7,7-Dimethyl-5H-di­benzo[e,i][1,4,8]triaza­cyclo­undecine-6,9,15(7H,8H,14H)-trione pyridine solvate

The X-ray crystal structure and hydrogen-bonding patterns of the title compound, C₁₈H₁₇N₃O₃·C₅H₅N, a non-N-alkyl­ated cyclotripeptide containing one α- and two β-amino acids, are reported. The amides in the 11-membered ring have an unprecedented all-transoid configuration. The torsion angles and Dunitz parameters describing non-planarity of the amides contained in the cyclotripeptide are discussed.

S1. Comment

N-Alkylated cyclo-tripeptides have often been synthesized as structural models for β- and γ-turn mimetics (Wels et al., 2002; Schumann et al., 2000), interesting antibacterial effects (Hamuro et al., 1999) and for solution versus solid phase comparisons (Bats & Fuess, 1980). Synthesis of non-N-alkylated cyclotripeptides is extremely difficult as the preferred transoid conformation of amide bonds prevents unassisted ring closure. Most reported cyclotripeptides contain proline residues, which lower the energy difference between the cisoid and transoid conformations. Crystallographically characterized examples of cyclotripeptide ten-membered rings (2α and 1β; Cerrini et al., 1988; Rothe et al., 1973; Wels et al., 2002) and 12-membered rings (3β) are all N-alkylated (Ollis & Stoddart, 1984). We are not aware of any reported examples of cyclotripeptide 11-membered rings. Incorporation of α- and β-amino acids into a single medium-sized ring gives unique qualities that may not occur in cyclopeptides containing solely α- or β -amino acids. Syntheses of non-N-alkylated cyclotripeptides have only been reported twice (Imagawa et al., 1987; Villalgordo & Heimgartner, 1997); however, the compounds were never characterized crystallographically. These results do not exclude the possibility that the peptide precursors may have dimerized before cyclization, thus forming cyclohexapeptides (Schröder & Lübke, 1965).

In this communication, we report the first crystal structure determination of a non-N-alkylated cyclotripeptide containing all-transoid amides, (I) (Fig. 1). Two of the amides are significantly non-planar. This contrasts with previously reported crystal structures of N-alkylated cyclotripeptides where at least one of the amides is in a cisoid configuration. The all-transoid configuration in (I) could make it a good candidate for studies in β-turn mimetics (Wels et al., 2002). However, the torsion angles for the α-amino acid (Table 2) are closer to those of an α-helix than a β-sheet on a Ramachandran plot. Hence, this particular transoid cyclotripeptide is not the most suitable candidate for β-turn mimetic studies. The torsion angles (ϕ,ψ) of the β-amino acids (Table 2) do show similarities to the calculated preferred minimum energy conformations for β-peptides in an H12-helix configuration (Günther & Hofmann, 2001). The θ torsion angles for the β-peptides differ from the normally preferred minimums because the aromatic ring constrains this angle to be close to zero (Günther & Hofmann, 2001). The fixed torsion angles inside the 11-membered ring may allow such rings to be used as possible scaffolds in drug development (Ro et al., 2002). This approach has been attempted using other peptide systems whose torsion angles mimic those of bioactive molecules (Ro et al., 2002).

The primary hydrogen-bonding motif (Fig. 2 and Table 1) consists of hydrogen-bonded dimers using the N1—H1···O1 links between adjacent molecules. The N3 hydrogen (H3) is potentially available for an intermolecular hydrogen bond; however, it is not sterically accessible with the geminal dimethyl group and aromatic rings on both macrocycles prohibiting approach from this side of the molecule. It seems possible that the pyridine solvate prevents the formation of a hydrogen-bonded supramolecular structure by binding (Table 1) an H atom (H2) that is internal to the ring. This would not normally be available for hydrogen bonding to another neighbouring ring.

