Bakers' yeast-catalyzed ring opening of benzofuroxans: An efficient green synthesis of aryl-1,2-diamines

Article abstract of DOI:10.1080/00397910802372509

A simple and inexpensive method for the reductive cleavage of N-O bond of benzofuroxans with bakers' yeast under nonfermenting condition in aqueous media was achieved. The procedure gives excellent yields of aryl-1,2-diamines. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802372509

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Bakers' Yeast–Catalyzed Ring
Opening of Benzofuroxans: An
Efficient Green Synthesis of
Aryl-1,2-diamines
Harsha N. Borah a , Dipak Prajapati a & Romesh C.
Boruah a
a Medicinal Chemistry Division , Northeast Institute
of Science and Technology , Jorhat, Assam, India
Published online: 22 Dec 2008.
To cite this article: Harsha N. Borah , Dipak Prajapati & Romesh C. Boruah (2008)
Bakers' Yeast–Catalyzed Ring Opening of Benzofuroxans: An Efficient Green
Synthesis of Aryl-1,2-diamines, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 39:2, 267-272, DOI:
10.1080/00397910802372509
To link to this article: http://dx.doi.org/10.1080/00397910802372509
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Synthetic Communications1, 39: 267–272, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802372509
Bakers’ Yeast–Catalyzed Ring Opening
of Benzofuroxans: An Efficient Green Synthesis
of Aryl-1,2-diamines
Harsha N. Borah, Dipak Prajapati, and Romesh C. Boruah
Medicinal Chemistry Division, Northeast Institute of Science and
Technology, Jorhat, Assam, India
Abstract: A simple and inexpensive method for the reductive cleavage of N–O
bond of benzofuroxans with bakers’ yeast under nonfermenting condition in
aqueous media was achieved. The procedure gives excellent yields of aryl-1,
2-diamines.
Keywords: Aryl-1,2-diamines, bakers’ yeast, benzofuroxans, reductive cleavage
INTRODUCTION
The use of bakers’ yeast (Saccharomyces cerevisiae BY) as a reagent in
synthesis has been applied[1,2] since the beginning of the century, and still
it continues to be of current interest.[3,4] A variety of new and novel appli-
cations of bakers’ yeast have been reported.[5–7] Some examples include
the biooxidative conversion of thio to an oxo functionality,[8] conversion
of aromatic nitro compounds to hydroxylamines,[4] ester hydrolysis, bio-
reduction of PEG-acetoacetate,[7] reduction of aromatic nitro[9–12] com-
pounds, reduction of aryl azides to aryl amines[13] and oximes to chiral
amines,[14] and Hantsch pyridine synthesis,[6] but on the top had been
enantioselective reduction of carbonyl function.[15,16] Bakers’ yeast has
been extensively used to carry out reductions of the aromatic nitro
Received March 13, 2008.
Address correspondence to Dipak Prajapati, Medicinal Chemistry Division,
Northeast Institute of Science and Technology, Jorhat 785 006, India. E-mail:
dr_dprajapati@yahoo.co.uk
267

268
H. N. Borah, D. Prajapati, and R. C. Boruah
Scheme 1. Bakers’ yeast–catalyzed synthesis of 1,3-diamines.
groups, but there has been little work on the application of this reagent to
the reductive cleavage of heterocycles, although they have been employed
for reductive cyclization.[5] Herein we have investigated bakers’ yeast as
a new catalyst for the reductive N–O bond cleavage of benzofuroxans
1, leading to aryl-1,2-diamines 2 under aqueous and nonfermenting
conditions in excellent yields (Scheme 1).
RESULTS AND DISCUSSION
Accordingly, treatment of 5(6)-chloro benzofuroxn 1a with bakers’ yeast
at ambient temperature for 6 h, at pH 7.0 (monitored by thin-layer chro-
matography, TLC), followed by aqueous workup, yielded the correspond-
ing 4-chloro-1,2-phenylenediamine predominantly in 90% yield without
the formation of any side products. Similarly, other 5(6)-bromo and
5(6)-methyl benzofuroxans were reacted in presence of bakers’ yeast at
pH 7.0, and the corresponding 1,2-diamines were isolated in 92 and
80% yields respectively without the formation of any side products.
The 4(7)-nitro and 5(6)-nitro benzofuroxans also gave the corresponding
3-nitro- and 4-nitro-1,2-phenylenediamines respectively in excellent yields
without any further reduction of the nitro group. Further, in reaction
with 4(7)-nitro and 5(6)-nitro benzofuroxans, when we doubled the
amount of yeast, we did not observe the formation of any nitro group
reduced products. Certainly, nitro groups remain intact in the final pro-
ducts, diamines. This finding is in contrast to an earlier report[17] where
bakers’ yeast reduced the nitro group to their corresponding amines. It

