KHSO4-catalyzed synthesis of 1,1-oxybis(2-bromoethane-1,1-diyl) dibenzenes and 1-(1-(benzyloxy)-2-bromoethyl)benzenes under solvent-free conditions

Article abstract of DOI:10.1080/00397911.2011.604816

An economical and green conversion of 2-bromo-1-phenylethanols and benzylic alcohols into 1,1-oxybis(2-bromoethane-1,1-diyl)dibenzenes and 1-(1-(benyloxy)-2-bromomethy)benzenes catalyzed by KHSO⁴ under neat condition is described. The present p

Full text of DOI:10.1080/00397911.2011.604816

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KHSO4-Catalyzed Synthesis of
1,1′-Oxybis(2-bromoethane-1,1-
diyl)dibenzenes and 1-(1-(Benzyloxy)-2-
bromoethyl)benzenes Under Solvent-
Free Conditions
Girdhar Joshi a , Eringathodi Suresh a & Subbarayappa Adimurthy a
a Central Salt and Marine Chemicals Research Institute, Council of
Scientific and Industrial Research (CSIR), Bhavnagar, Gujarat, India
Accepted author version posted online: 13 Feb 2012.Version of
record first published: 08 Nov 2012.
To cite this article: Girdhar Joshi , Eringathodi Suresh & Subbarayappa Adimurthy (2013): KHSO4-
Catalyzed Synthesis of 1,1′-Oxybis(2-bromoethane-1,1-diyl)dibenzenes and 1-(1-(Benzyloxy)-2-
bromoethyl)benzenes Under Solvent-Free Conditions, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 43:4, 587-599
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Synthetic Communications1, 43: 587–599, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.604816
KHSO4-CATALYZED SYNTHESIS OF
1,1’-OXYBIS(2-BROMOETHANE-1,1-DIYL)DIBENZENES
AND 1-(1-(BENZYLOXY)-2-BROMOETHYL)BENZENES
UNDER SOLVENT-FREE CONDITIONS
Girdhar Joshi, Eringathodi Suresh, and
Subbarayappa Adimurthy
Central Salt and Marine Chemicals Research Institute, Council of Scientific
and Industrial Research (CSIR), Bhavnagar, Gujarat, India
GRAPHICAL ABSTRACT
Abstract An economical and green conversion of 2-bromo-1-phenylethanols and benzylic
alcohols into 1,10-oxybis(2-bromoethane-1,1-diyl)dibenzenes and 1-(1-(benyloxy)-2-
bromomethy)benzenes catalyzed by KHSO4 under neat condition is described. The present
protocol is facile and chemoselective without transition-metal catalyst/solvent, and the
KHSO4 catalyst is recyclable.
Keywords Benzylic alcohols; 2-bromo-1-phenylethanol; dibenzenes; KHSO4; solvent free
INTRODUCTION
Green chemistry and sustainability are becoming more important in modern
organic synthesis. Screening of green methods for chemical transformation is chal-
lenging in day-to-day life because to the adverse consequences of substances used
and generated.[1] Solvent-free chemistry has received renewed interest because of
Received June 8, 2011.
Address correspondence to Subbarayappa Adimurthy, Central Salt and Marine Chemicals
Research Institute, Council of Scientific and Industrial Research (CSIR), Gijubhai Badheka Marg,
Bhavnagar 364002, Gujarat, India. E-mail: adimurthy@csmcri.org
587

588
G. JOSHI, E. SURESH, AND S. ADIMURTHY
Figure 1. b-Bromo alkoxy natural product.
environmental concern.[2] A green chemical process for sustainable development
always involves considerations such as use of cost-effective catalysts without any
additives, employing water as a green solvent, or solvent-free system. In addition,
a simple purification procedure is also desirable.
Haloalkoxy derivatives have been used as versatile intermediates in the synth-
eses of various bioactive compounds and natural product synthesis.[3] In particular,
bromo-alkoxy ethers are very useful synthons employed for Prins cyclizations,[4]
direct synthesis of substituted tetrahydrofuran derivatives,[5] polymer synthesis,[6]
and stereoselective organic transformations.[7] Bromo-alkoxy ethers such as natural
products derived from red alga laurencia nipponica were identified as major second-
ary metabolites (Fig. 1).[8]
Hence, the development of a convenient and efficient methodology for the syn-
thesis of dibromo alkyl=aryl ethers are target of investigation (Scheme 1) and are
rarely reported in the literature.
However, b-bromo-alkyl ethyl ethers, b-bromo-ethers, and bis-bromoalkyl
ethers with stoicheometric use of reagents [such as Grignard reagents (alkyl magnes-
ium bromides),[9] CuBr2,[10]N-bromosuccinimide,[11] N,N-dibromo-p-toluene sulfo-
namide (TsNBr2),[12] thionyl bromide,[13] silver nitrate=Br2[14]), and synthesis of
c-chloro cyclic ethers with ZrCl4 as catalyst have been reported.[15] In continuation
of our interest in KHSO4-mediated selective dehalogenation of polyhalophenols,[16]
selective catalyst for hydroarylation of styrenes,[17] and more recently KHSO4, which
has attracted much attention in organic transformations[18] probably because of its
ecofriendliness, ready availability, and fairly insensitive nature, and because of our
ongoing efforts to explore environmentally benign synthetic reactions,[19] herein we
report a simple and green protocol for the synthesis of 1,10-oxybis(2-bromoethane-
1,1-diyl)dibenzenes (OBDB) and 1-(1- (benzyloxy)-2-bromomethy)benzenes
(BBMB) through self-condensation of 2-bromo-1-phenylethanols (or with benzylic
alcohols) catalyzed by KHSO4 under solvent-free conditions. It may be noted that
2-bromo-1-phenylethanol with KHSO4 at high temperature and pressure afforded
the eliminated product b-bromostyrene.[20] In the present study, we optimized the
reaction conditions to obtain selectively the intermolecular condensation products
(bromoethers) rather than elimination products.[20]
Scheme 1.

