1,3-Dipolar cycloaddition of N-[4-nitrophenyl]-C-[2-furyl] nitrilimine with some dipolarophiles: A combined experimental and theoretical study

Article abstract of DOI:10.1016/j.molstruc.2010.01.059

Reaction of vinyl acetate (3), 2-propyne-1-ol (4) and styrene (5) as dipolarphiles with N-[4-nitrophenyl]-C-[2-furyl] nitrilimine which was generated in situ has been shown to afford 3-(furan-2-yl)-1-(4-nitrophenyl)-4,5-dihydro-1H-pyrazol-5-yl acetate (6), (3-(furan-2-yl)-1-(4-nitrophenyl)-1H-pyrazol-5-yl)methanol (8) and 3-(furan-2-yl)-1-(4-nitrophenyl)-5-phenyl-4,5-dihydro-1H-pyrazole (10). Reactivity and regiochemistry of these reactions were investigated using DFT-based reactivity indexes.

Full text of DOI:10.1016/j.molstruc.2010.01.059

Journal of Molecular Structure 969 (2010) 139–144
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
1,3-Dipolar cycloaddition of N-[4-nitrophenyl]-C-[2-furyl] nitrilimine with some
dipolarophiles: A combined experimental and theoretical study
*
M. Bakavoli , F. Moeinpour, A. Davoodnia, A. Morsali
Department of Chemistry, School of Sciences, Islamic Azad University, Mashhad Branch, Mashhad, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Reaction of vinyl acetate (3), 2-propyne-1-ol (4) and styrene (5) as dipolarphiles with N-[4-nitro-
phenyl]-C-[2-furyl] nitrilimine which was generated in situ has been shown to afford 3-(furan-2-yl)
-1-(4-nitrophenyl)-4,5-dihydro-1H-pyrazol-5-yl acetate (6), (3-(furan-2-yl)-1-(4-nitrophenyl)-1H-pyra-
zol-5-yl)methanol (8) and 3-(furan-2-yl)-1-(4-nitrophenyl)-5-phenyl-4,5-dihydro-1H-pyrazole (10).
Reactivity and regiochemistry of these reactions were investigated using DFT-based reactivity indexes.
Ó 2010 Elsevier B.V. All rights reserved.
Received 19 October 2009
Received in revised form 31 December 2009
Accepted 25 January 2010
Available online 1 February 2010
Keywords:
Regioselectivity
1,3-Dipolar cycloaddition
Nitrilimine
Pyrazoles
DFT-based reactivity indexes
B3LYP calculations
1. Introduction
Furthermore, transition-state calculations are often very time
consuming when bulky substituents are present in reactive
The cycloaddition of 1,3-dipolar species to an alkene for the
synthesis of five-membered rings is a classic and important reac-
tion in organic chemistry [1]. These 1,3-dipolar cycloaddition
(1,3-DC) reactions are used for both academia and industrial pur-
poses [2]. These reactions are one of the most important processes
with both synthetic and mechanistic interest in organic chemistry.
Current understanding of the underlying principles in the Diels–Al-
der (DA) reactions and the 1,3-dipolar cycloadditions (1,3-DC) has
grown from a fruitful interplay between theory and experiment
[2–4]. The development of the 1,3-DC reactions has in recent years
entered a new stage as control of the stereochemistry in the addi-
tion step is now the major challenge. The stereochemistry of these
reactions may be controlled either by choosing the appropriate
substrates or by controlling the reaction using a metal complex
acting as catalyst [5]. Two major factors i.e. the steric and elec-
tronic effects can influence the regioselectivity of these reactions
[2]. Although transition state theory remains the most widely used
and the most rigorous approach for the study of the mechanism
and the regiochemistry of these reactions, the localization of tran-
sition states is not always easier.
systems.
