Alkoxybromination of olefins using ammonium bromide and oxone

Article abstract of DOI:10.1080/00397911.2012.761238

A mild, efficient, and highly regio- and stereoselective method for the methoxy and ethoxy bromination of olefins has been developed using NH ₄Br as a bromine source and Oxone as an oxidant. Various kinds of olefins (aromatic, linear, and cyclic olefins) afforded the corresponding alkoxy brominated products in moderate to excellent yields. Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397911.2012.761238

This article was downloaded by: [Istanbul Universitesi Kutuphane ve Dok]
On: 02 August 2013, At: 11:23
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
Alkoxybromination of Olefins Using Ammonium
Bromide and Oxone®
Macharla Arun Kumar a , Mameda Naresh a , Chozhiyath Nappunni Rohitha a & Nama
Narender a
a I&PC Division , CSIR-Indian Institute of Chemical Technology , Hyderabad , India
Accepted author version posted online: 03 Jul 2013.
To cite this article: Synthetic Communications (2013): Alkoxybromination of Olefins Using Ammonium Bromide and Oxone®,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, DOI:
10.1080/00397911.2012.761238
To link to this article: http://dx.doi.org/10.1080/00397911.2012.761238
Disclaimer: This is a version of an unedited manuscript that has been accepted for publication. As a service
to authors and researchers we are providing this version of the accepted manuscript (AM). Copyediting,
typesetting, and review of the resulting proof will be undertaken on this manuscript before final publication of
the Version of Record (VoR). During production and pre-press, errors may be discovered which could affect the
content, and all legal disclaimers that apply to the journal relate to this version also.
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the
Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and
should be independently verified with primary sources of information. Taylor and Francis shall not be liable for
any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of
the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

ACCEPTED MANUSCRIPT
Alkoxybromination of Olefins Using Ammonium Bromide and Oxone
Macharla Arun Kumar1, Mameda Naresh1, Chozhiyath Nappunni Rohitha1, Nama
Narender1
1I&PC Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, India
Address correspondence to Nama Narender, I&PC Division, CSIR-Indian Institute of
Chemical Technology, Hyderabad, India 500 007. E-mail: narendern33@yahoo.co.in
Abstract
A mild, efficient and highly regio- and stereoselective method for the methoxy and
ethoxy bromination of olefins has been developed by using NH4Br as a bromine source
and Oxone as an oxidant. Various kinds of olefins (aromatic, linear and cyclic olefins)
afforded the corresponding alkoxy brominated products in moderate to excellent yields.
[Supplementary materials are available for this article. Go to the publisher’s online
edition of Synthetic Communications® for the following free supplemental resource(s):
Full experimental and spectral details.]
KEYWORDS: alkenes; alkoxybromination; oxone regioselectivity; vicinal
;
functionalization
INTRODUCTION
ACCEPTED MANUSCRIPT
1

ACCEPTED MANUSCRIPT
Halogenated organic molecules are found in many products, such as agrochemicals,
pharmaceuticals, and molecules for advanced technologies. In organic synthesis, they are
important intermediates in reactions involving metal cross-coupling reactions and
organometallic preparations.[1]
The vicinal functionalization of olefins is an important process in synthetic organic
chemistry, especially when the reaction is carried out in regio- and stereoselective
fashion. Among the several methodologies found in the literature,[2]
halofunctionalization[3] of alkenes towards synthetically useful substrates attract much
more attention. For example, bromoalkoxylation of olefins is an important transformation
in organic chemistry and the resulting alkoxybromides are important building blocks in
organic, medicinal as well as industrial chemistry.[4]
Conventional bromination methods which typically use elemental bromine, is difficult to
manipulate due to its toxicity, corrosiveness and high vapour pressure.[5] However, it is
still being used by industry as well as academia due to its easy availability, low cost, and
lack of a better alternative. In order to circumvent these problems, some alternative
methods have been developed for the alkoxybromination of olefins such as isocyanuric
acid,[6] (Ni,Al)-LDH-WO4 -NH4Br-H2O2,[7] TSNBr2,[8] select fluor-KBr,[9] NBSP-
2-
KBr,[10] NaIO4-LiBr,[11] Yb(OTf)3-NBS,[12] NBS,[13] 2,4,4,6-tetrabromo-2,5-
cyclohexadien-1-one,[14] N,NI-dibromo-2,5-piperazinedione,[15] AgNO3-Ag2O-Br2,
[16]
methyl hypobromite,[17] KBr/KBrO3.[18] However, most of these methodologies suffer
from one or more disadvantages, such as use of expensive and hazardous/toxic reagents,
ACCEPTED MANUSCRIPT
2

