Synthesis, crystal structure and Hirshfeld surface analysis of Fmoc-β-amino butyric acid and Fmoc carbamate

Abubakar Magaji, M.; Chen, B.; Robertson, C.C.

doi:10.1107/S2056989025003810

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Volume 81| Part 6| June 2025|

https://doi.org/10.1107/S2056989025003810

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Synthesis, crystal structure and Hirshfeld surface analysis of Fmoc-β-amino butyric acid and Fmoc carbamate

Mubarak Abubakar Magaji,^a Beining Chen ^a ^* and Craig Collumbine Robertson ^a ^*

^aSchool of Mathematical and Physical Sciences, Dainton Building, University of Sheffield, Brook Hill, Sheffield, S3 7HF, United Kingdom
^*Correspondence e-mail: b.chen@sheffield.ac.uk, craig.robertson@sheffield.ac.uk

Edited by F. Di Salvo, University of Buenos Aires, Argentina (Received 4 November 2024; accepted 28 April 2025; online 13 May 2025)

In the context of the development of synthetic routes that facilitate the incorporation of β-amino acids into peptide synthesis, the synthesis, crystal structure and Hirshfeld surface analysis are reported of fluorenylmethoxycarbonyl (Fmoc) protected β-amino butyric acid, namely, 3-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}butanoic acid, C₁₉H₁₉NO₄. The importance of pH control in the reaction employing Fmoc-N₃ is demonstrated with another β-amino acid analogue from which Fmoc carbamate was identified as the major product.

Keywords: crystal structure; Fmoc-β-amino butyric acid and Fmoc carbamate.

CCDC references: 2447425; 2447424

1. Chemical context

The increasing application of non-natural amino acids, particularly β-amino acids, in drug development, specifically peptide drugs necessitates the development of an economical and cost-effective method for producing modified β-amino acids. Modern peptide synthesis predominantly employs solid-phase peptide synthesis (SPPS) using the Fmoc strategy to mask the reactivity of the amine group with a temporary protective group (Behrendt et al., 2016 ). Peptide chain elongation can then be performed through sequential cycles involving the removal of the protective group, followed by the coupling of N-protected amino acids (Hlebowicz et al., 2005 ; Isidro-Llobet et al., 2007 ). This strategy allows efficient and controlled peptide assembly. Fmoc chemistry, while seemingly straightforward, presents challenges, particularly with β-amino acids due to the additional α-carbon, which serves as a potential reactive site. During the optimization of the synthesis of Fmoc-β-amino acids using alternatives to Fmoc-Cl, Fmoc-R-β-aminobutyric acid (Fmoc-R-βABA) 1 was synthesized to a high yield and purity after the in situ preparation of Fmoc-N₃ (Cruz et al., 2004 ). When the same technique was applied to the synthesis of Fmoc-DL-β-phenylalanine, Fmoc-carbamate 2 was obtained.

2. Structural commentary

Compound 1 crystallizes in the orthorhombic space group P2₁2₁2₁, its asymmetric unit comprising of a single molecule (Fig. 1). The tricyclic fluorenyl group is planar (r.m.s. deviation 0.025 Å). The carbamate group adopts the trans geometry and is planar (r.m.s. deviation 0.005 Å). The absolute configuration of an R stereogenic centre is confirmed to a high degree of certainty. The Hooft parameter of −0.05 (14) demonstrates that a single enantiomer is present. Compound 2 crystallizes in the orthorhombic space group Pca2₁, its asymmetric unit comprising of two molecules (Fig. 2). The two tricyclic fluorenyl groups are both planar (r.m.s. deviation of C16–C28 = 0.020 Å and C1–C13 = 0.025 Å). The carbamate group is planar (r.m.s. deviation 0.001 Å). The absolute configuration of an R stereogenic centre is confirmed to a high degree of certainty. The Hooft parameter of −0.05 (14) demonstrates that a single enantiomer is present.

