Crystal structure of 1-(1-chloro­eth­yl)-6,7-dimeth­oxy-1,2,3,4-tetra­hydro­isoquinolinium chloride

Urunbaeva, Z.E.; Turgunov, K.K.; Saidov, A.Sh.; Vinogradova, V.I.

doi:10.1107/S2056989024011277

research communications

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 80| Part 12| December 2024| Pages 1322-1325

https://doi.org/10.1107/S2056989024011277

Open

access

Crystal structure of 1-(1-chloroethyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolinium chloride

Ziroat E. Urunbaeva,^a Kambarali K. Turgunov,^b,^c ^* Abdusalom Sh. Saidov ^a and Valentina I. Vinogradova ^b

^aSamarkand State University named after Sh. Rashidov, University blv. 15, Samarkand 140104, Uzbekistan, ^bS. Yunusov Institute of the Chemistry of Plant Substances Academy of Sciences of Uzbekistan, Mirzo Ulugbek Str., 77, Tashkent 100170, Uzbekistan, and ^cTurin Polytechnic University in Tashkent 100095, 17 Little Ring Road, Tashkent, Uzbekistan
^*Correspondence e-mail: kk_turgunov@rambler.ru

Edited by N. Alvarez Failache, Universidad de la Repüblica, Uruguay (Received 10 July 2024; accepted 19 November 2024; online 28 November 2024)

1-(1-Chloroethyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline was synthesized through the reaction of homoveratrylamine with racemic lactic acid. The formation of two enantiomers, RR and SS, was detected by performing X-ray diffraction analysis on their chloride salts. The asymmetric unit of the crystal consists of a C₁₃H₁₉ClNO₂⁺ molecular cation and a Cl⁻ anion. Two protonated enantiomers of the title compound, with RR and SS configurations of the chiral atoms, are connected into hydrogen-bonded dimers bridged by Cl⁻ anions. Weak C—H⋯Cl interactions lead to the formation of a chain running along the a-axis direction of the unit cell, which corresponds to the longest dimension (the preferential growth direction) of the needle-shaped monocrystal. The crystal studied was refined as a two-component twin.

Keywords: crystal structure; enantiomer; homoveratrylamine; lactic acid; tetrahydroisoquinoline.

CCDC reference: 2403944

1. Chemical context

Isoquinoline alkaloids, widely distributed in the plant and animal kingdoms, have received much attention because of their important biological activities (Lundstorom, 1983 ). For example, 1.2.3.4-tetrahydroisoquinoline and 2-methyl-1.2.3.4-tetrahydroisoquinoline, present in mammalian brains, are known to induce Parkinson's disease (Ohta et al., 1987 ; Niwa et al. 1987 ). Effective synthetic methods for preparing of 1.2.3.4-tetrahydroisoquinoline derivatives have been found (Shinohara et al. 1997 ). 1-Substituted-1,2,3,4-tetrahydroisoquinolines are especially intriguing among the synthetic derivatives of the isoquinoline alkaloid. They feature biologically active compounds, for example, an antiepileptic agent (Gitto et al., 2003 ) and a derivative with inhibitory activity against bladder contraction (Naito et al., 2005 ). A lot of work has been done on the synthesis and structural studies of 1-substituted-1,2,3,4-tetrahydroisoquinolines in search of active compounds (Olszak et al., 1996 $[Olszak, T. A., Ste\,pień, A., Grabowski, M. J. & Brzezińska, E. (1996). Acta Cryst. C52, 1038-1040.]$ ; Pashev et al., 2020 ; Turgunov et al. 2016 ).

In this context, we treated homoveratrylamine with lactic acid and obtained the corresponding amide intermediate. Cyclization of the amide with POCl₃ and NaBH₄ afforded the title compound (Fig. 1). Racemic lactic acid was used in the synthesis, so four stereoisomers (R,R; R,S; S,S; S,R) of 1-(1-chloroethyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline were expected. Currently, we have detected the formation of two enantiomers, RR and SS, packed in a single crystal by X-ray diffraction (XRD) analysis. A detailed analysis of the reaction products is ongoing and will be published in our future work. To obtain good crystals suitable for XRD analysis, hydrochlorides of the isoquinolines were used.

Figure 1
Synthesis scheme of the title compound.

