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CHAPTER 2
Reduction of Nitro Compounds
Rapid and selective reduction of nitro compounds is of importance for the
preparation of amino derivatives in the organic synthesis both practically and
industrially, particularly when a molecule has other reducible moieties.28'i39-i42
The synthesis and biological evaluation of amines and their derivatives
constitute one of the active and most important areas of research.*^'^^
Numerous new reagents have been developed for the reduction of nitro
compounds. *5-i5o Most of the methods, viz., metal/acid reduction,i5i catalytic
hydrogenation,i52 electrolytic reduction,i53 homogeneous catalytic transfer
hydrogenation,i54 heterogeneous catalytic transfer hydrogenation^ss etc., are in
practice. However, these methods have one or more limitations:
1) Metal/acid system lacks selectivity and it needs strong acid medium.
2) Catalytic hydrogenation employs highly diffusible, low molecular
weight, flammable hydrogen gas and vacuum pump to create high
pressure within reaction flask.
3) Electrolytic reduction requires acidic or alkaline catholite; yields are
low and lack practical utility in academic institutions.
4) Homogeneous catalytic transfer hydrogenation requires expensive
complexes as catalysts; work up and isolation of the products are not
easy.
5) Heterogeneous catalytic transfer hydrogenation employs expensive
bulk or supported metals like palladium, platinum, ruthenium,
Raney nickel etc. The supported catalysts require stringent
precautions, because of their flammable nature in the presence of air.
55
Reduction of Nitro Compounds Chapter 2
Recently, metal mediated reactions have been foimd to have wide scope in
organic synthesis, because of their simple work-up and selectivity. Several
methods have been developed based on the use of a variety of metals such as
magnesium,i56 indium,i57,i58 tin,i59 zinc. ^" Magnesium is a powerful reducing
agent; it is used in the preparation of Grignard reagents^^i and for reduction of
various alkyl and aryl halides in protic solvents^^^ ^ also readily reduces
conjugated double bonds of esterS/i^nitriles^^ and amides,i*5,i66 as well as a, p-
acetylenic esters and triple bonds conjugated to two aromatic rings. ^^ Under
the same conditions, unactivated double and triple bonds are reduced in the
presence of Pd-C,^^ while desulfonation was also effected with magnesium in
methanol.!*' In aprotic solvents magnesium effects pinacol reductive coupling
of aldehydes and ketones.*^" In our earlier investigations, we had reported the
utility of magnesium^!* for deblocking of some commonly used protecting
groups in peptide synthesis and the utility of zinc for the synthesis of p-y
unsaturated ketones by a reaction of an acid chloride with allyl bromide^^ and
homoallylic alcohols^^^ has been demonstrated. Further, the zinc mediated
preparation of triphenyl phosphonium ylides,!^^ Friedel-Crafts acylation,!^*
carbamates formation!^ and zinc^ for the reductive cleavage of azo
compounds to corresponding amine/s has been demonstrated.
In this context, we have established two methods of reducing nitro compounds
to corresponding amines, which involve the use of cheaper metals. Magnesium
powder has been used with ammoniuni formate and Zinc dust is used with
Polymer supported formate (PSF). These systems are cost effective and chemo-
selective.
2.1: Magnesiuir/Ammonium Formate Promoted Rapid, Low-Cost and
Selective Reduction of Nitro Compounds.
The application of ammonium formate in the field of catalytic transfer
hydrogenation for the reduction of variety of organic compounds and the
synthesis of peptide has been reviewed. ^^^^^ The application of catalytic
56
Reduction of Nitro Compounds Chapter 2
transfer hydrogenation for reduction and reductive cleavage of organic
compounds and in peptide synthesis is mainly centered on the use of expensive
catalysts like Pd-Q Ru-Ca, Pt-Q Pt02, Pd-CaCOs, Ru-C and Raney Ni.io5,i55,i76
Some systems like HC02NH4/Pd-C,29'i78 HC02NH4/Pt-C,« HCO2NH4/
Raney-Ni,^ BioHi2/Pd-C,^o triethylammonium formate/Pd-C32 and
cyclohexene/Pd-O^' have been developed for the reduction of nitro
compounds to the corresponding amines. These systems require longer
reaction time at reflux and expensive catalysts like Pd-C, Pt-C and Raney-Ni.
