Steric-Hindrance-Induced Regio- and Chemoselective Oxidation of Aromatic Amines

Article abstract of DOI:10.1021/acs.joc.5b00582

Unusual regio- and chemoselective oxidation of aromatic amines hindered with ortho substituents (except -NH₂, -NHCH₃, and -OH) to the corresponding nitro compounds is described by use of nonanebis(peroxoic acid). The mechanistic investigation for selective oxidation of amines ortho-substituted with -NH₂ or -OH showed the involvement of H-bonding between the ortho hydrogen of the adjacent -XH group (where X = NH, NR, or O) and an oxygen atom from the diperoxy acid. Various mono- and diamines are oxidized into corresponding mononitro derivatives in high yield and purity without employing any protection strategies. The protocol was also found to successful on the gram scale.

Full text of DOI:10.1021/acs.joc.5b00582

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Steric hindrance induced regio and chemo selective oxidation of
aromatic amine
Vilas Venunath Patil, Ganapati Subray Shankarling,*
Department of Dyestuff Technology, Institute of Chemical Technology, N. P. Marg, Matunga, Mumbai - 400019, India
gsshankarling@gmail.com, gs.shankarling@ictmumbai.edu.in
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ABSTRACT
The ortho substituent hindered (except –NH , –NHCH ꢀOH) unusual regio and chemo selective oxidation of aromatic amine in
2
3
to corresponding nitro compound is described using nonanebis(peroxoic acid). The mechanistic investigation for selective
oxidation of amine ortho substituted with –NH , ꢀOH showed the involvement of Hꢀbonding between ortho hydrogen of adjacent
2
–
XH (ꢀX = ꢀNH, ꢀNR, ꢀO) group with oxygen atom from diperoxy acid. Various mono and diamines are oxidized into
corresponding mono nitro derivatives in high yield and purity without employing any protection strategies. The protocol was also
found to successful on gram scale.
INTRODUCTION
The oxidation of amines into nitro compound is considered as one of the indispensable transformations in organic
synthesis as it is a direct route for the synthesis of nitro compounds. Aromatic nitro compounds are well established industrially
1
,2
3,4
5,6
as these compounds work as a backbone to many commercially important chemicals such as dyes, polymers, perfumes,
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8,10
pharmaceuticals, pesticide and extensively in explosives.
They serves as important reagents for the synthesis of complex
1
1
target molecules. Numerous oxidation strategies have been employed for this purpose using various oxidants (Scheme 1) such
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15–17
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as HOFꢀCH CN,
Dimethyldioxirane,
peracetic acid, peroxytriflouro acetic acid, mꢀCPBA, oxone, sodium
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perborate with tungstophosphoric acid and CTAB, sodium perborate with acetic acid, tetra alkyl ammonium bromate,
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combination of tertꢀbutyl hydroperoxide (TBHP) with various catalysts such as KI, chromium silicate, zirconium and Fe
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(
III) and Mn (III) tetra aryl porphyrins, superoxide and H O mixture and titanium superoxide. The major short come in
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most of these oxidation protocol was the uncontrolled oxidation which results in to formation of multiple products such as
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nitroso, azo, azoxybenzene, hydroxyl amine, oxime which in turn, lack the selectivity. Further some of those systems suffers
various disadvantages. The hazardous halogenated solvents such as chloroform, dichloromethane and dichloroethane were most
preferred to carry out this oxidation. The peracids such as peracetic acid, peroxytrifluoro acetic acid are difficult to handle in
anhydrous condition. The peroxytrifluoro acetic acid, itself attack on the benzene ring to give phenol containing complex
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mixtures. This reagent was also found to be ineffective to oxidize pꢀmethoxy aniline to pꢀmethoxy nitrobenzene. Whereas
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oxidation with mꢀCPBA in 1,2ꢀdichloroethane occurred in 10 h under reflux condition. The most studied oxidant HOFꢀCH CN
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required hazardous fluorine gas for the preparation as well as this reagent is quite unstable and need to prepare in situ. The
oxidizing systems such as KIꢀTBHP, Sodium perborateꢀtugastophosphoric acid with CTAB though follow some principles of
green chemistry but reaction requires longer time (12 to 15 h) for completion with moderate to good yields. The heterogeneous
catalytic system reported by Sudalai et. al. was found to be most effective not only for selective oxidation of amine to nitro as
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well as it gives good yield in shorter period with recycling the catalyst. It is noticeable that, in all above mentioned reports
attempts were made to give selective nitro as a product, but none of the chemical method successful to give chemo or regio
selective oxidation. For instant, the oxidation of oꢀdiamine results into formation of dinitro compounds (Scheme 1) and if mono
13
nitro derivative is desired then one need to protect one of the amine to avoid di nitro product formation.
On other hand,
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enzymes were served as a better option to achieve chemo and regio selectivity for this transformation.
Hertweck and coꢀ
workers have reported the chemo and regio selective oxidation of various para amino benzoic acid derivatives using paraꢀ
aminobenzoate Nꢀoxygenase (AurF) enzyme from Streptomyces thioluteus. The interaction between positively charged protein
residue and anionic part of acid is responsible for higher selectivity of this protocol. Owing to this acid selective interaction, this
protocol was relevant to only amines with anionic acid part at para position. Thus the need to develop a chemical method which
will overcome all above short comes as well as provide certain sort of selectivity drive our attention towards this transformation.
In our previous work, we have demonstrated that the long chain diperoxy acid, nonanebis(peroxoic acid) can overcome various
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short comes of conventional peracids and can be a good alternative for them. It is easy to prepare and handle, nonꢀshock
35,36
sensitive in nature and stable at room temperature.
