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Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 70| Part 11| November 2014| Pages 272-277
doi:10.1107/S1600536814020777

Conformation and crystal structures of 1-amino­cyclo­hexa­ne­acetic acid (β3,3Ac6c) in N-protected derivatives†

Naiem Ahmad Wani,a Vivek K. Gupta,b Rajni Kant,b Subrayashastry Aravindaa* and Rajkishor Raia*

aMedicinal Chemistry Division, Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi 180 001, India, and bX-ray Crystallography Laboratory, Post-Graduate Department of Physics & Electronics, University of Jammu, Jammu Tawi 180 006, India
*Correspondence e-mail: saravinda@iiim.ac.in, raj@iiim.ac.in

Edited by G. Smith, Queensland University of Technology, Australia (Received 25 August 2014; accepted 16 September 2014; online 4 October 2014)

N-Protected derivatives of 1-amino­cyclo­hexa­neacetic acid (β3,3-Ac6c), namely Valeroyl-β3,3-Ac6c-OH [2-(1-pentanamidocyclohexyl)acetic acid, C13H23NO3], (I), Fmoc-β3,3-Ac6c-OH [2-(1-{[(9H-fluoren-9-yloxy)carbonyl]amino}cyclohexyl)acetic acid, C23H25NO4], (II), and Pyr-β3,3-Ac6c-OH {2-[1-(pyrazine-2-amido)cyclohexyl]acetic acid, C13H17N3O3}, (III), were synthesized and their conformational properties were determined by X-ray diffraction analysis. The backbone torsion angles (φ, θ) for β3,3-Ac6c-OH are restricted to gauche conformations in all the derivatives, with a chair conformation of the cyclo­hexane ring. In the crystal structure of (I), the packing of mol­ecules shows both carb­oxy­lic acid R22(8) O—H⋯O and centrosymmetric R22(14) N—H⋯O hydrogen-bonding inter­actions, giving rise to chains along the c-axis direction. In (II), centrosymmetric carb­oxy­lic acid R22(8) O—H⋯O dimers are extended through N—H⋯O hydrogen bonds and together with inter-ring π–π inter­actions between Fmoc groups [ring centroid distance = 3.786 (2) Å], generate a layered structure lying parallel to (010). In the case of compound (III), carb­oxy­lic acid O—H⋯Npyrazine hydrogen bonds give rise to zigzag ribbon structures extending along the c-axis direction.

CCDC references: 1024488; 1024489; 1024490

1. Chemical context

β-Amino acids are homologues of α-amino acids, which are constituents of several bioactive natural and synthetic products. β-Amino acids have been used as building blocks in peptidomimetic drug design (Cheng et al. 2001[Cheng, R. P., Gellman, S. H. & DeGrado, W. F. (2001). Chem. Rev. 101, 3219-3232.]). The introduction of β-amino acids into pharmacologically active peptide sequences has shown improved biological activity and metabolic stability (Yamazaki et al., 1991[Yamazaki, T., Pröbsti, A., Schiller, P. W. & Goodman, M. (1991). Int. J. Pept. Protein Res. 37, 364-381.]; Huang et al., 1993[Huang, Z., Pröbstl, A., Spencer, J. R., Yamazaki, T. & Goodman, M. (1993). Int. J. Pept. Protein Res. 42, 352-365.]). The backbone conformation of a β-amino acid is defined by the torsional angles φ, θ and ψ (Banerjee & Balaram, 1997[Banerjee, A. & Balaram, P. (1997). Curr. Sci. 73, 1067-1077.]), as shown in Fig. 1[link]. The monosubstitution at the α- and β-carbon atoms plays an important role in the folding of oligomers of β-amino acids (Seebach et al., 2009[Seebach, D., Beck, A. K., Capone, S., Deniau, G., Grošelj, U. & Zass, E. (2009). Synthesis, 1, 1-32.]).

[Scheme 1]
[Figure 1]
Figure 1
Definition of backbone torsion angles for β-amino acids.

In order to investigate the effect of protecting groups and disubstitution on the conformation of β-amino acids, N-protected derivatives of 1-amino­cyclo­hexa­neacetic acid (β3,3Ac6c), i.e. Valeroyl-β3,3-Ac6c-OH (I)[link], Fmoc-β3,3-Ac6c-OH (II)[link] and Pyr-β3,3-Ac6c-OH (III)[link] were synthesized. The crystal structures of the three compounds were determined and are reported herein, together with their comparative conformational features.

[Scheme 2]

2. Structural commentary

The mol­ecular conformations of Valeroyl-β3,3-Ac6c-OH (I)[link], Fmoc-β3,3-Ac6c-OH (II)[link] and Pyr-β3,3-Ac6c-OH (III)[link] are shown in Fig. 2[link]. The backbone torsion angles (φ, θ) (C0′—N1—C1B —C1A and N1—C1B—C1A—C1′) adopt a gauche conformation in all three compounds [φ = 61.9 (3)°, θ = 57.2 (3)° for (I)[link]; φ = 56.7 (3)°, θ = 66.1 (3)° for (II)[link] and φ = 65.5 (2)°, θ = 55.0 (2)° for (III)[link]. The torsional angle ψ restricts the extended (trans) conformation for (I)[link] [166.9 (2)°] and (III)[link] [157.9 (2)°]. In the case of (II)[link], it is restricted to a gauche conformation [i.e. ψ = −63.6 (3)°]. In a 3,3-disubstituted β-amino acid residue, β3,3-Ac6c-OH, the cyclo­hexane ring imposes a restriction on the torsion angles φ and θ. The protecting groups at the N-terminus of (I)[link] adopts a trans geometry [ω0 (C4—C0′—N1—C1B) = 177.4 (2) for (I)[link], ω0 (O—C0′—N1—C1B) = −175.64 (19) for (II)[link] and ω0 (C6—C0—N1— C1A) = −170.04 (17)° for (III)]. In the case of the N-protected tert-butyl­oxycarbonyl (Boc) group, the protecting group adopts a cis geometry with ω0 = 14.50° (Vasudev et al., 2008[Vasudev, P. G., Rai, R., Shamala, N. & Balaram, P. (2008). Biopolymers, 90, 138-150.]). The cyclo­hexane ring adopts a chair conformation with axial amino and equatorial CH2CO groups in all the derivatives. In Pyr-β3,3-Ac6c-OH (III)[link], an intra­molecular N—H⋯N inter­action is observed between NH of the β3,3-Ac6c-OH residue and N3 of the pyrazine ring as shown in Fig. 3[link]c. There are no intra­molecular hydrogen bonding inter­actions observed in the crystal structures of derivatives (I)[link] and (II)[link].

[Figure 2]
Figure 2
ORTEP view of the mol­ecular conformation with the atom-labelling scheme. for Valeroyl-β3,3-Ac6c-OH (I)[link], (b) Fmoc-β3,3-Ac6c-OH (II)[link] and (c) Pyr-β3,3-Ac6c-OH (III)[link]. The displacement ellipsoids are drawn at the 40% probability level. H atoms are shown as small spheres of arbitrary radii.
[Figure 3]
Figure 3
(a) Packing of Valeroyl-β3,3-Ac6c-OH (I)[link] down the b-axis showing the alternative hydro­philic and hydro­phobic layers (b) space-filling model.

3. Supra­molecular features

In the crystals of compounds (I)[link] and (II)[link], inter­molecular hydrogen-bonding inter­actions generate primary centrosymmetric dimeric but different substructures (Figs. 4[link] and 5[link]). In (I)[link], N1—H⋯O1ii bond pairs (Table 1[link]) give a cyclic R22(14) motif which is extended into a ribbon structure along the c-axis direction through a second but non-centrosymmetric cyclic carb­oxy­lic acid R22(8) O2—H⋯Oi hydrogen-bond motif (Fig. 4[link]a). In (II)[link], the inter­molecular dimeric association is through the centrosymmetric R22(8) carb­oxy­lic acid hydrogen-bonding motif. Structure extension is through N1—H⋯O1′ (carbox­yl) hydrogen bonds (Table 2[link]), generating a two-dimensional layered structure lying parallel to (010) (Fig. 4[link]c). Also present in the structure are π–π inter­actions between the Fmoc groups with an inter­centroid distance of 3.786 (2) Å. Fig. 4[link]c shows the aromatic rings of Fmoc groups stacked in a face-to-face and edge-to-face manner, together with inter-plane distances that are within the range for stabilizing π–π inter­actions (Burley & Petsko, 1985[Burley, S. K. & Petsko, G. A. (1985). Science, 229, 23-28.]; Sengupta et al., 2005[Sengupta, A., Mahalakshmi, R., Shamala, N. & Balaram, P. (2005). J. Pept. Res. 65, 113-129.]) and have been reported to induce self-assembly in peptides (Wang & Chau, 2011[Wang, W. & Chau, Y. (2011). Chem. Commun. 47, 10224.]). In the case of (I)[link] and (II)[link], the mol­ecular packing in the crystals leads to the formation of alternating hydro­phobic and hydro­philic layers. In the crystals of (III)[link], in which no dimer substructure formation is present, the mol­ecules are linked by an inter­molecular carb­oxy­lic acid O2—H⋯N2i hydrogen bond (Table 3[link]) with a pyrazine N-atom acceptor, leading to the formation of a zigzag ribbon structure extending along the c-axis direction.

Table 1
Hydrogen-bond geometry (Å, °) for (I)[link]

D—H⋯A D—H H⋯A D⋯A D—H⋯A
O2—H2O⋯O0i 0.87 (4) 1.74 (4) 2.599 (3) 166 (4)
N1—H1N⋯O1ii 0.82 (3) 2.16 (3) 2.981 (3) 172 (2)
Symmetry codes: (i) [-x, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]; (ii) -x, -y, -z.

Table 2
Hydrogen-bond geometry (Å, °) for (II)[link]

D—H⋯A D—H H⋯A D⋯A D—H⋯A
N1—H1N⋯O1i 0.86 (2) 2.35 (2) 3.182 (3) 161 (2)
O2—H2O⋯O1ii 0.84 (3) 1.83 (3) 2.673 (3) 177 (1)
Symmetry codes: (i) x+1, y, z; (ii) -x, -y, -z.

