5-But­yl-5-ethyl­barbituric acid: a phase transition at low temperature

The room-temperature crystal structure of 5-but­yl-5-ethyl­barbituric acid (generally known as butobarbitone), C₁₀H₁₆N₂O₃, was reported in space group C2/c [Bideau (1971). C. R. Acad. Sci. Paris Ser. C, 272, 757–760]. A redetermination at 120 K using synchrotron radiation shows the space group at this temperature to be P2₁/n and not C2/c. There are two crystallographically independent mol­ecules in the asymmetric unit, but no solvent. Reported issues concerning possible disorder of the mol­ecule are addressed; the but­yl substituent of one of the mol­ecules adopts an unusual conformation in being not fully extended. A subsequent re-collection at room temperature shows that the space group is indeed C2/c (A2/a with the axes selected in this report), and so the crystal structure undergoes a phase change upon cooling to 120 K.

Comment

Derivatives of barbituric acid, often called `barbiturates', are a well known class of sedative drugs. The parent barbituric acid has no pharmacological activity but its 5,5-disubstituted derivatives do, in particular those with large substituents, for example, ethyl, amyl, butyl or cyclo­hexyl groups. The mol­ecule must also possess hydrogen-bonding capability to be active, since it is this which facilitates binding of the drug to the acceptor site (Craven et al., 1969).

Crystals of 5-but­yl-5-ethyl­barbituric acid, (I), hereafter referred to as `butobarbitone', were obtained from a failed attempt to react ammonium carbonate with butobarbitone. The crystals were obtained as large plates but were very weakly diffracting, too weak even for a laboratory rotating-anode X-ray source. Data for this crystal were collected at Station 9.8 of the Synchrotron Radiation Source (SRS) at Daresbury Laboratory, Cheshire, England, via the EPSRC National X-ray Crystallography Service based in Southampton, England, where rotating-anode screening was carried out.

The structure of (I) at 120 K is presented in Fig. 1. At this temperature, the space group is P2₁/n; there are two crystallographically independent butobarbitone mol­ecules in the asymmetric unit, which form an infinite hydrogen-bonded ribbon (Fig. 2 and Table 2). A packing diagram viewed along the a axis (Fig. 3) shows how the large butyl substituent and the smaller ethyl substituent act together to separate the hydrogen-bonded ribbons. With the exception of the butyl group torsion angles, discussed below (Table 1), mol­ecular dimensions are unexceptional.

The two mol­ecules in the asymmetric unit have some similar and some different characteristics. Firstly, despite the size of the displacement ellipsoids, which would tend to suggest that the butyl groups are disordered, attempts to model this disorder have brought no improvement. With a disorder model it proved necessary to use geometrical restraints and the final R factors are not significantly better than for the ordered model. Secondly, the geometry of the butyl substituent of one mol­ecule is rather unusual; Fig. 4 shows two Newman projections (created with PLATON; Spek, 2003) along the C9—C10 and C19—C20 bonds. The positions of atoms C18 and C21 are staggered antiperiplanar with respect to each other, a perfectly normal observation for an alkyl chain. However, atoms C8 and C11 are gauche, with a C8—C9—C10—C11 torsion angle of −72.5 (4)°, a rather less common observation for a butyl substituent on a planar ring. The Cambridge Structural Database (CSD; Version 5.26 plus one update; Allen, 2002), searched using MOGUL (Bruno et al., 2004), contains only a relatively small number of entries that exhibit such geometry.

After the solution and refinement of the structure, a structural search of the CSD showed that the structure had already been published (CSD refcode ETBBAR; Bideau, 1971). However, it is not found by a search based on the unit-cell parameters. The room-temperature structure is in space group C2/c, with Z′ = 1 and Z = 8, and the final R value is 0.094. The short structural discussion in the previous paper reports unusual geometry of the butyl substituent, which the author attributed to disorder he was unable to resolve. The final sentence of the paper states `The study of this structure will be repeated at low temperature with the view of specifying the position of C54 [the terminal but­yl C atom]'. No such repeated study was ever published, as far as we can tell.