Recently, reactivity descriptors based on the density functional
theory (DFT), such as Fukui indexes, local softnesses and local elec-
trophilicity, have been extensively used for the prediction of the
regioselectivity. For instance, several treatments of 1,3-DC reac-
tions of nitrilimines with various dipolarophiles can be found in
the literature [6–8]. 1,3-Dipolar cycloadditions of nitrilimines to
olefins have been utilized extensively to synthesize pyrazoles
and pyrazolidines [9]. Furyl-substituted nitrilimines as useful
1,3-dipoles have received much less attention than their aryl ana-
logues or furyl-substituted nitrile oxides or nitrones. In fact, only a
few papers that deal specifically with 2-furannitrilimines have
been published [10–12]. This situation most likely reflects the
instability of available precursors and presents a relatively unex-
plored area suitable for further studies. In this context, we became
interested in the reactivity of N-[4-nitrophenyl]-C-[2-furyl] nitrili-
mine (2) as an electron-poor dipole towards several electron-rich
dipolarophiles such as vinyl acetate (3), 2-propyne-1-ol (4) and
styrene (5) as dipolarphiles in order to synthesize the new 3-(fur-
an-2-yl)-1-(4-nitrophenyl)-4,5-dihydro-1H-pyrazol-5-yl
acetate
(6), (3-(furan-2-yl)-1-(4-nitrophenyl)-1H-pyrazol-5-yl)methanol
(8) and 3-(furan-2-yl)-1-(4-nitrophenyl)-5-phenyl-4,5-dihydro-
1H-pyrazole (10) (Scheme 1). In addition, we found it worthwhile
to analyze the regioselectivity of these 1,3-DC reactions by DFT-
based reactivity indexes. Finally, the gauge-invariant atomic orbi-
* Corresponding author.
E-mail address: MBakavoli1@yahoo.com (M. Bakavoli).
0022-2860/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2010.01.059

140
M. Bakavoli et al. / Journal of Molecular Structure 969 (2010) 139–144
R
N
R
N
R
N
R
N
H
C
3
O
)
O
(
N
NH
2
1
C
O
(Not observed) (a)
(Not observed) (b)
(7)
N
1
+
(3)
(4)
2
R'
O
O
C
CAT
-H2
(6)
(
O
R'
+
)
C
H
N
R
N
R
N
3
HC
H
2O
H
C
C
N
N
2
1
1
OH
(9)
R'
2
+
+
(8)
R'
C
R'
R'
H
(1)
2 O
H
R
N
(2)
R
N
N
2
(5)
N
1
1
R'
2
(10)
R'
(11)
(Not observed) (c)
O2N
R=
R'=
Scheme 1. The regioisomeric pathways for 1,3-DC of nitrilimine (2) and dipolarophiles (3), (4) and (5).
O
tal (GIAO) method [13] was used to calculate NMR chemical shift,
to help the experimental cycloadduct determination, because it has
shown to yield data comparable to those of the experiment [14].
In the present work, the two following possible mechanisms are
considered:
markedly polar character, where the transition structure associ-
ated with the rate-determining step mostly involves the formation
of one single bond between the most electrophilic and other nucle-
ophilic sites. According to the model recently proposed by Chatt-
araj [19,20], during an electrophile–nucleophile interaction
process, when two reactants approach each other from a large dis-
tance, they feel only the effect of the global electrophilicity of each
(i) The mechanism corresponding to a four-center reaction.
This is the case of asynchronous or a very low asynchronous
cycloaddition.
(ii) The mechanism corresponding to a two-center reaction fol-
lowed by a ring closure. This is the case of a stepwise or a
high asynchronous cycloaddition. We note that the predic-
tion of the formation of the first favored bond is sufficient
for predicting the regioisomeric pathways.
other and not its local counterpart. The molecule with the larger
x
value will act as an electrophile, and the other will be have as the
nucleophile. The preferred interaction will be through the most
electrophilic site of the former and the most nucleophilic site of
the latter. Local electrophilicity index defined in Eq. (11), is there-
fore expected to be useful descriptor of regional electrophilicity/
nucleophilicity patterns that may account for the observed regiose-
lectivity in two-center reactions with a significant polar character.
