Tetra­hydro­berberine, a pharmacologically active naturally occurring alkaloid

Tetra­hydro­berberine (systematic name: 9,10-dimeth­oxy-5,8,13,13a-tetra­hydro-6H-benzo[g][1,3]benzodioxolo[5,6-a]quinolizine), C₂₀H₂₁NO₄, a widely distributed naturally occurring alkaloid, has been crystallized as a racemic mixture about an inversion center. A bent conformation of the mol­ecule is observed, with an angle of 24.72 (5)° between the arene rings at the two ends of the reduced quinolizinium core. The inter­molecular hydrogen bonds that play an apparent role in crystal packing are 1,3-benzodioxole –CH₂...OCH₃ and –OCH₃...OCH₃ inter­actions between neighboring mol­ecules.

Computing details

Data collection: APEX2 (Bruker, 2010); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXS (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: SHELXTL (Bruker, 2008); software used to prepare material for publication: SHELXTL (Bruker, 2008).

9,10-Dimethoxy-5,8,13,13a-tetrahydro-6H-benzo[g][1,3]benzodioxolo[5,6-a]quinolizine

Crystal data

C20H21NO4	F(000) = 720
Mr = 339.38	Dx = 1.395 Mg m^−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
a = 10.516 (3) Å	Cell parameters from 7019 reflections
b = 14.796 (5) Å	θ = 2.4–28.8°
c = 10.620 (3) Å	µ = 0.10 mm^−1
β = 101.986 (4)°	T = 150 K
V = 1616.3 (9) Å^3	Needle, pale yellow
Z = 4	0.39 × 0.17 × 0.03 mm

Data collection

Bruker SMART APEX CCD diffractometer	3306 independent reflections
Radiation source: fine-focus sealed tube	2468 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.069
φ and ω scans	θmax = 26.4°, θmin = 2.4°
Absorption correction: multi-scan (SADABS; Sheldrick, 2009)	h = −13→13
Tmin = 0.650, Tmax = 0.997	k = −18→18
23937 measured reflections	l = −13→13

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.050	Hydrogen site location: difference Fourier map
wR(F^2) = 0.132	All H-atom parameters refined
S = 1.09	w = 1/[σ^2(Fo^2) + (0.0723P)^2 + 0.074P] where P = (Fo^2 + 2Fc^2)/3
3306 reflections	(Δ/σ)max < 0.001
310 parameters	Δρmax = 0.25 e Å^−3
0 restraints	Δρmin = −0.28 e Å^−3

Special details

Experimental. The diffraction data were obtained from 3 sets of 400 frames, each of width 0.5° in ω, collected at φ = 0.00, 90.00 and 180.00° and 2 sets of 800 frames, each of width 0.45° in φ, collected at ω = -30.00 and 210.00°. The scan time was 60 sec per frame.

