t-3-Iso­propyl-1-methyl-r-2,c-6-di­phenyl­piperidin-4-one thio­semi­carbazone

The piperidine ring in the title compound, C₂₂H₂₈N₄S, exhibits a chair conformation. The thio­semicarbazone moiety adopts an extended conformation, and the planar phenyl rings are oriented equatorially with respect to the piperidine ring. Two intermol­ecular hydrogen bonds involving the S atom form molecular pairs, and the crystal structure is stabilized by weak C-H...[pi] interactions in addition to van der Waals forces.

S1. Comment

Thiosemicarbazone (TSC) derivatives of Schiff-base compounds containing N—S donor chromophores and metal complexes exhibit non-linear optical properties (Tian et al., 1997; Duan et al., 1996; Liu et al., 1999). The wide range of biological activities possessed by these substituted thiosemicarbazones include antitumour and antileukemic properties (French & Blanz, 1966; Agarwal et al., 1972), antibacterial and antiviral activities (Nandi et al., 1986; Chattopadhyay et al., 1987), and antimalarial activities (Klayman et al., 1979). The fact that heterocyclic thiosemicarbazones possess antitumour properties is partly related to their ability to inhibit the ribonucleoside diphosphate reductase (RDR) enzyme, which is essential in DNA synthesis (Moore et al., 1970). The biological activity of these N,S donor ligands has been correlated with their metal-chelating abilities (Kirschner et al., 1966) and reductive capacity (Palenik et al., 1974). As a part of our study of thiosemicarbazone derivatives, the title compound, (I), was prepared and the crystal structure was determined to establish the conformational features of various functional groups.

The bond lengths of the thiosemicarbazone moiety (Fig. 1 and Table 1) show resonance character when compared with the typical lengths of single and double bonds in cyclohexanone thiosemicarbazone (Casas et al., 2001). The fact that the least-squares plane consists of atoms C4, N10, N11, C12, N13 and S1 [maximum deviation = −0.064 (19) Å] clearly supports the resonance effect in this moiety (Scheme 2). The thiosemicarbazone moiety adopts an extended conformation, as evidenced by the torsion angles listed in Table 1. The trans configuration of the thiocarbonyl S atom with respect to the hydrazinic N atom is evident from the S1—C12—N11—N10 torsion angle of −175.5 (2)°, in accordance with unprotonated thiosemicarbazones (Chattopadhyay et al., 1987).

The C14–C19 (A) and C20–C25 (B) phenyl rings are planar and oriented at angles of 63.4 (7)° and 81.8 (3)° to the plane of the piperidine ring. The torsion angles, asymmetry parameters and least-squares plane calculation show that the piperidine ring adopts a chair conformation (QT=0.534; Nardelli, 1995). Atoms N1, C2, C4 and C5 constitute the best-fitting plane of the piperidine ring, and atoms C3 and C6 deviate by 0.652 (2) Å and −0.607 (2) Å, respectively, on either side of the plane.

The isopropyl group is equatorially substituted at the 5-position of the piperidine ring, as confirmed by the torsion angles (Table 1). The imine N atom is cis to the isopropyl group, and the N-methyl group is equatorially substituted at the 1-position of the piperidine ring. Parthasarathi et al. (1986) reported a related structure with similar substitution, which leads to equatorial orientation.

Pairs of intermolecular N—H···S hydrogen bond across the center of inversion result in the formation of dimers, a common feature that is observed in similar thiosemicarbazone compounds (Palenik et al., 1974; Restivo & Palenik, 1970). An intramolecular N13—H13A···N10 hydrogen bond (Table 2) facilitates? the formation of a five membered ring. Interestingly, two C—H···π (Desiraju, 1989) interactions stabilize the crystal structure in (I), viz. the C8—H8···Cg1ⁱⁱ and C24—H24···Cg1ⁱⁱⁱ interactions (see Table 2 for symmetry codes and geometric parameters), where Cg1 is the centroid of ring A.