2. Structural commentary

The title compound crystallizes in the monoclinic P2₁/c (No. 14) space group. The asymmetric unit of the crystal contains one independent molecule with an 1S, 11S configuration of chiral carbon atoms, so the crystal consists of RR and SS enantiomers. The C4A/C4–C8/C8A aromatic ring is twisted slightly with a slightly high value for the r.m.s. deviation (0.0245 Å) of the fitted atoms from the mean plane of the ring. The methoxy groups at C6 and C7 atoms are slightly rotated around the C6—O1 and C7—O2 bonds (Fig. 2), the dihedral angles between the plane of the aromatic ring and the planes defined by atoms C6/O1/C9 and C7/O2/C10 being 13.0 (3) and 6.5 (3)°, respectively. The C4A—C4 and C8A–-C1 bonds are slightly out of the plane, the deviations of C1 and C4 from the mean plane of aromatic ring being 0.206 (2) and −0.147 (2) Å, respectively. The heterocyclic ring of tetrahydroisoquinoline adopts a half chair conformation.

Figure 2
Displacement ellipsoid plot of the title compound with atom labels. Ellipsoids are drawn at the 50% probability level. The hydrogen bond formed between the molecular cation and the chlorine anion is showed as a dashed line.

3. Supramolecular features

The presence of both enantiomers of the title compound in the crystal allows the molecules to link into inversion dimers through N2—H2A⋯Cl2 and N2—H2B⋯Cl2ⁱ [symmetry code: (i) 2 − x, 1 − y, 2 − z] intermolecular interactions, forming rings with the graph-set motif R₂²(8) (Fig. 3, Table 1) where the Cl2 anions act as double hydrogen-bond acceptors. In addition, pairs of C1—H1A⋯Cl2 weak interactions lead to chain formation along the a-axis direction, which is the longest cell dimension (preferential growth direction) of the monocrystal. A C12—H12A⋯Cl2 weak interaction leads to the formation of hydrogen-bonded layers parallel to the bc plane.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C1—H1A⋯Cl2ⁱ	0.98	2.62	3.450 (2)	143
N2—H2A⋯Cl2ⁱⁱ	0.95 (2)	2.14 (2)	3.0895 (19)	177 (2)
N2—H2B⋯Cl1	0.92 (2)	2.75 (3)	3.1828 (19)	110 (2)
N2—H2B⋯Cl2	0.92 (2)	2.27 (2)	3.0751 (19)	146 (2)
C11—H11A⋯Cl1ⁱⁱⁱ	0.98	2.93	3.767 (2)	144
C12—H12A⋯Cl2ⁱⁱⁱ	0.96	2.75	3.710 (3)	174
Symmetry codes: (i) ; (ii) ; (iii) $[x, -y+{\script{3\over 2}}, z-{\script{1\over 2}}]$ .

Figure 3
Hydrogen bonding in the crystal of the title compound.

4. Database survey

A search in the Cambridge Structural Database (CSD, version 5.43, update of November 2022; Groom et al., 2016 ) revealed 123 structures of 1-substituted and 2-substituted 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines. Among these, 15 structures correspond to 1-substituted 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines. Enantiopure crystal structures were determined for (R)-1-hydroxymethyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (refcode: BIMCEG) and (S)-1-hydroxymethyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline chloride (refcode: BIMCIK), alkaloids isolated from seeds of Calycotome Villosa (Antri et al., 2004 ). A search in the Cambridge Structural Database for the cationic form of 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline resulted in 13 hits. Ten of these, where the molecule contains a chiral atom, are enantiopure crystals containing only proper symmetry elements. Therefore, in these crystal structures, the interlinking of molecules by hydrogen bonds differs from our case.

5. Synthesis and crystallization

N-(3,4-Dimethoxyphenylethyl)-2-hydroxypropanamide. A mixture of 1.81 g (0.01 mol) of homoveratrilamine and 0.9 g (0.01 mol) of lactic acid was dissolved in 5 ml of methanol. Self-heating occurred. Then the mixture was heated in an oil bath for 2 h at a temperature of 451–453 K. The progress of the reaction was monitored by TLC. The reaction mixture was dissolved in 100 mL of chloroform. The chloroform layer was first washed three times with 3% hydrochloric acid. The chloroform solution was then washed with water until neutral, followed by washing with 2% sodium hydroxide solution and water until neutral. The resulting chloroform solution was dried over Na₂SO₄ and then evaporated. The residue was crystallized from a mixture (acetone-hexane). White crystals with m.p. 343–344 K. Yield 70% (1.77 g). R_f = 0.40 chloroform-methanol (8:2).

