Solvent-free oxidations of alcohols, oximes, aldehydes and cyclic acetals by pyridinium chlorochromate

Article abstract of DOI:10.1055/s-2001-18443

Oxidative transformations of alcohols, oximes and cyclic acetals to carbonyl compounds proceed efficiently by pyridinium chlorochromate (PCC) under solvent-free conditions. The oxidation of aromatic and cinnamylic aldehydes to carboxylic acids, which does not occur by PCC in solution, is achieved satisfactorily in the absence of solvent.

Full text of DOI:10.1055/s-2001-18443

PAPER
2273
Solvent-Free Oxidations of Alcohols, Oximes, Aldehydes and Cyclic Acetals by
Pyridinium Chlorochromate
Solvent-Free
O
e
xidations
o
y
f
Alcohols,
m
O
ximes,
A
ldehydes
a
andCyclic
n
A
cetals by
P
CC Salehi,*a Habib Firouzabadi,b Afsaneh Farrokhi,c Mostafa Gholizadehd
a
Department of Phytochemistry, Medicinal Plants Research Institute, Shahid Beheshti University, Evin, Tehran, Iran
Fax +98(21)2418679; E-mail: p-salehi@cc.sbu.ac.ir
b
c
d
Department of Chemistry, Shiraz University, Shiraz 71454, Iran
Department of Chemistry, Razi University, Kermanshah, Iran
Department of Chemistry, Sabzevar Teacher Training University, Sabzevar, Iran
Received 17 January 2001; revised 25 August 2001
Benzylic alcohols with electron-releasing and electron-
withdrawing substituents were oxidized in the presence of
an equimolar amount of the oxidant and the corresponding
carbonyl compounds were isolated in excellent yields af-
Abstract: Oxidative transformations of alcohols, oximes and cyclic
acetals to carbonyl compounds proceed efficiently by pyridinium
chlorochromate (PCC) under solvent-free conditions. The oxidation
of aromatic and cinnamylic aldehydes to carboxylic acids, which
does not occur by PCC in solution, is achieved satisfactorily in the ter short reaction times (Table 1, entries 1–12). The oxida-
absence of solvent.
tion of 2-nitrobenzyl alcohol (Table 1, entry 5) in 94%
yield is an outstanding point since a similar reaction has
not been reported with other oxidants. In the oxidation of
furfuryl alcohol and 2-thienyl methanol (Table 1, entries
8,9) the heterocyclic ring remained intact during the
course of the reaction. Allylic model compounds as well
as saturated linear and cyclic alcohols were also converted
to the corresponding aldehydes and ketones in good to ex-
cellent yields (Table 1, entries 13–20).
Key words: oxidations, alcohols, aldehydes, acetals, pyridinium
chlorochromate
Recently considerable attention has been paid to solvent-
free reactions.1,2 These reactions are not only of interest
from an ecological point of view, but in many cases also
offer considerable synthetic advantages in terms of yield,
selectivity and simplicity of the reaction procedure.
Oximes are useful intermediates in organic chemistry and
are utilized for purification and characterization of alde-
hydes and ketones. An alternative pathway to aldehydes
and ketones is the synthesis of oximes from non-carbonyl
substrates followed by a deoximation step.8 Chromium
oxidizing agents are not very efficient deoximating com-
pounds.9,10 Chromium oxidants coupled with hydrogen
peroxide or t-butyl hydroperoxide seem to improve the
yield of deoximation.11 However, they are still not satis-
factory for the regeneration of aldehydes and other sensi-
tive carbonyl compounds. Oxidative deoximation by PCC
in dichloromethane has already been reported, however,
carbonyl compounds were produced in low yields with
long reaction times.12 By performing similar reactions in
the absence of solvent the corresponding carbonyl com-
pounds were produced in good to excellent yields without
any overoxidation of aldehydes (Scheme 2). Several ex-
amples of oxidative deoximation of different types of sub-
strates including allylic and benzylic aldoximes and
ketoximes together with saturated cyclic and linear model
compounds are represented in Table 2.
After introduction of pyridinium chlorochromate (PCC)
as a reagent for oxidation of primary and secondary alco-
hols,3 this oxidant has found wide applications in organic
synthesis.4–6 In continuation of our studies on the prepara-
tion and application of chlorochromate derivatives in or-
ganic synthesis,7 we wish to report the unexplored
potentials of PCC for the oxidative transformations of or-
ganic functional groups in the absence of solvent.
One of the most important reactions of alcohols, which
have long been the objective of many research papers, is
their oxidation to carbonyl compounds. We have investi-
gated the reaction of different types of primary and sec-
ondary alcohols under solvent-free conditions by PCC at
room temperature (Scheme1, Table 1).
H
R1
PCC, r.t.
R1
C
OH
C
O
Solvent-free
R2
R2
R3
R4
84-96%
R3
R4
PCC, r.t.
C
NOH
C
O
Scheme 1
Solvent-free
79-93%
Synthesis 2001, No. 15, 12 11 2001. Article Identifier:
1437-210X,E;2001,0,15,2273,2276,ftx,en;Z00801SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881
Scheme 2

