research communications\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 71| Part 10| October 2015| Pages 1207-1211
doi:10.1107/S2056989015017119

Crystal structures of two chiral piperidine derivatives: 1-[(1R)-2-hy­dr­oxy-1-phenyl­eth­yl]piperidin-4-one and 8-[(1S)-1-phenyl­eth­yl]-1,4-dioxa-8-aza­spiro­[4.5]decane-7-thione

CROSSMARK_Color_square_no_text.svg
Nancy Romero,a Sylvain Bernès,b* Luis F. Roa,a Joel L. Teránc and Dino Gneccoc

aUniversidad Juárez Autónoma de Tabasco, División Académica de Ciencias Básicas, Km. 1 carretera Cunduacán, Jalpa de Méndez AP 24, Cunduacán, Tabasco, Mexico, bInstituto de Física, Benemérita Universidad Autónoma de Puebla, Av. San Claudio y 18 Sur, 72570 Puebla, Pue., Mexico, and cCentro de Química, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, 72570 Puebla, Pue., Mexico
*Correspondence e-mail: sylvain_bernes@hotmail.com

Edited by D.-J. Xu, Zhejiang University (Yuquan Campus), China (Received 29 August 2015; accepted 11 September 2015; online 26 September 2015)

The crystal structures of the two title piperidine derivatives show different conformations for the six-membered heterocycle. The N-substituted 4-piperidinone 1-[(1R)-2-hy­droxy-1-phenyl­eth­yl]piperidin-4-one, C13H17NO2, (I), has a chair conformation, while the piperidine substituted in position 2 with a thio­carbonyl group, 8-[(1S)-1-phenyl­eth­yl]-1,4-dioxa-8-aza­spiro­[4.5]decane-7-thione, C15H19NO2S, (II), features a half-chair conformation. Comparison of the two structures, and data retrieved from the literature, suggests that the conformational flexibility is mainly related to the hybridization state of the C atom α to the piperidinic N atom: a Csp3 atom favours the chair conformer, while a Csp2 atom distorts the ring towards a half-chair conformer. In the crystal structure of (I), weak C—H⋯O hydrogen bonds link the mol­ecules into supra­molecular chains propagating along the b-axis direction. In the crystal of (II), the mol­ecules are linked by weak C—H⋯S contacts into supra­molecular chains propagating along the b-axis direction.

CCDC references: 1424094; 1424093

1. Chemical context

The 4-piperidone scaffold has been used as a building block for the synthesis of more complex heterocyclic compounds. An example is the one-pot three-step synthesis of fentanyl [N-(1-phenethyl-4-piperid­yl) propionanilide], a strong agonist of μ-opioid receptors, used for its potent analgesic activity. This industrial synthesis, patented by Janssen Pharmaceutica (Gupta et al., 2010[Gupta, P. K., Manral, L., Ganesan, K., Malhotra, R. C. & Sekhar, K. (2010). Patent WO 2009116084 A2.]) employs 4-piperidone hydro­chloride monohydrate as the starting material. The range of biological activity for 4-piperidone derivatives is quite broad, including anti-inflammatory, anti­cancer, anti­bacterial and anti­fungal properties. For this reason, new synthetic methods are being sought proactively in this field (e.g. Tortolani & Poss, 1999[Tortolani, D. R. & Poss, M. A. (1999). Org. Lett. 1, 1261-1262.]; Davis et al., 2001[Davis, F. A., Chao, B. & Rao, A. (2001). Org. Lett. 3, 3169-3171.]; Das et al., 2010[Das, U., Sakagami, H., Chu, Q., Wang, Q., Kawase, M., Selvakumar, P., Sharma, R. K. & Dimmock, J. R. (2010). Bioorg. Med. Chem. Lett. 20, 912-917.]). For our part, our emphasis is on the synthesis of chiral N-substituted piperidone derivatives (e.g. Romero et al., 2007[Romero, N., Gnecco, D., Terán, J., Juárez, J. & Galindo, A. (2007). J. Sulfur Chem. 28, 239-243.]).

[Scheme 1]

In this context, X-ray crystallography is a potent tool to assess the conformational modifications experienced by the piperidine heterocycle while its substitution pattern is altered along a synthetic route. The pair of structures reported here illustrates such conformational flexibility in this chemistry.

2. Structural commentary

The first piperidin-4-one derivative [(I), Fig. 1[link]] is a non-sterically hindered mol­ecule, and thus adopts the most stable chair conformation for the six-membered heterocycle. The total puckering amplitude is Q = 0.553 (3) Å, and the Cremer parameters are θ = 168.8 (3)° and φ = 171.8 (18)°. The deviation from the ideal conformation, θ = 180°, may be related to the heterocyclic nature of the ring, with short C—N bond lengths and longer C—C bond lengths, as expected. Moreover, atom C4 has a geometry consistent with its sp2 hybridization state, while N1 is essentially tetra­hedral, with the lone pair occupying the axial position. The equatorial group substituting this N atom is rigid, as a result of its chiral character. However, the spatial orientation of this group allows the hydroxyl group to inter­act with the nitro­gen lone pair, stabilizing the observed mol­ecular conformation.

[Figure 1]
Figure 1
The mol­ecular structure of (I)[link], with displacement ellipsoids for non-H atoms at the 30% probability level.

The chair conformation for the piperidone in (I)[link] was previously observed in related compounds based on the same heterocycle (Vijayakumar et al., 2010[Vijayakumar, V., Rajesh, K., Suresh, J., Narasimhamurthy, T. & Lakshman, P. L. N. (2010). Acta Cryst. E66, o170.]; Rajesh et al., 2010a[Rajesh, K., Vijayakumar, V., Sarveswari, S., Narasimhamurthy, T. & Tiekink, E. R. T. (2010a). Acta Cryst. E66, o1306-o1307.], 2012[Rajesh, K., Reddy, B. P. & Vijayakumar, V. (2012). Ultrason. Sonochem. 19, 522-531.]). Apparently, the only significant variation allowed for this system is for the N atom, which may approach a planar–trigonal geometry (Shahani et al., 2010[Shahani, T., Fun, H.-K., Ragavan, R. V., Vijayakumar, V. & Venkatesh, M. (2010). Acta Cryst. E66, o3233-o3234.]; Rajesh et al., 2010b[Rajesh, K., Vijayakumar, V., Sarveswari, S., Narasimhamurthy, T. & Tiekink, E. R. T. (2010b). Acta Cryst. E66, o1988.]).

The chair conformation of (I)[link] is, however, different from that observed for (II)[link], derived from piperidine-2-thione (Fig. 2[link]). In that case, the half-chair form is found in the crystal structure, characterized by a puckering amplitude Q = 0.513 (3) Å, and Cremer parameters θ = 127.5 (3)° and φ = 29.29 (5)° (ideal values: θ = 129.2° and φ = 30°). The N atom has a planar environment, the sum of angles about this center being 360°. This conformer is identical to one of the stable forms reported for piperidin-2-one (known as δ-valerolatcam): microwave spectroscopy indicated that for δ-valerolatcam, two conformers are stabilized in the gas phase, the half-chair form and the twist form (Kuze et al., 1999[Kuze, N., Funahashi, H., Ogawa, M., Tajiri, H., Ohta, Y., Usami, T., Sakaizumi, T. & Ohashi, O. (1999). J. Mol. Spectrosc. 198, 381-386.]). δ-Valerolatcam is actually comparable to (II)[link], because in both mol­ecules C4 has the same sp3 hybridization. In (II)[link], the spiro atom C4 is part of the 1,3-dioxolane ring. The slightly twisted half-chair conformation for this ring is common. The two rings are almost perpendicular, as reflected in the dihedral angle between their mean-planes of 76.4 (2)°.