Table 3
Hydrogen-bond geometry (Å, °) for (III)[link]

D—H⋯A D—H H⋯A D⋯A D—H⋯A
O2—H21⋯N2i 0.93 (4) 1.86 (4) 2.791 (3) 177 (4)
N1—H1N⋯N3 0.79 (2) 2.34 (2) 2.729 (2) 111.3 (19)
Symmetry code: (i) [-x+{\script{3\over 2}}, y, z+{\script{1\over 2}}].
[Figure 4]
Figure 4
(a) Packing of Fmoc-β3,3-Ac6c-OH (II)[link] down the a-axis. (b) Space-filling model showing the alternative hydro­philic and hydro­phobic layers (packing down the c-axis). (c) The environment of the Fmoc group showing the aromatic inter­action. The centroid–centroid distances are shown.
[Figure 5]
Figure 5
(a) Packing of Pyr-β3,3-Ac6c-OH (III)[link] down the a-axis showing the ribbon structure. (b) Zigzag arrangement of the ribbons along the c-axis.

4. Synthesis and crystallization

Preparation of Valeroyl-β3,3Ac6c-OH (I)[link]: β3,3Ac6c-OH (5 mmol, 785 mg) was dissolved in 5 ml of a 2M NaOH solution and a solution of 5 mmol of valeric anhydride (931 mg) dissolved in 1,4-dioxane was added, after which the mixture was stirred for 4 h at room temperature. On completion of the reaction, the 1,4-dioxane was evaporated and the product was extracted with diethyl ether (3 × 5 ml). The aqueous layer was acidified with 2M HCl and extracted with ethyl acetate (3 × 10ml) and the combined organic layer was washed with brine solution. The organic layer was passed over anhydrous Na2SO4 and evaporated to give Valeroyl-β3Ac6c-OH (yield: 1.1 g, 85.2%). Single crystals were grown by slow evaporation from a solution in methanol/water.

Preparation of Fmoc-β3,3Ac6c-OH (II)[link]: β3,3Ac6c-OH (10 mmol, 1.57 g) was dissolved in 1M Na2CO3 solution and Fmoc-OSu (10 mmol, 3.37 g) dissolved in CH3CN was added. The reaction mixture was stirred at room temperature for 6 h. After completion of the reaction, the CH3CN was evaporated and the residue was extracted with diethyl ether (3 × 10 ml). The aqueous layer was acidified with 2M HCl and extracted with ethyl acetate (3 × 15 ml). The combined organic layer was washed with brine solution. The ethyl acetate layer was passed over anhydrous Na2SO4 and evaporated. The residue was purified by crystallization in ethyl acetate/n-hexane, affording Fmoc-β3,3Ac6c-OH (yield: 3.0 g, 79%). Single crystals were obtained by slow evaporation from an ethyl acetate/n-hexane solution.

Preparation of Pyr-β3,3Ac6c-OH (III)[link]: Pyrazine carb­oxy­lic acid (3 mmol, 372 mg) was dissolved in dry CH2Cl2 and then 200 µl of N-methyl­morpholine was added, followed by β3,3Ac6c-OMe. HCl (3 mmol, 622.5 mg) and EDCI. HCl (3 mmol,576 mg) at 273 K. The reaction mixture was stirred at room temperature for 12 h. After completion of the reaction, water was added and the reaction mixture was extracted with CH2Cl2 (3 × 5ml). The combined organic layer was washed with 2M HCl (2 × 5ml), Na2CO3 (2 × 5ml) and brine solution (2 × 5ml). The organic layer was passed over anhydrous Na2SO4 and evaporated to give Pyr-β3,3Ac6c-OMe (Yield: 600 mg, 72.2%). Pyr-β3,3Ac6c-OMe (2 mmol, 554 mg) was dissolved in 2 ml of methanol and 1 ml of 2M NaOH, and the reaction mixture was stirred at room temperature for 4 h. Methanol was evaporated and the residue was extracted with diethyl ether (2 × 5ml). The aqueous layer was acidified with 2M HCl and extracted with ethyl acetate (3 × 5ml). The combined organic layer was washed with brine solution (1 × 5ml). The ethyl acetate layer was passed over anhydrous Na2SO4 and evaporated to give Pyr-β3,3Ac6c-OH (yield: 370 mg, 70.3%). Single crystals were grown from an ethanol/water solution.

5. Refinement details

Crystal data, data collection and structure refinement details are summarized in Table 4[link]. For derivative (I)[link], H atoms for N1 and O2 were located in a difference Fourier map and both their coordinates and Uiso values were refined. The remaining H atoms were positioned geometrically and were treated as riding on their parent C atoms, with C—H distances of 0.96–0.98 Å and with Uiso(H) = 1.2Ueq(C) or 1.5Ueq(methyl C). For derivatives (II)[link] and (III)[link], all hydrogen atoms were located from a difference Fourier map and both their coordinates and Uiso values were refined. In (II)[link], the carboxyl O—H distance was constrained to 0.84 Å. Although not of consequence with the achiral mol­ecule of (III)[link], which crystallized in the non-centrosymmetric space group Pca21, the structure was inverted in the final cycles of refinement as the Flack parameter was 0.8 (14). The inverted structure gave a value of 0.2 (14) for 1585 Friedel pairs.

Table 4
Experimental details

  (I) (II) (III)
Crystal data
Chemical formula C13H23NO3 C23H25NO4 C13H17N3O3
Mr 241.32 379.44 263.30
Crystal system, space group Monoclinic, P21/c Triclinic, P[\overline{1}] Orthorhombic, Pca21
Temperature (K) 291 291 291
a, b, c (Å) 9.5894 (5), 12.5007 (7), 12.3709 (8) 6.0834 (4), 12.7642 (9), 12.8399 (9) 8.7135 (1), 10.5321 (1), 14.3907 (2)
α, β, γ (°) 90, 109.984 (7), 90 94.018 (6), 92.295 (6), 100.489 (6) 90, 90, 90
V (Å3) 1393.66 (14) 976.53 (12) 1320.66 (3)
Z 4 2 4
Radiation type Mo Kα Mo Kα Mo Kα
μ (mm−1) 0.08 0.09 0.10
Crystal size (mm) 0.30 × 0.08 × 0.08 0.30 × 0.05 × 0.03 0.25 × 0.25 × 0.25
 
Data collection
Diffractometer Oxford Diffraction Xcalibur, Sapphire3 CCD Oxford Diffraction Xcalibur, Sapphire3 CCD Oxford Difraction Xcalibur, Sapphire3 CCD
Absorption correction Multi-scan (CrysAlis PRO; Oxford Diffraction, 2010[Oxford Diffraction (2010). CrysAlis PRO. Oxford Diffraction Ltd, Yarnton, England.]) Multi-scan (CrysAlis PRO; Oxford Diffraction, 2010[Oxford Diffraction (2010). CrysAlis PRO. Oxford Diffraction Ltd, Yarnton, England.]) Multi-scan (CrysAlis PRO; Oxford Diffraction, 2010[Oxford Diffraction (2010). CrysAlis PRO. Oxford Diffraction Ltd, Yarnton, England.])
Tmin, Tmax 0.797, 1.000 0.947, 1.000 0.931, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections 14087, 2737, 1717 7781, 4166, 2037 68869, 2878, 2670
Rint 0.047 0.047 0.034
(sin θ/λ)max (Å−1) 0.617 0.639 0.639
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.068, 0.213, 1.03 0.054, 0.086, 0.97 0.042, 0.106, 1.04
No. of reflections 2737 4166 2878
No. of parameters 162 353 240
No. of restraints 0 1 1
H-atom treatment H atoms treated by a mixture of independent and constrained refinement All H-atom parameters refined All H-atom parameters refined
Δρmax, Δρmin (e Å−3) 0.36, −0.30 0.15, −0.20 0.27, −0.26
Absolute structure – – (Flack, 1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.]): 1585 Friedel pairs
Absolute structure parameter – – 0.2 (14)
Computer programs: CrysAlis PRO (Oxford Diffraction, 2010[Oxford Diffraction (2010). CrysAlis PRO. Oxford Diffraction Ltd, Yarnton, England.]), SHELXS97 and SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), ORTEP-3 for Windows (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]) and PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]).

Supporting information

CCDC references: 1024488; 1024489; 1024490

Crystal structure: contains datablocks I, II, III, New_Global_Publ_Block. DOI: 10.1107/S1600536814020777/zs2313sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536814020777/zs2313Isup2.hkl

Structure factors: contains datablock II. DOI: 10.1107/S1600536814020777/zs2313IIsup3.hkl

Structure factors: contains datablock III. DOI: 10.1107/S1600536814020777/zs2313IIIsup4.hkl

Supporting information file. DOI: 10.1107/S1600536814020777/zs2313Isup5.cml

Supporting information file. DOI: 10.1107/S1600536814020777/zs2313IIsup6.cml

Supporting information file. DOI: 10.1107/S1600536814020777/zs2313IIIsup7.cml

checkCIF report


Chemical context top

β-Amino acids are homologues of α-amino acids, which are constituents of several bioactive natural and synthetic products. β-Amino acids have been used as building blocks in peptidomimetic drug design (Cheng et al. 2001). The introduction of β-amino acids into pharmacologically active peptide sequences has shown improved biological activity and metabolic stability (Yamazaki et al., 1991; Huang et al., 1993). The backbone conformation of a β-amino acid is defined by the torsional angles ϕ, θ and ψ (Banerjee & Balaram, 1997), as shown in Fig. 1. The monosubstitution at the α- and β-carbons plays an important role in the folding of oligomers of β-amino acids (Seebach et al., 2009). In order to investigate the effect of protecting groups and disubstitution on the conformation of β-amino acids, N-protected derivatives of 1-amino­cyclo­hexane­acetic acid (β3,3Ac6c), i.e. Valeroyl-β3,3-Ac6c-OH (I), Fmoc-β3,3-Ac6c-OH (II) and Pyr-β3,3-Ac6c-OH (III) were synthesized. The crystal structures of the three compounds were determined and are reported herein, together with their comparative conformational features.

