Graphene Oxide Promoted Oxidative Bromination of Anilines and Phenols in Water

Article abstract of DOI:10.1021/acs.joc.8b00188

The mildly acidic and oxidative nature of graphene oxide, with its large surface area available for catalytic activity, has been explored in aromatic nuclear bromination chemistry for the first time. The versatile catalytic activity of graphene oxide (GO) has been used to selectively and rapidly brominate anilines and phenols in water. The best results were obtained at ambient temperatures using molecular bromine in a protocol promoted by oxidative bromination catalyzed by GO; these transformations proceeded with 100% atom economy with respect to bromine and high selectivities for the tribromoanilines and -phenols. Reduced graphene oxide (r-GO) was observed to form after the second recycle (third use) of GO. This technique is also effective with N-bromosuccinimide (NBS) as the brominating reagent. In the case of NBS, reactions were instantaneous and the GO displayed excellent recyclability without any loss of activity over several cycles.

Full text of DOI:10.1021/acs.joc.8b00188

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Graphene oxide promoted oxidative
bromination of anilines and phenols in water
Prashant V Ghorpade, Dattatray Appassa Pethsangave, Surajit Some, and Ganapati S. Shankarling
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00188 • Publication Date (Web): 24 Apr 2018
Downloaded from http://pubs.acs.org on April 24, 2018
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The Journal of Organic Chemistry
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Graphene oxide promoted oxidative bromination of anilines and
phenols in water
Prashant Vasantrao Ghorpade, Dattatray Appassa Pethsangave, Surajit Some* and Ganapati Subray
Shankarling*
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Department of Dyestuff Technology, Institute of Chemical Technology, N. P. Marg, Matunga, Mumbai,
India.
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Eꢀmail: gs.shankarling@ictmumbai.edu.in.
Abstract: The mildly acidic and oxidative nature of graphene oxide, with its large surface area
available for catalytic activity, has been explored in aromatic nuclear bromination chemistry for the
first time. The versatile catalytic activity of graphene oxide (GO) has been used to selectively and
rapidly brominate anilines and phenols in water. The best results were obtained at ambient
temperatures using molecular bromine in a protocol promoted by oxidative bromination catalyzed by
GO; these transformations proceeded with 100% atom economy with respect to bromine, and high
selectivities for the tribromoanilines and ꢀphenols. Reduced graphene oxide (rꢀGO) was observed to
form after the second recycle (third use) of GO. This technique is also effective with Nꢀ
bromosuccinimide (NBS) as the brominating reagent. In case of NBS, reactions were instantaneous
and the GO displayed excellent recyclability without any loss of activity over several cycles.
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Introduction: The nuclear bromination of aromatic compounds is a fundamental process1 and one
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of the most important CꢀH bondꢀfunctionalizing reactions in synthetic chemistry.2 Among aromatic
compounds, anilines and phenols are favored substrates for these reactions due to their good
reactivities and high product utilities; these compounds are promising intermediates in the syntheses
of fine chemicals, agrochemicals, pharmaceuticals, and dyes. In addition, brominated aromatic
compounds play vital roles in preparative methods for specialty chemicals such as herbicides,
pesticides, and fire retardants.3 Moreover, many brominated compounds exhibit antitumor,
antibacterial, antifungal, antineoplastic, antiviral, and antioxidant properties.4
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A plethora of information is available for the bromination of unprotected anilines and phenols.
Most of these methods are devoted to the generation of paraꢀmonobrominated products,5–15 while
others are dedicated to meta selectivity,2 and only a few result in ortho selectivity.16 There are very
few reports that describe selectivity for tribrominated products.4,17,18 Salakhov and coworkers obtained
tribrominated products in high yields through oxidative bromination with KBr and hydrogen peroxide in
HCl;17 however, they were unable to avoid the use of a hazardous protic acid. The use of TsNBr2 (as
the brominating agent) and organic solvents are shortcomings of the method employed by Saikiya
and coworkers.4 In another report by Kumar et al. aimed at tribrominated products from phenols and
anilines employing molecular bromine, atom economy was of concern as only 50% of the bromine
was delivered to the final products.18 Considering the cost of bromine, the use of molecular bromine in
100% atom economy during the direct bromination of aromatic substrates in water is highly desirable.
It is difficult to consider aromatic bromination without molecular bromine.19 Molecular bromine
is an inherently hazardous reagent because of its toxicity, corrosive nature, and high volatility.