S2. Experimental

The title compound, (I), was synthesized by the Mannich condensation reaction. Benzaldehyde, 2-methyl-4-pentanone and methylamine in a 2:1:1 molar ratio were treated (Noller & Baliah, 1948) in ethyl alcohol (99%), refluxed for 1 h and left overnight. Colorless crystals were recrystallized from ethanol. The resulting compound was treated with thiosemicarbazide (1 mol) in ethanol and refluxed for 6 h. A purified sample of (I) was recrystallized from ethanol by slow evoporation. Good quality crystals were selected for structural studies.

S3. Refinement

All the H atoms were fixed geometrically and allowed to ride on their corresponding non-H atoms.

Computing details

Data collection: SMART (Siemens, 2000); cell refinement: SAINT (Siemens, 2000); data reduction: SAINT (Siemens, 2000); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ZORTEP (Zsolnai, 1998) and PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97 and PARST (Nardelli, 1995).

Figures

	Fig. 1. ZORTEP (Zsolnai, 1998) diagram of (I), showing displacement ellipsoids at the 50% probability level. Ring A contains atoms C14–C19 and ring B contains atoms C20–C25.
	Fig. 2. The crystal packing of (I), viewed along the b axis. Dashed lines represent hydrogen bonds.

1-N-Methyl-t-3-isopropyl-r-2,c-6-diphenylpiperidone Thiosemicarbazone

Crystal data

C22H28N4S	F(000) = 816
Mr = 380.55	Dx = 1.149 Mg m^−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
a = 11.1794 (17) Å	Cell parameters from 4891 reflections
b = 10.0720 (16) Å	θ = 2.0–27.9°
c = 19.591 (3) Å	µ = 0.16 mm^−1
β = 94.317 (3)°	T = 293 K
V = 2199.7 (6) Å^3	Needle, colorless
Z = 4	0.40 × 0.36 × 0.24 mm

Data collection

Siemens SMART CCD area detector diffractometer	3490 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.053
Graphite monochromator	θmax = 27.9°, θmin = 2.0°
ω scans	h = −14→14
23481 measured reflections	k = −12→13
4891 independent reflections	l = −25→24

