Crystallographic and Computational Studies on N-Furfuryl-N-(3-Hydroxybenzyl)amine and N-Furfuryl-N-(4-Hydroxybenzyl)amine

Article abstract of DOI:10.1134/S0022476618010067

Crystal structures of N-furfuryl-N-(3-hydroxybenzyl)amine (1) and N-furfuryl-N-(4-hydroxybenzyl)amine (2) are reported. The furyl ring is coplanar with the C–N–C plane in 1 and perpendicular to the C–N–C plane in 2. Intermolecular O–H ? N and C–H ? O hydr

Full text of DOI:10.1134/S0022476618010067

Journal of Structural Chemistry. Vol. 59, No. 1, pp. 36-42, 2018.
Original Russian Text © 2018 E. Sathiyaraj, S. Thirumaran, S. Ciattini.
CRYSTALLOGRAPHIC AND COMPUTATIONAL STUDIES
ON N-FURFURYL-N-(3-HYDROXYBENZYL)AMINE
AND N-FURFURYL-N-(4-HYDROXYBENZYL)AMINE
1,2
E. Sathiyaraj , S. Thirumaran , and S. Ciattini
1
3
Crystal structures of N-furfuryl-N-(3-hydroxybenzyl)amine (1) and N-furfuryl-N-(4-hydroxybenzyl)amine
(2) are reported. The furyl ring is coplanar with the C–N–C plane in 1 and perpendicular to the C–N–C
plane in 2. Intermolecular O–H⋯N and C–H⋯O hydrogen bonds stabilize the crystal structures and play
a crucial role in crystal packing. In addition, the molecular geometry and molecular vibrations are
calculated using the DFT/B3LYP method with the 6-31G(d,p) basis set and the calculated geometrical
parameters are correlated with the corresponding experimental data. The obtained HOMO and LUMO
energies are negative, indicating that the compounds are in the stable state. FT-IR spectra of compounds 1
and 2 are measured in order to elucidate the spectroscopic properties of the compounds in the spectral range
–1
4000-500 cm . The recorded FT-IR spectral measurements are further supported by spectral simulations.
DOI: 10.1134/S0022476618010067
Keywords: crystal structures, DFT, HOMO-LUMO, vibrational spectra.
INTRODUCTION
The five-membered heterocyclic furyl ring system commonly occurs in many natural products. Heterocyclic
compounds are important due to their pharmacological, agrochemical, and biological activities. Due to a higher production of
furfurylamine and its derivatives compared to benzylamine and its derivatives, furfurylamine and its derivatives are used to
replace benzylamine and its derivatives on an industrial scale for manufacturing fertilizers [1] and drugs [2]. Schiff bases can
be obtained in good yields and high purity by a simple condensation reaction of primary amines with aldehydes (or) ketones
[3]. The reduction of Schiff bases yielded amines. The synthesis of heterocyclic compounds and their anticancer, antimoebic,
antibacterial, antifungal, antiviral, anti-HIV [4, 5] and tuberculosis [6] activities have also been reported. The study of amines
and their derivatives is important due to the presence of amines in natural products and nucleic acids [7]. Amines are widely
used in many industries as basic intermediates for the preparation of fine chemicals, pharmaceuticals, agro chemicals, etc. [8].
Particularly, secondary amines are extremely important pharmacophores in numerous biologically active compounds, which
have greatly been touted in the area of drug discovery [9]. In view of the growing importance of amines in biological field
and in order to study hydrogen bonding interactions due to the presence of OH and NH groups in the compounds, the single
crystal structural analysis of compounds 1 and 2 has been carried out. In addition, the molecular geometry and molecular
1
Department of Chemistry, Annamalai University, Annamalainagar, India; chemsathya2010@gmail.com.
3
2
Department of Chemistry, Kalasalingam University, Krishnan koil, India. Centro di Cristallografia Strutturale, Polo
Scientifio di Sesto Fiorentino, Firenze, Italy. The text was submitted by the authors in English. Zhurnal Strukturnoi Khimii,
Vol. 59, No. 1, pp. 44-50, January-February, 2018. Original article submitted February 4, 2016; revised May 24, 2016.
36
0022-4766/18/5901-0036 © 2018 by Pleiades Publishing, Ltd.

