LiClO4-catalyzed ring-opening of aziridines with aromatic amines

Article abstract of DOI:10.1055/s-2002-19317

A variety of N-tosylaziridines undergo smoothly ring opening with aromatic amines using a catalytic amount of lithium perchlorate in acetonitrile at ambient temperature to afford the corresponding 1,2-diamines in excellent yields.

Full text of DOI:10.1055/s-2002-19317

LETTER
53
LiClO4-Catalyzed Ring-Opening of Aziridines with Aromatic Amines
L
iClO -Ca
.
talyzed
R
ing
S
-Openingof
A
.
ziridines
w
Y
A
min
a
es dav,* B. V. S. Reddy, B. Jyothirmai, M. S. R. Murty
4
Organic Chemistry Division-1, Indian Institute of Chemical Technology, Hyderabad-500007, India
Fax +91(40)7170512; E-mail: madugula51@yahoo.com
Received 25 June 2001
for amino acids,3 heterocycles4,5 and alkaloids.6 The ring
opening of N-substituted aziridines with several nucleo-
philes such as organometallic reagents, Wittig reagents,
TMS azide, TMS cyanide, amines, hydroxyl compounds
and halides has been studied using Lewis acids.7–11 How-
ever, many Lewis acids are deactivated or sometimes de-
composed by nitrogen containing reactants and, even
when the desired reaction proceeds, more than stoichio-
metric amounts of the Lewis acids are required because
the acids are trapped by nitrogen.12 Lithium perchlorate is
found to retain its activity even in the presence of
amines.13 Furthermore, the development of a neutral alter-
native like lithium perchlorate, would extend the scope of
this transformation. In recent years, LiClO4 in diethyl
ether has emerged as a Lewis acid for effecting various or-
ganic transformations.14 The LPDE medium offers a con-
venient procedure to carry out the reactions under neutral
reaction and work-up conditions.15
Abstract: A variety of N-tosylaziridines undergo smoothly ring
opening with aromatic amines using a catalytic amount of lithium
perchlorate in acetonitrile at ambient temperature to afford the cor-
responding 1,2-diamines in excellent yields.
Key words: lithium perchlorate, aziridines, aryl amines, 1,2-di-
amines
Several antiretroviral drugs, reverse transcriptase inhibi-
tors and protease inhibitors have been developed at a rapid
pace over the last few years. These drugs work mainly by
inhibiting the reproduction of HIV but do not cure HIV in-
fection. Studies are taking place to deactivate the special
HIV enzyme, which is attached to the white blood cells.
Zanamivir (I) and Oseltamivir phosphate (II) are potent
neuraminidase inhibitors (Figure).1
Substituted 1,2-diamines are a biologically, medicinally
and synthetically important class of compounds in the
field of anti-HIV drugs and other pharmaceuticals.2 One
of the most straightforward synthetic procedures for the
preparation of vicinal diamines is the ring opening of azir-
idines with amines. Currently, there is a significant inter-
est in the synthesis and reactions of aziridines for the
construction of nitrogen-containing molecules especially
In our ongoing programme towards the total synthesis of
anti-HIV molecules such as Zanamivir and Oseltamivir
phosphate we herein describe a novel and convenient pro-
cedure for the synthesis of 1,2- diamines from aziridines
using a catalytic amount of lithium perchlorate
(Scheme 1).
Figure
Scheme 1
Synlett 2002, No. 1, 28 12 2001. Article Identifier:
1437-2096,E;2002,0,01,0053,0056,ftx,en;D15301ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

