One-pot catalytic synthesis of 2-(1,2-dihydroxypropyl)phenol derivatives from 2-allylphenols in aqueous media

Article abstract of DOI:10.1055/s-2005-872175

Catalytic amounts of the hydrophilic ligand [(HOCH₂CH ₂NHCOCH₂)₂NCH₂]₂ and palladium(II) salts, in the presence of hydrogen peroxide, water and alcohol, allow the direct transformation of 2

Full text of DOI:10.1055/s-2005-872175

SPECIAL TOPIC
2615
One-Pot Catalytic Synthesis of 2-(1,2-Dihydroxypropyl)phenol Derivatives
from 2-Allylphenols in Aqueous Media
(D
ihydroxypropy
a
l)phenol
D
r
erivative
o
s
from 2-All
l
ylpheno
e
ls in
A
queous
M
C
edia hevrin, Jean Le Bras,* Françoise Hénin, Jacques Muzart
Unité Mixte de Recherche ‘Réactions Sélectives et Applications’, CNRS-Université de Reims, Champagne-Ardenne,
BP 1039, 51687 Reims cedex 2, France
Fax +33(326)913166; E-mail: jean.lebras@univ-reims.fr
Received 14 June 2005
Changing Pd(OCOCF3)2 for Pd(OAc)2, PdCl2 or a mix-
ture of PdCl2(MeCN)2–AgX (X = SO3CF3, BF4) was not
beneficial to the process. With EtOH or i-PrOH as co-sol-
vent, the expected products 3a, 5a and 6a were obtained
Abstract: Catalytic amounts of the hydrophilic ligand
[(HOCH2CH2NHCOCH2)2NCH2]2 and palladium(II) salts, in the
presence of hydrogen peroxide, water and alcohol, allow the direct
transformation of 2-allylphenols into 2-(1,2-dihydroxypropyl)phe-
nol derivatives. The mechanism involves sequential isomerisation, in similar yields (runs 2 and 3). MeOH as solvent yielded
epoxidation, and oxirane-opening.
75% of 4a but water present in aqueous H2O2 produced
20% of 3a (run 4). In water, only 50% of 3a has been ob-
tained (run 5). Oxidation of 2-allyl-4-methylphenol (1b)
in H2O–MeOH was less efficient, affording expected
products 3b and 4b in 9 and 19% yield, respectively (run
6). Such a decrease in the efficiency of the process could
be related to the low solubility of the substrate in this
aqueous medium. Performing the reaction at room tem-
perature and increasing the amount of alcohol improved
the total yield to 59% (run 7). EtOH and i-PrOH as co-sol-
vents afforded fair yields (runs 8, 9). 2-Allyl-6-meth-
ylphenol (1c) was oxidized in water–alcohol mixtures in
45–59% yields (runs 10,11).
Keywords: alcohols, oxidations, phenols, palladium, epoxidations
Aqueous phase organometallic chemistry has received
considerable attention for environmental, economic, and
safety reasons.1 We have recently applied the hydrophilic
ligand [(HOCH2CH2NHCOCH2)2NCH2]2 (LH) in copper-
catalyzed allylic oxidations2 and palladium-catalyzed al-
lylic substitutions.3 We report here that the association of
LH and palladium(II) salts allows the one-pot oxidation of
2-allylphenols into 2-(1,2-dihydroxypropyl)phenol deriv-
atives, which are potentially physiologically active com-
pounds.4
A plausible mechanism, depicted in Scheme 1, would in-
volve three successive reactions which could be Pd(II)-
mediated: isomerisation of the substrate,6 epoxidation of
the double bond,8,9 and hydrolysis or alcoholysis of the
oxirane.10
The intramolecular Wacker oxidation of allylphenol (1a)
is well known,5 and we were interested in performing such
a reaction with Pd(II)–LH in aqueous media. Preliminary
experiments in aqueous methanol, using a mixture of
PdX2 (X = Cl, OCOCF3) and LH as the catalyst, and ben-
zoquinone, Cu(II), NaOCl or oxone® as oxidizing agents,
led, at the best, to traces of oxidized products; the isomer-
ization of 1a into 2-[(E)-prop-1-enyl)phenol (2a) being
the main reaction with Pd(OCOCF3)2–LH as catalyst.6
However, the use of Pd(OCOCF3)2–LH with aqueous t-
BuOOH (70%) afforded 2-(1,2-dihydroxypropyl)phenol
(3a) and 2-(2-hydroxy-1-methoxypropyl)phenol (4a) in
34% yield. Interestingly, 35% aqueous H2O2 improved to
92% the yield of 3a + 4a (Equation 1, Table 1, run 1).7
In agreement with the above proposals, subjecting 2a to
the conditions used in Table 1 (H2O–MeOH) led to 3a and
4a in 88% yield (Equation 2). Furthermore, the fixation of
the methoxy group exclusively at the benzylic position by
methanolysis of aryl epoxides under acidic conditions has
already been reported.10,11 Surprisingly, 3a and 4a were
also obtained from 2a in the absence of any palladium cat-
alyst, but with a lower yield (Equation 2).
