Synthesis, characterization and density functional theory investigations of the N,N-diacylaniline derivatives

2.1 General procedure for di-acylation of aniline derivatives (DAA)

To a solution of the monoacyl aniline derivative (details can be found in Supporting Information) (1) (1 mol. eq.), in dry dichloromethane (2 cm³/g) containing dry pyridine (1.5 mol. eq.), was added acid chloride (2–3 mol. eq.) dropwise over 10 min. and the mixture was stirred and heated under reflux for 2–4 days, monitoring the disappearance of the starting N-acylanthranilate by TLC. After cooling, additional dichloromethane was added, the solution washed with aqueous sodium hydrogen carbonate, then water, dried and the solvent removed under reduced pressure to give the di acyl aniline DAA (2). General synthetic procedure for such kind of materials can be found in references (Al-Sehemi et al., 2013).

2.2 N-acetyl-N-(2-methoxyphenyl)acetamide (2a)

The general procedure for the N-acylation of amines was followed using 2-methoxy phenyl acetamide (1a) (2 g, 16.2 mmol), pyridine (3.86 g, 48.8 mmol) and acetyl chloride (3.83 g, 48.8 mmol). After work-up, N-acetyl-N-(2-methoxyphenyl) acetamide (2a) was obtained as a light brown oil (2.8 g, 83%). b.p $185-{199}^{°}\text{C}$ , δ ¹H NMR (CDCl₃) 2.06 (6H, s, 2 × CH₃CO), 3.59 (3H, s, CH₃O), 6.85, 6.94 and 7.20 [4H, m, 4 × CH (ph)]; δ C (CDCl₃, 125 MHz) 26.27 and 26.39 (2 × CH₃CO), 55.55 (OCH₃), 112.3, 120.9, 128.1 and 129.6 [4 × CH (Ar) ], 121.3 (C = CN), 154.75 (OCH₃) and 172.67 and 172.99 (2 × CO).

2.3 N-acetyl-N-(2-Methoxy-phenyl)-4-nitro-benzamide (2b)

The general procedure for the N-acylation of amines was followed using N-(2-Methoxy-phenyl)-4-nitro-benzamide (1b) (1 g, 3.7 mmol), pyridine (0.72 g, 9.2 mmol) and acetyl chloride (0.73 g, 9.2 mmol). After work-up, N-acetyl-N-(2-Methoxy-phenyl)-4-nitro-benzamide (2b) was obtained as a light brown powder (0.8 g, 69%). m. p ${132}^{°}\text{C}$ , δ ¹H NMR (DMSO) 2.48–2.5 (3H, overlap with DMSO signal, s, CH₃CO), 3.84 (3H, s, OCH₃), 6.99 [1H, ddd, J 8.6, 7.6 and 1.1, CH (Ar) ], 7.12 [1H, dd, J 8.6 and 1.1, CH (Ar)], 7.23 [1H, ddd, J 8.6, 7.6 and 1.1, CH (Ar)], 7.72 [1H, ddd, J 8.6, 7.6 and 1.1, CH (Ar)], 8.19 and 8.36 [4H, m, CH (Ar)]; δ C (DMSO_d, 125 MHz) 39.2 (CH₃CO), 55.7 (OCH₃), 111.5, 123.6, 124.9, 125.0, 126.1, 126.2, 126.4 and 129.1 [8 × CH (Ar) ], 140 (C-CO), 149.1 (C-NO₂) and 151.8 and 151.9 (2 × CO).

2.4 N-(4-nitrobenzamide)-N-(2-Methoxy-phenyl)-4-bromo-benzamide (2c)

The general procedure for the N-acylation of amines was followed using N-(2-Methoxy-phenyl)-4-bromo-benzamide (1c) (1 g, 3,3 mmol), pyridine (0.65 g, 8.2 mmol) and 4-nitrobenzoyl chloride (1.52 g, 8.2 mmol). After work-up, N-(4-nitrobenzamide)-N-(2-Methoxy-phenyl)-4-bromo-benzamide (2c) was obtained as a yellowish white powder (1 g, 67%). m. p $139-{142}^{°}\text{C}$ , δ ¹H NMR (CDCl₃) 3.86 (3H, s, OCH₃), 6.85 [1H, dd, J 8.1 and 1.3, CH (Ar)], 6.95 [1H, ddd, J 9.1, 7.8 and 1.4, CH (Ar)], 7.03 [1H, ddd, J 9.1, 7.8 and 1.4, CH (Ar)], 7.56 [3H, m, CH (Ar)], 7.68–7.7 [3H, m, CH (Ar)], and 8.40–8.45 [2H, m, CH (Ar)]; δ C (DMSO_d, 125 MHz) 55.9 (OCH₃), 109.9, 119.9, 121.3, 124.1, 126.4, 127.5, 128.7, 132.0 and 134.2 [CH (Ar)], 148.3 [C = C–NO₂] and 164.3 (CO); FTIR ν/cm⁻¹:3409 (N–C = O), 1717(C = O),1667(C = O), 1490(N–O), 1480(N = O), 1341(C–O–C).

