Crystallographic and spectroscopic characterization of 2-[(7-acetyl-4-cyano-6-hy­droxy-1,6-dimethyl-8-phenyl-5,6,7,8-tetra­hydro­isoquinolin-3-yl)sulfan­yl]-N-phenyl­acetamide

Al-Taifi, E.A.; Maraei, I.S.; Bakhite, E.A.; Demirtas, G.; Mague, J.T.; Mohamed, S.K.; Ramli, Y.

doi:10.1107/S2056989021000372

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ISSN: 2056-9890

Volume 77| Part 2| February 2021| Pages 121-125

https://doi.org/10.1107/S2056989021000372

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Crystallographic and spectroscopic characterization of 2-[(7-acetyl-4-cyano-6-hydroxy-1,6-dimethyl-8-phenyl-5,6,7,8-tetrahydroisoquinolin-3-yl)sulfanyl]-N-phenylacetamide

Elham A. Al-Taifi,^a ^* Islam S. Maraei,^b Etify A. Bakhite,^b Güneş Demirtas,^c Joel. T. Mague,^d Shaaban K. Mohamed ^e,^f and Youssef Ramli ^g ^*

^aDepartment of Chemistry, Faculty of Science, Sana'a University, Sana'a, Yemen, ^bDepartment of Chemistry, Faculty of Science, Assiut University, Assiut, Egypt, ^cOndokuz Mayıs University, Faculty of Arts and Sciences, Department of Physics, 55139, Samsun, Turkey, ^dDepartment of Chemistry, Tulane University, New Orleans, LA 70118, USA, ^eChemistry and Environmental Division, Manchester Metropolitan University, Manchester M1 5GD, England, ^fChemistry Department, Faculty of Science, Minia University, 61519 El-Minia, Egypt, and ^gLaboratory of Medicinal Chemistry, Drug Sciences Research Center, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Morocco
^*Correspondence e-mail: shaabankamel@yahoo.com, y.ramli@um5s.net.ma

Edited by L. Van Meervelt, Katholieke Universiteit Leuven, Belgium (Received 21 December 2020; accepted 11 January 2021; online 15 January 2021)

In the title molecule, C₂₈H₂₇N₃O₃S, the heterocyclic portion of the tetrahydroisoquinoline unit is planar and an intramolecular N—H⋯N hydrogen bond and a C—H⋯π(ring) interaction help to determine the overall conformation. In the crystal, a layer structure with the layers parallel to (10 $[\overline{1}]$ ) is generated by O—H⋯O and C—H⋯O hydrogen bonds.

Keywords: crystal structure; tetrahydroisoquinoline; phenylacetamide; hydrogen bond; C—H⋯π(ring) interaction.

CCDC reference: 2055318

1. Chemical context

Tetrahydroisoquinolines exhibit important pharmacological activities including antitumor (Scott & Williams, 2002 ), antimicrobial (Bernan et al., 1994 ), and dopaminergic activities (Andujar et al., 2012 ). They are used as starting materials in the syntheses of pharmacologically active, constrained conformations of N-substituted-2-aminopyridines as antinociceptive agents (Dukat et al., 2004 ) and constrained conformations of nicotine to improve nicotine vaccines (Xu et al., 2002 ; Meijler et al., 2003 ; Carroll et al., 2007 ). These examples demonstrate the utility of the tetrahydroisoquinoline core and why these types of compounds are of great interest. In this context, we report here the synthesis and crystal structure of the title compound.

2. Structural commentary

The title compound crystallizes in space group P2₁/n with one molecule in the asymmetric unit (Fig. 1). The C5/C6/C7/N1/C8/C9 ring is approximately planar (r.m.s. deviation = 0.011 Å) with the largest deviation of 0.020 (1) Å being for atom C6. The best planes through the C10–C15 and C23–C28 rings are inclined to the above plane by 85.19 (6) and 64.22 (7)°, respectively. The orientation of the former ring is due in part to the C20—H20A⋯Cg3 (Cg3 is the centroid of the C10–C15 benzene ring) interaction while the intramolecular N3—H3A⋯N1 hydrogen bond affects the orientation of the second ring (Table 1 and Fig. 1) and places the two rings on the same side of the tetrahydroquinoxaline unit. The acetyl group on C2 is in an equatorial position while the hydroxyl group on C3 is axial and these are syn to one another. The C10–C15 ring attached to C1 is close to equatorial and anti with respect to both other subsituents (Fig. 1). Although the O2—H2A hydroxyl group is favorably oriented for forming an intramolecular hydrogen bond with O1 as has been seen in some related molecules (Mague & Mohamed, 2020 ), the H⋯O distance of ca 2.54 Å is long and a stronger, intermolecular interaction is favored (vide infra). A puckering analysis (Cremer & Pople, 1975 ) of the C1–C5/C9 ring yielded the following parameters: Q = 0.5267 (13) Å, θ = 128.52 (14)° and φ = 286.46 (18)°. The conformation of this ring approximates an envelope with C3 as the flap.

Table 1
Hydrogen-bond geometry (Å, °)

Cg3 is the centroid of the C10–C15 benzene ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2A⋯O1ⁱ	0.86 (2)	2.04 (2)	2.8674 (13)	161.9 (19)
N3—H3A⋯N1	0.887 (18)	2.306 (18)	3.1148 (15)	151.6 (15)
C13—H13⋯O2ⁱⁱ	0.94 (2)	2.40 (2)	3.2520 (19)	150.5 (17)
C20—H20A⋯Cg3	1.00 (2)	2.975 (19)	3.6866 (16)	128.7 (13)
Symmetry codes: (i) ; (ii) $[-x+{\script{3\over 2}}, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ .

