = 7.1, J = 1.1);
7.34 (dddd.d,
J = 8.1, J = 0.5,
J = 0.5, J = 0.5,
J = 0.5), 7.81 (d,
J = 8.0)
6.72 (d, J = 2.6);
7.10 (ddd, J = 8.1,
J = 6.8, J = 1.1);
7.15 (ddd, J = 8.1,
J = 7.5, J = 1.0);
7.20 (d, J = 7.9);
7.55 (d, J = 8.1)
* Chemical shifts for the overlapping multiplets determined from the 2D 13C—1H NMR experiments on direct couplings
1JC—H are given in brackets.
azole atom was detected. This is due apparently to the less
steric hindrance upon formation of this product in conꢀ
trast to the "normal" product. The specific behavior of
ꢀpinene nitrosochloride associated with steric hindrance
of the bicyclic pinane framework in the reactions with
some nucleophiles is known. Thus, the reactions of
Table 4. 13C NMR spectra (CDCl3) of (+)ꢀlimonene derivatives 8, 9, 10a, and 10b
C Atom

C Atom
Ar

C
C
8
9
10a
10b
8
9
10a
10b
1
60.65
157.02
26.15
43.66
25.95
37.72
147.34
109.63
20.49
28.11
65.31
159.12
26.74
44.41
26.66
38.51
147.34
109.63
20.42
24.91
45.34
164.57
26.80
42.19
27.61
39.12
148.47
109.03
20.65
27.62
40.79
162.82
25.64
43.03
26.21
37.63
148.00
109.68
21.02
25.47
116.40 (d);
128.69 (d);
134.87 (d)
111.18 (d); 111.03 (d); 111.33 (d);
119.91 (d); 119.44 (d); 118.62 (d);
123.82 (d); 120.00 (s); 121.22 (d);
127.26 (d); 120.41 (d); 121.24 (d);
132.20 (s);
146.47 (s)
2
3
4
5
6
7
8
9
10
121.25 (d); 121.38 (s);
121.78 (d); 121.49 (d);
125.89 (s); 125.39 (s);
136.76 (s)
137.05 (s)

Reactions of terpene nitrosochlorides
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 3, March, 2012
593
Table 5. 1H NMR spectra of (–)ꢀꢀpinene derivatives 13, 14a, 14b, and 15
H Atom
H (J/Hz)
13 (CCl4—CDCl3)
14a (CDCl3—DMSOꢀd6
14b (CDCl3—DMSOꢀd6
15 (DMSOꢀd6)
(4 : 1, v/v))
(4 : 1, v/v))
1
2.41 (dd, J = 5.5, J = 5.5)
3.02 (ddd, J = 18.8,
J = 2.9, J = 2.6)
2.57 (dd, J = 18.8, J = 2.6)
2.03 (dddd, J = 6.3,
J = 5.5, J = 2.9, J = 2.6)
0.92 (d, J = 10.9)
2.31 (dddd, J = 10.9,
J = 6.3, J = 6.3, J = 2.6)
1.01 (s)
2.81 (dd, J = 5.7, J = 5.7)
3.13 (ddd, J = 18.4,
J = 3.0, J = 3.0)
2.59 (dd, J = 18.4, J = 2.5)
2.01 (dddd, J = 5.8,
J = 5.8, J = 3.3, J = 2.6)
0.50 (d, J = 10.5)
2.05 (dddd, J = 10.5,
J = 5.9, J = 5.9, J = 3.3)
1.02 (s)
2.69 (dd, J = 5.7, J = 5.7)
3.11 (ddd, J = 18.2,
J = 3.3, J = 3.3)
2.63 (dd, J = 18.4, J = 2.2)
