Convenient, mild catalytic deprotection of oximes to carbonyl compounds with hydrogen peroxide and iodine catalyst in aqueous acetonitrile

Article abstract of DOI:10.1080/00397910902883678

A clean, mild, and efficient catalytic deoximation procedure compatible with several common functional groups has been developed using 30% hydrogen peroxide activated by iodine catalyst in aqueous acetonitrile under essentially neutral conditions. The mechanistic features of an iodonium ion-driven nucleophilic cleavage of oximic C=N have been revealed.

Full text of DOI:10.1080/00397910902883678

This article was downloaded by: [California Institute of Technology]
On: 02 May 2013, At: 11:52
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic
Organic Chemistry
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
Convenient, Mild Catalytic
Deprotection of Oximes to
Carbonyl Compounds with
Hydrogen Peroxide and
Iodine Catalyst in Aqueous
Acetonitrile
Nemai C. Ganguly a , Subhasis Nayek a & Sujoy
Kumar Barik a
a Department of Chemistry, University of Kalyani,
Kalyani, India
Published online: 16 Oct 2009.
To cite this article: Nemai C. Ganguly , Subhasis Nayek & Sujoy Kumar Barik
(2009): Convenient, Mild Catalytic Deprotection of Oximes to Carbonyl Compounds
with Hydrogen Peroxide and Iodine Catalyst in Aqueous Acetonitrile, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 39:22, 4053-4061
To link to this article: http://dx.doi.org/10.1080/00397910902883678
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-
and-conditions

This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden.
The publisher does not give any warranty express or implied or make any
representation that the contents will be complete or accurate or up to
date. The accuracy of any instructions, formulae, and drug doses should be
independently verified with primary sources. The publisher shall not be liable
for any loss, actions, claims, proceedings, demand, or costs or damages
whatsoever or howsoever caused arising directly or indirectly in connection
with or arising out of the use of this material.

Synthetic Communications1, 39: 4053–4061, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902883678
Convenient, Mild Catalytic Deprotection of
Oximes to Carbonyl Compounds with Hydrogen
Peroxide and Iodine Catalyst
in Aqueous Acetonitrile
Nemai C. Ganguly, Subhasis Nayek, and Sujoy Kumar Barik
Department of Chemistry, University of Kalyani, Kalyani, India
Abstract: A clean, mild, and efficient catalytic deoximation procedure compatible
with several common functional groups has been developed using 30% hydrogen
peroxide activated by iodine catalyst in aqueous acetonitrile under essentially neu-
tral conditions. The mechanistic features of an iodonium ion–driven nucleophilic
=
cleavage of oximic C N have been revealed.
Keywords: Aldehyde, 30% hydrogen peroxide, iodine, ketone, oxime
Oximes serve as useful carbonyl protecting groups largely because of
their ease of preparation and utilization for isolation, characterization,
and purification of carbonyl compounds. Preparation of oximes from
noncarbonyl sources followed by their cleavage also provides useful
alternative entries to carbonyl compounds.[1] A host of oxidative,
reductive, and acid-catalyzed procedures of deoximation[2] are cur-
rently available, of which a good number involve expensive or often
inaccessible or hazardous reagents including heavy-metal compounds
of Cr, Ni, Mn, and Zn in stoichiometric or excess amounts, causing
waste-disposal problems. With the current global awareness of envir-
onmental effects of reaction methods and the paradigm shift away
from stoichiometric methods to clean catalytic ones, the development
Received November 19, 2008.
Address correspondence to Nemai C. Ganguly, Department of Chemistry,
University of Kalyani, Kalyani 741235, WB, India. E-mail: nemai_g@yahoo.
co.in
4053

