Crystal structure of 2-(2,3-di­methyl­anilino)-N′-[(1E)-2-hy­droxy­benzyl­idene]benzohydrazide

Shaaban K Mohamed; Joel T Mague; Mehmet Akkurt; Alaa F Mohamed; Mustafa R Albayati

doi:10.1107/S2056989015021532

. 2015 Nov 21;71(Pt 12):o957–o958. doi: 10.1107/S2056989015021532

Crystal structure of 2-(2,3-dimethylanilino)-N′-[(1E)-2-hydroxybenzylidene]benzohydrazide

Shaaban K Mohamed ^a,^b, Joel T Mague ^c, Mehmet Akkurt ^d, Alaa F Mohamed ^e, Mustafa R Albayati ^f,^*

PMCID: PMC4719921 PMID: 26870549

Abstract

The asymmetric unit of the title compound, C₂₂H₂₁N₃O₂, consists of two independent molecules (A and B) having differing conformations. The differences mainly concern the dihedral angles which the hydroxyphenyl and dimethylphenyl rings subtend to the central phenylene ring, these being 30.16 (6) and 58.60 (6)° in molecule A and 13.42 (7) and 60.31 (7)° in B. With the exception of the dimethyphenyl substituent, the conformations of the rest of each molecule are largely determined by intramolecular O—H⋯N and N—H⋯O hydrogen bonds. In the crystal, N—H⋯O hydrogen bonds link the molecules into chains extending parallel to the a axis in which the types of molecules alternate in an …A…B…A…B… fashion.

Keywords: crystal structure, non-steroidal anti-inflammatory drugs (NSAIDs) mefenamic acid (MA), hydrazide-hydrazone compounds, hydrogen bonding

Related literature

For the medicinal use of mefenamic acid (MA), see: Nawaz et al. (2007 ▸); Joo et al. (2006 ▸). For the effects of masking the free acidic group in MA and other NSAIDs, see: Arun & Ashok (2009 ▸); Tammara et al. (1994 ▸). For various biological activities of hydrazide-hydrazone compounds, see: Bedia et al. (2006 ▸); Rollas et al. (2002 ▸); Palaska et al. (2002 ▸); Rollas & Küçükgüzel (2007 ▸). graphic file with name e-71-0o957-scheme1.jpg

Experimental

Crystal data

C₂₂H₂₁N₃O₂
M _r = 359.42
Monoclinic,
a = 10.8056 (8) Å
b = 14.7141 (12) Å
c = 23.0408 (18) Å
β = 96.181 (1)°
V = 3642.1 (5) Å³
Z = 8
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 150 K
0.24 × 0.16 × 0.11 mm

Data collection

Bruker SMART APEX CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2015 ▸) T _min = 0.86, T _max = 0.99
70656 measured reflections
10033 independent reflections
6949 reflections with I > 2σ(I)
R _int = 0.050

Refinement

R[F ² > 2σ(F ²)] = 0.047
wR(F ²) = 0.133
S = 1.06
10033 reflections
515 parameters
6 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.32 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Data collection: APEX2 (Bruker, 2015 ▸); cell refinement: SAINT (Bruker, 2015 ▸); data reduction: SAINT; program(s) used to solve structure: SHELXS2014 (Sheldrick, 2008 ▸); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015 ▸); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ▸); software used to prepare material for publication: PLATON (Spek, 2009 ▸).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S2056989015021532/bg2574sup1.cif

e-71-0o957-sup1.cif^{(44KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989015021532/bg2574Isup2.hkl

e-71-0o957-Isup2.hkl^{(549.4KB, hkl)}

Click here for additional data file.^{(7.4KB, cml)}

Supporting information file. DOI: 10.1107/S2056989015021532/bg2574Isup3.cml

Click here for additional data file.^{(1.4MB, tif)}

. DOI: 10.1107/S2056989015021532/bg2574fig1.tif

The asymmetric unit with labeling scheme and 50% probability ellipsoids. O—H⋯N and N—H⋯O hydrogen bonds are shown.

Click here for additional data file.^{(1.5MB, tif)}

c a x y z b x y z . DOI: 10.1107/S2056989015021532/bg2574fig2.tif

The cell-packing diagram of the title compound viewed down the c axis. Symmetry codes: (a) 1 + x, y, z; (b) 2 − x, − Inline graphic + y, − z.

CCDC reference: 1436917

Additional supporting information: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1O⋯N1	0.87 (2)	1.83 (2)	2.6048 (14)	149 (2)
N2—H2N⋯O3	0.86 (1)	2.22 (1)	3.0640 (14)	167 (1)
N3—H3N⋯O2	0.87 (2)	2.01 (1)	2.7114 (15)	138 (1)
O3—H3O⋯N4	0.87 (2)	1.81 (2)	2.5854 (14)	149 (2)
N5—H5N⋯O1ⁱ	0.87 (1)	2.38 (1)	3.2164 (14)	162 (1)
N6—H6N⋯O4	0.86 (1)	1.98 (1)	2.6675 (15)	136 (1)

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Symmetry code: (i) Inline graphic .

Acknowledgments

The support of NSF–MRI Grant No.1228232 for the purchase of the diffractometer and Tulane University for support of the Tulane Crystallography Laboratory are gratefully acknowledged.

supplementary crystallographic information

S1. Comment

The antiphlogistic non-steroidal anti-inflammatory drugs (NSAIDs) mefenamic acid [2-(2,3-dimethylphenylamino)-benzoic acid], is a potent cyclo-oxygenase inhibitor (Nawaz et al., 2007). Mefenamic (MA) acid also has therapeutic potential in Alzheimer's disease (Joo et al., 2006). Masking the free carboxylic group in MA like other NSAIDs could suppress the side effect such as gastrointestinal toxicity (Arun & Ashok, 2009; Tammara et al., 1994). On other hand, hydrazide-hydrazone compounds are found to be associated with various biological activities such as antimicrobial, anti-convulsant, analgesic, anti-inflammatory, anti-platelet, anti-tubercular and anti-tumor properties (Bedia et al., 2006; Rollas et al., 2002; Palaska et al., 2002; Rollas & Küçükgüzel, 2007). Based on such facts, and as part of our ongoing study on the functionalization of (NSAIDs), we report herein the synthesis and the crystal structure of the title compound.

The asymmetric unit of the title compound consists of two independent molecules (A and B) having differing conformations. Differences reside mainly in the dihedral angles which the hydroxyphenyl and dimethylphenyl rings make with the central phenylene ring, being 30.16 (6) and 58.60 (6)° in one of the molecules (A) and 13.42 (7) and 60.31 (7)° in the remaining one (B). With the exception of the dimethyphenyl substituent, the conformations of the rest of each molecule are largely determined by intramolecular O—H···N and N—H···O hydrogen bonds (Fig. 1 and Table 1). Intermolecular N—H···O hydrogen bonds form chains extending parallel to the a axis (Fig. 2 and Table 1) where molecules on both types alternate in a.. A···B···A···B.. fashion.

S2. Experimental

A mixture of equimolar ratio of Mefenamic acid hydrazide (1 mmol, 255 mg) and salicaldehyde (1 mmol, 122 mg) with catalytic amount of glacial acetic acid was refluxed for 5 h. On cooling, the precipitate was separated then collected and recrystallized from ethanol to furnish the title compound as brown crystals with m.p= 457–459 K.