1,10-OXYBIS(2-BROMOETHANE-1,1-DIYL)DIBENZENES
589
RESULTS AND DISCUSSION
Initially, we selected 2-bromo-1-p-tolylethanol 1 as a model substrate for this
investigation. First, the reaction was carried out in the presence of 5 mol% of KHSO4
under solvent-free conditions, and 69% yield of the desired product 2 was obtained
(Table 1, entry 1). By increasing the amount of catalyst to 7 mol%, product 2 yield
was raised to 74% (Table 1, entry 2). When 10 mol% KHSO4 was employed, the con-
version substantially increased and 91% yield of 2 was obtained (Table 1, entry 3).
The effect of reaction temperature was also studied, and the results showed that
lower temperatures disfavored the reaction (Table 1, entries 4–6). Many other cata-
lysts such as H2SO4, oxalic acid, FeCl3, HBO3, and p-toluenesulfonic acid (p-TsOH)
were also tested for this transformation; with these catalysts lower yields of product
2 were observed (Table 1, entries 7–11). We paid attention to KHSO4 and set it as
optimized catalyst (10 mol%) for this transformation (Table 1, entry 3).
The new observation of self-condensation product 2 was also confirmed by
single-crystal x-ray diffraction (Fig. 2). However, the recemic mixture of four enan-
tiomers corresponding to two stereocenters present in the molecule 2 was observed.
Further study on the stereochemical aspects was not performed.
Table 1. Catalyst and temperature screening for self condensation of 1a
Entry
Catalyst
Temp. (ꢀC)
Time (h)
Yields (%)b
1
2
KHSO4
KHSO4
KHSO4
KHSO4
KHSO4
KHSO4
H2SO4
100
100
100
40
5
5
69c
74d
91
00
50
80
63
35
00
3
5
4
10
10
10
10
10
10
10
10
5
5
65
80
6
7
100
100
100
100
100
100
8
(COOH)2
FeCl3
HBO3
9
e
10
11
12f
—
p-TsOH
KHSO4
76
89
aConditions: 1 (5 mmol), catalyst (10 mol%), solvent free.
bIsolated yield.
c5 mol% catalyst was used.
d7 mol% catalyst was used.
eTrace product was obtained.
f1 (reaction conducted at 13.9-mmol scale).

590
G. JOSHI, E. SURESH, AND S. ADIMURTHY
Figure 2. ORTEP diagram of product 2. (Figure is provided in color online.)
After optimization of conditions, we extended the scope of the catalytic system
to synthesize various 1,10-oxybis(2- bromoethane-1,1-diyl)diaryls (OBDB). As shown
in Table 2, 2-bromo-1-phenylethanols, having different functionality reacted
smoothly to afford OBDBs in good yields. 2-Bromo-1-phenyl ethanol provided
Table 2. KHSO4-catalyzed synthesis of 1,10-oxybis(2-bromoethane-1,1-diyl)dibenzenesa
Entry
R1
Product
Yield (%)b
1
-H (3a)
4-Br(3b)
4-Cl(3c)
4a
4b
4c
4d
4e
4f
86
89
2
3
87
4
4-t-Bu(3d)
2-CH3(3e)
3-NO2(3f)
91
81
5
6c
No reaction
aConditions: 1 (5 mmol), catalyst (10 mol%), solvent free.
bIsolated yield.
cCatalyst (10 mol%), reaction time 10 h.

1,10-OXYBIS(2-BROMOETHANE-1,1-DIYL)DIBENZENES
591
[oxybis(2-bromoethane-1,1-diyl))dibenzene 4a in 86% yield (Table 2, entry 1). When
the para-substituents were bromo and chloro, the yields were decreased as their
electronegativity increased (Table 2, entries 2 and 3). On the other hand,
Table 3. KHSO4 Catalyzed tandem reactions of 1 and 3d with other alcoholsa
Entry
1
Substrate
Coupling partner
Product
Yield (%)b
89c
2
3
1
1
87
88
4
1
1
89
5
6
7
91
84
88
3d
aConditions: 1 (5 mmol), catalyst (10 mol%), solvent free.
bIsolated yield.
cIncluding 12% mixture of homo coupled products 2 and 4a.

