1-Bromo­acetyl-2,6-bis­(4-methoxy­phen­yl)-3,5-dimethyl­piperidin-4-one

Ramachandran, R.; Aridoss, G.; Velmurugan, D.; Kabilan, S.; Jeong, Y.T.

doi:10.1107/S1600536808030213

organic compounds

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 64| Part 10| October 2008| Pages o2009-o2010

doi:10.1107/S1600536808030213

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1-Bromoacetyl-2,6-bis(4-methoxyphenyl)-3,5-dimethylpiperidin-4-one

R. Ramachandran,^a G. Aridoss,^b D. Velmurugan,^c S. Kabilan ^a and Y. T. Jeong ^b ^*

^aDepartment of Chemistry, Annamalai University, Annamalai Nagar 608 002, India, ^bDivision of Image and Information Engineering, Pukyong National University, Busan 608-739, Republic of Korea, and ^cCentre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600 025, India
^*Correspondence e-mail: ytjeong@pknu.ac.kr

(Received 15 September 2008; accepted 19 September 2008; online 27 September 2008)

In the title compound, C₂₃H₂₆BrNO₄, the piperidinone ring adopts a boat conformation. The dihedral angle between the two benzene rings is 70.9 (1)°. The two methoxy groups are close to coplanar with the attached benzene rings [C—C—O—C torsion angles of 6.3 (5) and 16.4 (4)°]. A weak C—H⋯Br intramolecular interaction is observed. In the crystal structure, molecules are linked into a chain along [101] by intermolecular C—H⋯O hydrogen bonds. A short intermolecular Br⋯O contact [3.063 (2) Å] is observed.

Related literature

For background on the piperidine ring system, see: O'Hagan (2000 ); Pinder (1992 ). For information on the arylpiperidine scaffold, see: Horton et al. (2003 ). For piperidone derivatives, see: Baluja et al. (1964 ); Mutus et al. (1989 ). For the biological activities of compounds possessing an amide bond linkage, see: Priya et al. (2007 ); Bylov et al. (1999 ); Dollery (1999 ). For the activivities of chloroacetyl and heterocyclicacetyl derivatives of variously functionalized 2,6-diarylpiperidin-4-ones, see: Aridoss et al. (2007a ,b ; 2008a ). For a related structure, see: Aridoss et al. (2008b ). For ring conformational analysis, see: Cremer & Pople (1975 ); Nardelli (1983 ).

Experimental

Crystal data

C₂₃H₂₆BrNO₄
M_r = 460.36
Monoclinic, C c
a = 12.9487 (9) Å
b = 25.2882 (18) Å
c = 8.9701 (6) Å
β = 132.930 (1)°
V = 2150.6 (3) Å³
Z = 4
Mo Kα radiation
μ = 1.94 mm⁻¹
T = 293 (2) K
0.30 × 0.20 × 0.16 mm

Data collection

Bruker Kappa APEXII diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 1999 ) T_min = 0.594, T_max = 0.747
13660 measured reflections
5139 independent reflections
3748 reflections with I > 2σ(I)
R_int = 0.023

Refinement

R[F² > 2σ(F²)] = 0.033
wR(F²) = 0.098
S = 1.02
5139 reflections
266 parameters
2 restraints
H-atom parameters constrained
Δρ_max = 0.42 e Å⁻³
Δρ_min = −0.22 e Å⁻³
Absolute structure: Flack (1983 ), 1651 Friedel pairs
Flack parameter: 0.004 (7)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C1—H1⋯Br1	0.98	2.82	3.523 (3)	129
C20—H20C⋯O1ⁱ	0.96	2.60	3.357 (7)	136
Symmetry code: (i) $[x-1, -y+1, z-{\script{3\over 2}}]$ .

