Microwave-assisted copper promoted N-arylation of amines with aryl boronic acids/salts on a KF-alumina surface

Article abstract of DOI:10.1081/SCC-120038497

An experimentally simple microwave-assisted solvent-free N-arylation of primary amines with sodium tetraphenylborate or arylboronic acids, promoted by inexpensive cupric acetate, on the surface of KF-alumina is reported. The reaction is selective for mono-N-arylation, and a variety of functional groups are tolerated in the process.

Full text of DOI:10.1081/SCC-120038497

This article was downloaded by: [New York University]
On: 23 May 2015, At: 07:51
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
Microwave‐Assisted Copper Promoted N‐Arylation
of Amines with Aryl Boronic Acids/Salts on a
KF–Alumina Surface
Pralay Das a & Basudeb Basu a
a Department of Chemistry , North Bengal University , Darjeeling, 734 430, India
Published online: 17 Aug 2006.
To cite this article: Pralay Das & Basudeb Basu (2004) Microwave‐Assisted Copper Promoted N‐Arylation of Amines
with Aryl Boronic Acids/Salts on a KF–Alumina Surface, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 34:12, 2177-2184, DOI: 10.1081/SCC-120038497
To link to this article: http://dx.doi.org/10.1081/SCC-120038497
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

SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 12, pp. 2177–2184, 2004
Microwave-Assisted Copper Promoted
N-Arylation of Amines with Aryl Boronic
Acids/Salts on a KF–Alumina Surface
*
Pralay Das and Basudeb Basu
Department of Chemistry, North Bengal University, Darjeeling, India
ABSTRACT
An experimentally simple microwave-assisted solvent-free N-arylation
of primary amines with sodium tetraphenylborate or arylboronic acids,
promoted by inexpensive cupric acetate, on the surface of KF–alumina
is reported. The reaction is selective for mono-N-arylation, and a variety
of functional groups are tolerated in the process.
Key Words: N-Arylation; Cupric acetate; Tetraphenylborate salt;
Arylboronic acids; KF–alumina; Microwaves.
Aryl amines are an important class of compounds and are widely used as
drugs, dyes, polymers, and other fine chemicals.[1,2] Transition metal mediated
*
Correspondence: Basudeb Basu, Department of Chemistry, North Bengal University,
Darjeeling 734 430, India; E-mail: basu_nbu@indiatimes.com.
2177
DOI: 10.1081/SCC-120038497
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

ORDER
REPRINTS
2178
Das and Basu
C–N bond-forming processes are important fundamental transformations and
are extensively utilized for N-arylation reactions. Besides copper promoted
N-arylation of amines (the Ullmann reaction)[3] (for a review, see Ref.[3b]),
a significant discovery, during the last few years independently made by
Buchwald and Hartwig, is the palladium catalyzed cross-coupling of aryl
halides or triflates with amines (for reviews, see Ref.[4]). Although this process
requires much milder reaction conditions than those of the Ullmann reaction,
some limitations, such as difficulties associated with aryl halides possessing
free N–H groups[5] along with the use of expensive palladium sources and
ligands, still remain. On the other hand, traditional protocols for the Ullmann
reaction prescribe stoichiometric use of copper salts and rely generally on
high temperatures. Recently, N-arylation of aryl halides with amines has been
achieved using a catalytic amount of CuI, complexing ligands, and a strong
base. In the absence of ligands, the copper salts exhibited poor catalytic activity
(see Ref.[6] and references cited therein). Chan and co-workers have reported an
important alternative, where arylboronic acids are used as arylating agents
instead of aryl halides.[7] Lam and others further investigated this reaction
(for leading references, see Ref.[8]). Although the reaction proceeds at room
temperature, the use of dichloromethane as the solvent, a tertiary amine as
the base, prolonged reaction times, as well as poor yields in some cases were
still a few disadvantages, and thus the procedure required improvements.
With the advent of easy access to a variety of organoboron compounds
as well as in connection with our interests in palladium mediated solvent-
free C–C and C–N bond-forming processes on KF–alumina surfaces,[9] we
investigated copper promoted N-arylation of amines using tetraphenylborate
salts or arylboronic acids. In this paper, we wish to report our results, which
constitute a convenient method for N-arylation of primary amines using
tetraphenylborate salts or arylboronic acids under microwave irradiation
(Sch. 1). The reaction is operationally simple, solvent-free, fast, and does
not require any fastidious work-up.a
aRepresentative experimental procedure: A mixture of p-bromoaniline (172 mg,
1 mmol), phenylboronic acid (244 mg, 2 mmol), and anhydrous cupric acetate
(200 mg, 1 mmol) was intimately mixed with KF–alumina[9a] (1 g) and irradiated
using a household microwave oven at 160 W for 10 min. After cooling, the solid
mass was placed on a column of silica gel and eluted with petroleum-ether : ethyl
acetate (49 : 1) to afford (p-bromophenyl)phenylamine as colorless flakes (181 mg,
73%); m.p. 84–868C; 1H-NMR (CDCl3, 300 MHz): d 6.88 (d, 2H, J ¼ 8.8 Hz),
6.87–6.93 (m, 1H), 6.99–7.02 (m, 2H), 7.20 (d, 2H, J ¼ 8.8 Hz), 7.18–7.29 (m, 2H);
13C-NMR (CDCl3, 75 MHz): d 114.7, 120.1, 120.9, 123.6, 131.0, 131.1, 133.8, 143.7.