Figure 1
The molecular structure of Fmoc-β-amino butyric acid 1 showing 50% displacement ellipsoids

Figure 2
The molecular structure of Fmoc carbamate 2 showing 50% displacement ellipsoids

3. Supramolecular features

In the molecular packing of crystal 1 (Fig. 3), two hydrogen-bonded (Table 1) chains are observed (Fig. 4). One chain forms from the carbamate hydrogen atom (H1) and the carbonyl oxygen atom (O1) of an adjacent molecule (−1 + x, y, z) and continues parallel to the a axis (Fig. 4). The second chain observed is formed by the carboxylic acid group hydrogen atom (H4) and the carbonyl oxygen atom (O3) of the adjacent molecule ( $[{1\over 2}]$ + x, $[{1\over 2}]$ − y, 1 − z). These chains are not linear but have an angle of 47.9 (10)° between the carboxylic acid planes of each molecule. Hydrogen-bond statistical analysis (Mercury 2024.1.0; Macrae et al., 2020 ) was performed, which highlighted the hydrogen bonds to be not unusual. The transamide chain hydrogen bond [2.844 (2) Å] is a little below average in distance (2.97 Å) from 1428 hits. The carboxylic acid chain hydrogen bond [2.656 (2) Å] was found to be of average distance (2.66 Å) from 3072 hits.

Table 1
Hydrogen-bond geometry (Å, °) for 1

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O4—H4⋯O3ⁱ	0.94 (4)	1.72 (4)	2.656 (2)	177 (3)
N1—H1⋯O1ⁱⁱ	0.88 (3)	2.04 (3)	2.844 (3)	152 (2)
Symmetry codes: (i) $[x+{\script{1\over 2}}, -y+{\script{1\over 2}}, -z+1]$ ; (ii) .

Figure 3
Packing of 1 as viewed along the a axis

Figure 4
Hydrogen bonding present in 1

Strong face–face π–π interactions (as investigated with the CSD Materials Aromatics Analyser tool) are observed in the packing of 1, running parallel to the a axis. The rings C1–C6 and C8–13 form columns stacking on top and below with symmetry equivalents (x, y, z and −1 + x, y, z), with a centroid–centroid distance of 4.8393 (2) Å and twist plane angle of 0.0 (3)°. These interactions can be visualised later in the Hirshfield surface analysis plot (Fig. 7, 2nd from top) showing the C⋯H/H⋯C interactions primarily around the Fmoc group.In the molecular packing of crystal 2 (Fig. 5), the two molecules in the asymmetric unit dimerize with hydrogen bonds (Table 2) formed between the carbamate hydrogen atom (H2A) and oxygen atom (O1), as well as the carbamate hydrogen atom (H1B) and oxygen atom (O3). The other carbamate hydrogen atoms of each of the two molecules then form a further hydrogen bond to an adjacent molecule to form a 1D hydrogen-bonded network (Fig. 6). The carbamate hydrogen atom (H1A) forms a hydrogen bond with oxygen atom (O1) (x, −1 + y, z) and the carbamate hydrogen atom (H2B) with oxygen atom (O3) (x, 1 + y, z). Hydrogen-bond statistical analysis (Mercury 2024.1.0; Macrae et al., 2020) was performed, which allowed comparison to 3268 structures. This showed that the dimeric hydrogen bonds (N2—H2A⋯O1) and (N1—H1B⋯O3) were not unusual. The hydrogen bonds (N1—H1A⋯O1) and (N2—H2B⋯O3) were found to be unusual on account of their hydrogen bonds having shorter lengths and more acute angles [2.8549 (3) Å, 149 (3)° and 2.827 (3) Å, 152 (3)°, respectively] below the mean (2.94 Å and 173.35°). A strong face–face π–π interaction is observed in the packing of 2 between the rings C17–C22 and C23–-28 (x, −1 + y, z) as well as between C2–C7 and C8–C13(x, 1 + y, z) columns stacking on top and below with symmetry equivalents), with a centroid–centroid distance of 4.4182 (15) Å and relative orientation of 2.55 (9)°. These interactions can also be visualised later in the Hirshfield surface analysis plot (Fig. 8, 2nd from top) showing the ⋯H/H⋯C interactions around the Fmoc group.