Data collection: APEX2 (Bruker, 2004 ); cell refinement: SAINT (Bruker, 2004); data reduction: SAINT; program(s) used to solve structure: SIR92 (Altomare et al., 1993 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ); molecular graphics: PLATON (Spek, 2003 ); software used to prepare material for publication: SHELXL97.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808030213/ci2672sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536808030213/ci2672Isup2.hkl

checkCIF report

Comment top

The piperidine ring system is ubiquitous structural component of naturally occurring alkaloid and pharmaceuticals (O'Hagan, 2000; Pinder, 1992). Its biological properties are highly dependent on the type and location of substituents on the heterocyclic ring. The arylpiperidine scaffold is a key element involved in binding to a variety of receptors and therefore can be described as a privileged structure (Horton et al., 2003). Similarly, piperidone derivatives have also received wide interest among chemists and biologists due to their envisaged mode of interaction with cellular thiols, with modest or no affinity for the hydroxy and amine groups found in nucleic acids (Baluja et al., 1964; Mutus et al., 1989). Generally, compounds possessing an amide bond linkage have a wide range of biological activities such as antimicrobial (Priya et al., 2007), anti-inflammatory (Bylov et al., 1999), antiviral, antimalarial and general anesthetics (Dollery, 1999). Recently, we have explored the antimicrobial, analgesic and antipyretic activities associated with chloroacetyl and heterocyclicacetyl derivatives of variously functionalized 2,6-diarylpiperidin-4-ones besides the change in piperidone ring conformation (Aridoss et al., 2007a,b, 2008a). Thus, it has spurred our interest to synthesize diversely substituted 2,6-diarylpiperidin-4-ones and their derivatives. In order to establish the change in molecular conformation of piperidone ring upon bromoacetylation, the present investigation was made and confirmed by X-ray diffraction study.

The bond lengths and angles in the title molecule (Fig.1) are comparable to those observed in a related structure (Aridoss et al., 2008b). The sum of the angles at N1 (359.0 (6)°) is in accordance with sp² hybridization. The decrease in the N1—C22 bond length (1.368 (3) Å) when compared to C1—N1 (1.481 (3) Å) and C5—N1 (1.481 (3) Å) lengths indicates the effective conjugation between lone pair of nitrogen with carbonyl group. The N-COCH₂ group is coplanar as confirmed by the torsion angles C1—N1—C22—C23 of -4.0 (4)° and C5—N1—C22—O1 of -172.4 (2)°. The dihedral angle between the two benzene rings is 70.9 (1)°. The C10—C9—O3—C20 (6.3 (5)°) and C16—C15—O4—C21 (16.4 (4)°) torsion angles indicate that the methoxy groups almost lie in the plane of the phenyl rings C6—C11 and C12—C17, respectively, to which they are attached.

The piperidinone ring adopts a boat conformation with the puckering parameters (Cremer & Pople, 1975) and the smallest displacement asymmetry parameters (Nardelli, 1983) being q₂ = 0.673 (4) Å, q₃ = -0.051 (4) Å, Q_T = 0.675 (4)Å, θ = 94.3 (3)° and ΔC_s(C2) = 10.0 (3)°. A weak C—H···Br intramolecular interaction is observed in the molecular structure. In the crystal packing, the molecules are linked into a chain along [101] by intermolecular C—H···O hydrogen bonds (Fig. 2). A short intermolecular Br1···O4 (1+x, y, 1+z) contact of 3.063 (2) Å has been observed.

Related literature top

For background on the piperidine ring system, see: O'Hagan (2000); Pinder (1992). For information on the arylpiperidine scaffold, see: Horton et al. (2003). For piperidone derivatives, see:

Baluja et al. (1964); Mutus et al. (1989). For the biological activities of compounds possessing an amide bond linkage, see:

Priya et al. (2007); Bylov et al. (1999); Dollery (1999). For the activivities of chloroacetyl and heterocyclicacetyl derivatives of variously functionalized 2,6-diarylpiperidin-4-ones, see:

Aridoss et al. (2007a,b; 2008a). For a related structure, see: Aridoss et al. (2008b). For ring conformational analysis, see: Cremer & Pople (1975); Nardelli (1983).

Experimental top

The title compound was obtained by adopting our earlier method (Aridoss et al., 2007a). To a well stirred solution of 3,5-dimethyl-2,6-bis(p-methoxyphenyl)piperidin-4-one (1 equiv.) and triethylamine (1 equiv.) in freshly distilled benzene, bromoacetyl chloride (1 equiv.) in benzene was added in drop wise through the addition funnel for about half an hour. Stirring was continued until the completion of reaction. Later, it was poured into water and extracted with DCM. The combined DCM extracts was then washed well with 3% sodium bicarbonate solution and dried over anhydrous sodium sulfate. This upon evaporation and subsequent recrystallization in distilled ethanol furnished the diffraction-quality crystals of the title compound.