1.97 (dddd, J = 5.9,
J = 5.9, J = 3.3, J = 2.3)
0.61 (d, J = 10.1)
2.00 (dddd, J = 10.1,
J = 6.0, J = 6.0, J = 2.6)
0.99 (s)
2.55 (dd, J = 6.0, J = 6.0)
3.02 (ddd, (J = 18.5,
J = 3.6, J = 2.8)
2.45 (dd, J = 18.5, J = 2.6)
1.86 (dddd, J = 5.8,
J = 5.8, J = 3.2, J = 2.4)
0.94 (d, J = 10.5)
1.98 (dddd, J = 10.5,
J = 6.4, J = 6.4, J = 2.6)
0.98 (s)
4 (proꢀR)
4 (proꢀS)
5
7 (proꢀR)
7 (proꢀS)
8
9
1.37 (s)
1.31 (s)
1.29 (s)
1.27 (s)
10
1.73 (s)
2.09 (s)
2.04 (s)
1.70 (s)
=NOH
NH
ArH
12.5 (W1/2 = 700)
11.43 (br.s)
10.82 (br.s)
9.87 (br.s)
10.08 (s)
6.81 (dd, J = 1.1, J = 1.1);
6.99 (dd, J = 1.1, J = 1.1);
7.93 (dd, J = 1.1, J = 1.1)
7.27 (ddd, J = 8.5, J = 7.1,
7.26 (dd, J = 6.6, J = 3.0);
6.80 (d, J = 2.6); 6.88
(ddd, J = 8.0, J = 7.2,
J = 1.2); 6.98 (ddd,
J = 8.0, J = 7.0, J = 1.0);
7.25 (ddd, J = 8.1,
J = 0.8, J = 0.8); 7.58
(d, J = 8.0)
J = 1.0); 7.38 (ddd, J = 8.5, 7.76 (dd, J = 6.6, J = 3.0)
J = 6.9, J = 1.2); 7.50 (ddd,
J = 8.7, J = 0.9, J = 0.9);
7.93 (ddd, J = 8.5, J = 0.9,
J = 0.9)
Table 6. 13C NMR spectra of (–)ꢀꢀpinene derivatives 13, 14a, 14b, and 15
C Atom
C (JC—H/Hz)
13 (CCl4—CDCl3)
14a (CDCl3—DMSOꢀd6
14b (CDCl3—DMSOꢀd6
15 (DMSOꢀd6)
(4 : 1, v/v))
(4 : 1, v/v))
1
2
51.30
65.35
52.67 (J = 145.7)
69.75
53.13 (J = 148.9)
73.77
50.20
46.42
3
4
5
6
154.75
29.50
37.47
154.23
30.51 (2 C—H, J = 131.0)
37.04 (J = 146.6)
154.45
160.59
29.85
37.35
38.45
29.41 (2 C—H, J = 130.8)
37.34 (J = 143.5)
39.00
38.94
38.77
7
8
9
10
Ar
30.31
22.46
27.81
30.01
115.59 (d);
128.07 (d);
137.23 (d)
28.11 (2 C—H, J = 137.9)
21.57 (3 C—H, J = 124.1)
26.95 (3 C—H, J = 125.9)
26.80 (3 C—H, J = 129.3)
112.07 (d, J = 169.0);
119.12 (d, J = 163.8);
122.90 (d, J = 162.1);
126.55 (d, J = 162.1);
132.22 (s); 145.26 (s)
27.76 (2 C—H, J = 140.3)
21.42 (3 C—H, J = 124.4)
27.00 (3 C—H, J = 125.4)
26.59 (3 C—H, J = 130.0)
117.58 (d, 2 C,
J = 165.5); 125.41
(d, 2 C, J = 160.1);
142.95 (s, 2 C)
30.04
21.94
27.44
26.70
111.10 (d);
117.54 (d);
120.06 (d);
120.13 (d);
122.52 (d);
123.62 (s);
124.57 (s);
136.84 (s)
nitrosochlorides of 3ꢀcarene and limonene with aniline
gave the products of nucleophilic displacement of the chloꢀ
rine to the amino group, while in the case of ꢀpinene
nitrosochloride no products of such displacement formed.