2.5 N-Acetyl-4-nitro-N-o-tolyl-benzamide (2d)

The general procedure for the N-acylation of amines was followed using 4-Nitro-N-o-tolyl-benzamide (1d) (1 g, 3.9 mmol), pyridine (0.77 g, 9.8 mmol) and acetyl chloride (0.77 g, 9.8 mmol). After work-up, N-Acetyl-4-nitro-N-o-tolyl-benzamide (2d) was obtained as a yellowish brown powder (0.8 g, 69%). m. p $120-{123}^{°}$ C, δ ¹H NMR (CDCl₃) 2.20 (3H, s, CH₃), 2.21 (3H, s, CH₃CO), 7.0–7.3 [4H, m, CH (Ar)], 7.62 [2H, m, CH (Ar)] and 8.13 [2H, m, CH (Ar)]; δC (DMSO_d, 125 MHz) 17.9 (CH₃), 25.5 (CH₃CO), 123.5, 127.6, 128.8, 129.1, 129.6, 131.7, 135.9 and 137.3 [8 × CH (Ar)], 134.5 (C = C–CH₃), 138.2 (C = C–N), 141.5 (C = C–CO), 149.0 (C = C–NO₂) and 170.6 and (CO).

2.6 N-Acetyl-N-o-tolyl-acetamide (2e)

The general procedure for the N-acylation of amines was followed using 2-methyl aniline (2 g, 18.7 mmol), pyridine (4.43 g, 56 mmol) and acetyl chloride (4.4 g, 56 mmol). After work-up, N-Acetyl-N-o-tolyl-acetamide (2e) was obtained as a clear pale yellow liquid (3.1 g, 87%). b. p $139-{142}^{°}$ C, δ ¹H NMR (CDCl₃) 1.96 (3H, br s, CH₃), 2.03 (6H, br s, CH₃CO), 6.8–7.13 [4H, br m, CH (Ar)]; δ C (DMSO_d, 125 MHz) 17.6 (CH₃), 26.3 (2 × CH₃CO), 126.9, 127.2, 127.4 and 131.1 [4 × CH(Ar)], 135.9 (C = C–CH₃), 138.5(C = C–N) and 127.2 (C = O).

2.7 2-Chloro-N-(2-chloro-acetyl)-N-o-tolyl-acetamide (2f)

The general procedure for the N-acylation of amines was followed using 2-methyl aniline (2 g, 18.7 mmol), pyridine (4.43 g, 56 mmol) and chloro acetyl chloride (6.32 g, 56 mmol). After work-up, 2-Chloro-N-(2-chloro-acetyl)-N-o-tolyl-acetamide (2f) was obtained as a beige powder (3.9 g, 80%). m. p $103-{108}^{°}\text{C}$ , δ ¹H NMR (CDCl₃) 2.10 (3H, s, CH₃), 4.23 and 4.36 (4H, br m, CH₂) and 7.0–7.4 [4H, br m, CH (Ar)]; δ C (DMSO_d, 125 MHz) 17.5 (CH₃), 45.3 (2 × CH₂), 127.9, 128.7, 130.5 and 131.9 [4 × CH(Ar)], 135.1 (C = C–CH₃), 136.3 (C = C–N) and 168.5 (CO).

