Regioselective and stereospecific synthesis, crystal structure and NMR assignments of N-[(Z)-1-oxo-1,3-diphenylprop-2-en-2-yl]-4-nitrobenzamide

Article abstract of DOI:10.3184/174751914X13998313245571

Isomerisation of cis and trans N-acyl-2-benzoyl-3-phenylaziridines to the corresponding N-(E ) and N-[(Z )-1-oxo-1-aryl-3- phenylprop-2-en-2-yl]-4- benzamide, respectively, in the presence of diethyl thiourea is described. The structure of N-[(Z )-1-oxo- 1-phenyl-3-phenylprop-2-en-2-yl]-4-nitrobenzamide is also confirmed by the single crystal X-ray diffraction study. A mechanism for this regiospecific rearrangement is proposed.

Full text of DOI:10.3184/174751914X13998313245571

358 RESEARCH PAPER
VOL. 38 JUNE, 358–361
JOURNAL OF CHEMICAL RESEARCH 2014
Regioselective and stereospecific synthesis, crystal structure and NMR
assignments of N-[(Z)-1-oxo-1,3-diphenylprop-2-en-2-yl]-4-nitrobenzamide
Heshmat Allah Samimia* and Bohari M. Yaminb
aDepartment of Chemistry, Faculty of Sciences, Shahrekord University, PO Box 115, Shahrekord, Iran
bLow Carbon Research Group, School of Chemical Sciences and Food Technology, Universiti Kebangsaan Malaysia, UKM 43500
Bangi Selangor, Malaysia
Isomerisation of cis and trans N‑acyl‑2‑benzoyl‑3‑phenylaziridines to the corresponding N‑(E) and N‑[(Z)‑1‑oxo‑1‑aryl‑3‑
phenylprop‑2‑en‑2‑yl]‑4‑benzamide, respectively, in the presence of diethyl thiourea is described. The structure of N‑[(Z)‑1‑oxo‑
1‑phenyl‑3‑phenylprop‑2‑en‑2‑yl]‑4‑nitrobenzamide is also confirmed by the single crystal X‑ray diffraction study. A mechanism
for this regiospecific rearrangement is proposed.
Keywords: ketoaziridine, ring expansion, regio-controlled, stereospecific rearrangement
The earliest example of an acid catalysed isomerisations of
an aziridine was described by Gabriel in 1895.l The reaction
lay dormant until the late 1950s when a number of workers
confirmed2 and extended3,4 isomerisations of several aziridines
utilising other aqueous mineral acid catalysts.5
diaroyl-3-arylaziridines to the derivatives N-[(Z) or N-[(E)-1-
oxo-1,3-diphenylprop-2-en-2-yl] benzamide by a C–N bond
cleavage in a regio- and stereo-selective manner.
Benzoyl chloride were added to a solution of trans-2-benzoyl-
3-phenylaziridines (trans-1a) in the presence of Et3N in CH2Cl2
at 0 °C to furnish 2-benzoyl-1-benzoyl-3-phenylaziridine
Thermal or non-thermal,6 acids or nucleophilic reagents7–10
and/or photochemical isomerisations11,12 of aziridines are
valuable intermediates in organic synthesis as they undergo
a variety of transformations and are easily available and
versatile. Some of the major reaction pathways followed by
these systems include intramolecular hydrogen atom transfer,
electrocyclic ring opening to give azomethine ylides, and C–N
bond cleavage leading to oxazolidines, deamination and other
reactions. The molecular changes involved in the isomerisation
of the 1-benzyl-2-phenyl-3 benzoylaziridine system are
markedly dependent on the initial stereochemistry and reaction
conditions.13–15
Although a large variety of 1-aroylaziridines are known
to be isomerised into oxazolines,16–20 few examples of the
isomerisation of the 2-benzoyl-3-phenylaziridines have been
reported (Scheme 1).21–24
Our interests in C–N bond or C–C bond cleavage of the
aziridine ring into oxazoles,24 thiazoles,25 oxazolines,26–28
motivated our studies of the isomerisation of cis and trans-1,2-
(trans-2a) (Scheme 2)26
which was treated with diethyl thiourea
in CH2Cl2. The reaction afforded the desired product N-[(Z)-
1-oxo-1,3-diphenylprop-2-en-2-yl] benzamide (Z-3a) (93%).
