Mild, convenient and efficient synthesis of novel 2,2-dichloro-1,3- diarylaziridines from Schiff bases by phase transfer CTAB catalysis under low concentration alkaline conditions

Article abstract of DOI:10.1016/j.cclet.2011.05.027

A mild and efficient method for preparation of novel 2,2-dichloro-1,3- diarylaziridines from Schiff base compounds in the presence of N-cetyl-N,N,N-trimethyl ammonium bromide (CTAB) as phase transfer catalyst has been described. The reaction is dramatical

Full text of DOI:10.1016/j.cclet.2011.05.027

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Chinese Chemical Letters 22 (2011) 1273–1276
www.elsevier.com/locate/cclet
Mild, convenient and efficient synthesis of novel 2,2-dichloro-1,
3-diarylaziridines from Schiff bases by phase transfer CTAB
catalysis under low concentration alkaline conditions
*
Hossein Naeimi , Khadijeh Rabiei
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan 87317, Iran
Received 3 March 2011
Available online 28 July 2011
Abstract
A mild and efficient method for preparation of novel 2,2-dichloro-1,3-diarylaziridines from Schiff base compounds in the
presence of N-cetyl-N,N,N-trimethyl ammonium bromide (CTAB) as phase transfer catalyst has been described. The reaction is
dramatically enhanced in the presence of quaternary ammonium salt. The corresponding products have been obtained in excellent
yields, high purity and short reaction times.
# 2011 Hossein Naeimi. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Aziridine; Synthesis; Schiff base; CTAB; Phase transfer catalyst
Aziridines, three-membered nitrogen heterocycles, are highly reactive molecules, in part due to ring strain [1]. As a
consequence of their high reactivity, these small heterocycles play an important role as intermediates in synthesis of
both organic [2], pharmaceutical and natural product. Among three-membered heterocycles, aziridines constitute a
particularly versatile class of molecule, and as discussed in recent book [3], both physical properties and chemical
reactions of aziridines have been the subject of numerous theoretical and experimental investigations which have
proved invaluable in understanding the mechanism of drug action of pharmaceuticals containing azriridine warheads
[4]. The preparation of substituted aziridines and also, modern catalytic synthesis of aziridines from diazo compounds
and imines has been extensively reviewed [5,6]. While, 2,2-dihalodiarylaziridines have been very poorly investigated.
The development of new efficient syntheses of halogenated nitrogen heterocycles and their precursors is a rather
persisting problem in organic chemistry [7–10].
Schiff bases that contain an imine or azomethine have prepared from condensation of primary amines with carbonyl
compounds [11–13]. These compounds have been extensively studied in chemistry due to their facile syntheses,
electronic properties, good solubility in common solvents and numerous applications in organic synthesis,
pharmacology [14] and etc. Phase transfer catalysis (PTC) technology has recently been widely applied to synthesize
specially chemicals from organic reactions [15,16]. Many chemists have investigated phase transfer catalysis in
numerous reactions, such as: substitution, displacement, condensation, electro-reduction and etc. As a result, PTC
considered having great potential for industrial-scale application [17,18].
* Corresponding author.
E-mail address: naeimi@kashanu.ac.ir (H. Naeimi).
1001-8417/$ – see front matter # 2011 Hossein Naeimi. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2011.05.027

