C-H...O and C-H...N inter­actions in three hexa­hydro­cyclo­octa­[b]pyridine-3-carbo­nitriles

The structures of three new pyridine derivatives, 2-meth­oxy-4-(4-meth­oxy­phenyl)-5,6,7,8,9,10-hexa­hydro­cyclo­octa­[b]pyridine-3-carbo­nitrile, C₂₀H₂₂N₂O₂, (I), 2-eth­oxy-4-(3-nitrophenyl)-5,6,7,8,9,10-hexa­hydro­cyclo­octa­[b]pyridine-3-carbonitrile, C₂₀H₂₁N₃O₃, (II), and 2-eth­oxy-4-(4-meth­oxy­phenyl)-5,6,7,8,9,10-hexa­hydro­cyclo­octa­[b]pyridine-3-carbo­nitrile, C₂₁H₂₄N₂O₂, (III), differ in the nature of the substituents either at the 2-position of the central pyridine ring or on the pendent aryl ring. This simple change in the structure substantially alters the inter­molecular inter­action patterns. The substituted phenyl group adopts a synclinal geometry with respect to the plane of the pyridine ring in all three compounds. In (I), a C-H...N inter­action results in a one-dimensional chain parallel to the b axis. In (II), there are two C-H...N(nitrile) inter­actions from different symmetry-related mol­ecules, resulting in a two-dimensional network parallel to the bc plane. There is also a weak C-H...O inter­action from the eth­oxy group to an adjacent nitro O atom. The present work is an example of how the simple replacement of a substituent in the main mol­ecular scaffold may transform the structure type, paving the way for a variety of supra­molecular motifs and consequently altering the complexity of the inter­molecular inter­action patterns.

S1. Introduction

The title compounds, (I)–(III), belong to the cyclo­alkeno­pyridine class of compounds. It is observed that many naturally occurring biologically active compounds feature a cyclo­alkeno­pyridine ring as the basic skeleton. This observation prompted the development of a range of synthetic methods to prepare pharmaceuticals and agrochemicals containing the cyclo­alkeno­pyridine ring as an important building block (Thummel, 2008). The synthesis of hydrogenated compounds has been extensively studied due to their inter­esting biological properties. For example, derivatives of 1,4-di­hydro­pyridine exhibit high biological activities as calcium channel blockers (Bossert et al., 1981) and as calcium agonists or antagonists (Triggle et al., 1980; Kokubun & Reuter, 1984; Bossert & Vater, 1989; Wang et al., 1989; Alajarin et al., 1995). Cyclo­octane compounds exhibit moderate to high anti­bacterial and anti­fungal effects against pathogenic microorganisms. For example, 2-[(4-sulfonamido­phenyl)­methyl­idene]cyclo­octa­none has an excellent activity against Listeria monocytogenes (Korany et al., 2011). The above observations prompted us to synthesize the title compounds containing cyclo­alkeno­pyridine carbo­nitrile groups and substituted pyridine scaffolds and to determine their crystal structures.

S2. Experimental

S2.1. Synthesis and crystallization

The solvent used in the reaction is incorporated in the product at position 2. In (I), methanol was used, whereas in (II) and (III) ethanol was the solvent.

The general reaction procedure is as follows. A mixture of cyclo­octa­none (1 mmol), 4-meth­oxy­benzaldehyde/3-nitro­benzaldehyde (1 mmol), malono­nitrile (1 mmol) and lithium ethoxide (1 equivalent) was heated to reflux in methanol or ethanol (10 ml) for 2–3 h. After completion of the reaction, as evidenced by thin-layer chromatograpy, the reaction mixture was poured into crushed ice and the resultant precipitate was extracted with ethyl acetate. The excess solvent was removed under vacuum and the residue was subjected to column chromatography using a petroleum ether–ethyl acetate mixture (95:5 v/v) as eluent to obtain the pure products. For (I), yield 74%, m.p. 460–461 K; for (II), yield 64%, m.p. 394–396 K; for (III), yield 65%, m.p. 399–400 K.

S2.2. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1. H atoms were placed at calculated positions and allowed to ride on their carrier atoms, with C—H = 0.93–0.98 Å, and with U_iso = 1.5U_eq(C) for methyl H atoms or 1.2U_eq(C) otherwise. In (III), atoms C4 and C5 of the cyclo­octane ring are each disordered over two sites and were refined with site-occupancy factors of 0.652 (9) and 0.348 (9).

S3. Results and discussion

In the molecular structures of (I) (Fig. 1), (II) (Fig. 2) and (III) (Fig. 3), the cyclo­octane ring adopts a twist-boat-chair conformation, as found in related structures (Xiong et al., 2007; Fun et al., 2010; Suresh et al., 2007).

The bond lengths and angles of the phenyl rings of (I)–(III) are consistent with those observed in similar structures (Patel et al., 2002a,b,c; Black et al., 1992; Hussain et al., 1996). The deviations of the nitrile atoms (C12 and N2) from the mean plane of the pyridine ring system (N1/C1/C8–C11) are -0.0422 (1) and -0.0896 (5) Å, respectively, in (I), -0.0081 (5) and -0.0416 (2) Å, respectively, in (II), and -0.0624 (4) and -0.1038 (1) Å, respectively, in (III), indicative of coplanarity.

The phenyl substituent at C9 of the pyridine ring has a (+)synclinal conformation in (I) and a (-)synclinal conformation in (II) and (III), which is evidenced by the C96—C91—C9—C10 torsion angles (see Tables 2, 3 and 4). The C10—C12 (Csp²—Csp) bonds in (I)–(III) tend towards aromatic bond lengths (see Table 1) rather than a σ-bond (~1.50 Å), presumably due to conjugation. However, the C12≡N2 bond lengths in (I)–(III) are apparently normal. The meth­oxy group in (I) and the eth­oxy group in (II) and (III) are coplanar with the plane of the attached pyridine ring, as can be seen from the C10—C11—O1—C13 and N1—C11—O1—C13 torsion angles. These torsion angles are similar to those in related structures (Ramesh, Subbiahpandi et al., 2009; Ramesh, Sundaresan et al., 2009).

There are phenyl–nitrile C—H···N inter­actions within the extended structures of (I) and (II) that are not present in (III). This inter­action results in a chain with graph-set motif of C(7) (Bernstein et al., 1995) (Figs. 4 and 5). The C92···N2ⁱ distance in (II) is noticeably lengthened compared with the same contact in (I) [see Tables 5, 6 and 7; symmetry code: (i) -x, y - 1/2, -z + 1/2]. However, the geometries of these hydrogen bonds remain essentially identical. The C···N contact in (II) is recognized as a perfect hydrogen bond, since the angle tends towards linearity.

In (I), a C92—H92···N2ⁱ inter­action links the molecules into pairs (Fig. 4). These pairs are further connected through a significant π–π stacking inter­action, Cg1···Cg1ⁱⁱ (Cg1 is the centroid of the pyridine ring), generating a linear chain, with Cg1···Cg1ⁱⁱ separations of 3.7526 (2) Å [symmetry code: (ii) -x, -y, -z + 1].

In the crystal structure of (II) (Fig. 5), atom C94 of the nitro­phenyl ring is involved in weak inter­molecular C94···H94···N2ⁱⁱ inter­action with cyano atom N2 of an inversion-related molecule, forming a hydrogen-bonded dimer and generating an R₂²(18) graph-set motif; these motifs are in turn linked through the C92—H92···N2ⁱ inter­action [symmetry codes: (i) -x, y - 1/2, -z + 1/2; (ii) -x, -y + 1, -z]. Meth­oxy atom C14 is involved in a C14—H14···O2ⁱⁱⁱ inter­action with nitro atom O2 of a symmetry-related molecule, generating a continuous parallel double chain with graph-set motif C(12) [symmetry code: (iii) x, y, z + 1].

The crystal structure of (III) (Fig. 6) has bifurcated intra­molecular C—H···O inter­actions. An inter­molecular C97—H97A···O2ⁱⁱ inter­action links inversion-related molecules into an aggregate, forming an R₂²(6) ring motif [symmetry code: (ii) -x + 1, -y, -z + 1] [Not the same definition as given in caption to Fig. 6 - please clarify]. An inter­molecular C92—H92···O1ⁱ inter­action forms a chain pattern running along the a axis generating a C(7) graph-set motif [symmetry code: (i) x - 1, y, z].

Related literature

For related literature, see: Alajarin et al. (1995); Bernstein et al. (1995); Black et al. (1992); Bossert & Vater (1989); Bossert et al. (1981); Fun et al. (2010); Hussain et al. (1996); Kokubun & Reuter (1984); Korany et al. (2011); Patel et al. (2002a, 2002b, 2002c); Ramesh, Subbiahpandi, Thirumurugan, Perumal & Ponnuswamy (2009); Ramesh, Sundaresan, Thirumurugan, Perumal & Ponnuswamy (2009); Suresh et al. (2007); Thummel (2008); Triggle et al. (1980); Wang et al. (1989); Xiong et al. (2007).