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)] = 0.064	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.154	H-atom parameters constrained
S = 1.07	w = 1/[σ^2(Fo^2) + (0.0674P)^2 + 0.3252P] where P = (Fo^2 + 2Fc^2)/3'
4891 reflections	(Δ/σ)max < 0.001
244 parameters	Δρmax = 0.31 e Å^−3
0 restraints	Δρmin = −0.14 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
S1	0.87389 (5)	0.62864 (5)	0.05643 (3)	0.0602 (2)
N1	1.20047 (15)	1.23460 (16)	0.18267 (8)	0.0489 (4)
C2	1.09113 (19)	1.15872 (19)	0.19209 (11)	0.0508 (5)
H2	1.1117	1.0841	0.2229	0.061*
C3	1.03793 (19)	1.1038 (2)	0.12424 (12)	0.0541 (6)
H3A	0.9692	1.0486	0.1321	0.065*
H3B	1.0106	1.1766	0.0946	0.065*
C4	1.12863 (18)	1.02354 (19)	0.08989 (10)	0.0475 (5)
C5	1.24152 (17)	1.09914 (19)	0.07923 (10)	0.0457 (5)
H5	1.2164	1.1745	0.0500	0.055*
C6	1.29236 (18)	1.1608 (2)	0.14770 (10)	0.0481 (5)
H6	1.3232	1.0890	0.1779	0.058*
C7	1.33780 (18)	1.0258 (2)	0.04102 (10)	0.0502 (5)
H7	1.4043	1.0888	0.0388	0.060*
C8	1.3921 (2)	0.9021 (2)	0.07686 (13)	0.0641 (6)
H8A	1.4196	0.9239	0.1231	0.096*
H8B	1.4584	0.8711	0.0528	0.096*
H8C	1.3323	0.8337	0.0771	0.096*
C9	1.2935 (2)	0.9976 (2)	−0.03316 (11)	0.0618 (6)
H9A	1.2615	1.0776	−0.0540	0.093*
H9B	1.2321	0.9309	−0.0343	0.093*
H9C	1.3592	0.9667	−0.0578	0.093*
N10	1.11988 (15)	0.90296 (16)	0.06982 (9)	0.0504 (4)
N11	1.01446 (15)	0.83461 (16)	0.07729 (10)	0.0572 (5)
H11	0.9566	0.8712	0.0969	0.069*
C12	1.00414 (19)	0.70923 (19)	0.05313 (11)	0.0488 (5)
N13	1.10012 (17)	0.66045 (19)	0.02694 (12)	0.0795 (7)
H13A	1.1639	0.7080	0.0261	0.095*
H13B	1.0990	0.5811	0.0107	0.095*
C14	0.99709 (19)	1.2431 (2)	0.22341 (10)	0.0501 (5)
C15	0.9337 (2)	1.1945 (2)	0.27554 (12)	0.0643 (6)
H15	0.9509	1.1103	0.2930	0.077*
C16	0.8448 (2)	1.2696 (3)	0.30220 (13)	0.0770 (8)
H16	0.8024	1.2350	0.3372	0.092*
C17	0.8187 (2)	1.3935 (3)	0.27775 (14)	0.0755 (8)
H17	0.7598	1.4443	0.2964	0.091*
C18	0.8798 (2)	1.4423 (3)	0.22569 (13)	0.0719 (7)
H18	0.8611	1.5263	0.2082	0.086*
C19	0.9689 (2)	1.3692 (2)	0.19852 (12)	0.0614 (6)
H19	1.0103	1.4044	0.1633	0.074*
C20	1.39508 (19)	1.2528 (2)	0.13467 (11)	0.0513 (5)
C21	1.3733 (2)	1.3710 (2)	0.10059 (13)	0.0678 (7)
H21	1.2949	1.3963	0.0877	0.081*
C22	1.4679 (3)	1.4525 (3)	0.08530 (15)	0.0937 (10)
H22	1.4529	1.5323	0.0624	0.112*
C23	1.5828 (3)	1.4151 (4)	0.1040 (2)	0.1087 (14)
H23	1.6461	1.4690	0.0930	0.130*
