1 , 3-Oxazepane-4 , 7-Diones Compounds : 1 H and 13 CNMR High-Resolution Spectroscopy ( 1 D and 2 D )

“Oxazepine” refers to any seven-membered ring containing an oxygen and nitrogen atom. The 1,3-oxazepine is a branch of many types of the heterocyclic oxazepine [1–7]. The core structure of 1,3-oxazepane-4,7diones consists of a sevenmemebred ring along with two carbonyl group. Over the years, the syntheses of oxazepine derivatives have been investigated and documented. The result is important of heterocyclic compounds having significant biological uses [8– 13]. Recently, we prepared a variety of 1,3-oxazepinediones in order to study the spectroscopic and liquid crystal properties [14]. In this paper, we present the structural elucidation by 1D and 2D NMR experiments of 3-alkyl2-(3-hydroxyphenyl)-1,3-oxazepane-4,7-diones with general formula(HOC6H4)CONCnH2n+1CH-CH(CO)2 (where n = 2, 4, 6, 8, 10, 12, 14, 16, and 18). Here, the hydroxyphenyl and the terminal alkyl chain are attached to the oxazepane ring.


Experimental
2.1.Material.The experimental part for the synthesized of 1,3-oxazepane-4,7-dione compounds and recording of CHN, FT-IR, and all proton and carbon NMR spectra have been reported elsewhere [15].

Physical Measurements.
Melting points were recorded by GALLENKAMP digital melting point apparatus.The elemental microanalyses (CHN) were performed using a Perkin Elmer 2400 LS Series CHNS/O analyzer.The NMR spectra were recorded in deuterated methyl sulphoxide (DMSO-d 6 ) at 298 K on a Bruker 400 MHz Ultrashied FT-NMR spectrometer equipped with a 5 mm BBI inverse gradient probe.Chemical shifts were referenced to internal tetramethylsilane (TMS).The concentration of solute molecules was 50 mg in 1.0 mL of (DMSO-d 6 ).Standard Bruker pulse programs [16] were used throughout the entire experiment.The spectroscopic details of NMR are summarized in Table 1.

