Twisted imide bond in noncyclic imides. Synthesis and structural and vibrational properties of N, N -bis(furan-2-carbonyl)-4-chloroaniline

Article abstract of DOI:10.1021/jo300360b

A novel imide compound (C₁₆H₁₀ClNO₄) was synthesized in a single step by the reaction of 2-furoic acid with 4-chloroaniline in a 2:1 molar ratio using carbonyldiimidazole (CDI) in dry THF. The structure was supported by spectroscopic and elemental analyses and the single-crystal X-ray diffraction data. Crystallographic studies revealed that the compound crystallized in a monoclinic system with space group P2 ₁/c and unit cell dimensions a = 12.2575(5) A, b = 7.7596(2) A, c = 15.0234(7) A, α = γ = 90°, β = 92.771(4)°, V = 1427.25(10) A³, Z = 4. The imide bond is twisted, and the O=C-N-C(O) units deviate significantly from planarity with dihedral angles around the imide group reaching ca. -150.3° (C1-N1-C2-O21 = -148.8° and C2-N1-C1-O11 = -151.9°). The nonplanarity of the imide moiety and the related conformational properties are discussed in a combined approach that includes the analysis of the vibrational spectra together with theoretical calculation methods, especially in terms of natural bond orbital (NBO) calculations.

Full text of DOI:10.1021/jo300360b

Article
pubs.acs.org/joc
Twisted Imide Bond in Noncyclic Imides. Synthesis and Structural
and Vibrational Properties of N,N-Bis(furan-2-carbonyl)-4-chloroaniline
Aamer Saeed,*,† Mauricio F. Erben,‡ and Michael Bolte§
†Department of Chemistry, Quaid-I-Azam University, Islamabad 45320, Pakistan
‡CEQUINOR (UNLP, CONICET-CCT La Plata), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional
de La Plata, C.C. 962 (1900), La Plata, Republica Argentina
́
§Institut fur Anorganische Chemie, J.W.-Goethe-Universitat, Max-von-Laue-Strasse 7, D-60438 Frankfurt/Main, Germany
̈
̈
S
* Supporting Information
ABSTRACT: A novel imide compound (C16H10ClNO4) was synthesized in a single step by the reaction of 2-furoic acid with
4-chloroaniline in a 2:1 molar ratio using carbonyldiimidazole (CDI) in dry THF. The structure was supported by spectroscopic
and elemental analyses and the single-crystal X-ray diffraction data. Crystallographic studies revealed that the compound
crystallized in a monoclinic system with space group P21/c and unit cell dimensions a = 12.2575(5) Å, b = 7.7596(2) Å,
c = 15.0234(7) Å, α = γ = 90°, β = 92.771(4)°, V = 1427.25(10) Å3, Z = 4. The imide bond is twisted, and the OC−N−C(O)
units deviate significantly from planarity with dihedral angles around the imide group reaching ca. −150.3° (C1−N1−C2−O21 =
−148.8° and C2−N1−C1−O11 = −151.9°). The nonplanarity of the imide moiety and the related conformational properties are
discussed in a combined approach that includes the analysis of the vibrational spectra together with theoretical calculation
methods, especially in terms of natural bond orbital (NBO) calculations.
Scheme 1. Planar Conformations Expected for Symmetrical
Imide Compounds
1. INTRODUCTION
The strong tendency for the amide bond to preserve planarity is
usually explained in terms of the conjugation of the nitrogen
lone pair with the CO double bond. This interaction leads to
a weakening of the CO bond and to a partial double bond
character of the N−C(O) motif, reflected in hindered internal
rotation around this bond. Thus, the planarity of the amide
bond usually includes also the directly bound neighbors. The
same applied for symmetrical imide compounds [R1N(COR2)2],
and it was established that three planar conformations are
stabilized by amide conjugation (see Scheme 1).1 Two other
factors, dipole−dipole interactions and steric interactions, are
also of primary importance in determining conformational pref-
erences of imides.2
Nevertheless, compounds with a twisted or distorted amide
bond are very well-described, including several secondary and
tertiary lactams,3 including β-lactam antibiotics. Bicyclic amides
adopt intrinsically nonplanar structures, and the tilt angles of
N-aroyl-7-azabicyclo[2.2.1]heptanes range from 26 to 31° in
the X-ray crystal structures.4,5 Deviation from planarity is fre-
quently accompanied by geometry changes at nitrogen. Thus,
β-peptides containing β-amino acids bearing nonplanar amides
display great flexibility of the backbone structure, promoted by
facile cis−trans isomerization of the amide bonds.6 Tertiary
aromatic amides with hindered nitrogen substituents have been
studied by Clayden and co-workers.7 As recently remarked by
́
Szostak and Aube, there exists a strong motivation for organic
chemists to prepare and study amides with a range of degrees of
twist.8
In the present work, the novel N,N-bis(furan-2-carbonyl)-4-
chloroaniline species has been prepared by the condensation
Received: March 7, 2012
Published: April 27, 2012
© 2012 American Chemical Society
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Scheme 2. Synthesis of the N,N-Difuran-2-carbonyl-4-chloroaniline
Figure 1. Molecular structure with atom numbering for N,N-bis(furan-2-carbonyl)-4-chloroaniline. Displacement ellipsoids are shown at the 50%
probability level.
reaction between 2-furoic acid with 4-chloroaniline in the pre-
sence of carbonyldiimidazole. The title compound belongs
to N,N-disubstituted anilines, a unique class of compounds.