In changing from room temperature to low temperature, the crystal structure has undergone a phase transition. At 120 K, there is nothing in the data to suggest that a centred unit cell is present. To verify the validity of the original report, we re-collected data at room temperature and found that the structure is indeed in space group C2/c (actually A2/a with the choice of axes made here, a and c being exchanged from those used in the room-temperature study), with Z′ = 1 and Z = 8. This observation, although unusual, is not entirely surprising; we recently determined that barbituric acid dihydrate also undergoes a phase transition at low temperatures (Nichol & Clegg, 2005). Unlike barbituric acid dihydrate, here there is no significant change in the crystal packing between the room-temperature and 120 K structures. The two independent mol­ecules at 120 K become symmetry-equivalent at room temperature, leading to the C-centring of the unit cell (with the a and c axes exchanged from our setting), which otherwise has similar cell parameters. This transition must involve torsional changes in the n-butyl groups and could lead to some minor disorder, as reported by Bideau (1971).

Figure 1 A displacement ellipsoid view (50% probability) of the asymmetric unit of (I). H atoms not involved in hydrogen bonding have been omitted for clarity.

Figure 2 The hydrogen-bonding ribbon motif. H atoms not involved in hydrogen bonding have been omitted for clarity.

Figure 3 A projection along the a axis, showing the separation of the ribbons by the ethyl and butyl substituents. H atoms not involved in hydrogen bonding have been omitted for clarity.

Figure 4 Two Newman projections, showing the difference in torsion angles between the butyl substituents of the two independent mol­ecules.

Experimental

Equimolar amounts of butobarbitone and ammonium carbonate were dissolved in distilled water and heated until boiling. Colourless crystals of (I) grew over a period of two days when the solution was left to stand at room temperature in a sealed sample vial.

Crystal data

• C₁₀H₁₆N₂O₃

• M_r = 212.25

• Monoclinic, P 2₁ /n

• a = 10.2220 (9) Å

• b = 11.0636 (10) Å

• c = 20.9787 (18) Å

• β = 96.728 (1)°

• V = 2356.2 (4) ų

• Z = 8

• D_x = 1.197 Mg m⁻³

• Synchrotron radiation

• λ = 0.6933 Å

• Cell parameters from 7041 reflections

• θ = 2.3–30.4°

• μ = 0.09 mm⁻¹

• T = 120 (2) K

• Plate, colourless

• 0.20 × 0.10 × 0.04 mm

Data collection

• Bruker APEX2 CCD diffractometer

• Thin-slice ω scans

• Absorption correction: multi-scan(SADABS; Sheldrick, 2003)T_min = 0.842, T_max = 0.997

• 17 357 measured reflections

• 4049 independent reflections

• 3432 reflections with I > 2σ(I)

• R_int = 0.033

• θ_max = 24.3°

• h = −12 → 12

• k = −13 → 13

• l = −24 → 24

Refinement

• Refinement on F²

• R[F² > 2σ(F²)] = 0.062

• wR(F²) = 0.175

• S = 1.05

• 4049 reflections

• 288 parameters

• H atoms treated by a mixture of independent and constrained refinement

• w = 1/[σ²(F_o²) + (0.097P)² + 1.2316P] where P = (F_o² + 2F_c²)/3

• (Δ/σ)_max < 0.001

• Δρ_max = 0.54 e Å⁻³

• Δρ_min = −0.30 e Å⁻³

Table 1
Selected torsion angles (°)

C7—C4—C8—C9	177.00 (19)
C4—C8—C9—C10	173.7 (2)
C8—C9—C10—C11	−72.4 (4)
C16—C15—C18—C19	−179.20 (18)
C15—C18—C19—C20	175.4 (2)
C18—C19—C20—C21	−178.9 (3)

Table 2
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O4	0.83 (2)	2.02 (3)	2.840 (2)	171 (2)
N2—H2⋯O5^i	0.86 (2)	2.00 (3)	2.838 (2)	166 (2)
N3—H3⋯O1	0.83 (3)	2.03 (3)	2.856 (2)	174 (2)
N4—H4⋯O2^ii	0.86 (3)	2.01 (3)	2.856 (2)	169 (2)
Symmetry codes: (i) x+1, y, z; (ii) x-1, y, z.

SADABS (Sheldrick, 2003) was used to correct for the synchrotron beam decay through frame scaling; absorption effects are small by comparison. All H atoms were identified in a difference map. CH₂ H atoms were then idealized (C—H = 0.99 Å) and refined as riding [U_iso(H) = 1.2U_eq(C)]. Methyl H atoms were positioned geometrically (C—H = 0.98 Å) and refined as riding [U_iso(H) = 1.5U_eq(C)], with free rotation about the C—C bond. N-bound H atoms were refined with unconstrained coordinates [U_iso(H) = 1.2U_eq(N)]; N—H distances range from 0.83 (3) to 0.86 (3) Å.