Experimental
The following reactants were used: Sꢀ(–)ꢀꢀpinene (96% ee)
(Fluka AG, cat. No. 80600), (R)ꢀ(+)ꢀlimonene (98% ee) (Aldꢀ

594
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 3, March, 2012
Bizyaev and Tkachev
18
rich, cat. No. 18.316ꢀ4), (+)ꢀ3ꢀcarene (99.5% ee) with
MeCN), []578 +125 (c 2.64, MeOH). Found (%): C, 66.9;
H, 8.58; N, 17.6. C13H15N3O. Calculated: (%): C, 66.92; H, 8.21;
N, 18.01. High resolution MS: found, m/z 233.15273 [M]+.
C13H19N3O. Calculated: M = 233.15281. MS, m/z (Irel (%)): 233
(17.08), 166 (10), 110 (15), 107 (19), 93 (22), 79 (14), 69 (100),
67 (10), 55 (17). IR (CHCl3), /cm–1: 3581 (O—H). IR (KBr),
/cm–1: 1641 (C=CH2), 963 (N—O), 897 (C=CH2).
20
20
[]578 +16.0 (d4 = 0.863) obtained by distillation of turpenꢀ
tine of an ordinary pine; imidazole, benzotriazole, and indole
(reagent grade, ReaKhim). Nitrosochlorides of (+)ꢀ3ꢀcarene and
(–)ꢀꢀpinene were synthesized by passing gaseous nitrosyl chloꢀ
ride over a solution of terpene in dichloromethane.1 transꢀNitroꢀ
sochloride of Rꢀ(+)ꢀlimonene was prepared according to the
standard procedure by treatment of a terpene solution with
isoamyl nitrite.1 All solvents were distilled prior to use. TLC
were performed on an aluminum foil Sorbfil plates coated with
silica gel. The spots were visualized by spaying the plates with
developing solutions and further heating at 100—150 C. The
solutions of vanilin (1 g of vanilin + 5 mL of conc. H2SO4 + 100 mL
of 95% EtOH) and iron chloride (10 g of FeCl3•6H2O + 100 mL
of 95% EtOH) were used for the plates developing. The column
chromatography was performed on a silica gel with the particle
size 0.100—0.140 mm (grinding and fractionation were made in
the Experimental Chemical Production of NIOCh SB RAS).
NMR spectra were recorded on a Bruker DRXꢀ500 instruꢀ
ment (500.13 MHz for 1H, 125.75 MHz for 13C) for the solutions
with concentrations 70—100 mg mL–1 at 25—27 C. The solvent
signals were used as internal standard:  7.24 and  76.90 for
(1R,2R,5R)ꢀ2ꢀ(1HꢀImidazolꢀ1ꢀyl)pinanꢀ3ꢀone (E)ꢀoxime
(13). Yield 30%, colorless crystals, m.p. 172—173 C (from
18
MeCN), []578 –175 (c 2.17, MeOH). Found (%): C, 67.1;
H, 8.65; N, 17.6. C13H19N3O. Calculated (%): C, 66.92; H, 8.21;
N, 18.01. High resolution MS: found, m/z 233.15378 [M]+;
C13H19N3O. Calculated: M = 233.15281. MS, m/z (Irel (%)): 233
(19.37), 166 (38), 165 (20), 124 (21), 110 (97), 107 (17), 106 (38),
79 (28), 69 (100), 53 (20). IR (CHCl3), /cm–1: 3580 (O—H).
IR (KBr), /cm–1: 1638 (C=N), 925 (N—O).
Synthesis of benzotriazole derivatives 4, 9, and 14 (general
procedure). To a solution of benzotriazole (1.79 g, 15 mmol) in
MeOH (50 mL), Mg(ClO4)2 (1.85 g, 15 mmol), K2CO3 (4.14 g,
30 mmol), and dimeric nitrosochloride of (+)ꢀ3ꢀcarene 2,
(+)ꢀlimonene 7 or (–)ꢀꢀpinene 12 (powdered, 2.00 g, 5 mmol)
were added, and the reaction mixture was stirred at 35 C for
10 h. The solvent was removed in vacuo (waterꢀjet pump), the
residue was mixed with water (30 mL) and extracted with EtOAc
(3Ѕ30 mL). The combined organics were washed with brine
(15 mL), dried with Na2SO4, and concentrated in vacuo. Purifiꢀ
cation of the residue (SiO2, elution with hexane—EtOAc) and
further recrystallization from MeCN afforded target products.