It contains an N,N-disubstituted benzamide structure, a well-
known class of drugs that contain many analogues having
radio- and chemosensitizing and bioactive properties.9 Furan,
a 5-membered unsaturated oxygen heterocycle, is the basic
ring structure found in industrially significant products and in a
large number of biologically active natural products.10,11
In order to gain additional experimental and theoretical
information about the structural properties of imides, we also
report here an X-ray diffraction study for the title species,
drawing on its vibrational spectra (IR and Raman). Moreover,
quantum chemical calculations have been performed in order to
assist the interpretation of the experimental data, and the
natural bond orbital (NBO) population analyses were applied
to rationalize the effect of electronic interaction in the struc-
tural, conformational, and configurational properties around the
imide group.
NMR and infrared spectroscopic data were in complete agree-
ment with the proposed structure (see Table S1 in the Supporting
Information). The main absorption bands in the infrared spectrum
at 1665(vs), 1337(s), 1275(m), 1138(s), and 769(s) cm−1 allow to
identify the main functional groups, as will be discussed below.
1
The H NMR of compound 3 as CDCl3 solution shows 10
aromatic hydrogen signals between 6.47 and 7.47 ppm. Thus,
double doublets integrating for two hydrogens at δ 7.08 (d, J =
3.3 Hz, 2H, H-3′) and another for one hydrogen at 6.47 ppm
(J1 = 1.8, J2 = 1.8 Hz, 2H, H-4′) are assigned to the furan ring,
and doublets at 7.19 ppm (d, 2H, J = 8.7 Hz H-3,H-5), 7.38
(H-3,H-5) and a coupling constant of 8.7 Hz are assigned to
the aromatic protons.
The 13C NMR study of 3 in CDCl3 showed nine chemical
shifts indicating nine unequivalent carbons. Of these, five were
assigned to the quaternary carbons including that at δ 161.04
ppm for carbonyl and four to the tertiary aromatic carbons. The
benzene aromatic carbons have chemical shifts of δ 119.84 (C2,
C6, Ar), 129.79 (C3, C5, Ar), 134.07 (C4, Ar), and 137.40 (C1,
Ar) ppm, and the carbons of the furan ring have chemical shifts
of δ 112.41 (C4′) 115.58 (C′3), 146.44 (C5′), and 147.31 (C2′)
ppm, respectively.
2. RESULTS AND DISCUSSION
2.1. Synthesis and Characterization. The reaction of
2-furoic acid (1) with 4-chloroaniline (2) in a 2:1 molar ratio
using carbonyldiimidazole (CDI) in dry THF produces N,N-
bis(furan-2-carbonyl)-4-chloroaniline (3) according to Scheme 2
in 85% yield. This one-pot method is important because it does
not require the conversion of acids to acid chloride.12
The GC chromatogram shows a peak at retention times of
19.7 min with a very simple mass spectrum that was assigned
to the expected ionic fragments from logical ruptures of the
corresponding M•+ molecular ions (see Table S1 in the
Supporting Information). A second, less intense peak was found
at 15.5 min probably corresponding to the monosubstituted
4-chloroaniline, with a molecular ion with m/z = 221, in agree-
ment with C11H8ClNO2.
The new compound is an air-stable brownish prismatic solid
with mp = 157−159 °C. The molecular formula was confirmed
1
by elemental analysis and GC−mass spectral data. H and 13C
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Figure 2. Crystal packing of N,N-bis(furan-2-carbonyl)-4-chloroaniline.
2.2. -X-ray Analysis and Molecular Structure. The
molecular structure for the title compound, showing the atomic
numbering, as determined in the crystalline phase is shown in
Figure 1. The crystal packing (Figure 2) of title compounds is
stabilized by several nonbonded interactions. The molecules are
associated by weak hydrogen bonding C−H(furan)···O as well
as pseudo-offset-stacked parallel aromatic interactions involving
the chlorophenyl group.13 In this compound, the tertiary
nitrogen atom is not involved in intermolecular interactions.
Table 1 gives a comparison between the experimental values
of the most important geometrical parameters and the
The C−N imide bond lengths equal 1.4087(13) and
1.4134(12) Å, distances which are considerably shorter than
that expected for the single C(sp2)−N(sp2) bond length
(average value of 1.472(5) Å.14) while the carbonyl bond
lengths are in the range expected for imide carbonyl bonds.
These facts have been usually attributed to the importance of
the resonance form in the amide-like structures, a point that
will be discussed in a next section. However, it should be noted
that much shorter C−N amide bond distances (typically ca.
1.32 Å) have been found for related compounds.15,16
The N atom shows a trigonal planar coordination (sum of the
bond angles around N 360°). The observed C(1)−N(1)−C(2)
bond angle is higher [124.87(9)°] than the ideal value, the
same is valid for the vacuum isolated computed structure
(125.5°). Thus, is it plausible that steric hindrance between
the 2-carbonyl furan rings is acting in the title species. This effect
is also reflected in the torsion angles of the OC−N−C(O)
units, which deviate significantly from planarity [C(1)−N(1)−
C(2)−O(21) = −148.8° and C(2)−N(1)−C(1)−O(11) =
−151.9°] and neither of the furan rings is coplanar with the
imide unit [torsion angles: N(1)−C(1)−C(11)−C(15) =
21.7°; N(1)−C(2)−C(31)-C(35) = −167.2°]. The phenyl
ring is almost perpendicular to both furan rings (dihedral angles
between the ring planes are 92.0° and 89.0°).