Synthesis of Aryl-1,2-diamines
269
is also notable that the halogen-substituted benzofuroxans were rapidly
reduced to give their corresponding 1,2-diamines without any dehaloge-
nation. The common reducing agents were reported to provide dehaloge-
nated side products or recovered starting material.[18–20] It is worth
mentioning here that Easton et al. reported[21] a yeast-catalyzed cleavage
of heterocyclic ring under fermenting conditions (cleavage of either an
aromatic ring or a single bond), where they employed 75 g of sucrose
in 400 ml of water for 0.5 g of the substrate in 24% yield after 24 h of reac-
tion time. Our method is entirely different, and we did not employ any
sucrose solution to get the corresponding 1,2-diamines during 6–6.5 h.
The scope of this general procedure is shown in Table 1. Notably, when
1,4-dinitrosobenzene was reacted under similar conditions, the corres-
ponding 1,4-diaminobenzene (Mp 143–145 ꢀC) was obtained in 90% yield.
Devey et al. have reported the reduction of only one nitro group in the
case of a dinitro compound.[10] Also, the reduction of 2,20-dinitrobiphenyl
using bakers’ yeast–NaOH system yields benzo[c]cinnoline N-oxide and
benzo[c]cinnoline.[16] It must be emphasized here in the present investiga-
tion that we did not observe the formation of any azo or azoxy type of
compounds or any other product, which is the problem with other chemi-
cal methods.[22] Convincingly, the yeast reduction of benzofuroxans is
selective, mild, and most efficient over the existing chemical methods
known.[23,24]
We have developed an efficient metal-free method for the reductive
cleavage of N-O bond of benzofuroxans to afford medicinally impor-
tant building blocks, employing a biocatalyst under nonfermenting and
aqueous conditions that is inexpensive, nontoxic, environment friendly,
Table 1. Bakers’ yeast–catalyzed synthesis of aryl-1,2-diamines 2
Mp (ꢀC)
Reaction
Yielda (%) timeb (h)
Entry Product No. R1
R2 Found
Lit.
1
2
3
4
5
6
2a
2b
2c
2d
2e
2f
H
Cl
Br
CH3
NO2
H
H
H
H
H
H
NO2
103
75
60
89
200
158
103–105[25]
75–76[25]
95
90
92
80
80
80
6.0
6.5
6.5
6.5
6.0
6.0
59–60[25]
89–90[25]
200–201[25]
157–159[25]
aYield refer, to the yield of pure isolated products.
bProducts were identified by the comparision of IR and NMR spectra and
melting points with those of authentic samples.

270
H. N. Borah, D. Prajapati, and R. C. Boruah
and highly selective. It is beneficial that halogen and nitro groups were
not suffered. Also yeast did not require sucrose or glucose in this reac-
tion, resulting in appropriate regulation of the reducing ability of the
yeast. This biotransformation technique will constitute a useful alterna-
tive to the commonly accepted chemical methods (when other sensitive
groups or catalyst poisons are present in the molecule) for the synthesis
of aryl-1,2-diamines.
EXPERIMENTAL
Melting points are determined by using a Buchi melting-point apparatus
and are uncorrected. IR spectra are recorded for KBr discs on a Perkin-
Elmer 240C analyzer. 1H NMR spectra are recorded on 90-MHz spectro-
meters, and chemical shift values are recorded in d units (ppm) relative to
Me4Si as internal standard. The 100-MHz NMR spectra are recorded
with tetramethylsilane as internal standard (by RSIC, Shillong). Mass
spectra are recorded in an AEIMS-30 spectrometer. Elemental analyses
are performed on a Hitachi 026 CHN analyser.
Bakers’ Yeast–Catalyzed Preparation of Aryl-1,2-diamines 2:
General Procedure
To a well-stirred suspension of bakers’ yeast (10 g) in buffer solution, pH
7.0 (30 ml), a solution of benzofuroxan (0.136 g) in methanol (15 ml) was
added. The resulting mixture was kept at room temperature with occa-
sional shaking for 6 h (monitored by TLC). After completion, ethylaceto-
acetate=dichloromethane (40 ml) was added, and the organic layer was
filtered through a Celite pad. The organic layer was then dried over anhy-
drous sodium sulphate and concentrated under reduced pressure. The
residue thus obtained 1,2-phenylenediamine in 95% yield, Mp 103–105ꢀC.
The product gave a single spot on TLC (silica-gel plates with benzene as
mobile phase). Similarly, other substituted benzofuroxans were reacted,
and the corresponding 1-2-diamines were isolated in 80–92% yields
(Table 1). The structure of the products 5 thus obtained were established
by spectroscopic analysis and by comparison with authentic sample pre-
pared by following the literature procedure.[25]
ACKNOWLEDGMENT
We thank the director, Northeast Institute of Science and Technology,
Jorhat, for his keen interest and constant encouragement to perform this
work.

Synthesis of Aryl-1,2-diamines
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