2. Regioselectivity criteria for four-center reactions
4. Computational details
In order to explain the regiochemistry of four-center reactions,
Gazquez and Mendez proposed a local version of HSAB (Hard and
Soft Acid–Base) principle, which generally states that ‘‘the interac-
tion between any two chemical species will occur through the centers
with nearly equal condensed Fukui function” [15,16]. This can deter-
mine the behavior of different reactive sites with respect to the
hard and soft reagents. Chandra and Nguyen have correlated the
idea of the local HSAB concept and regioselectivity defining a quan-
tity, said ‘delta’ (Dkijl), that suggests a measure of predominance of
one reaction over the other on the base of local softnesses [17,18].
This quantity is so defined as Eq. (1):
All calculations were performed with the Gaussian98 program
suite [21]. For DFT calculations, the B3LYP/6-31G(d) level of theory
was employed. The optimizations of equilibrium geometries of
reactants were performed using the Berny analytical gradient opti-
mization method [22]. The atomic electronic populations were
evaluated according to Merz–Kollman scheme (MK option)
[23,24]. This scheme, which already proved to be reliable [25],
has been used in most DFT calculation of regiochemistry of 1,3-
DCs, and it has also been recently considered as an appropriate lo-
cal descriptor of charge. Chandra and Nguyen studied the 1,3-dipo-
lar cycloaddition reactions of diazoalkanes with alkyl-substituted
phosphaalkynes. They recommended that the atomic charges were
calculated by using the technique of electrostatic potential (ESP)-
driven charges are reliable. It is well known that Mulliken charges
are highly basis set dependent, whereas ESP-driven charges show
less basis set dependence and are better descriptors of the molec-
ular density distribution [26]. Therefore, the atomic charges were
calculated using the MK option. Parr et al. [27] proposed that the
2
2
kl
ij
D
¼ ðsi ꢀ skÞ þ ðsj ꢀ slÞ
ð1Þ
where i and j are the atoms of a molecule A involved in the forma-
tion of a cycloadduct with atoms k and l of a molecule B, and si ‘s are
the appropriate type of atomic softnesses (if si and sj are electro-
philic then sk and sl are obviously nucleophilic). The idea is based
on the simultaneous fulfillment of the local HSAB concept at both
termini. This is because, in the case of a multicenter addition reac-
tion, it is not the similarities of softness at one-center that are
important. (Dkijl) can be considered as a measure of how extensively
the HSAB principle is satisfied. The reaction associated with a lower
‘‘electrophilicity index”
ity for a variety of reactions including 1,3-dipolar and Diels–Alder
cycloadditions. is the chemical potential squared divided by two
x, has been used as a measure for reactiv-
x
times the hardness value (Eq. (2)):
(
Dkijl) value will be the preferred one.
l2
x
¼
ð2Þ
2
g
3. Regioselectivity criteria for two-center reactions
In Eq. (2)
l
and
g
are the electronic chemical potential and the
A useful simplification for the study of the regioselectivity in
reactions may be obtained by looking at those processes having a
chemical hardness of the ground state (GS) of atoms and mole-
cules, respectively.

M. Bakavoli et al. / Journal of Molecular Structure 969 (2010) 139–144
141
based on the reactivity indexes of the reactants involved in these
reactions will be performed.
5.1. Analysis of the 1,3-DC reaction between nitrilimine 2 with
dipolarophiles 3, 4 and 5
Nitrilimine 2 was generated in situ from the appropriate alde-
hyde hydrazone by refluxing a mixture of chloramine-T trihydrate
(N-chloro-N-sodio-4-methylbenzene sulfonamide, CAT) and the
dipolarophile in an appropriate solvent. Dipolar cycloaddition of
nitrilimine 2 to the dipolarophiles proceeded with complete regi-
oselectivity, thereby affording only 6, 8 and 10 in very good yields
(Scheme 1).