Another major drawback of the use of bromine involves the formation of highly corrosive HBr gas
which has its own postꢀformation hazards under different reaction conditions; however, HBr formed in
this manner can be used wisely for further bromination through its oxidation. This inevitably demands
the use of metal catalysts and oxidizing agents that make the process expensive and environmentally
unsafe.18 Oxidative bromination, in which the brominating reagent is prepared in situ from a bromide
salt, is considered to be biomimetic and ecofriendly,19 and various oxidative bromination reactions
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have been reported in the literature. Iskara et al. have painstakingly reviewed halogenations of this
kind over the past five decades in an excellent review.19
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Nonꢀtoxicity, abundance, recyclability, low cost, and minimal ecological impact are desirable
properties of a green catalyst.20 Bielawski et al. have elegantly reviewed the wide synthetic utility of
heterogeneous carbon materials.21 In the quest for sustainability, graphene oxide (GO) is a good
alternative to many hazardous catalysts, such as transition metals, for oxidation reactions.20 GO is
also used as a support for the immobilization of metals during heterogeneous catalysis.22–24 A review
by Bielawski et al. provides inꢀdepth understanding of the basic structural properties, characterization
methodologies, catalytic, and biomedical applications of GO.25 As GO is highly functionalized by
oxygen, it has been effectively employed as an oxidant in a variety of reactions;20 oxidations of
sulfides,26 primary amines,27 alkenes, and alcohols28 have been demonstrated recently. Owing to its
large surface area and the presence of acidic functional groups (phenolic, hydroxylic, and
carboxylic),29 GO has been fruitfully explored for the catalysis of a variety of fundamental reactions,
such as Friedel–Crafts reactions,30 hydrations, azaꢀMichael additions, condensations, ringꢀopening
polymerizations31, Michael addition reactions, and CꢀH bond oxidation reactions32 and has been
extensively reviewed by Mohammadi et al.33 Very recently Gong and coworkers reported the
iodination of aromatics and ketones34 and the trifluoromethylation of arenes35 using GO as a metalꢀ
free catalyst. The surface chemistry of GO can also be tailored to achieve desired physical and
chemical properties.29 Nagai et al. meticulously examined the catalytic activities of graphite and
graphene oxides for the FriedelꢀCrafts alkylation or bromination of phenol with tꢀbutyl bromide.36 As
part of this study, they showed that Brꢀ is oxidized to Br2Br+ on the GO surface. This groundꢀbreaking
study, and knowledge of the catalytic properties of GO, inspired us to investigate the oxidative
bromination of anilines and phenols by directly employing molecular bromine. This innovation was
expected to improve bromination efficiency, atom economy, and streamline bromination conditions by
removing the need for intermediate reagents, such as tꢀbutyl bromine, that are themselves prepared
using Br2 or HBr. To our delight, not only did we realize this objective, but the protocol developed in
this work provided 2,4,6ꢀtribrominated products that complement the mixtures of 4ꢀbromo and 2,4ꢀ
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dibromophenols prepared by Nagai et al.; indeed 2,4,6ꢀtribromophenol was not formed in reactions
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using tꢀbutyl bromide and GO.
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Although molecular bromine is used extensively for the bromination of anilines and phenols,
complex mixtures of monoꢀ, diꢀ, triꢀ, and even tetrabrominated products often result.18 In the above
context, a metalꢀfree process that utilizes molecular bromine completely and offers high selectivity for
a tribrominated product is of unquestionable importance. Herein we report GO as an allꢀinꢀone
catalyst that initiates and effects rapid oxidative bromination through the dual activation of the
substrate and molecular bromine in water.
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Result and Discussion: In preliminary experiments, the desired amount of GO was dispersed
(exfoliated by sonication) in a sufficient quantity of water, and the required amount of aniline was
added under vigorous stirring. Interestingly, we observed that the added aniline is adsorbed onto the
GO surface. This adsorption is visibly noticeable and was further supported by IR spectroscopy. This
adsorption is attributable to strong Hꢀbonding between the protons of aniline and the oxygen
functionalities on the GO surface and is evidenced by shifts in the IR absorptions of the oxirane
groups on the GO surface to lower frequencies, and changes in carbonyl absorption intensities from
strong to very weak. The IR absorption peaks for aniline supported on GO (GOS2) observed at 3439
cmꢀ1 and 3380 cmꢀ1 merged in peak centered around 3340 cmꢀ1 which corresponds to stretching of –
NH2 group of aniline. Peaks at 1725 cmꢀ1 of carbonyl group of GO shriveled to very weak band as an
effect of Hꢀbonding with hydrogen of –NH2 group of aniline. A new strong band at 1610 cmꢀ1 appeared
corresponding to ꢀNH2 scissoring and had shift of around 10 cmꢀ1 from its standard value due to Hꢀ
bonding with oxygen present on GO surface. Also, a red shift is observed in epoxide peak from 1045
to 1040 cmꢀ1 due to Hꢀbonding of aniline hydrogens to oxygen of epoxide (Figure S1 in SI).
Subsequently, the required amount of bromine was added dropwise to the reaction mixture.
To our surprise, the bromine color disappeared instantaneously, and no brown fumes were observed
over the surface of the reaction mixture, even at room temperature; this indicates complete
engagement of the reagent with the GO surface during the reaction. Upon optimization of the reaction
of aniline with molecular bromine, we found that only 1.5 mol equiv of molecular bromine was
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sufficient to drive the reaction to completion, furnishing the 2,4,6ꢀtribromoaniline product in excellent
yield. This result clearly indicates that both of the Br atoms of molecular bromine are utilized during
the bromination of aniline. Encouraged by these results, we developed an optimized synthetic
protocol.
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Scheme 1: Where G = -NH2, -OH. R = -H, -NO2, -Cl, -OMe, -CHO, -COOH, -F,-CH3, n-butyl.
We found that 2.0 wt % (w.r.t. substrate) of GO is sufficient to complete the reaction. Ambient
temperature was observed to be optimal for this process (Table1). When Br2 was used in limiting
quantities, i.e., 1.0 mol equiv, the major product formed was tribromoaniline (57%). In control
experiments (without GO) 1.5 and 3 mol equiv of bromine afforded 2,4,6ꢀtribromoaniline in 31% and
76% yields respectively. Interestingly, we found that GO significantly enhances the product yields to
93% with the same equivalents of bromine. This clearly validates the atom economy of the process.