Structural commentary top

The molecular conformations of Valeroyl-β3,3-Ac6c-OH (I), Fmoc-β3,3-Ac6c-OH (II) and Pyr-β3,3-Ac6c-OH (III) are shown in Fig. 2. The backbone torsion angles (ϕ, θ) (C0'—N1—C1B —C1A and N1—C1B—C1A—C1') adopt a gauche conformation in all three compounds [ϕ = 61.9 (3)°, θ = 57.2 (3)° for (I); ϕ = 56.7 (3)°, θ = 66.1 (3)° for (II) and ϕ = 65.5 (2)°, θ = 55.0 (2)° for (III). The torsional angle ψ restricts the extended (trans) conformation for (I) [166.9 (2)°] and (III) [157.9 (2)°]. In the case of (II), it is restricted to a gauche conformation [i.e. ψ = -63.6 (3)°]. In a 3,3-disubstituted β-amino acid residue, β3,3-Ac6c-OH, the cyclo­hexane ring imposes a restriction on the torsion angles ϕ and θ. The protecting groups at the N-terminus of (I) adopts a trans geometry [ω0 (C4—C0'—N1—C1B) = 177.4 (2) for (I), ω0 (O—C0'—N1—C1B) = -175.64 (19) for (II) and ω0 (C6—C0—N1— C1A) = -170.04 (17)° for (III)]. In the case of the N-protected tert-butyl­oxycarbonyl (Boc) group, the protecting group adopts a cis geometry with ω0 = 14.50° (Vasudev et al., 2008). The cyclo­hexane ring adopts a chair conformation with axial amino and equatorial CH2CO groups in all the derivatives. In Pyr-β3,3-Ac6c-OH (III), an intra­molecular N—H···N inter­action is observed between NH of the β3,3-Ac6c-OH residue and N3 of the pyrazine ring as shown in Fig. 3c. There are no intra­molecular hydrogen bonding inter­actions observed in the crystal structures of derivatives (I) and (II).

Supra­molecular features top

In the crystals of compounds (I) and (II), inter­molecular hydrogen-bonding inter­actions generate primary centrosymmetric dimeric but different substructures (Figs. 4 and 5). In (I), N1—H···O1ii bond pairs (Table 1) give a cyclic R22(14) motif which is extended into a ribbon structure along the c-axis direction through a second but non-centrosymmetric cyclic carb­oxy­lic acid R22(8) O2—H···Oi hydrogen-bond motif (Fig. 4a). In (II), the inter­molecular dimeric association is through the centrosymmetric R22(8) carb­oxy­lic acid hydrogen-bonding motif. Structure extension is through N1—H···O1' (carboxyl) hydrogen bonds (Table 2), generating a two-dimensional layered structure lying parallel to (010) (Fig. 5c). Also present in the structure are π–π inter­actions between the Fmoc groups with an inter­centroid distance of 3.786 (2) Å. Fig. 5c shows the aromatic rings of Fmoc groups stacked in a face-to-face and edge-to-face manner, together with inter-plane distances which are within the range for stabilizing the π–π inter­actions (Burley & Petsko, 1985; Sengupta et al., 2005) and have been reported to induce self-assembly in peptides (Wang & Chau, 2011). In the case of (I) and (II), the molecular packing in the crystals leads to the formation of alternating hydro­phobic and hydro­philic layers. In the crystals of (III), in which no dimer substructure formation is present, the molecules are stabilized through an inter­molecular carb­oxy­lic acid O2—H···N2i hydrogen bond (Table 3) with a pyrazine N-atom acceptor, leading to the formation of a zigzag ribbon structure extending along the c-axis direction.

Synthesis and crystallization top

Preparation of Valeroyl-β3,3Ac6c-OH (I): β3,3Ac6c-OH (5 mmol, 785 mg) was dissolved in 5 ml of a 2M NaOH solution and a solution of 5 mmol of valeric anhydride (931 mg) dissolved in 1,4-dioxane was added, after which the mixture was stirred for 4 h at room temperature. On completion of the reaction, the 1,4-dioxane was evaporated and the product was extracted with di­ethyl ether (3 x 5 ml). The aqueous layer was acidified with 2M HCl and extracted with ethyl acetate (3 x 10ml) and the combined organic layer was washed with brine solution. The organic layer was passed over anhydrous Na2SO4 and evaporated to give Valeroyl-β3Ac6c-OH (Yield: 1.1 g, 85.2%). Single crystals were grown by slow evaporation from a solution in methanol/water.

Preparation of Fmoc-β3,3Ac6c-OH (2) (II): β3,3Ac6c-OH (10 mmol, 1.57 g) was dissolved in 1M Na2CO3 solution and Fmoc-OSu (10 mmol, 3.37 g) dissolved in CH3CN was added. The reaction mixture was stirred at room temperature for 6 h. After completion of the reaction, the CH3CN was evaporated and the residue was extracted with di­ethyl ether (3 x 10 ml). The aqueous layer was acidified with 2M HCl and extracted with ethyl acetate (3 x 15 ml). The combined organic layer was washed with brine solution. The ethyl acetate layer was passed over anhydrous Na2SO4 and evaporated. The residue was purified by crystallization in ethyl acetate/n-hexane, affording Fmoc-β3,3Ac6c-OH (Yield: 3.0 g, 79%). Single crystals were obtained by slow evaporation from an ethyl acetate/n-hexane solution.

Preparation of Pyr-β3,3Ac6c-OH (3) (III): Pyrazine carb­oxy­lic acid (3 mmol, 372 mg) was dissolved in dry CH2Cl2 and then 200 µl of N-methyl­morpholine was added, followed by β3,3Ac6c-OMe. HCl (3 mmol, 622.5 mg) and EDCI. HCl (3 mmol,576 mg) at 273 K. The reaction mixture was stirred at room temperature for 12 h. After completion of the reaction, water was added and the reaction mixture was extracted with CH2Cl2 (3 x 5ml). The combined organic layer was washed with 2M HCl (2 x 5ml), Na2CO3 (2 x 5ml) and brine solution (2 x 5ml). The organic layer was passed over anhydrous Na2SO4 and evaporated to give Pyr-β3,3Ac6c-OMe (Yield: 600 mg, 72.2%). Pyr-β3,3Ac6c-OMe (2 mmol, 554 mg) was dissolved in 2 ml of methanol and 1 ml of 2M NaOH, and the reaction mixture was stirred at room temperature for 4 h. Methanol was evaporated and the residue was extracted with di­ethyl ether (2 x 5ml). The aqueous layer was acidified with 2M HCl and extracted with ethyl acetate (3 x 5ml). The combined organic layer was washed with brine solution (1 x 5ml). The ethyl acetate layer was passed over anhydrous Na2SO4 and evaporated to give Pyr-β3,3Ac6c-OH (Yield: 370 mg, 70.3%). Single crystals were grown from an ethanol/water solution.

Refinement details top

Crystal data, data collection and structure refinement details are summarized in Table 4. For derivative (I), H atoms for N1 and O2 were located in a difference Fourier map and both their coordinates and Uiso values were refined. The remaining H atoms were positioned geometrically and were treated as riding on their parent C atoms, with C—H distances of 0.96–0.98 Å and with Uiso(H) = 1.2Ueq(C) or 1.5Ueq(methyl C). For derivatives (II) and (III), all hydrogen atoms were located from a difference Fourier map and both their coordinates and Uiso values were refined. In (II), the carboxyl O—H distance was constrained to 0.84 Å. Although not of consequence with the achiral molecule of (III), which crystallized in the non-centrosymmetric space group Pca21, the structure was inverted in the final cycles of refinement as the Flack parameter was 0.8 (14). The inverted structure gave a value of 0.02 (14) for 1585 Friedel pairs.

Related literature top

For related literature, see: Banerjee & Balaram (1997); Burley & Petsko (1985); Cheng et al. (2001); Huang et al. (1993); Seebach et al. (2009); Sengupta et al. (2005); Vasudev et al. (2008); Wang & Chau (2011); Yamazaki et al. (1991).

Computing details top

For all compounds, data collection: CrysAlis PRO (Oxford Diffraction, 2010); cell refinement: CrysAlis PRO (Oxford Diffraction, 2010); data reduction: CrysAlis PRO (Oxford Diffraction, 2010); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: PLATON (Spek, 2009).

Figures top
Definition of backbone torsion angles for β-amino acids.

ORTEP view of the molecular conformation with the atom-labelling scheme. for Valeroyl-β3,3-Ac6c-OH (I), (b) Fmoc-β3,3-Ac6c-OH (II) and (c) Pyr-β3,3-Ac6c-OH (III). The displacement ellipsoids are drawn at the 40% probability level. H atoms are shown as small spheres of arbitrary radii.

(a) Packing of Valeroyl-β3,3-Ac6c-OH (I) down the b-axis showing the alternative hydrophilic and hydrophobic layers (b) space-filling model.

(a) Packing of Fmoc-β3,3-Ac6c-OH (II) down the a-axis. (b) Space-filling model showing the alternative hydrophilic and hydrophobic layers (packing down the c-axis). (c) The environment of the Fmoc group showing the aromatic interaction. The centroid–centroid distances are shown.

(a) Packing of Pyr-β3,3-Ac6c-OH (III) down the a-axis showing the ribbon structure. (b) Zigzag arrangement of the ribbons along the c-axis.
(I) 2-(1-Pentanamidocyclohexyl)acetic acid top
Crystal data top
C13H23NO3F(000) = 528
Mr = 241.32Dx = 1.150 Mg m−3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 4978 reflections
a = 9.5894 (5) Åθ = 3.5–29.1°
b = 12.5007 (7) ŵ = 0.08 mm−1
c = 12.3709 (8) ÅT = 291 K
β = 109.984 (7)°Needle, colourless
V = 1393.66 (14) Å30.30 × 0.08 × 0.08 mm
Z = 4
Data collection top
Oxford Diffraction Xcalibur, Sapphire3 CCD
diffractometer		2737 independent reflections
Radiation source: fine-focus sealed tube1717 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.047
Detector resolution: 16.1049 pixels mm-1θmax = 26.0°, θmin = 3.5°
ω scanh = −11→11
Absorption correction: multi-scan
(CrysAlis PRO; Oxford Diffraction, 2010)		k = −15→15
Tmin = 0.797, Tmax = 1.000l = −15→15
14087 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.068Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.213H atoms treated by a mixture of independent and constrained refinement
S = 1.03 w = 1/[σ2(Fo2) + (0.0999P)2 + 0.474P]
where P = (Fo2 + 2Fc2)/3
2737 reflections(Δ/σ)max < 0.001
162 parametersΔρmax = 0.36 e Å−3
0 restraintsΔρmin = −0.30 e Å−3
Crystal data top
C13H23NO3V = 1393.66 (14) Å3
Mr = 241.32Z = 4
Monoclinic, P21/cMo Kα radiation
a = 9.5894 (5) ŵ = 0.08 mm−1
b = 12.5007 (7) ÅT = 291 K
c = 12.3709 (8) Å0.30 × 0.08 × 0.08 mm
β = 109.984 (7)°
Data collection top
Oxford Diffraction Xcalibur, Sapphire3 CCD
diffractometer		2737 independent reflections
Absorption correction: multi-scan
(CrysAlis PRO; Oxford Diffraction, 2010)		1717 reflections with I > 2σ(I)
Tmin = 0.797, Tmax = 1.000Rint = 0.047
14087 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0680 restraints
wR(F2) = 0.213H atoms treated by a mixture of independent and constrained refinement
S = 1.03Δρmax = 0.36 e Å−3
2737 reflectionsΔρmin = −0.30 e Å−3
162 parameters
Special details top

Experimental. CrysAlis PRO, Oxford Diffraction Ltd., Version 1.171.34.40 (release 27–08-2010 CrysAlis171. NET) (compiled Aug 27 2010,11:50:40) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm.