Data collection: APEX2 (Bruker, 2003); cell refinement and data reduction: SAINT (Bruker, 2001); program(s) used to solve and refine structure: SHELXTL (Sheldrick, 2001); molecular graphics: DIAMOND (Brandenburg & Putz, 2004) and MERCURY (Bruno et al., 2002); software used to prepare material for publication: SHELXTL and local programs.

Supporting information

S1. Comment

Derivatives of barbituric acid, often called `barbiturates', are a well known class of sedative drugs. The parent barbituric acid has no pharmacological activity but its 5,5-disubstituted derivatives do, in particular those with large substituents, for example, ethyl, amyl, butyl or cyclohexyl groups. The molecule must also possess hydrogen-bonding capability to be active, since it is this which facilitates binding of the drug to the acceptor site (Craven et al., 1969).

Crystals of 5-butyl-5-ethylbarbituric acid, (I), hereafter referred to as `butobarbitone', were obtained from a failed attempt to react ammonium carbonate with butobarbitone. The crystals were obtained as large plates but were very weakly diffracting, too weak even for a laboratory rotating-anode X-ray source. Data for this crystal were collected at Station 9.8 of the Synchrotron Radiation Source (SRS) at Daresbury Laboratory, Cheshire, England, via the EPSRC National X-ray Crystallography Service based in Southampton, England, where rotating-anode screening was carried out.

The structure of (I) at 120 K is presented in Fig. 1. A t this temperature, the space group is P2₁/n, and there are two crystallographically independent butobarbitone molecules in the asymmetric unit, which form an infinite hydrogen-bonded ribbon, as indicated in Fig. 2. A packing diagram viewed along the a axis (Fig. 3) shows how the large butyl subsituent and the smaller ethyl substituent act together to separate the hydrogen-bonded ribbons. With the exception of the butyl group torsion angles, discussed below, molecular dimensions are unexceptional.

The two molecules in the asymmetric unit have some similar and some different characteristics. Firstly, despite the size of the displacement ellipsoids, which would tend to suggest that the butyl groups are disordered, attempts to model this disorder have brought no improvement. With a disorder model, it proved necessary to use geometrical restraints and the final R factors are not significantly better than for the ordered model. Secondly, the geometry of the butyl substituent of one molecule is rather unusual; Fig. 4 shows two Newman projections (created with PLATON; Spek, 2003) along the C9—C10 and C19—C20 bonds. The positions of atoms C18 and C21 are staggered antiperiplanar with respect to each other, a perfectly normal observation for an alkyl chain. However, atoms C8 and C11 are gauche, with a C8–C9–C10–C11 torsion angle of −72.5 (4)°, a rather less common observation for a butyl substituent on a planar ring. The Cambridge Structural Database (CSD; Version 5.26 plus one update; Allen, 2002), searched using Mogul (Bruno et al., 2004), contains only a relatively small number of entries that exhibit such geometry.

After the solution and refinement of the structure, a structural search of the CSD showed that the structure was already published (CSD code ETBBAR; Bideau, 1971). However, it is not found by a search based on the unit-cell parameters. The room-temperature structure is in space group C2/c, with Z' = 1 and Z = 8, and the final R value is 0.094. The short structural discussion in the previous paper reports unusual geometry of the butyl substituent, which the author attributed to disorder he was unable to resolve. The final sentence of the paper states `The study of this structure will be repeated at low temperature with the view of specifying the position of C54 [the terminal butyl carbon]'. No such repeated study was ever published, as far as we can tell.

In changing from room temperature to low temperature, the crystal structure has undergone a phase transition. At 120 K, there is nothing in the data to suggest that a centred unit cell is present. To verify the validity of the original report, we recollected data at room temperature and found that the structure is indeed in space group C2/c (actually A2/a with the choice of axes made here, a and c being exchanged from those used in the room-temperature study) with Z' = 1 and Z = 8. This observation, although unusual, is not entirely surprising; we recently determined that barbituric acid dihydrate also undergoes a phase transition at low temperatures (Nichol & Clegg, 2005). Unlike barbituric acid dihydrate, here there is no significant change in the crystal packing between the room-temperature and 120 K structures. The two independent molecules at 120 K become symmetry-equivalent at room temperature, leading to the C-centring of the unit cell (with the a and c axes exchanged from our setting), which otherwise has similar similar cell parameters. This change must involve torsional changes in the n-butyl groups, and could lead to some minor disorder as reported by Bideau (1971).

