Di-2-pyridyl ketone 4-methyl-4-phenyl­thio­semicarbazone

The mol­ecule of the title compound, C₁₉H₁₇N₅S, adopts a Z configuration about the azomethine bond and exists as the thione tautomer. The overall structure of the mol­ecule is distributed in four different planes. An intramolecular hydrogen bond involving the pyridyl N atom and the H atom attached to the hydrazine N atom leads to the formation of a six-membered ring.

S1. Comment

Thiosemicarbazones are an important group of multidentate ligands with potential binding sites available for a wide variety of metal ions. These thiourea derivatives find substantial applications in different facets of contemporary scientific research. Biological activity depends on the parent aldehyde or ketone (Padhye & Kauffman, 1985; Lukevics et al., 1995) and their potential use as antimicrobial agents was first recognized with N⁴-substituted 2-acetylpyridine thiosemicarbazones (Klayman et al., 1979). The versatile antimicrobial nature of thiosemicarbazones and their metal complexes has been the focus of our research for the past decade, with successful single-crystal X-ray diffraction studies having been conducted for many of these compounds (John et al., 2002; Sreekanth & Kurup, 2003; Sreekanth et al., 2004; Philip et al., 2004).

The present report of the title compound, (I), is the first report of a di-2-pyridyl ketone thiosemicarbazone in which the N⁴-position of the thiosemicarbazone moiety is disubstituted. The compound is also found to exist in the cis-conformation, ZZ. There is only one previous report of a similar di-2-pyridyl ketone N⁴-methylthiosemicarbazone, which is monosubstituted at the N⁴-position (Swearingen & West, 2001) but is perceived to exist in a ZE conformation. Previously, we have reported a di-2-pyridyl ketone thiosemicarbazone that was also found to exist in the ZZ conformation (Usman et al., 2002), in which the N⁴-position forms part of a pentamethyleneimine five-membered ring. Similar conformations are also observed when a piperidyl or hexamethyleneiminyl ring occupies the N⁴-position (Swearingen et al., 2002). However, there are no previous observations of a ZZ conformation in mono/disubstituted thiosemicarbazones of di-2-pyridyl ketone.

A perspective view of the molecular structure of (I), along with the atom-labeling scheme, is given in Fig. 1. A ZZ conformation is exhibited by the molecule, since cis configurations are adopted with respect to the C6—N3 and C12—N4 bonds. The S1—C12—N4—N3 torsion angle value [−5.8 (3)°] indicates that thiocarbonyl atom S1 is positioned cis to hydrazine atom N3. Compound (I) exhibits the least deviation between the planes of the thiosemicarbazone moiety and the coordinating pyridyl ring among the di-2-pyridyl ketone and benzoylpyridine thiosemicarbazones; the lower value of 16.98 (5)° for the dihedral angle between the thiosemicarbazone moiety and the pyridyl ring (Cg2, comprising atoms C7–C11 and N2) for (I) can be compared with the corresponding values of 23.56 (9) and 28.14 (8)° for di-2-pyridyl ketone N⁴,N⁴-(butane-1,4-diyl)thiosemicarbazone (Usman et al., 2002) and 2-benzoylpyridine-N⁴,N⁴-(butane-1,4-diyl) thiosemicarbazone (Sreekanth & Kurup, 2004).

The molecule of (I) consists of four fragments, viz. two planar pyridine rings (Cg1, comprising atoms C1–C5 and N1, and Cg2), the phenyl ring (Cg3) and the thiosemicarbazone moiety. The four different planes associated with the structure of (I) are shown in Figs. 1 and 2. The thiosemicarbazone (TSC) moiety, comprising atoms N3, N4, C12, S1 and N5, is almost planar, the maximum deviation being 0.0449 (15) Å for atom N4, and the view along the TSC axis substantiates the non-planar nature of the molecule. The two pyridyl rings, Cg1 and Cg2, are also planar, with maximum deviations of −0.0097 (19) and −0.0124 (31) Å for atoms C5 and C10, respectively, and are inclined at a dihedral angle of 46.09 (7)°. The phenyl ring is planar, having an r.m.s. deviation from the mean plane of 0.0060 (23) Å, while the value of the C13—N5—C12—S1 torsion angle [−178.90 (15)°] implies the trans alignment of the phenyl ring with respect to the thiosemicarbazone moiety. The phenyl ring is twisted significantly from the thiosemicarbazone plane, with a dihedral angle of 81.74 (5)° between the corresponding least-squares planes.