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 (Å2) top
xyzUiso*/Ueq
C10.2941 (6)−0.4516 (4)−0.0262 (5)0.141 (2)
H1A0.3775−0.4719−0.04790.211*
H1B0.2304−0.5123−0.03280.211*
H1C0.3286−0.42660.05190.211*
C20.2142 (5)−0.3689 (4)−0.0997 (4)0.1151 (15)
H2A0.1810−0.3938−0.17870.138*
H2B0.2790−0.3080−0.09370.138*
C30.0798 (4)−0.3343 (3)−0.0684 (4)0.0977 (13)
H3A0.0124−0.2948−0.13260.117*
H3B0.0282−0.3977−0.05710.117*
C40.1176 (3)−0.2653 (2)0.0389 (2)0.0560 (7)
H4A0.1902−0.30190.10260.067*
H4B0.1610−0.19850.02610.067*
C0'−0.0183 (3)−0.2422 (2)0.0688 (2)0.0471 (6)
O0−0.0486 (2)−0.29372 (16)0.14429 (16)0.0630 (6)
N1−0.1087 (2)−0.16761 (17)0.00548 (18)0.0442 (5)
C1B−0.2512 (3)−0.1329 (2)0.0135 (2)0.0435 (6)
C1A−0.2298 (3)−0.0852 (2)0.1317 (2)0.0476 (6)
H1A1−0.3261−0.06270.13280.057*
H1A2−0.1946−0.14150.18840.057*
C1'−0.1254 (3)0.0078 (2)0.1691 (2)0.0467 (6)
O1−0.0372 (2)0.03565 (17)0.12608 (18)0.0726 (7)
O2−0.1390 (3)0.0553 (2)0.2593 (2)0.0803 (8)
C1B1−0.3163 (3)−0.0502 (2)−0.0824 (2)0.0586 (7)
H1B3−0.4034−0.0182−0.07270.070*
H1B4−0.24390.0061−0.07450.070*
C1B2−0.3582 (3)−0.2283 (2)−0.0062 (2)0.0558 (7)
H1B5−0.3131−0.28340.05010.067*
H1B6−0.4487−0.20530.00530.067*
C1D−0.4625 (4)−0.1922 (3)−0.2179 (3)0.0884 (12)
H1D1−0.5568−0.1683−0.21380.106*
H1D2−0.4809−0.2238−0.29320.106*
C1G1−0.3594 (4)−0.0972 (3)−0.2031 (3)0.0772 (10)
H1G1−0.4080−0.0425−0.25890.093*
H1G2−0.2706−0.1194−0.21760.093*
C1G2−0.3966 (4)−0.2751 (3)−0.1265 (3)0.0744 (10)
H1G3−0.3075−0.3042−0.13580.089*
H1G4−0.4667−0.3333−0.13580.089*
H2O−0.074 (5)0.107 (3)0.281 (3)0.106 (14)*
H1N−0.076 (3)−0.1325 (19)−0.037 (2)0.035 (6)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.140 (4)0.134 (4)0.153 (5)0.044 (4)0.056 (4)−0.004 (4)
C20.101 (3)0.127 (4)0.123 (4)0.025 (3)0.046 (3)−0.021 (3)
C30.081 (2)0.120 (3)0.100 (3)0.006 (2)0.040 (2)−0.039 (2)
C40.0516 (15)0.0561 (16)0.0601 (17)0.0054 (12)0.0187 (13)0.0066 (13)
C0'0.0490 (14)0.0473 (14)0.0439 (14)−0.0011 (11)0.0146 (11)−0.0019 (12)
O00.0706 (13)0.0647 (12)0.0586 (12)0.0133 (10)0.0284 (10)0.0201 (10)
N10.0458 (12)0.0478 (12)0.0420 (12)−0.0006 (9)0.0190 (10)0.0062 (10)
C1B0.0407 (12)0.0485 (14)0.0420 (13)−0.0018 (10)0.0150 (10)0.0008 (11)
C1A0.0489 (14)0.0520 (15)0.0461 (14)−0.0040 (11)0.0215 (11)−0.0007 (12)
C1'0.0503 (14)0.0480 (14)0.0426 (14)0.0015 (11)0.0170 (12)0.0011 (12)
O10.0871 (15)0.0757 (14)0.0694 (13)−0.0327 (12)0.0452 (12)−0.0172 (11)
O20.0884 (16)0.0858 (17)0.0840 (16)−0.0313 (13)0.0519 (13)−0.0394 (13)
C1B10.0521 (15)0.0675 (18)0.0536 (16)0.0124 (13)0.0148 (12)0.0101 (14)
C1B20.0504 (15)0.0630 (17)0.0563 (17)−0.0102 (12)0.0209 (13)−0.0064 (13)
C1D0.064 (2)0.138 (3)0.0529 (19)−0.009 (2)0.0072 (16)−0.020 (2)
C1G10.0656 (19)0.109 (3)0.0491 (18)0.0071 (18)0.0090 (14)0.0109 (17)
C1G20.0663 (19)0.084 (2)0.073 (2)−0.0235 (17)0.0246 (16)−0.0300 (18)
Geometric parameters (Å, º) top
C1—C21.416 (7)C1A—C1'1.500 (3)
C1—H1A0.9600C1A—H1A10.9700
C1—H1B0.9600C1A—H1A20.9700
C1—H1C0.9600C1'—O11.194 (3)
C2—C31.529 (5)C1'—O21.309 (3)
C2—H2A0.9700O2—H2O0.88 (4)
C2—H2B0.9700C1B1—C1G11.524 (4)
C3—C41.519 (4)C1B1—H1B30.9700
C3—H3A0.9700C1B1—H1B40.9700
C3—H3B0.9700C1B2—C1G21.523 (4)
C4—C0'1.499 (3)C1B2—H1B50.9700
C4—H4A0.9700C1B2—H1B60.9700
C4—H4B0.9700C1D—C1G21.505 (5)
C0'—O01.248 (3)C1D—C1G11.516 (5)
C0'—N11.331 (3)C1D—H1D10.9700
N1—C1B1.469 (3)C1D—H1D20.9700
N1—H1N0.82 (2)C1G1—H1G10.9700
C1B—C1A1.526 (3)C1G1—H1G20.9700
C1B—C1B11.535 (4)C1G2—H1G30.9700
C1B—C1B21.538 (3)C1G2—H1G40.9700
C2—C1—H1A109.5C1B—C1A—H1A1108.0
C2—C1—H1B109.5C1'—C1A—H1A2108.0
H1A—C1—H1B109.5C1B—C1A—H1A2108.0
C2—C1—H1C109.5H1A1—C1A—H1A2107.3
H1A—C1—H1C109.5O1—C1'—O2122.7 (2)
H1B—C1—H1C109.5O1—C1'—C1A126.0 (2)
C1—C2—C3111.2 (4)O2—C1'—C1A111.3 (2)
C1—C2—H2A109.4C1'—O2—H2O109 (3)
C3—C2—H2A109.4C1G1—C1B1—C1B113.6 (2)
C1—C2—H2B109.4C1G1—C1B1—H1B3108.8
C3—C2—H2B109.4C1B—C1B1—H1B3108.8
H2A—C2—H2B108.0C1G1—C1B1—H1B4108.8
C4—C3—C2114.3 (3)C1B—C1B1—H1B4108.8
C4—C3—H3A108.7H1B3—C1B1—H1B4107.7
C2—C3—H3A108.7C1G2—C1B2—C1B112.3 (2)
C4—C3—H3B108.7C1G2—C1B2—H1B5109.2
C2—C3—H3B108.7C1B—C1B2—H1B5109.2
H3A—C3—H3B107.6C1G2—C1B2—H1B6109.2
C0'—C4—C3110.9 (2)C1B—C1B2—H1B6109.2
C0'—C4—H4A109.5H1B5—C1B2—H1B6107.9
C3—C4—H4A109.5C1G2—C1D—C1G1111.1 (3)
C0'—C4—H4B109.5C1G2—C1D—H1D1109.4
C3—C4—H4B109.5C1G1—C1D—H1D1109.4
H4A—C4—H4B108.0C1G2—C1D—H1D2109.4
O0—C0'—N1122.0 (2)C1G1—C1D—H1D2109.4
O0—C0'—C4122.0 (2)H1D1—C1D—H1D2108.0
N1—C0'—C4115.9 (2)C1D—C1G1—C1B1111.6 (3)
C0'—N1—C1B127.0 (2)C1D—C1G1—H1G1109.3
C0'—N1—H1N115.9 (16)C1B1—C1G1—H1G1109.3
C1B—N1—H1N116.7 (16)C1D—C1G1—H1G2109.3
N1—C1B—C1A110.86 (19)C1B1—C1G1—H1G2109.3
N1—C1B—C1B1106.79 (19)H1G1—C1G1—H1G2108.0
C1A—C1B—C1B1111.3 (2)C1D—C1G2—C1B2111.6 (3)
N1—C1B—C1B2110.2 (2)C1D—C1G2—H1G3109.3
C1A—C1B—C1B2108.6 (2)C1B2—C1G2—H1G3109.3
C1B1—C1B—C1B2109.1 (2)C1D—C1G2—H1G4109.3
C1'—C1A—C1B117.1 (2)C1B2—C1G2—H1G4109.3
C1'—C1A—H1A1108.0H1G3—C1G2—H1G4108.0
C1—C2—C3—C475.6 (5)C1B—C1A—C1'—O1−14.9 (4)
C2—C3—C4—C0'−175.5 (3)C1B—C1A—C1'—O2166.9 (2)
C3—C4—C0'—O099.1 (3)N1—C1B—C1B1—C1G166.6 (3)
C3—C4—C0'—N1−77.3 (3)C1A—C1B—C1B1—C1G1−172.3 (2)
O0—C0'—N1—C1B1.0 (4)C1B2—C1B—C1B1—C1G1−52.5 (3)
C4—C0'—N1—C1B177.4 (2)N1—C1B—C1B2—C1G2−63.3 (3)
C0'—N1—C1B—C1A61.9 (3)C1A—C1B—C1B2—C1G2175.1 (2)
C0'—N1—C1B—C1B1−176.7 (2)C1B1—C1B—C1B2—C1G253.6 (3)
C0'—N1—C1B—C1B2−58.4 (3)C1G2—C1D—C1G1—C1B1−54.3 (4)
N1—C1B—C1A—C1'57.2 (3)C1B—C1B1—C1G1—C1D53.7 (3)
C1B1—C1B—C1A—C1'−61.5 (3)C1G1—C1D—C1G2—C1B256.2 (4)
C1B2—C1B—C1A—C1'178.5 (2)C1B—C1B2—C1G2—C1D−57.0 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O2—H2O···O0i0.87 (4)1.74 (4)2.599 (3)166 (4)
N1—H1N···O1ii0.82 (3)2.16 (3)2.981 (3)172 (2)
Symmetry codes: (i) −x, y+1/2, −z+1/2; (ii) −x, −y, −z.
(II) 2-(1-{[(9H-fluoren-9-yloxy)carbonyl]amino}cyclohexyl)acetic acid top
Crystal data top
C23H25NO4Z = 2
Mr = 379.44F(000) = 404
Triclinic, P1Dx = 1.290 Mg m−3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 6.0834 (4) ÅCell parameters from 2812 reflections
b = 12.7642 (9) Åθ = 3.5–27.0°
c = 12.8399 (9) ŵ = 0.09 mm−1
α = 94.018 (6)°T = 291 K
β = 92.295 (6)°Needle, colorless
γ = 100.489 (6)°0.30 × 0.05 × 0.03 mm
V = 976.53 (12) Å3
Data collection top
Oxford Diffraction Xcalibur, Sapphire3 CCD
diffractometer		4166 independent reflections
Radiation source: fine-focus sealed tube2037 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.047
Detector resolution: 16.1049 pixels mm-1θmax = 27.0°, θmin = 3.5°
ω scansh = −7→6
Absorption correction: multi-scan
(CrysAlis PRO; Oxford Diffraction, 2010)		k = −15→16
Tmin = 0.947, Tmax = 1.000l = −16→16
7781 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.054Hydrogen site location: difference Fourier map
wR(F2) = 0.086All H-atom parameters refined
S = 0.97 w = 1/[σ2(Fo2) + (0.0085P)2]
where P = (Fo2 + 2Fc2)/3
4166 reflections(Δ/σ)max < 0.001
353 parametersΔρmax = 0.15 e Å−3
1 restraintΔρmin = −0.20 e Å−3
Crystal data top
C23H25NO4γ = 100.489 (6)°
Mr = 379.44V = 976.53 (12) Å3
Triclinic, P1Z = 2
a = 6.0834 (4) ÅMo Kα radiation
b = 12.7642 (9) ŵ = 0.09 mm−1
c = 12.8399 (9) ÅT = 291 K
α = 94.018 (6)°0.30 × 0.05 × 0.03 mm
β = 92.295 (6)°
Data collection top
Oxford Diffraction Xcalibur, Sapphire3 CCD
diffractometer		4166 independent reflections
Absorption correction: multi-scan
(CrysAlis PRO; Oxford Diffraction, 2010)		2037 reflections with I > 2σ(I)
Tmin = 0.947, Tmax = 1.000Rint = 0.047
7781 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0541 restraint
wR(F2) = 0.086All H-atom parameters refined
S = 0.97Δρmax = 0.15 e Å−3
4166 reflectionsΔρmin = −0.20 e Å−3
353 parameters
Special details top