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	0.01598 (13)	0.06160 (9)	0.36706 (14)	0.0336 (4)
O3	0.22930 (14)	0.01051 (9)	0.41434 (14)	0.0354 (4)
O9	0.17222 (12)	0.72123 (8)	0.45030 (11)	0.0239 (3)
O10	−0.04453 (12)	0.79326 (8)	0.30532 (13)	0.0280 (3)
N7	0.25961 (14)	0.44323 (10)	0.43049 (14)	0.0221 (4)
C2	0.0985 (2)	−0.01444 (14)	0.3572 (2)	0.0343 (5)
H2A	0.0936 (18)	−0.0300 (14)	0.259 (2)	0.031 (5)*
H2B	0.073 (2)	−0.0622 (16)	0.405 (2)	0.042 (6)*
C3A	0.22800 (19)	0.10373 (12)	0.41602 (18)	0.0268 (4)
C4	0.33017 (19)	0.16167 (13)	0.44905 (18)	0.0272 (4)
H4	0.425 (2)	0.1429 (13)	0.4669 (19)	0.035 (6)*
C4A	0.30206 (18)	0.25497 (13)	0.45153 (17)	0.0238 (4)
C5	0.41270 (19)	0.32064 (14)	0.4927 (2)	0.0287 (5)
H5A	0.461 (2)	0.3298 (15)	0.426 (2)	0.039 (6)*
H5B	0.479 (2)	0.2963 (13)	0.563 (2)	0.033 (6)*
C6	0.36381 (18)	0.40983 (13)	0.5335 (2)	0.0262 (4)
H6A	0.4355 (16)	0.4541 (12)	0.5470 (17)	0.017 (5)*
H6B	0.3344 (18)	0.4026 (13)	0.617 (2)	0.026 (5)*
C8	0.22941 (18)	0.53680 (12)	0.4588 (2)	0.0242 (4)
H8A	0.3083 (19)	0.5739 (15)	0.452 (2)	0.036 (6)*
H8B	0.2145 (17)	0.5424 (13)	0.5490 (19)	0.024 (5)*
C8A	0.10988 (16)	0.57312 (12)	0.37059 (17)	0.0212 (4)
C9	0.08419 (17)	0.66546 (12)	0.37020 (17)	0.0219 (4)
C10	−0.02979 (18)	0.70131 (12)	0.29698 (17)	0.0226 (4)
C11	−0.11958 (18)	0.64397 (13)	0.22179 (18)	0.0255 (4)
H11	−0.2030 (19)	0.6661 (13)	0.1691 (19)	0.028 (5)*
C12	−0.09305 (18)	0.55190 (13)	0.22067 (18)	0.0251 (4)
H12	−0.1505 (19)	0.5118 (13)	0.1677 (19)	0.029 (5)*
C12A	0.01994 (17)	0.51544 (12)	0.29443 (17)	0.0223 (4)
C13	0.04806 (19)	0.41507 (12)	0.29529 (19)	0.0254 (4)
H13A	0.0904 (17)	0.3990 (13)	0.216 (2)	0.028 (5)*
H13B	−0.0306 (19)	0.3836 (13)	0.2815 (19)	0.029 (5)*
C13A	0.14229 (17)	0.38655 (12)	0.41905 (18)	0.0225 (4)
H13C	0.1002 (19)	0.3994 (14)	0.499 (2)	0.039 (6)*
C13B	0.17429 (17)	0.28614 (12)	0.41996 (17)	0.0215 (4)
C14	0.07047 (18)	0.22417 (12)	0.38865 (18)	0.0244 (4)
H14	−0.023 (2)	0.2423 (14)	0.3727 (19)	0.033 (6)*
C14A	0.10102 (18)	0.13438 (12)	0.38828 (18)	0.0257 (4)
C15	0.2498 (2)	0.77260 (14)	0.3804 (2)	0.0272 (5)
H15A	0.3058 (19)	0.7324 (14)	0.3347 (19)	0.030 (5)*
