A facile cleavage of ketone N,N-dimethylhydrazones by CeCl3·7H2O-SiO2

Article abstract of DOI:10.1055/s-2001-15161

Ketone N,N-dimethylhydrazones are rapidly and chemoselectively deprotected to the corresponding ketones in high yields by CeCl₃·7H₂O supported on silica gel under microwave irradiation. The method is compatible with acid sensitive substrates.

Full text of DOI:10.1055/s-2001-15161

1134
LETTER
A Facile Cleavage of Ketone N,N-Dimethylhydrazones by CeCl3 7H2O-SiO2
Jhillu S. Yadav, Basi V. Subba Reddy, M. Shashi K. Reddy, G. Sabitha
Organic Chemistry Division-1, Indian Institute of Chemical Technology, Hyderabad-500 007, India
Fax: +91 40 7170512; E-mail: yadav@iict.ap.nic.in
Received 23 April 2001
The irradiations were carried out at 450W using BPL,
Abstract: Ketone N,N-dimethylhydrazones are rapidly and
BMO 700-T, domestic microwave oven. The reaction
temperature was controlled by operating the microwave
chemoselectively deprotected to the corresponding ketones in high
yields by CeCl3·7H2O supported on silica gel under microwave ir-
oven using pulsed irradiation technique (1 min with 20 s
interval). The deprotection was clean, high yielding and
completed with in 3-5 min. Under thermal conditions, the
cleavage required longer reaction times (5-8 h) to achieve
comparable yields those that are obtained by microwave
irradiation. The cleavage of ketone N,N-dimethylhydra-
zone was proceeded smoothly by CeCl3 7H2O-SiO2 in
solvent-free conditions. Similarly several substituted hy-
drazones were selectively deprotected to the correspond-
ing ketones in high yields. The products are obtained in
high purity (>95% by GLC analysis) after filtration. Sev-
eral examples illustrating this novel and rapid procedure
for the cleavage of ketone hydrazones are summarized in
the Table. The method is compatible with various func-
tional groups such as ethers, olefins, and halides present in
the substrate. The reaction rates and yields are dramatical-
ly improved by microwave irradiation compared to con-
ventional heating. The rate enhancement may be
attributed to the more absorption of microwave energy by
polar media that generates heat energy required to pro-
mote the reaction. Thus, microwave promoted reactions
are quick, more convenient and high yielding. Further the
method is effective only for the hydrolysis of ketone N,N-
dimethyl hydrazones. Other carbonyl derivatives such as
oximes and tosylhydrazones are stable under the present
reaction conditions. Probably, the lower reactivity of alde-
hyde hydrazones compared to ketone hydrozones did not
yield any product under the present reaction conditions.
This gives an added selectivity to deprotect the ketone hy-
drazone leaving the aldehyde hydrazone free for further
manipulation.
radiation. The method is compatible with acid sensitive substrates.
Key words: CeCl3 7H2O-SiO2, N,N-dimethylhydrazones, ketones,
microwaves
Hydrazones are widely used as protecting groups for alde-
hydes and ketones in multi-step synthesis of many natural
products.1 In addition to carbonyl protection, they serve as
equivalents of carbanions derived from aldehydes and ke-
tones, in carbon-carbon bond forming reactions.2,3 How-
ever, the final stage of chemical process frequently
require their cleavage so as to regenerate the parent carbo-
nyl compounds. As a result, a variety of procedures have
been developed under both hydrolytic4,5 and oxidative
conditions.6,7 However, inspite of their potential utility,
many of these procedures require strongly acidic, oxidiz-
ing and/or reducing agents and also involve expensive re-
agents or harsh reaction conditions. Consequently, the
development of new reagents that are more efficient and
lead to convenient procedures and better yields is desir-
able. In recent years, there has been increasing interest in
various chemical transformations involving environmen-
tally friendly reagents such as solid supported catalysts8
and those that are assisted by microwaves9 under solvent-
free conditions. Enhanced reaction rates, improved yields,
greater selectivity, milder reaction conditions and the pos-
sibility of recycling the catalysts are the main advantages
in the use of solid supported reagents in dry media. Fur-
ther, lanthanide halides are unique Lewis acids10 that are
currently of great research interest due to their low toxic-
ity, ease of handling, low cost, stability to air or water and
recoverability
In summary, we have described a mild and chemoselec-
tive procedure for the hydrolysis of ketone N,N-dimethyl-
hydrazones using CeCl3 7H2O supported on silica gel
under microwave irradiation conditions. The method of-
fers several advantages including mild reaction condi-
tions, high yields of products, short reaction times, greater
selectivity, experimental simplicity, inexpensive and low
toxicity of cerium salts which makes it a useful and attrac-
tive process for this transformation.
In this report, we describe a rapid and efficient procedure
for the regeneration of ketones from their N,N-dimethyl-
hydrazones using CeCl3 7H2O-SiO2. The cleavage was
effected by cerium(III) chloride heptahydrate supported
on silica gel under microwave irradiation (Scheme 1).11
Acknowledgement
Scheme 1
BVS and MSKR thank CSIR, New Delhi for the award of fel-
lowships.
Synlett 2001, No. 7, 1134–1136 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
A Facile Cleavage of Ketone N,N-Dimethylhydrazones by CeCl3 7H2O-SiO2
Table Regeneration of ketones from N,N-dimethylhydrazones
1135
a Pulsed irradiation (1 min with 20 s interval) operated at 450 W using BPL,
BMO-700T-microwave oven. b Isolated yields after filtration
References and Notes
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# IICT Commun. No: 4721
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Synlett 2001, No. 7, 1134–1136 ISSN 0936-5214 © Thieme Stuttgart · New York

