An efficient regioselective bromination protocol of activated coumarins using 2,4,4,6-tetrabromo-2,5-cyclohexadienone

Article abstract of DOI:10.1139/cjc-2013-0230

2,4,4,6-Tetrabromo-2,5-cyclohexadienone mediated bromination of a wide assortment of activated coumarins in acetonitrile has been accomplished with high regioselectivity and good to excellent yields. The selectivity and efficiency of bromination were found to be markedly dependent on electronic factors, particularly degree of electron withdrawal from electron-releasing 7-oxygenated substituents to the C-3 position of the α-pyrone moiety by vinylogous resonance and the presence of nucleophilic additives such as water and tetra-n-butylammonium bromide in the reaction medium. The sole by-product of the reaction was converted back to the reagent by oxidation with KBr-KBrO ₃, which was recycled three times without significant loss of efficiency.

Full text of DOI:10.1139/cjc-2013-0230

1155
ARTICLE
An efficient regioselective bromination protocol of activated
coumarins using 2,4,4,6-tetrabromo-2,5-cyclohexadienone
Nemai C. Ganguly, Subhasis Nayek, and Sumanta Chandra
Abstract: 2,4,4,6-Tetrabromo-2,5-cyclohexadienone mediated bromination of a wide assortment of activated coumarins in
acetonitrile has been accomplished with high regioselectivity and good to excellent yields. The selectivity and efficiency of
bromination were found to be markedly dependent on electronic factors, particularly degree of electron withdrawal from
electron-releasing 7-oxygenated substituents to the C-3 position of the ␣-pyrone moiety by vinylogous resonance and the
presence of nucleophilic additives such as water and tetra-n-butylammonium bromide in the reaction medium. The sole
by-product of the reaction was converted back to the reagent by oxidation with KBr−KBrO3, which was recycled three times
without significant loss of efficiency.
Key words: regioselective bromination, TBCHD, activated coumarins, nucleophilic additives, recyclability of reagent.
Résumé : La bromation d’une grande gamme de coumarines activées a été effectuée avec une très haute régiosélectivité et des
rendements bons a` excellents par réaction avec de la 2,4,4,6-tétrabromo-2,5-cyclohexadiénone dans l’acétonitrile. La sélectivité
et l’efficacité de la bromation dépendent fortement de facteurs électroniques, notamment le degré de transfert d’électrons des
substituants donneurs d’électrons oxygénés en position 7 a` la position C-3 du groupe ␣-pyrone par résonance vinylogue et la
présence d’additifs nucléophiles, tels que l’eau et le bromure de tétra-n-butylammonium, dans le milieu réactionnel. Le seul
sous-produit de la réaction a été reconverti par oxydation avec du KBr−KBrO3 en réactif qui a été recyclé trois fois sans perte
appréciable d’efficacité. [Traduit par la Rédaction]
Mots-clés : bromation régioselective, TBCHD, coumarines activées, additifs nucléophiles, recyclabilité du réactif.
ane dibromide.14 However, the existing methods have certain draw-
Introduction
backs such as use of harsh reaction conditions and focus on specific
Regioselective bromination of activated coumarins is an impor-
target,7a use of halogenated and volatile organic solvents,11a and re-
tant synthetic transformation of considerable contemporary
lease of hazardous HBr during bromination.11b,14 In continuation of
interest owing to diverse synthetic and biological utilities of bro-
our interest in development of environmentally friendly synthetic
mocoumarins. Bromoheteroarenes and bromocoumarins in par-
methodologies,15 we became interested in developing a selective bro-
ticular are useful synthons for transition metal mediated C−C1
mination protocol for activated coumarins based on a mild, easily
and C−N2 bond formations in view of their ready accessibility
accessible solid brominating agent. To this end, we identified 2,4,4,6-
as compared with iodo derivatives and relatively high reactivity
tetrabromo-2,5-cyclohexadienone (TBCHD) that essentially relies on
compared with corresponding chloro compounds. The coumarin
abstraction of Br+ by a nucleophile from its sterically encumbered
core is represented in a host of biologically active compounds
C-4 position and concomitant release of corresponding phenolate
including anticoagulants,3 antitumour agents,4 and anti-HIV
anion (Scheme 1). The selectivity of bromination by this reagent is
agents.5 3-Bromocoumarins serve as building blocks for the syn-
dependent on the steric situation in the vicinity of C-4.