For metaꢀsubstituted anilines and phenols, 1.5 mol equiv of bromine was required to provide the
corresponding triꢀbrominated product. Half or one mol equiv of bromine was sufficient to convert
ortho and/or para monoꢀ or diꢀ substituted compounds to the desired product (Scheme 1). A number
of different anilines and phenols were subsequently screened using the developed protocol (Table 2).
Table 1: Optimization study of bromination of aniline.
Entry GO loading
(mg)
Amount of Br2
(mole equivalent)
Temperature
(in °C)
Time (in GC Yield [a]
minutes)
Isolated
Yield (%)
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1.5
1.5
1.5
2.0
1.0
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1.5
1.5
RT[b]
RT
RT
RT
RT
RT
RT
RT
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1.5
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1.5
RT
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92
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RT
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120
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control
control
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RT
RT
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Table 1: Optimization study in bromination of aniline to 2,4,6-tribromoaniline. [a] calculated by area under peak
normalization [b] RT = ambient temperature. [c]= 3 mol equiv. of butylated hydroxyl toluene (BHT) was used as radical
scavenger. [d] NBS was used as a bromine source and BHT used as a radical scavenger.
No specific trends were observed in relation to product yields and the time taken for the
reactions to proceed to completion in the presence of electron withdrawing/donating groups.
Interestingly, no benzylic bromination was observed in case of pꢀtoluidine (Table 2 entry 8) or 4ꢀ(nꢀ
butyl) aniline (Table 2 entry 4). A variety of phenols furnished goodꢀtoꢀexcellent product yields and
selectivities under similar reaction conditions.
Table 2: Various important anilines and phenols in substrate study.
Yielda
Melting point °C
Entry
Substrate
Product
Time (Min)
(%)
Observed
Literature
93b
98e
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30
121
12018
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3
30
10
91c
95
93ꢀ9537
92c
206
20618
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98c
119
103
ꢀꢀꢀꢀꢀꢀꢀ
95c
103ꢀ10438
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20
84b
98
83
6939
95b
83ꢀ8440
NH2
Br
Br
92c
98e
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25
78
74ꢀ7541
8A
94b
95e
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10
170
17017
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98c
89
8942
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90b
130
89ꢀ9043
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OH
2p
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96b
98c
96c
95
92
93ꢀ9444
75ꢀ7645
11418
110
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10
96c
98c
89c
182
226
272
18318
22618
270ꢀ27318
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95d
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96c
82
68
80ꢀ8218
88d
69ꢀ7139
Table 2. [a] Isolated yields, Amount of bromine used (per mole equivalents of substrate) [b] = 1.5, [c] = 1.0, [d] = 0.5. [e] = % yield using
NBS.
While studying catalyst recyclability, we observed that product yields were only slightly lower
during the second use (first recycle) of the catalyst, compared to the first. However, during the second
recycle (third use) the yield was reduced by 10%, and it dropped to 69% during the third recycle
(Figure 1).
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Isolated yield using Bromine
97
Isolated yield using NBS
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100
80
60
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0
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69
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Fresh Load
First
Second
Third
Fourth
Fifth
Recycles
Figure 1: Recyclability study of GO as a catalyst using Br2 and NBS in synthesis of 2,4,6-
tribromoaniline from aniline
We characterized the GO surface after the second recycle by Xꢀray diffraction (XRD), Xꢀray
Photoelectron Spectroscopy (XPS) and infrared (IR) spectroscopy. A strong peak at a θ value of
24.80°, which corresponds to rꢀGO, is clearly observed to be as strong as the GO peak at 11.39°. The
band at 1725 cm−1 observed in the IR spectrum of pristine GO is very weak in the spectrum of GO
after the second recycle, suggesting that the carbonyl groups have been reduced. Bands originally at
3341 and 1040 cm−1 are completely absent indicating the loss of –OH and epoxy groups from the GO
surface. The results of these analyses clearly indicate that GO is gradually converted into rꢀGO
because the functional groups on the surface of the catalyst become reduced during oxidation of Br–
to Br+ (Figure S1 in the SI). We also carried out elemental analysis of GO before and after use. We
observed that the oxygen content of GO after the second recycle is reduced to 15%, compared to
29% prior to use (Table S1 in SI). XPS was used to study the chemical structure and electronic state
of the as made materials. According to the XPS analysis as made GO and GOS1 contains 2.67 and
4.49 C/O ratios respectively. It shows improved C/O ratio from GO to GOS1. This increase is
attributed to reduction of GO surface during oxidative bromination. High resolution XPS spectra of GO
and GOS1 showed C1s and O1 speaks (Figure S4 and S5 in SI). Additionally N1s, Br3d, and Br3p
peaks clearly observed in XPS spectra of GOS1 (Figure S4ꢀS10 in SI). This analysis also reveals
presence of 5.9% of bromine remnant on GO surface after exhaustive use. These observations are in
good agreement with the elemental analysis.
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To investigate the role of oxygen (air) we carried out the reaction under an inert atmosphere.
In a typical experiment the reaction medium was purged with N2 for an hour prior to the addition of
bromine. The reaction was subsequently carried out under N2 for 30 min and the yield of the 2,4,6ꢀ
tribromoaniline was found to be 50%. In addition, monobromoaniline and dibromoaniline were also
observed to be formed in 5% and 6% yields respectively; 39% of unreacted aniline was recovered.
