Synthesis of quaternary allylammonium salts via ring opening of 1-benzyl-2-(bromomethyl)aziridines

Article abstract of DOI:10.1016/S0040-4020(03)00771-3

Treatment of 1-benzyl-2-(bromomethyl)aziridine, and some aryl substituted analogues, with an excess of iodomethane resulted in N-allyl-N-benzyl-N,N-dimethylammonium salts, in good yields. These quaternary allylammonium salts are of importance in different

Full text of DOI:10.1016/S0040-4020(03)00771-3

Tetrahedron 59 (2003) 5383–5386
Synthesis of quaternary allylammonium salts via ring opening of
1-benzyl-2-(bromomethyl)aziridines
*
Matthias D’hooghe, Willem Van Brabandt and Norbert De Kimpe
Department of Organic Chemistry, Faculty of Agricultural and Applied Biological Sciences, Ghent University, Coupure Links 653,
B-9000 Ghent, Belgium
Received 26 September 2002; revised 21 November 2002; accepted 27 November 2002
Abstract—Treatment of 1-benzyl-2-(bromomethyl)aziridine, and some aryl substituted analogues, with an excess of iodomethane resulted
in N-allyl-N-benzyl-N,N-dimethylammonium salts, in good yields. These quaternary allylammonium salts are of importance in different
fields, from organic synthesis and polymeric chemistry to agricultural use. q 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
textiles12 and as emulsion stabilizers, for example in
polymerisation processes.13 – 16 Ammonium salts in
general,17 –23 and N-allyl-N-benzyl-N,N-dimethylammo-
nium salts in particular,24 are of significant importance in
agriculture, because of their plant growth regulating
activity. Related ammonium salts also exhibit anti-
microbial activity, which makes them attractive as potential
antibiotics.25–27 As a final example of the applicability of
the title compounds, improved antistatic properties of
photographic material can be mentioned.28 The majority
of the contributions concerning allylammonium salts was
found in the patent literature.
At present, little is known about the chemistry of
2-(halomethyl)aziridines, a potential class of b-haloamines
to serve as building blocks in synthetic organic chemistry. In
former research, allylic amines were prepared via a radical-
induced ring opening1,2,3 or via sonochemical cleavage4 of
2-(bromomethyl)aziridines. 2-(Bromomethyl)aziridines
were also transformed into pyrrolizidines by cascade
reactions of N-alkenylaziridinylmethyl radicals,5 and
2-methyleneaziridines were synthesised by dehydrobromi-
nation.6 The aim of the presented research was to evaluate
the reactivity of 1-benzyl-2-(bromomethyl)aziridines with
regard to iodoalkanes. Due to the absence of an electron
withdrawing group at the nitrogen atom, the aziridine ring is
less susceptible to direct ring opening, and the lone pair at
nitrogen can react as a nucleophile in for example a
substitution reaction with an alkyl halide. When 1-sub-
stituted 2-(bromomethyl)aziridines and iodomethane were
used, N-allyl-N-benzyl-N,N-dimethylammonium salts were
formed in an exclusive way, via an unexpected ring
opening. The importance of a general method for the
preparation of N-allyl-N-benzyl-N,N-dimethylammonium
salts can be concluded from the various applications of
these compounds. Like many other quaternary ammonium
salts, N-allyl-N-benzyl-N,N-dimethylammonium salts are
useful in organic synthesis for phase transfer catalysis7 and
also as starting material or reagent,8–11 for example for the
synthesis of heterocyclic compounds by debenzylation of
quaternary ammonium salts.9 Due to their intrinsic proper-
ties, they are used for dyeing and printing cellulose
2. Results and discussion
In the present report 1-benzyl-2-(bromomethyl)aziridines 1,
including benzyl substituted derivatives, were synthesized
via a known procedure, starting from 4-substituted benzal-
dehydes.4 Treatment of these benzaldehydes with allyl-
amine yielded the corresponding aldimines, which were
then treated with bromine, followed by a reduction step in
order to form the aziridines 1 in high yields. The obtained
1-benzyl-2-(bromomethyl)aziridines 1 were treated with an
excess of iodomethane in dry ether. After 15 hours at room
temperature, N-allyl-N-benzyl-N,N-dimethylammonium
iodides 2 were isolated in good yields (Scheme 1).
These results were quite unexpected, based upon the
reaction intermediates. The nucleophilic nitrogen atom of
the aziridine attacked iodomethane in a SN2 reaction,
resulting in an intermediate aziridinium salt. Because of the
presence of a fairly good nucleophilic counter ion, i.e.
iodide, ring opening of this activated aziridinium salt via a
SN2 or SN1 type reaction onto an aziridine carbon atom was
expected. The obtained results indicate that in fact another
Keywords: allylation; ring opening; 2-(bromomethyl)aziridines;
ammonium salts.
*
Corresponding author. Tel.: þ0032(9)-2645951; fax: þ0032(9)-2646243;
e-mail: norbert.dekimpe@UGent.be
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00771-3