Jacobs et al. have reported the phenol-mediated epoxida-
tion of alkenes by H2O2 without metal catalyst. They pro-
posed that intermolecular hydrogen bonding between
phenol and H2O2 activates this latter for oxygen-atom
transfer.12 Therefore, we suspect an activation by the phe-
nolic OH in the metal-free process leading to 2-(3-methyl-
oxiran-2-yl)phenols; their high instability13 would lead to
a spontaneous ring opening. However, the strong acceler-
ation of the palladium catalyzed reaction of 2a
OR
Pd(OCOCF3)2 (0.05 equiv)
LH (0.05 equiv)
35% aq H2O2 (4 equiv)
X
X
OH
H2O/ROH
OH
X = H (1a)
OH
X = H: R = H (3a), Me (4a), Et (5a), i-Pr (6a)
X = 4-Me: R = H (3b), Me (4b), Et (5b), i-Pr (6b)
X = 6-Me: R = H (3c), Me (4c), Et (5c)
X = 4-Me (1b)
X = 6-Me (1c)
(Equation 2)
indicates
some
Pd(OCOCF3)2–LH in the process.
participation
of
Equation 1
In conclusion, the association Pd(OCOCF3)2–LH in aque-
ous media catalyses the oxidation with H2O2 of 2-al-
lylphenols to 2-(1,2-dihydroxypropyl)phenol derivatives.
This process occurs via a cascade reaction involving the
SYNTHESIS 2005, No. 15, pp 2615–2618
x
x.
x
x
.
2
0
0
5
Advanced online publication: 16.08.2005
DOI: 10.1055/s-2005-872175; Art ID: C04105SS
© Georg Thieme Verlag Stuttgart · New York

2616
C. Chevrin et al.
SPECIAL TOPIC
Table 1 Oxidation of 2-Allylphenolsa
Run
1
Substrate
1a
Temp (°C)
Time (h)
24
Solvent (ratio)
H2O–MeOH (1:1)
H2O–EtOH (1:1)
H2O–i-PrOH (1:1)
MeOH
Products (%)b
3a (35), 4a (47)
3a (43), 5a (38)
3a (38), 6a (38)
3a (20), 4a (75)
4a (50)
50
50
50
50
50
50
r.t.
r.t.
r.t.
r.t.
r.t.
2
1a
24
3
1a
24
4
1a
24
5
1a
24
H2O
6
1b
24
H2O–MeOH (1:1)
H2O–MeOH (1:2)
H2O–EtOH (1:2)
H2O–i-PrOH (1:2)
H2O–MeOH (1:2)
H2O–EtOH (1:2)
3b (9), 4b (19)
3b (18), 4b (41)
3b (21), 5b (31)
3b (20), 6b (24)
3c (15), 4c (30)
3c (18), 5c (41)
7
1b
72
8
1b
72
9
1b
72
10
11
1c
72
1c
72
a Experimental conditions are those depicted in Equation 1 (see also the experimental part).
b Isolated yields.
OR
OH
O
X
X
X
X
Pd-LH
OH
H2O2, ROH
OH
OH
OH
Scheme 1
OMe
OH
OH
Pd(II)/LH (0 or 0.05 equiv)
35% aq H2O2 (4 equiv)
+
OH
OH
H2O/MeOH (1:1)
OH
OH
2a
3a
4a
with the Pd catalyst, 24 h; conv.: 100%, yield:
without the Pd catalyst, 60 h; conv.: 55%, yield:
33%
7%
55%
20%
Equation 2
h, Et2O (3 × 5 mL) was added. The organic layer was separated and
dried (MgSO4). After evaporation of the solvent under vacuum,
products were isolated from chromatography column (petroleum
ether–EtOAc, 70:30) as yellow pastes.
isomerisation of the C=C bond, followed by the epoxida-
tion and the opening of the resulting oxirane.