ACCEPTED MANUSCRIPT
high reaction temperature, long reaction times, low yields, and tedious work-up
procedures, which limit their use under the aspect of environmental benign process.
Therefore replacement of such reagents by non-toxic, mild, selective, and easy-to-handle
reagents is very desirable and represents an important goal in the context of clean
synthesis.
Oxone is a versatile oxidizing agent, which is easy to handle, water soluble, non-toxic,
relatively inexpensive, and produces non-polluting byproducts. As a result, Oxone has
become an increasingly popular reagent for oxidative transformations.[19]
In continuation of our interest on the halogenation reactions using environmentally
benign, easy to handle, and relatively inexpensive reagents,[20] recently we reported the
hydroxy bromination and dibromination of olefins using NH4Br/Oxone.[21] Herein, we
report, a simple method for the alkoxy bromination of olefins using NH4Br/Oxone.
However, alkoxy bromination of olefins using NH4Br/Oxone has not been studied so
far.
DISCUSSION
Initially methanolic solution of 1 equivalent of styrene was treated with 1.1 equivalents of
NH4Br and 1.1 equivalents of Oxone at room temperature. After 50 minutes, complete
disappearance of styrene was observed (indicated by TLC) and 2-bromo-1-
methoxystyrene was formed in excellent yield (Table 1, entry 1). Here methanol served
as the reaction medium as well as the nucleophile source. Encouraged by this result, we
ACCEPTED MANUSCRIPT
3

ACCEPTED MANUSCRIPT
decided to test the scope of other alcohols in the alkoxybromination of styrene at room
temperature and 80°C and the data obtained were presented in Table 1. Among the
different alcohols, primary alcohols (such as EtOH, n-PrOH and n-BuOH) gave the
corresponding alkoxybromo products in good yields, while secondary (2-PrOH, 2-BuOH)
and tertiary alcohols (t-BuOH) provided poor yields due to steric hindrance.
A number of different olefins were used as reactants in the methoxy and
ethoxybromination with NH4Br/Oxone reagent system and results were summarized in
Table 2 and 3. Activated, inactivated and moderately activated aromatic olefins furnished
the respective 2-bromo-1-methoxy and 2-bromo-1-ethoxy products in high yields with-
out forming any side-chain and ring brominated products (Table 2, entries 2-7).
Selectively erythro isomer was formed when asymmetric trans-alkenes were subjected to
alkoxybromination (Table 2, entries 10-14). In ethanol a distinct difference of products
were observed between room and reflux temperature with 4-phenyl-3-butene-2-one (5).
At reflux temperature, the corresponding α-brominated product i.e. 1-bromo-4-phenyl-3-
butene-2-one (6) was obtained in 50% yield. On the contrary, reaction at room
temperature resulted in the formation of the respective double bond addition products i.e.
ethoxybrominated (mixture of erythro and threo (65:35)) and dibrominated product
(Scheme 1).
In case of symmetric olefins (Table 2, entries 15 and 16), trans-stilbene produced the
corresponding erythro-methoxybromo product (4o), whereas cis-stilbene gave the
ACCEPTED MANUSCRIPT
4