[Figure 2]
Figure 2
The mol­ecular structure of (II)[link], with displacement ellipsoids for non-H atoms at the 30% probability level.

3. Effect of hybridization on ring conformation

Since the ring conformation in (II)[link] seems not to be related to any intra­molecular strong inter­action nor the hybridization modification from sp2 to sp3 at C4, it should be a consequence of the presence of the thio­carbonyl functionality at C2. This center is in a state very close to pure sp2 hybridization. This is reflected in the bond length for the C=S group, 1.677 (3) Å, close to the mean value of 1.669 Å computed from almost 10000 thio­carbonyl bonds retrieved from the organics subset of the CSD (Version 5.36 with all updates; Groom & Allen, 2014[Groom, C. R. & Allen, F. H. (2014). Angew. Chem. Int. Ed. 53, 662-671.]. The restriction to sp2-C centers is applied by requiring the C atom to be linked to exactly three atoms and the S atom to be linked to exactly one atom). Indeed, long C=S bonds, above 1.75 Å, are found in compounds including mol­ecules having a propensity to form hydrogen bonds, like thio­urea (Weber, 1984[Weber, G. (1984). J. Inclusion Phenom. 1, 339-347.]), thio­urea derivatives (Busschaert et al., 2011[Busschaert, N., Wenzel, M., Light, M. E., Iglesias-Hernández, P., Pérez-Tomás, R. & Gale, P. A. (2011). J. Am. Chem. Soc. 133, 14136-14148.]; Chumakov et al., 2006[Chumakov, Yu. M., Samus', N. M., Bocelli, G., Suponitskii, K. Yu., Tsapkov, V. I. & Gulya, A. P. (2006). Russ. J. Coord. Chem. 32, 14-20.]), and tri­thio­carbonic acid (Krebs & Gattow, 1965[Krebs, B. & Gattow, G. (1965). Z. Anorg. Allg. Chem. 340, 294-311.]), among others. In the case of a single C—S bond based on a sp3-hybridized C atom, the bond length is sharply distributed around 1.81 Å.

The other factor contributing to the ring conformation in (II)[link] is the absence of the hydroxyl group in the chiral moiety, making the heterocyclic N atom inert towards potential inter­actions. The lone pair should thus be oriented randomly above and below the piperidine mean plane, through nitro­gen inversion, characterized by a low energy barrier in the gas and solution phases. Both features, the planar N atom and the neighboring sp2-C atom, generate the half-chair conformation observed for the piperidine-2-thione core. In the present case, it is difficult to determine whether one feature dominates, or both are of importance for stabilizing the half-chair conformation. However, for the 25 hits corresponding to piperidine-2-ones deposited in the CSD, 21 of them present the same conformation as in (II)[link], with C4 as the flap atom for the half-chair. In three cases, the puckering amplitude of the half-chair is close to 0 Å (Woydt et al., 1991[Woydt, M., Rademacher, P., Brett, W. A. & Boese, R. (1991). Acta Cryst. C47, 1936-1938.]; Bolla et al., 2014[Bolla, G., Mittapalli, S. & Nangia, A. (2014). CrystEngComm, 16, 24-27.]), and in one case, the ring presents a twist-boat conformation (Sanfilippo et al., 1992[Sanfilippo, P. J., McNally, J. J., Press, J. B., Fitzpatrick, L. J., Urbanski, M. J., Katz, L. B., Giardino, E., Falotico, R., Salata, J., Moore, J. B. Jr & Miller, W. (1992). J. Med. Chem. 35, 4425-4433.]). In contrast, piperidine derivatives are stabilized almost universally in the chair conformation, with very few exceptions in some disordered structures (Thirumaran et al., 2009[Thirumaran, S., Ramalingam, K., Bocelli, G. & Righi, L. (2009). Polyhedron, 28, 263-268.]). These rules hold regardless of the substituent on the N atom. Applying these general rules to compounds (I)[link] and (II)[link], we thus infer that the ring conformation is mainly determined by the hybridization state of the C atom in position α to the piperidinic N atom.

4. Supra­molecular features

In the crystal of (I)[link], weak C—H⋯O hydrogen bonds link the mol­ecules into supra­molecular chains propagating along the b-axis direction (Table 1[link]).

Table 1
Hydrogen-bond geometry (Å, °) for (I)[link]

D—H⋯A D—H H⋯A D⋯A D—H⋯A
C3—H3A⋯O1i 0.97 2.49 3.246 (4) 135
Symmetry code: (i) [-x+2, y-{\script{1\over 2}}, -z+1].

The crystal structure of (II)[link] is based on weak inter­molecular C—H⋯S contacts involving one methyl­ene group of the dioxolane ring and the thio­carbonyl functionality (Table 2[link]), which forms chains along the 21 symmetry axis parallel to [010].

Table 2
Hydrogen-bond geometry (Å, °) for (II)[link]

D—H⋯A D—H H⋯A D⋯A D—H⋯A
C16—H16B⋯S1i 0.97 2.85 3.709 (5) 148
Symmetry code: (i) [-x+2, y+{\script{1\over 2}}, -z+{\script{3\over 2}}].

5. Synthesis and crystallization

Compound (I). The synthesis is illustrated in Fig. 3[link]. A solution of compound (1), (R)-(−)-2-phenyl­glycinol (5.65 g, 41.2 mmol) with an excess of ethyl acrylate in methanol (60 mL), was stirred overnight at 298 K. The reaction mixture was concentrated, and the crude purified by column chromatography (SiO2, CH2Cl2:MeOH, 97:3), to afford (2) as a colorless oil (98%). An amount of (2) (40.6 mmol) was added to a mixture of MeONa in anh. benzene. After refluxing the mixture for 5 h, a solid was obtained, which was filtered and dried in air. This solid was treated with AcOH:water (30%, v/v) until pH = 1, initiating the deca­rboxylation process. The mixture was refluxed until gas evolution stopped. After cooling down to 298 K, pH was adjusted to 7 with NaHCO3, and the mixture was washed with CH2Cl2 (3 × 50 ml). The organic phase was dried over Na2SO4, and concentrated. Compound (I)[link] was purified by column chromatography (SiO2, CH2Cl2:MeOH, 95:5). Compound (I)[link] was obtained in 80% yield, and was recrystallized from an AcOEt:n-hexane mixture (1:1).

[Figure 3]
Figure 3
Synthesis of (I)[link]. Reaction conditions: (i) ethyl acrylate, MeOH, 298 K, 12 h; (ii) Na/MeOH, benzene, reflux, 5 h; (iii) AcOH/H2O (30% v/v), reflux.

