Development of a metal-free oxidation of alcohols with dimethyl sulfoxide (DMSO) activated by tosyl chloride

Article abstract of DOI:10.1080/00397911.2014.916303

In this article we propose an efficient metal-free method for the mild oxidation of alcohols using dimethyl sulfoxide/tosyl chloride at ambient temperature. The procedure described here is an easy and practical method for the oxidation of primary, secondary, allylic, and benzylic alcohols into their corresponding aldehydes and ketones. The notable advantages of this protocol are mild reaction conditions, good yields and selectivity, and simple workup with minimal waste containing no metallic components. The mechanism of the transformation is also investigated.

Full text of DOI:10.1080/00397911.2014.916303

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Development of a Metal-Free Oxidation of Alcohols
with Dimethyl Sulfoxide (DMSO) Activated by Tosyl
Chloride
Fariba Saadati a & Kobra Yousefi a
a Department of Chemistry , Faculty of Science, University of Zanjan , Zanjan , Iran
Accepted author version posted online: 29 May 2014.
To cite this article: Fariba Saadati & Kobra Yousefi (2014): Development of a Metal-Free Oxidation of Alcohols with Dimethyl
Sulfoxide (DMSO) Activated by Tosyl Chloride, Synthetic Communications: An International Journal for Rapid Communication
of Synthetic Organic Chemistry, DOI: 10.1080/00397911.2014.916303
To link to this article: http://dx.doi.org/10.1080/00397911.2014.916303
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Development of a Metal-Free Oxidation of Alcohols with Dimethyl Sulfoxide
(DMSO) Activated by Tosyl Chloride
Fariba Saadati1, Kobra Yousefi1
1Department of Chemistry, Faculty of Science, University of Zanjan, Zanjan, Iran
Corresponding Department of Chemistry, Faculty of Science, University of Zanjan, P.O.
Box 45195-313, Zanjan, Iran E-mail: saadati@znu.ac.ir
Abstract
This paper proposes an efficient metal-free method for the mild oxidation of alcohols
using dimethyl sulfoxide/tosyl chloride at ambient temperature. The procedure described
here is an easy and practical method for the oxidation of primary, secondary, allylic, and
benzylic alcohols into their corresponding aldehydes and ketones. The notable
advantages of this protocol are mild reaction conditions, high yields, high selectivity, and
the simple work-up with minimal waste containing no metallic components. The
mechanism of the transformation is also investigated.
KEYWORDS: Metal-free; oxidation; Alcohol; Dimethyl sulfoxide; Tosyl chloride;
Aldehyde; Ketone.
INTRODUCTION
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The green chemistry revolution has recently resulted in much attention being directed
toward establishing green chemical processes for the synthesis of aldehydes and ketones
which are versatile intermediates of valuable compounds in organic chemistry from both
academic and industrial perspectives.
Oxidation is a very appropriate transformation for preparing carbonyl derivatives as
makes it unnecessary to introduce any new group to the substrate.[1]
There are numerous oxidation methods, such as using transition metal derivatives
involving homogeneous [2]and heterogeneous catalysts,[3] organic compounds itself
arguably an even more important backbone such as Dess–Martin periodinane (1,1,1-
triacetoxy-1,1-dihydro-1,2-benziodo-3(1H)-one),[4] IBX (1-hydroxy-1,2-benziodoxol-
3(1H)-one),[5] Bis-IBX,[6] tetrapropylammonium perruthenate (TPAP),[7] 2,2,6,6-
tetramethylpiperidine-1-oxyl (TEMPO),[8] and N-tert-Butylbenzenesulfenamide.[9]
A useful environmentally benign and metal-free method for oxidation of hydroxyl groups
in aliphatic and aromatic compounds is using a combination of dimethyl sulfoxide
(DMSO) and an electrophilic species at low temperature (-60 to -10 °C).[10] Following the
discovery of transformation of an alcohol dissolved in dry DMSO with N,N'-
dicyclohexylcarbodiimide (DCC) to a corresponding aldehyde or ketone,[11] the
intermediacy of "activated" sulfoxide derivatives has been substantiated by scientists.[12]
This type of oxidation of alcohols can be carried out under very mild conditions, avoids
the use of toxic metals, and no further oxidation to give carboxylic acids.
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On this basis, various agents have been reported to be effective in the oxidation of
alcohols. A few examples are acetic anhydride,[13]phosphorus pentoxide,[14] sulfur trioxide
in the form of its pyridine complex,[15] trifluoroacetic anhydride,[16] oxalyl chloride
(Swern oxidation),[17] thionyl chloride,[18] HBr[19], O-(Benzotriazol-1-yl)-N,N,N′,N′-
tetramethyluronium tetrafluoroborate (TBTU) [20] in combination with DMSO, and
heterogenous Swern oxidation by DMSO/SiO2-Cl system.[21]
During the investigations, Albright briefly mentioned cyanuric chloride, p-
toluenesulfonyl chloride, p-toluenesulfonic anhydride, and methanesulfonic anhydride
with dimethyl sulfoxide as mild oxidative reagents for oxidizing alcohols to carbonyl
derivatives in hexamethylphosphoramide (HMPA) at -20°C. [22]
However, some of presented methods restricted by poor yields, result in undesired
products (i.e., methylthiomethyl ethers and Pummerer rearrangement), cryogenic
temperatures (-60 to -10°C) for successful activation, and the use of expensive oxidizing
agents. It should be noted that some activators react violently and exothermically with
DMSO at room temperature and the excess of the activator necessary for efficient
conversion. Also, there are solubility problems at low temperature.