Figure 1
The title molecule with labeling scheme and 50% probability ellipsoids. The intramolecular hydrogen bond and C—H⋯π(ring) interaction are depicted, respectively, by blue and green dashed lines.

3. Supramolecular features

In the crystal, inversion dimers are formed by O2—H2A⋯O1 hydrogen bonds (Table 1), which results in O1⋯O1ⁱ and O1⋯O2ⁱ [symmetry code: (i) −x + 1, −y + 1, −z] contacts of 2.8774 (16) and 2.8674 (14) Å (0.16 and 0.17 Å less than the sum of the van der Waals radii), respectively. The dimers are connected by C13—H13⋯O2 hydrogen bonds (Table 1), forming layers parallel to (10 $[\overline{1}]$ ) (Figs. 2 and 3).

Figure 2
Packing viewed along the a-axis direction with intermolecular O—H⋯O and C—H⋯O hydrogen bonds depicted, respectively, by red and black dashed lines.

Figure 3
Packing viewed along the b-axis direction with intermolecular O—H⋯O and C—H⋯O hydrogen bonds depicted, respectively, by red and black dashed lines.

4. Database survey

A search of the Cambridge Structural Database (CSD, updated to December 2020, Groom et al., 2016 ) found three analogs of the title molecule, one with a methyl group on sulfur (refcode AXUXOH; Dyachenko et al., 2010 ) and two with a 4-chlorophenyl group on C1 in place of the phenyl group, one with an ethyl group on sulfur (NAQRIJ; Mague et al., 2017a ) and the other with a CH₂CO₂CH₃ group on sulfur (PAWCEY; Mague et al., 2017b ). In all three, the acetyl group is equatorial and the hydroxyl group is axial while the phenyl or 4-chlorophenyl group is close to equatorial, as is the case with the title molecule. The puckering amplitudes of the cyclohexene ring in the second and third molecule are, respectively, 0.521 (2) and 0.524 (3) Å, which are essentially the same as in the title molecule. One notable difference between the four molecules is the orientation of the hydroxyl hydrogen. In AXUXOH there is an intramolecular hydrogen bond with the acetyl group leading to an H⋯O distance of 2.23 Å. In the other three, intermolecular hydrogen bonding of the hydroxyl group predominates and the intramolecular H⋯O distances are 2.55, 2.71 and 3.18 Å for the title molecule, PAWCEY and NAQRIJ, respectively.

5. Hirshfeld surface analysis

Hirshfeld surface analysis is an effective means of probing intermolecular interactions (McKinnon et al., 2007 ; Spackman & Jayatilaka, 2009 ), which can be conveniently carried out with Crystal Explorer 17 (Turner et al., 2017 ). A detailed description of the use of Crystal Explorer 17 and the plots obtained is given by Tan et al. (2019 ). From the surface mapped over d_norm (Fig. 4a), the sites of the intermolecular O—H⋯O and C—H⋯O hydrogen bonds can be seen on the left side near the bottom and at the top, respectively. A weaker point of interaction is at O3 on the lower right of the diagram, which might indicate a weak, intermolecular C4—H4B⋯O3 hydrogen bond since the O⋯H distance is 2.605 (15) Å. The surfaces mapped over shape-index (Fig. 4b) and curvedness (Fig. 5c) show a relatively flat region over the C23–C28 benzene ring in the latter and a red triangular area over the edge of the ring in the former. This is suggestive of a C—H⋯π(ring) interaction and can be identified with the C20—H20A⋯Cg3 interaction noted in Section 2. The fingerprint plots derived from the Hirshfeld surface enable the apportionment of the intermolecular interactions into specific sets. Fig. 5a displays the plot for all interactions while Fig. 5b–5d show those delineated into H⋯H, H⋯O/O⋯H and H⋯N/N⋯H interactions, which constitute 47.3%, 11.8% and 10.6% of the total interactions, respectively.

Figure 4
The Hirshfeld surface of the title molecule mapped over (a) d_norm, (b) shape-index, and (c) curvedness.

Figure 5
Fingerprint plots for the title molecule showing (a) all contacts and those delineated into (b) H⋯H contacts, (c) H⋯O/O⋯H contacts, and (d) H⋯N/N⋯H contacts.

6. Synthesis and crystallization

A mixture of 7-acetyl-4-cyano-1,5-dimethyl-6-hydroxy-8-phenyl-5,6,7,8-tetrahydroisoquinoline-3(2H)-thione (10 mmol), N-phenyl-2-chloroacetamide (10 mmol) and sodium acetate trihydrate (1.50 g, 11 mmol) in ethanol (100 mL) was heated under reflux for one hour. The precipitate that formed after standing at room temperature overnight was collected, washed with water, dried in air and then recrystallized from ethanol to afford the title compound in the form of colorless crystals. Yield: 4.00 g, 82%; m. p.: 470-472 K.

7. Spectroscopic characterization

The chemical structure of the compound has also been confirmed using analytical and spectroscopic methods. The FT–IR spectrum shows mainly the characteristic NH peak of the acetamide group at 3277 cm⁻¹ and the C=O bond of the amide group at 1667 cm⁻¹. In addition, characteristic peaks of the precursor are observed: OH at 3522 cm⁻¹, aromatic C—H at 3058 cm⁻¹, aliphatic C—H at 2920, 2970, 2991 cm⁻¹, nitrile at 2217 cm⁻¹ and acetyl at 1694 cm⁻¹, also confirming the structure of the compound.