These catalysts are flammable nature in the presence of air and presents
considerable hazards during handling. In addition to above mentioned
limitations, most of these methods are unfortunately subject to substantial
limitations as concerns the reducible functionalities and lack therefore desired
generality for the true synthetic utility. Moreover, poor selectivity was reported
in the reduction of aromatic nitro compounds, which have halogen, nitrile,
carboxyl, hydroxyl etc., as substituents. Reduction at reflux temperature^^sAso
for hours together can cause rearrangements and cyclization in poly-functional
nitro compounds. Therefore, we examined several methods to improve
reduction process, and especially to obtain selectivity over reducible or other
labile substituents.
In this context, we found that Mg/HC02NH4 system could be conveniently
employed for the rapid and simple reduction of both aliphatic and aromatic
{Scheme 2.1) nitro compounds to corresponding amino derivatives. This new
system reduced with ease a wide variety of nitro compounds to corresponding
amines. Many primary and secondary functional groups like -CH3, -OH,
-OCH3, CONH2, -COOH, -CI, -Br, -CN, -COOR, etc., are tolerated.
Mg/HCOoNH. R — N O , ^ R — N H 2
2 CH3OH, r.t ^
R= alkyl or aryl
Scheme 2.1
57
Reduction of Nitro Compounds Chapter 2
The reduction of both alkyl {Table 2.1) and aryl {Table 2.2) nitiro compounds in
the presence of Mg/HCOaNHj was completed within two to ten min. The
course of reaction was monitored by thin layer chromatography and IR spectra.
Table 2.1: Mg/HC02NH4 Promoted Reduction of Alkyl Niti-o Compounds.
SI -T-x_ J Time -T Nitrocompound , . . No. ^ (mm) A m i n e
Yield. "PCq (O/Q\ Found
(Lit.)i8i
1 CH3-NO2
2 CH3-CH2-NO2
3 CH3-CH2-CH2-NO2
CH3-CH2-CH2-CH2-NO2
3
3
CH3-NH2
CH3-CH2-NH2
CH3-CH2-CH2-NH2
CH3-CH2-CH2-CH2-NH2
81^
83*
81^
74b
230-232 (232-234) 106-108
(107-108) 158-161
(160-162) 77-79 (78)182
^ Isolated yields are based on single experiment and the yields were not optimized. b Boiling point. <: Isolated as hydrochloride salt.
Table 2.2: M g / H C C h N H i P romoted Selective Reduct ion of Aromat ic Ni t ro Compounds.
SI No
Nitroarene Time (min) Amine
Yield. "P'^Q /o/„\ Found
(Lit.)i8i
W // NO, Q^m
2 MeH^^N02
3 " 0 ~ { ^ N O a
2
2
NO,
{_J-^o,
90b
91
93
93
182-185 (184-186)
44-45(45)
189-190 (188-190)
110-112 (111-123)182
94c 58-60 (60)182
Table Cont inued . .
58
Reduction of Nitro Compounds Chapter 2
.. .Table Continued
6
7
8
9
10
11
12
13
14
15
16
17
18
19
21
H a N H ^ ^ N O s
H 2 N ^ / = \
0 r<=^^°^
CI—<^^^N02
CI
^ - N O ,
Br^(^J>-N02
Br
NO2
< Q - N 0 2
COOH
HOOC—(v ^ N O a
MeO—^ ))—NO2
N C - ^ ^ ^ N 0 2
NC ^^^-^
0 r^^°^ H a C ^ N " ^
^ H
3
3
3
3
5
5
5
4
8
5
7
6
4
6
5
H a N H ^ ^ ^ N H a
H2N / = \
0 f ^ ' ^ '
C I — < ^ ^ N H 2
CI
Q K N H 2
Q ^ N H 2
Br-^^^NH2
Br
< Q - N H 2
NH2
< ( ^ N H 2
^COOH
< ^ N H 2
HOOC—(( V-NHj
MeO—^ /—NH2
N C H ^ ^ ^ N H 2
, , ^ - ^ ^ " ^
H
95
92
93d
93
90b
89^
90
94c
93
88
89
93
90
91
92
142-144 (141)
115-116 (114)
148-151 (150)182
70-72(71)
208(206-208)
230(228-229)
66-67 (65-67)
115-118 (116)
103-104 (102-104)
146 (144-146)
186-187 (183-185)
58-66 (56-59)
84-85 (83-85)
46-48 (45-48)
163-165 (163)
^Isolated yields are based on single experiment and the yields were not optimized. ''BoUing point. ^Isolated as benzoyl derivative. ^Isolated as acetyl derivative.