As a part of our research to explore the applicability of diperoxy acids in
the organic synthesis we decided to investigate above oxidation reaction in this peroxy acid. During this attempt we found that
this diperoxy acid was not only capable to oxidize amino to nitro in shorter period and under mild conditions but also show one
unusual selectivity trend which was not yet reported in the literature for any chemical oxidation method of this kind. The steric
hindrance of ortho substituent and the interaction between diperoxy acids and hydrogen atom present on heteroatom (X= ꢀN/ꢀO)
ortho to amine play vital role to induce an interesting selectivity which to the best our knowledge not yet explored in organic
synthesis. This trend was also found in the other diperoxy acids we investigated here. It is noticeable that the protocol which we
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report here is found to be effective to synthesize the commercially important molecules such as “Dichloran” which is widely used
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as a fungicide from 2,6ꢀdichlorobenzeneꢀ1,4ꢀdiamine . The molecules such as 2ꢀaminoꢀ3ꢀbromoꢀ5ꢀnitrobenzonitrile , 2ꢀ
4
0
methylꢀ4ꢀnitroaniline which are used as intermediate to synthesize azo dyes for NLO, for dying polymers were also prepared by
using present approach. 2ꢀmethoxyꢀ4ꢀnitroaniline which is widely used for textile dying, in the printing industry, as intermediate
for the synthesis of azo dyes for tattoo inks, emulsion paints and toy enamels was also synthesized under present protocol.
Thus here we report, a metal catalyst free, mild and efficient approach for regio and chemo selective oxidation of
aromatic amine to nitro using nonanebis(peroxoic acid) as a oxidant. This work highlighted the important properties of these
diperoxy acids which was still remained unnoticed from their discovery.
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Scheme 1. Previous report
RESULTS AND DISCUSSION
The reaction conditions were optimized by taking aniline 1a (1 equiv.) as a key substrate and nonanebis(peroxoic acid)
as an oxidant at 50 °C (Table 1). The oxidant equivalent study illustrated that the formation of nitro product proceeds through azo
2
a and azoxy benzene 2b as intermediate products (Table 1, entries 1ꢀ3) and three equivalents of oxidant were required for the
formation of nitro product 3a (Table 1, entry 4). The influence of solvents for conversion studies revealed acetonitrile to be the
most appropriate solvent as 100% conversion into nitro benzene was achieved within 20 min (Table 1, entry 4). On the contrary
when hexane was used as a solvent, selectively azoxybenzene 2b formation was observed (Table 1, entry 5). The other solvents
gave mixture of both azoxy benzene and nitro benzene (Table 1, entries 6–13). It was also observed that the rate of formation of
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nitro product increases as temperature increased from 20 °C to 50 °C (Table 1, entries 13ꢀ15). Further rise in the temperature has
not shown any influence on time as well as yield (Table 1, entry 16).
a
Table 1. Optimization of reaction conditions
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b
Oxidant
% conversion
Entry
Solvent
equiv.
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2.5
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3
2a
2b
59
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ꢀ
100
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20
8
3a
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100
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80
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100
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Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
Hexane
Toluene
Chloroform
DCM
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4
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
Ethyl acetate
DMF
Ethanol
1
1
0
1
12
Water
c
1
1
1
1
3
4
5
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
d
e
f
6
ꢀ
Comparision with other oxidants
Oxidant
equiv.
3a %
conversion
Entry
Oxidant
50% H
70% TBHP
mꢀCPBA
b
g
1
18
1
2
2
7
2
O
2
6
6
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NR
NR
30%
traces
traces
NR
ꢀ
g
h
g
h
g
9
0
1
Sodium perborate
Oxone
Potassium peroxy disulphate
Performic acid
Peracetic acid
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23
2
4
ꢀ
a
Reaction conditions: 1a (1.07 mmol), oxidant : nonanebis(peroxoic acid) , solvent 5 mL; All reactions were performed in 20 min at 50 °C unless
b
c
d
e
otherwise indicated. Conversion determined by GC. Reaction kept for 24 h at 20 °C; Reaction kept for 24 h at 30 °C; Reaction kept for 1 h at
40 °C; Reaction kept for 20 min at 60 °C. Reaction maintanined for 2h at 50 °C. Reaction maintanined for 30 min at 50 °C. NR: No Reaction.
f
g
h
We also examined feasibility of other commonly peroxides under present conditions (Table 1, entries 17ꢀ24). It was
observed that, except mꢀCPBA (Table 1, entry 19) none other oxidants show formation of nitro benzene under optimized
conditions. In case of 50% H O , 70% TBHP, and potassium peroxy disulphate only starting aniline was observed on TLC even
2
2
after keeping reaction for 2 h at 50 °C (Table 1, entries 17, 18 and 22). Whereas in sodium perborate traces nitro benzene
formation was observed under optimized conditions (Table 1, entry 20). The reaction with performic acid gives 6% of Nꢀ
formylated product, 9% of 2a and 85% of the 2b (Table 1, entry 23). Similarly in case of peracetic acid, 10% of Nꢀacylated
product was formed with 90% of 2b (Table 1, entry 24). In both peracids formation of 3a was not observed.
Encouraged by these promising results, we applied the optimized reaction conditions to examine the substrate scope.