Table 2
Hydrogen-bond geometry (Å, °) for 2

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1B⋯O3	0.91 (3)	2.06 (3)	2.955 (3)	169 (3)
N1—H1A⋯O1ⁱ	0.86 (3)	2.08 (3)	2.849 (3)	149 (3)
N2—H2A⋯O1	0.85 (3)	2.13 (3)	2.967 (3)	169 (3)
N2—H2B⋯O3ⁱⁱ	0.87 (4)	2.03 (4)	2.827 (3)	152 (3)
Symmetry codes: (i) ; (ii) .

Figure 5
Packing of 2 as viewed along the b axis

Figure 6
Hydrogen bonding between the carbamate groups present in 2

4. Database survey

A search of the Cambridge Structural Database (CSD version 5.46, November 2024; Groom et al., 2016 ) highlighted that the crystal structures of compounds 1 and 2 have not been reported. Searches for structural motifs similar to 1 began with Fmoc-protected α-amino acids and discovered 51 results of various natural amino acids, synthetic derivatives and co-crystals, the most closely related structure being CUWKIO (Valle et al., 1984 ), a Fmoc-protected alanine monohydrate that differs in structure by the one carbon atom as well as co-crystallizing with a molecule of water. Despite crystallizing in the same space group as 1, CUWKIO has a different set of hydrogen bonds formed within the crystal structure. Instead of the amide hydrogen-bonded chains seen in 1, the amide H atom of CUWKIO forms a hydrogen bond to the carboxylic acid carbonyl whereas the co-crystallized water forms a hydrogen bond to the amide carbonyl. The co-crystallized water then satisfies its remaining hydrogen-bond formation with the carboxylic acid carbonyl and the carboxylic acid hydrogen is satisfied by forming a hydrogen bond to the water. In total, four hydrogen bonds are reported in CUWKIO in contrast to 1, which has two. Aromatic interactions, as investigated with the CSD Materials Aromatics Analyser tool, highlight a change in packing of the π–π interactions of the Fmoc groups. Strong face-face interactions in 1 are no longer present but instead strong edge-to-face interactions seen in CUWKIO. Further investigation of structural similarities lead us to look for Fmoc-protected β-amino acids, the structural motif of which was found the related structure BOMRAY (Ahmad Wani et al., 2014 ), which differs as there is a spiro-centred carbon with cyclic six-membered ring at the β carbon, in contrast to 1, which has the methyl group as well as being a racemate. BOMRAY crystallises in the P $[\overline{1}]$ space group and the primary hydrogen-bond interactions are a not unusual dimerization of the carboxylic acid as well as a long amide N—H to carboxylic acid carbonyl bond. The amide carbonyl in this case only forms a long weak intermolecular interaction with a CH₂ group. Analysis of the aromatic interactions in BOMRAY reveals strong face-face π-stacking interactions, albeit with an offset, meaning only one of the phenyl rings is involved in the interaction.

5. Hirshfeld surface analysis

In order to visualise the intermolecular interactions in 1 and 2, Hirshfeld surface analysis was carried out using CrystalExplorer 21.5 (Spackman et al., 2021 ) and visualised via two-dimensional fingerprint plots (McKinnon et al., 2007 ). The Hirshfeld surface analysis of 2 was carried out with the asymmetric unit of the two molecules. The left columns of Fig. 7 (top) and 8 (top) show the Hirshfeld surfaces of 1 and 2, respectively, each mapped with the function d_norm, which is the sum of the distances from a surface point to the nearest interior (d_i) and exterior(d_e) atom, normalized by the van der Waals (vdW) radii of the corresponding atom (r_vdW). Contacts shorter than the sum of their vdW radii are shown in red, those longer in blue and those approximately equal to their vdW radii in white. In the structure of 1, Fig. 7, the shortest contacts, with the most intense red spots, are shown to be the hydrogen-bonding sites, as shown in Fig. 4, the carboxylic acid and amide. The fingerprint plots (Tan et al., 2019 ) for 1 and 2 are given in the right columns of Figs. 7 and 8 and the intermolecular interactions shown in Tables 3 and 4, respectively. The overall fingerprint plots are shown first (top) followed by those delineated into C⋯H/H⋯C, H/H, N⋯H/H⋯N and O⋯H/H⋯O. For 1, the most important overall contribution is H⋯H, Fig. 7, contributing 51.8% with the tip of d_e = d_i at 1.12 Å. The shortest interactions, the hydrogen bonding at the carboxylic acid and amide sites, as highlighted by the d_norm surface plot, are clearly visualized in the bottom O⋯H/H⋯O plot with the shortest distances. The C⋯H⋯π interactions are shown in the the surface of the C⋯H/H⋯C highlighted figure as well as the characteristic wings revealed in the fingerprint plot. For structure 2, while the dimerization of the amine and carbonyl within the asymmetric unit is occluded from the view, the surface map shows the brightest red spots corresponding to the hydrogen bond formed from the amine to carbonyl, clearly highlighted in Fig. 8 (bottom) surface displaying O⋯H/H⋯O contacts and its corresponding plot demonstrating the shortest distance. In 2, the most important contribution again is H⋯H, contributing 51.9% with the tip of d_e = d_i at 1.16 Å.