1H and 13C NMR spectral data were recorded on a Bruker AC 250
spectrometer at 250 MHz and 67.5 MHz, respectively, in CDCl3 us-
ing TMS as internal standard. FTIR spectra were recorded on an
Avatar 320 FT-IR instrument as KBr pellets or films. Column chro-
matography was performed on silica gel (70–230 mesh). All sol-
vents and reagents were from commercial sources and were used as
received. LH was synthesized as previously described.2 Mass spec-
tra using electrospray ionization were performed with a Q-TOF mi-
cro from Micromass. Petroleum ether refers to the fraction with
boiling point (40–60 °C).
2-(1,2-Dihydroxypropyl)phenol (3a)
IR: 3326, 1590, 1490, 1456, 1242, 1021 cm–1.
1H NMR: d = 1.11 (d, J = 6.0 Hz, 3 H), 4.08 (quint, J = 6.5 Hz, 1
H), 4.58 (d, J = 8.0 Hz, 1 H), 6.82–7.27 (4 H).
13C NMR: d = 19.1, 70.2, 80.3, 117.2, 119.7, 123.9, 128.9, 129.4,
131.5.
HRMS: m/z calcd for C9H12O3Na: 191.0684; found: 191.0681.
2-(2-Hydroxy-1-methoxypropyl)phenol (4a)
IR: 3336, 1606, 1458, 1240, 1100 cm–1.
General Procedure
To a stirred solution of Pd(OCOCF3)2 (24.9 mg, 0.075 mmol) and
ligand LH (34.8 mg, 0.075 mmol) in H2O (1 mL), was added the al-
lylphenol (1.5 mmol), H2O2 (35% in H2O, 0.51 mL, 6 mmol) and the
alcohol (1 or 2 mL). After stirring at 50 °C for 24 h or at r.t. for 72
1H NMR: d = 1.05 (d, J = 6.3 Hz, 3 H), 3.44 (s, 3 H), 4.03–4.15 (2
H), 6.84–7.27 (4 H).
Synthesis 2005, No. 15, 2615–2618 © Thieme Stuttgart · New York

SPECIAL TOPIC
(Dihydroxypropyl)phenol Derivatives from 2-Allylphenols in Aqueous Media
2617
13C NMR: d = 18.5, 57.7, 69.3, 90.4, 117.0, 117.3, 119.9, 129.7,
129.9, 155.4.
1H NMR: d = 1.12 (d, J = 6.3 Hz, 3 H), 2.23 (s, 3 H), 4.07 (quint,
J = 6.3 Hz, 1 H), 4.48 (d, J = 8.1 Hz, 1 H), 6.74 (t, J = 7.5 Hz, 1 H),
6.83 (d, J = 7.6 Hz, 1 H), 7.07 (d, J = 7.3 Hz, 1 H).
HRMS: m/z calcd for C10H14O3Na: 205.0841; found: 205.0839.
13C NMR: d = 16.1, 19.9, 70.4, 81.5, 119.6, 121.9, 126.9, 128.1,
131.1, 154.0.
2-(1-Ethoxy-2-hydroxypropyl)phenol (5a)
IR: 3346, 1586, 1489, 1456, 1240, 1079 cm–1.
HRMS: m/z calcd for C10H14O3Na: 205.0841; found: 205.0847.
1H NMR: d = 1.05 (d, J = 6.1 Hz, 3 H), 1.26–1.31 (3 H), 2.90–3.75
(2 H), 4.03 (quint, J = 6.8 Hz, 1 H), 4.13 (d, J = 8.1 Hz, 1 H), 6.83–
7.26 (4 H).
2-(2-Hydroxy-1-methoxypropyl)-6-methylphenol (4c)
IR: 3373, 1596, 1471, 1232, 1084 cm–1.
13C NMR: d = 15.2, 18.6, 66.0, 69.2, 89.1, 117.2, 119.9, 121.9,
129.8, 129.9, 155.8.
1H NMR: d = 1.04 (d, J = 5.8 Hz, 3 H), 2.23 (s, 3 H), 3.45 (s, 3 H),
3.99–4.14 (2 H), 6.79 (t, J = 7.6 Hz, 1 H), 6.85 (d, J = 7.5 Hz, 1 H),
7.09 (d, J = 7.1 Hz, 1 H).
HRMS: m/z calcd for C11H16O3Na: 219.0997; found: 219.1000.
13C NMR: d = 16.0, 18.7, 58.1, 69.4, 91.4, 119.7, 120.7, 126.2,
128.0, 131.1, 153.9.
