Highly selective regeneration of carbonyl compounds from their oximes and semicarbazones in aqueous medium

Article abstract of DOI:10.1081/SCC-200054761

Chemoselective regeneration of aryl alkyl ketone, α-tetralone, and cycloalkanone by hydrolysis of their oximes and semicarbazones has been accomplished using aqueous phosphoric acid without involvement of any organic cosolvent in the reaction medium, where the similar derivatives of aryl aldehyde, diaryl ketone, aliphatic acyclic aldehyde and ketone remain mostly inert. Copyright Taylor & Francis, Inc.

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Highly Selective Regeneration
of Carbonyl Compounds
from Their Oximes and
Semicarbazones in Aqueous
Medium
Sanjay Bhar a & Sharmistha Guha a
a Department of Chemistry, Organic Chemistry
Section, Jadavpur University, Kolkata, India
Published online: 16 Aug 2006.
To cite this article: Sanjay Bhar & Sharmistha Guha (2005): Highly Selective
Regeneration of Carbonyl Compounds from Their Oximes and Semicarbazones in
Aqueous Medium, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 35:9, 1183-1188
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Synthetic Communicationsw, 35: 1183–1188, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200054761
Highly Selective Regeneration of Carbonyl
Compounds from Their Oximes and
Semicarbazones in Aqueous Medium
Sanjay Bhar and Sharmistha Guha
Department of Chemistry, Organic Chemistry Section,
Jadavpur University, Kolkata, India
Abstract: Chemoselective regeneration of aryl alkyl ketone, a-tetralone, and cyclo-
alkanone by hydrolysis of their oximes and semicarbazones has been accomplished
using aqueous phosphoric acid without involvement of any organic cosolvent in the
reaction medium, where the similar derivatives of aryl aldehyde, diaryl ketone,
aliphatic acyclic aldehyde and ketone remain mostly inert.
Keywords: Aldehyde and ketone, chemoselectivity, hydrolysis, oxime and
semicarbazone
INTRODUCTION
Protection of carbonyl compounds[1] as oximes and semicarbazones is of great
interest to synthetic organic chemists because of their high stability and the
ease of preparation, which were also utilized classically for the characteriz-
ation[2] of the parent carbonyl compounds. Numerous reagents[1,3] have
been developed for regeneration of carbonyl compounds from these deriva-
tives. There are only a few reports of preferential regeneration of ketones
from ketoximes.[3b] However, many of the aforementioned reagents are
Received in India December 20, 2004
Address correspondence to Sanjay Bhar, Department of Chemistry, Organic
Chemistry Section, Jadavpur University, Kolkata 700032, India. E-mail:
sanjaybharin@yahoo.com

1184
S. Bhar and S. Guha
toxic and promote undesired side reactions[3b] such as polymerization of
aldoximes, oxidation of aldoximes to nitrile oxide, and overoxidation. Even
in some very recent reports using ionic liquid-silica gel,[4a] 50% aq.
glyoxylic acid,[4b] photosensitized reactions[4c] and imidazolium dichro-
mate,[4d] very little chemoselectivity has been observed. As a part of our
endeavor[5] to develop new methodologies for selective organic transform-
ations, we report herein a simple and novel hydrolytic protocol for chemose-
lective regeneration of aryl alkyl ketones from their oximes and
semicarbazones in 1.5 (M) aqueous phosphoric acid, as shown in Scheme 1.
The results are given in Table 1 and Table 2.
As evident from Table 1, oximes[2] and semicarbazones[2] of structurally
varied aldehydes[6] and ketones[6] were subjected to the hydrolytic cleavage in
1.5 (M) aqueous phosphoric acid at 958C without involvement of any organic
cosolvent in the reaction medium. The aryl alkyl ketones (entries 2, 3, 5, 7, 8, 9
in Table 1) and cycloalkanone (entry 10 in Table 1) were regenerated from
their oximes and semicarbazones in high yield and good purity. Interestingly,
oximes and semicarbazones of aryl aldehydes (entries 1, 4, 6, in Table 1), alkyl
aldehyde (entry 11 in Table 1), and dialkyl ketone (entry 12 in Table 1)
remained mostly unaffected under the present hydrolytic conditions. In the
presence of 1.5 (M) phosphoric acid, the aryl aldoximes were converted slug-
gishly to the parent aldehydes and the aryl aldehyde semicarbazones remained
practically inert (entries 1, 4, 6 in Table 1). In the same timeframe, aryl
aldoximes and aldehyde semicarbazones were completely hydrolyzed to the
parent aldehydes with 1.5 (M) hydrochloric acid and 1.5 (M) acetic acid.
Diaryl ketoxime was also resistant to the present hydrolytic protocol (entry
1 in Table 2). Formation of various side products from the unreacted
aldoximes and aldehyde semicarbazones (which is a serious limitation of
many existing methods[3]) was negligible in the present method, where very
little conversion took place; the recovered materials contained the correspond-
ing substrates intact. Therefore, the present phosphoric acid–mediated
protocol in aqueous medium can serve as an excellent method for chemoselec-
tive deprotection of oximes and semicarbazones of aryl alkyl ketone,
a-tetralone, and cycloalkanone in preference to the similar derivatives of
aryl aldehyde, alkyl aldehyde, aliphatic acyclic ketone, and diaryl ketone.
Scheme 1. Y ¼ OH and NHCONH2, for R1 ¼ aryl, R2 ¼ alkyl, and R1 2 R2 ¼
cycloalkyl; for R1 ¼ aryl, R2 ¼ H or aryl and for R1 ¼ alkyl, R2 ¼ H or alkyl, little
or no reaction.