The oxidation of various aniline derivatives under optimized reaction conditions gives corresponding nitro product in 20 min
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(
Table 2). It was found that the aniline derivatives with ꢀm and/or ꢀ p substituents such as ꢀCl, ꢀNO , ꢀOCH , ꢀCH , ꢀCOOH, ꢀOH,
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ꢀNHCOCH , ꢀCN, ꢀOCF , ꢀCOCH were oxidized smoothly into corresponding nitro derivatives in 20 min (Table 2, entries 3b to
3
3
3
3
r). While the oꢀsubstituted derivatives of aniline such as 2ꢀchloro aniline, 2ꢀnitro aniline, 2ꢀanisidine, 2ꢀtoluidine, 2ꢀamino
benzonitrile failed to undergo oxidation under existing conditions even after exceeding reaction conditions for 2 h at 50 °C. In
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case of amino phenols no quinone formation was observed only nitro derivative was formed (Table 2, entries 3l, 3m, 3s). The
protocol was also found to be compatible with various functional groups such as ꢀCOOH, ꢀNHCOCH , ꢀCN, ꢀOCF , ꢀCOCH ꢀ
3,
3
3
CH OH (Table 1, entries 3j, 3k, 3n-3r). The substrate which contain oxidizable groups such as ꢀCN, ꢀCOCH and ꢀCH OH no
2
3
2
oxidation products of respective functional group such as Nꢀoxide, ester and aldehyde or acid was detected (Table 1, 3o, 3q and
r). The protocol was found to be unsuccessful when we tried competitive reaction in presence of styrene, it was found that,
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styrene undergoes oxidation along with aniline under present conditions to give mixture of oxidation products of both substrates.
Similarly the protocol was failed with substrate containing aldehyde as reaction gives multiple products.
[
a]
Table 2. Regio and chemo selective oxidation of various aromatic mono amine
a
Reaction conditions: amine (1 equiv.), nonanebis(peroxoic acid) (3 equiv.), acetonitrile 5 mL, All reactions were performed in 20 min. Yields
b
given are isolated yields. The reaction mass was quenched by 0.1 M sodium thiosulphate solution, extracted in ethyl acetate and purified with
column chromatography using hexane: ethyl acetate as a eluting system.
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To our surprise, the oxidation of benzeneꢀ1,2ꢀdiamine under present conditions, selectively gave 2ꢀnitro aniline as a
product (Scheme 2). Addition of extra oxidant (3 equivalents) failed to show formation of 1,2ꢀdinitro benzene.
Scheme 2. Selective oxidation of benzene-1,2-diamine into 2-nitroaniline
NH2
NH2
NO2
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NH2
NO2
NO2
benzene-1,2-diamine
GC Conversion - 100%,
Isolated yield - 95%
No reaction
This result was further confirmed from the reaction of 2ꢀnitro aniline which does not undergo oxidation under present
conditions. From this, it was confirmed that once one of the o–NH groups of benzeneꢀ1,2ꢀdiamine gets oxidized, it prevents
2
further oxidation of amino group at ortho position. Again, we also understood that amine bearing hydrogen on heteroatom at
ortho position only get oxidized to corresponding nitro derivative. To check feasibility, we carried out reactions with 2ꢀamino
phenol and 2ꢀamino thiophenol. It was found that, the reaction with 2ꢀamino phenol gave 2ꢀnitro phenol as a product (Table 2,
entry 3s). But in case of 2ꢀamino thiophenol, the protocol was found to be unsuccessful as the reaction yields, mixture of
oxidation products of both sulphur and amine instead of 2ꢀnitro thiophenol. From the above fallouts, it was clear that, only those
ortho substituted amines get oxidized to corresponding nitro derivative which possess hydrogen on heteroatom. We believe that,
the reason for this selectivity could be the hydrogen bonding between hydrogen on ortho –XH group with oxygen of per acid
which in turn facilitates the oxidation reaction (scheme 3).
Scheme 3. Hydrogen bonding between hydrogen atom on ortho –XH substituent (-NH /-NHCH /-OH) with carbonyl
2
3
oxygen of diperoxy acid
1
1
1
To validate this assumption, we carried out reaction on N ꢀmethylbenzeneꢀ1,2ꢀdiamine and N ,N ꢀdimethylbenzeneꢀ
1
,2ꢀdiamine (scheme 4- a, b). The GC analysis shows that, the former amine derivative get oxidized to Nꢀmethylꢀ2ꢀnitroaniline
whereas latter persisted as it is. This assumption was further confirmed from the reaction 2ꢀamino phenol and 2ꢀmethoxy aniline,
as former get oxidized to 2ꢀnitro phenol whereas 2ꢀmethoxy aniline failed to undergo any oxidation reaction under present
conditions. Further validation of this assumption was done by carrying out reactions with Nꢀ(2ꢀaminophenyl)acetamide and 4ꢀ
1
chloroꢀN ꢀphenylbenzeneꢀ1,2ꢀdiamine to give 4m 87% and 4n 90% respectively in 20 min (Table 3, entries 4m, 4n).
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Scheme 4. Influence of hydrogen atom of ortho –NH group on oxidation of o-diamine
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This confirmed the significant importance of hydrogen atom present on hetero atom at ortho position in the selective
oxidation of diamine and amino phenol. In order to study chemo selectivity further, we carried out oxidation of various diamine
in which one of the amino groups was ortho substituted with group other than –NH , ꢀOH (Table 3). The results obtained shows
2
that amine with ortho substituents (other than ꢀNH and ꢀOH) remained unaffected under present reaction conditions. While the
2
amine without any ortho substituents or ortho substituted with –NH ,ꢀOH undergo oxidation into corresponding nitro group
2
(Table 3, entries 4a-4i). The further advantage of this protocol was the easy synthesis of the important fungicide “Dichloran”.
The oxidation of 2,6ꢀdichloro paraphenylene diamine gives 92% yield of “Dichloran” in 20 min (Table 3, entry 4e). The reaction
of benzeneꢀ1,4ꢀdiamine with 6 equiv. of peroxy acid give 1,4ꢀdinitro benzene (Table 3, entry 4i) but in case of benzneꢀ1,3ꢀ
diamine polar spot was observed on TLC instead of 1,3ꢀdinitro benzene. It was noticeable that, in case of substrate like 4ꢀ
nitrobenzeneꢀ1,2ꢀdiamine, with strong electron withdrawing –NO group at para position, showed pronounce effect on oxidation
2
of pꢀNH group as 2,4ꢀdinitro aniline (4j-a) was formed as a major product over 2,5ꢀdinitro aniline (4j-b) (Table 3, entry 4j).