59
Reduction of Nitro Compounds Chapter 2
The disappearance of asymmetric and symmetric stretching bands near 1520
cm-i and 1345 cirr^ due to the N-TTTTTO of NO2 and the appearance of two
strong bands near 3500-3300 cm-i of -NH2 stretching (due to primary amine) in
the IR spectra clearly indicated the conversion(Fi^res 2.1-2.3) . The work-up
and isolation of the products were easy. Thus, all the compounds reduced by
this system were obtained in good yields (90-95%). All the products were
characterized by comparison of their TLQ IR spectra and melting points with
authentic samples. A control experiment was carried out using nitro
compounds with ammonium formate in absence of magnesium powder and
this does not yield the desired product. No other intermediates, such as
nitroso or hydroxylamine could be detected in the reaction mixture. The
magnesium/HCO2NH4 system is more effective than either triethylammoiuum
foramte/5% Pd-C" or cyclohexene /10% Pd-C2 or hydrazine hydrate/Fe(III)25
and equally compatible with the systems like HCO2NH4/10%Pd-C28 and
HC02NH4/5% Pt-C.48 A plausible mechanism for the reduction of nitro
compounds to amines is proposed (Scheme 2.2).
Studies were also carried out to determine the optimum conditions for
reduction. These include the excess of donor required, the catalyst, solvent and
concentration. An excess of 2-3 equiv. of ammonium formate was found to be
ideal. The rate of transfer reduction decreased substantially when orUy
1 equiv. of ammonium formate was used. On the other hand, a large excess of
ammonium formate (20 equiv.) produced only a marginal increase in the rate
of reaction. A large excess of catalyst improved the rate of transfer
hydrogenation. We have also observed that, 1 equiv. of catalyst were ideal.
Larger amounts of catalyst resulted in only minor improvement. Methanol was
the most effective solvent. The reduction proceeded at the rate described above
when the concentrations of substrate are in the range of 0.75 - 0.5 mmol/mL.
At lower concentration, the rate of reaction decreases substantially.
60
Reduction of Nitro Compounds Chapter 2
I I I I I ' l r j ' l M I ' I "I "I r"i I T\ 1 1 I" !• M I
O H O
8 ^ 8 t 0 o 6
62
Reduction of Nitro Compounds Chapter 2
.s
•a <
u OH
Pi
O 1- O
,S * 8 o g
o o d s
o 8
o 5?
o Q 6 N
a 6
o d
63
Reduction of Nitro Compounds Chapter 2
Plausible Mechanism of Reduction of Nitro Compounds by M^HC02NH4
HCO2NH4 ^S=
o - X- .
H O + NH^
Mg
O u
-*- H—Mg O
R-N
n^fX^o-H\
-H,0 R-N=0
O ' " 1 +
R-N-H I o_
H t o
I O - M g ^ O ^
" R ^ - H -Mg,-CO„-NH3 ^_
O
X H — M g ^ ^ O
H
- P»A- "T". ) ^ ^ 0—Me
R—N-H
-Mg.-COj,-NH3 '^^-N R ^ . ^ H
H\ ^H
-Mg, -CO,, -NH, H
R—NH, R-N-Mg H
H-N—H' I H
R = alkyl or aryl residue
-Hfi H
O X R - ^ M ^ ^ ^ O
O H
Scheme 2.2
Thus the reduction of nitro compounds can be accomplished with magnesium
powder instead of expensive platinum or palladium etc., without effecting the
reduction of any reducible or hydrogenolysable substituents. The yields are
virtually quantitative and analytically pure. The obvious advantages of
proposed method over previous methods are: (i) selective reduction of nitro
compounds, in the presence of other reducible or hydrogenolysable groups.
64
Reduction of Nitro Compounds Chapter 2
(ii) ready availability and ease of operation, (iii) rapid reduction, (iv) high
yields of substituted amines, (v) avoidance of strong acid media, (vi) no
requirement of pressure apparatus and (vii) cost effective. This procedure will
therefore be of general use, especially in the cases where rapid, mild and
selective reduction is required.
