Tantalum (V) chloride catalyzed ring opening of aziridines with aromatic amines

Article abstract of DOI:10.1081/SCC-200034759

Tantalum (V) Chloride adsorbed on silicagel has been utilized as an efficient catalyst for ring opening of aziridines with aromatic amines for the synthesis of 1,2-diamines. Mild reaction conditions, high yields, operational simplicity, relatively less am

Full text of DOI:10.1081/SCC-200034759

This article was downloaded by: [Brown University]
On: 19 July 2012, At: 02:58
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
Tantalum (V) Chloride
Catalyzed Ring Opening of
Aziridines with Aromatic
Amines
a
a
S. Chandrasekhar , S. Jaya Prakash , T.
a
a
Shyamsunder & T. Ramachandar
a
Indian Institute of Chemical Technology,
Hyderabad, 500 007, India
Version of record first published: 10 Jan 2011
To cite this article: S. Chandrasekhar, S. Jaya Prakash, T. Shyamsunder & T.
Ramachandar (2004): Tantalum (V) Chloride Catalyzed Ring Opening of Aziridines
with Aromatic Amines, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 34:21, 3865-3873
To link to this article: http://dx.doi.org/10.1081/SCC-200034759
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-
and-conditions
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.
The publisher does not give any warranty express or implied or make any
representation that the contents will be complete or accurate or up to
date. The accuracy of any instructions, formulae, and drug doses should
be independently verified with primary sources. The publisher shall not
be liable for any loss, actions, claims, proceedings, demand, or costs or
damages whatsoever or howsoever caused arising directly or indirectly in
connection with or arising out of the use of this material.

w
SYNTHETIC COMMUNICATIONS
Vol. 34, No. 21, pp. 3865–3873, 2004
Tantalum (V) Chloride Catalyzed
Ring Opening of Aziridines with
#
Aromatic Amines
*
S. Chandrasekhar, S. Jaya Prakash, T. Shyamsunder,
and T. Ramachandar
Indian Institute of Chemical Technology, Hyderabad, India
ABSTRACT
Tantalum (V) Chloride adsorbed on silicagel has been utilized as an
efficient catalyst for ring opening of aziridines with aromatic amines
for the synthesis of 1,2-diamines. Mild reaction conditions, high yields,
operational simplicity, relatively less amount of catalyst and high
regioselectivity are some of the major advantages of the procedure
described herein.
Key Words: Tantalum (V) chloride; Aliphatic amines; Aromatic
amines.
#
IICT Communication No. 4756.
*
Correspondence: S. Chandrasekhar, Indian Institute of Chemical Technology,
Hyderabad 500 007, India; Fax: (þ91)-40-27160512; E-mail: srivaric@iict.res.in.
3
865
DOI: 10.1081/SCC-200034759
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

3
866
Chandrasekhar et al.
INTRODUCTION
[1]
Vicinal diamines are a biologically, medicinally, and synthetically
important class of compounds in the field of chemistry. To name a few,
[2]
anti-HIV drugs such as GG167, GS4104, GS4071, and Oseltamivir phos-
[
phate; antipsychotic agents such as emonapride and APDC; the indolizidine
3]
[
4]
[5]
alkaloid Slaframine and potent inhibitor of protein kinase C Balanol;
glycosylceramide synthase inhibitor PDMP and other pharmaceuticals
[6]
having the vicinal diamine function as a common feature. Diamines have
extensively been used as chiral ligands in a variety of transformations
[
7]
[8]
such as Mukaiyama aldol reactions,
Michael additions,
[10]
dihydroxylation, and desymmetrization of meso ketones.
Sharpless
Thus, the
[9]
fact that 1,2-diamines are reliable building blocks is established in organic
[
11]
synthesis.
unsymmetric and C -symmetric 1,2-diamines from simple starting materials
Hence, a versatile route for the chiral synthesis of both
2
would be highly desirable. One of the most straightforward synthetic
procedures for the preparation of vicinal diamines is the ring opening of
aziridines with amines. A good number of reports are available in the
literature for the ring opening of aziridines under Lewis acid catalysis
[12,13]
employing amines.
However, many of these procedures involve larger
amounts of the catalyst (10–20 mol%), longer reaction times, and unsatis-
factory yields. Silicagel alone catalyzed ring opening of aziridines with
[
14]
amines became sluggish.
Therefore, the development of new, more effi-
cient reagents with convenient procedures and better yields is an ongoing
process.
TaCl on silicagel has been introduced for the first time by our group
5
[15]
as an efficient Lewis acid catalyst system for various reactions.
In our
ongoing program towards further utilization of this Lewis acid we have
developed a simple and efficient procedure for the synthesis of vicinal
diamines from aziridines using 2.5 mol% of TaCl on silicagel (Sch. 1) in
5
good yields.
Scheme 1.