¹H NMR: (400 MHz, CDCl₃, δ, ppm., J/Hz): 1.34 (3H, d, J = 6.7, H-3′), 2.73 (2H, t, J = 7.1, H-α), 3.46 (2H, q, J = 6.7, H-β), 3.81 (3H, s, OCH₃), 3.82 (3H, s, OCH₃), 4.10 (1H, wide s, OH), 4.17 (1H, q, J = 6.8 H −2′), 6.69 (2H, top – top, H-2,6), 6.77 (1H, d, J = 8.6, H-5), 6.90 (1H, wide s, NH).

¹³C NMR: 21.26 C-3, 35.19 C-α; 40.60 C-β, 55.96 C-OCH₃, 55.96 C-OCH₃, 68.10 C-2I, 111.44 C-2, 111.97 C-5, 131 C-1, 120.73 C-6, 147.73 C-3, 149.01 C-4, 175.59 C-1-CO.

MS m/z (M⁺) 253, 224, 165, 123.9 (124), 59.8 (60).

1-(1-Chloroethyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline. 1.550 mg (0.0061 mol) of N-(3,4-dimethoxyphenylethyl)-2-hydroxypropanamide were dissolved in 30 ml of absolute benzene, then 0.9404 mg (0.0061 mol) or 0.6–1 ml of POCl₃ were added. The reaction mixture was refluxed with a calcium chloride tube for 2 h. The progress of the reaction was monitored by TLC. After the reaction was complete after 2.5 h, benzene and residual POCl₃ were removed and the residue was dried. The residue was then dissolved in 50 mL of methanol. 0.6 g of NaBH₄ was added in small portions at 273–323 K for 3 h with constant stirring. This mixture was left overnight. The solvent was then removed and the residue was dissolved in distilled water. The aqueous layer was extracted several times with chloroform. The chloroform layer was combined and washed with water. After that, the chloroform layer was dried with Na₂SO₄. The residue was dissolved in methanol and precipitated as the hydrochloride using concentrated HCl solution. The precipitate was filtered, washed in acetone and dried. Yield 0.843 g (59%) (0.843 g), m.p. 476–477 K, R_f = 0.57 (chloroform–methanol 8:1.5).

¹H NMR (400 MHz, CDCl₃, δ, ppm, J / Hz): 1.87 (3H, d, J = 7, H-3′), 2.91 (2H, m, H-3a), 3.23 (2H, m, H-4), 3.84 (1H, m, H-3e), 3.85 (3H, s, OCH₃), 3.86 (3H, s, OCH₃), 4.59 (1H, q, J = 3.5, H-2′), 4.74 (1H, d, J = 3.3, H-1), 6.61 (1H, s, H-8), 6.69 (1H, s, H-5).

5.1. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. The crystal under investigation exhibited twinning, which was identified during the initial analysis of the diffraction data. The twin law was determined based on the symmetry of the crystal and the diffraction analysis. In this case, a twofold rotation axis (along the c axis) related the two twin domains, with each domain contributing to the overall diffraction pattern. The twin fraction was estimated to be approximately 0.60 for component 1 and 0.40 for component 2, based on the refinement of the intensity data. Reflections in the HKLF 5 format were used for structure determination and refinement. The H atoms bonded to C atoms were placed geometrically (with C—H distances of 0.98 Å for CH, 0.97 Å for CH₂, 0.96 Å for CH₃ and 0.93 Å for C_ar) and included in the refinement in a riding-motion approximation with U_iso(H) = 1.2U_eq(C) [U_iso = 1.5U_eq(C) for methyl H atoms]. The hydrogen atoms on the N1 were located in difference-Fourier maps and refined freely.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₃H₁₉ClNO₂⁺·Cl⁻
M_r	292.19
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	293
a, b, c (Å)	16.1298 (3), 12.3736 (3), 7.46745 (16)
β (°)	100.190 (2)
V (Å³)	1466.87 (6)
Z	4
Radiation type	Cu Kα
μ (mm⁻¹)	3.94
Crystal size (mm)	0.25 × 0.10 × 0.05

Data collection
Diffractometer	XtaLAB Synergy, Single source at home/near, HyPix3000
Absorption correction	Multi-scan (CrysAlis PRO; Rigaku OD, 2018 )
T_min, T_max	0.784, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	12790, 4641, 4142
R_int	0.061
(sin θ/λ)_max (Å⁻¹)	0.602

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.050, 0.155, 1.09
No. of reflections	4641
No. of parameters	170
No. of restraints	2
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.32, −0.26
Computer programs: CrysAlis PRO (Rigaku OD, 2018), SHELXT2018/2 (Sheldrick, 2015a ), SHELXL2018/3 (Sheldrick, 2015b ), Mercury (Macrae et al., 2020 ), SHELXL2014/7 (Sheldrick, 2015b).

