Quetiapine N-oxide-fumaric acid (2/1).

THE TITLE COMPOUND (SYSTEMATIC NAME: 2-{2-[4-(dibenzo[b,f][1,4]thia-zepin-11-yl)piperazin-1-yl 1-oxide]eth-oxy}ethanol-fumaric acid (2/1)), C(21)H(25)N(3)O(3)S·0.5C(4)H(4)O(4), is one of the oxidation products of quetiapine hemifumaric acid. In the tricyclic fragment, the central thia-zepine ring displays a boat conformation and the benzene rings are inclined to each other at a dihedral angle of 72.0 (2)°. The piperazine ring adopts a chair conformation with its eth-oxy-ethanol side chain oriented equatorially. In addition to the main mol-ecule, the asymmetric unit contains one-half mol-ecule of fumaric acid, the complete mol-ecule being generated by inversion symmetry. In the crystal, O-H⋯O hydrogen bonds link the components into corrugated layers parallel to bc plane.

Related literature

For the identification, isolation, synthesis and characterization of quetiapine N-oxide, see: Mittapelli et al. (2010 ▶). For quanti­tative determination of quetiapine impurities, degradation products in pharmaceutical dosage form or in bulk, tablets, and in human plasma, see: Trivedi & Patel (2011 ▶); Belal et al. (2008 ▶). For the use of quetiapine as an anti­psychotic drug, see: Lieberman (1996 ▶). For the crystal structure of quetiapine hemifumarate, see: Ravikumar & Sridhar (2005 ▶).

Experimental

Crystal data

C21H25N3O3S·0.5C4H4O4

M = 457.54

Monoclinic,

a = 13.1299 (9) Å

b = 12.5047 (8) Å

c = 13.9950 (9) Å

β = 101.59 (2)°

V = 2250.9 (3) Å3

Z = 4

Mo Kα radiation

μ = 0.18 mm−1

T = 296 K

0.27 × 0.25 × 0.10 mm

Data collection

Rigaku R-AXIS RAPID/ZJUG diffractometer

Absorption correction: multi-scan (ABSCOR; Higashi, 1995 ▶) T min = 0.947, T max = 0.982

17003 measured reflections

3970 independent reflections

2453 reflections with I > 2σ(I)

R int = 0.069

Refinement

R[F 2 > 2σ(F 2)] = 0.070

wR(F 2) = 0.193

S = 1.00

3970 reflections

291 parameters

H-atom parameters constrained

Δρmax = 0.37 e Å−3

Δρmin = −0.39 e Å−3

Data collection: PROCESS-AUTO (Rigaku, 2006 ▶); cell refinement: PROCESS-AUTO; data reduction: CrystalStructure (Rigaku, 2007 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812020818/cv5294sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812020818/cv5294Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C21H25N3O3S·0.5C4H4O4	F(000) = 968
Mr = 457.54	Dx = 1.350 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 10875 reflections
a = 13.1299 (9) Å	θ = 3.1–27.5°
b = 12.5047 (8) Å	µ = 0.18 mm−1
c = 13.9950 (9) Å	T = 296 K
β = 101.59 (2)°	Platelet, colourless
V = 2250.9 (3) Å3	0.27 × 0.25 × 0.10 mm
Z = 4

Rigaku R-AXIS RAPID/ZJUG diffractometer	3970 independent reflections
Radiation source: rolling anode	2453 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.069
Detector resolution: 10.00 pixels mm-1	θmax = 25.0°, θmin = 3.1°
ω scans	h = −15→15
Absorption correction: multi-scan (ABSCOR; Higashi, 1995)	k = −14→14
Tmin = 0.947, Tmax = 0.982	l = −16→16
17003 measured reflections

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)] = 0.070	H-atom parameters constrained
wR(F2) = 0.193	w = 1/[σ2(Fo2) + (0.0701P)2 + 3.2854P] where P = (Fo2 + 2Fc2)/3
S = 1.00	(Δ/σ)max < 0.001
3970 reflections	Δρmax = 0.37 e Å−3
291 parameters	Δρmin = −0.39 e Å−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0142 (18)

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.