Table 1. Selected Experimental (X-ray) and Computed
(B3YLP/6-311++G**) Bond Lengths (Å) and Angles (deg)
around the Imide Moiety of the Title Compound
a
b
c
geometrical parameter
exptl
calcd
N(1)−C(2)/N(1)−C(1)
N(1)−C(21)
1.4087(13)/1.4134(12)
1.4383(13)
1.416/1.428
1.442
C(1)−O(11)/C(2)−O(21)
C(1)−C(11)/C(2)−C(31)
C(2)−N(1)−C(1)
1.2103(13)/1.2177(12)
1.4552(14)/1.4588(14)
124.87(9)
1.208/1.216
1.469/1.470
125.5
C(2)−N(1)−C(21)/C(1)−
N(1)−C(21)
117.42(8) /117.69(8)
117.1/117.4
O(11)−C(1)−N(1)/O(21)−
C(2)−N(1)
O(11)−C(1)−C(11)/O(21)−
C(2)−C(31)
N(1)−C(1)−C(11)/N(1)−
C(2)−C(31)
121.02(10)/121.06(9)
122.99(9)/121.39(9)
115.77(9)/117.37(9)
121.5/121.6
122.9/120.3
115.1/118.0
The central R2−OC−N(R1)−CO−R2 (R1 = C6H4Cl,
R2 = 2-furan) imide group adopts a nonplanar E,E-like
configuration. As remarked previously by Noe and Raban,2
the Z,Z configuration might have been anticipated to be favored
in simple imides;17 however, it is also expected that imide
substitution strongly affect the balance between dipole−dipole
and steric interactions and thus the conformational behavior.18
To better understand how the substituents affect the
conformational preference for the sterically congested com-
pound here studied, quantum chemical calculations have been
applied. Several attempts to characterize the Z,Z form have
been made without success, probable due to steric repulsion
between the furan groups. Indeed, the optimization procedure
converges to the E,E form in many trails. Both, the intermediate
E,Z-like and the E,E conformers have been determined as a true
minimum in the conformational space for the title compound,
having very similar electronic energies. The computed differ-
ence in the electronic energy (ΔE0, corrected by zero-point
vibrational energies), ΔE0, amounts to 0.2 kcal/mol at the
B3LYP/6-311++G** level of approximation, the E,E form
C(2)−N(1)−C(1)−O(11)/
C(1)−N(1)−C(2)−O(21)
−151.94(11)/−148.83(11) −146.5/−152.4
C(21)−N(1)−C(1)−O(11)/
C(21)−N(1)−C(2)−O(21)
C(2)−N(1)−C(1)−C(11)/
C(1)−N(1)−C(2)−C(31)
29.74(15)/ 29.50(15)
33.33(14)/36.00(14)
32.5/28.6
31.8/39.6
C(21)−N(1)−C(1)−C(11)/
−144.99(10)/−145.68(9)
−141.4/−147.2
C(21)−N(1)−C(2)−C(31)
a
b
For atom numbering, see Figure 1. For complete crystallographic
c
information, see the Supporting Information. Syn−anti conformer
computed at the B3YLP/6-311++G** level of approximation.
optimized structure at the B3LYP/6-311++G** level of
approximation. The agreement between the experimental and
computed results is very good, especially for the central imide
group.
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being the most stable one. Thus, taking into account these
results for the vacuum-isolated species, which are in perfect
agreement with the conformer observed in the crystalline phase,
the following discussion will be centered in the most stable E,E
form for the imide group.
[symmetry code: (1 − x, 1/2 + y, 1/2 − z)] distances of
3.387 and 3.495 Å, respectively (for further details see the
Supporting Information).
2.3. Vibrational Analysis. The FTIR and FT-Raman
spectra for the title compound in the solid phase are shown in
Figure 4. The observed and calculated (B3LYP/6-311++G**)
The conformational properties of carbonyl furans were
studied, and two planar conformations have been identified.
These planar forms are named as syn and anti, depending
on the mutual orientation of the CO double bond and
the oxygen atom in the ring.19,20 From early IR and variable-
temperature NMR studies, it is known that the syn isomer of
2-furaldehyde is the more stable form in the gas phase and
nonpolar solvents, with the anti conformer being about only
1 kcal/mol higher in energy.21 Similar rotational isomerism has
been observed for related 2-carbonylfuran species, and both
experimental and theoretical results indicate that for all species
the energy difference between the two planar configurations is
small, with a low barrier to interconversion.22
For the title species, the X-ray structure analysis reveals that
the 2-carbonyl furan groups are not equivalents in the solid
phase, mainly differing in the conformation adopted by the CO
double bond with respect to the furan ring. Indeed, one of the
2-carbonyl furan is in syn while the second is clearly in anti
orientation, as showed in the Figure 1. For better understand
this conformational equilibrium, quantum chemical calculations
have been performed for the three most relevant conformations
for the title species: syn-syn, syn-anti and anti-anti. The
B3LYP/6-311++G** (vacuum-isolated) optimized structures
are shown in Figure 3.
