Diethyl 4-(2,5-di­methoxy­phenyl)-2,6-di­methyl-1,4-di­hydro­pyridine-3,5-di­carboxyl­ate, conformational change with solvent of crystallization

The title compound, C₂₁H₂₇NO₆, has been crystallized from ethanol containing nitro­benzene and shows the phenyl ring, B, in an ap conformation. This structure may be compared with that of the mol­ecule crystallized from ethanol alone, in which the B ring is seen in an sp conformation. The isolation of this rotamer has implications for the understanding of the docking of calcium beta-blocking di­hydro­pyridine mol­ecules with their receptor site.

S1. Comment

1,4-Dihydropyridine compounds (DHPs) are widely prescribed as calcium beta blockers. Structure-activity relationship studies (Triggle et al., 1989) of DHP molecules have indicated that certain conformational details correlate with high binding efficiency: The A ring should be in a flattened boat form (however total planarity when the A ring is aromatic is detrimental to activity, Rowan & Holt, 1995, 1996); ring B should be in a pseudo axial position relative to the floor of the boat; rings A and B should display a nearly orthogonal relationship; electron-withdrawing substituents on the B ring improve activity in the order o>m>>p; ortho substituents on the B ring should be in the prow or forward position and not projecting backwards over the B ring. The conformation of the carbonyl groups of the ester moieties at C3 and C5 of ring A may be either ap or sp relative to the near double bond of the DHP ring. \sch

Previous work in this laboratory suggests that carbonyl groups which are not involved in hydrogen bonding exist in sp conformation (Caignan & Holt, 2000, 2001; Caignan et al., 2001; Metcalf & Holt, 2000) whereas the molecule responds to a hydrogen bonding opportunity by rotating the carbonyl group about the C3—C3' or C5—C5' bond to place the carbonyl group in ap conformation.

The conformation of a crystallized molecule represents a structure of minimum energy in the environment of neighboring molecules. It does not necessarily represent the conformation of the molecule in its receptor site where the neighbors are different molecules. However the process of crystallization, of maximizing hydrogen bonding, dipole-dipole and van der Waals type interactions within the solid must mimic the behavior of a molecule approaching its docking site. Both are processes of molecular recognition.

In an effort to understand the range of conformational adjustments possible for DHP molecules as they recognize their receptor sites, we have embarked on a series of co-crystallization experiments, crystallizing DHP molecules from solutions including hydrogen bond donors or acceptors and looking for the range of conformational behavior possible under these varied circumstances.

We have previously reported the single-crystal of diethyl 4-(2,5-dimethoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, (I), crystallized from ethanol, for which the ortho or 2-methoxy substituent on the A ring is found in prow position. When we recrystallized this material from ethanol containing nitrobenzene we were surprised to isolate a rotamer (II) of the published molecule in which the ortho or 2-methoxy group is seen rotated back over the A ring.

Compounds (I) and (II) crystallize with the A ring in flattened boat form. The sum of the absolute values of the six successive torsional angles of the A ring are 91.0 (4)°. This sum is 78.8 (4)° for rotamer (II). The theoretical values of these totals are zero if the ring is totally flat and 240 degrees if the six-membered ring is in classic boat form. Thus both rotamers display flattened A rings.

In (I), near orthogonality between the B ring and the base of the flattened boat is indicated by the 88.3 (3)° between the plane of atoms C7—C12 of the B ring and the plane of atoms, C2, C3, C5 and C6 of the base of the boat conformation of the A ring. Rotamer(II) shows a 92.6 (4)° angle between these planes.

Both rotamers show near coplanarity of the carbonyl C═O bonds with the conjugated double bond of the DHP ring. The torsion angles, C6—C5—C5'-O5' and C2—C3—C3'-O3' are -0.2 (3) and -176.2 (3)° for (I), and 3.5 (6) and 166.4 (3)° for the rotamer. These torsional angles indicate sp, ap conformations at C5 and C3, respectively, for both rotamers.

Thus the two rotamers show nearly identical molecular conformation despite the differing orientations the bulky orthomethoxy group in the ortho position on the B ring.

