3-(2-Pyridyl)-N'-salicylidenepropionohydrazide

The Schiff base-type title compound, C₁₅H₁₅N₃O₂, was obtained by the reaction of 3-(2-pyrid­yl)propionohydrazide with salicylaldehyde in ethanol. Whereas the ¹H NMR spectrum in solution points to a mixture of two isomers, only one isomer was found in the solid state. The phenolic OH group forms an intra­molecular hydrogen bond with the imino N atom. Inter­molecular hydrogen bonds between the amido NH function and the pyridyl N atom join the mol­ecules into chains parallel to the a axis. The compound is achiral, but crystallizes in the space group P2₁2₁2₁, with the mol­ecule adopting a chiral conformation.

Key indicators

• Single-crystal X-ray study
• T = 183 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.035
• wR factor = 0.087
• Data-to-parameter ratio = 9.9

checkCIF/PLATON results

No syntax errors found



Alert level B
PLAT063_ALERT_3_B Crystal Probably too Large for Beam Size .......       0.90 mm

Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           27.46
           From the CIF: _reflns_number_total               1793
           Count of symmetry unique reflns         1797
           Completeness (_total/calc)             99.78%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured         0
           Fraction of Friedel pairs measured     0.000
           Are heavy atom types Z>Si present         no

   0 ALERT level A = In general: serious problem
   1 ALERT level B = Potentially serious problem
   0 ALERT level C = Check and explain
   1 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   1 ALERT type 3 Indicator that the structure quality may be low
   1 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. Comment

N-Salicylidenehydrazides and their metal complexes show a wide range of biological activities (Johnson et al., 1982; Mohan et al., 1987a; Koh et al., 1998; Mohan et al., 1987b; Ainscough et al., 1999}. Most of the N-salicylidenehydrazide ligands reported so far provide hydrophobic alkylic or arylic side chains. However, in the past few years, new Schiff-base ligands bearing hydroxy and amino functions in the side chains have been synthesized to enable assembly of molecules in the crystal via hydrogen-bond interactions (Nica et al., 2005; Pohlmann et al., 2005; Becher et al., 2006; Roth et al., 2007). In this paper we report the crystal structure of the new Schiff-base ligand N-salicylidene-3-(2-pyridyl)-propionic acid hydrazide (H₂salhypyp).

The compound was obtained by Schiff-base reaction of 3-(2-pyridyl)-propionic acid hydrazide with salicylaldehyde in ethanol. The NMR spectra revealed a splitting of most signals, indicating the presence of two isomers in solution, probably caused by cis/trans isomerization of the amide function. According to the ¹H NMR spetra (DMSO, 300 K), the ratio of isomers is 1.8:1. The crystal structure of H₂salhypyp revealed only one isomer, with trans configuration of the amide group (Fig. 1). The phenolic O–H group forms an intramolecular hydrogen bond to the imino nitrogen atom N1. Intermolecular hydrogen bonds between the amido N–H function and the pyridyl nitrogen N3 join the molecules into chains parallel to the a axis. H₂salhypyp, which is achiral, crystallizes in the orthorhombic space group P2₁2₁2₁, with the molecules adopting a chiral conformation.

Related literature

For related literature on N-salicylidenehydrazides and their metal complexes, see: Johnson et al. (1982); Mohan et al. (1987a,b); Koh et al. (1998); Ainscough et al. (1999); Nica et al. (2005); Pohlmann et al. (2005); Becher et al. (2006); Roth et al. (2007). For synthetic procedures, see: Walter et al. (1941); Doering et al. (1947); Hallinan et al. (1993).

S2. Experimental

IR spectra were measured on a Bruker IFS55/Equinox spectrometer. Mass spectra were carried out on a MATSSQ-710 Bruker instrument. Elemental analyses were acquired by use of a LECO CHN/932 elemental analyzer. NMR spectra were recorded on a Bruker Avance 400 MHz s pectrometer.

3-(2-Pyridyl)-propionic acid hydrazide was prepared according to described methods, i.e. reaction of potassium cyanide with 2-(2-pyridyl)-ethylbromide (Walter et al., 1941), hydrolysis of 3-(2-pyridyl)-propionitrile with hydrochloric acid (Doering et al., 1947), acid catalyzed esterification of 3-(2-pyridyl)-propionic acid in dry ethanol, and hydrazinolysis of the corresponding ethylester (Hallinan et al., 1993).