592
G. JOSHI, E. SURESH, AND S. ADIMURTHY
electron-donating groups such as methyl and t-butyl at the para-position provided
91% yield in each case (Table 1, entry 3, and Table 2, entry 4). Methyl group at
ortho-position gave 81% yield (Table 2, entry 5). However, when a strong
electron-withdrawing nitro group was present, no reaction observed, even after
enhancing the catalyst (KHSO4) loading to 0.5 equivalents and prolonging the reac-
tion period (Table 2, entry 6). This indicates significant effect of electron-donating or
electron-withdrawing substituents.
Finally, we investigated the scope and the limitation of this transformation for
tandem hetero-condensation reactions with various alcohols. As can be seen from
Table 3, 2-bromo-1-p-tolylethanol 1 reacted smoothly with 2-bromo-1-phenyletha-
nol as well as with various substituted benzylic alcohols and afforded good yields
of products (Table 3, entries 1–5). Similarly, 2-bromo-1-(4-(tert-butyl)phenyl)etha-
nol 3d reacted with 2-bromo-1-(4-bromophenyl)ethanol 3b and with 3-nitro benzyl
alcohol to yield the corresponding ethers in 84% and 89% respectively (Table 3,
entries 6 and 7). As is evident from Table 3, reactions of 2-bromo-1-phenylethanols
with other alcohols having either electron-donating or electron-withdrawing groups
reacted smoothly to afford good to excellent yields (Table 3, entries 2–7). These reac-
tions indicate the independence of the substituents in the other coupling partner to
afford good yields of products (Table 3).
As to the mechanism, a possible process for the synthesis of OBDB is described
in Scheme 2. As shown in Scheme 2, protonation of secondary hydroxyl group of
2-bromo-1-phenylethanol with KHSO4 and subsequent dehydration provided the
carbocation intermediate I. Reaction of another alcohol with the intermediate I
led to the formation of second intermediate II. Finally deprotonation afforded
OBDB=BBMB. The strong electron-withdrawing nitro groups in 2-bromo-1-
phenylethanols do not undergo dehydration to generate carbocation intermediate
(as indicated in Scheme 2) under the present conditions, which may be due to the
destabilization of benzylic carbocation. Thus the present system is not applicable
Scheme 2. Possible mechanism for the synthesis of 1,10-oxybis(2-bromoethane-1,1-diyl)dibenzenes.

1,10-OXYBIS(2-BROMOETHANE-1,1-DIYL)DIBENZENES
593
Figure 3. Recycling chart. (Figure is provided in color online.)
for such transformations. Importantly, water is the only by-product in the whole
process.
To assess the reusability of KHSO4, after completion of the reaction the cata-
lyst was retrieved from the reaction mixture by simple filtration, dried, and recycled
under the same experimental conditions up to three consecutive times without signifi-
cant loss of catalytic activity (Fig. 3).
CONCLUSIONS
In conclusion, we have developed a simple and green method for the
synthesis of 1,10-oxybis(2-bromoethane-1,1-diyl) dibenzenes and 1-(1-(benzyloxy)-2-
bromoethyl)benzenes catalyzed by KHSO4 under neat conditions. The major
advantages of the method are the cheap catalyst, neat condition and excellent yields.
Furthermore, water is the only by-product in this reaction, which makes the present
process environmentally benign.
EXPERIMENTAL
All commercially available reagents were used without further purification
unless otherwise indicated. All reactions were carried out in air without any special
precautions. 1H (13C) NMR spectra were recorded at 200 MHz (50 MHz) using
1
CDCl3 as a solvent unless otherwise stated. The H and 13C chemical shifts were
referenced to residual solvent signals at dH=C 7.26=77.28 (CDCl3) relative to tetra-
methylsilane (TMS) as internal standards. Infrared (IR) spectra were recorded on a
Fourier transform (FT)–IR spectrometer. Gas chromatography was recorded using
a HP-5 column. Column chromatography for purification was carried out on silica
gel (100–200 mesh). Melting points were obtained on a Mettler Toledo FP62
melting-point apparatus with open capillary tubes and are uncorrected. Analytical
thin-layer chromatography (TLC) was performed on a precoated Aluchrosep
silica-gel 60=UV254 plate. Mass spectra (MS) of samples were recorded on electro-
spray ionization (ESI) þve mode. (Note: The peak that appeared in 1H NMR spectra
around 1.6–1.7 ppm corresponds to the residual H2O from the deuterated solvent
CDCl3).