In continuation of this study, it was considered that the more efficient methods are
needed for the oxidation of alcohols under ambient conditions with high yield.
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The p-toluenesulfonyl chloride (Tosyl chloride, TsCl) is a commercially available and
inexpensive reagent that exhibits a variety of interesting and useful properties. The p-
toluenesulfonate (tosylate) group has been successfully used as a good leaving group in
nucleophilic substitution (SN) reactions.[23] The formation of an O–S bond by replacing
chlorine in sulfonyl chloride makes this group a practical intermediate.
The present research is a report on a general method for effective oxidation of hydroxyl
group under mild reaction conditions using DMSO/TsCl as a highly selective and
efficient oxidant.
In this procedure, transformation starts at 0°C and then mildly rises to the ambient
temperature. To our knowledge, activation of DMSO at ambient temperature has rarely
been tried due to the formation of side products, and indeed a large number of previous
studies focused on low temperature conditions.
Our methodology is considerably simple and selective. It considers room temperature
conditions and produces good yields with minimal waste streams. The reaction was
carried out with oxidation of a wide range of alcohols.
DISCUSSION
As discussed elsewhere, temperature control is necessary for activating agents that react
exothermically with DMSO at room temperature. A particular drawback from an
industrial point of view is that the activated DMSO intermediate is unstable at or above
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about -20°C. It was reasoned that a revision in reaction conditions may turn the reaction
into a mild and efficient procedure.
To study the combination of tosyl chloride and DMSO in alcohol oxidation, the solvent,
temperature, and molar ratio were screened as the common factors affecting the reaction.
For this purpose, a model reaction of benzyl alcohol in DMSO and tosyl chloride was
initially performed in the presence of triethylamine.
As for the solvent effect, the reaction was carried out using 1.5 equivalents TsCl and 3
equivalents DMSO in tetrahydrofuran (THF), toluene, and dichloromethane (DCM) at
ambient temperature and -25°C. In the presence of DCM and THF, at low temperature
any product was produced, but the result of oxidation in toluene was trace. Although the
solvents, toluene and DCM are satisfactory at ambient temperature, distilled dry toluene
is better because it leads to cleaner products. Since dry toluene produced the best
conversion and yield at ambient temperature, it was chosen as the preferred solvent for
the reaction.
The corresponding benzaldehyd was obtained with the dropwise addition of benzyl
alcohol to the stirred mixture of DMSO/TsCl in toluene at 0°C, and the mixed
temperature became ambient. After 90 min, triethylamine was added, and the mixture
was stirred for 10 min.
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Under the same conditions, four variations of the molar ratio of TsCl to DMSO to
triethylamine (1: 1: 3; 2: 2: 3; 2: 3: 3; 1.5: 3: 3) were examined. The ratio 1.5: 3: 3 was
the best. The excess of base is necessary for the consumption of the acids produced in
reaction media and for the efficient conversion of hydroxyl group to carbonyl function.
We further used TsCl (1.5 equivalent) in DMSO (3.0 equivalent) in toluene at ambient
temperature under air atmosphere as the optimized reaction condition to probe the scope
of oxidation of various types of alcohols (Scheme 1).
Table 1 shows that oxidation of various types of alcohol is completed under desired
reaction conditions with good to excellent yields. All the products are pure. An important
observation was the generality of the method for the oxidation of a wide range of
hydroxyl compounds to carbonyl derivatives.
In addition, this method was successfully applied to the transformation of benzylic
derivatives. The slight decrease in the conversion of 2-substituted benzylic alcohols can
be ascribed to steric hindrance (Table 1, Entries 1-7).
An attractive feature of this reagent is that it can selectively oxidate allylic alcohol to
afford a corresponding α,β-unsaturated carbonyl compound within a few minutes and
with excellent yield (Table 1, Entry 8).
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In particular, the method showed excellent activity for the oxidation of primary aliphatic
alcohols under the same reaction conditions furnished the corresponding product with
excellent yields in all cases. As can be seen in Table 1 (Entries 9–13), the yield rises with
an increase in the number of carbons (Table 1, Entries 9–13).
On a comparative basis, the oxidation of secondary aliphatic alcohols produced good
yields of the corresponding ketones (Table 1, Entries 14-17). Increasing the bulk of the
substituents attached to the hydroxyl group reduces yields of carbonyls as compared with
benzylic derivatives.
The mechanistic illustration of these reactions prompted us to envision the in situ
formation of tosyloxydimethylsulfonium chloride 3 or chlorodimethylsulfonium tosylate
4 from the interaction of DMSO and tosyl chloride. The first intermediate quickly reacts
with alcohol 1 to give the key alkoxydimethylsulfonium salt 5. The additions of
triethylamine will deprotonate the alkoxydimethylsulfonium ion to give intermediate 6
[12] which is alternatively converted to dimethyl sulfide (DMS) and the desired ketone or
aldehyde (Scheme 2).