In both rotamers, the carbonyl group at C3 is seen in ap conformation, and is hydrogen bonded to the hydrogen atom of the amino group of an adjacent molecule. In the folded back rotamer, the hydrogen-bonding details are N1—H1A···O3' (1 + x, y, z) 2.21 Å, N—H1A···O3', 161°: N1···O3' 3.073 (3) Å.

There have been only two other observations of rotamers in the DHP family. 4-(2-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-bis(methoxycarbonyl) has been observed with two molecules per asymmetric unit, one of which has the 2-chloro substituent in the prow position and carbonyl groups in sp and ap conformation whereas the other molecule has the chloride in folded back orientation and ap ap conformation of the carbonyl groups (Rovnyak, et al. 1988).

Two examinations of 4-(2-thiophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-bis(alkoxycarbonyl) which differ only in the identity of the alkoxy group (methyl or ethyl) have shown both ap,ap carbonyl orientation and the ortho sulfur group predominately in the prow position when the esterification group is methyl whereas sp,ap orientation of the carbonyl groups and roughly 50/50 prow/folded back over the A ring orientation of the bulky sulfur group when the esterification group is ethyl (Caignan et al., 2001).

These results indicate that DHP molecules which bear ortho substituents or bulky hetero atoms in the ortho position of the B ring can freely change between prow forward and folded back rotamers. Rotation of the B ring does not influence carbonyl orientation nor the degree of orthogonality between A and B rings. Thus docking of DHP molecules in their receptor may involve either of the two rotamers.

Related literature

For related literature, see: Caignan & Holt (2000, 2001); Caignan, Metcalf & Holt (2001); Metcalf & Holt (2000); Rovnyak et al. (1988); Rowan & Holt (1995, 1996); Triggle et al. (1989).

S2. Experimental

An ethanol solution (40 ml) of 2,5-dimethoxybenzaldehyde (6.4 g, 0.0386 mol), ethyl acetoacetate (10.036 g, 0.0772 mol), and ammonium hydroxide (2.027 g, 0,0579 mol) was refluxed for 6 h. Acetonitrile was added to the resulting immiscible liquids, following which all solvent was removed under reduced pressure. The remaining solid was recrystallized from methanol giving large yellow cubes (rotamer I). This crystalline material was dissolved in nitrobenzene and allowed to stand for 30 days. Large yellow rhombs were observed to form (rotamer II).

S3. Refinement

Hydrogen atom positions were calculated using idealized geometry and a C—H distance of 0.97 Å. Hydrogen atoms H1a and the disordered hydrogen positions at C2', C3''' and C6' were located from a difference Fourier synthesis and then constrained to idealized geometry.

Computing details

Data collection: XSCANS (Siemens, 1991); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XP (Siemens, 1990).

Figures

Fig. 1. View of (I) with ellipsoids shown at the 50% probability level. Only a single set of hydrogen positions is shown for the disordered hydrogen positions at C2', C3"' and C6'.

4-(2,5-dimethoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-bis(ethoxycarbo nyl)

Crystal data

C21H27NO6	F(000) = 832
Mr = 389.44	Dx = 1.298 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 7.640 (2) Å	Cell parameters from 21 reflections
b = 8.606 (6) Å	θ = 5.0–10.7°
c = 30.307 (17) Å	µ = 0.10 mm^−1
β = 90.25 (3)°	T = 293 K
V = 1992.7 (19) Å^3	Rhomb, yellow
Z = 4	0.2 × 0.15 × 0.15 mm

Data collection

Syntex P4 4-circle- diffractometer	Rint = 0.079
Radiation source: fine-focus sealed tube	θmax = 24.7°, θmin = 2.5°
Graphite monochromator	h = −8→1
θ/2θ scans	k = −10→1
4802 measured reflections	l = −35→35
3380 independent reflections	3 standard reflections every 97 reflections
2030 reflections with I > 2σ(I)	intensity decay: none

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)] = 0.057	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.113	H-atom parameters constrained
S = 1.03	w = 1/[σ^2(Fo^2) + (0.0609P)^2 + 0.757P] where P = (Fo^2 + 2Fc^2)/3
3380 reflections	(Δ/σ)max < 0.001
253 parameters	Δρmax = 0.02 e Å^−3
0 restraints	Δρmin = −0.02 e Å^−3