Regeneration of Carbonyl Compounds
1185
Table 1. Selective regeneration of carbonyl compounds[2,6] from their oximes and
semicarbazones in 1.5 (M) aq. H3PO4
Regeneration of parent carbonyl compound
From oxime
From semicarbazone
Parent carbonyl
compound[2,6]
Time
(h)
Yielda
(%)
Time
(h)
Yielda
(%)
Entry
1
2
3
4
PhCHO
PhCOMe
PhCOEt
6
4
4
6
8b
90
6
4
4
6
0
83
85
0
89
14b
5
6
4
6
92
4
6
89
0
20b
7
8
3
6
86
83
3
4
89
80
9
4
3
93
88
3
3
91
86
10
11
12
36
8
15b
0
34
6
0
0
aYield of isolated products, fully characterized spectroscopically.
1
b% of conversion by H-NMR, remainder starting material.

1186
S. Bhar and S. Guha
Table 2. Selective deoximation of ketones in 1.5 (M) aq. H3PO4
Regeneration of parent carbonyl
compound from their oxime
Parent carbonyl
compound[2]
Entry
1[2,6]
Time (h)
8
Yielda (%)
0
2[2,6]
3[2]
12
12
2
9b
52b
75b
4[2]
5[2]
2
1
89
85
6[2]
aYield of isolated products, fully characterized spectroscopically.
1
b% of conversion by H-NMR, remainder starting material.
Such chemoselectivity, which was not observed in most of the earlier
methods,[3,4] is an important attribute of this hydrolytic process. This was
also supported by intermolecular competition experiment, in which an equi-
molecular mixture of benzaldoxime and acetophenone oxime under the
1
present conditions afforded 48% of acetophenone (determined by H-NMR,
300 MHz) after 1 h, whereas the benzaldoxime was found almost
unchanged with no formation of benzaldeyde. The excellent chemoselectivity
has also been elegantly demonstrated by an intramolecular competition exper-
iment, in which the dioxime of 4-acetylbenzaldehyde[6] underwent selective
hydrolysis of ketoxime in preference to aldoxime (the extent of conversion
1
was measured by H-NMR), as delineated in Scheme 2.

Regeneration of Carbonyl Compounds
1187
Scheme 2. 4 h, 40% cleavage of ketoxime, no cleavage of aldoxime; 6 h, 82%
cleavage of ketoxime, no cleavage of aldoxime; 8 h, 87% cleavage of ketoxime, no
cleavage of aldoxime.
Besides excellent selectivity, another interesting feature of this metho-
dology is the survival of the acid-labile carbomethoxy, ferrocenyl, and thio-
phenyl moieties during the hydrolytic removal of the oximes (entries 4, 5, 6
in Table 2). Addition of a few drops of saturated sodium nitrite solution
toward the end of the reaction was needed to complete the cleavage of semi-
carbazones. No cleavage occurred upon addition of nitrite at the beginning of
the reaction, and the phenolic ketone did not undergo nitrosation under this
condition. Therefore, it was proved that the cleavage was not initiated by
the nitrous acid produced by the reaction of nitrite ion in acidic medium.
Rather, nitrite assisted driving the reaction equilibrium towards the product
side through removal of the liberated semicarbazide salt by oxidative
decomposition.
Although the exact reason for this selectivity is not yet clear, it seems to
be critically dependent on the electronic and steric character of the latent
carbonyl center of the substrates. The carbocations obtained by protonation
of the aryl oximes and semicarbazones are more stable than those attained
from aliphatic ones, and so the former are hydrolyzed at faster rate. The
aryl ketoximes form the carbocations, which are, in turn, more stable than
those from the aryl aldoximes, so the former undergo preferential protonation
and hydrolysis. The electron-donating substituents at ortho- and para-
positions in the aromatic rings of aryl aldoximes render some extra stabiliz-
ation to the carbocationic intermediates, resulting in a greater extent of
hydrolysis than the unsubstituted one. Electron-rich moieties, such as thiophe-
nyl and ferrocenyl, make the hydrolysis faster. Decreased electron density
of the aromatic ring by attachment with an electron-withdrawing moiety
retards the reaction (Scheme 2), as compared to that of the unsubstituted
aryl ketoximes.
EXPERIMENTAL
Representative procedure for the hydrolysis of oximes: Aceto phenone oxime
(675 mg, 5 mmol) was stirred at 958C in 1.5 (M) aqueous phosphoric acid
(5 mL) for 4 h until the completion of reaction, as monitored by TLC (silica

1188
S. Bhar and S. Guha
gel). It was diluted with water (5 mL), extracted with diethyl ether
(3 Â 10 mL), washed with water (2 Â 5 mL), aqueous sodium bicarbonate
solution (3 Â 5 mL), and brine(1 Â 5 mL) and dried over anhydrous sodium
sulfate. The solvent evaporated to furnish acetophenone, (540 mg, 90%) in
1
practically pure form, which was fully characterized by IR and H-NMR
spectral data and compared with those of authentic samples. The same
procedure has been followed in cases of semicarbazones; toward the end of
the reactions, a few drops of sodium nitrite solution was added. In some
cases, the products were further purified by short-path distillation or by fil-
tration chromatography on a short column of silica gel using petroleum
ether (60–808C) or 5% ethyl acetate-petroleum ether, if needed.
ACKNOWLEDGMENT
This study enjoyed financial support from CSIR, New Delhi [Grant No.
01(1673)/00/EMR-II dated December 7, 2000], which is gratefully acknow-
ledged. Thanks to N. Dutta of IACS for necessary assistance.
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