594
G. JOSHI, E. SURESH, AND S. ADIMURTHY
General Procedure: 4,4’-(1,1’-Oxybis(2-bromoethane-
1,1-diyl))bis(methylbenzene) (Entry 3, Table 1)
A mixture of 2-bromo-1-p-tolylethanol 1 (1 g; 4.65 mmol) and KHSO4
(10 mol%) (0.063 g, 0.465 mmol) was heated under neat conditions, at 100ꢀC for a
period of 5 h. The progress of the reaction was monitored by TLC. After complete
disappearance of 2-bromo-1-p-tolylethanol, the reaction mixture was allowed to
attain room temperature (25ꢀC) and diluted with 5 mL of ethyl acetate, and KHSO4
was removed by filtration; the residue was washed with 5 mL of ethyl acetate. The
ethyl acetate was stripped out, and the residue left was purified by column chroma-
tography on silica gel (petroleum ether as eluting solvent) to obtain pure product 2 in
91% (1.75 g, 4.24 mmol) yield as a white crystalline solid, mp 74.5ꢀC. IR vmax
(KBr) ¼ 2955, 2882, 1901, 1586, 1481, 1411, 1374, 1203, 1075, 1001, 881, 719, 617,
1
501 cmꢁ1. H NMR (200 MHz, CDCl3): d (ppm) 7.2 (s, 8H), 4.3 (q, J ¼ 10.5 Hz,
2H), 3.6 (t, J ¼ 26 Hz, 2H), 3.3 (q, J ¼ 10.5 Hz, 2H), 2.3 (s, 6H). 13C NMR
(50 MHz, CDCl3): ((ppm) 138.6, 135.3, 129.3, 127.3, 78.3, 36.2, 21.2. Elemental
analysis calcd. for C18H20Br2O: C, 52.54;H, 4.89. Found: C,51.31; H,4.12. ESI-MS
calcd. for C18H20Br2O [H]þ: 410.9. Found: 410.2.
Characterization Data for Synthesized Compounds
(1,1’-Oxybis(2-bromoethane-1,1-diyl))dibenzene 4a (Entry 1, Table 2).
White crystalline solid, mp 81.4ꢀC. IR vmax (KBr) ¼ 3061, 2961, 2902, 1906, 1489,
1
1450, 1414, 1343, 1317, 1209, 1092, 1011, 885, 763, 703, 664, 600, 503 cmꢁ1. H
NMR (200 MHz, CDCl3): ((ppm) 7.3 (s, 10H), 4.3 (q, J ¼ 10.5 Hz, 2H), 3.6 (t,
J ¼ 26 Hz, 2H), 3.4 (q, J ¼ 10.5 Hz, 2H). 13C NMR (50 MHz, CDCl3): d (ppm) 138.3,
128.8, 127.5, 78.7, 36.1. Elemental analysis calcd. for C16H16Br2O: C, 50.03; H, 4.20,
Found: C, 49.84; H, 3.89. ESI-MS calcd. for C16H16Br2O [H]þ: 382.9, Found: 382.4.
4,4’-(1,1’-Oxybis(2-bromoethane-1,1-diyl))bis(bromobenzene) 4b (Entry2,
table 2). White crystalline solid, mp 104.0ꢀC. IR vmax (KBr) ¼ 2957, 2881, 1904,
1586, 1481, 1409, 1326, 1204, 1087, 1071, 1004, 819, 720, 688, 617, 504 cmꢁ1
.
1H NMR (200 MHz, CDCl3): d (ppm) 7.4 (d, J ¼ 21 Hz, 4H), 7.0 (d, J ¼ 31.5 Hz,
4H), 4.6 (t, J ¼ 14.5 Hz, 2H), 3.6 (q, J ¼ 17 Hz, 2H), 3.5 (q, J ¼ 13.5 Hz, 2H).
13C NMR (50 MHz, CDCl3): d (ppm) 137.9, 131.6, 128.5, 122.5, 80.2, 35.3. Elemen-
tal analysis calcd. for C16H14Br4O: C, 35.46; H, 2.60, Found: C, 35.31; H, 2.34.
ESI-MS calcd. for C16H14Br4O [H]þ: 538.7, Found: 538.3.
4,4’-(1,1’-Oxybis(2-bromoethane-1,1-diyl))bis(chlorobenzene) 4c (Entry 3,
Table 2). White crystalline solid, mp 44.3ꢀC. IR vmax (KBr) ¼ 3057, 2982, 2927,
1908, 1591, 1489, 1433, 1413, 1345, 1232, 1195, 1092, 1009, 907, 828, 778, 666,
588, 508 cmꢁ1. 1H NMR (200 MHz, CDCl3): d (ppm) 7.3 (s, 8H), 5.1 (q, J ¼ 13.5 Hz,
Hz, 2H), 4.1 (m4H). 13C NMR (50 MHz, CDCl3): d (ppm) 137.2, 135.0, 129.1, 122.5,
49.6, 34.3. Elemental analysis calcd. for C16H14Br2Cl2O: C, 42.42; H, 3.12, Found:
C, 41.93; H, 3.02. ESI-MS calcd. for C16H14Br2Cl2O [H]þ: 450.8, Found: 450.3.
4,4’-(1,1’-Oxybis(2-bromoethane-1,1-diyl))bis(tert-butylbenzene) 4d
(Entry 4, Table 2). White crystalline solid, mp 111.9ꢀC. IR vmax (KBr) ¼ 2980,
2910, 2827, 1905, 1580, 1486, 1401, 1367, 1206, 1085, 1011, 888, 717, 619, 508 cmꢁ1
.

