Oxidation of secondary terpene alcohols by chlorine dioxide

Article abstract of DOI:10.1007/s10600-009-9190-8

Secondary terpene alcohols cis- and trans-verbenol, neo-iso-verbanol, borneol, iso-borneol, and menthol were oxidized by chlorine dioxide into the corresponding ketones. It was shown that the nature of the solvent and catalyst and the structure of the starting compound, including the stereochemistry of the hydroxyl, influenced the oxidation process.

Full text of DOI:10.1007/s10600-009-9190-8

Chemistry of Natural Compounds, Vol. 44, No. 6, 2008
OXIDATION OF SECONDARY TERPENE ALCOHOLS BY
CHLORINE DIOXIDE
*
L. L. Frolova, A. V. Popov, S. A. Rubtsova, and A. V. Kuchin
UDC 547.425.5
cis
Secondary terpene alcohols -and
trans
-verbenol,
neo iso
iso
-
-verbanol, borneol, -borneol, andmenthol were
oxidized by chlorine dioxide into the corresponding ketones. It was shown that the nature of the solvent and
catalyst and the structure of the starting compound, including the stereochemistry of the hydroxyl, influenced
the oxidation process.
Key words: - and
cis
-verbenol,
trans
-
-verbanol, borneol, -borneol, menthol, chlorine dioxide, oxidation,
neo iso iso
catalysts.
The search for new selective oxidants is a critical task for organic synthesis. Chlorine dioxide (ClO ), which is an
2
industrial compound and is used to bleach cellulose and purifydrinking and wastewater, is of definite interest [1]. It was shown
earlier that the use of ClO in organic synthesis is convenient and promising using oxidation of sulfides, thiols, certain
2
organoboron and organometallic compounds, terpene primary allyl alcohols and α,β-unsaturated aldehydes [2-7], and simple
alcohols and phenols [8] as examples.
Herein we report oxidation byClO of secondaryterpene alcohols cis- (1) and trans-verbenol (2), neo-iso-verbanol (3),
2
borneol (4), iso-borneol (5), and menthol (6) in various solvents with or without catalysts.
ClO
ClO
2
ClO
2
2
OH
O
OH
O
OH
8
1
7
2
3
OH
H
O
ClO
ClO
2
2
OH
H
4
9
5
It is known that C–H bonds of secondary C atoms located in the α-position to a double bond are most easily oxidized.
This has been confirmed byClO oxidation of secondaryallyl (1, 2) and saturated (3-5) alcohols. Oxidation of 1 and 2 proceeds
2
readily without a catalyst in EtOH or Py in 1.5-4 h at room temperature with 89-100% conversion and verbenone (7) content
68-79% according to GC (Table 1) whereas oxidation of 3 and 4 is best carried out with a catalyst (Table 2). Furthermore, the
selectivity of camphor formation (97-100%) was much greater than that for verbenone formation (73-79%).
The best solvent for all substrates was Py. A significant amount of side products, including chloroderivatives, formed
in CCl . Thus, oxidation of trans-verbenol with 65% conversion gave only30% verbenone; camphor, 23 and 30% with 41 and
4
54% conversion of borneol and iso-borneol, respectively (Tables 1 and 2).
Institute of Chemistry, Komi Scientific Center, Ural Branch, Russian Academy of Sciences, Russian Federation,
167982, Syktyvkar, ul. Pervomaiskaya, 48, fax:(8212)218477, e-mail:frolova-ll@chemi.komisc.ru. Translatedfrom Khimiya
Prirodnykh Soedinenii, No. 6, pp. 585-587, November-December, 2008. Original article submitted May 29, 2008.
0009-3130/08/4406-0724 ©2008 Springer Science+Business Media, Inc.
724