Compound (II). The synthesis is illustrated in Fig. 4[link]. The synthesis of compound (3), (S)-(−)-phenyl­ethyl­piperi-2,4-dione, has been reported previously (Romero et al., 2013[Romero, N., Gnecco, D., Terán, J. & Bernès, S. (2013). Acta Cryst. E69, o408-o409.]; see compound 5 in Fig. 1[link] of this report). To a solution of (3) in 50 mL of dry benzene, was added ethyl­ene glycol (0.2 mL, 3.4 mmol) and a catalytic amount of p-TSA. The mixture was refluxed until water formation, collected with a Dean–Stark trap, stopped. Then, the reaction mixture was cooled down to room temperature, treated with brine, and washed with CH2Cl2 (3 × 50 mL). The organic phase was dried over Na2SO4, and then concentrated under reduced pressure. The crude reaction was purified by column chromatography (SiO2, AcOEt:petroleum benzine), to afford compound (4) as a white oil, in 95% yield. Next, a suspension of Lawesson's reagent (0.234 g, 0.578 mmol) in dry toluene (60 mL) was refluxed until complete dissolution of the reagent. The solution was cooled to 313 K, and a solution of (4) in anh. toluene (0.151 g, 0.578 mmol, 20 mL) was added (Romero et al., 2007[Romero, N., Gnecco, D., Terán, J., Juárez, J. & Galindo, A. (2007). J. Sulfur Chem. 28, 239-243.]). The reaction mixture was stirred for 1 h to give (II)[link] in 90% yield, after purification by column chromatography (SiO2, petroleum ether:dicloro­methane). The product was recrystallized from CH2Cl2:n-hexane (1:1).

[Figure 4]
Figure 4
Synthesis of (II)[link]. Reaction conditions: (i) ethyl­ene glycol, p-TSA, anhydrous benzene, reflux, 4 h; (ii) Lawesson's reagent in anhydrous toluene, 313 K, 1 h.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 3[link]. All C-bound H atoms were placed in calculated positions, and refined as riding on their carrier atoms, and with C—H bond lengths fixed at 0.93 (aromatic CH), 0.96 (methyl CH3), 0.97 (methyl­ene CH2), or 0.98 Å (methine CH). For (I)[link], the hydroxyl H atom, H2, was first found in a difference map. Its position was fixed in the last least-squares cycles, with O2—H2 = 0.91 Å. For all H atoms, the isotropic displacement parameters were calculated as Uiso(H) = xUeq(carrier atom), where x = 1.5 for methyl and hydroxyl H atoms, and x = 1.2 otherwise. The absolute configuration for chiral centers C7 in (I)[link] and (II)[link] was assumed from the chirality of starting materials used for the synthesis (see previous section). In the case of (II)[link], which contains one site producing anomalous scattering, the expected enanti­omer was confirmed by the refinement of the Flack parameter (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.]).

Table 3
Experimental details

  (I) (II)
Crystal data
Chemical formula C13H17NO2 C15H19NO2S
Mr 219.27 277.37
Crystal system, space group Monoclinic, P21 Orthorhombic, P212121
Temperature (K) 296 296
a, b, c (Å) 9.7590 (11), 6.8952 (10), 9.7980 (14) 5.9731 (13), 14.948 (3), 16.127 (3)
α, β, γ (°) 90, 114.348 (9), 90 90, 90, 90
V (Å3) 600.67 (15) 1439.9 (5)
Z 2 4
Radiation type Mo Kα Mo Kα
μ (mm−1) 0.08 0.22
Crystal size (mm) 0.60 × 0.17 × 0.12 0.60 × 0.38 × 0.36
 
Data collection
Diffractometer Bruker P4 Bruker P4 diffractometer
Absorption correction – ψ scan (XSCANS; Fait, 1996[Fait, J. (1996). XSCANS. Siemens Analytical X-ray Instruments Inc., Madison, Wisconsin, USA.])
Tmin, Tmax – 0.760, 0.922
No. of measured, independent and observed [I > 2σ(I)] reflections 2700, 1341, 1050 3886, 2631, 2007
Rint 0.021 0.029
(sin θ/λ)max (Å−1) 0.595 0.650
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.036, 0.083, 1.04 0.044, 0.120, 1.06
No. of reflections 1341 2631
No. of parameters 146 174
No. of restraints 1 0
H-atom treatment H-atom parameters constrained H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.11, −0.11 0.19, −0.24
Absolute structure Assigned from the synthesis Flack x determined using 483 quotients [(I+)−(I−)]/[(I+)+(I−)] (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.])
Absolute structure parameter – 0.08 (7)
Computer programs: XSCANS (Fait, 1996[Fait, J. (1996). XSCANS. Siemens Analytical X-ray Instruments Inc., Madison, Wisconsin, USA.]), SHELXS97 and SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]) and SHELXL2014 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]).

Supporting information

CCDC references: 1424094; 1424093

Crystal structure: contains datablocks I, II, global. DOI: 10.1107/S2056989015017119/xu5868sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S2056989015017119/xu5868Isup2.hkl

Structure factors: contains datablock II. DOI: 10.1107/S2056989015017119/xu5868IIsup3.hkl

Supporting information file. DOI: 10.1107/S2056989015017119/xu5868Isup4.cml

Supporting information file. DOI: 10.1107/S2056989015017119/xu5868IIsup5.cml

checkCIF report


Chemical context top

The 4-piperidone scaffold has been used as a building block for the synthesis of more complex heterocyclic compounds. An example is the one-pot three-step synthesis of fentanyl [N-(1-phenethyl-4-piperidyl) propionanilide], a strong agonist of µ-opioid receptors, used for its potent analgesic activity. This industrial synthesis, patented by Janssen Pharmaceutica (Gupta et al., 2010) employs 4-piperidone hydro­chloride monohydrate as the starting material. The range of biological activity for 4-piperidone derivatives is quite broad, including anti-inflammatory, anti­cancer, anti­bacterial and anti­fungal properties. For this reason, new synthetic methods are being sought proactively in this field (e.g. Tortolani & Poss, 1999; Davis et al., 2001; Das et al., 2010). For our part, our emphasis is on the synthesis of chiral N-substituted piperidone derivatives (e.g. Romero et al., 2007).

In this context, X-ray crystallography is a potent tool to assess the conformational modifications experienced by the piperidine heterocycle while its substitution pattern is altered along a synthetic route. The pair of structures reported here illustrates such conformational flexibility in this chemistry.

Structural commentary top

The first piperidin-4-one derivative [(I), Fig. 1] is a non-sterically hindered molecule, and thus adopts the most stable chair conformation for the six-membered heterocycle. The total puckering amplitude is Q = 0.553 (3) Å, and the Cremer parameters are θ = 168.8 (3)° and φ = 171.8 (18)°. The deviation from the ideal conformation, θ = 180°, may be related to the heterocyclic nature of the ring, with short C—N bond lengths and longer C—C bond lengths, as expected. Moreover, atom C4 has a geometry consistent with its sp2 hybridization state, while N1 is essentially tetra­hedral, with the lone pair occupying the axial position. The equatorial group substituting this N atom is rigid, as a result of its chiral character. However, the spatial orientation of this group allows the hydroxyl group to inter­act with the nitro­gen lone pair, stabilizing the observed molecular conformation.