Figure 4. Selected region of the IR (in KBr pellet) and Raman spectra
for the solid phase of the title species.
wavenumbers, together with a tentative assignment of the bands,
are given in Table 2. A tentative assignment of the observed
bands has been carried out by comparison with theoretical
wavenumbers, as well as on comparison with the reported data
for related molecules, especially imides,17 tertiary amides,23−25
and 2-carbonylfuran species.26 Very good agreement between
the experimental and computed vibrational data support the
proposed assignment.
The following analysis is dedicated to the discussion of
normal modes related to the central imide moiety. In the CO
stretching region of the infrared spectrum, an absorption with
strong intensity is observed centered at 1665 cm−1, while a
shoulder is pronounced at higher wavenumbers (1691 cm−1).
These features are better defined in the Raman spectrum where
a strong signal appearing at 1691 cm−1 is observed and a
second, less intense signal is defined at 1664 cm−1. Thus, the
complementary analysis of both infrared and Raman spectra
shows that the carbonyl oscillators are coupled, the symmetric
motion being assigned to the higher frequency mode, in very
good agreement with the computed carbonyl stretching normal
modes.
The complex character of the νCN mode in imides and
tertiary amides has already been mentioned.27 From a potential
energy distribution analysis, Desseyn et al.23 suggested that the
C−N stretching can be identified by an intense Raman signal
and less intense infrared absorption in the 1530 cm−1 region.
However, it should be noted that this mode is strongly coupled
with methyl deformations modes and the potential energy
distribution calculated considerable νCN contributions in 10
fundamentals in the 1650−600 cm−1 region for the compounds
studied by these authors. In Figure 4, it is clearly observed that
both the infrared and Raman spectra for the title species shows
the presence of a series of signals, with strong bands at 1468
and 1469 cm−1, respectively. However, it is well-known that the
Figure 3. Molecular structure of the main conformers of the title
species found theoretically (B3LYP/6-311++G**). Hydrogen atoms
are omitted for clarity.
The computed differences in the electronic energy (ΔE0,
corrected by zero point vibrational energies) suggest that
the most stable form corresponds to the anti−anti conformer,
the least favorable conformer being the syn−syn form (ΔE0 =
2.0 kcal/mol). The intermediate syn−anti conformation is only
1.1 kcal/mol above the anti−anti one. The same ordering is
obtained when Gibbs free energies of the isolated structures are
compared, with difference Gibbs free energy values of 1.5 and
2.5 kcal/mol for the syn−anti and syn−syn, with respect to the
most stable anti−anti form, respectively. Thus, it is plausible
that intermolecular interactions present in the crystal affect the
conformational equilibrium described for the gas phase. In
effect, the crystal packing for the title species shows distinct
nonbonded interactions between the 2-carbonyl furan moieties
and the furan hydrogen atoms In particular, a bifurcated
hydrogen bond is observed between the furan hydrogen and
the CO and the furan oxygen mutually oriented in syn form,
with nonbonded CO(11)···C(13) and O(12)···C(13)
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Table 2. FTIR and FT-Raman Experimental Data for the Title Compound, Together with the Computed B3LYP/6-311++G**
Values and Tentative Normal Mode Assignment
a
b
a
b
exptl
FTIR (KBr
calcd
exptl
FTIR (KBr
calcd
FT-Raman
(solid)
B3LYP/6-311+
FT-Raman
(solid)
B3LYP/6-311+
c
c
pellets)
+G**
tentative assignment
pellets)
+G**
tentative assignment
3150 w
3150 vvw
3124 vvw
3146 (0.1)
3145 (0.03)
3133 (1.4)
3126 (0.6)
3119 (1.2)
3116 (2.0)
3078(0.1)
ν C−H, Fur
ν C−H, Fur
ν C−H, Fur
ν C−H, Fur
ν C−H, Fur
ν C−H, Fur
ν C−H, Cl-Ph
ν C−H, Cl-Ph
ν C−H, Cl-Ph
ν C−H, Cl-Ph
νs CO
1066 (6.3)
1057 (57.3)
1051 (50.0)
1000 (29.7)
992 (27.0)
990 (64.3)
936 (2.4)
933 (12.7)
915 (3.0)
907 (16.7)
874 (2.5)
869 (7.1)
868 (2.0)
867 (11.8)
836 (81.2)
827 (35.1)
822 (5.8)
802 (57.3)
792 (0.01)
787 (66.8)
742 (27.1)
740 (95.5)