thesis of heat-shock protein 90 (Hsp 90) inhibitor novobiocin an-
TBCHD and its derivatives have been utilized for selective bro-
alogues6 CK2 (casein kinase) inhibitors and antineoplastic drug
mination for activated aromatic and heteroaromatic compounds
candidates.6b,7 8-Bromo-7-O-allylated coumarins offer facile entries
including phenols,16 anilines,16b and flavones17 as well as for
to natural and unnatural linear coumarins by Claisen rearrange-
␣-bromination of aldehydes, ketones,18 and acid chlorides.19 It is
ment where the bromine atom plays crucial role in directing the
migrating allyl moiety to the 6 position and thereafter acts as a
inexpensive, readily accessible from phenol,16a and compatible
with several common organic solvents. TBCHD is more selective
than NBS in bromination reactions20 and this motivated us to
evaluate its hitherto unexplored efficacy for selective bromina-
tion of activated coumarins. Herein, we reveal the results of
TBCHD-mediated bromination of a wide variety of activated cou-
marins in acetonitrile (Table 1).
thermolabile group.8 They are also synthetic precursors of linear and
angular furano- and dihydrofuranocoumarins such as marmesin
and psoralin, which are photosensitizers and widely used as an-
tipsoriasis agents.9 Brominated methylcoumarins also provide ac-
cess to several biologically relevant compounds.10 Notably,
usefulness of these molecules hinges upon the specific location of
bromine in the coumarin moiety. This prompted several recent
initiatives towards development of regioselective bromination
protocols of coumarins based on N-bromosuccinimide (NBS),7a,11
including one previously reported by us using NBS in molten
tetra-n-butylammonium bromide (TBAB),11c CuBr2/Al2O3,12 Et4N+
Br− in the presence of hypervalent iodine compounds,13 and diox-
Results and discussion
Initially, coumarin was treated with TBCHD to assess the sus-
ceptibility of the ␣-pyrone double bond towards bromination. It
was thoroughly resistant even under forcing reaction conditions
(TBCHD (2 mol equiv.), acetonitrile, reflux, 15 h). This result is in
Received 23 May 2013. Accepted 16 July 2013.
N.C. Ganguly, S. Nayek, and S. Chandra. Department of Chemistry, University of Kalyani, Kalyani-741235, India.
Corresponding author: Nemai C. Ganguly (e-mail: nemai_g@yahoo.co.in).
Can. J. Chem. 91: 1155–1159 (2013) dx.doi.org/10.1139/cjc-2013-0230
Published at www.nrcresearchpress.com/cjc on 26 July 2013.

1156
Can. J. Chem. Vol. 91, 2013
Scheme 1. Nucleophile-induced bromination by TBCHD.