2.2: Polymer-Supported Formate (PSF) and Zinc: A Novel System for the
Transfer Hydrogenation of Aromatic Nitro Compounds.
In recent years, polymer-supported reagents, catalysts, and scavengers are
ubiquitous throughout the fields of combinatorial chemistry, organic synthesis
and catalysis.18^ '5 xhe use of polymer-supported reagents couples the
advantages of solution phase chemistry (ease of monitoring the progress of the
reaction by using chromatographic and spectroscopic techniques) with those of
solid phase methods (use of excess reagents and easy isolation and purification
of products). The utility and power of such reagents has been exquisitely
demonstrated by the groups of Ley and others in synthesizing several complex
natural products by multi-step sequences requiring many different kinds of
heterogenized reagents, which can be removed by simple filtration.^*^ '
However, in view of the rapid development in the field of polymer-supported
chemistry over the last few years, there is a pressing need for the proper
exploitation of functionalized polymer-supported reagents in organic
synthesis.
In this section, we report that the PSF can be conveniently employed as
hydrogen donor for the clean and efficient reduction of aromatic nitro
compounds to the corresponding anilines in excellent yields using readily
available inexpensive commercial zinc dust as catalyst under ambient
temperature {Scheme 2.3).
65
Reduction of Nitro Compounds Chapter 2
^—^ HCOONHj/Zn „ ,,
R — M^OH.r.t. ^
R = halogen, -CH=CH2, -CN, -CHO, -COR, -COOR, -CONH2, -OCH3 and -OH.
Scheme 2.3
The scope of this new system is illustrated in Table 2.3, where we examined
series of aromatic nitro compounds with a variety of substituents. All the
products were characterized by comparison of their TLC, melting points, IR
spectra (Figures 2.4-2.6), and ^H-NMR spectra with authentic samples. The
reactions are, on the whole, reasonably fast and high yielding (92-98%). It is
worth to note, our system selectively reduced aromatic nitro compounds to the
corresponding amines in the presence of other sensitive functional groups such
as halogen (Table 2.3, entries 1-3), alkene (Table 2.3, entry 4), nitrile (Table 2.3,
entry 5), and carbonyl (Table 2.3, entries 6 & 7), groups which are susceptible to
reduction under transfer hydrogenation conditions. In addition, many other
functional groups such as ester, amide, methoxy, acid, and hydroxyl groups are
also compatible with the present system. A plausible mechanism for the
reduction of rutro compounds to amines is proposed (Scheme 2.4).
The separation of products from the reaction mixture is simple and involves, in
most of the cases, direct removal of the catalyst and resin by filtration and
evaporation of the solvent under vacuum. The crude product, so isolated, was
of excellent purity for most purposes. Hence, this procedure is highly
advantageous to obtain water-soluble aromatic amines in high yields
(Table 2.3, entries 1, 3, 7, 12-15). It is noteworthy here that the polymer-
supported formate was regenerated and could be reused for further
hydrogenolysis process. In total, ten successive recycle runs were possible
before there was an appreciable decrease in the reaction yield (Table 2.4).
66
Reduction of Nitro Compounds Chapter 2
Table 2.3: CTH of Aromatic Nitro Compounds Using PSF/Zinc.
Entry Substrate Time
_JhL_ Product Yield^ mp
(%) (°C)181
1 CI \ \ //
-NO,
2 I—<\ />—NO, \ \ / /
Br
COOH
NO,
' M=r'°^ NC \ \ /
-NO,
6 O H C — / V - N O ,
7 HXOC
8 H,NOC
W /
w /
NO,
NO,
OMe
10
11 ^ '
1.0 CI
1.0 H,COC
1.0 H,NOC
OMe
2.0
1.5
CH,
^ NH,
96 71
98 62
93 217-219182
95 212-214b'C
98 46-48
97 70-72
96 104-106182
95 114-116
94 86-87d
92 205-207
97 110-112^
12 HOOC-iv />—NO, 2.5 HOOC \ /
NH, 96 186-187
Table continued
67
Reduction of Nitro Compounds Chapter 2
Table continued
13 3.0 N NO, N ^ N H ,
95 57-58182
14 ^^3C0CHN^ ^ N O , ^ 5 H,COCHN-<v A-NH, 98 163-164
15
16
HOOC
CHo
2.0
2.5
HOOC 96 150-152182
90 143-144
CH,
17 (HgQjN—{^ / - N O 2 2.5 (HgQjN-d^ / ) -NH2 85 113-115
18 3.0 NH,
93 110-112 (112)182
^Yields of isolated products; ''Boiling point; <='Yhe spectra were compared to those of a commercial sample; " Isolated as acetyl derivative;
Table 2.4: Recycling of Polymer-Supported Formate for the Reduction of p-Chloro Nitrobenzene.