Computing details top

Data collection: APEX2 (Bruker, 2004); cell refinement: APEX2 (Bruker, 2004); data reduction: SAINT (Bruker, 2004); program(s) used to solve structure: SIR92 (Altomare et al., 1993); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top

	Fig. 1. The molecular structure of title compound, showing 30% probability displacement ellipsoids.
	Fig. 2. The crystal packing of the title compound. H atoms not involved in hydrogen bonding (dashed lines) have been omitted for clarity.

1-Bromoacetyl-2,6-bis(4-methoxyphenyl)-3,5-dimethylpiperidin-4-one top

Crystal data top

C₂₃H₂₆BrNO₄	F(000) = 952
M_r = 460.36	D_x = 1.422 Mg m⁻³
Monoclinic, Cc	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: C -2yc	Cell parameters from 5872 reflections
a = 12.9487 (9) Å	θ = 1.6–31.2°
b = 25.2882 (18) Å	µ = 1.94 mm⁻¹
c = 8.9701 (6) Å	T = 293 K
β = 132.930 (1)°	Prism, colourless
V = 2150.6 (3) Å³	0.30 × 0.20 × 0.16 mm
Z = 4

Data collection top

Bruker Kappa APEXII CCD diffractometer	5139 independent reflections
Radiation source: fine-focus sealed tube	3748 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.023
ω and ϕ scans	θ_max = 31.2°, θ_min = 1.6°
Absorption correction: multi-scan (SADABS; Bruker, 1999)	h = −11→18
T_min = 0.594, T_max = 0.747	k = −36→34
13660 measured reflections	l = −13→6

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.033	H-atom parameters constrained
wR(F²) = 0.098	w = 1/[σ²(F_o²) + (0.0517P)²] where P = (F_o² + 2F_c²)/3
S = 1.02	(Δ/σ)_max = 0.001
5139 reflections	Δρ_max = 0.42 e Å⁻³
266 parameters	Δρ_min = −0.22 e Å⁻³
2 restraints	Absolute structure: Flack (1983), 1651 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.004 (7)

Crystal data top

C₂₃H₂₆BrNO₄	V = 2150.6 (3) Å³
M_r = 460.36	Z = 4
Monoclinic, Cc	Mo Kα radiation
a = 12.9487 (9) Å	µ = 1.94 mm⁻¹
b = 25.2882 (18) Å	T = 293 K
c = 8.9701 (6) Å	0.30 × 0.20 × 0.16 mm
β = 132.930 (1)°

Data collection top

Bruker Kappa APEXII CCD diffractometer	5139 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 1999)	3748 reflections with I > 2σ(I)
T_min = 0.594, T_max = 0.747	R_int = 0.023
13660 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.033	H-atom parameters constrained
wR(F²) = 0.098	Δρ_max = 0.42 e Å⁻³
S = 1.02	Δρ_min = −0.22 e Å⁻³
5139 reflections	Absolute structure: Flack (1983), 1651 Friedel pairs
266 parameters	Absolute structure parameter: 0.004 (7)
2 restraints