ORDER
REPRINTS
Copper Promoted N-Arylation of Amines
2179
Scheme 1.
Representative results of the copper promoted N-arylation of several
amines are summarized in Table 1. Primary amines were monoarylated
successfully using either sodium tetraphenylborate or arylboronic acids.
Aromatic amines bearing either electron donating (entries 7 and 8) or elec-
tron withdrawing groups (entries 5 and 6) gave the corresponding unsymme-
trical diarylamines in good to excellent yields. Aliphatic primary amines
(entries 3 and 4) and benzylamine (entry 10) also produced N-arylated
products in 70–75% yields. Halo-substitutions, either on the aryl amine or
the arylboronic acid remained unaffected under these reaction conditions.
Thus, reaction of p-bromoaniline with phenylboronic acid (entry 9) or with
p-iodophenylboronic acid (entry 12) yielded the desired secondary amines
in good yields. Since triarylamines represent an important class of com-
pounds, we studied N-arylation of secondary amines with phenylboronic
acids. Attempts with both aliphatic and aromatic secondary amines (entries
13 and 14) were unsuccessful. Thus, the reaction is selective for mono-
N-arylation and requires the use of a stoichiometric amount of the copper(II)
salt. Catalytic amounts of cupric acetate with or without a ligand did not
result in reaction. In most cases, small amounts of the corresponding biaryls
(,5%) were formed as detected by TLC. In general, a mixture of sodium
tetraphenylborate (1 mmol) or arylboronic acid (2 mmol), the amine
(1 mmol), and cupric acetate (1 mmol) was intimately mixed on KF–alumina
(1 g/1 mmol) and irradiated using a domestic microwave oven (Kenstar;
Model: OM-9925E) at the appropriate power and time (Table 1). The desired
product was obtained by column chromatography on silica gel. Yields are
much better using microwave irradiation in comparison to thermal reaction
(for reviews, see Ref.[10]).
In summary, we have devised a rapid and operationally simple technique
for conducting selective mono-N-arylation of primary amines using sodium
tetraphenylborate or arylboronic acids as the arylating agent in a copper
promoted reaction and using an unmodified household microwave oven.
The reaction was performed in the air and under solvent-free conditions
with good to excellent yields of products and where a variety of functional
groups were tolerated. Furthermore, the N-arylation has been found to be