The thiosemicarbazone moiety adopts an extended conjugation, with electron delocalization along the N5/C12/S1/N4/N3 group. The fact that the compound exists in the thione form is confirmed by the N3—N4, N4—C12 and C12—S1 bond distances (Table 1). The C12—S1 bond distance is close to that expected for a C=S double bond (1.60 Å; Huheey et al., 1993). The potential resonance forms of the structure observed as a result of extended conjugation are depicted in the scheme. The N3—N4 bond distance in (I) is shorter than the corresponding distance of 1.44 Å in unsubstituted thiosemicarbazides (Palenik et al., 1974). The resonance form involving pyridine ring Cg1 would account for the shortening of the N—N distance through extensive electron delocalization, which suggests that canonical form (III) might exist. The net result would be a small negative charge residing on pyridine atom N1, which is reported to be important in terms of biological activity (Restivo & Palenik, 1970; Gabe et al., 1969).

An intramolecular N4—H4···N2 hydrogen bond leads to the formation of a six-membered ring comprising atom N2, C7, C6, N3, N4 and H4. In determining the stability and structure of the molecule, some weak C—H···π interactions are observed (Table 2). The packing arrangement of adjacent molecules in an offset fashion contributes towards minimizing any repulsive interations of the bulky pyridyl groups. Table 2. Hydrogen bonding and C—H···π interactions in (1) (for definitions see text).

S2. Experimental

A solution of di-2-pyridyl ketone (10 mmol, 1.84 g) in methanol (5 ml) was treated with of N⁴-methyl, N⁴-phenyl-thiosemicarbazide (1.81 g, 10 mmol) in methanol (25 ml) and refluxed for 2 h. On slow evaporation at room temperature, bright-yellow crystals of the title compound separated out. These crystals were collected, washed with methanol and dried over P₄O₁₀ in vacuo. Single crystals of (I) suitable for X-ray analysis were obtained by slow evaporation from a methanol solution. Analyses found: C 66.11, H 4.98, N 19.94%; calculated: C 65.70, H 4.89, N 20.17%.

S3. Refinement

H atoms were located in a difference Fourier map and refined using a riding model, with U_iso(H) values of 1.2U_eq of the parent atom. The H atoms of the methyl group (C19), being disordered, were constrained geometrically over six sites (each with an occupancy factor of 1/2).

Computing details

Data collection: CAD-4 ARGUS Software (Nonius, 1996)?; cell refinement: CAD-4 ARGUS Software; data reduction: CAD-4 ARGUS Software; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP Version? (reference?); software used to prepare material for publication: SHELXL97.

Figures

	Fig. 1. An ORTEP diagram of (I); displacement ellipsoids are drawn at the 50% probability level. H atoms attached to atom C19 each have an occupancy of 0.5.
	Fig. 2. An ORTEP view of (I), along the thiosemicarbazone axis; displacement ellipsoids are drawn at the 10% probability level.