1,10-OXYBIS(2-BROMOETHANE-1,1-DIYL)DIBENZENES
595
1H NMR (200 MHz, CDCl3): d (ppm) 7.4 (d, J ¼ 21Hz, 4H), 7.2 (d, J ¼ 17.0Hz, 4H),
4.4 (q, J ¼ 10.0 Hz, 2H), 3.6 (q, J ¼ 21.5 Hz, 2H), 3.4 (d, J ¼ 10.5 Hz, 1H), 3.3 (d,
J ¼ 10.5Hz, 1H), 1.3 (s, 18H). 13C NMR (50 MHz, CDCl3): d (ppm) 151.7, 135.3,
127.1, 125.5, 82.8, 36.4, 34.6, 31.3. Elemental analysis calcd. for C24H32Br2O: C,
58.08; H, 6.50, Found: C, 57.12; H, 6.18. ESI-MS calcd. for C24H32Br2O [H]þ:
495.0, Found: 494.8.
2,2’-(1,1’-Oxybis(2-bromoethane-1,1-diyl))bis(methylbenzene)
4e
(Entry 5, Table 2). Viscous brownish liquid. IR vmax (KBr) ¼ 3053, 2980, 2927,
1906, 1582, 1462, 1377, 1206, 1166, 1086, 1025, 888, 820, 661, 611, 588, 503,
1
460 cmꢁ1. H NMR (200 MHz, CDCl3): d (ppm) 7.2 (m, 8H), 4.3 (q, J ¼ 4.0 Hz,
2H), 3.6 (t, J ¼ 10.0 Hz, 2H), 3.3 (q, J ¼ 4.0 Hz, 2H), 2.36 (s, 6H). 13C NMR
(50 MHz, CDCl3): d (ppm) 136.2, 130.3, 128.5, 128.1, 126.6, 74.5, 35.3, 18.9. Elemen-
tal analysis calcd. for C18H20Br2O: C, 52.45; H, 4.89, Found: C, 51.13; H, 4.03.
ESI-MS calcd. for C18H20Br2O [H]þ: 410.9, Found: 410.5.
1-(2-Bromo-1-(2-bromo-1-phenylethoxy)ethyl)-4-methylbenzene (Entry 1,
Table 3). Viscous brownish liquid. IR vmax (KBr) ¼ 3028, 2961, 2923, 1905, 1511,
1452, 1422, 1374, 1308, 1207, 1092, 1019, 911, 818, 761, 730, 702, 648, 603,
1
515 cmꢁ1. H NMR (200 MHz, CDCl3): d (ppm) 7.4 (s, 3H), 7.3 (m, 5H), 7.1 (d,
J ¼ 5.5 Hz, 2H), 4.8 (t, J ¼ 13.5 Hz, 1H), 4.4 (m, 1H), 3.8 (m, 3H), 3.4 (m, 1H).
13C NMR (50 MHz, CDCl3): d (ppm) 138.5, 138.1, 135.4, 129.5, 128.8, 128.4,
127.5, 126.9, 80.4, 78.6, 36.0, 21.3. Elemental analysis calcd. for C17H18Br2O: C,
51.28; H, 4.56, Found: C, 50.81; H, 4.13. ESI-MS calcd. for C17H18Br2O [H]þ:
396.9, Found: 396.2.
1-(2-Bromo-1-(4-methylbenzyloxy)ethyl)-4-methylbenzene (Entry 2,
Table 3). Viscous colorless liquid. IR vmax (KBr) ¼ 2980, 2902, 1911, 1581, 1476,
1
1409, 1377, 1195, 1085, 1011, 888, 739, 627, 530, 501 cmꢁ1. H NMR (200 MHz,
CDCl3): d (ppm) 7.3 (m, 8H), 4.6 (m, 2H), 4.3 (d, J ¼ 29 Hz, 1H), 3.6 (m, 2H), 2.4
(s, 6H). 13C NMR (50 MHz, CDCl3): d (ppm) 140.3, 138.8, 135.6, 133.5, 129.6,
129.3, 126.1, 122.5, 122.3, 81.7, 69.7, 36.3, 21.3. Elemental analysis calcd. for
C17H19BrO: C, 65.33; H, 7.21, Found: C, 64.93; H, 7.07. ESI-MS calcd. for
C17H19BrO [H]þ: 319.0, Found: 318.6.
1-(1-(Benzyloxy)-2-bromoethyl)-4-methylbenzene (Entry 3, Table 3).
Viscous brownish liquid. IR vmax (KBr) ¼ 3028, 2942, 2890, 1910, 1507, 1465,
1421, 1367, 1308, 1190, 1106, 1030, 911, 808, 745, 730, 702, 638, 594, 515 cmꢁ1
.
1H NMR (200 MHz, CDCl3): d (ppm) 7.2 (d, J ¼ 14.0 Hz, 3H), 7.2 (d, J ¼ 6.0 Hz,
2H), 7.1 (t, J ¼ 11.5 Hz, 4H), 4.5 (q, J ¼ 8.5 Hz, 2H), 4.3 (t, J ¼ 9.5 Hz, 1H), 3.5
(m, 2H), 2.2 (s, 3H). 13C NMR (50 MHz, CDCl3): d (ppm) 138.5, 138.1, 136.4,
129.7, 128.6, 128.0, 127.1, 80.9, 71.1, 36.8, 21.5. Elemental analysis calcd. for
C16H17BrO: C, 64.48; H, 6.91, Found: C, 63.81; H, 6.34. ESI-MS calcd. for
C16H17BrO [H]þ: 305.0, Found: 304.8.
1-Bromo-4-((2-bromo-1-p-tolylethoxy)methyl)benzene (Entry 4,
Table 3). Viscous brownish liquid. IR vmax (KBr) ¼ 2957, 2880, 1906, 1588,
1
1485, 1415, 1356, 1206, 1075, 1071, 1001, 827, 719, 688, 617, 501 cmꢁ1. HNMR
(200 MHz, CDCl3): d (ppm) 7.4 (t, J ¼ 16 Hz, 2H), 7.2 (dd, J ¼ 11.5 Hz, 6H), 4.5