Cycle
1
2
3
4
5
6
7
8
9
10
Time (hr)
1.0
1.0
1.0
1.0
1.5
1.5
1.5
2.0
2.0
2.5
Yield
(%)
96
95
95
94
94
94
93
94
93
93
68
Reduction of Nitro Compounds Chapter 2
Plausible Mechanism of Reduction of Nitro Compounds by Zi^PSF
NH3 HCOO H 0 + NH,
O u
Zn+ H^'^6
0 R^K,"°
- H- Zr/^6 R- ti{ X-J' 0-^—-^ Q-
H
O . R-N=o "—:H;O"
H-Z)
o
r R-N—H
a
NH. 2 t .0
H' £M. o--Za-CO, ^ _ ^ ^ ^
y i i i 111MIM11111 Z J r O
NHo-
-Zn,-C02 TM o
NH,
®^>^, NH2 -
Zn, -CO2 R-
H il -H,0
NH,
H"
R-NH2
Scheme 2.4
^N
O—H
P ^
O
ZiAb
? X-O—H H
72
Reduction of Nitro Compounds Chapter 2
A control experiment was carried out using nitro compounds with polymer
supported formate, but without zinc powder, does not yield any reduced
product and the starting material is recovered in 100%. This confirms the role
of zinc as catalyst. Further, another control experiment was carried out by
refluxing r\itro compounds with zinc powder in methanol and in the absence of
polymer supported formate yielded no desired product. Even after long
duration we could not obtain any reduced product. This clearly confirms that
methanol serves only as solvent and not as hydrogen source.
In conclusion, we have developed a novel CTH system for the clean and
efficient reduction of aromatic nitro compounds to the corresponding amines
using polymer-supported formate and zinc. The major advantages of this
method include the ability to obtain aromatic anunes in pure form with no
work-up, and the enhanced chemo-selectivity. Thus, the use of resin bound
hydrogen donor combines the advantages of polymer-supported chemistry
with the flexibility of CTH technique. The catalyst is non-pyrophoric in nature
and another interesting behavior of Zn dust lies in the fact that it can be
recycled after simple washing with EtaO and dilute HCl, rendering thus
process more economic. The present method offers an economical safe and
environmentally benign alternative to available procedures.
2.3: Experimental.
2.3.1: General. The ^H NMR spectra were recorded on an AMX-400 MHz
spectrometer using CDCI3 as the solvent and TMS as internal standard and IR
spectra on a Shimadzu FTIR- 8300 spectrometer. The melting points were
determined by using Thomas-Hoover melting point apparatus and are
uncorrected. Thin layer chromatography was carried out on silica gel plates
obtained from Whatman Inc., using the solvent systems; 100:0 chloroform,
80:20 chloroform:methanol, 85:15 chloroform:methanol, 90:10
chloroform:methanol, 95:5 chloroform:methanol. The compounds on TLC
plates were detected by UV light, by ninhydrin or by exposing to iodine
73
Reduction of Nitro Compounds Chapter 2
vapors. The substrates were either commercial products and were used as
purchased or were prepared according to literature procedures. Merrifield
resin was purchased from Advanced Chem tech (1% DVB cross-linked, 100-200
mesh, 2 nunol/g). Ammonium formate was purchased from Aldrich chemical
company (USA). Zinc dust (Particle size < 45 |im) was purchased from E-Merck
(India) Ltd. Magnesium powder purchased from SISCO Research Laboratories
Pvt. Ltd., Bombay (India), was treated with O.OIN hydrochloric acid for about 2
min. It was filtered through a sintered glass funnel and washed with water, dry
methanol and dry ether. This magnesium was then vacuum dried and stored.