736 (9.1)
729 (20.8)
689 (0.4)
655 (0.04)
629 (9.2)
618 (3.3)
605 (8.1)
583 (6.3)
581 (6.2)
566 (7.0)
501 (21.1)
500 (4.1)
450 (30.6)
νs (C−O−C)Fur
δ(C−H)Fur
δ(C−H)Fur
δ(C−H)Fur
δ(C−H)Fur
δ(C−C)Ph
ρ(C−H)Ph
ρ(C−H)Fur
ρ(C−H)Ph
ρ(C−H)Fur
ρ(C−H)Fur
ρ(C−H)Fur
δ(C−C)Fur
δ(C−C)Fur
δ(C−C)Fur
δ(C−C)Fur
δ C−N−C
1091 s
1089 w
1076 br
3137 sh
3131 w
1078 w
1071 w
1031 m, br
3123 m
1031 w
1023 w
3112 vw
1021 s
1014 s
957 m
943 m
929 s
3077 (2.3)
3061 (3.0)
3059 (5.0)
1689 (227.0)
1644 (389.3)
1567 (10.9)
1554 (0.4)
1541 (68.2)
1529 (26.8)
1460 (113.7)
1436 (169.0)
1431 (31.5)
1376 (1.49)
1363 (42.6)
1359 (8.7)
1286 (343.8)
1271 (2.6)
1262 (1.3)
1230 (234.0)
1208 (17.3)
1203 (0.4)
1193 (20.1)
1150 (6.3)
1148 (84.6)
1136 (51.3)
1107 (124.6)
1084 (5.6)
1081 (50.8)
3097 sh
1691 sh
1665 vs
1630 sh
1610 vw
1691 s
1664 m
νas CO
900 m
883 m
901 vvw
882 w
ν CC, Ph
ν CC, Ph
ν CC, Fur
ν CC, Fur
ν CC, Fur
ν CC, Fur
ν CC, Ph
ν CC, Ph
ν CC, Fur
ν CC, Fur
νs N−C(O)
ν CC, Ph
ν CC, Ph
νas N−C(O)
ν N−C(Ph)
δ(C−H)Fur
δ(C−H)Fur
δ(C−H)Ph
1592 w
1572 w
1493 m
1469 vs
1393 sh
1385 m
1560 m, br
857 s
864 vw
854 vw
831 w
819 w
830 m
819 sh
810 vs
782 m
773 s
1469 s
1393 s
1384 sh
oop(C−H)Fur
δ(C−C)Ph
oop(C−H)Ph
oop(C−H)Ph
oopCO
785 vvw
769 s
753 w
oop(C−H)Fur
oopCO
1337 s
1332 br, w
1326 w
745 s
oop(CC)Ph
1295 vw
676 vvw
νC−Cl
1281 s
639 vw
627 sh
622 w
594 w
588 w
oop(CC)fur
δ(C−C)Ph
oop(CC)fur
ρ(C−H)Fur
ρ(C−H)Fur
δ(OCNCO)
oop(CC)Ph
δCCC
1275 m
1249 m
1238 sh
1233 m
1181 s
1273 vw
1249 w
1238 w
630 br, w
623 w
597 vw
588 m
νas (C−O−C)Fur
νas (C−O−C)Fur
νas N−C/δC−H Ph
δ(C−H)Ph
1165 m
1138 s
1165 m
513 m
500 vw
454 w
516 vw
1141 vw
446 br
227 m
oop N
1109 m
νs (C−O−C)Fur
a
b
Band intensities and shape: vs = very strong; s = strong; m = medium; w = weak; vw = very weak, sh: shoulder, br: broad. Scaled computed
c
frequency and intensity values at the B3LYP/6-311++G** level of approximation. Computed IR intensities (km/mol) are given in parentheses. ν: stretching
(subscripts s and as refer to symmetric and antisymmetric modes, respectively). δ: deformation. ρ: rocking. oop: out of plane deformation modes.
furan28,29 and benzyl groups also show intense features in this
region, associated with the ν(CC) stretching and δ(C−H)
bending modes, respectively. Thus, on the basis of these reports
and on the calculated displacement vectors calculated for the
harmonic normal modes, we tentatively assign the intense band
observed at 1337 cm−1 in the infrared spectrum to the sym-
metric motion of the stretching mode of the N−C(O) bonds,
with the antisymmetric counterpart at 1281 cm−1. The last
absorption originates from a broad band in the infrared spec-
trum, with two clearly defined maxima; the second observed at
1275 cm−1 can be assigned with confidence to the ν(N−C(Ph))
fundamental.13 These frequency values and the relative inten-
sities are in very good agreement with the computed ones,
as showed in Table 2. Such low frequency values for the
ν(N−C(O)) fundamental, and the associated low force con-
stants predicted for the amide-like C−N bonds, can be related
with the relatively long carbon−nitrogen bond distances observed
in the crystal (see previous section). It is postulated that the
nonplanarity around the imide bonds causes these effects,
mainly through a moderate disruption in the electronic conjuga-
tion. The electronic features associated with this aspect will be
discussed in the next section.
2-4. Natural Bond Orbital Analysis. The resonance
model of the amide bond has been generally accepted by
considering a conjugation of the nitrogen lone pair with the
CO double bond in terms of resonance between structures I
and II (Scheme 3). On the basis of comparisons of the
Scheme 3. Main Resonance Structures for the Amide Moiety
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The atomic charges obtained using the natural population
analysis (NPA) approach reveal that negative charges −0.67
and −0.62 are located at the both the nitrogen and the carbonyl
oxygen atoms, while the carbon atoms in the CO groups
bear a strong positive charge (+0.81), denoting the con-
tribution of the resonance structure III in the description of the
imide bond of the title compound.