Results and Discussion
The data of the 1 H and 13 C NMR chemical shifts for title compounds in DMSO solution are listed in respective Tables 2 and 3. H NMR Spectral Assignment.A complete assignment for the title compounds can be given based on the representative compound 18oxa (Figure 1).The 1 H NMR spectra of 2oxa-18oxa shows three different regions of chemical shift.The signals of the aromatic proton, which appear as a doublet in the region of δ = 7.05-7.14ppm is assigned to the H4 proton, while a doublet in the range of   δ = 6.64-6.94ppm attributed to H6.The singlet in the region of δ = 7.10-7.24ppm is due to the H2 proton.The triplet in the region δ = 7.24-7.45ppm can be ascribed to the H5 proton.The protons (H2, H4, H5, and H6) are found to be nonequivalent.The hydroxyl proton appears as a singlet at δ = 9.19-9.94ppm. 1 H NMR spectra of all these compounds show two two-proton triplets in the high field region of about δ = 2.21-2.35ppm and 2.40-2.48ppm due to the heterocyclic ring protons H9 and H10, respectively.The chemical shift of the H7 proton is a singlet in the range of δ = 7.56-7.93ppm.The alkyl group shows four signals and a quintet in the range of δ = 1.71-1.76ppm.This quintet is attributed to the H13.The two triplets in the range of δ = 0.85-0.94ppm and δ = 3.01-3.22ppm can be assigned to the methyl protons (Hy) and the methylene protons (H12), respectively.The signals of the alkyl protons from H14 to H27 are confirmed by multiplets in the range of δ = 1.23-1.30ppm.The assignments of the 1 H NMR spectra of these compounds were aided by 2D COSY experiments.The COSY experiments further substantiated the correlation between the equivalent proton pairs with the adjacent protons, wherein the cross peak resulting from these correlations appear at the same region.A typical COSY spectrum of the 1 H-1 H connectivities in 6oxa is shown in Figure 2. At the upper field, H9 in heterocyclic ring correlated with the proton H10 in the same ring observed as triplets at δ = 2.27 and 2.41 ppm, respectively.The quintet at δ = 1.71 ppm is assigned to H13 proton which correlated with the multiplets at δ = 1.30ppm.A similar phenomenon can also be found for Hx at δ = 1.32 ppm which correlated with Hy at δ = 0.86 ppm.However, the H14 to H27 protons for compounds (8oxa to 18oxa) exhibit complexity which cannot be resolved using homonuclear decoupling.The COSY correlation also reveals that the NMR signal of proton H5 at δ = 7.38 ppm had correlated with the NMR signal of aromatic protons H4 (δ = 7.14) and H6 (δ = 6.68) ppm, respectively.In the same way, the aromatic proton (H2) in the region of δ = 7.12 ppm was found to be not correlated with any other aromatic protons.However, COSY data also reveals that the (OH) proton at δ = 9.23 ppm was found to be correlated with the signal assigned to the singlet in the region of δ = 7.12 ppm but not with doublet assigned at δ = 7.14 ppm (H4).This result helps to show the hydrogen atom of the hydroxyl group is not coplanar with the phenyl ring.Select relationship for compound 6oxa was shown in Figure 3. 13 C NMR and 2D Spectral Assignment.Compounds 2oxa-18oxa were also characterized by 13 C NMR and DEPT135 for the protonated carbons which are governed by the additive rules and substitution effect.The 13 C NMR spectra of these compounds were all similar.Two downfield signals observed at δ = 171.54-172.35ppm and δ = 174.64-176.70 ppm are attributed to the carbonyl carbons (C8 and C11) of the seven-membered ring.However, the highfield signal in the region of δ = 13.80-15.03ppm is assigned for Cy of the methyl in the alkyl chain.The signals in the range of δ = 39.36-40.15ppm, 29.60-30.85ppm, 26.40-34.93ppm, and 22.50-23.12ppm are attributed to the respective C12, C13, C14 to C25, and Cx in the aliphatic chain.In addition to the aliphatic carbons, the signal for C9 and C10 of the seven-membered ring appear in the range of δ = 27.20-28.80ppm and δ = 29.50-29.98ppm, respectively.The signal in the region of δ = 67.56-70.58ppm is attributed to C7.The resonance due to the aromatic carbon at δ = 137.16-138.74,114.10-115.80,119.42-122.49,130.18-132.66,and 121.12-123.05ppm are assigned to C1, C2, C4, C5, and C6.The 13 C NMR signal for C3 (δ = 158.43-161.06ppm) showed comparatively downfield shift as compared to the other phenyl carbons in all the title compounds due to adjacent to hydroxyl group.The only difference observed was the increase in the number of aliphatic carbon signals by two each time when compound 2oxa to 18oxa was analyzed.