Tantalum (V) Chloride Catalyzed Ring Opening of Aziridines
RESULTS AND DISCUSSION
3867
In the first place, we examined the reaction of N-tosylcyclohexeneimine
with p-anisidine and TaCl on silica gel in anhydrous CH Cl at ambient
5
2
2
temperature to give the corresponding 1,2-diamine in 93% yield (entry 5).
Similar results were obtained with other cyclic aziridines (entries 6–8).
We found that, although TaCl alone was able to catalyze the ring opening
5
of aziridines, its catalytic activity was augmented by doping silicagel with
TaCl in a solid solution. After a thorough study, we found that 2.5 mol% of
5
TaCl on silicagel was an optimum catalytic mixture for these transformations.
5
The reaction times and yields are depicted in the form of a table (Table 1).
In the case of unsymmetrical aliphatic aziridines, only one product was
isolated and it was due to the attack of amines at the less hindered terminal
carbon atom (entries 9–18). 2-phenyl or 2-aryl aziridines (entries 19–24)
have exhibited a phenomenal difference in the regioselectivity of ring
opening as the attack of amine occurs from the benzylic carbon atom selec-
tively. Aliphatic amines such as benzyl amines and pyrrolidine failed to
react with aziridines at room temperature and also at reflux temperature for
prolonged hours. This behavior has also been previously reported with
[
13]
metal triflates as catalysts.
the mechanism, we presume that doping TaCl on silicagel would increase
Although we do not have any proof for
5
the catalytic activity, probably due to an increase in the surface area of the
catalyst. It coordinates to the nitrogen atom of the aziridines and facilitates
the ring opening with aromatic amines.
CONCLUSION
In conclusion, we have demonstrated a novel, efficient, and regioselec-
tive method for the ring opening of aziridines with aromatic amines using
2
.5 mol% of TaCl on silicagel. The notable advantages of this method are
5
mild reaction conditions, operational simplicity, requirement of a minimum
amount of catalyst (2.5 mol%), and high yields.
EXPERIMENTAL SECTION
General Procedure for the Ring Opening of Aziridines with
Aromatic Amines
Aziridine (10 mmol) and aromatic amines (12 mmol) were added to a
stirred solution of TaCl5 (2.5 mol%) on silicagel in anhydrous CH Cl2
2

3
868
Chandrasekhar et al.
Table 1. TaCl
5
silicagel catalyzed ring opening of aziridines with aromatic amines.
Time
(h)
Yield
a
(%)
Entry
Aziridines
Diamines
1
.
6.0
85
2
3
4
.
.
.
”
”
”
1b R
1c R
1d R
1
¼ H, Ar ¼ C
6
H
4
-p-F
6.0
6.0
5.0
83
90
92
1
¼ Me, Ar ¼ C
6 5
H
1
¼ H,
Ar ¼ C H -o,p-di-Ome
6
3
5
.
.
”
1e R ¼ H,
5.0
6.0
93
82
1
Ar ¼ C
6 5 3
H -p-OCH
6
b
7
.
.
”
2b R
1
¼ Me, Ar ¼ C
6
H
5
5.0
6.0
80
8
83
9
.
5.0
87
91
1
1
0.
1.
”
”
4b R
4c R
1
¼ Et, Ar ¼ C
¼ H,
6
H
5
6.0
5.0
b
1
78
Ar ¼ C H -o,p-di-Ome
4d R ¼ H, Ar ¼ C H -p-Br
6
3
1
2.
3.
”
6.0
6.0
80
1
6 4
b
1
79
1
4.
5.
”
”
5b R ¼ Et, Ar ¼ C H
5.0
5.0
89
81
1
6 5
1
5c R ¼ H,
1
Ar ¼ C
6 3
H -o,p-di-Ome
1
6.
6.0
85

