Deprotection of ketone dimethylhydrazones using lipases

Article abstract of DOI:10.1016/S0040-4039(99)02318-7

Deprotection of ketone dimethylhydrazone compounds with porcine pancreatic lipase (PPL) as a biocatalyst is described. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(99)02318-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 1461–1463
Deprotection of ketone dimethylhydrazones using lipases
Takashi Mino,a,∗ Terumi Matsuda,b Dai Hiramatsu b and Masakazu Yamashita b
aDepartment of Materials Technology, Faculty of Engineering, Chiba University, Inage-ku, Chiba 263-8522, Japan
bDepartment of Molecular Science and Technology, Faculty of Engineering, Doshisha University, Kyotanabe,
Kyoto 610-0394, Japan
Received 21 October 1999; revised 8 December 1999; accepted 10 December 1999
Abstract
Deprotection of ketone dimethylhydrazone compounds with porcine pancreatic lipase (PPL) as a biocatalyst is
described. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: hydrazones; hydrazines; ketones; enzymes; hydrolysis.
Hydrazones have been found to be one of the most useful synthetic precursors of aldehydes and
ketones.1 In this method, the key point is the deprotection of hydrazones2 to their corresponding carbonyl
compounds. Recently, the bi-catalyzed,3 oxalic acid,4 and TMSCl/NaI methods5 have been reported.
We have also previously reported the CuCl2-catalyzed6 and Pd(OAc)2-catalyzed methods.7 Kamal has
reported hydrazone hydrolysis by using baker’s yeast as a biocatalyst.8 However, this method requires a
large amount of baker’s yeast compared to that of dimethylhydrazone.
On the other hand, lipases have been widely used over the past decade as a routine reagent for the
preparation of chiral synthons and optically active natural products in organic synthesis.9
We describe here the lipase-catalyzed deprotection of ketone dimethylhydrazones to their corres-
ponding ketones. This reaction is promoted by using lipases such as porcine pancreatic lipase, lipase
from Rhizopus arrhizus, Rhizopus niveus, and Mucor javanicus. We used a catalytic amount of porcine
pancreatic lipase (PPL) (Scheme 1) because PPL is the most economic of these lipases.
Scheme 1.
Table 1 shows representative results of the cleavage of ketone dimethylhydrazones. When the depro-
tection of aliphatic and alicyclic ketone dimethylhydrazones was carried out in the presence of PPL in
∗
Corresponding authors. Tel: +81 43 290 3385; fax: +81 43 290 3401; e-mail: tmino@planet.tc.chiba-u.ac.jp (T. Mino)
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02318-7
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acetone/H2O at room temperature, the corresponding deprotected compounds were obtained in good
yields (Entries 1–4). However, menthone dimethylhydrazone (1e), which has bulky functional groups,
such as iso-propyl at α-position, was used, and menthone was obtained in only an 11% yield (Entry 5).
On the other hand, aromatic ketone dimethylhydrazones such as acetophenone dimethylhydrazone (1f)
and others were hydrolyzed slowly (Entries 6–12).
Table 1
Deprotection of dimethylhydrazone 1
In conclusion, the deprotection of hydrazone compounds was smoothly promoted using a porcine
pancreatic lipase (PPL) in an acetone/H2O system at room temperature and the reactivities depended on
the substrate structures.

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1. Typical procedure of deprotection
A solution of ketone dimethylhydrazone10 (0.5 mmol) in acetone (3 mL) was added to a suspension
of PPL (50 mg) in H2O (5 mL). The reaction mixture was stirred at room temperature for 24 h, and then
diluted with ether, washed with brine, and dried over MgSO4. The evaporation of the solvent and the bulb-
to-bulb distillation or silica gel column chromatography gave pure corresponding carbonyl compounds.11
The yields were determined by GLC using biphenyl as an internal standard.
References
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1991; Vol. 2, pp. 503–526, and references cited therein.
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(b) Kocienski, P. J. Protecting Groups; Thieme: Stuttgart, 1994.
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7. (a) Mino, T.; Hirota, T.; Yamashita, M. Synlett 1996, 999–1000. (b) Mino, T.; Hirota, T.; Fujita, N.; Yamashita, M. Synthesis
1999, 2024–2026.
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1
11. The carbonyl compounds were identified by comparing the retention time of GLC with those of authentic samples or H
NMR (400 MHz) and GC–MS.