Special details

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 (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
N1	0.7998 (3)	0.4352 (3)	0.57065 (9)	0.0495 (7)
H1A	0.9082	0.4690	0.5642	0.080*
C2	0.6599 (4)	0.5303 (4)	0.56147 (10)	0.0449 (8)
C2'	0.7116 (4)	0.6712 (4)	0.53518 (12)	0.0613 (10)
H2'A	0.6101	0.7343	0.5297	0.080*	0.50
H2'B	0.7970	0.7304	0.5513	0.080*	0.50
H2'C	0.7604	0.6384	0.5076	0.080*	0.50
H2'D	0.8291	0.6768	0.5242	0.080*	0.50
H2'E	0.6875	0.7641	0.5516	0.080*	0.50
H2'F	0.6311	0.6827	0.5110	0.080*	0.50
C3	0.4981 (3)	0.4906 (3)	0.57586 (9)	0.0408 (7)
C3'	0.3368 (4)	0.5711 (4)	0.56398 (10)	0.0429 (7)
C3"	0.2034 (4)	0.7967 (4)	0.53365 (12)	0.0569 (9)
H3"A	0.1406	0.7441	0.5106	0.080*
H3"B	0.1275	0.8080	0.5586	0.080*
C3'"	0.2647 (4)	0.9509 (4)	0.51736 (14)	0.0700 (11)
H3'A	0.1657	1.0130	0.5089	0.080*	0.50
H3'B	0.3274	1.0019	0.5408	0.080*	0.50
H3'C	0.3406	0.9377	0.4925	0.080*	0.50
H3'D	0.2424	1.0171	0.5422	0.080*	0.50
H3'E	0.3788	0.9839	0.5081	0.080*	0.50
H3'F	0.1754	0.9817	0.4968	0.080*	0.50
O3'	0.1905 (3)	0.5198 (3)	0.57044 (8)	0.0623 (7)
O3"	0.3586 (2)	0.7113 (3)	0.54570 (7)	0.0554 (6)
C4	0.4742 (3)	0.3551 (3)	0.60774 (10)	0.0411 (7)
H4A	0.3722	0.2988	0.5983	0.080*
C5	0.6275 (4)	0.2438 (3)	0.60497 (10)	0.0415 (7)
C5'	0.6062 (4)	0.0841 (4)	0.62133 (11)	0.0527 (8)
C5"	0.4117 (5)	−0.1022 (4)	0.65056 (12)	0.0608 (9)
H5"A	0.4378	−0.1776	0.6282	0.080*
H5"B	0.4863	−0.1213	0.6755	0.080*
C5'"	0.2281 (5)	−0.1168 (5)	0.66351 (16)	0.0891 (14)
H5'A	0.2052	−0.2190	0.6748	0.080*
H5'B	0.2036	−0.0411	0.6859	0.080*
H5'C	0.1549	−0.0977	0.6383	0.080*
O5'	0.7190 (4)	−0.0126 (3)	0.62408 (13)	0.1030 (11)
O5"	0.4417 (3)	0.0531 (2)	0.63355 (7)	0.0543 (6)
C6	0.7843 (4)	0.2897 (4)	0.58914 (10)	0.0456 (8)
C6'	0.9504 (4)	0.1968 (4)	0.58776 (12)	0.0588 (9)
H6'A	0.9305	0.0971	0.6010	0.080*	0.50
H6'B	0.9852	0.1830	0.5576	0.080*	0.50
H6'C	1.0413	0.2502	0.6036	0.080*	0.50
H6'D	1.0442	0.2528	0.5740	0.080*	0.50
H6'E	0.9823	0.1659	0.6172	0.080*	0.50
H6'F	0.9289	0.1051	0.5705	0.084*	0.50
C7	0.4386 (4)	0.4118 (3)	0.65474 (10)	0.0414 (7)
C8	0.5580 (4)	0.5035 (4)	0.67781 (11)	0.0500 (8)
O8	0.7116 (3)	0.5372 (3)	0.65643 (8)	0.0639 (7)
C13	0.8308 (5)	0.6460 (4)	0.67450 (15)	0.0781 (12)
H13A	0.9304	0.6551	0.6555	0.080*
H13B	0.7746	0.7453	0.6772	0.080*
H13C	0.8684	0.6113	0.7031	0.080*
C9	0.5191 (5)	0.5547 (4)	0.72034 (12)	0.0626 (10)
H9A	0.6021	0.6178	0.7361	0.080*
C10	0.3634 (5)	0.5128 (4)	0.73969 (12)	0.0637 (10)
H10A	0.3359	0.5492	0.7688	0.080*
