First synthesis of hydroxy-pinonaldehyde and hydroxy-pinonic acid, monoterpene degradation products present in atmosphere

Article abstract of DOI:10.1016/S0040-4039(02)00337-4

Hydroxy-pinonaldehyde and hydroxy-pinonic acid, monoterpene degradation products have been for the first time isolated by synthesis and fully characterized. The key step of the synthesis is an oxidation using the RuCl₃/NaIO₄ system.

Full text of DOI:10.1016/S0040-4039(02)00337-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 2511–2513
First synthesis of hydroxy-pinonaldehyde and hydroxy-pinonic
acid, monoterpene degradation products present in atmosphere
Fabienne Fache,a,* Olivier Pivaa,* and Philippe Mirabelb
aLaboratoire de Chimie Organique, Photochimie et Synthe`se, Universite´ Claude Bernard Lyon I, CNRS UMR 5622, Baˆteau J.
Raulin, 43 Boulevard du 11 Novembre 1918, F-69622 Villeurbanne cedex, France
bCentre de Ge´ochimie de la Surface, Universite´ Louis Pasteur Strasbourg I, 1 rue Blessig, F-67084 Strasbourg cedex, France
Received 28 January 2002; revised 14 February 2002; accepted 16 February 2002
Abstract—Hydroxy-pinonaldehyde and hydroxy-pinonic acid, monoterpene degradation products have been for the first time
isolated by synthesis and fully characterized. The key step of the synthesis is an oxidation using the RuCl3/NaIO4 system. © 2002
Elsevier Science Ltd. All rights reserved.
Monoterpenes constitute about 10% of the mass of the
nonemethane organic compounds emitted into the
atmosphere.1 Their degradation by hydroxyl radicals
and ozone produces organic aerosols formed by partic-
ulated matter. The terpene double-bond oxidation leads
to the formation of numerous products containing car-
bonyl, carboxy, and/or hydroxy functional groups.2 All
these compounds have been already detected in ioniza-
tion chambers and identified most of the time only
thanks to their GC-EI and GC-CI mass spectra. As
some of them exist at trace levels, identification and
quantification are extremely difficult. Even if some
derivatization techniques2,3 have been developed to
ensure better analyses of these degradation products,
we assume that the synthesis of pure samples will be
better to confirm the proposed structures. Moreover,
other experiments to elucidate the atmospheric hydro-
carbon reaction mechanism4,5 should be performed
starting from these authentic compounds. Among all
the oxidation products6 hydroxy-pinonaldehyde 1 and
hydroxy-pinonic acid 2 have been often detected in
aerosols but neither isolated nor synthesized before,
probably because of their high polarity and low stabil-
ity of the aldehyde derivative, toward oxidative pro-
cesses (Scheme 1).
We started the synthesis from commercially available
(−)-myrtenol 4 and protected the hydroxy function with
an acetate group7 which could resist under oxidative
conditions (Scheme 2).
The key step of the synthesis was the oxidation of
product 5 into 7. We tested two different pathways. The
first one used the classical OsO4/NMO dihydroxylation
system8 leading to 6 which after treatment with NaIO4
without further purification, gave the aldehyde 7. The
second method consisted of a one-pot oxidation proce-
dure using RuCl3/NaIO4. Such a procedure has been
already used for the oxidation of (−)-a-pinene into
pinonic acid9 3. The authors did not mention the
presence of the corresponding aldehyde at the end of
the reaction. In our case, we nether isolated the acid
OH
OH
O
[Ox]
O
O
O
COOH
COOH
α-pinene
cis-pinonic acid 3
hydroxy-pinonic acid 2
hydroxy-pinonaldehyde 1
Scheme 1.
Keywords: hydroxy-pinonaldehyde; hydroxy-pinonic acid; monoterpenes; oxidation.
* Corresponding authors. Fax: 00 33 (0)4 72 44 81 36; e-mail: fache@univ-lyon1.fr
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00337-4