The chair conformation for the piperidone in (I) was previously observed in related compounds based on the same heterocycle (Vijayakumar et al., 2010; Rajesh et al., 2010a, 2012). Apparently, the only significant variation allowed for this system is for the N atom, which may approach a planar–trigonal geometry (Shahani et al., 2010; Rajesh et al., 2010b).

The chair conformation of (I) is, however ,different from that observed for (II), derived from piperidine-2-thione (Fig. 2). In that case, the half-chair form is found in the crystal structure, characterized by a puckering amplitude Q = 0.513 (3) Å, and Cremer parameters θ = 127.5 (3)° and φ = 29.29 (5)° (ideal values: θ = 129.2° and φ = 30°). The N atom has a planar environment, the sum of angles about this center being 360°. This conformer is identical to one of the stable forms reported for piperidin-2-one (known as δ-valerolatcam): microwave spectroscopy indicated that for δ-valerolatcam, two conformers are stabilized in the gas phase, the half-chair form and the twist form (Kuze et al., 1999). δ-Valerolatcam is actually comparable to (II), because in both molecules C4 has the same sp3 hybridization. In (II), the spiro atom C4 is part of the 1,3-dioxolane ring. The slightly twisted half-chair conformation for this ring is common. The two rings are almost perpendicular, as reflected in the dihedral angle between their mean-planes of 76.4 (2)°.

Effect of hybridization on ring conformation top

Since the ring conformation in (II) seems not to be related to any intra­molecular strong inter­action nor the hybridization modification from sp2 to sp3 at C4, it should be a consequence of the presence of the thio­carbonyl functionality at C2. This center is in a state very close to pure sp2 hybridization. This is reflected in the bond length for the C═S group, 1.677 (3) Å, close to the mean value of 1.669 Å computed from almost 10000 thio­carbonyl bonds retrieved from the organics subset of the CSD (Version 5.36 with all updates; Groom & Allen, 2014. The restriction to sp2-C centers is applied by requiring the C atom to be linked to exactly three atoms and the S atom to be linked to exactly one atom). Indeed, long C═S bonds, above 1.75 Å, are found in compounds including molecules having a propensity to form hydrogen bonds, like thio­urea (Weber, 1984), thio­urea derivatives (Busschaert et al., 2011; Chumakov et al., 2006), and tri­thio­carbonic acid (Krebs & Gattow, 1965), among others. In the case of a single C–S bond based on a sp3 hybridized C atom, the bond length is sharply distributed around 1.81 Å.

The other factor contributing to the ring conformation in (II) is the absence of the hydroxyl group in the chiral moiety, making the heterocyclic N atom inert towards potential inter­actions. The lone pair should thus be oriented randomly above and below the piperidine mean plane, through nitro­gen inversion, characterized by a low energy barrier in the gas and solution phases. Both features, the planar N atom and the neighboring sp2-C atom, generate the half-chair conformation observed for the piperidine-2-thione core. In the present case, it is difficult to determine whether one feature dominates, or both are of importance for stabilizing the half-chair conformation. However, for the 25 hits corresponding to piperidine-2-ones deposited in the CSD, 21 of them present the same conformation as in (II), with C4 as the flap atom for the half-chair. In three cases, the puckering amplitude of the half-chair is close to 0 Å (Woydt et al., 1991; Bolla et al., 2014), and in one case, the ring presents a twist-boat conformation (Sanfilippo et al., 1992). In contrast, piperidine derivatives are stabilized almost universally in the chair conformation, with very few exceptions in some disordered structures (Thirumaran et al., 2009). These rules hold regardless of the substituent on the N atom. Applying these general rules to compounds (I) and (II), we thus infer that the ring conformation is mainly determined by the hybridization state of the C atom in position α to the piperidinic N atom.

Supra­molecular features top

In the crystal of (I), weak C—H···O hydrogen bonds link the molecules into supra­molecular chains propagating along the b-axis direction (Table 1).

The crystal structure of (II) is based on weak inter­molecular C—H···S contacts involving one methyl­ene group of the dioxolane ring and the thio­carbonyl functionality (Table 2), which forms chains along the 21 symmetry axis parallel to [010].

Synthesis and crystallization top

Compound (I). The synthesis is illustrated in Fig. 3. A solution of compound (1), (R)-(–)-2-phenyl­glycinol (5.65 g, 41.2 mmol) with an excess of ethyl acrylate in methanol (60 mL), was stirred overnight at 298 K. The reaction mixture was concentrated, and the crude purified by column chromatography (SiO2, CH2Cl2:MeOH, 97:3), to afford (2) as a colorless oil (98 %). An amount of (2) (40.6 mmol) was added to a mixture of MeONa in anh. benzene. After refluxing the mixture for 5 h, a solid was obtained, which was filtered and dried in air. This solid was treated with AcOH:water (30%, v/v) until pH = 1, initiating the de­carboxyl­ation process. The mixture was refluxed until gas evolution stopped. After cooling down to 298 K, pH was adjusted to 7 with NaHCO3, and the mixture was washed with CH2Cl2 (3 × 50 ml). The organic phase was dried over Na2SO4, and concentrated. Compound (I) was purified by column chromatography (SiO2, CH2Cl2:MeOH, 95:5). Compound (I) was obtained in 80% yield, and was recrystallized from an AcOEt:n-hexane mixture (1:1).

Compound (II). The synthesis is illustrated in Fig. 4. The synthesis of compound (3), (S)-(–)-phenyl­ethyl­piperi-2,4-dione, has been reported previously (Romero et al., 2013; see compound 5 in Fig. 1 of this report). To a solution of (3) in 50 mL of dry benzene, was added ethyl­ene glycol (0.2 mL, 3.4 mmol) and a catalytic amount of p-TSA. The mixture was refluxed until water formation, collected with a Dean–Stark trap, stopped. Then, the reaction mixture was cooled down to room temperature, treated with brine, and washed with CH2Cl2 (3 × 50 mL). The organic phase was dried over Na2SO4, and then concentrated under reduced pressure. The crude reaction was purified by column chromatography (SiO2, AcOEt:petroleum benzine), to afford compound (4) as a white oil, in 95 % yield. Next, a suspension of Lawesson's reagent (0.234 g, 0.578 mmol) in dry toluene (60 mL) was refluxed until complete dissolution of the reagent. The solution was cooled to 313 K, and a solution of (4) in anh. toluene (0.151 g, 0.578 mmol, 20 mL) was added (Romero et al., 2007). The reaction mixture was stirred for 1 h to give (II) in 90% yield, after purification by column chromatography (SiO2, petroleum ether:dicloro­methane). The product was recrystallized from CH2Cl2:n-hexane (1:1).