H15B	0.313 (2)	0.8061 (16)	0.440 (2)	0.049 (7)*
H15C	0.1959 (18)	0.8084 (13)	0.3141 (19)	0.024 (5)*
C16	−0.1724 (2)	0.82776 (15)	0.2625 (2)	0.0320 (5)
H16A	−0.199 (2)	0.8207 (15)	0.172 (2)	0.040 (6)*
H16B	−0.234 (2)	0.7982 (15)	0.311 (2)	0.046 (7)*
H16C	−0.167 (2)	0.8946 (16)	0.283 (2)	0.038 (6)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0357 (8)	0.0156 (7)	0.0466 (9)	−0.0020 (6)	0.0016 (7)	−0.0014 (6)
O3	0.0438 (9)	0.0155 (7)	0.0424 (9)	0.0039 (6)	−0.0016 (7)	0.0015 (6)
O9	0.0281 (7)	0.0195 (7)	0.0224 (7)	−0.0054 (5)	0.0010 (5)	−0.0020 (5)
O10	0.0313 (7)	0.0163 (7)	0.0340 (8)	0.0037 (5)	0.0010 (6)	0.0012 (6)
N7	0.0207 (8)	0.0176 (8)	0.0252 (8)	0.0000 (6)	−0.0014 (6)	0.0002 (6)
C2	0.0428 (12)	0.0173 (10)	0.0401 (13)	0.0012 (9)	0.0021 (10)	−0.0018 (9)
C3A	0.0382 (11)	0.0154 (9)	0.0249 (10)	0.0035 (8)	0.0019 (8)	0.0020 (8)
C4	0.0284 (10)	0.0256 (10)	0.0258 (10)	0.0050 (8)	0.0015 (8)	0.0037 (9)
C4A	0.0271 (10)	0.0212 (10)	0.0221 (10)	0.0029 (8)	0.0027 (8)	0.0020 (8)
C5	0.0239 (10)	0.0251 (11)	0.0341 (12)	0.0017 (8)	−0.0012 (9)	0.0039 (9)
C6	0.0247 (10)	0.0220 (10)	0.0288 (11)	−0.0003 (8)	−0.0014 (8)	0.0018 (8)
C8	0.0248 (10)	0.0174 (9)	0.0276 (11)	−0.0018 (8)	−0.0012 (8)	−0.0024 (8)
C8A	0.0224 (9)	0.0201 (9)	0.0202 (9)	−0.0003 (7)	0.0025 (7)	0.0008 (8)
C9	0.0235 (9)	0.0198 (9)	0.0214 (9)	−0.0039 (7)	0.0022 (7)	−0.0010 (8)
C10	0.0290 (10)	0.0171 (9)	0.0219 (9)	0.0023 (7)	0.0057 (8)	0.0023 (7)
C11	0.0252 (10)	0.0242 (10)	0.0251 (10)	0.0015 (8)	0.0004 (8)	0.0046 (8)
C12	0.0256 (10)	0.0231 (10)	0.0237 (10)	−0.0029 (8)	−0.0015 (8)	−0.0010 (8)
C12A	0.0253 (9)	0.0189 (9)	0.0216 (9)	−0.0003 (7)	0.0025 (7)	0.0001 (8)
C13	0.0254 (10)	0.0167 (9)	0.0296 (11)	0.0004 (8)	−0.0047 (8)	−0.0020 (8)
C13A	0.0220 (9)	0.0173 (9)	0.0268 (10)	−0.0012 (7)	0.0016 (8)	−0.0011 (8)
C13B	0.0253 (9)	0.0195 (9)	0.0186 (9)	0.0014 (7)	0.0019 (7)	0.0004 (7)
C14	0.0251 (10)	0.0204 (10)	0.0264 (10)	0.0015 (8)	0.0022 (8)	0.0017 (8)
C14A	0.0306 (10)	0.0206 (10)	0.0243 (10)	−0.0039 (8)	0.0019 (8)	−0.0006 (8)
C15	0.0289 (11)	0.0236 (11)	0.0270 (11)	−0.0054 (9)	0.0014 (9)	0.0016 (9)
C16	0.0360 (12)	0.0234 (11)	0.0323 (12)	0.0096 (9)	−0.0031 (9)	0.0030 (9)