C11	0.2442 (4)	0.4219 (4)	0.71754 (11)	0.0545 (8)
O11	0.0911 (3)	0.3888 (3)	0.73968 (8)	0.0730 (7)
C14	−0.0271 (5)	0.2853 (5)	0.71924 (14)	0.0787 (12)
H14A	−0.1274	0.2731	0.7379	0.080*
H14B	−0.0635	0.3259	0.6912	0.080*
H14C	0.0283	0.1863	0.7151	0.080*
C12	0.2833 (4)	0.3719 (4)	0.67535 (10)	0.0475 (8)
H12A	0.2002	0.3075	0.6601	0.080*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0324 (13)	0.0508 (16)	0.0655 (17)	−0.0018 (12)	−0.0013 (12)	0.0099 (14)
C2	0.0357 (16)	0.0477 (18)	0.0512 (18)	−0.0031 (14)	−0.0045 (13)	0.0087 (15)
C2'	0.0375 (17)	0.065 (2)	0.082 (2)	−0.0040 (16)	0.0059 (16)	0.022 (2)
C3	0.0343 (15)	0.0424 (17)	0.0457 (17)	−0.0026 (13)	−0.0033 (13)	0.0042 (14)
C3'	0.0327 (16)	0.0500 (19)	0.0459 (17)	−0.0044 (15)	−0.0044 (13)	0.0067 (15)
C3"	0.0369 (17)	0.066 (2)	0.067 (2)	0.0077 (16)	−0.0045 (15)	0.0171 (19)
C3'"	0.054 (2)	0.069 (3)	0.087 (3)	0.0096 (19)	−0.0043 (19)	0.024 (2)
O3'	0.0327 (12)	0.0686 (16)	0.0856 (18)	−0.0049 (11)	−0.0030 (11)	0.0249 (13)
O3"	0.0364 (11)	0.0566 (14)	0.0733 (15)	0.0027 (10)	−0.0039 (10)	0.0192 (13)
C4	0.0324 (15)	0.0442 (17)	0.0467 (17)	−0.0068 (14)	−0.0028 (13)	0.0033 (14)
C5	0.0354 (15)	0.0395 (17)	0.0497 (18)	−0.0022 (14)	−0.0054 (13)	−0.0016 (14)
C5'	0.0457 (19)	0.0486 (19)	0.064 (2)	−0.0004 (17)	−0.0059 (16)	0.0053 (18)
C5"	0.070 (2)	0.044 (2)	0.069 (2)	−0.0121 (18)	−0.0072 (18)	0.0118 (18)
C5'"	0.075 (3)	0.075 (3)	0.118 (4)	−0.016 (2)	−0.001 (2)	0.033 (3)
O5'	0.0627 (17)	0.0632 (17)	0.183 (3)	0.0126 (15)	0.0167 (18)	0.042 (2)
O5"	0.0492 (13)	0.0436 (13)	0.0700 (15)	−0.0068 (10)	−0.0014 (11)	0.0094 (11)
C6	0.0367 (17)	0.0451 (18)	0.0548 (19)	0.0010 (15)	−0.0098 (14)	−0.0006 (16)
C6'	0.0404 (17)	0.063 (2)	0.072 (2)	0.0031 (16)	−0.0037 (16)	0.0067 (19)
C7	0.0389 (16)	0.0397 (17)	0.0457 (17)	−0.0004 (14)	−0.0071 (13)	0.0046 (15)
C8	0.0449 (18)	0.0473 (19)	0.058 (2)	0.0025 (16)	−0.0109 (15)	0.0053 (17)
O8	0.0511 (14)	0.0702 (16)	0.0701 (16)	−0.0173 (12)	−0.0155 (12)	−0.0080 (13)
C13	0.060 (2)	0.059 (2)	0.115 (3)	−0.0140 (19)	−0.033 (2)	−0.003 (2)
C9	0.072 (2)	0.055 (2)	0.060 (2)	0.0074 (19)	−0.0264 (19)	−0.0087 (19)
C10	0.080 (3)	0.066 (2)	0.0450 (19)	0.017 (2)	−0.0065 (18)	−0.0029 (18)
C11	0.061 (2)	0.054 (2)	0.0488 (19)	0.0099 (18)	0.0017 (16)	0.0064 (18)
O11	0.0746 (17)	0.088 (2)	0.0563 (15)	0.0019 (16)	0.0168 (13)	0.0037 (15)
C14	0.072 (3)	0.080 (3)	0.084 (3)	0.000 (2)	0.030 (2)	0.011 (2)
C12	0.0481 (18)	0.0478 (19)	0.0466 (18)	0.0029 (15)	−0.0037 (14)	0.0039 (16)