The research by Kornblum and colleagues demonstrated that the sulfonates of primary
alcohols react with DMSO to yield carbonyl compounds.[24]
So it can be proposed that oxidation proceeds via alkyl tosylate. In this manner, the
alcoholic compound was first converted to alkyl tosylate 7 by TsCl. Under these
conditions, the alkyl tosylate 7 is consumed by DMSO as a nucleophilic ionizing solvent
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to form the alkoxydimethylsulfonium tosylate 8. Then, the alkoxydimethylsulfonium
tosylate 8 collapses to carbonyl and dimethylsulfide (DMS) via the formation of the
intermediate 6 after the addition of triethylamine (Scheme 3).
To better clarify the role of tosyl chloride in this protocol, another experiment was
performed.
First, benzyl tosylate was prepared with p-toluenesulfonyl chloride in pyridine using the
Tipson's method. [25] The oxidation of benzyl tosylate was then conducted under the same
reaction conditions as before. Interestingly, the corresponding benzaldehyde was not
observed. Therefore, the formation of aldehyde can be conveniently accommodated by
the first pathway.
CONCLUSIONS
This research found that a very efficient agent in the oxidation of alcohols is dimethyl
sulfoxide in the presence of tosyl chloride. The generality of the procedure, mild reaction
conditions, selectivity, and good to excellent yields could make this method a useful
addition to previously reported methods. In view of exploiting the transformation, metal-
free oxidation at ambient temperature was employed.
EXPERIMENTAL
Instrumentation
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All chemicals were purchased from commercial suppliers and were distilled or
recrystallized before use. NMR spectra (1H NMR and 13C NMR) were obtained using a
250 Bruker Avance instrument with the chemical shifts being reported as δ parts per
million and the couplings being expressed in hertz. The IR spectra were recorded using
an FT-IR Brucker-Vector in KBr/Nujol mull. The analysis of the organic phases was
performed via Gas-liquid chromatography (GLC) using a 6890 network GC system of
Agilent on an HP-5 (30.0 m × 0.320 mm × 0.25 µm) column. Merck silica gel 60 F254
plates were used to monitor the reaction progress in thin-layer chromatography (TLC).
General Procedure
The Dimethyl sulfoxide (DMSO) (0.23 gr; 3 mmol) was added dropwise to the stirred
mixture of tosyl chloride (0.29 gr; 1.5 mmol) and dry toluene (2.0 ml) at 0°C for 10 min
and stirring was continued for another 15 min. A solution of alcohol (1.0 mmol) in dry
toluene (1 ml) was then injected into the solution, and the temperature of the resulting
mixture was brought to the ambient temperature. The mixture was stirred at ambient
temperature for 90 min before triethylamine (0.30 gr; 3.0 mmol) was added dropwise in
ca. 10 min. Once the reaction was complete, the complex was treated with water (5 mL),
and the mixture was extracted using toluene (2×5 mL). The organic layer was dried over
sodium sulfate (Na2SO4). Samples of the reaction mixture were monitored by GC. The
products of the reaction were determined via comparison with those of authentic samples
of carbonyl compounds.[26]
Full experimental data are available in the online supplemental section.
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SUPPORTING INFORMATION
Supplemental data for this article can be accessed on the publisher’s website.
ACKNOWLEDGMENTS
The author acknowledges the financial support of the Research Council of University of
Zanjan.
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Table 1. Oxidation of alcohols using DMSO /TsCl a
Entr R1
y
R2
Tim Yiel
e
d
(min (%)c
b
)
1
2
3
4
5
6
C6H5
H
H
H
H
H
H
10
10
10
10
10
10
>99
>99
94
2-BrC6H4
2,4-Cl2C6H3
4- CH3OC6H4
4-CH3C6H4
4-
>99
>99
>99
(CH3)2CHC6H4
4-NO2C6H4
C6H5CH=CHCH
7
8
H
H
20
20
95
>99
2
9
C6H5CH2 CH2
H
H
25
20
90
95
10
C6H5CH2
CH2CH2
11
12
13
14
15
CH3(CH2)5
CH3(CH2)6
CH3(CH2)7
CH3(CH2)5
C6H5CH2
H
25
25
25
25
25
87
H
95
H
>99
90
CH3
CH3
80
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CH2
16
17
Cyclohexanol
25
25
85
87
2-Adamantanol
a Conditions: Substrate: DMSO: TsCl 1:3:1.5 (molar ratio); (CH3CH2)3N (3mmol);
toluene as solvent; r.t.
b After addition of triethylamine.
c GC yield.
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Scheme 1. Oxidation of alcohol derivatives
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Scheme 2. The proposed mechanism for the oxidation of alcohol derivatives in the
presence of DMSO/TsCl
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Scheme 3. The proposed mechanism for the oxidation of alcohol derivatives in the
presence of DMSO/TsCl via alkyl tosylate formation
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