Supporting information

CCDC reference: 2403944

Crystal structure: contains datablocks I, GLOBAL. DOI: https://doi.org/10.1107/S2056989024011277/ny2008sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989024011277/ny2008Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989024011277/ny2008Isup3.cml

checkCIF report

Computing details top

1-(1-Chloroethyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolinium chloride top

Crystal data top

C₁₃H₁₉ClNO₂⁺·Cl⁻	D_x = 1.323 Mg m⁻³
M_r = 292.19	Melting point: 476(2) K
Monoclinic, P2₁/c	Cu Kα radiation, λ = 1.54184 Å
a = 16.1298 (3) Å	Cell parameters from 5593 reflections
b = 12.3736 (3) Å	θ = 2.8–68.0°
c = 7.46745 (16) Å	µ = 3.94 mm⁻¹
β = 100.190 (2)°	T = 293 K
V = 1466.87 (6) Å³	Prism, colourless
Z = 4	0.25 × 0.10 × 0.05 mm
F(000) = 616

Data collection top

XtaLAB Synergy, Single source at home/near, HyPix3000 diffractometer	4641 independent reflections
Radiation source: micro-focus sealed X-ray tube, PhotonJet (Cu) X-ray Source	4142 reflections with I > 2σ(I)
Mirror monochromator	R_int = 0.061
Detector resolution: 10.0000 pixels mm^-1	θ_max = 68.2°, θ_min = 7.0°
wσcans	h = −17→19
Absorption correction: multi-scan (CrysAlisPro; Rigaku OD, 2018)	k = −14→14
T_min = 0.784, T_max = 1.000	l = −8→7
12790 measured reflections

Refinement top

Refinement on F²	Primary atom site location: iterative
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.050	Hydrogen site location: mixed
wR(F²) = 0.155	H atoms treated by a mixture of independent and constrained refinement
S = 1.09	w = 1/[σ²(F_o²) + (0.1122P)² + 0.0537P] where P = (F_o² + 2F_c²)/3
4641 reflections	(Δ/σ)_max < 0.001
170 parameters	Δρ_max = 0.32 e Å⁻³
2 restraints	Δρ_min = −0.26 e Å⁻³

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. Refined as a 2-component twin