5384
M. D’hooghe et al. / Tetrahedron 59 (2003) 5383–5386
Scheme 1.
mechanism is occurring. Apparently the iodide anion
attacked the bromo atom (halophilic reaction), resulting in
bromoiodide and the corresponding allylic amine. This
tertiary allylic amine reacted then further with the excess of
iodomethane, yielding the quaternary allylammonium salts
2 (Scheme 2).
FT-IR. Mass spectra were recorded with an Agilent 1100,
series: MS, detector: VL, 70 eV, ES 4000 V. Diethyl ether
was dried by distillation over sodium benzophenone ketyl;
ethanol was used as received from the supplier.
1-Benzyl-2-(bromomethyl)aziridines 1 were synthesized
via a known procedure.4
3.1.1. 2-(Bromomethyl)-1-(4-fluorobenzyl)aziridine 1e
(96%). Spectral data of 2-(bromomethyl)aziridines 1a–d
have been reported elsewhere.1,6
1H NMR (270 MHz, CDCl3): d¼1.61 (d, JH,H¼6.27 Hz,
1H, N(HcisCH)CH), 1.79 (d, JH,H¼3.30 Hz, 1H,
N(HCHtrans)CH), 1.88–1.96 (m, 1H, NCH), 3.26 and 3.30
(2£d£d, JH,H¼10.48, 5.45, 7.26 Hz, 2H, CH2Br), 3.36 and
3.49 (2£d, JH,H¼13.37 Hz, 2H, NCH2C6H4), 6.97–7.08 and
7.31–7.33 (m, 4H, C6H4). 13C NMR (68 MHz, CDCl3):
d¼35.27 (CH2Br), 35.54 (NCH2CH), 40.14 (NCH), 63.27
(NCH2C6H4), 114.88 and 115.18, 129.63 and 129.74
(2£FHCortho and 2£FHCmeta), 134.43 and 134.46
(NCH2C), 160.11 and 163.70 (FC). IR (NaCl):
n¼3048 cm21, 2985, 2900, 2835, 1605, 1510. MS (70
eV): m/z (%): 244/6(Mþþ1, 87), 109(100).
Scheme 2.
3.2. General procedure for the synthesis of N-allyl-N-
benzyl-N,N-dimethylammonium salts 2
When 1-benzyl-2-(bromomethyl)aziridines 1 were treated
with iodomethane in dry dichloromethane at room tem-
perature, no reaction was observed, and the starting
aziridines were recovered completely. Extension of the
conversion of aziridines 1 to allylammonium salts 2 using
other electrophiles was also evaluated. After treatment of
1-benzyl-2-(bromomethyl)aziridine 1a with an excess of
iodoethane, 1-iodopropane or 1-iodobutane in ether at room
temperature, no selective reaction occurred and complex
reaction mixtures were isolated, pointing to the peculiar role
of the reactive iodomethane and the etheral solvent in this
reaction.
The synthesis of N-allyl-N-benzyl-N,N-dimethylammonium
iodide 2a from 1-benzyl-2-(bromomethyl)aziridine 1a is
representative for all other preparations.
To a solution of 1-benzyl-2-(bromomethyl)aziridine 1a
(0.23 g, 1.0 mmol),4 in dry diethyl ether (2 mL), iodo-
methane (0.43 g, 3.0 mmol) was added dropwise at room
temperature. The reaction mixture was then stirred for 15
hours at room temperature. The solvent was decanted and
the precipitated salt was washed with dry ether (3£5 mL).
After removal of the residual solvent in vacuo, a viscous
brown ammonium salt was obtained. The salt was purified
by recrystallisation from ethanol. Due to the hygroscopic
nature of these salts no accurate melting points could be
measured, and IR spectra had to be recorded in CDCl3.
3. Experimental
3.1. General
3.2.1. N-Allyl-N-benzyl-N,N-dimethylammonium iodide
1
1H NMR spectra were recorded at 270 MHz (JEOL JNM-
EX 270) with CDCl3 as solvent and tetramethylsilane as
internal standard. 13C NMR spectra were recorded at
68 MHz (JEOL JNM-EX 270) with CDCl3 as solvent. IR
spectra were measured with a Perkin Elmer Spectrum One
2a (85%). H NMR (270 MHz, CDCl3): d¼3.15 (s, 6H,
(CH3)2Nþ), 4.20 (d, JH,H¼7.25 Hz, 2H, CHCH2Nþ), 4.73
(s, 2H, PhCH2Nþ), 5.85–5.94 (m, 2H, CHvCH2), 6.05–
6.18 (m, 1H, CHvCH2), 7.29–7.65 (m, 5H, C6H5). 13C
NMR (68 MHz, CDCl3): d¼49.99 ((CH3)2Nþ), 67.01 and

M. D’hooghe et al. / Tetrahedron 59 (2003) 5383–5386
5385
68.36 (2£CH2Nþ), 123.92 (CHvCH2), 126.16 (Carom,quat),
(CH¼CH2 and Cpara). IR (NaCl, CDCl3): n¼3028 cm21
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1
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4.84 (s, 2H, PhCH2Nþ), 5.83–5.94 (m, 2H, CHvCH2),
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