Tantalum (V) Chloride Catalyzed Ring Opening of Aziridines
3869
1
7.
6.0
87
b
1
8.
9.
6.0
5.0
72
1
88
20.
21.
22.
”
”
”
9b R ¼ Et, Ar ¼ C H
5.0
6.0
6.0
92
87
82
1
6 5
9c R ¼ H, Ar ¼ C H -p-Br
1
6 4
9d R ¼ H,
1
6 3
Ar ¼ C H -o,p-di-Ome
2
3.
6.0
6.0
90
87
2
4.
a
Isolated yield.
Under reflux.
b
(
20 mL). The mixture was stirred at room temperature or reflux under a
nitrogen atmosphere for an appropriate time (see Table 1). Upon completion
TLC) the reaction was filtered through celite, diluted with water (10 mL),
and extracted with CH Cl (2 ꢀ 10 mL). The organic layers were washed
(
2
2
with brine and dried over Na SO . The solvent was removed in vacuum and
2
4
the crude product was column chromatographed on a silicagel column to
afford pure trans 1,2-diamine.
Spectroscopic Data for New Compounds
2
1d): viscous liquid; IR (neat): 3279 cm ; H NMR (CDCl ): d 1.20–1.24
m, 2H), 1.42–1.47 (m, 2H), 1.72–1.76 (m, 2H), 2.0–2.4 (m, 2H), 2.45
s, 3H), 2.85–2.98 (m, 1H), 3.08–3.12 (m, 1H), 3.80 (s, 6H), 3.85–3.92
m, 1H), 4.92–5.10 (m, 1H), 6.15–6.20 (m, 2H), 6.65 (d, J ¼ 8.2 Hz, 1H),
-(2,4-Dimethoxyanilino)-1-(4-methylphenylsulfonamido) cyclohexane
2
1 1
(
(
(
(
3