C24	1.6058 (3)	1.3001 (4)	0.1386 (2)	0.1006 (11)
H24	1.6845	1.2761	0.1517	0.121*
C25	1.5123 (2)	1.2189 (3)	0.15409 (13)	0.0730 (7)
H25	1.5284	1.1403	0.1779	0.088*
C26	1.2535 (2)	1.2789 (3)	0.25018 (13)	0.0772 (8)
H26A	1.3245	1.3300	0.2443	0.116*
H26B	1.2739	1.2028	0.2782	0.116*
H26C	1.1965	1.3327	0.2720	0.116*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0608 (4)	0.0414 (3)	0.0807 (4)	−0.0143 (3)	0.0213 (3)	−0.0090 (3)
N1	0.0543 (10)	0.0453 (10)	0.0481 (10)	−0.0085 (8)	0.0096 (8)	−0.0110 (8)
C2	0.0606 (13)	0.0401 (11)	0.0531 (13)	−0.0011 (10)	0.0140 (10)	−0.0016 (9)
C3	0.0505 (12)	0.0467 (12)	0.0663 (14)	−0.0079 (9)	0.0124 (10)	−0.0162 (10)
C4	0.0479 (12)	0.0423 (11)	0.0530 (12)	−0.0065 (9)	0.0091 (9)	−0.0108 (9)
C5	0.0497 (12)	0.0399 (11)	0.0482 (12)	−0.0070 (9)	0.0075 (9)	−0.0049 (9)
C6	0.0526 (12)	0.0430 (11)	0.0490 (12)	−0.0047 (9)	0.0058 (9)	−0.0042 (9)
C7	0.0485 (12)	0.0508 (12)	0.0528 (12)	−0.0093 (9)	0.0131 (9)	−0.0101 (10)
C8	0.0555 (14)	0.0642 (15)	0.0737 (16)	0.0035 (11)	0.0127 (12)	−0.0046 (12)
C9	0.0636 (15)	0.0675 (15)	0.0563 (13)	−0.0081 (12)	0.0169 (11)	−0.0127 (12)
N10	0.0472 (10)	0.0420 (9)	0.0634 (11)	−0.0091 (8)	0.0139 (8)	−0.0128 (8)
N11	0.0504 (10)	0.0423 (10)	0.0818 (13)	−0.0105 (8)	0.0233 (9)	−0.0195 (9)
C12	0.0532 (12)	0.0365 (10)	0.0574 (13)	−0.0041 (9)	0.0082 (10)	−0.0039 (9)
N13	0.0587 (12)	0.0473 (11)	0.136 (2)	−0.0126 (9)	0.0293 (12)	−0.0362 (12)
C14	0.0598 (13)	0.0449 (12)	0.0468 (12)	−0.0069 (10)	0.0115 (10)	−0.0074 (9)
C15	0.0787 (17)	0.0579 (14)	0.0585 (14)	−0.0093 (12)	0.0207 (12)	−0.0015 (11)
C16	0.0758 (18)	0.095 (2)	0.0641 (16)	−0.0142 (16)	0.0313 (14)	−0.0131 (15)
C17	0.0673 (17)	0.088 (2)	0.0724 (18)	0.0100 (15)	0.0142 (13)	−0.0278 (15)
C18	0.0868 (19)	0.0620 (15)	0.0671 (16)	0.0153 (14)	0.0066 (14)	−0.0114 (13)
C19	0.0786 (16)	0.0525 (13)	0.0552 (14)	0.0020 (12)	0.0195 (12)	−0.0042 (11)
C20	0.0531 (13)	0.0519 (13)	0.0488 (12)	−0.0120 (10)	0.0036 (10)	−0.0137 (10)
C21	0.0764 (17)	0.0596 (15)	0.0667 (16)	−0.0237 (13)	0.0007 (13)	−0.0032 (12)
C22	0.120 (3)	0.083 (2)	0.080 (2)	−0.049 (2)	0.0182 (19)	−0.0046 (16)
C23	0.096 (3)	0.122 (3)	0.114 (3)	−0.067 (2)	0.045 (2)	−0.054 (2)
C24	0.0555 (17)	0.121 (3)	0.126 (3)	−0.0268 (19)	0.0084 (17)	−0.059 (2)
C25	0.0597 (16)	0.0779 (17)	0.0801 (18)	−0.0076 (13)	−0.0038 (13)	−0.0273 (14)
C26	0.0761 (17)	0.097 (2)	0.0591 (15)	−0.0133 (15)	0.0084 (12)	−0.0270 (14)