Structure description

The title compounds, (I)–(III), belong to the cyclo­alkeno­pyridine class of compounds. It is observed that many naturally occurring biologically active compounds feature a cyclo­alkeno­pyridine ring as the basic skeleton. This observation prompted the development of a range of synthetic methods to prepare pharmaceuticals and agrochemicals containing the cyclo­alkeno­pyridine ring as an important building block (Thummel, 2008). The synthesis of hydrogenated compounds has been extensively studied due to their inter­esting biological properties. For example, derivatives of 1,4-di­hydro­pyridine exhibit high biological activities as calcium channel blockers (Bossert et al., 1981) and as calcium agonists or antagonists (Triggle et al., 1980; Kokubun & Reuter, 1984; Bossert & Vater, 1989; Wang et al., 1989; Alajarin et al., 1995). Cyclo­octane compounds exhibit moderate to high anti­bacterial and anti­fungal effects against pathogenic microorganisms. For example, 2-[(4-sulfonamido­phenyl)­methyl­idene]cyclo­octa­none has an excellent activity against Listeria monocytogenes (Korany et al., 2011). The above observations prompted us to synthesize the title compounds containing cyclo­alkeno­pyridine carbo­nitrile groups and substituted pyridine scaffolds and to determine their crystal structures.

In the molecular structures of (I) (Fig. 1), (II) (Fig. 2) and (III) (Fig. 3), the cyclo­octane ring adopts a twist-boat-chair conformation, as found in related structures (Xiong et al., 2007; Fun et al., 2010; Suresh et al., 2007).

The bond lengths and angles of the phenyl rings of (I)–(III) are consistent with those observed in similar structures (Patel et al., 2002a,b,c; Black et al., 1992; Hussain et al., 1996). The deviations of the nitrile atoms (C12 and N2) from the mean plane of the pyridine ring system (N1/C1/C8–C11) are -0.0422 (1) and -0.0896 (5) Å, respectively, in (I), -0.0081 (5) and -0.0416 (2) Å, respectively, in (II), and -0.0624 (4) and -0.1038 (1) Å, respectively, in (III), indicative of coplanarity.

The phenyl substituent at C9 of the pyridine ring has a (+)synclinal conformation in (I) and a (-)synclinal conformation in (II) and (III), which is evidenced by the C96—C91—C9—C10 torsion angles (see Tables 2, 3 and 4). The C10—C12 (Csp²—Csp) bonds in (I)–(III) tend towards aromatic bond lengths (see Table 1) rather than a σ-bond (~1.50 Å), presumably due to conjugation. However, the C12≡N2 bond lengths in (I)–(III) are apparently normal. The meth­oxy group in (I) and the eth­oxy group in (II) and (III) are coplanar with the plane of the attached pyridine ring, as can be seen from the C10—C11—O1—C13 and N1—C11—O1—C13 torsion angles. These torsion angles are similar to those in related structures (Ramesh, Subbiahpandi et al., 2009; Ramesh, Sundaresan et al., 2009).

There are phenyl–nitrile C—H···N inter­actions within the extended structures of (I) and (II) that are not present in (III). This inter­action results in a chain with graph-set motif of C(7) (Bernstein et al., 1995) (Figs. 4 and 5). The C92···N2ⁱ distance in (II) is noticeably lengthened compared with the same contact in (I) [see Tables 5, 6 and 7; symmetry code: (i) -x, y - 1/2, -z + 1/2]. However, the geometries of these hydrogen bonds remain essentially identical. The C···N contact in (II) is recognized as a perfect hydrogen bond, since the angle tends towards linearity.

In (I), a C92—H92···N2ⁱ inter­action links the molecules into pairs (Fig. 4). These pairs are further connected through a significant π–π stacking inter­action, Cg1···Cg1ⁱⁱ (Cg1 is the centroid of the pyridine ring), generating a linear chain, with Cg1···Cg1ⁱⁱ separations of 3.7526 (2) Å [symmetry code: (ii) -x, -y, -z + 1].

In the crystal structure of (II) (Fig. 5), atom C94 of the nitro­phenyl ring is involved in weak inter­molecular C94···H94···N2ⁱⁱ inter­action with cyano atom N2 of an inversion-related molecule, forming a hydrogen-bonded dimer and generating an R₂²(18) graph-set motif; these motifs are in turn linked through the C92—H92···N2ⁱ inter­action [symmetry codes: (i) -x, y - 1/2, -z + 1/2; (ii) -x, -y + 1, -z]. Meth­oxy atom C14 is involved in a C14—H14···O2ⁱⁱⁱ inter­action with nitro atom O2 of a symmetry-related molecule, generating a continuous parallel double chain with graph-set motif C(12) [symmetry code: (iii) x, y, z + 1].

The crystal structure of (III) (Fig. 6) has bifurcated intra­molecular C—H···O inter­actions. An inter­molecular C97—H97A···O2ⁱⁱ inter­action links inversion-related molecules into an aggregate, forming an R₂²(6) ring motif [symmetry code: (ii) -x + 1, -y, -z + 1] [Not the same definition as given in caption to Fig. 6 - please clarify]. An inter­molecular C92—H92···O1ⁱ inter­action forms a chain pattern running along the a axis generating a C(7) graph-set motif [symmetry code: (i) x - 1, y, z].

For related literature, see: Alajarin et al. (1995); Bernstein et al. (1995); Black et al. (1992); Bossert & Vater (1989); Bossert et al. (1981); Fun et al. (2010); Hussain et al. (1996); Kokubun & Reuter (1984); Korany et al. (2011); Patel et al. (2002a, 2002b, 2002c); Ramesh, Subbiahpandi, Thirumurugan, Perumal & Ponnuswamy (2009); Ramesh, Sundaresan, Thirumurugan, Perumal & Ponnuswamy (2009); Suresh et al. (2007); Thummel (2008); Triggle et al. (1980); Wang et al. (1989); Xiong et al. (2007).

Synthesis and crystallization

The solvent used in the reaction is incorporated in the product at position 2. In (I), methanol was used, whereas in (II) and (III) ethanol was the solvent.

The general reaction procedure is as follows. A mixture of cyclo­octa­none (1 mmol), 4-meth­oxy­benzaldehyde/3-nitro­benzaldehyde (1 mmol), malono­nitrile (1 mmol) and lithium ethoxide (1 equivalent) was heated to reflux in methanol or ethanol (10 ml) for 2–3 h. After completion of the reaction, as evidenced by thin-layer chromatograpy, the reaction mixture was poured into crushed ice and the resultant precipitate was extracted with ethyl acetate. The excess solvent was removed under vacuum and the residue was subjected to column chromatography using a petroleum ether–ethyl acetate mixture (95:5 v/v) as eluent to obtain the pure products. For (I), yield 74%, m.p. 460–461 K; for (II), yield 64%, m.p. 394–396 K; for (III), yield 65%, m.p. 399–400 K.

Refinement details

Crystal data, data collection and structure refinement details are summarized in Table 1. H atoms were placed at calculated positions and allowed to ride on their carrier atoms, with C—H = 0.93–0.98 Å, and with U_iso = 1.5U_eq(C) for methyl H atoms or 1.2U_eq(C) otherwise. In (III), atoms C4 and C5 of the cyclo­octane ring are each disordered over two sites and were refined with site-occupancy factors of 0.652 (9) and 0.348 (9).

Computing details

For all compounds, data collection: APEX2 (Bruker, 2004); cell refinement: SAINT (Bruker, 2004); data reduction: SAINT (Bruker, 2004); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures

Fig. 1. The molecular structure of (I), showing 30% probability displacement ellipsoids and the atom-numbering scheme.

Fig. 2. The molecular structure of (II), showing 30% probability displacement ellipsoids and the atom-numbering scheme.

Fig. 3. The molecular structure of (III), showing 30% probability displacement ellipsoids and the atom-numbering scheme. The minor disorder components of atoms C4 (C4') and C5 (C5') are indicated by dashed lines. [Added text OK?]

Fig. 4. A partial packing view of (I). A pair of molecules are interconnected through a π–π stacking interaction (dotted lines; symmetry code: -x, -y, -z + 1) and further linked through a C—H···N interaction (dashed lines), generating C(7) chain motifs. [Symmetry code: (i) x + 1, y, z.]