Special details top

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

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

	x	y	z	U_iso*/U_eq
Br1	0.66353 (4)	0.384464 (14)	1.04369 (5)	0.06848 (12)
O1	0.5273 (2)	0.48401 (7)	0.6690 (3)	0.0532 (5)
O2	0.6012 (3)	0.29025 (9)	0.3780 (5)	0.0771 (8)
O3	−0.0290 (3)	0.45775 (10)	−0.4164 (4)	0.0731 (7)
O4	−0.0766 (2)	0.31531 (9)	0.3554 (3)	0.0559 (5)
N1	0.4607 (2)	0.40235 (8)	0.5255 (3)	0.0345 (4)
C1	0.4291 (3)	0.34626 (9)	0.5282 (4)	0.0364 (5)
H1	0.5069	0.3326	0.6654	0.044*
C2	0.4229 (3)	0.31286 (10)	0.3780 (4)	0.0416 (5)
H2	0.3356	0.3223	0.2401	0.050*
C3	0.5436 (3)	0.32436 (11)	0.3917 (4)	0.0461 (6)
C4	0.5906 (4)	0.38105 (11)	0.4261 (6)	0.0446 (7)
H4	0.6004	0.3901	0.3300	0.054*
C5	0.4839 (3)	0.41869 (9)	0.3917 (4)	0.0381 (5)
H5	0.5306	0.4532	0.4424	0.046*
C6	0.3462 (3)	0.42782 (9)	0.1749 (4)	0.0393 (5)
C7	0.3089 (3)	0.40271 (11)	0.0059 (4)	0.0486 (6)
H7	0.3699	0.3780	0.0241	0.058*
C8	0.1835 (4)	0.41381 (12)	−0.1874 (5)	0.0561 (7)
H8	0.1600	0.3961	−0.2979	0.067*
C9	0.0921 (3)	0.45079 (11)	−0.2196 (4)	0.0513 (7)
C10	0.1278 (3)	0.47738 (12)	−0.0556 (5)	0.0516 (7)
H10	0.0682	0.5031	−0.0752	0.062*
C11	0.2541 (3)	0.46518 (10)	0.1394 (4)	0.0455 (6)
H11	0.2772	0.4828	0.2497	0.055*
C12	0.2944 (3)	0.33861 (9)	0.4838 (4)	0.0364 (5)
C13	0.1691 (3)	0.36284 (11)	0.3213 (4)	0.0432 (6)
H13	0.1668	0.3853	0.2371	0.052*
C14	0.0474 (3)	0.35416 (10)	0.2822 (4)	0.0447 (6)
H14	−0.0360	0.3709	0.1725	0.054*
C15	0.0489 (3)	0.32085 (10)	0.4052 (4)	0.0408 (5)
C16	0.1720 (4)	0.29517 (10)	0.5642 (5)	0.0492 (6)
H16	0.1732	0.2717	0.6453	0.059*
C17	0.2921 (3)	0.30430 (11)	0.6021 (5)	0.0488 (6)
H17	0.3747	0.2870	0.7105	0.059*
C18	0.4147 (5)	0.25375 (12)	0.4064 (7)	0.0680 (9)
H18A	0.4945	0.2439	0.5445	0.102*
H18B	0.4151	0.2337	0.3159	0.102*
H18C	0.3294	0.2466	0.3765	0.102*
C19	0.7355 (4)	0.38566 (13)	0.6430 (7)	0.0598 (10)
H19A	0.7995	0.3610	0.6607	0.090*
H19B	0.7269	0.3779	0.7389	0.090*
H19C	0.7708	0.4210	0.6653	0.090*
C20	−0.1223 (5)	0.49859 (18)	−0.4644 (7)	0.0873 (12)
H20A	−0.0771	0.5322	−0.4334	0.131*
H20B	−0.1470	0.4941	−0.3857	0.131*
H20C	−0.2060	0.4971	−0.6068	0.131*
C21	−0.0739 (4)	0.29285 (15)	0.5013 (6)	0.0656 (9)
H21A	−0.0047	0.3107	0.6291	0.098*
H21B	−0.0501	0.2560	0.5174	0.098*
H21C	−0.1650	0.2965	0.4571	0.098*
C22	0.4945 (3)	0.43860 (10)	0.6661 (4)	0.0384 (5)
C23	0.4904 (3)	0.42170 (11)	0.8232 (4)	0.0434 (6)
H23A	0.4100	0.3987	0.7608	0.052*
H23B	0.4802	0.4525	0.8766	0.052*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Br1	0.05974 (18)	0.0974 (3)	0.04260 (14)	0.01855 (19)	0.03263 (13)	0.01594 (17)
O1	0.0652 (13)	0.0408 (10)	0.0590 (12)	−0.0060 (9)	0.0444 (11)	−0.0084 (9)
O2	0.0764 (17)	0.0581 (13)	0.123 (2)	−0.0063 (11)	0.0782 (18)	−0.0271 (13)
O3	0.0637 (15)	0.0801 (15)	0.0478 (12)	0.0042 (12)	0.0271 (12)	0.0110 (11)
O4	0.0489 (12)	0.0669 (13)	0.0613 (12)	−0.0003 (9)	0.0412 (11)	0.0063 (10)
N1	0.0395 (11)	0.0334 (9)	0.0376 (10)	−0.0026 (8)	0.0290 (9)	−0.0018 (8)
C1	0.0388 (12)	0.0350 (12)	0.0381 (12)	0.0030 (10)	0.0272 (11)	0.0031 (9)
C2	0.0473 (14)	0.0346 (12)	0.0520 (14)	−0.0020 (10)	0.0374 (13)	−0.0035 (11)
C3	0.0457 (15)	0.0475 (15)	0.0512 (14)	0.0007 (12)	0.0354 (13)	−0.0075 (12)
C4	0.0461 (19)	0.0498 (16)	0.0493 (19)	−0.0023 (11)	0.0370 (17)	−0.0005 (12)
C5	0.0482 (15)	0.0341 (12)	0.0449 (13)	−0.0028 (10)	0.0369 (13)	−0.0007 (10)
C6	0.0513 (15)	0.0337 (12)	0.0431 (12)	−0.0033 (10)	0.0362 (12)	0.0015 (9)
C7	0.0624 (18)	0.0442 (13)	0.0469 (15)	0.0056 (12)	0.0402 (15)	0.0020 (11)
C8	0.073 (2)	0.0501 (16)	0.0428 (14)	0.0030 (15)	0.0384 (16)	0.0000 (12)
C9	0.0532 (17)	0.0517 (16)	0.0436 (14)	−0.0031 (13)	0.0308 (14)	0.0089 (12)
C10	0.0560 (18)	0.0474 (15)	0.0543 (16)	0.0074 (13)	0.0387 (15)	0.0074 (12)
C11	0.0581 (17)	0.0417 (14)	0.0470 (14)	0.0004 (12)	0.0399 (14)	0.0006 (11)
C12	0.0423 (14)	0.0329 (11)	0.0405 (12)	−0.0008 (10)	0.0307 (11)	0.0005 (9)
C13	0.0485 (15)	0.0404 (13)	0.0439 (13)	−0.0005 (11)	0.0327 (13)	0.0079 (11)
C14	0.0392 (14)	0.0450 (16)	0.0425 (13)	0.0041 (11)	0.0250 (12)	0.0089 (11)
C15	0.0422 (14)	0.0377 (13)	0.0486 (14)	−0.0060 (11)	0.0333 (13)	−0.0068 (11)
C16	0.0549 (16)	0.0480 (14)	0.0563 (17)	0.0030 (14)	0.0424 (15)	0.0127 (13)
C17	0.0492 (16)	0.0482 (15)	0.0551 (16)	0.0106 (12)	0.0379 (15)	0.0188 (13)
C18	0.099 (3)	0.0367 (15)	0.105 (3)	−0.0042 (15)	0.084 (3)	−0.0081 (16)
C19	0.043 (2)	0.060 (2)	0.068 (3)	−0.0046 (13)	0.035 (2)	−0.0127 (15)
C20	0.076 (3)	0.091 (3)	0.078 (3)	0.021 (2)	0.046 (2)	0.030 (2)
C21	0.066 (2)	0.087 (2)	0.065 (2)	−0.0187 (17)	0.0529 (19)	−0.0098 (17)
C22	0.0332 (12)	0.0415 (13)	0.0373 (12)	0.0018 (10)	0.0227 (11)	−0.0022 (10)
C23	0.0412 (14)	0.0541 (16)	0.0376 (12)	0.0032 (11)	0.0278 (12)	−0.0022 (11)