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
Cl1	0.77537 (4)	0.66403 (6)	0.75105 (11)	0.0673 (3)
Cl2	0.91248 (3)	0.52447 (5)	1.18130 (7)	0.0506 (2)
O1	0.51533 (12)	0.3579 (2)	0.3763 (3)	0.0747 (6)
O2	0.58615 (12)	0.47214 (18)	0.1566 (3)	0.0644 (6)
C1	0.85038 (13)	0.49829 (17)	0.5981 (3)	0.0358 (5)
H1A	0.884823	0.477867	0.507792	0.043*
N2	0.89415 (11)	0.45706 (15)	0.7799 (2)	0.0374 (4)
H2A	0.9536 (13)	0.465 (2)	0.791 (4)	0.045*
H2B	0.8830 (17)	0.498 (2)	0.876 (3)	0.045*
C3	0.87520 (15)	0.34188 (19)	0.8137 (3)	0.0465 (5)
H3A	0.908683	0.318072	0.927730	0.056*
H3B	0.889133	0.296935	0.716790	0.056*
C4	0.78257 (15)	0.3314 (2)	0.8215 (3)	0.0496 (6)
H4A	0.770169	0.370253	0.926464	0.060*
H4B	0.768603	0.255903	0.834578	0.060*
C4A	0.72980 (14)	0.37668 (19)	0.6497 (3)	0.0416 (5)
C5	0.64592 (15)	0.3445 (2)	0.5957 (3)	0.0503 (6)
H5A	0.621781	0.297843	0.669519	0.060*
C6	0.59837 (15)	0.3808 (2)	0.4351 (4)	0.0512 (6)
C7	0.63650 (15)	0.4458 (2)	0.3182 (3)	0.0473 (6)
C8	0.71844 (14)	0.47887 (19)	0.3714 (3)	0.0414 (5)
H8A	0.743570	0.522290	0.294466	0.050*
C8A	0.76461 (13)	0.44768 (17)	0.5409 (3)	0.0369 (5)
C9	0.4704 (2)	0.3114 (4)	0.5026 (6)	0.1007 (14)
H9A	0.413028	0.299237	0.445017	0.151*
H9B	0.495855	0.243834	0.544775	0.151*
H9C	0.471544	0.359488	0.603867	0.151*
C10	0.6234 (2)	0.5306 (3)	0.0284 (4)	0.0711 (9)
H10A	0.581969	0.544019	−0.078361	0.107*
H10B	0.644673	0.598139	0.080729	0.107*
H10C	0.668884	0.489221	−0.004100	0.107*
C11	0.84659 (14)	0.62126 (19)	0.6022 (3)	0.0455 (5)
H11A	0.822722	0.645643	0.478997	0.055*
C12	0.93059 (18)	0.6771 (2)	0.6574 (4)	0.0650 (7)
H12A	0.922258	0.753986	0.656226	0.097*
H12B	0.955872	0.654494	0.777642	0.097*
H12C	0.966957	0.658458	0.573374	0.097*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0646 (4)	0.0535 (4)	0.0826 (5)	0.0072 (3)	0.0094 (4)	−0.0177 (3)
Cl2	0.0439 (3)	0.0715 (5)	0.0365 (3)	0.0006 (2)	0.0075 (2)	−0.0008 (2)
O1	0.0424 (9)	0.0996 (16)	0.0760 (12)	−0.0225 (10)	−0.0063 (9)	0.0100 (12)
O2	0.0483 (10)	0.0862 (15)	0.0512 (11)	−0.0048 (9)	−0.0120 (9)	0.0104 (9)
C1	0.0369 (10)	0.0382 (11)	0.0306 (10)	−0.0027 (8)	0.0019 (8)	0.0023 (8)
N2	0.0359 (9)	0.0418 (10)	0.0326 (9)	−0.0012 (7)	0.0008 (7)	0.0016 (7)
C3	0.0476 (12)	0.0411 (13)	0.0471 (12)	0.0041 (9)	−0.0015 (10)	0.0066 (9)
C4	0.0517 (13)	0.0465 (14)	0.0478 (12)	−0.0070 (10)	0.0009 (10)	0.0129 (10)
C4A	0.0426 (11)	0.0403 (12)	0.0405 (11)	−0.0027 (9)	0.0040 (9)	0.0012 (9)
C5	0.0455 (12)	0.0496 (14)	0.0552 (13)	−0.0112 (10)	0.0073 (10)	0.0035 (11)
C6	0.0390 (11)	0.0559 (15)	0.0555 (13)	−0.0083 (10)	0.0000 (10)	−0.0027 (11)
C7	0.0428 (11)	0.0532 (14)	0.0418 (12)	−0.0003 (10)	−0.0036 (9)	−0.0009 (10)
C8	0.0396 (11)	0.0455 (13)	0.0377 (11)	−0.0032 (9)	0.0032 (9)	0.0009 (9)
C8A	0.0371 (10)	0.0367 (11)	0.0353 (10)	−0.0010 (8)	0.0022 (8)	−0.0024 (8)
C9	0.0469 (16)	0.137 (4)	0.114 (3)	−0.030 (2)	0.0021 (18)	0.028 (3)
C10	0.0628 (17)	0.096 (2)	0.0488 (15)	0.0066 (16)	−0.0060 (13)	0.0178 (14)
C11	0.0465 (11)	0.0380 (12)	0.0482 (12)	−0.0029 (9)	−0.0019 (9)	0.0039 (9)
C12	0.0558 (15)	0.0462 (15)	0.0872 (19)	−0.0150 (12)	−0.0029 (14)	0.0039 (13)

