Direct NH-aziridination of α,β-unsaturated ketones

Article abstract of DOI:10.1039/b200046f

1-Aryl-α,β-unsaturated ketones were directly aziridinated, N-unsubstituted, in a one-pot reaction with satisfactory yields by N,N′-diamino-1,4-diazoniabicyclo[2.2.2]octane dinitrate, a nitrogen-nitrogen ylide precursor, in the presence of sodium hydride.

Full text of DOI:10.1039/b200046f

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Direct NH-aziridination of ꢀ,ꢁ-unsaturated ketones
Jiaxi Xu* and Peng Jiao
Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education,
College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China
1
Received (in Cambridge, UK) 8th January 2002, Accepted 12th April 2002
First published as an Advance Article on the web 7th May 2002
1-Aryl-α,β-unsaturated ketones were directly aziridinated, N-unsubstituted, in a one-pot reaction with satisfactory
yields by N,NЈ-diamino-1,4-diazoniabicyclo[2.2.2]octane dinitrate, a nitrogen–nitrogen ylide precursor, in the
presence of sodium hydride.
pared from tertiary amines and hydroxylamine-O-sulfonic
Introduction
acid.12 We rationalize that hydrazinium nitrates could become
amine imides, which could aziridinate olefins with electron-
withdrawing groups, after reaction with bases. We therefore
decided to investigate this aziridination and undertake a survey
of various olefins to ascertain the generality of the reaction.
A hydrazinium nitrate, N,NЈ-diamino-1,4-diazoniabicyclo-
[2.2.2]octane dinitrate, was prepared from 1,4-diaza-
bicyclo[2.2.2]octane (DABCO) and hydroxylamine-O-sulfonic
acid in the presence of calcium oxide and calcium nitrate
according to the literature procedure.12 A solution of equimolar
N,NЈ-diamino-1,4-diazoniabicyclo[2.2.2]octane dinitrate and
chalcone in a mixture of isopropanol and benzene (2 : 1, v/v)
was added portionwise to sodium hydride over 30 min while
stirring at room temperature. Chalcone was converted to
aziridine in a yield of 63%. After the ratio of N,NЈ-diamino-
1,4-diazoniabicyclo[2.2.2]octane dinitrate and chalcone was
increased to 2 : 1 and the reaction was carried out at 0 ЊC, the
aziridinated product was obtained in 95% yield (Scheme 1). A
Aziridines are very important intermediates in organic syn-
thesis1 and have found widespread use in asymmetric syn-
thesis.2 A variety of methods for the preparation of aziridines
have been developed.3 However, most of the methods produce
N-substituted aziridines, such as N-arenesulfonyl, alkoxycarbo-
nyl, or aryl substituted aziridines. Removal of these substitu-
ents is carried out, in most cases, under harsh conditions. Only
a few methods have been reported for the direct preparation of
N-unsubstituted aziridines until now. The early preparative
routes to N-unsubstituted aziridines involved cycloelimination
processes in which one, sometimes two, bonds were formed
directly to the nitrogen atom. These routes include two intra-
molecular cyclization pathways involving either nucleophilic
displacement by the amine nitrogen on the β-carbon in the
cycloelimination of β-haloamines, β-aminohydrosulfate esters
and their equivalents, or nucleophilic displacement by a β-
carbanionic center (rendered suitably acidic by the presence
of a contiguous carbonyl function) on the amine nitrogen with
concomitant departure of a suitable leaving group (alkoxy, tri-
alkylammonium or halide).3a As an alternative route, both 1,2-
dihalides4 and α-halo-α,β-unsaturated carbonyl compounds5
react with ammonia to give N-unsubstituted aziridines. It
was also reported that oximes could be converted into N-
unsubstituted aziridines by treatment with Grignard reagents6
or by reduction with lithium aluminium hydride in certain
cases.7 3,3-Pentamethyleneoxaziridine can transfer its NH
group to electron-deficient olefins to give N-unsubstituted
aziridines in low yields and with a limited group of substrates.8
3,3-Pentamethylenediaziridine can only transfer its NH group
Scheme 1
variety of chalcone derivatives were also aziridinated in high
yields following the same procedure except for nitro substituted
chalcones (15–17%, Table 1 entries 12 and 13). For aziridin-
ation of aliphatic α,β-unsaturated ketones (but-3-en-2-one
and cyclohex-2-en-1-one) with N,NЈ-diamino-1,4-diazonia-
bicyclo[2.2.2]octane dinitrate, no aziridination products were
isolated. Although 4-phenylbut-3-en-2-one did not give the
desired aziridine product in this aziridination, 1-arylbut-2-en-1-
ones [1-phenylbut-2-en-1-one and 1-(4-methoxyphenyl)but-2-
en-1-one] were aziridinated in almost quantitative yields.
The results are summarized in Table 1.11,13,14 A comparison of
the coupling constants of their methine protons with those
reported in the literature10b,15 demonstrates that the aziridines
have a trans-configuration.
Attempts to aziridinate electron-rich olefins, styrene and
allylbenzene, with N,NЈ-diamino-1,4-diazoniabicyclo[2.2.2]-
octane dinitrate were unsuccessful indicating that this azirid-
ination process is not a nitrene addition to an alkene, but a
nitrogen ylide addition to an α,β-unsaturated ketone. It is
assumed that N,NЈ-diamino-1,4-diazoniabicyclo[2.2.2]octane
dinitrate could convert into a diamine imide after reaction with
sodium hydride. The diamine imide undergoes Michael
addition to the α,β-unsaturated ketone followed by cyclization
to the C᎐C double bond of α,β-unsaturated N,N-disubstituted
᎐
amides.9
Nitrogen ylides are another kind of potential NH transfer
agent. Free sulfimides HN᎐SR , sulfur–nitrogen ylides, are used
᎐
2
for the direct synthesis of N-unsubstituted aziridines. However,
the yields are unsatisfactory and enaminoketones are obtained
as major byproducts in moderate yields.10 A direct aziridination
of chalcone is needed in order to prepare N-unsubstituted
aziridines in satisfactory yields by an amine imide, which is
formed in situ from N,N-dimethylhydrazine and oxirane
(propene oxide).11 The search for nitrogen transfer agents for
the direct aziridination of olefins to prepare N-unsubstituted
aziridines is currently an attractive field of research.
Results and discussion
An amine imide, as a type of nitrogen–nitrogen ylide, is an
effective NH source for N-unsubstituted aziridination of
electron-deficient olefins. Hydrazinium nitrates are readily pre-
DOI: 10.1039/b200046f
J. Chem. Soc., Perkin Trans. 1, 2002, 1491–1493
This journal is © The Royal Society of Chemistry 2002
1491

