Simple reduction of heteroaromatic esters to alcohols using a sodium borohydride-methanol system

Article abstract of DOI:10.1080/00397910500214482

Some heteroaromatic esters were reduced to the corresponding alcohols by using a sodium borohydride-methanol system. The reduction was completed within 0.15-2.0 h in refluxing THF. The alcohol products were isolated after aqueous workup in moderate to excellent yield (48-97%). Copyright Taylor & Francis, Inc.

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Simple Reduction of Heteroaromatic
Esters to Alcohols Using a Sodium
Borohydride–Methanol System
Núbia Boechat a , Jorge Carlos Santos da Costa a , Jorge de Souza Mendonça
a , Karla Ceodaro Paes a , Elisa Lopes Fernandes a , Pedro Santos Mello de
Oliveira a , Thatyana Rocha Alves Vasconcelos a & Marcus Vinícius Nora de
Souza a
a FioCruz-Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos‐Far
Manguinhos, Manguinhos, Rio de Janeiro, Brazil
Available online: 20 Aug 2006
To cite this article: Núbia Boechat, Jorge Carlos Santos da Costa, Jorge de Souza Mendonça, Karla Ceodaro
Paes, Elisa Lopes Fernandes, Pedro Santos Mello de Oliveira, Thatyana Rocha Alves Vasconcelos & Marcus
Vinícius Nora de Souza (2005): Simple Reduction of Heteroaromatic Esters to Alcohols Using a Sodium
Borohydride–Methanol System, Synthetic Communications: An International Journal for Rapid Communication
of Synthetic Organic Chemistry, 35:24, 3187-3190
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Synthetic Communicationsw, 35: 3187–3190, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500214482
Simple Reduction of Heteroaromatic
Esters to Alcohols Using a Sodium
Borohydride–Methanol System
´
Nubia Boechat, Jorge Carlos Santos da Costa,
Jorge de Souza Mendonc¸a, Karla Ceodaro Paes,
Elisa Lopes Fernandes, Pedro Santos Mello de Oliveira,
Thatyana Rocha Alves Vasconcelos, and
´
Marcus Vinıcius Nora de Souza
FioCruz-Fundac¸a˜o Oswaldo Cruz, Instituto de Tecnologia em
´
Farmacos-Far Manguinhos, Manguinhos, Rio de Janeiro, Brazil
Abstract: Some heteroaromatic esters were reduced to the corresponding alcohols by
using a sodium borohydride–methanol system. The reduction was completed within
0.15–2.0 h in refluxing THF. The alcohol products were isolated after aqueous
workup in moderate to excellent yield (48–97%).
Keywords: Heteroaromatic esters, sodium borohydride–methanol, reduction
INTRODUCTION
Reduction is a fundamental transformation in organic synthesis and numerous
reagents have been reported. One common reduction reagent used in organic
chemistry is sodium borohydride, discovery by Brown, Schlesinger, and
coworkers.[1] The reduction using this reagent employes mild reaction con-
ditions, is inexpensive and safe, and gives good yields. It can be applied to
a wide range of functional groups.[2–4] However, this methodology has not
Received in the USA May 18, 2005
Address correspondence to Marcus Vinıcius Nora de Souza, FioCruz-Fundac¸a˜o
´
´
Oswaldo Cruz, Instituto de Tecnologia em Farmacos-Far Manguinhos, Rua
Sizenando Nabuco, 100, Manguinhos, 21041-250 Rio de Janeiro, Brazil. E-mail:
marcos_souza@far.fiocruz.br
3187

3188
N. Boechat et al.
been widely applied to specific cases of esters and similar groups that are not
easily reduced.[5,6] Nevertheless, the reactivity of sodium borohydride can be
enhanced by carrying out the reaction in the presence of certain additives.[7]
For example, addition of iodine to NaBH4 in THF provides H3B–THF,
which is useful for hydroborations, reduction of esters and various others func-
tional groups.[8] Another example is the ZrCl4–NaBH4 reagent system, which
reduces both aliphatic and aromatic carboxylic acids to the corresponding
alcohols under mild conditions.[7]
In this context, the present article describes a simple one-pot reduction of
heteroaromatic esters into the corresponding alcohol using a NaBH4-MeOH
system. In our group, this methodology has already been applied successfully
to methyl aromatic esters.[9] The general procedure presented is simple, safe,
and inexpensive, and the reduction of different heteroaromatic esters was
completed within 0.15–2.0 h in refluxing THF. The respective alcohol
products were isolated after aqueous workup in moderate to excellent yield
(48–97%) (Table 1).
In conclusion, we have developed an inexpensive, simple, safe and
general protocol for the one-pot reduction of heteroaromatic esters to the
corresponding alcohols.
EXPERIMENTAL
Materials and Methods
Mass spectra (CG/MS) were recorded on a Agilent Technologies 6890/
5972A mass spectrometer using a fused capillary column (30.0 m, 250 mm
i.d., and film thickness of 0.25 mm) with polyphenylmethylsiloxane
(HP5MS) as the stationary phase. Helium was employed as the carrier gas.
NMR spectra were recorded on a Bruker Avance 500 spectrometer
operating at 500.00 MHz (1H) and 125.0 MHz (13C), in deuterated chloroform.
Chemical shifts are reported in ppm (d) relative to tetramethylsilane. Proton
and carbon spectra were typically obtained at room temperature. TLC plates
coated with silica gel were run in an ethyl acetate/hexane mixture and
spots were developed in ultraviolet and alcoholic phosphomolibdic acid
solution 7% p/v.
General Procedure
Finely powdered sodium borohydride (6 eq., 24–30 mmol) was suspended in
THF (40 mL) with the respective ester (1 g, 4–5 mmol). The resulting mixture
was stirred for 15 min at 708C. Methanol (8 ml) was then added dropwise
during 15 min and effervescence was observed. Stirring at 708C was main-
tained during a period of 0.5–2 h, depending on the ester. The reaction was

Heteroaromatic Esters to Alcohols
3189
Table 1. Reduction of heteroaromatic esters to alcohols using the sodium
borohydride–methanol system
Time
(h)
Yield
(%)
CGMS
(%)a
Number
Substrate
Product
a 0.15
b 0.15
c 0.15
93
91
88
97
97
95
1a–c
2
1.0
52
92
3
1.0
82
90
a 1.0
b 1.0
c 1.0
93
94
85
98
93
95
4a–c
5
2.0
48
86
a 0.15
b 0.15
c 0.15
97
94
68
99
99
97
6a–c
7
2.0
56
85
a ¼ CH3, b ¼ –CH2CH3, c ¼ –CH(CH3)2.
aDetermined by area normalization.
cooled to room temperature, and quenched with satd. aq. NH4Cl (15 mL).
Stirring was continued for 1.5 h. The organic layer was separated and the
aqueous phase extracted with ethyl acetate (2 Â 20 mL). The combined
extracts and organic phase were dried over MgSO4 and concentrated to give
the respective spectroscopically pure alcohol. All the alcohols were fully
1
characterized by MS and H and 13C NMR spectra and are known in the
literature 2, 3, 6, 7,[10] 1,[11] 4,[12] and 5.[13]
ACKNOWLEDGMENT
We thank the Brazilian Ministry of Education CNPq.

3190
N. Boechat et al.
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