Fig. 5. A partial packing view of (II). Two C—H···N interactions are shown (dashed lines), one forming an inversion-related dimer generating an R₂²(18) motif [symmetry code: (ii) -x, -y + 1, -z] and the other linked by a C(7) motif [symmetry code: (i) x + 1, y, z]. A C14—H14···O2 interaction (dashed lines) forms a C(12) motif that lies along the c axis of the unit cell [symmetry code: (iii) x, y, z + 1]. [No symmetry code iii visible - please clarify]

Fig. 6. A partial packing view of (III). A C14—H14···O2 [labels are C97—H97A···O2ⁱⁱ - please clarify] interaction (dashed lines) generates an R₂²(6) ring motif [symmetry code: (i) -x, -y + 1, -z]. A C92—H92···O1ⁱ interaction (dashed lines) forms a C(7) motif that lies along the a axis of the unit cell [rymmetry code: (ii) x - 1, y, z].

(I) 2-Methoxy-4-(4-methoxyphenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine-3-carbonitrile

Crystal data

C20H22N2O2	F(000) = 688
Mr = 322.40	Dx = 1.272 Mg m^−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 2000 reflections
a = 9.1018 (3) Å	θ = 2–27°
b = 13.6319 (4) Å	µ = 0.08 mm^−1
c = 13.5920 (4) Å	T = 293 K
β = 93.545 (2)°	Block, colourless
V = 1683.20 (9) Å^3	0.24 × 0.22 × 0.20 mm
Z = 4

Data collection

Bruker Kappa APEXII area-detector diffractometer	3312 independent reflections
Radiation source: fine-focus sealed tube	2605 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.028
Detector resolution: 0 pixels mm^-1	θmax = 26.0°, θmin = 2.1°
ω and φ scans	h = −9→11
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	k = −16→16
Tmin = 0.983, Tmax = 0.984	l = −16→16
14067 measured reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.036	H-atom parameters constrained
wR(F^2) = 0.106	w = 1/[σ^2(Fo^2) + (0.0532P)^2 + 0.2615P] where P = (Fo^2 + 2Fc^2)/3
S = 1.04	(Δ/σ)max < 0.001
3312 reflections	Δρmax = 0.17 e Å^−3
220 parameters	Δρmin = −0.13 e Å^−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0068 (15)

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
C1	0.01417 (15)	0.15522 (9)	0.53767 (9)	0.0416 (3)
C2	−0.06148 (18)	0.19261 (10)	0.62518 (10)	0.0529 (4)
H2A	−0.0598	0.1420	0.6754	0.064*
H2B	−0.1636	0.2067	0.6056	0.064*
C3	0.0114 (2)	0.28537 (11)	0.66878 (11)	0.0615 (4)
H3A	−0.0436	0.3071	0.7236	0.074*
H3B	0.1100	0.2689	0.6947	0.074*
C4	0.02150 (18)	0.36973 (11)	0.59681 (11)	0.0566 (4)
H4A	0.0939	0.3529	0.5501	0.068*
H4B	0.0578	0.4269	0.6331	0.068*
C5	−0.12138 (18)	0.39771 (11)	0.53902 (11)	0.0562 (4)
H5A	−0.2032	0.3730	0.5742	0.067*
H5B	−0.1289	0.4687	0.5377	0.067*
C6	−0.13748 (18)	0.36008 (11)	0.43330 (11)	0.0546 (4)
H6A	−0.0502	0.3792	0.4006	0.066*
H6B	−0.2205	0.3935	0.4000	0.066*
C7	−0.15963 (15)	0.24967 (10)	0.41844 (10)	0.0479 (3)
H7A	−0.2379	0.2289	0.4590	0.058*
H7B	−0.1937	0.2388	0.3503	0.058*
C8	−0.02809 (14)	0.18353 (9)	0.44138 (9)	0.0389 (3)
C9	0.05028 (13)	0.14299 (8)	0.36540 (9)	0.0357 (3)
C10	0.16528 (14)	0.07805 (9)	0.38998 (9)	0.0379 (3)
C11	0.19909 (14)	0.05635 (9)	0.48967 (9)	0.0409 (3)
C12	0.24790 (14)	0.03207 (9)	0.31657 (9)	0.0408 (3)
C13	0.34950 (18)	−0.02813 (12)	0.61122 (11)	0.0583 (4)
H13A	0.3778	0.0312	0.6455	0.087*
H13B	0.4300	−0.0737	0.6157	0.087*
H13C	0.2661	−0.0565	0.6405	0.087*
C91	0.01389 (13)	0.16478 (9)	0.25910 (9)	0.0366 (3)
C92	0.04014 (15)	0.25691 (9)	0.21951 (10)	0.0431 (3)
H92	0.0780	0.3067	0.2605	0.052*
C93	0.01094 (15)	0.27545 (10)	0.12073 (10)	0.0465 (3)
H93	0.0305	0.3371	0.0953	0.056*
C94	−0.04749 (14)	0.20262 (10)	0.05899 (9)	0.0430 (3)
C95	−0.07455 (15)	0.11079 (10)	0.09681 (9)	0.0450 (3)
H95	−0.1134	0.0614	0.0558	0.054*
C96	−0.04344 (15)	0.09281 (9)	0.19631 (9)	0.0426 (3)
H96	−0.0616	0.0308	0.2214	0.051*
C97	−0.1339 (2)	0.15810 (14)	−0.10359 (11)	0.0693 (5)
H97A	−0.0670	0.1039	−0.1067	0.104*
H97B	−0.1500	0.1867	−0.1679	0.104*
H97C	−0.2259	0.1353	−0.0812	0.104*
N1	0.12650 (13)	0.09321 (8)	0.56144 (8)	0.0439 (3)
N2	0.31438 (14)	−0.00665 (9)	0.25930 (9)	0.0555 (3)
O1	0.31150 (11)	−0.00624 (8)	0.50960 (7)	0.0537 (3)
O2	−0.07348 (13)	0.22916 (8)	−0.03738 (7)	0.0627 (3)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0499 (8)	0.0371 (7)	0.0383 (7)	−0.0094 (6)	0.0072 (6)	−0.0019 (5)
C2	0.0710 (10)	0.0479 (8)	0.0418 (7)	−0.0061 (7)	0.0186 (7)	−0.0004 (6)
C3	0.0879 (12)	0.0550 (9)	0.0421 (8)	−0.0043 (8)	0.0094 (8)	−0.0091 (7)
C4	0.0680 (10)	0.0472 (8)	0.0551 (9)	−0.0094 (7)	0.0073 (7)	−0.0076 (7)
C5	0.0651 (10)	0.0433 (8)	0.0616 (9)	0.0007 (7)	0.0141 (7)	−0.0064 (7)
C6	0.0583 (9)	0.0482 (8)	0.0573 (9)	0.0115 (7)	0.0037 (7)	−0.0021 (7)
C7	0.0440 (8)	0.0511 (8)	0.0488 (8)	0.0012 (6)	0.0031 (6)	−0.0078 (6)
C8	0.0407 (7)	0.0355 (6)	0.0408 (7)	−0.0061 (5)	0.0038 (5)	−0.0036 (5)
C9	0.0384 (7)	0.0323 (6)	0.0361 (6)	−0.0064 (5)	−0.0001 (5)	−0.0018 (5)
C10	0.0409 (7)	0.0372 (7)	0.0356 (6)	−0.0040 (5)	0.0022 (5)	0.0006 (5)
C11	0.0437 (7)	0.0393 (7)	0.0391 (7)	−0.0040 (6)	−0.0014 (5)	0.0038 (5)
C12	0.0426 (7)	0.0404 (7)	0.0392 (7)	0.0012 (6)	0.0003 (6)	0.0041 (5)
C13	0.0603 (9)	0.0637 (9)	0.0488 (8)	−0.0056 (7)	−0.0127 (7)	0.0166 (7)
C91	0.0373 (7)	0.0373 (6)	0.0351 (6)	0.0012 (5)	0.0012 (5)	−0.0007 (5)
C92	0.0491 (8)	0.0379 (7)	0.0418 (7)	−0.0027 (6)	−0.0006 (6)	−0.0028 (5)
C93	0.0548 (8)	0.0392 (7)	0.0455 (7)	0.0014 (6)	0.0028 (6)	0.0069 (6)
C94	0.0436 (7)	0.0503 (8)	0.0349 (6)	0.0056 (6)	0.0012 (5)	0.0035 (5)
C95	0.0505 (8)	0.0454 (7)	0.0384 (7)	−0.0028 (6)	−0.0033 (6)	−0.0064 (6)
C96	0.0503 (8)	0.0365 (7)	0.0407 (7)	−0.0028 (6)	−0.0002 (6)	0.0007 (5)
C97	0.0867 (12)	0.0876 (12)	0.0330 (7)	−0.0011 (10)	−0.0018 (7)	−0.0023 (8)
N1	0.0532 (7)	0.0436 (6)	0.0349 (6)	−0.0062 (5)	0.0024 (5)	0.0020 (4)
N2	0.0590 (8)	0.0597 (8)	0.0484 (7)	0.0113 (6)	0.0080 (6)	0.0010 (6)
O1	0.0534 (6)	0.0635 (6)	0.0434 (5)	0.0102 (5)	−0.0034 (4)	0.0110 (4)
O2	0.0832 (8)	0.0671 (7)	0.0369 (5)	−0.0011 (6)	−0.0053 (5)	0.0075 (5)