N-[(Z)-1-oxo-1,3-diphenylprop-2-en-2-yl]-4-nitro benzamide
(Z-3b) was also prepared by the same procedure (Scheme 2). A
mixture of trans-2a in CH2Cl2 and absence of diethyl thiourea
was stirred for 2 days, but 2a was recovered unchanged.
1
Since the spectral data (e.g., H and 13C NMR, IR, and
elemental analysis) were not conclusive enough to assign
the stereochemistry of 3a and 3b, X-ray crystallographic
analysis was conducted on 3b to verify product structure.
X-ray analysis of the representative product Z-3b confirms the
diastereoselectivity of the reaction (Fig. 1).
We next explored the isomerisation of cis-isomer of N-acyl
ketoaziridines for evaluation of the reaction. In another
attempt, treatment of cis-1,2-dibenzoyl-3-phenylaziridines (cis-
2a) in the presence of diethylthiourea gave N-[(E)-1-oxo-1,3-
diphenylprop-2-en-2-yl]-4-benzamide (E-3a) (Scheme 3).
Ph
Ph
O
N
N
O
Ph
Ph
Ph
ref. 26,27
O
O
Ph
Ph
ref. 28
R
O
PhO2C
Ph
H
N
Ph
t-ButHN
Ph
O
Ph
CHPh
O
N
H
ref. 21
ref. 14
H
N
O
Ph
Ph
ref. 11
Ph
H
Ph
This work
Ph
N
H
Ph
NHCOPh
O
Scheme 1 Isomerisation of some trans‑2‑benzoyl‑3‑phenylaziridines to the corresponding isomers.
* Correspondent. E-mail: samimi-h@sci.sku.ac.ir
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JOURNAL OF CHEMICAL RESEARCH 2014 359
H
N
R
N
O
R
H
O
i or ii
iii
O
O
HN
Z-3(a), Z-3(b)
confirmed by X-Ray
2(a) =C6H5CO
2(b) =4-NO2C6H4CO
trans-1
(i) C6H5COCl/CH2Cl2/Et3N/RT
(ii) 4-NO2C6H4COCl/CH2Cl2/Et3N/RT
(iii) ENHCSNHEt/CH2Cl2/RT
Scheme 2 Isomerisation of trans‑N‑acyl‑2‑benzoyl‑3‑phenylaziridines (trans-2a, 2b to N‑[(Z)‑1‑oxo‑1,3‑diphenylprop‑2‑en‑2‑yl) benzamide (Z-3a, 3b).
O
H
N
O
N
O
ii
i
O
O
HN
H
E-3a
cis-1a
cis-2a
(i) C6H5COCl/CH2Cl2/Et3N/RT
(ii) ENHCSNHEt/CH2Cl2/RT
Scheme 3 Isomerisation of cis‑N‑acyl‑2‑benzoyl‑3‑phenylaziridine (cis-2a) to N‑[(E)‑1‑oxo‑1,3‑diphenylprop‑2‑en‑2‑yl] benzamide (E-3a).
Ar
Ar
O
Ar
H
O
O
C2-N cleavage
O
Ph
O
H
O
N
H
O
N
N
S
Ph
NHCOAr
Ph
Ph
Ph
H
Ph
Ph
H
S
Ph
Z-3
A
EtHN
NHEt
trans-1
Scheme 4
EtHN
NHEt
Mechanism for the isomerisation of trans‑N‑acyl‑2‑benzoyl‑3‑phenylaziridines.
According to Scheme 4, isomerisation of trans-N-acyl
ketoaziridines proceeds via an addition–elimination reaction
usingdiethylthioureainaC–Nbondcleavageoftrans-aziridine.