These findings establish the important role of molecular oxygen during oxidative bromination. Ambient
oxygen is able to reꢀoxidize GO and behaves as a terminal oxidant.28 Bielawski et al. studied this kind
of reꢀoxidation of GO with atmospheric oxygen; their computational study revealed that the catalyst
recharging process is energetically favorable.47
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When considering a possible mechanism for the transformations observed herein, it is
important to note that GO appears to participate in the ionization of the BrꢀBr bond. Upon addition, the
bromine color disappeared instantaneously and brown fumes were not observed over the reaction
mixture, as was seen in the case of the control reaction, consistent with the adsorption of bromine
onto the GO surface. As shown in the mechanism, the oxygen of the epoxide group on the catalyst
surface polarizes Br2 (Scheme 2). This eventually leads to the opening of the epoxide ring, providing
space for the attachment of Br– to the surface (Scheme 3). This was evidenced by the FTIR analysis
of GOBr1 (Figure S2 in SI) (sample of GO obtained after reacting GO and bromine under optimized
reaction conditions) which exhibits band at 483 cmꢀ1 corresponding to CꢀBr stretching frequency.48
This particular CꢀBr bond formation via epoxide ring opening is also evidenced in various reaction
conditions as studied by Z. Sofer et al.48,49,50. The CꢀBr band as expected is absent in pristine GO and
GOBrR (GO obtained after the reaction of aniline and bromine) suggest the subsequent oxidative
elimination of Br furnishing the desired products. Attachment of Br+ to the oxygen of the ringꢀopened
epoxide increases its reactivity and facilitates the more rapid and efficient attack of Br+ at the GOꢀ
surfaceꢀattached substrate. H+ is expelled from the substrate to restore its aromaticity (Scheme 4).
The hydroxyl group formed in this manner polarizes a second molecule of bromine and the complete
polarization of molecular bromine leaves the oxygen atom positively charged. The bromide anion
formed during this process subsequently abstracts a bromine atom attached to carbon atom present
on the catalyst surface (Scheme 5). The oxonium ion leaves the GO surface with an electron pair to
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produce hypobromous acid and the simultaneous formation of molecular bromine restores the CꢀC
double bond on the catalyst surface (Scheme 6). Bielawski and coꢀworkers showed that the reduction
of the GO surface by removal of epoxide groups and their regeneration in presence of air are
energetically favorable processes.47 Increasing conjugation or the acquisition of aromaticity may be
the driving forces behind the formation of the CꢀC double bond on the catalyst surface. In this manner,
GO oxidizes bromine, resulting in 100% atom economy during the bromination process.
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Plausible mechanism:
Scheme 2: Attachment of aniline on GO surface and Polarization of Bromine by Oxirane.
Scheme 3: Opening of Oxirane and stabilization of Br anion.
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Scheme 4: Bromination of aromatic carbon by reactive –OBr species and restoration of aromaticity in
substrate.
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Scheme 5: Attack of second Br2 on hydroxyl group formed by oxirane opening and Attack of Brꢀ on Br
attached to catalyst surface induces breaking of CꢀO bond and Formation of Hypobromous acid and
Bromine.
Scheme 6: Formation of double bond on GO surface driven by increase in the conjugation.
To authenticate the mechanistic pathway, we performed experiments using 2,6ꢀdiꢀtꢀbutylꢀ4ꢀ
methylphenol (butylated hydroxy toluene, BHT), a known radical scavenger. Both reactions (with Br2
and NBS) proceed normally in the presence of BHT. Aniline was found to be completely consumed
yielding 2,4,6ꢀtribromoaniline in 85% and 89% yields respectively (Table 1 entry 15 and 16). These
findings eliminate the possibility of a radical mechanism. To check the capacity of GO for oxidizing Br–
to Br+, we attempted the reaction using KBr as a bromide source; however the reaction did not
proceed under the optimized conditions. KBr as a stable ionic salt, is unable to open the epoxide ring
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which is essential for the rapid oxidation of bromide according to the proposed mechanism; otherwise
bromide ions accumulate gently and interact with GO for longer time for effective oxidation.36 In water
as the solvent, KBrꢀsolvent interaction outweigh GOꢀKBr interactions. When bromine is used, the
epoxide ring opens easily to initiate the rapid oxidation process. To overcome the KBr problem, we
employed sodium dodecyl sulfate (SDS) as a phaseꢀtransfer catalysts (PTC) to improve the number
of effective collisions. Unfortunately, 2,4,6ꢀtribromoaniline, dibromoaniline, and 4ꢀbromoaniline were
obtained in 3%, 1%, and 10% yields respectively when SDS was added to the reaction at 60 °C
(Table 3).
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Table 3: Results of reactions done to support the mechanism:
Entry
No.
Reaction
conditions
Aniline
(unreacted)
Yield of the products (%)[a]
4ꢀBromoaniline
Dibromoaniline
2,4,6ꢀtribromoaniline
(11A)[b]
5
(12A)[b]
(1A)[b]
50
%
39
96
1
2
Inert atm. (N2)
In presence of
KBr and SDS
In presence of
KBr and SDS
at 60 °C
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1
ꢀꢀꢀꢀꢀ
2
3
85
10
1
3
Table 3: Study in mechanism of bromination of aniline to 2,4,6-tribromoaniline. [a] calculated by area under peak
normalization [b] confirmed by GCMS.