(1R,3S,6R)ꢀ3ꢀ(1HꢀBenzo[d][1,2,3]triazolꢀ1ꢀyl)caranꢀ4ꢀone
(E)ꢀoxime (4). Yield 47%, colorless crystals, m.p. 154—155 C
H
C
CDCl3,  2.50 and  39.50 for DMSOꢀd6. The signals were
H
C
attributed using Jꢀresolved 13C NMR spectra (noise proton deꢀ
coupling, the opposite phase for the signals of the atoms with
even number of bonded protons with tuning on the constant
1
J = 135 Hz), the homonuclear 2D H—1H and heteronuclear
2D 13C—1H NMR experiments on the direct couplings (J = 135 Hz)
and heteronuclear 2D 13C—1H NMR experiments on the longꢀ
range couplings (J = 10 Hz). UV spectra were recorded on a HP
8453 UV/Vis spectrophotometer; IR spectra were run on a Bruker
TENSOR 27 Fourierꢀtransform IR spectrometer for the soluꢀ
tions in CHCl3 (C = 0.5%) or in KBr pellets (C = 0.25%). Optiꢀ
cal rotation was measured on a Polamat A polarimeter. Melting
points were determined on a Koefler apparatus. Mass spectra
were recorded on a Finnigan MATꢀ8200 mass spectrometer (EI,
70 eV). Elemental analyses were performed on Hewlett Packard
185 and Carlo Erba 1106 microanalysers.
14
(decomp., from MeCN), []578 +116 (c 1.50, MeOH).
Found (%): C, 67.2; H, 7.17; N, 19.8. C16H20N4O. Calculatꢀ
ed (%): C, 67.58; H, 7.09; N, 19.70. High resolution MS: found,
m/z 284.16379 [M]+. C16H20N4O. Calculated: M = 284.16371.
MS, m/z (Irel)): 284 (100), 267 (20), 150 (21), 148 (52), 120 (41),
91 (18), 78 (12), 77 (26), 69 (19), 41 (29). UV (EtOH), max/nm
(lg ): 257 (3.84), 262 (3.83), 281 (3.62). IR (CHCl3), /cm–1
:
3581 (O—H). IR (KBr), /cm—1: 1632 (C=N), 957 (N—O),
750 (H—Ar).
Synthesis of imidazole derivatives 3, 8, and 13 (general proceꢀ
dure). To a solution of imidazole (1.36 g, 20 mmol) and NaOH
(0.8 g, 20 mmol) in MeOH (50 mL), dimeric nitrosochloride of
(+)ꢀ3ꢀcarene 2, (+)ꢀlimonene 7 or (–)ꢀꢀpinene 12 (powdered,
2.00 g, 5 mmol) was added, and the reaction mixture was stirred
at 30 C for 15 h. The solvent was removed in vacuo (waterꢀjet
pump), the residue was mixed with water (30 mL), and extracted
with EtOAc (3Ѕ30 mL). The combined organics were washed
with brine (15 mL), dried with Na2SO4, and the solvent was
removed in vacuo. Column chromatography (SiO2, elution with
hexane—EtOAc) and further recrystallization from MeCN afꢀ
forded target product.
(1S,4R)ꢀ1ꢀ(1HꢀBenzo[d][1,2,3]triazolꢀ1ꢀyl)ꢀpꢀmenthꢀ7ꢀ
eneꢀ2ꢀone (E)ꢀoxime (9). Yield 50%, colorless crystals, m.p.