Based on the X-ray crystallographic analysis as shown in Fig. 1,
the product of Z-3 will be formed. The aryl moiety at position
3 makes it a suitable position for nucleophilic attack by N,Nʹ-
diethylthiourea. It might be expected that the isomerisation
involves initial attack by N,Nʹ-diethylthiourea on an aziridinyl
carbon adjacent to the aryl group with concurrent breaking of
the three-membered ring (C2–N bond) to form an intermediate
A. In a subsequent step, negatively charged oxygen abstracts
hydrogen adjacent to aroyl group synchronous and/or then with
anti-elimination of diethyl thiourea affords Z-3.
The same stereo- and regioselective manner is generalised
for formation of E-3 from cis-N-acyl ketoaziridines by an
addition–elimination reaction (Scheme 5).
The rearrangement of cis- and trans-2 to 3 occurred in a
regiospecific and stereoselective manner, and it is suggested that
the regioselectivity entirely depends on the stereo-electronic
nature of the substituents on aziridinyl carbons (phenyl and
benzoyl). It means N,Nʹ-diethylthiourea prefers to attack the
carbon bearing phenyl. In addition, in the proposed mechanisms
(Schemes 3 and 4) the inability of one of the reactions to form
both of isomers (Z and E) suggests that either the isomerisation
is a concerted process or else negatively charged oxygen in A
and B abstracts hydrogen adjacent to aroyl faster than it can be
rotated to form others isomers.
Crystal structure of 3b
Crystals suitable for X-ray investigation were obtained after
several attempts of recrystallisation. Despite the slightly low
quality crystals the structural solution could still be obtained.
Fig. 1 Crystal structure of compound Z‑3b drawn at 50% probability
ellipsoids.
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360 JOURNAL OF CHEMICAL RESEARCH 2014
Ph
N
O
Ph
O
H
O
Ph
NHCOPh
O
Ph
H
C2-N cleavage
H
N
H
H
O
O
N
Ph
Ph
Ph
O
S
Ph
Ph
Ph
EtHN
Ph
S
E-3
NHEt
cis-1
EtHN
B
NHEt
Scheme 5 Mechanism for the isomerisation of cis‑1,2‑dibenzoyl‑3‑phenylaziridines.
The compound crystallised in monoclinic system with space
group P 21/c, a=7.6429(7), b=25.433(2), c=9.9223(8) Å;
β=107.841(3)º, Z=4 and V=1835.9(1) Å3. The crystal system
and structural refinement parameters are shown in Table 1.
The molecular structure with the numbering scheme is shown
in Fig. 1. The benzyl, benzoyl and p-nitrobenzamide groups are
connected at C6 atom in such a way that the benzene (C11–
C22) ring is in the cis and trans configuration with respect
to p-nitrobenzamide and benzoyl groups respectively, across
the C8–C16 double bond of 1.337(4) Å. Other bond lengths
and angles are in normal ranges29 as shown in Table 2. The
O1/N1/(C6–C7) nitrobenzyl, (C10–C15) benzene and benzyl
(C16–C22) groups are each planar with maximum deviation
of 0.034(5)A for N1 atom from the least square plane of the
nitrobenzyl group. The O1/N1/(C6–C7) nitrobenzyl fragment
makes dihedral angle with the (C16–C22) benzyl and (C10–
C15) benzene ring of 26.59(15) and 70.33(15)º respectively.
The benzene ring is almost perpendicular to the benzyl group
with dihedral angle of 80.02(16)º. The structure is stabilised
by N2–H2A…O3 (x, 1/2–y, –1/2+z, D–H= 0.86, H…A=2.11,
D…A=2.920(3), D–H–A=159º) intermolecular hydrogen
bond to form one-dimensional chains.
of the pathway, which has been confirmed by X-ray analysis. A
proposed mechanism has been described for this rearrangement.
Experimental
Single-crystal X-ray experiment was performed on Bruker D-QUEST
diffractometer using graphite-monochromated Mo-Kα radiation
(λ=0.71073 Å). Intensity data was measured at 301(2) K by the ω-scan.