Geometric parameters (Å, º)

S1—C12	1.673 (2)	C12—N13	1.319 (3)
N1—C2	1.465 (2)	N13—H13A	0.8600
N1—C26	1.477 (3)	N13—H13B	0.8600
N1—C6	1.478 (2)	C14—C15	1.376 (3)
C2—C14	1.517 (3)	C14—C19	1.388 (3)
C2—C3	1.519 (3)	C15—C16	1.382 (3)
C2—H2	0.9800	C15—H15	0.9300
C3—C4	1.496 (3)	C16—C17	1.361 (4)
C3—H3A	0.9700	C16—H16	0.9300
C3—H3B	0.9700	C17—C18	1.361 (4)
C4—N10	1.278 (2)	C17—H17	0.9300
C4—C5	1.502 (3)	C18—C19	1.378 (3)
C5—C7	1.544 (3)	C18—H18	0.9300
C5—C6	1.547 (3)	C19—H19	0.9300
C5—H5	0.9800	C20—C21	1.378 (3)
C6—C20	1.512 (3)	C20—C25	1.379 (3)
C6—H6	0.9800	C21—C22	1.389 (3)
C7—C9	1.526 (3)	C21—H21	0.9300
C7—C8	1.534 (3)	C22—C23	1.362 (5)
C7—H7	0.9800	C22—H22	0.9300
C8—H8A	0.9600	C23—C24	1.356 (5)
C8—H8B	0.9600	C23—H23	0.9300
C8—H8C	0.9600	C24—C25	1.380 (4)
C9—H9A	0.9600	C24—H24	0.9300
C9—H9B	0.9600	C25—H25	0.9300
C9—H9C	0.9600	C26—H26A	0.9600
N10—N11	1.382 (2)	C26—H26B	0.9600
N11—C12	1.350 (2)	C26—H26C	0.9600
N11—H11	0.8600
C2—N1—C26	109.10 (17)	C12—N11—H11	120.7
C2—N1—C6	114.30 (15)	N10—N11—H11	120.7
C26—N1—C6	108.73 (17)	N13—C12—N11	115.74 (18)
N1—C2—C14	111.66 (16)	N13—C12—S1	124.78 (16)
N1—C2—C3	110.81 (17)	N11—C12—S1	119.47 (16)
C14—C2—C3	108.68 (17)	C12—N13—H13A	120.0
N1—C2—H2	108.5	C12—N13—H13B	120.0
C14—C2—H2	108.5	H13A—N13—H13B	120.0
C3—C2—H2	108.5	C15—C14—C19	118.0 (2)
C4—C3—C2	110.88 (18)	C15—C14—C2	120.8 (2)
C4—C3—H3A	109.5	C19—C14—C2	121.10 (19)
C2—C3—H3A	109.5	C14—C15—C16	120.8 (2)
C4—C3—H3B	109.5	C14—C15—H15	119.6
C2—C3—H3B	109.5	C16—C15—H15	119.6
H3A—C3—H3B	108.1	C17—C16—C15	120.7 (2)
N10—C4—C3	127.83 (18)	C17—C16—H16	119.7
N10—C4—C5	118.99 (17)	C15—C16—H16	119.7
C3—C4—C5	113.18 (16)	C16—C17—C18	119.2 (2)
C4—C5—C7	116.65 (16)	C16—C17—H17	120.4
C4—C5—C6	109.91 (16)	C18—C17—H17	120.4
C7—C5—C6	112.84 (17)	C17—C18—C19	120.9 (3)
C4—C5—H5	105.5	C17—C18—H18	119.5
C7—C5—H5	105.5	C19—C18—H18	119.5
C6—C5—H5	105.5	C18—C19—C14	120.4 (2)
N1—C6—C20	109.46 (16)	C18—C19—H19	119.8
N1—C6—C5	112.40 (16)	C14—C19—H19	119.8
C20—C6—C5	109.49 (16)	C21—C20—C25	118.5 (2)
N1—C6—H6	108.5	C21—C20—C6	120.2 (2)
C20—C6—H6	108.5	C25—C20—C6	121.3 (2)
C5—C6—H6	108.5	C20—C21—C22	120.4 (3)
C9—C7—C8	111.93 (18)	C20—C21—H21	119.8
C9—C7—C5	111.27 (18)	C22—C21—H21	119.8