The most relevant donor−acceptor interactions have also
been evaluated for the main conformers (showed in Table S2 in
the Supporting Information). The same description for the
imide bond is valid for the three forms here analyzed, remark-
able differences being observed depending on the orientation of
the furan ring with respect to the carbonyl double bonds. Thus,
the mesomeric effect, reflected mainly by the lpp(N) →
π*(CO) interaction, is definite larger when the CO
double bond is oriented in anti position with respect to the
furan ring. On the other hand, the lpπ(O) → σ*(N−C)
anomeric interaction is slightly higher for the syn conformation.
The complex interplay between these and other interactions
that depend on the conformation adopted around the central
imide bond is responsible for the stabilities of the different
conformers isolated in a vacuum.
Table 3. Crystal Data and Structure Refinement for the Title
Compound
emp formula
C16 H10 Cl N O4
formula wt
315.70
temp (K)
173(2)
wavelength (Å)
crystal system
space group
0.71073
monoclinic
P21/c
unit cell dimens (Å, deg)
a = 12.2575(5), α = 90
b = 7.7596(2), β = 92.771(4)
c = 15.0234(7), γ = 90
volume (Å3)
1427.25(10)
Z
4
density (calcd) (Mg/
1.469
m3)
absorption coeff (mm−1
F(000)
)
0.285
648
crystal size (mm3)
0.39 × 0.37 × 0.37
3.36 to 29.61
θ range for data
collection (deg)
index ranges
−16 ≤ h ≤ 16, −10 ≤ k ≤ 10, −20 ≤ l ≤ 20
reflections collected
independent reflections
40234
3999 [R(int) = 0.0445]
completeness to θ =
25.00° (%)
absorption correction
99.7
3. CONCLUSION
N,N-Bis(furan-2-carbonyl)-4-chloroaniline was synthesized in a
one-pot procedure by the reaction of 2-furoic acid with 4-
chloroaniline using carbonyldiimidazole. The X-ray crystal
structure revealed that the two carbonyls double bonds are
twisted with respect to the plane around the tertiary nitrogen
atom. The nonplanarity of the imide group seems to be related
with steric hindrances of the 2-carbonyl furan rings. Intra-
molecular donor→ acceptor electronic interactions within the
imide moiety were evaluated and the nonplanarity is mainly
reflected in the computation of relatively low resonance interac-
tion values. These results invite to synthesize related species with
substituted furan and benzyl rings in order to analyze the effect of
bulky substituent on the molecular structure, not only in the solid
phase but also in solution.
semiempirical from equivalents
0.9018 and 0.8969
max and min
transmission
refinement method
full-matrix least-squares on F2
data/restraints/
parameters
goodness-of-fit on F2
3999/0/200
1.043
final R indices
[I > 2σ(I)]
R1 = 0.0352, wR2 = 0.0907
R indices (all data)
extinction coefficient
R1 = 0.0378, wR2 = 0.0924
0.149(5)
largest diff peak and hole
(e·Å−3
0.290 and −0.404
)
calculated electron densities in amide bonds, Wiber and
Breneman30 suggested a third resonance structure III. These
resonances also apply for the carbonyls in the imide group.
NBO analysis for the syn−anti conformer of the title
molecule clearly indicates the presence of one lone pair orbital
formally attached at the nitrogen atom. The nature of this
orbital is a pure p-type [lpp(N)], with a low electron occupancy
of 1.76 e, indicating the electron-donating capacity for this
orbital. Delocalizing interactions evaluated by a second-order
perturbation approach reveals that the lone pair orbital
contributes to a strong resonance interactions with both
carbonyl bonds lpp(N) → π*(CO), leading to the “amide
resonance” (form II in Scheme 2). The computed E(2)
interaction values are 32.3 and 44.4 kcal/mol for the CO
groups oriented in syn and anti conformations, respectively.
This electron donation into the π*(CO) antibonding
orbitals is reflected also in its high electronic occupancy
of ca. 0.16 e. For planar amide groups, however, much higher reso-
nance interaction values are computed, reaching 59.8 kcal/mol
for formamide.31
4. EXPERIMENTAL SECTION
4.1. Synthesis and Characterization. Carbonyldiimidazole
(CDI) (10 mmol) was dissolved in 30 mL of dry THF with stirr-
ing at room temperature under nitrogen atmosphere, and 2-furoic acid
(10 mmol) (1) was added carefully. The reaction mixture was further
stirred for 15 min, and then after the evolution of CO2 ceased,
4-chloroaniline (5 mmol) (2) was added slowly. The stirring was con-
tinued for additional 10 min at room temperature and then refluxed
for 10 h. After completion of the reaction, monitored by TLC, reaction
mixture was concentrated to obtain crude product (3) purified by
column chromatography using 20% EtOAc in hexane. Commercial
carbonyldiimidazole (CDI) was used without further purification.
THF was distilled from sodium/benzophenone prior to use. The melt-
ing points were recorded using conventional apparatus. H and 13C
NMR spectra were recorded in CDCl3 at 300 and 75 MHz, respec-
tively. Standard IR spectra were recorded as KBr pellets, and elemental
analyses were conducted using a standard analyzer.
4.2. Vibrational Spectroscopy. Solid-phase IR spectra were
recorded with a resolution of 2 cm−1 in the 4000−400 cm−1 range,
whereas the FT-Raman spectra were recorded in the region 4000−
100 cm−1 using a Nd:YAG laser source operating at 1.064 μm line with
200 mW power of spectral width 2 cm−1.