	x	y	z	Uiso*/Ueq
C1	0.4958 (3)	0.6665 (3)	0.5761 (3)	0.0441 (9)
C2	0.6017 (3)	0.6567 (3)	0.5537 (3)	0.0433 (9)
C3	0.6156 (3)	0.6002 (3)	0.4723 (3)	0.0490 (10)
H3	0.5591	0.5665	0.4332	0.059*
C4	0.7121 (4)	0.5933 (3)	0.4486 (3)	0.0586 (11)
H4	0.7205	0.5554	0.3936	0.070*
C5	0.7957 (4)	0.6424 (4)	0.5060 (4)	0.0688 (13)
H5	0.8601	0.6407	0.4880	0.083*
C6	0.7850 (4)	0.6941 (4)	0.5900 (4)	0.0648 (12)
H6	0.8430	0.7235	0.6306	0.078*
C7	0.6881 (3)	0.7027 (3)	0.6146 (3)	0.0486 (10)
C8	0.6330 (3)	0.6545 (3)	0.7814 (3)	0.0522 (10)
C9	0.6911 (4)	0.6175 (4)	0.8694 (3)	0.0683 (13)
H9	0.7536	0.6507	0.8964	0.082*
C10	0.6572 (4)	0.5327 (4)	0.9169 (3)	0.0775 (15)
H10	0.6963	0.5090	0.9760	0.093*
C11	0.5653 (4)	0.4833 (4)	0.8767 (3)	0.0718 (14)
H11	0.5429	0.4249	0.9082	0.086*
C12	0.5060 (4)	0.5190 (3)	0.7908 (3)	0.0564 (11)
H12	0.4430	0.4858	0.7655	0.068*
C13	0.5391 (3)	0.6045 (3)	0.7405 (3)	0.0477 (10)
C14	0.4310 (3)	0.7560 (3)	0.4149 (3)	0.0501 (10)
H14A	0.5038	0.7567	0.4103	0.060*
H14B	0.4092	0.8292	0.4217	0.060*
C15	0.3672 (3)	0.7076 (3)	0.3242 (3)	0.0519 (10)
H15A	0.3912	0.6354	0.3162	0.062*
H15B	0.3760	0.7491	0.2679	0.062*
C16	0.2418 (3)	0.6465 (3)	0.4204 (3)	0.0472 (10)
H16A	0.2592	0.5718	0.4142	0.057*
H16B	0.1697	0.6503	0.4269	0.057*
C17	0.3100 (3)	0.6920 (3)	0.5109 (3)	0.0491 (10)
H17A	0.2876	0.7641	0.5220	0.059*
H17B	0.3037	0.6487	0.5670	0.059*
C18	0.1943 (3)	0.6514 (4)	0.2394 (3)	0.0634 (12)
H18A	0.2070	0.6898	0.1827	0.076*
H18B	0.2207	0.5793	0.2364	0.076*
C19	0.0792 (4)	0.6461 (4)	0.2346 (3)	0.0675 (13)
H19A	0.0563	0.7106	0.2625	0.081*
H19B	0.0431	0.6413	0.1671	0.081*
C21	−0.0675 (4)	0.4476 (4)	0.3412 (4)	0.0770 (15)
H21A	−0.0322	0.3870	0.3192	0.092*
H21B	−0.0360	0.4607	0.4090	0.092*
C22	0.0380 (8)	0.8697 (5)	0.4497 (6)	0.119 (3)
C23	−0.0191 (6)	0.9488 (5)	0.4871 (6)	0.119 (2)
H23	−0.0859	0.9320	0.4952	0.142*
C20	−0.0523 (3)	0.5435 (4)	0.2823 (4)	0.0687 (13)
H20A	−0.0884	0.5340	0.2152	0.082*
H20B	−0.0802	0.6065	0.3084	0.082*
N1	0.4694 (2)	0.6414 (3)	0.6578 (2)	0.0464 (8)
N2	0.4178 (2)	0.6936 (3)	0.4998 (2)	0.0474 (8)
N3	0.2541 (2)	0.7051 (2)	0.3299 (2)	0.0464 (8)
O1	0.2203 (2)	0.8100 (2)	0.3328 (2)	0.0617 (8)
O2	0.0553 (2)	0.5560 (2)	0.2866 (2)	0.0664 (9)
O3	−0.1721 (3)	0.4219 (3)	0.3344 (3)	0.0910 (12)
H301	−0.1962	0.3992	0.2796	0.136*
O4	0.1258 (4)	0.8974 (4)	0.4401 (4)	0.1291 (18)
H401	0.1599	0.8556	0.4147	0.194*
O5	0.0062 (6)	0.7872 (6)	0.4257 (6)	0.195 (3)
S1	0.67581 (9)	0.76727 (9)	0.72389 (9)	0.0615 (4)