To further study the catalytic activity of GO during the bromination of aniline with bromineꢀ
carrying reagents, we explored the process using NBS as the brominating agent. To our delight, GO
catalyzed the bromination of aniline to 2,4,6ꢀtribromoaniline in excellent yield; the reaction was
observed to be complete within 5 min. The recyclability of GO was also studied. No drop in yield was
observed up to the fifth recycle, confirming the unswerving catalytic activity of GO for over six cycles
of use. The IR spectrum of reused GO (GOꢀS0 Figure S1 in SI) obtained after the sixth cycle is very
similar to that of pristine GO. This result indicates that GO acts as an acid catalyst for the reaction,
with the acidic groups regenerated during the course of the reaction, which nullifies any changes in
the functional groups on the surface of the catalyst. The bromination of pꢀtoluidine and 3ꢀ
aminobenzoic acid were also investigated using NBS. As previously noted for reactions with Br2, no
benzylic bromination was observed and the selectivity for nuclear bromination was maintained.
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Conclusion: In conclusion, we introduce an environmentally benign, selective, and rapid method for
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the oxidative bromination of anilines and phenols using GO, which acts as a dual enhancer for the
substrate and the reagent. GO also oxidizes bromide to an effective electrophile, resulting in 100%
atom economy for the reagent. No hazardous materials, such as HBr, are involved, making this
process safe and green. The uninterrupted recyclability of the GO catalyst with NBS is appealing for
use in laboratoryꢀscale experiments. Since GO is a nonꢀtoxic, abundant, inexpensive, and ecoꢀfriendly
catalyst, this protocol provides a sustainable process for industrial use. In addition, the use of water
as the solvent minimizes the detrimental impact to the environment. We envisage that this protocol
will open up new avenues for the nuclear bromination of aromatic compounds by directly employing
molecular bromine. We believe that a study into the properties of the rꢀGO formed after exhaustive
reuse of GO as a bromination oxidant would be interesting.
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Experimental Section:
General Experimental Methods:
Materials: Natural graphite powder (325 mesh, Alfa Aeasar), sulphuric acid (98% assay with 99%
purity, Merck), hydrochloric acid, hydrogen peroxide (30%, S D Fine Chem. Ltd.), sodium nitrate
(NaNO3), and PVA (Sigma Aldrich) were procured and used without any further purification. Anilines
and phenols were purchased from Thomas Baker (chemicals) Pvt. Ltd, s. d. fineꢀchem. Ltd and Avra
Synthesis pvt Ltd, India. KMnO4, H2O2, NaNO3, were obtained from Sigma Aldrich. Bromine was
purchased from Central Drug House (P) Ltd, New Delhi. Chemicals and solvents were used as
obtained without further purifications.
Methods: All the reactions were carried out at ambient temperature and pressure conditions without
any inert atmosphere. All the products were purified from suitable solvents and isolated yields are
noted. Conversions and yields are determined by GC with area normalization method. Reactions
were monitored by thin layer chromatography (TLC) using aluminum sheets coated with silica (60,
F254) visualized under UV light (254 nm).
Instruments: Proton nuclear magnetic resonance (1H NMR) spectra were recorded on a Agilent 500
MHz instruments. 1H NMR chemical shifts are reported in part per million (ppm) downfield from TMS.
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And are referenced to residual proton in NMR solvent (CHCl3 = δ 7.26 ppm, acetone = δ 2.05 ppm,
Water = d 1.50 ppm). NMR data are repesented as follows: chemical shifts (δ ppm), multiplicity (s =
singlet, d = doublet, t = triplet, q = quartet, quintet, m = multiplet), coupling constant (J) in Hertz (Hz),
No. of hyrogens = xH. All NMR spectra were recorded at 25 °C. Fourier transform infrared
spectroscopy (FTꢀIR) was measured on
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Perkin–Elmer spectrophotometer. As prepared GO, GOS1, GOS2 were characterized by Xꢀ
ray diffractometer (Shimadzu XRDꢀ6100 using Cu Ka radiations = 1.5405 A°) with scanning
rate 2°per min and 2 theta (θ) angle ranging from 20° to 80° at current 30.0 mA and voltage
40.0 kV. Gas Chromatographic (GC) analysis, for optimization of reaction conditions, was
carried out with Thermo scientific, columnꢀTRꢀ1, 30mX0.25mm, IDX0.25um film, FID detector
and sample size 0.1 l ꢁl. Melting points were recorded on M/s Sunder ind. Product and are
uncorrected. Elemental analysis were carried out on ThermoFinnigan instrument. GCMS
analysis was performed on Shimadzu GCMS QP 2010.
a) Synthesis of graphene oxide (GO): GO was prepared from graphite powder by using modified
Hummer’s method.51
b) Reaction optimization and control experiments: As the process aimed to eliminate organic
solvents all experiments were performed in water. For optimization reaction bromination of aniline
in water was selected as model reaction. Initially 10 mg of GO was taken in 10 mL of water in 50
mL round bottomed flask. Flask was then placed in sonication bath to disperse GO in water. Thus
exfoliation was achieved which is necessary to increase the surface area of the catalyst. Then 0.5
g (0.0053 moles) of aniline was added to the reaction mixture with vigorous stirring till it got
adsorbed on the surface of GO. Association of aniline on GO was clearly noticeable. To this
molecular bromine 1.29 g (0.008 moles, i.e. 1.5 mole equivalents) were added with stirring
keeping the RBF in water bath. Reaction was monitored on TLC. For monitoring the reaction a
small amount of sample was taken from well stirred reaction mixture. Sample was neutralized with
NaHCO3. Then it was extracted with ethyl acetate and spotted on TLC. TLC was developed with
5% ethyl acetate: hexane (v/v). After completion of the reaction 20 mL of water was added to the
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reaction flask. Reaction mass was then filtered through Whatman nylon membrane filter (pore size
0.2 ꢂm). This was thoroughly washed with water twice and the water filtrate was discarded. Then
the precipitate was washed with 5 mL ethanol and then with ethyl acetate to extract the product.