4.3. Quantum Chemical Calculations. All quantum chemical
calculations were performed with the GAUSSIAN 03 program pack-
age.32 The molecular geometries were optimized to standard con-
vergence criteria by using B3LYP DFT hybrid methods employing the
1
The lone pair orbital at the carbonyl oxygen atom donates
electronic density mainly to the vacant C−N antibonding
orbital via a negative hyperconjugation interaction; lpπ(O) →
σ*(N−C), with a E(2) value of 38.5 and 36.1 kcal/mol for the
CO groups in syn and anti conformations, respectively.
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Pople-type33 extended valence triple-ξ basis set augmented with diffuse
and polarization functions in both the hydrogen and weighty atoms
[6-311++G**]. The calculated vibrational properties corresponded in
all cases to potential energy minima for which no imaginary frequency
was found. Scott and Radom derived the scaling factors for the
theoretical harmonic vibrational frequencies at 19 levels utilizing a
total of 1066 individual vibrations for small molecules.34 Zhou and co-
workers35 demonstrated that scaled B3LYP calculations are powerful
approaches for understanding the vibrational spectra of medium-sized
organic compounds and the recommended factors of 0.96 was used to
scale the theoretical frequencies (1.0013 for frequencies lower than
500 cm−1). Natural population analysis and second-order Donor→
acceptor interaction energies were estimated at the HF/6-311++G**
level by using the NBO analysis36 as implemented in the GAUSSIAN
03 program.
ACKNOWLEDGMENTS
■
M.F.E. is member of the Carrera del Investigador of CONICET
(Republica Argentina). M.F.E. thanks the Consejo Nacional de
́
́
́
Investigaciones Cientıficas y Tecnicas (CONICET), the
ANPCYT, and the Facultad de Ciencias Exactas, Universidad
Nacional de La Plata for financial support. A.S. gratefully
acknowledges a research grant from higher Education Commis-
sion of Pakistan under the project No.4-279/PAK-US/HEC
2010-917 (Pakistan-US Science & Technology Cooperation
Program).
REFERENCES
■
(1) Breugst, M.; Tokuyasu, T.; Mayr, H. J. Org. Chem. 2010, 75,
5250.
(2) Noe, E. A.; Raban, M. J. Am. Chem. Soc. 1975, 97, 5811.
(3) Kirby, A. J.; Komarov, I. V.; Kowski, K.; Rademacher, P. J. Chem.
Soc., Perkin Trans. 2 1999, 1313.
4.5. X-ray Data Collection, Structure Solution, and Refine-
ment. An alcohol solution of compound 3 was stood at room
temperature, and upon slowly evaporating alcohol from the solution,
yellow crystals suitable for X-ray diffraction analysis were isolated one
week later.
(4) Ohwada, T.; Achiwa, T.; Okamoto, I.; Shudo, K.; Yamaguchi, K.
A two-circle diffractometer equipped with an image plate area
detector was used. Pertinent crystal and refinement data for 3 are given
in Table 3. The structure was solved by direct methods, full-matrix
least-squares refinement based on F2. All but H atoms were refined
anisotropically. Hydrogen atoms were located from difference Fourier
maps and refined at idealized positions riding on the relevant carbon
with C−H = 0.95 Å and with isotropic displacement parameters
Uiso(H) = 1.2Ueq(C). Crystallographic data (excluding structure
factors) for the structure in this paper has been deposited with the
Cambridge Crystallographic Data Centre as supplementary publica-
tion. Copies of the data can be obtained, free of charge, on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK, (fax: +44-(0)1223-
336033 or e-mail: deposit@ccdc.cam.ac.uk. Any request for this material
should quote the full literature citation and the reference number CCDC
852552.
4.6. GC−MS Determination. The GC−MS measurements were
recorded using gaseous helium as the mobile phase with the pressure
in the column head equal to 100 kPa. A 1 μL volume of the compound
dissolved in CHCl3 was chromatographed under the following con-
ditions: injector temperature was 210 °C, the initial column tem-
perature (100 °C) was held for 3 min, then increased to 200 at 20 °C/min
and held for 2 min after elevated to 300 at 35 °C/min and held for 2 min.
In the spectrometer the source was kept at 200 °C.
Tetrahedron Lett. 1998, 39, 865.
(5) Otani, Y.; Nagae, O.; Naruse, Y.; Inagaki, S.; Ohno, M.;
Yamaguchi, K.; Yamamoto, G.; Uchiyama, M.; Ohwada, T. J. Am.
Chem. Soc. 2003, 125, 15191.
(6) Otani, Y.; Futaki, S.; Kiwada, T.; Sugiura, Y.; Muranaka, A.;
Kobayashi, N.; Uchiyama, M.; Yamaguchi, K.; Ohwada, T. Tetrahedron
2006, 62, 11635.
(7) Ahmed, A.; Bragg, R. A.; Clayden, J.; Lai, L. W.; McCarthy, C.;
Pink, J. H.; Westlund, N.; Yasin, S. A. Tetrahedron 1998, 54, 13277.
(8) Szostak, M.; Aube, J. Org. Biomol. Chem. 2011, 9, 27.
(9) Pero, R. W.; Qisson, A.; Amir Amiri, M. D.; Chaplin, D. Cancer
Detect. Prev. 1998, 22, 225.