With regard to the ¹H NMR spectrum, several characteristic signals can be clearly attributed to the title compound, such as a doublet of doublets between 4.09 and 4.19 ppm with a coupling constant of 16 Hz due to SCH₂, and a singlet at 10.22 ppm due to NH. In addition, we note the presence of characteristic peaks related to the starting compound: multiplets between 7.17 and 7.29 ppm due to aromatic protons, singlets at 1.28, 1.92, 2.11 and 4.84 ppm referring to a methyl group attached to a pyridine ring, the CH₃ of the acetamide group and the hydroxy group, respectively. The doublets between 7.53–7.55 (J = 8 Hz) and 7.02–7.04 (J = 8 Hz) can be attributed to the aromatic protons.

IR (cm⁻¹): 3522 (OH); 3277 (NH); 3058 (C—H, aromatic); 2920, 2970, 2991 (C—H aliphatic); 2217 (C≡N); 1694 (C=O, acetyl); 1667 (C=O, amide).

¹H NMR (400 MHz, CDCl₃): 10.22 (s, 1H, NH); 7.53–7.55 (d, J = 8 Hz, 2H, Ar-H); 7.23–7.29 (m, 4H, Ar-H); 7.17–7.20 (m, 1H, Ar-H); 7.02–7.04 (d, J = 8 Hz, 3H, Ar-H); 4.84 (s, 1H, OH); 4.52–4.54 (d, J = 8 Hz, 1H, CH at C-8); 4.09–4.19 (dd, J = 16 Hz, 2H, SCH₂); 3.25–3.29 (d, J = 16 Hz, 1H, CH₂); 2.94–2.96 (d, J = 8 Hz, 1H, CH at C-7); 2.89–2.94 (d, J = 20 Hz, 1H, CH₂), 2.11 (s, 3H, COCH₃); 1.92 (s, 3H, CH₃ attached to pyridine ring); 1.28 (s, 3H, CH₃).

8. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. All hydrogen atoms were independently refined. Twelve reflections were not accessible due to the configuration of the goniometer and the low-temperature attachment.

Table 2
Experimental details

Crystal data
Chemical formula	C₂₈H₂₇N₃O₃S
M_r	485.58
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	150
a, b, c (Å)	12.0487 (4), 13.9821 (5), 15.0239 (5)
β (°)	106.606 (1)
V (Å³)	2425.46 (14)
Z	4
Radiation type	Cu Kα
μ (mm⁻¹)	1.47
Crystal size (mm)	0.26 × 0.14 × 0.08

Data collection
Diffractometer	Bruker D8 VENTURE PHOTON 100 CMOS
Absorption correction	Multi-scan (SADABS; Krause et al., 2015 )
T_min, T_max	0.79, 0.89
No. of measured, independent and observed [I > 2σ(I)] reflections	18194, 4734, 4284
R_int	0.030
(sin θ/λ)_max (Å⁻¹)	0.618

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.032, 0.083, 1.06
No. of reflections	4734
No. of parameters	425
H-atom treatment	All H-atom parameters refined
Δρ_max, Δρ_min (e Å⁻³)	0.22, −0.21
Computer programs: APEX3 and SAINT (Bruker, 2016 ), SHELXT/5 (Sheldrick, 2015a ), SHELXL 2018/3 (Sheldrick, 2015b ), DIAMOND (Brandenburg & Putz, 2012 ), and SHELXTL (Sheldrick, 2008 ).

Supporting information

CCDC reference: 2055318

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S2056989021000372/vm2243sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989021000372/vm2243Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989021000372/vm2243Isup3.cml

checkCIF report

Computing details top

Data collection: APEX3 (Bruker, 2016); cell refinement: SAINT (Bruker, 2016); data reduction: SAINT (Bruker, 2016); program(s) used to solve structure: SHELXT/5 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL 2018/3 (Sheldrick, 2015b); molecular graphics: DIAMOND (Brandenburg & Putz, 2012); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

2-[(7-Acetyl-4-cyano-6-hydroxy-1,6-dimethyl-8-phenyl-5,6,7,8-tetrahydroisoquinolin-3-yl)sulfanyl]-N-phenylacetamide top

Crystal data top

C₂₈H₂₇N₃O₃S	F(000) = 1024
M_r = 485.58	D_x = 1.330 Mg m⁻³
Monoclinic, P2₁/n	Cu Kα radiation, λ = 1.54178 Å
a = 12.0487 (4) Å	Cell parameters from 9855 reflections
b = 13.9821 (5) Å	θ = 4.4–72.5°
c = 15.0239 (5) Å	µ = 1.47 mm⁻¹
β = 106.606 (1)°	T = 150 K
V = 2425.46 (14) Å³	Column, colourless
Z = 4	0.26 × 0.14 × 0.08 mm

Data collection top

Bruker D8 VENTURE PHOTON 100 CMOS diffractometer	4734 independent reflections
Radiation source: INCOATEC IµS micro–focus source	4284 reflections with I > 2σ(I)
Mirror monochromator	R_int = 0.030
Detector resolution: 10.4167 pixels mm^-1	θ_max = 72.4°, θ_min = 4.4°
ω scans	h = −14→14
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	k = −15→17
T_min = 0.79, T_max = 0.89	l = −17→18
18194 measured reflections

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: difference Fourier map
R[F² > 2σ(F²)] = 0.032	All H-atom parameters refined
wR(F²) = 0.083	w = 1/[σ²(F_o²) + (0.0386P)² + 0.7971P] where P = (F_o² + 2F_c²)/3
S = 1.06	(Δ/σ)_max = 0.001
4734 reflections	Δρ_max = 0.22 e Å⁻³
425 parameters	Δρ_min = −0.21 e Å⁻³
0 restraints	Extinction correction: SHELXL 2018/3 (Sheldrick, 2015b), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: dual	Extinction coefficient: 0.0039 (2)