	U11	U22	U33	U12	U13	U23
C1	0.049 (2)	0.039 (2)	0.044 (2)	−0.0020 (17)	0.0103 (18)	−0.0027 (17)
C2	0.048 (2)	0.038 (2)	0.045 (2)	0.0006 (17)	0.0131 (18)	0.0029 (17)
C3	0.055 (3)	0.045 (2)	0.048 (2)	0.0017 (19)	0.0126 (19)	0.0013 (19)
C4	0.068 (3)	0.053 (3)	0.059 (3)	0.015 (2)	0.022 (2)	0.011 (2)
C5	0.055 (3)	0.081 (3)	0.075 (3)	0.015 (3)	0.025 (2)	0.012 (3)
C6	0.049 (3)	0.068 (3)	0.076 (3)	−0.003 (2)	0.011 (2)	0.004 (3)
C7	0.047 (2)	0.046 (2)	0.052 (2)	−0.0020 (18)	0.0093 (18)	−0.0001 (18)
C8	0.058 (3)	0.048 (2)	0.050 (2)	0.004 (2)	0.008 (2)	−0.0079 (19)
C9	0.069 (3)	0.069 (3)	0.058 (3)	0.014 (2)	−0.008 (2)	−0.010 (2)
C10	0.100 (4)	0.073 (3)	0.052 (3)	0.024 (3)	−0.003 (3)	0.008 (3)
C11	0.102 (4)	0.059 (3)	0.053 (3)	0.013 (3)	0.012 (3)	0.009 (2)
C12	0.070 (3)	0.050 (2)	0.049 (2)	0.000 (2)	0.011 (2)	0.002 (2)
C13	0.054 (3)	0.047 (2)	0.042 (2)	0.0098 (19)	0.0086 (18)	−0.0052 (18)
C14	0.051 (2)	0.050 (2)	0.050 (2)	−0.0017 (19)	0.0119 (18)	0.0117 (19)
C15	0.052 (3)	0.057 (3)	0.049 (2)	−0.002 (2)	0.0166 (19)	0.0071 (19)
C16	0.047 (2)	0.048 (2)	0.049 (2)	0.0000 (18)	0.0159 (18)	0.0054 (18)
C17	0.041 (2)	0.062 (2)	0.045 (2)	0.0010 (19)	0.0085 (17)	0.0048 (19)
C18	0.060 (3)	0.079 (3)	0.049 (2)	−0.014 (2)	0.006 (2)	−0.007 (2)
C19	0.065 (3)	0.070 (3)	0.060 (3)	−0.012 (2)	−0.003 (2)	0.004 (2)
C21	0.078 (4)	0.069 (3)	0.083 (3)	−0.025 (3)	0.014 (3)	−0.020 (3)
C22	0.200 (9)	0.055 (4)	0.130 (6)	−0.020 (5)	0.103 (6)	−0.027 (4)
C23	0.113 (6)	0.108 (5)	0.133 (6)	0.004 (5)	0.018 (4)	−0.013 (5)
C20	0.050 (3)	0.065 (3)	0.090 (4)	−0.011 (2)	0.012 (2)	−0.018 (3)
N1	0.048 (2)	0.0485 (19)	0.0425 (18)	0.0038 (15)	0.0094 (15)	−0.0007 (15)
N2	0.0392 (18)	0.059 (2)	0.0435 (18)	0.0003 (15)	0.0064 (14)	0.0105 (15)
N3	0.049 (2)	0.0425 (18)	0.0467 (18)	0.0004 (15)	0.0072 (15)	0.0051 (14)
O1	0.065 (2)	0.0447 (16)	0.0709 (19)	0.0053 (14)	0.0028 (15)	0.0099 (14)
O2	0.0531 (19)	0.0605 (19)	0.083 (2)	−0.0114 (15)	0.0065 (15)	−0.0023 (17)
O3	0.087 (3)	0.091 (3)	0.108 (3)	−0.033 (2)	0.051 (2)	−0.045 (2)
O4	0.103 (4)	0.108 (4)	0.163 (5)	0.011 (3)	−0.003 (3)	−0.033 (3)
O5	0.197 (7)	0.132 (5)	0.292 (9)	−0.037 (5)	0.133 (6)	−0.052 (6)
S1	0.0640 (8)	0.0544 (7)	0.0645 (7)	−0.0083 (5)	0.0087 (5)	−0.0151 (6)