as in the case of 2, entails that vinylogous bromination occurred
prior to its hydrolysis or these are concomitant events. Notably,
the allylic double bond was generally well tolerated under the
conditions of the present method (entries 4, 8, 9, 11, 14, and 15),
further attesting to the absence of free bromine or bromonium
ion in the reaction medium. In an attempt to control hydrolytic
cleavage of the acetoxy group of 7-acetoxy-8-allylcoumarin (6), the
reaction was performed in dry acetonitrile under mild warming
conditions (50–60 °C). Under these conditions, the hydrolysis of
the acetoxy group was totally suppressed and it was recovered
unchanged, demonstrating that the 7-AcO group neither partici-
pated in heterocyclization nor was activating enough to ensure
ring bromination. However, when it was submitted to reaction
with TBCHD (1.2 mol equiv.) in dry acetonitrile in the presence of
TBAB (1.5 mol equiv.), addition of bromine occurred in the allylic
side chain (entry 6 6 h). This is reminiscent of nucleophilic activa-
tion of NBS by the unsolvated bromide ion provided by TBAB, as
previously reported by us.11c
sharp contrast with the reported ease of formation of coumarin-
3,4-dibromide with dioxane dibromide14 that acts as a surrogate
of bromine. It is also slowly formed in low yield (23%, 10 h) by the
reaction of coumarin with NH4Br (4 mmol) and Oxone in acetoni-
trile under reflux that proceeds via bromonium ion intermedi-
ate.21 These results suggest a different mechanistic paradigm for
TBCHD-mediated bromination. Inasmuch as bromination of acti-
vated aromatics by TBCHD is a nucleophile-driven process, we felt
that the activation of the coumarin moiety was imperative for
bromination, and therefore, we explored the feasibility of bromi-
nation of 4,7-dimethylcoumarin (1) that represents a substrate
with modest activation in both benzene and pyrone ring. Bromi-
nation of 1 with TBCHD (1 mol equiv.) in acetonitrile under reflux
cleanly delivered 3-bromo-4,7-dimethylcoumarin (1a) in 85% yield
(entry 1). Notably, side-chain bromination and nuclear bromina-
tion of the benzene did not occur. Encouraged by this result, we
proceeded to explore the bromination of 7-hydroxycoumarin (2), a
naturally occurring coumarin of immense importance in the bio-
genetic map of coumarins and precursor of several coumarin mo-
tifs. It is endowed with substantial nucleophilic activity due to
ionization to its oxyanion and three nucleophilic sites at the C-3,
C-6, and C-8 positions. Gratifyingly, it underwent selective mono-
bromination to 8-bromo-7-hydroxycoumarin (2a), albeit slowly, in
68% yield (entry 2 8 h). This presumably stems from its sparing
solubility in acetonitrile and also partly due to unfavourable steric
factor associated with ortho nucleophilic attack at C-4 of the re-
agent. Interestingly, bromination of 2 with NBS (1.1 mol equiv.,
CH3CN, room temperature, 3 h) was found to be unselective, pro-
viding 3,6,8-tribromo-7-hydroxycoumarin in 26% yield. In fact,
one-pot selective bromination at C-8 is unprecedented and 2a was
previously accessed by a multistep sequence in low overall yield.13
We reasoned that water might act as a nucleophilic activator to
generate a more potent bromonium ion equivalent, H2OBr+ from
TBCHD22 (Scheme 1). Coupled with substrate activation by facili-
tating ionization, bromination in aqueous acetonitrile was antic-
ipated to be faster and more efficient. Treatment of 2 in aqueous
acetonitrile (CH3CN−H2O, 90:10) for 6 h afforded 2a as the major
product (50%) together with a substantial amount of its regioiso-
mer, 3-bromo-7-hydroxycoumarin 2b (32%). Thus, the selectivity
was compromised to attain higher overall yield (entry 2 6 h). In
contrast, 7-methoxycoumarin (3) underwent surprisingly expedi-
tious and selective monobromination at C-3 to give 3a (entry 3
3 h). Higher solubility in CH3CN and less steric hindrance involved
in C−Br bond formation at C-3 account for this observation. The
marginally higher yield of 3a and its increased rate of formation
(85%, 1 h, entry 3 1 h) in aqueous acetonitrile suggested the implica-
