Reactions of terpene alcohols and diols with chlorine dioxide in dimethylformamide

Article abstract of DOI:10.1134/S107036321603018X

The system chlorine dioxide–dimethylformamide in combination with or without a catalytic amount of MoCl₅, CeCl₃, ZrOCl₂, or VO(acac)₂ induces oxidative chlorination of a number of bicyclic terpene alcohols and v

Full text of DOI:10.1134/S107036321603018X

ISSN 1070-3632, Russian Journal of General Chemistry, 2016, Vol. 86, No. 3, pp. 613–621. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © L.L. Frolova, A.V. Popov, L.V. Bezuglaya, I.N. Alekseev, P.A. Slepukhin, A.V. Kutchin, 2016, published in Zhurnal Obshchei Khimii,
2016, Vol. 86, No. 3, pp. 472–480.
To the 100th Anniversary of A.N. Pudovik
Reactions of Terpene Alcohols and Diols with Chlorine Dioxide
in Dimethylformamide
L. L. Frolovaa, A. V. Popova, L. V. Bezuglayaa, I. N. Alekseeva,
P. A. Slepukhinb,c, and A. V. Kutchina
a Institute of Chemistry, Komi Research Center, Ural Branch, Russian Academy of Sciences,
ul. Pervomaiskaya 48, Syktyvkar, 167982 Russia
e-mail: frolova-ll@chemi.komisc.ru
b Postovskii Institute of Organic Synthesis, Ural Branch, Russian Academy of Sciences,
ul. S. Kovalevskoi/Akademicheskaya 22/20, Yekaterinburg, 620990 Russia
c Yeltsin Ural Federal University, ul. Mira 19, Yekaterinburg, 620002 Russia
Received January 14, 2016
Abstract—The system chlorine dioxide–dimethylformamide in combination with or without a catalytic
amount of MoCl5, CeCl3, ZrOCl2, or VO(acac)2 induces oxidative chlorination of a number of bicyclic terpene
alcohols and vicinal diols. 2α-Chloropinan-3-one, 3α-chloro-10β-pinan-4-one, 5α-chloro-3α-hydroxycaran-4-
one, 5β-chloro-3β-hydroxycaran-4-one, and 4α-chloro-2α-hydroxypinan-3-one were thus synthesized in good
preparative yields.
Keywords: terpene alcohols, diols, α-chloroketones, α-chlorohydroxyketones, chlorine dioxide, selectivity
DOI: 10.1134/S107036321603018X
α-Chloroketones are widely used as intermediate
products in the synthesis of heterocyclic compounds,
epoxides (Darsens condensation), α-alkyl(aryl) thio-
carbonyl compounds, β-ketoesters, etc. Numerous
methods for the preparation of α-chloroketones are
known, most of which are based on the α-chlorination
of ketones with gaseous chlorine [1], N-chloro-
succinimide [2], sulfuryl chloride [3], selenonyl
chloride [4], copper(II) chloride [5], trichloroiso-
cyanuric acid [6], NaClO2–Mn(acac)3–Al2O3 [7], and a
polymeric analog of N,N-dichloro-4-methylbenzene-
sulfonamide in the presence of acid catalysts [8].
However, only a few examples of direct transformation
of secondary alcohols into α-chloroketones have been
reported. For instance, 2-chloroacetophenone was
obtained in 16% yield by treatment of 1-phenylethanol
with Cl2 in methylene chloride at –50°C [9]. Oxidative
chlorination of steroidal alcohols with tert-butyl
hypochlorite in acetic acid at 70°C afforded about 50%
of 2-chloro-3-keto steroids [10]. The yield of α-chloro-
3-ketosteroids increased to 57–84% when N-
chlorosuccinimide or t-BuOCl in tert-butyl alcohol
containing a small amount of water was used [11].
Kim et al. [12] proposed a one-pot procedure for
the synthesis of α-chloroketones from secondary
benzylic alcohols using the system m-chloro-
peroxybenzoic acid (m-CPBA)–HCl–DMF. The selec-
tivity for the target products was 80–98%, and the
yield reached 80–84%. Oxidative chlorination of the
same substrates was also accomplished with N,N-
dichloro-4-methylbenzenesulfonamide in acetonitrile,
the yield being 92–94% [13]. The direct transformation
of 1,2,3,4-tetrahydronaphthalen-1-ol into 2-chloro-
1,2,3,4-tetrahydronaphthalen-1-one by the action of N-
chlorosuccinimide in methylene chloride in the
presence of a composite catalyst was reported in [14].
α-Chloroketones were also synthesized in 38–79%
yield by direct oxidation of di- and trisubstituted
ethenes with chromyl chloride (CrO2Cl2) in acetone at
–70°C [15]. Swern oxidation of secondary alcohols
with excess (necessary condition) oxalyl chloride–
DMSO afforded ~50% of α-chloroketones [16].
