N-chloro-3-methyl-2,6-diphenylpiperidin-4-one (NCP) - An efficient, mild, stable oxidant for cleavage of carbon-nitrogen double bonds of oximes

Article abstract of DOI:10.1081/SCC-120022470

Aldoximes and ketoximes are effectively deoximated to regenerate the carbonyl compound by an efficient, mild, stable oxidant N-chloro-3-methyl-2,6-diphenylpiperidin-4-one (NCP).

Full text of DOI:10.1081/SCC-120022470

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 17, pp. 2979–2984, 2003
N-Chloro-3-methyl-2,6-diphenylpiperidin-
4-one (NCP) – An Efficient, Mild, Stable
Oxidant for Cleavage of Carbon-Nitrogen
Double Bonds of Oximes
*
S. Balasubramanian, C. Ramalingan, and S. Kabilan
Department of Chemistry, Annamalai University,
Annamalainagar, India
ABSTRACT
Aldoximes and ketoximes are effectively deoximated to regenerate
the carbonyl compound by an efficient, mild, stable oxidant
N-chloro-3-methyl-2,6-diphenylpiperidin-4-one (NCP).
Key Words: Piperidin-4-one; Oxidant; Oxime; Deoximation.
Oximes are important precursors in organic synthesis because of their
use in protection of carbonyl compounds.[1] Regeneration of carbonyl
compounds from stable and readily prepared aldoximes and ketoximes
*Correspondence: S. Kabilan, Department of Chemistry, Annamalai University,
Annamalainagar, 608 002, India; E-mail: kabilan@satyam.net.in.
2979
DOI: 10.1081/SCC-120022470
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
2980
Balasubramanian, Ramalingan, and Kabilan
under mild condition is an important process in synthetic organic chem-
istry. There are several methods for regeneration of carbonyl compounds
from oximes, such as manganese triacetate,[2] dinitrogentetroxide,[3]
titanium silicate,[4] ammonium persulfate–silicagel,[5] tetrabutyl ammo-
nium persulfate,[6] zirconium sulfophenyl phosphonate,[7] zinc
bismuthate,[8] sodium perborate,[9] iodine,[10] sodium periodate,[11]
Dess–Martin periodinane,[12] raney nickel,[13] chromiumtrioxide–silica-
gel–microwave,[14] ferric chloride–silicagel,[15] bismuth trichloride,[16]
trimethylsilylchlorochromate,[17] triethylammonium chlorochromate,[18]
pyridinium chlorochromate–microwave,[19] methylammonium chloro-
chromate–alumina[20] and halochromates prepared from quinoline,[21]
2,20 bipyridine,[22] imidazole,[23] and 1-methyl imidazole.[24]
Howevermany of these methods do not describe the deoximation of
aldoximes orgive low yields orthe liberated aldehydes are overoxidized.
Moreover, the reagents used are often hazardous or toxic and having
expensive transition metals. In some cases the reagents need to be freshly
prepared or the reactions require anaerobic conditions and long reaction
times. Some of the reported reagents suffer from instability, hygroscopi-
city, low selectivity, and need for a large excess of the reagent. Thus there
is still demand for development of a facile and new procedure,
which works under milder condition for the regeneration of the carbonyl
compounds from oximes. These observations prompted us to investigate
further new methodology for the deprotection of oximes using an
efficient, mild, and stable reagent, which lead to high recoveries of
carbonyl compounds. Herein we report the deoximation of aldoximes
and ketoximes with the use of N-chloro-3-methyl-2,6-diphenylpiperidin-
4-one (NCP) (Scheme 1).
NCP is a stable crystalline solid. Its alcoholic solution can be kept
well for a long time. It is moderately soluble in ethanol–water mixture.
It liberates iodine quantitatively from slightly acidified iodide ion solu-
Scheme 1.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
N-Chloro-3-methyl-2,6-diphenylpiperidin-4-one (NCP)
2981
tion instantaneously (even at a very low concentration). Kinetics and
mechanistic aspects of deoximation of benzophenone oximes,[25] cyclo-
hexanone oximes[26] and oxidation of allyl alcohol to acrolein[27] by NCP
have been reported only from our laboratory.
The optimum ratio of the substrate to the reagent for deoximation is
found to be 1:1 (mole/mole). The reaction remains incomplete if lower
amounts of the reagent are used. It is note worthy that unlike other
oxidative hydrolytic methods, the major draw back of over oxidation
of the ensuing aldehydes is not observed under the reaction conditions.
Interestingly a,b-unsaturated oxime underwent deoximation very
efficiently without affecting the C¼C bond and the reaction is essentially
chemo selective.
NCP brings about the oxidative deoximation of aldoximes and
ketoximes to the corresponding carbonyl compounds in high yields and
the results are summarized in Table 1. All resulting carbonyl compounds
are known compounds. They are identified by comparison of their
physical data and NMR spectra with those of authentic samples and
they are superimposable.
All resulting carbonyl compounds were also confirmed by superim-
[28]
position of theirIR spectar with that of authentic samples.
The
melting point of their mixture with respective authentic sample was not
depressed.
At the end of the deoximation, NCP is converted into 3-methyl-2,6-
diphenylpiperidin-4-one (I) as shown in Scheme 1. Alcoholic solution of
NCP and oxime are kept with small amount of perchloric acid and
sodium chloride in water for one day. After that, the reaction mixture
was transferred to a china dish and allowed to evaporate. The solid
that was thrown out was collected and washed well with water. After
recrystallization from ethanol–water mixture, it melted at 225ꢀC. The
melting point of its mixture with an authentic sample of 3-methyl-2,6-
diphenylpiperidin-4-one[29] was not depressed. Hence the formation of
3-methyl-2,6-dipenylpiperidin-4-one during the reaction was confirmed.
A summary of the result show that NCP is a convenient reagent
for the oxidation of oximes to their parent carbonyl compounds with
advantages of easy work-up and high yield.
EXPERIMENTAL
The aldehydes and ketones were of extra pure quality (E. Merck,
Aldrich & Fluka) and were used without further purification. Oximes
were prepared by the standard synthetic procedures. Melting points