tion of a more potent bromonium ion equivalent, presumably
H2OBr+, as substrate activation by acid ionization is precluded
here. Similar bias towards selective vinylogous bromination was a
persistent feature of 7-allyloxy and 7-acetoxycoumarin (entries 4
and 5). This feature can be explained by substantial electron with-
drawal from these substituents to C-3 and consequent depletion
of electron density at ortho positions, discouraging bromination at
these positions. In fact, the electron withdrawal by the ␣-pyrone
moiety from the benzene ring in the case of 7-acetoxycoumarin (5)
activates its carbonyl towards nucleophilic attack by water, result-
ing in hydrolytic cleavage. Absence of ortho-brominated products,
However, the juxtaposition of 7-oxyanion and pendant epoxi-
dized allyl moiety of complementary reactivities triggered facile
heterocyclization of 7 to hydroxypyranocoumarin and its bromi-
nation to 7a in aqueous acetonitrile. The rate and selectivity of
bromination were comparable with those of 7-methoxycoumarin
(3), suggesting heterocyclization occurred as a prelude to C-3 bro-
mination. There was substantial erosion of selectivity for bromination
of 8-allyl-7-hydroxycoumarin (8) and 6-allyl-7-hydroxycoumarin (9). In-
stallation of the allyl moiety adjacent to 7-OH made bromination
at the vacant ortho position further sterically demanding, thereby
prolonging reaction time and allowing competing C-3 bromina-
tion (entries 8 and 9). The presence of an activating 4-Me group
invariably promoted C-3 bromination in the ␣-pyrone ring. Dibromi-
nation of 7-hydroxy-4-methylcoumarin (10) afforded 3,8-dibromo-
4-methyl-7-hydroxycoumarin (10a) (12h, 40%) (entry10 12 h),
which exhibits specific ATP site directed inhibitory activity to-
wards protein kinases, particularly CK2, in the low micromolar
range and is a potential antineoplastic drug candidate.6b,7 The
yield of 10a was substantially improved by using 2.1 mol equiv. of
the reagent in aqueous acetonitrile (entry 10 7 h). 3,6,8-Tribromo-
4-methyl-7-hydroxycoumarin (10b), a potent pesticide used to con-
trol vectors Culex quinquefasciatus and Aedes aegypti23 responsible
for tropical diseases such as malaria and dengue, could also be
accessed with ease and efficiency employing further excess of the
reagent (3.4 mol equiv.) in aqueous acetonitrile (entry 10 8.5 h).
Surprisingly, 7-acetoxy-4-methylcoumarin (13) was less prone to
hydrolysis than its hydroxy counterpart and delivered 7-acetoxy-
3-bromo-4-methylcoumarin (13a) (entry 13). This is a reflection of
reduced electron demand from 7-OAc to C-3 due to the presence of
electron-releasing 4-Me, making it less susceptible to hydrolytic
cleavage. Unlike 7-oxygenated coumarins, there is no significant
electron withdrawal from electron-releasing substituents at C-6 by
vinylogous resonance. This difference in electronic situation for
6-methoxy/-aminocoumarin allowed faster and predominant, if not
exclusive, ortho bromination at C-5 (entries 16 and 17). This was also
revealed by the unfavourable effect of water on rate and yield of
bromination for 6-methoxycoumarin (16). Addition of 10 mol% of
water to a solution of 16 in nonpolar dichloromethane considerably
slowed down the reaction to give 16a (60%, 1.5 h). The mechanistic
scenario of aromatic bromination generally involves late transition
state with predominant carbocation character.24 The stabilization of
the incipient carbocation intermediate is expected to be strongly
influenced by the electron releasing of the 6-OMe group. It acts as a
hydrogen bond base and its oxygen lone pairs of electrons become
engaged in hydrogen bonding in the presence of water and, there-
fore, less available for stabilizing the carbocation-like transition state
with resultant decrease in reaction rate and efficiency. As ex-
pected, 4-hydroxycoumarin (18) underwent exclusive bromina-
tion at C-3 (entry 18). In the absence of this ring bromination
site, as for the 3-allyl derivative 19, prompt heterocyclization to
Published by NRC Research Press

Ganguly et al.
1157
Table 1. Bromination of coumarins with TBCHD in acetonitrile.