C1—N1	1.299 (5)	C15—H15A	0.9700
C1—N2	1.366 (5)	C15—H15B	0.9700
C1—C2	1.491 (5)	C16—N3	1.500 (5)
C2—C3	1.384 (5)	C16—C17	1.508 (5)
C2—C7	1.398 (5)	C16—H16A	0.9700
C3—C4	1.375 (6)	C16—H16B	0.9700
C3—H3	0.9300	C17—N2	1.455 (5)
C4—C5	1.368 (6)	C17—H17A	0.9700
C4—H4	0.9300	C17—H17B	0.9700
C5—C6	1.374 (6)	C18—C19	1.501 (6)
C5—H5	0.9300	C18—N3	1.507 (5)
C6—C7	1.387 (6)	C18—H18A	0.9700
C6—H6	0.9300	C18—H18B	0.9700
C7—S1	1.765 (4)	C19—O2	1.410 (5)
C8—C9	1.390 (6)	C19—H19A	0.9700
C8—C13	1.398 (6)	C19—H19B	0.9700
C8—S1	1.771 (4)	C21—O3	1.394 (5)
C9—C10	1.372 (7)	C21—C20	1.491 (7)
C9—H9	0.9300	C21—H21A	0.9700
C10—C11	1.372 (7)	C21—H21B	0.9700
C10—H10	0.9300	C22—O5	1.138 (8)
C11—C12	1.370 (6)	C22—O4	1.237 (8)
C11—H11	0.9300	C22—C23	1.404 (9)
C12—C13	1.397 (6)	C23—C23i	1.396 (13)
C12—H12	0.9300	C23—H23	0.9300
C13—N1	1.401 (5)	C20—O2	1.411 (5)
C14—N2	1.461 (5)	C20—H20A	0.9700
C14—C15	1.501 (5)	C20—H20B	0.9700
C14—H14A	0.9700	N3—O1	1.388 (4)
C14—H14B	0.9700	O3—H301	0.8200
C15—N3	1.504 (5)	O4—H401	0.8139
N1—C1—N2	117.2 (4)	N3—C16—H16B	109.1
N1—C1—C2	126.2 (3)	C17—C16—H16B	109.1
N2—C1—C2	116.2 (3)	H16A—C16—H16B	107.9
C3—C2—C7	119.2 (4)	N2—C17—C16	109.9 (3)
C3—C2—C1	119.8 (3)	N2—C17—H17A	109.7
C7—C2—C1	121.0 (3)	C16—C17—H17A	109.7
C4—C3—C2	120.7 (4)	N2—C17—H17B	109.7
C4—C3—H3	119.6	C16—C17—H17B	109.7
C2—C3—H3	119.6	H17A—C17—H17B	108.2
C5—C4—C3	120.0 (4)	C19—C18—N3	114.0 (4)
C5—C4—H4	120.0	C19—C18—H18A	108.8
C3—C4—H4	120.0	N3—C18—H18A	108.8
C4—C5—C6	120.4 (4)	C19—C18—H18B	108.8
C4—C5—H5	119.8	N3—C18—H18B	108.8
C6—C5—H5	119.8	H18A—C18—H18B	107.7
C5—C6—C7	120.4 (4)	O2—C19—C18	109.8 (4)
C5—C6—H6	119.8	O2—C19—H19A	109.7
C7—C6—H6	119.8	C18—C19—H19A	109.7
C6—C7—C2	119.2 (4)	O2—C19—H19B	109.7
C6—C7—S1	119.9 (3)	C18—C19—H19B	109.7
C2—C7—S1	120.8 (3)	H19A—C19—H19B	108.2
C9—C8—C13	119.7 (4)	O3—C21—C20	112.8 (5)
C9—C8—S1	120.0 (4)	O3—C21—H21A	109.0
C13—C8—S1	120.2 (3)	C20—C21—H21A	109.0
C10—C9—C8	120.8 (5)	O3—C21—H21B	109.0
C10—C9—H9	119.6	C20—C21—H21B	109.0
C8—C9—H9	119.6	H21A—C21—H21B	107.8
C11—C10—C9	119.6 (4)	O5—C22—O4	121.1 (8)
C11—C10—H10	120.2	O5—C22—C23	123.8 (9)
C9—C10—H10	120.2	O4—C22—C23	115.0 (7)
C12—C11—C10	120.7 (5)	C23i—C23—C22	123.5 (10)
C12—C11—H11	119.7	C23i—C23—H23	118.3
C10—C11—H11	119.7	C22—C23—H23	118.3
C11—C12—C13	120.9 (4)	O2—C20—C21	108.1 (4)
C11—C12—H12	119.6	O2—C20—H20A	110.1