154—155 C (decomp., from MeCN), []578 +134 (c 1.91,
14
MeOH). Found (%): C, 67.3; H, 7.35; N, 19.3. C16H20N4O.
Calculated (%): C, 67.58; H, 7.09; N, 19.70. High resolution
MS: found, m/z 284.16341 [M]+. C16H20N4O. Calculated:
M = 284.16371. MS, m/z (Irel (%)): 284 (2), 269 (27), 120 (21),
91 (11), 78 (12), 77 (10), 72 (37), 71 (34), 43 (24), 42 (100).
UV (EtOH), max/nm (lg ): 256 (3.86), 262 (3.85), 281 (3.66).
IR (CHCl3), /cm–1: 3582 (O—H). IR (KBr), /cm–1: 1645
(C=CH2), 958 (N—O), 896 (=CH2), 748 (H—Ar).
(1R,3S,6R)ꢀ3ꢀ(1HꢀImidazolꢀ1ꢀyl)carnanꢀ4ꢀone (E)ꢀoxime
(3). Yield 50%, colorless crystals, m.p. 140—142 C (from
MeCN), []578 +181 (c 1.79, MeOH). Found (%): C, 66.6;
(1R,2R,5R)ꢀ2ꢀ(1HꢀBenzo[d][1,2,3]triazolꢀ1ꢀyl)pinanꢀ3ꢀone
(E)ꢀoxime (14a). Yield 40%, colorless crystals, m.p. 154—155 C
(decomp., from MeCN), []578 –138 (c 1.37, MeOH).
18
14
H, 8.49; N, 17.7. C13H19N3O. Calculated (%): C, 66.92; H, 8.21;
N, 18.01. High resolution MS: found, m/z 233.15372 [M]+.
C13H19N3O. Calculated: M = 233.15281. MS, m/z (Irel (%)): 233
(17), 216 (10), 165 (28), 164 (100), 150 (15), 148 (13), 137 (30),
123 (16), 106 (23), 79 (23), 69 (77). IR (CHCl3), /cm–1: 3582
(O—H). IR (KBr), /cm–1: 1636 (C=N), 980—920 (N—O).
(1S,4R)ꢀ1ꢀ(1HꢀImidazolꢀ1ꢀyl)ꢀpꢀmenthꢀ7ꢀeneꢀ2ꢀone (E)ꢀoxime
(8). Yield 40%, colorless crystals, m.p. 160—162 C (from
Found (%): C, 67.2; H, 7.17; N, 19.8. C16H20N4O. Calculatꢀ
ed (%): C, 67.58; H, 7.09; N, 19.70. High resolution MS:
found, m/z 284.16379 [M]+. C16H20N4O. Calculated:
M = 284.16371. MS, m/z (Irel)): 284 (100), 267 (20), 150 (21),
148 (52), 120 (41), 91 (18), 78 (12), 77 (26), 69 (19), 41 (29).
UV (EtOH), max/nm (lg ): 257 (3.82), 263 (3.81), 282 (3.60).
IR (CHCl3), /cm–1: 3581 (O—H). IR (KBr), /cm–1: 1611
(C=N), 976 (N—O), 750 (H—Ar).

Reactions of terpene nitrosochlorides
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 3, March, 2012
595
(2HꢀBenzo[d][1,2,3]triazolꢀ2ꢀyl)pinanꢀ3ꢀone (E)ꢀoxime
(14b). Yield 7%, colorless crystals, m.p. 154—155 C (decomp.,
from MeCN), []578 –21.3 (c 0.66, MeOH). Found (%):
(16), 118 (45), 117 (50), 115 (22), 43 (50), 41 (14). IR (CHCl3),
/cm–1: 3582 (O—H), 3479 (N—H). IR (KBr), /cm–1: 1645
(C=CH2), 936 (N—O), 890 (=CH2), 745 (H—Ar).