ORDER
REPRINTS
2180
Das and Basu

ORDER
REPRINTS
Copper Promoted N-Arylation of Amines
2181

ORDER
REPRINTS
2182
Das and Basu
effective either with the boronic acid or with the tetraalkylborate salt. Future
work will include studies aimed towards determining a specific microwave
effect in addition to broadening the scope of using highly functionalized
amines.
ACKNOWLEDGMENT
We gratefully acknowledge financial assistance from the Department of
Science and Technology, New Delhi (Grant No. SP/S1/G13/97). P.D. is a
Junior Research Fellow under this project.
REFERENCES
1. (a) Negwer, M. Organic–Chemicals Drugs and Their Synonyms: An
International Survey, 7th Ed.; Akademic: Berlin, 1994; (b) Hong, Y.P.;
Tanoury, G.J.; Wilkinson, H.S.; Bakale, R.P.; Wald, S.A.;
Senanayake, C.H. Palladium catalyzed amination of 2-chloro-1,3-azole
derivatives: mild entry to potent H1-antihistaminic norastemizole. Tetra-
hedron Lett. 1997, 38, 5607.
2. (a) MacDiarmid, A.G.; Epstein, A.J. Science and Applications of
Conducting Polymers; Salaneck, W.R., Clark, D.T., Samuelsen, E.J.,
Eds.; Hilger: New York, 1991; (b) Thayumanavan, S.; Barlow, S.;
Marder, S.R. Synthesis of unsymmetrical triarylamines for photonic
applications via one-pot palladium-catalyzed aminations. Chem. Mater.
1997, 9, 3231.
3. (a) Ullman, F. Ber. Dtsch. Chem. Ges. 1903, 36, 2382; (b) Lindley, J.
Copper assisted nucleophilic substitution of aryl halogen. Tetrahedron
1984, 40, 1433; (c) Gauthier, S.; Frechet, J.M.J. Phase-transfer catalysis
in the Ullmann synthesis of substituted triphenylamines. Synthesis
1987, 383; (d) Paine, A.J. Mechanisms and models for copper mediated
nucleophilic aromatic substitution. 2. Single catalytic species from
three different oxidation states of copper in an Ullmann synthesis of tri-
arylamines. J. Am. Chem. Soc. 1987, 109, 1496; (e) Goodbrand, H.B.;
Hu, N.-X. Ligand-accelerated catalysis of the Ullmann condensation:
application to hole conducting triarylamines. J. Org. Chem. 1999, 64,
670; (f) Arterburn, J.B.; Pannala, M.; Gonzalez, A.M. Catalytic amination
of 5-iodouracil derivatives. Tetrahedron Lett. 2001, 42, 1475;
(g) Kwong, F.Y.; Klapars, A.; Buchwald, S.L. Copper-catalyzed coupling
of alkylamines and aryl iodides: an efficient system even in an air atmos-
phere. Org. Lett. 2002, 4, 581.

ORDER
REPRINTS
Copper Promoted N-Arylation of Amines
2183
4. (a) Wolfe, J.P.; Wagaw, S.; Marcoux, J.-F.; Buchwald, S.L. Rational devel-
opment of practical catalysts for aromatic carbon–nitrogen bond for-
mation. Acc. Chem. Res. 1998, 31, 805; (b) Yang, B.H.; Buchwald, S.L.
Palladium-catalyzed amination of aryl halides and sulfonates.
J. Organomet. Chem. 1999, 576, 125; (c) Hartwig, J.F. Carbon–hetero-
atom bond-forming reductive eliminations of amines, ethers, and sulfides.
Acc. Chem. Res. 1998, 31, 853; (d) Hartwig, J.F. Synthesis, structure, and
reactivity of a palladium hydrazonato complex: a new type of reductive
elimination reaction to form C–N bonds and catalytic arylation of benzo-
phenone hydrazone. Angew. Chem. Int. Ed. Engl. 1998, 37, 2046;
(e) Muci, A.R.; Buchwald, S.L. Practical palladium catalysts for C–N
and C–O bond formation. In Topics in Current Chemistry; Miyaura, N.,
Ed.; Springer-Verlag: Berlin, 2002; Vol. 219, 133.
5. (a) Prashad, M.; Hu, B.; Lu, Y.; Draper, R.; Har, D.; Repic, O.;
Blacklock, T.J. b-Hydrogen-containing sodium alkoxides as suitable
bases in palladium-catalyzed aminations of aryl halides. J. Org. Chem.
2000, 65, 2612; (b) Link, J.T.; Sorensen, B.; Liu, G.; Pei, Z.;
Reilly, E.B.; Leitza, S.; Okasinski, G. Discovery and SAR of diarylsulfide
cyclopropylamide LFA-1/ICAM-1 interaction antagonists. Bioorg. Med.
Chem. Lett. 2001, 11, 973.
6. (a) Kiyomori, A.; Marcoux, J.-F.; Buchwald, S.L. An efficient copper-
catalyzed coupling of aryl halides with imidazoles. Tetrahedron Lett.
1999, 40, 2657; (b) Kelkar, A.A.; Patil, N.M.; Chaudhari, R.V. Copper-
catalyzed amination of aryl halides: single-step synthesis of triarylamines.
Tetrahedron Lett. 2002, 43, 7143.
7. Chan, D.M.T.; Monaco Wang, R.-P.; Winters, M.P. New N- and O-aryl-
ations with phenylboronic acids and cupric acetate. Tetrahedron Lett.
1998, 39, 2933.
8. (a) Lam, P.Y.S.; Clark, C.G.; Saubern, S.; Adams, J.; Winters, M.P.;
Chan, D.M.T.; Combs, A. New aryl/heteroaryl C–N bond cross-coupling
reactions via arylboronic acid/cupric acetate arylation. Tetrahedron Lett.
1998, 39, 2941; (b) Combs, A.; Saubern, S.; Rafalski, M.; Lam, P.Y.S.
Solid supported aryl/heteroaryl C–N cross-coupling reactions. Tetrahe-
dron Lett. 1999, 40, 1623; (c) Lam, P.Y.S.; Clark, C.G.; Saubern, S.;
Adams, J.; Averill, K.; Chan, D.M.T.; Combs, A. Copper promoted aryl/
saturated heterocyclic C–N bond cross-coupling with arylboronic acid
and arylstannane. Synlett. 2000, 674; (d) Evans, D.A.; Katz, J.L.;
West, T.R. Synthesis of diaryl ethers through the copper-promoted arylation
of phenols with arylboronic acids. An expedient synthesis of thyroxine. Tet-
rahedron Lett. 1998, 39, 2937; (e) Collman, J.P.; Zhong, M.; Zeng, L.;
.
Costanzo, S. The [Cu(OH) TMEDA]2Cl2-catalyzed coupling of arylboro-
nic acids with imidazoles in water. J. Org. Chem. 2001, 66, 1528.

