VO(acac)2 catalyzed oxidative deprotection of oximes, hydrazones, and semicarbazones

Article abstract of DOI:10.1081/SCC-200039490

Oximes, hydrazones, and semicarbazones undergo facile deprotection in the presence of a catalytic amount of vanadyl acetylacetonate and hydrogen peroxide in acetone at room temperature.

Full text of DOI:10.1081/SCC-200039490

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VO(acac)2 Catalyzed
Oxidative Deprotection of
Oximes, Hydrazones, and
Semicarbazones
Surya Kanta De a
a Department of Medicinal Chemistry and
Molecular Pharmacology, School of Pharmacy ,
Purdue Cancer Center, Purdue University , West
Lafayette, IN, 47907, USA
Published online: 12 Jan 2011.
To cite this article: Surya Kanta De (2004) VO(acac)2 Catalyzed Oxidative
Deprotection of Oximes, Hydrazones, and Semicarbazones, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 34:23, 4409-4415, DOI: 10.1081/SCC-200039490
To link to this article: http://dx.doi.org/10.1081/SCC-200039490
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 23, pp. 4409–4415, 2004
VO(acac)2 Catalyzed Oxidative
Deprotection of Oximes, Hydrazones,
and Semicarbazones
*
Surya Kanta De
Department of Medicinal Chemistry and Molecular Pharmacology,
School of Pharmacy, Purdue Cancer Center, Purdue University,
West Lafayette, IN, USA
ABSTRACT
Oximes, hydrazones, and semicarbazones undergo facile deprotection in
the presence of a catalytic amount of vanadyl acetylacetonate and
hydrogen peroxide in acetone at room temperature.
Key Words: Hydrazones; Oximes; Semicarbazones; Vanadyl acetyl-
acetonate.
Oximes, hydrazones, and semicarbazones are useful protecting[1] groups
and are used for the identification and characterization of carbonyl
*
Correspondence: Surya Kanta De, Department of Medicinal Chemistry and Molecular
Pharmacology, School of Pharmacy, Purdue Cancer Center, Purdue University,
West Lafayette, IN 47907, USA; E-mail: skd125@yahoo.com.
4409
DOI: 10.1081/SCC-200039490
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

4410
De
compounds. Because oximes can be synthesized from noncarbonyl com-
pounds, the regeneration of carbonyl compounds from oximes provides an
alternative pathway for preparation of aldehydes and ketones.[2] Therefore,
the regeneration of carbonyl compounds from their oximes has received
much attention. The classical acid hydrolytic method[3] requires strong
mineral acids and often results in low yields. Furthermore, it is not suitable
for acid-sensitive compounds. Hence, a number of oxidative methods have
been developed for cleavage of oximes. Some examples include the Dess–
Martin periodane,[4] IBX-DMSO,[5] PCC,[6] PCC-H2O2,[7] PDC-TBHP,[8]
TBHP in refluxing carbon tetrachloride,[9] manganese acetate in refluxing
benzene,[10] and poly[4-vinyl-N,N-dichlorobenzenesulfonamide] in refluxing
carbon tetrachloride.[11] However, many of the reagents or solvent systems
used are toxic (DMSO), corrosive, carcinogenic (chromium, benzene),
expensive, and noncatalytic. Additionally, some reagents are not readily avail-
able, need to be freshly prepared,[11] require tedious workup procedures, and,
in some cases, may explode while using peroxide at a higher temperature.[9]
With increasing environmental concerns, it is important to investigate a new
method using less hazardous reagents and solvents. Recently, some environ-
mentally benign procedures have been reported, such as Bi(OTf)3,[12]
Bi(NO3)5,[13,14] DOWEX-50[15] as catalysts or stoichiometric reagents. But,
Bi(OTf)3 is expensive, not commercially available, and works well only
with ketoximes in refluxing temperature. Some microwave irradiation tech-
niques[16,17] have been developed for this purpose that are valuable from the
synthetic standpoint, but extreme precautions have to be taken, as these reac-
tions were performance under microwave irradiation or ultrasonic irradiation
with an oxidant. Moreover, most of the known methods deal with the regen-
eration of carbonyl compounds from oximes only, and little attention has been
paid to oxidative cleavage of carbon–nitrogen double bonds of hydrazones
and semicarbazones.[4,5] In view of the recent trend with catalytic processes
toward the development of clean and green chemical processes, investigation
of new, less hazardous chemical oxidants has become a priority in synthetic
organic chemistry. In continuation of my work to develop new synthetic meth-
odologies,[18,19] in this paper, I wish to report a convenient and efficient
method for the regeneration of carbonyl compounds from oximes, hydrazones,
and semicarbazones using a relatively less toxic catalyst and solvent.
Vanadyl acetylacetonate (or oxovanadium bisacetylacetonate) is an
inexpensive reagent that has been used as a catalyst in several organic reac-
tions.[20] Treatment of oximes (both ketoximes and aldoximes) with 30%
hydrogen peroxide in the presence of a catalytic amount of VO(acac)2 in
acetone at room temperature gave the corresponding carbonyl compounds
in good yields (Scheme 1). Presumably, the yields of carbonyl compounds
from ketone derivatives were of higher order than aldedyde derivatives due