ACCEPTED MANUSCRIPT
respective threo-methoxybromo product (4p) in methanol. In ethanol trans-stilbene
yielded selectively erythro-ethoxybromo product (4O), whilst cis-stilbene furnished
mixture of threo and erythro isomers.
Linear and cyclic olefins also provided good results with this reagent system (Table 3,
entries 1-6). In case of linear olefins regioselectivity was not observed, for example 1-
dodecene gave the corresponding Markovnikov’s product (4q/4Q) and anti-Markovnikov
product (4qI/4QI), while mixed regioselectivity was observed for trans-2-octene (Table
3, entry 2). Exclusively Markovnikov’s product was formed with 3-methyl-3-butene-1-ol
and 1-methyl-1-cyclohexane (Table 3, entries 3 and 5). 1,4-naphthoquinone furnished the
2-bromo-1,4-naphthoquinone instead of the expected alkoxybrominated product in
excellent yield (Table 3, entry 7). The stereochemistry of the products is confirmed by
comparing the 1H NMR coupling constant data of protons attached to the carbons bearing
-OR and -Br groups of the alkoxybromides with previously reported data (see
Supplymentary material).
EXPERIMENTAL
General
All chemicals used were reagent grade and used as received without further purification.
1H NMR spectra were recorded at 300, 400 and 500 MHz and 13C NMR spectra 75 MHz
in CDCl3 or DMSO-D6. The chemical shifts (δ) are reported in ppm units relative to TMS
as an internal standard for 1H NMR and CDCl3 for 13C NMR spectra. Coupling constants
(J) are reported in hertz (Hz) and multiplicities are indicated as follows: s (singlet), bs
ACCEPTED MANUSCRIPT
5

ACCEPTED MANUSCRIPT
(broad singlet), d (doublet), dd (doublet of doublet), t (triplet), m (multiplet). Mass
spectra were recorded under impact (EI) conditions at 70 eV. Column chromatography
was carried out using silica gel (finer than 200 mesh)
General Procedure For The Synthesis Of Alkoxybromides
To a solution of olefin (2 mmol) in MeOH/EtOH (10 ml) were added NH4Br (2.2 mmol)
and Oxone (2.2 mmol) and the mixture was stirred at room/reflux temperature for the
time shown in Table 2 and 3. After completion (as indicated by TLC), the reaction
mixture was filtered and the solvent evaporated under reduced pressure. The products
were purified by column chromatography over silica gel.
CONCLUSION
In summary, we have reported a general and efficient protocol for the regio- and
stereoselective alkoxybromination of olefins using NH4Br/Oxone without catalyst. This
method is applicable to different kinds of olefins, such as aromatic, linear, and cyclic
olefins. The noteworthy feature of the present method is the use of NH4Br/Oxone
system as a mild, non-toxic, inexpensive reagent system coupled with simple operation
and formation of cleaner products with high yields. Another notable benefit of this
system is that, in ethanol, 4-phenyl-3-butene-2-one gave the corresponding α-brominated
product at room temperature and double bond addition products (ethoxybrominated and
dibrominated product) at reflux temperature.
SUPPORTING INFORMATION
ACCEPTED MANUSCRIPT
6

