1-(1-Benzoylpropen-2-yl)-3-methylisothiosemicarbazide

The structure of the title S-alkyl­ated iso­thio­semicarbazide, C₁₂H₁₅N₃OS, was determined by single-crystal diffractometry and compared with the structures of other compounds containing the S-alkyl­thio­semicarbazide moiety. Such structures cluster into two groups, according to the different orientation of the –SR group with respect to the hydrazine N atom of the thio­semicarbazide. The cis arrangement is preferred by most mol­ecules in the solid state, in spite of the possibility of intramolecular N—H...N interactions in the opposite orientation.

S1. Comment

Thiosemicarbazones represent an important class of potential ligands for complexing metal cations to obtain coordination compounds of biomedical relevance (Campbell, 1975; Padhyé & Kauffman, 1985; West et al., 1993; Casas et al., 2000). Thiosemicarbazide itself, N¹H₂—N²H—C(═S)—N³H₂ (thsc), behaves as both a monodentate and a bidentate ligand. In the first case, coordination occurs through the S atom, while in the second case it occurs through the S and the N¹ atom. Thsc derivatives having additional coordinating functionalities can further act as tridentate ligands, and bis(thiosemicarbazones) can be used as tetra- and pentadentate ligands.

When the S atom is alkylated, such as in S-alkylisothiosemicarbazide, N¹H₂—N²═C(—SR)—N³H₂ (SR-thsc), and its derivatives R¹N¹H—N²═C(—SR)—N³H₂ or R¹N¹H—N²═C(—SR)—N³HR², coordination systematically occurs through the two terminal N atoms, due to a decrease in the donor ability of S after alkylation (Gerbeleu et al., 1999).

In the solid state, the thiosemicarbazide backbone is usually almost planar, allowing, in some cases, extended π-charge delocalization. In thsc (Andreetti et al., 1970) and its derivatives, the S atom is trans to the N¹ hydrazine N atom, thus placing the N¹ and N³ atoms in suitable positions for intramolecular hydrogen bonding (Chattopadhyay et al., 1989; Casas et al., 2000). On the other hand, SR-thsc compounds prefer the Z form (Shova et al., 1985; Gerbeleu et al., 1999; Casas et al., 2000), and are then subjected to reorientation in the E form on complexation to a central atom, allowing N¹,N³-chelation.

In this work, we report on the structure of the tridentate ligand 1-(1-benzoylpropen2-yl)-3-methylisothiosemicarbazide, (I). This ligand has been used to prepare square-planar Ni^II complexes, the synthesis, structure and physicochemical characterization of which have been reported elsewhere (Gradinaru et al., 2002). \sch

A perspective view of (I) is shown in Fig. 1. The crystal structure consists of near-planar molecules where a strong intramolecular N1—H1···O interaction takes place (Table 1).

The phenyl ring is tilted by 9.97 (6)° with respect to the least-squares plane of the atoms O, C5, C6, C7 and N1. A similar rotation was observed in the above-mentioned Ni^II complexes (Gradinaru et al., 2002) and in the complex [Ni(HL²)py] (where HL² is 1-phenylbutane-1,3-dione mono-S-methylisothiosemicarbazone; Bogdanović et al., 1999), where it was ascribed to the balancing of two opposite effects, firstly H···H repulsion (H6···H3 = 2.04 Å) and secondly, the formation of an intramolecular C11—H11···O hydrogen bond (Table 1). A significantly greater value of this angle, equal to 23.41°, was obtained from RHF/6–31G** geometry optimization of the gas-phase isolated molecule (Frisch et al., 1998), indicating that packing forces, besides intramolecular effects, contribute to determine the orientation of the phenyl ring in the solid state.

The planarity of the molecular backbone of (I) allows an extended conjugation along the benzoylacetoniminate arm, with shortened C5—C6 and C7—N1 single bonds and lengthened C5═O and C6═C7 double bonds [1.400 (3), 1.327 (3), 1.267 (3) and 1.370 (3) Å, respectively]. In order to characterize the SR-thsc moiety, the geometry of (I) was compared with that of molecules having the N—N═C(SC)N fragment, the structures of which were retrieved from the Cambridge Structural Database (CSD; April 2001 release; Allen et al., 1983). The search was performed using the criteria of an agreement index R < 0.1, no disorder and only organic compounds. Structures where C, N or S atoms of the requested fragment were constrained by formation of a ring were obviously excluded from this search. Since only a restricted number of structures were retrieved (17), comprising both protonated [DITRAZ (Shova et al., 1985) and MITCHZ (Bigoli et al., 1978)] and neutral molecules (all the other compounds), the relevant bond lengths and torsion angles are presented in Table 2 for comparison, together with the corresponding values for (I). Please check the added references are the correct ones. A study of corresponding bond lengths across all 18 compounds indicates a large variation in the geometry of the SR-thsc fragment, due to the differing extent of the degree of conjugation. In the case of (I), the long N1—N2 bond and the short N2═C1 distance, corresponding to the minimum value observed for this bond within the SR-thsc series, denote scarce conjugation.