3
870
Chandrasekhar et al.
7
C H N O S 404.522; Found 404.518.
.30 (d, J ¼ 7.8 Hz, 1H), 7.80 (d, J ¼ 7.8 Hz, 2H). HRMS (EI) m/z calcd for
2
1 28 2 4
1-N-(2-Methylanilinocyclopentyl)-4-methyl-1-benzenesulfonamide (2b):
viscous liquid; IR (neat): 3275 cm ; H NMR (CDCl ): d 1.28–1.32 (m, 2H),
2
1 1
3
1
.42–1.47 (m, 2H), 1.72–1.76 (m, 2H), 2.45 (s, 3H), 2.45 (s, 3H), 3.38–3.43
m, 1H), 3.83–3.87 (m, 1H), 5.25 (bs, 1H), 6.58–6.63 (m, 1H), 7.24–7.28
(
(
H, 7.02; N, 6.29; Found: C, 66.35; H, 7.00; N, 6.22.
m, 4H), 7.70 (d, J ¼ 7.9 Hz, 2H). Anal Calcd for C H N O S: C, 66.15;
1
9 24 2 2
1
-N-(1-Ethylaminomethylpentyl)-4-methyl-1-benzenesulfonamide (4b):
2
1 1
viscous liquid; IR (neat) 3288 cm ; H NMR (CDCl ): d 0.75 (t, J ¼ 4.1 Hz,
3
3
H), 1.05 (t, J ¼ 5.58 Hz, 3H), 1.13–1.18 (m, 4H), 1.35–1.45 (m, 2H), 2.45
(
s, 3H), 3.15–3.25 (m, 4H), 3.40–3.50 (m, 1H), 5.15–5.25 (m, 1H),
.55 (d, J ¼ 8.8 Hz, 2H), 6.65–6.75 (m, 1H), 7.10–7.20 (m, 4H), 7.75
6
þ
(
C H N O S: C, 67.34; H, 8.07; N, 7.48; Found: C, 67.36; H, 8.11; N, 7.49.
d, J ¼ 7.5 Hz, 2H). MS: 374 (M ), 239, 155, 120, 91, 57. Anal Calcd for
2
1 30 2 2
4
benzene (5a): viscous liquid; IR (neat) 3282 cm ; H NMR (CDCl ): d
-Fluoro-1-[4-methyl-2-(4-methylphenylsulfonamido)pentylamino]
2
1 1
3
0
1
3
6
.65 (d, J ¼ 5.9 Hz, 3H), 0.85 (d, J ¼ 5.9 Hz, 3H), 1.20–1.30 (m, 2H),
.45–1.55 (m, 1H), 2.40 (s, 3H), 2.93–2.97 (m, 1H), 3.10 (dd, J ¼ 10.8,
.3 Hz, 1H), 3.41–3.48 (m, 1H), 3.80 (bs, 1H), 5.03–5.07 (m, 1H),
.42–6.46 (m, 2H), 6.78–6.83 (m, 2H), 7.25 (d, J ¼ 7.7 Hz, 2H), 7.85
(
d, J ¼ 7.7 Hz, 2H). HRMS (EI) m/z calcd for C H FN O S 364.476,
1
9
25
2 2
found 364.474.
1
viscous liquid; IR (neat) 3275 cm
-N-(1-Ethylanilinomethylnonyl)-4-methyl-1-benzenesulfonamide (7):
2
1
1
;
H NMR (CDCl ): d 0.80
3
(
t, J ¼ 4.2 Hz, 3H), 0.85 (t, J ¼ 5.5 Hz, 3H), 1.23–1.28 (m, 12H), 1.63–
1
4
.68 (m, 2H), 2.45 (s, 3H), 3.43–3.48 (m, 3H), 3.40–3.50 (m, 2H),
.68–4.73 (m, 1H), 6.60–6.70 (m, 2H), 7.20–7.30 (m, 5H), 7.70
(
d, J ¼ 8.1 Hz, 2H). Anal Calcd for C H N O S: C, 69.73; H, 8.89; N,
2
5 38 2 2
6
.50; Found: C, 69.75; H, 8.93; N, 6.55.
-Bromo-1-[1-(4-bromoanilino)-2-(4-ethylphenylsulfonamido)ethyl]-
4
benzene (10): semi solid; IR (KBr) 3279 cm ; H NMR (CDCl ): d
1
1
3
2
.45 (s, 3H), 3.08–3.12 (m, 2H), 4.15–4.25 (m, 2H), 5.55 (bs, 1H), 6.30
(
d, J ¼ 8.4 Hz, 2H), 7.05 (d, J ¼ 8.4 Hz, 2H), 7.18–7.25 (m, 4H), 7.40 (d,
J ¼ 7.1 Hz, 2H), 7.75 (d, J ¼ 8.2 Hz, 2H). Anal Calcd for C H Br N O S:
2
1
20
2 2 2
C, 48.11; H, 3.84; N, 5.34; Found: C, 48.17; H, 3.88; N, 5.36.
ACKNOWLEDGMENTS
Three of us (S.J.P., T.S., and T.R.) are thankful to CSIR, New Delhi for
financial assistance.