C13—C12—H12	119.6	C21—C20—H20A	110.1
C12—C13—C8	118.2 (4)	O2—C20—H20B	110.1
C12—C13—N1	116.8 (4)	C21—C20—H20B	110.1
C8—C13—N1	124.6 (4)	H20A—C20—H20B	108.4
N2—C14—C15	109.5 (3)	C1—N1—C13	124.2 (3)
N2—C14—H14A	109.8	C1—N2—C17	120.4 (3)
C15—C14—H14A	109.8	C1—N2—C14	125.1 (3)
N2—C14—H14B	109.8	C17—N2—C14	111.9 (3)
C15—C14—H14B	109.8	O1—N3—C16	110.3 (3)
H14A—C14—H14B	108.2	O1—N3—C15	107.9 (3)
C14—C15—N3	110.7 (3)	C16—N3—C15	109.2 (3)
C14—C15—H15A	109.5	O1—N3—C18	109.3 (3)
N3—C15—H15A	109.5	C16—N3—C18	111.4 (3)
C14—C15—H15B	109.5	C15—N3—C18	108.5 (3)
N3—C15—H15B	109.5	C19—O2—C20	113.1 (4)
H15A—C15—H15B	108.1	C21—O3—H301	109.5
N3—C16—C17	112.3 (3)	C22—O4—H401	118.3
N3—C16—H16A	109.1	C7—S1—C8	97.02 (19)
C17—C16—H16A	109.1
N1—C1—C2—C3	125.9 (4)	O4—C22—C23—C23i	−0.5 (15)
N2—C1—C2—C3	−46.7 (5)	O3—C21—C20—O2	−174.3 (4)
N1—C1—C2—C7	−53.2 (6)	N2—C1—N1—C13	175.3 (3)
N2—C1—C2—C7	134.2 (4)	C2—C1—N1—C13	2.7 (6)
C7—C2—C3—C4	−3.0 (6)	C12—C13—N1—C1	−137.1 (4)
C1—C2—C3—C4	177.8 (4)	C8—C13—N1—C1	50.3 (6)
C2—C3—C4—C5	0.2 (6)	N1—C1—N2—C17	−1.1 (5)
C3—C4—C5—C6	3.3 (7)	C2—C1—N2—C17	172.2 (3)
C4—C5—C6—C7	−3.9 (7)	N1—C1—N2—C14	158.9 (4)
C5—C6—C7—C2	1.0 (7)	C2—C1—N2—C14	−27.8 (5)
C5—C6—C7—S1	178.8 (4)	C16—C17—N2—C1	−139.4 (4)
C3—C2—C7—C6	2.4 (6)	C16—C17—N2—C14	58.1 (4)
C1—C2—C7—C6	−178.4 (4)	C15—C14—N2—C1	137.9 (4)
C3—C2—C7—S1	−175.4 (3)	C15—C14—N2—C17	−60.6 (4)
C1—C2—C7—S1	3.7 (5)	C17—C16—N3—O1	−64.5 (4)
C13—C8—C9—C10	−0.2 (7)	C17—C16—N3—C15	54.0 (4)
S1—C8—C9—C10	177.5 (4)	C17—C16—N3—C18	173.9 (3)
C8—C9—C10—C11	0.5 (7)	C14—C15—N3—O1	64.2 (4)
C9—C10—C11—C12	−1.3 (8)	C14—C15—N3—C16	−55.8 (4)
C10—C11—C12—C13	1.8 (7)	C14—C15—N3—C18	−177.5 (3)
C11—C12—C13—C8	−1.5 (6)	C19—C18—N3—O1	−61.1 (5)
C11—C12—C13—N1	−174.6 (4)	C19—C18—N3—C16	61.1 (5)
C9—C8—C13—C12	0.7 (6)	C19—C18—N3—C15	−178.6 (4)
S1—C8—C13—C12	−177.0 (3)	C18—C19—O2—C20	−177.8 (4)
C9—C8—C13—N1	173.3 (4)	C21—C20—O2—C19	−178.9 (4)
S1—C8—C13—N1	−4.5 (5)	C6—C7—S1—C8	−116.3 (4)
N2—C14—C15—N3	59.1 (4)	C2—C7—S1—C8	61.6 (4)
N3—C16—C17—N2	−55.0 (4)	C9—C8—S1—C7	119.6 (4)
N3—C18—C19—O2	−84.5 (5)	C13—C8—S1—C7	−62.6 (4)
O5—C22—C23—C23i	−177.4 (11)

D—H···A	D—H	H···A	D···A	D—H···A
O4—H401···O1	0.81	1.62	2.394 (6)	157
O3—H301···O1ii	0.82	1.90	2.691 (4)	161

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O4—H401⋯O1	0.81	1.62	2.394 (6)	157
O3—H301⋯O1i	0.82	1.90	2.691 (4)	161

Symmetry code: (i) .