Stereo-controlled deamination of ketoaziridines using Ph3P, I2

Article abstract of DOI:10.3184/174751913X13646666428217

Ph₃P, I₂is an efficient reagent for the stereo-controlled deamination of non-activated aziridines, N-H and N-alkyl aziridines, using. The method works gives the corresponding trans-alkenes from both cis and trans-aziridines. A plausible mechanism is proposed for the ring opening and deamination of keto-aziridines in the presence of Ph₃P, I₂.

Full text of DOI:10.3184/174751913X13646666428217

282 RESEARCH PAPER
MAY, 282–284
JOURNAL OF CHEMICAL RESEARCH 2013
Stereo-controlled deamination of ketoaziridines using Ph3P/I2
Heshmat Allah Samimia*, Hamzeh Kiyanib and Zahra Shamsa
aDepartment of Chemistry, Faculty of Sciences, Shahrekord University, PO Box 115, Shahrekord, Iran
bSchool of Chemistry, Damghan University, Damghan, 36715-364, Iran
PPh3/I2 is an efficient reagent for the stereo-controlled deamination of non-activated aziridines, N–H and N-alkyl aziri-
dines, using. The method works gives the corresponding trans-alkenes from both cis and trans-aziridines. A plausible
mechanism is proposed for the ring opening and deamination of keto-aziridines in the presence of Ph3P/I2.
Keywords: ketoaziridine, non-activated aziridine, deamination, ring opening, Ph3P, I2
Aziridines, small ring heterocycles, are attractive building
blocks for the synthesis of a variety of nitrogen-containing
and other compounds.1–8 Aziridines have been classified as
‘activated’ or ‘non-activated’ according to whether or not
nucleophilic ring-opening reactions proceed in the absence of
a positive charge on the nitrogen. The presence of electron-
withdrawing substituents activates the ring, which then reacts
easily with nucleophiles to form ring-opened products.9–15
Among the reactions of aziridines, the deamination of
aziridines has been attractive for mechanistic, structural,
thermodynamic and theoretical reasons. Several methods have
been described for the deamination of a variety of aziridines
using some reagents such as N2O4,9 N-nitroso-3-nitrocarba-
zole,16 nitrosyl chloride,17 methyl nitrite,17 n-butyl nitrite18
and organosilyllithium.19 However these reagents suffer from
at least one of the following disadvantages: (1) high costs
of preparations, (2) expensive reagents (3) tedious work-up
procedures and (4) nitrosation agents. In contrast to activated
aziridines, non-activated aziridines are relatively inert towards
nucleophiles and the reaction of aziridines with halides as
nucleophiles are relatively unusual.20–24
product of the reaction with both cis and trans- 1-benzyl-2-
benzoyl-3-aryl aziridines (3,4) was identified as corresponding
trans-alkenes. The results are summarised in Table 3.
Another striking feature of this reaction is that keto-aziridi-
nes in the presence of Ph3P/I2 resulted in alkenes of the deami-
nation reaction, but dialkylaziridines produced β-halo-amines
though a ring opening reaction23 (Scheme 4).
Scheme 1
Table 1 Reaction of trans-2-benzoyl-3-phenyl aziridines (1a)
under various conditions in refluxing dichloromethane
Entry
Reagent (mmol)
Time/h
Yield/%a
1
2
3
4
5
6
7
8
I2 (1)
I2/Ph3P (1:1)
Br2 (1)
Br2/Ph3P (1:1)
Ph3P (1:1)
4
2
0
93
0
87
0
70
67
0
In continuation of our recent interest in the chemistry of
heterocyclic compounds25–26 as well as the ring expansion
and opening of keto-aziridines,27–34 we now report the reaction
of non-activated cis and trans-aziridines using PPh3/I2 which
gives the corresponding trans-alkenes in high yields under
mild conditions. In addition, it shows a substituent-reactivity
relationship for some different aziridines under the same
reaction conditions.
4
5
4
16
16
4
CCl4/Ph3P (1:1)
CBr4/Ph3P (1:1)
Ph3P/CCl3CO2H (1:1)
a Isolated yield after purification.
Initially, the reaction of trans-2-benzoyl-3-phenyl aziridine
(1a) was studied in the presence of I2 in dichloromethane. No
reaction between 1a and I2 occurs in refluxing dichlorometh-
ane even for 4h (Table 1, entry 1). The reaction of 1a with I2 in
the presence of Ph3P was also examined in refluxing dichloro-
methane. This only afforded the corresponding trans-alkene in
excellent yields by a deamination reaction (entry 2). Other
conditions were also examined with 1 as a starting material in
further investigations (entry 3–8). The best results were obtained
in the presence of Ph3P/I2 in refluxing dichloromethane
(entry 2).
The deamination reaction was then extended to a variety of
trans-2-aroyl-3-aryl aziridines. The results are summarised in
Table 2. All the aziridines gave the corresponding trans-
alkenes. The known alkenes were characterised by comparison
of their spectroscopic data (1H NMR, 13C NMR and IR) and
melting point with literature values. The analytical data for
new compounds are also given.
Scheme 2
Table 2 Reaction of trans-2-aroyl-3-aryl aziridines (1a–h) with
Ph3P/I2b in refluxing dichloromethane
Entry
R1
R2
Time Yield
M.p./°C
/h
/%a (2)
Found Reportedc
1a
1b
1c
1d
1e
1f
C6H5
4-ClC6H4
2,4-Cl2C6H3
4-NO2C6H4
4-OMeC6H4
3-NO2C6H4
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
2
2
2.5
2.5
2
93
91
88
91
81
82
86
93
55–58
114–115
210–211
162–163 155–157
69–72
55–57
–
210
After successfully applying the methodology to non-acti-
vated aziridines, we examined the reaction of some trans and
cis-1-benzyl-2-benzoyl-3-aryl aziridines (3,4) under the same
conditions as the others non-activated aziridines. Gratifyingly,
the same reaction conditions worked efficiently, and the
70–73
2.5
2
159–162
155–158
117–119
–
–
–
1g
1h
4-ClC6H4 4-ClC6H4
2,4-Cl2C6H3 4-ClC6H4 2.5
a Isolated yield after purification. b Reagent/aziridine (1:1).
c Identified by comparison of their melting points and spectro-
scopic data with those of the reported ones.35–36
* Correspondent. E-mail: samimi-h@sci.sku.ac.ir