ACCEPTED MANUSCRIPT
Full experimental detail, 1H, 13C NMR and mass spectra. This material can be found via
the ‘‘Supplementary Content’’ section of this article’s webpage.’’
ACKNOWLEDGEMENTS
M.A.K. and M.N. acknowledge the financial support from the CSIR, India in the form of
fellowships.
REFERENCES
1. (a) De Meijere, A.; Diederich, F., Eds. Metal-Catalyzed Cross-Coupling Reactions, 2nd
ed.; Wiley-VCH: Weinheim, Germany, 2004; (b) Yao, Q.; Kinney, E. P.; Yang, Z.
Ligand-free Heck reaction: Pd(OAc)2 as an active catalyst revisited. J. Org. Chem. 2003,
68, 7528-7531; (c) Seyferth, D. The grignard reagents. Organometallics 2009, 28, 1598-
1605; (d) Johnsson, R.; Meijer, A.; Ellervik, U. Mild and efficient direct aromatic
iodination. Tetrahedron 2005, 61, 11657-11663; (e) Liu, Y. H.; Zhou, S. L. Electrophilic
cyclization of 2-(1-alkynyl)-2-alken-1-ones using the I2/K3PO4 system: an efficient
synthesis of highly substituted iodofurans. Org. Lett. 2005, 7, 4609-4611.
2. (a) Zhang, X.; Corma, A. Effective Au(III)–CuCl2-catalyzed addition of alcohols to
alkenes. Chem. Commun. 2007, 3080-3082; (b) Taber, D. F.; Liang, J.-I. Single
enantiomer epoxides by bromomandelation of prochiral alkenes. J. Org. Chem. 2007, 72,
431-434; (c) Bras, J. L.; Chatterjee, D.; Muzart, J. A simple one-pot synthesis of β-alkoxy
alcohols from alkenes. Tetrahedron Lett. 2005, 46, 4741-4743; (d) Urankar, D.; Rutar, I.;
Modec, B.; Dolenc, D. Synthesis of bromo- and iodohydrins from deactivated alkenes by
use of N-bromo- and N-iodosaccharin. Eur. J. Org. Chem. 2005, 2349-2353; (e)
ACCEPTED MANUSCRIPT
7

ACCEPTED MANUSCRIPT
Minakata, S.; Yoneda, Y.; Oderaotoshi, Y.; Komatsu, M. Unprecedented CO2-promoted
aminochlorination of olefins with chloramine-T. Org. Lett. 2006, 8, 967-969; (f) Muniz,
K. The development of asymmetric diamination of alkenes with imido-osmium reagents.
New J. Chem. 2005, 29, 1371-1385; (g) Singh, S.; Singh, B. Synthesis of gemini
surfactants from N-halosuccinimide-dimercaptoethane cohalogenation of olefinic fatty
methyl esters. Int. Eng. Chem. Res. 2007, 46, 983-986.
3. (a) McCall, A. S.; Wang, H.; Desper, J. M.; Kraft, S. Bis-N-heterocyclic carbene
palladium(IV) tetrachloride complexes: synthesis, reactivity, and mechanisms of direct
chlorinations and oxidations of organic substrates. J. Am. Chem. Soc. 2011, 133, 1832-
1848; (b) Gottam, H.; Vinod, T. K. Versatile and iodine atom-economic co-iodination of
alkenes. J. Org. Chem. 2011, 76, 974-977; (c) Sun, H.; Zhang, G.; Zhi, S.; Han, J.; Li, G.;
Pan, Y. Copper-catalyzed aminobromination/elimination process: an efficient access to
α,β-unsaturated vicinal haloamino ketones and esters. Org. Biomol. Chem. 2010, 8, 4236-
4239; (d) Zhou, L.; Tan, C. K.; Zhou, J.; Yeung, Y.-Y. Facile, efficient, and catalyst-free
electrophilic aminoalkoxylation of olefins: scope and application. J. Am. Chem. Soc.
2010, 132, 10245-10247; (e) Yusubov, M. S.; Yusubova, R. Y.; Kirschning, A.; Park, J.
Y.; Chi, K.–W. m-Iodosylbenzoic acid, a tagged hypervalent iodine reagent for the iodo-
functionalization of alkenes and alkynes. Tetrahedron Lett. 2008, 49, 1506-1509; (f)
Damin, B.; Garapon. J.; Silion, B. A convenient synthesis of chlorohydrins using
chloramine-T. Synthesis 1981, 362-363; (g) Rolston, J. H.; Yates, K. Polar additions to
the styrene and 2-butene systems. I. Distribution stereochemistry of bromination products
in acetic acid. J. Am. Chem. Soc. 1969, 91, 1469-1476.
ACCEPTED MANUSCRIPT
8