3-(2-Pyridyl)-propionic acid hydrazide (650 mg, 3.94 mmol) dissolved in 10 ml e thanol was reacted at RT with one equivalent of salicylaldehyde and stirred for 1 h. The title compound (920 mg, 3.43 mmol) was obtained as microcrystalline colourless solid after leaving the reaction solution at 277 K over night. Recrystallization from ethanol (slow evaporation) lead to single crytals suitable for X-ray crystallography. The NMR spectra indicate the existence of two isomers in solution. C₁₅H₁₅N₃O₂ (269.3): calcd. C 66.90, H 5.6, N 15.60, found C 66.95, H 5.59, N 15.92. IR (KBr): 3156 (ν(N–H)), 1684 (Amid I and ν(C═N)) cm^{-1. 1}H-NMR (DMSO, 400 MHz): 2.68 (t, ³J=7.50 Hz, CH₂–CO, major isomer); 3.06 (m, CH₂–py, both isomers, and CH₂–CO, minor isomer); 6.86 (2H, m, HC_Ph); 7.24 (3H, m, 2 HC_py and 1 HC_Ph); 7.47 and 7.58 (1H, m, HC_Ph); 7.68 (1H, m, HC_py); 8.26 and 8.33 (1H, s, HC═N); 8.47 (1H, m, HC_py); 10.12 and 11.17 (1H, s, NH); 11.24 and 11.66 (1H, s, OH) p.p.m.. ¹³C-NMR (DMSO, 50 MHz): 31.3, 31.9, 32.4, and 32.9 (CH₂–py and CH₂–CO, both isomers); 116.1 and 116.3 (C_Ph), 118.6 and 119.9 (C_Ph), 119.2 and 119.4 (C_Ph), 121.2 and 121.3 (C_py), 122.8 (C_Ph), 126.8 and 129.4 (C_Ph), 130.8 and 131.1 (C_Ph), 136.3 and 136.4 (C_py), 141.0 and 146.4 (C═N), 148.9 (C_py), 156.3 and 157.3 (C–OH), 160.0 and 160.5 (C_py), 167.8 and 173.1 (C═O) p.p.m.. MS (EI): m/z = 269 (M⁺), 134 (100%, [py–CH₂–CH₂–CO]⁺), 106 ([py–CH₂–CH₂]⁺).

S3. Refinement

H atoms were positioned geometrically, C(sp²) –H = 0.95 Å, C(methylene)–H = 0.99 Å, O–H = 0.84 Å and N–H = 0.88 Å, and treated as riding atoms with displacement parameters, U_iso(H) = xU_eq(C), where x = 1.5 for O–H and 1.2 for all others. In the absence of significant anomalous scattering effects, Friedel pairs were averaged prior to the final refinement and the absolute structure was not determined.

Computing details

Data collection: COLLECT (Nonius 1998); cell refinement: DENZO (Otwinowski & Minor, 1997); data reduction: DENZO; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XP (Siemens, 1990); software used to prepare material for publication: SHELXL97.

Figures

	Fig. 1. Molecular structure of H2salpyph. Displacement ellipsoids are drawn at the 50% probability level. Hydrogen bonds are shown with dashed line.
	Fig. 2. Chains of H2salpyph molecules formed via N—H···N hydrogen bonding. Hydrogen bonds are shown with dashed lines. Only H atoms from the N—H and O—H groups are shown.

N'-(2-Hydroxybenzylidene)-3-(2-pyridyl)propionohydrazide

Crystal data

C15H15N3O2	F(000) = 568
Mr = 269.30	Dx = 1.333 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 1793 reflections
a = 5.6638 (2) Å	θ = 2.6–27.5°
b = 15.1845 (5) Å	µ = 0.09 mm^−1
c = 15.5994 (4) Å	T = 183 K
V = 1341.58 (7) Å^3	Prism, colourless
Z = 4	0.9 × 0.8 × 0.4 mm

Data collection

Nonius KappaCCD area-detector diffractometer	1592 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.040
Graphite monochromator	θmax = 27.5°, θmin = 2.6°
φ and ω scans	h = −7→6
9539 measured reflections	k = −18→19
1793 independent reflections	l = −20→20

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.035	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.087	H-atom parameters constrained
S = 1.06	w = 1/[σ^2(Fo^2) + (0.0423P)^2 + 0.2563P] where P = (Fo^2 + 2Fc^2)/3
1793 reflections	(Δ/σ)max < 0.001
182 parameters	Δρmax = 0.15 e Å^−3
0 restraints	Δρmin = −0.17 e Å^−3