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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 (Å²) top

	x	y	z	U_iso*/U_eq
S1	0.58184 (3)	0.71687 (2)	0.54963 (2)	0.02702 (10)
O1	0.55415 (10)	0.41602 (8)	0.04888 (7)	0.0389 (3)
O2	0.43190 (8)	0.56327 (6)	0.13750 (6)	0.02221 (19)
H2A	0.4361 (17)	0.5558 (14)	0.0816 (14)	0.053 (5)*
O3	0.80915 (12)	0.76450 (8)	0.74784 (7)	0.0463 (3)
N1	0.69752 (9)	0.60562 (7)	0.46015 (7)	0.0226 (2)
N2	0.29604 (10)	0.63554 (10)	0.43743 (8)	0.0363 (3)
N3	0.84869 (10)	0.64010 (8)	0.66349 (8)	0.0276 (2)
H3A	0.8267 (15)	0.6163 (12)	0.6064 (12)	0.036 (4)*
C1	0.61831 (10)	0.44233 (8)	0.24855 (8)	0.0192 (2)
H1	0.6482 (13)	0.4819 (11)	0.2084 (10)	0.024 (4)*
C2	0.50155 (10)	0.40139 (8)	0.18906 (8)	0.0201 (2)
H2	0.4796 (12)	0.3479 (10)	0.2233 (10)	0.020 (3)*
C3	0.40183 (10)	0.47505 (8)	0.17204 (8)	0.0195 (2)
C4	0.38587 (10)	0.49849 (9)	0.26679 (8)	0.0198 (2)
H4A	0.3566 (13)	0.4409 (11)	0.2914 (10)	0.026 (4)*
H4B	0.3263 (14)	0.5499 (11)	0.2593 (11)	0.029 (4)*
C5	0.49669 (10)	0.53100 (8)	0.33547 (8)	0.0184 (2)
C6	0.49119 (10)	0.59248 (8)	0.40793 (8)	0.0203 (2)
C7	0.59357 (11)	0.63014 (8)	0.46686 (8)	0.0211 (2)
C8	0.70418 (10)	0.54452 (8)	0.39243 (8)	0.0217 (2)
C9	0.60604 (10)	0.50545 (8)	0.32793 (8)	0.0190 (2)
C10	0.69924 (10)	0.35759 (8)	0.27879 (8)	0.0207 (2)
C11	0.68696 (11)	0.29760 (9)	0.34899 (9)	0.0260 (3)
H11	0.6323 (14)	0.3128 (12)	0.3811 (11)	0.031 (4)*
C12	0.75677 (13)	0.21739 (10)	0.37340 (11)	0.0376 (3)
H12	0.7497 (16)	0.1783 (14)	0.4238 (13)	0.049 (5)*
C13	0.83774 (13)	0.19569 (10)	0.32770 (13)	0.0425 (4)
H13	0.8869 (17)	0.1427 (15)	0.3467 (14)	0.055 (5)*
C14	0.85014 (13)	0.25445 (11)	0.25757 (12)	0.0401 (4)
H14	0.9087 (17)	0.2423 (14)	0.2239 (13)	0.048 (5)*
C15	0.78155 (12)	0.33535 (10)	0.23292 (10)	0.0305 (3)
H15	0.7883 (16)	0.3783 (13)	0.1832 (13)	0.046 (5)*
C16	0.51833 (11)	0.36283 (9)	0.09888 (8)	0.0265 (3)
C17	0.49321 (16)	0.25966 (11)	0.07668 (11)	0.0392 (4)
H17A	0.5448 (18)	0.2227 (14)	0.1245 (14)	0.052 (5)*
H17B	0.5020 (18)	0.2458 (15)	0.0139 (15)	0.060 (6)*
H17C	0.4129 (19)	0.2421 (15)	0.0793 (14)	0.056 (6)*
C18	0.29017 (12)	0.43558 (10)	0.10695 (9)	0.0268 (3)
H18A	0.2702 (14)	0.3705 (12)	0.1262 (11)	0.034 (4)*
H18B	0.2960 (14)	0.4305 (11)	0.0429 (12)	0.032 (4)*
H18C	0.2254 (14)	0.4804 (12)	0.1047 (11)	0.033 (4)*
C19	0.38188 (11)	0.61752 (9)	0.42231 (8)	0.0242 (3)
C20	0.82558 (12)	0.52338 (11)	0.39007 (11)	0.0325 (3)
H20A	0.8471 (16)	0.4556 (14)	0.4093 (13)	0.048 (5)*
H20B	0.8298 (17)	0.5294 (14)	0.3262 (14)	0.052 (5)*
H20C	0.8796 (15)	0.5671 (13)	0.4323 (12)	0.038 (4)*
C21	0.72565 (13)	0.76893 (9)	0.58406 (9)	0.0289 (3)
H21A	0.7616 (15)	0.7601 (12)	0.5336 (12)	0.034 (4)*
H21B	0.7122 (14)	0.8361 (12)	0.5963 (11)	0.034 (4)*
C22	0.79955 (12)	0.72541 (9)	0.67374 (9)	0.0284 (3)
C23	0.91089 (11)	0.57882 (10)	0.73536 (9)	0.0262 (3)
C24	0.92081 (13)	0.48300 (11)	0.71326 (10)	0.0331 (3)
H24	0.8859 (15)	0.4621 (13)	0.6506 (12)	0.039 (4)*