The ω angles (Winkler & Dunitz, 1971; Table 2) of the amide residues show that the H atoms of amides 2 and 3 lie out of their plane. Specifically, atom H2 is 0.229 (1) Å from the N2/C7/O1 plane and atom H3 is 0.207 (1) Å from the N3/C14/O2 plane. Amide non-planarity can arise from one of two possible distortions in the amide bond, which cannot be identified by the ω angle. The first distortion is from pyramidalization of the amide N atom or carbonyl C atom. The second distortion is from a twist of the amide C—N bond. A Dunitz analysis of amide non-planarity (Table 3) relates amide non-planarity to the precise distortion causing the non-planarity [τ is the non-planarity of the amide; for a planar trans-amide this should be close to 180°; χ_N and χ_C measure the angular pyramidalization of the amide N atom and carbonyl C atom, respectively]. The values of χ_N and χ_C suggest that the observed non-planarity for amide 2 (H2/N2/C7/O1) and amide 3 (H3/N3/C14/O2) is due to a twist in the amide bond, rather than pyramidalization of the N or carbonyl C atoms. Amide 1 (H1/N1/C16/O3) is relatively planar, with atom H1 0.079 (2) Å from the N1/C16/O3 plane.

Modelling (Spartan'04 Mechanics PC/x86 RB3LYP/6–311G*; Hehre, 2003; Kong et al., 2000) does predict that the all-trans system is favoured as the monomer by 22.5 kJ mol⁻¹, and by 93.7 kJ mol⁻¹ in the hydrogen-bonded dimer as the pyridine solvate. In the crystallographically determined hydrogen-bonded dimer (Fig. 2), the rings are equivalent because of a centre of symmetry. In the theoretical model for an isolated pyridine hydrogen-bonded dimer such as the one in Fig. 2, the two tripeptide rings contain different sets of torsion angles and different sources of amide non-planarity (Table 3). Dunitz analysis of the theoretical dimer system predicts amide non-planarity to be a combination of pyramidalization of the atoms and a twist of the amide bonds; this is in contrast to (I), which exhibits almost exclusive twisting of the amide bond. The (solid-state) hydrogen bonding (Table 1) here may also be affecting this distortion from planarity.

Amide non-planarity in (I) must help reduce the strain caused by having three rigorously transoid amides in the medium sized ring. Relieving ring strain through amide non-planarity has been seen in cyclotetrapeptides (with a 12-membered ring) such as dihydrochlamydocin, which also contains an all trans-configuration (Flippen & Karle, 1976). Dunitz analysis of dihydrochlamydocin indicates that there is a significant contribution from pyramidalization of the amide C or N atoms to the non-planarity, as opposed to a twist of the amide bond. To our knowledge, no other cyclotripeptide, containing α-amino acids, exhibits the all-trans configuration reported here. This leads us to believe that further study of this unusual structural type is warranted.

S2. Experimental

Compound (I) was synthesized using methods carried forward from Ollis & Stoddart (1984) and Imagawa et al. (1987). Dimethyl sulfoxide and dimethylformamide solvent systems were also attempted, but did not yield X-ray quality crystals. 2-[2-(2-Amino-benzoylamino)benzoylamino]-2-methylpropionic acid methyl ester (0.996 g, 0.0028 mol) was dissolved in freshly distilled tetrhydrofuran (THF, 25 ml), and sodium hydride 60% in mineral oil was added. The solution was refluxed for three days and then quenched in 150 ml of ice–cold water. The THF was distilled out of the solution at ambient pressure. The resulting cloudy solution was cooled and filtered. The isolated solid (0.600 g after air drying) is the macrocyclic product with 95–98% purity (crystallization from hot/cold pyridine). For other spectroscopic data, see the CIF.

S3. Refinement

H atoms were placed in calculated positions and refined using a riding model (C—H = = 0.93 and 0.96 Å, and N—H = 0.86 Å), with U_iso(H) values of 1.2 or 1.5 times U_eq(C,N).

Computing details

Data collection: SMART (Siemens, 1995); cell refinement: SAINT (Siemens, 1995); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPIII (Burnett & Johnson, 1996); software used to prepare material for publication: SHELXTL (Siemens, 1995).

Figures

	Fig. 1. ORTEPIII (Burnett & Johnson, 1996) diagram of the X-ray crystal structure of (I). Displacement ellipsoids are drawn at the 50% probability level and non-amide H atoms have been omitted for clarity.
	Fig. 2. Hydrogen bonding in (I). H atoms have been omitted for clarity. The two halves of the dimer are related by a crystallographic centre of symmetry [symmetry code: (*) 1 − x, 2 − y, −z.]

