Synthesis , Molecular Structure of Diethyl Phenylenebis ( Methylene ) Dicarbamates and FTIR Spectroscopy Molecular Recognition Study with Benzenediols

The synthesis, density functional theory (DFT) molecular structure and Fourier transform infrared spectroscopy (FTIR) molecular recognition study of diethyl phenylenebis(methylene) dicarbamates with 1,2and 1,3-benzenediols is described. The formation of the complexes was confirmed by the shift of the O-H stretching bands in the IR spectra of the complexes compared with the IR spectra of the noncomplexed benzenediols.


Introduction
Molecular recognition is the basis of supramolecular chemistry.It involves complementarily that should exist between the functional groups of two molecules to form a host-guest complex by noncovalent interactions. 1ydrogen bond (HB) is the most important noncovalent interaction used in the design of supramolecular systems.HB is particularly important from a biological point of view because of its involvement in several biological processes, such as the stabilization of the double helix of DNA, 2 peptide three-dimensional structures (helices, sheets or turns), 3 enzyme-substrate interactions, 4 recognition among proteins 5 and drug-acceptor interactions. 68][9] Carbamates are composed by N-H, C=O and O-R functionalities, which allow them to form HB interactions.In this context, xylylenediamine amide derivatives have been exploited as molecular hosts in macrocyclic [10][11][12] and non-macrocyclic 13,14 forms.

Synthesis of the compounds
The compounds were synthesized by the condensation of meta-and para-xylylenediamine with ethyl chloroformate Vol. 26, No. 2, 2015   (Scheme 2).The structures of 1a and 2a were confirmed by the spectral data (Table 1).The N-H frequencies in IR and 1 H NMR spectra [see Supplementary Information (SI) section] confirmed the formation of the compounds.The IR spectra of compounds 1a and 2a displayed characteristic absorption bands at 3310 cm −1 and 3308 cm −1 for N-H, at 1687 cm −1 and 1685 cm −1 strong bands for the C=O groups and, in the region of 1247-1248 cm −1 corresponding to C-O vibrations, respectively.The 1 H NMR spectra showed the NH signal at 5.03 ppm for 1a and 5.01 ppm for 1b.The 13 C NMR chemical shift C(7)-N bond appeared at 44.8 and 44.6 ppm for 1a and 2a, respectively; the carbonyl chemical shifts were observed at the characteristic high frequencies of 156.6 ppm in both compounds.

FTIR molecular recognition study
T h e m o l e c u l a r r e c o g n i t i o n a b i l i t y o f t h e phenylenebis(methylene)dicarbamates to benzenediols was evaluated by a mechanochemical complexation study.Mixtures in a 1:1 ratio of crystalline powders of 1a or 2a with the 1,2-or 1,3-benzenediol (3-6) were ground with dichloromethane in a porcelain mortar until complete 5 min.1,4-benzenediols were not included in this study because in these positions, the O-H groups are located at 180° between them.At the end of the grinding time, in all the experiments performed, a semisolid sticky (similar to honey) product was obtained as consequence of the grinding process (1a•3-6 and 2a•3-6 complexes).FTIR spectra of the semisolid ground products, the phenylenebis(methylene) dicarbamates (1a and 2a) and the benzenediols (3-6) were obtained with a FTIR attenuated total reflection (ATR) system.The O-H and N-H stretching bands are presented in Figure 1 (full spectra of the compounds are presented as SI).
The complex formation was confirmed because the O-H stretching bands in the IR spectra of the semisolid product are shifted with respect to the O-H stretching bands in the spectra of the respective benzenediol.This shift suggests the formation of the phenylenebis(methylene)dicarbamate -benzenediol complex involving the intermolecular O-H•••O=C hydrogen bond interaction as consequence of the mechanochemical reaction. 17In all the IR spectra of the semisolid complexes (1a•3-6 and 2a•3-6) the O-H stretching bands are overlapped with the N-H stretching band of 1a or 2a.
The IR spectra of 6 showed two O-H stretching bands: the band at 3444 cm −1 belongs to the "free" O-H group, and the band at 3320 cm −1 is the band of the intramolecular hydrogen bonded O-H group.In the 1a•6 and 2a•6 complexes (Figure 1d and 1h), both, the "free" and the intramolecular hydrogen bonded O-H bands are shifted to lower frequencies as consequence of the intermolecular hydrogen bond.This has been reported in the complexation between catechol and hydrogen bonding acceptors. 18,19n very diluted solutions of alcohols and phenols, the "free" O-H stretching frequencies are observed as sharp and strong bands in the 3700-3584 cm −1 range.As the concentration increases, the O-H band is shifted to lower frequencies (3550-3200 cm −1 ) and broadens, as consequence of the intermolecular hydrogen bonding between the O-H groups, leading to the formation of self-assembled O-H•••O-H polymeric structures. 26The O-H stretching bands of the noncomplexed forms of 3 and 4 are in the lower limit of the intermolecular hydrogen bonded frequencies (3183 cm −1 and 3227 cm −1 , respectively), due to their great ability to form intermolecular hydrogen bonds.Meanwhile, in the noncomplexed forms of 5 and 6, the steric hindrance and the formation of intramolecular hydrogen bonds respectively, decreases this ability, causing the O-H stretching bands to appear at higher frequencies than 3 and 4.
It is noteworthy that, after the complexation, the frequency of the O-H stretching bands in the IR spectra of 1a•3-6 and 2a•3-6 complexes, measured from the semisolid ground product, are in the 3308-3339 cm −1 intermolecular hydrogen bond range, suggesting a rearrangement in the intermolecular hydrogen bond pattern, from the O-H•••O-H in the noncomplexed forms, to the C=O•••O-H in the complexes.This is in agreement with the reported for phenyldioxalamate-1,3-benzenediols complexes. 17This rearrangement "breaks" the highly O-H•••O-H intermolecular hydrogen bonded self assembly of the noncomplexed form of 3 and 4, and shifts to higher frequencies the O-H stretching band in the complexes 1a•3-4 and 2a•3-4.Unlike 4 and 5, whose formation of the 1a•5-6 and 2a•5-6 complexes favors the formation of intermolecular hydrogen bonds and shifts to lower frequencies de O-H stretching bands with regard to the noncomplexed form.
The small shifts of the C=O stretching bands are characteristic of the O-H•••O=C complexes. 17,27,28On the other hand, the small shift of the N-H stretching bands indicates that the N-H group is not involved in the complex formation.