C25	0.97905 (15)	0.41944 (12)	0.78136 (12)	0.0416 (4)
H25	0.9834 (17)	0.3516 (15)	0.7626 (14)	0.055 (5)*
C26	1.02900 (13)	0.45021 (12)	0.87153 (11)	0.0388 (3)
H26	1.0692 (16)	0.4050 (13)	0.9198 (13)	0.045 (5)*
C27	1.02052 (13)	0.54563 (12)	0.89285 (10)	0.0351 (3)
H27	1.0570 (15)	0.5694 (13)	0.9570 (13)	0.044 (5)*
C28	0.96158 (12)	0.61022 (11)	0.82593 (9)	0.0304 (3)
H28	0.9531 (14)	0.6768 (13)	0.8419 (11)	0.037 (4)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.03021 (18)	0.02522 (17)	0.02499 (17)	0.00004 (12)	0.00686 (13)	−0.00720 (11)
O1	0.0576 (7)	0.0405 (6)	0.0222 (5)	0.0128 (5)	0.0172 (5)	0.0055 (4)
O2	0.0282 (5)	0.0208 (4)	0.0193 (4)	0.0033 (3)	0.0096 (3)	0.0042 (3)
O3	0.0735 (8)	0.0346 (6)	0.0253 (5)	0.0090 (5)	0.0050 (5)	−0.0072 (4)
N1	0.0235 (5)	0.0207 (5)	0.0229 (5)	−0.0007 (4)	0.0055 (4)	−0.0007 (4)
N2	0.0281 (6)	0.0549 (8)	0.0271 (6)	0.0031 (5)	0.0096 (5)	−0.0098 (5)
N3	0.0293 (6)	0.0301 (6)	0.0211 (5)	−0.0012 (5)	0.0037 (4)	−0.0048 (4)
C1	0.0219 (6)	0.0191 (5)	0.0182 (5)	0.0013 (4)	0.0081 (5)	0.0023 (4)
C2	0.0238 (6)	0.0189 (5)	0.0170 (5)	0.0027 (5)	0.0050 (5)	0.0012 (4)
C3	0.0219 (6)	0.0193 (5)	0.0170 (5)	0.0019 (4)	0.0052 (4)	0.0015 (4)
C4	0.0196 (6)	0.0227 (6)	0.0176 (5)	−0.0008 (5)	0.0061 (5)	0.0006 (4)
C5	0.0218 (6)	0.0169 (5)	0.0169 (5)	0.0003 (4)	0.0062 (4)	0.0036 (4)
C6	0.0223 (6)	0.0206 (5)	0.0186 (5)	0.0018 (5)	0.0068 (4)	0.0017 (4)
C7	0.0267 (6)	0.0185 (5)	0.0182 (5)	0.0007 (5)	0.0063 (5)	0.0019 (4)
C8	0.0221 (6)	0.0198 (5)	0.0232 (6)	−0.0004 (5)	0.0066 (5)	0.0008 (4)
C9	0.0220 (6)	0.0167 (5)	0.0189 (5)	0.0011 (4)	0.0070 (5)	0.0024 (4)
C10	0.0199 (6)	0.0193 (5)	0.0218 (6)	0.0008 (4)	0.0043 (4)	−0.0026 (4)
C11	0.0250 (6)	0.0261 (6)	0.0243 (6)	0.0016 (5)	0.0028 (5)	0.0034 (5)
C12	0.0354 (8)	0.0261 (7)	0.0415 (8)	0.0009 (6)	−0.0049 (6)	0.0092 (6)
C13	0.0294 (7)	0.0235 (7)	0.0632 (10)	0.0078 (6)	−0.0053 (7)	−0.0087 (7)
C14	0.0268 (7)	0.0372 (8)	0.0558 (10)	0.0051 (6)	0.0109 (7)	−0.0174 (7)
C15	0.0273 (7)	0.0316 (7)	0.0355 (7)	0.0020 (5)	0.0134 (6)	−0.0055 (6)
C16	0.0286 (7)	0.0300 (6)	0.0183 (6)	0.0114 (5)	0.0024 (5)	0.0000 (5)
C17	0.0491 (10)	0.0322 (7)	0.0328 (8)	0.0075 (7)	0.0062 (7)	−0.0112 (6)
C18	0.0248 (7)	0.0293 (7)	0.0232 (6)	0.0008 (5)	0.0021 (5)	−0.0040 (5)
C19	0.0270 (7)	0.0285 (6)	0.0171 (5)	−0.0007 (5)	0.0062 (5)	−0.0035 (5)
C20	0.0209 (6)	0.0347 (8)	0.0412 (8)	−0.0030 (6)	0.0075 (6)	−0.0113 (6)
C21	0.0362 (7)	0.0226 (6)	0.0257 (6)	−0.0055 (5)	0.0055 (6)	−0.0021 (5)
C22	0.0337 (7)	0.0254 (6)	0.0245 (6)	−0.0065 (5)	0.0060 (5)	−0.0031 (5)
C23	0.0196 (6)	0.0333 (7)	0.0261 (6)	−0.0030 (5)	0.0071 (5)	−0.0016 (5)
C24	0.0313 (7)	0.0354 (7)	0.0314 (7)	0.0014 (6)	0.0069 (6)	−0.0060 (6)
C25	0.0431 (9)	0.0369 (8)	0.0443 (9)	0.0078 (7)	0.0116 (7)	−0.0006 (7)
C26	0.0348 (8)	0.0468 (9)	0.0349 (8)	0.0091 (7)	0.0101 (6)	0.0084 (7)
C27	0.0294 (7)	0.0492 (9)	0.0262 (7)	−0.0012 (6)	0.0073 (6)	0.0006 (6)
C28	0.0283 (7)	0.0358 (7)	0.0263 (7)	−0.0038 (6)	0.0065 (5)	−0.0032 (5)