α-Chloroisopulegone (a 3:2 mixture of stereo-
isomers) was synthesized in 75% yield by treatment of
pulegone with 1 equiv of HOCl in CH2Cl2 at –60°C
613

614
FROLOVA et al.
values due to presence of a strained four-membered
ring. The methylene group of the four-membered ring,
hydroxy group, and chlorine atom are located at one
side of the O1C1C2C3 mean-square plane. 4α-Chloro-
2α-hydroxypinan-4-one molecules in crystal are linked
to centrosymmetric dimers through intermolecular
hydrogen bonds O1–H···O1 [–x, 1 – y, 1 – z] between
the hydroxy group and carbonyl oxygen atom. The
other noticeable intermolecular contact is related to
acidity of the proton on C1 due to joint electron-
withdrawing effects of the carbonyl group and chlorine
atom on C1. As a result, hydrogen bond C1–H···O2 [–x,
0.5 + y, 0.5 – z] is formed with an H···O distance of
2.3 Å, which is shorter by 0.4 Å than the sum of the
corresponding van der Waals radii.
Fig. 1. Structure of the molecule of 4α-chloro-2α-hydroxy-
pinan-3-one according to the X-ray diffraction data with
atom numbering.
In continuation of this study, in the present work we
examined reactions of ClO2 with other terpene
alcohols and 1,2-diols in DMF in the absence and in
the presence of transition metal catalysts [MoCl5,
ZrOCl2, VO(acac)2, and CeCl3). The substrates were
isopinocampheol (1), neoisoverbanol (2), borneol (3),
isoborneol (4), isocaran-4-ol (5), cis-verbenol (6),
trans-verbenol (7), carane-3α,4α-diol (8), carane-
3β,4β-diol (9), carane-3β,4α-diol (10), pinane-2α,3α-
diol (11), and pinane-2α,3β-diol (12).
[17]. Pinocarveol reacted with HCl in anhydrous
diethyl ether, and subsequent oxidation of of the
corresponding hydrochloride afforded 2-chloropinan-
3-one [18].
We previously showed that the oxidation of 3α,4α-
caranediol with chlorine dioxide in DMF gave 40% of
5α-chloro-3α-hydroxycaran-4-one [19]. By treatment
of racemic 2α-hydroxypinan-3-one with ClO2 in DMF
for 4 days we obtained 45% (preparative yield) of
racemic 4α-chloro,2α-hydroxypinan-4-one whose
structure was later confirmed by X-ray analysis
(Fig. 1). According to the X-ray diffraction data, the
bond lengths in the molecule of 4α-chloro-2α-
hydroxypinan-4-one approach the corresponding
reference values, while bond angles at some sp3-carbon
atoms considerably deviate from the ideal tetrahedral
The oxidative chlorination of isopinocampheol (1)
in DMF in the absence of a catalyst was fairly slow.
The complete conversion of the substrate was attained
only in 12 h, but addition of a catalyst strongly
accelerated the reaction. The selectivity for α-chloro-
ketone 14 was 70–76% (Table 1). When the reaction
was carried out in pyridine for 2 h, the substrate
conversion was 95%, and isopinocamphone (13) was
formed in 95% yield, whereas no chlorine-containing
products were detected. Unlike initial alcohol 1, the 1H
NMR spectrum of 14 contained a singlet (rather than
doublet) from the C10H3 group, which was displaced
downfield, indicating the presence of a heteroatom
(chlorine or oxygen) on C2. In addition, no signal
assignable to CHOH proton was observed. Compound
14 showed in the 13C NMR spectrum signals from
three carbon atoms with no protons attached thereto,
including the carbonyl carbon signal at δC 206 ppm.
The formation of chloroketone rather than hydroxy-
ketone follows from comparison with the NMR spectra
of known 2α-hydroxypinan-3-one (29). The reaction
may be accompanied by epimerization at C2 after
eliminations of the 2-H proton. However, the observed
NOE between 8-H and 10-H indicated that the
configuration of C2 was retained (Scheme 1).
Table 1. Oxidation of compound 1 with chlorine dioxidea
Reaction
time, h
Conversion,
%
Selectivity
for 14, %
Catalyst
–
–
6
12
3
55
96
69
77
76
70
ZrOCl2
VO(acac)2
100
100
3
MoCl5
–
3
2
92
95b
76
–
a
Reaction conditions: DMF, 20°C, 1.5 mol % of catalyst.
In pyridine.
b
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REACTIONS OF TERPENE ALCOHOLC AND DIOLS WITH CHLORINE DIOXIDE
615
Table 2. Oxidation of compound 2 with chlorine dioxidea
Unlike compound 1, oxidative chlorination of
neoisoverbanol (2) was very fast in the absence of a
catalyst. By contrast, addition of catalysts reduced the
concentration of α-chloroketone 16 in the reaction
mixture (Table 2). In the NMR spectra of 16 we
observed signals of only one methylene group instead
of two methylene groups in 2, and a carbonyl carbon
signal appeared instead of CHOH. The configuration
of 16 was confirmed by the NOEs 3-H/8-H, 3-H/10-H,
8-H/10-H, and 2-H/7-endo-H. The fraction of dichloro-
ketone 17 among the products was 1–3%. This
compound was isolated and characterized by IR and
NMR spectra. The 13C NMR spectrum of 17 lacked
one methylene carbon signal, but a signal typical of
Csp3Cl2 group appeared at δC 89.3 ppm. The cis
orientation of the CMe2 group with respect to C10 was
confirmed by the NOEs 8-H/10-H and 2-H/7-endo-H.