vibrations have been calculated using the DFT/B3LYP method with the 6-31G(d,p) basis set and the calculated geometrical
parameters are correlated with the corresponding experimental data.
EXPERIMENTAL
Materials and methods. All chemicals were commercially available analytical grade materials and used as supplied
without further purification. FT-IR spectra were recorded on a thermo scientific NICOLET iS5 spectrophotometer. The
spectra were taken suitably as potassium bromide discs of the compounds.
Crystal structure determination and structure refinement. Details of the crystal data, data collection and
structure refinement parameters are summarized in Table 1. The intensity data were collected at ambient temperature
(293(2) K) for compound 1 and 150 K for compound 2 on an Oxford Diffraction Xcalibur 3 (with CCD) diffractometer using
graphite-monochromated MoK radiation (λ = 0.71069 Å and λ = 0.71073 Å). The structures were solved by SHELXS-97
α
[10] and refined by the full matrix least squares technique with SHELXL-97 [11]. All the non-hydrogen atoms were refined
anisotropically and hydrogen atoms were refined isotropically.
Computational procedure. The DFT calculation with the B3LYP hybrid function at the 6-31 basis set G(d,p) [12]
was performed by the Berny method. All theoretical calculations were made by the Gaussian03W [13] software package. The
optimized molecular geometry, theoretical IR spectra, and the molecular orbital descriptions (HOMO, LUMO) for the title
compounds were obtained from the computational calculations.
Preparation of N-furfuryl-N-substituted benzylamine. Furfurylamine (4.6 mmol) and substituted benzaldehydes
(3-OH, 4-OH) (5.1 mmol) were dissolved in methanol (30 ml) and the solution was stirred for 2 h at room temperature. The
TABLE 1. Crystal Data, Data Collection and Structure Refinement for Compounds 1 and 2
Compound
Empirical formula
Formula weight
1
2
C H N O
12 13 2
C H N O
12 13 2 4
4
203.23
293(2)
203.23
150(2)
Temperature, K
Wavelength, Å
0.71069
0.71073
Crystal system
Monoclinic
Orthorhombic
P2 2 2
Space group
C2/c
1
1 1
20.659(5), 7.929(5),
5.4506(5), 13.2560(10),
13.7800(10); 90
Unit cell dimensions a, b, c, Å; β, deg
17.176(5); 132.620(5)
3
Volume, V, Å
2070.4(15)
8; 1.304
995.65(14)
4; 1.356
0.093
3
Z; Calculated density, g/cm
–1
0.089
Absorption coefficient μ, cm
F(000)
864
432
Crystal size, mm
0.30×0.20×0.15
4.454 to 32.697
0.4×0.35×0.30
4.30 to 32.4
θ Range, deg.
Limiting indices
–29 ≤ h ≤ 31, –10 ≤ k ≤ 12,
–25 ≤ l ≤ 25
–7 ≤ h ≤ 5, –19 ≤ k ≤ 11,
–20 ≤ l ≤ 19,
5599 / 1639
Reflections collected / unique
Completeness to θ
10222 / 3471
25.24
32.46
Max. and min. transmission
Data / restraints / parameters
1.00000 and 0.80904
3471 / 0 / 188
1.00000 and 0.75000
2935 / 0 /188
2
Goodness-of-fit on F
1.011
1.038
R = 0.0537, wR = 0.1118
1 2
R = 0.0484, wR = 0.1039
1 2
Final R indices [I > 2σ(I)]
R indices (all data)
R = 0.1023, wR = 0.1389
1 2
R = 0.0643, wR = 0.1165
1 2
Largest diff. peak and hole
0.183, –0.219
0.278, –0.218
37