4054
N. C. Ganguly, S. Nayek, and S. K. Barik
of green oxidative,[3] catalytic,[4,5] photochemical,[6] and ionic
liquid–based[7] protocols continues to be a focus of attention. Our
interest in the development of environmentally friendly deprotection
methods based on hydrogen peroxide[8] prompted us to evaluate the
efficacy and scope of 30% aqueous hydrogen peroxide in catalytic
combination with iodine as deoximating reagent. Despite the use of
the 30% H2O2ꢀI2 reagent system in oxidative applications involving
[9]
=
=
C C and C O bonds, to the best of our knowledge, there is no
report of its utilization in oxime removal. We chose 3,4-methylene-
dioxybenzaldehyde oxime (piperonal oxime) 1 as a representative
oxime of oxidation-prone aryl aldehydes that also contains the hydro-
lytically labile methylenedioxy moiety and set out to optimize, under
aqueous conditions the regeneration of piperonal, a fragrant principle
and synthetic precursor of 3,4-dihydroxy phenyl alanine (DOPA).
Deprotection of 1 did not proceed with either 30% H2O2 (2 mmol)
or a catalytic amount of iodine (20 mol%) alone in water. A cleaving
combination of 30% H2O2 (2 mmol) and iodine (20 mol%) in water
without organic cosolvent also proved abortive. Encouraged by the
reported micellar activation of iodonium ion with anionic surfactant
sodium dodecyl sulfate (SDS),[10] the micellar solubilization route to
overcome the incompatibility of aromatic substrate and water seemed
to be attractive. However, only moderate success (12 h, 40% yield)
was accomplished employing 30% H2O2 (2 mmol) and iodine
(10 mol%) in water in the presence of SDS (5 cmc). Gratifyingly, clea-
vage of 1 (1 mmol) mediated with 30% H2O2 (0.22 mL, 2 mmol) and I2
(10 mol%) in acetonitrile–water (9:1 v=v) was found to be most
rewarding in terms of yield and reaction time (96%, 4 h) with no
detectable by-product formation. We proceeded to explore the scope
and limitations of the protocol on a range of oximes with varying
reactivity levels and steric encumbrances under the optimized condi-
tions, and the results are presented in Table 1.
Based on observed electronic and solvent effects on rates of
cleavage, we formulate a mechanistic hypothesis that is essentially an
electrophile-driven nucleophilic cleavage rather than an oxidative one
(Scheme 1).
=
Iodine acts as a Lewis acid to activate the C N bond by way of
formation of cyclic iodonium ion 2a, thereby persuading nucleophiles
to attack with resultant cleavage. Significantly, activated substrates
such as 4-hydroxyacetophenone oxime and its amino counterpart
(entries 8, 9; Table 1) underwent slow cleavage with concomitant ring
iodination, affording 4-hydroxy-3,5-diiodoacetophenone oxime (8a)
and 4-amino-3-iodoacetophenone oxime (9a) respectively as
by-products. Substantial cleavage rate enhancement was observed

Convenient, Mild Catalytic Deprotection
4055
Table 1. Deoximation with 30% H2O2 and I2 catalyst
Reactiona Yieldb of the carbonyl
Entry
Substrate
time (h)
compound (%)
1
2
4
3
96
90
3
6
98
4
5
6
15
12
16
85
90
80
7
8
7
98
(i) 12
(ii) 6c
92
60
(iii) 10d
20
9
10
11
20e
15
6
3
90
98
(Continued )

4056
N. C. Ganguly, S. Nayek, and S. K. Barik
Table 1. Continued
Reactiona Yieldb of the carbonyl
Entry
12
Substrate
time (h)
compound (%)
20
92
13
14
12
1
80
98
15
16
7
85
78
11
17
18
5
85
85
10
19
20
12
36
95
75
21
7
80
(Continued )