S2. Experimental

Equimolar amounts of butobarbitone and ammonium carbonate were dissolved in distilled water and heated until boiling. Colourless crystals of (I) grew over a period of two days when the solution was left to stand at room temperature in a sealed sample vial.

S3. Refinement

SADABS (Sheldrick, 2003) was used to correct for the synchrotron beam decay through frame scaling; absorption effects are small by comparison. All H atoms were identified in a difference map. CH₂ H atoms were then idealized (C—H = 0.99 Å) and refined as riding [U_iso(H) = 1.2U_eq(C)]. Methyl H atoms were positioned geometrically (C—H = 0.98 Å) and refined as riding [U_iso(H) = 1.5U_eq(C)], with free rotation about the C—C bond. N-bound H atoms were refined with unconstrained coordinates [U_iso(H) = 1.2U_eq(N)]; N—H distances range from 0.83 (3) to 0.86 (3) Å.

Computing details

Data collection: APEX2 (Bruker, 2003); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2001); program(s) used to refine structure: SHELXTL; molecular graphics: DIAMOND (Brandenburg & Putz, 2004) and Mercury 1.3 (Bruno et al., 2002); software used to prepare material for publication: SHELXTL and local programs.

Figures

	Fig. 1. A displacement ellipsoid view (50% probability) of the asymmetric unit of (I). H atoms not involved in hydrogen bonding have been omitted for clarity.
	Fig. 2. The hydrogen-bonding ribbon motif. H atoms not involved in hydrogen bonding have been omitted for clarity.
	Fig. 3. A projection along the a axis, showing the separation of the ribbons by the ethyl and butyl substituents. H atoms not involved in hydrogen bonding have been omitted for clarity.
	Fig. 4. Two Newman projections, showing the difference in torsion angles between the butyl substituents of the two independent molecules.

5-butyl-5-ethylbarbituric acid

Crystal data

C10H16N2O3	F(000) = 912
Mr = 212.25	Dx = 1.197 Mg m^−3
Monoclinic, P21/n	Synchrotron radiation, λ = 0.6933 Å
Hall symbol: -P 2yn	Cell parameters from 7041 reflections
a = 10.2220 (9) Å	θ = 2.3–30.4°
b = 11.0636 (10) Å	µ = 0.09 mm^−1
c = 20.9787 (18) Å	T = 120 K
β = 96.728 (1)°	Plate, colourless
V = 2356.2 (4) Å^3	0.20 × 0.10 × 0.04 mm
Z = 8

Data collection

Bruker APEX2 CCD diffractometer	4049 independent reflections
Radiation source: Daresbury SRS station 9.8	3432 reflections with I > 2σ(I)
Silicon 111 monochromator	Rint = 0.033
Thin–slice ω scans	θmax = 24.3°, θmin = 2.1°
Absorption correction: multi-scan (SADABS; Sheldrick, 2003)	h = −12→12
Tmin = 0.842, Tmax = 0.997	k = −13→13
17357 measured reflections	l = −24→24