Experimental. CrysAlis PRO, Oxford Diffraction Ltd., Version 1.171.34.40 (release 27–08-2010 CrysAlis171. NET) (compiled Aug 27 2010,11:50:40) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm.

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 (Å2) top
xyzUiso*/Ueq
C10.8803 (4)−0.19879 (17)−0.39027 (18)0.0398 (6)
C21.0680 (4)−0.1766 (2)−0.4476 (2)0.0490 (7)
C31.1160 (5)−0.2575 (2)−0.5173 (2)0.0548 (8)
C40.9775 (5)−0.3561 (2)−0.5289 (2)0.0544 (8)
C50.7899 (4)−0.3786 (2)−0.47135 (19)0.0471 (7)
C60.7413 (4)−0.29817 (17)−0.40208 (18)0.0381 (6)
C70.5582 (4)−0.29905 (18)−0.33106 (18)0.0399 (6)
C80.3733 (4)−0.3763 (2)−0.3161 (2)0.0503 (7)
C90.2213 (5)−0.3534 (3)−0.2458 (2)0.0598 (8)
C100.2509 (5)−0.2550 (3)−0.1896 (2)0.0631 (9)
C110.4356 (5)−0.1777 (2)−0.2032 (2)0.0555 (8)
C120.5888 (4)−0.19843 (17)−0.27442 (18)0.0411 (6)
C130.7945 (4)−0.12711 (19)−0.3089 (2)0.0437 (7)
C140.7453 (5)−0.0259 (2)−0.3520 (2)0.0478 (7)
O0.7045 (3)0.04337 (11)−0.26348 (13)0.0488 (5)
C0'0.5479 (4)0.10582 (18)−0.2765 (2)0.0395 (6)
O00.4294 (3)0.10122 (13)−0.35483 (14)0.0588 (5)
N10.5526 (3)0.17073 (15)−0.18907 (17)0.0372 (5)
C1B0.3973 (4)0.24494 (17)−0.17036 (18)0.0361 (6)
C1B10.4539 (4)0.2995 (2)−0.0596 (2)0.0430 (7)
C1G10.6806 (5)0.3738 (2)−0.0476 (2)0.0521 (8)
C1D0.7028 (6)0.4553 (2)−0.1294 (3)0.0630 (9)
C1G20.6576 (5)0.4007 (2)−0.2385 (2)0.0529 (8)
C1B20.4262 (4)0.3298 (2)−0.2497 (2)0.0455 (7)
C1A0.1535 (4)0.1842 (2)−0.1806 (2)0.0442 (7)
C1'0.0895 (4)0.10713 (19)−0.0994 (2)0.0435 (7)
O1−0.0602 (3)0.11924 (12)−0.03783 (13)0.0536 (5)
O20.1903 (3)0.02715 (16)−0.09706 (17)0.0658 (6)
H11.169 (3)−0.1087 (16)−0.4336 (16)0.057 (8)*
H21.250 (4)−0.2404 (17)−0.5581 (18)0.071 (8)*
H31.010 (3)−0.4159 (15)−0.5793 (17)0.057 (7)*
H40.697 (3)−0.4510 (15)−0.4749 (15)0.048 (7)*
H50.355 (3)−0.4462 (16)−0.3585 (17)0.057 (7)*
H60.086 (4)−0.4073 (18)−0.2391 (18)0.076 (9)*
H70.130 (4)−0.2404 (17)−0.1414 (19)0.079 (9)*
H80.465 (3)−0.1068 (16)−0.1668 (17)0.059 (8)*
H90.901 (3)−0.1079 (14)−0.2496 (15)0.034 (6)*
H100.877 (3)0.0150 (15)−0.3877 (16)0.047 (7)*
H110.613 (3)−0.0384 (15)−0.4024 (17)0.051 (7)*
H1N0.638 (4)0.1617 (17)−0.1365 (18)0.056 (9)*
H1B10.444 (3)0.2449 (15)−0.0120 (16)0.037 (7)*
H1B20.325 (3)0.3423 (15)−0.0449 (16)0.052 (7)*
H1G10.812 (4)0.3321 (16)−0.0523 (18)0.068 (8)*
H1G20.702 (3)0.4120 (15)0.0257 (18)0.060 (8)*
H1D10.587 (4)0.5056 (18)−0.116 (2)0.084 (9)*
H1D20.857 (4)0.4989 (18)−0.1182 (19)0.079 (9)*
H1G30.670 (3)0.4543 (16)−0.2899 (17)0.049 (7)*
H1G40.778 (4)0.3541 (16)−0.2585 (17)0.066 (8)*
H1B30.393 (3)0.2939 (14)−0.3222 (16)0.046 (7)*
H1B40.309 (3)0.3775 (16)−0.2388 (17)0.064 (8)*
H1A10.127 (3)0.1439 (15)−0.2528 (17)0.055 (7)*
H1A20.052 (3)0.2388 (15)−0.1722 (16)0.047 (7)*
H2O0.145 (7)−0.020 (2)−0.056 (3)0.24 (3)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0446 (16)0.0360 (14)0.0398 (16)0.0111 (12)−0.0001 (13)0.0028 (11)
C20.0463 (17)0.0416 (17)0.058 (2)0.0050 (14)0.0053 (15)0.0040 (14)
C30.0535 (19)0.061 (2)0.054 (2)0.0183 (16)0.0160 (16)0.0093 (15)
C40.067 (2)0.0512 (18)0.0471 (19)0.0202 (15)0.0060 (16)−0.0031 (14)
C50.0555 (18)0.0407 (16)0.0435 (17)0.0061 (14)0.0051 (14)−0.0028 (13)
C60.0416 (15)0.0383 (14)0.0353 (15)0.0102 (11)−0.0006 (12)0.0037 (11)
C70.0448 (15)0.0407 (15)0.0353 (15)0.0093 (12)0.0023 (12)0.0060 (11)
C80.0568 (18)0.0487 (18)0.0450 (18)0.0062 (14)0.0049 (15)0.0087 (14)
C90.054 (2)0.069 (2)0.056 (2)0.0042 (17)0.0124 (16)0.0213 (17)
C100.066 (2)0.077 (2)0.054 (2)0.0248 (18)0.0204 (17)0.0204 (17)
C110.071 (2)0.0522 (19)0.0488 (19)0.0232 (16)0.0135 (16)0.0056 (15)
C120.0479 (16)0.0407 (15)0.0379 (16)0.0143 (12)0.0042 (13)0.0072 (12)
C130.0486 (17)0.0367 (15)0.0454 (18)0.0107 (12)−0.0022 (14)−0.0042 (13)
C140.0536 (19)0.0356 (16)0.055 (2)0.0122 (14)0.0030 (16)−0.0020 (14)
O0.0498 (11)0.0413 (10)0.0570 (13)0.0208 (8)−0.0078 (9)−0.0100 (9)
C0'0.0348 (15)0.0326 (14)0.0521 (19)0.0067 (11)0.0058 (14)0.0065 (13)
O00.0638 (13)0.0649 (13)0.0499 (13)0.0251 (10)−0.0115 (10)−0.0056 (10)
N10.0358 (13)0.0366 (12)0.0408 (14)0.0120 (9)−0.0009 (11)0.0014 (10)
C1B0.0363 (14)0.0370 (14)0.0382 (15)0.0120 (11)0.0072 (12)0.0098 (11)
C1B10.0435 (17)0.0433 (17)0.0435 (18)0.0086 (13)0.0103 (14)0.0071 (14)
C1G10.0495 (18)0.0536 (19)0.050 (2)0.0031 (14)0.0040 (15)−0.0040 (15)
C1D0.065 (2)0.051 (2)0.068 (2)−0.0042 (17)0.0182 (19)−0.0004 (17)
C1G20.059 (2)0.0454 (18)0.058 (2)0.0103 (15)0.0223 (17)0.0186 (15)
C1B20.0498 (18)0.0445 (17)0.0470 (19)0.0172 (13)0.0094 (15)0.0112 (14)
C1A0.0352 (16)0.0480 (17)0.0523 (19)0.0111 (13)0.0065 (14)0.0121 (14)
C1'0.0312 (15)0.0429 (16)0.0561 (19)0.0070 (12)0.0001 (13)0.0035 (13)
O10.0495 (11)0.0609 (12)0.0569 (13)0.0208 (9)0.0189 (10)0.0115 (9)
O20.0678 (14)0.0521 (13)0.0884 (17)0.0271 (10)0.0316 (12)0.0240 (11)
Geometric parameters (Å, º) top
C1—C21.381 (3)O—C0'1.362 (3)
C1—C61.385 (3)C0'—O01.205 (3)
C1—C131.511 (3)C0'—N11.344 (3)
C2—C31.398 (3)N1—C1B1.469 (3)
C2—H10.967 (19)N1—H1N0.86 (2)
C3—C41.375 (3)C1B—C1B21.530 (3)
C3—H20.98 (2)C1B—C1B11.536 (3)
C4—C51.382 (3)C1B—C1A1.540 (3)
C4—H31.017 (18)C1B1—C1G11.521 (3)
C5—C61.391 (3)C1B1—H1B10.95 (2)
C5—H40.989 (18)C1B1—H1B21.048 (19)
C6—C71.467 (3)C1G1—C1D1.522 (4)
C7—C81.384 (3)C1G1—H1G11.04 (2)
C7—C121.409 (3)C1G1—H1G21.02 (2)
C8—C91.372 (3)C1D—C1G21.512 (4)
C8—H50.997 (18)C1D—H1D11.05 (2)
C9—C101.384 (3)C1D—H1D21.00 (2)
C9—H60.98 (2)C1G2—C1B21.524 (3)
C10—C111.379 (3)C1G2—H1G30.98 (2)
C10—H71.01 (2)C1G2—H1G41.05 (2)
C11—C121.378 (3)C1B2—H1B31.005 (19)
C11—H80.971 (19)C1B2—H1B41.03 (2)
C12—C131.509 (3)C1A—C1'1.497 (3)
C13—C141.514 (3)C1A—H1A11.020 (19)
C13—H90.968 (19)C1A—H1A21.015 (18)
C14—O1.449 (3)C1'—O11.253 (2)
C14—H101.017 (19)C1'—O21.284 (3)
C14—H110.99 (2)O2—H2O0.84 (1)
