Efficient chemoselective oxidation of phenylmethanols to aldehydes with iodosobenzene

Article abstract of DOI:10.1007/s00706-005-0364-1

Primary phenylmethanols are selectively and efficiently oxidized to the corresponding aldehydes by the system C₆H₅IO/(C ₆H₅)₄PBr/CH₂Cl₂, T = 298 K under aerobic conditions. The u

Full text of DOI:10.1007/s00706-005-0364-1

Monatshefte f€ur Chemie 136, 2035–2039 (2005)
DOI 10.1007/s00706-005-0364-1
Efficient Chemoselective Oxidation
of Phenylmethanols to Aldehydes
with Iodosobenzene
Patrina Paraskevopoulou1;ꢀ, Eleftheria Petalidou1,
Nikos Psaroudakis1, Pericles Stavropoulos2, and Konstantinos Mertis1;ꢀ
1
Department of Inorganic Chemistry, Faculty of Chemistry, University of Athens,
Panepistimioupoli Zographou 15771, Athens, Greece
2
Department of Chemistry, University of Missouri-Rolla, Rolla, MO 65409, USA
Received January 24, 2005; accepted (revised) March 1, 2005
Published online October 3, 2005 # Springer-Verlag 2005
Summary. Primary phenylmethanols are selectively and efficiently oxidized to the corresponding
aldehydes by the system C6H5IO=(C6H5)4PBr=CH2Cl2, T ¼ 298 K under aerobic conditions. The
use of the relatively stable iodosobenzene, an iodine(III) compound, in place of the usually
employed and potentially explosive iodine(V) reagents, the easy work-up procedure, and the facile
recycling of solvent and oxidant provides a convenient and environmentally benign oxidation
method.
Keywords. Alcohols; Chemoselectivity; Hypervalent compounds; Iodine; Oxidations.
Introduction
The selective oxidation of alcohols to the corresponding carbonyl compounds
(Scheme 1) plays a central role in organic chemistry, hence a variety of stoichio-
metric and catalytic reactions involving both metals and non-metals have been de-
veloped [1]. In particular, the conversion of primary alcohols to aldehydes is crucial
for the synthesis of fine chemicals, such as fragrances or food additives. However,
despite the spectacular progress in the oxidation of alcohols and the use of envir-
onmentally friendly systems [2], there are still severe limitations with respect to the
chemo-, regio-, and stereoselectivity of the reaction.
Hypervalent iodine(V) reagents, such as Dess-Martin periodinane [3] and o-
iodoxybenzoic acid [4] oxidize alcohols mildly and efficiently to carbonyl com-
pounds in high yields in organic solvents (CH2Cl2, DMSO, acetone), but despite
their utility, they are potentially explosive and require often an excess amount of
ꢀ
Corresponding author. E-mail: cmertis@cc.uoa.gr