2
While in case of substrate like 4ꢀchlorobenzeneꢀ1,2ꢀdiamine, with less electron withdrawing ꢀCl group, both products were
obtained almost in equal amount (Table 3, entry 4l). The oxidation of substrates bearing acyl and aryl groups on benzeneꢀ1,2ꢀ
diamine further confirmed the role of hydrogen on neighbouring heteroatom in the oxidation of ortho amine to nitro (Table 3,
entries 4m, 4n). Both substrates were smoothly oxidized in to corresponding nitro derivatives in 20 min to give 87% and 90%
yield respectively.
[
a]
Table 3. Selective oxidation of various aromatic di-amines
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NH2
CN
O N
2
4
g 93%
a
Reaction conditions: 1 (1 equiv.), nonanebis(peroxoic acid) (3 equiv.), acetonitrile 5 mL, All reactions were Kept for 20 min. Yields given are
isolated yields. Conversion determined by GC analysis and products were confirmed by GCꢀMS analysis.
b
Further, when we examined conventionally used oxidizing agents for above selectivity (Table 4, entries 1ꢀ6), it was
observed that except mꢀCPBA none of the oxidants show formation of ortho nitro aniline. In case of mꢀCPBA only 28% of 4a
formation was observed (Table 4, entry 6). In order to check this selectivity trend in other diperoxy acids, we carried out reaction
of benzeneꢀ1,2ꢀdiamine with hexanebis(peroxoic acid) and dodecanebis(peroxoic acid) (no. of carbon atoms are 6 and 12
respectively) which also give 100% conversion in to 2ꢀnitro aniline with 90% and 92% isolated yield respectively (Table 4,
entries 1ꢀ2). Reactions of other diperoxy acids with substrates such as oꢀnitro aniline and oꢀtoluidine were also failed to show any
oxidation of amino group under identical conditions. This confirms the regio and chemo selective nature of diperoxy acids for
oxidation of aromatic amines. The reaction of benzeneꢀ1,2ꢀdiamine 1 with aliphatic mono peroxy acids such as performic acid
not shows formation of 4a though we increased the peracid equivalents from 6 to 24 (Table 4, entry 9). In case of peracetic acid
4
a formation was not observed when 6 equivalents of Peracetic acid was used. As we increased equivalents of peracetic acid
from 6 to 24, the formation of 4a was observed. The moderate gives moderate yield of 4a due to formation of blackish insoluble
solid along with desired product which was not detected on GCꢀMS (Table 4, entry 10).
a
Table 4. Selective oxidation of benzene-1,2-diamine using conventional oxidants and other diperoxy acid’s
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a
b
Entry
Oxidant
conversion
(%)
1
2
3
4
5
6
7
8
50% H
2
O
2
ꢀ
70% TBHP
Oxone
ꢀ
ꢀ
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Sodium perborate
ꢀ
Potassium peroxy disulphate
mꢀCPBA
ꢀ
28
Hexanebis(peroxoic acid)
Dodecanebis(peroxoic acid)
Performic acid
100
100
c
9
ꢀ
d
e
1
0
Peracetic acid
100 (58)
a
Reaction conditions: 1 (1 equiv.), Oxidant (6 equiv. for entries 1ꢀ6 and 3 equiv. for entries 7,8), Acetonitrile 5 mL, time : 2 h (entries 1ꢀ6), 20 min (for
entries 7,8). Conversion: determined by GC. Reactions were carried out using 6, 12 and 24 equiv. of peracid. Using 24 equiv. of peracetic acid. islated
yield.
b
c
d
e
The present approach was also examined on gram scale. We carried out oxidation of aniline and benzeneꢀ1,2ꢀdiamine
on 5 g scale up of each. The reaction yields 97% nitrobenzene and 95% 2ꢀnitro aniline in 20 min respectively. Thus it was also
confirmed that the protocol can be successfully used on gram scale.
Conclusions
We have developed a simple, efficient and transition metal free protocol of oxidation of aromatic amine to nitro. The
reaction selectively yields desired nitro product in shorter period, with high yield and purity irrespective of the substituents
present on ring. The most exciting feature of the present approach is meta and para selective oxidation of amine whereas anilines
ortho substituted with groups other than (ꢀNH , ꢀNHCH , ꢀOH) remained unaffected. Such ortho substituent hindered selectivity
2
3
plays vital role for the selective oxidation of diamine into its mono nitro derivative in which amine with ortho substituent
remained unaffected. The protocol shows unexceptional selectivity for oxidation of benzneꢀ1,2ꢀdiamine to 2ꢀnitro aniline without
further oxidizing it in to 1,3ꢀdinitro compound. Although oxidation of amine by peroxy acid is well reported but such regio and
chemo selectivity was not yet reported in any of these peroxy acids. We have also shown that the protocol was successful on
gram scale.
Experimental Section
1
All products were confirmed by melting point, H NMR and mass spectrometry. All melting points are uncorrected and are
1
presented in degree Celsius. The H NMR spectroscopic data were recorded on 400 and 500 MHz instruments in CDCl and
3
DMSOꢀd6 as a solvent and chemical shifts are expressed in δ ppm using TMS as an internal standard. GC analysis were carried
out using TRꢀ1 column, 30mX0.25mm, IDX0.25um film, FID detector and sample size 0.1 l µl. Nitrogen was used as the carrier
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gas at a flow rate 2 mL/min, 80ꢀ250 °C at 10 °C/min. GC/MS was performed using Rtxꢀ17 column, 30 m, 25 mm internal
diameter, film thickness 0.25 ꢁm, column flow: 2 mL/min, 80–250 °C at 10 °C/min.