The ethyl acetate was evaporated and solid was then crystallized with ethyl alcohol. Pure product
thus formed was dried and weighed.
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c) General experimental procedure for bromination of anilines and phenols using molecular
bromine: In typical experiment of bromination of anilines and phenols, in 50 mL round bottomed
flask 10 mL of water 10 mg (2% by weight of substrate) of GO were taken and it was dispersed in
water by sonication. To the flask, substrate (0.5 g) was added dropwise (or finely powdered solid)
and stirred well. To this, bromine (1.5 mole equivalent or as required) was added dropwise
keeping the flak in waterꢀbath. The reaction was monitored on TLC and showed complete
conversion w.r.t. starting material within 10 to 35 minutes. To the reaction mass 20 mL of water
was added on completion of reaction. It was then filtered through Whatman nylon membrane
filter (pore size 0.2 ꢂm). The precipitate was washed with water twice. The water filtrate was
discarded. The residual solid was washed with ethanol (2 mL) and then thoroughly with ethanol
(8 mL) or ethyl acetate (7ꢀ8 mL) (depending on solubility of product). The products were
crystallized from the filtrate itself, if the washing solvent is ethanol. Product was obtained by
evaporating ethyl acetate under reduced pressure. The crude product was recrystallized from
ethanol (5ꢀ8 mL). The optimized conditions were applied for synthesis of varied anilines and
phenols. All the products were isolated by filtration and washing with appropriate solvent (ethyl
alcohol/ethyl acetate). Pure products were obtained by recrystallization. Melting points were
obtained and are uncorrected. Products were further conformed by mass, 1H and 13C NMR.
d) Procedure for recycling the catalyst: The catalyst was recovered from the membrane filter
paper after washing the product from it with a suitable solvent. It was dried in the oven at 65ꢀ70
°C for two hours. Thus dried GO was ready for reuse in next batch.
e) Experimental procedure for bromination of anilines using N-bromosuccinimide (NBS): 10
mg of GO was dispersed in 10 mL of water by sonication. To this, substrate was added and
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stirred thoroughly. NBS (3 mole equivalent) was added to the reaction mixture while resting the
flask in water bath. Reaction was monitored on TLC and was completed within five minutes.
f) Experiments in support of the mechanisms:
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i) Reaction using radical scavenger: To authenticate the mechanistic pathway, we have
performed experiments using butylated hydroxyl toluene (BHT) as a radical scavenger. In RBF
10 mL water was taken. To this GO was added and sonicated to exfoliate. Then aniline was
added to it with vigorous stirring. To this mixture BHT 3 mole equiv. was added. The reaction
mixture was stirred well. Now to this bromine or NBS was added and reaction was stirred for
optimized reaction time. Reactions were worked up and the results are tabulated in table S1. In
both the cases with Br2 and NBS, reactions proceed with normal course.
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ii) Reaction under inert atmosphere, (N2): To understand the role of oxygen (air) we carried out
reaction under inert atmosphere. In typical experiment, GO was sonicated in water and aniline
was adsorbed onto it. Then N2 was purged into the reaction media for an hour before addition of
bromine. Subsequently the reaction was carried out under N2 for 30 minutes. Reaction was
worked up and products are tabulated in Table 3.
iii) Reaction using KBr as bromide source: To check the oxidative capacity of GO for oxidizing Brꢀ
to Br+, we performed the reaction using KBr as a bromide source. In typical experiment after
adsorption of aniline SDS was added to the reaction mixture. Reaction was carried out at room
temperature using KBr for 12 hours. Reaction was worked up and products were GC analyzed. In
another experiment reaction was heated at 60 °C for 12 hours. Products are analyzed by gas
chromatography. Products were analyzed by GCMS.
iv) A reaction without substrate was done to know the effect of bromine on surface of catalyst. In
10 mL water 10 mg of GO was exfoliated by sonication, and bromine (1.29 g) was added.
Reaction mass was stirred for 30 minutes at ambient temperature. The catalyst was filtered and
washed four times with deionized water to ensure removal of adsorbed bromine. It was dried in
oven at 50 °C for an hour. Sample of thus formed catalyst was analyzed with FTIR.
Similarly, to compare the effect of bromine on surface of catalyst in presence of substrate, a
sample of GO after first use was analyzed by FTIR.
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Compound characterization data:
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1. 2,4,6-tribromoaniline (1A)4: (Solid, faint brown, yield = 1.69 g, 93%), Melting point = 121°C
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(120°C). H NMR (500 MHz, CDCl3) δ 7.51 (s, 2H), 4.57 (s, 2H); 13C NMR (101 MHz, CDCl3) δ
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167.38, 140.98, 133.91, 108.77; GCꢀMS (EI, 70 eV) m/z = 329 (M+), 265, 250,168, 90, 62, 52.