JOURNAL OF CHEMICAL RESEARCH 2013 283
Scheme 3
Table 3 Reaction of 1-benzyl-2-benzoyl-3-aryl aziridines (3,4)
with Ph3P/I2
Entry
R1
Time/h Yield/% (2)
M.p./°Cb
3a
3b
3c
3d
3e
3f
C6H5
2
1.5
1
2
2
1.5
2
1
95
93
91
93
89
97
88
89
54–57
113–115
209–211
161–163
69–72
160–162
55–57
210–212
4-ClC6H4
2,4-Cl2C6H3
4-NO2C6H4
4-OMeC6H4
3-NO2C6H4
C6H5
4a
4c
2,4-Cl2C6H3
Scheme 5
a Isolated yield after purification.
b Identified by comparison of their melting points and spectro-
scopic data with those of the reported ones.35–36
Experimental
1H NMR spectra were obtained on a Bruker DRX-500 and 13C NMR
spectra on a Bruker DRX-125 Avance spectrometer. FTIR spectra
were recorded on a Shimadzu FTIR- 8400S spectrometer. Chemical
shifts of 1H and 13C NMR spectra are expressed in ppm downfield
from tetramethylsilane. Melting points were measured on a Buchi
melting point B-540 instrument and are uncorrected. Elemental analy-
ses were made by a Carlo-Erba EA1110 CNO-S analyser and agreed
with the calculated values. All the chemicals were purchased from
Merck and used without further purification.
Deamination of aziridines (1, 3 or 4); general procedure
PPh3/I2 (1 mmol) was added to a solution of aziridine (1 mmol) in
dichloromethane (5 mL) and the mixture was heated for 1–2.5 hour.
The reaction was monitored by TLC, After the completion of reaction,
evaporation of the solvent under reduced pressure and subsequent
purification of the residue by column chromatography (silica gel,
EtOAc-Hexane: 1/4) gave corresponding trans-alkene (Tables 2 and
3). A crystalline or powdered solid was obtained in good yields.
(E)-3-(4-Chlorophenyl)-1-phenylprop-2-en-1-one (2b): Yellow
Scheme 4
Our results shows (Table 1) that the deamination of keto-
aziridines occurs in the presence of Ph3P and some halogenat-
ing agents such as Br2, I2, CCl4 or CBr4. We propose that the
reaction proceeds with the nucleophilic reaction of Ph3P and
the halogenating agents to give Ph3P+X X− as an efficient
reagent for the deamination or ring opening of the aziridines
(Scheme 5). The aziridine can be activated by a nucleophilic
reaction on the halogen of Ph3P+X. Aziridine would be active
in this stage and suitable for ring opening. The carbonyl group
in a keto-aziridine with its electron-withdrawing characteris-
tics makes C-2 as a suitable site for nucleophilic reaction
with iodide (A), leading to this regio-controlled reaction.29
Subsequent reaction of Ph3P on iodide (B) produces an anionic
intermediate (C, D) which, after an elimination reaction,
give a chalcone. cis-Aziridines under these thermodynamic
conditions give corresponding trans-chalcon as the more stable
product. In the absence of a carbonyl group the reaction gives
a β-halo-amines by a ring-opening reaction23 (Scheme 5).
Without an electron-withdrawing group on C2 or C3 of
aziridine, the enolate (C, D) would not be produced, so β-halo-
