A new and efficient method for oxidation of various alcohols by using N-tert-butyl phenylsulfinimidoyl chloride

Article abstract of DOI:10.1246/cl.2000.1072

Various primary and secondary alcohols were smoothly oxidized to afford the corresponding aldehydes and ketones in excellent yields by using N-terf-butyl phenylsulfinimidoyl chloride (1) in the presence of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene). The oxi

Full text of DOI:10.1246/cl.2000.1072

1072
Chemistry Letters 2000
A New and Efficient Method for Oxidation of Various Alcohols
by Using N-tert-Butyl Phenylsulfinimidoyl Chloride
Teruaki Mukaiyama,* Jun-ichi Matsuo, and Manabu Yanagisawa
Department of Applied Chemistry, Faculty of Science, Science University of Tokyo, Kagurazaka, Shinjuku-ku, Tokyo 162-8601
(Received June 23, 2000; CL-000617)
Various primary and secondary alcohols were smoothly oxi-
dized to afford the corresponding aldehydes and ketones in excel-
lent yields by using N-tert-butyl phenylsulfinimidoyl chloride (1)
in the presence of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene).
The oxidation of alcohols was carried out in a simple manner by
using the isolable oxidizing agent 1 under basic conditions.
Oxidation of alcohols is one of the most fundamental
organic transformations and many useful oxidation methods
have been developed. Among them, oxidation of alcohols by
using activated dimethyl sulfoxides1 was more frequently
employed in the key step of various synthetic strategies. It is
generally known that an alcohol reacts with the activated
dimethyl sulfoxides to form an alkoxysulfonium salt (3), which
is in turn deprotonated by bases such as Et3N to form a
dimethylalkoxysulfonium ylide (4). Oxidized products are
formed by an intramolecular proton transfer of 4 below the tem-
perature of Pummerer rearrangement as shown in Scheme 1, eq
1. Swern et al. demonstrated2 that a combination of dimethyl
sulfoxide and oxalyl chloride proved to be the most useful and
practical method among many oxidation methods by using acti-
vated dimethyl sulfoxides. However, the control of reaction
temperature at each step was crucial for successful oxidation of
alcohols because the intermediates formed stepwise in Swern
oxidation were quite unstable. For example, it was reported
that 2, an activated intermediate of Swern oxidation, was no
longer stable at 20 °C and yields of carbonyl compounds
dropped down even at 0 °C.2 On the other hand,
Parikh–Doering oxidation,1d in which dimethyl sulfoxide was
activated by SO3–pyridine, could be conducted at room temper-
ature. However, more than 3 equivalents of SO3–pyridine were
generally required in this procedure.
It was considered then that an alkoxysulfilimine (5) would
behave as a key intermediate to afford oxidation products more
conveniently in comparison with the alkoxysulfonium ylide (4)
(Scheme 1, eq 2) since the reactivity of the sulfilimine (5)-nitro-
gen was lower than that of sulfonium ylide (4)-carbon. In addi-
tion, it was easily assumed that the intermediate 5 would be
more stable than 4 because of its inherent zwitter ionic struc-
ture.3 To the best of our knowledge, however, there are no
reports on oxidation reaction of alcohols via 5. Now, we would
like to report here a new and efficient method for oxidation of
various alcohols via novel intermediate 5, which is formed by
the reaction of alcohols with N-tert-butyl phenylsulfinimidoyl
chloride (1) in the presence of DBU.
cedure: i.e., a mixture of phenyl thioacetate (5.4 g, 35.5 mmol)
and N,N-dichloro-tert-butylamine5 (5.3 g, 37.3 mmol) in ben-
zene (15 mL) was refluxed for 1 h. The volatiles were evapo-
rated and the crude product was purified by distillation
(112–116 °C/0.5 mmHg) to give 16 (4.4 g, 20.3 mmol, 57% as a
red-orange liquid). This reagent 1 can be stored for a long time
within a sealed bottle at room temperature.
In order to find appropriate reaction conditions, an oxida-
tion of benzyl alcohol using 1 was tried as a model, and effects
of bases and solvents in the present oxidation reaction were
examined (Table 1). When benzyl alcohol and 1 were simply
mixed in dichloromethane at –78 °C without using any base,
the desired oxidation reaction hardly took place and benzyl
chloride was formed in a small amount (entry 1). However,
when bases were used for trapping hydrogen chloride generated
during the formation of 5, the desired oxidation smoothly pro-
ceeded (entries 2–5). Among the bases examined, the best
result was obtained when 2 equivalents of DBU were used
(entry 3). It was obvious that 2 equivalents of DBU were nec-
essary for the inhibition of the above mentioned chloride forma-