Entry
1
Substrate
Products
Time (h)a
9
Yield (%)b
85
2
(i) 8
(ii) 6
2a, 68
2a, 50; 2b, 32c
3
4
(i) 3
(ii) 1
80
85c
8
80
5
6
10
55c
(i) 4
(ii) 6
No reaction
45
7
8
0.5
90c
13
12
8a, 40; 8b, 15
9
46
10
(i) 12
(ii) 7
(iii) 8.5
10a, 40
10a, 82d
10b, 75e
11
7
78
50
60
45
12
13
14
2
9
15
15
10
40
16
17
(i) 0.75
(ii) 1.5
82
60
1
17a, 70; 17b, 10
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1158
Can. J. Chem. Vol. 91, 2013
Table 1 (concluded).
Entry
18
Substrate
Products
Time (h)a
3
Yield (%)b
75
19
1.5
85
aReaction conditions: substrate (1 mmol), TBCHD (1.1 mol equiv.), acetonitrile (4 mL), reflux, unless otherwise stated.
bYields refer to chromatographically pure products characterized by spectroscopic data (IR, 1H NMR, 13C NMR, and EIMS).
cReaction conditions: substrate (1 mmol), TBCHD (1.1 mol equiv.), acetonitrile−water (9:1) (4 mL), reflux.
dReaction conditions: substrate: TBCHD (1:2.1 mol equiv.), acetonitrile (4 mL), reflux.
eReaction conditions: substrate: TBCHD (1:3.4 mol equiv.), acetonitrile−water (9:1) (4 mL), reflux.
brominated pyranocoumarin was the only course of the reaction
(entry 19). TBCHD was recovered from 2,4,6-tribromophenol by a
simple green procedure using KBr−KBrO3 as a source of electro-
philic bromine. Exploratory bromination of 7-methoxycoumarin
(3) recycling-recovered TBCHD gave yields comparable with the orig-
inal one (entry 3 3 h) for three successive runs (66%, 65%, and 62%,
respectively).
Acknowledgements
S.C. thanks the Council of Scientific and Industrial Research
(SRF-NET), New Delhi, for financial assistance by way of a research
fellowship. Facilities provided by the DST-FIST programme and
UGC-SAP programmes, Government of India, are also acknowl-
edged.
Density functional theory calculations were performed at the
B3LYP level (Gaussian-09 software) for estimation of electron den-
sity at different ring carbons of activated coumarins. It was re-
vealed that C-8 of 7-hydroxycoumarin (2) clearly surpasses other
ring carbons, C-3 in particular, in electron density. On the other
hand, in the case of 7-methoxycoumarin (3), this difference in
electron density is significantly reduced in favour of C-3, suggest-
ing a greater degree of electron withdrawal from electron-
releasing 7-MeO to electron-deficient C-3. The 7-oxyanion of 2
exhibits a highly delocalized structure where substantial deple-
tion of negative charge results in its almost even distribution at
all possible nucleophilic sites. 7-Hydroxy-4-methylcoumarin (10),
as expected, possesses C-3 and C-8 of comparable activation
levels and, therefore, both qualify as bromination sites. For
6-methoxycoumarin (16), the ambiphilic nature of the coumarin
ring system is evident, with the electron-rich benzene ring being
segregated from the electron-withdrawing pyrone ring. The C-5 is
decidedly the seat of highest electron density in this case and,
therefore, the exclusive bromination site. These data corroborate
the contention that nucleophilicity is the defining element of
selectivity of bromination of these coumarins with TBCHD.
References
(1) (a) Stille, J. K. Pure Appl. Chem. 1985, 57, 1771. doi:10.1351/pac198557121771;
(b) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457. doi:10.1021/cr00039a007.
(2) (a) Hartwig, J. F. Angew. Chem. Int. Ed. 1998, 37, 2046. doi:10.1002/(SICI)1521-
3773(19980817)37:15<2046::AID-ANIE2046>3.0.CO;2-L; (b) Wolfe, J. P.;
Wagaw, S.; Marcoux, J.-F.; Buchwald, S. L. Acc. Chem. Res. 1998, 31, 805.
doi:10.1021/ar9600650.