The major product of the oxidation of 2 in pyridine
was cis-verbanone 15 (Scheme 2).
Catalyst
–
Conversion, %
100
Selectivity for 16, %
75
61
48
28
5
VO(acac)2
ZrOCl2
MoCl5
–
100
100
59
100b
a
Reaction conditions: DMF, 20°C, 2 h, 1.5 mol % of catalyst.
In pyridine.
b
(~15 h) [19]. In order to accelerate oxidative
chlorination of 8, the reaction temperature was raised
to 40°C, catalysts (ZrOCl2, MoCl5, CeCl3) were added,
and the concentration of CeCl3 was increased from 1.5
to 9.0 mol % (Table 4). The optimal conditions for the
formation of 22 were room temperature, reaction time
7 h, and CeCl3 concentration 5–9 mol %. The isolated
yield of 22 was 51% (after column chromatography on
silica gel). We also succeeded in isolating pure isomer
23 whose fraction in the product mixture was as low as
3–5% (Scheme 4).
Under analogous conditions, borneol (3),
isoborneol (4), and cis- and trans-verbenols 6 and 7
were converted, respectively, into camphor (18) and
verbenone (20) with high selectivity [20] (Scheme 3).
Unexpectedly, isocaran-4-ol (5) in DMF was neither
oxidized nor chlorinated, whereas in pyridine ketone
19 was formed with a selectivity of 81–91% (Table 3).
The oxidation of carane-3β,4β-diol (9) with ClO2 in
DMF (5–6 h) afforded 5α-chloro-3β-hydroxycaran-4-
one (25, tR = 16.56 min) with a selectivity of 91%. It
was identified by NMR spectroscopy without isolation
Compound 22 was synthesized previously by
prolonged oxidation of diol 8 at room temperature
Scheme 1.
Scheme 3.
10
Cl
O
OH
O
ClO2
DMF
2
ClO2
DMF
8
OH
O
OH
ClO2
DMF
ClO2
DMF
14
1
13
3
18
4
Scheme 2.
OH
O
ClO2
Py
ClO2
ClO2
DMF
×
DMF
OH
O
2
15
5
19
10
2
Cl
Cl
Cl
3
ClO2
DMF
ClO2
DMF
ClO2
DMF
8
+
7
OH
O
OH
O
O
6
7
16
17
20
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 3 2016

616
FROLOVA et al.
Table 3. Oxidation of compounds 3–7 with chlorine dioxidea
Comp. no.
3
Solvent
Catalyst
Reaction time, h Conversion, %
Selectivity for 18–20, %
DMF
DMF
VO(acac)2
3
3
3
3
3
3
3
3
2
3
4
3
98
99
100
100
98
ZrOCl2
4
5
DMF
VO(acac)2
100
100
DMF
ZrOCl2
99
DMF
VO(acac)2, ZrOCl2, MoCl5
No reaction
Pyridine
Pyridine
Pyridine
Pyridine
DMF
–
78
94
91
81
83
79
88
76
84
VO(acac)2
MoCl5
100
100
100
89
6
7
–
–
–
–
Pyridine
DMF
100
a Reaction conditions: 20°C, 1.5 mol % of catalyst.
Table 4. Oxidation of compounds 8 and 9 with chlorine dioxide in DMF
Comp. no.
Catalyst, mol %
–
Reaction time, h Temperature, °C Conversion, %
Selectivity for 22 or 25, %
8
5
10
15
15
15
7
40
40
20
40
20
20
20
20
20
20
60
81
83
47
63
77
93
98
90
100
53
–
ZrOCl2 (1,5)
MoCl5 (1,5)
CeCl3 (1,5)
CeCl3 (2,5)
CeCl3 (5,0)
CeCl3 (9,0)
–
75
65
72
76
57
72
80
67
91
7
7
9
2
–
6
(Table 4). An attempt to isolate chloroketone 25 by
silica gel column chromatography (hexane–Et2O) led
to its complete isomerization to 5β-chloro-3β-hyd-
roxycaran-4-one (26, tR = 17.61 min) whose structure
was determined by X-ray analysis (Fig. 2, Scheme 5).
According to the X-ray diffraction data, compound 26
crystallized in a chiral space group belonging to the
monoclinic crystal system. Its unit cell included two
crystallographically independent molecules with S
configuration of the CCl carbon atom. The configura-
tion was determined on the basis of anomalous
scattering data. The Flack parameter was characterized
by a significant error. Nevertheless, the absolute
configuration determined in this way was consistent
with that expected from the corresponding chemical
transformations. Figure 2 shows the structure of
molecule 26 with atom numbering, where atoms of the
second molecule are marked with additional
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 3 2016

REACTIONS OF TERPENE ALCOHOLC AND DIOLS WITH CHLORINE DIOXIDE
superscript “A.” The geometric parameters of both
617
molecules are close to the corresponding standard
values with insignificant differences from each other.
