Synthesis of 2-hydroxybenzophenones by oxidation of 3-aryl-3H-benzofuran-2- ones

Article abstract of DOI:10.1081/SCC-200026225

Oxidation of 5,7-di-terf-butyl-3-aryl-3H-benzofuran-2-ones 1 with alkaline potassium hexacyanoferrate (III) affords 3,5-di-terf-butyl-2- hydroxybenzophenones 2 in good to moderate yields.

Full text of DOI:10.1081/SCC-200026225

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Synthesis of
2‐Hydroxybenzophenones
by Oxidation of
3‐Aryl‐3H‐benzofuran‐2‐ones
Peter Nesvadba a , Lucienne Bugnon a & Marvin
Scheffel a
a Ciba Specialty Chemicals Inc., CH‐4002, Basel,
Switzerland
Available online: 10 Jan 2011
To cite this article: Peter Nesvadba, Lucienne Bugnon & Marvin Scheffel (2004):
Synthesis of 2‐Hydroxybenzophenones by Oxidation of 3‐Aryl‐3H‐benzofuran‐2‐ones,
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 34:15, 2797-2802
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 15, pp. 2797–2802, 2004
Synthesis of 2-Hydroxybenzophenones by
Oxidation of 3-Aryl-3H-benzofuran-2-ones
*
Peter Nesvadba, Lucienne Bugnon, and Marvin Scheffel
Ciba Specialty Chemicals Inc., Basel, Switzerland
ABSTRACT
Oxidation of 5,7-di-tert-butyl-3-aryl-3H-benzofuran-2-ones 1 with alka-
line potassium hexacyanoferrate (III) affords 3,5-di-tert-butyl-2-hydroxy-
benzophenones 2 in good to moderate yields.
Key Words: 2-Hydroxybenzophenones; 3-Aryl-3H-benzofuran-2-ones;
Oxidation; Potassium hexacyanoferrate (III).
RESULTS AND DISCUSSION
2-Hydroxybenzophenones have found use as intermediates in the
synthesis of pharmaceuticals, dyes, agrochemicals, or as ultraviolet (UV)
light absorbers for the protection of human skin or organic materials such
*
Correspondence: Peter Nesvadba, Ciba Specialty Chemicals Inc., CH-4002 Basel,
Switzerland; E-mail: peter.nesvadba@cibasc.com.
2797
DOI: 10.1081/SCC-200026225
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

2798
Nesvadba, Bugnon, and Scheffel
as polymers and coatings against UV-damage.[1] Different syntheses of
2-hydroxybenzophenones are known,[1] for example: Fries[2] or Photo-Fries
rearrangement of O-aroylphenols, 2-aroylation[3] of o-lithiated phenoxides,
Pd-catalyzed coupling[4] of 2-hydroxyaryl aldehydes with hypervalent iodo-
nium salts or with aryl iodides,[5] or condensation[6] of trichloromethyl
benzene with phenols in alkaline aqueous solution. Unfortunately, these
methods are not ideal with respect to the scope of applicability, yield or
readily available starting materials. New synthetic methods for 2-hydroxyben-
zophenones are therefore still of interest.
We would like to report in this paper that 3,5-di-tert-butyl substituted
2-hydroxybenzophenones 2 can be obtained easily in moderate to good
yields by treatment of 3-aryl-5,7-di-tert-butyl-3H-benzofuran-2-ones 1 with
an alkaline aqueous solution of potassium hexacyanoferrate (III) (Sch. 1 and
Table 1). The starting 3-aryl-3H-benzofuran-2-ones are easily accessible[7]
compounds. Particularly straightforward is the synthesis of 5,7-di-tert-butyl
substituted benzofuranones 1 for which several methods starting from the
cheap 2,4-di-tert-butyl-phenol (DBP) are available. Thus, 1a was made by
the condensation[7] of DBP with glyoxylic acid and o-xylene. Thermal con-
densation of DBP with the corresponding mandelic acids was employed[8]
for the synthesis of 1b–d.
To our knowledge, preparative oxidative transformation of 3-aryl-3H-
benzofuran-2-ones into 2-hydroxybenzophenones was never reported. Only
traces of 2-hydroxybenzophenone, among other products, were observed[9]
when 3-phenyl-3H-benzofuran-2-one was UV-irradiated in the presence of
singlet oxygen or when the DMF solution of its sodium enolate was
exposed[10] to oxygen. The first step of the transformation of 1 into 2 is the
alkaline hydrolysis of the lactone ring of 1 leading to the corresponding
water soluble substituted diphenylacetic acid salt. This is manifested by the
formation of a homogeneous solution from the water insoluble 1 upon heating
with the aqueous NaOH. The site where the hexacyanoferrate (III) oxidation
starts is not clear. It may be the phenolic or phenolate ion group; indeed
oxidations of phenols with alkaline hexacyanoferrate (III) affording quinone
Scheme 1.