ACCEPTED MANUSCRIPT
4. (a) Tenaglia, A.; Pardigon, O.; Buono, G. Regio- and stereoselective functionalization
of deltacyclenes: a route to the synthesis of optically active (+)-deltacyclan-8-one. J. Org.
Chem. 1996, 61, 1129-1132; (b) Dubois, J. E.; Mouvier, G. Essai de correlation
reactivite-structuren relative aux vitesses d'addition du brome sur les olefines
aliphatiques. Tetrahedron Lett. 1963, 20, 1325-1331; (c) Dubois, J. E.; Garbier, F. The
role of transitory charge-transfer complexes in the bromination of olefins. J. Chem. Soc.,
Chem. Commun. 1968, 241-242; (d) Ruasse, M. F.; Dubois, J. E. Role of the solvent in
bromine additions to olefins. Solvent independence of the charge distribution in transition
states and intermediates. J. Am. Chem. Soc. 1975, 97, 1977-1978; (e) Grosjean, D.;
Mouvier, G.; Dubois, J. E. Bromination of ethylenic compounds. Isoreactivity of
trisubstituted geometrical isomers. J. Org. Chem. 1976, 41, 3869-3872; (f) Chretien, J.
R.; Coudert, J.-D.; Ruasse, M.-F. Solvation and steric effects on electrophilic reactivity of
ethylenic compounds. Stereo-, regio-, and chemoselectivity of alkene bromination in
methanol. J. Org. Chem. 1993, 58, 1917-1921; (g) Ruasse, M.-F.; Lo Moro, G.; Galland,
B.; Bianchini, R.; Chiappe, C.; Bellucci, G. Preassociation, free-ion, and ion-pair
pathways in the electrophilic bromination of substituted cis- and trans-stilbenes in protic
solvents. J. Am. Chem. Soc. 1997, 119, 12492-12502; (h) Ruasse, M. F. Bromonium ions
or .beta.-bromocarbocations in olefin bromination. A kinetic approach to product
selectivities. Acc. Chem. Res. 1990, 23, 87-93; (i) Achim, B.; Stefan, I.; Frieder, W. L.
On the alkoxybromination of glucal esters: 2-acetamido-α-D-mannosyl bromides from 2-
acetamidoglucal. Tetrahedron: Asymmetry 2007, 18, 1108-1114; (j) Karade, N. N.;
Gampawar, S. V.; Tiwari, G. B. A regioselective and stereoselective methoxy-
ACCEPTED MANUSCRIPT
9

ACCEPTED MANUSCRIPT
bromination of olefins using (diacetoxyiodo)benzene and lithium bromide. Lett. Org.
Chem. 2007, 4, 419-422.
5. Budavari, S.; O’Neil, M. J.; Smith, A.; Heckelman, P. E.; Kinneary, J. F., Eds. The
Merck Index, 12th ed.; Merck: Rahway, 1996.
6. (a) De Almeida, L. S.; Esteves, P. M.; De Mattos, M. C. S. Tribromoisocyanuric acid:
a new reagent for regioselective cobromination of alkenes. Synlett 2006, 1515–1518; (b)
De Almeida, L. S.; Esteves, P. M.; De Mattos, M. C. S. Efficient electrophilic
cobromination of alkenes and bromination of activated arenes with
bromodichloroisocyanuric acid under mild conditions. Synlett 2007, 1687–1690.
7. Sels, B. F.; De Vos, D. E.; Jacobs, P. A. Use of WO42- on layered double hydroxides
for mild oxidative bromination and bromide-assisted epoxidation with H2O2. J. Am.
Chem. Soc. 2001, 123, 8350-8359.
8. 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.
9. Ye, C.; Shreeve, J. M. Structure-dependent oxidative bromination of unsaturated C-C
bonds mediated by selectfluor. J. Org. Chem. 2004, 69, 8561-8563.
10. Yoshida, M.; Mochizuki, H.; Suzuki, T.; Kamigata, N. A novel method for the
conversion of halide anion to the positive halogen by nitrobenzenesulfonyl peroxide.
application to oxyhalogenation of olefin. Bull. Chem. Soc. Jpn. 1990, 63, 3704-3706.
11. Dewkar, G.; Narina, S. V.; Sudalai, A. NaIO4-Mediated selective oxidative
halogenation of alkenes and aromatics using alkali metal halides. Org. Lett. 2003, 5,
4501-4504.
ACCEPTED MANUSCRIPT
10