The cyclohexane fragment has
a
pseudo-sofa
conformation in which five ring atoms lie in one plane
within 0.070 and 0.085 Å, and the carbon atom bearing
hydroxy group deviates from that plane by 0.719 and
0.651 Å, respectively. The OH oxygen atom is located
in the equatorial plane, and the chlorine atom occupies
pseudoequatorial position. The molecular conforma-
tion is determined by intra- and intermolecular
hydrogen bonds which link molecules 26 to dimers,
and the latter underlie the crystal packing motif. In
addition, strongly shortened ClC–H···O contact with
the OH oxygen atom should be noted due to acidity of
the ClCH proton in the α-position with respect to the
carbonyl group.
Fig. 2. Structure of the molecule of 5β-chloro-3β-hydroxy-
caran-3-one (26) according to the X-ray diffraction data with
atom numbering.
The NMR spectra of 25 and 26, as well as of the
other two isomers 22 and 23, differed not only by the
signal position and multiplicity of the 5-H signal but
also by the character of NOE correlations.
Scheme 4.
OH
OH
The oxidation of carane-3β,4α-diol (10) with
chlorine dioxide in DMF was not selective. Among the
products, we succeeded in isolating only two minor
ones, meta-menthane derivatives 27 and 28 (Scheme 6).
Opening of the three-membered ring in carane
derivatives usually gives para-menthane structures,
whereas the formation of meta-menthane or
cycloheptane skeleton is observed much more rarely.
In our case, it was impossible to assign the entire set of
functional groups to para-menthane or cycloheptane
structure on the basis of spectral data. Compound 27
contained a cis-configured disubstituted double bond
O
OH
ClO2
DMF
21
8
OH
OH
O
O
ClO2
DMF
+
Cl
Cl
23
22
Scheme 6.
Scheme 5.
OH
OH
OH
OH
O
OH
ClO2
DMF
24
10
9
OH
OH
Cl
OH
O
O
O
O
ClO2
DMF
6
SiO2
ClO2
DMF
1
+
5
8
Cl
Cl
Cl
Cl
HO
25
26
27
28
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 3 2016

618
FROLOVA et al.
Table 5. Oxidation of compounds 11 and 12 with chlorine
pure initial compounds were recovered from the
reaction mixtures.
dioxidea
Comp.
no.
Reaction Conversion, Selectivity
Diol 11 was fairly rapidly oxidized with ClO2–
DMF even in the absence of a catalyst (7 h, 100%
conversion); however, the chlorination of 2α-
hydroxypinan-3-one thus obtained was much slower.
Only after 48 h in the presence of 5 mol % of CeCl3
the concentration of chloro hydroxy ketone 30 attained
90%. The product was isolated by crystallization. The
oxidative chlorination of isomeric pinane-2α,3β-diol
(12) was characterized by lower rate and selectivity.
After 6 h, the conversion of diol 12 was 79%, and the
product mixture contained (according to the GLV
data), 45% of hydroxy ketone 29 and 9% of chloro
hydroxy ketone 30, while the other products were not
identified (Table 5, Scheme 7).
Catalyst
–
time, h
%
for 30, %
11
7
7
100
100
100
100
100
100
100
64
17
21
23
20
35
62
90
11
11
MoCl5
VO(acac)2
CeCl3
CeCl3
CeCl3
CeCl3
–
7
7
15
24
48
2
12
Thus, the system ClO2–DMF acts as not only
oxidant but also chlorinating agent. The product
structure (α-chloroketone or α-chlorohydroxyketone) is
determined by both substrate nature and stereo-
chemical orientation of the hydroxy groups in initial
isomeric terpene diols. cis-Diols are converted into the
corresponding chlorohydroxyketones with fairly high
selectivity, whereas the oxidatibe chlorination of trans-
diols is much less selective. In some cases, the system
ClO2–DMF may be recommended for one-pot prepara-
tion of α-chloroketones or α-chlorohydroxyketones.
–
6
79
a Reaction conditions: DMF, 20°C, 5 mol % of catalyst.
conjugated with a carbonyl group, as followed from
the presence of an absorption band at 1690 cm–1 in the
IR spectrum and of a signal at δC 197 ppm in the C
13
NMR spectrum. Two quaternary carbon signals were
observed in the region δC 84–85 ppm, which is typical
of chloro derivatives. Analogous reasoning lead to
structure 28 which also possesses a carbonyl group
conjugated with a double bond, but the latter is
trisubstituted. The double-bonded carbon atom
attached to heteroatom resonated at δC 130 ppm, and
two signals at δC 73–74 ppm were typical of C–OH
carbon atoms.