General procedure for the synthesis of nonanebis(peroxoic acid):
35,36
Nonanebis(peroxoic acid) was synthesized as per the procedure given in literature on 10 g scale.
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General procedure for oxidation of aromatic amines using nonanebis(peroxoic acid):
In 50 mL round bottom flask, 0.1 g amine was stirred in 5 mL acetonitrile for 5 min. To this nonanebis(peroxoic acid) (3 equiv.)
was added in 10 min. with constant stirring. The reaction mass was heated to 50 °C for 20 min. The reaction mass was quenched
by saturated sodium thiosulphate solution (2 mL) and extracted in ethyl acetate (3 x 10 mL). The organic layer was treated with
saturated sodium bicarbonate solution till acid get neutralized and then with water and were dried over anhydrous Na SO . The
2
4
crude product was obtained after evaporating the solvent under vacuum which was further purified by column chromatography
on silica gel with hexane/ ethyl acetate as the eluent.
Procedure for scale up reaction:
In 500 mL 3N RBF equipped with a mercury sealed stirrer 5 g amine (aniline, benzneꢀ1,2ꢀdiamine) was taken in 250 mL
acetonitrile. The reaction mass was stirred for 5 min at room temperature. To this reaction mass 6 equiv. of nonanebis(peroxoic
acid) (71 g for aniline and 61 g for benzneꢀ1,2ꢀdiamine) was carefully and slowly added over 45 to 50 min at room temperature.
The reaction mass maintained at 50 °C for 20 min and then the reaction mass was quenched by saturated 50 mL sodium
thiosulphate and extracted in ethyl acetate (3 x 20 mL). The organic layer was further treated with saturated sodium bicarbonate
solution till it free from acids and then further with water. It was the dried over anhydrous Na SO The solvent was evaporated
2
4.
under vacuum to give 97% nitro benzene and 95% 2ꢀnitro aniline.
Spectral Data
2
0
1
1
.
Nitrobenzene (3a) : Yellow oil ; yield 0.127 g, 96%; purity 99.4% (GC); B.P. 208ꢀ210 °C; HꢀNMR (CDCl , 500 MHz): δ
3
=
7.54ꢀ7.58 (m, 2H), 7.69ꢀ7.72 (m, 1H), 8.23ꢀ8.25 (m, J = 8.5 Hz, J = 1 Hz 2 H). GCꢀMS (EI, 70 eV): m/z (%) = 123 (52.8)
+
[M] , 93 (10.8), 77 (100).
2
0
1
2. 3-Chloronitrobenzene (3b) : Light yellow solid; yield 0.114 g,92%; purity 99.1% (GC); M.P. 46ꢀ47 °C; HꢀNMR (CDCl ,
3
5
00 MHz): δ = 7.50ꢀ7.53 (t, J = 8 Hz, J = 8.5 Hz, 1H), 7.68ꢀ7.70 (q, J = 7.5 Hz, J = 1 Hz1H), 8.13ꢀ8.15 (q, J = 7 Hz, J = 1.5
+
Hz, 1H), 8.23ꢀ8.24 (t, J = 2 Hz, 1H); GCꢀMS (EI, 70 eV): m/z (%) = 157 (87.6) [M] , 159 (28), 127 (41.6), 129 (13.6), 113
(31), 111 (98.4), 101 (11.2), 99 (33.6), 75 (100).
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.
.
4-Chloronitrobenzene (3c) : Light yellow solid; yield 0.117 g, 94%; M.P. 82ꢀ83 °C; purity 99.0% (GC); HꢀNMR
(CDCl , 500 MHz): δ = 7.52ꢀ7.53 (q, J = 2 Hz, J = 7 Hz, 2H), 8.18ꢀ8.20 (q, J = 2.5 Hz, J = 6.5 Hz, 2H); GCꢀMS (EI, 70
3
+
eV): m/z (%) = 157 [M] , 127, 11, 75 (100).
4
1
1
1,3-Dinitrobenzene (3d) : Yellow solid; yield0.111 g 91%; M.P. 89ꢀ90 °C; purity 98.6 % (GC); HꢀNMR (CDCl , 500
3
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MHz): δ = 7.81ꢀ7.84 (t, J = 8 Hz, J = 8 Hz, 1H), 8.58ꢀ8.60 (q, J = 8 Hz, J = 2 Hz, 2H), 9.08ꢀ9.09 (t, J = 8 Hz, J = 2 Hz, 1H);
+
GCꢀMS (EI, 70 eV): m/z (%) = 168 (94.4) [M] , 122 (36.4), 92 (44.0), 76 (80), 75 (78.8), 74 (22.8).
2
0
1
5. 1,4-dinitrobenzene (3e) : Yellow solid; yield 0.112 g 92%; M.P. 165ꢀ166 °C; purity 98.9% (GC); H NMR (500 MHz,
+
CDCl ) δ 8.43 (s, 4H); GCꢀMS (EI, 70 eV): m/z (%) = 168 (60) [M] , 122 (20), 90 (19), 76 (46), 30 (100).
3
4
2
1
6. 1-methoxy-3-nitrobenzene (3f) : Yellow solid, yield 0.116 g 93%; purity 99.2% (GC); HꢀNMR (CDCl , 300 MHz): δ
3
=3.90 (s, 3H), 7.17ꢀ7.20 (d, J = 8.3 Hz, 1H), 7.38ꢀ743 (t, J = 8.1 Hz, 1H), 7.70 (s, 1H), 7.79ꢀ7.82 (d, J = 7.4 Hz, 1H) ; GCꢀ
+
MS (EI, 70 eV): m/z (%) = 153 (100) [M] , 107 (53), 92 (74), 77 (92).