Accurate cell parameters and orientation matrix were determined by
the least-squares fit of 25 reflections. Intensity data were collected
for Lorentz and polarisation effects. Empirical absorption correction
was carried out using multi-scan. The structure was solved by direct
methods and least-squares refinement of the structure was performed
by the SHELXL-97 program [15]. All the non-hydrogen atoms
were refined anisotropically. The hydrogen atoms were placed in
calculated positions, allowing them to ride on their parent C atom with
Uiso(H)=1.2Ueq (C). The disordered O2 atom was separated into O2A
and O2B atoms and refined with occupancy of 0.35(14) and 0.65(14)
respectively. A summary of the data collections and details of the
structure refinement is given in Table 1.
Crystallographic data for the structural determination has been
deposited with the Cambridge Crystallographic Data Centre, CCDC
No 994782 of this information may be obtained free of charge from the
Director, CCDC, 12 Union Road, CambridgeCB2, 1EZ, UK (fax:+44
12233 36033; E-mail:deposit@ccdc.cam.uk or http://www.ccdc.co.uk).
All yields refer to isolated products after purification by column
chromatography or distillation in vacuum. Products were characterised
by IR, 1HNMR and 13CNMR spectra, TLC, melting points. NMR
spectra were recorded on a Bruker AMX-400 spectrometer (1H at
400 MHz and 13C at 100 MHz) in CDCl3with chemical shift values in
ppm downfield from TMS and IR spectra were recorded on FT Infrared
spectroscope JASCO, FT/IR-6300. All solvents used were dried and
distilled according to standard procedures.
In conclusion, we have described synthesis of two regio-
isomers of N-(1-oxo-1,3-diphenylprop-2-en-2-yl)benzamide
via isomerisation of cis and trans-N-acylaziridines. The main
advantages of this method are the regio- and stereoselectivity
Table 1 Crystal data and structure refinement details for Z-3b
Empirical formula
C22H16N2O4
Formula weight
372.37
0.500×0.08×0.060
Yellow
Crystal size/mm–3
Crystal colour
Crystal system
Space group
Table 2 Selected bond lengths (Å) and angles (°) of Z-3b
Monoclinic
P21/c
O1–N1
1.216(5)
O2)–N1
O2B–N1
N2–C7
N1–C3
N2–C8
C7–O3
C8–C9
C9–O4
C9–C10
C7–N2–C8
N2–C8–C9
O4–C9–C10
O4–C9–C8
O3–C7–N2
1.21(4)
1.208(17)
1.352(3)
1.484(5)
1.406(3)
1.225(3)
1.497(4)
1.217(4)
1.482(4)
119.9(2)º
115.9(3)
121.7(3)
119.6(3)
121.4(3)
121.0(2)
118.1(3)
a, b,
c/Å; β/deg
V/Å3
7.6429 (7), 25.433 (2),
9.9223 (8), 107.841
1835.9 (3)
Z
4
D (calcd)/g cm−3
μ/mm−1
1.347
0.094
F(000)/e
θ range/deg
776
3.0–25.0
Index range
–9<h<9, –30<k<30, –11 <l<11
40566/3229 [R(int)=0.1488]
99
Reflections collected/unique
Completeness to θ=25.0
Refinement on
Data, restraints, parameters
R (Fo2 >2σ(Fo2))
R (all data)
Goodness‑of‑fit=F
Extinction coefficient
Largest diff. peak and hole/e Å−3
F2
O3–C7–C6
C6–C8–C9
3229/0/263
R1 =0.0783, wR2 = 0.1200
R1 =0.1285, wR2 = 0.1353
1.111
Torsion angles
O3–C7–N2–C8
O4–C9–C8–N2
O4–C9–C8–C16
C7–N2–C8–C9
–5.2(4)
–47.7(4)
127.5(3)
–43.2(4)
0.0040(6)
0.16 and –0.19
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Synthesis of 1-oxo-1,3-diphenylprop-2-en-2-yl benzamides (Z-3a,
Z-3b and E-3a) from the corresponding ketoaziridines (1a-b); general
procedure
Received 28 January 2014; accepted 21 April 2014
Paper 1402433 doi: 10.3184/174751914X13998313245571
Published: 10 June 2014
To the mixture of N-acylaziridine (1 mmol) in dichloromethane in at
room temperature, N,Nʹ-diethylthiourea (1 mmol) were added and the
mixture was stirred. The progress of the reaction was monitored by
TLC (EtOAc-Hexane: 1/4)). After completion of the reaction, organic
layer was rinsed twice with dilute HCl(10%) and water, then dried with
anhydrous Na2SO4. Evaporation of the solvent under reduced pressure
and subsequent purification of the residue by column chromatography
(silica gel, EtOAc:hexane, 1:4) provided the desired products (Z-3a,
Z-3b and E-3a) (88–93%). Z-3b was recrystallised using ethanol:water
(1:1) to give target compounds.