Di-2-pyridyl ketone 4-methyl-4-phenylthiosemicarbazone

Crystal data

C19H17N5S	Z = 2
Mr = 347.44	F(000) = 364
Triclinic, P1	Dx = 1.301 Mg m^−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 9.3059 (10) Å	Cell parameters from 25 reflections
b = 9.4966 (10) Å	θ = 2.0–25.0°
c = 10.5689 (10) Å	µ = 0.19 mm^−1
α = 92.544 (1)°	T = 293 K
β = 99.256 (1)°	Block, light green
γ = 104.917 (1)°	0.28 × 0.23 × 0.23 mm
V = 887.18 (16) Å^3

Data collection

Enraf–Nonius CAD-4 diffractometer	Rint = 0.011
Radiation source: fine-focus sealed tube	θmax = 25.0°, θmin = 2.0°
Graphite monochromator	h = −11→10
ω/q scan	k = 0→11
3316 measured reflections	l = −12→12
3111 independent reflections	3 standard reflections every 3600 min
2251 reflections with I > 2σ(I)	intensity decay: 2%

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.037	H-atom parameters constrained
wR(F^2) = 0.104	w = 1/[σ^2(Fo^2) + (0.0496P)^2 + 0.2064P] where P = (Fo^2 + 2Fc^2)/3
S = 1.02	(Δ/σ)max < 0.001
3111 reflections	Δρmax = 0.16 e Å^−3
228 parameters	Δρmin = −0.20 e Å^−3
0 restraints	Extinction correction: SHELXL97, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.012 (2)

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 > σ(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	Occ. (<1)
S1	0.20140 (7)	0.14408 (5)	0.23881 (6)	0.0589 (2)
N1	0.82768 (18)	0.40967 (18)	0.11140 (17)	0.0502 (4)
N2	0.5963 (2)	0.66304 (19)	0.28148 (19)	0.0685 (6)
N3	0.46739 (17)	0.36099 (16)	0.18314 (15)	0.0390 (4)
N4	0.37638 (16)	0.41769 (15)	0.24711 (15)	0.0402 (4)
H4	0.3954	0.5106	0.2650	0.048*
N5	0.17828 (18)	0.38998 (16)	0.35478 (16)	0.0442 (4)
C1	0.9047 (2)	0.3274 (2)	0.0599 (2)	0.0571 (6)
H1	1.0095	0.3615	0.0744	0.069*
C2	0.8399 (3)	0.1974 (2)	−0.0120 (2)	0.0565 (6)
H2	0.8988	0.1441	−0.0448	0.068*
C3	0.6852 (3)	0.1472 (2)	−0.0349 (2)	0.0635 (6)
H3	0.6371	0.0596	−0.0849	0.076*
C4	0.6020 (2)	0.2284 (2)	0.0171 (2)	0.0549 (6)
H4A	0.4971	0.1963	0.0028	0.066*
C5	0.6774 (2)	0.3588 (2)	0.09130 (18)	0.0384 (4)
C6	0.5909 (2)	0.44410 (19)	0.15681 (17)	0.0376 (4)
C7	0.6508 (2)	0.6050 (2)	0.18792 (19)	0.0417 (5)
C8	0.7519 (2)	0.6927 (2)	0.1217 (2)	0.0519 (5)
H8	0.7865	0.6515	0.0552	0.062*
C9	0.8005 (3)	0.8414 (2)	0.1557 (3)	0.0655 (7)
H9	0.8686	0.9014	0.1125	0.079*
C10	0.7480 (3)	0.8995 (3)	0.2529 (3)	0.0867 (9)
H10	0.7806	0.9992	0.2784	0.104*
C11	0.6456 (4)	0.8074 (3)	0.3123 (3)	0.0989 (12)
H11	0.6083	0.8476	0.3776	0.119*
C12	0.2532 (2)	0.32346 (19)	0.28260 (18)	0.0389 (4)
C13	0.2227 (2)	0.54592 (19)	0.39031 (18)	0.0394 (5)
C14	0.3310 (2)	0.6033 (2)	0.4974 (2)	0.0514 (5)
H14	0.3781	0.5427	0.5454	0.062*
C15	0.3695 (3)	0.7527 (2)	0.5335 (2)	0.0622 (6)
H15	0.4427	0.7927	0.6057	0.075*
C16	0.2990 (3)	0.8410 (2)	0.4620 (2)	0.0597 (6)
H16	0.3253	0.9411	0.4857	0.072*
C17	0.1905 (3)	0.7830 (2)	0.3565 (2)	0.0602 (6)
H17	0.1431	0.8438	0.3089	0.072*
C18	0.1505 (3)	0.6342 (2)	0.3197 (2)	0.0501 (5)
H18	0.0759	0.5945	0.2483	0.060*
C19	0.0463 (3)	0.3068 (2)	0.4045 (3)	0.0699 (7)
H19A	0.0077	0.3727	0.4523	0.105*	0.50
H19B	0.0754	0.2377	0.4599	0.105*	0.50
H19C	−0.0306	0.2555	0.3340	0.105*	0.50
H19D	0.0274	0.2045	0.3785	0.105*	0.50
H19E	−0.0404	0.3396	0.3709	0.105*	0.50
H19F	0.0656	0.3217	0.4968	0.105*	0.50