All the solvents used were of analytical grade or were of purified according to
standard procedures. For preparative TLC, the plates were prepared from
Kieselgel 60 GF254, Merck, Darmstadt and for column chromatography 60-120
mesh silica gel was used obtained from SISCO Research Laboratories. For
further purification/separation of products, the residue was purified either by
preparative TLC or subjected to column chromatography by using 60-120 mesh
silica gel and a suitable eluting system (50:50 chloroform:benzene, 60:40
chloroform:benzene, 80:20 chloroform:benzene, 90:10 chloroform:benzene,
50:50 chloroform:hexene, 60:40 chloroform:hexene, 80:20 chloroform:hexene,
90:10 chloroform:hexane, 100:0 chloroform, 80:20 chloroform:methanol, 85:15
chloroform:methanol, 90:10 chloroform:methanol, 95:5 chloroform:methanol).
2.3.2: Preparation of Phthalimidomethylpolystyrene Resin.
Chloromethylpolystyrene (Advanced Chemtech, 1% DVB cross-linked, 100-200
mesh, 2 mmol/g) was suspended in 150 ml of dry distilled dimethylformamide
(DMF) and 2.77 g of potassium phthalimide was added. The mixture was
stirred at 50 °C for 18 hours, after which the resin was washed three times each
with DMF, methanol, water and methanol and dried in vacuum overnight to
obtain Phthalimidomethylpolystyrene in good yield.
74
Reduction of Nitro Compounds ^ Chapter 2
2.3.3: Preparation of Aminomethylpolystyrene Resin.
Phthalimidomethylpolystyrene 20 g was treated overnight with 1.5 ml of
hydrazine hydrate in refluxing ethanol. The resin was filtered froni the hot
ethanol and washed three times with ethanol, 5% aqueous KOH, water, and
ethanol and dried in vacuum overnight to obtain aminomethylpolystyrene
resin in good yield.
2.3.4: Preparation of Polymer-Supported Formate.
The aminomethylpolystyrene was washed with an excess of 50% solution of
formic acid in dichloromethane. The resulting polymer was washed thoroughly
and successively with dichloromethane and ether, and dried under vacuum.
The obtained resin was used as such for the reduction.
2.3.5: General Procedure for the Reduction of Nitro Compounds Using
Mg/HCOONH4.
A suspension of an appropriate nitro compound (5 mmol) and magnesium
powder (10 mmol) in methanol or in any other suitable solvent (5 mL) was
stirred under nitrogen atmosphere with ammoruum formate (0.5 g), at room
temperature. After the completion of the reaction (morutored by TLC), the
catalyst was filtered off. The residue was extracted with chloroform or
dichloromethane or ether (15 mL). The extract was washed twice with
saturated sodium chloride solution (15 mL) and then with water (10 mL). The
organic layer was dried (Na2S04) and then evaporated to obtain the desired
anuno derivative.
In order to obtain good yield of volatile aliphatic amine, the reaction was
carried out using a condenser cooled with ice water and by immersing the
reaction flask in a cold-water bath. After filtration, the reaction mixture was
neutralized with HCl. The solvent was evaporated under reduced pressure.
The residue was lyophilized or subjected to column chromatography by using
75
Reduction of Nitro Compounds Chapter 2
60-120 mesh silica gel and a suitable eluting system. Aliphatic amines were
obtained as their hydrochloride salts in up to 80% yield.
2.3.6: General Procedure for the Reduction of Nitro Compounds Using
PSF/Zinc.
To a solution of nitro compound (1 mmol) in methanol (15 mL) taken in a
horizontal solid phase vessel, polymer-supported formate (1 g) and zinc dust
(1 mmol) were added. The suspension was shaken well (The reaction mixture
was subjected to shaking using a manual shaker as the shaking of the polymer-
supported formate instead of stirring increases its life for recycling purpose)
for the specified time at room temperature {Table 2.3). After consumption of
the starting material, as monitored by TLC, the reaction mixture was filtered
and washed thoroughly with methanol. The combined washings and filtrate
were evaporated under reduced pressure. The crude product was found to be
analytically pure in most cases. Where necessary, the crude product was taken
into organic layer and washed with saturated sodium chloride.
For recycling purposes, the residue containing polymer-supported formate and
the catalyst was washed thoroughly and successively with DMF,
dichloromethane, 50% solution of formic acid in dichloromethane,
dichloromethane and ether. Thus activated resin along with the catalyst was
dried under vacuum and used as such for further reduction reactions.
76