Synthesis of 2-Hydroxybenzophenones
2799
Table 1. Synthesis of 2-hydroxybenzophenones 2 by oxidation of
3-arylbenzofuranones 1.
Entry
R1
R2
R3
Yield (%)
2a
2b
2c
2d
Me
Me
H
Me
H
87
43
66
52
OMe
OEt
H
Me
H
H
H
methides are well known.[11] On the other hand, oxidative decarboxylation
of carboxylic acids under the same conditions is also known.[12] The scope of
our new reaction in its current form seems to be limited to oxidation of 5,7-
di-tert-butyl substituted benzofuranones 1. Thus, 2-hydroxybenzophenones could
not be isolated from the oxidation of 3-(4-ethoxy-phenyl)-5-methoxy-3H-ben-
zofuran-2-one,[8] 5,7-bis-benzylsulfanyl-methyl-3-phenyl-3H-benzofuran-2-
one[13] or 4,6,7-trimethyl-3-phenyl-3H-benzofuran-2-one.[14]
EXPERIMENTAL
1
The spectra were measured with the following equipments: H-NMR
(300 MHz) and 13C-NMR (75.37 MHz) on a Bruker 300 spectrometer in
CDCl3 with TMS as an internal standard, IR on a Nicolet Magna-IR 750
spectrometer using the ATR technique, MS (direct inlet, 70 eV) on a Finnigan
SSQ 710 apparatus. The melting points were not corrected. The solvents and
reagents were of p.a. grade from Fluka.
Typical Procedure for the Oxidation of 1
3,5-Di-tert-butyl-2-hydroxy-phenyl-(3,4-dimethyl-phenyl)-methanone (2a).
To a solution of 0.8 g (0.040 mol) NaOH in 30 mL water were added 3.51 g
(0.010mol) of 5,7-di-tert-butyl-3-(3,4-dimethyl-phenyl)-3H-benzofuran-2-one
1a and the stirred suspension was refluxed for 1 hr under nitrogen. The result-
ing slightly turbid solution was cooled to 708C. Toluene (30 mL) was added
and thereafter a solution of 13.17 g (0.040 mol) potassium hexacyanoferrate
(III) and 1.2 g (0.030 mol) of NaOH in 30 mL water was added dropwise
over 10 min. The mixture was stirred for 5 hr at 708C, cooled to r.t. and
diluted with toluene (20 mL). The organic layer was separated, washed with
5% HCl and water (20 mL each), dried over MgSO4 and evaporated under

2800
Nesvadba, Bugnon, and Scheffel
reduced pressure. The yellow residue (3.41 g) was purified by chromatography
on silica gel (380 g, hexanes: CH2Cl2, 1 : 1) to afford 2.95 g (87%) 2a,
mp 119–1218C (MeOH). Calculated/found for C23H30O2 (338.49): C
81.61/81.46, H 8.93/9.14. MS, m/e (%): 338 (53, Mþ), 323 (100), 217
1
(71). H-NMR, d ppm: 12.70 (s, OH), 7.61 (m, 1ArH), 7.53 (m, 2ArH),
7.45 (d, 1ArH, J ¼ 7.6 Hz), 7.27 (d, 1ArH, J ¼ 7.6 Hz), 2.39 (s, Me), 2.37
(s, Me), 1.60 (s, t-Bu), 1.29 (s, t-Bu). 13C-NMR, d ppm: 202.34, 160.49,
141.08, 139.57, 137.73, 136.69, 136.31, 130.80, 130.70, 129.29, 128.01,
127.25, 118.42, 35.22, 34.25, 31.35, 29.45, 19.97, 19.72. IR (nCO, cm21):
1615, 1596.
The following products were made in the similar manner.
(2b). 43%, mp 89–918C (EtOH). calculated/found for C24H32O3
(368.52): C 78.22/77.90, H 8.75/8.85. MS, m/e (%): 368 (Mþ, 36), 353
(41), 217 (100). 1H-NMR, d ppm: 12.67 (s, OH), 7.61 (d, 1ArH, J ¼ 2.4 Hz),
7.52 (d, 1ArH, J ¼ 2.4 Hz), 7.51 (s, 2ArH), 3.83 (s, OMe), 2.38 (s, 2ꢀ Me),
1.50 (s, t-Bu); 1.29 (s, t-Bu). 13C-NMR, d ppm: 202.19, 160.81, 160.52,
139.94, 138.13, 134.48, 131.32, 131.15, 130.96, 128.40, 118.77, 60.16,
35.61, 34.63, 31.73, 29.84, 16.56. IR (nCO, cm21): 1612, 1576.
(2c). 66%, mp 99–1018C (EtOH). calculated/found for C23H30O3
(354.49): C 77.93/78.04, H 8.53/8.70. MS, m/e (%): 354 (Mþ, 30), 339
1
(28), 217 (100). H-NMR, d ppm: 12.64 (s, OH), 7.73 (m, 2ArH), 7.60
(d, 1ArH, J ¼ 2.4 Hz), 7.51 (d, 1ArH, J ¼ 2.4 Hz), 7.01 (m, 2ArH), 4.16
(q, 2H, J ¼ 7.2 Hz), 1.49 (t, Me, J ¼ 7.2 Hz), 1.48 (s, t-Bu), 1.30 (s, t-Bu).
13C-NMR, d ppm: 201.45, 162.51, 160.65, 139.98, 138.14, 132.27, 131.35,
130.97, 128.07, 118.92, 114.34, 64.15, 35.61, 34.65, 31.77, 29.86, 15.13. IR
(nCO, cm21): 1607, 1588.
(2d). 52%, mp 59–618C (EtOH). 15mp 60–628C (EtOH–H2O). MS
(C21H26O2, M ¼ 310.44), m/e (%): 310 (Mþ, 37), 295 (100), 217 (23).
1H-NMR, d ppm: 12.73 (s, OH), 7.71–7.29 (m, 7ArH), 1.58 (s, t-Bu), 1.27
(s, t-Bu). 13C-NMR, d ppm: 202.54, 160.70, 139.81, 138.71, 137.91,
131.62, 131.23, 129.22, 128.18, 127.86, 118.23, 35.23, 34.24, 31.30, 29.43.
IR (nCO, cm21): 1618, 1595, 1575.
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Synthesis of 2-Hydroxybenzophenones
2801
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Nesvadba, Bugnon, and Scheffel
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Received in Poland April 5, 2004