The corresponding regioisomers (compounds 7, 9 and 11 in
Scheme 1) have not been detected in the crude reaction mixture
by 1H and 13C NMR spectroscopy. The assignment of the regio-
chemistry in products 6, 8 and 10 was confirmed on the basis of
1H and 13C NMR spectral data and comparing with calculated 1H
and 13C NMR spectral data of the two possible regioisomers (see
Scheme 1 and Table 1).
Scheme 2. Electrophilicity index values for ethylenes for reactions of cyclopenta-
diene with ethylene, mono-, di-, and tetracyanoethylenes [27].
A representative application of the electrophilicity index was
reported by Domingo and co-workers [27] who investigated the
polarity of Diels–Alder cycloaddition between cyclopentadiene
and mono-, di-, tri-, and tetracyanoethylenes. Scheme 2 shows
the
x
values for cyclopentadiene and cyanoethylenes. Cyclopenta-
and shows that the direction of charge
diene has a lower value of
x
transfer is from diene to cyanoethylenes.
Reactivity indexes [28] were computed in the usual finite differ-
ence approximation within the framework of DFT. The global in-
dexes are the molecular hardness
As it can be seen in Table 1, we obtained the theoretical 1H and
13C NMR chemical shifts values for the products through the GIAO
method and compared it with the observed values. The observed
values for C1 and C2 in each of the isolated products are in closer
proximity to the theoretical values for compounds 6, 8 and 10. It
seems likely that the isolated regioisomers are structurally similar
to 6, 8 and 10.
g
¼ ðIP ꢀ EAÞ
and the electron chemical potential
¼ ꢀðIP þ EAÞ=2
ð3Þ
l
ð4Þ
where IP and EA are the ionization potential and electron affinity,
respectively. The latter are computed as vertical differences in
molecular energy between the neutral system and the mono-cation
and -anion, respectively, i.e.
5.2. Prediction of the NED/IED character
IP ¼ EðcationÞ ꢀ EðneutralÞ
EA ¼ EðneutralÞ ꢀ EðanionÞ
ð5Þ
ð6Þ
The NED (normal electron demand) or IED (inverse electron de-
mand) character of the cycloaddition reactions has been predicted
by three approaches, namely, the calculation of HOMO/LUMO gaps
As usual, local indexes are computed in atomic condensed form
[29]. The well-known Fukui function [30,31] for electrophilic (fkꢀ)
and nucleophilic attack (fkþ) can be written as
(Table 2a), electronic chemical potentials
l
and electrophilicity
indexes
x (Table 2b). Table 2a turns out that the |LUMO (dipo-
fkꢀ ¼ ½qkðNÞ ꢀ qkðN ꢀ 1Þꢁ
fkþ ¼ ½qkðN þ 1Þ ꢀ qkðNÞꢁ
ð7Þ
ð8Þ
Table 1
The comparison of theoretical 1H and 13C NMR chemical shifts data (d, ppm) of C-1
and C-2 of each pair of regioisomers with those obtained from the experimental
spectroscopy.
where
q
k(N),
q
k(N ꢀ 1) and
q
k(N + 1) are the gross electronic popu-
lations of the site k in neutral, cationic, and anionic systems,
Compound Atom
number 13C
chemical
shift
Calculated Calculated Experimental Experimental
1H
13C chemical 1H chemical
respectively.