amines give a ring-opening reaction. This shows that substitu-
ents on the aziridines have an important role in determining the
reactions, ring-opening or deamination.
1
crystals; m.p. 114–115 °C; IR (KBr): 3045, 1651, 1591. H NMR
(400 MHz, CDCl3) (δ, ppm): 8.1 (dd, J = 7.5, 2.00 Hz, 2H), 7.75 (d,
J = 15.6 Hz, 1H), 7.70 (m, 2H), 7.58 (m, 2H), 7.55 (dd, J = 7.7,
1.8 Hz, 1H), 7.50 (m, 3H), 190.6, 143.2, 138.1, 136.5, 133.4, 132.7,
129.5, 129.2, 128.7, 128.4, 122.3. Anal. Calcd for C15H11ClO: C,
74.23; H, 4.57. Found: C, 74.19; H, 4.55%.
(E)-3-(3-Nitrophenyl)-1-phenylprop-2-en-1-one (2f): Off yellow
solid; m.p. 159–162 °C; IR (KBr): 3047, 1661, 1605, 1580, 1524, 858,
1
780, 743, 682, 666. H NMR (400 MHz, CDCl3) (δ, ppm): 8.49 (s,
1H), 8.26–8.28 (dt, J = 2.1, 8.1 Hz, 1H),. 8.0 (q, J = 1.4, 7.2 Hz, 2H),
7.9 (d, J = 7.7 Hz, 1H), 7.80–7.86 (d, J = 15.6 Hz, 1H), 7.65–7.67 (d,
J = 15.6 Hz, 1H), 7.62–7.63 (m, 2H), 7.52–7.56 (q, J = 0.6, 7.5 Hz,
2H). 13C NMR (100 MHz, CDCl3) (δ, ppm): 189.6, 148.7, 141.5,
137.5, 136.6, 134.3, 133.3, 130.0, 128.8, 128.6, 124.6, 124.5, 122.4.
Anal. Calcd for C15H11NO3: C, 71.14; H, 4.38; N, 5.53. Found: C,
71.13; H, 4.39; N, 5.51%.
(E)-3-(4-Chlorophenyl)-1-(4-chlorophenyl)prop-2-en-1-one (2g):
1
Yellow crystals; m.p. 155–158 °C; IR (KBr): 3042, 1653, 1594. H
NMR (400 MHz, CDCl3) (δ, ppm): 8.2 (dd, J = 7.6, 2.1 Hz, 2H),
7.77 (d, J = 15.4 Hz, 1H), 7.71 (m, 2H),.7.59 (m, 2H), 7.52 (dd,
J = 7.6, 1.8 Hz, 1H), 7.50 (m, 2H), 189.9, 144.0, 139.1, 136.7, 133.9,
132.1, 129.5, 129.3, 128.6, 128.5, 122.1. Anal. Calcd for C15H10Cl2O:
C, 65.01; H, 3.64. Found: C, 65.04; H, 3.67%.
(E)-3-(2,4-Dichlorophenyl)-1-(4-chlorophenyl)prop-2-en-1-one
In conclusion, this work describes an efficient and novel
method for the deamination of cis and trans-2-aroyl aziridines
in a completely stereo-controlled reaction in the presence
of Ph3P/I2, which paves the way for further studies about
substituent-reactivity relationship and mechanistic aspects. A
conceivable pathway could involve ring opening cis- and
trans-aziridines followed by thermodynamic control to give
solely the trans-alkene. Research on this topic is under way.
(2h): Yellow solid; m.p. 117–119 °C; IR (KBr): 3039, 1659, 1598,
1
1495. H NMR (400 MHz, CDCl3) (δ, ppm): 8.53 (s, 1H), 8.2 (dd,
J = 7.6, 2.1 Hz, 2H), 8.14 (dd, J = 7.6, 2.1 Hz, 1H), 8.10 (d, J =
8.1 Hz, 1H), 7.80 (d, J = 15.6 Hz, 1H), 7.64 (d, J = 15.6 Hz, 1H),
7.63–7.73 (m, 2H). 13C NMR (100 MHz, CDCl3) (δ, ppm): 189.7,
142.4, 138.5, 136.4, 134.7, 133.3, 132.4, 129.8, 129.4, 128.7, 128.4,
128.2, 123.4. Anal. Calcd for C15H9Cl3O: C, 57.82; H, 2.91. Found: C,
57.80; H, 2.93%.

284 JOURNAL OF CHEMICAL RESEARCH 2013
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Received 27 January 2013; accepted 21 February 2013
Paper 1301755 doi: 10.3184/174751913X13646666428217
Published online: 15 May 2013
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