Table 3
Summary of the percentages of intermolecular contacts contributed to the HSA surface of Fmoc-protected β-aminobutyric acid 1

Inside atom		Outside atom			Total contributions
	C	H	N	O
C	2.0	13.0	0.0	0.2	15.3
H	9.8	51.8	0.5	9.8	71.9
N	0.0	0.5	0.0	0.0	0.5
O	0.2	11.6	0.0	0.5	12.3
Total contributions	12.0	77.0	0.5	10.5

Table 4
Summary of the percentages of intermolecular contacts contributed to the HSA surface of Fmoc carbamate 2

Inside atom		Outside atom			Total contributions
	C	H	N	O
C	2.6	17.9	0.0	0.1	20.7
H	13.6	51.9	1.2	4.9	71.6
N	0.0	1.2	0.0	0.2	1.4
O	0.1	5.5	0.1	0.6	6.4
Total contributions	16.3	76.6	1.3	5.8

Figure 7
Hirshfeld surfaces of 1 mapped with d_norm (left image of each pair) with the corresponding two-dimensional fingerprint plot (right image of each pair) showing firstly all contributions and then the major contributions of C⋯H/H⋯C, H⋯H, N⋯H/H⋯N and O⋯H/H⋯O contacts.

Figure 8
Hirshfeld surfaces of 2 mapped with d_norm (left image of each pair) with the corresponding two-dimensional fingerprint plot (right image of each pair) showing firstly all contributions and then the major contributions of C⋯H/H⋯C, H⋯H, N⋯H/H⋯N and O⋯H/H⋯O contacts.

6. Synthesis and crystallization

Fmoc-Cl was initially derivatized into Fmoc-N₃ to prepare it for addition to solutions of the β-amino acid. Specifically, 10 mmol of Fmoc-Cl were dissolved in dioxane (5 ml), while 12 mmol of NaN₃ were dissolved in a 2:1 mixture of dioxane/water (10 ml). The Fmoc-Cl solution was then added to the NaN₃ solution, and the resulting mixture was stirred at 323 K for 2 h.>

For the synthesis of 1, (Fig. 9)11 mmol of R-βABA were dissolved in a 2:1 mixture of dioxane/10% NaHCO₃, which maintains the pH at 8–9. The Fmoc-N₃ solution was cautiously added in three portions to the β-amino acid over a period of 1 h. The reaction mixture was then stirred for 15 h at room temperature. Following the reaction, the mixture was poured into 5 mL of ice-cold water and subjected to three extractions with petroleum ether. The aqueous layers were separated using a separation funnel and chilled on ice for 2 h. Subsequently, the aqueous layer was acidified to pH 1 with 2 M HCl. The resulting precipitate was filtered and washed with ice-cold water until a pH of about 5 was attained. The collected white solid was placed in a petri dish covered with a paper towel and left to dry overnight within the fume hood. X-ray quality single crystals were grown by recrystallization from ethyl acetate/pet ether. NMR: ¹H NMR (400 MHz, DMSO) δ = 12.18 (s, 1H), 7.89 (dd, J = 7.3, 5.9, 3H), 7.73–7.62 (m, 3H), 7.47–7.26 (m, 7H), 4.63 (d, J = 6.2, 1H), 4.38–4.17 (m, 3H), 3.88 (hept, J = 6.8, 1H), 2.50–2.42 (m, 1H), 2.30 (dd, J = 15.4, 7.3, 1H), 1.10 (d, J = 6.6, 2H). ¹³C NMR (101 MHz, DMSO) δ 128.03, 127.32, 125.56, 125.21, 120.29, 69.65, 65.78, 65.43, 47.14, 47.14, 46.44, 44.33, 41.51, 41.51, 41.16, 40.11, 21.12, 20.77. MP:120-125 °C HRMS Analysis: m/z (ES⁺) 326.1401. C₁₉H₂₀NO₄ requires 326.1387.