(10) Joule, J. A.; Mills, K.; Smith, G. F. Heterocyclic Chemistry;
Chapman & Hall: London, 1995.
(11) Searle, P. A.; Molinski, T. F. Tetrahedron 1994, 50, 9893.
(12) Asano, T.; Yoshikawa, T.; Usui, T.; Yamamoto, H.; Yamamoto,
Y.; Uehara, Y.; Nakamura, H. Bioorg. Med. Chem. 2004, 12, 3529.
(13) Jennings, W. B.; Farrell, B. M.; Malone, J. F. Acc. Chem. Res.
2001, 34, 885.
(14) Allen, F. H.; Kennard, O.; Watson, D. G.; Brammer, L.; Orpen,
A. G.; Taylor, R. J. Chem. Soc., Perkin Trans. 2 1987, S1.
(15) Adiwidjaja, G.; Voß, J. Chem. Ber. 1977, 110, 1159.
(16) Desseyn, H. O.; Jacob, W. A.; Herman, M. A. Spectrochim. Acta
1972, 28A, 1329.
(17) Narula, P. M.; Day, C. S.; Powers, B. A.; Odian, M. A.; Lachgar,
A.; Pennington, W. T.; Noftle, R. E. Polyhedron 1999, 18, 1751.
(18) Iriarte, A. G.; Erben, M. F.; Gholivand, K.; Jios, J. L.; Ulic, S. E.;
ASSOCIATED CONTENT
■
S
* Supporting Information
Della Ved
(19) Kim, K. B.; Volker, J.; Alex, D. B. J. Chem. Phys. 2000, 113, 7519.
(20) Gholivand, K.; Della Vedova, C. O.; Erben, M. F.; Mahzouni, H. R.;
́
ova, C. O. J. Mol. Struct. 2008, 886, 66.
Analytical data for the title compound (Table S1). NBO
stabilization energies values (kcal/mol) for the main orbital
interactions around the imide group for relevant conformers
(Table S2). The whole geometrical parameters derived from
the X-ray analysis together with atomic coordinates, equivalent
isotropic displacement coefficients, and anisotropic displace-
ment parameters (Tables S2−S6). Atom coordinates for
optimized (B3LYP/6-311++G**) structures (Tables S7−S11).
́
Shariatinia, Z.; Amiri, S. J. Mol. Struct. 2008, 874, 178.
(21) Chadwick, D. J.; Cliffe, I. A. Khim. Geterotsikl. Soedin, Engl.
Transl. 1984, 5, 579.
́
(22) Klapstein, D.; MacPherson, C. D.; OBrien, R. T. Can. J. Chem.
1990, 68, 747.
(23) Desseyn, H. O.; Herrebout, W. A.; Clou, K. Spectrochim. Acta
2003, 59A, 835.
(24) Dorris, K. L.; Siddall Iii, T. H.; Stewart, W. E.; Good, M. L.
Spectrochim. Acta 1967, 23A, 1657.
UV−vis spectrum (Figure S1) and H and 13C NMR spectra
1
(Figures S2 and S3) for the title compound. This material is
available free of charge via the Internet at http://pubs.acs.org.
(25) Gholivand, K.; Della Ved
Alizadehgan, A. M. J. Mol. Struct. 2007, 840, 66.
(26) Adamek, P.; Volka, K.; Ksandr, Z.; Stibor, I. J. Mol. Spectrosc.
́
ova, C. O.; Erben, M. F.; Mojahed, F.;
́
AUTHOR INFORMATION
■
1973, 47, 252.
Corresponding Author
(27) Randall, E. W.; Yoder, C. M. S.; Zuckerman, J. J. Inorg. Chem.
1966, 5, 2240.
*Tel: +92-51-9064-2128. Fax: +92-51-9064-2241. E-mail:
aamersaeed@yahoo.com.
(28) Kim, T.; Assary, R. S.; Curtiss, L. A.; Marshall, C. L.; Stair, P. C.
J. Raman Spectrosc. 2011, 42, 2069−2076.
(29) Chadwick, D. J.; Cliffe, I. A. Chem. Heterocycl. Compd. 1984, 20,
461.
Notes
The authors declare no competing financial interest.
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Article
(30) Wiberg, K. B.; Breneman, C. M. J. Am. Chem. Soc. 1992, 114,
831.
(31) Weinhold, F.; Landis, C. R. Valency and Bonding: A Natural
Bond Orbital Donor-Acceptor Perspective; Cambridge University Press:
Cambridge, 2005.
(32) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.;
Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.;
Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.;
Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.;
Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao,
O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross,
J. B.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev,
O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.;
Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.;
Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.;
Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman,
J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.;
Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.;
Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.;
Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen,
W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03; Revision
B.04 ed.; Gaussian, Inc.: Pittsburgh PA, 2003.
(33) Frisch, M. J.; Pople, J. A.; Binkley, J. S. J. Chem. Phys. 1984, 80,
3265.
(34) Scott, A. P.; Radom, L. J. Phys. Chem. 1996, 100, 16502.
(35) Fu, A.; Du, D.; Zhou, Z. Spectrochim. Acta 2003, 59A, 245.
(36) Reed, A. E.; Curtiss, L. A.; Weinhold, F. Chem. Rev. 1988, 88,
899.
4695
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