Geometric parameters (Å, º)

O1—C14A	1.388 (2)	C8—H8A	1.01 (2)
O1—C2	1.438 (2)	C8—H8B	1.005 (19)
O3—C3A	1.379 (2)	C8A—C9	1.393 (3)
O3—C2	1.431 (3)	C8A—C12A	1.400 (2)
O9—C9	1.391 (2)	C9—C10	1.391 (2)
O9—C15	1.430 (2)	C10—C11	1.391 (3)
O10—C10	1.374 (2)	C11—C12	1.391 (3)
O10—C16	1.422 (2)	C11—H11	0.99 (2)
N7—C6	1.464 (2)	C12—C12A	1.389 (3)
N7—C8	1.466 (2)	C12—H12	0.94 (2)
N7—C13A	1.476 (2)	C12A—C13	1.514 (2)
C2—H2A	1.06 (2)	C13—C13A	1.532 (3)
C2—H2B	0.94 (2)	C13—H13A	1.06 (2)
C3A—C4	1.362 (3)	C13—H13B	0.93 (2)
C3A—C14A	1.383 (3)	C13A—C13B	1.523 (2)
C4—C4A	1.413 (3)	C13A—H13C	1.05 (2)
C4—H4	1.01 (2)	C13B—C14	1.411 (3)
C4A—C13B	1.394 (3)	C14—C14A	1.367 (3)
C4A—C5	1.509 (3)	C14—H14	1.00 (2)
C5—C6	1.512 (3)	C15—H15A	1.03 (2)
C5—H5A	0.96 (2)	C15—H15B	0.96 (2)
C5—H5B	0.98 (2)	C15—H15C	0.97 (2)
C6—H6A	0.987 (18)	C16—H16A	0.95 (2)
C6—H6B	1.00 (2)	C16—H16B	1.01 (2)
C8—C8A	1.503 (2)	C16—H16C	1.01 (2)
C14A—O1—C2	103.91 (15)	O10—C10—C9	115.91 (16)
C3A—O3—C2	104.61 (14)	O10—C10—C11	124.64 (16)
C9—O9—C15	112.13 (14)	C9—C10—C11	119.45 (17)
C10—O10—C16	116.53 (15)	C12—C11—C10	119.25 (17)
C6—N7—C8	109.01 (14)	C12—C11—H11	118.2 (12)
C6—N7—C13A	110.66 (14)	C10—C11—H11	122.5 (12)
C8—N7—C13A	109.92 (14)	C12A—C12—C11	121.67 (17)
O3—C2—O1	107.99 (16)	C12A—C12—H12	117.3 (12)
O3—C2—H2A	108.7 (11)	C11—C12—H12	121.0 (12)
O1—C2—H2A	109.6 (11)	C12—C12A—C8A	119.03 (17)
O3—C2—H2B	108.7 (13)	C12—C12A—C13	121.83 (16)
O1—C2—H2B	107.9 (14)	C8A—C12A—C13	119.14 (16)
H2A—C2—H2B	113.9 (18)	C12A—C13—C13A	111.48 (15)
C4—C3A—O3	128.55 (17)	C12A—C13—H13A	109.2 (11)
C4—C3A—C14A	121.57 (17)	C13A—C13—H13A	108.5 (10)
O3—C3A—C14A	109.69 (16)	C12A—C13—H13B	108.8 (12)
C3A—C4—C4A	117.56 (17)	C13A—C13—H13B	113.0 (12)
C3A—C4—H4	124.6 (11)	H13A—C13—H13B	105.6 (16)
C4A—C4—H4	117.8 (11)	N7—C13A—C13B	111.97 (15)
C13B—C4A—C4	120.90 (17)	N7—C13A—C13	107.14 (15)
C13B—C4A—C5	120.22 (17)	C13B—C13A—C13	112.15 (15)
C4—C4A—C5	118.86 (16)	N7—C13A—H13C	108.4 (11)
C4A—C5—C6	110.94 (16)	C13B—C13A—H13C	107.5 (12)
C4A—C5—H5A	111.9 (13)	C13—C13A—H13C	109.6 (11)
C6—C5—H5A	110.6 (13)	C4A—C13B—C14	120.10 (17)
C4A—C5—H5B	111.7 (12)	C4A—C13B—C13A	121.66 (16)
C6—C5—H5B	109.3 (12)	C14—C13B—C13A	118.23 (16)
H5A—C5—H5B	102.0 (17)	C14A—C14—C13B	117.47 (17)
N7—C6—C5	109.04 (16)	C14A—C14—H14	119.0 (12)
N7—C6—H6A	108.4 (10)	C13B—C14—H14	123.4 (12)
C5—C6—H6A	109.0 (10)	C14—C14A—C3A	122.36 (17)
N7—C6—H6B	112.1 (11)	C14—C14A—O1	127.64 (17)
C5—C6—H6B	110.2 (11)	C3A—C14A—O1	109.95 (16)
H6A—C6—H6B	108.1 (15)	O9—C15—H15A	112.4 (11)
N7—C8—C8A	113.50 (15)	O9—C15—H15B	108.8 (14)
N7—C8—H8A	106.5 (12)	H15A—C15—H15B	103.1 (17)
C8A—C8—H8A	110.9 (12)	O9—C15—H15C	111.0 (11)
N7—C8—H8B	110.9 (11)	H15A—C15—H15C	106.3 (16)
C8A—C8—H8B	106.8 (10)	H15B—C15—H15C	114.9 (18)
H8A—C8—H8B	108.2 (16)	O10—C16—H16A	110.4 (13)
C9—C8A—C12A	119.28 (16)	O10—C16—H16B	110.4 (13)
C9—C8A—C8	119.31 (15)	H16A—C16—H16B	112.3 (19)
C12A—C8A—C8	121.31 (16)	O10—C16—H16C	105.8 (12)
O9—C9—C10	120.16 (16)	H16A—C16—H16C	108.3 (19)
O9—C9—C8A	118.43 (15)	H16B—C16—H16C	109.3 (18)
C10—C9—C8A	121.32 (16)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C2—H2B···O10^i	0.94 (2)	2.58 (2)	3.212 (3)	124.5 (17)
C16—H16A···O9^ii	0.95 (2)	2.53 (2)	3.455 (3)	162.9 (18)

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