7,7-dimethyl-7,8-dihydro-5H-dibenzo[e,i][1,4,8] triazacycloundecine-6,9,15(14H)-trione pyridine solvate

Crystal data

C18H17N3O3·C5H5N	F(000) = 848
Mr = 402.45	Dx = 1.373 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 7879 reflections
a = 12.107 (2) Å	θ = 1.7–26.4°
b = 11.050 (2) Å	µ = 0.09 mm^−1
c = 14.627 (3) Å	T = 85 K
β = 92.42 (3)°	Plate, colourless
V = 1955.1 (7) Å^3	0.28 × 0.24 × 0.20 mm
Z = 4

Data collection

Siemens SMART CCD area-detector diffractometer	4001 independent reflections
Radiation source: fine-focus sealed tube	3360 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.023
ω scans	θmax = 26.4°, θmin = 1.7°
Absorption correction: multi-scan (SADABS; Sheldrick, 1997)	h = −15→15
Tmin = 0.757, Tmax = 0.978	k = 0→13
11782 measured reflections	l = 0→18

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)] = 0.039	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.100	H-atom parameters constrained
S = 1.03	w = 1/[σ^2(Fo^2) + (0.0409P)^2 + 1.2338P] where P = (Fo^2 + 2Fc^2)/3
4001 reflections	(Δ/σ)max < 0.001
273 parameters	Δρmax = 0.53 e Å^−3
0 restraints	Δρmin = −0.52 e Å^−3

Special details

Experimental. ¹H (d6dmso) 500 MHz: 9.52(1H, s, amideNH), 8.89(1H,s, amideNH), 8.72(1H, s, amide NH), 7,83(1H, d, ar, J=8.12 Hz), 7.731 (1H, d, ar, J=7.94 Hz), 7.56(1H, d, ar, J=7.55 Hz), 7.51(1H, t, ar, J= 7.44 Hz), 7.48(1H, t, ar, J=8.84 Hz), 7.60(1H, d, ar, J=7.39 Hz), 7.26(2H, q, ar, J=7.56 Hz), 1.53(6H, s, me)

¹³C{¹H} (d6dmso) 500 MHz:172.7, 169.6, 166.3, 134.8, 134.3, 132.7, 130.6, 129.6, 129.3, 128.4, 124.9, 124.5, 124.48, 124.41, 124.2, 58.4, 24.6