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > 2σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	0.0597 (2)	0.55099 (9)	0.02570 (8)	0.0313 (3)
H1	0.0539	0.5574	0.0792	0.047*
O2	0.2491 (3)	0.54059 (11)	0.25857 (9)	0.0450 (4)
N1	−0.1275 (3)	0.59566 (9)	0.17046 (9)	0.0271 (3)
N2	−0.1174 (3)	0.60063 (10)	0.25852 (9)	0.0289 (4)
H2	−0.2369	0.6212	0.2885	0.035*
N3	0.5681 (3)	0.72701 (10)	0.34594 (9)	0.0297 (4)
C1	−0.1289 (3)	0.59146 (11)	−0.01074 (11)	0.0260 (4)
C2	−0.1355 (4)	0.59712 (12)	−0.10001 (12)	0.0311 (4)
H2A	−0.0104	0.5733	−0.1333	0.037*
C3	−0.3244 (4)	0.63740 (13)	−0.13968 (12)	0.0353 (5)
H3	−0.3287	0.6405	−0.2005	0.042*
C4	−0.5084 (4)	0.67347 (13)	−0.09247 (13)	0.0345 (5)
H4	−0.6372	0.7012	−0.1207	0.041*
C5	−0.5022 (4)	0.66865 (12)	−0.00396 (12)	0.0306 (4)
H5	−0.6273	0.6936	0.0285	0.037*
C6	−0.3142 (3)	0.62750 (11)	0.03849 (11)	0.0256 (4)
C7	−0.3087 (3)	0.62669 (12)	0.13202 (11)	0.0279 (4)
H7	−0.4383	0.6490	0.1640	0.033*
C8	0.0833 (4)	0.57268 (12)	0.29746 (11)	0.0283 (4)
C9	0.0853 (4)	0.58529 (12)	0.39373 (11)	0.0288 (4)
H9A	0.0566	0.5280	0.4222	0.035*
H9B	−0.0435	0.6259	0.4103	0.035*
C10	0.3216 (3)	0.62271 (12)	0.42386 (11)	0.0284 (4)
H10A	0.3242	0.6225	0.4873	0.034*
H10B	0.4496	0.5834	0.4038	0.034*
C11	0.3724 (3)	0.71506 (11)	0.39298 (10)	0.0240 (4)
C12	0.2289 (4)	0.78513 (12)	0.41561 (12)	0.0322 (4)
H12	0.0887	0.7750	0.4475	0.039*
C13	0.2894 (4)	0.86972 (13)	0.39182 (13)	0.0389 (5)
H13	0.1929	0.9182	0.4078	0.047*
C14	0.4915 (4)	0.88287 (13)	0.34455 (13)	0.0381 (5)
H14	0.5389	0.9403	0.3276	0.046*
C15	0.6227 (4)	0.80995 (13)	0.32266 (12)	0.0362 (5)
H15	0.7604	0.8187	0.2890	0.043*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0280 (7)	0.0345 (7)	0.0314 (6)	0.0050 (6)	0.0022 (6)	−0.0032 (5)
O2	0.0366 (9)	0.0611 (10)	0.0375 (7)	0.0196 (8)	0.0029 (7)	−0.0125 (7)
N1	0.0303 (9)	0.0258 (7)	0.0251 (7)	0.0002 (7)	0.0025 (7)	−0.0022 (6)
N2	0.0299 (9)	0.0330 (8)	0.0237 (7)	0.0046 (8)	0.0035 (7)	−0.0039 (6)
N3	0.0266 (8)	0.0333 (8)	0.0293 (7)	0.0028 (7)	0.0031 (7)	−0.0002 (6)
C1	0.0260 (9)	0.0208 (8)	0.0311 (9)	−0.0023 (8)	0.0006 (8)	−0.0001 (6)
C2	0.0322 (11)	0.0305 (9)	0.0307 (9)	−0.0016 (9)	0.0049 (8)	−0.0025 (7)
C3	0.0425 (12)	0.0348 (10)	0.0285 (9)	−0.0014 (10)	−0.0009 (9)	0.0011 (7)
C4	0.0353 (11)	0.0320 (9)	0.0363 (10)	0.0011 (9)	−0.0050 (9)	0.0032 (8)
C5	0.0278 (10)	0.0285 (9)	0.0354 (10)	0.0002 (8)	0.0014 (8)	−0.0018 (7)
C6	0.0270 (10)	0.0205 (8)	0.0293 (9)	−0.0024 (8)	0.0012 (8)	−0.0010 (6)
C7	0.0293 (10)	0.0238 (8)	0.0306 (9)	−0.0011 (8)	0.0037 (8)	−0.0017 (7)
C8	0.0283 (10)	0.0261 (8)	0.0304 (9)	0.0016 (8)	0.0006 (8)	−0.0038 (7)
C9	0.0307 (10)	0.0278 (9)	0.0277 (9)	−0.0014 (8)	0.0017 (8)	0.0006 (7)
C10	0.0303 (10)	0.0258 (9)	0.0292 (9)	0.0015 (8)	−0.0030 (8)	0.0031 (7)
C11	0.0249 (9)	0.0268 (8)	0.0204 (7)	0.0007 (8)	−0.0016 (7)	−0.0002 (6)
C12	0.0332 (10)	0.0312 (9)	0.0324 (9)	0.0037 (9)	0.0111 (9)	−0.0003 (8)
C13	0.0494 (13)	0.0265 (9)	0.0408 (11)	0.0067 (10)	0.0058 (10)	−0.0007 (8)
C14	0.0485 (13)	0.0298 (10)	0.0358 (10)	−0.0072 (10)	−0.0002 (10)	0.0050 (8)
C15	0.0334 (11)	0.0443 (11)	0.0309 (9)	−0.0055 (10)	0.0063 (9)	0.0050 (8)