Convenient, Mild Catalytic Deprotection
4057
Table 1. Continued
Reactiona Yieldb of the carbonyl
time (h) compound (%)
Entry
Substrate
22
1.5
85
23
1.5f
98
24
25
26
10
20
40
96
50
NRg
aReaction conditions: 30% H2O2 (0.22 mL) and I2 (10 mol%) per mmol of
substrate in acetonitrile–water (9:1), rt.
bIsolated yield upon column chromatography; the carbonyl compounds
1
were characterized by their spectral data (FTIR, H NMR), mp, and com-
parison with authentic sample.[12]
cReaction conditions: 30% H2O2 (0.22 ml) and I2 (10 mol%) per mmol of
substrate, MeOH, rt.
dReaction conditions: 30% H2O2 (0.22 mL) and I2 (50 mol%), and MeOH
(2 mL) per mmol of substrate; 4-hydroxy-3,5-diiodoacetophenone oxime
(8a) was formed in a yield of 10%.
eThe low yield of acetophenone is due to concomitant formation of
4-amino-3-iodoacetophenone oxime (9a) in 8% yield.
fAcetic acid was used as the solvent because of the low solubility of the
substrate in aqueous acetonitrile.
gNR indicates no reaction.

4058
N. C. Ganguly, S. Nayek, and S. K. Barik
Scheme 1. Proposed mechanism of cleavage of oximes with H2O2ꢀI2 in
acetonitrile–water.
upon replacing aqueous acetonitrile with methanol. In contrast, tert-
butanol that lacks nucleophilicity proved to be a disappointingly poor
solvent, yielding the parent ketone in a meager yield of 20% along with
recovered starting material (60%) even after extended reaction time
(30 h). Slow rates of cleavage of electron-rich substrates are incompa-
tible with an oxidative mechanism. Electron release of para=ortho
hydroxy or amino group in the aromatic ring makes the oximic carbon
an incompetent electrophilic partner for subsequent nucleophilic
cleavage, presumably in a rate-determining step. Methanol provides
better nucleophilic assistance than water by attacking 2a or its open b-
iodobenzylic carbocation equivalent in this crucial step. Methanol is
analogously preferred to water for nucleophilic attack in iodofunction-
lization of alkenes[9b] with I2ꢀH2O2. However, it is reported to pro-
mote undesirable ring iodination[11] of activated substrates as well,
thereby precluding its use as a solvent of choice for deoximation.
Notably, deceleration in cleavage rate of activated substrates
allows for competitive ring iodination. This in turn depletes effective
iodine concentration, making formation of 2a more difficult. Acetyl
derivatives of both the substrates (entries 10, 11) provided the
optimum level of activations required for faster deoximation without
attendant iodination.
To summarize, we have developed a clean, mild, economic, and oper-
ationally simple protocol of deoximation utilizing dilute aqueous hydro-
gen peroxide activated with a catalytic amount of iodine in aqueous
acetonitrile under essentially neutral conditions.