C8—C7—C5	115.67 (18)	C23—C22—C21	119.8 (3)
C9—C7—H7	105.7	C23—C22—H22	120.1
C8—C7—H7	105.7	C21—C22—H22	120.1
C5—C7—H7	105.7	C24—C23—C22	120.7 (3)
C7—C8—H8A	109.5	C24—C23—H23	119.7
C7—C8—H8B	109.5	C22—C23—H23	119.7
H8A—C8—H8B	109.5	C23—C24—C25	119.8 (3)
C7—C8—H8C	109.5	C23—C24—H24	120.1
H8A—C8—H8C	109.5	C25—C24—H24	120.1
H8B—C8—H8C	109.5	C20—C25—C24	120.8 (3)
C7—C9—H9A	109.5	C20—C25—H25	119.6
C7—C9—H9B	109.5	C24—C25—H25	119.6
H9A—C9—H9B	109.5	N1—C26—H26A	109.5
C7—C9—H9C	109.5	N1—C26—H26B	109.5
H9A—C9—H9C	109.5	H26A—C26—H26B	109.5
H9B—C9—H9C	109.5	N1—C26—H26C	109.5
C4—N10—N11	119.13 (16)	H26A—C26—H26C	109.5
C12—N11—N10	118.66 (17)	H26B—C26—H26C	109.5
C26—N1—C2—C14	62.3 (2)	N10—N11—C12—N13	3.1 (3)
C6—N1—C2—C14	−175.77 (17)	N10—N11—C12—S1	−175.54 (15)
C26—N1—C2—C3	−176.42 (18)	N1—C2—C14—C15	−135.7 (2)
C6—N1—C2—C3	−54.5 (2)	C3—C2—C14—C15	101.8 (2)
N1—C2—C3—C4	54.9 (2)	N1—C2—C14—C19	47.0 (3)
C14—C2—C3—C4	177.99 (17)	C3—C2—C14—C19	−75.5 (2)
C2—C3—C4—N10	124.0 (2)	C19—C14—C15—C16	−0.1 (4)
C2—C3—C4—C5	−55.9 (2)	C2—C14—C15—C16	−177.5 (2)
N10—C4—C5—C7	2.8 (3)	C14—C15—C16—C17	−0.5 (4)
C3—C4—C5—C7	−177.23 (18)	C15—C16—C17—C18	1.2 (4)
N10—C4—C5—C6	−127.2 (2)	C16—C17—C18—C19	−1.3 (4)
C3—C4—C5—C6	52.7 (2)	C17—C18—C19—C14	0.7 (4)
C2—N1—C6—C20	174.42 (17)	C15—C14—C19—C18	0.0 (3)
C26—N1—C6—C20	−63.4 (2)	C2—C14—C19—C18	177.3 (2)
C2—N1—C6—C5	52.5 (2)	N1—C6—C20—C21	−53.8 (3)
C26—N1—C6—C5	174.69 (18)	C5—C6—C20—C21	69.8 (2)
C4—C5—C6—N1	−49.9 (2)	N1—C6—C20—C25	128.6 (2)
C7—C5—C6—N1	178.01 (16)	C5—C6—C20—C25	−107.8 (2)
C4—C5—C6—C20	−171.78 (17)	C25—C20—C21—C22	1.1 (3)
C7—C5—C6—C20	56.1 (2)	C6—C20—C21—C22	−176.6 (2)
C4—C5—C7—C9	65.9 (2)	C20—C21—C22—C23	0.1 (4)
C6—C5—C7—C9	−165.44 (17)	C21—C22—C23—C24	−1.2 (5)
C4—C5—C7—C8	−63.3 (3)	C22—C23—C24—C25	1.0 (5)
C6—C5—C7—C8	65.4 (2)	C21—C20—C25—C24	−1.3 (3)
C3—C4—N10—N11	2.4 (3)	C6—C20—C25—C24	176.3 (2)
C5—C4—N10—N11	−177.67 (18)	C23—C24—C25—C20	0.3 (4)
C4—N10—N11—C12	177.1 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N13—H13B···S1^i	0.86	2.52	3.362 (2)	167
N13—H13A···N10	0.86	2.21	2.587 (3)	106
C8—H8···Cg1^ii	0.96	3.21	4.004	142
C24—H24···Cg1^iii	0.93	3.07	3.884	148

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