2036
P. Paraskevopoulou et al.
Scheme 1
reagent. Therefore, replacement with relatively stable iodine(III) reagents is
highly desirable.
Oxo(phenyl)-ꢀ3-iodane (iodosobenzene, C6H5I ¼ O, 1) is capable of oxidizing
activated alcohols [5], e.g. phenylmethanol, to carbonyl compounds under drastic
conditions (dry dioxane, reflux, 12 h). Activation of 1 with ruthenium catalysts, such
as RuCl2(P(C6H5)3)2, Ru3(CO)12, RuCl3 ꢁ H2O, or ruthenocene [6] results in the oxi-
dation of a variety of alcohols to carbonyl compounds and carboxylic acids, whereas
in the presence of ytterbium(III) salts [7] aldehydes or ketones are selectively pro-
duced at 80ꢂC in 1,2-dichloroethane solutions. The combination of 1 and potassium
bromide (KBr) in water induces the oxidation of primary alcohols exclusively to their
carboxylic acids, and of secondary alcohols to the corresponding ketones [8, 9].
Herein, as an extension of our studies on the catalytic oxidation of alcohols
with rhenium complexes [10], we report that by replacing the system 1=KBr=H2O
with 1=(C6H5)4PBr=CH2Cl2, overoxidation to the acids can be avoided and the
corresponding aldehydes can be obtained instead.
Results and Discussion
Reagent 1 oxidizes C6H5CH2OH to C6H5CHO in CH2Cl2 in a non-catalytic reac-
tion, in poor yields (Table 1, Entry 1). In contrast, upon addition of tetraphenylpho-
sphonium bromide, the reaction becomes catalytic and the yield is dramatically
improved. Specifically, for a ratio of 1:(C6H5)4PBr ¼ 1:0.1 the reaction becomes
quantitative at 24 h (Table 1, Entry 5). Use of (C6H5)4PI was proved to be less
effective (Table 1, Entries 14–17) and employment of (C6H5)4PCl is ineffective
(Table 1, Entry 18). Under anaerobic conditions the yield is decreased (Table 1,
Entries 6–9). Excess moisture poisons the reaction (Table 1, Entry 11).
Thus, the typical system, which was used for the oxidation of a range of alcohols
consists of 1 (1 eq), (C6H5)4PBr (0.1 eq), and alcohol (1 eq). The reaction was per-
formed aerobically at T ¼ 298 K and some representative results are shown in Table 2.
Substituted phenylmethanols in general are efficiently oxidized (Table 2,
Entries 3–9, 13). Lower yields (e.g. Entries 2, 10) can be significantly improved
by changing the molar ratio 1:(C6H5)4PBr:alcohol (e.g. 1:0.2:1 gives 80% yield for
o-CH3OC6H4CH2OH and 67% for o-O2NC6H4CH2OH). Para- or ortho-substitu-
ents with electron releasing or withdrawing properties do not induce any change in
the selectivity of the reaction except in the cases of p-CH3OC6H4CH2OH (Table 2,
Entry 3) and p-CF3C6H4CH2OH (Table 2, Entry 13), where the esters (ca. 0.2%
and 10%) were formed. In the first case, traces of the chloride (<1%) were detected
at the end of the reaction. Introduction of ꢃNO2 groups lowers the yield (Table 2,
Entries 10–12). Primary aliphatic alcohols were not oxidized. Secondary alcohols

Efficient Chemoselective Oxidation
2037
Table 1. Oxidation of C6H5CH2OH with 1=(C6H5)4PX (X ¼ Cl, Br, I)a
Entry
X
Molar ratio
C6H5CHO=%
1:(C6H5)4PX:C6H5CH2OH
1
2
–
1:0:1
10b
31b
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
I
1:1:1
3
1:0.5:1
1:0.2:1
1:0.1:1
1:1:1
48b
4
70b
5
>99b
13c
6
7
1:0.5:1
1:0.2:1
1:0.1:1
1:0.1:1
1:0.1:1
1:0.1:1
1:0.1:1
1:1:1
45c
8
68c
9
80c
10
11
12
13
14
15
16
17
18
46c,d
1c,e
24c,f
60f,g
14b
I
1:0.5:1
1:0.2:1
1:0.1:1
1:0.5:1
32b
I
35b
I
22b
Cl
18c
Reaction conditions: CH2Cl2 (15.0 cm3), T ¼ 298 K, t ¼ 24 h; aerobically; anaerobically;
a
b
c
d
e
CH2Cl2 not dried over CaH2; CH2Cl2 saturated in H2O; molecular sieves (type 3A) were
f
˚
g
used; strictly in the absence of H2O, in an atmosphere of dry O2
Table 2. Oxidation of alcohols by 1=(C6H5)4PBra
Entry
Alcohol
Carbonyl compound
Yield=%(blanc)b
1
2
Ph–CH2–OH
Ph–CHO
>99 (10)
61 (26)
96 (44)
74 (15)
80 (36)
92 (26)
92 (12)
91 (28)
>99 (29)
45 (3)
2-CH3O–Ph–CH2OH
4-CH3O–Ph–CH2OH
2-CH3–Ph–CH2OH
3-CH3–Ph–CH2OH
4-CH3–Ph–CH2OH
2-Cl–Ph–CH2OH
3-Cl–Ph–CH2OH
4-Cl–Ph–CH2OH
2-O2N–Ph–CH2OH
3-O2N–Ph–CH2OH
4-O2N–Ph–CH2OH
4-F3C–Ph–CH2OH
PhCHOHCH3
2-CH3O–Ph–CHO
4-CH3O–Ph–CHO
2-CH3–Ph–CHO
3-CH3–Ph–CHO
4-CH3–Ph–CHO
2-Cl–Ph–CHO
3-Cl–Ph–CHO
4-Cl–Ph–CHO
2-O2N–Ph–CHO
3-O2N–Ph–CHO
4-O2N–Ph–CHO
4-F3C–Ph–CHO
PhCOCH3
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
72 (29)
55 (20)
89 (32)
53 (3)
cyclohexanol
cyclohexanone
2-propanone
50 (0)
2-propanol
10 (0)
2-octanol
2-octanone
28 (0)
a
Reaction conditions: 1 (1 mmol), (C6H5)4PBr (0.1 mmol), alcohol (1 mmol), CH2Cl2 (15.0 cm3),
b
T ¼ 298 K, P ¼ 1 atm, t ¼ 24 h; in the absence of (C6H5)4PBr