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H. Naeimi, K. Rabiei / Chinese Chemical Letters 22 (2011) 1273–1276
Because of these economical and environmental reasons and in conjunction with ongoing work in our laboratory on
the preparation of Schiff base derivatives [19,20], here we decided to report the synthesis of various dichloroaziridines
through the reaction of Schiff base compounds and chloroform in the presence of N-cetyl-N,N,N-trimethyl ammonium
bromide (CTAB) as phase transfer catalyst under alkaline condition at room temperature.
1. Experimental
All the materials were of commercial reagent grade. All the Schiff bases have been prepared according with
previously reported procedure [21,22]. IR spectra were recorded as KBr pellets on a Perkin-Elmer 781
1
spectrophotometer and an Impact 400 Nicolet FTIR spectrophotometer. H NMR and 13C NMR were recorded in
DMSO/CDCl3 solvents on a Bruker DRX-400 spectrometer with TMS as internal reference. Mass spectra were
recorded on a Finnigan MAT 44S by electron ionization (EI) mode with an ionization voltage of 70 eV. The elemental
analyses (C.H.N) were obtained from a Carlo ERBA Model EA 1108 analyzer. Melting points obtained with a
Yanagimoto micro melting point apparatus are uncorrected.
Typical procedure for the synthesis of 2,2-dichloro-1,3-diphenylaziridine: NaOH (0.095 mol, 3.8 g) and CTAB
(0.00082 mol, 0.3 g) were dissolved in 30 mL of water. The mixed solution was introduced to a 100 mL flask and
uniformly agitated at isothermal condition for 10 min. Then, Schiff base (organic reactant; 0.027 mol) dissolved in
10 mL chloroform was gradually added drop wise to the mixed solution. The progress of the reaction was monitored
by TLC. After the completion of the reaction, the solution was separated and the portion of aqueous solution was
extracted twice by ether. Magnesium sulfate was also added to adsorb the residual water. The organic solvent
(chloroform) and other residues were stripped in a vacuum evaporator. The pale yellow solid, 2,2-dichloro-1,3-
diphenylaziridine, was obtained in 90% yield (0.024 mol). All of the diarylaziridine products were identified by
physical and spectroscopic data as following:
2,2-Dichloro-1,3-diphenylaziridine (2a): pale yellow solid; 0.024 mol; mp: 100–102 8C, (98–99 8C, Ref. [23,24]);
IR (KBr)/y (cmÀ1): 3090, 2930, 1600, 1520 (C C, Ar); 1H NMR (400 MHz, CDCl3): d 4.20 (s, 1H, HCN), 7.01–7.80
(m, 10H, Ar); 13C NMR (100 MHz, CDCl3): d 52.1, 74.1, 119.0, 120.1, 125.1, 126.1, 127.1, 128.3, 134.2, 140.1; MS:
m/z 267 (M+4 + 4, 7), 265 (M+2 + 2, 29), 263 (M+, 45), 230 (67), 228 (100), 77 (95); Anal. Calcd. For C14H11NCl2: C,
63.64 5; H, 4.17; N, 30, Found: C, 63.67; H, 4.19 5; N, 30.
2,2-Dichloro-1-(4-bromophenyl)-3-phenylaziridine (2b): white solid; 0.025 mol; mp: 110–112 8C; IR (KBr)/y
(cmÀ1): 3100, 2914, 1600, 1524 (C C, Ar); 1H NMR (400 MHz, DMSO-d6): d 4.34 (s, 1H, HCN), 7.14 (d, 2H, Ar),
7.45 (d, 2H, Ar), 7.50–7.55 (m, 5 H, Ar); 13C NMR (100 MHz, CDCl3): d 50.0, 71.0, 119.4, 122.7, 128.9, 129.0, 131.9,
132.3, 136.2, 151; MS: m/z: 347 (M+6 + 6, 8), 345 (M+4 + 4, 20), 343 (M+2 + 2, 45), 341 (M+, 27), 308 (80), 306 (100),
229 (75), 227 (50), 77 (85); Anal. Calcd. For C14H10NBrCl2: C, 49.12; H, 2.92; N. 4.11. Found: C, 49.15; H, 2.95; N.
4.12.
2,2-Dichloro-1-(4-chlorophenyl)-3-phenylaziridine (2c): pale yellow solid; 0.0248 mol; mp: 72–74 8C, (71–72 8C,
Ref. [25]); IR (KBr)/y (cmÀ1): 3090, 2900, 1598, 1499 (C C, Ar); 1H NMR (400 MHz, CDCl3): d 4.21 (s, 1 H, HCN),
7.10 (d, 2 H, Ar), 7.32 (d, 2 H, Ar), 7.48–7.55 (m, 5 H, Ar); 13C NMR (100 MHz, CDCl3): d 53.1, 76.9, 119.1, 120.8,
121.1, 127.9, 128.1, 130.1, 131.2, 135.1, 142.2; MS: m/z 233 (M+6 + 6, 7), 231 (M+4 + 4, 15), 299 (M+2+2, 32), 297
(M+, 35), 264 (96), 262 (100), 174 (75), 172 (80), 91 (95), 77 (45); Anal. Calcd. For C14H10NCl3: C, 56.28; H. 3.35; N,
4.69, Found: C, 56.31; H. 3.38; N, 4.70.
2. Results and discussion
In this research, the phase transfer catalyzed reaction of dichloro aziridination of Schiff base compounds has been
studied. When 0.027 mol of Schiff base compound was reacted with dichlorocarbene intermediate obtained in situ
from the reaction of chloroform and base in the presence of CTAB as a phase transfer catalyst, corresponding products,
2,2-dichloro-1,3-diarylaziridine compounds was obtained at room temperature (Scheme 1).
Firstly, we have carried out this reaction in the presence and without of two-phase transfer catalysts, such as: CTAB
and N-cetyl pyridinium bromide (CPB). The corresponding results are indicated in Table 1.
As can be seen in this Table, desired product was obtained with excellent yield in the presence of CTAB rather than
CPB as phase transfer catalyst. Also, any product was obtained in the reaction without phase transfer catalyst in
alkaline solution (Table 1, entries 9 and 10). It has also been investigated the reaction in the presence of various