The atomic softness is computed as
chemical
shift
shift
shift
sꢂk ¼ fkꢂS
ð9Þ
6
C-1
C-2
C-1
C-2
C-1
C-2
C-1
C-2
C-1
C-2
C-1
C-2
83.1
35.7
77.3
4.34
3.37; 3.12
4.81
3.51; 3.23
–
6.23
–
8.24
5.19
3.90; 3.65
3.32
83.3
35.7
4.26
3.33; 3.10
where S is the global softness and computed as [28]
7
47.0
1
S ¼
g
ð10Þ
8
134.9
108.5
118.4
121.9
58.0
38.2
42.2
49.5
136.1
108.6
–
6.24
9
The local electrophilicity index,
xk, condensed to atom k is eas-
ily obtained by projecting the global quantity onto any atomic cen-
ter k in the molecule by using the electrophilic Fukui function (i.e.
the Fukui function for nucleophilic attack, fkþ [32])
10
11
58.6
38.7
5.19
3.86; 3.60
3.30; 3.12
xk
¼
x
fkþ
ð11Þ
The 1H and 13C and NMR chemical shifts were calculated by
Table 2a
means of the GIAO method [13], using the tetramethylsilane
(TMS) as 1H and 13C reference, at the B3LYP/6-31G(d) level of the-
ory (reference values of 13C = 1845307 ppm and 1H = 322892 ppm).
Energy difference between the two possible HOMO/LUMO combinations for the
dipole and the dipolarophiles (values in eV).
Dipolarophile
LUMO
Dipole
HOMO
Dipole
LUMO
Dipolarophile
HOMO
Reaction
jE
ꢀ E
j (NED
jE
ꢀ E
j (IED
character)
character)
5. Result and discussion
a
b
c
5.799
6.808
5.233
4.553
4.800
3.804
Firstly, the 1,3-DC reaction between nitrilimine 2 and dipolaro-
philes 3, 4 and 5 (Scheme 1) will be analyzed. Then, a DFT analysis

142
M. Bakavoli et al. / Journal of Molecular Structure 969 (2010) 139–144
Table 2b
HOMO, LUMO energies (in a.u.), ionization potential (IP, in a.u.), electron affinity (EA, in a.u.), electronic chemical potential (
l
in a.u.), chemical hardness (g, in a.u.), global softness
(S, in a.u.) and global electrophilicity ( , in eV) for dipole and dipolarophile systems.
x
System
HOMO
LUMO
IP
EA
0.023
ꢀ0.072
ꢀ0.110
ꢀ0.033
l
g
S
x
Nitrilimine 2
Vinyl acetate 3
2-Propyne-1-ol 4
Styrene 5
ꢀ0.224
ꢀ0.250
ꢀ0.259
ꢀ0.222
ꢀ0.082
ꢀ0.011
0.027
ꢀ0.031
0.283
0.343
0.356
0.295
ꢀ0.153
ꢀ0.136
ꢀ0.123
ꢀ0.131
0.260
0.415
0.466
0.328
3.846
2.408
2.146
3.049
1.225
0.606
0.442
0.712
le) ꢀ HOMO (dipolarophile)| gaps for the dipole and dipolarophiles
are smaller than the |LUMO (dipolarophile) ꢀ HOMO (dipole)|.
Furthermore, as it can be seen in Table 2b, the electronic chem-
ical potential of dipolarophiles is greater than that of nitrilimine
(dipole), which indicates the charge transfer is taking place from
dipolarophile to nitrilimine. On the other hand Table 2b shows that
the electrophilicity power of nitrilimine is greater than those of
dipolarophiles, and consequently, the nitrilimine can act an elec-
trophile for the 1,3-DC reactions. In conclusion, the 1,3-DC reac-
tions treated in this work have IED character.
The Fukui indexes and local softnesses for the atoms N1 and C3
of the dipole (nitrilimine) and for the atoms C4, C5 of the dipolaro-
O
N
O
N
O
1
N
1
N
O
4
N
2
N
2
5
O
C
C
3
3
O
O
O
(3)
(4)
5.3. Prediction of regiochemistry
O
N
O
N
OH
In order to put in evidence the preferential cyclization mode
and consequently the major cycloadduct of 1,3-DC reactions under
investigation, we will consider two possibilities (two-center/four-
center) of the reaction mechanism. Our theoretical predictions of
the regioselectivity will be based on the conceptual DFT theories.