596
G. JOSHI, E. SURESH, AND S. ADIMURTHY
(m, 2H), 4.2 (d, J ¼ 30 Hz, 1H), 3.6 (m, 2H), 2.3 (s, 3H). 13C NMR (50 MHz, CDCl3):
d (ppm) 138.6, 137.0, 136.0, 131.6, 129.6, 126.9, 121.7, 81.0, 70.2, 36.5, 21.4. Elemen-
tal analysis calcd. for C16H16Br2O: C, 50.03; H, 4.20, Found: C, 49.51; H, 4.03.
ESI-MS calcd. for C16H16Br2O [H]þ: 382.9, Found: 382.4.
1-((2-Bromo-1-p-tolylethoxy)methyl)-3-nitrobenzene (Entry 5, Table 3).
Viscous yellowish liquid. IR vmax (KBr) ¼ 3089, 2955, 2885, 1903, 1580, 1488, 1415,
1
1377, 1348, 1205, 1110, 1011, 881, 737, 647, 560, 512 cmꢁ1. H NMR (200 MHz,
CDCl3): d (ppm) 8.2 (s, 1H), 8.1 (d, J ¼ 18 Hz, 1H), 7.7 (d, J ¼ 19 Hz, 1H), 7.5
(t, J ¼ 20 Hz, 1H), 7.2 (d, J ¼ 10 Hz, 4H), 4.6 (m, 3H), 3.6 (m, 2H), 2.3 (s, 3H).
13C NMR (50 MHz, CDCl3): d (ppm) 148.3, 140.2, 138.8, 135.6, 133.5, 129.6,
126.8, 122.5, 122.4, 81.6, 69.6, 36.2, 21.2. Elemental analysis calcd. for
C16H16BrNO3: C, 54.87; H, 4.61; N, 4.00, Found: C, 54.13; H, 4.21; N, 4.21. ESI-MS
calcd. for C16H16BrNO3 [H]þ: 350.0, Found: 349.6.
1-Bromo-4-(2-bromo-1-(2-bromo-1-(4-tert-butylphenyl)ethoxy)ethyl)-
benzene (Entry 6, Table 3). Viscous brownish liquid. IR vmax (KBr) ¼ 2977, 2910,
2854, 1908, 1580, 1486, 1401, 1367, 1326, 1206, 1085, 1071, 1011, 825, 717, 688, 619,
506 cmꢁ1
.
1H NMR (200 MHz, CDCl3): d (ppm) 7.4 (d, J ¼ 21 Hz, 4H), 7.2
(d, J ¼ 20.0 Hz, 4H), 4.4 (q, J ¼ 10.0 Hz, 2H), 3.6 (t, J ¼ 21.5 Hz, 2H), 3.4 (q,
J ¼ 10.5 Hz, 2H), 1.3 (s, 9H). 13C NMR (50 MHz, CDCl3): d (ppm) 138.6, 137.0,
136.0, 131.6, 129.6, 126.9, 121,7, 82.8, 36.4, 34.6, 31.3. Elemental analysis calcd.
for C20H23Br3O: C, 57.79; H, 6.34, Found: C, 57.61; H, 6.21. ESI-MS calcd. for
C20H23Br3O [H]þ: 516.9, Found: 516.5.
1-((2-Bromo-1-(4-tert-butylphenyl)ethoxy)methyl)-3-nitrobenzene (Entry
7, Table 3). Viscous yellowish liquid. IR vmax (KBr) ¼ 3076, 2945, 2855, 1910, 1585,
1
1488, 1405, 1375, 1348, 1205, 1090, 1006, 871, 737, 647, 560, 512 cmꢁ1. H NMR
(200 MHz, CDCl3): d (ppm) 8.2 (s, 1H), 8.1 (d, J ¼ 18 Hz, 1H), 7.7 (d, J ¼ 19 Hz,
1H), 7.5 (t, J ¼ 20 Hz, 1H), 7.2 (d, J ¼ 10 Hz, 4H), 4.6 (m, 3H), 3.6 (m, 2H), 1.3 (s,
9H). 13C NMR (50 MHz, CDCl3): d (ppm) 148.3, 140.2, 138.8, 135.6, 133.5, 129.6,
126.8, 122.5, 122.4, 81.6, 69.6, 36.4, 34.6, 31.3. Elemental analysis calcd. for
C19H22BrNO3: C, 58.17; H, 5.65; N, 3.57, Found: C, 57.31; H, 5.41; N, 3.24. ESI-MS
calcd. for C19H22BrNO3 [H]þ: 516.9, Found: 516.5.
X-Ray Crystal Data for 2a (CCDC number 793716)
Empirical formula: C18H20Br2O, formula weight: 412.16, T ¼ 293(2) K,
k ¼ 0.71073, crystal system: monoclinic, space group: C2=c, unit cell dimensions: a ¼
3
ꢀ
˚
˚
˚
˚
15.559(9) A, b ¼ 12.162(7) A, c ¼ 10.185(6) A, b ¼ 115.118(9) , V ¼ 1745.0(18) A ,
Z ¼ 4, density (calcd.) ¼ .569 Mg=m3, absorption coefficient: 4.642 mmꢁ1, F (000) ¼
824, crystal size: 0.45 ꢂ 0.30 ꢂ 20 mm, reflections collected: 5075, independent reflec-
tions: 2046, R(int) ¼ 0.0276, data=restraints=parameters 2046=0=97, goodness-of-fit
on F2 ¼ 0.902. Final R indices [I ꢃ 2r(I)] R1 ¼ 0.0351, wR2 ¼ 0.0926, R indices (all
data): R1 ¼ 0.0537, wR2 ¼ 0.1028, largest diff. peak and hole: 0.660 and ꢁ0.343
3
˚
e.A . CCDC 793716 contains the supplementary crystallographic data for this arti-
cle. These data can be obtained free of charge from Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