20
1
7
8
.
.
1-methoxy-4-nitrobenzene (3g) : White solid; yield 0.118 g 95%; M.P. 51ꢀ52 °C; purity 98.8% (GC); H NMR (500
+
MHz, CDCl ) δ 3.89 (s, 3H), 6.96 – 6.92 (m, 2H), 8.19 – 8.15 (m, 2H); GCꢀMS (EI, 70 eV): m/z (%) = 153 (100) [M] , 123
3
(47), 107 (12), 92 (56), 77 (56).
4
3,44
1
3-Nitro toluene (3h)
: Light yellow liquid; yield 0.119 g 95%; B.P. 230ꢀ232 °C; purity 99.5% (GC); HꢀNMR (CDCl ,
3
5
00 MHz): δ = 2.47 (s, 3H,), 7.40ꢀ7.44 (t, 1H), 7.49ꢀ7.51 (d, 1H), 8.02ꢀ8.05 (t, 2H). GCꢀMS (EI, 70 eV): m/z (%) = 137 (75)
+
[
M] , 107 (20), 91 (100), 79 (12).
2
0
1
9. 4-Nitro toluene (3i) : Light yellow solid; yield 0.116 g 92%; M.P. 52ꢀ53 °C; purity 99.3% (GC); HꢀNMR (CDCl , 500
3
+
MHz): δ = 7.31ꢀ7.33 (d, J = 8.5 Hz, 2H), 8.11ꢀ8.13 (d, J = 8.5 Hz, 2H); GCꢀMS (EI, 70 eV): m/z (%) = 137 (100) [M] , 107
(32.8), 91 (90), 79 (17.6), 77 (19.6).
42
1
1
1
1
0. 3-Nitro benzoic acid (3j) : Light yellow solid; yield 0.101 g 83%; M.P. 140ꢀ142 °C; purity 98.5% (HPLC); HꢀNMR
(DMSO, 500 MHz): δ = 7.78ꢀ7.81 (t, J = 8 Hz, 1H), 8.32ꢀ8.34 (t, J = 7.5 Hz, 1H), 8.44ꢀ8.46 (m, 1H), 8.601ꢀ8.604 (d, J = 1.5
Hz, 1H). 13.6 (s, broad, 1H); EIꢀMS = 165.90 [MꢀH].
4
2
1
1. 4-Nitro benzoic acid (3k) : Light yellow solid; yield 0.104 g 85% yield; M.P. 235ꢀ236 °C; purity 98.8% (HPLC); Hꢀ
NMR (DMSO, 400 MHz): δ = 8.17ꢀ8.20 (m, J = 9.08 Hz, J = 1.84 Hz, 2H), 8.29ꢀ8.32 (m, J = 9.08 Hz, J = 1.88 Hz, 2H),
13.18 (s, broad, 1H); EIꢀMS= 165.93 [MꢀH].
4
5,46
1
2. 3-Nitrophenol (3l)
: White solid; yield 0.105 g 82%; M.P. 96ꢀ97 °C; purity 98.6% (GC); HꢀNMR (CDCl , 400 MHz): δ
3
=
5.96 (s, 1H), 7.22ꢀ7.19 (m, 1H), 7.41 (t, J = 8.2 Hz, 1H), 7.72 (t, J = 2.0 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1 H); GCꢀMS (EI,
+
7
0 eV): m/z (%) = 139 (100) [M] , 93 (52.4), 81 (23.2).
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3. 4-Nitrophenol (3m)
: Light yellow solid; yield 0.106 g83%; M.P. 114ꢀ116 °C; purity 99.0% (GC); HꢀNMR (DMSO,
500 MHz): δ = 6.065 (s, 1H), 6.935ꢀ6.953 (d, J = 9 Hz, 2H); 8.18ꢀ8.198 (d, J = 9 Hz, 2H). GCꢀMS (EI, 70 eV): m/z (%) =
+
1
39 (100) [M] , 93 (31.2), 81 (20), 65 (86.8).
4
8
1
4. N-(4-nitrophenyl)acetamide (3n) : colorless solid; yield 0.103 g86%; M. P. 209ꢀ211; purity 98.7% (GC); H NMR (500
MHz, DMSO) δ 2.10 (s, 3H), 7.80ꢀ7.79 (d, J = 5 Hz, 2H), 8.18ꢀ8.17 (d, J = 5 Hz, 2H), 10.52 (s, 1H). GCꢀMS (EI, 70 eV):
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4
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8
9
0
+
m/z (%) = 180 (33) [M] , 138 (100), 122 (5.59), 108 (28.4), 92 (26.3).
4
9,50
1
1
5. 4-nitrobenzonitrile (3o)
: Light yellow solid; yield 0.110 g 88%; M.P. 145ꢀ146 °C; purity 99.1% (GC); HꢀNMR
(
CDCl 400 MHz): δ = 7.87ꢀ7.91 (m, J = 8.0, 2H), 8.35ꢀ8.38 (m, J = 8.8, 2H); GCꢀMS (EI, 70 eV): m/z (%) = 148 (60)
3,
+
[M] ,118 (10.6), 102 (100), 90 (29.4), 75 (47.5).
5
1
16. 1-nitro-3-(trifluoromethoxy)benzene (3p) : Pale yellow liquid; yield 0.105 g 90%; B.P. 208ꢀ210 °C; purity 98.1% (GC);
1
H NMR (500 MHz, CDCl ) δ 7.34 (dd, J = 15.4, 9.1 Hz, 2H), 8.28 – 8.24 (m, 1H), 8.39 – 8.35 (m, 1H); GCꢀMS (EI, 70
3
+
eV): m/z (%) = 207 (66) [M] , 177 (28), 161 (13), 95 (100), 92 (27), 75 (27).