Convenient, Mild Catalytic Deprotection
4059
EXPERIMENTAL
General Experimental Procedure
Solid iodine (46 mg, 0.18 mmol) and 30% hydrogen peroxide (0.4 ml)
were added to a solution of 3,4-methylenedioxybenzaldehyde oxime
(298 mg, 1.8 mmol) in acetonitrile–water (3.6 ml, 9:1 v=v), and the reac-
tion mixture was stirred at room temperature for 4 h (monitoring with
thin-layer chromatography, TLC). The reaction was quenched with
10% sodium thiosulfate solution and extracted with ethyl acetate
(2 ꢁ 4 mL). The combined organic extract was washed with water
(5 mL) and brine (3 mL) and dried (Na2SO4). Concentration of the
organic extract under reduced pressure, elution with ethyl acetate–light
petrol (5:95), and filtration through a short column of silica gel (60–120
mesh, Spectrochem, India) gave 3,4-methylenedioxybenzaldehyde
(260 mg, 96%), mp (35–37ꢂC) (lit.[12] 37ꢂC). It was identical in all
1
respects (mixed mp, superimposable IR, H NMR) with an authentic
sample of 3,4-methylenedioxybenzaldehyde.
Spectral Data for Selected Compounds
4-Hydroxy-3,5-diiodoacetophenone Oxime (8a)
White crystals; mp 176–178ꢂC; IR (KBr): 3323, 2927, 1639, 1606, 1516,
;
1286, 1220, 1092, 720, 594 cmꢀ1 1H NMR (DMSO-d6, 300 MHz):
dH 2.04 (3H, s, -CH3), 7.92 (2H, s, H-2,6), 9.69 (1H, bs, -OH) 11.13
(1H, s, NOH); 13C NMR (DMSO-d6, 75 MHz): dC 11.3 (-CH3), 86.8
=
=
(C-3,5), 132.9 (C-1), 136.1 (C-2,6), 150.4 (C NOH), 155.8 (C-4);
DEPT-135 (DMSO-d6, 75 MHz): dC 11.3 (-CH3), 136.1 (C-2,6); TOF
MS m=z (%): 425.67 [(M þ Na-H)þ, 28%], 403.68 [Mþ, 100%].
4-Amino-3-iodoacetophenone Oxime (9a)
Orange crystals; mp 146–148ꢂC; IR (KBr): 3375, 3300, 2925, 1655,
1612, 1581, 1287, 1247, 817, 585 cmꢀ1
;
1H NMR (DMSO-d6,
400 MHz,): dH 2.05 (3H, s, -CH3), 5.41 (2H, s, 4-NH2), 6.72 (1H, d,
J ¼ 8.4 Hz, H-5), 7.38 (1H, d, J ¼ 8.3 Hz, H-6), 7.8 (1H, s, H-2),
10.79 (1H, s, N-OH); 13C NMR (CDCl3, 75 MHz): dC 11.9 (-CH3),
83.5 (C-3), 114.0 (C-5), 127.1 (C-6), 127.9 (C-1), 136.7 (C-2), 147.7
=
þ
=
(C NOH), 154.6 (C-4); TOF MS m=z (%): 298.91 [(M þ Na) , 70%],
276.94 [(M þ 1)þ, 100%].

4060
N. C. Ganguly, S. Nayek, and S. K. Barik
ACKNOWLEDGMENTS
S. K. B. thanks the University of Kalyani for financial assistance by way
of a research fellowship. Facilities provided by the Department of Science
and Technology–Funding for Infrastructure in Science and Technology
and the University Grants Commission, Government of India, are also
acknowledged.
REFERENCES
1. (a) Kabalka, G. W.; Pace, R. D.; Wadgaonkar, P. P. The palladium assisted
transfer reduction of a,b-unsaturated nitroalkenes to oximes using ammo-
nium formate. Synth. Commun. 1990, 20, 2453–2458; (b) Larock, R. C.
Comprehensive Organic Transformations; Wiley-VCH: New York, 1999;
p. 1227; (c) Barton, D. H. R.; Beaton, J. M.; Geller, L. E.; Pechet, M. M.
A new photochemical reaction. J. Am. Chem. Soc. 1961, 83, 4076–4083;
ꢀ
(d) Coma, A.; Serna, P.; Garcia, H. Gold catalyst opens a new general che-
moselective route to synthesize oximes by hydrogenation of a,b-unsaturated
nitro compounds with H2. J. Am. Chem. Soc. 2007, 129, 6358–6359.
2. (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 3rd
ed.; John Wiley and Sons: New York, 1997; pp. 355–356; (b) Corsaro, A.;
ꢀ
Chiacchio, U.; Pistara, V. Regeneration of carbonyl compounds from the
corresponding oximes. Synthesis 2001, 1903–1934.
3. (a) DMP: Chaudhuri, S. S.; Akamanchi, K. G. Deoximation using Dess–
Martin periodinane: Regeneration of ketones from ketoximes. Tetrahedron
Lett. 1998, 39, 3209–3212; (b) Oxone: Bose, D. S.; Srinivas, P. Oxidative clea-
vage of oximes with peroxymonosulfate ion. Synth. Commun. 1997, 27, 3835–
3838; (c) (NH4)2S2O8-silica, microwave: Varma, R. S.; Meshram, H. M.
Solid-state deoximation with ammonium persulfate-silica gel: regeneration
of carbonyl compounds using microwaves. Tetrahedron Lett. 1997, 38,
5427–5428; (d) Chloramine T: Gupta, K. P.; Manral, L.; Ganesan, K. An effi-
cient approach for the conversion of oximes into carbonyl compounds using
dichloramine0-T. Synthesis 2007, 1930–1932.
´
´
´
4. (a) Ph3P, 2,2 -dipyridyl diselenide catalyst: Martın, M.; Martınez, G.; Urpı,
F.; Vilarrasa, J. Conversion of ketoximes to ketones with trimethylphosphine
and 2,20-dipyridyldiselenide. Tetrahedron Lett. 2004, 45, 5559–5561; (b) IBX-
b-CD catalyst: Krishnaveni, N. S.; Surendra, K.; Nageshwar, Y. V. D.; Rao,
K. R. Deoximation of oximes with 2-iodylbenzoic acid in water in the pre-
sence of b-cyclodextrin. Synthesis 2003, 1968–1970.
5. I2, H2O-SDS: Gogai, P.; Hazarika, P.; Konwar, D. Surfactant=I2=water: An
efficient system for deprotection of oximes and imines to carbonyls under
neutral conditions in water. J. Org. Chem. 2005, 70, 1934–1936.
6. (a) Yang, Y.; Zhang, D.; Wu, L.-Z.; Chen, B.; Zhang, L.-P.; Tung, C.-H.
Photosensitized oxidative deprotection of oximes to their corresponding
carbonyl compounds by platinum(II) terpyridyl acetylide complex. J. Org.

