Novel chemoselective reduction of aryldiazonium fluoroborates with Zn- NiCl2·6H2O-THF

Article abstract of DOI:10.1039/a905588f

Substituted aryldiazonium fluoroborates are selectively reduced to the corresponding phenylhydrazines by using Zn-NiCl₂·6H₂O in THF as a reducing agent.

Full text of DOI:10.1039/a905588f

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714 J. CHEM. RESEARCH (S), 1999
J. Chem. Research (S),
1999, 714^715y
Novel Chemoselective Reduction of
Aryldiazonium Fluoroborates with
Zn^NiCl2 6H2O^THF
B. P. Bandgar* and L. S. Uppalla
School of Chemical Sciences, Swami Ramanand Teerth Marathwada University, Vishnupuri,
Nanded-431 606, Maharashtra, India
Substituted aryldiazonium fluoroborates are selectively reduced to the corresponding phenylhydrazines by using
Zn^NiCl2 6H2O in THF as a reducing agent.
Substituted phenylhydrazines are important for the syn-
thesis of diphenylcarbazones which are used as analytical
reagents1 and antibacterial agents against mycobacterium
tuberculosis.2 Recently diphenylcarbazones have been used
for in vitro study of human cell lines derived from nine types
of cancer : leukemia, lung cancer, colon cancer, CNS cancer,
melanoma, ovarian cancer, renal cancer, prostate cancer
and breast cancer.3 The Fischer indolization between sub-
stituted phenylhydrazines and appropriate carbonyl com-
pounds4 has been used for the synthesis of 1,8-diethyl-
1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid (Etodolac)
and similar derivatives which are important non-steroidal
analgesic and anti-in£ammatory drugs.5 Phenylhydrazines
have commonly been prepared by reduction of diazonium
salts with an excess of SnCl2 in the presence of hydrochloric
acid. However, this is not a selective method because other
labile substituents also undergo simultaneous reduction.
Recently reduction of substituted aryldiazonium £uoro-
borates to the corresponding phenylhydrazines has been
carried out using borohydride exchange resin (BER) in
methanol.6 However, the long reaction time (6 h) required
to prepare BER using an excess of the expensive NaBH4
is a signi¢cant drawback of this methodology.
9 and 10). Furthermore, haloaryldiazonium £uoroborates
showed remarkable selectivity to give the
halophenylhydrazines without any dehalogenation (entries
2^7). In addition, it was worth commenting that
4-acetylphenyldiazonium £uoroborate was converted to
the 4-acetylphenylhydrazine and the sensitive carbonyl
group remains intact (entry 11).
Table
1 Chemoselective reduction of aryldiazonium fluoro-
borates by using Zn^NiCl2 6H2O^THF
Mp/Bp (Torr)
[lit.]7 / ˚C
Yieldb (%)
Producta
Entry Diazonium fluoroborate
+
–
N2BF4
NHNH2
1
2
80
75
242 (760)
[243 (760)]
+
–
N2BF4
NHNH2
201c
[200–203]
Cl
+
N2BF4
Cl
–
NHNH2
3
78
236c
[236]
Cl
Cl
+
Herein, we report a novel and inexpensive reduction sys-
tem consisting of zinc^nickel chloride hexahydrate in
tetrahydrofuran for the chemoselective reduction of various
substituted aryldiazonium £uoroborates to the correspond-
ing phenylhydrazines (Scheme 1). The reductions generally
proceeded with high yields under mild conditions (0 8C)
and showed selectivity over other labile substituents.
–
N2BF4
NHNH2
4
5
6
82
72
71
236c
[200–205]
F
F
+
–
N2BF4
NHNH2
265c
[268]
F
F
+
–
N2BF4
NHNH2
206c
[209]
+
–
Br
Br
Br
Br
N2BF4
NHNH2
+
–
Zn–NiCl2•6H2O
THF, 0 ˚C
N2BF4
NHNH2
Br
Br
X
X
7
70
146
[146]
X = F, Cl, Br, MeO, NO 2, COMe
Br
Br
+
–
N2BF4
NHNH2
NHNH2
Scheme 1
8
9
85
75
161c
[160–162]
MeO
MeO
+
The high yields of the reduction products demonstrates
the e¤ciency of this new method. Table 1 summarizes
our results on reduction of substituted aryldiazonium
£uoroborates. In all the reductions, aryldiazonium £uoro-
borates are reduced to the corresponding arylhydrazines
and not to the hydrocarbons. At the same time,
aryldiazonium £uoroborates are selectively reduced in the
presence of an aromatic methoxy group (entry 8). For
nitro-substituted aryldiazonium £uoroborates, the corre-
sponding nitrophenylhydrazines were selectively obtained
without any further reduction of the nitro group (entries
–
N2BF4
195c
[195–197]
NO2
NO2
+
–
N2BF4
NHNH2
NHNH2
10
11
90
70
156
[156]
O2N
O2N
+
–
N2BF4
184
(760)
[—]
MeOC
MeOC
* To receive any correspondence.
aProducts were characterised by their physical constants, spectral
characteristics (IR, 1H NMR) and comparison with authentic
samples. bYields are of pure isolated products. cAs hydrochloride
salt.
This is a Short Paper as de¢ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1999, Issue 1]; there is
therefore no corresponding material in J. Chem. Research (M).

View Article Online
J. CHEM. RESEARCH (S), 1999 715
In conclusion, the present results demonstrate the novelty
of zinc^nickel chloride hexahydrate^THF combination sys-
tem which shows unique selectivity and constitutes a useful
alternative to the commonly accepted procedure for the syn-
thesis of various arylhydrazines. Moreover, this simple and
easily reducible technique a¡ords products in excellent
yields without involvement of expensive materials and
without formation of any undesirable side-products of
the classical methods.
Received, 12th July 1999; Accepted, 27th August 1999
Paper E/9/05588F
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Experimental
All chemicals were of analytical grade. The solvents were freshly
distilled before use. Commercially available zinc powder and nickel
chloride hexahydrate were used as received. All aryldiazonium
£uoroborates were prepared by using standard synthetic methods.8
General Procedure for Chemoselective Reduction of Substituted
Aryldiazonium Fluoroborates.öA mixture of zinc powder (2 mmol)
and nickel chloride hexahydrate (3 mmol) and aryldiazonium
£uoroborate (2 mmol) in tetrahydrofuran (10 ml) at 0 8C was stirred.
A vigorous exothermic reaction takes place immediately which is
controlled by keeping the reaction mixture in an ice-bath. After
completion of the reaction, THF was removed under vacuum and the
product was extracted with diethyl ether (3 Â 10 ml). The ether layer
was dried with anhydrous sodium sulfate and removal of the solvent
under reduced pressure affords the arylhydrazine in almost pure
form; further puri®cation, if required, can be performed by
chromatography.
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8