5
2
1
1
1
1
7. 1-(4-nitrophenyl)ethanone (3q) : Light yellow solid; yield 0.115 g 94%; M.P. 76ꢀ78 °C; purity 99.2% (GC); HꢀNMR
(CDCl , 400 MHz): δ = 2.69 (s, 3H), 8.11ꢀ8.14 (m, J = 8.0 Hz, J = 2.16 Hz, 2H), 8.30ꢀ8.34 (m, J = 8.0 Hz, J = 2.24 Hz, 2H);
3
+
GCꢀMS (EI, 70 eV); m/z (%) = 165 (17.8) [M] , 150 (100), 120 (20.8), 104 (41.6), 92 (24.9), 76 (25.9).
4
2
1
8. (4-nitrophenyl)methanol (3r) : Pale yellow solid; yield 0.104 g 84%; M.P. 92ꢀ94 °C; purity 99.5% (GC); H NMR (500
MHz, CDCl ) δ 2.00 (d, broad 1H), 4.84 (d, J = 5.7 Hz, 2H), 7.54 (dd, J = 8.8 Hz, 2H), 8.22 (dd, J = 8.6 Hz, 2H); GCꢀMS
3
+
(EI, 70 eV): m/z (%) = 153 (18) [M] , 136 (14), 107 (53), 89 (35), 77 (100), 63 (20).
5
3
1
9. 2-nitrophenol (3s) : Light yellow solid; yield 0.113g 89%; M.P. 43ꢀ44 °C; purity 99.5% (GC); HꢀNMR (CDCl , 400
3
MHz): δ = 6.97ꢀ7.02 (m, J = 7.24 Hz, 1H), 7.15ꢀ7.17 (dd, J = 8.48 Hz, 1H), 7.57ꢀ7.61(m, J = 7.28 Hz, 1H), 8.10ꢀ8.12 (dd, J
+
=
8.52 Hz, 1H), 10.59 (s, 1H); GCꢀMS (EI, 70 eV): m/z (%) = 139 (100) [M] , 122 (6.70), 109 (25.2), 93 (10), 84 (28.8), 65
(
39.2), 64 (21.1), 63 (32.7).
5
4
1
20. 2-nitroaniline (4a) : Orange solid; yield 0.121 g 95%; M.P. 72ꢀ73 °C; 99.8% (GC); HꢀNMR (CDCl , 400 MHz): δ = 6.06
3
(
s, 2H, 6.68ꢀ6.72 (m, J = 8.48 Hz, 1H), 6.79ꢀ6.82 (dd, J = 8.4 Hz, 1H), 7.34 ꢀ 7.38(m, J = 8.44 Hz, 1H), 8.1ꢀ 8.13 (dd, J =
+
8
.64 Hz, 1H); GCꢀMS (EI, 70 eV): m/z (%) = 138 (100) [m] , 108 (19.2), 92 (59.2), 80 (20.4), 65 (88.8).
55,56
1
2
2
1. 2,4-Dinitroaniline (4b)
: Yellow orange solid; yield 0.109 g 89%; purity 99.4% (HPLC); M.P. 182ꢀ183 °C; HꢀNMR
(DMSO, 400 MHz): δ = 7.09ꢀ7.11 (d, J = 9.44 Hz, 1H), 8.09ꢀ8.12 (m, J = 9.4 Hz, J = 2.68 Hz, 1H), 8.31ꢀ8.33 (s broad, 2H),
8
.801ꢀ8.808 (d, J = 2.64 Hz, 1H); EIꢀMS = 182.09 [MꢀH].
5
7,58
1
2. 2-Methyl-4-nitro aniline (4c)
: Yellow solid; yield 0.117 g 87%; M.P. 130ꢀ132 °C; 99.3% (GC); HꢀNMR (CDCl , 400
3
MHz): δ =2.23 (s, 3H), 3.93 (s, 2H), 7.13ꢀ7.15 (d, J = 8.12 Hz, 1H), 7.48ꢀ7.49 (d, J = 2.24 Hz, 1H), 7.51ꢀ7.54 (dd, J = 8.16
+
Hz, 1H); GCꢀMS (EI, 70 eV): m/z (%) = 152 (89) [M] , 122 (10.57), 106 (77.49), 94 (21.94), 77 (83.1).
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2
3. 2-methoxy-4-nitroaniline (4d)
: Yellow solid; yield 0.110 g 90%; M.P. 140ꢀ141 °C; purity 99.3% (GC); H NMR (500
MHz, DMSO) δ 3.86 (s, 3H), 6.43 (s, 2H), 6.64 (d, J = 8.8 Hz, 1H), 7.56 (d, J = 2.2 Hz, 1H), 7.73 (dd, J = 8.8, 2.3 Hz, 1H);
+
GCꢀMS (EI, 70 eV): m/z (%) = 168 (100) [M] , 153 (40), 122 (29), 107 (16), 95 (37), 92 (13).
6
1
1
2
4. 2,6-Dichloro-4-nitro aniline (4e) : Yellow solid; yield 0.108 g 92%; M.P. 189ꢀ190 °C; purity 99.1% (GC); HꢀNMR
10
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19
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58
59
60
+
(
CDCl , 400 MHz): δ = 5.17 (s, 2H), 8.16 (s, 2H); GCꢀMS (EI, 70 eV): m/z (%) = 208 (54) [M] , 178 (54.8), 160 (51.6), 135
3
(17.2), 124 (100), 90 (28.4), 63 (30.8).