On examining the N1—N2═C1—S torsion angles reported in Table 2, the above-mentioned preference of SR-thsc derivatives towards the cis orientation of the –SR group with respect to atom N1 (Z configuration) is evidenced.

It is noteworthy that in SR-thsc derivatives, atom C8 is preferentially coplanar with the molecular backbone, as indicated by the N3—C1—S—C8 torsion angles in Table 2, but significant deviation from planarity is observed for some derivatives.

An inspection of the structures reported in Table 2 indicates that, in all cases, the E configuration should allow the formation of one or more intramolecular N—H···N bonds, with the only exception of DISKIZ (Reference?), where no N—H potential donor is present. In compound (I), which is one of the few trans derivatives, atom N3 acts as both donor and acceptor (Table 1).

These considerations suggest that, as a rule, other intra- and/or intermolecular effects do prevail over a possible N—H···N interaction in fixing the orientation of the –SR group in SR-thsc derivatives. A theoretical investigation of some representative structures, aimed at discerning the relative importance of intra- and intermolecular forces in determining the relative stability of the two conformations, is in progress.

S2. Experimental

All reagents were commercially available. The C, H, N analysis was carried out by standard micromethods. The IR spectrum was recorded as a KBr disc (4000–400 cm^-1) using a Perkin-Elmer FT—IR spectrometer 1720X. The electronic spectra were recorded on a UVIKON 930 spectrophotometer (190–900 nm). The mass spectrometric analysis was performed with a Finnigan LCQ mass spectrometer using electrospray ionization and a Finnigan MAT 958 double-focusing mass spectrometer using electron ionosation (70 ev) and standard resolution conditions, m/Δm = 2300. Melting points were determined with a Buchi 510 apparatus.

The synthesis of (I) was carried out according to the procedure reported by Leovac et al. (1994). Crystals were obtained by dissolving a mixture of benzoylacetone (3.25 g, 20 mmol) and S-methylisothiosemicarbazide hydrogen iodide (4.60 g, 20 mmol) in ethanol (15 ml) with heating. An NaOH solution (1.2 g in 15 ml H₂O) was added to the reaction mixture at room temperature. The next day, yellow crystals of (I) were filtrated, washed with water and ethanol, and dried in air (yield 2.3 g, 46.12%; m.p. 363–365 K). Analysis found: C 57.56, H 5.83, N 17.07%; calculated for C₁₂H₁₅N₃OS: C 57.81, H 6.06, N 16.85%. ESI mass spectrum: m/z = 249 (I, 100%), [M]⁺. EI mass spectrum: m/z = 249 (I, 36.4%), [M]⁺; 202 (I, 9.5%), [M - SCH₃]⁺; 234 (I, 4.3%), [M - CH₃]⁺; 216 (I, 2.5%), [M - SH]. IR data: 1535–1600 cm^-1 (C═O, C═N and C═C); 3313 and 3189 cm^-1 (NH₂); 1637 cm^-1 (NH₂). Compound (I) gave two bands in the near ultraviolet region at 371–385 nm and 244–248 nm, in agreement with what has been reported for a series of vinylogous amides, i.e., β-amino α,β-unsaturated ketones, –N—RC═CR'-C(O)- (Ostercamp, 1970) [λ_max, nm (ε, dm³ cm^-1 mol^-1): 376 (13892) and 245 (16844) in n-hexane; 385 (10275) and 248 (17200) in chloroform; 382 (16400) and 244 (11504) in acetonitrile; 384 (10892) and 247 (11032) in methanol; 371 (4159) and 248 (13710) in water].

S3. Refinement

H atoms were treated as riding, with N—H = 0.86 Å and C—H = 0.93–0.96 Å, and with U_iso(H) = 1.2 or 1.5U_eq of the parent atom. Are these the correct constraints?

Computing details

Data collection: SMART (Bruker, 1997); cell refinement: SAINT (Bruker, 1997); data reduction: SAINT; program(s) used to solve structure: SIR92 (Altomare et al.,1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: SHELXL97 and PARST (Nardelli, 1995).

Figures

Fig. 1. A view of the molecule of (I) with atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii.