tion as shown in the experiments using 1 or 2 equivalents of
DBU (entries 2 and 3). In addition to dichloromethane, toluene,
THF, and acetonitrile were tried as solvents in this oxidation
reaction. In the cases of using toluene and THF, the reaction
mixtures turned to be suspensions and the oxidation reaction
proceeded very slowly. Therefore, dichloromethane was found
to be the most suitable solvent for the present oxidation reac-
tion.
In order to form the key intermediate 5 readily from alco-
hols, N-tert-butyl phenylsulfinimidoyl chloride (1), which had
already been synthesized by Markovskii et al.,4 was chosen as
an oxidizing agent. In the present experiment, 1 was conve-
niently prepared by a slight modification of Markovskii’s pro-
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
1073
Oxidation of various alcohols other than benzyl alcohol was
performed in excellent yields by using 1 and DBU in
dichloromethane (Table 2). Benzylic and allylic alcohols were
oxidized even at –78 °C and normal primary alcohols and second-
ary alcohols were oxidized at temperatures ranging from 0 °C to
room temperature. Overoxidation to form carboxylic acids was
not observed when primary alcohols were converted to aldehydes
by using 1. It is noted that in the present oxidation reaction, the
reaction temperature is not necesssarily kept below –20 °C,
because 1 is quite stable and no other competing reactions such as
rearrangements occurred during the oxidation reaction.
Interestingly enough, trimetylsilyloxy group was not cleaved
under the present oxidation condition (entry 6) whereas dioxidized
product was obtained by Swern oxidation, presumably because of
the deprotection of the trimetylsilyloxy group with hydrogen chlo-
ride before the addition of triethylamine (cf., Scheme 1, eq 1).
This result shows that the combination of 1 and DBU would also
be useful for oxidation of acid-labile compounds.
Typical experimental procedure (Table 1, entry 3) is as fol-
lows: under an argon atmosphere, a solution of 1 (266 mg, 1.23
mmol) in CH2Cl2 (1.5 mL) was added to a mixture of benzyl
alcohol (103 mg, 0.82 mmol), DBU (251 mg, 1.65 mmol) and
CH2Cl2 (1.5 mL) at –78 °C. The yellow color of 1 disappeared
immediately after the addition of 1. The resulted colorless reac-
tion mixture was stirred for 30 min at the same temperature and
the reaction was quenched by adding 1% aqueous HCl (5 mL).
The mixture was extracted with CH2Cl2 and the yield of ben-
zaldehyde was determined by GC analysis using an internal stan-
dard (0.80 mmol, 98%).7
pounds since the present reaction can be conducted under basic
conditions.
Further investigations on preparing more suitable N-alkyl
sulfinimidoyl chlorides together with their application to the
oxidation reaction are now in progress.
References and Notes
1
a) W. W. Epstein and F. W. Sweat, Chem. Rev., 67, 247 (1967).
b) T. V. Lee, “Comprehensive Organic Synthesis,” ed. by B. M.
Trost, Pergamon Press, Oxford (1991), Vol. 7, p. 291. c) K. E.
Pitzner and J. G. Moffatt, J. Am. Chem. Soc., 87, 5661/5670
(1965). d) J. R. Parikh and W. E. Doering, J. Am. Chem. Soc.,
89, 5505 (1967). e) K. Omura, A. K. Sharma, and D. Swern, J.
Org. Chem., 41, 957 (1976).
2
a) K. Omura and D. Swern, Tetrahedron, 34, 1651 (1978).
Review: b) A. J. Mancuso and D. Swern, Synthesis, 1981, 165.
T. L. Gilchrist and C. J. Moody, Chem. Rev., 77, 409 (1977).
L. N. Markovskii, T. N. Dubinina, E. S. Levchenco, and A. V.
Kirsanov, J. Org. Chem. USSR., 9, 1435 (1973).
3
4
5
6
J. T. Roberts, B. R. Rittberg, and P. Kovacic, J. Org. Chem., 46,
4111 (1981).
Thus, a novel and efficient method for oxidation of various
kinds of alcohols by using 1 in the presence of DBU was
explored. The oxidation reaction of alcohols would proceed via a
mechanistically new intermediate, alkoxysulfilimine (5).8
Further, this oxidation method has some advantages over Swern
oxidation. (i) The oxidizing agent 1 is quite stable and can be
used directly without any treatment. (ii) The reaction conditions
are not required to be strictly controlled and the oxidation reac-
tion can be conducted even at room temperature. (iii) The oxida-
tion reaction is applicable to the oxidation of acid-labile com-
1H NMR (270 MHz, CDCl3, TMS) δ 1.58 (9H, s), 7.5–7.7 (3H,
m), 8.1–8.2 (2H, m). 13C NMR (67.5 MHz, CDCl3) δ 29.53,
64.15, 125.91, 129.19, 133.17, 142.63. The sulfinimidoyl chlo-
ride 1 was decomposed at ca. above 160 °C. Markovskii et al.
described that 1 was purified by crystallization in petroleum
ether and ether (3 : 1) at –50 °C.4
7
8
The carbonyl compounds were isolated by silica gel-column
chromatography. The major co-product was diphenyl disulfide.
H-U. Wagner and A. Judelbaum, Angew. Chem., 90, 487
(1978).