2-(2-Hydroxy-1-isopropoxypropyl)phenol (6a)
IR: 3353, 1587, 1488, 1456, 1239 cm–1.
HRMS: m/z calcd for C11H16O3Na: 219.0997; found: 219.1002.
1H NMR: d = 1.04 (d, J = 6.3 Hz, 3 H), 1.17–1.26 (6 H), 3.77 (sept,
J = 6.1 Hz, 1 H), 4.00 (quint, J = 6.3 Hz, 1 H), 4.20 (d, J = 8.2 Hz,
1 H), 6.81–7.25 (4 H).
2-(1-Ethoxy-2-hydroxypropyl)-6-methylphenol (5c)
IR: 3358, 1596, 1470, 1235, 1074 cm–1.
13C NMR: d = 18.7, 21.5, 23.3, 69.3, 71.8, 86.9, 117.5, 120.1, 122.7,
129.9, 130.0, 156.2.
1H NMR: d = 1.03 (d, J = 5.9 Hz, 3 H), 1.21–1.31 (3 H), 2.21 (s, 3
H), 3.48–3.73 (2 H), 3.97–4.24 (2 H), 6.78 (t, J = 7.3 Hz, 1 H), 6.84
(d, J = 7.6 Hz, 1 H), 7.08 (d, J = 6.1 Hz, 1 H).
HRMS: m/z calcd for C12H18O3Na: 233.1154; found: 233.1146.
13C NMR: d = 15.4, 16.0, 18.8, 66.1, 69.3, 89.6, 119.6, 121.1, 126.2,
127.8, 131.2, 154.1.
2-(1,2-Dihydroxypropyl)-4-methylphenol (3b)
IR: 3352, 1615, 1504, 1254, 1029 cm–1.
HRMS: m/z calcd for C12H18O3Na: 233.1154; found: 233.1161.
1H NMR: d = 1.11 (d, J = 6.2 Hz, 3 H), 2.28 (s, 3 H), 4.08 (quint,
J = 7.0 Hz, 1 H), 4.58 (d, J = 7.8 Hz, 1 H), 6.82–7.27 (3 H).
Acknowledgment
13C NMR: d = 19.1, 20.3, 70.1, 80.2, 116.9, 123.5, 128.9, 129.1,
129.8, 153.0.
We are grateful to ‘Région Champagne-Ardenne’ for a PhD stu-
dentship to C.C.
HRMS: m/z calcd for C10H14O3Na: 205.0841; found: 205.0840.
2-(2-Hydroxy-1-methoxypropyl)-4-methylphenol (4b)
IR: 3444, 1615, 1507, 1449, 1264, 1090 cm–1.
References
1H NMR: d = 1.06 (d, J = 5.7 Hz, 3 H), 2.26 (s, 3 H), 3.41 (s, 3 H),
4.03–4.13 (2 H), 6.76 (d, J = 8.2 Hz, 1 H), 6.82 (s, 1 H), 7.01 (d,
J = 8.2 Hz, 1 H).
(1) Cornils, B.; Herrmann, W. A. Aqueous-Phase
Organometallic Catalysis; Wiley: New York, 1998.
(2) Le Bras, J.; Muzart, J. Tetrahedron Lett. 2002, 43, 431.
(3) Chevrin, C.; Le Bras, J.; Hénin, F.; Muzart, J.; Pla-Quintana,
A.; Roglans, A.; Pleixats, R. Organometallics 2004, 23,
4796.
13C NMR: d = 18.7, 20.7, 57.9, 69.7, 90.3, 117.0, 121.5, 129.3,
130.4, 130.5, 153.4.
(4) 2-(1,2-Dihydroxypropyl)phenol derivatives were extracted
from the roots of Pimpinella thellungiana and show
antihypertensive and ischemic cardiac disease-preventing
activities: (a) Fu-Xian, L.; Chang-Dai, W.; Cai-Feng, M.;
Hui-Li, S.; Bo-Ling, Q. Zhiwu Xuebao 1998, 40, 88; Chem.
Abstr. 1999, 130, 78694. (b) Junko, T.; Akiko, U.; Juji, A.;
Chotai, O.; Seien, K.; Hiroaki, K. Jpn. Kokai Tokkyo Koho
JP 92-39561 19920226, 1997; Chem. Abstr. 1997, 126,
203698.
(5) (a) Meulemans, T. M.; Kiers, N. H.; Feringa, B. L.; van
Leeuwen, P. W. N. M. Tetrahedron Lett. 1994, 35, 455.