Refinement top

Crystal data, data collection and structure refinement details are summarized in Table 3. All C-bound H atoms were placed in calculated positions, and refined as riding on their carrier atoms, and with C—H bond lengths fixed at 0.93 (aromatic CH), 0.96 (methyl CH3), 0.97 (methyl­ene CH2), or 0.98 Å (methine CH). For (I), the hydroxyl H atom, H2, was first found in a difference map. Its position was fixed in the last least-squares cycles, with O2—H2 = 0.91 Å. For all H atoms, the isotropic displacement parameters were calculated as Uiso(H) = xUeq(carrier atom), where x = 1.5 for methyl and hydroxyl H atoms, and x = 1.2 otherwise. The absolute configuration for chiral centers C7 in (I) and (II) was assumed from the chirality of starting materials used for the synthesis (see previous section). In the case of (II), which contains one site producing anomalous scattering, the expected enanti­omer was confirmed by the refinement of the Flack parameter (Parsons et al., 2013).

Computing details top

For both compounds, data collection: XSCANS (Fait, 1996); cell refinement: XSCANS (Fait, 1996); data reduction: XSCANS (Fait, 1996); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015).

Figures top
[Figure 1] Fig. 1. The molecular structure of (I), with displacement ellipsoids for non-H atoms at the 30% probability level.
[Figure 2] Fig. 2. The molecular structure of (II), with displacement ellipsoids for non-H atoms at the 30% probability level.
[Figure 3] Fig. 3. Synthesis of (I). Reaction conditions: (i) ethyl acrylate, MeOH, 298 K, 12 h; (ii) Na/MeOH, benzene, reflux, 5 h; (iii) AcOH/H2O (30% v/v), reflux.
[Figure 4] Fig. 4. Synthesis of (II). Reaction conditions: (i) ethylene glycol, p-TSA, anhydrous benzene, reflux, 4 h; (ii) Lawesson's reagent in anhydrous toluene, 313 K, 1 h.
(I) 1-[(1R)-2-Hydroxy-1-phenylethyl]piperidin-4-one top
Crystal data top
C13H17NO2F(000) = 236
Mr = 219.27Dx = 1.212 Mg m−3
Monoclinic, P21Mo Kα radiation, λ = 0.71073 Å
a = 9.7590 (11) ÅCell parameters from 53 reflections
b = 6.8952 (10) Åθ = 3.7–11.1°
c = 9.7980 (14) ŵ = 0.08 mm−1
β = 114.348 (9)°T = 296 K
V = 600.67 (15) Å3Plate, pale yellow
Z = 20.60 × 0.17 × 0.12 mm
Data collection top
Bruker P4
diffractometer		Rint = 0.021
Radiation source: fine-focus sealed tubeθmax = 25.0°, θmin = 2.3°
Graphite monochromatorh = −11→4
2θ/ω scansk = −1→8
2700 measured reflectionsl = −10→11
1341 independent reflections3 standard reflections every 97 reflections
1050 reflections with I > 2σ(I) intensity decay: 0.5%
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.036H-atom parameters constrained
wR(F2) = 0.083 w = 1/[σ2(Fo2) + (0.0372P)2 + 0.0246P]
where P = (Fo2 + 2Fc2)/3
S = 1.04(Δ/σ)max < 0.001
1341 reflectionsΔρmax = 0.11 e Å−3
146 parametersΔρmin = −0.11 e Å−3
1 restraintExtinction correction: SHELXL2014 (Sheldrick, 2015), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
0 constraintsExtinction coefficient: 0.040 (6)
Primary atom site location: structure-invariant direct methodsAbsolute structure: Assigned from the synthesis
Crystal data top
C13H17NO2V = 600.67 (15) Å3
Mr = 219.27Z = 2
Monoclinic, P21Mo Kα radiation
a = 9.7590 (11) ŵ = 0.08 mm−1
b = 6.8952 (10) ÅT = 296 K
c = 9.7980 (14) Å0.60 × 0.17 × 0.12 mm
β = 114.348 (9)°
Data collection top
Bruker P4
diffractometer		Rint = 0.021
2700 measured reflections3 standard reflections every 97 reflections
1341 independent reflections intensity decay: 0.5%
1050 reflections with I > 2σ(I)
Refinement top
R[F2 > 2σ(F2)] = 0.0361 restraint
wR(F2) = 0.083H-atom parameters constrained
S = 1.04Δρmax = 0.11 e Å−3
1341 reflectionsΔρmin = −0.11 e Å−3
146 parametersAbsolute structure: Assigned from the synthesis
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
N10.8276 (2)0.3211 (3)0.1078 (2)0.0427 (5)
O10.9225 (3)0.7423 (5)0.4197 (3)0.1214 (11)
O20.7952 (2)−0.0767 (3)0.0760 (3)0.0797 (7)
H20.83890.00520.15430.120*
C20.9480 (3)0.4619 (4)0.1324 (3)0.0502 (7)
H2B0.90680.57500.07000.060*
H2C1.02290.40470.10360.060*
C31.0222 (3)0.5237 (5)0.2969 (3)0.0629 (9)
H3A1.07730.41500.35750.075*
H3B1.09340.62730.30820.075*
C40.9084 (4)0.5914 (6)0.3506 (3)0.0708 (10)
C50.7746 (3)0.4646 (5)0.3102 (3)0.0613 (9)
H5A0.69830.53130.33180.074*
H5B0.80250.34760.37050.074*
C60.7102 (3)0.4101 (4)0.1448 (2)0.0491 (7)
H6A0.62770.31960.12260.059*
H6B0.67160.52520.08400.059*
C70.7704 (3)0.2371 (4)−0.0447 (3)0.0461 (7)
H7A0.85960.2074−0.06310.055*
C80.6978 (3)0.0421 (4)−0.0420 (3)0.0626 (8)
H8A0.60540.0634−0.02960.075*
H8B0.6726−0.0237−0.13680.075*
C90.6741 (3)0.3692 (4)−0.1714 (2)0.0460 (7)
C100.7397 (3)0.4820 (5)−0.2455 (3)0.0570 (8)
H10A0.84280.4733−0.21800.068*
C110.6544 (4)0.6079 (6)−0.3602 (3)0.0737 (9)
H11A0.70100.6837−0.40720.088*
C120.5013 (4)0.6203 (6)−0.4042 (3)0.0786 (10)
H12A0.44400.7028−0.48190.094*
C130.4338 (4)0.5101 (5)−0.3326 (3)0.0684 (9)
H13A0.33040.5181−0.36200.082*
C140.5188 (3)0.3872 (4)−0.2169 (3)0.0541 (7)
H14A0.47160.3151−0.16840.065*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0361 (11)0.0413 (12)0.0519 (12)0.0012 (11)0.0192 (9)0.0002 (11)
O10.130 (2)0.119 (2)0.104 (2)−0.022 (2)0.0365 (16)−0.062 (2)
O20.0924 (15)0.0412 (12)0.1027 (14)0.0085 (13)0.0374 (12)0.0124 (13)
C20.0445 (14)0.0492 (17)0.0558 (14)−0.0064 (15)0.0194 (11)0.0027 (14)
C30.0533 (16)0.068 (2)0.0566 (15)−0.0138 (18)0.0114 (13)0.0026 (17)
C40.080 (2)0.077 (3)0.0418 (14)0.003 (2)0.0114 (15)−0.0097 (18)
C50.0580 (16)0.080 (2)0.0481 (14)0.0064 (19)0.0243 (13)−0.0025 (17)
C60.0442 (13)0.0563 (18)0.0487 (13)0.0012 (16)0.0210 (11)−0.0009 (15)