TABLE 1. Oxidation of 1-3 by Chlorine Dioxide
Substrate
Solvent
T, °C
Time, h
Conversion, %
Content of 7 or 8, GC, %
Selectivity, %
1
EtOH
Py
CCl4
Py
Py
EtOH
EtOH
Py
20
20
30-35
20
50-55
20
1.5
2
3
4
3
2
3
1
100
100
65
73
79
30
68
78
Trace
24
11
73
79
46
76
78
-
2
89
100
Poor
34
3
30-35
20
70
71
16
TABLE 2. Oxidation of 4 and 5 by Chlorine Dioxide at 20°C
Substrate
Solvent
Catalyst
Time, h
Conversion, %
Content of 9, GC, %
Selectivity, %
4
CCl4
Py
Py
CCl4
Py
Py
Py
-
-
5
5
5
5
2
5
3
41
33
100
54
56
100
23
32
100
30
55
98
56
97
100
56
98
98
ZrOCl2
5
-
-
-
ZrOCl2
100
100
100
TABLE 3. Oxidation of 6 by Chlorine Dioxide in Py at 20°C
Catalyst
Time, h
Conversion, %
-
-
4
5
1
2
3
53
79
42
59
100
ZrOCl2
ZrOCl2
ZrOCl2
______
In CCl4: T = 20-50°C; time, 8 h; conversion, %; poor, no catalyst.
The stereochemical location of the hydroxyls also affected the oxidation. Compounds 1 and 5 with OH groups in the
exo-position were oxidized faster than the corresponding epimers, i.e., the oxidation pathwaywas easier from the less sterically
hindered side of the starting material. Menthol (6) was rather stable to oxidation by ClO . It was practically not oxidized in
2
CCl at room temperature or with heating to 50°C. The conversion was 79% in Py after 5 h (Table 3). The exclusive reaction
4
+6
product was menthone (10). Oxidation of 6 by Cr compounds almost always produces a certain amount of iso-menthone [9].
However, treatment of the reaction mixture with dilute H SO over 1 d produced an equilibrium mixture of menthone and iso-
2
4
menthone (∼70:30), which were isolated pure by chromatography over SiO and characterized by spectral methods.
2
ClO
2
OH
O
6
10
725

Catalysts had a favorable effect on oxidation by ClO . Thus, the time for oxidation of iso-borneol was halved and the
2
conversion of borneol increased from 33% (without catalyst) to 100% in the presence of ZrOCl , which was used previously to
2
accelerate the reaction of ClO with propan-2-ol [10]. The yield of menthone (10) was quantitative at room temperature after
2
3 h in the presence of catalytic amounts of ZrOCl .
2
+2
+2
+2
+2
Next we studied the effect of the metal in certain acetylacetonates (Fe , Cu , Co , VO ), which are widely used
for hydroperoxide oxidation [11, 12], the amount of catalyst, and the duration of the oxidation of borneol. The oxidation was
accelerated by acetylacetonates of Cu, Co, and VO. The yield of camphor reached 100%. Iron(II) acetylacetonate precipitated
presumably as iron oxide, which inhibited the oxidation. According to the results, VO(acac) was the most active catalyst for
2
borneol oxidation. The yield of camphor was quantitative in 3 h using 1.5% catalyst. Increasing the amount of catalyst from
0.8 to 10% did not affect the conversion of 4 and the yield of camphor, which was almost 100% (Py solvent, 5 h).
The effect of the metal of the catalyst on borneol oxidation by ClO (Py, 5 h, 10% catalyst) can be seen from the
2
following data:
Catalyst
Conversion, %
Content of 9, GC, %
-
33
9
45-49
73-98
100
32
6
45-48
72-98
100
Fe(acac)2
Cu(acac)2
Co(acac)2
VO(acac)2
Oxidation of borneol by ClO in the presence of VO(acac) (1.5%, Py solvent, T = 20°C) depended on time. The
2
2
content of 9 was 38% after 1 h; 69%, after 2 h; 100%, after 3 h.
Thus, the results showed that the optimal conditions for oxidizing terpene alcohols 1-6 byClO were Py solvent, room
2
temperature, catalytic amounts of ZrOCl and VO or Co acetylacetonates. Cyclic allyl alcohols and alcohols with an exo-OH
2
group were oxidized easier than saturated alcohols and those with an endo-OH group, respectively. ClO was also a selective,
2
mild, and convenient oxidant that can compete with certain traditional oxidants, particularly, hexavalent Cr compounds.
EXPERIMENTAL
GC was performed on a Kristall-2000M chromatograph with a flame-ionization detector, capillary column (60 m,
0.251 mm, HP-5MS phase, Ar carrier gas). Reaction products were identified by comparison with authentic compounds using
GC and TLC. TLC was performed on Silufol and Sorbfil plates with elution by diethylether:heptane and vanillin developer in
EtOH (3%). The concentration of ClO , which was supplied by OAO MBP Syktyvkar LPK as an aqueous solution of 5-7 g/L,
2
was determined by iodometric titration by the literature method [13]. We used commercially available borneol, iso-borneol,
menthol, and camphor that were purified by crystallization. neo-iso-Verbanol and cis-verbenol [14], trans-verbenol [15], and
verbenone [16] were prepared as before. We used chemicallypure solvents and freshlydistilled Py. Metal acetylacetonates were
prepared by the literature method [17].
General Method for Oxidizing Terpene Alcohols. Starting compound (0.5-1 g, 1-6) was dissolved in solvent (10-
15 mL) with or without catalyst, stirred, and treated with a stream of ClO in air. The reaction was monitored byTLC. Solvent
2
was distilled off. The mixture was diluted with diethylether, washed with H SO (5-10%, if Py was used) and saturated NaCl
2
4
solution, and dried over Na SO or MgSO . The ether was removed. The mixture was analyzed by GC by comparison with
2
4
4
known compounds (7-10). The yields of oxidation products were 82-91%.
ACKNOWLEDGMENT
The work was supported by the RF President (Program of Support for Leading Scientific Schools, Grant NSh-
4028.2008.3) and the Russian Foundation for Basic Research (Grant No. 05-03-33005).
726