N-[(Z)-1-Oxo-1,3-diphenylprop-2-en-2-yl]-benzamide (Z-3a): White
solid, m.p. 160–162 °C; 1H NMR (400 MHz, CDCl3): δ 8.33 (br, NH),
7.88 (dd, J=8.6, 2.1 Hz, 2H), 7.80 (s, 1H); 7.75 (dd, J=8.4, 2.1 Hz, 2H),
7.86–7.4 (m, 10H), 7.01 (s, 1H) ppm; 13C NMR (400 MHz, CDCl3): δ;
13C NMR (100 MHz, CDCl3): δ 192.9, 162.9, 139.7, 138.2, 136.8, 134.9,
133.1, 131.2, 131.0, 130.0, 129.9, 129.8, 129.0, 128.6, 126.8, 124.0 ppm.
Anal. calcd for C22H17NO2: C, 80.71; H, 5.23; N, 4.28; found: C, 80.68;
H, 5.25; N, 4.27%.
References
1
2
3
S. Gabriel and R. Stelzner, Chem. Ber., 1895, 28, 2929.
A.S. Deutsch and P.E. Fanta, J. Org. Chem., 1956, 21, 892.
Y. lwakura and A. Nabeya, J. Chem. Soc. Jpn., Pure Chem. Sect., 1965, 77,
773.
4
5
6
7
8
M. Tisler, Arch. Pharm. (Weinheim, Ger.), 1958, 291, 457.
H.W. Heine, Angew. Chem., Int. Ed. Engl., 1962, 1, 528.
N. Besbes, Tetrahedron Lett., 1999, 40, 6569.
G. Cardillo, L. Gentilucci and G.P. Mohr, Eur. J. Org. Chem., 2001, 3545.
C.S. Park, M.S. Kim, T.B. Sim, D.K. Pyun, C.H. Lee, D. Choi, W.K. Lee,
J.W. Chang and H.J. Ha, J. Org. Chem., 2003, 68, 43.
L. Testa, M. Akssira, E. Zaballos-Garcia, P. Arroyo, L.R. Domingo and J.
Sepulveda-Arques, Tetrahedron, 2003, 59, 677.
9
10 S. Dalili and A.K. Yudin, Org. Lett., 2005, 7, 1161.
11 D. Ramaiah, M. Muneer, K.R.; Gopidas, P.K. Das, N.P. Rath and M.V.
George, J. Org. Chem., 1996, 61, 4240.
12 N. Haffmann, G. Hugel, J.M. Nuzillard and D. Royer, Tetrahedron Lett.,
1998, 39, 7503.
N-[(Z)-1-Oxo-1,3-phenylprop-2-en-2-yl]-4-nitrobenzamide
(Z-3b):White solid, m.p. 203–205 °C; IR (KBr): v (cm–1) 3217, 3067,
13 J.N. Jr. Pitts, J.K.S. Wan and E.A. Schuck, J. Am. Chem. Soc., 1964, 86,
3606.
1
1666, 1664, 1598, 1525, 1480, 1447; H NMR (400 MHz, CDCl3): δ
14 A. Padwa and W. Eisenhardt, J. Am. Chem. Soc., 1971, 93, 1400.
15 D. Ramaiah, K. Ashok, R. Barik, D. Venugopal, N.P. Rath, K.
Bhattacharyya, P.K. Das and M.V. George, J. Org. Chem., 1992, 57, 6032.