Fig. 1. ORTEP diagram of compounds 1 (a) and 2 (b).
solvent was removed by evaporation. The resulting yellow oil was dissolved in a methanol-dichloromethane solvent mixture
(1:1, 20 ml) and sodium borohydride (13.8 mmol) was added slowly and stirred for 2 h at 5 °C. The mixture was stirred at
room temperature for 20 h. After evaporation of the solvent, the resulting viscous liquid was washed with water and
dichloromethane was added in order to extract the product. Evaporation of the organic layer gave N-furfuryl-N-substituted
benzylamine as yellow oil. Suitable single crystals for the X-ray structural analysis were obtained by repeated
recrystallization from ethanol for 1 and dichloromethane for 2.
RESULTS AND DISCUSSION
Structure analysis. The ORTEP diagrams of 1 and 2 are shown in Fig. 1. Selected bond distances and bond angles
are listed in Table 2. Bond lengths of compounds 1 and 2 are in the normal range (mean: C–C = 1.381(2) Å,
C–O = 1.365(2) Å, and C–N = 1.466(2) Å for compound 1 and C–C = 1.407 Å, C–O = 1.364(2) Å, and C–N = 1.476(2) Å for
compound 2). The bond parameters associated with phenyl and furyl rings are also normal. In compound 1, the furyl ring is
coplanar with the C7–N1–C8 plane (the dihedral angle of the furyl ring and C7–N1–C8 planes is 5.96° and the torsion angle
C9–C8–N1–C7 = 175.41°). However, in compound 2, the furyl ring is perpendicular to the C1–N3–C6 plane (the dihedral
angle of the furyl ring and C1–N3–C6 planes is 89.27°). The phenyl ring deviates from the C–N–C plane with dihedral angles
of 76.56° and 69.47° for compounds 1 and 2, respectively.
In the crystal structure of compound 1, the O–H⋯N intermolecular interaction provides a linear chain structure
(Fig. 2a). The H⋯N separation is short (H1⋯N1 = 1.779 Å). Furthermore, two O⋯H interactions lead to the 32-membered
macrocyclic ring. One of the O⋯H distances (O1⋯H12 = 2.475 Å) is short (Fig. 2b). It may be assumed that these two
hydrogen atoms are more acidic in terms of the identities of their adjacent atoms [14]. The crystal structure of 2 is stabilized
by intermolecular O–H⋯N and C–H⋯O interactions (Fig. 3a, b). The two C–H⋯O interactions in compound 2 are linked to
the same acceptor O atom. Both O⋯H distances are almost equal (O2⋯H3 = 2.569 Å and O2⋯H12 = 2.583 Å). The
C–H⋯O intermolecular hydrogen bonding with another oxygen atom (furyl) is also observed (O1⋯H5 = 2.623 Å). In
addition to the C–H⋯O interactions, the amine N atom is linked with O–H of another molecule. The H···N distance is
1.946 Å. The packing is further stabilized by two additional edge-to-face C–H⋯π interactions. The C–H⋯Cg1 and
TABLE 2. Hydrogen Bond Geometry for Compounds 1 and 2
Interactions
D–H
H⋯A
D⋯A D–H⋯A
Interactions
D–H
H⋯A
D⋯A D–H⋯A
Compound 1
0.99 1.78
0.97 2.58
2.48
Compound 2
0.86 1.95
0.95
O(1)–H(1)⋯N(1)
C(1)–H(1)⋯O(1)
2.7642
3.4688
3.3922
173
153
156
O(2)–H(3)⋯N(3)
C(3)–H(3)⋯O(1)
2.787
3.412
3.349
3.388
166
148
134
139
2.56
2.58
2.62
C(12)–H(12)⋯O(1) 0.98
C(12)–H(12)⋯O(1) 0.99
C(5)–H(5)⋯O(1)
0.94
38

Fig. 2. Supramolecular linear chain formation via the
O–H⋯N hydrogen interaction in compound (a);
perspective view of the 32-membered macrocyclic ring
1
present in compound 1 (b).
C–H⋯Cg2 distances are 2.665 Å and 2.911 Å, respectively (Fig. 3c and Table 2). In both compounds, intermolecular
O–H⋯N hydrogen bonds form a C(9) and C(10) chain in the unit cell for 1 and 2, respectively (Figs. 2a and 3a).
Optimized geometry. A comparison of the experimental bond parameters with the calculated values shows that the
largest bond length difference is 0.14 Å and 0.11 Å for C–C distances in compounds 1 and 2, respectively and the bond angle
difference is 3.8° (C11–C12–O2) and 2.7° (N1–C1–C6) in compounds 1 and 2, respectively. As for the largest difference in
the bond lengths and bond angles, it can result from two reasons: (i) all the calculated data are for the molecule in the gas
phase, while the experimental data are for the molecules in the solid state, and (ii) various hydrogen bonding interactions are
observed in the solid state but the calculated values are for the isolated molecule. The C–C bond lengths in the phenyl rings
lie between 1.372-1.399 Å (DFT) and 1.374(3)-1.385(2) Å (XRD) for compound 1 and 1.393-1.514 Å (DFT) and 1.391(2)-
1.503(3) Å (XRD) for compound 2, and the bond lengths are in between the normal values for single (1.54 Å) and double
(1.33 Å) bonds [15].
HOMO-LUMO. The HOMO-LUMO and HOMO-1-LUMO+1 energy values are 6.1960 eV and 6.5927 eV for 1
and 5.7644 eV and 6.1612 eV for 2, respectively. HOMO and LUMO represent the ability to donate and accept an electron,
respectively. For compound 1, the π electron density of HOMO is localized fully and partially on the furyl and phenyl rings,
respectively, and the electron density of HOMO-1 is localized fully only on the phenyl ring, whereas the electron density on
LUMO and LUMO+1 are localized overall the molecule.
In the case of HOMO and HOMO-1, the electron density is localized overall the molecule in compound 2, whereas
in LUMO, the electron density is localized only on the phenyl ring, and LUMO+1 is fully localized on the phenyl ring and
partially on the furyl ring. The HOMO-LUMO energy gap in compound 1 is larger than that found in compound 2. This
indicates that compound 1 is more stable compared to compound 2. Moreover, the lower HOMO-LUMO energy gap explains
the eventual charge transfer interactions taking place within the molecule.
Molecular electronic potential (MEP). MEPs of compounds 1 and 2 were determined using the B3LYP/6-
31G(d,p) method. This is a very useful descriptor to understand the partial charges and chemical reactivity of the molecule
[16]. The MEP studies of 1 and 2 show that the negative charge covers the OH oxygen atoms and furyl groups and the
positive charge is localized on the hydrogen atoms of OH and NH groups. Oxygen is the the most reactive part in the
molecule due to the presence of higher electronegativity on O atoms of OH and furyl groups.
39