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
2982
Balasubramanian, Ramalingan, and Kabilan
Table 1. Oxidative cleavage of carbon-nitrogen double bonds with NCP.
Entry
R1
R2
Solvent
Time (h)
Yielda (%)
1
2
Ph
H
H
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CH2Cl2
CH2Cl2
2.5
3.0
2.5
2.0
2.5
2.0
2.5
4.0
1.5
2.0
2.5
3.0
2.5
2.0
2.0
2.5
3.0
3.5
2.5
2.5
3.0
3.0
2.5
4.0
2.5
84
79
83
87
85
83
78
64
86
95
88
84
80
68
90
86
72
70
84
80
72
76
79
51
72
2-NO2 Ph
4-NO2 Ph
4-CH3 Ph
4-CH3O Ph
4-Cl Ph
3
H
4
H
5
H
6
H
7
2,4-(CH3)2 Ph
Furfuryl
H
8
H
9
Ph-CH¼CH-
Ph
H
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
CH3
CH3
CH3
CH3
C2H5
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
3-NO2 Ph
4-Cl Ph
4-BrPh
C2H5
Ph
4-OCH3 Ph
4-CH3 Ph
4-C2H5 Ph
4-Cl Ph
4-I Ph
4-NO2 Ph
4-COOH Ph
4-CN Ph
R1, R2 ¼ -(CH2)4-
R1, R2 ¼ -(CH2)5-
aYield of isolated pure carbonyl compound.
were determined in open capillaries. Reported melting and boiling points
are uncorrected. IR spectra were recorded on Perkin-Elmer 237B grating
spectrophotometer and 1H NMR spectra on DPX 200 MHz spectrophoto-
meter with TMS as the internal standard. TLC were performed on silica
gel (E. Merck) and the plates were activated at 100ꢀC for1 h before use.
N-Chloro-3-methyl-2,6-diphenylpiperidin-4-one (NCP)
3-Methyl-2,6-diphenylpiperidin-4-one hydrochloride[29] (10 g) was
dissolved in 200 mL of 50–60% ethanol–watermixture (v/v) by warming.
Through the solution free chlorine gas was passed gently for about