ACCEPTED MANUSCRIPT
12. Saumen, H.; Manishabrata, B.; Ananta, K. Lewis acid catalyzed asymmetric
halohydrin reactions of chiral α,β-unsaturated carboxylic acid derivatives with N-
halosuccinimide (NXS) as the halogen source. Tetrahedron Lett. 2005, 46, 3073–3077.
13. Karunakaran, C.; Venkatachalapathy, C. Methoxybromination of cinnamic acid by N-
bromosuccinimide. Bull. Chem. Soc. Jpn. 1990, 63, 2404-2407.
14. Tsubota, M.; Iso, M.; Suzuki, K. Reactions of 2,4,4,6-tetrabromo-2,5-cyclohexadien-
1-one with alkenes in the presence of weak bases. Bull. Chem. Soc. Jpn. 1972, 45, 1252-
1253.
15. Sera, A.; Yamada, H.; Itoh, K. Photo-induced alkoxybromination of olefins by N,N′-
dibromo-2,5-piperazinedione. Bull. Chem. Soc. Jpn. 1980, 53, 219-221.
16. Saumen, H.; Ananta, K.; Manishabrata, B. Silver(I)-promoted asymmetric
halomethoxylation of chiral α,β-unsaturated carboxylic acid derivatives: enantioselective
synthesis of N-protected syn-β-methoxy-α-amino acids. Tetrahedron: Asymmetry 2006,
17, 210–222.
17. Victor, L. H.; Charles, L. F.; Gene, E. H.; Kenneth, A. M.; David, A. R.; Paul, S. W.
The reactions of methyl hypobromite and acetyl hypobromite with olefins. Tetrahedron
Lett. 1970, 18, 1573-1576.
18. Agarwal, M. K.; Adimurthy, S.; Ganguly, B.; Ghosh, P. K. Comparative study of the
vicinal functionalization of olefins with 2:1 bromide/bromate and iodide/iodate reagents.
Tetrahedron 2009, 65, 2791-2797.
19. (a) Travis, B. R.; Sivakumar, M.; Hollist, G. O.; Borhan, B. Facile oxidation of
aldehydes to acids and esters with oxone. Org. Lett. 2003, 5, 1031-1034; (b) Yang, D.;
Zhang, C. Ruthenium-catalyzed oxidative cleavage of olefins to aldehydes. J. Org. Chem.
ACCEPTED MANUSCRIPT
11