14
C, 67.2; H, 7.17; N, 19.8. C16H20N4O. Calculated (%): C, 67.58;
H, 7.09; N, 19.70. High resolution MS: found, m/z 284.16373
[M]+. C16H20N4O. Calculated: M = 284.16371. MS, m/z (Irel (%)):
284 (100), 267 (20), 150 (21), 148 (52), 120 (41), 91 (18), 78 (12),
77 (26), 69 (19), 41 (29). UV (EtOH), max/nm (lg ): 268 sh
(4.04), 275 sh (4.14), 279 (4.17), 285 sh (4.10). IR (CHCl3),
/cm–1: 3582 (O—H). IR (KBr), /cm–1: 1620 (C=N), 971
(N—O), 760 (H—Ar).
(1R,2R,5R)ꢀ2ꢀ(1HꢀIndolꢀ3ꢀyl)pinanꢀ3ꢀone (E)ꢀoxime (15).
Yield 54%, colorless crystals, m.p. 211—212 C (from CHCl3),
[]57813 –92 (c 1.87, THF). Found (%): C, 76.8; H, 7.99; N, 9.62.
C18H22N2O. Calculated (%): C, 76.56; H, 7.85; N, 9.92. High
resolution MS: found, m/z 282.17319 [M]+. C18H22N2O. Calcuꢀ
lated: M = 282.17321. MS, m/z (Irel (%)): 282 (4), 267 (43),
265 (46), 213 (36), 211 (55), 195 (18), 184 (100), 169 (31), 157
(11), 154 (16), 143 (44), 130 (34),117 (30), 41 (17). IR (CHCl3),
/cm–1: 3582 (O—H), 3480 (N—H). IR (KBr), /cm–1: 1618
(C=N), 935 (N—O), 741 (H—Ar).
Synthesis of indole derivatives 5, 10, and 15 (general proceꢀ
dure). To a solution of indole manganese salt (obtained from
indole (2.34 g, 20 mmol) and EtMgBr (20 mmol) in Et2O
(50 mL)), dimeric nitrosochloride of (+)ꢀ3ꢀcarene 2, (+)ꢀliꢀ
monene 7 or (–)ꢀꢀpinene 12 (powdered, 2.00 g, 5 mmol) was
added, the reaction mixture was stirred at 15 C for 10 h under
nitrogen. The solvent was removed in vacuo (waterꢀjet pump),
the residue was mixed with 5% aqueous NH4Cl (30 mL) and
extracted with EtOAc (3Ѕ30 mL). The combined organics were
washed with brine (15 mL), dried with Na2SO4, and concentratꢀ
ed in vacuo. Chromatography of the reddish oily residue (Al2O3,
elution with CCl4—methyl tertꢀbutylate) afforded target product.
(1R,3S,6R)ꢀ3ꢀ(1HꢀIndolꢀ3ꢀyl)caranꢀ4ꢀone (E)ꢀoxime (5).
Yield 60%, yellowish crystals, m.p. 183—184 C (from C6H6),
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 10ꢀ03ꢀ00346ꢀa).
References
1. A. V. Tkachev, Ross. Khim. Zh., 1998, 42, 42 [Mendeleev
Chem. J. (Engl. Transl.), 1998, 42].
2. S. V. Larionov, A. V. Tkachev, Ross. Khim. Zh., 2004, 48,
154 [Mendeleev Chem. J. (Engl. Transl.), 2004, 48].
3. S. N. Bizjaev, T. V. Rybalova, Yu. V. Gatilov, A. V. Tkachev,
Mendeleev Commun., 2004, 14, 18.
4. N. B. Gorshkov, A. M. Agafontsev, A. V. Tkachev, Izv. Akad.
Nauk, Ser. Khim., 2010, 1434 [Russ. Chem. Bull., Int. Ed.,
2010, 59, 1467].
5. A. V. Tkachev, A. V. Rukavishnikov, T. O. Korobeinicheva,
Yu. V. Gatilov, I. Yu. Bagrjanskaja, Zh. Org. Khim., 1990, 26,
1939 [Russ. J. Org. Chem. (Engl. Transl.), 1990, 26].