Geometric parameters (Å, º)

O1—C1	1.357 (2)	C5—H5	0.9500
O1—H1	0.8400	C6—C7	1.459 (2)
O2—C8	1.219 (2)	C7—H7	0.9500
N1—C7	1.279 (2)	C8—C9	1.514 (2)
N1—N2	1.377 (2)	C9—C10	1.528 (3)
N2—C8	1.357 (3)	C9—H9A	0.9900
N2—H2	0.8800	C9—H9B	0.9900
N3—C11	1.342 (2)	C10—C11	1.510 (2)
N3—C15	1.347 (3)	C10—H10A	0.9900
C1—C2	1.396 (2)	C10—H10B	0.9900
C1—C6	1.411 (3)	C11—C12	1.385 (3)
C2—C3	1.379 (3)	C12—C13	1.380 (3)
C2—H2A	0.9500	C12—H12	0.9500
C3—C4	1.389 (3)	C13—C14	1.376 (3)
C3—H3	0.9500	C13—H13	0.9500
C4—C5	1.383 (3)	C14—C15	1.376 (3)
C4—H4	0.9500	C14—H14	0.9500
C5—C6	1.401 (3)	C15—H15	0.9500
C1—O1—H1	109.5	N2—C8—C9	114.24 (17)
C7—N1—N2	118.75 (16)	C8—C9—C10	111.02 (16)
C8—N2—N1	117.65 (16)	C8—C9—H9A	109.4
C8—N2—H2	121.2	C10—C9—H9A	109.4
N1—N2—H2	121.2	C8—C9—H9B	109.4
C11—N3—C15	117.62 (17)	C10—C9—H9B	109.4
O1—C1—C2	117.85 (17)	H9A—C9—H9B	108.0
O1—C1—C6	122.21 (15)	C11—C10—C9	114.47 (15)
C2—C1—C6	119.94 (18)	C11—C10—H10A	108.6
C3—C2—C1	119.73 (19)	C9—C10—H10A	108.6
C3—C2—H2A	120.1	C11—C10—H10B	108.6
C1—C2—H2A	120.1	C9—C10—H10B	108.6
C2—C3—C4	121.29 (17)	H10A—C10—H10B	107.6
C2—C3—H3	119.4	N3—C11—C12	121.37 (17)
C4—C3—H3	119.4	N3—C11—C10	117.23 (16)
C5—C4—C3	119.29 (19)	C12—C11—C10	121.34 (17)
C5—C4—H4	120.4	C13—C12—C11	120.05 (18)
C3—C4—H4	120.4	C13—C12—H12	120.0
C4—C5—C6	120.99 (19)	C11—C12—H12	120.0
C4—C5—H5	119.5	C14—C13—C12	119.05 (19)
C6—C5—H5	119.5	C14—C13—H13	120.5
C5—C6—C1	118.76 (16)	C12—C13—H13	120.5
C5—C6—C7	119.51 (17)	C13—C14—C15	117.72 (19)
C1—C6—C7	121.65 (17)	C13—C14—H14	121.1
N1—C7—C6	119.29 (17)	C15—C14—H14	121.1
N1—C7—H7	120.4	N3—C15—C14	124.16 (19)
C6—C7—H7	120.4	N3—C15—H15	117.9
O2—C8—N2	123.18 (16)	C14—C15—H15	117.9
O2—C8—C9	122.58 (18)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···N1	0.84	1.85	2.585 (2)	145
N2—H2···N3^i	0.88	2.15	2.952 (2)	152

Symmetry code: (i) x−1, y, z.