Studies on the indium-mediated reduction of imines

Article abstract of DOI:10.1081/SCC-100104072

Indium-ammonium chloride-mediated reduction of imines was investigated and the products were found to be monoamines.

Full text of DOI:10.1081/SCC-100104072

This article was downloaded by: [York University Libraries]
On: 20 November 2014, At: 19:45
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
STUDIES ON THE INDIUM-
MEDIATED REDUCTION OF
IMINES
Bimal K. Banik a , Linda Hackfeld a & Frederick F.
Becker a
a Department of Molecular Pathology , The
University of Texas, M. D. Anderson Cancer
Center , Box 89, 1515, Holcombe Blvd., Houston,
TX, 77030, U.S.A.
Published online: 02 Aug 2010.
To cite this article: Bimal K. Banik , Linda Hackfeld & Frederick F. Becker
(2001) STUDIES ON THE INDIUM-MEDIATED REDUCTION OF IMINES, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 31:10, 1581-1586, DOI: 10.1081/SCC-100104072
To link to this article: http://dx.doi.org/10.1081/SCC-100104072
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 COMMUNICATIONS, 31(10), 1581–1586 (2001)
STUDIES ON THE INDIUM-MEDIATED
REDUCTION OF IMINES
Bimal K. Banik,* Linda Hackfeld,
and Frederick F. Becker
The University of Texas, M. D. Anderson Cancer Center,
Department of Molecular Pathology, Box 89, 1515
Holcombe Blvd., Houston, TX 77030
ABSTRACT
Indium-ammonium chloride-mediated reduction of imines
was investigated and the products were found to be monoa-
mines.
In our earlier publications,1–4 we demonstrated a novel reduction
study of aromatic nitro compounds and imines by samarium-induced
iodine-catalyzed reaction. The imines produced monoamines or diamines,
depending on the substituents.2 A most probable mechanism was advanced
based on their production. The synthesis of polyaromatic mono-amino deri-
vatives is of considerable interest to us. We have already established that
suitably substituted polyaromatic chrysene derivatives can serve as anti-
tumor agents5 (Scheme 1).
The formation of diamines with aryl alkyl imines in the samarium-
induced reaction prevented us from doing a systematic structure-activity
study of a series of polycyclic amino derivatives that have only one chromo-
phore.2 For this reason, we became interested in other metal-catalyzed
* Corresponding author.
1581
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

1582
BANIK, HACKFELD, AND BECKER
Scheme 1.
processes that might make possible the synthesis of substituted monoamines
with different side groups. We report here a systematic indium-mediated
reduction study of the imines of widely different structures to the
monoamines.
The use of indium in synthetic organic chemistry is gaining increasing
attention as the reactions with it can be carried out in aqueous solution.6–11
The reducing ability of indium is also known. We noted a reduction
reaction of the imines to the dimeric products by indium-rod in aqueous
ammonium chloride.12,13 Realizing the problem associated with the use
of water in the reduction of imines that are susceptible to hydrolysis
under aqueous solution, we previously carried out their reduction under
non-aqueous conditions. Repetition of the reduction of the known imine
(entry 5) by indium powder and ammonium chloride in ethanol unexpect-
edly produced the monoamine (Table 1). This is in contrast with the obser-
vation reported earlier.12 Encouraged by this result, we selected several
imines (Table 1) and performed a systematic reduction study by indium
powder-ammonium chloride in ethanol. The products from the reactions
were found to be a monoamine and no dimeric products could be detected.
The imines that have alkyl groups produced a complex mixture of products
in which the presence of monoamines could be detected (entries 6 and 7).
However, as expected because of the mild acidity of ammonium chlor-
ide, a small amount of primary amine arising from the decomposition of the
starting material was also isolated. Nevertheless, reduction of the imines to
the monoamines is noteworthy because of its generality. The applicability
of the prior report12 is limited as only aryl-aryl imines were reactive and the
products were diamines under the published procedure.
Although the mechanism of the indium-mediated reaction is not
clearly understood at this time, it seems probable that it takes place
via a single electron transfer to the unsaturated imine bond. Mangeney
et al.14 studied the reduction of imines by low valent titanium and suggested
a single electron transfer to the imine bond. By applying their mechanism
and as an extension of our earlier hypothesis,2 we postulated initial electron
transfer to generate the ion-radical (A), which, upon further electron
transfer, can generate the dianion (B) (Scheme 2). Alternatively, the

IMINE REDUCTION
Table 1. In/NH4Cl-Induced Reduction of Imines
1583
Entry
Imines
In (eq.)
Reflux Time (h)
Product
1
2.5
10
1
2
3
2.5
2.5
3
2
3
11
4
5
2.5
2.5
11
4
5
3
6
7
2.5
2.5
11
8