ACCEPTED MANUSCRIPT
2001, 66, 4814-4818; (c) Gomzalez-Nunez, M. E.; Mello, R.; Olmos, A.; Asensio, G.
Baeyer-Villiger oxidation in supercritical CO2 with potassium peroxomonosulfate
supported on acidic silica gel. J. Org. Chem. 2006, 71, 6432-6436; (d) Ashford, S. W.;
Grega, K. C. Oxidative cleavage of 1,3-dicarbonyls to carboxylic acids with oxone. J.
Org. Chem. 2001, 66, 1523-1524; (e) Molander, G. A.; Cavalcanti, L. N. Oxidation of
organotrifluoroborates via oxone. J. Org. Chem. 2011, 76, 623-630; (f) Moorthy, J. N.;
Senapati, K.; Parida, K. N.; Jhulki, S.; Sooraj, K.; Nair, N. N. Twist does a twist to the
reactivity: stoichiometric and catalytic oxidations with twisted tetramethyl-IBX. J. Org.
Chem. 2011, 76, 9593-9601; (g) Dominique, L.; Joseph, D.; Rejane, G.; Peter, G. G.
Epoxidation of glycals with oxone-acetone-tetrabutylammonium hydrogen sulfate: a
convenient access to simple β-D-glycosides and to α-D-mannosamine and D-talosamine
donors. Tetrahedron: Asymmetry 2011, 22, 1197-1204; (h) Stefan, B.; Anna, C.;
Agnieszka, S. New and efficient technique for the synthesis of -caprolactone using
KHSO5 as an oxidising agent in the presence of a phase transfer catalyst. Appl. Catal. A
2011, 395, 49-52; (i) Lopa V. D.; Hasnain A. M.; Melanie S. S. Oxone as an inexpensive,
safe, and environmentally benign oxidant for C-H bond oxygenation. Org. Lett. 2006, 8,
1141-1144.
20. (a) Mohan, K. V. V. K.; Narender, N. Ecofriendly oxidative nuclear halogenation of
aromatic compounds using potassium and ammonium halides. Synthesis 2012, 44, 15; (b)
Kumar, M. A.; Rohitha, C. N.; Reddy, M. M.; Swamy, P.; Narender, N. Oxidative
bromination of ketones using ammonium bromide and oxone. Tetrahedron Lett. 2012,
53, 191-195; (c) Reddy, M. M.; Kumar, M. A.; Swamy, P.; Narender, N. Oxidative
ACCEPTED MANUSCRIPT
12

ACCEPTED MANUSCRIPT
iodination of carbonyl compounds using ammonium iodide and oxone. Tetrahedron Lett.
2011, 52, 6554-6559.
21. Kumar, M. A.; Rohitha, C. N.; Narender, N. Regio- and stereoselective
hydroxybromination and dibromination of olefins using ammonium bromide and oxone.
Tetrahedron Lett. 2012, 53, 1401-1405.
ACCEPTED MANUSCRIPT
13

ACCEPTED MANUSCRIPT
Table 1. Alkoxybromination of styrene using various alcoholsa
OR
Br
NH4Br, Oxone
+
Ph
Ph
Ph
ROH
Br
Br
1
2
3
Entry
ROH
Time
Yield (%)b
2
3
1
MeOH
EtOH
,,
50 minc
24 hc
85
64
84
55
70
30
35
50
61
6
<5
14
<5
22
9
2
3
2.45 hd
24 hc
4
n-PrOH
5
,,
11 hd
24 hc
6
i-PrOH
41
12
15
<5
12
<5
19
10
30
55
7
,,
10 hd
24 hc
8
n-BuOH
9
,,
10 hd
24 hc
10
11
12
13
14
15
2-BuOH
,,
12 hd
24 hc
8
i-BuOH
25
34
7
,,
12.3 hd
42 hc
t-BuOH
,,
10.3 hd
22
aStyrene (2 mmol), NH4Br (2.2 mmol), Oxone (2.2 mmol), ROH (10 mL).
bIsolated yields.
ACCEPTED MANUSCRIPT
14

ACCEPTED MANUSCRIPT
cAt room temperature.
dAt 80˚C.
ACCEPTED MANUSCRIPT
15

ACCEPTED MANUSCRIPT
Table 2. Methoxy and Ethoxybromination of various aromatic olefins
Entry
1
Olefin
Product
R
Time
Yield (%)a
85 (4a)/<5e
Me
Et
50 minb
2.45 hc
OR
Br
84 (4A)/<5e
OR
Br
2
3
Me
Et
40 minb
2 hc
90 (4b)
O
O
92 (4B)
OR
Br
Me
Et
15 minb
45 minc
93 (4c)
84 (4C)/<5e
OR
4
5
Me
Et
6 minb
1.15 hc
80 (4d)/<5e
75(4D)/<5e
Br
OR
Me
Et
15 minb
2.30 hc
76 (4e)/<5e
80 (4E)
Br
OR
Br
6
7
Me
Et
30 minb
3 hc
91 (4f)
Cl
Br
Cl
Br
85 (4F)
OR
Br
Me
Et
1 hb
84 (4g)/<5e
85 (4G)
3 hc
13 minb
2.15 hc
92 (4h)
83 (4H)
OR
Br
8
Me
Et
ACCEPTED MANUSCRIPT
16