C70.0480 (14)0.0403 (14)0.0555 (15)0.0030 (14)0.0270 (12)−0.0042 (14)
C80.0660 (19)0.0403 (16)0.0795 (19)−0.0022 (16)0.0281 (16)−0.0061 (16)
C90.0559 (15)0.0404 (17)0.0435 (13)−0.0022 (15)0.0222 (12)−0.0068 (14)
C100.0677 (17)0.0555 (18)0.0520 (15)−0.0106 (17)0.0287 (14)−0.0061 (16)
C110.104 (3)0.061 (2)0.0584 (17)−0.011 (2)0.0357 (18)0.0015 (19)
C120.101 (3)0.065 (2)0.0548 (17)0.008 (2)0.0177 (19)0.0020 (19)
C130.0633 (18)0.071 (2)0.0594 (17)0.0094 (19)0.0132 (15)−0.0004 (18)
C140.0546 (15)0.0540 (19)0.0515 (14)−0.0038 (16)0.0195 (13)−0.0051 (15)
Geometric parameters (Å, º) top
N1—C21.466 (3)C6—H6B0.9700
N1—C61.469 (3)C7—C91.514 (4)
N1—C71.481 (3)C7—C81.525 (4)
O1—C41.217 (4)C7—H7A0.9800
O2—C81.416 (3)C8—H8A0.9700
O2—H20.9051C8—H8B0.9700
C2—C31.530 (4)C9—C101.387 (4)
C2—H2B0.9700C9—C141.398 (3)
C2—H2C0.9700C10—C111.392 (5)
C3—C41.487 (5)C10—H10A0.9300
C3—H3A0.9700C11—C121.376 (4)
C3—H3B0.9700C11—H11A0.9300
C4—C51.483 (5)C12—C131.373 (5)
C5—C61.524 (3)C12—H12A0.9300
C5—H5A0.9700C13—C141.385 (4)
C5—H5B0.9700C13—H13A0.9300
C6—H6A0.9700C14—H14A0.9300
C2—N1—C6109.7 (2)N1—C7—C9116.1 (2)
C2—N1—C7111.57 (19)N1—C7—C8108.1 (2)
C6—N1—C7113.85 (17)C9—C7—C8114.2 (2)
C8—O2—H2104.7N1—C7—H7A105.9
N1—C2—C3110.9 (2)C9—C7—H7A105.9
N1—C2—H2B109.5C8—C7—H7A105.9
C3—C2—H2B109.5O2—C8—C7111.4 (2)
N1—C2—H2C109.5O2—C8—H8A109.4
C3—C2—H2C109.5C7—C8—H8A109.4
H2B—C2—H2C108.0O2—C8—H8B109.4
C4—C3—C2111.2 (2)C7—C8—H8B109.4
C4—C3—H3A109.4H8A—C8—H8B108.0
C2—C3—H3A109.4C10—C9—C14117.2 (2)
C4—C3—H3B109.4C10—C9—C7120.1 (2)
C2—C3—H3B109.4C14—C9—C7122.7 (2)
H3A—C3—H3B108.0C9—C10—C11121.4 (3)
O1—C4—C5122.6 (3)C9—C10—H10A119.3
O1—C4—C3122.3 (4)C11—C10—H10A119.3
C5—C4—C3115.1 (3)C12—C11—C10120.2 (3)
C4—C5—C6111.1 (2)C12—C11—H11A119.9
C4—C5—H5A109.4C10—C11—H11A119.9
C6—C5—H5A109.4C13—C12—C11119.5 (3)
C4—C5—H5B109.4C13—C12—H12A120.2
C6—C5—H5B109.4C11—C12—H12A120.2
H5A—C5—H5B108.0C12—C13—C14120.4 (3)
N1—C6—C5110.09 (19)C12—C13—H13A119.8
N1—C6—H6A109.6C14—C13—H13A119.8
C5—C6—H6A109.6C13—C14—C9121.4 (3)
N1—C6—H6B109.6C13—C14—H14A119.3
C5—C6—H6B109.6C9—C14—H14A119.3
H6A—C6—H6B108.2
C6—N1—C2—C361.7 (3)N1—C7—C8—O2−50.9 (3)
C7—N1—C2—C3−171.2 (2)C9—C7—C8—O2178.2 (2)
N1—C2—C3—C4−52.6 (4)N1—C7—C9—C1091.9 (3)
C2—C3—C4—O1−131.9 (3)C8—C7—C9—C10−141.3 (2)
C2—C3—C4—C546.5 (4)N1—C7—C9—C14−86.8 (3)
O1—C4—C5—C6130.5 (3)C8—C7—C9—C1440.1 (3)
C3—C4—C5—C6−47.9 (4)C14—C9—C10—C110.1 (4)
C2—N1—C6—C5−62.8 (3)C7—C9—C10—C11−178.6 (3)
C7—N1—C6—C5171.4 (2)C9—C10—C11—C12−1.1 (5)
C4—C5—C6—N155.1 (4)C10—C11—C12—C131.0 (5)
C2—N1—C7—C9−73.2 (3)C11—C12—C13—C140.0 (5)
C6—N1—C7—C951.5 (3)C12—C13—C14—C9−1.0 (5)
C2—N1—C7—C8157.0 (2)C10—C9—C14—C131.0 (4)
C6—N1—C7—C8−78.3 (3)C7—C9—C14—C13179.6 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O2—H2···N10.912.222.764 (3)118
C2—H2B···O2i0.972.653.460 (4)142
C3—H3A···O1ii0.972.493.246 (4)135
Symmetry codes: (i) x, y+1, z; (ii) −x+2, y−1/2, −z+1.
(II) 8-[(1S)-1-Phenylethyl]-1,4-dioxa-8-azaspiro[4.5]decane-7-thione top
Crystal data top
C15H19NO2SDx = 1.279 Mg m−3
Mr = 277.37Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P212121Cell parameters from 58 reflections
a = 5.9731 (13) Åθ = 4.7–12.5°
b = 14.948 (3) ŵ = 0.22 mm−1
c = 16.127 (3) ÅT = 296 K
V = 1439.9 (5) Å3Irregular, colourless
Z = 40.60 × 0.38 × 0.36 mm
F(000) = 592
Data collection top
Bruker P4
diffractometer		2007 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.029
Graphite monochromatorθmax = 27.5°, θmin = 1.9°
2θ/ω scansh = −7→3
Absorption correction: ψ scan
(XSCANS; Fait, 1996)		k = −19→19
Tmin = 0.760, Tmax = 0.922l = −20→20
3886 measured reflections3 standard reflections every 97 reflections
2631 independent reflections intensity decay: 1.5%
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.044 w = 1/[σ2(Fo2) + (0.0668P)2 + 0.0631P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.120(Δ/σ)max < 0.001
S = 1.06Δρmax = 0.19 e Å−3
2631 reflectionsΔρmin = −0.24 e Å−3
174 parametersExtinction correction: SHELXL2014 (Sheldrick, 2015), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
0 restraintsExtinction coefficient: 0.014 (4)
0 constraintsAbsolute structure: Flack x determined using 483 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
Primary atom site location: structure-invariant direct methodsAbsolute structure parameter: 0.08 (7)
Secondary atom site location: difference Fourier map
Crystal data top
C15H19NO2SV = 1439.9 (5) Å3
Mr = 277.37Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 5.9731 (13) ŵ = 0.22 mm−1
b = 14.948 (3) ÅT = 296 K
c = 16.127 (3) Å0.60 × 0.38 × 0.36 mm
Data collection top
Bruker P4
diffractometer		2007 reflections with I > 2σ(I)
Absorption correction: ψ scan
(XSCANS; Fait, 1996)		Rint = 0.029
Tmin = 0.760, Tmax = 0.9223 standard reflections every 97 reflections
3886 measured reflections intensity decay: 1.5%
2631 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.044H-atom parameters constrained
wR(F2) = 0.120Δρmax = 0.19 e Å−3
S = 1.06Δρmin = −0.24 e Å−3
2631 reflectionsAbsolute structure: Flack x determined using 483 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
174 parametersAbsolute structure parameter: 0.08 (7)
0 restraints
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
S10.90206 (18)0.38336 (6)0.64284 (6)0.0676 (3)
N10.5705 (4)0.49810 (13)0.61607 (13)0.0409 (6)
C20.7114 (5)0.46066 (19)0.66903 (18)0.0435 (7)
C30.6996 (6)0.4875 (2)0.75975 (18)0.0522 (8)
H3A0.63500.43830.79090.063*
H3B0.85090.49640.78000.063*
C40.5660 (6)0.57054 (18)0.77730 (17)0.0459 (7)
C50.3483 (6)0.5637 (2)0.73219 (19)0.0532 (8)
H5A0.25470.61470.74560.064*
H5B0.27020.50980.74900.064*