Fig. 3. View of compound 2 showing O–H…N chain interactions (a); view of
compound 2 showing C–H…O interactions (b); view of edge-to-face interactions
between the adjacent phenyl and furyl moieties of compound 2 (c).
FT-IR spectra. Vibrational frequencies calculated at the B3LYP/6-31G(d,p) level of theory were scaled by the dual
–1 –1
scaling factor (<1800 cm for 0.9927 cm and >1800 cm for 0.9659 cm ) for this method [17, 18].
Selected primary calculated harmonic frequencies and the experimental data are listed in Table 3. Due to the
possible mixing of several bands in the C–N stretching frequency region [19], the C–N stretching vibrations are assigned with
the help of computational studies. The C–N stretching vibration coupled with the N–H scissoring one is moderately to
–1
strongly active in the region 1275 55 cm [20]. The bands observed at 1259 cm for 1 and 1250 cm for 2 are assigned to
–1
–1
C–N stretching vibrations, and these stretching frequencies show excellent agreement with the theoretically calculated values
–1 –1
(1258 cm and 1247 cm for 1 and 2, respectively). The N–H stretching vibration appears strongly and broadly in the region
–1
3500-3300 cm [21]. In this study, the N–H frequencies are observed at 3284 cm and 3305 cm for 1 and 2, respectively.
–1
–1
–1 –1
The O–H frequencies are observed at 3441 cm and 3450 cm [22]. Large differences observed between the calculated and
experimental O–H stretching vibrations are mainly due to O–H⋯N interactions in the solid state.
40

TABLE 3. Important Infrared Spectral Data of Compounds 1 and 2
Compound 1
B3LYP/6-31G(d,p)
Compound 2
Functional group
Experimental
Experimental
B3LYP/6-31G(d,p)
C–N
1281
3111
3284
3441
1297
3127
3164
3668
1250
3116
3305
3450
1288
3130
3372
3670
Furyl
N–H
O–H
CONCLUSIONS
Crystal structures of 1 and 2 were analysed by single crystal X-ray diffraction. The crystal structure is stabilized by
intermolecular C–H⋯O and O–H⋯N hydrogen bonds in which the intermolecular O–H⋯N hydrogen bond generates a C9
and C10 chain motif in compounds 1 and 2. Density functional theory calculations of the structures, vibrational spectra,
HOMO-LUMO, and MEP analyses of compounds 1 and 2 were also carried out. The equilibrium geometry is obtained at the
B3LYP/6-31G(d,p) level for both bond lengths and bond angles. The vibrational frequency analysis by the B3LYP/6-
31G(d,p) method agrees satisfactorily with the experimental results. Any differences observed between the experimental and
computed values may be due to the fact that the computations were performed for a single molecule in the gas phase, whereas
the experimental values were recorded in the solid phase in the presence of intermolecular interactions. The lower HOMO-
LUMO band gap supports the bioactive property of the compounds.
The crystallographic data for the structural analysis of compounds 1 and 2 have been deposited with the Cambridge
Crystallographic Data Centre, CCDC No. for 1 is 1025267 and 1025410 for 2. Copy of this information may be obtained free
of charge from the Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (Tel.:þ44 (0) 1223 762911; E-mail:
kamila@ccdc.cam.ac.uk).
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