Geometric parameters (Å, º) top

Cl1—C11	1.813 (3)	C4A—C5	1.399 (3)
O1—C6	1.364 (3)	C5—C6	1.379 (4)
O1—C9	1.410 (4)	C5—H5A	0.9300
O2—C7	1.369 (3)	C6—C7	1.407 (4)
O2—C10	1.416 (4)	C7—C8	1.374 (3)
C1—N2	1.504 (3)	C8—C8A	1.405 (3)
C1—C8A	1.510 (3)	C8—H8A	0.9300
C1—C11	1.523 (3)	C9—H9A	0.9600
C1—H1A	0.9800	C9—H9B	0.9600
N2—C3	1.488 (3)	C9—H9C	0.9600
N2—H2A	0.95 (2)	C10—H10A	0.9600
N2—H2B	0.92 (2)	C10—H10B	0.9600
C3—C4	1.511 (3)	C10—H10C	0.9600
C3—H3A	0.9700	C11—C12	1.512 (3)
C3—H3B	0.9700	C11—H11A	0.9800
C4—C4A	1.516 (3)	C12—H12A	0.9600
C4—H4A	0.9700	C12—H12B	0.9600
C4—H4B	0.9700	C12—H12C	0.9600
C4A—C8A	1.382 (3)

C6—O1—C9	117.5 (2)	C5—C6—C7	119.3 (2)
C7—O2—C10	117.4 (2)	O2—C7—C8	125.1 (2)
N2—C1—C8A	112.04 (17)	O2—C7—C6	115.3 (2)
N2—C1—C11	109.57 (17)	C8—C7—C6	119.7 (2)
C8A—C1—C11	112.46 (18)	C7—C8—C8A	120.6 (2)
N2—C1—H1A	107.5	C7—C8—H8A	119.7
C8A—C1—H1A	107.5	C8A—C8—H8A	119.7
C11—C1—H1A	107.5	C4A—C8A—C8	119.9 (2)
C3—N2—C1	113.60 (16)	C4A—C8A—C1	123.00 (18)
C3—N2—H2A	108.8 (15)	C8—C8A—C1	117.02 (19)
C1—N2—H2A	110.2 (16)	O1—C9—H9A	109.5
C3—N2—H2B	108.3 (17)	O1—C9—H9B	109.5
C1—N2—H2B	113.2 (17)	H9A—C9—H9B	109.5
H2A—N2—H2B	102 (2)	O1—C9—H9C	109.5
N2—C3—C4	108.83 (18)	H9A—C9—H9C	109.5
N2—C3—H3A	109.9	H9B—C9—H9C	109.5
C4—C3—H3A	109.9	O2—C10—H10A	109.5
N2—C3—H3B	109.9	O2—C10—H10B	109.5
C4—C3—H3B	109.9	H10A—C10—H10B	109.5
H3A—C3—H3B	108.3	O2—C10—H10C	109.5
C3—C4—C4A	110.28 (19)	H10A—C10—H10C	109.5
C3—C4—H4A	109.6	H10B—C10—H10C	109.5
C4A—C4—H4A	109.6	C12—C11—C1	115.2 (2)
C3—C4—H4B	109.6	C12—C11—Cl1	109.50 (19)
C4A—C4—H4B	109.6	C1—C11—Cl1	109.62 (16)
H4A—C4—H4B	108.1	C12—C11—H11A	107.4
C8A—C4A—C5	119.0 (2)	C1—C11—H11A	107.4
C8A—C4A—C4	120.46 (19)	Cl1—C11—H11A	107.4
C5—C4A—C4	120.6 (2)	C11—C12—H12A	109.5
C6—C5—C4A	121.2 (2)	C11—C12—H12B	109.5
C6—C5—H5A	119.4	H12A—C12—H12B	109.5
C4A—C5—H5A	119.4	C11—C12—H12C	109.5
O1—C6—C5	125.2 (2)	H12A—C12—H12C	109.5
O1—C6—C7	115.6 (2)	H12B—C12—H12C	109.5