HRMS(EI): M⁺= 323.1263 (2.2ppm), Calculated: 323.13

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	0.53265 (8)	1.12612 (9)	0.05641 (7)	0.0184 (2)
O2	0.67481 (8)	0.70289 (9)	0.17448 (7)	0.0186 (2)
O3	0.85282 (8)	0.72607 (10)	0.00508 (8)	0.0223 (2)
N1	0.71062 (10)	0.85908 (11)	−0.02253 (8)	0.0158 (3)
N2	0.60747 (10)	0.96591 (10)	0.13562 (8)	0.0151 (3)
N3	0.57187 (10)	0.67927 (11)	0.04178 (8)	0.0152 (3)
N4	0.83737 (11)	0.92499 (12)	0.21275 (9)	0.0225 (3)
C1	0.76725 (12)	0.97150 (13)	−0.01692 (9)	0.0159 (3)
C2	0.86623 (12)	0.98911 (14)	−0.06011 (10)	0.0190 (3)
C3	0.91613 (12)	1.10250 (14)	−0.05964 (10)	0.0210 (3)
C4	0.86600 (12)	1.20021 (14)	−0.01859 (10)	0.0206 (3)
C5	0.76625 (12)	1.18424 (13)	0.02342 (10)	0.0183 (3)
C6	0.71765 (11)	1.06969 (13)	0.02656 (9)	0.0155 (3)
C7	0.61073 (12)	1.05716 (13)	0.07404 (9)	0.0149 (3)
C8	0.50821 (12)	0.91686 (13)	0.16945 (9)	0.0149 (3)
C9	0.42532 (12)	0.98943 (13)	0.20229 (9)	0.0167 (3)
C10	0.32818 (12)	0.93700 (14)	0.23067 (10)	0.0190 (3)
C11	0.31384 (12)	0.81246 (14)	0.22702 (10)	0.0213 (3)
C12	0.39735 (12)	0.73920 (14)	0.19474 (10)	0.0192 (3)
C13	0.49450 (12)	0.79044 (13)	0.16592 (9)	0.0155 (3)
C14	0.58844 (12)	0.71779 (12)	0.12915 (10)	0.0149 (3)
C15	0.66584 (12)	0.64399 (13)	−0.01414 (10)	0.0164 (3)
C16	0.75467 (12)	0.74617 (13)	−0.00838 (9)	0.0160 (3)
C17	0.71618 (13)	0.52423 (13)	0.01832 (11)	0.0205 (3)
C18	0.62069 (12)	0.63123 (13)	−0.11292 (10)	0.0192 (3)
C19	0.88451 (13)	0.82911 (15)	0.25446 (11)	0.0250 (3)
C20	0.96838 (14)	0.83802 (17)	0.32092 (13)	0.0328 (4)
C21	1.00587 (15)	0.95127 (19)	0.34694 (12)	0.0371 (4)
C22	0.95917 (16)	1.05184 (18)	0.30446 (13)	0.0355 (4)
C23	0.87673 (14)	1.03392 (15)	0.23785 (12)	0.0289 (4)
H1	0.6409	0.8622	−0.0364	0.019*
H2	0.6693	0.9355	0.1556	0.018*
H2A	0.8992	0.9247	−0.0895	0.023*
H3	0.5056	0.6752	0.0183	0.018*
H3A	0.9834	1.1129	−0.0870	0.025*
H4	0.8991	1.2762	−0.0192	0.025*
H5	0.7317	1.2501	0.0496	0.022*
H9	0.4347	1.0729	0.2053	0.020*
H10	0.2724	0.9858	0.2523	0.023*
H11	0.2486	0.7780	0.2461	0.026*
H12	0.3879	0.6557	0.1925	0.023*
H17A	0.7449	0.5327	0.0802	0.031*
H17B	0.7750	0.5022	−0.0204	0.031*
H17C	0.6604	0.4624	0.0157	0.031*
H18A	0.5656	0.5688	−0.1162	0.029*
H18B	0.6799	0.6104	−0.1516	0.029*
H18C	0.5883	0.7065	−0.1329	0.029*
H19	0.8594	0.7524	0.2377	0.030*