1,10-OXYBIS(2-BROMOETHANE-1,1-DIYL)DIBENZENES
597
ACKNOWLEDGMENTS
We thank Mr. Hitesh, Mr. A. K. Das, and Mr. H. Brahmbhatt, and Mr. V.
Agrawal of our Analytical Division for supporting NMR, mass, IR, and elemental
analyses respectively. G. J. is thankful to the Council of Scientific and Industrial
Research, New Delhi, India, for the award of a senior research fellowship.
REFERENCES
1. (a) Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice; Oxford University
Press: Oxford, 1998; (b) Winterton, N. Twelve more green chemistry principles. Green
´
Chem. 2001, 3, G73–G75; (b) Horvath, I. T. Innovations and green chemistry. Chem.
Rev. 2007, 107, 2169–2173; (c) Sheldon, R. A. E factors, green chemistry, and catalysis:
An odyssey. Chem. Commun. 2008, 3352–3365; (d) Anastas, P. T.; Zimmermann, J. B.
Peer reviewed: Design through the 12 principles of green engineering. Environ. Sci.
Technol. 2003, 37, 94A–101A; (e) Tang, S. L. Y.; Smith, R. L. S.; Poliakoff, M. Principles
of green chemistry: Productively. Green Chem. 2005, 7, 761–762.
2. (a) Tanaka, K.; Toda, F. Solvent-free organic synthesis. Chem. Rev. 2000, 100, 1025–1074;
(b) Rothenberg, G.; Downie, A. P.; Raston, C. L.; Scott, J. L. Understanding solid=solid
organic reactions. J. Am. Chem. Soc. 2001, 123, 8701–8708; (c) Tanaka, K.; Toda, F.
Solvent-Free Organic Synthesis; Wiley-VCH: Weinheim, Germany, 2003.
3. (a) Sugahara, T.; Fukuda, H.; Iwabuchi, Y. Total synthesis and absolute stereochemistry
of pentenocin B, a novel interleukin-1b converting enzyme inhibitor. J. Org. Chem. 2004,
69, 1744–1747; (b) Trost, B. M.; Tang, W. An enantioselective strategy to macrocyclic
bisindolylmaleimides: An efficient formal synthesis of LY 333531. Org. Lett. 2001,
3(21), 3409–3411; (c) Kohll, M. J.; Lejeune, R. G. Coupling of biologically active steroids
to conjugating arms through ether linkages for use in immunochemistry. Steroids 2002 67,
71–75; (d) Izuhara, T.; Katoh, T. Studies toward the total synthesis of scyphostatin: First
entry to the highly functionalized cyclohexenone segment. Org. Lett. 2001, 3, 1653–1656;
(e) Adhikari, S.; Roy, S. C. Stereoselective radical annulation route to the synthesis of
(ꢄ)-paulownin and (ꢄ)-isogmelinol. Tetrahedron Lett. 1992, 33, 6025–6026; (f) Maiti,
G.; Adhikari, S.; Roy, S. C. Stereoselective total synthesis of (ꢄ)-samin and the dimethoxy
analogue, the general furofuran lignan precursors. Tetrahedron 1995, 51, 8389–8396.
4. (a) Jasti, R.; Vitale, J.; Rychnovsky, S. D. Axial-selective prins cyclizations by solvolysis
of a -bromo ethers. J. Am. Chem. Soc. 2004, 126, 9904–9905; (b) Guindon, Y.; Ogilvie, W.
W.; Bordeleau, J.; Cui, W. L.; Durkin, K.; Gorys, V.; Juteau, H.; Lemieux, M.; Liotta, D.;
Simoneau, B.; Yoakim, C. Axial-selective prins cyclizations by solvolysis of a-bromo
ethers. J. Am. Chem. Soc. 2003, 125, 428–436; (c) Van-Orden, L. J. Patterson, B. D.;
Rychnovsky, S. D. Total synthesis of leucascandrolide A: A new application of the
mukaiyama aldolꢁprins reaction. J. Org. Chem. 2007, 72, 5784–5793
5. (a) Esteves, A. P.; Ferreira, E. C.; Medeiros, M. J. Selective radical cyclisation of propar-
gyl bromoethers to tetrahydrofuran derivatives via electrogenerated nickel(I) tetramethyl-
cyclam. Tetrahedron 2007, 63, 3006–3009; (b) Dunach, E.; Esteves, A. P.; Medeiros, M. J.;
Oliverob, S. Electrochemical intramolecular cyclisation of propargyl bromoethers cata-
lysed by nickel complexes. New J. Chem. 2005, 29, 633–636.
6. Montorne, J. M.; Reina, J. A.; Ronda, J. C. Studies on the modification of
poly(x-bromoalkyl-1-glycidylether)s with 40-methoxybiphenyl-4-oxy mesogenic groups.
J. Poly. Sci. Part A: Poly. Chem. 2005, 43, 5998–6006.
7. (a) Yu, W.; Jin, Z. A highly stereoselective synthesis of a -halo vinyl ethers and their appli-
cations in organic synthesis. J. Am. Chem. Soc. 2000, 122, 9840–9841; (b) Tanuwidjaja, J.;