Convenient, Mild Catalytic Deprotection
4061
Chem. 2004, 69, 4788–4791; (b) Lijser, H. J. P.; Fardoun, F. H.; Sawyer, J. R.;
Quant, M. Photosensitized regeneration of carbonyl compounds from
oximes. Org. Lett. 2002, 4, 2325–2328.
7. Li, D.; Shi, F.; Guo, S.; Deng, Y. One-pot synthesis of silica gel confined
functional liquids: Effective catalyst for deoximation under mild conditions.
Tetrahedron Lett. 2004, 45, 265–268.
8. Ganguly, N. C.; Barik, S. K. A facile catalytic method of deoximation with
potassium bromide and ammonium molybdate in the presence of hydrogen
peroxide in aqueous medium. Synthesis 2008, 425–428 and references cited
therein.
ˇ
9. (a) Zmitek, K.; Zupan, M.; Stavber, S.; Iskra, J. The effect of iodine on the
peroxidation of carbonyl compounds. J. Org. Chem. 2007, 72, 6534–6540; (b)
Jereb, M.; Zupan, M.; Stavber, S. Hydrogen peroxide induced iodine transfer
into alkenes. Green Chem. 2005, 7, 100.
10. Cerritelli, S.; Chiarini, M.; Cerichelli, G.; Capone, M.; Marsili, M. Supramo-
lecular assemblies as promoters of iodohydrin formation. Eur. J. Org. Chem.
2004, 623–630.
11. Kajigaeshi, S.; Kakinama, T.; Yamasaki, H.; Fujisaki, S.; Kondo, M.;
Okamoto, T. Iodination of phenols by use of benzyltrimethylammonium
dichloroiodate. Chem. Lett. 1987, 2109–2112.
12. Oximes were generally prepared in excellent yields from the corresponding
carbonyl compounds by treatment with hydroxylamine hydrochloride (1.2
equiv) and pyridine (2 equiv) in refluxing ethanol. For preparation of Z-ben-
zil monooxime and characterization of carbonyl compounds, see Vogel, A. I.
A Textbook of Practical Organic Chemistry, 3rd ed.; ELBS and Longman
Group: London, 1973. The E=Z isomers of oximes were not separated
unless stated.