Figure 9
The synthesis of the title compounds.

For the synthesis of 2, 11 mmol of DL-β-phenylalanine were dissolved in a 2:1 mixture of dioxane/10% NaHCO₃ along with NH₄OH (1 mL), which maintains the pH at 12. As above, the Fmoc-N₃ solution was cautiously added in three portions to the β-amino acid over a period of 1 h. The reaction mixture was then stirred for 15 h at room temperature. Following the reaction, the mixture was poured into 5 mL of ice-cold water and subjected to three extractions with petroleum ether. The aqueous layers were separated using a separation funnel and chilled on ice for 2 h. Subsequently, the aqueous layer was acidified to pH 1 with 2 M HCl. The resulting precipitate was filtered and washed with ice-cold water until a pH of about 5 was attained. The collected white solid was placed in a Petri dish covered with a paper towel and left to dry overnight within the fume hood. X-ray quality single crystals were grown by recrystallization from ethyl acetate/pet ether. M.p. 471–473 K NMR: ¹H NMR (400 MHz, DMSO) δ = 7.89 (d, J = 7.5, 2H), 7.70 (d, J = 7.4, 2H), 7.46–7.38 (m, 2H), 7.34 (td, J = 7.4, 1.2, 2H), 6.75 (s, 1H), 6.55 (s, 1H), 4.28 (d, J = 1.6, 1H), 4.27 (s, 1H), 4.22 (dd, J = 8.0, 5.7, 1H). ¹³C NMR (101 MHz, DMSO) δ = 157.20, 157.13, 144.45, 143.05, 141.21, 139.90, 137.90, 129.39, 128.06, 127.76, 127.52, 125.62, 121.85, 120.57, 120.49, 110.19, 65.48, 47.22. HRMS Analysis: m/z (ES⁺) C₁₅H₁₃NO₂ requires 239.26.

7. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 5. All carbon-bound H atoms were positioned geometrically and refined as riding, with aromatic C—H = 0.95 Å, sp³ C—H = 1.00 Å, sp³ C—H₂ 0.99 Å and with U_iso(H) = 1.2 U_eq(C) and sp³ C—H₃ = 0.98 Å with U_iso(H) = 1.5U_eq(methyl C). Hydrogen atoms involved in hydrogen-bonding interactions were refined isotropically.

Table 5
Experimental details

	1	2
Crystal data
Chemical formula	C₁₉H₁₉NO₄	C₁₅H₁₃NO₂
M_r	325.35	239.26
Crystal system, space group	Orthorhombic, P2₁2₁2₁	Orthorhombic, Pca2₁
Temperature (K)	100	100
a, b, c (Å)	4.8393 (2), 12.4928 (4), 27.3101 (9)	15.3560 (3), 5.0400 (1), 31.0254 (7)
V (Å³)	1651.07 (10)	2401.19 (9)
Z	4	8
Radiation type	Cu Kα	Cu Kα
μ (mm⁻¹)	0.75	0.71
Crystal size (mm)	0.3 × 0.03 × 0.01	0.25 × 0.03 × 0.01

