4-[(2,4-Dichlorophenyl)carbamoyl]butanoic Acid Acid

: The synthesis and spectroscopic characterization of the glutaric acid-amide derivative, 2,4-Cl 2 C 6 H 3 N(H)C(=O)(CH 2 ) 3 C(=O)OH ( 1 ), are described. The X-ray crystal structure determination of ( 1 ) shows the backbone of the molecule to be kinked about the methylene-C–N(amide) bond as seen in the C(p)–N–C(m)–C(m) torsion angle of − 157.0(2) ◦ ; m = methylene and p = phenyl. An additional twist in the molecule is noted between the amide and phenyl groups as reﬂected in the C(m)–N–C(p)–C(p) torsion angle of 138.2(2) ◦ . The most prominent feature of the molecular packing is the formation of supramolecular tapes assembled through carboxylic acid-O–H ... O(carbonyl) and amide-N–H ... O(amide) hydrogen bonding. Abstract: The synthesis and spectroscopic characterization of the glutaric acid-amide derivative, 2,4-Cl 2 C 6 H 3 N(H)C(=O)(CH 2 ) 3 C(=O)OH ( 1 ), are described. The X-ray crystal structure determination of ( 1 ) shows the backbone of the molecule to be kinked about the methylene-C–N(amide) bond as seen in the C(p)–N–C(m)–C(m) torsion angle of −157.0(2)°; m = methylene and p = phenyl. An additional twist in the molecule is noted between the amide and phenyl groups as reflected in the C(m)–N– C(p)–C(p) torsion angle of 138.2(2)°. The most prominent feature of the molecular packing is the formation of supramolecular tapes assembled through carboxylic acid-O–H … O(carbonyl) and am-ide-N–H … O(amide) hydrogen


Results and Discussion
Compound (1) was prepared in 85% yield as colorless crystals from the 1:1 reaction of 2,4-dichloro aniline and glutaric anhydride in toluene. Spectroscopic characterization was performed by IR, 1 H and 13 C{ 1 H} NMR, UV, and MS spectroscopy; spectra are available in the Supplementary Materials as Figures S1-S7. In the IR spectrum, characteristic absorptions assigned to ν(COO stretching ), ν(amide C=O), and ν(COO bending ) were observed at 1695, 1653, and 1415 cm −1 , respectively. The NMR assignments were based on the previous literature [1][2][3][4][5][6][7], COSY and HMBC spectra, and simulation [9]. The 1 H NMR (DMSO-d 6 .) 2 of 6 featured broad resonances at δ 11.23 and 9.57 ppm which were ascribed to COOH and NH, respectively. The most notable features in the 13 C{ 1 H} NMR (DMSO-d 6 ) spectrum were downfield resonances at δ 174.6 and 171.7 ppm which were assigned to carboxylic acid and amide functionalities, respectively. Three well-defined absorptions are noted in the UV (acetonitrile) spectrum, at 259.0, 209.0, and 191.0 nm. These are ascribed to n-π*(C=O), π − π*(C=O), and π − π*(C=C) transitions, respectively, and are red-shifted compared to those reported for the 4-chloro analogue [7]. In the mass spectrum, the [M] + ion peak was noted at 275.03 m/e and the base peak, [C 6 H 4 NCl 2 ] + , at 161.02 m/e. Figure 2 shows the molecular structure of (1). The rather disparate values of the C1-O1 and C1-O2 bond lengths of 1.219(3) and 1.300(3) Å, respectively, confirm the presence of a carboxylic acid group; further support for this assignment is seen in the supramolecular association (see below). An all-trans configuration in the carbon side chain is precluded owing to a twist about the C4-C5 bond as seen in the sequence of  featured broad resonances at δ 11.23 and 9.57 ppm which were ascribed to COOH and NH, respectively. The most notable features in the 13 C{ 1 H} NMR (DMSO-d6) spectrum were downfield resonances at δ 174.6 and 171.7 ppm which were assigned to carboxylic acid and amide functionalities, respectively. Three well-defined absorptions are noted in the UV (acetonitrile) spectrum, at 259.0, 209.0, and 191.0 nm. These are ascribed to nπ*(C=O), π − π*(C=O), and π − π*(C=C) transitions, respectively, and are red-shifted compared to those reported for the 4-chloro analogue [7]. In the mass spectrum, the [M] + ion peak was noted at 275.03 m/e and the base peak, [C6H4NCl2] + , at 161.02 m/e. Figure 2 shows the molecular structure of (1). The rather disparate values of the C1-O1 and C1-O2 bond lengths of 1.219(3) and 1.300(3) Å, respectively, confirm the presence of a carboxylic acid group; further support for this assignment is seen in the supramolecular association (see below). An all-trans configuration in the carbon side chain is precluded owing to a twist about the C4-C5 bond as seen in the sequence of C1-C2-C3-C4   (1) showing atom labeling and displacement ellipsoids at the 35% probability level.