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)] = 0.062	Hydrogen site location: difference Fourier map
wR(F^2) = 0.175	H atoms treated by a mixture of independent and constrained refinement
S = 1.05	w = 1/[σ^2(Fo^2) + (0.097P)^2 + 1.2316P] where P = (Fo^2 + 2Fc^2)/3
4049 reflections	(Δ/σ)max < 0.001
288 parameters	Δρmax = 0.54 e Å^−3
0 restraints	Δρmin = −0.30 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
O1	0.21206 (12)	0.15114 (17)	0.41860 (6)	0.0498 (5)
O2	0.60351 (12)	0.13147 (15)	0.53953 (6)	0.0426 (4)
O3	0.61071 (14)	0.24458 (19)	0.33382 (7)	0.0586 (5)
O4	0.27298 (12)	0.11274 (16)	0.58758 (6)	0.0429 (4)
O5	−0.12115 (12)	0.14504 (15)	0.46892 (6)	0.0406 (4)
O6	−0.12111 (13)	0.14735 (16)	0.68411 (6)	0.0464 (4)
N1	0.40834 (15)	0.15225 (16)	0.47869 (7)	0.0334 (4)
H1	0.372 (2)	0.133 (2)	0.5106 (12)	0.040*
N2	0.60494 (15)	0.18345 (17)	0.43519 (7)	0.0348 (4)
H2	0.689 (3)	0.184 (2)	0.4419 (11)	0.042*
N3	0.07553 (14)	0.13599 (16)	0.52959 (7)	0.0333 (4)
H3	0.111 (2)	0.137 (2)	0.4962 (12)	0.040*
N4	−0.11912 (15)	0.14412 (16)	0.57718 (7)	0.0335 (4)
H4	−0.204 (3)	0.143 (2)	0.5711 (11)	0.040*
C1	0.33080 (18)	0.1675 (2)	0.42181 (9)	0.0383 (5)
C2	0.54340 (17)	0.15429 (18)	0.48750 (8)	0.0306 (4)
C3	0.54474 (18)	0.2152 (2)	0.37551 (9)	0.0406 (5)
C4	0.39502 (18)	0.2125 (2)	0.36432 (9)	0.0430 (6)
C6	0.4107 (2)	0.0048 (3)	0.31126 (11)	0.0574 (7)
H6A	0.5071	0.0100	0.3164	0.086*
H6B	0.3809	−0.0409	0.2722	0.086*
H6C	0.3817	−0.0363	0.3485	0.086*
C7	0.3530 (2)	0.1305 (3)	0.30602 (9)	0.0496 (6)
H7A	0.2557	0.1239	0.3004	0.060*
H7B	0.3795	0.1695	0.2671	0.060*
C8	0.3467 (2)	0.3442 (3)	0.35030 (11)	0.0563 (7)
H8A	0.3879	0.3747	0.3130	0.068*
H8B	0.2503	0.3423	0.3377	0.068*
C9	0.3754 (3)	0.4332 (3)	0.40504 (13)	0.0669 (8)
H9A	0.4704	0.4292	0.4209	0.080*
H9B	0.3258	0.4083	0.4407	0.080*
C10	0.3394 (4)	0.5657 (3)	0.38688 (19)	0.0920 (11)
H10A	0.2488	0.5679	0.3643	0.110*
H10B	0.3400	0.6137	0.4267	0.110*
C11	0.4294 (5)	0.6228 (4)	0.3457 (2)	0.1069 (13)
H11A	0.5188	0.6244	0.3684	0.160*
H11B	0.4001	0.7056	0.3354	0.160*
H11C	0.4291	0.5763	0.3059	0.160*
C12	0.15489 (17)	0.1293 (2)	0.58673 (9)	0.0346 (5)
C13	−0.05940 (17)	0.14272 (18)	0.52201 (8)	0.0314 (4)
C14	−0.05690 (18)	0.14643 (19)	0.63916 (9)	0.0348 (5)
C15	0.09266 (18)	0.1529 (2)	0.64801 (9)	0.0372 (5)
C16	0.14613 (19)	0.0639 (2)	0.70094 (9)	0.0446 (6)
H16A	0.2435	0.0691	0.7068	0.053*
H16B	0.1145	0.0892	0.7417	0.053*
C17	0.1067 (3)	−0.0664 (3)	0.68777 (10)	0.0553 (7)
H17A	0.0104	−0.0723	0.6804	0.083*
H17B	0.1397	−0.1164	0.7248	0.083*
H17C	0.1444	−0.0949	0.6496	0.083*
C18	0.1315 (2)	0.2841 (2)	0.66880 (10)	0.0472 (6)
H18A	0.0966	0.3010	0.7100	0.057*