REFERENCES
1.
2.
B. G. Gordon, R. G. Kieffer, and D. H. Rosenblatt, J. Prog. Inorg. Chem., 15, 201 (1972).
O. M. Lezina, S. A. Rubtsova, and A. V. Kuchin, Izv. Akad. Nauk, Ser. Khim., 1779 (2003) [Engl. transl., Russ.
Chem. Bull., 8, 1877 (2003)].
3.
4.
5.
6.
A. V. Kuchin, S. A. Rubtsova, and I. V. Loginova, Izv. Akad. Nauk, Ser. Khim., 3, 813 (2001) [Engl. transl., Russ.
Chem. Bull., 3, 432 (2001)].
A. V. Kuchin and L. L. Frolova, Izv. Akad. Nauk, Ser. Khim., 1658 (2000) [Engl. transl., Russ. Chem. Bull., 49,
1647 (2000)].
A. V. Kuchin, I. A. Dvornikova, and I. Yu. Nalimova, Izv. Akad. Nauk, Ser. Khim., 2025 (1999) [Engl. transl.,
Russ. Chem. Bull., 48, 2001 (1999)].
A. V. Kuchin, S. A. Rubtsova, and L. P. Karmanova, Izv. Akad. Nauk, Ser. Khim., 2110 (1998) [Engl. transl.,
Russ. Chem. Bull., 47, 2051 (1998)].
7.
8.
RF Pat. No. 2,260,580; Byull. Izobret., 26 (2005).
E. S. Suvorkina, Candidate Dissertation in Chemical Sciences, Ufa State Petroleum Technical University, Ufa
(2002).
9.
10.
11.
12.
13.
H. C. Brown and C. P. Jang, J. Am. Chem. Soc., 83, 2952 (1961).
C. B. Sharma, Rev. Roum. Chim., 28, 11-12, 967 (1983).
T. Hirao, Chem. Rev., 97, 8, 2707 (1997).
G. A. Tolstikov, Hydroperoxide Oxidation Reactions [in Russian], Nauka, Moscow (1976).
T. A. Tumanova and I. E. Flis, Physico-Chemical Principles of Cellulose Bleaching [in Russian], Lesnaya
Promyshlennost′, Moscow (1972), p. 236.
14.
L. L. Frolova, I. V. Dreval′, M. V. Panteleeva, E. U. Ipatova, and A. V. Kuchin, Izv. Akad. Nauk, Ser. Khim., 475
(2003) [Engl. transl., Russ. Chem. Bull., 52, 498 (2003)].
15.
16.
17.
R. Mori, Agric. Biol. Chem., 40, 415 (1976).
RF Pat. No. 2,250,208; Byull. Izobret., 11 (2005).
H. M. Colquhoun, New Pathways for Organic Synthesis: Practical Applications of Transition Metals, Plenum
Press, New York (1984).
727