6
2,63
1
25. 2-Cyano-4-nitro aniline (4f)
: Light yellow solid; yield 0.113 g 90%; M.P. 210ꢀ211 °C; purity 99.0% (GC); HꢀNMR
(
DMSO, 400 MHz): δ = 6.85ꢀ6.87 (d, J = 9.4 Hz, 1H), 7.38 (s, 2H), 8.06ꢀ8.09 (m, J = 9.36 Hz, J = 2.68 Hz, 1H), 8.30ꢀ8.31
+
(
d, J = 2.68 Hz, 1H). GCꢀMS (EI, 70 eV): m/z (%) = 163 (97.6) [M] , 147 (4.6), 133 (70.4), 117 (63.2), 90 (100), 78 (13.2),
6
3 (56).
6
4
1
26. 2-Bromo-6-cyano-4-nitroaniline (4g) : Yellow solid; yield 0.106 g 93%. M.P. 183ꢀ184 °C, purity 98.7% (HPLC); Hꢀ
NMR (DMSO, 400 MHz): δ = 7.42 (s, 2H), 8.42ꢀ8.44 (m, J = 2.56 Hz, 2H). GCꢀMS (EI, 70 eV): m/z (%) = 243 (19.79)
+
[
M] , 241 (19.93), 211 (17.90), 195 (9.04), 168ꢀ(6.01), 143 (1.23), 116 (36.98), 103 (3.06), 88 (14.45), 77 (7.04), 65 (11.95),
5
2ꢀ(10.63), 40 (100%).
6
5,66
1
27. 4-nitro-N-phenylaniline (4h)
: Yellow solid; yield 0.099 g 85%; M. P. 132ꢀ134 °C; purity 99.2% (GC); H NMR (500
MHz, CDCl ) δ 6.30 (s, 1H), 6.97 – 6.93 (m, 2H), 7.18 (t, J = 7.4 Hz, 1H), 7.22 (d, J = 7.6 Hz, 2H), 7.42 – 7.37 (m, 2H),
3
+
8
.15 – 8.11 (m, 2H); GCꢀMS (EI, 70 eV): m/z (%) = 214 (65) [M] , 184 (26), 167 (61), 142 (12), 77 (24).
67,68
1
2
2
8. N-methyl-2-nitro aniline (4k)
: Brown orange solid; yield 0.111 g 89%; M.P. 34ꢀ35 °C; purity 99.7% (GC); HꢀNMR
(
CDCl , 400 MHz): δ = 2.95 (s, 3H), 6.56ꢀ6.60 (m, J = 8.36 Hz, 1H), 6.76ꢀ6.78 (m, J = 8.72 Hz, 1H), 7.37ꢀ7.41 (m, J = 8.0
3
Hz, J = 1.52 Hz, 1H), 7.97 (s, broad, 2H), 8.09ꢀ8.11 (m, J = 8.6 Hz, J = 1.6 Hz, 1H); GCꢀMS (EI, 70 eV): m/z (%) = 152
+
(51) [M] , 106 (33.6), 105 (53.2), 77 (100), 51 (41).
6
9
1
9. 4-chloro-2-nitroaniline (4l-a) : Orange solid; M.P. 96ꢀ97 °C; purity 99.6% (GC); H NMR (500 MHz, CDCl ) δ 6.79 (d,
3
+
J = 8.9 Hz, 1H), 7.32 (dd, J = 8.9, 2.5 Hz, 1H), 8.13 (d, J = 2.4 Hz, 1H); GCꢀMS (EI, 70 eV): m/z (%) = 172 (100) [M] ,
142 (92), 114 (17), 101 (19), 90 (48).
7
0
1
5
-chloro-2-nitroaniline (4l-b) :Yellow solid; M.P. 130ꢀ131 °C; purity 99.4% (GC); H NMR (500 MHz, CDCl ) δ 6.13 (s,
3
2
H), 6.68 (dd, J = 9.1, 2.2 Hz, 1H), 6.83 (d, J = 2.1 Hz, 1H), 8.08 (d, J = 9.1 Hz, 1H); GCꢀMS (EI, 70 eV): m/z (%) = 172
+
(88) [M] , 174 (28), 142 (100), 101 (30), 114 (30), 90 (63), 78 (13).
7
1
1
3
0. N-(2-nitrophenyl)acetamide (4m) : Pale yellow solid; yield 0.104 g 87%; M.P. 92ꢀ94 °C; purity 99.5% (GC); H NMR
(
500 MHz, CDCl ) δ 2.32 – 2.27 (m, 3H), 7.18 (dd, J = 8.5, 1.3 Hz, 1H), 7.67 – 7.61 (m, 1H), 8.20 (d, J = 8.4, 1.5 Hz, 1H),
3
+
8.78 – 8.74 (m, 1H), 10.33 (s, 1H); GCꢀMS (EI, 70 eV): m/z (%) = 180 (26) [M] , 138 (79), 92 (46), 65 (21), 43 (100).
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1. 4-chloro-N -phenylbenzene-1,2-diamin (4n)
: Orange solid; yield 0.102 g 90%; M.P. 58ꢀ60 °C; purity 99.1% (GC); H
NMR (500 MHz, CDCl3) δ 7.17 (d, J = 9.2 Hz, 1H), 7.33 – 7.26 (m, 3H), 7.46 – 7.42 (m, 2H), 8.21 (d, J = 2.5 Hz, 2H),
+
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.45 (s, 1H).GCꢀMS (EI, 70 eV): m/z (%) =248 (100) [M] , 214 (31), 201 (59), 167 (85), 139 (26), 77 (44).
ACKNOWLEDGEMENTS
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Authors are thankful to the Institute of Chemical Technology and UGCꢀCAS for providing financial assistance and
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Panjab University for recording H NMR spectra, MS Indoco Remedies Ltd, Rabale Navi Mumbai and IIT SAIF for recording
MS spectra.
SUPPORTING INFORMATION AVAILABLE
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H NMR and MS spectra. This material is available free of charge via the Internet at “http://pubs.acs.org."
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