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Table 1 Direct aziridination of α,β-unsaturated ketones with N,NЈ-diamino-1,4-diazoniabicyclo[2.2.2]octane dinitrate
Aziridine
R
Substituent on Ar group
Yield (%)
Mp/ЊC (lit.)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Ph
Ph
2-ClPh
4-MeOPh
Ph
4-ClPh
Ph
H
4-Cl
H
H
4-MeO
H
4-Br
4-Me
H
H
H
95
79
88
84
82
79
81
89
76
87
91
17
15
99
99
100–101 (99–10111
)
)
76–78 (75–811
)
92–94 (92.5–4.511
53–54
71–72 (71–213
)
88–89 (88.513
102–104 (98–10413
)
)
Ph
89–90 (89–9013
)
4-BrPh
4-MePh
2-MeOPh
2-NO2Ph
4-NO2Ph
Me
110–111 (111–213
106–107 (105–613
104–105 (104–513
113–115 (113–513
)
)
)
)
H
H
H
4-MeO
142–143 (142.513
oil14
)
Me
59–60
Scheme 2
to form an aziridine after departure of the good leaving-
group tertiary amine, 1,4-diazabicyclo[2.2.2]octane (Scheme 2).
The diamine imide can also decompose into 1,4-diaza-
bicyclo[2.2.2]octane, which is a competitive reaction with
aziridination, and is why excess hydrazinium nitrate is needed
in the reaction. Scheme 2 shows both of the imide moieties in
N,NЈ-diamino-1,4-diazoniabicyclo[2.2.2]octane dinitrate parti-
cipating in aziridination reactions. However, sometimes just one
imide reacts. In the aziridination reactions in most cases
Michael addition could be the rate-determining step. However,
for the nitro substituted chalcones, ring-closure is possibly
disadvantageous because the carbanion could be stabilized by
a strong electron-withdrawing group, the nitro group. Thus, the
yields of the corresponding aziridines are low.
Two other hydrazinium salts, 1,1,1-triethylhydrazinium
nitrate, an acyclic hydrazinium salt, and 1-aminopyridinium
nitrate, an aromatic hydrazinium salt, were also prepared and
were tested for aziridination. Aziridination of chalcone with
1,1,1-triethylhydrazinium nitrate gave a very low yield (12%).
It might be assumed that the 1,1,1-triethylammonium imide
anion attached to the nitrogen of triethylamine is more
sterically hindered than those attached to the nitrogens of 1,4-
diazabicyclo[2.2.2]octane. No desired aziridine was found in
the reaction of 1-aminopyridinium nitrate with chalcone. This
could be ascribed to the aromaticity of pyridine. After reaction
with sodium hydride, the pyridinium N-imide anion is very
unstable and is prone to forming stable aromatic pyridine by
loss of imide. In competitive reactions, pyridinium N-imide
decomposes faster than the Michael addition occurs.
In conclusion, N,NЈ-diamino-1,4-diazoniabicyclo[2.2.2]-
octane dinitrate is an efficient reagent for the conversion of 1-
aryl-α,β-unsaturated ketones to their N-unsubstituted aziridine
derivatives.
Experimental
Melting points were measured on a Yanaco MP-500 melting
1
point apparatus and are uncorrected. H NMR spectra were
recorded on a Varian Mercury 200 (200 MHz) spectrometer in
CDCl3 with tetramethylsilane (TMS) as an internal standard.
Mass spectra were obtained on a VG-ZAB-HS mass spec-
trometer. CHN analyses were recorded on an Elementar Vario
EL analyzer. IR spectra were taken on a Bruker Vector 22
FT-IR spectrophotometer using KBr pellets.
Caution: Hydrazinium salts should be considered potential
chemical hazards16 and extreme care must be exercised in
working with them. However no problems were encountered
during our studies. N,NЈ-Diamino-1,4-diazoniabicyclo[2.2.2]-
octane dinitrate was prepared according to the literature pro-
cedure and was reported stable, but highly energetic.12 The
known aziridine derivatives gave satisfactory data as reported in
the literature.11,13,14
General aziridination procedure
N,NЈ-Diamino-1,4-diazoniabicyclo[2.2.2]octane dinitrate (268
mg, 1.0 mmol) and α,β-unsaturated ketone (104 mg, 0.5 mmol)
were dissolved in 9 mL of a mixture of anhydrous isopropanol
and benzene (2 : 1, v/v). NaH (30 mg, 95%, ∼1.0 mmol) was
added portionwise over 30 min with stirring at 0 ЊC. The
mixture was stirred overnight. Water was added to the reaction
mixture. After extracting with benzene, the organic layer was
washed with water and brine and dried over sodium sulfate.
In order to extend this aziridination, attempts to aziridinate
α,β-unsaturated esters (ethyl cinnamate and ethyl acrylate)
and α,β-unsaturated N,N-disubstituted amides (N,N-dimethyl-
cinnamamide and N,N-dimethylacrylamide) with N,NЈ-di-
amino-1,4-diazoniabicyclo[2.2.2]octane dinitrate failed.
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J. Chem. Soc., Perkin Trans. 1, 2002, 1491–1493