EXPERIMENTAL
GLC analysis was performed on a Shimadzu GC-
2010AF chromatograph (HP1 column, flame ioniza-
tion detector, carrier gas helium). The IR spectra were
recorded from thin films or KBr pellets on a Shimadzu
Neither oxidation nor chlorination occurred when
diols 9 and 10 dissolved in DMF were treated with an
aqueous solution of chlorine dioxide. After 24 h, the
1
IR Prestige 21 spectrometer. The H and 13C NMR
spectra were recorded on a Bruker Avance II-300
spectrometer at 300 and 75 MHz, respectively, using
CDCl3 or DMSO-d6 as solvent. The melting points
were determined on a TP melting point apparatus. The
optical rotations were measured on a Kruss P3002RS
automated polarimeter. Silica gel 60 (70–230 mesh,
Alfa Aesar) was used for column chromatography.
Analytical TLC was performed on Sorbfil plates using
hexane and petroleum ether–diethyl ether as eluents;
spots were visualized by treatment with a 10% solution
of phosphomolybdic acid in ethanol or a 3% solution
of vanillin in ethanol.
Scheme 7.
OH
OH
10
OH
OH
11
12
O
O
ClO2
DMF
ClO2
DMF
8
4
OH
Cl
OH
29
30
An aqueous solution of chlorine dioxide with a
concentration of 8–9 g/L was provided by Mondi
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 3 2016

REACTIONS OF TERPENE ALCOHOLC AND DIOLS WITH CHLORINE DIOXIDE
619
Syktyvkarskii LPK public corporation. All reactions
were carried out in freshly distilled solvents.
(for all reflections); goodness of fit 1.002; residual
electron density Δρē = 0.234/–0.211 ē/Å3.
General procedure for the oxidation of terpene
alcohols and diols. Gaseous chlorine dioxide was
passed through a solution of 0.2–0.5 g of compound 1–
12 in dimethylformamide containing MoCl5, ZrOCl2,
VO(acac)2, or CeCl3 as catalyst (or not). The progress
of the reaction was monitored by TLC and GLC. When
the reaction was complete, the solvent was distilled
off, and the residue was diluted with water and
extracted with diethyl ether. The extract was washed
with brine and dried over anhydrous. The solvent was
removed, and the residue was analyzed by GLC. The
products were isolated by column chromatography on
silica gel or by crystallization. Isopinocamphone (13),
cis-verbanone (15), camphor (18), verbenone (20), 3α-
hydroxycaran-4-one (21), 3β-hydroxycaran-4-one (24),
and 2α-hydroxypinan-3-one (29) were identified by GLC.
X-Ray analysis of compound 30. Intensities of
9524 reflections, including 2651 independent reflec-
tions (Rint = 0.0272) and 1147 reflections with I > 2σ(I),
were measured on an Xcalibur S automated diffrac-
tometer according to standard procedure (MoKα radia-
tion, graphite monochromator; 295 K; ω-scanning with
a step of 1°; 3.18° < θ < 28.31°). No correction for
absorption was applied (μ = 0.323 mm–1). Monoclinic
crystal system, space group P21/c; unit cell parameters:
a = 7.7339(9), b = 11.5784(14), c = 12.0715(12) Å;
β = 96.824(9)°; V = 1073.3(2) Å3; Z = 4. The structure
was solved by the direct method and refined against F2
by the full-matrix least-squares procedure in aniso-
tropic approximation for all non-hydrogen atoms using
SHELXTL package [21]. Hydrogen atoms were placed
in geometrically calculated positions, and their
positions were refined according to the riding model
with dependent isotropic thermal parameters. The OH
proton was refined independently in isotropic
approximation. Final divergence factors: R1 = 0.0499,
wR2 = 0.1371 [for reflections with I > 2σ(I)]; R1 =
0.1069, wR2 = 0.1464 (all reflections); goodness of fit
1.008; residual electron density Δρē = 0.371/–0.398 ē/Å3.
2α-Chloropinan-3-one (14). Yield 0.355
g
(71.0%), mp 51–52°C, Rf 0.72 (hexane–Et2O, 2:1),
[α]D25 = 96.4 (c = 1.1, EtOH). IR spectrum, ν, cm–1:
2978, 2935, 2875, 1728 (C=O), 1471, 1448, 1409,
1373, 1321, 1267, 1240, 1209, 1145, 1099, 1047, 945,
914, 866, 831, 729 (C–Cl), 628, 551. 1H NMR
spectrum (CDCl3), δ, ppm, (J, Hz): 0.93 s (3H, C8H3),
1.41 s (3H, C9H3), 1.79 s (3H, C10H3), 1.91 d (1H, 7-H,
J = 11), 2.17 m (1H, 5-H, J = 2.4, 6.1), 2.41 d.d (1H,
1-H, J = 6.1, 6.2), 2.59 m (1H, 7-H, J = 11.0), 2.70
d.d.d (1H, 4-H, J = 3.0, 6.2, 19.0), 2.77 d.d (1H, 4-H,
X-Ray analysis of compound 26. Intensities of
5054 reflections, including 3740 independent reflec-
tions (Rint = 0.0265) and 3430 reflections with I > 2σ(I)
were measured on an Xcalibur S automated diffrac-
tometer according to standard procedure [MoKα
radiation, graphite monochromator; 150.01(10) K; ω-
scanning with a step of 1°; 1.90° < θ < 30.67°]. A
correction for absorption was applied empirically
μ(MoKα) = 0.329 mm–1. Monoclinic crystal system,
space group P21; unit cell parameters: a = 8.8353(4),
b = 11.1445(5), c = 10.7336(4) Å; β = 92.638(4)°; V =
1055.77(8) Å3; Z = 4; Flack parameter –0.07(6). The
structure was solved by the direct method and refined
against F2 by the full-matrix least-squares procedure in
anisotropic approximation for non-hydrogen atoms
using Olex2 [22] and SHELXTL packages [21].