H. Naeimi, K. Rabiei / Chinese Chemical Letters 22 (2011) 1273–1276
1275
Cl
N
Cl
N
CTAB
, NaOH
CHCl3
+
2
H2O, r.t.
R
R
R
R
1
1
2
1a-i
2a-i
R1 = H, CH3, NO2, Cl
R2 = H, CH3 , Cl, Br
Scheme 1. Preparation of 2,2-dichloro-1,3-diarylaziridine compounds from Schiff bases.
amounts of sodium hydroxide. The optimum amount of used NaOH was resulted 12.6 wt% in which 2,2-dichloro-1,3-
diphenylaziridine was obtained in excellent yield and appropriate reaction time.
With attention to above results, several Schiff base compounds were reacted with CHCl3 in the presence of mixture
of NaOH (12.6%) and CTAB as phase transfer catalyst and desired dichloroaziridine derivatives were prepared. The
results are summarized in Table 2. As shown in this Table, the reaction of the various Schiff bases with chloroform and
optimum amount of NaOH, were catalyzed by CTAB as two-phase transfer. The corresponding products were
obtained in excellent yields and appropriate reaction times.
Table 1
Enhancement of phase transfer catalyst (PTC) and amount of NaOH on the formation of 2,2-dichloro-1-(4-bromophenyl),3-(4-chlorophenyl)
aziridine.
Entry
PTC
NaOH (%)
Time (h)
Yield (%)
1
2
CTAB
CTAB
CTAB
CTAB
CTAB
CPB
8
12
9
10
25
55
98
98
10
15
20
–
10
3
11
6
4
12.6
14
2.3
2.3
12
16
24
96
96
5
6
12.6
12.6
12.6
22.5
30
7
CPB
8
CPB
9
None
None
10
–
Table 2
Synthesis of 2,2-dichloro-1,3-diarylaziridines in the presence of CTAB catalyst and 12.6 wt% NaOH.
Entry
Substrate
R1
Product
M.P. (8C)
Time (h)
Yielda (%)
R2
1
2
3
4
5
6
7
8
9
H
H
2a
2b
2c
2d
2e
2f
100–102
110–112
72–74
4
90, (61)b, (55)c
H
Br
3.20
3.25, (16)d
2.40
2.30
4.40
4.45
3.45
3.30
94
92,(68)d
H
Cl
Cl
Cl
139–141
134–136
141–143
140–142
146–148
128–130
98
Cl
Br
98
NO2
NO2
CH3
Cl
Br
90
CH3
Br
2g
2h
2i
92
96
CH3
97
a
Isolated yields.
b
c
d
By hexachloroacetone and sodium methoxide, Ref. [23].
By sodium methoxide and chloroform, Ref. [24].
By potassium t-butoxide and chloroform, Ref. [25].