Data collection
Diffractometer	Bruker D8 Venture Photon III	Bruker D8 Venture Photon III
Absorption correction	Multi-scan (SADABS; Krause et al., 2015 )	Multi-scan (SADABS; Krause et al., 2015)
T_min, T_max	0.664, 0.753	0.683, 0.753
No. of measured, independent and observed [I > 2σ(I)] reflections	25780, 2922, 2590	18874, 4069, 3754
R_int	0.081	0.051
(sin θ/λ)_max (Å⁻¹)	0.596	0.596

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.032, 0.073, 1.06	0.030, 0.068, 1.05
No. of reflections	2922	4069
No. of parameters	226	341
No. of restraints	0	1
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.12, −0.17	0.14, −0.17
Absolute structure	Flack x determined using 992 quotients [(I⁺)−(I⁻)]/[(I⁺)+(I⁻)] (Parsons et al., 2013 )	Flack x determined using 1617 quotients [(I⁺)−(I⁻)]/[(I⁺)+(I⁻)] (Parsons et al., 2013)
Absolute structure parameter	−0.05 (14)	−0.26 (13)
Computer programs: APEX5 and SAINT V8.40B (Bruker, 2023 ), SHELXT2018/2 (Sheldrick, 2015a ), SHELXL (Sheldrick, 2015b ) and OLEX2 (Dolomanov et al., 2009 ).

Supporting information

CCDC references: 2447425; 2447424

Crystal structure: contains datablocks 1, 2. DOI: https://doi.org/10.1107/S2056989025003810/vu2009sup1.cif

Structure factors: contains datablock 1. DOI: https://doi.org/10.1107/S2056989025003810/vu20091sup2.hkl

Structure factors: contains datablock 2. DOI: https://doi.org/10.1107/S2056989025003810/vu20092sup3.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989025003810/vu20091sup4.cml

checkCIF report

Computing details top

3-{[(9H-Fluoren-9-ylmethoxy)carbonyl]amino}butanoic acid (1) top

Crystal data top

C₁₉H₁₉NO₄	D_x = 1.309 Mg m⁻³
M_r = 325.35	Cu Kα radiation, λ = 1.54178 Å
Orthorhombic, P2₁2₁2₁	Cell parameters from 3582 reflections
a = 4.8393 (2) Å	θ = 3.2–66.6°
b = 12.4928 (4) Å	µ = 0.75 mm⁻¹
c = 27.3101 (9) Å	T = 100 K
V = 1651.07 (10) Å³	Needle, colourless
Z = 4	0.3 × 0.03 × 0.01 mm
F(000) = 688

Data collection top

Bruker D8 Venture Photon III diffractometer	2590 reflections with I > 2σ(I)
φ and ω scans	R_int = 0.081
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	θ_max = 66.8°, θ_min = 3.2°
T_min = 0.664, T_max = 0.753	h = −5→5
25780 measured reflections	k = −14→14
2922 independent reflections	l = −32→31

Refinement top

Refinement on F²	Hydrogen site location: mixed
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F² > 2σ(F²)] = 0.032	w = 1/[σ²(F_o²) + (0.0304P)² + 0.2044P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.073	(Δ/σ)_max < 0.001
S = 1.06	Δρ_max = 0.12 e Å⁻³
2922 reflections	Δρ_min = −0.17 e Å⁻³
226 parameters	Absolute structure: Flack x determined using 992 quotients [(I⁺)-(I^-)]/[(I⁺)+(I^-)] (Parsons et al., 2013)
0 restraints	Absolute structure parameter: −0.05 (14)
Primary atom site location: dual