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except for yellow nitro substituted aziridines.
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2-Benzoyl-3-(4-methoxyphenyl)aziridine 4. Colorless crystals,
1
yield 84%; H NMR (CDCl3, 300 MHz) δ 8.02–7.23 (9H, m,
ArH), 3.47 (dd, 1H, J = 2.4, 8.1 Hz, CH), 3.14 (dd, 1H, J = 2.4,
9.6 Hz, CH), 2.66 (dd, 1H, J = 8.1, 9.6 Hz, NH); IR (KBr)
ν/cmϪ1 3264 (N–H), 1667 (C᎐O); MS (m/z) 253 (Mϩ, 41), 238
᎐
(Mϩ Ϫ Me, 100), 105 (PhCO, 75). Anal. calcd for C16H15NO2
(253.30) C, 75.87; H, 5.97; N, 5.53. Found C, 75.60; H, 6.04; N,
5.61%.
2-(4-Methoxybenzoyl)-3-methylaziridine
15.
Colorless
crystals, yield 99%; 1H NMR (CDCl3, 300 MHz) δ 8.01 (d, 2H,
J = 9.3 Hz, ArH), 6.99 (d, 2H, J = 9.3 Hz, ArH), 3.90 (s, 3H,
MeO), 3.18 (d, 1H, J = 2.5 Hz, CH), 2.19 (m, 1H, CH), 2.10
(br s, 1H, NH), 1.35 (d, 3H, J = 5.2 Hz, Me); IR (KBr) ν/cmϪ1
3209 (N–H), 1653 (C᎐O); MS (m/z): 191 (Mϩ, 33), 176 (Mϩ
Ϫ
᎐
Me, 100), 135 (MeOPhCO, 78). Anal. calcd for C11H13NO2
(191.23) C, 69.09; H, 6.85; N, 7.32. Found C, 69.30; H, 6.60;
N, 7.37%.
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