Hydrogen atoms of the OH groups and those attached
to tertiary carbon atoms were refined independently in
isotropic approximation. The other hydrogen atoms
were placed in geometrically calculated positions, and
their positions were refined according to the riding
model with dependent thermal parameters. Final
divergence factors: R1 = 0.0368, wR2 = 0.0908 [for
reflections with I > 2σ(I)]; R1 = 0.0419, wR2 = 0.0990
13
J = 2.4, 19.0). C NMR spectrum, (CDCl3), δC, ppm:
206.02 (C3), 73.98 (C2), 52.84 (C1), 43.06 (C4), 40.26
(C6), 38.27 (C5), 31.55 (C7), 27.47 (C9), 27.50 (C10),
22.79 (C8).
3α-Chloro-10β-pinan-4-one (16). Yield 0.164 g
(63.0%), mp 65–66°C, Rf 0.58 (hexane–Et2O, 1:1),
[α]D25 = 1.8 (c = 0.4, EtOH). IR spectrum, ν, cm–1:
2958, 2939, 2879, 1728 (C=O), 1467, 1382, 1294,
1249, 1188, 983, 881, 773 (C–Cl), 650, 626, 586, 503.
1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 0.98 s
(3H, C8H3), 1.24 d (3H, C10H3, J = 7.4), 1.32 s (3H,
C9H3), 1.39 d (1H, 7-H, J = 11.0), 2.16 d.d.d (1H, 1-H,
J = 2.3, 5.7, 5.8), 2.42 d.d.q (1H, 2-H, J = 2.3, 5.7,
7.4), 2.68 d.d (1H, 5-H, J = 5.5, 5.8), 2.77 d.d.d (1H,
13
7-H, J = 4.8, 6.0, 11.0), 4.59 d (1H, 3-H, J = 5.7). C
NMR spectrum (DMSO-d6), δC, ppm: 206.08 (C4),
62.25 (C3), 58.49 (C5), 47.80 (C1), 45.38 (C2), 39.62
(C6), 29.37 (C7), 26.96 (C9), 24.93 (C8), 19.11 (C10).
3,3-Dichloro-10β-pinan-4-one (17). IR spectrum,
ν, cm–1: 2932, 2878, 1736 (C=O), 1474, 1385, 1244,
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FROLOVA et al.
1
1186, 1096, 980, 808, 772 (C–Cl), 681, 569. H NMR
spectrum (DMSO-d6), δ, ppm (J, Hz): 0.93 s (3H,
C8H3), 1.35 d (3H, C10H3, J = 7.5), 1.37 s (3H, C9H3),
2.02 d (1H, 7-H, J = 11.0), 2.29 d.d.d (1H, 1-H, J =
2.8, 5.6, 7.0), 2.70 d.d.d (1H, 7-H, J = 5.5, 7.0, 11),
2.86 d.d (1H, 5-H, J = 5.5, 5.6), 3.36 d.q (1H, 2-H, J =
2.8, 7.5). 13C NMR spectrum (DMSO-d6), δC, ppm:
199.59 (C4), 89.35 (C3), 56.86 (C5), 51.28 (C2), 47.74
(C1), 43.52 (C6), 26.84 (C9), 26.64 (C7), 25.05 (C8),
19.76 (C10).
14.3), 2.00 d.d (1H, 2-H, J = 7.7, 14.3), 4.57 d (1H,
5-H, J = 6.6). 13C NMR spectrum (DMSO-d6), δC,
ppm: 206.6 (C4), 74.0 (C3), 59.3 (C5), 33.0 (C2), 28.0
(C6), 27.3 (C8), 25.7 (C10), 21.1 (C7), 20.6 (C1), 14.4
(C9).
