Fischer's base as a protecting group: Protection and deprotection of 2- hydroxybenzaldehydes

Article abstract of DOI:10.1016/S0040-4039(00)00516-5

The hydroxyl and aldehyde groups of 2-hydroxybenzaldehydes were protected by the reaction with Fischer's base and deprotected by the ozonolysis in methanol at -78°C to give the corresponding 2- hydroxybenzaldehydes in good to high yields. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00516-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 3915–3917
Fischer’s base† as a protecting group: protection and deprotection
of 2-hydroxybenzaldehydes
Young Jin Cho,a Seung Hwan Lee,a Jong Woo Bae,a Hyung-Jung Pyun b and
Cheol Min Yoon a,∗
aDepartment of Life Science and Biotechnology, Graduate School of Biotechnology, Korea University, Seoul, South Korea
bDepartment of Chemistry, Kwang-Won University, South Korea
Received 18 February 2000; revised 21 March 2000; accepted 24 March 2000
Abstract
The hydroxyl and aldehyde groups of 2-hydroxybenzaldehydes were protected by the reaction with Fischer’s
base and deprotected by the ozonolysis in methanol at −78°C to give the corresponding 2-hydroxybenzaldehydes
in good to high yields. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: 2-hydroxybenzaldehyde; protection; deprotection; Fischer’s base; spiropyran; ozonolysis.
The selective chemical modifications of 2-hydroxybenzaldehydes having other functional groups are
very important, because 2-hydroxybenzaldehydes have been known as good substrates for salen Schiff’s
base derivatives which were useful in various fields.1 However, the selective chemical modification of
2-hydroxybenzaldehydes having hydroxyl and/or aldehyde groups is not easy due to the preexistence of
these functional groups in these molecules. One reported method for the selective functional transforma-
tion of 2,4-dihydroxybenzaldehydes is limited to the alkylation at the 4-hydroxyl group using so called
regioselective modification under basic conditions.2 This selective method is very specific and limited
to the 2,4-dihydroxybenzaldehyde. Therefore, the development of the selective and general protecting
groups for 2-hydroxybenzaldehydes might be very useful.
Here we report an efficient protecting method of 2-hydroxybenzaldehydes 2 using Fischer’s base 1:
the protection and deprotection of the hydroxyl and aldehyde group of 2-hydroxybenzaldehydes is also
reported.
The reaction of 2-hydroxybenzaldehydes 2 with Fischer’s base 1 in ethanol under reflux gave the
corresponding spiropyrans 3 in high yield by the known conditions3 (Scheme 1). The treatment of
4a
4b
spiropyran 3a with reagents such as KMnO4 or NaIO4 gave a 2-hydroxybenzaldehyde 2a in various
solvent systems in low yield (less than 20%) and unidentified side products. However, when spiropyran
∗
†
Corresponding author. E-mail: cmyoon@tiger.korea.ac.kr (C. M. Yoon)
Fischer’s base is available commercially as 2-methylene-1,3,3-trimethylindoline.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00516-5
tetl 16795

3916
3a was treated with ozone at −78°C in methanol, 2-hydroxybenzaldehyde 2a was obtained in 85% yield.5
The results for the protection and the deprotection are shown in Scheme 1.
Scheme 1.
A representative experimental procedure for the deprotection is as follows: Ozone was passed through
a solution of spiropyran 3a (100 mg, 0.248 mmol) in methanol (5 ml), cooled to −78°C for 5 min.
Excess ozone was then purged from the system by bubbling oxygen through the reaction mixture for 10
min, quenched by addition of excess amount of methyl sulfide. The solvent was then removed by the
evaporation under reduced pressure. The concentrate was chromatographed on silica gel column using a
mixture of ethyl acetate and n-hexane (1:30) to give a 2-hydroxyaldehyde 2a.
The chemical transformations of spiropyrans as protected forms followed by the deprotection were
tried (Scheme 2). The formylspiropyran 3c was reduced using sodium borohydride in ethanol at room
temperature to give an alcohol 3e,6 which was treated with ozone in methanol at −78°C to give 2-
hydroxy-5-hydroxymethylbenzaldehyde 2e in 84%. The 6-hydroxyspiropyran 3d was benzylated by the
reaction with benzyl bromide in the presence of potassium carbonate in acetonitrile at reflux to give an
ether 3f in 85% yield7 and acetylated using acetic anhydride in the presence of triethylamine in methylene
chloride at rt to give an ester 3g in 97% yield.8 The ozonolysis of the ether 3f and the ester 3g gave the
corresponding 2-hydroxybenzaldehydes 2f and 2g in 74% and 82% yield, respectively.
Scheme 2. (a) NaBH4 in ethanol at rt, 5 min; (b) benzyl bromide and K2CO3 in acetonitrile at reflux, 3 h /Ac2O and Et3N in
methylene chloride at rt, 30 min; (c) ozonolysis in methanol at −78°C
In conclusion, the hydroxyl and aldehyde group of 2-hydroxybenzaldehydes were protected at the same
time by their reaction with Fischer’s base in ethanol under reflux to give the corresponding spiropyrans,
the protected form of 2-hydroxybenzaldehydes. The spiropyrans were efficiently cleaved by ozonolysis
to give the corresponding 2-hydroxybenzaldehydes in high yields.
Acknowledgements
This work was supported by the Korea Research Foundation made in the year 1998.

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