16 B. Zwanenburg, Pure Appl. Chem., 1996, 68, 735.
17 B. Olofsson, U. Khamrai and P. Somfai, Org. Lett., 2000, 2, 4087.
18 V.K. Aggrawal and J. Vasse, Org. Lett., 2003, 5, 3987.
19 B.F. Bonini, M. Fochi, M. Comes-Franchini, A. Ricci, L. Thijs and B.
Zwanenburg, Tetrahedron Lett., 2005, 46, 4103.
8.76 (br, NH), 8.29 (d, J=8.7 Hz, 2H), 8.07 (d, J=8.6 Hz, 2H), 7.90 (d,
J=7.3 Hz, 2H), 7.62 (t, J=7.5 Hz, 1H), 7.52–7.48 (m, 4H), 7.43–7.36
(m, 3H), 6.92 (s, 1H) ppm; 13C NMR (100 MHz) (CDCl3) δ 193.7, 163.1,
149.9, 138.5, 136.4, 133.5, 133.3, 133.1, 132.9, 129.9, 129.8, 129.4, 128.9,
128.8, 128.5, 123.9 ppm. Anal. calcd for C22H16N2O4: C, 70.96; H, 4.33;
N, 7.52; found: C, 70.93; H, 4.37; N, 7.50%.
N-[(E)-1-Oxo-1,3-diphenylprop-2-en-2-yl]-benzamide (E-3a): White
solid, m.p. 137–139 °C; H NMR (400 MHz, CDCl3): δ 8.74 (br, NH),
20 A. Padwa and W. Eisenhardt, Chem. Commun., 1969, 1215.
21 F.W. Eastwood, P. Perimutter and Q. Yang, Tetrahedron Lett., 1994, 35,
2039.
22 M.A. Kuznetsov and V.V. Voronin, Chem. Heterocyclic Commun., 2011,
47, 173.
23 E.V. Beletskii and M.A. Kuznetsov, Russ. J. Org. Chem., 2009, 45, 1229.
24 H.A. Samimi and S. Mohammadi, Synlett, 2013, 24, 223.
25 H.A. Samimi and S. Mohammadi, J. Iran. Chem. Soc., 2014, 11, 69.
26 H.A. Samimi, M. Mamaghani and K. Tabatabeian, J. Heterocyclic Chem.,
2008, 45, 1765.
1
8.27 (d, J=8.2 Hz, 2H), 8.07 (d, J=8.6 Hz, 2H), 7.82 (d, J=7.3 Hz,
2H), 7.65 (t, J=4.5 Hz, 1H), 7.54–7.46 (m, 3H), 7.43 (d, J=7.1 Hz, 2H),
7.38–7.35 (m, 3H), 6.92 (s, 1H) ppm; 13C NMR (400 MHz, CDCl3): δ;
13C NMR (100 MHz, CDCl3): δ 191.2, 161.3, 149.7, 139.1, 138.4, 137.1,
134.5, 133.2, 132.8, 129.8, 129.0, 128.8, 128.7, 128.6, 127.9, 123.6 ppm.
Anal. calcd for C22H17NO2: C, 80.71; H, 5.23; N, 4.28; found: C, 80.61;
H, 5.29; N, 4.21%.
27 M. Mamaghani, K. Tabatabeian and H.A. Samimi, Z. Kristallogr. New.
Cryst. Struct., 2008, 223, 390.
28 H.A. Samimi, Z. Shams, J. Iran. Chem. Soc., 2014 (doi: 10.1007/s13738-
013-0364-8).
29 F.K. Allen, O. Kennard, D.G. Watson, L. Brammer, A.G. Orpen and R.
Taylor J. Chem. Soc. Perkins Trans., 1987, 2, S1–S19.
We are grateful to Research Council of Shahrekord University
for supporting this work and the University Kebangsaan
Malaysia for the analytical service grant DIP-UKM-2012-11
and CRIM for the facilities.
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