1584
BANIK, HACKFELD, AND BECKER
Scheme 2.
ion-radical (A) can undergo self-coupling and produce the diamines (C).
However, the formation of monoamines by the present method ruled out
the radical-radical coupling mechanism. It appears that the dimeric product
that the earlier work12 isolated in the presence of water was formed through
the self-coupling process. This indicates water has a profound effect in the
maintenance of the stability of the intermediates. How the presence of water
molecule facilitates the radical-radical coupling process is not known to us
at this time.
In conclusion, synthesis of monoamines in good isolated yield was
achieved by the reduction of imines.
EXPERIMENTAL
General Experimental Procedure
Imine (0.55 mol) was added to EtOH (2 mL) containing In (1.38mol)
and NH4Cl (1.2 mol). The reaction was refluxed until complete. Ethyl
acetate (2 mL) was added, filtered through Na2SO4, and evaporated to
dryness. The product was isolated by column chromatography over basic
1
alumina or by crystallization from dichloromethane–hexanes. All H NMR
were taken on a Bruker 300 MHz Avance NMR and all IR data were taken
on a Perkin Elmer Spectrum 2000.
(1): yield: 80%; m.p. 30ꢀ–31ꢀC; IR (neat) cmꢁ1: 3415, 1725, 1602; H
1
NMR (CDCl3) d: 4.33 (s, 2H), 6.50–6.55 (m, 1H), 6.62–6.74 (m, 3H), 7.08–
7.39 (m, 7H); m/e: 184 (MþH)þ; Anal. calc. for C13H13N: C, 85.2; H, 7.2; N,
7.6. Found: C, 84.29; H, 7.06; N, 8.15.
(2): yield: 85%; m.p. 42ꢀ–43ꢀC; IR (neat) cmꢁ1: 3410, 1727, 1624,
1
1602; H NMR (CDCl3) d: 3.74 (s, 3H), 4.28(s, 2H), 6.59–6.62 (m, 2H),

IMINE REDUCTION
1585
6.77–6.79 (m, 2H), 7.26–7.36 (m, 6H); m/e: 214 (MþH)þ; Anal. calc. for
C14H15NO: C, 78.8; H, 7.1; N, 6.6. Found: C, 79.03; H, 7.28; N, 6.71.
(3): yield: 75%; m.p. 64ꢀ–65ꢀC; IR (neat) cmꢁ1: 3380, 1722, 1656,
1626, 1600; 1H NMR (CDCl3) d: 4.45 (s, 2H), 7.26–7.47 (m, 10H),
7.78–7.87 (m, 3H); m/e: 234 (MþH)þ; Anal. calc. for C17H15N: C, 87.5;
H, 6.5; N, 6.0. Found: C, 87.53; H, 6.31; N, 6.27.
(4): yield: 65%; m.p. 168ꢀ–169ꢀC; IR (neat) cmꢁ1: 3438, 1722, 1700,
1651, 1621; 1H NMR (CDCl3) d: 4.74 (s, 2H), 7.38–7.48 (m, 3H), 7.59–7.78
(m, 9H), 7.99–8.00 (m, 2H), 8.60–8.62 (m, 2H), 8.81–8.84 (d, 1H); m/e: 334
(MþH)þ; Anal. calc. for C25H19N: C, 90.1; H, 5.7; N, 4.2. Found: C, 89.90;
H, 5.64; N, 4.20.
(5): yield: 80%; oil; IR (neat) cmꢁ1; 3315, 3227, 1724, 1662, 1604;
1H NMR (CDCl3) d: 4.08 (s, 4H), 6.89–7.54 (m, 7H), 7.79–7.82 (m, 4H);
m/e: 198(M þH)þ.
ACKNOWLEDGMENTS
We gratefully acknowledge the funding support received for this
research project from the Golden Family fund for Cancer Research and
NIH cancer Center Support Grant, 50P30-CA-16672-25, in particular, the
shared resources of the Pharmacology and Analytical Center Facility.
REFERENCES
1. Banik, B.K.; Mukhopadhyay, C.; Venkatraman, M.S.; Becker, F.F.
Tetrahedron Lett. 1998, 39, 7243.
2. Banik, B.K.; Zegrocka, O.; Banik, I.; Hackfeld, L.; Becker, F.F.
Tetrahedron Lett. 1999, 40, 6731.
3. Ghatak, A.; Becker, F.F.; Banik, B.K. Tetrahedron Lett. 2000, 41,
3793.
4. Banik, B.K.; Zegrocka, O.; Becker, F.F. J. Chem. Res. 2000, 7, 321.
5. Becker, F.F.; Banik, B.K. Bioorg. Med. Chem. Lett. 1998, 8, 2877.
6. Li, C.J. Chem. Rev. 1993, 93, 2023.
7. Li, C.J. Tetrahedron 1996, 52, 5643.
8. Li, C.J.; Chan, T.H. Organic Reactions in Aqueous Media; J. Wiley &
Sons: New York, 1997.
9. Paquette, L.A.; Rothhaar, R.R.; Isaac, M.; Rogers, L.M.; Rogers, R.D.
J. Org. Chem. 1998, 63, 5463.
10. Hoppe, H.A.; Lloyd-Jones, C.G.; Murray, M.; Peakman, T.M.;
Walsh, K.E. Angew Chem., Int. Ed. Engl. 1998, 37, 1545.

1586
BANIK, HACKFELD, AND BECKER
11. Ranu, B.C.; Dutta, P.; Sarkar, A. Tetrahedron Lett. 1998, 39, 9557.
12. Kalyanam, N.; Rao, G.V. Tetrahedron Lett. 1993, 34, 1647.
13. Banik, B.K.; Suhendra, M.; Banik, I.; Becker, F.F. Synth. Commun.
2000, 20, 3745.
14. Mangeney, P.; Tejero, T.; Grosjean, A.F.; Normant, G.J. Synthesis
1988, 255.
Received in the USA August 3, 2000