Geometric parameters (Å, º)

C1—N1	1.3503 (17)	C10—C11	1.4023 (17)
C1—C8	1.3956 (17)	C10—C12	1.4306 (18)
C1—C2	1.5000 (18)	C11—N1	1.3115 (17)
C2—C3	1.530 (2)	C11—O1	1.3468 (16)
C2—H2A	0.9700	C12—N2	1.1441 (17)
C2—H2B	0.9700	C13—O1	1.4343 (16)
C3—C4	1.516 (2)	C13—H13A	0.9600
C3—H3A	0.9700	C13—H13B	0.9600
C3—H3B	0.9700	C13—H13C	0.9600
C4—C5	1.526 (2)	C91—C96	1.3813 (17)
C4—H4A	0.9700	C91—C92	1.3928 (18)
C4—H4B	0.9700	C92—C93	1.3758 (18)
C5—C6	1.524 (2)	C92—H92	0.9300
C5—H5A	0.9700	C93—C94	1.3847 (19)
C5—H5B	0.9700	C93—H93	0.9300
C6—C7	1.530 (2)	C94—O2	1.3654 (15)
C6—H6A	0.9700	C94—C95	1.3812 (19)
C6—H6B	0.9700	C95—C96	1.3863 (18)
C7—C8	1.5157 (19)	C95—H95	0.9300
C7—H7A	0.9700	C96—H96	0.9300
C7—H7B	0.9700	C97—O2	1.411 (2)
C8—C9	1.4042 (17)	C97—H97A	0.9600
C9—C10	1.3956 (17)	C97—H97B	0.9600
C9—C91	1.4921 (16)	C97—H97C	0.9600
N1—C1—C8	123.93 (12)	C10—C9—C91	118.45 (10)
N1—C1—C2	113.63 (12)	C8—C9—C91	122.78 (11)
C8—C1—C2	122.43 (13)	C9—C10—C11	118.79 (11)
C1—C2—C3	112.25 (12)	C9—C10—C12	121.99 (11)
C1—C2—H2A	109.2	C11—C10—C12	119.21 (12)
C3—C2—H2A	109.2	N1—C11—O1	120.30 (11)
C1—C2—H2B	109.2	N1—C11—C10	123.18 (12)
C3—C2—H2B	109.2	O1—C11—C10	116.52 (12)
H2A—C2—H2B	107.9	N2—C12—C10	178.35 (14)
C4—C3—C2	114.78 (12)	O1—C13—H13A	109.5
C4—C3—H3A	108.6	O1—C13—H13B	109.5
C2—C3—H3A	108.6	H13A—C13—H13B	109.5
C4—C3—H3B	108.6	O1—C13—H13C	109.5
C2—C3—H3B	108.6	H13A—C13—H13C	109.5
H3A—C3—H3B	107.5	H13B—C13—H13C	109.5
C3—C4—C5	115.98 (14)	C96—C91—C92	117.97 (11)
C3—C4—H4A	108.3	C96—C91—C9	120.64 (11)
C5—C4—H4A	108.3	C92—C91—C9	121.37 (11)
C3—C4—H4B	108.3	C93—C92—C91	121.01 (12)
C5—C4—H4B	108.3	C93—C92—H92	119.5
H4A—C4—H4B	107.4	C91—C92—H92	119.5
C6—C5—C4	115.49 (13)	C92—C93—C94	120.23 (12)
C6—C5—H5A	108.4	C92—C93—H93	119.9
C4—C5—H5A	108.4	C94—C93—H93	119.9
C6—C5—H5B	108.4	O2—C94—C95	124.95 (12)
C4—C5—H5B	108.4	O2—C94—C93	115.38 (12)
H5A—C5—H5B	107.5	C95—C94—C93	119.66 (12)
C5—C6—C7	117.36 (13)	C94—C95—C96	119.53 (12)
C5—C6—H6A	108.0	C94—C95—H95	120.2
C7—C6—H6A	108.0	C96—C95—H95	120.2
C5—C6—H6B	108.0	C91—C96—C95	121.59 (12)
C7—C6—H6B	108.0	C91—C96—H96	119.2
H6A—C6—H6B	107.2	C95—C96—H96	119.2
C8—C7—C6	117.52 (12)	O2—C97—H97A	109.5
C8—C7—H7A	107.9	O2—C97—H97B	109.5
C6—C7—H7A	107.9	H97A—C97—H97B	109.5
C8—C7—H7B	107.9	O2—C97—H97C	109.5
C6—C7—H7B	107.9	H97A—C97—H97C	109.5
H7A—C7—H7B	107.2	H97B—C97—H97C	109.5
C1—C8—C9	117.25 (12)	C11—N1—C1	118.08 (11)
C1—C8—C7	121.72 (11)	C11—O1—C13	117.41 (11)
C9—C8—C7	120.90 (11)	C94—O2—C97	117.88 (12)
C10—C9—C8	118.76 (11)
N1—C1—C2—C3	87.92 (15)	C12—C10—C11—O1	1.29 (18)
C8—C1—C2—C3	−91.42 (17)	C10—C9—C91—C96	66.95 (16)
C1—C2—C3—C4	56.67 (19)	C8—C9—C91—C96	−111.77 (14)
C2—C3—C4—C5	51.18 (19)	C10—C9—C91—C92	−111.28 (14)
C3—C4—C5—C6	−101.25 (16)	C8—C9—C91—C92	70.01 (17)
C4—C5—C6—C7	69.96 (18)	C96—C91—C92—C93	−0.50 (19)
C5—C6—C7—C8	−72.66 (18)	C9—C91—C92—C93	177.77 (12)
N1—C1—C8—C9	1.24 (18)	C91—C92—C93—C94	1.0 (2)
C2—C1—C8—C9	−179.49 (11)	C92—C93—C94—O2	179.40 (12)
N1—C1—C8—C7	177.09 (12)	C92—C93—C94—C95	−0.9 (2)
C2—C1—C8—C7	−3.64 (19)	O2—C94—C95—C96	−179.98 (12)
C6—C7—C8—C1	80.76 (17)	C93—C94—C95—C96	0.3 (2)
C6—C7—C8—C9	−103.54 (14)	C92—C91—C96—C95	−0.1 (2)
C1—C8—C9—C10	−0.46 (17)	C9—C91—C96—C95	−178.35 (12)
C7—C8—C9—C10	−176.35 (11)	C94—C95—C96—C91	0.2 (2)
C1—C8—C9—C91	178.25 (11)	O1—C11—N1—C1	−179.65 (11)
C7—C8—C9—C91	2.36 (18)	C10—C11—N1—C1	−0.20 (19)
C8—C9—C10—C11	−0.53 (17)	C8—C1—N1—C11	−0.91 (19)
C91—C9—C10—C11	−179.30 (11)	C2—C1—N1—C11	179.76 (11)
C8—C9—C10—C12	178.53 (11)	N1—C11—O1—C13	−1.54 (18)
C91—C9—C10—C12	−0.24 (17)	C10—C11—O1—C13	178.97 (12)
C9—C10—C11—N1	0.91 (19)	C95—C94—O2—C97	0.7 (2)
C12—C10—C11—N1	−178.18 (12)	C93—C94—O2—C97	−179.58 (14)
C9—C10—C11—O1	−179.62 (11)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C92—H92···N2^i	0.93	2.75	3.490 (2)	138

Symmetry code: (i) −x+1/2, y+1/2, −z+1/2.