Geometric parameters (Å, º) top

Br1—C23	1.945 (3)	C10—C11	1.390 (4)
O1—C22	1.219 (3)	C10—H10	0.93
O2—C3	1.201 (3)	C11—H11	0.93
O3—C9	1.354 (4)	C12—C13	1.382 (4)
O3—C20	1.415 (5)	C12—C17	1.387 (4)
O4—C15	1.367 (3)	C13—C14	1.379 (4)
O4—C21	1.406 (4)	C13—H13	0.93
N1—C22	1.368 (3)	C14—C15	1.377 (4)
N1—C5	1.481 (3)	C14—H14	0.93
N1—C1	1.481 (3)	C15—C16	1.378 (4)
C1—C12	1.513 (3)	C16—C17	1.366 (5)
C1—C2	1.546 (3)	C16—H16	0.93
C1—H1	0.9800	C17—H17	0.93
C2—C3	1.509 (4)	C18—H18A	0.96
C2—C18	1.532 (4)	C18—H18B	0.96
C2—H2	0.98	C18—H18C	0.96
C3—C4	1.505 (4)	C19—H19A	0.96
C4—C5	1.526 (4)	C19—H19B	0.96
C4—C19	1.532 (4)	C19—H19C	0.96
C4—H4	0.98	C20—H20A	0.96
C5—C6	1.514 (4)	C20—H20B	0.96
C5—H5	0.98	C20—H20C	0.96
C6—C11	1.378 (4)	C21—H21A	0.96
C6—C7	1.392 (4)	C21—H21B	0.96
C7—C8	1.374 (4)	C21—H21C	0.96
C7—H7	0.93	C22—C23	1.507 (4)
C8—C9	1.375 (5)	C23—H23A	0.97
C8—H8	0.93	C23—H23B	0.97
C9—C10	1.380 (4)