C60.3927 (6)0.5612 (2)0.63970 (17)0.0564 (8)
H6A0.25570.54470.61130.068*
H6B0.43420.62070.62130.068*
C70.5849 (6)0.47717 (17)0.52588 (16)0.0454 (7)
H7A0.73630.45450.51560.054*
C80.4240 (8)0.40247 (19)0.5035 (2)0.0663 (10)
H8A0.46110.34980.53460.099*
H8B0.43530.38980.44530.099*
H8C0.27380.42050.51640.099*
C90.5595 (6)0.56255 (18)0.47498 (16)0.0434 (7)
C100.3737 (6)0.5799 (2)0.42688 (18)0.0525 (8)
H10A0.25660.53900.42500.063*
C110.3612 (8)0.6593 (2)0.38083 (18)0.0635 (10)
H11A0.23480.67120.34900.076*
C120.5336 (8)0.7192 (2)0.3824 (2)0.0689 (11)
H12A0.52560.77140.35120.083*
C130.7186 (8)0.7023 (2)0.4302 (2)0.0684 (11)
H13A0.83560.74330.43190.082*
C140.7310 (6)0.6238 (2)0.4760 (2)0.0559 (8)
H14A0.85760.61250.50790.067*
O150.6883 (5)0.64740 (15)0.75095 (14)0.0743 (8)
C160.6637 (12)0.7128 (3)0.8120 (3)0.120 (2)
H16A0.57990.76320.79020.144*
H16B0.80950.73410.82970.144*
C170.5447 (8)0.6734 (2)0.8821 (2)0.0666 (11)
H17A0.62410.68450.93350.080*
H17B0.39480.69790.88650.080*
O180.5371 (4)0.57972 (13)0.86428 (12)0.0553 (6)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0725 (6)0.0688 (6)0.0615 (5)0.0339 (5)−0.0020 (5)−0.0005 (4)
N10.0465 (14)0.0369 (11)0.0393 (11)0.0038 (12)0.0012 (12)0.0018 (10)
C20.0438 (16)0.0412 (14)0.0456 (15)0.0002 (14)−0.0005 (14)0.0061 (12)
C30.0563 (19)0.0588 (18)0.0414 (15)0.0078 (18)−0.0023 (15)0.0039 (14)
C40.0578 (19)0.0404 (14)0.0393 (13)−0.0059 (16)0.0102 (15)0.0043 (12)
C50.054 (2)0.0551 (17)0.0501 (16)0.0096 (17)0.0064 (16)0.0031 (14)
C60.065 (2)0.0605 (18)0.0440 (15)0.0239 (18)0.0021 (18)0.0016 (14)
C70.0583 (19)0.0392 (13)0.0386 (13)0.0007 (16)0.0001 (16)0.0003 (11)
C80.093 (3)0.0462 (17)0.0593 (18)−0.013 (2)−0.008 (2)0.0002 (13)
C90.0552 (19)0.0385 (13)0.0365 (12)0.0012 (15)0.0025 (14)−0.0025 (11)
C100.059 (2)0.0548 (16)0.0431 (14)−0.0025 (17)−0.0062 (17)0.0039 (13)
C110.074 (3)0.071 (2)0.0461 (16)0.010 (2)−0.0115 (18)0.0122 (16)
C120.099 (3)0.0540 (18)0.0543 (17)0.003 (2)0.008 (2)0.0160 (16)
C130.084 (3)0.0496 (19)0.072 (2)−0.015 (2)0.003 (2)0.0105 (16)
C140.0551 (19)0.0547 (18)0.0580 (18)−0.0086 (18)−0.0075 (17)0.0077 (16)
O150.108 (2)0.0544 (12)0.0601 (13)−0.0289 (14)0.0275 (15)−0.0022 (11)
C160.200 (7)0.062 (2)0.097 (3)−0.060 (4)0.057 (4)−0.022 (2)
C170.100 (3)0.0484 (17)0.0516 (17)−0.005 (2)0.006 (2)−0.0045 (14)
O180.0793 (17)0.0454 (10)0.0412 (10)−0.0079 (12)0.0118 (11)0.0009 (8)
Geometric parameters (Å, º) top
S1—C21.677 (3)C8—H8B0.9600
N1—C21.323 (4)C8—H8C0.9600
N1—C61.471 (4)C9—C141.375 (5)
N1—C71.490 (3)C9—C101.379 (5)
C2—C31.519 (4)C10—C111.402 (4)
C3—C41.503 (4)C10—H10A0.9300
C3—H3A0.9700C11—C121.365 (6)
C3—H3B0.9700C11—H11A0.9300
C4—O181.420 (3)C12—C131.370 (6)
C4—O151.426 (3)C12—H12A0.9300
C4—C51.493 (5)C13—C141.388 (5)
C5—C61.515 (4)C13—H13A0.9300
C5—H5A0.9700C14—H14A0.9300
C5—H5B0.9700O15—C161.395 (4)
C6—H6A0.9700C16—C171.459 (5)
C6—H6B0.9700C16—H16A0.9700
C7—C81.517 (4)C16—H16B0.9700
C7—C91.525 (4)C17—O181.430 (3)
C7—H7A0.9800C17—H17A0.9700
C8—H8A0.9600C17—H17B0.9700
C2—N1—C6124.3 (2)C7—C8—H8B109.5
C2—N1—C7120.3 (3)H8A—C8—H8B109.5
C6—N1—C7115.4 (2)C7—C8—H8C109.5
N1—C2—C3118.7 (3)H8A—C8—H8C109.5
N1—C2—S1124.1 (2)H8B—C8—H8C109.5
C3—C2—S1117.1 (2)C14—C9—C10118.8 (3)
C4—C3—C2115.1 (2)C14—C9—C7118.5 (3)
C4—C3—H3A108.5C10—C9—C7122.7 (3)
C2—C3—H3A108.5C9—C10—C11120.0 (3)
C4—C3—H3B108.5C9—C10—H10A120.0
C2—C3—H3B108.5C11—C10—H10A120.0
H3A—C3—H3B107.5C12—C11—C10120.3 (4)
O18—C4—O15106.2 (2)C12—C11—H11A119.8
O18—C4—C5112.5 (3)C10—C11—H11A119.8
O15—C4—C5110.8 (3)C11—C12—C13119.9 (3)
O18—C4—C3109.3 (2)C11—C12—H12A120.0
O15—C4—C3109.7 (3)C13—C12—H12A120.0
C5—C4—C3108.3 (3)C12—C13—C14119.8 (4)
C4—C5—C6109.2 (3)C12—C13—H13A120.1
C4—C5—H5A109.8C14—C13—H13A120.1
C6—C5—H5A109.8C9—C14—C13121.1 (3)
C4—C5—H5B109.8C9—C14—H14A119.4
C6—C5—H5B109.8C13—C14—H14A119.4
H5A—C5—H5B108.3C16—O15—C4107.5 (3)
N1—C6—C5113.4 (2)O15—C16—C17108.3 (3)
N1—C6—H6A108.9O15—C16—H16A110.0
C5—C6—H6A108.9C17—C16—H16A110.0
N1—C6—H6B108.9O15—C16—H16B110.0
C5—C6—H6B108.9C17—C16—H16B110.0
H6A—C6—H6B107.7H16A—C16—H16B108.4
N1—C7—C8110.5 (3)O18—C17—C16104.8 (3)
N1—C7—C9110.1 (2)O18—C17—H17A110.8
C8—C7—C9115.2 (3)C16—C17—H17A110.8
N1—C7—H7A106.9O18—C17—H17B110.8
C8—C7—H7A106.9C16—C17—H17B110.8
C9—C7—H7A106.9H17A—C17—H17B108.9
C7—C8—H8A109.5C4—O18—C17106.8 (2)
C6—N1—C2—C3−3.5 (4)C8—C7—C9—C14−163.6 (3)
C7—N1—C2—C3176.7 (3)N1—C7—C9—C10−110.5 (3)
C6—N1—C2—S1175.5 (2)C8—C7—C9—C1015.2 (4)
C7—N1—C2—S1−4.3 (4)C14—C9—C10—C11−0.6 (5)
N1—C2—C3—C4−14.3 (4)C7—C9—C10—C11−179.4 (3)
S1—C2—C3—C4166.7 (2)C9—C10—C11—C120.9 (5)
C2—C3—C4—O18170.4 (3)C10—C11—C12—C13−0.9 (6)
C2—C3—C4—O15−73.6 (4)C11—C12—C13—C140.8 (6)
C2—C3—C4—C547.6 (4)C10—C9—C14—C130.5 (5)
O18—C4—C5—C6175.7 (2)C7—C9—C14—C13179.3 (3)
O15—C4—C5—C657.1 (3)C12—C13—C14—C9−0.5 (5)
C3—C4—C5—C6−63.4 (3)O18—C4—O15—C16−19.9 (5)
C2—N1—C6—C5−13.5 (4)C5—C4—O15—C16102.5 (4)
C7—N1—C6—C5166.3 (3)C3—C4—O15—C16−137.9 (4)
C4—C5—C6—N147.2 (4)C4—O15—C16—C176.2 (6)
C2—N1—C7—C894.8 (4)O15—C16—C17—O189.6 (6)
C6—N1—C7—C8−85.0 (3)O15—C4—O18—C1726.1 (4)
C2—N1—C7—C9−136.8 (3)C5—C4—O18—C17−95.3 (3)
C6—N1—C7—C943.4 (4)C3—C4—O18—C17144.4 (3)
N1—C7—C9—C1470.7 (4)C16—C17—O18—C4−21.9 (5)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C7—H7A···S10.982.513.019 (3)112
C16—H16B···S1i0.972.853.709 (5)148
Symmetry code: (i) −x+2, y+1/2, −z+3/2.
Hydrogen-bond geometry (Å, º) for (I) top
D—H···AD—HH···AD···AD—H···A
C3—H3A···O1i0.972.493.246 (4)135.0
Symmetry code: (i) −x+2, y−1/2, −z+1.
Hydrogen-bond geometry (Å, º) for (II) top
D—H···AD—HH···AD···AD—H···A
C16—H16B···S1i0.972.853.709 (5)147.6
Symmetry code: (i) −x+2, y+1/2, −z+3/2.