1136
J.S. Yadav et al.
LETTER
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(11) General procedure - Microwave irradiation: Ketone N,N-
dimethyl hydrazone (5 mmol) and CeCl3 7H2O (5 mmol) were
admixed with silica gel (1.5 g Merck, finer than 200 mesh) and
subjected to microwave irradiation at 450 W for 3-5 min.
After completion of the reaction as indicated by TLC, the
reaction mixture was filtered and washed with
dichloromethane (2 20 mL). The combined organic layers
were concentrated in vacuo to give the parent ketone (>95%
purity). Spectral data for compounds 2c: 1H NMR (CDCl3) :
2.15 (m, 2H) 2.65 (t, 2H, J = 7.0 Hz), 2.95 (t, 2H, J = 7.0 Hz),
7.20 (d, 1H, J = 8.5 Hz), 7.25 (t, 1H, J = 8.5 Hz), 7.45 (t, 1H,
J = 8.5 Hz), 8.0 (d, 1H, J = 8.5 Hz). 2h: 1H NMR (CDCl3)
:
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1.05 (t, 3H, J = 6.9 Hz), 1.50 (m, 2H), 2.25 (t, 2H, J = 6.9 Hz),
2.55 (m, 2H), 5.05 (m, 2H), 5.95 (m, 1H), 6.90 (d, 2H, J = 8.4
Hz), 7.90 (d, 2H, J = 8.4 Hz). 2I: 1H NMR (CDCl3) : 2.75 (s,
3H), 7.55 (m, 2H), 7.85-8.05 (m, 4H), 8.50 (s, 1H). 2k: 1H
NMR (CDCl3) : 2.55 (s, 3H), 7.05 (t, 1H, J = 8.0 Hz), 7.60 (d,
1H, J = 8.0 Hz), 7.65 (d, 1H, J = 8.0 Hz). 2q: 1H NMR
(CDCl3) : 1.10-1.30 (m, 4H), 1.75-1.90 (m, 2H), 2.06 (s, 3H),
2.16-2.25 (m, 2H), 3.40 (t, 2H, J = 7 Hz), 4.50 (s, 2H), 7.30-
7.40 (m, 5H, aromatic). 2r:1H NMR (CDCl3) : 1.10-1.25 (m,
4H), 1.85-1.95 (m, 2H), 2.05 (s, 3H), 2.15-2.25 (m, 2H), 3.45
(t, 2H, J = 6.8 Hz), 3.50 (s, 3H), 5.20 (s, 2H). 2s: 1H NMR
(CDCl3) : 1.15-1.30 (m, 4H), 1.80-1.95 (m, 2H), 2.05 (s, 3H),
2.25 (m, 2H), 3.45 (t, 2H, J = 6.8 Hz), 3.75 (s, 3H), 4.40 (s,
2H), 6.80 (d, 2H, J = 8 Hz), 7.25 (d, 2H, J = 8 Hz).
Article Identifier:
1437-2096,E;2001,0,07,1134,1136,ftx,en;S11500ST.pdf
Synlett 2001, No. 7, 1134–1136 ISSN 0936-5214 © Thieme Stuttgart · New York