C9—O3—C20	118.8 (3)	C13—C12—C1	122.4 (2)
C15—O4—C21	117.8 (2)	C17—C12—C1	120.0 (2)
C22—N1—C5	116.5 (2)	C14—C13—C12	121.0 (2)
C22—N1—C1	123.0 (2)	C14—C13—H13	119.5
C5—N1—C1	119.5 (2)	C12—C13—H13	119.5
N1—C1—C12	113.59 (19)	C15—C14—C13	120.2 (2)
N1—C1—C2	111.07 (19)	C15—C14—H14	119.9
C12—C1—C2	109.6 (2)	C13—C14—H14	119.9
N1—C1—H1	107.5	O4—C15—C14	115.8 (2)
C12—C1—H1	107.5	O4—C15—C16	124.7 (2)
C2—C1—H1	107.5	C14—C15—C16	119.5 (3)
C3—C2—C18	111.1 (2)	C17—C16—C15	119.7 (3)
C3—C2—C1	112.8 (2)	C17—C16—H16	120.1
C18—C2—C1	110.9 (2)	C15—C16—H16	120.1
C3—C2—H2	107.3	C16—C17—C12	122.0 (3)
C18—C2—H2	107.3	C16—C17—H17	119.0
C1—C2—H2	107.3	C12—C17—H17	119.0
O2—C3—C4	120.8 (3)	C2—C18—H18A	109.5
O2—C3—C2	122.3 (3)	C2—C18—H18B	109.5
C4—C3—C2	116.9 (2)	H18A—C18—H18B	109.5
C3—C4—C5	111.6 (3)	C2—C18—H18C	109.5
C3—C4—C19	107.9 (3)	H18A—C18—H18C	109.5
C5—C4—C19	111.5 (2)	H18B—C18—H18C	109.5
C3—C4—H4	108.6	C4—C19—H19A	109.5
C5—C4—H4	108.6	C4—C19—H19B	109.5
C19—C4—H4	108.6	H19A—C19—H19B	109.5
N1—C5—C6	111.9 (2)	C4—C19—H19C	109.5
N1—C5—C4	108.5 (2)	H19A—C19—H19C	109.5
C6—C5—C4	117.8 (2)	H19B—C19—H19C	109.5
N1—C5—H5	105.9	O3—C20—H20A	109.5
C6—C5—H5	105.9	O3—C20—H20B	109.5
C4—C5—H5	105.9	H20A—C20—H20B	109.5
C11—C6—C7	117.2 (3)	O3—C20—H20C	109.5
C11—C6—C5	118.5 (2)	H20A—C20—H20C	109.5
C7—C6—C5	124.2 (2)	H20B—C20—H20C	109.5
C8—C7—C6	121.1 (3)	O4—C21—H21A	109.5
C8—C7—H7	119.4	O4—C21—H21B	109.5
C6—C7—H7	119.4	H21A—C21—H21B	109.5
C7—C8—C9	120.8 (3)	O4—C21—H21C	109.5
C7—C8—H8	119.6	H21A—C21—H21C	109.5
C9—C8—H8	119.6	H21B—C21—H21C	109.5
O3—C9—C8	115.4 (3)	O1—C22—N1	122.6 (2)
O3—C9—C10	125.2 (3)	O1—C22—C23	118.8 (2)
C8—C9—C10	119.4 (3)	N1—C22—C23	118.6 (2)
C9—C10—C11	119.1 (3)	C22—C23—Br1	109.78 (17)
C9—C10—H10	120.5	C22—C23—H23A	109.7
C11—C10—H10	120.5	Br1—C23—H23A	109.7
C6—C11—C10	122.3 (3)	C22—C23—H23B	109.7
C6—C11—H11	118.9	Br1—C23—H23B	109.7
C10—C11—H11	118.9	H23A—C23—H23B	108.2
C13—C12—C17	117.5 (2)