1
N
1
N
5
N
2
N
2
C
C
3
3
OH
O
O
5.3.1. Use of DFT-based reactivity indexes
(5)
(6)
5.3.1.1. Case of a four-centered process. The regioselectivity of four-
center reactions is conveniently explained by the Gazquez–Men-
dez rule [33] which stipulates that ‘‘the interaction between two
chemical species A and B is favored when it occurs through those
atoms whose softnesses are approximately equal”. In our cases,
the application of the Gazquez–Mendez rule is reduced to the cal-
culation of the quantities s3, s4, s5, s6, s7 and s8 corresponding to the
regioisomeric pathways (Scheme 2). These quantities are ex-
pressed by (see the Scheme 2 for atom numbering)
O
N
O
N
1
N
4
1
N
N
2
5
5
N
2
C
3
4
C
O
3
O
(7)
(8)
2
2
2
s3 ¼ ðsþC3 ꢀ sꢀC4Þ þ ðsNþ1 ꢀ sꢀC5
Þ
Þ
ð12Þ
ð13Þ
Scheme 3. The two possible cyclization modes and atom numbering.
2
s4 ¼ ðsþC3 ꢀ sꢀC5Þ þ ðsNþ1 ꢀ sꢀC4
The s5, s6, s7 and s8 values are also calculated in similar manner.
O2N
O2N
O
OH
0.194
N
0.194
N
Table 3a
O
-0.106
0.211
Fukui indexes for the N1 and C3 atoms of the nitrilimine and for atoms C4 and C5 of
-0.231
the dipolarophiles and related local softnesses (sþk ; skꢀ) values (in a.u.).
N
N
0.415
skꢀ
fkþ
skþ
C
0.415
fkꢀ
C
Atom number
0.415
Nitrilimine
Vinyl acetate
2-Propyn-1-ol
Styrene
N1
C3
C4
C5
C4
C5
C4
C5
0.086
0.184
0.330
0.707
O
O
(3)
(5)
0.431
1.037
ꢀ0.240
ꢀ0.578
O2N
0.328
0.704
ꢀ0.165
0.314
ꢀ0.002
ꢀ0.353
0.958
ꢀ0.006
0.194
N
N
C
-0.002
0.360
0.415
O
Table 3b
Values of s3, s4, s5, s6, s7 and s8 quantities calculated with MK population analysis.
(7)
Scheme 4. Local nucleophilicities xꢀk (in eV), for dipolarophile centers, and local
electrophilicities, xþk (in eV), for the nitrilimine centers, calculated with MK
population analysis.
s3
s4
s5
s6
s7
s8
0.933
2.151
0.466
1.264
0.176
0.902

M. Bakavoli et al. / Journal of Molecular Structure 969 (2010) 139–144
143
philes (vinyl acetate, 2-propyne-1-ol and styrene), calculated with
MK population analysis are given in Table 3a. The values of the
quantities of s3, s4, s5, s6, s7 and s8 are given in Table 3b. The small
value of s3 compared to s4, for the reaction a, s5 compared to s6 for
reaction b and s7 compared to s8 for reaction c shows that the
cycloaddition channel leading to the cycloadduct 3, 5 and 7 (see
Scheme 3) is the most favored. Thus, the experimental regioselec-
tivity is correctly predicted using DFT-based indexes.
1H, CH), 6.62 (t, 1H, CH, 2-furan ring), 6.84 (d, 1H, CH, 2-furan ring),
7.12 (d, 2H, CH, phenyl ring), 7.71 (d, 1H, CH, 2-furan ring), 8.13 (d,
2H, CH, phenyl ring); 13C NMR (DMSO-d6) dC: 21.8 (CH3), 35.7
(CH2), 83.3 (CH), 109.6, 109.8, 112.1, 126.5, 136.1, 142.3, 142.7,
150.7 (CPh and CFu), 156.4 (C@N), 169.3 (C@O).