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H. Naeimi, K. Rabiei / Chinese Chemical Letters 22 (2011) 1273–1276
The structure of products has been confirmed by physical and spectroscopic data such as; IR, 1H NMR, 13C NMR,
Mass spectroscopy and C. H. N. analyses. In the IR spectra of compound 2b, the stretching frequency of aromatic C C
is formed in the region 1587 cmÀ1 and 1487 cmÀ1. The stretching vibration of C–H in the alkyl groups was appeared at
region 2928 cmÀ1. In the 1H NMR spectra, one proton of CH–N was appeared in d 4.34 as a singlet. Two aromatic
protons were appeared in d 7.14 as a doublet. The appeared signal in d 7.45 is belong to another two aromatic protons.
The signals around d 7.50–7.55 are assigned by other five protons of aromatic rings. In the 13C NMR spectra, one
carbon of C–N has chemical shift in d 50.0 and the signal in d 71.0 is assigned by one carbon of CCl2 of aziridine ring.
The signal around d 119.4–150.0 is assigned by carbons of aromatic rings. Appearance of molecular ion peak with m/z
341was confirmed the formation of this product.
In conclusion, we have synthesized dichloroaziridine derivatives through the reaction of various Schiff base
compounds with chloroform in the presence of CTAB at room temperature. The corresponding products have been
obtained in excellent yields, high purity and short reaction times. The products have been confirmed by physical and
1
spectroscopic data such as; IR, H NMR, 13C NMR, MS spectroscopy and C. H. N. analyses.
Acknowledgments
We are grateful to the University of Kashan research council for the partial support of this work.
References
[1] J.B. Sweeney, Chem. Soc. Rev. 31 (2002) 247.
[2] V.H. Dahanukar, L.A. Zavialov, Curr. Opin. Drug Discov. Dev. 5 (2002) 918.
[3] A.K. Yudin (Ed.), Aziridines and Epoxides in Organic Synthesis, Wiley-VCH Weinheim, 494, 2006.
[4] A.M. Sapse, R. Rothchild, D.C. Jain, G.A. Hernandez, J. Mol. Model. 13 (2007) 1169.
[5] (a) A.H. Li, L.X. Dai, Chem. Rev. 97 (1997) 2341;
(b) W.K. Lee, H.J. Ha, Aldrichim. Acta 36 (2003) 57;
(c) R.S. Atkinson, Tetrahedron 55 (1999) 1519;
(d) D. Tanner, Angew. Chem. Int. Ed. Engl. 33 (1994) 599.
[6] Z. Xue, A. Mazumdar, L.J. Hope-Weeks, et al. Tetrahedron Lett. 49 (2008) 4601.
[7] A.F. Khlebnikov, M.S. Novikov, R.R. Kostikov, Russ. Chem. Rev. 74 (2005) 171.
[8] E.Y. Shinkevich, M.S. Novikov, A.F. Khlebnikov, Synthesis (2007) 225.
[9] M. Mihara, Y. Ishino, S. Minakata, M. Komatsu, J. Org. Chem. 70 (2005) 5320.
[10] A.F. Khlebnikov, M.S. Novikov, E.Y. Kusei, et al. Russ. J. Org. Chem. 39 (2003) 559, Translated from Zh. Org. Khim 39 (2003) 595.
[11] H. Schiff, Ann. Chem. Pharm. Suppl. 3 (1864) 343.
[12] H. Schiff, Justus Liebigs Ann. Chem. 210 (1881) 119.
[13] C.R. Laurent, Gerhard, Trav. Chim. (1850) 117.
[14] J. Jarrouse, C.R. Hebd, Seances Acad. Sci., Ser. C232 (1951) 1424.
[15] P. Auzeloux, J. Papon, R. Pasqualini, J.C. Madelmont, J. Med. Chem. 44 (2001) 1116.
[16] E. Benoist, G.C. Jobic, C. Courseille, et al. New J. Chem. 22 (1998) 615.
[17] S. Diltz, G. Aguirre, F. Ortega, P.J. Walsh, Tetrahedron: Asymm. 8 (1997) 3559.
[18] M.L. Tommasino, M.J. Casalta, A.J. Breuzard, M. Lemaire, Tetrahedron: Asymm. 11 (2000) 4835.
[19] H. Naeimi, K. Rabiei, F. Salimi, Bull. Korean Chem. Soc. 29 (2008) 2445.
[20] H. Naeimi, K. Rabiei, F. Salimi, Phosphorus Sulfur, Silicon Relat. Elem. 184 (2009) 2351.
[21] H. Naeimi, H. Sharghi, F. Salimi, K. Rabiei, Heteroatom. Chem. 19 (2008) 43.
[22] H. Naeimi, F. Salimi, K. Rabiei, J. Mol. Catal. A: Chem. 260 (2006) 100.
[23] P.K. Kadaba, J.O. Edwards, J. Org. Chem. 25 (1960) 1431.
[24] E.K. Fields, J.M. Sandri, Chem. Ind. (Lond.) (1959) 1216.
[25] A.G. Cook, E.K. Fields, J. Org. Chem. 27 (1962) 3686.