(II) 2-Ethoxy-4-(3-nitrophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine-3-carbonitrile

Crystal data

C20H21N3O3	F(000) = 744
Mr = 351.40	Dx = 1.276 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 2000 reflections
a = 13.2948 (6) Å	θ = 2–26°
b = 11.0251 (4) Å	µ = 0.09 mm^−1
c = 14.0788 (5) Å	T = 293 K
β = 117.566 (2)°	Block, colourless
V = 1829.36 (12) Å^3	0.21 × 0.20 × 0.19 mm
Z = 4

Data collection

Bruker Kappa APEXII area-detector diffractometer	3399 independent reflections
Radiation source: fine-focus sealed tube	2571 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.030
Detector resolution: 0 pixels mm^-1	θmax = 25.5°, θmin = 2.5°
ω and φ scans	h = −12→16
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	k = −13→13
Tmin = 0.980, Tmax = 0.984	l = −17→11
16156 measured reflections

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)] = 0.043	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.130	H-atom parameters constrained
S = 1.07	w = 1/[σ^2(Fo^2) + (0.0645P)^2 + 0.3091P] where P = (Fo^2 + 2Fc^2)/3
3399 reflections	(Δ/σ)max < 0.001
236 parameters	Δρmax = 0.30 e Å^−3
0 restraints	Δρmin = −0.23 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
C1	0.36597 (13)	0.41011 (14)	0.52565 (12)	0.0452 (4)
C2	0.46750 (15)	0.34889 (16)	0.61207 (13)	0.0547 (4)
H2A	0.4883	0.3909	0.6791	0.066*
H2B	0.5305	0.3566	0.5956	0.066*
C3	0.45028 (17)	0.21487 (17)	0.62719 (14)	0.0627 (5)
H3A	0.5092	0.1900	0.6970	0.075*
H3B	0.3781	0.2060	0.6281	0.075*
C4	0.45164 (18)	0.12803 (17)	0.54357 (16)	0.0677 (5)
H4A	0.5217	0.1406	0.5394	0.081*
H4B	0.4531	0.0458	0.5686	0.081*
C5	0.35358 (17)	0.13832 (16)	0.43116 (16)	0.0640 (5)
H5A	0.3299	0.0571	0.4034	0.077*
H5B	0.2904	0.1765	0.4360	0.077*
C6	0.37691 (17)	0.20869 (16)	0.35095 (15)	0.0595 (5)
H6A	0.3086	0.2084	0.2827	0.071*
H6B	0.4352	0.1664	0.3409	0.071*
C7	0.41459 (15)	0.33994 (15)	0.38117 (13)	0.0503 (4)
H7A	0.4922	0.3407	0.4379	0.060*
H7B	0.4133	0.3809	0.3196	0.060*
C8	0.34122 (13)	0.40896 (13)	0.41786 (12)	0.0432 (4)
C9	0.24267 (13)	0.46828 (13)	0.34510 (12)	0.0424 (4)
C10	0.17521 (13)	0.52697 (14)	0.38253 (12)	0.0451 (4)
C11	0.20782 (14)	0.52080 (15)	0.49244 (13)	0.0494 (4)
C12	0.07292 (16)	0.58885 (15)	0.31150 (13)	0.0506 (4)
C13	0.1672 (2)	0.5605 (2)	0.63766 (16)	0.0784 (6)
H13A	0.2460	0.5812	0.6837	0.094*
H13B	0.1551	0.4769	0.6513	0.094*
C14	0.0923 (2)	0.64137 (19)	0.65899 (17)	0.0779 (6)
H14A	0.1065	0.7239	0.6471	0.117*
H14B	0.1068	0.6318	0.7320	0.117*
H14C	0.0146	0.6213	0.6118	0.117*
C91	0.20771 (12)	0.46913 (14)	0.22788 (12)	0.0442 (4)
C92	0.13633 (16)	0.38019 (17)	0.16128 (15)	0.0617 (5)
H92	0.1084	0.3204	0.1894	0.074*
C93	0.10621 (17)	0.3797 (2)	0.05310 (17)	0.0750 (6)
H93	0.0590	0.3190	0.0093	0.090*
C94	0.14530 (17)	0.4679 (2)	0.00973 (14)	0.0680 (6)
H94	0.1247	0.4681	−0.0630	0.082*
C95	0.21497 (14)	0.55493 (17)	0.07608 (13)	0.0541 (4)
C96	0.24723 (13)	0.55742 (15)	0.18423 (12)	0.0464 (4)
H96	0.2952	0.6181	0.2274	0.056*
N1	0.29927 (12)	0.46418 (12)	0.56137 (10)	0.0510 (3)
N3	0.26034 (18)	0.64955 (18)	0.03254 (14)	0.0762 (5)
N2	−0.00905 (15)	0.63649 (15)	0.25574 (13)	0.0691 (4)
O1	0.13996 (11)	0.57615 (12)	0.52573 (9)	0.0633 (4)
O2	0.2225 (2)	0.65610 (18)	−0.06352 (13)	0.1267 (8)
O3	0.33311 (16)	0.71707 (19)	0.09448 (15)	0.1031 (6)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0487 (9)	0.0458 (8)	0.0422 (8)	−0.0024 (7)	0.0219 (7)	−0.0005 (7)
C2	0.0538 (10)	0.0650 (10)	0.0421 (9)	0.0037 (8)	0.0195 (8)	0.0010 (8)
C3	0.0697 (12)	0.0686 (11)	0.0517 (10)	0.0151 (9)	0.0296 (9)	0.0147 (9)
C4	0.0848 (14)	0.0555 (10)	0.0706 (13)	0.0134 (10)	0.0426 (12)	0.0117 (9)
C5	0.0777 (13)	0.0489 (9)	0.0726 (13)	−0.0017 (9)	0.0409 (11)	−0.0024 (9)
C6	0.0693 (11)	0.0592 (10)	0.0566 (10)	0.0074 (9)	0.0347 (9)	−0.0042 (8)
C7	0.0539 (9)	0.0563 (9)	0.0475 (9)	0.0049 (8)	0.0290 (8)	0.0041 (7)
C8	0.0460 (9)	0.0434 (8)	0.0421 (8)	−0.0030 (7)	0.0219 (7)	−0.0005 (6)
C9	0.0476 (9)	0.0415 (8)	0.0407 (8)	−0.0063 (7)	0.0227 (7)	−0.0032 (6)
C10	0.0491 (9)	0.0469 (8)	0.0415 (9)	0.0014 (7)	0.0230 (7)	0.0007 (7)
C11	0.0583 (10)	0.0523 (9)	0.0452 (9)	0.0044 (8)	0.0304 (8)	0.0003 (7)
C12	0.0578 (10)	0.0548 (9)	0.0449 (9)	0.0042 (8)	0.0287 (9)	0.0002 (8)
C13	0.1018 (16)	0.0961 (15)	0.0561 (11)	0.0344 (13)	0.0524 (12)	0.0201 (11)
C14	0.1026 (16)	0.0831 (14)	0.0646 (12)	0.0099 (12)	0.0527 (13)	0.0007 (11)
C91	0.0423 (8)	0.0516 (9)	0.0389 (8)	0.0027 (7)	0.0191 (7)	−0.0041 (7)
C92	0.0595 (11)	0.0641 (11)	0.0582 (11)	−0.0098 (9)	0.0245 (9)	−0.0140 (9)
C93	0.0622 (12)	0.0878 (14)	0.0568 (12)	−0.0054 (11)	0.0122 (10)	−0.0334 (11)
C94	0.0644 (12)	0.0950 (15)	0.0362 (9)	0.0212 (11)	0.0160 (9)	−0.0072 (10)
C95	0.0521 (10)	0.0729 (11)	0.0375 (9)	0.0194 (9)	0.0209 (8)	0.0081 (8)
C96	0.0442 (8)	0.0572 (9)	0.0349 (8)	0.0048 (7)	0.0157 (7)	0.0011 (7)
N1	0.0595 (8)	0.0560 (8)	0.0401 (7)	0.0062 (7)	0.0254 (7)	0.0026 (6)
N3	0.0924 (14)	0.0938 (13)	0.0529 (11)	0.0309 (11)	0.0425 (10)	0.0276 (10)
N2	0.0669 (10)	0.0798 (11)	0.0576 (10)	0.0188 (9)	0.0263 (9)	0.0075 (8)
O1	0.0737 (8)	0.0818 (8)	0.0452 (7)	0.0237 (7)	0.0367 (6)	0.0083 (6)
O2	0.204 (2)	0.1275 (15)	0.0590 (10)	0.0287 (15)	0.0699 (13)	0.0315 (10)
O3	0.0989 (12)	0.1287 (15)	0.0851 (12)	−0.0155 (12)	0.0455 (10)	0.0329 (11)

Geometric parameters (Å, º)