Molecular structure of 1a and 2a
In order to gain more information about the molecular structure of the 1a and 2a compounds, DFT calculations at B3LYP/6-31+G** level were performed using the GAUSSIAN 09 program. 29In order to obtain the most stable conformer according to the arrangement of the diethyl carbamate "side arms" with respect to the plane of the aromatic ring, each conformer was obtained by the twisting of the C(2)-C(1)-C(7)-N(7) torsion angle (see SI).Each 10° turn conformer was geometry optimized to a local minimum.
In the global minimum energy conformations of 1a and 2a (Figure 2), the ethyl carbamate side "arms" are trans-positioned between them, in relation to the mean plane of the phenylene ring.In 1a, the values of the C(2)-C(1)-C(7)-N (7)   noteworthy that the trans conformation is also adopted by X-ray diffraction structures of similar compounds. 30,31 the other hand, the torsion angles from H(7)-C(7)-N( 7)-H moiety of 1a and 2a are 55.52° and 67.05°, respectively for a synperiplanar conformation, meanwhile for an antiperiplanar conformation the values are 171.24°and −177.24°,respectively.Using the experimental heteronuclear Karplus curves, 24,25 which correlates the NMR coupling constants with the dihedral angle, we found that the torsion angles of theoretical optimization are according to the 3 J H7-NH coupling constant of 5.6 Hz and 6.0 Hz obtained from the 1 H NMR spectra of 1a and 2a (Table 1), which denote a torsion angle from 28° and 23° for synperplanar, and 134° and 137° for antiperiplanar conformation, respectively.

Conclusions
It was synthesized and characterized two new diethyl phenylenebis(methylene)-dicarbamates and its minimum energy molecular structure was determined by DFT calculations and 1 H NMR. The FTIR spectroscopy study allowed to determinate the mechanochemical complexation of the phenylenebis(methylene)dicarbamates and benzenediols by the shift of the phenolic O-H stretching bands.This shift suggests a rearrangement in the intermolecular hydrogen bond pattern, from the O-H•••O-H in the noncomplexed forms, to the C=O•••O-H in the complexes.As consequence of the results of the FTIR molecular recognition study, future studies with solution and solid state techniques will be performed in order to gain more information about the molecular structure of the complexes and their binding constants.

Experimental
Melting points (m.p.) were determined using an Electrothermal IA9300 apparatus and are uncorrected.IR spectra were recorded from solid samples on a Bruker Tensor-27 FTIR spectrophotometer with ATR system.Mass spectra were obtained in a Bruker Esquire 6000 spectrometer with an electron ionization mode. 1 H and 13 C NMR spectra were recorded on a Bruker Avance III 400 ( 1 H, 400.1 MHz; 13 C, 100.6 MHz) instrument in CDCl 3 solutions, measured with SiMe 4 as the internal reference, the chemical shift values are recorded on d scale and are in ppm; the coupling constants (J) are in Hertz.
General procedure for the synthesis of the diethyl phenylenebis(methylene)-dicarbamates (1a-2a) To a THF (100 mL) solution of 5 g (36.7 mmol) of the xylylenediamine and 10.2 mL (7.4 g, 73.4 mmol) of TEA were added dropwise 7.0 mL (7.9 g, 73.4 mmol) of ethyl chloroformate with vigorous stirring in an ice bath.The reaction mixture was additionally stirred for 24 h at room temperature.The suspension was filtered and the THF solution was evaporated to dryness.The obtained solid was solubilized in ethyl acetate and filtered to separate the insoluble solids.The ethyl acetate solution was evaporated to obtain the solid product.4.15 (q, 4H, J = 7.2 Hz, O-CH 2 -CH 3 ), 4.35 (d, 4H, J 6.0 Hz, Ar-CH 2 ), 5.01 (s, 2H, NH), 7.27 (s, 4H, Ar); 13

Mechanochemical complexation with benzenediols
Benzendiols 3-6 were purchased from commercial sources and used as received.
Mixtures in a ratio of 1:1 of 0.1 g of the xylylene biscarbamate (1a, 2a) and the equivalent of benzenediol (3-6)  were ground in a porcelain mortar with aid of 0.5 mL of dichloromethane.The grind time was completed until 5 min.A semisolid (similar to honey) product was obtained.

Theoretical calculations
The density functional theory (DFT) [32][33][34] calculations were performed using the GAUSSIAN 09 package. 263LYP hybrid functional 35 was employed.6-31+G** basis set [36][37][38] for C, H, O, and N atoms was also employed.Harmonic frequency analysis was made to verify optimized minima at the potential energy surface.The results were visualized in the Chemcraft program. 39

Scheme 1 .Scheme 2 .
Scheme 1.Compounds involved in the molecular recognition study.

Figure 2 .
Figure 2. Optimized molecular structures and atomic numbering of 1a and 2a.