H18B	0.2288	0.2888	0.6768	0.057*
C19	0.0837 (3)	0.3817 (2)	0.62156 (12)	0.0583 (7)
H19A	−0.0128	0.3737	0.6108	0.070*
H19B	0.1247	0.3696	0.5815	0.070*
C20	0.1148 (4)	0.5084 (3)	0.64639 (15)	0.0828 (10)
H20A	0.0753	0.5201	0.6868	0.099*
H20B	0.2115	0.5170	0.6563	0.099*
C21	0.0649 (5)	0.6049 (3)	0.5998 (2)	0.1168 (16)
H21A	0.1093	0.5982	0.5610	0.175*
H21B	0.0830	0.6845	0.6194	0.175*
H21C	−0.0303	0.5952	0.5885	0.175*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0176 (7)	0.1086 (14)	0.0237 (7)	−0.0006 (7)	0.0051 (5)	0.0087 (7)
O2	0.0201 (7)	0.0845 (11)	0.0234 (7)	−0.0008 (6)	0.0040 (5)	0.0110 (7)
O3	0.0281 (7)	0.1159 (15)	0.0340 (8)	0.0005 (8)	0.0128 (6)	0.0284 (9)
O4	0.0172 (7)	0.0890 (12)	0.0231 (7)	0.0011 (6)	0.0053 (5)	0.0017 (7)
O5	0.0204 (7)	0.0802 (11)	0.0216 (7)	0.0006 (6)	0.0037 (5)	0.0006 (6)
O6	0.0270 (7)	0.0881 (12)	0.0262 (7)	−0.0019 (7)	0.0117 (6)	−0.0076 (7)
N1	0.0184 (8)	0.0629 (11)	0.0200 (8)	−0.0009 (7)	0.0072 (6)	0.0075 (7)
N2	0.0161 (7)	0.0627 (11)	0.0264 (8)	−0.0013 (7)	0.0065 (6)	0.0088 (7)
N3	0.0180 (8)	0.0645 (11)	0.0185 (8)	−0.0002 (7)	0.0070 (6)	−0.0015 (7)
N4	0.0157 (8)	0.0616 (11)	0.0239 (8)	−0.0006 (7)	0.0056 (6)	−0.0031 (7)
C1	0.0211 (9)	0.0713 (14)	0.0233 (9)	0.0029 (9)	0.0064 (7)	0.0060 (9)
C2	0.0194 (9)	0.0502 (11)	0.0230 (9)	−0.0009 (7)	0.0054 (7)	0.0034 (8)
C3	0.0248 (10)	0.0704 (15)	0.0278 (10)	0.0024 (9)	0.0084 (8)	0.0125 (9)
C4	0.0226 (9)	0.0824 (16)	0.0249 (9)	0.0044 (9)	0.0070 (7)	0.0166 (10)
C6	0.0481 (13)	0.095 (2)	0.0311 (11)	−0.0093 (13)	0.0120 (9)	0.0019 (12)
C7	0.0261 (10)	0.102 (2)	0.0215 (10)	0.0012 (11)	0.0055 (8)	0.0103 (10)
C8	0.0356 (11)	0.093 (2)	0.0423 (12)	0.0175 (12)	0.0149 (9)	0.0312 (13)
C9	0.0692 (17)	0.0765 (19)	0.0576 (16)	0.0116 (14)	0.0188 (13)	0.0177 (14)
C10	0.091 (2)	0.093 (2)	0.100 (3)	0.0307 (19)	0.043 (2)	0.033 (2)
C11	0.137 (4)	0.081 (2)	0.110 (3)	0.008 (2)	0.050 (3)	0.018 (2)
C12	0.0208 (9)	0.0619 (13)	0.0220 (9)	−0.0029 (8)	0.0057 (7)	−0.0021 (8)
C13	0.0211 (9)	0.0507 (11)	0.0230 (9)	−0.0004 (7)	0.0054 (7)	−0.0014 (8)
C14	0.0237 (9)	0.0579 (13)	0.0240 (9)	−0.0012 (8)	0.0075 (7)	−0.0065 (8)
C15	0.0213 (9)	0.0706 (14)	0.0202 (9)	−0.0032 (8)	0.0052 (7)	−0.0064 (8)
C16	0.0270 (10)	0.0880 (17)	0.0193 (9)	0.0035 (10)	0.0057 (7)	−0.0007 (10)
C17	0.0591 (14)	0.0813 (18)	0.0265 (10)	0.0166 (13)	0.0090 (9)	0.0059 (11)
C18	0.0345 (11)	0.0786 (16)	0.0292 (10)	−0.0140 (10)	0.0066 (8)	−0.0135 (10)
C19	0.0622 (16)	0.0687 (16)	0.0443 (13)	−0.0175 (13)	0.0070 (11)	−0.0121 (12)
C20	0.116 (3)	0.076 (2)	0.0575 (17)	−0.0355 (19)	0.0174 (17)	−0.0124 (15)
C21	0.194 (5)	0.063 (2)	0.096 (3)	−0.030 (3)	0.026 (3)	−0.005 (2)