Compound (8) orange solid: yield: 80%, m.p.: 143 °C, MS m/z
285(M+), Anal. Calcd for C14H11N3O4: C, 58.95; H, 3.89; N, 14.73.
Found: C, 58.92; H, 3.86; N, 14.70., IR (KBr) cmꢀ1: 1558 (NO2)as,
1336 (NO2)s,1672(C@N), 3650 (OH), 1H NMR (DMSO-d6) dH: 3.64
(s, 1H, OH), 4.82 (s, 2H, CH2), 6.24 (s, 1H, CH), 6.83 (t, 1H, CH, 2-fur-
an ring), 7.71 (d, 1H, CH, 2-furan ring), 7.89 (d, 1H, CH, 2-furan
ring), 8.13 (d, 2H, CH, phenyl ring), 8.44 (d, 2H, CH, phenyl ring);
13C NMR (DMSO-d6) dC: 55.0 (OCH2), 107.6, 112.1, 126.5, 142.7,
146.5, 156.4 (CPh and CFu), 108.6(CH@C), 136.1(C@CH),
139.1(C@N).
Compound (10) light red solid: yield: 85%, m.p.: 114 °C, MS m/z
333(M+), Anal. Calcd for C19H15N3O3: C, 68.46; H, 4.54; N, 12.61.
Found: C, 68.48; H, 4.58; N, 12.62. IR (KBr) cmꢀ1: 1647 (C@N),
1558 (NO2)as, 1336 (NO2)s. 1H NMR (DMSO-d6) dH: 3.60 (dd, 1H,
CH2), 3.86 (dd, 1H, CH2), 5.11 (t, 1H, CH), 6.52 (t, 1H, CH, 2-furan
ring), 6.81 (d, 1H, 2-furan ring), 7.12 (d, 2H, CH, phenyl ring),
7.21 (m, 1H, CH, phenyl ring), 7.25 (m, 2H, CH, phenyl ring), 7.40
(m, 2H, CH, phenyl ring), 7.72 (d, 1H, CH, 2-furan ring), 8.12 (d,
2H, CH, phenyl ring); 13C NMR (DMSO-d6) dC: 38.7 (CH2), 58.6
(CH), 108.9, 110.1, 111.3, 124.8, 126.6, 126.9, 129.1, 136.8, 140.1,
141.3, 144.2, 149.9 (CPh and CFu), 155.9 (C@N).
5.3.1.2. Case of a two-center process. In Scheme 4, we have reported
the values of local electrophilicities xþk for atoms N1 and C3 (nitril-
imine) and the local nucleophilicities xꢀk for atoms C4 and C5 of
dipolarophiles. According to the Chattaraj’s model [19,20], the local
philicity indexes (xþk xkꢀ) seem to be a reliable tool for the predic-
;
tion of the most favored interaction in a two-center polar process.
The results show that the most favored interaction will take place
between C3 center of nitrilimine (possessing the highest value of
xþk ) and the C4 center of dipolarophiles (possessing the highest va-
lue of xꢀk ). Consequently, the experimental regioselectivity is cor-
rectly predicted by Chattaraj’s model.
6. Conclusion
The regioselectivity for the 1,3-dipolar cycloaddition reactions
of nitrilimine (2) with vinyl acetate (3), 2-propyn-1-ol (4) and sty-
rene (5) has been investigated using experimental and theoretical
1H and 13C NMR studies together with the DFT-based reactivity in-
dexes at the B3LYP/6-31G(d) level of theory. The results obtained
in this work clearly predict the regiochemistry of the isolated
cycloadducts.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.molstruc.2010.01.059.
7. Experimental
References
The melting points were recorded on an electrothermal type
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144
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