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2. 2,6-dibromo-4-chloroaniline (2A)52: (Solid, white, yield = 1.02 g, 91%), Melting point = 95°C. 1H
NMR (500 MHz, CDCl3) δ 7.39 (s, 2H), 4.55 (s, 2H); 13C NMR (101 MHz, CDCl3) δ 140.91,
131.19 , 122.57 , 108.36; GCꢀMS (EI, 70 eV) m/z = 285 (M+),206, 124, 90, 62.
1
3. 2,6-dibromo-4-nitroaniline (3A)4: (Solid, yellow, yield = 0.98 g, 92%) Melting point = 206°C. H
NMR (500 MHz, CDCl3) δ 8.35 (s, 1H), 5.30 (s, 1H); 13C NMR (101 MHz, DMSO) δ 149.62,
136.91, 128.41, 105.77; GCꢀMS (EI, 70 eV) m/z = 296 (M+), 266, 250, 168, 90, 63, 52.
4. 2,6-dibromo-4-butylaniline (4A)53: (Solid, dark red, yield = 0.99 g, 98%) Melting point = 119°C.
1H NMR (500 MHz, CDCl3) δ 7.20 (s, 2H), 4.40 (s, 7.5 Hz, 2H), 2.46 (t, 2H), 1.53 (quintet, J =
15.3, 7.5 Hz, 2H), 1.33 (sextet, J = 14.6, 7.3 Hz, 2H), 0.92 (t, J = 7.3 Hz, 3H); 13C NMR (101
MHz, CDCl3) δ 139.61, 134.53, 131.52, 108.72, 34.06, 33.50, 22.10, 13.84; GCꢀMS (EI, 70 eV)
m/z = 309 (M+), 264, 183, 104, 90, 77, 65, 52.
5. 2,4-dibromo-6-chloroaniline (5A)54: (Solid, reddish brown, yield = 1.06 g, 95%) Melting point =
1
103°C. H NMR (500 MHz, CDCl3) δ 7.48 (d, J = 2.1 Hz, 1H), 7.37 (d, J = 2.1 Hz, 1H), 4.52 (s,
2H); 13C NMR (101 MHz, CDCl3) δ 140.39 (s), 133.10, 130.85, 119.59, 109.20, 108.36; GCꢀMS
(EI, 70 eV) m/z = 285 (M+), 206, 168, 124, 90, 62, 52.
6. 2,4,6-tribromo-3-nitroaniline (6A)18: (Solid, yellow, yield =1.13 g, 84%) Melting point = 98°C. 1H
NMR (500 MHz, CDCl3) δ 7.70 (s, 1H), 4.92 (s, 2H); 13C NMR (101 MHz, DMSO) δ 151.44,
144.87, 135.29, 109.54, 98.01, 96.41; GCꢀMS (EI, 70 eV) m/z = 374 (M+), 328, 316, 301, 265,
249, 214, 168, 89, 61, 52.
7. 2,4,6-tribromo-3-methoxyaniline (7A)55: (Solid, buff, yield =1.39 g, 95%) Melting point = 83°C.
1H NMR (500 MHz, CDCl3) δ 7.59 (s, 1H), 4.65 (s, 2H), 3.86 (s, 3H); 13C NMR (101 MHz, CDCl3)
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δ 153.98, 142.73, 134.06, 104.76, 104.02, 103.50, 60.46; GCꢀMS (EI, 70 eV) m/z = 359 (M+),
316, 199, 156, 76, 61, 52.
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8. 2,6-dibromo-4-methylaniline (8A)4: (Solid, white, yield = 1.14 g, 92%) Melting point = 78°C. 1H
NMR (500 MHz, CDCl3) δ 7.21 (s, 2H), 4.39 (s, 2H), 2.22 (s, 3H); 13C NMR (101 MHz, CDCl3) δ
139.49, 132.12, 129.29, 108.68, 19.77; GCꢀMS (EI, 70 eV) m/z = 267 (M+), 184, 104, 92, 77, 65,
52.
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9. 3-amino-2,4,6-tribromobenzoic acid (9A)56: (Solid, buff, yield = 1.28 g, 94%) Melting point =
1
170°C. H NMR (500 MHz, CDCl3) δ 7.65 (s, 1H), 4.77 (s, 2H); 13C NMR (101 MHz, DMSO) δ
167.21, 143.39, 139.14, 134.49, 108.01, 104.13, 102.67; GCꢀMS (EI, 70 eV) m/z = 375 (M+), 329,
250, 168, 90, 62, 52.
10. 2,4-dibromo-3,6-dichloroaniline (10A)57: (Solid, buff, yield = 0.96 g, 98%) Melting point = 89°C.
1H NMR (500 MHz, CDCl3) δ 7.53 (s, 1H), 4.72 (s, 2H); 13C NMR (101 MHz, CDCl3) δ 141.89,
133.64, 131.56, 117.33, 109.51, 108.73; GCꢀMS (EI, 70 eV) m/z = 319 (M+), 240, 204, 159, 124,
89, 61, 52.
11. 2,4,6-tribromo-3-nitrophenol (1P)58: (Solid, grey, yield = 1.21 g, 90%) Melting point = 130°C.
1H NMR (500 MHz, CDCl3) δ 7.81 (s, 1H), 6.23 (s, 1H); 13C NMR (101 MHz, DMSO) δ 152.83,
151.39, 135.84, 115.30, 104.69, 102.23; GCꢀMS (EI, 70 eV) m/z = 374 (M+), 330, 301, 268, 250,
237, 221, 168, 140, 90, 77, 61, 53.