5β-Chloro-3β-hydroxycaran-4-one (26). Yield
0.161 g (77%), mp 85–87°C, Rf 0.38 (Et2O–hexane,
1:1), [α]D25 = 179.1 (c = 0.3, EtOH). IR spectrum, ν,
cm–1: 3495 (OH), 3012, 2983, 2954, 2933, 2912, 1724
(C=O), 1450, 1382, 1361, 1282, 1226, 1186, 1145,
Isocaran-4-one (19). Yield 65%, [α]D25 = –134° (c =
1.5, EtOH). IR spectrum: ν 1710 cm–1 (C=O). 1H NMR
spectrum (CDCl3), δ, ppm (J, Hz): 0.80 s (3H, C8H3),
0.91 d (3H, C10H3, J = 6.5), 0.99 s (3H, C9H3), 0.90–
1.10 m (2H, 1-H, 6-H), 1.21 m and 2.23 m (1H each,
2-H), 2.30 m (1H, 5-H), 2.32 m (1H, 3-H), 2.48 d.d
(1H, 5-H, J = 8.3, 18). 13C NMR spectrum (CDCl3),
δC, ppm: 216.48 (C4), 41.88 (C3), 36.74 (C5), 29.71
(C2), 27.83 (C9), 20.28 and 22.78 (C1, C6), 19.37 (C7),
14.78 (C8), 14.02 (C10).
1089, 1033, 970, 939, 812, 790, 759 (C–Cl), 734. H
1
NMR spectrum (DMSO-d6), δ, ppm, (J, Hz): 0.84 s
(3H, C8H3), 1.04 s (3H, C9H3), 1.16 d.d.d (H, 1-H, J =
3.9, 8.5, 9.8), 1.39 s (3H, C10H3), 1.72 d.d (1H, 2-H,
J = 3.8, 14.6), 1.76 d.d (1H, 6-H, J = 8.5, 8.5), 2.23 d.d
(1H, 2-H, J = 9.8, 14.6), 5.73 d (1H, 5-H, J = 8.4). 13C
NMR spectrum (DMSO-d6), δC, ppm: 207.8 (C4), 76.7
(C3), 64.8 (C5), 37.4 (C2), 33.0 (C6), 28.2 (C9), 25.7
(C10), 22.3 (C7), 22.2 (C1), 16.0 (C8).
6-Chloro-4-(2-chloropropan-2-yl)-6-methylcyclohex-
2-en-1-one (27). Concentration 97% (GLC). IR spec-
trum, ν, cm–1: 3041 (=C–H), 2978, 2933, 1691 (C=O),
1462, 1373, 1275, 1255, 1196, 1173, 1126, 1085, 968,
893, 827 (C–Cl), 678, 521. 1H NMR spectrum
(DMSO-d6), δ, ppm (J, Hz): 1.10 s (3H, C10H3), 1.27 s
(3H, C7H3), 1.38 s (3H, C9H3), 1.95 d (1H, 5-H, J =
12.0), 2.35 d.d.d (1H, 5-H, J = 1.5, 4.0, 12), 2.92 d.d
(1H, 4-H, J = 4.0, 7.0), 6.00 d (1H, 2-H, J = 9.5), 7.40
5α-Chloro-3α-hydroxycaran-4-one (22). Yield
0.26 g (51%), mp 97–98°C, Rf 0.62 (Et2O–hexane, 2 : 1),
[α]D25 = –340.8 (c = 0.3, CHCl3). IR spectrum, ν, cm–1:
1
3516 (OH), 1730 (C=O), 1139 (C–O), 769 (C–Cl). H
NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 0.9–1.2 m
(2H, 1-H, 6-H); 1.10 s, 1.15 s, and 1.19 s (3H each,
C8H3, C9H3, C10H3), 1.57 d.d (1H, 2-H, J = 9.4, 15.3),
1.97 d.d (1H, 2-H, J = 7.4, 15.3), 4.75 d (1H, 5-H, J =
8.0), 5.53 s (1H, OH). 13C NMR spectrum (DMSO-d6),
δC, ppm: 206.17 (C4), 74.39 (C3), 61.02 (C5), 32.81
(C2), 29.30 (C6), 27.76 (C9), 25.39 (C10), 21.55 (C7),
21.44 (C1), 14.31 (C8).
13
d.d.d (1H, 3-H, J = 1.5, 7.0, 9.5). C NMR spectrum
(DMSO-d6), δC, ppm: 197.27 (C1), 155.56 (C3), 128.05
(C2), 85.32 and 84.11 (C6, C8), 47.91 (C4), 45.74 (C5),
29.96 (C9), 25.64 (C10), 19.28 (C7).