Geometric parameters (Å, º)

O1—C1	1.221 (2)	C9—H9A	0.990
O2—C2	1.215 (2)	C9—H9B	0.990
O3—C3	1.210 (2)	C9—C10	1.548 (4)
O4—C12	1.219 (2)	C10—H10A	0.990
O5—C13	1.214 (2)	C10—H10B	0.990
O6—C14	1.210 (2)	C10—C11	1.476 (5)
N1—H1	0.83 (2)	C11—H11A	0.980
N1—C1	1.363 (2)	C11—H11B	0.980
N1—C2	1.371 (2)	C11—H11C	0.980
N2—H2	0.86 (2)	C12—C15	1.522 (2)
N2—C2	1.366 (2)	C14—C15	1.520 (2)
N2—C3	1.374 (2)	C15—C16	1.536 (3)
N3—H3	0.83 (3)	C15—C18	1.553 (3)
N3—C12	1.368 (2)	C16—H16A	0.990
N3—C13	1.372 (2)	C16—H16B	0.990
N4—H4	0.86 (3)	C16—C17	1.514 (4)
N4—C13	1.371 (2)	C17—H17A	0.980
N4—C14	1.379 (2)	C17—H17B	0.980
C1—C4	1.523 (3)	C17—H17C	0.980
C3—C4	1.521 (3)	C18—H18A	0.990
C4—C7	1.543 (3)	C18—H18B	0.990
C4—C8	1.555 (4)	C18—C19	1.508 (4)
C6—H6A	0.980	C19—H19A	0.990
C6—H6B	0.980	C19—H19B	0.990
C6—H6C	0.980	C19—C20	1.517 (4)
C6—C7	1.510 (4)	C20—H20A	0.990
C7—H7A	0.990	C20—H20B	0.990
C7—H7B	0.990	C20—C21	1.496 (5)
C8—H8A	0.990	C21—H21A	0.980
C8—H8B	0.990	C21—H21B	0.980
C8—C9	1.515 (4)	C21—H21C	0.980
H1—N1—C1	118.1 (16)	C10—C11—H11A	109.5
H1—N1—C2	115.5 (16)	C10—C11—H11B	109.5
C1—N1—C2	126.07 (15)	C10—C11—H11C	109.5
H2—N2—C2	114.6 (16)	H11A—C11—H11B	109.5
H2—N2—C3	119.0 (16)	H11A—C11—H11C	109.5
C2—N2—C3	126.37 (16)	H11B—C11—H11C	109.5
H3—N3—C12	118.2 (16)	O4—C12—N3	120.35 (16)
H3—N3—C13	115.7 (16)	O4—C12—C15	121.63 (16)
C12—N3—C13	126.11 (15)	N3—C12—C15	117.85 (16)
H4—N4—C13	114.5 (15)	O5—C13—N3	121.00 (16)
H4—N4—C14	119.1 (15)	O5—C13—N4	122.64 (16)
C13—N4—C14	126.48 (15)	N3—C13—N4	116.35 (16)
O1—C1—N1	120.13 (16)	O6—C14—N4	120.16 (16)
O1—C1—C4	121.51 (17)	O6—C14—C15	122.26 (17)
N1—C1—C4	118.25 (16)	N4—C14—C15	117.54 (15)
O2—C2—N1	120.86 (16)	C12—C15—C14	113.73 (15)
O2—C2—N2	122.61 (16)	C12—C15—C16	110.62 (17)
N1—C2—N2	116.53 (16)	C12—C15—C18	106.19 (16)
O3—C3—N2	119.94 (17)	C14—C15—C16	109.01 (16)
O3—C3—C4	121.98 (17)	C14—C15—C18	107.40 (17)
N2—C3—C4	118.07 (15)	C16—C15—C18	109.77 (16)
C1—C4—C3	113.79 (15)	C15—C16—H16A	108.6
C1—C4—C7	109.25 (18)	C15—C16—H16B	108.6
C1—C4—C8	107.41 (17)	C15—C16—C17	114.46 (17)
C3—C4—C7	108.38 (17)	H16A—C16—H16B	107.6
C3—C4—C8	107.61 (19)	H16A—C16—C17	108.6
C7—C4—C8	110.38 (17)	H16B—C16—C17	108.6
H6A—C6—H6B	109.5	C16—C17—H17A	109.5
H6A—C6—H6C	109.5	C16—C17—H17B	109.5
H6A—C6—C7	109.5	C16—C17—H17C	109.5
H6B—C6—H6C	109.5	H17A—C17—H17B	109.5
H6B—C6—C7	109.5	H17A—C17—H17C	109.5
H6C—C6—C7	109.5	H17B—C17—H17C	109.5
C4—C7—C6	114.45 (17)	C15—C18—H18A	108.4
C4—C7—H7A	108.6	C15—C18—H18B	108.4