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0583 (4)	0.0267 (3)	0.0913 (5)	0.0032 (2)	0.0287 (3)	−0.0053 (3)
N1	0.0363 (9)	0.0506 (10)	0.0630 (11)	0.0112 (8)	0.0115 (8)	−0.0091 (8)
N2	0.0796 (14)	0.0393 (9)	0.0793 (14)	−0.0126 (9)	0.0463 (12)	−0.0201 (9)
N3	0.0359 (8)	0.0371 (8)	0.0443 (9)	0.0082 (7)	0.0129 (7)	−0.0042 (7)
N4	0.0402 (9)	0.0278 (7)	0.0533 (10)	0.0048 (6)	0.0196 (8)	−0.0045 (7)
N5	0.0446 (9)	0.0293 (8)	0.0605 (11)	0.0037 (7)	0.0263 (8)	−0.0004 (7)
C1	0.0421 (12)	0.0599 (14)	0.0734 (16)	0.0170 (10)	0.0191 (11)	−0.0036 (12)
C2	0.0586 (14)	0.0517 (12)	0.0694 (15)	0.0254 (11)	0.0262 (12)	−0.0033 (11)
C3	0.0624 (15)	0.0481 (13)	0.0783 (17)	0.0125 (11)	0.0179 (13)	−0.0177 (11)
C4	0.0401 (11)	0.0492 (12)	0.0717 (15)	0.0073 (9)	0.0121 (11)	−0.0151 (11)
C5	0.0382 (10)	0.0384 (10)	0.0401 (11)	0.0113 (8)	0.0107 (8)	0.0000 (8)
C6	0.0356 (10)	0.0386 (10)	0.0372 (10)	0.0072 (8)	0.0084 (8)	−0.0012 (8)
C7	0.0352 (10)	0.0403 (10)	0.0481 (12)	0.0057 (8)	0.0122 (9)	−0.0024 (9)
C8	0.0466 (12)	0.0486 (12)	0.0672 (14)	0.0147 (10)	0.0257 (11)	0.0071 (10)
C9	0.0525 (14)	0.0444 (12)	0.102 (2)	0.0034 (10)	0.0350 (14)	0.0129 (12)
C10	0.0860 (19)	0.0417 (13)	0.122 (2)	−0.0150 (12)	0.0482 (18)	−0.0183 (14)
C11	0.119 (2)	0.0475 (14)	0.119 (2)	−0.0224 (15)	0.075 (2)	−0.0369 (15)
C12	0.0377 (10)	0.0311 (9)	0.0476 (11)	0.0057 (8)	0.0132 (9)	0.0020 (8)
C13	0.0421 (11)	0.0322 (9)	0.0455 (11)	0.0055 (8)	0.0209 (9)	−0.0008 (8)
C14	0.0546 (13)	0.0490 (12)	0.0508 (13)	0.0159 (10)	0.0085 (10)	−0.0016 (10)
C15	0.0629 (15)	0.0577 (14)	0.0560 (14)	0.0055 (12)	0.0053 (12)	−0.0170 (11)
C16	0.0758 (16)	0.0348 (11)	0.0659 (15)	0.0044 (11)	0.0258 (13)	−0.0108 (11)
C17	0.0816 (17)	0.0390 (11)	0.0617 (15)	0.0177 (11)	0.0150 (13)	0.0040 (11)
C18	0.0595 (13)	0.0416 (11)	0.0462 (12)	0.0102 (10)	0.0074 (10)	−0.0020 (9)
C19	0.0667 (15)	0.0481 (12)	0.101 (2)	0.0022 (11)	0.0538 (15)	0.0041 (13)