C8A—C1—N2—C3	34.0 (2)	C5—C6—C7—C8	−4.8 (4)
C11—C1—N2—C3	159.49 (19)	O2—C7—C8—C8A	179.7 (2)
C1—N2—C3—C4	−64.4 (2)	C6—C7—C8—C8A	0.5 (4)
N2—C3—C4—C4A	55.1 (3)	C5—C4A—C8A—C8	−5.6 (3)
C3—C4—C4A—C8A	−19.8 (3)	C4—C4A—C8A—C8	172.3 (2)
C3—C4—C4A—C5	158.0 (2)	C5—C4A—C8A—C1	171.9 (2)
C8A—C4A—C5—C6	1.2 (4)	C4—C4A—C8A—C1	−10.1 (3)
C4—C4A—C5—C6	−176.7 (2)	C7—C8—C8A—C4A	4.8 (4)
C9—O1—C6—C5	12.7 (5)	C7—C8—C8A—C1	−172.9 (2)
C9—O1—C6—C7	−167.9 (3)	N2—C1—C8A—C4A	3.4 (3)
C4A—C5—C6—O1	−176.7 (3)	C11—C1—C8A—C4A	−120.5 (2)
C4A—C5—C6—C7	4.0 (4)	N2—C1—C8A—C8	−178.93 (18)
C10—O2—C7—C8	5.4 (4)	C11—C1—C8A—C8	57.1 (3)
C10—O2—C7—C6	−175.3 (3)	N2—C1—C11—C12	55.1 (3)
O1—C6—C7—O2	−3.5 (4)	C8A—C1—C11—C12	−179.6 (2)
C5—C6—C7—O2	175.9 (2)	N2—C1—C11—Cl1	−68.91 (19)
O1—C6—C7—C8	175.8 (2)	C8A—C1—C11—Cl1	56.4 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C1—H1A···Cl2ⁱ	0.98	2.62	3.450 (2)	143
N2—H2A···Cl2ⁱⁱ	0.95 (2)	2.14 (2)	3.0895 (19)	177 (2)
N2—H2B···Cl1	0.92 (2)	2.75 (3)	3.1828 (19)	110 (2)
N2—H2B···Cl2	0.92 (2)	2.27 (2)	3.0751 (19)	146 (2)
C11—H11A···Cl1ⁱⁱⁱ	0.98	2.93	3.767 (2)	144
C12—H12A···Cl2ⁱⁱⁱ	0.96	2.75	3.710 (3)	174

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

Acknowledgements

X-ray diffraction studies were performed at the Centre of Collective Usage of Equipment of the Institute of Bioorganic Chemistry of the Uzbekistan Academy of Sciences. Professor Bakhtiyar Ibragimov is acknowledged for support of the diffraction measurements.

References

El Antri, A., Messouri, I., Bouktaib, M., El Alami, R., Bolte, M., El Bali, B. & Lachkar, M. (2004). Molecules, 9, 650–657. Web of Science CrossRef PubMed CAS Google Scholar
Gitto, R., Barreca, M. L., De Luca, L., De Sarro, G., Ferreri, G., Quartarone, S., Russo, E., Constanti, A. & Chimirri, A. (2003). J. Med. Chem. 46, 197–200. Web of Science CrossRef PubMed 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
Lundstorom, J. (1983). The Alkaloids, Vol. 21 edited by A. Brossi, pp. 255–327. New York: Academic Press. Google Scholar
Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M. & Wood, P. A. (2020). J. Appl. Cryst. 53, 226–235. Web of Science CrossRef CAS IUCr Journals Google Scholar
Naito, R., Yonetoku, Y., Okamoto, Y., Toyoshima, A., Ikeda, K. & Takeuchi, M. (2005). J. Med. Chem. 48, 6597–6606. Web of Science CSD CrossRef PubMed CAS Google Scholar
Niwa, T., Takeda, N., Kaneda, N., Hashizume, Y. & Nagatsu, T. (1987). Biochem. Biophys. Res. Commun. 144, 1084–1089. CrossRef CAS PubMed Google Scholar
Ohta, S., Kohno, M., Makino, Y., Tachikawa, O. & Hirobe, M. (1987). Biomed. Res. 8, 453–456. CrossRef Google Scholar
Olszak, T. A., Ste\,pień, A., Grabowski, M. J. & Brzezińska, E. (1996). Acta Cryst. C52, 1038–1040. Google Scholar
Pashev, A., Burdzhiev, N. & Stanoeva, E. (2020). Beilstein J. Org. Chem. 16, 1456–1464. CrossRef CAS PubMed Google Scholar
Rigaku OD (2018). CrysAlis PRO. Rigaku OD, Yarnton, England. 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
Shinohara, T., Toda, J. & Sano, T. (1997). Chem. Pharm. Bull. 45, 813–819. CrossRef CAS Google Scholar
Turgunov, K. K., Zhurakulov, Sh. N., Englert, U., Vinogradova, V. I. & Tashkhodjaev, B. (2016). Acta Cryst. C72, 607–611. Web of Science CSD CrossRef IUCr Journals Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.