Geometric parameters (Å, º) top

S1—C7	1.7712 (12)	C11—H11	0.945 (17)
S1—C21	1.8132 (14)	C12—C13	1.378 (2)
O1—C16	1.2203 (17)	C12—H12	0.957 (19)
O2—C3	1.4245 (14)	C13—C14	1.378 (3)
O2—H2A	0.86 (2)	C13—H13	0.94 (2)
O3—C22	1.2157 (17)	C14—C15	1.387 (2)
N1—C7	1.3299 (16)	C14—H14	0.99 (2)
N1—C8	1.3484 (16)	C15—H15	0.980 (19)
N2—C19	1.1486 (17)	C16—C17	1.492 (2)
N3—C22	1.3599 (18)	C17—H17A	0.96 (2)
N3—C23	1.4138 (17)	C17—H17B	1.00 (2)
N3—H3A	0.887 (18)	C17—H17C	1.01 (2)
C1—C10	1.5192 (16)	C18—H18A	1.004 (17)
C1—C9	1.5244 (16)	C18—H18B	0.987 (17)
C1—C2	1.5450 (16)	C18—H18C	0.995 (17)
C1—H1	0.961 (15)	C20—H20A	1.00 (2)
C2—C16	1.5245 (16)	C20—H20B	0.98 (2)
C2—C3	1.5473 (16)	C20—H20C	0.981 (18)
C2—H2	0.986 (14)	C21—C22	1.5141 (19)
C3—C18	1.5228 (17)	C21—H21A	0.982 (18)
C3—C4	1.5255 (16)	C21—H21B	0.980 (17)
C4—C5	1.5056 (16)	C23—C24	1.394 (2)
C4—H4A	0.992 (16)	C23—C28	1.3938 (18)
C4—H4B	0.999 (16)	C24—C25	1.385 (2)
C5—C9	1.4006 (16)	C24—H24	0.960 (18)
C5—C6	1.4034 (16)	C25—C26	1.384 (2)
C6—C7	1.3995 (17)	C25—H25	1.00 (2)
C6—C19	1.4374 (17)	C26—C27	1.383 (2)
C8—C9	1.4074 (17)	C26—H26	0.979 (19)
C8—C20	1.5026 (18)	C27—C28	1.387 (2)
C10—C11	1.3882 (18)	C27—H27	0.995 (18)
C10—C15	1.3949 (18)	C28—H28	0.974 (18)
C11—C12	1.3869 (19)

C7—S1—C21	102.34 (6)	C12—C13—H13	119.8 (12)
C3—O2—H2A	110.0 (13)	C13—C14—C15	120.26 (14)
C7—N1—C8	118.75 (11)	C13—C14—H14	122.4 (11)
C22—N3—C23	126.73 (11)	C15—C14—H14	117.3 (11)
C22—N3—H3A	114.8 (11)	C14—C15—C10	120.22 (14)
C23—N3—H3A	117.3 (11)	C14—C15—H15	122.0 (11)
C10—C1—C9	114.52 (9)	C10—C15—H15	117.8 (11)
C10—C1—C2	106.53 (9)	O1—C16—C17	122.45 (13)
C9—C1—C2	113.03 (10)	O1—C16—C2	119.45 (12)
C10—C1—H1	108.2 (9)	C17—C16—C2	118.08 (12)
C9—C1—H1	107.2 (9)	C16—C17—H17A	108.0 (12)
C2—C1—H1	107.0 (9)	C16—C17—H17B	109.3 (12)
C16—C2—C1	108.36 (10)	H17A—C17—H17B	112.5 (17)
C16—C2—C3	112.49 (9)	C16—C17—H17C	111.2 (12)
C1—C2—C3	112.62 (9)	H17A—C17—H17C	105.3 (16)
C16—C2—H2	108.6 (8)	H17B—C17—H17C	110.6 (16)
C1—C2—H2	108.4 (8)	C3—C18—H18A	112.6 (9)
C3—C2—H2	106.2 (8)	C3—C18—H18B	110.8 (9)
O2—C3—C18	110.48 (10)	H18A—C18—H18B	107.8 (13)
O2—C3—C4	105.48 (9)	C3—C18—H18C	109.5 (9)
C18—C3—C4	110.69 (10)	H18A—C18—H18C	109.3 (13)
O2—C3—C2	111.73 (9)	H18B—C18—H18C	106.7 (13)
C18—C3—C2	111.51 (10)	N2—C19—C6	177.04 (14)
C4—C3—C2	106.72 (9)	C8—C20—H20A	110.6 (11)
C5—C4—C3	112.38 (10)	C8—C20—H20B	109.3 (11)
C5—C4—H4A	109.2 (9)	H20A—C20—H20B	106.3 (15)
C3—C4—H4A	109.1 (9)	C8—C20—H20C	109.4 (10)
C5—C4—H4B	109.1 (9)	H20A—C20—H20C	109.5 (15)
C3—C4—H4B	109.2 (9)	H20B—C20—H20C	111.7 (15)
H4A—C4—H4B	107.7 (12)	C22—C21—S1	111.32 (9)
C9—C5—C6	118.23 (11)	C22—C21—H21A	111.0 (10)
C9—C5—C4	122.55 (10)	S1—C21—H21A	109.0 (10)
C6—C5—C4	119.16 (10)	C22—C21—H21B	107.8 (10)
C7—C6—C5	119.52 (11)	S1—C21—H21B	104.0 (10)
C7—C6—C19	119.54 (11)	H21A—C21—H21B	113.5 (13)
C5—C6—C19	120.94 (11)	O3—C22—N3	124.57 (13)
N1—C7—C6	122.27 (11)	O3—C22—C21	120.80 (13)
N1—C7—S1	119.70 (9)	N3—C22—C21	114.59 (11)
C6—C7—S1	117.97 (9)	C24—C23—C28	119.47 (13)
N1—C8—C9	123.09 (11)	C24—C23—N3	117.61 (12)
N1—C8—C20	114.24 (11)	C28—C23—N3	122.92 (12)
C9—C8—C20	122.65 (11)	C25—C24—C23	120.04 (14)
C5—C9—C8	118.03 (11)	C25—C24—H24	121.1 (11)
C5—C9—C1	120.98 (10)	C23—C24—H24	118.9 (11)
C8—C9—C1	120.87 (10)	C26—C25—C24	120.68 (15)
C11—C10—C15	119.07 (12)	C26—C25—H25	122.0 (12)
C11—C10—C1	119.99 (11)	C24—C25—H25	117.3 (12)
C15—C10—C1	120.82 (11)	C27—C26—C25	119.10 (14)
C12—C11—C10	120.08 (13)	C27—C26—H26	120.3 (11)
C12—C11—H11	120.3 (10)	C25—C26—H26	120.6 (11)
C10—C11—H11	119.6 (10)	C26—C27—C28	121.13 (14)
C13—C12—C11	120.58 (15)	C26—C27—H27	120.4 (10)
C13—C12—H12	120.3 (11)	C28—C27—H27	118.5 (11)
C11—C12—H12	119.1 (12)	C27—C28—C23	119.57 (14)
C14—C13—C12	119.79 (13)	C27—C28—H28	120.8 (10)
C14—C13—H13	120.3 (12)	C23—C28—H28	119.6 (10)