3.2.
The HMQC spectra of all the compounds were recorded, and the chemical shifts are assigned.The HMQC spectra provide information regarding the through bond connection between the protons and the carbon atoms to which they are directly attached.The data of compound 18oxa are discussed as an example.The HMQC experiment enabled the assignment of the one-bond connectivity in the proton singlet at δ = 7.21 ppm, which correlated with carbon signal at δ = 115.54ppm, a doublet at δ = 7.08 ppm with the methine at δ = 121.91ppm, the triplet at δ = 7.38 ppm with the signal at δ = 131.13ppm, and the doublet at δ = 6.94 ppm shows the correlation with the signal at δ = 122.65.The signals were observed at δ = 27.23 ppm and 29.51 ppm which are assigned to carbon atoms in the heterocyclic ring (C9 and C10) due to its interaction with proton resonances at δ = 2.28 ppm and 2.41 ppm.The proton singlet for H7 at δ = 7.91 ppm is correlated with the carbon signal δ = 69.21ppm.At upper field, we were able to assign the three proton triplet at δ = 0.86 ppm which correlated with the carbon signal at δ = 14.89 ppm, and also a signal at δ = 1.28 ppm correlated with the carbon signal at δ = 22.90 ppm.In the same way, the multiplets of the aliphatic proton signal at δ = 1.23 ppm is correlated with the carbon signals at δ = 27.80 ppm to 33.87 ppm.
As for the HMBC spectra, the assignment for the carbon nuclei can also be supported by long-range connectivities.The HMBC spectra of compounds help to observe the correlation of aromatic quaternary carbon and its neighboring proton.In addition, the HMBC experiment allowed the assignment of the aromatic nonprotonated and protonated carbons.For example, in 16oxa Figure 4, the proton singlet at δ = 7.24 ppm correlated through 2 J bond with the aromatic carbons at δ = 137.16and 158.82 ppm, respectively, and with the aromatic carbon at δ = 122.95ppm via 3 J, while it also correlated with the aromatic carbon at δ = 132.66ppm through 4 J. Finally, the long-range connectivities through intramolecular interaction ( intra J) of this proton correlate with the carbon at δ = 39.90 ppm.Likewise, the doublet at δ = 7.11 ppm which was assigned to the H4 proton is correlated through 2 J, 3 J, and 4 J with the respective aromatic carbons at δ = 132.66ppm, 122.95 ppm, and 137.16 ppm.The one proton doublet at δ = 6.92 ppm was also shown to be correlated with the carbons at δ = 132.66ppm, 120.49ppm, 69.86 ppm, and 158.82 ppm through the long-range connectivities via 2 J, 3 J, and 4 J, respectively.The aromatic proton, observed as a triplet at δ = 7.36 ppm was correlated with the aromatic carbons at δ = 120.49,122.95 ppm, 137.16 ppm, and 115.49ppm through the respective longrange connectivities of 2 J, 3 J, and 4 J.The spectrum also allowed the assignment of the protons of the heterocyclic ring which was observed as a triplet at δ = 2.29 ppm which correlated with the carbonyl carbon at δ = 171.56ppm and with the carbon at δ = 29.56ppm through the long-range connectivity 2 J.It also correlated with the carbon signal at δ = 174.71through the long range connectivity 3 J.In the same way the triplet of the seven-membered ring at δ = 2.42 ppm, is correlated with the carbon at δ = 27.25 ppm and the carbonyl carbon at δ = 174.71ppm through 2 J. Furthermore, the singlet at δ = 7.92 ppm which was assigned for proton H7 was observed to correlate with the aromatic carbon at δ = 137.16ppm through 2 J, with the carbons at δ = 171.56ppm and 39.90 ppm through 3 J, and finally with the carbon at δ = 29.96ppm through the long-range connectivity 4 J.
The aliphatic chain protons is assigned from the triplet at δ = 3.01 ppm which correlated with carbon at δ = 29.96through 2 J, with carbons at δ = 69.86 and 27.44 ppm through 3 J, and with the aromatic carbon at δ = 137.16    Additional correlation for the aliphatic protons were detected from the observed triplet at δ = 0.85 ppm which was assigned to the Hy protons with the carbon at δ = 22.95 ppm, with the carbon at δ = 33.57ppm, and with carbon at δ = 31.19ppm in the respective, long-range connectivities 2 J, 3 J, and 4 J.These data help to confirm the correlation between the proton signal at δ = 1.30ppm with the carbon signals at δ = 14.76 ppm and 33.57ppm, 31.19 ppm and 31.30ppm through the long-range connectivities 2 J, 3 J, and 4 J, respectively.Selected intramolecular through bond connectivities from HMBC spectrum for compound 16oxa is shown in Figure 5.

Conclusions
In this paper, we present some new heterocyclic compounds with 1,3-oxazepane cores.The detail NMR assignments of these compounds have been discussed by 1 H, 13 C NMR, and DEPT135 spectra along with two-dimensional COSY, 1 H- 13 C HMQC, and HMBC spectra.Synthesis results of this work could be useful for other chemists working on the field of heterocyclic oxazepine.

Figure 1 :
Figure 1: Molecular structure with numbering scheme for compound 18oxa.

Figure 2 : 1 H
Figure 2: 1 H-1 H connectiveities in the COSY spectra with select relationship for compound 6oxa.(a) Expansion of aliphatic and hetero cyclic proton spectrum.(b) Expansion of heterocyclic proton spectrum.(c) Expansion of aliphatic proton region.(d) full 1 H-1 H COSY spectrum.

Figure 4 :
Figure 4: Long range C-H correlations in the HMBC spectra of compound 16oxa.From (a) to (d) Expansion of aliphatic and hetero cyclic proton spectra.(e) HMBC spectrum of 16oxa.

Table 1 :
Acquisition parameter used in the NMR measurements.