1-(1-Benzoylpropen2-yl)-3-methylisothiosemicarbazide

Crystal data

C12H15N3OS	F(000) = 528
Mr = 249.33	Dx = 1.325 Mg m^−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
a = 8.932 (1) Å	Cell parameters from 1875 reflections
b = 5.324 (1) Å	θ = 2.4–23.1°
c = 26.316 (2) Å	µ = 0.25 mm^−1
β = 92.80 (1)°	T = 288 K
V = 1249.9 (3) Å^3	Prism, yellow
Z = 4	0.32 × 0.13 × 0.08 mm

Data collection

Bruker SMART Apex area-detector diffractometer	2858 independent reflections
Radiation source: fine-focus sealed tube	1566 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.036
ω scans	θmax = 27.5°, θmin = 1.6°
Absorption correction: multi-scan (SADABS in SAINT; Bruker, 1997)	h = −11→11
Tmin = 0.858, Tmax = 1.000	k = −6→6
11930 measured reflections	l = −33→34

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)] = 0.050	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.151	H-atom parameters constrained
S = 0.88	w = 1/[σ^2(Fo^2) + (0.0866P)^2] where P = (Fo^2 + 2Fc^2)/3
2858 reflections	(Δ/σ)max < 0.001
154 parameters	Δρmax = 0.33 e Å^−3
0 restraints	Δρmin = −0.25 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 > 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
S	0.72212 (8)	−0.11508 (13)	−0.11368 (2)	0.0650 (3)
O	0.5825 (2)	−0.3019 (3)	0.10011 (7)	0.0680 (5)
N1	0.7209 (2)	−0.0502 (4)	0.03292 (7)	0.0580 (5)
H1	0.6639	−0.1750	0.0395	0.070*
N2	0.7548 (2)	−0.0042 (4)	−0.01687 (7)	0.0566 (5)
N3	0.5951 (2)	−0.3419 (4)	−0.03965 (8)	0.0762 (7)
H3A	0.5746	−0.3761	−0.0088	0.091*
H3B	0.5560	−0.4297	−0.0643	0.091*
C1	0.6893 (3)	−0.1490 (5)	−0.04943 (9)	0.0538 (6)
C2	0.5835 (3)	−0.1658 (4)	0.18553 (9)	0.0520 (6)
C3	0.6207 (3)	0.0079 (5)	0.22269 (9)	0.0646 (7)
H3	0.6856	0.1384	0.2155	0.078*
C4	0.5637 (3)	−0.0074 (6)	0.27045 (10)	0.0724 (8)
H4	0.5906	0.1116	0.2951	0.087*
C5	0.6340 (3)	−0.1454 (5)	0.13273 (9)	0.0545 (6)
C6	0.7328 (3)	0.0449 (5)	0.11928 (9)	0.0582 (7)
H6	0.7734	0.1461	0.1453	0.070*
C7	0.7742 (2)	0.0936 (4)	0.07081 (8)	0.0490 (6)
C8	0.8304 (4)	0.1644 (5)	−0.11397 (11)	0.0809 (9)
H8A	0.8556	0.2024	−0.1482	0.121*
H8B	0.9207	0.1414	−0.0931	0.121*
H8C	0.7736	0.3005	−0.1007	0.121*
C9	0.4684 (3)	−0.1962 (6)	0.28136 (10)	0.0707 (8)
H9	0.4282	−0.2056	0.3132	0.085*
C10	0.4321 (3)	−0.3720 (6)	0.24518 (11)	0.0796 (9)
H10	0.3674	−0.5021	0.2527	0.096*
C11	0.4899 (3)	−0.3596 (5)	0.19783 (10)	0.0686 (7)
H11	0.4655	−0.4833	0.1739	0.082*
C12	0.8779 (3)	0.3000 (5)	0.05865 (10)	0.0705 (8)
H12A	0.8921	0.3016	0.0227	0.106*
H12B	0.9727	0.2744	0.0767	0.106*
H12C	0.8362	0.4576	0.0686	0.106*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S	0.0756 (5)	0.0696 (5)	0.0507 (4)	0.0015 (4)	0.0124 (3)	0.0033 (3)
O	0.0780 (12)	0.0660 (11)	0.0608 (10)	−0.0115 (10)	0.0122 (9)	−0.0128 (9)
N1	0.0599 (12)	0.0622 (13)	0.0528 (12)	−0.0061 (10)	0.0125 (10)	0.0030 (10)
N2	0.0589 (12)	0.0620 (13)	0.0493 (11)	−0.0024 (11)	0.0076 (10)	0.0007 (10)
N3	0.0817 (16)	0.0959 (19)	0.0515 (12)	−0.0290 (14)	0.0082 (11)	0.0012 (12)
C1	0.0480 (13)	0.0602 (15)	0.0539 (14)	0.0026 (12)	0.0087 (11)	0.0038 (12)
C2	0.0484 (13)	0.0551 (15)	0.0525 (13)	0.0064 (12)	0.0017 (11)	0.0052 (11)
C3	0.0710 (17)	0.0646 (16)	0.0594 (16)	−0.0080 (14)	0.0144 (13)	−0.0016 (13)
C4	0.0811 (19)	0.0806 (19)	0.0564 (16)	−0.0020 (17)	0.0133 (14)	−0.0080 (14)
C5	0.0533 (14)	0.0558 (15)	0.0542 (14)	0.0048 (12)	0.0012 (11)	−0.0030 (12)
C6	0.0550 (14)	0.0664 (17)	0.0531 (14)	−0.0058 (13)	0.0006 (11)	−0.0048 (12)
C7	0.0452 (12)	0.0529 (14)	0.0485 (13)	−0.0007 (11)	−0.0016 (10)	−0.0016 (11)
C8	0.110 (2)	0.0616 (18)	0.0737 (19)	−0.0069 (17)	0.0291 (17)	0.0084 (14)
C9	0.0684 (18)	0.088 (2)	0.0565 (16)	0.0040 (16)	0.0118 (14)	0.0127 (15)
C10	0.078 (2)	0.086 (2)	0.0747 (19)	−0.0185 (17)	0.0069 (16)	0.0226 (17)
C11	0.0791 (19)	0.0664 (17)	0.0599 (16)	−0.0144 (15)	0.0005 (14)	0.0057 (13)
C12	0.0699 (18)	0.0773 (19)	0.0643 (16)	−0.0130 (15)	0.0041 (13)	0.0024 (14)