Experimental details

(I)(II)
Crystal data
Chemical formulaC13H17NO2C15H19NO2S
Mr219.27277.37
Crystal system, space groupMonoclinic, P21Orthorhombic, P212121
Temperature (K)296296
a, b, c (Å)9.7590 (11), 6.8952 (10), 9.7980 (14)5.9731 (13), 14.948 (3), 16.127 (3)
α, β, γ (°)90, 114.348 (9), 9090, 90, 90
V (Å3)600.67 (15)1439.9 (5)
Z24
Radiation typeMo KαMo Kα
µ (mm−1)0.080.22
Crystal size (mm)0.60 × 0.17 × 0.120.60 × 0.38 × 0.36
Data collection
DiffractometerBruker P4
diffractometer		Bruker P4
diffractometer
Absorption correction–ψ scan
(XSCANS; Fait, 1996)
Tmin, Tmax–0.760, 0.922
No. of measured, independent and
observed [I > 2σ(I)] reflections		2700, 1341, 1050 3886, 2631, 2007
Rint0.0210.029
(sin θ/λ)max (Å−1)0.5950.650
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.036, 0.083, 1.04 0.044, 0.120, 1.06
No. of reflections13412631
No. of parameters146174
No. of restraints10
H-atom treatmentH-atom parameters constrainedH-atom parameters constrained
Δρmax, Δρmin (e Å−3)0.11, −0.110.19, −0.24
Absolute structureAssigned from the synthesisFlack x determined using 483 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
Absolute structure parameter?0.08 (7)

Computer programs: XSCANS (Fait, 1996), SHELXS97 (Sheldrick, 2008), SHELXL2014 (Sheldrick, 2015), SHELXTL (Sheldrick, 2008).

 

Acknowledgements

The authors thank the `Programa de Fortalecimiento a la Investigación' of the Universidad Juárez Autónoma de Tabasco for financial support via the project UJAT-2013-IB-13.

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ISSN: 2056-9890
Volume 71| Part 10| October 2015| Pages 1207-1211
doi:10.1107/S2056989015017119
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