C10—C1—C2—C16	−68.29 (11)	C20—C8—C9—C1	−2.86 (18)
C9—C1—C2—C16	165.08 (9)	C10—C1—C9—C5	−129.80 (11)
C10—C1—C2—C3	166.61 (9)	C2—C1—C9—C5	−7.55 (15)
C9—C1—C2—C3	39.99 (13)	C10—C1—C9—C8	54.15 (15)
C16—C2—C3—O2	−71.57 (13)	C2—C1—C9—C8	176.41 (10)
C1—C2—C3—O2	51.24 (12)	C9—C1—C10—C11	49.93 (15)
C16—C2—C3—C18	52.61 (14)	C2—C1—C10—C11	−75.80 (13)
C1—C2—C3—C18	175.42 (10)	C9—C1—C10—C15	−134.18 (12)
C16—C2—C3—C4	173.61 (10)	C2—C1—C10—C15	100.09 (13)
C1—C2—C3—C4	−63.58 (12)	C15—C10—C11—C12	0.68 (19)
O2—C3—C4—C5	−64.66 (12)	C1—C10—C11—C12	176.64 (12)
C18—C3—C4—C5	175.83 (10)	C10—C11—C12—C13	−0.8 (2)
C2—C3—C4—C5	54.32 (12)	C11—C12—C13—C14	0.5 (2)
C3—C4—C5—C9	−24.80 (15)	C12—C13—C14—C15	0.1 (2)
C3—C4—C5—C6	152.52 (10)	C13—C14—C15—C10	−0.2 (2)
C9—C5—C6—C7	3.36 (16)	C11—C10—C15—C14	−0.16 (19)
C4—C5—C6—C7	−174.07 (10)	C1—C10—C15—C14	−176.09 (12)
C9—C5—C6—C19	−176.81 (11)	C1—C2—C16—O1	−57.14 (15)
C4—C5—C6—C19	5.76 (17)	C3—C2—C16—O1	68.03 (15)
C8—N1—C7—C6	2.00 (17)	C1—C2—C16—C17	121.08 (13)
C8—N1—C7—S1	−175.41 (9)	C3—C2—C16—C17	−113.75 (13)
C5—C6—C7—N1	−3.85 (18)	C7—S1—C21—C22	−98.03 (10)
C19—C6—C7—N1	176.32 (11)	C23—N3—C22—O3	5.2 (2)
C5—C6—C7—S1	173.60 (9)	C23—N3—C22—C21	−172.63 (12)
C19—C6—C7—S1	−6.23 (15)	S1—C21—C22—O3	−96.36 (14)
C21—S1—C7—N1	13.60 (11)	S1—C21—C22—N3	81.57 (14)
C21—S1—C7—C6	−163.92 (9)	C22—N3—C23—C24	158.95 (13)
C7—N1—C8—C9	0.24 (17)	C22—N3—C23—C28	−20.9 (2)
C7—N1—C8—C20	178.81 (11)	C28—C23—C24—C25	1.0 (2)
C6—C5—C9—C8	−1.26 (16)	N3—C23—C24—C25	−178.86 (13)
C4—C5—C9—C8	176.08 (10)	C23—C24—C25—C26	−0.7 (2)
C6—C5—C9—C1	−177.42 (10)	C24—C25—C26—C27	−0.3 (2)
C4—C5—C9—C1	−0.08 (16)	C25—C26—C27—C28	1.0 (2)
N1—C8—C9—C5	−0.58 (17)	C26—C27—C28—C23	−0.6 (2)
C20—C8—C9—C5	−179.02 (12)	C24—C23—C28—C27	−0.4 (2)
N1—C8—C9—C1	175.58 (10)	N3—C23—C28—C27	179.51 (13)

Hydrogen-bond geometry (Å, º) top

Cg3 is the centroid of the C10–C15 benzene ring.