C22—N1—C1—C12	66.9 (3)	C20—O3—C9—C8	−174.0 (3)
C5—N1—C1—C12	−125.1 (2)	C20—O3—C9—C10	6.3 (5)
C22—N1—C1—C2	−169.1 (2)	C7—C8—C9—O3	−179.1 (3)
C5—N1—C1—C2	−1.1 (3)	C7—C8—C9—C10	0.6 (4)
N1—C1—C2—C3	45.3 (3)	O3—C9—C10—C11	178.2 (3)
C12—C1—C2—C3	171.6 (2)	C8—C9—C10—C11	−1.6 (4)
N1—C1—C2—C18	170.6 (2)	C7—C6—C11—C10	0.8 (4)
C12—C1—C2—C18	−63.1 (3)	C5—C6—C11—C10	177.7 (3)
C18—C2—C3—O2	16.2 (4)	C9—C10—C11—C6	0.9 (4)
C1—C2—C3—O2	141.4 (3)	N1—C1—C12—C13	48.1 (3)
C18—C2—C3—C4	−163.2 (3)	C2—C1—C12—C13	−76.8 (3)
C1—C2—C3—C4	−38.0 (3)	N1—C1—C12—C17	−135.1 (2)
O2—C3—C4—C5	167.3 (3)	C2—C1—C12—C17	100.1 (3)
C2—C3—C4—C5	−13.3 (4)	C17—C12—C13—C14	1.7 (4)
O2—C3—C4—C19	−69.9 (4)	C1—C12—C13—C14	178.6 (2)
C2—C3—C4—C19	109.5 (3)	C12—C13—C14—C15	−0.2 (4)
C22—N1—C5—C6	−109.2 (2)	C21—O4—C15—C14	−164.6 (3)
C1—N1—C5—C6	82.0 (3)	C21—O4—C15—C16	16.4 (4)
C22—N1—C5—C4	119.1 (2)	C13—C14—C15—O4	179.3 (2)
C1—N1—C5—C4	−49.7 (3)	C13—C14—C15—C16	−1.7 (4)
C3—C4—C5—N1	55.9 (3)	O4—C15—C16—C17	−179.0 (3)
C19—C4—C5—N1	−64.8 (3)	C14—C15—C16—C17	2.1 (4)
C3—C4—C5—C6	−72.5 (3)	C15—C16—C17—C12	−0.6 (5)
C19—C4—C5—C6	166.8 (2)	C13—C12—C17—C16	−1.3 (4)
N1—C5—C6—C11	58.9 (3)	C1—C12—C17—C16	−178.3 (3)
C4—C5—C6—C11	−174.3 (2)	C5—N1—C22—O1	7.8 (4)
N1—C5—C6—C7	−124.5 (3)	C1—N1—C22—O1	176.2 (2)
C4—C5—C6—C7	2.3 (4)	C5—N1—C22—C23	−172.4 (2)
C11—C6—C7—C8	−1.8 (4)	C1—N1—C22—C23	−4.0 (4)
C5—C6—C7—C8	−178.4 (3)	O1—C22—C23—Br1	−98.9 (3)
C6—C7—C8—C9	1.1 (5)	N1—C22—C23—Br1	81.2 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C1—H1···Br1	0.98	2.82	3.523 (3)	129
C20—H20C···O1ⁱ	0.96	2.60	3.357 (7)	136

Symmetry code: (i) x−1, −y+1, z−3/2.