C2—C1—C6121.1 (2)N1—C0'—O108.3 (2)
C2—C1—C13128.7 (2)C0'—N1—C1B124.5 (2)
C6—C1—C13110.2 (2)C0'—N1—H1N118.0 (15)
C1—C2—C3118.2 (2)C1B—N1—H1N116.8 (15)
C1—C2—H1119.2 (12)N1—C1B—C1B2110.33 (19)
C3—C2—H1122.3 (12)N1—C1B—C1B1107.6 (2)
C4—C3—C2120.5 (3)C1B2—C1B—C1B1109.3 (2)
C4—C3—H2122.1 (13)N1—C1B—C1A110.39 (19)
C2—C3—H2117.4 (13)C1B2—C1B—C1A108.7 (2)
C3—C4—C5121.3 (2)C1B1—C1B—C1A110.59 (19)
C3—C4—H3121.6 (12)C1G1—C1B1—C1B113.6 (2)
C5—C4—H3117.0 (12)C1G1—C1B1—H1B1111.6 (13)
C4—C5—C6118.3 (2)C1B—C1B1—H1B1107.8 (12)
C4—C5—H4121.6 (11)C1G1—C1B1—H1B2110.5 (10)
C6—C5—H4119.9 (11)C1B—C1B1—H1B2105.2 (12)
C5—C6—C1120.5 (2)H1B1—C1B1—H1B2107.7 (15)
C5—C6—C7130.4 (2)C1D—C1G1—C1B1111.4 (3)
C1—C6—C7109.07 (18)C1D—C1G1—H1G1109.3 (13)
C8—C7—C12120.0 (2)C1B1—C1G1—H1G1112.1 (12)
C8—C7—C6131.7 (2)C1D—C1G1—H1G2110.1 (12)
C12—C7—C6108.2 (2)C1B1—C1G1—H1G2109.5 (12)
C9—C8—C7119.2 (2)H1G1—C1G1—H1G2104.4 (18)
C9—C8—H5122.7 (12)C1G2—C1D—C1G1111.0 (2)
C7—C8—H5118.1 (12)C1G2—C1D—H1D1108.9 (15)
C8—C9—C10121.1 (3)C1G1—C1D—H1D1109.0 (15)
C8—C9—H6118.4 (13)C1G2—C1D—H1D2112.7 (14)
C10—C9—H6120.4 (13)C1G1—C1D—H1D2106.5 (16)
C11—C10—C9120.2 (3)H1D1—C1D—H1D2108.6 (18)
C11—C10—H7121.5 (13)C1D—C1G2—C1B2110.8 (2)
C9—C10—H7118.2 (13)C1D—C1G2—H1G3109.8 (12)
C10—C11—C12119.6 (3)C1B2—C1G2—H1G3110.1 (13)
C10—C11—H8124.3 (13)C1D—C1G2—H1G4112.2 (13)
C12—C11—H8116.0 (13)C1B2—C1G2—H1G4109.0 (11)
C11—C12—C7119.8 (2)H1G3—C1G2—H1G4104.7 (16)
C11—C12—C13130.4 (2)C1G2—C1B2—C1B112.3 (2)
C7—C12—C13109.7 (2)C1G2—C1B2—H1B3111.5 (11)
C1—C13—C12102.78 (18)C1B—C1B2—H1B3109.3 (11)
C1—C13—C14112.5 (2)C1G2—C1B2—H1B4108.2 (12)
C12—C13—C14113.2 (2)C1B—C1B2—H1B4109.2 (13)
C1—C13—H9110.8 (11)H1B3—C1B2—H1B4106.1 (17)
C12—C13—H9108.6 (12)C1'—C1A—C1B115.4 (2)
C14—C13—H9108.9 (11)C1'—C1A—H1A1109.0 (12)
O—C14—C13106.8 (2)C1B—C1A—H1A1108.1 (12)
O—C14—H10106.4 (11)C1'—C1A—H1A2105.6 (12)
C13—C14—H10113.1 (12)C1B—C1A—H1A2107.8 (11)
O—C14—H11109.1 (11)H1A1—C1A—H1A2110.9 (17)
C13—C14—H11113.5 (12)O1—C1'—O2121.5 (2)
H10—C14—H11107.6 (18)O1—C1'—C1A121.1 (2)
C0'—O—C14118.1 (2)O2—C1'—C1A117.4 (2)
O0—C0'—N1127.8 (2)C1'—O2—H2O118 (3)
O0—C0'—O123.9 (2)
C6—C1—C2—C3−0.7 (4)C11—C12—C13—C1−178.4 (3)
C13—C1—C2—C3178.6 (3)C7—C12—C13—C1−0.9 (3)
C1—C2—C3—C40.8 (4)C11—C12—C13—C14−56.8 (4)
C2—C3—C4—C5−1.0 (5)C7—C12—C13—C14120.6 (2)
C3—C4—C5—C61.1 (4)C1—C13—C14—O−169.9 (2)
C4—C5—C6—C1−1.0 (4)C12—C13—C14—O74.2 (3)
C4—C5—C6—C7−179.3 (3)C13—C14—O—C0'−144.5 (2)
C2—C1—C6—C50.9 (4)C14—O—C0'—O05.7 (4)
C13—C1—C6—C5−178.5 (2)C14—O—C0'—N1−174.0 (2)
C2—C1—C6—C7179.4 (2)O0—C0'—N1—C1B4.6 (4)
C13—C1—C6—C70.0 (3)O—C0'—N1—C1B−175.64 (19)
C5—C6—C7—C8−4.6 (5)C0'—N1—C1B—C1B2−63.4 (3)
C1—C6—C7—C8177.0 (3)C0'—N1—C1B—C1B1177.4 (2)
C5—C6—C7—C12177.7 (3)C0'—N1—C1B—C1A56.7 (3)
C1—C6—C7—C12−0.6 (3)N1—C1B—C1B1—C1G167.5 (3)
C12—C7—C8—C90.1 (4)C1B2—C1B—C1B1—C1G1−52.3 (3)
C6—C7—C8—C9−177.3 (3)C1A—C1B—C1B1—C1G1−171.9 (2)
C7—C8—C9—C10−0.4 (5)C1B—C1B1—C1G1—C1D53.3 (3)
C8—C9—C10—C11−0.2 (5)C1B1—C1G1—C1D—C1G2−54.8 (3)
C9—C10—C11—C121.1 (5)C1G1—C1D—C1G2—C1B257.1 (3)
C10—C11—C12—C7−1.4 (4)C1D—C1G2—C1B2—C1B−57.8 (3)
C10—C11—C12—C13175.9 (3)N1—C1B—C1B2—C1G2−63.9 (3)
C8—C7—C12—C110.8 (4)C1B1—C1B—C1B2—C1G254.1 (3)
C6—C7—C12—C11178.8 (2)C1A—C1B—C1B2—C1G2174.9 (2)
C8—C7—C12—C13−177.0 (2)N1—C1B—C1A—C1'66.1 (3)
C6—C7—C12—C131.0 (3)C1B2—C1B—C1A—C1'−172.8 (2)
C2—C1—C13—C12−178.8 (3)C1B1—C1B—C1A—C1'−52.8 (3)
C6—C1—C13—C120.5 (3)C1B—C1A—C1'—O1117.9 (2)
C2—C1—C13—C1459.1 (4)C1B—C1A—C1'—O2−63.6 (3)
C6—C1—C13—C14−121.5 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1N···O1i0.86 (2)2.35 (2)3.182 (3)161 (2)
O2—H2O···O1ii0.84 (3)1.83 (3)2.673 (3)177 (1)
Symmetry codes: (i) x+1, y, z; (ii) −x, −y, −z.
(III) 2-[1-(Pyrazine-2-amido)cyclohexyl]acetic acid top
Crystal data top
C13H17N3O3F(000) = 560
Mr = 263.30Dx = 1.324 Mg m−3
Orthorhombic, Pca21Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2c -2acCell parameters from 28796 reflections
a = 8.7135 (1) Åθ = 3.7–27.0°
b = 10.5321 (1) ŵ = 0.10 mm−1
c = 14.3907 (2) ÅT = 291 K
V = 1320.66 (3) Å3Cube, colorless
Z = 40.25 × 0.25 × 0.25 mm
Data collection top
Oxford Difraction Xcalibur, Sapphire3 CCD
diffractometer		2878 independent reflections
Radiation source: fine-focus sealed tube2670 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.034
Detector resolution: 16.1049 pixels mm-1θmax = 27.0°, θmin = 3.9°
ω scansh = −11→11
Absorption correction: multi-scan
(CrysAlis PRO; Oxford Diffraction, 2010)		k = −13→13
Tmin = 0.931, Tmax = 1.000l = −18→18
68869 measured reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.042All H-atom parameters refined
wR(F2) = 0.106 w = 1/[σ2(Fo2) + (0.048P)2 + 0.4913P]
where P = (Fo2 + 2Fc2)/3
S = 1.04(Δ/σ)max = 0.032
2878 reflectionsΔρmax = 0.27 e Å−3
240 parametersΔρmin = −0.26 e Å−3
1 restraintAbsolute structure: (Flack, 1983): 1585 Friedel pairs
Primary atom site location: structure-invariant direct methodsAbsolute structure parameter: 0.2 (14)
Crystal data top
C13H17N3O3V = 1320.66 (3) Å3
Mr = 263.30Z = 4
Orthorhombic, Pca21Mo Kα radiation
a = 8.7135 (1) ŵ = 0.10 mm−1
b = 10.5321 (1) ÅT = 291 K
c = 14.3907 (2) Å0.25 × 0.25 × 0.25 mm
Data collection top
Oxford Difraction Xcalibur, Sapphire3 CCD
diffractometer		2878 independent reflections
Absorption correction: multi-scan
(CrysAlis PRO; Oxford Diffraction, 2010)		2670 reflections with I > 2σ(I)
Tmin = 0.931, Tmax = 1.000Rint = 0.034
68869 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.042All H-atom parameters refined
wR(F2) = 0.106Δρmax = 0.27 e Å−3
S = 1.04Δρmin = −0.26 e Å−3
2878 reflectionsAbsolute structure: (Flack, 1983): 1585 Friedel pairs
240 parametersAbsolute structure parameter: 0.2 (14)
1 restraint
Special details top