598
G. JOSHI, E. SURESH, AND S. ADIMURTHY
Ng, S. S.; Jamison, T. F. Total synthesis of ent-dioxepandehydrothyrsiferol via a
bromonium-initiated epoxide-opening cascade. J. Am. Chem. Soc. 2009, 131, 12084–
12085.
8. (a) Suzuki, T.; Suzuki, M. Diversity of halogenated secondary metabolites in the red alga
Laurencia Nipponica (rhodamelaceae, ceramiale). J. Phycol. 1997, 33, 196–208; (b) Brito,
I.; Dias, T.; Dıaz-Marrero, A. R.; Darias, J.; Cueto, M. Aplysiadiol from Aplysia dacty-
lomela suggested a key intermediate for a unified biogenesis of regular and irregular
marine algal bisabolene-type metabolites. Tetrahedron 2006, 62, 9655–9660.
9. Swallen, L. C.; Boor, C. E. The synthesis of b-bromo-alkyl ethers and their use in further
synthesis. J. Am. Chem. Soc. 1930, 52, 651–660.
10. Skumov, M. Y.; Brailovskii, S. M.; Temkin, O. N. New approaches to syntheses of
diethers and haloethers from cyclopentadiene. Russ. Chem. Bull., Int. Ed. 2002, 51,
616–624.
11. (a) Zolotarev, R. N.; Yakovlev, M. E.; Razin, V. V. Synthesis of 3-oxatricyclo[4.4.0.02,7]-
decene derivatives. Russ, J. Org. Chem. 2006, 42, 1636–1642; (b) Cwynar, V.; Donahue,
M. G.; Hart D. J.; Yang, D. Quassinoid support studies: Fused carbocycle synthesis from
benzoic acid derivatives via 5-hexynyl and 6-heptynyl radical cyclizations. Org. Lett. 2006,
8, 4577–4580.
12. Phukan, P.; Chakraborty, P.; Kataki, D. A simple and efficient method for regioselective
and stereoselective synthesis of vicinal bromohydrins and alkoxybromides from an olefin.
J. Org. Chem. 2006, 71, 7533–7537
13. James, M. P. Process for preparing bis-bromoalkyl ethers. U.S. Patent 4629814, 1986.
14. Hajra, S.; Karmakar, A.; Bhowmick, M. Silver(I)-promoted asymmetric halomethoxyla-
tion of chiral a,b-unsaturated carboxylic acid derivatives: Enantioselective synthesis of
N-protected syn-b-methoxy-a -amino acids. Tetrahedron: Asymmetry 2006, 17, 210–222.
15. Zhang, Z.-H.; Li, T.-S. Applications of zirconium(IV) compounds in organic synthesis.
Curr. Org. Chem. 2009, 13, 1–30.
16. Adimurthy, S.; Ramachandraiah, G. Reductive dehalogenation of halophenols in sulfite–
bisulfate medium. Tetrahedron Lett. 2004, 45, 5251–5252.
17. Patil, R. D.; Joshi, G.; Adimurthy, S. KHSO4: A highly efficient and reusable hetero-
geneous catalyst for hydroarylation of styrenes. Monatsh Chem. 2010, 141, 1093–1099
18. (a) Ayta, W. E. F.; Dantas, N. O.; Silva, A. C. A.; Cano, N. F. First evidence of crystalline
KHSO4:Mn grown by an aqueous solution method and the investigation of the effect of
ionizing radiation exposure. J. Cryst. Growth 2010, 312, 563–567; (b) Knudsen, C. B.;
Kalampounias, A. G.; Fehrmann, R.; Boghosian, S. Thermal dissociation of molten
KHSO4: Temperature dependence of Raman spectra and thermodynamics. J. Phys.
Chem. B 2008, 112, 11996–12000; (c) Gowsami, A.; Das, R. N.; Borthakur, N. KHSO4-
SiO2-MeOH: An efficient selective solid-supported system for deprotection of alcohols
from esters. Indian J. Chem. 2007, 46B, 1893–1895; (e) Bita, B.; Majid, M. H.; Hossein,
A. O. Practical and efficient synthesis of 3-aryl-2H-benzo[1,4]thiazine derivatives cata-
lyzed by KHSO4. Synth. Commun. 2011, 41, 589–593.
19. (a) Adimurthy, S.; Ramachandraiah, G.; Bedekar, A. V.; Ghosh, S.; Ranu, B. C.; Ghosh,
P. K. Eco-friendly and versatile brominating reagent prepared from a liquid bromine pre-
cursor. Green Chem. 2006, 8, 916–922; (b) Adimurthy, S.; Ghosh, S.; Patoliya, P. U.;
Ramachandraiah, G.; Agrawal, M.; Gandhi, M. R.; Upadhyay, S. C.; Ghosh, P. K.;
Ranu, B. C. An alternative method for the regio- and stereoselective bromination of
alkenes, alkynes, toluene derivatives, and ketones using a bromide=bromate couple. Green
Chem. 2008, 10, 232–237; (c) Patil, R. D.; Joshi, G.; Adimurthy, S.; Ranu, B. C. Facile
one-pot synthesis of a-bromoketones from olefins using bromide=bromate couple as a
nonhazardous brominating agent. Tetrahedron Lett. 2009, 50, 2529–2532; (d) Agrawal,
M. K.; Adimurthy, S.; Ganguly, B.; Ghosh, P. K. Comparative study of the vicinal

1,10-OXYBIS(2-BROMOETHANE-1,1-DIYL)DIBENZENES
599
functionalization of olefins with 2:1 bromide=bromate and iodide=iodate reagents.
Tetrahedron 2009, 65, 2791–2797; (e) Joshi, G.; Bhadra, S.; Ghosh, S.; Agrawal, M. K.;
Ganguly, B.; Adimurthy, S.; Ghosh, P. K.; Ranu, B. C. Making full use of the oxidizing
equivalents in nromate in the selective oxidation of thiols, sulfides and benzylic=secondary
alcohols in to disulfides, sulfoxides, and aldehydes=ketones. Ind. Eng. Chem. Res. 2010, 49,
1236–1241; (f) Patil, R. D.; Joshi, G.; Adimurthy, S. HBr-H2O2: A facile protocol for the
regioselective synthesis of bromohydrins and a -bromoketones and oxidation of benzylic=
secondary alcohols to carbonyl compounds under very mild aqueous conditions. Ind. Eng.
Chem. Res. 2010, 49, 8100–8105.
20. (a) Jolles, Z. E.; Oxtoby, A. H.; Radford, P. J. M. Bromine and Its Compounds; Ernest
Benn. Limited: London, 1966; p. 527; (b) Jan, B. M. G.; Alexander, D. E. Process for
the preparation of omega-bromostyrene and 4-methyl-omega-bromostyrene, U.S. Patent
2,824,144, 1958.