Experimental details

Crystal data
Chemical formula	C₂₃H₂₆BrNO₄
M_r	460.36
Crystal system, space group	Monoclinic, Cc
Temperature (K)	293
a, b, c (Å)	12.9487 (9), 25.2882 (18), 8.9701 (6)
β (°)	132.930 (1)
V (Å³)	2150.6 (3)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	1.94
Crystal size (mm)	0.30 × 0.20 × 0.16

Data collection
Diffractometer	Bruker Kappa APEXII CCD diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 1999)
T_min, T_max	0.594, 0.747
No. of measured, independent and observed [I > 2σ(I)] reflections	13660, 5139, 3748
R_int	0.023
(sin θ/λ)_max (Å⁻¹)	0.729

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.033, 0.098, 1.02
No. of reflections	5139
No. of parameters	266
No. of restraints	2
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.42, −0.22
Absolute structure	Flack (1983), 1651 Friedel pairs
Absolute structure parameter	0.004 (7)

Computer programs: APEX2 (Bruker, 2004), SAINT (Bruker, 2004), SIR92 (Altomare et al., 1993), SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2003).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C1—H1···Br1	0.98	2.82	3.523 (3)	129
C20—H20C···O1ⁱ	0.96	2.60	3.357 (7)	136

Symmetry code: (i) x−1, −y+1, z−3/2.

Acknowledgements

GA and YTJ acknowledge support provided by the second stage of the BK21 program, Republic of Korea. Financial support from the University Grants Commission (UGC–SAP) and the Department of Science & Technology (DST–FIST), Government of India, are acknowledged by DV for providing facilities to the department.

References

Altomare, A., Cascarano, G., Giacovazzo, C. & Guagliardi, A. (1993). J. Appl. Cryst. 26, 343–350. CrossRef Web of Science IUCr Journals Google Scholar
Aridoss, G., Amirthaganesan, S., Kim, M. S., Cho, B. G., Lim, K. T. & Jeong, Y. T. (2008b). Arkivoc, XV, 133–158. CrossRef Google Scholar
Aridoss, G., Balasubramanian, S., Parthiban, P. & Kabilan, S. (2007b). Eur. J. Med. Chem. 42, 851–860. Web of Science CrossRef PubMed CAS Google Scholar
Aridoss, G., Balasubramanian, S., Parthiban, P., Ramachandran, R. & Kabilan, S. (2007a). Med. Chem. Res. 16, 188–204. Web of Science CrossRef CAS Google Scholar
Aridoss, G., Parthiban, P., Ramachandran, R., Prakash, M., Kabilan, S. & Jeong, Y. T. (2008a). Eur. J. Med. Chem. 10, doi:10.1016/j.ejmech.2008.03.031. Google Scholar
Baluja, G., Municio, A. M. & Vega, S. (1964). Chem. Ind. pp. 2053–2054. Google Scholar
Bruker (1999). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Bruker (2004). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Bylov, I. E., Vasylev, M. V. & Bilokin, Y. V. (1999). Eur. J. Med. Chem. 34, 997–1001. 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
Dollery, C. (1999). Therapeutic Drugs. Edinburgh, Scotland: Churchill Livingstone. Google Scholar
Flack, H. D. (1983). Acta Cryst. A39, 876–881. CrossRef CAS Web of Science IUCr Journals Google Scholar
Horton, D. A., Bourne, G. T. & Smythe, M. L. (2003). Chem. Rev. 103, 893–930. Web of Science CrossRef PubMed CAS Google Scholar
Mutus, B., Wagner, J. D., Talpas, C. J., Dimmock, J. R., Phillips, O. A. & Reid, R. S. (1989). Anal. Biochem. 177, 237–243. CrossRef CAS PubMed Web of Science Google Scholar
Nardelli, M. (1983). Acta Cryst. C39, 1141–1142. CrossRef CAS Web of Science IUCr Journals Google Scholar
O'Hagan, D. (2000). Nat. Prod. Rep. 17, 435–446. Web of Science CrossRef PubMed CAS Google Scholar
Pinder, A. R. (1992). Nat. Prod. Rep. 9, 491–504. CrossRef CAS Web of Science Google Scholar
Priya, B. S., Anil Kumar, C., Nanjunda Swamy, S., Basappa, S., Naveen, S., Shashidhara Prasad, J. & Rangappa, K. S. (2007). Bioorg. Med. Chem. Lett. 17, 2775–2780. Web of Science CSD CrossRef PubMed CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Spek, A. L. (2003). J. Appl. Cryst. 36, 7–13. Web of Science CrossRef CAS IUCr Journals Google Scholar