2274
P. Salehi et al.
PAPER
Table 1 Oxidation of Alcohols by PCC under Solvent-Free Conditions at Room Temperature.
Entry
1
R1
R2
H
Time (min)
Oxid./Sub. (mole ratio)
Yield(%) mp of 2,4-DNPa (Lit.)b
Ph
15
15
5
1
1.5
1
96c
96
94
93
94
96
92
96
94
95
96
95
95
95
84
85
88
95
91
233–235 (237)
2
4-BrC6H4
4-MeOC6H4
4-ClC6H4
2-NO2C6H4
2-MeC6H4
4-PhCH2OC6H4
2-thienyl
2-furyl
H
253–255 (256–258)18
251–252 (253–254)19
253–254 (254)
3
H
4
H
10
20
10
20
1
1
5
H
1
264 (264)
6
H
1
191–193 (193–194)
227–229 (231–232)20
240–241 (242)21
228–230 (230)
7
H
1.5
1
8
H
9
H
1
1
10
11
12
13
14
15
16
17
18
19
1-naphthyl
Ph
Me
Ph
Me
H
1
1
182–184 (184)22
238–240 (238–239)
248–250 (249–250)
253–255 (255)
1
1
Ph
10
15
1
1
PhCH=CH
PhCH=CH
CH2=CH
C6H13
1
Ph
C5H11
H
1
243–244 (244)
110
150
120
100
80
1.5
2.5
2
121–123
105–107 (108)
C5H11
Me
73–75 (73–74)23
146–148 (148)
-CH2(CH2)4CH2-
-CH2(CH2)5CH2-
1.5
1.5
173–175 (173–177)24
a Mp of 2,4-dinitrophenylhydrazone derivatives.
b Ref. 17 unless otherwise stated.
c Based on the weight of 2,4-dinitrophenylhydrazone derivative.
Table 2 Oxidation of Oximes to Carbonyl Compounds by PCC, under Solvent-Free Conditions at Room Temperature.
Entry
R3
R4
H
Time (h)
2
Oxid./Sub. (mole ratio)
Yield (%) mp of 2,4-DNPa (Lit.)b
1
2
Ph
2
2
3
1
3
4
2
3
3
5
80c
79
83
93
90
80
80
89
83
80
235–236 (237)
253–254 (254)
318–319 (320)
247–249 (248–252)
256–257
4-ClC6H4
4-NO2C6H4
2-OHC6H4
2,4-(MeO)2C6H3
4-MeC6H4
Ph
H
4.5
5.5
1.5
4.5
20
3
H
4
H
5
H
6
Me
Ph
258–260 (260)
239–240 (238–239)
161–162 (162)
103 (104)
7
3.5
5
8
-CH2(CH2)3CH2-
C9H19
9
H
H
5.5
9
10
PhCH=CH
253–254 (255)
a Mp of 2,4-dinitrophenylhydrazone derivatives.
b Ref.17
c Based on the weight of 2,4-dinitrophenylhydrazone derivative.
Synthesis 2001, No. 15, 2273–2276 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Solvent-Free Oxidations of Alcohols, Oximes, Aldehydes and Cyclic Acetals by PCC
2275
Table 3 Oxidation of Aldehydes to Carboxylic Acids by PCC, under Solvent-Free Conditions.
Entry
R5
Time (h)
Oxid./Sub. (mole ratio)
Temp.(ºC)
Yield (%) mp (Lit.)a
1
Ph
2
4
3
5
3
4
4
4
4
4
5
r.t.
45
r.t.
45
45
r.t.
r.t.
r.t.
45
90
121–122 (122)
238–240 (241)
2
4-NO2C6H4
2-MeC6H4
3-BrC6H4
4-ClC6H4
2-furyl
75
3
2.5
3.5
5
81
106–108 (107–108)
154 (155)
4
89
5
81
240–242 (240–243)
131–132 (132)
132–133 (133)
241 (242)
6
6
82
85
7
PhCH=CH
4-Me2NC6H4CH=CH
C9H19
4
8
4
80
9
24
no reaction
a Ref.17
PCC, rt or 45oC
Solvent-free
Oxidation of aldehydes to carboxylic acids does not occur
at all by PCC in solution. There are only a few reports on
the cyclization of some special kinds of aromatic alde-
hydes in dichloromethane by PCC.13 However by the
present method the oxidation of aromatic and cinnamylic
aldehydes by PCC in the absence of solvent is reported for
the first time (Scheme 3, Table 3). The furan ring re-
mained untouched in the oxidation of furfural at room
temperature (Table 3, entry 6). Attempted oxidation of
linear saturated aldehydes failed and substrates remained
intact in the reaction conditions after several hours
(Table 3, entry 9).
R5
CHO
R5
COOH
75-90%
Scheme 3
Several examples of different substituted 1,3-dioxolanes
were converted satisfactorily to their corresponding alde-
hydes and ketones by PCC under neat conditions without
any overoxidation of the aldehydes (Scheme 4, Table 4).
Benzaldehyde, 4-chlorobenzaldehyde, and butyraldehyde
as aromatic and aliphatic aldehydes were produced safely
by the present method (Table 4, entries 1,2,7). Regenera-
tion of other aromatic and aliphatic ketones were also
achieved in few hours in good yields.
Selective protection and deprotection of carbonyl groups
frequently represent essential steps in synthetic organic
chemistry.14,15 Mild regeneration of parent compounds
under non-aqueous conditions is vital for complex com-
pounds with sensitive functional groups. Many reagents
have been used for this purpose in solution but solvent-
free deprotections are rare.16
Table 4 Oxidation of Cyclic Acetals to Carbonyl Compounds by PCC, under Solvent-Free Conditions.
Entry
R6
R7
H
Time (h)
Oxid./Sub. (mole ratio)
Temp. (ºC)
Yield (%) mp of 2,4-DNPa(Lit.)b
1
2
3
4
5
6
7
8
Ph
1.5
2
5
5
3
3
3
5
3
4
45
45
45
45
50
50
45
45
80c
80
77
75
85
83
89c
91
236–237 (237)
254 (254)
4-ClC6H4
Ph
H
Me
Me
Me
3
248–250 (249–250)
257–259 (260)
155–156 (156)23
161–162 (162)
104–106 (106)23
85–87 (89)23
4-MeC6H4
PhCH2
CH2(CH2)3CH2
Bu
3
2
1.5
1.5
2.5
H
C5H11
Me
a Mp of 2,4-dinitrophenylhydrazone derivatives.
b Ref.17 unless otherwise stated.
c Based on the weight of 2,4-dinitrophenylhydrazone derivative.
Synthesis 2001, No. 15, 2273–2276 ISSN 0039-7881 © Thieme Stuttgart · New York