(3) Hamdi, N.; Saoud, M.; Romerosa, A. Top. Heterocycl. Chem. 2007, 11, 283.
doi:10.1007/7081_2007_062.
(4) (a) Kempen, I.; Papapostolou, D.; Thierry, N.; Pochet, L.; Counerotte, S.;
Masereel, B.; Foidart, J. M.; Reboud-Ravaux, M. J.; Noel, A.; Pirotte, B. Br. J.
Cancer 2003, 88, 1111. doi:10.1038/sj.bjc.6600856; (b) Reutrakul, V.;
Leewanich, P.; Tuchinda, P.; Pohmakotr, M.; Jaipetch, T.; Sophasan, S.;
T. Santisuk, T. Planta Med. 2003, 69, 1048. doi:10.1055/s-2003-45154.
(5) Spino, C.; Dodier, M.; Sotheeswaran, S.; Bioorg . Bioorg. Med. Chem. Lett. 1998,
8, 3475. doi:10.1016/S0960-894X(98)00628-3.
(6) (a) Marcu, M. G.; Chadli, A.; Bouhouche, I.; Catelli, M.; Neckers, L. M. J. Biol.
Chem. 2000, 275, 37181. doi:10.1074/jbc.M003701200; (b) Burlison, J. A.;
Neckers, L.; Smith, A. B.; Maxwell, A.; Blagg, B. S. J. Am. Chem. Soc. 2006, 128,
15529. doi:10.1021/ja065793p.
(7) (a) Audisio, D.; Messaoudi, S.; Brion, J.-D.; Alami, M. , Eur. J. Org. Chem. 2010,
1046. doi:10.1002/ejoc.200901107; (b) Messaoudi, S.; Peyrat, J.-F.; Brion, J.-D.;
Alami, M. Anticancer Agents Med. Chem. 2008, 8, 761. doi:10.2174/
187152008785914824.
(8) Pardanani, N. H.; Trivedi, K. N. Aus. J. Chem. 1972, 25, 1537. doi:10.1071/
CH9721537.
(9) Meggio, F.; Pagano, M. A.; Moro, S.; Zagotto, G.; Ruzzene, M.; Sarno, S.; Cozza, G.;
Bain, J.; Elliott, M.; Deana, A. D.; Brunati, A. M.; Pinna, L. A. Biochemistry 2004, 43,
12931. doi:10.1021/bi048999g.
(10) Chattopadhyay, K.; Fenster, E.; Grenning, J. A.; Tunge, J. A. Beilstein J. Org.
Chem. 2012, 8, 1200. doi:10.3762/bjoc.8.133.
(11) (a) Das, B.; Venkateswarlu, K.; Krishnaiah, M.; Holla, H. Tetrahedron Lett. 2006,
47, 8693. doi:10.1016/j.tetlet.2006.10.029; (b) Das, B.; Venkateswarlu, K.;
Majhi, A.; Siddaiah, V.; Reddy, K. R. J. Mol. Catal. A: Chem. 2006, 267, 30.
doi:10.1016/j.molcata.2006.11.002; (c) Ganguly, N. C.; De, P.; Dutta, S. Synthesis
2005, 1103. doi:10.1055/s-2005-861866.
(12) Thapliyal, P. C.; Singh, P. K.; Khanna, R. N. Synth. Commun. 1993, 23, 2821.
doi:10.1080/00397919308012602.
Conclusion
To summarize, bromination of activated coumarins has been
achieved with high selectivity and good to excellent yields in
acetonitrile under refluxing conditions. The reaction time and
selectivity of bromination exhibited marked dependence on nu-
cleophilicity of the bromination site that is related to electron
withdrawal from electron-releasing substituents in the benzene
ring to C-3 of the ␣-pyrone ring by vinylogous resonance. The
␣-pyrone double bond as well as the allyl moiety were generally
tolerated under the conditions of the current method. The selec-
tivity, yield, and reaction time could be effectively tuned by addi-
tion of nucleophilic additives such as water and TBAB. The sole
by-product of bromination viz. 2,4,6-tribromophenol could be
converted back to TBCHD for recycling, adding to the synthetic
utility of the method.