ACCEPTED MANUSCRIPT
15 minb
2 hc
88 (4i)
OR
9
Me
Br
Cl
Et
72 (4I)/6e
84f (4j)/<5e
89f (4J)
Cl
10
Me
Et
40 minb
3.30 hc
CH2OH
OR
Ph
CH2OH
Ph
Br
COCH3
COOH
OR
11
12
Me
2.15 hb
76f (4k)/5e
Ph
Ph
COCH3
COOH
Ph
Ph
Br
OR
Br
Me
Et
2.30 hb
24 hd
76f (4l)/<5e
31f (4L)/29e
3 hb
71f (4m)/14e
20f (4M)/35e
COOMe
OR
13
Me
Et
Ph
COOMe
Ph
24 hd
Br
OR
COPh
14
15
Me
Et
1 hb
70f (4n)/10e
Ph
Ph
COPh
Ph
Ph
3.3 hc
75h /<5e
Br
Ph
OR
Me
Et
1.3 hb
3.3 hc
80f (4o)/<5e
76f (4O)/6e
Ph
Br
ACCEPTED MANUSCRIPT
17

ACCEPTED MANUSCRIPT
1 hb
73g (4p)/5e
OR
16
Me
Ph
Ph
Ph
Br
Ph
Et
1.3 hc
40i /10e
aIsolated yields.
bOlefin (2 mmol), NH4Br (2.2 mmol), Oxone (2.2 mmol), MeOH (10 mL) at room
temperature.
cOlefin (2 mmol), NH4Br (2.2 mmol), Oxone (2.2 mmol), EtOH (10 mL) at reflux
temperature.
dAt room temperature.
eDibromo product.
ferythro products.
gthreo products.
hMolar ratio of erythro and threo 62:38, determined by 1H NMR.
iMolar ratio of threo and erythro 33:67, determined by 1H NMR.
ACCEPTED MANUSCRIPT
18

ACCEPTED MANUSCRIPT
Table 3. Methoxy and Ethoxybromination of various linear and cyclic olefins
Entry Olefin
Products
Time
R=Me R=Et R=Me
Yield (%)a
R=Et
1
45 minb 4 hc
60 (4q)/12e 54 (4Q)/20e
5 (4qI) 5 (4QI)
OR
CH3(CH2)9
CH3(CH2)9
CH3(CH2)9
Br
Br
OR
45 minb 4 hc
24 (4r)/16e 18 (4R)/21e
OR
2
CH3(CH2)4
CH3(CH2)4
CH3(CH2)4
39 (4rI)
33 (4RI)
Br
Br
OR
30 minb 2.3 hc 75 (4s)/6e
63 (4S)/20e
OR
Br
3
HO
HO
5 minb 24 hd 64 (4t)/15e 34(4T)/32e
10 minb 24 hd 71 (4u)/10e 66(4U)/14e
OR
4
5
Br
OR
Br
15 minb 4 hc
76 (4v)/5e 81 (4V)/<5e
OR
6
Br
ACCEPTED MANUSCRIPT
19

ACCEPTED MANUSCRIPT
24 hb
5.3 hc 68 (4w)
73(4w)
O
O
7
Br
O
O
aIsolated yields.
bOlefin (2 mmol), NH4Br (2.2 mmol), Oxone (2.2 mmol), MeOH (10 mL) at room
temperature.
cOlefin (2 mmol), NH4Br (2.2 mmol), Oxone (2.2 mmol), EtOH (10 mL) at reflux
temperature.
dAt room temperature.
eDibromo product.
ACCEPTED MANUSCRIPT
20

ACCEPTED MANUSCRIPT
Scheme 1. Bromination of 4-phenyl-3-butene-2-one in ethanol
ACCEPTED MANUSCRIPT
21