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
N-Chloro-3-methyl-2,6-diphenylpiperidin-4-one (NCP)
2983
30 min, excess water was added to precipitate the NCP. It was filtered and
washed well with water. After repeated crystallization from ethanol, the
compound melted at 144–146ꢀC (found: C, 72.25; H, 6.27. C18H18ClNO
1
requires C, 72.12; H, 6.01%) H NMR (ꢀ ppm) 7.4 (m, 10H, Phenyl
protons) 4.3 (q, 1H, C6-benzylic proton) 3.5 (q, 1H, C5-axial methylene
proton) 3.2 (q, 1H, C5-equatorial methylene proton) 0.9 (d, 3H, C3-
methyl protons).
Deoximation of Oximes to Carbonyl Compounds:
General Procedure
To a solution of 0.1 M oxime in ethanol, 0.1 M NCP in ethanol is
added. To this mixture, 12 mL of 0.05 N perchloric acid in 3:1 v/v etha-
nol–water is added. The entire mixture is stirred under warm to the time
as indicated in Table 1. The progress of the reaction was monitored by
TLC. After the completion of the reaction, the reaction mixture is
extracted with suitable solvent (CH2Cl2 orCHCl 3). The solvent was
removed under reduced pressure after drying over anhydrous NaSO4.
The residue (on purification by column chromatography on silicagel)
or the liquid (upon distillation) gave the corresponding carbonyl com-
pound and there was no evidence for the formation of side products.
Mixed melting point orboiling point with authentic sample did not
show depression. It may be noted that in the cases of aldehydes, the
crude product is filtered through a small bed of neutral alumina with
dichloromethane.
REFERENCES
1. Green, T.W.; Wuts, P.G.M. Protective Groups in Organic Synthesis,
Wiley : New York, 1991, 214.
2. Ayhan, S.D.; Cihangir, T.; Ertan, A. Tetrahedron Lett. 1997, 38, 7267.
3. Shim, S.B.; Kim, K.; Kim, Y.H. Tetrahedron Lett. 1987, 28, 645.
4. Joseph, R.; Sudalai, A.; Ravindranathan, Y. Tetrahedron Lett. 1994,
35, 5493.
5. Varma, R.S.; Meshram, H.M. Tetrahedron Lett. 1997, 38, 5427.
6. Chen, F.; Lin, A.; Yan, Q. Synthetic Commun. 1999, 29, 1049.
7. Curini, M.; Rosati, O.; Pisani, E.; Costantino, U. Synlett. 1996, 333.
8. Firouzabadi, H.; Mohammadpour-Baltork, I. Synthetic Commun.
1994, 24, 489.
9. Bandgar, B.P.; Shaikh, S.I.; Iyer, S. Synthetic Commun. 1996, 26,
1163.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
2984
Balasubramanian, Ramalingan, and Kabilan
10. Yadav, J.S.; Sasmal, P.K.; Chand, P.K. Synthetic Commun. 1999,
29, 3667.
11. Varma, R.S.; Dahiya, R.; Saini, R.K. Tetrahedron Lett. 1997, 38,
8819.
12. Bose, D.S.; Narsaiah, A.V.; Synthetic Commun. 1999, 29, 937;
Chaudhari, S.S.; Akamanchi, K.G. Synthesis. 1999, 760.
13. Curran, D.P.; Brill, J.F.; Rakiewicz, D.M. J. Org. Chem. 1984, 49,
1654.
14. Bevidale, P.M.; Khadilkar, B.M. Tetrahedron Lett. 1998, 39, 5867.
15. Bose, D.S.; Narsaiah, A.V.; Goud, P.R. Indian J. Chem. 2001,
40B, 719.
16. Boruah, A.; Baruah, B.; Prajapati, D.; Sandhu, J.S. Tetrahedron
Lett. 1997, 38, 4267.
17. Aizpurua, J.M.; Juaristi, M.; Lecea, B.; Palomo, C. Tetrahedron
1987, 41, 2903.
18. Rao, C.; Radhakrishna, A.S.; Singh, B.B.; Bhatnagar, S.P.
Synthesis. 1983, 808.
19. Chakraborthy, V.; Bardoloi, M. J. Chem. Res (S). 1999, 120.
20. Gui-Sheng, Z.; De-Hang, D.; Mi-Feng, C.; Kun, C. Synthetic
Commun. 1998, 28, 2221.
21. Abraham Rajkumar, G., Banumathi Arabindoo; Murugesan, V.
Indian J. Chem. 2000, 39B, 74.
22. Guziec (Jr), F.S.; Zuzzio, F.A. Synthesis. 1980, 691.
23. Agarwal, S.; Tiwari, H.P.; Sharma, J.P. Tetrahedron 1990, 46, 1963.
24. Agarwal, S.; Tiwari, H.P.; Sharma, J.P. J. Heterocyclic Chem. 1992,
29, 257.
25. Kabilan, S.; Vasanthi, G.; Suganya, K.; Palanivel, C. Oxidation
Commun. 2000, 23(4), 524.
26. Ganapathy, K.; Kumarachakravarthy, T.; Vijayan, B. Indian J.
Chem. 1980, 19B, 76.
27. Ganapathy, K.; Vijayan, B. J. Indian Chem. Soc. 1978, 55, 957.
28. Buckingham, J.; Donaghy, S.M.; Codogan, J.I.G.; Raphael, R.A.;
Rees, C.W. Dictionary of Organic Compounds, 5th Ed.; Eds.;
Chapman and Hall: New York, 1982; Aldrich Library of IR Spectra,
2nd Ed.; Jones, R.N.; Forbes, W.F.; Mueller, W.A. Can. J. Chem.
1957, 35, 504; Brown, H.C.; Okamoto,Y. J. Am. Chem. Soc. 1958, 80,
4979; Fuson, N.; Josien, M.L.; Shelton, E.M. J. Am. Chem. Soc. 1954,
76, 2526; Vasanthi, G. M. Phil Thesis, Annamalai University, 1987.
29. Noller, C.R.; Baliah, V. J. Am. Chem. Soc. 1948, 70, 3853.
Received in the UK September9, 2002

Copyright of Synthetic Communications is the property of Taylor & Francis Ltd and its content may not be
copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written
permission. However, users may print, download, or email articles for individual use.