ORDER
REPRINTS
2184
Das and Basu
9. (a) Basu, B.; Jha, S.; Mridha, N.K.; Bhuiyan, M.M.H. Palladium-catalysed
amination of halopyridines on a KF-alumina surface. Tetrahedron Lett.
2002, 43, 7967; (b) Basu, B.; Das, P.; Bhuiyan, M.M.H.; Jha, S. Micro-
wave-assisted Suzuki coupling on a KF–alumina surface: synthesis of poly-
aryls. Tetrahedron Lett. 2003, 44, 3817.
10. (a) Loupy, A.; Petit, A.; Hamelin, J.; Texier-Boullet, F.; Jacquault, P.;
Mathe, D. New solvent-free organic synthesis using focused microwaves.
Synthesis 1998, 1213; (b) Deshayes, S.; Liagre, M.; Loupy, A.; Luche,
J.-L.; Petit, A. Microwave activation in phase transfer catalysis. Tetrahe-
dron 1999, 55, 10851; (c) de la Hoz, A.; Daiz-Ortis, A.; Moreno, A.;
Langa, F. Cycloadditions under microwave irradiation conditions:
methods and applications. Eur. J. Org. Chem. 2000, 3659;
(d) Perreux, L.; Loupy, A. A tentative rationalization of microwave
effects in organic synthesis according to the reaction medium, and
mechanistic considerations. Tetrahedron 2001, 57, 9199; (e) Verma, R.S.
Advances in Green Chemistry: Chemical Syntheses Using Microwave
Irradiation; Astra Zeneca Research Foundation: Bangalore, 2002.
Received in India February 20, 2004

Request Permission or Order Reprints Instantly!
Interested in copying and sharing this article? In most cases, U.S. Copyright
Law requires that you get permission from the article’s rightsholder before
using copyrighted content.
All information and materials found in this article, including but not limited
to text, trademarks, patents, logos, graphics and images (the "Materials"), are
the copyrighted works and other forms of intellectual property of Marcel
Dekker, Inc., or its licensors. All rights not expressly granted are reserved.
Get permission to lawfully reproduce and distribute the Materials or order
reprints quickly and painlessly. Simply click on the "Request Permission/
Order Reprints" link below and follow the instructions. Visit the
U.S. Copyright Office for information on Fair Use limitations of U.S.
copyright law. Please refer to The Association of American Publishers’
Fair Use in the Classroom.
(AAP) website for guidelines on
The Materials are for your personal use only and cannot be reformatted,
reposted, resold or distributed by electronic means or otherwise without
permission from Marcel Dekker, Inc. Marcel Dekker, Inc. grants you the
limited right to display the Materials only on your personal computer or
personal wireless device, and to copy and download single copies of such
Materials provided that any copyright, trademark or other notice appearing
on such Materials is also retained by, displayed, copied or downloaded as
part of the Materials and is not removed or obscured, and provided you do
not edit, modify, alter or enhance the Materials. Please refer to our
Website
User Agreement for more details.
Request Permission/Order Reprints
Reprints of this article can also be ordered at
http://www.dekker.com/servlet/product/DOI/101081SCC120038497