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2A···O1ⁱ	0.86 (2)	2.04 (2)	2.8674 (13)	161.9 (19)
N3—H3A···N1	0.887 (18)	2.306 (18)	3.1148 (15)	151.6 (15)
C13—H13···O2ⁱⁱ	0.94 (2)	2.40 (2)	3.2520 (19)	150.5 (17)
C20—H20A···Cg3	1.00 (2)	2.975 (19)	3.6866 (16)	128.7 (13)

Symmetry codes: (i) −x+1, −y+1, −z; (ii) −x+3/2, y−1/2, −z+1/2.

Funding information

The support of NSF–MRI grant No. 1228232 for the purchase of the diffractometer and Tulane University for support of the Tulane Crystallography Laboratory are gratefully acknowledged.

References

Andujar, S., Suvire, F., Berenguer, I., Cabedo, N., Marín, P., Moreno, L., Ivorra, M. D., Cortes, D. & Enriz, R. D. (2012). J. Mol. Model. 18, 419–431. Web of Science CrossRef CAS PubMed Google Scholar
Bernan, V. S., Montenegro, D. A., Korshalla, J. D., Maiese, W. M., Steinberg, D. A. & Greenstein, M. (1994). J. Antibiot. 47, 1417–1424. CrossRef CAS Web of Science Google Scholar
Brandenburg, K. & Putz, H. (2012). DIAMOND, Crystal Impact GbR, Bonn, Germany. Google Scholar
Bruker (2016). APEX3, SAINT, and SADABS. Bruker AXS, Inc., Madison, Wisconsin, USA. Google Scholar
Carroll, F. I., Robinson, T. P., Brieaddy, L. E., Atkinson, R. N., Mascarella, S. W., Damaj, M., Martin, B. R. & Navarro, H. A. (2007). J. Med. Chem. 50, 6383–6391. Web of Science CrossRef PubMed CAS Google Scholar
Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354–1358. CrossRef CAS Web of Science Google Scholar
Dukat, M., Taroua, M., Dahdouh, A., Siripurapu, U., Damaj, M. I., Martin, B. R. & Glennon, R. A. (2004). Bioorg. Med. Chem. Lett. 14, 3651–3654. Web of Science CrossRef PubMed CAS Google Scholar
Dyachenko, V. D., Sukach, S. M., Dyachenko, A. D., Zubatyuk, R. I. & Shishkin, O. V. (2010). Russ. J. Gen. Chem. 80, 2037–2042. Web of Science CrossRef CAS Google Scholar
Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179. Web of Science CrossRef IUCr Journals Google Scholar
Krause, L., Herbst-Irmer, R., Sheldrick, G. M. & Stalke, D. (2015). J. Appl. Cryst. 48, 3–10. Web of Science CSD CrossRef ICSD CAS IUCr Journals Google Scholar
Mague, J. T., Al-Taifi, E. A., Mohamed, S. K., Akkurt, M. & Bakhite, E. A. (2017b). IUCrData, 2, x170868. Google Scholar
Mague, J. T. & Mohamed, S. K. (2020). Unpublished data. Google Scholar
Mague, J. T., Mohamed, S. K., Akkurt, M., Bakhite, E. A. & Albayati, M. R. (2017a). IUCrData, 2, x170390. Google Scholar
McKinnon, J. J., Jayatilaka, D. & Spackman, M. A. (2007). Chem. Commun. pp. 3814–3816. Web of Science CrossRef Google Scholar
Meijler, M. M., Matsushita, M., Altobell, L. J., Wirsching, P. & Janda, K. D. (2003). J. Am. Chem. Soc. 125, 7164–7165. Web of Science CrossRef PubMed CAS Google Scholar
Scott, J. D. & Williams, R. M. (2002). Chem. Rev. 102, 1669–1730. Web of Science CrossRef PubMed CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Spackman, M. A. & Jayatilaka, D. (2009). CrystEngComm, 11, 19–32. Web of Science CrossRef CAS Google Scholar
Tan, S. L., Jotani, M. M. & Tiekink, E. R. T. (2019). Acta Cryst. E75, 308–318. Web of Science CrossRef IUCr Journals Google Scholar
Turner, M. J., McKinnon, J. J., Wolff, S. K., Grimwood, D. J., Spackman, P. R., Jayatilaka, D. & Spackman, M. A. (2017). Crystal Explorer 17. The University of Western Australia. Google Scholar
Xu, R., Dwoskin, L. P., Grinevich, V., Sumithran, S. P. & Crooks, P. A. (2002). Drug Dev. Res. 55, 173–186. Web of Science CrossRef CAS Google Scholar

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Volume 77| Part 2| February 2021| Pages 121-125

https://doi.org/10.1107/S2056989021000372

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

Crystallographic and spectroscopic characterization of 2-[(7-acetyl-4-cyano-6-hy­dr­oxy-1,6-di­methyl-8-phenyl-5,6,7,8-tetra­hydro­isoquinolin-3-yl)sulfan­yl]-N-phenyl­acetamide

1. Chemical context

2. Structural commentary

3. Supra­molecular features

4. Database survey

5. Hirshfeld surface analysis

6. Synthesis and crystallization

7. Spectroscopic characterization

8. Refinement

Supporting information

Funding information

References

research communications

Crystallographic and spectroscopic characterization of 2-[(7-acetyl-4-cyano-6-hydroxy-1,6-dimethyl-8-phenyl-5,6,7,8-tetrahydroisoquinolin-3-yl)sulfanyl]-N-phenylacetamide

3. Supramolecular features