C1—N1	1.344 (2)	C10—C12	1.434 (2)
C1—C8	1.396 (2)	C11—N1	1.311 (2)
C1—C2	1.496 (2)	C11—O1	1.3406 (19)
C2—C3	1.525 (3)	C12—N2	1.135 (2)
C2—H2A	0.9700	C13—O1	1.455 (2)
C2—H2B	0.9700	C13—C14	1.468 (3)
C3—C4	1.524 (3)	C13—H13A	0.9700
C3—H3A	0.9700	C13—H13B	0.9700
C3—H3B	0.9700	C14—H14A	0.9600
C4—C5	1.519 (3)	C14—H14B	0.9600
C4—H4A	0.9700	C14—H14C	0.9600
C4—H4B	0.9700	C91—C96	1.378 (2)
C5—C6	1.516 (3)	C91—C92	1.385 (2)
C5—H5A	0.9700	C92—C93	1.384 (3)
C5—H5B	0.9700	C92—H92	0.9300
C6—C7	1.526 (2)	C93—C94	1.372 (3)
C6—H6A	0.9700	C93—H93	0.9300
C6—H6B	0.9700	C94—C95	1.360 (3)
C7—C8	1.505 (2)	C94—H94	0.9300
C7—H7A	0.9700	C95—C96	1.378 (2)
C7—H7B	0.9700	C95—N3	1.473 (3)
C8—C9	1.397 (2)	C96—H96	0.9300
C9—C10	1.392 (2)	N3—O2	1.207 (2)
C9—C91	1.493 (2)	N3—O3	1.212 (2)
C10—C11	1.402 (2)
N1—C1—C8	123.10 (14)	C8—C9—C91	121.33 (13)
N1—C1—C2	113.51 (13)	C9—C10—C11	118.09 (14)
C8—C1—C2	123.37 (14)	C9—C10—C12	121.76 (14)
C1—C2—C3	114.42 (15)	C11—C10—C12	120.12 (14)
C1—C2—H2A	108.7	N1—C11—O1	120.12 (14)
C3—C2—H2A	108.7	N1—C11—C10	123.18 (14)
C1—C2—H2B	108.7	O1—C11—C10	116.70 (14)
C3—C2—H2B	108.7	N2—C12—C10	178.85 (19)
H2A—C2—H2B	107.6	O1—C13—C14	107.30 (16)
C4—C3—C2	116.40 (15)	O1—C13—H13A	110.3
C4—C3—H3A	108.2	C14—C13—H13A	110.3
C2—C3—H3A	108.2	O1—C13—H13B	110.3
C4—C3—H3B	108.2	C14—C13—H13B	110.3
C2—C3—H3B	108.2	H13A—C13—H13B	108.5
H3A—C3—H3B	107.3	C13—C14—H14A	109.5
C5—C4—C3	116.53 (16)	C13—C14—H14B	109.5
C5—C4—H4A	108.2	H14A—C14—H14B	109.5
C3—C4—H4A	108.2	C13—C14—H14C	109.5
C5—C4—H4B	108.2	H14A—C14—H14C	109.5
C3—C4—H4B	108.2	H14B—C14—H14C	109.5
H4A—C4—H4B	107.3	C96—C91—C92	118.77 (15)
C6—C5—C4	116.21 (17)	C96—C91—C9	120.61 (14)
C6—C5—H5A	108.2	C92—C91—C9	120.61 (15)
C4—C5—H5A	108.2	C93—C92—C91	120.42 (18)
C6—C5—H5B	108.2	C93—C92—H92	119.8
C4—C5—H5B	108.2	C91—C92—H92	119.8
H5A—C5—H5B	107.4	C94—C93—C92	120.73 (18)
C5—C6—C7	115.57 (14)	C94—C93—H93	119.6
C5—C6—H6A	108.4	C92—C93—H93	119.6
C7—C6—H6A	108.4	C95—C94—C93	118.17 (16)
C5—C6—H6B	108.4	C95—C94—H94	120.9
C7—C6—H6B	108.4	C93—C94—H94	120.9
H6A—C6—H6B	107.4	C94—C95—C96	122.53 (18)
C8—C7—C6	113.20 (13)	C94—C95—N3	119.57 (16)
C8—C7—H7A	108.9	C96—C95—N3	117.89 (17)
C6—C7—H7A	108.9	C95—C96—C91	119.38 (16)
C8—C7—H7B	108.9	C95—C96—H96	120.3
C6—C7—H7B	108.9	C91—C96—H96	120.3
H7A—C7—H7B	107.8	C11—N1—C1	118.73 (13)
C1—C8—C9	117.52 (13)	O2—N3—O3	123.3 (2)
C1—C8—C7	120.91 (14)	O2—N3—C95	118.0 (2)
C9—C8—C7	121.47 (13)	O3—N3—C95	118.65 (16)
C10—C9—C8	119.33 (14)	C11—O1—C13	117.02 (14)
C10—C9—C91	119.33 (14)
N1—C1—C2—C3	93.08 (17)	C10—C9—C91—C96	92.78 (18)
C8—C1—C2—C3	−85.51 (19)	C8—C9—C91—C96	−87.75 (19)
C1—C2—C3—C4	75.8 (2)	C10—C9—C91—C92	−88.19 (19)
C2—C3—C4—C5	−67.7 (2)	C8—C9—C91—C92	91.29 (19)
C3—C4—C5—C6	99.8 (2)	C96—C91—C92—C93	0.5 (3)
C4—C5—C6—C7	−58.5 (2)	C9—C91—C92—C93	−178.51 (16)
C5—C6—C7—C8	−47.9 (2)	C91—C92—C93—C94	−0.8 (3)
N1—C1—C8—C9	0.6 (2)	C92—C93—C94—C95	0.5 (3)
C2—C1—C8—C9	179.08 (14)	C93—C94—C95—C96	0.0 (3)
N1—C1—C8—C7	−175.83 (14)	C93—C94—C95—N3	178.77 (17)
C2—C1—C8—C7	2.6 (2)	C94—C95—C96—C91	−0.2 (2)
C6—C7—C8—C1	89.35 (19)	N3—C95—C96—C91	−179.02 (14)
C6—C7—C8—C9	−86.96 (18)	C92—C91—C96—C95	0.0 (2)
C1—C8—C9—C10	1.1 (2)	C9—C91—C96—C95	179.01 (14)
C7—C8—C9—C10	177.51 (14)	O1—C11—N1—C1	−179.64 (14)
C1—C8—C9—C91	−178.40 (14)	C10—C11—N1—C1	0.6 (2)
C7—C8—C9—C91	−2.0 (2)	C8—C1—N1—C11	−1.5 (2)
C8—C9—C10—C11	−1.9 (2)	C2—C1—N1—C11	179.93 (15)
C91—C9—C10—C11	177.63 (14)	C94—C95—N3—O2	9.4 (3)
C8—C9—C10—C12	−179.72 (14)	C96—C95—N3—O2	−171.74 (18)
C91—C9—C10—C12	−0.2 (2)	C94—C95—N3—O3	−170.87 (19)
C9—C10—C11—N1	1.1 (2)	C96—C95—N3—O3	8.0 (3)
C12—C10—C11—N1	178.95 (16)	N1—C11—O1—C13	−5.4 (3)
C9—C10—C11—O1	−178.71 (14)	C10—C11—O1—C13	174.34 (17)
C12—C10—C11—O1	−0.8 (2)	C14—C13—O1—C11	172.45 (17)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C92—H92···N2^i	0.93	2.72	3.644 (2)	172
C94—H94···N2^ii	0.93	2.68	3.508 (2)	148
C14—H14B···O2^iii	0.96	2.57	3.468 (3)	155

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

(III) 2-Ethoxy-4-(4-methoxyphenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine-3-carbonitrile

Crystal data

C21H24N2O2	F(000) = 720
Mr = 336.42	Dx = 1.211 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 2000 reflections
a = 6.9763 (4) Å	θ = 2–26°
b = 17.8163 (8) Å	µ = 0.08 mm^−1
c = 14.9545 (8) Å	T = 293 K
β = 96.751 (2)°	Block, colourless
V = 1845.83 (17) Å^3	0.23 × 0.21 × 0.18 mm
Z = 4

Data collection

Bruker Kappa APEXII are-detector diffractometer	3433 independent reflections
Radiation source: fine-focus sealed tube	2330 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.034
Detector resolution: 0 pixels mm^-1	θmax = 25.5°, θmin = 2.3°
ω and φ scans	h = −8→8
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	k = −15→21
Tmin = 0.982, Tmax = 0.986	l = −18→18
17391 measured reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.044	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.124	w = 1/[σ^2(Fo^2) + (0.0565P)^2 + 0.3095P] where P = (Fo^2 + 2Fc^2)/3
S = 1.03	(Δ/σ)max < 0.001
3432 reflections	Δρmax = 0.16 e Å^−3
247 parameters	Δρmin = −0.14 e Å^−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.019 (2)

Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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)
C4	0.3917 (7)	0.0614 (3)	0.3831 (3)	0.0767 (18)	0.650 (10)
H4A	0.4061	0.1154	0.3792	0.092*	0.650 (10)
H4B	0.5063	0.0417	0.4183	0.092*	0.650 (10)
C5	0.2144 (9)	0.0436 (4)	0.4314 (4)	0.0824 (16)	0.650 (10)
H5A	0.2581	0.0282	0.4927	0.099*	0.650 (10)
H5B	0.1459	0.0016	0.4014	0.099*	0.650 (10)
C4'	0.2985 (15)	0.0132 (6)	0.3829 (6)	0.084 (3)	0.350 (10)
H4'A	0.163 (6)	−0.0141 (15)	0.3720 (8)	0.101*	0.350 (10)
H4'B	0.395 (5)	−0.0229 (19)	0.4218 (18)	0.101*	0.350 (10)
C5'	0.2768 (14)	0.0850 (7)	0.4349 (6)	0.077 (3)	0.350 (10)
H5'A	0.3326	0.0776	0.4968	0.092*	0.350 (10)
H5'B	0.3494	0.1244	0.4095	0.092*	0.350 (10)
C1	0.1900 (2)	0.13976 (9)	0.22592 (11)	0.0462 (4)
C2	0.2111 (3)	0.05650 (9)	0.22168 (13)	0.0581 (5)
H2A	0.2335	0.0422	0.1612	0.070*
H2B	0.0919	0.0330	0.2345	0.070*
C3	0.3762 (3)	0.02800 (12)	0.28812 (15)	0.0781 (6)
H3A	0.4962	0.0378	0.2634	0.094*
H3B	0.3636	−0.0260	0.2930	0.094*
C6	0.0715 (3)	0.11027 (12)	0.43436 (13)	0.0763 (6)
H6A	−0.0199	0.0980	0.4763	0.092*
H6B	0.1434	0.1541	0.4576	0.092*
C7	−0.0406 (3)	0.13033 (10)	0.34406 (12)	0.0580 (5)
H7A	−0.0846	0.0843	0.3136	0.070*
H7B	−0.1539	0.1589	0.3548	0.070*
C8	0.0726 (2)	0.17505 (9)	0.28252 (11)	0.0447 (4)
C9	0.0722 (2)	0.25347 (9)	0.28436 (10)	0.0412 (4)
C10	0.1861 (2)	0.29233 (8)	0.22914 (10)	0.0425 (4)
C11	0.3014 (2)	0.25129 (9)	0.17668 (10)	0.0450 (4)
C12	0.1862 (2)	0.37244 (11)	0.22536 (12)	0.0519 (4)
C13	0.5493 (3)	0.25098 (12)	0.07986 (15)	0.0738 (6)
H13A	0.4811	0.2290	0.0259	0.089*
H13B	0.6101	0.2109	0.1169	0.089*
C14	0.6963 (3)	0.30398 (13)	0.05557 (15)	0.0805 (7)
H14A	0.7863	0.2780	0.0228	0.121*
H14B	0.7636	0.3253	0.1093	0.121*
H14C	0.6349	0.3433	0.0187	0.121*
C91	−0.0421 (2)	0.29784 (8)	0.34408 (10)	0.0422 (4)
C92	−0.2375 (2)	0.30997 (11)	0.32232 (11)	0.0583 (5)
H92	−0.3010	0.2882	0.2706	0.070*
C93	−0.3392 (3)	0.35351 (11)	0.37575 (12)	0.0619 (5)
H93	−0.4703	0.3616	0.3594	0.074*
C94	−0.2495 (3)	0.38536 (9)	0.45333 (11)	0.0517 (4)
C95	−0.0566 (3)	0.37365 (10)	0.47637 (12)	0.0584 (5)
H95	0.0059	0.3947	0.5288	0.070*
C96	0.0453 (2)	0.33042 (10)	0.42164 (12)	0.0558 (5)
H96	0.1769	0.3231	0.4377	0.067*
C97	−0.2842 (3)	0.45843 (13)	0.58435 (14)	0.0813 (7)
H97A	−0.3814	0.4860	0.6108	0.122*
H97B	−0.1808	0.4916	0.5737	0.122*
H97C	−0.2350	0.4191	0.6246	0.122*
N1	0.30327 (19)	0.17777 (8)	0.17410 (9)	0.0486 (4)
N2	0.1864 (2)	0.43630 (10)	0.22199 (13)	0.0786 (5)
O1	0.41666 (17)	0.29140 (6)	0.12873 (8)	0.0588 (4)
O2	−0.3659 (2)	0.42667 (8)	0.50144 (9)	0.0728 (4)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C4	0.074 (3)	0.077 (3)	0.077 (3)	0.018 (3)	0.002 (2)	0.019 (2)
C5	0.101 (4)	0.074 (4)	0.074 (3)	0.014 (3)	0.017 (2)	0.024 (3)
C4'	0.095 (6)	0.067 (6)	0.087 (5)	0.008 (5)	−0.005 (4)	0.014 (4)
C5'	0.089 (6)	0.069 (7)	0.071 (4)	0.002 (5)	0.001 (4)	0.006 (4)
C1	0.0453 (9)	0.0424 (10)	0.0510 (9)	−0.0013 (7)	0.0068 (7)	−0.0020 (7)
C2	0.0660 (12)	0.0411 (11)	0.0698 (12)	0.0003 (8)	0.0189 (9)	−0.0068 (8)
C3	0.0842 (15)	0.0621 (14)	0.0901 (16)	0.0247 (11)	0.0196 (12)	0.0065 (11)
C6	0.0966 (17)	0.0705 (15)	0.0671 (13)	0.0069 (12)	0.0321 (12)	0.0141 (10)
C7	0.0590 (11)	0.0438 (11)	0.0758 (12)	−0.0006 (8)	0.0273 (9)	0.0036 (9)
C8	0.0415 (9)	0.0408 (10)	0.0523 (9)	−0.0001 (7)	0.0086 (7)	−0.0005 (7)
C9	0.0366 (8)	0.0421 (10)	0.0445 (9)	0.0014 (7)	0.0036 (7)	−0.0008 (7)
C10	0.0403 (8)	0.0378 (10)	0.0500 (9)	0.0016 (7)	0.0075 (7)	0.0005 (7)
C11	0.0421 (9)	0.0454 (11)	0.0485 (9)	−0.0011 (7)	0.0099 (7)	0.0020 (7)
C12	0.0459 (10)	0.0461 (12)	0.0660 (11)	0.0015 (8)	0.0169 (8)	0.0019 (8)
C13	0.0742 (13)	0.0734 (14)	0.0824 (14)	−0.0078 (10)	0.0456 (11)	−0.0175 (11)
C14	0.0745 (14)	0.0931 (17)	0.0806 (15)	−0.0051 (12)	0.0368 (12)	0.0017 (12)
C91	0.0414 (9)	0.0377 (9)	0.0486 (9)	0.0022 (7)	0.0100 (7)	0.0011 (7)
C92	0.0459 (10)	0.0800 (14)	0.0482 (10)	0.0092 (9)	0.0022 (8)	−0.0102 (9)
C93	0.0443 (10)	0.0835 (14)	0.0579 (11)	0.0178 (9)	0.0062 (8)	−0.0036 (9)
C94	0.0573 (11)	0.0476 (11)	0.0531 (10)	0.0093 (8)	0.0180 (8)	−0.0002 (8)
C95	0.0585 (11)	0.0603 (12)	0.0562 (11)	−0.0035 (9)	0.0054 (9)	−0.0156 (9)
C96	0.0422 (9)	0.0618 (12)	0.0630 (11)	0.0026 (8)	0.0045 (8)	−0.0120 (9)
C97	0.1011 (17)	0.0747 (15)	0.0724 (14)	0.0071 (12)	0.0284 (12)	−0.0233 (11)
N1	0.0519 (8)	0.0436 (9)	0.0521 (8)	0.0016 (6)	0.0135 (6)	−0.0039 (6)
N2	0.0770 (12)	0.0446 (11)	0.1192 (15)	0.0031 (8)	0.0328 (11)	0.0055 (9)
O1	0.0623 (8)	0.0517 (8)	0.0682 (8)	−0.0001 (5)	0.0312 (6)	0.0039 (6)
O2	0.0760 (9)	0.0771 (10)	0.0684 (9)	0.0215 (7)	0.0209 (7)	−0.0143 (7)

Geometric parameters (Å, º)