VO(acac)2 Catalyzed Oxidative Deprotection
4411
Scheme 1.
to overoxidation of regenerated aldehydes to the corresponding acids
(although only 5–10%). It should be noted that this method gave much
better yields for aldoximes than reported oxidative methods at higher tempera-
tures. Similarly, hydrazones and semicarbazones were deprotected to give the
corresponding carbonyl compounds. Hydrazones were deprotected more
rapidly than oximes or semicarbazones the results have been summarized in
Table 1, which clearly indicates the scope and generality of the reaction
with respect to different aromatic, aliphatic, and unsaturated oximes, hydra-
zones, and semicarbazones. Interestingly, acid-sensitive allyloxyacetophe-
none oxime (entry 19) underwent deprotection reaction giving good yield
without any side products. The method has the ability to tolerate a variety
of other protected groups, such as methoxy, allyloxy, and benzyloxy.
This method can be applied in large-scale reactions without any difficulty.
It should be noted that the above-mentioned reactions did not proceed using
vanadyl acetylacetonate alone. Oximes were treated first with hydrogen
peroxide without catalyst at room temperature. After 50h, only 10–15% con-
versions were observed, indicating the necessity of the catalyst [VO(acac)2].
The oximes, hydrazones, and semicarbazones used were prepared by standard
procedures.[21]
EXPERIMENTAL
Most of the products are known and were identified by comparison of
their spectral data and physical properties (mp or bp) with those of authentic
samples. The progress of reaction was monitored by thin-layer chromato-
graphy (TLC) on silica gel. All yields refer to isolated products.
A Typical Procedure for Deprotection of Oxime
To a stirred mixture of 4-allyloxy-3,5-dimethoxyacetophenone oxime
(471 mg, 2 mmol) and vanadyl acetylacetonate (53 mg, 10 mol%) in acetone

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VO(acac)2 Catalyzed Oxidative Deprotection
4413
(5 mL) was added 30 wt% hydrogen peroxide (1 mL) drop-wise at room
temperature. The reaction mixture was stirred at room temperature for 2 h
(TLC monitored), and then the solvent was removed. The reaction mixture
was extracted with ethyl acetate (60 mL) and washed with 10% Na2S2O3
solution, water, and brine, respectively. The organic layer was dried over mag-
nesium sulfate and concentrated in vacuo. The residue was chromatographed
over silica gel (eluted hexane-ethyl acetate, 9/1–8/2) to afford pure
product. Similar treatment of phenylhydrazones and semicarbazones gave
the corresponding carbonyl compounds in 75–92% yields, as summarized
in Table 1.
Selected Data for Unknown Compounds
1
4-Allyloxy-3,5-dimethoxyacetophenone oxime: mp 83–848C; H NMR
(500 MHz, CDCl3) d 2.26 (s, 3H), 3.88 (s, 6H), 4.54 (d, J ¼ 5.5 Hz, 2H),
5.17–5.32 (m, 2H), 6.01–6.11 (m, 1H), 6.85 (s, 2H), Ar-H); MS m/z 252
(M þ 1)þ; 4-Alloxy-3,5-dimethoxyacetophenone (22): mp 56–578C; 1H
NMR (500 MHz, CDCl3) d 2.58 (s, 3H), 3.91 (s, 6H), 4.61 (d, J ¼ 6 Hz,
2H); 5.18–5.35 (m, 2H), 6.01–6.12 (m, 1H), 7.21 (s, 2H, Ar-H); MS m/z
237 (M þ 1)þ. 4-Benzyloxy-3,5-dimethoxyacetophenone oxime: 1H NMR
(500 MHz, CDCl3) d 2.28 (s, 3H), 3.89 (s, 6H), 5.10 (s, 2H), 6.84 (s, 2H),
7.28–7.40 (m, 3H), 7.45–7.55 (m, 2H); MS m/z 302 (M þ 1)þ; 4-Benzy-
1
loxy-3,5-dimethoxyacetophenone (23): H NMR (500 MHz, CDCl3) d 2.30
(s, 3H), 3.95 (s, 6H), 5.14 (s, 2H), 6.98–7.79 (m, 7H); MS m/z 287 (M þ 1).
Product Characterization Data for Known Compounds
(Compounds are Numbered as the Entries—Table 1)
1: bp 230–2318C; lit.[22] 2328C. 2: mp 46–478C. 3: bp 200–2028C;
lit.[22] 2028C. 4: mp 34–358C; lit.[22] 36–388C. 5: bp 178–1798C; lit.[22]
179–180.6. 7: mp 55–578C; lit.[22] 56–588C. 8: bp 150–1538C; lit.[22]
1558C. 9: bp 245–2478C; lit.[22] 2488C. 10: mp 46–478C; lit.[22] 48–498C.
11: bp 230–2328C; lit.[22] 2328C. 12: mp 55–578C; lit.[22] 56–588C.
13: mp 43–458C; lit.[22] 45–468C. 14: bp 246–2488C; lit.[22] 2488C. 15: bp
217–2188C; lit.[22] 219–2028C. 16: bp 1268C; lit.[22] 1278C. 17: bp 150–
1538C; lit.[22] 1558C. 18: bp 200–2028C; lit.[22] 2028C. 19: mp 46–478C;
lit.[22] 48–498C. 20: bp 178–1798C; lit.[22] 179–1808C. 21: mp 55–578C;
lit.[22] 55–588C. 24: bp 74–778C; lit.[22] 758C. 25: mp 174–1758C; lit.[22]
175–1778C.

4414
De
In summary, a new and useful method has been developed for the regen-
eration of carbonyl compounds from the corresponding oximes, hydrazones,
and semicarbazones. The advantages of this method include (a) operational
simplicity, (b) inexpensive reagents, (c) no need for any additive (Adogen
464 or other) to promote the reaction, (d) the use of relatively nontoxic
reagents and solvents, and (e) compatibility of other protecting groups.
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Received in the USA July 30, 2004