(13) Ramanarayanan, G. V.; Shukla, V. G.; Akamanchi, K. G. Synlett 2002, 2059.
doi:10.1055/s-2002-35600.
(14) Chaudhuri, S. K.; Roy, S.; Bhar, S. Beilstein J. Org. Chem. 2012, 8, 323. doi:10.
3762/bjoc.8.35.
(15) (a) Ganguly, N. C.; Chandra, S.; Barik, S. K. ; Synth. Commun. 2013, 43, 1351.
doi:10.1080/00397911.2011.633734; (b) Ganguly, N. C.; Roy, S.; Mondal, P.;
Saha, R. Tetrahedron Lett. 2012, 53, 7067. doi:10.1016/j.tetlet.2012.10.055;
(c) Ganguly, N. C.; Roy, S.; Mondal, P. Tetrahedron Lett. 2012, 53, 1413. doi:10.
1016/j.tetlet.2012.01.029; (d) Ganguly, N. C.; Barik, S. K. ; Synthesis 2011, 828.
doi:10.1055/s-0030-1258441; (e) Ganguly, N. C.; Mondal, P. Synthesis 2010,
1467. doi:10.1055/s-0029-1218698.
(16) (a) Calo, V.; Ciminale, F.; Lopez, L.; Todesco, P. E. J. Chem. Soc. (C) 1971, 3652.
doi:10.1039/J39710003652; (b) Toda, F.; Schmeyers, J. Green Chem. 2003, 5,
701. doi:10.1039/B306612F; (c) Attanasi, O. A.; Berretta, S.; Favi, G.;
Filippone, P.; Mele, G.; Moscatelli, G.; Saladino, P. Org. Lett. 2006, 8, 4291.
doi:10.1021/ol061637b.
Supplementary data
Supplementary material is available with the article through
the journal Web site at http://nrcresearchpress.com/doi/suppl/
10.1139/cjc-2013-0230. Supplementary data include full experi-
mental procedures, characterization data for all new compounds,
and Mulliken charges calculated for some representative cases.
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Ganguly et al.
1159
(17) Joo, Y. H.; Kim, J. K.; Kang, S. H. Synth. Commun. 2002, 32, 1653. doi:10.1081/
SCC-120004255.
(21) Macharla, A. K.; Nappunni, R. C.; Nama, N. Tetrahedron Lett. 2012, 53, 1401.
doi:10.1016/j.tetlet.2012.01.026.
(22) Taylor, R. Electrophilic aromatic substitution; John Wiley & Sons: New York,
1990.
(23) Desmukh, M.; Pawar, P.; Joseph, M.; Phalgune, U.; Kashalkar, R.;
Deshpande, N. R. Indian J. Exp. Biol. 2008, 46, 788. PMID:19090351.
(24) Carey, F. A.; Sundberg, R. J. Advanced organic chemistry Part A: structure and
mechanism; 5th ed. Springer: New York, 2007.
(18) Bertelsen, S.; Halland, N.; Bachmann, S.; Marigo, M.; Braunton, A.;
Jørgensen, K. A. Chem. Commun. 2005, 4821. doi:10.1039/B509366J.
(19) Isonagie, C. D.; Bekele, T.; France, S.; Wolfer, J.; Weatherwax, A.; Taggi, A. E.;
Lectka, T. J. Org. Chem. 2006, 71, 8946. doi:10.1021/jo061522l.
(20) (a) Sabot, C.; Berard, D.; Canesi, S. Org. Lett. 2008, 10, 4629. doi:10.1021/
ol801921d; (b) Fox, G. T.; Hallas, G.; Hepworth, J. D.; Paskins, K. N. Org. Synth.
Coll. Vol. 1988, 6, 181. doi:10.1002/0471264180.os055.06.
Published by NRC Research Press