C4—C3	1.532 (5)	C9—C10	1.395 (2)
C4—C5	1.538 (10)	C9—C91	1.492 (2)
C4—H4A	0.9700	C10—C11	1.395 (2)
C4—H4B	0.9700	C10—C12	1.428 (2)
C5—C6	1.555 (6)	C11—N1	1.311 (2)
C5—H5A	0.9700	C11—O1	1.3443 (18)
C5—H5B	0.9700	C12—N2	1.139 (2)
C4'—C5'	1.513 (19)	C13—O1	1.438 (2)
C4'—C3	1.599 (10)	C13—C14	1.470 (3)
C4'—H4'A	1.0554	C13—H13A	0.9700
C4'—H4'B	1.0554	C13—H13B	0.9700
C5'—C6	1.501 (10)	C14—H14A	0.9600
C5'—H5'A	0.9700	C14—H14B	0.9600
C5'—H5'B	0.9700	C14—H14C	0.9600
C1—N1	1.3517 (19)	C91—C96	1.374 (2)
C1—C8	1.395 (2)	C91—C92	1.380 (2)
C1—C2	1.493 (2)	C92—C93	1.370 (2)
C2—C3	1.518 (3)	C92—H92	0.9300
C2—H2A	0.9700	C93—C94	1.375 (2)
C2—H2B	0.9700	C93—H93	0.9300
C3—H3A	0.9700	C94—O2	1.3625 (19)
C3—H3B	0.9700	C94—C95	1.365 (2)
C6—C7	1.521 (3)	C95—C96	1.380 (2)
C6—H6A	0.9700	C95—H95	0.9300
C6—H6B	0.9700	C96—H96	0.9300
C7—C8	1.508 (2)	C97—O2	1.420 (2)
C7—H7A	0.9700	C97—H97A	0.9600
C7—H7B	0.9700	C97—H97B	0.9600
C8—C9	1.397 (2)	C97—H97C	0.9600
C3—C4—C5	112.5 (6)	C6—C7—H7B	108.6
C3—C4—H4A	109.1	H7A—C7—H7B	107.6
C5—C4—H4A	109.1	C1—C8—C9	117.72 (14)
C3—C4—H4B	109.1	C1—C8—C7	121.26 (14)
C5—C4—H4B	109.1	C9—C8—C7	120.91 (14)
H4A—C4—H4B	107.8	C10—C9—C8	118.81 (14)
C4—C5—C6	114.2 (5)	C10—C9—C91	118.23 (14)
C4—C5—H5A	108.7	C8—C9—C91	122.95 (13)
C6—C5—H5A	108.7	C11—C10—C9	118.61 (14)
C4—C5—H5B	108.7	C11—C10—C12	119.90 (14)
C6—C5—H5B	108.7	C9—C10—C12	121.49 (14)
H5A—C5—H5B	107.6	N1—C11—O1	120.46 (14)
C5'—C4'—C3	112.4 (10)	N1—C11—C10	123.30 (14)
C5'—C4'—H4'A	109.1	O1—C11—C10	116.23 (14)
C3—C4'—H4'A	109.1	N2—C12—C10	179.73 (19)
C5'—C4'—H4'B	109.1	O1—C13—C14	108.25 (17)
C3—C4'—H4'B	109.1	O1—C13—H13A	110.0
H4'A—C4'—H4'B	107.9	C14—C13—H13A	110.0
C6—C5'—C4'	113.8 (9)	O1—C13—H13B	110.0
C6—C5'—H5'A	108.8	C14—C13—H13B	110.0
C4'—C5'—H5'A	108.8	H13A—C13—H13B	108.4
C6—C5'—H5'B	108.8	C13—C14—H14A	109.5
C4'—C5'—H5'B	108.8	C13—C14—H14B	109.5
H5'A—C5'—H5'B	107.7	H14A—C14—H14B	109.5
N1—C1—C8	123.14 (14)	C13—C14—H14C	109.5
N1—C1—C2	113.98 (14)	H14A—C14—H14C	109.5
C8—C1—C2	122.78 (14)	H14B—C14—H14C	109.5
C1—C2—C3	112.06 (16)	C96—C91—C92	117.45 (15)
C1—C2—H2A	109.2	C96—C91—C9	120.89 (14)
C3—C2—H2A	109.2	C92—C91—C9	121.62 (14)
C1—C2—H2B	109.2	C93—C92—C91	121.06 (16)
C3—C2—H2B	109.2	C93—C92—H92	119.5
H2A—C2—H2B	107.9	C91—C92—H92	119.5
C2—C3—C4	116.3 (2)	C92—C93—C94	120.68 (16)
C2—C3—C4'	109.0 (3)	C92—C93—H93	119.7
C2—C3—H3A	108.2	C94—C93—H93	119.7
C4—C3—H3A	108.2	O2—C94—C95	125.48 (17)
C4'—C3—H3A	140.0	O2—C94—C93	115.34 (16)
C2—C3—H3B	108.2	C95—C94—C93	119.17 (15)
C4—C3—H3B	108.2	C94—C95—C96	119.78 (16)
C4'—C3—H3B	74.1	C94—C95—H95	120.1
H3A—C3—H3B	107.4	C96—C95—H95	120.1
C5'—C6—C7	117.8 (4)	C91—C96—C95	121.85 (16)
C7—C6—C5	114.8 (2)	C91—C96—H96	119.1
C5'—C6—H6A	128.9	C95—C96—H96	119.1
C7—C6—H6A	108.6	O2—C97—H97A	109.5
C5—C6—H6A	108.6	O2—C97—H97B	109.5
C5'—C6—H6B	77.7	H97A—C97—H97B	109.5
C7—C6—H6B	108.6	O2—C97—H97C	109.5
C5—C6—H6B	108.6	H97A—C97—H97C	109.5
H6A—C6—H6B	107.6	H97B—C97—H97C	109.5
C8—C7—C6	114.50 (15)	C11—N1—C1	118.38 (13)
C8—C7—H7A	108.6	C11—O1—C13	117.77 (14)
C6—C7—H7A	108.6	C94—O2—C97	118.24 (16)
C8—C7—H7B	108.6
C3—C4—C5—C6	−103.1 (6)	C91—C9—C10—C12	−3.5 (2)
C3—C4'—C5'—C6	104.7 (10)	C9—C10—C11—N1	2.5 (2)
N1—C1—C2—C3	85.97 (19)	C12—C10—C11—N1	−177.37 (15)
C8—C1—C2—C3	−90.4 (2)	C9—C10—C11—O1	−176.25 (14)
C1—C2—C3—C4	44.3 (4)	C12—C10—C11—O1	3.9 (2)
C1—C2—C3—C4'	87.3 (5)	C10—C9—C91—C96	−76.2 (2)
C5—C4—C3—C2	62.5 (5)	C8—C9—C91—C96	102.68 (19)
C5—C4—C3—C4'	−26.3 (5)	C10—C9—C91—C92	101.52 (19)
C5'—C4'—C3—C2	−77.8 (8)	C8—C9—C91—C92	−79.6 (2)
C5'—C4'—C3—C4	30.7 (6)	C96—C91—C92—C93	0.7 (3)
C4'—C5'—C6—C7	−62.5 (10)	C9—C91—C92—C93	−177.16 (16)
C4'—C5'—C6—C5	30.6 (7)	C91—C92—C93—C94	−1.0 (3)
C4—C5—C6—C5'	−33.1 (7)	C92—C93—C94—O2	−179.21 (17)
C4—C5—C6—C7	70.3 (6)	C92—C93—C94—C95	0.5 (3)
C5'—C6—C7—C8	−42.0 (6)	O2—C94—C95—C96	179.93 (17)
C5—C6—C7—C8	−78.1 (4)	C93—C94—C95—C96	0.2 (3)
N1—C1—C8—C9	0.6 (2)	C92—C91—C96—C95	0.1 (3)
C2—C1—C8—C9	176.61 (15)	C9—C91—C96—C95	177.93 (16)
N1—C1—C8—C7	−175.59 (15)	C94—C95—C96—C91	−0.5 (3)
C2—C1—C8—C7	0.4 (2)	O1—C11—N1—C1	177.65 (14)
C6—C7—C8—C1	85.6 (2)	C10—C11—N1—C1	−1.0 (2)
C6—C7—C8—C9	−90.47 (19)	C8—C1—N1—C11	−0.6 (2)
C1—C8—C9—C10	0.9 (2)	C2—C1—N1—C11	−176.88 (14)
C7—C8—C9—C10	177.09 (15)	N1—C11—O1—C13	−3.9 (2)
C1—C8—C9—C91	−178.02 (14)	C10—C11—O1—C13	174.85 (15)
C7—C8—C9—C91	−1.8 (2)	C14—C13—O1—C11	−163.43 (17)
C8—C9—C10—C11	−2.3 (2)	C95—C94—O2—C97	−2.4 (3)
C91—C9—C10—C11	176.62 (14)	C93—C94—O2—C97	177.29 (17)
C8—C9—C10—C12	177.54 (15)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C92—H92···O1^i	0.93	2.72	3.559 (2)	150
C97—H97A···O2^ii	0.96	2.76	3.324 (2)	118

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