2038
P. Paraskevopoulou et al.
Scheme 2
were oxidized in lower yields (Table 2, Entries 14–17). Allylic and homoallylic
alcohols (2-propen-1-ol, 3-buten-1-ol) were unreactive.
Electrospray ionization mass spectrometric (ESI-MS) studies for the aqueous
system suggested [9] that the reaction proceeds through the formation of a highly
reactive iodine species C6H5I(Br)OꢃKþ (Scheme 2). This type of activation is very
different from the mechanism involving transition metals or 2,2,6,6-tetramethyl-1-
piperidinyloxy free radical, where metal-oxo or N-oxoammonium salt moieties
function as reactive species.
However, it is noteworthy that in the present system water and=or dioxygen
seem to be essential components for successful oxidation (Table 1, Entries 12, 13),
which implies that more subtle aspects may be involved in the mechanism of the
reaction with the 1=KBr=H2O system.
In summary, the system 1=(C6H5)4PBr=CH2Cl2 oxidizes efficiently, aerobi-
cally, and selectively primary phenylmethanols to aldehydes. In addition, the use
of the relatively stable iodosobenzene, the easy work-up procedure, and the facile
recycling of solvent and oxidant provides a convenient and environmentally benign
oxidation method. Further studies to improve the rate of the reaction and obtain
mechanistic insight are in progress.
Experimental
CH2Cl2 and n-hexane were distilled over CaH2 by fractional distillation (Vigreux column). Diethyl
ether was distilled over Na=Ph2CO in an inert atmosphere. Anaerobic reactions were performed under
Ar or N2 atmosphere, using Schlenk and syringe techniques on an inert gas=vacuum manifold. The
solvent was degassed by three freeze-pump-thaw cycles. C6H5CH2OH and Na2SO4 were purified and
dried according to Ref. [11]. O2 was dried by passing through a tube of anhydrous P2O5. All chemicals
and solvents were purchased from Aldrich, except for decahydronaphthalene (C10H18, cis and trans
mixture of isomers, Riedel-de-Haen). Reagent 1 was prepared according to Ref. [12]. H and 13C NMR
1
€
spectra were obtained on a Varian 300 Unity Plus spectrometer. GC-MS experiments were performed
on a Varian Star 3400CX GC coupled with a Varian Saturn 2000MS. Column: 30mꢄ0.25 mm ID,
0.25ꢁm, CP-Sil 8 CB; LB=MS column with 2 m fused Silica precolumn; injection: 1 mm3, 50:1 split;
flow: 1 cm3=min He, constant flow; oven: 50ꢂC=hold 3.00 min, 7ꢂC=min to 150ꢂC, 50ꢂC=min to
280ꢂC, 280ꢂC=hold 2.12 min, 5ꢂC=min to 300ꢂC, 300ꢂC=hold 4.00 min; injector: 280ꢂC; transfer line:
280ꢂC; MSD scan range: 10–600 amu.
Typical Procedure
To 8.1 mg (C6H5)4PBr (19 ꢁmol) dissolved in 15.0 cm3 CH2Cl2 42.5 mg 1 (193 ꢁmol) and
20ꢄ 10ꢃ3 cm3 C6H5CH2OH (21 mg, 193 ꢁmol) were added. The mixture was stirred for 24h at

Efficient Chemoselective Oxidation
2039
T ¼ 298 K. The same procedure was also followed in the anaerobic reactions. The analysis of the
samples by GC-MS was performed as follows: C10H18 (internal standard for quantification) was added
to the mixture at the end of the reaction and the solvent was removed under vacuum. The organic
compounds were extracted with n-hexane or diethyl ether, depending on their solubility, and were dried
1
(Na2SO4). The organic products were also analyzed by H and 13C NMR in CDCl3.
Acknowledgements
We thank the Research Account of the University of Athens (70=4=3342) for financial assistance.
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