Experimental. CrysAlis PRO, Oxford Diffraction Ltd., Version 1.171.34.40 (release 27–08-2010 CrysAlis171. NET) (compiled Aug 27 2010,11:50:40) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm.

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 (Å2) top
xyzUiso*/Ueq
H10.902 (2)0.412 (2)1.0592 (15)0.030 (5)*
H1B21.400 (3)0.435 (2)1.2329 (16)0.041 (6)*
H1B51.272 (3)0.384 (2)1.4161 (18)0.049 (7)*
H1B61.183 (3)0.442 (2)1.3342 (17)0.048 (6)*
H1B11.499 (2)0.380 (2)1.3191 (16)0.033 (5)*
H1D21.651 (3)0.100 (3)1.200 (2)0.061 (7)*
H1N1.161 (2)0.172 (2)1.2259 (16)0.036 (6)*
H1G11.481 (3)0.256 (2)1.1391 (19)0.045 (6)*
H20.709 (3)0.107 (2)0.971 (2)0.051 (7)*
H30.894 (3)−0.021 (2)1.0429 (17)0.047 (6)*
H1B41.269 (3)0.107 (2)1.3669 (17)0.045 (6)*
H1G41.401 (3)0.050 (3)1.232 (2)0.061 (7)*
H1G21.616 (3)0.323 (3)1.173 (2)0.066 (8)*
H1B31.415 (3)0.192 (2)1.3989 (19)0.046 (6)*
H1G31.502 (3)0.005 (3)1.3184 (19)0.065 (8)*
H1D11.667 (4)0.176 (3)1.298 (2)0.071 (9)*
H210.885 (5)0.352 (4)1.458 (3)0.106 (13)*
C10.9028 (2)0.3259 (2)1.05370 (16)0.0401 (4)
N20.7893 (2)0.27249 (19)1.00502 (14)0.0442 (4)
C30.7875 (3)0.1459 (2)1.00191 (15)0.0433 (5)
C40.8954 (3)0.0736 (2)1.04730 (16)0.0450 (5)
N31.0074 (2)0.12584 (16)1.09722 (13)0.0398 (4)
C61.0105 (2)0.25193 (18)1.10026 (14)0.0343 (4)
C01.1318 (2)0.31669 (18)1.15876 (15)0.0382 (4)
O0'1.1604 (2)0.42890 (15)1.14626 (15)0.0658 (6)
N11.19610 (18)0.24153 (15)1.22264 (12)0.0348 (4)
C1A1.2995 (2)0.28157 (17)1.29864 (13)0.0311 (4)
C1B1.2100 (2)0.36660 (19)1.36671 (16)0.0381 (4)
C1'1.0648 (2)0.31013 (19)1.40619 (15)0.0423 (5)
O11.0357 (3)0.2011 (2)1.4129 (3)0.1197 (13)
O20.9700 (2)0.39599 (18)1.43574 (16)0.0677 (6)
C1B11.4369 (2)0.3562 (2)1.26078 (16)0.0394 (4)
C1G11.5373 (3)0.2777 (2)1.19617 (18)0.0504 (5)
C1D1.5948 (3)0.1582 (3)1.2448 (2)0.0575 (6)
C1B21.3586 (2)0.15966 (19)1.34564 (14)0.0366 (4)
C1G21.4634 (3)0.0817 (2)1.28311 (18)0.0483 (5)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0386 (10)0.0391 (10)0.0428 (10)0.0036 (9)−0.0049 (9)0.0025 (10)
N20.0374 (8)0.0538 (11)0.0414 (9)0.0036 (8)−0.0067 (7)0.0039 (8)
C30.0402 (11)0.0513 (13)0.0386 (11)−0.0063 (9)−0.0045 (9)−0.0018 (10)
C40.0510 (12)0.0399 (11)0.0440 (10)−0.0049 (10)−0.0066 (9)−0.0016 (9)
N30.0445 (9)0.0361 (8)0.0389 (9)−0.0002 (7)−0.0048 (8)0.0035 (7)
C60.0340 (9)0.0368 (10)0.0321 (9)0.0012 (7)0.0002 (7)0.0023 (8)
C00.0388 (10)0.0335 (9)0.0422 (11)0.0024 (8)−0.0048 (8)0.0032 (8)
O0'0.0769 (12)0.0360 (8)0.0843 (13)−0.0095 (8)−0.0359 (11)0.0160 (8)
N10.0365 (8)0.0291 (8)0.0388 (9)−0.0040 (6)−0.0074 (7)0.0016 (6)
C1A0.0299 (8)0.0305 (9)0.0329 (9)−0.0015 (7)0.0010 (7)−0.0030 (7)
C1B0.0352 (10)0.0327 (10)0.0464 (11)−0.0002 (8)0.0058 (9)−0.0069 (8)
C1'0.0418 (11)0.0358 (10)0.0494 (12)−0.0009 (9)0.0134 (9)−0.0037 (9)
O10.0886 (16)0.0440 (10)0.227 (3)−0.0088 (10)0.099 (2)−0.0111 (15)
O20.0533 (10)0.0462 (9)0.1035 (15)0.0071 (8)0.0373 (10)0.0115 (9)
C1B10.0322 (9)0.0395 (11)0.0464 (11)−0.0066 (8)0.0044 (9)−0.0020 (9)
C1G10.0453 (12)0.0557 (13)0.0500 (13)−0.0058 (11)0.0180 (11)−0.0036 (11)
C1D0.0454 (12)0.0660 (16)0.0611 (16)0.0172 (11)0.0121 (12)−0.0050 (12)
C1B20.0371 (10)0.0398 (9)0.0329 (10)0.0042 (8)−0.0012 (8)0.0026 (8)
C1G20.0551 (13)0.0404 (11)0.0493 (12)0.0171 (10)0.0039 (11)−0.0012 (9)
Geometric parameters (Å, º) top
C1—N21.337 (3)C1B—H1B60.95 (3)
C1—C61.391 (3)C1'—O11.180 (3)
C1—H10.91 (2)C1'—O21.297 (3)
N2—C31.334 (3)O2—H210.93 (5)
C3—C41.375 (3)C1B1—C1G11.521 (3)
C3—H20.91 (3)C1B1—H1B20.97 (2)
C4—N31.331 (3)C1B1—H1B11.03 (2)
C4—H31.00 (3)C1G1—C1D1.525 (4)
N3—C61.329 (3)C1G1—H1G10.98 (3)
C6—C01.514 (3)C1G1—H1G20.90 (3)
C0—O0'1.221 (2)C1D—C1G21.505 (4)
C0—N11.336 (3)C1D—H1D21.01 (3)
N1—C1A1.478 (2)C1D—H1D11.00 (3)
N1—H1N0.79 (2)C1B2—C1G21.523 (3)
C1A—C1B11.532 (3)C1B2—H1B41.00 (2)
C1A—C1B1.539 (2)C1B2—H1B30.97 (3)
C1A—C1B21.540 (3)C1G2—H1G40.97 (3)
C1B—C1'1.509 (3)C1G2—H1G31.01 (3)
C1B—H1B50.91 (3)
N2—C1—C6121.03 (19)O1—C1'—C1B126.5 (2)
N2—C1—H1117.5 (14)O2—C1'—C1B112.51 (18)
C6—C1—H1121.3 (14)C1'—O2—H21106 (3)
C3—N2—C1116.57 (18)C1G1—C1B1—C1A112.85 (17)
N2—C3—C4122.0 (2)C1G1—C1B1—H1B2113.6 (14)
N2—C3—H2118.2 (16)C1A—C1B1—H1B2109.0 (14)
C4—C3—H2119.8 (16)C1G1—C1B1—H1B1108.9 (12)
N3—C4—C3121.9 (2)C1A—C1B1—H1B1104.3 (12)
N3—C4—H3117.3 (15)H1B2—C1B1—H1B1107.7 (18)
C3—C4—H3120.8 (15)C1B1—C1G1—C1D110.9 (2)
C6—N3—C4116.44 (19)C1B1—C1G1—H1G1110.5 (15)
N3—C6—C1122.0 (2)C1D—C1G1—H1G1111.0 (15)
N3—C6—C0118.85 (18)C1B1—C1G1—H1G2112.3 (19)
C1—C6—C0119.08 (17)C1D—C1G1—H1G2111.1 (19)
O0'—C0—N1126.08 (19)H1G1—C1G1—H1G2101 (2)
O0'—C0—C6119.79 (18)C1G2—C1D—C1G1111.1 (2)
N1—C0—C6114.12 (17)C1G2—C1D—H1D2106.1 (16)
C0—N1—C1A126.55 (16)C1G1—C1D—H1D2111.2 (16)
C0—N1—H1N115.3 (17)C1G2—C1D—H1D1107.4 (17)