As indicated in the introduction, there are several closely related ArN(H)C(=O)(CH2)3C(=O)OH structures in the crystallographic literature [3][4][5][6][7]. As seen in the overlay diagram of Figure 3, there is considerable conformational flexibility in these molecules. This flexibility relates to the relationship between the Ar ring and attached amide group, between the carboxylic acid group and the chain it is connected to, and in the conformation of the side chain. The latter is nicely illustrated for the two independent molecules comprising the asymmetric unit of the Ar = 2-MeOC6H4 compound, where the C3-C4-C5-N1 torsion angles of −117.9(3) and −161.8(2)°, respectively, indicate a distinctive kink in the former. It is noted that the substituents in the 2-position, when present, are consistently, approximately syn to the amide-N-H atom.  As indicated in the introduction, there are several closely related ArN(H)C(=O)(CH 2 ) 3 C(=O)OH structures in the crystallographic literature [3][4][5][6][7]. As seen in the overlay diagram of Figure 3, there is considerable conformational flexibility in these molecules. This flexibility relates to the relationship between the Ar ring and attached amide group, between the carboxylic acid group and the chain it is connected to, and in the conformation of the side chain. The latter is nicely illustrated for the two independent molecules comprising the asymmetric unit of the Ar = 2-MeOC 6 H 4 compound, where the C3-C4-C5-N1 torsion angles of −117.9(3) and −161.8(2) • , respectively, indicate a distinctive kink in the former. It is noted that the substituents in the 2-position, when present, are consistently, approximately syn to the amide-N-H atom.
molecules. This flexibility relates to the relationship between the Ar ring and attached amide group, between the carboxylic acid group and the chain it is connected to, and in the conformation of the side chain. The latter is nicely illustrated for the two independent molecules comprising the asymmetric unit of the Ar = 2-MeOC6H4 compound, where the C3-C4-C5-N1 torsion angles of −117.9(3) and −161.8(2)°, respectively, indicate a distinctive kink in the former. It is noted that the substituents in the 2-position, when present, are consistently, approximately syn to the amide-N-H atom.  The aforementioned flexibility in the molecules is reflected in the ranges of torsion angle. Thus, the C5-N1-C6-C7 torsion angles relating the amide to Ar rings range from −16.4(5)° for the first independent molecule of the 2-methoxy derivative [4] to −133.95(18)° for the 3,5-dichloro molecule [5]. The range of O1-C1-C2-C3 torsion angles, relating to the relative orientation of the carboxylic acid residue and the chain it is connected to, is smaller, that is, 0.6(4)° for the first independent molecule of the 2-methoxy molecule [4] to 13.9(5)° for the 4-chloro derivative [7]. The deviations from coplanarity in the terminal C1-C2-C3-C4 and C4-C5-N1-C6 torsion angles are relatively minor, with maximum deviations manifested in the 171.1(2) and −173.66 (14)° values, respectively for the first independent molecule of the 2-methoxy derivative [4] and the 3-methoxy derivative [6]. A prominent kink is noted about the C3-C4 bond in the 3,5-dichloro molecule [5], with C2-C3-C4-C5 = 78.5(2)°. Similarly, a major twist is noted about the C4-C5 bond for the first independent molecule of the 2-methoxy derivative [4], with C2-C3-C4-C5 = 117.9(3)°.