Geometric parameters (Å, º)

N1—C2	1.374 (4)	C5"—C5'"	1.464 (5)
N1—C6	1.377 (4)	C5"—H5"A	0.9600
N1—H1A	0.9000	C5"—H5"B	0.9599
C2—C3	1.356 (4)	C5'"—H5'A	0.9600
C2—C2'	1.505 (4)	C5'"—H5'B	0.9600
C2'—H2'A	0.9600	C5'"—H5'C	0.9601
C2'—H2'B	0.9600	C6—C6'	1.501 (4)
C2'—H2'C	0.9599	C6'—H6'A	0.9599
C2'—H2'D	0.9601	C6'—H6'B	0.9599
C2'—H2'E	0.9600	C6'—H6'C	0.9601
C2'—H2'F	0.9600	C6'—H6'D	0.9600
C3—C3'	1.458 (4)	C6'—H6'E	0.9599
C3—C4	1.526 (4)	C6'—H6'F	0.9599
C3'—O3'	1.218 (3)	C7—C12	1.387 (4)
C3'—O3"	1.339 (4)	C7—C8	1.392 (4)
C3"—O3"	1.441 (3)	C8—O8	1.374 (4)
C3"—C3'"	1.492 (5)	C8—C9	1.395 (5)
C3"—H3"A	0.9599	O8—C13	1.414 (4)
C3"—H3"B	0.9599	C13—H13A	0.9600
C3'"—H3'A	0.9600	C13—H13B	0.9600
C3'"—H3'B	0.9600	C13—H13C	0.9601
C3'"—H3'C	0.9600	C9—C10	1.376 (5)
C3'"—H3'D	0.9600	C9—H9A	0.9600
C3'"—H3'E	0.9600	C10—C11	1.373 (5)
C3'"—H3'F	0.9600	C10—H10A	0.9599
C4—C5	1.515 (4)	C11—O11	1.381 (4)
C4—C7	1.531 (4)	C11—C12	1.383 (4)
C4—H4A	0.9601	O11—C14	1.410 (5)
C5—C6	1.352 (4)	C14—H14A	0.9600
C5—C5'	1.470 (5)	C14—H14B	0.9599
C5'—O5'	1.201 (4)	C14—H14C	0.9600
C5'—O5"	1.339 (4)	C12—H12A	0.9600
C5"—O5"	1.451 (4)
C2—N1—C6	123.8 (2)	O5"—C5"—H5"B	110.1
C2—N1—H1A	118.6	C5'"—C5"—H5"B	109.9
C6—N1—H1A	117.6	H5"A—C5"—H5"B	108.5
C3—C2—N1	119.6 (3)	C5"—C5'"—H5'A	110.5
C3—C2—C2'	127.9 (3)	C5"—C5'"—H5'B	108.8
N1—C2—C2'	112.4 (2)	H5'A—C5'"—H5'B	109.5
C2—C2'—H2'A	109.5	C5"—C5'"—H5'C	109.1
C2—C2'—H2'B	109.8	H5'A—C5'"—H5'C	109.5
H2'A—C2'—H2'B	109.5	H5'B—C5'"—H5'C	109.5
C2—C2'—H2'C	109.1	C5'—O5"—C5"	115.6 (3)
H2'A—C2'—H2'C	109.5	C5—C6—N1	119.2 (3)
H2'B—C2'—H2'C	109.5	C5—C6—C6'	127.3 (3)
C2—C2'—H2'D	118.2	N1—C6—C6'	113.5 (3)
C2—C2'—H2'E	110.2	C6—C6'—H6'A	109.2
H2'D—C2'—H2'E	108.7	C6—C6'—H6'B	109.3
C2—C2'—H2'F	108.6	H6'A—C6'—H6'B	109.5