1
12. 2,4,6-tribromophenol (2P)4: (Solid, white, yield = 1.69 g, 96%) Melting point = 95°C. H NMR
(500 MHz, CDCl3) δ 7.60 (s, 2H), 5.88 (s, 1H); 13C NMR (101 MHz, CDCl3) δ 148.92, 134.19,
112.65, 110.38; GCꢀMS (EI, 70 eV) m/z = 332 (M+), 250, 222, 141, 111, 91, 62, 53.
13. 2,4-dibromo-6-chlorophenol (3P)59: (Solid, white, yield = 1.09 g, 98%) Melting point = 92°C. 1H
NMR (500 MHz, CDCl3) δ 7.56 (d, J = 2.2 Hz, 1H), 7.46 (d, J = 2.2 Hz, 1H), 5.87 (s, 1H); 13C
NMR (101 MHz, CDCl3) δ 148.15, 133.56, 131.37, 121.49, 112.18, 110.79; GCꢀMS (EI, 70 eV)
m/z = 286 (M+), 250, 222, 206, 178, 143, 97, 62, 53.
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14. 2,4-dibromo-6-nitrophenol (4P)60: (Solid, yellow, yield = 1.02 g, 96%) Melting point = 110°C. 1H
NMR (500 MHz, CDCl3) δ 11.06 (s, 1H), 8.26 (d, J = 2.4 Hz, 1H), 8.00 (d, J = 2.4 Hz, 1H); 13C
NMR (101 MHz, CDCl3) δ 151.37, 142.88, 134.34, 126.71, 114.48, 111.48; GCꢀMS (EI, 70 eV)
m/z = 297 (M+), 265, 239, 223, 170, 141, 91, 62, 53.
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15. 3,5-dibromo-4-hydroxybenzaldehyde (5P)61: (Solid, buff, yield = 1.02 g, 96%) Melting point =
182°C. 1H NMR (500 MHz, CDCl3) δ 9.81 (s, 1H), 8.01 (s, 2H), 6.43 (s, 1H); 13C NMR (101 MHz,
CDCl3) δ 188.04, 154.34, 133.61, 110.70; GCꢀMS (EI, 70 eV) m/z = 279 (M+), 251, 223, 170,
143, 91, 63, 53.
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16. 3,5-dibromo-2-hydroxybenzoic acid (6P)18: (Solid, white, yield = 0.97 g, 98%) Melting point =
1
226°C. H NMR (500 MHz, CDCl3) δ 7.60 (s, 2H), 5.88 (s, 1H); 13C NMR (101 MHz, DMSO) δ
170.71, 158.10, 139.70, 132.06, 117.22, 112.08, 109.60; GCꢀMS (EI, 70 eV) m/z = 297 (M+), 252,
133, 119, 105, 91, 71, 57, 43, 41.
17. 3,5-dibromo-4-hydroxybenzoic acid (7P)62: (Solid, white, yield = 0.88 g, 89%) Melting point =
1
272°C. H NMR (500 MHz, CDCl3) δ 7.60 (s, 2H), 5.89 (s, 1H); 13C NMR (101 MHz, DMSO) δ
151.35, 134.45, 113.41, 111.50; GCꢀMS (EI, 70 eV) m/z = 295 (M+), 230, 252, 204, 147, 119,
105, 91, 71, 57, 43, 41.
18. 2-bromo-4-chloro-6-nitrophenol (8P)46: (Solid, yellow, yield = 0.69 g, 95%) Melting point =
117°C. 1H NMR (500 MHz, CDCl3) δ 11.04 (s, 1H), 8.12 (d, J = 2.5 Hz, 1H), 7.87 (d, J = 2.5 Hz,
1H); 13C NMR (101 MHz, CDCl3) δ 150.97, 140.34, 133.90, 125.26, 123.76, 114.21; GCꢀMS (EI,
70 eV) m/z = 253 (M+), 236, 206, 195, 179, 126, 113, 97, 73, 62, 53.
19. 3,5-dibromo-2-hydroxybenzaldehyde (9P)53: (Solid, pale brown, yield = 1.10 g, 96%) Melting
1
point = 82°C. H NMR (500 MHz, CDCl3) δ 11.52 (s, 1H), 9.82 (s, 1H), 7.91 (d, J = 2.3 Hz, 1H),
7.67 (d, J = 2.3 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 194.86, 157.15, 141.85, 134.86, 121.80,
112.42, 111.48; GCꢀMS (EI, 70 eV) m/z = 280 (M+), 223, 170, 155, 143, 119, 63, 53.
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20. 2-bromo-4-methyl-6-nitrophenol (10P)53: (Solid, yellow, yield = 0.667 g, 88%) Melting point
1
2
1
3
4
= 68°C. H NMR (500 MHz, CDCl3) δ 10.98 (s, 1H), 7.91 (s, 1H), 7.71 (s, 1H), 2.36 (s,
5
6
7
8
3H); 13C NMR (101 MHz, CDCl3) δ 149.99, 141.68, 133.71, 130.59, 123.97, 112.74,
20.10; GCꢀMS (EI, 70 eV) m/z = 231 (M+), 186, 135, 94, 77, 65, 51.
9
Supporting Information. Characterization of GO, NMR and Mass spectral graphs.
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