A simple reduction of methyl aromatic esters to alcohols using sodium borohydride-methanol system

Article abstract of DOI:10.1016/j.tetlet.2004.06.034

Several aromatic esters were reduced to the corresponding alcohol by using sodium borohydride-methanol system. The reduction was completed within 2.0-4.0h after refluxing in THF. The alcohol products were isolated after aqueous workup in good yields (88-97%).

Full text of DOI:10.1016/j.tetlet.2004.06.034

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 6021–6022
A simple reduction of methyl aromatic esters to alcohols using
sodium borohydride–methanol system
N uꢀ bia Boechat, Jorge Carlos Santos da Costa, Jorge de Souza Mendonßca, Pedro Santos
*
Mello de Oliveira and Marcus Vin ꢀı cius Nora De Souza
FioCruz–Fundaßc ~a o Oswaldo Cruz, Instituto de Tecnologia em F ꢀa rmacos–Far Manguinhos. Rua Sizenando Nabuco, 100,
Manguinhos, 21041-250 Rio de Janeiro-RJ, Brazil
Received 8 December 2003; revised 8 June 2004; accepted 8 June 2004
Available online 24 June 2004
Abstract—Several aromatic esters were reduced to the corresponding alcohol by using sodium borohydride–methanol system. The
reduction was completed within 2.0–4.0 h after refluxing in THF. The alcohol products were isolated after aqueous workup in good
yields (88–97%).
Ó 2004 Elsevier Ltd. All rights reserved.
7
1. Introduction
THF. The respective alcohol products were isolated
after aqueous workup in good yields (88–97%) (see
Table 1). This methodology could also be a good pro-
cedure to employ in an industry process.
Reduction is a fundamental transformation in organic
1
synthesis. Since its discovery by Brown and co-workers,
sodium borohydride is the most frequently hydride used
in reduction process. It is a mild, inexpensive and
invaluable reagent with applications in a wide range of
2
Table 1. Reduction of methyl aromatic esters to alcohols using sodium
functional groups. However, the reduction of ester and
similar functional groups using sodium borohydride is
relatively difficult to obtain and it has not been widely
borohydride–methanol system
OH
CO Me
2
3
used. However, the reactivity of sodium borohydride
can be enhanced by carrying out the reaction in the
R4
R1
R4
R1
4
NaBH4 (6.0 eq.), MeOH (8 mL)
presence of certain additives. For example, addition of
iodine to NaBH in THF provides H B–THF, which is
0
4
3
THF, 70 C
5
R2
R2
useful for hydroborations, reduction of esters and
4
2
.0 - 4.0 h
2 4
various others functional groups. The ZnCl –NaBH
R3
88 - 97%
R3
reagent system exhibits also powerful reducing proper-
ties in the presence of tertiary amine and it is another
Number
Substrate
Time (h) Yield (%)
6
1
2
3
4
example of esters reductions.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
R ¼ R ¼ R ¼ R ¼ H
4.0
2.0
4.0
4.0
4.0
4.0
4.0
2.0
4.0
2.5
2.0
3.5
4.0
3.5
90
97
88
90
88
90
88
96
88
95
93
96
91
90
1
2
3
4
R ¼ Cl, R ¼ R ¼ R ¼ H
R ¼ Br, R ¼ R ¼ R ¼ H
R ¼ F, R ¼ R ¼ R ¼ H
R ¼ R ¼ R ¼ H, R ¼ F
R ¼ R ¼ R ¼ H, R ¼ OMe
R ¼ R ¼ R ¼ H, R ¼ OMe
R ¼ R ¼ R ¼ H, R ¼ Cl
R ¼ R ¼ R ¼ H, R ¼ F
R ¼ R ¼ Cl, R ¼ R ¼ H
R ¼ R ¼ Cl, R ¼ R ¼ H
R ¼ R ¼ F, R ¼ R ¼ H
R ¼ R ¼ Cl, R ¼ R ¼ H
R ¼ Cl, R ¼ R ¼ H, R ¼ F
1
2
3
4
Considering this context, the aim of the present article is
to describe a simple one-pot methyl aromatic esters
reduction into the corresponding alcohol using NaBH –
4
MeOH system. This methodology is simple, safe, inex-
pensive, general and the reduction of methyl aromatic
esters was completed within 2.0–4.0 h after refluxing in
1
2
3
4
1
3
4
2
1
3
4
2
1
2
4
3
1
2
4
3
1
2
4
3
1
2
3
4
0
1
2
3
4
1
3
2
4
1
3
2
4
Keywords: NaBH
4
; Aromatic esters.
1
4
2
4
*
Corresponding author. Tel.: +55-2139772404; fax: +55-2125602518;
e-mail: marcos_souza@far.fiocruz.br
1
2
4
3
0
040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.06.034

6022
N. Boechat et al. / Tetrahedron Letters 45 (2004) 6021–6022
In conclusion, we developed an inexpensive, simple, safe
and general protocol for the one-pot reduction of
aromatic esters to the corresponding alcohols with a
good perspective for industry process.
Guerrier, L.; Royer, J.; Grierson, D.; Husson, H. P.. J. Am.
Chem. Soc. 1983, 105, 7754; (e) Marco, J. L.; Royer, J.;
Husson, H. P.. Synth. Commun. 1987, 17, 669; (f) Banfi, E.
N.; Riva, R. Reagents for Organic Synthesis; Wiley: New
York, 1995.
3
4
5
6
7
. Brown, H. C.; Narasimhan, S.; Choi, Y. M. J. Org. Chem.
1
982, 47, 4702.
. Periasamy, M.; Thirumalaikumar, M. J. Organometal.
Chem. 2000, 609, 137.
Acknowledgements
. Prasad, A. B. S.; Kanth, J. V. B.; Periassamy, M.
Tetrahedron 1992, 48, 4623.
. Yamakawa, T.; Masaki, M.; Nohira, H. Bull. Chem. Soc.
Jpn. 1991, 64, 2730.
We thank the Brazilian Ministry of Education (PIBIC)
for a fellowship (De Oliveira, P. S. M.). We are also
grateful to Solange Wandell for proofreading this
article.
. General Procedure: Finely powdered sodium borohydride
was suspended in THF with the respective ester. The
resulting mixture was stirred for 15 min at 65 °C. Methanol
(
8 mL) was then added dropwise during 0.5 h and efferves-
cence was observed. Stirring at 65 °C was maintained
during a further period of 2–4 h, depending on the ester.
The reaction was cooled to room temperature, and
References and notes
4
quenched with satd aq NH Cl (15 mL). Stirring was then
1
2
. Schlesinger, H. I.; Brown, H. C.; Hoekstra, H. R.; Rapp, L.
R. J. Am. Chem. Soc. 1953, 75, 199.
. (a) Brown, H. C. Boranes in Organic Chemistry; Cornell
University Press: Ithaca, 1972; (b) Brown, H. C.; Krishna-
murthy, R. Tetrahedron 1979, 35, 567; (c) Grilble, G. W.;
Nutaitis, C. F.. Org. Prep. Proc. Int. 1985, 17, 317; (d)
continued for 1.5 h. The organic layer was separated and
the aqueous phase extracted with ethyl acetate (2 ꢀ 20 mL).
The combined extracts and organic phase were dried over
MgSO
spectroscopically pure. All the alcohols were fully charac-
4
and concentrated to give the respective alcohol
1
13
terized by GC–MS, H and C NMR spectra.