N′-[(E)-2-Chloro­benzyl­idene]-2-(6-meth­oxy­naphthalen-2-yl)propano­hydrazide

Joel T Mague; Shaaban K Mohamed; Mehmet Akkurt; Herman Potgieter; Mustafa R Albayati

doi:10.1107/S1600536814008629

. 2014 May 3;70(Pt 6):o631–o632. doi: 10.1107/S1600536814008629

N′-[(E)-2-Chlorobenzylidene]-2-(6-methoxynaphthalen-2-yl)propanohydrazide

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

PMCID: PMC4051055 PMID: 24940221

Abstract

In the title compound, C₂₁H₁₉ClN₂O₂, the benzene ring and the naphthalene ring system are oriented at a dihedral angle of 65.24 (10)°. In the crystal, N—H⋯O, C—H⋯N and C—H⋯O hydrogen bonds link the molecules, forming chains along the b-axis direction. Further C—H⋯O hydrogen bonds link the chains, forming corrugated sheets lying parallel to (10-1).

Related literature

For the use of Naproxen [systematic name: (+)-(S)-2-(6-methoxynaphthalen-2-yl)propanoic acid] and hydrazide-hydrazones in the treatment of disease and inflammation, see: Merlet et al. (2013 ▶); Almasirad et al. (2005 ▶, 2006 ▶). For the harmful side-effects of non-steroidal anti-inflammatory drugs (NSAIDs), see: Uzgören-Baran et al. (2012 ▶); Tozkoparan et al. (2012 ▶). For the synthesis of NSAIDS with safer pro-drug profiles and enhanced chromphore efficacy, see: Koopaei et al. (2013 ▶). For bond-length data, see: Allen et al. (1987 ▶).

Experimental

Crystal data

C₂₁H₁₉ClN₂O₂
M _r = 366.83
Monoclinic,
a = 6.5703 (2) Å
b = 8.6166 (2) Å
c = 16.3411 (4) Å
β = 98.6850 (9)°
V = 914.52 (4) Å³
Z = 2
Cu Kα radiation
μ = 1.99 mm⁻¹
T = 100 K
0.23 × 0.09 × 0.02 mm

Data collection

Bruker D8 VENTURE PHOTON 100 CMOS diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2013 ▶) T _min = 0.87, T _max = 0.96
13492 measured reflections
3243 independent reflections
3122 reflections with I > 2σ(I)
R _int = 0.030

Refinement

R[F ² > 2σ(F ²)] = 0.026
wR(F ²) = 0.064
S = 1.05
3243 reflections
237 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.20 e Å⁻³
Δρ_min = −0.12 e Å⁻³
Absolute structure: Flack parameter determined using 1358 quotients [(I ⁺)−(I ⁻)]/[(I ⁺)+(I ⁻)] (Parsons et al., 2013 ▶)
Absolute structure parameter: 0.056 (5)

Data collection: APEX2 (Bruker, 2013 ▶); cell refinement: SAINT (Bruker, 2013 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXT (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL (Sheldrick, 2008 ▶); molecular graphics: DIAMOND (Brandenburg & Putz, 2012 ▶); software used to prepare material for publication: SHELXTL (Sheldrick, 2008 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536814008629/sj5398sup1.cif

e-70-0o631-sup1.cif^{(27KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536814008629/sj5398Isup2.hkl

e-70-0o631-Isup2.hkl^{(178KB, hkl)}

Click here for additional data file.^{(6.9KB, cml)}

Supporting information file. DOI: 10.1107/S1600536814008629/sj5398Isup3.cml

CCDC reference: 997601

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
N1—H1⋯O2ⁱ	0.91	1.93	2.829 (2)	169
C12—H12⋯N2ⁱ	1.00	2.48	3.444 (3)	163
C15—H15⋯O2ⁱ	0.95	2.48	3.259 (3)	139
C19—H19⋯O1ⁱⁱ	0.95	2.57	3.486 (3)	163

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

The support of NSF–MRI grant No. 1228232 for the purchase of the diffractometer is gratefully acknowledged.

supplementary crystallographic information

1. Comment

Naproxen ((+)-(S)-2-(6-methoxynaphthalen-2-yl)propanoic acid), among many non-steroidal anti-inflammatory drugs (NSAIDs), is used mainly in the treatment of pain, rehumatiod and inflammatory diseases (Merlet et al., 2013). It was reported that the presence of a carboxylic acid group in the parent drug leads to many undesirable side-effects such as gastrointestinal toxicity and ulceration (Uzgören-Baran et al., 2012; Tozkoparan et al., 2012). Recently, it was found that masking the carboxylic acid residue in the parent drug of NSAIDs led to safer pro-drug profiles and enhanced the chromophore efficacy (Koopaei et al., 2013). On the other hand, hydrazide-hydrazone scaffold compounds have been found to possess significant anti-inflammatory effects (Almasirad et al., 2005; Almasirad et al., 2006). Based on these findings the title compound was designed to be a hydrazone profile incorporating the Naproxen core structure without a carboxylic acid substituent.

The naphthalene ring system of the title compound (I, Fig.-1) is essentialy planar [maximum deviation = 0.025 (2) Å for C7 and -0.022 (2) Å for C9]. The dihedral angle between the mean planes of the naphthalene and phenyl groups is 65.24 (10)°. The C1–O1–C2–C11, C6–C7–C12–C13, C7–C12–C14–O2, C7–C12–C14–N1, C12–C14–N1–N2, O2–C14–N1–N2 and C14–N1–N2–C15 torsion angles are -3.6 (3), 28.5 (3), 82.8 (2), -95.9 (2), 177.67 (18), -3.6 (3) and 177.4 (2) °, respectively. In (I), the bond lengths (Allen et al., 1987) and angles are within normal ranges.

In the crystal structure, the N—H···O and C—H···N hydrogen bonds link the molecules, forming chains along the b-axis (Table 1 and Fig. 2). However, sensible C—H···O contacts are also present that link molecules into chains along c and extend the packing along the c axis.

2. Experimental

A mixture of 1 mmol (244 mg) Naproxen acid hydrazide [2-(6-methoxy-2-naphthyl)propanehydrazide] and 1 mmol (141 mg) 2-chlorobenzaldehyde was refluxed in 30 ml ethanol for 5hr in the presence of a few catalytic drops of glacial acetic acid. The mixture was cooled and separated, the solid filtered off, dried under vacuum and recrytallized from ethanol to furnish white crystals in a good quality suitable for X-ray diffraction. Mp 488–451 K.