54
J. S. Yadav et al.
LETTER
The treatment of N-tosyl aziridines with aromatic amines dines using catalytic amount of lithium perchlorate under
in the presence of 10 mol% LiClO4 in acetonitrile resulted neutral reaction and work-up conditions. The method has
in the formation of 1,2-diamines in 83–95% yield.16 The advantages of mild reaction conditions, operational sim-
reactions proceeded efficiently at ambient temperature plicity, inexpensive catalyst, high yields of products and
and the products were obtained in excellent yields. Sty- simple experimental/isolation procedure, which makes it
rene-N-tosyl aziridine underwent cleavage in a regioselec- a useful and attractive process for the synthesis of vicinal
tive manner with preferential attack at benzylic position diamines.
(entry j–m). Futhermore, alkyl-N-tosyl aziridines gave
predominantly the ring product 4 with trace amounts of 3
(entry p–r) resulting from terminal attack as well as inter-
Acknowledgement
B.V.S thanks CSIR New Delhi, for the award of fellowship.
nal attack of amine, as has been observed by others in
most of the aziridine ring opening reactions.17 However,
the reaction of cycloalkyl-N-tosyl aziridines with aromat-
ic amines afforded the product as a single isomer
(Scheme 2).
References
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Scheme 2
In the case of cycloalkyl aziridines, the stereochemistry of
the ring product 3a was found to be trans from the cou-
pling constants of the ring protons at 2.95 ppm (ddd, J =
(3) (a) Tanner, D. Angew. Chem. Int. Ed. Engl. 1994, 33, 599.
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Sweeney, J. B.; Howson, B. Synlett 1994, 145.
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1
4.0, 10.0, and 10.0 Hz, 1 H) for (NCH) in the H NMR
spectrum. Likewise the peak at 3.10 ppm for (CHN)
showed a similar kind of splitting pattern (ddd, J = 3.9,
10.0, and 10.0 Hz, 1 H).
The method described herein is clean and highly regiose-
lective, affording 1,2-diamines in excellent yields. The re-
action conditions are mild and no side products or
decomposition of the products are observed. Albeit, a va-
riety of anilines reacted well to give the corresponding
1,2-diamines in excellent yields, the aliphatic amines
failed to react with aziridines even after a long reaction
time at ambient temperature. Other substrates like vinyl
aziridines also reacted smoothly with anilines to afford the
corresponding ring opened products in high yields with
preferential attack at benzylic position (entry n, o). All the
products are fully characterized by 1HNMR, IR, 13C NMR
and mass spectral data. The efficacy of other Lewis acids,
such as InCl3, CeCl3, YCl3 and YbCl3 was studied for this
reaction. Among these catalysts, lithium perchlorate was
found to be an excellent catalyst in terms of conversion
and reaction time. This is because of the mild Lewis acid-
ity of the lithium ion, which coordinates the nitrogen atom
of the aziridine and facilitates the ring opening reaction
with amines. Furthermore, the products were easily trans-
formed to t-butyl sulphonyl carbamates by DMAP-cata-
lyzed acylation,18a and these in turn may be converted into
the corresponding carbamates using magnesium in meth-
anol.18b Several examples illustrating this novel and gen-
eral method for the synthesis of 1,2-diamines are
summarized in the Table.
(13) Heydari, A.; Larijani, H.; Emami, J.; Karami, B.
Tetrahedron Lett. 2000, 41, 2471.
(14) (a) Sankara Raman, S.; Nesakumar, J. E. Eur. J. Org. Chem.
2000, 2003. (b) Aggarwal, V. K.; Mereu, A.; Tarver, G. J.;
McCague, R. J. Org. Chem. 1998, 63, 7183.
(15) (a) Yadav, J. S.; Reddy, B. V. S.; Murthy, C. V. S. R.;
Kumar, G. M.; Madan, C. Synthesis 2001, 783. (b) Yadav,
J. S.; Reddy, B. V. S.; Srinivas, R.; Madhuri, C.;
Ramalingam, T. Synlett 2001, 240.
(16) General procedure: A mixture of aziridine (5 mmol), aniline
(5 mmol) and LiClO4 (10 mol%) in acetonitrile (10 mL) was
In conclusion, we have demonstrated a novel and efficient
protocol for the preparation of 1,2 diamines from aziri-
Synlett 2002, No. 1, 53–56 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
LiClO4-Catalyzed Ring-Opening of Aziridines with Aromatic Amines
55
Table LiClO4-Catalyzed Ring Opening of Aziridines with Aryl Amines
Entry
a
Aziridine
Amine
Reaction time (h) Yield a (%)
Ratio 3:4
C6H5NH2
5.5
5.0
6.0
6.5
6.5
6.0
5.0
5.5
7.0
4.0
3.5
4.0
5.5
6.5
90
95
83
89
90
92
92
88
85
90
88
91
85
82
–
b
c
d
e
f
4-MeOC6H4NH2
4-CIC6H4NH2
4-MeC6H4NH2
2,5-(MeO)2C6H3NH2
C6H5NH2
–
–
–
–
–
g
h
i
4-MeOC6H4NH2
4-MeC6H4NH2
2-Naphthylamine
C6H5NH2
–
–
–
j
78:22b
85:15b
87:13b
95:5b
75:25b
k
l
4-MeC6H4NH2
4-MeOC6H4NH2
4-CIC6H4NH2
C6H5NH2
m
n
o
4-MeC6H4NH2
6.0
85
70:30b
p
q
r
C6H5NH2
5.0
6.5
7.5
90
87
85
5:95c
10:90c
8:92c
2-Naphthylamine
4-MeOC6H4NH2
a Isolated and unoptimized yield.
b Ratio of products from internal attack vs. terminal.
c Ratio of products from terminal attack vs. internal attack.
Synlett 2002, No. 1, 53–56 ISSN 0936-5214 © Thieme Stuttgart · New York