(b) Ori, K.; Kitagawa, H.; Miyoshi, A.; Ohta, T.; Furukawa,
I. Chem. Lett. 1998, 1083. (c) Larock, R. C.; Wei, I.;
Hightower, T. R. Synlett 1998, 522. (d) Roshchin, A. I.;
Kel’chevski, S. M.; Bumagin, N. A. J. Organomet. Chem.
1998, 560, 163.
HRMS: m/z calcd for C11H16O3Na: 219.0997; found: 219.0997.
2-(1-Ethoxy-2-hydroxypropyl)-4-methylphenol (5b)
IR: 3361, 1615, 1504, 1452, 1257, 1077 cm–1.
1H NMR: d = 1.05 (d, J = 5.7 Hz, 3 H), 1.24–1.30 (3 H), 2.25 (s, 3
H), 3.47–3.72 (2 H), 3.99–4.09 (2 H), 6.75 (d, J = 8.2 Hz, 1 H), 6.78
(s, 1 H), 7.01 (d, J = 8.1 Hz, 1 H).
13C NMR: d = 15.4, 18.8, 20.8, 66.1, 69.4, 89.3, 117.2, 121.7, 129.3,
130.4, 130.5, 153.4.
HRMS: m/z calcd for C12H18O3Na: 233.1154; found: 233.1160.
2-(2-Hydroxy-1-isopropoxypropyl)-4-methylphenol (6b)
IR: 3356, 1615, 1502, 1456, 1261, 1046 cm–1.
1H NMR: d = 1.05 (d, J = 6.2 Hz, 3 H), 1.18–1.25 (6 H), 2.25 (s, 3
H), 3.75 (sept, J = 6.0 Hz, 1 H), 4.00 (quint, J = 6.4 Hz, 1 H), 4.15
(d, J = 8.0 Hz, 1 H), 6.76 (d, J = 7.7 Hz, 1 H), 6.78 (s, 1 H), 7.00 (d,
J = 8.1 Hz, 1 H).
(6) For the palladium-catalyzed isomerisation of 2-allylphenol,
see: (a) Golborn, P.; Scheinmann, F. J. Chem. Soc., Perkin
Trans 1 1973, 2870. (b) Davies, N. R.; DiMichiel, A. D.
Aust. J. Chem. 1973, 26, 1529. (c) Gross, J. L. Tetrahedron
Lett. 2003, 44, 8563.
13C NMR: d = 18.7, 20.7, 21.4, 23.3, 69.3, 71.7, 86.7, 117.2, 122.3,
129.2, 130.2, 130.4, 153.8.
(7) Less than 55% yield was obtained from this reaction when
carried out in the absence of LH.
HRMS: m/z calcd for C13H20O3Na: 247.1310; found: 247.1315.
(8) For the palladium-catalyzed epoxidation of alkenes with
peroxides, see: (a) Nagata, R.; Matsumura, T.; Saito, I.
2-(1,2-Dihydroxypropyl)-6-methylphenol (3c)
IR: 3356, 1596, 1471, 1222, 1028 cm–1.
Synthesis 2005, No. 15, 2615–2618 © Thieme Stuttgart · New York

2618
C. Chevrin et al.
SPECIAL TOPIC
(10) For Lewis acid catalyzed alcoholysis of epoxides, see:
Tetrahedron Lett. 1984, 25, 2691. (b) Zhou, X.-G.; Huang,
J.-S.; Yu, X.-Q.; Zhou, Z.-Y.; Che, C.-M. J. Chem. Soc.,
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Kokai Tokkyo Koho JP 187 792, 2001; Chem. Abstr. 2001,
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(a) Chini, M.; Crotti, P.; Gardelli, C.; Macchia, F. Synlett
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Macchia, F. Synlett 1992, 673.
(9) For the epoxidation of alkenes with palladium superoxo
complexes obtained from reaction of Pd(II) with H2O2, see:
(a) Talsi, E. P.; Babenko, V. P.; Likholobov, V. A.;
Nekipelov, V. M.; Chinakov, V. D. J. Chem. Soc., Chem.
Commun. 1985, 1768. (b) Talsi, E. P.; Babenko, V. P.;
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K. I. Inorg. Chem. 1987, 26, 3871.
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1777.
(13) Lattanzi, A.; Senatore, A.; Massa, A.; Scettri, A. J. Org.
Chem. 2003, 68, 3691.
Synthesis 2005, No. 15, 2615–2618 © Thieme Stuttgart · New York