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F. Fache et al. / Tetrahedron Letters 43 (2002) 2511–2513
OAc
OH
OH
OAc
ii)
OAc
O
OH
O
OH
iii)
6
i)
v)
O
O
iv)
7 (ii + iii : 28%)
(iv: 32%)
5 (91%)
1 (70%)
4
vi)
OAc
OH
O
vii)
O
COOH
8 (50%)
COOH
2 (15%)
Scheme 2. (i) CH3COCl, Et3N; (ii) OsO4, NMO tBuOH, H2O; (iii) NaIO4; (iv) RuCl3, NaIO4; (v) K2CO3, MeOH, H2O (vi)
NaClO2, H2O2; (vii) K2CO3, MeOH, H2O.
derivative. During the reaction, we detected an interme-
diate product which should be diol 6 in agreement with
the results published by Shing et al.10 for the synthesis
of a diol from alkenes with the same system. After two
hours we added a new portion of NaIO4 to go to
completion. As the two procedures led to the same
isolated yield (30%), we chose the second one, which is
easier to carry out. Moreover, catalytic amounts of
RuCl3 were necessary (7%) against 20% for OsO4.
Compound 7 was oxidized into 8 with H2O2·NaClO2, a
mild selective method for the oxidation of aldehyde
into acid.11 We have also tested the procedure devel-
oped by Noyori et al.12 which allowed the selective
oxidation by H2O2 of an aldehyde in the presence of an
hydroxy function on the same molecule but without
success. Starting from 1, we never obtained 2. In both
cases (7 and 8) the desired products 1 and 2 were finally
obtained by deprotection according to a classical proce-
dure.13 In the case of the acid 2, the isolated yield after
deprotection was quite low probably due to its high
solubility into water. Nevertheless, the conditions have
not been optimized. It is noted that both aldehydes 1
and 7 can be stored several days at −15 °C without
degradation.
of RuCl3·3H2O (18.3 mg) and 1.5 mmol of NaIO4 (321
mg) in 2 mL of H2O were added. After a few minutes,
we noticed the appearance of the intermediate diol 6
and after 2 h, all the starting material was consumed.
Then 1.3 mmol of NaIO4 (285 mg) in 6 mL of H2O
were added again and the reaction mixture was allowed
to stir for 5 additional h. The organic phase was
washed with a saturated aqueous solution of Na2S2O3
and the aqueous phase extracted with CH2Cl2. The
combined organic layers were dried over MgSO4. After
evaporation and chromatography on silica (AcOEt–
petroleum ether: 1/3) the desired product 7 was isolated
1
with 32% yield. H NMR (CDCl3, 300 MHz) 0.85 (s,
3H), 1.31 (s, 3H), 2.05 (m, 3H), 2.15 (s, 3H), 2.4 (m,
2H), 2.95 (dd, J=7.2 Hz, J=12 Hz, 1H), 4.54 (d,
J=3.7 Hz, 2H), 9.72 (s, 1H); 13C NMR (75 MHz) 17.7,
20.5, 22.1, 30.5, 35.9, 43.8, 45.1, 50.1, 68.4, 170.1, 201.1,
202.2.
Product 1: 3.34 mmol of 7 (764 mg) were stirred under
nitrogen with 8.54 mmol of K2CO3 (1.18 g) in 118 mL
of MeOH and 12 mL of H2O. After 1.5 h the reaction
medium was poured into ice water and extracted with
CH2Cl2 to give 435 mg of pure product 1 (70% isolated
1
yield) without further purification. H NMR 0.82 (s,
In conclusion, even if the synthesis of these products
should be improved, we have realized the first synthesis
of hydroxy-pinonaldehyde and hydroxy-pinonic acid,
terpene degradation products present in the atmo-
sphere. These products are now currently tested to
verify previous studies and to contribute to the elucida-
tion of the terpene atmospheric degradation pathway.
3H), 1.28 (s, 3H), 2.05 (m, 3H), 2.47 (m, 2H), 2.91 (dd,
J=7.7 Hz, J=12 Hz, 1H), 3.15 (m, 1H), 4.05 (dd,
J
AB=12 Hz, J=2 Hz, 1H), 4.10 (dd, JAB=12 Hz, J=2
Hz, 1H), 9.72 (s, 1H); 13C NMR: 17.8, 22.3, 30.5, 36.1,
43.8, 45.1, 49.8, 68.7, 201.1, 207.9; [h]2D1=−39 (c 0.49,
CHCl3).
Product 8: 8.14 mmol of NaClO2 (80% purity, 920 mg)
in 8 mL of water were added dropwise in 15 min to a
stirred mixture of 5.8 mmol of 7 (1.3 g) in 5.8 mL of
CH3CN, 1.54 mmol of NaH2PO4·H2O (212 mg) in 2.3
mL of water and 6 mmol of 35% H2O2 (575 mL). The
All the compounds have been fully characterized.
Selected data:
Product 7: 1 mmol of 5 (194 mg) was dissolved in 12
mL (v/v) of AcOEt–CH3CN. Then at 0°C, 0.07 mmol

F. Fache et al. / Tetrahedron Letters 43 (2002) 2511–2513
2513
temperature was kept below 10°C. The solution became
immediately yellow and oxygen evolved from the solu-
tion. After a few minutes, a precipitate appeared. After
1 h, 0.36 mmol of Na2S2O3 (57 mg) were added to
destroy the unreacted HOCl and H2O2. The solution
was acidified until pH 1 with 10% aqueous HCl. The
precipitate was dissolved with CH2Cl2 and all the reac-
tion mixture was extracted with the same solvent. The
organic layer was dried over MgSO4 and the product
was purified by chromatography on silica (AcOEt–
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1
petroleum ether: 1/3). Isolated yield 50% (702 mg). H
NMR 0.90 (s, 3H), 1.3 (s, 3H), 2.08 (m, 3H), 2.16 (s,
3H), 2.37 (m, 2H), 2.92 (dd, J=8.1 Hz, J=10.3 Hz,
1H), 4.55 (d, J=2.2 Hz, 2H).
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Product 2 was synthesized from 8 according to the
1
same procedure described for 1. H NMR: 0.81 (s, 3H),
1.24 (s, 3H), 2.05 (m, 3H), 2.32 (m, 2H), 2.85 (dd,
J=7.5 Hz, J=10.5 Hz, 1H), 4.03 (d, J=15 Hz, 1H),
4.15 (d, J=15 Hz, 1H), 13C NMR: 17.4, 22.4, 30.3,
34.8, 38.0, 43.8, 49.6, 68.5, 177.9, 208.1; [h]2D1=−25 (c
0.79, CHCl3).
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