H20	0.9991	0.7688	0.3477	0.039*
H21	1.0616	0.9598	0.3922	0.044*
H22	0.9827	1.1295	0.3204	0.043*
H23	0.8466	1.1017	0.2085	0.035*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C18	0.0226 (7)	0.0178 (7)	0.0173 (7)	0.0009 (6)	0.0006 (6)	−0.0031 (6)
O2	0.0191 (5)	0.0174 (5)	0.0192 (5)	0.0009 (4)	−0.0018 (4)	0.0005 (4)
O1	0.0174 (5)	0.0164 (5)	0.0214 (5)	0.0031 (4)	0.0010 (4)	0.0028 (4)
O3	0.0168 (5)	0.0207 (6)	0.0294 (6)	0.0027 (4)	0.0007 (4)	0.0001 (4)
N2	0.0151 (6)	0.0140 (6)	0.0160 (6)	0.0012 (5)	−0.0003 (4)	0.0017 (5)
N3	0.0139 (6)	0.0150 (6)	0.0167 (6)	−0.0008 (4)	−0.0003 (5)	−0.0004 (5)
N1	0.0131 (6)	0.0146 (6)	0.0198 (6)	−0.0004 (5)	0.0002 (4)	−0.0009 (5)
C17	0.0224 (8)	0.0150 (7)	0.0242 (8)	0.0025 (6)	0.0016 (6)	0.0002 (6)
N4	0.0204 (6)	0.0232 (7)	0.0239 (7)	0.0031 (5)	0.0019 (5)	0.0009 (5)
C1	0.0170 (7)	0.0150 (7)	0.0154 (7)	0.0002 (5)	−0.0023 (5)	0.0028 (5)
C5	0.0212 (7)	0.0145 (7)	0.0190 (7)	0.0004 (6)	−0.0004 (6)	0.0014 (6)
C4	0.0207 (7)	0.0183 (7)	0.0225 (8)	−0.0049 (6)	−0.0016 (6)	0.0035 (6)
C14	0.0183 (7)	0.0099 (6)	0.0166 (7)	−0.0028 (5)	0.0022 (5)	0.0022 (5)
C16	0.0179 (7)	0.0168 (7)	0.0136 (7)	0.0016 (6)	0.0027 (5)	−0.0013 (5)
C9	0.0207 (7)	0.0162 (7)	0.0130 (6)	0.0010 (6)	−0.0004 (5)	−0.0005 (5)
C10	0.0189 (7)	0.0237 (8)	0.0146 (7)	0.0034 (6)	0.0024 (5)	−0.0011 (6)
C15	0.0176 (7)	0.0148 (7)	0.0169 (7)	0.0015 (5)	0.0020 (5)	−0.0008 (5)
C13	0.0187 (7)	0.0164 (7)	0.0114 (6)	0.0010 (5)	−0.0004 (5)	0.0011 (5)
C20	0.0230 (8)	0.0368 (10)	0.0381 (10)	−0.0037 (7)	−0.0055 (7)	0.0165 (8)
C7	0.0172 (7)	0.0133 (7)	0.0142 (7)	−0.0013 (5)	−0.0010 (5)	−0.0020 (5)
C6	0.0150 (7)	0.0160 (7)	0.0154 (7)	−0.0001 (5)	−0.0019 (5)	0.0023 (5)
C3	0.0149 (7)	0.0263 (8)	0.0219 (7)	−0.0014 (6)	0.0016 (6)	0.0045 (6)
C12	0.0217 (7)	0.0171 (7)	0.0189 (7)	−0.0021 (6)	0.0014 (6)	0.0013 (6)
C11	0.0186 (7)	0.0263 (8)	0.0192 (7)	−0.0034 (6)	0.0041 (6)	0.0021 (6)
C2	0.0177 (7)	0.0193 (7)	0.0201 (7)	0.0016 (6)	0.0010 (6)	0.0017 (6)
C8	0.0173 (7)	0.0166 (7)	0.0108 (6)	−0.0011 (5)	−0.0008 (5)	0.0013 (5)
C22	0.0388 (10)	0.0347 (10)	0.0330 (9)	−0.0095 (8)	0.0016 (8)	−0.0058 (8)
C19	0.0206 (8)	0.0246 (8)	0.0296 (8)	−0.0005 (6)	0.0007 (6)	0.0053 (7)
C23	0.0314 (9)	0.0237 (8)	0.0316 (9)	0.0035 (7)	0.0016 (7)	−0.0004 (7)
C21	0.0291 (9)	0.0526 (12)	0.0287 (9)	−0.0146 (8)	−0.0071 (7)	0.0075 (8)