5β-Chloro-3α-hydroxycaran-4-one (23). Yield
0.06 g (2%), mp 128–129°C (decomp.), [α]D25 = 195.1°
(c = 0.3, EtOH). IR spectrum, ν, cm–1: 3512 (OH),
3021, 2984, 2949, 2926, 1730 (C=O), 1450, 1373,
2-Chloro-6-hydroxy-4-(2-hydroxypropan-2-yl)-
6-methylcyclohex-2-en-1-one (28). Concentration
80% (GLC). IR spectrum, ν, cm–1: 3520 (OH), 3491
(OH), 2978, 2933, 1703 (C=O), 1606, 1450, 1371,
1342, 1257, 1213, 1142, 1089, 977, 918, 889, 862 (C–
1
1134, 926, 858, 752 (C–Cl), 503. H NMR spectrum
(DMSO-d6), δ, ppm (J, Hz): 0.82 s (3H, C8H3), 1.05 s
(3H, C9H3), 1.10 d.d.d (1H, 1-H, J = 3.3, 8.7, 9.5), 1.15
s (3H, C10H3), 1.62 d.d (1H, 2-H, J = 3.3, 15.5), 1.83
d.d (1H, 6-H, J = 8.5, 8.7), 2.35 d.d (1H, 2-H, J = 9.5,
Cl), 808, 472. H NMR spectrum (DMSO-d6), δ, ppm
1
(J, Hz): 1.27 (3H, C7H3), 1.59 (3H, C10H3), 1.73 (3H,
C9H3), 1.97 d.d (1H, 5-H, J = 11, 12), 2.14 d.d.d (1H,
5-H, J = 1.8, 4.7, 12), 3.06 d.d.d (1H, 4-H, J = 1.8, 4.7,
11), 5.59 br.s (1H, OH), 7.36 d.d (1H, 3-H, J = 1.8,
13
15.5), 5.70 s (1H, OH), 5.74 d (1H, 5-H, J = 8.5). C
NMR spectrum (DMSO-d6), δC, ppm: 207.6 (C4), 75.4
(C3), 65.0 (C5), 37.0 (C2), 34.4 (C6), 28.6 (C9), 23.9
(C10), 22.2 (C7), 22.1 (C1), 15.5 (C8).
2.1). C NMR spectrum (DMSO-d6), δC, ppm: 195.29
13
(C1), 146.68 (C3), 130.26 (C2), 74.04 and 73.57 (C6,
C8), 47.65 (C4), 38.91 (C5), 30.96 and 30.16 (C9, C10),
24.54 (C7).
1
5α-Chloro-3β-hydroxycaran-4-one (25). H NMR
spectrum (DMSO-d6), δ, ppm (J, Hz): 0.95–1.05 m
(2H, 1-H, 6-H), 1.09 s and 1.11 s (3H each, C8H3,
C9H3), 1.35 s (3H, C10H3), 1.59 d.d (1H, 2-H, J = 8.8,
4α-Chloro-2α-hydroxypinan-3-one (30). Yield
0.36 g (72%), mp 69–70°C, Rf 0.52 (Et2O–hexane,
1:1), [α]D25 = –9.3 (c = 0.6, CHCl3), [α]D25 = 6.6 (c =
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REACTIONS OF TERPENE ALCOHOLC AND DIOLS WITH CHLORINE DIOXIDE
621
0.8, EtOH). IR spectrum, ν, cm–1: 3477 (OH), 1724
(C=O), 719 (C–Cl). H NMR spectrum (DMSO-d6), δ,
vol. 34, no. 8, p. 1429. DOI: 10.1080/10601329708011054.
1
9. Yamauchi, T., Hattori, K., Mizutaki, S., Tamaki, K., and
Uemura, S., Bull. Chem. Soc. Jpn., 1986, vol. 59, no. 11,
p. 3617. DOI: 10.1246/bcsj.59.3617.
10. Beereboom, J.J., Djerassi, C., Ginsburg, D., and Fieser, L.F.,
J. Am. Chem. Soc., 1953, vol. 75, no. 14, p. 3500. DOI:
10.1021/ja01110a057.
11. Hanze, A.R., Fonken, G.S., McIntosh, A.V., Searcy, A.M.,
and Levin, R.H., J. Am. Chem. Soc., 1954, vol. 76,
no. 12, p. 3179. DOI: 10.1021/ja01641a020.
ppm (J, Hz): 0.83 s (3H, C8H3), 1.29 s (3H, C10H3),
1.36 s (3H, C9H3), 2.02 d (1H, 7-H, J = 10), 2.03 d.d
(1H, 1-H, J = 5.8, 6.3), 2.30 m (1H, 5-H), 2.32 m (1H,
7-H, J = 10), 4.69 d.d (1H, 4-H, J = 2.8, 3.1). 13C
NMR spectrum (DMSO-d6), δC, ppm: 207.7 (C3), 76.4
(C2), 61.7 (C4), 50.4 (C1), 46.3 (C5), 39.2 (C6), 27.8
(C9), 25.4 (C10), 24.6 (C7), 22.3 (C8).
12. Kim, H.J., Kim, H.R., and Ryu, E.K., Synth. Commun.,
1990, vol. 20, no. 11, p. 1625. DOI: 10.1080/
00397919008053082.
13. Kim, Y.H., Lee, I.S., and Lim, S.C., Chem. Lett., 1990,
vol. 19, no. 7, p. 1125. DOI: 10.1246/cl.1990.1125.
14. Tripathi, C.B. and Mukherjee, S., J. Org. Chem., 2012,
ACKNOWLEDGMENTS
This study was performed under partial financial
support by the Ural Branch of the Russian Academy of
Sciences (project no. 15-21-3-16) using the equipment
of the Khimiya Joint Center (Komi Research Center,
Ural Branch, Russian Academy of Sciences).
vol. 77, no. 3, p. 1592. DOI: 10.1021/jo202269p.
15. Sharpless, K.B. and Teranishi, A.Y., J. Org. Chem.,
1973, vol. 38, p. 185. DOI: 10.1021/jo00941a054.
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