Tantalum (V) Chloride Catalyzed Ring Opening of Aziridines
REFERENCES
3871
1
. For reviews see: (a) Chang, A.-C.; Takemori, A.E.; Ojala, W.H.;
Gleason, W.B.; Portoghese, P.S. Kappa. Opioid receptor selective affinity
labels: Electrophilic benzeneacetamides as Kappa.-selective opioid
antagonists. J. Med. Chem. 1994, 37, 4490; (b) Weerawarna, S.A.;
Davis, R.D.; Nelson, W.L. Isothiocyanate-substituted Kappa-selective
opioid receptor ligands derived from N-methyl–N-[(1S)-1-phenyl-2-
(1-pyrrolidinyl) ethyl]phenyl acetamide. J. Med. Chem. 1994, 37, 2856.
2
. (a) Smith, P.W.; Sollis, S.L.; Howes, P.D.; Cherry, P.C.; Starkey, I.D.;
Cobley, K.N.; Weston, H.; Scicinski, J.; Merritt, A.; Whittington, A.;
Wyatt, P.; Taylor, N.; Green, D.; Bethell, R.C.; Madar, S.; Fenton, R.J.;
Morley, P.J.; Patemann, T.; Beresford, A. Dihydro pyrano carboxamides
related to Zanamivir: A new series of inhibitors of influenza virus siali-
dases. 1. Discovery, synthesis, biological activity, and structure-activity
relationships of 4-guanidino and 4-amino-4H-pyran-6-carboxamides.
J. Med. Chem. 1998, 41, 787; (b) Smith, P.W.; Robinson, J.E.;
Evans, D.N.; Sollis, S.L.; Howes, P.D.; Trivedi, N.; Bethell, R.C. Siali-
dase inhibitors related to Zanamivir: synthesis and biological evaluation
of 4H-pyran 6-ether and ketone. Bioorg. Med. Chem. Lett. 1999, 9, 601.
. Chan, P.W.H.; Cottrell, I.F.; Moloney, M.G. Azasugar analogues: Confir-
mationally restricted vicinal diamine derived from (S)-(2) Pyroglutamic
acid. Tetrahedron Asymmetry 1999, 10, 3887.
3
4
5
. Gardiner, R.A.; Rinehart, K.L., Jr.; Snyder, J.J.; Broquist, H.P. Slafra-
mine. Absolute stereochemistry and a revised structure. J. Am. Chem.
Soc. 1968, 90, 5639.
. Kulanthaivel, P.; Hallock, Y.F.; Boros, C.; Hamilton, S.M.; Janzen, W.P.;
Ballas, L.M.; Loomis, C.R.; Jiang, J.B.; Katz, B.; Steinev, J.R.; Clardy, J.
Balanal: a novel and potent inhibitor of protein kinase C from the fungus
verticillium balaniodes. J. Am. Chem. Soc. 1993, 115, 6452.
6
. Reetz, M.T.; Jaeger, R.; Drewlies, R.; Hubel, M. Stereo selective
synthesis of vicinal diamines. Angew. Chem. Int. Ed. Engl. 1991, 30,
1
03 (and references cited therein).
7
. (a) Uragami, M.; Tomiaka, k.; Koga, K. Highly enantioselective aldol
reaction mediated by mixed aggregates derived from a lithium ester
enolate and tetradentate chiral lithium amides. Tetrahedron Asymmetry
1
995, 6, 701; (b) Kobayashi, S.; Hayashi, T. Chiral lewis acid-controlled
synthesis of both diastereomers. Enantioselective synthesis of both syn-
and anti-2,3-dihydroxy ester derivatives from the same starting materials
via asymmetric aldol reactions by choice of chiral ligands. J. Org. Chem.
1
995, 60, 1098.