2.8 Synthesis of 2-Substituted N,N-Diacylanilines

Ortho-(or 2-) Substituted anilines (1) undergo N-N-diacetylation more easily than ortho-unsubstituted ones (Scheme 1). On the basis of our investigations on the N,N-diacetylation of ortho-substituted anilines (1), we planned to explore the potential applications of the ortho-substituted N,N-diacetylanilines in acetylation reaction. The imide character of the N,N-diacetylanilines (2), which was easily prepared from the corresponding ortho-substituted anilines (1). It is expecting that it would serve as a good acetylating reagent to nucleophiles. Acetylation of amines is one of the most fundamental transformations in organic chemistry and selective acetylation of the less hindered amino group in polyamines is often required. In this work a simple but powerful reagent for selective acetylation in a series of structurally diverse diamines is described. The general route for the synthesis of N-N-diacetylation aniline derivative is shown in Scheme 1. In general diacylation of the aniline with acid chloride and pyridine proceeded in high yields and in most of the products diacylanline was crystalline with short reaction times and absence of excess acid chloride.

4.1 Molecular geometries

The optimized structures of the DAA (2a–2f) for the most stable conformers and atomic numbering are presented in Fig. 1. The optimized geometric parameters (bond lengths, bond angles and dihedral angles) calculated by DFT/B3LYP with 6–31G∗ basis set are listed in Tables S1–S3.

Since it is known that the electron correlation should be taken into account when dealing with rotational barriers in imide in order to keep the computational effort within reasonable limits we choose the DFT approach as a theoretical method. It is known that this method may achieve a greater accuracy than the Hartree–Fock (HF) theory. Recently we showed that DFT is good to reproduce the experimental data (Al-Sehemi et al., 2012, 2013; Al-Sehemi and Irfan, 2017; Irfan et al., 2008, 2009, 2010, 2011, 2012, 2013; Irfan and Al-Sehemi et al., 2011, 2012). The DFT approach overcomes the major limitation of the HF theory, i.e., the negligence of electron correlation, by including some of the electron correlation effects. Also it has been shown that DFT calculations provide the torsional barriers in good accord with the experimental values.

The amide functional group contains planar, sp²-hybridized nitrogen resulting from the conjugation of the nitrogen lone pair with the adjacent carbonyl functionality granting the carbonyl-nitrogen bond a partial double bond character. Unsymmetrical N,N-disubstituted imides have two possible ground states that interconvert by a single rotation of the N-carbonyl bond. We expect the barrier to rotation around N-CO bond to be too high, due to the both steric and electronic effects of substituents. The steric effect of o-substituents (such as OMe and Me in the present case) twists the aromatic ring out of planarity with the imide moieties, creating an axis of chirality. The DFT calculations showed that the amide and aryl planes were roughly perpendicular to one another with torsion angles of 94°, 112°, 51°, 100°, 83° and 72° for the C1–C6–N1–C8 and 90°, 87°, 107°, 93°, 96° and 101° for torsion angle C1–C6–N1–C15.

The optimized structures have been compared with some available previous studies having similar parent compounds. The introduction of different substituent groups on the benzene ring causes some changes in the ring C–C bond distances. Changing the position of the substituents in the benzene ring also affects the C–C bond distances. The electron donor/acceptor capabilities play a very important role in shaping the structural and electronic properties of the molecules. The optimized bond lengths of C-C in the phenyl ring fall in the range from 1.388 to 1.418 Å at B3LYP/6–311G∗ level of theory while 1.375 to 1.407 Å at HF/6–311 + G∗∗ level of theory, which are in good agreement with experimental evidences 1.378–1.407 Å (Rofouei et al., 2010). The optimized C6–N2 bond length is in range 1.438–1.454 Å at B3LYP/6–31G∗ level of theory. The experimental C6-N2 bond length is reported as 1.413 Å (Rofouei et al., 2010).

4.2 Experimental and Calculated FTIR Assignments

The 2f molecule consists of 27 atoms, so it has 75 normal vibrational modes. The observed vibrational assignments and analysis of 2f are discussed in terms of fundamental bands. The FTIR spectrum of 2f has been illustrated in Fig. 2. Table 1 summarizes the experimental and calculated vibrational frequencies. According to the theoretical calculations, the 2f has C1 point group symmetry. The comparison of the frequencies calculated by DFT with the experimental values reveals good agreement with calculated vibrational modes due to the inclusion of electron correlation for this method. It should be noted that calculations were made for a free molecule in vacuum, while experiments were performed for solid sample. In this study, we have used the scaling factor of 0.9585.

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Figure 2 Experimental and calculated FTIR spectra of the DAA (2f) at B3LYP/6–31G∗ level of theory.

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