C1A—N1—H1N116.8 (17)C1G1—C1D—H1D1113.3 (18)
N1—C1A—C1B1111.06 (16)H1D2—C1D—H1D1107 (2)
N1—C1A—C1B109.15 (15)C1G2—C1B2—C1A113.00 (17)
C1B1—C1A—C1B108.90 (15)C1G2—C1B2—H1B4110.6 (13)
N1—C1A—C1B2106.91 (15)C1A—C1B2—H1B4109.3 (13)
C1B1—C1A—C1B2108.81 (16)C1G2—C1B2—H1B3110.4 (15)
C1B—C1A—C1B2112.02 (16)C1A—C1B2—H1B3102.9 (15)
C1'—C1B—C1A115.79 (16)H1B4—C1B2—H1B3110 (2)
C1'—C1B—H1B5106.5 (16)C1D—C1G2—C1B2112.6 (2)
C1A—C1B—H1B5108.4 (17)C1D—C1G2—H1G4109.7 (17)
C1'—C1B—H1B6108.0 (15)C1B2—C1G2—H1G4107.0 (16)
C1A—C1B—H1B6107.2 (15)C1D—C1G2—H1G3111.0 (17)
H1B5—C1B—H1B6111 (2)C1B2—C1G2—H1G3109.4 (16)
O1—C1'—O2121.0 (2)H1G4—C1G2—H1G3107 (2)
C6—C1—N2—C3−1.5 (3)C0—N1—C1A—C1B2−173.2 (2)
C1—N2—C3—C40.8 (3)N1—C1A—C1B—C1'55.0 (2)
N2—C3—C4—N30.3 (4)C1B1—C1A—C1B—C1'176.42 (19)
C3—C4—N3—C6−0.6 (3)C1B2—C1A—C1B—C1'−63.2 (2)
C4—N3—C6—C1−0.2 (3)C1A—C1B—C1'—O123.6 (4)
C4—N3—C6—C0177.82 (19)C1A—C1B—C1'—O2−157.9 (2)
N2—C1—C6—N31.3 (3)N1—C1A—C1B1—C1G1−62.6 (2)
N2—C1—C6—C0−176.68 (19)C1B—C1A—C1B1—C1G1177.20 (19)
N3—C6—C0—O0'162.9 (2)C1B2—C1A—C1B1—C1G154.8 (2)
C1—C6—C0—O0'−19.1 (3)C1A—C1B1—C1G1—C1D−57.0 (3)
N3—C6—C0—N1−18.5 (3)C1B1—C1G1—C1D—C1G255.1 (3)
C1—C6—C0—N1159.53 (19)N1—C1A—C1B2—C1G267.3 (2)
O0'—C0—N1—C1A8.4 (4)C1B1—C1A—C1B2—C1G2−52.7 (2)
C6—C0—N1—C1A−170.04 (17)C1B—C1A—C1B2—C1G2−173.13 (18)
C0—N1—C1A—C1B1−54.6 (2)C1G1—C1D—C1G2—C1B2−53.8 (3)
C0—N1—C1A—C1B65.5 (2)C1A—C1B2—C1G2—C1D53.7 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O2—H21···N2i0.93 (4)1.86 (4)2.791 (3)177 (4)
N1—H1N···N30.79 (2)2.34 (2)2.729 (2)111.3 (19)
Symmetry code: (i) −x+3/2, y, z+1/2.
Hydrogen-bond geometry (Å, º) for (I) top
D—H···AD—HH···AD···AD—H···A
O2—H2O···O0i0.87 (4)1.74 (4)2.599 (3)166 (4)
N1—H1N···O1ii0.82 (3)2.16 (3)2.981 (3)172 (2)
Symmetry codes: (i) −x, y+1/2, −z+1/2; (ii) −x, −y, −z.
Hydrogen-bond geometry (Å, º) for (II) top
D—H···AD—HH···AD···AD—H···A
N1—H1N···O1i0.86 (2)2.35 (2)3.182 (3)161 (2)
O2—H2O···O1ii0.84 (3)1.83 (3)2.673 (3)176.9 (13)
Symmetry codes: (i) x+1, y, z; (ii) −x, −y, −z.
Hydrogen-bond geometry (Å, º) for (III) top
D—H···AD—HH···AD···AD—H···A
O2—H21···N2i0.93 (4)1.86 (4)2.791 (3)177 (4)
N1—H1N···N30.79 (2)2.34 (2)2.729 (2)111.3 (19)
Symmetry code: (i) −x+3/2, y, z+1/2.

Experimental details

(I)(II)(III)
Crystal data
Chemical formulaC13H23NO3C23H25NO4C13H17N3O3
Mr241.32379.44263.30
Crystal system, space groupMonoclinic, P21/cTriclinic, P1Orthorhombic, Pca21
Temperature (K)291291291
a, b, c (Å)9.5894 (5), 12.5007 (7), 12.3709 (8)6.0834 (4), 12.7642 (9), 12.8399 (9)8.7135 (1), 10.5321 (1), 14.3907 (2)
α, β, γ (°)90, 109.984 (7), 9094.018 (6), 92.295 (6), 100.489 (6)90, 90, 90
V (Å3)1393.66 (14)976.53 (12)1320.66 (3)
Z424
Radiation typeMo KαMo KαMo Kα
µ (mm−1)0.080.090.10
Crystal size (mm)0.30 × 0.08 × 0.080.30 × 0.05 × 0.030.25 × 0.25 × 0.25
Data collection
DiffractometerOxford Diffraction Xcalibur, Sapphire3 CCD
diffractometer		Oxford Diffraction Xcalibur, Sapphire3 CCD
diffractometer		Oxford Difraction Xcalibur, Sapphire3 CCD
diffractometer
Absorption correctionMulti-scan
(CrysAlis PRO; Oxford Diffraction, 2010)		Multi-scan
(CrysAlis PRO; Oxford Diffraction, 2010)		Multi-scan
(CrysAlis PRO; Oxford Diffraction, 2010)
Tmin, Tmax0.797, 1.0000.947, 1.0000.931, 1.000
No. of measured, independent and
observed [I > 2σ(I)] reflections		14087, 2737, 1717 7781, 4166, 2037 68869, 2878, 2670
Rint0.0470.0470.034
(sin θ/λ)max (Å−1)0.6170.6390.639
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.068, 0.213, 1.03 0.054, 0.086, 0.97 0.042, 0.106, 1.04
No. of reflections273741662878
No. of parameters162353240
No. of restraints011
H-atom treatmentH atoms treated by a mixture of independent and constrained refinementAll H-atom parameters refinedAll H-atom parameters refined
Δρmax, Δρmin (e Å−3)0.36, −0.300.15, −0.200.27, −0.26
Absolute structure??(Flack, 1983): 1585 Friedel pairs
Absolute structure parameter??0.2 (14)

Computer programs: CrysAlis PRO (Oxford Diffraction, 2010), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 2012), PLATON (Spek, 2009).

 

Footnotes

†IIIM Communication number: IIIM/1553/2013.

Acknowledgements

RR acknowledges the Council of Scientific and Industrial Research (CSIR), India, for financial assistance under MLP5009and BSC-120. RK wishes to acknowledge the Department of Science and Technology, India, for sanctioning the single-crystal X-ray diffractometer as a National Facility under project No: SR/S2 /CMP/47.

References

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Journal logoCRYSTALLOGRAPHIC
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ISSN: 2056-9890
Volume 70| Part 11| November 2014| Pages 272-277
doi:10.1107/S1600536814020777
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