2276
P. Salehi et al.
PAPER
added and extracted with Et2O (3 25 mL). Concentration of the or-
ganic layer under reduced pressure afforded the desired carboxylic
acids in 75–90% yields.
R6
O
R6
R7
PCC, 45-50 oC
Solvent-free
C
O
C
R7
O
Acknowledgement
75-91%
We are grateful to Razi University and Shiraz University Research
Councils for financial support of this work.
Scheme 4
In conclusion, PCC as a well-known oxidant can be used
for the oxidation of organic functional groups in the ab-
sence of solvent. These transformations enjoy the chemi-
cal and environmental advantages of solvent-free
reactions. Also some reactions, which do not proceed sat-
isfactorily in solution occur under solid phase conditions.
The results are quite reproducible and the reactions could
be carried out on a gram scale.
References
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All of the products are known compounds and were characterized
by comparison of their spectral data (1H NMR, IR) and physical
properties with those of authentic samples. Progresses of the reac-
tions were followed by TLC using silica gel polygrams SIL G/UV
254 sheets. Yields refer to isolated products or for slightly volatile
carbonyl compounds are based on the weight of their 2,4-dinitro-
phenylhydrazone derivatives. Melting points were determined in
open capillaries with a Galen-Kamp melting point apparatus and are
corrected.
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General Procedure for the Oxidation of Alcohols, Oximes or
Cyclic Acetals to Carbonyl Compounds by Pyridinium
Chlorochromate under Solvent-Free Conditions
PCC (3–15 mmol) was added to the substrate (3 mmol) in a mortar.
Starting materials were instantly mixed and then stored for the ap-
propriate period at room temperature or in an oven without any fur-
ther agitation (see Tables 1, 2 and 4). The progress of the reaction
was monitored by dissolving a sample in acetone and using TLC on
silica gel (hexane–Et2O, 3:1). Upon completion of the reaction HCl
(20%, 30 mL) was added and extracted with Et2O (3 25 mL). The
organic layer was separated and dried (MgSO4). Evaporation of the
solvent gave the corresponding carbonyl compounds in 75–96%
yields.
Oxidation of Aldehydes to Carboxylic Acids by PCC under
Solvent-Free Conditions; General Procedure
A mixture of aldehyde (3 mmol) and PCC (9–15 mmol) was pre-
pared in a mortar. Starting materials were stored at appropriate tem-
perature (see Table 3) until the presence of aldehyde could not be
further detected. The progress of the reaction was followed by dis-
solving a sample in CH2Cl2 and monitoring by TLC sheets (hexane–
Et2O, 2:1). Upon completion of the reaction HCl (20%, 30 mL) was
(24) Farrissey, W. J.; Perry, R. H.; Stehling, F. C.; Chamberlain,
N. F. Tetrahedron Lett. 1964, 3635.
Synthesis 2001, No. 15, 2273–2276 ISSN 0039-7881 © Thieme Stuttgart · New York