C4—C7—H7B	108.6	C15—C18—C19	115.58 (17)
C6—C7—H7A	108.6	H18A—C18—H18B	107.4
C6—C7—H7B	108.6	H18A—C18—C19	108.4
H7A—C7—H7B	107.6	H18B—C18—C19	108.4
C4—C8—H8A	108.3	C18—C19—H19A	108.9
C4—C8—H8B	108.3	C18—C19—H19B	108.9
C4—C8—C9	115.87 (19)	C18—C19—C20	113.4 (2)
H8A—C8—H8B	107.4	H19A—C19—H19B	107.7
H8A—C8—C9	108.3	H19A—C19—C20	108.9
H8B—C8—C9	108.3	H19B—C19—C20	108.9
C8—C9—H9A	108.7	C19—C20—H20A	108.9
C8—C9—H9B	108.7	C19—C20—H20B	108.9
C8—C9—C10	114.2 (3)	C19—C20—C21	113.2 (3)
H9A—C9—H9B	107.6	H20A—C20—H20B	107.8
H9A—C9—C10	108.7	H20A—C20—C21	108.9
H9B—C9—C10	108.7	H20B—C20—C21	108.9
C9—C10—H10A	108.8	C20—C21—H21A	109.5
C9—C10—H10B	108.8	C20—C21—H21B	109.5
C9—C10—C11	113.8 (3)	C20—C21—H21C	109.5
H10A—C10—H10B	107.7	H21A—C21—H21B	109.5
H10A—C10—C11	108.8	H21A—C21—H21C	109.5
H10B—C10—C11	108.8	H21B—C21—H21C	109.5
C2—N1—C1—O1	172.2 (2)	C13—N3—C12—O4	173.4 (2)
C2—N1—C1—C4	−11.5 (3)	C13—N3—C12—C15	−11.3 (3)
C3—N2—C2—O2	−177.2 (2)	C14—N4—C13—O5	−177.3 (2)
C3—N2—C2—N1	2.6 (3)	C14—N4—C13—N3	4.0 (3)
C1—N1—C2—O2	−174.9 (2)	C12—N3—C13—O5	−178.0 (2)
C1—N1—C2—N2	5.3 (3)	C12—N3—C13—N4	0.7 (3)
C2—N2—C3—O3	176.5 (2)	C13—N4—C14—O6	−179.9 (2)
C2—N2—C3—C4	−3.2 (3)	C13—N4—C14—C15	2.5 (3)
O3—C3—C4—C1	177.4 (2)	O6—C14—C15—C12	170.3 (2)
O3—C3—C4—C7	55.6 (3)	O6—C14—C15—C16	46.3 (3)
O3—C3—C4—C8	−63.8 (3)	O6—C14—C15—C18	−72.6 (3)
N2—C3—C4—C1	−3.0 (3)	N4—C14—C15—C12	−12.2 (3)
N2—C3—C4—C7	−124.7 (2)	N4—C14—C15—C16	−136.17 (19)
N2—C3—C4—C8	115.9 (2)	N4—C14—C15—C18	105.0 (2)
O1—C1—C4—C3	−174.1 (2)	O4—C12—C15—C14	−168.4 (2)
O1—C1—C4—C7	−52.9 (3)	O4—C12—C15—C16	−45.4 (3)
O1—C1—C4—C8	66.9 (3)	O4—C12—C15—C18	73.7 (3)
N1—C1—C4—C3	9.6 (3)	N3—C12—C15—C14	16.2 (3)
N1—C1—C4—C7	130.9 (2)	N3—C12—C15—C16	139.31 (19)
N1—C1—C4—C8	−109.4 (2)	N3—C12—C15—C18	−101.6 (2)
C1—C4—C7—C6	−70.0 (2)	C12—C15—C16—C17	−66.9 (2)
C3—C4—C7—C6	54.5 (2)	C14—C15—C16—C17	58.9 (2)
C8—C4—C7—C6	172.11 (18)	C18—C15—C16—C17	176.26 (17)
C1—C4—C8—C9	58.0 (2)	C12—C15—C18—C19	61.2 (2)
C3—C4—C8—C9	−64.9 (2)	C14—C15—C18—C19	−60.8 (2)
C7—C4—C8—C9	177.00 (19)	C16—C15—C18—C19	−179.20 (18)
C4—C8—C9—C10	173.7 (2)	C15—C18—C19—C20	175.4 (2)
C8—C9—C10—C11	−72.4 (4)	C18—C19—C20—C21	−178.9 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O4	0.83 (2)	2.02 (3)	2.840 (2)	171 (2)
N2—H2···O5^i	0.86 (2)	2.00 (3)	2.838 (2)	166 (2)
N3—H3···O1	0.83 (3)	2.03 (3)	2.856 (2)	174 (2)
N4—H4···O2^ii	0.86 (3)	2.01 (3)	2.856 (2)	169 (2)

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