H2'D—C2'—H2'F	109.1	C6—C6'—H6'C	110.0
H2'E—C2'—H2'F	100.7	H6'A—C6'—H6'C	109.5
C2—C3—C3'	124.9 (3)	H6'B—C6'—H6'C	109.5
C2—C3—C4	120.5 (3)	C6—C6'—H6'D	112.2
C3'—C3—C4	114.6 (2)	C6—C6'—H6'E	109.4
O3'—C3'—O3"	120.6 (3)	H6'D—C6'—H6'E	110.9
O3'—C3'—C3	124.3 (3)	C6—C6'—H6'F	108.1
O3"—C3'—C3	115.1 (2)	H6'D—C6'—H6'F	107.6
O3"—C3"—C3'"	106.2 (3)	H6'E—C6'—H6'F	108.6
O3"—C3"—H3"A	110.6	C12—C7—C8	118.3 (3)
C3'"—C3"—H3"A	109.6	C12—C7—C4	119.7 (3)
O3"—C3"—H3"B	110.6	C8—C7—C4	122.0 (3)
C3'"—C3"—H3"B	111.2	O8—C8—C7	116.2 (3)
H3"A—C3"—H3"B	108.7	O8—C8—C9	123.7 (3)
C3"—C3'"—H3'A	109.6	C7—C8—C9	120.1 (3)
C3"—C3'"—H3'B	108.6	C8—O8—C13	120.5 (3)
H3'A—C3'"—H3'B	109.5	O8—C13—H13A	109.4
C3"—C3'"—H3'C	110.2	O8—C13—H13B	109.5
H3'A—C3'"—H3'C	109.5	H13A—C13—H13B	109.5
H3'B—C3'"—H3'C	109.5	O8—C13—H13C	109.5
C3"—C3'"—H3'D	102.2	H13A—C13—H13C	109.5
C3"—C3'"—H3'E	130.3	H13B—C13—H13C	109.5
H3'D—C3'"—H3'E	102.6	C10—C9—C8	119.9 (3)
C3"—C3'"—H3'F	103.7	C10—C9—H9A	120.5
H3'D—C3'"—H3'F	102.6	C8—C9—H9A	119.6
H3'E—C3'"—H3'F	111.8	C11—C10—C9	120.9 (3)
C3'—O3"—C3"	117.4 (2)	C11—C10—H10A	119.2
C5—C4—C3	110.7 (2)	C9—C10—H10A	119.9
C5—C4—C7	113.2 (2)	C10—C11—O11	116.2 (3)
C3—C4—C7	111.6 (2)	C10—C11—C12	118.9 (3)
C5—C4—H4A	106.9	O11—C11—C12	124.9 (3)
C3—C4—H4A	107.2	C11—O11—C14	117.3 (3)
C7—C4—H4A	107.0	O11—C14—H14A	108.8
C6—C5—C5'	119.5 (3)	O11—C14—H14B	110.0
C6—C5—C4	121.5 (3)	H14A—C14—H14B	109.5
C5'—C5—C4	119.0 (3)	O11—C14—H14C	109.6
O5'—C5'—O5"	121.1 (3)	H14A—C14—H14C	109.5
O5'—C5'—C5	126.3 (3)	H14B—C14—H14C	109.5
O5"—C5'—C5	112.6 (3)	C11—C12—C7	121.9 (3)
O5"—C5"—C5'"	109.1 (3)	C11—C12—H12A	118.7
O5"—C5"—H5"A	109.7	C7—C12—H12A	119.4
C5'"—C5"—H5"A	109.5

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O3′^i	0.90	2.21	3.073 (3)	161

Symmetry code: (i) x+1, y, z.