Geometric parameters (Å, º)

S1—C12	1.6685 (18)	C9—C10	1.360 (3)
N1—C5	1.335 (2)	C9—H9	0.9300
N2—C7	1.340 (2)	C10—C11	1.371 (3)
N3—C6	1.295 (2)	C10—H10	0.9300
N3—N4	1.361 (2)	C11—H11	0.9300
N4—C12	1.377 (2)	C13—C14	1.375 (3)
N5—C13	1.446 (2)	C13—C18	1.377 (3)
N5—C19	1.468 (2)	C14—C15	1.391 (3)
C5—C6	1.499 (2)	C14—H14	0.9300
C6—C7	1.487 (2)	C15—C16	1.372 (3)
N1—C1	1.340 (2)	C15—H15	0.9300
N4—H4	0.8600	C16—C17	1.366 (3)
C1—C2	1.361 (3)	C16—H16	0.9300
C1—H1	0.9300	C17—C18	1.385 (3)
C2—C3	1.372 (3)	C17—H17	0.9300
C2—H2	0.9300	C18—H18	0.9300
C3—C4	1.380 (3)	C19—H19A	0.9600
C3—H3	0.9300	C19—H19B	0.9600
C4—C5	1.390 (3)	C19—H19C	0.9600
C4—H4A	0.9300	C19—H19D	0.9600
C7—C8	1.388 (3)	C19—H19E	0.9600
C8—C9	1.379 (3)	C19—H19F	0.9600
C8—H8	0.9300
C6—N3—N4	120.87 (15)	N2—C11—C10	123.6 (2)
N3—N4—C12	118.72 (14)	N2—C11—H11	118.2
C12—N5—C13	123.01 (14)	C10—C11—H11	118.2
C12—N5—C19	121.59 (15)	C14—C13—C18	120.81 (18)
C13—N5—C19	115.39 (15)	C14—C13—N5	119.76 (18)
N1—C5—C6	117.68 (16)	C18—C13—N5	119.36 (18)
N3—C6—C7	127.07 (16)	C13—C14—C15	119.4 (2)
N3—C6—C5	112.18 (16)	C13—C14—H14	120.3
C7—C6—C5	120.73 (15)	C15—C14—H14	120.3
N5—C12—N4	113.74 (15)	C16—C15—C14	119.7 (2)
N5—C12—S1	123.48 (13)	C16—C15—H15	120.1
N4—C12—S1	122.77 (14)	C14—C15—H15	120.1
C5—N1—C1	117.26 (17)	C17—C16—C15	120.5 (2)
C11—N2—C7	118.16 (18)	C17—C16—H16	119.8
N3—N4—H4	120.6	C15—C16—H16	119.8
C12—N4—H4	120.6	C16—C17—C18	120.4 (2)
N1—C1—C2	124.4 (2)	C16—C17—H17	119.8
N1—C1—H1	117.8	C18—C17—H17	119.8
C2—C1—H1	117.8	C13—C18—C17	119.1 (2)
C1—C2—C3	118.12 (19)	C13—C18—H18	120.5
C1—C2—H2	120.9	C17—C18—H18	120.5
C3—C2—H2	120.9	N5—C19—H19A	109.5
C2—C3—C4	119.1 (2)	N5—C19—H19B	109.5
C2—C3—H3	120.4	H19A—C19—H19B	109.5
C4—C3—H3	120.4	N5—C19—H19C	109.5
C3—C4—C5	119.04 (19)	H19A—C19—H19C	109.5
C3—C4—H4A	120.5	H19B—C19—H19C	109.5