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J. S. Yadav et al.
LETTER
stirred at ambient temperature for a specified time (see
Table). After complete conversion, as indicated by TLC, the
reaction mixture was quenched with water (10 mL) and
extracted with ethyl acetate (2 15 mL). The combined
organic layers were dried over anhydrous Na2SO4,
H), 3.40 (br s, 1 H), 3.10 (ddd, J = 3.9, 10.0, 10.0, Hz, NCH,
1 H), 2.95 (ddd, J = 4.0, 10.0, 10.0, Hz, NCH, 1 H), 2.46 (s,
3 H), 2.03–2-20 (m, 2 H), 1.65–1.70 (m, 2 H), 1.55–1.58 (m,
1 H), 1.17–1.38 (m, 2 H), 0.94–1.11 (m, 1 H); IR(neat):
3400, 3290, 1600, 1510 1450, 1330, 1300, 1160, 900 cm–1.
Anal. Calcd for C19H24N2O2S: C, 66.25; H, 7.02; N, 8.13.
Found: C, 66.25; H, 6.85; N, 8.06.
concentrated in vacuo and purified by column
chromatography on silica gel (Merck, 100–200 mesh, ethyl
acetate–hexane, 1:9) to afford pure 1,2-diamine. Spectral
data for product 3a: trans-N-(4-methylbenzene sulfonyl)-2
anilinocyclohexamine: 1H NMR (400 MHz, CDCl3) : 7.70–
7.80 (m, 2 H), 7.30–7.35 (m, 2 H), 7.14–7.20 (m, 2 H), 6.71–
6.75 (m, 1 H), 6.47–6.50 (m, 2 H), 4.84 (br d, J = 5.1, Hz, 1
(17) Wu, J.; Hou, X.-L.; Dai, L.-X. J. Org. Chem. 2000, 65, 1344.
(18) (a) Nyasse, B.; Grehn, L.; Ragnarsson, U.; Maia, H. L. S.;
Monteiro, L. S.; Leito, I.; Koppel, I.; Koppel, J. J. Chem.
Soc. Perkin Trans. 1 1995, 2025. (b) Nyasse, B.; Grehn, L.;
Ragnarsson, U. J. Chem. Soc. Chem. Commun. 1997, 1017.
Synlett 2002, No. 1, 53–56 ISSN 0936-5214 © Thieme Stuttgart · New York