3
872
Chandrasekhar et al.
8
9
. Yasuda, K.; Shindo, M.; Koga, K. Enantioselective michael reaction of
ketone lithium enolates using a chiral amine ligand. Tetrahedron Lett.
1
. Kubota, H.; Nakajima, M.; Koga, K. Enantioselective Palladium
996, 37, 6343.
catalyzed allylic alkylation with C -symmetric chiral diamine ligands.
2
Tetrahedron Lett. 1993, 34, 8135.
1
0. (a) Shirai, R.; Tanaka, M.; Koga, K. Enantioselective deprotonation by
chiral lithium amide bases: asymmetric synthesis of trimethyl silyl enol
ethers from 4-alkylcyclohexanones. J. Am. Chem. Soc. 1986, 108, 544;
(b) Imai, M.; Hagihara, A.; Kawasaki, H.; Manabe, K.; Koga, K. Catalytic
asymmetric benzylation of achiral lithium enolates using a chiral ligand
for lithium in the presence of an achiral ligand. J. Am. Chem. Soc.
1
994, 116, 8829; (c) Shirai, R.; Sato, D.; Avoki, K.; Tanaka, M.;
Kawasaki, H.; Koga, K. Stereo selective reactions 25. Tetrahedron
997, 53, 5963; (d) Mangus, P.; Sebhat, I.K. Synthesis of the antitumor
1
alkaloid (þ)-Pancratistatin using the b-Azidonation reaction via a
prochiral 4-arylcyclohexanone derivative. J. Am. Chem. Soc. 1998,
20, 5341.
1
1
1
1. (a) Lueet, D.; Gall, T.C.; Miskowski, C. The chemistry of vicinal
diamines. Angew. Chem. Int. Ed. Engl. 1998, 37, 2580; (b) Bennai, Y.L.;
Hanessian, S. Trans-1,2-diamino cyclohexane derivatives as chiral
reagents, Scaffolds and ligands for catalysis: Applications in asymmetric
synthesis and molecular recognition. Chem. Rev. 1997, 97, 3161.
2. (a) Meguro, M.; Asao, N.; Yamamoto, Y. Ytterbium triflate catalyzed ring
opening of aziridines with amines. Tetrahedron Lett. 1994, 35, 7395;
(
b) Meguro, M.; Yamamoto, Y. Ytterbium triflate catalyzed ring
opening of aziridines with amines. Heterocycles 1996, 43, 2473;
c) Yadav, J.S.; Reddy, B.V.S.; Rao, V.K.; Raj, S.K.; Prasad, A.R.
(
Indium tribromide catalyzed aminolysis of aziridnes: An efficient
synthesis of vicinal-diamines. Synthesis 2002, 8, 1061; (d) Yadav, J.S.;
Reddy, B.V.S.; Jyothirmai, B.; Murthy, M.S.R. LiClO -Catalyzed ring
4
opening of aziridines with aromatic amines. Synlett 2002, 0053.
3. Sekar, G.; Singh, V.K. Efficient method for cleavage of aziridines with
aromatic amines. J. Org. Chem. 1999, 64, 2537.
4. Anand, R.V.; Panday, G.; Singh, V.K. Silicagel induced cleavage of
aziridines by aromatic amines under solvent free conditions. Tetrahedron
Lett. 2002, 43, 3975.
1
1
1
5. (a) Chandrasekhar, S.; Takhi, M.; Reddy, Y.R.; Mohapatra, S.; Rama
Rao, C.; Reddy, K.V. TaCl Silicagel and TaCl as new lewis acid
systems for selective tetrahydropyranylation of alcohols and thioacetali-
5
5
sation, trimerisation, and aldolisation of aldehydes. Tetrahedron 1997,
5
3, 14997; (b) Chandrasekhar, S.; Takhi, M.; Uma, G. Solvent free

Tantalum (V) Chloride Catalyzed Ring Opening of Aziridines
3873
N-alkyl and N-arylimides preparation from anhydrides catalyzed by
TaCl -Silicagel. Tetrahedron Lett. 1997, 38, 8089; (c) Chandrasekhar, S.;
5
Ramachandar, T.; Takhi, M. Acylation of alcohols with acetic anhydride
catalyzed by TaCl : Some implications in kinetic resolution. Tetrahedron
5
Lett. 1998, 39, 3263; (d) Chandrasekhar, S.; Prakash, S.J.;
Jagadeshwar, V.; Narsihmulu, Ch. Three component coupling catalyzed
by TaCl -SiO : Synthesis of a-amino phosphonates. Tetrahedron Lett.
5
2
2
TaCl -Catalyzed cleavage of epoxides with aromatic amines. Synthesis
001, 42, 5561; (e) Chandrasekhar, S.; Ramachandar, T.; Prakash, S.J.
5
2
000, 1817.
Received in India June 14, 2004