C5—C4—H4A	120.5	N5—C19—H19D	109.5
N1—C5—C4	122.00 (17)	H19A—C19—H19D	141.1
C4—C5—C6	120.27 (17)	H19B—C19—H19D	56.3
N2—C7—C8	121.09 (17)	H19C—C19—H19D	56.3
N2—C7—C6	115.84 (16)	N5—C19—H19E	109.5
C8—C7—C6	123.01 (17)	H19A—C19—H19E	56.3
C9—C8—C7	119.34 (19)	H19B—C19—H19E	141.1
C9—C8—H8	120.3	H19C—C19—H19E	56.3
C7—C8—H8	120.3	H19D—C19—H19E	109.5
C10—C9—C8	119.4 (2)	N5—C19—H19F	109.5
C10—C9—H9	120.3	H19A—C19—H19F	56.3
C8—C9—H9	120.3	H19B—C19—H19F	56.3
C9—C10—C11	118.3 (2)	H19C—C19—H19F	141.1
C9—C10—H10	120.8	H19D—C19—H19F	109.5
C11—C10—H10	120.8	H19E—C19—H19F	109.5
C6—N3—N4—C12	−174.50 (17)	N2—C7—C8—C9	2.0 (3)
N4—N3—C6—C5	177.49 (16)	C6—C7—C8—C9	179.2 (2)
C13—N5—C12—S1	−178.90 (15)	C7—C8—C9—C10	−0.3 (4)
N3—N4—C12—S1	−5.8 (3)	C8—C9—C10—C11	−1.2 (5)
C5—N1—C1—C2	0.8 (3)	C7—N2—C11—C10	0.4 (5)
N1—C1—C2—C3	0.7 (4)	C9—C10—C11—N2	1.2 (6)
C1—C2—C3—C4	−1.1 (4)	C13—N5—C12—N4	0.6 (3)
C2—C3—C4—C5	0.0 (4)	C19—N5—C12—N4	−178.36 (19)
C1—N1—C5—C4	−1.9 (3)	C19—N5—C12—S1	2.2 (3)
C1—N1—C5—C6	175.37 (18)	N3—N4—C12—N5	174.70 (16)
C3—C4—C5—N1	1.5 (3)	C12—N5—C13—C14	−85.3 (2)
C3—C4—C5—C6	−175.7 (2)	C19—N5—C13—C14	93.6 (2)
N4—N3—C6—C7	−0.7 (3)	C12—N5—C13—C18	97.8 (2)
N1—C5—C6—N3	−149.49 (18)	C19—N5—C13—C18	−83.2 (2)
C4—C5—C6—N3	27.8 (3)	C18—C13—C14—C15	−1.0 (3)
N1—C5—C6—C7	28.9 (3)	N5—C13—C14—C15	−177.86 (18)
C4—C5—C6—C7	−153.86 (19)	C13—C14—C15—C16	0.1 (3)
C11—N2—C7—C8	−2.0 (4)	C14—C15—C16—C17	0.6 (3)
C11—N2—C7—C6	−179.4 (3)	C15—C16—C17—C18	−0.3 (4)
N3—C6—C7—N2	19.8 (3)	C14—C13—C18—C17	1.3 (3)
C5—C6—C7—N2	−158.3 (2)	N5—C13—C18—C17	178.15 (18)
N3—C6—C7—C8	−157.5 (2)	C16—C17—C18—C13	−0.6 (3)
C5—C6—C7—C8	24.4 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N4—H4···N2	0.86	2.03	2.642 (2)	128
C4—H4A···Cg(2)^i	0.93	2.87	3.487 (2)	125
C11—H11···Cg(3)	0.93	3.32	3.871 (4)	120

Symmetry code: (i) −x+1, −y+1, −z.