Geometric parameters (Å, º)

C18—C15	1.530 (2)	C4—C3	1.388 (2)
C18—H18A	0.9600	C4—H4	0.9300
C18—H18B	0.9600	C14—C13	1.510 (2)
C18—H18C	0.9600	C16—C15	1.559 (2)
O2—C14	1.2255 (18)	C9—C8	1.386 (2)
O1—C7	1.2330 (17)	C9—C10	1.390 (2)
O3—C16	1.2167 (18)	C9—H9	0.9300
N2—C7	1.3537 (18)	C10—C11	1.388 (2)
N2—C8	1.4258 (18)	C10—H10	0.9300
N2—H2	0.8600	C13—C12	1.387 (2)
N3—C14	1.3538 (18)	C13—C8	1.407 (2)
N3—C15	1.4811 (18)	C20—C21	1.379 (3)
N3—H3	0.8600	C20—C19	1.379 (2)
N1—C16	1.3691 (19)	C20—H20	0.9300
N1—C1	1.4196 (18)	C7—C6	1.5011 (19)
N1—H1	0.8600	C3—C2	1.391 (2)
C17—C15	1.524 (2)	C3—H3A	0.9300
C17—H17A	0.9600	C12—C11	1.393 (2)
C17—H17B	0.9600	C12—H12	0.9300
C17—H17C	0.9600	C11—H11	0.9300
N4—C19	1.338 (2)	C2—H2A	0.9300
N4—C23	1.340 (2)	C22—C23	1.379 (3)
C1—C2	1.392 (2)	C22—C21	1.382 (3)
C1—C6	1.405 (2)	C22—H22	0.9300
C5—C4	1.389 (2)	C19—H19	0.9300
C5—C6	1.397 (2)	C23—H23	0.9300
C5—H5	0.9300	C21—H21	0.9300
C15—C18—H18A	109.5	N3—C15—C18	107.08 (12)
C15—C18—H18B	109.5	C17—C15—C18	109.66 (12)
H18A—C18—H18B	109.5	N3—C15—C16	108.89 (11)
C15—C18—H18C	109.5	C17—C15—C16	110.24 (12)
H18A—C18—H18C	109.5	C18—C15—C16	109.64 (12)
H18B—C18—H18C	109.5	C12—C13—C8	119.62 (13)
C7—N2—C8	124.24 (12)	C12—C13—C14	123.55 (13)
C7—N2—H2	117.9	C8—C13—C14	116.83 (12)
C8—N2—H2	117.9	C21—C20—C19	118.90 (16)
C14—N3—C15	121.15 (12)	C21—C20—H20	120.6
C14—N3—H3	119.4	C19—C20—H20	120.6
C15—N3—H3	119.4	O1—C7—N2	123.77 (13)
C16—N1—C1	127.19 (12)	O1—C7—C6	120.99 (13)
C16—N1—H1	116.4	N2—C7—C6	115.24 (12)
C1—N1—H1	116.4	C5—C6—C1	119.73 (13)
C15—C17—H17A	109.5	C5—C6—C7	118.12 (13)
C15—C17—H17B	109.5	C1—C6—C7	122.11 (13)
H17A—C17—H17B	109.5	C4—C3—C2	120.35 (14)
C15—C17—H17C	109.5	C4—C3—H3A	119.8
H17A—C17—H17C	109.5	C2—C3—H3A	119.8
H17B—C17—H17C	109.5	C13—C12—C11	120.18 (14)
C19—N4—C23	116.50 (14)	C13—C12—H12	119.9
C2—C1—C6	119.35 (13)	C11—C12—H12	119.9
C2—C1—N1	121.27 (13)	C10—C11—C12	119.86 (14)
C6—C1—N1	119.16 (13)	C10—C11—H11	120.1
C4—C5—C6	120.32 (14)	C12—C11—H11	120.1
C4—C5—H5	119.8	C3—C2—C1	120.39 (14)
C6—C5—H5	119.8	C3—C2—H2A	119.8
C3—C4—C5	119.79 (14)	C1—C2—H2A	119.8
C3—C4—H4	120.1	C9—C8—C13	120.06 (13)
C5—C4—H4	120.1	C9—C8—N2	122.25 (13)
O2—C14—N3	123.89 (13)	C13—C8—N2	117.66 (12)
O2—C14—C13	121.14 (13)	C23—C22—C21	118.17 (17)
N3—C14—C13	114.81 (12)	C23—C22—H22	120.9
O3—C16—N1	124.22 (13)	C21—C22—H22	120.9
O3—C16—C15	122.91 (13)	N4—C19—C20	123.50 (16)
N1—C16—C15	112.85 (12)	N4—C19—H19	118.3
C8—C9—C10	119.76 (14)	C20—C19—H19	118.3
C8—C9—H9	120.1	N4—C23—C22	124.12 (16)
C10—C9—H9	120.1	N4—C23—H23	117.9
C11—C10—C9	120.52 (14)	C22—C23—H23	117.9
C11—C10—H10	119.7	C20—C21—C22	118.80 (16)
C9—C10—H10	119.7	C20—C21—H21	120.6
N3—C15—C17	111.27 (12)	C22—C21—H21	120.6