Geometric parameters (Å, º)

S—C1	1.739 (2)	C4—H4	0.9300
S—C8	1.775 (3)	C5—C6	1.400 (3)
O—C5	1.267 (3)	C6—C7	1.370 (3)
N1—C7	1.327 (3)	C6—H6	0.9300
N1—N2	1.381 (3)	C7—C12	1.482 (3)
N1—H1	0.8600	C8—H8A	0.9600
N2—C1	1.274 (3)	C8—H8B	0.9600
N3—C1	1.361 (3)	C8—H8C	0.9600
N3—H3A	0.8600	C9—C10	1.363 (4)
N3—H3B	0.8600	C9—H9	0.9300
C2—C3	1.375 (3)	C10—C11	1.373 (4)
C2—C11	1.377 (3)	C10—H10	0.9300
C2—C5	1.486 (3)	C11—H11	0.9300
C3—C4	1.381 (3)	C12—H12A	0.9600
C3—H3	0.9300	C12—H12B	0.9600
C4—C9	1.357 (4)	C12—H12C	0.9600
C1—S—C8	102.05 (13)	C5—C6—H6	117.5
C7—N1—N2	121.5 (2)	N1—C7—C6	119.2 (2)
C7—N1—H1	119.2	N1—C7—C12	118.1 (2)
N2—N1—H1	119.2	C6—C7—C12	122.8 (2)
C1—N2—N1	114.6 (2)	S—C8—H8A	109.5
C1—N3—H3A	120.0	S—C8—H8B	109.5
C1—N3—H3B	120.0	H8A—C8—H8B	109.5
H3A—N3—H3B	120.0	S—C8—H8C	109.5
N2—C1—N3	126.7 (2)	H8A—C8—H8C	109.5
N2—C1—S	119.85 (19)	H8B—C8—H8C	109.5
N3—C1—S	113.41 (19)	C4—C9—C10	119.4 (3)
C3—C2—C11	117.7 (2)	C4—C9—H9	120.3
C3—C2—C5	122.8 (2)	C10—C9—H9	120.3
C11—C2—C5	119.4 (2)	C9—C10—C11	120.9 (3)
C2—C3—C4	121.4 (3)	C9—C10—H10	119.5
C2—C3—H3	119.3	C11—C10—H10	119.5
C4—C3—H3	119.3	C10—C11—C2	120.6 (3)
C9—C4—C3	119.9 (3)	C10—C11—H11	119.7
C9—C4—H4	120.0	C2—C11—H11	119.7
C3—C4—H4	120.0	C7—C12—H12A	109.5
O—C5—C6	121.1 (2)	C7—C12—H12B	109.5
O—C5—C2	117.9 (2)	H12A—C12—H12B	109.5
C6—C5—C2	120.9 (2)	C7—C12—H12C	109.5
C7—C6—C5	125.1 (2)	H12A—C12—H12C	109.5
C7—C6—H6	117.5	H12B—C12—H12C	109.5

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O	0.86	1.91	2.581 (3)	134
N1—H1···N3	0.86	2.32	2.667 (3)	104
N3—H3A···N1	0.86	2.40	2.667 (3)	98
C11—H11···O	0.93	2.45	2.757 (4)	99
N3—H3B···O^i	0.86	2.08	2.898 (3)	157
N3—H3A···N3^i	0.86	2.52	3.228 (4)	140
C9—H9···S^ii	0.93	2.89	3.751 (3)	155

Symmetry codes: (i) −x+1, −y−1, −z; (ii) x−1/2, −y−1/2, z+1/2.