6. A. V. Tkachev, A. M. Chibiryaev, A. Yu. Denisov, Yu. V.
Gatilov, Tetrahedron, 1995, 51, 1789.
7. G. Widmark, Arkiv Kemi, 1957, 11, 195.
8. C. Bordenca, R. K. Allison, P. H. Dirstine, Ind. Eng. Chem.,
1951, 43, 1196.
9. Yu. G. Putsykin, V. P. Tashchi, A. F. Rukasov, Yu. A. Baskaꢀ
kov, V. V. Negrebetskii, L. Ya. Bogel´fer, Zh. Vsesoyuz. Khim.
Obshch. im. D. I. Mendeleeva, 1979, 24, 652 [Mendeleev Chem.
J. (Engl. Transl.), 1979, 24].
10. A. V. Tkachev, A. V. Rukavishnikov, Yu. V. Gatilov, I. Yu.
Bagrjanskaja, Zh. Org. Khim., 1990, 26, 1693 [J. Org. Chem.
USSR (Engl. Transl.), 1990, 26, No. 8].
23
[]578 +131 (c 0.86, MeOH). Found (%): C, 76.7; H, 7.99;
N, 9.52. C18H22N2O. Calculated (%): C, 76.56; H, 7.85;
N, 9.92. High resolution MS: found, m/z 282.17323 [M]+.
C18H22N2O. Calculated: M = 282.17321. MS, m/z (Irel (%)):
282 (4), 267 (43), 265 (46), 213 (36), 211 (55), 195 (18), 184 (100),
169 (31), 157 (11), 154 (16), 143 (44), 130 (34), 117 (30), 41 (17).
IR (CHCl3), /cm–1: 3583 (O—H), 3480 (N—H). IR (KBr),
/cm–1: 1618 (C=N), 935 (N—O), 744 (H—Ar).
(1R,4R)ꢀ1ꢀ(1HꢀIndolꢀ3ꢀyl)ꢀpꢀmenthꢀ7ꢀeneꢀ2ꢀone (E)ꢀoxime
(10a). Yield 40%, yellowish crystals, m.p. 165—167 C (from
CCl4), []57814 +153 (c 0.89, MeOH). Found (%): C, 76.2; H, 7.80;
N, 9.65. C18H22N2O. Calculated (%): C, 76.56; H, 7.85; N, 9.92.
High resolution MS: found, m/z 282.17294 [M]+. C18H22N2O.
Calculated: M = 282.17321. MS, m/z (Irel (%)): 282 (100), 264
(30), 265 (45), 249 (5), 170 (25), 142 (20), 130 (50), 117 (60), 105
(20), 43 (20), 41 (35). IR (CHCl3), /cm–1: 3583 (O—H), 3480
(N—H). IR (KBr), /cm–1: 1644 (C=CH2), 922 (N—O), 893
(=CH2), 745 (H—Ar).
(1S,4R)ꢀ1ꢀ(1HꢀIndolꢀ3ꢀyl)ꢀpꢀmenthꢀ7ꢀeneꢀ2ꢀone (E)ꢀoxime
(10b). Yield 10%, colorless crystals, m.p. 165—167 C (from
11. A. V. Tkachev, A. Yu. Denisov, A. V. Rukavishnikov, A. M.
Chibirjaev, Yu. V. Gatilov, I. Yu. Bagrjanskaja, Aust. J. Chem.,
1992, 45, 1077.
15
MeCN), []578 +114 (c 3.03, MeOH). Found (%): C, 76.6;
H, 7.50; N, 9.52. C18H22N2O. Calculated (%): C, 76.56; H, 7.85;
N, 9.92. High resolution MS: found, m/z 282.17388 [M]+.
C18H22N2O. Calculated: M = 282.17321. MS, m/z (Irel (%)):
282 (100), 267 (33), 265 (55), 182 (10), 170 (27), 165 (10), 148
Received February 15, 2011;
in revised form January 20, 2012