As often observed in the crystals of ArN(H)C(=O)(CH2)3C(=O)OH [3][4][5][6][7], the carboxylic acid residues form eight-membered { … OCOH}2 synthons to assemble a pair of molecules about a center of inversion; geometric parameters describing the identified intermolecular interactions are given in the caption to Figure 3. The resulting two molecule aggregates are connected into a supramolecular tape by amide-N-H … O(amide) hydrogen bonds as shown in Figure 4. The tapes pack in the crystal without directional interactions between according to the distance criteria assumed in PLATON [10]. The availability of seven closely related crystals offers the opportunities of ascertaining any trends. First and foremost, three of the molecules crystallize in the triclinic space group P1, namely (1), Ar = 2-MeOC6H4 [4], and 3-MeOC6H4 [6] and the three remaining molecules, namely Ar = 4-ClC6H4 [7], 3,5-Cl2C6H3 [5], and 2-NO2, 4-MeOC6H3 [3] crystallize in the monoclinic space group P21/c. Despite this, no isostructural relationships exist between any of the crystals. However, five of the crystals feature supramolecular tapes akin to that shown in Figure 3 for (1). This common supramolecular feature is reflected in similar unit cell edges along which the amide chains are propagated, that is, corresponding to the pitch of the supramolecular polymer; these range from 4.7931 (2) for Ar = 4-ClC6H4 [7]   The availability of seven closely related crystals offers the opportunities of ascertaining any trends. First and foremost, three of the molecules crystallize in the triclinic space group P 1, namely (1), Ar = 2-MeOC 6 H 4 [4], and 3-MeOC 6 H 4 [6] and the three remaining molecules, namely Ar = 4-ClC 6 H 4 [7], 3,5-Cl 2 C 6 H 3 [5], and 2-NO 2 , 4-MeOC 6 H 3 [3] crystallize in the monoclinic space group P2 1 /c. Despite this, no isostructural relationships exist between any of the crystals. However, five of the crystals feature supramolecular tapes akin to that shown in Figure 3 for (1). This common supramolecular feature is reflected in similar unit cell edges along which the amide chains are propagated, that is, corresponding to the pitch of the supramolecular polymer; these range from 4.7931(2) for Ar = 4-ClC 6 H 4 [7] to 5.0167(2) for Ar = 3-MeOC 6 H 4 [6]. The Ar = 2-MeOC 6 H 4 [4] compound adopts a distinct mode of supramolecular association whereby the two independent molecules associate via an eight-membered { . . . OCOH} 2 synthon and amide-N-H . . . O(amide) hydrogen bonds giving rise to a twisted chain. The amide oxygen atom not participating in a conventional hydrogen bond forms C-H . . . O interactions and the amide-N-H does not form a close intermolecular contact [4].
In summary, a new ArN(H)C(=O)(CH 2 ) 3 C(=O)OH derivative with Ar = 2,4-dichlorophenyl has been synthesized. X-ray crystallography shows a twist about the C(amide)-C(methylene) bond as well as between the Ar ring and amide group, and between the carboxylic acid residue and chain. In the crystal, supramolecular tapes mediated by carboxylic acid-O-H . . . O(carbonyl) and amide-N-H . . . O(amide) hydrogen bonding are prominent.  (1) 2,4-Dichloro aniline (0.81 g, 5 mmol) and glutaric anhydride (0.57 g, 5 mmol) were dissolved separately in about 10-15 mL analytical grade toluene. The two solutions were combined slowly followed by stirring at room temperature until the appearance of a precipitate. This solution was filtered, and the filtrate was washed with a minimum amount of toluene (for the removal of any unreacted reactants) followed by water (for the removal of any glutaric acid formed during the reaction). The product was air-dried and recrystallized in the solvent mixture acetone/ethanol (1:1 v/v) to yield colorless crystals after one week. Yield: 85%. m.p.
The structure was solved by direct methods [12] and refined (anisotropic displacement parameters and C-bound H atoms in the riding model approximation) on F 2 [13]. The O-H and N-H atoms were located from a difference map and refined with O-H and N-H distance restraints of 0.82 ± 0.01 and 0.86 ± 0.01 Å, respectively. A weighting scheme of the form w = 1/[σ 2 (F o 2 ) + (0.110P) 2 + 0.038P] was introduced, where P = (F o 2 + 2F c 2 )/3). Based on the refinement of 160 parameters, the final values of R[I ≥ 2σ(I)] and wR (all data) were 0.055 and 0.165, respectively. The molecular structure diagram was generated with ORTEP for Windows [14] and the packing diagram using DIAMOND [15].
Crystal data for C 11