Special details top

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. For 1, a needle crystal with dimensions 0.01 x 0.026 x 0.3 mm was selected and for 2, a needle crystal with dimensions 0.012 x 0.026 x 0.25 was selected. Intensity data for each was collected on a Bruker Venture Photon III diffractometer operating with a CuKα microfocus X-ray source with the crystal mounted in fomblin oil on a MicroMount (MiTeGen, USA) and cooled to 100 K in a stream of cold nitrogen gas using an Oxford Cryosystems 700 Cryostream. Data were corrected for absorption using empirical methods (SADABS; Bruker, 2023) based upon symmetry equivalent reflections combined with measurements at different azimuthal angles (Krause et al., 2015). The crystal structures were solved and refined against F² values using ShelXT (Sheldrick, 2015a) for solution and ShelXL (Sheldrick, 2015b) for refinement accessed via the Olex2 program (Dolomanov et al., 2009). Non-hydrogen atoms were refined anisotropically.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
O1	0.6114 (3)	0.65660 (13)	0.60381 (6)	0.0260 (4)
O2	0.2958 (3)	0.76326 (12)	0.64093 (6)	0.0254 (4)
O3	−0.0146 (4)	0.30716 (13)	0.53156 (6)	0.0309 (4)
O4	0.3887 (4)	0.38097 (14)	0.51041 (7)	0.0331 (4)
H4	0.422 (8)	0.314 (3)	0.4965 (14)	0.078 (12)*
N1	0.1735 (4)	0.67252 (15)	0.57425 (7)	0.0215 (4)
H1	0.005 (6)	0.691 (2)	0.5827 (9)	0.032 (7)*
C1	0.4148 (5)	0.89471 (18)	0.70131 (8)	0.0230 (5)
H1A	0.227847	0.885997	0.716402	0.028*
C2	0.4183 (5)	0.99043 (18)	0.66703 (8)	0.0231 (5)
C3	0.2681 (5)	1.0088 (2)	0.62449 (9)	0.0309 (6)
H3	0.133824	0.958606	0.613666	0.037*
C4	0.3181 (6)	1.1019 (2)	0.59806 (10)	0.0372 (7)
H4A	0.216012	1.115393	0.568994	0.045*
C5	0.5141 (6)	1.1755 (2)	0.61339 (10)	0.0374 (7)
H5	0.546508	1.238106	0.594522	0.045*
C6	0.6638 (6)	1.15843 (19)	0.65610 (10)	0.0326 (6)
H6	0.797817	1.208928	0.666704	0.039*
C7	0.6136 (5)	1.06620 (19)	0.68294 (9)	0.0250 (5)
C8	0.7377 (5)	1.02758 (18)	0.72875 (9)	0.0239 (5)
C9	0.9348 (5)	1.0736 (2)	0.75932 (10)	0.0304 (6)
H9	1.010016	1.142041	0.751993	0.037*
C10	1.0195 (6)	1.0182 (2)	0.80057 (9)	0.0346 (6)
H10	1.151438	1.049315	0.822029	0.042*
C11	0.9134 (6)	0.9177 (2)	0.81081 (9)	0.0322 (6)
H11	0.977890	0.879868	0.838730	0.039*
C12	0.7136 (5)	0.8712 (2)	0.78084 (9)	0.0273 (6)
H12	0.639459	0.802678	0.788335	0.033*
C13	0.6254 (5)	0.92702 (18)	0.73987 (8)	0.0229 (5)
C14	0.5056 (5)	0.79107 (19)	0.67675 (9)	0.0249 (5)
H14A	0.686512	0.801056	0.660463	0.030*
H14B	0.523900	0.733348	0.701367	0.030*
C15	0.3773 (5)	0.69342 (17)	0.60606 (9)	0.0213 (5)
C16	0.2032 (5)	0.58643 (17)	0.53839 (8)	0.0212 (5)
H16	0.404379	0.576644	0.531365	0.025*
C17	0.0920 (5)	0.48249 (18)	0.56036 (9)	0.0255 (5)
H17A	0.172825	0.473954	0.593435	0.031*
H17B	−0.110285	0.490126	0.564482	0.031*
C18	0.1454 (5)	0.38223 (18)	0.53224 (9)	0.0230 (5)
C19	0.0586 (6)	0.6161 (2)	0.49085 (9)	0.0314 (6)
H19A	−0.139338	0.625852	0.497011	0.047*
H19B	0.084998	0.558750	0.466822	0.047*
H19C	0.136876	0.682848	0.478078	0.047*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0159 (8)	0.0299 (9)	0.0323 (9)	0.0033 (7)	−0.0010 (7)	−0.0065 (8)
O2	0.0174 (8)	0.0265 (8)	0.0322 (9)	0.0008 (7)	−0.0031 (7)	−0.0098 (7)
O3	0.0281 (9)	0.0220 (8)	0.0427 (11)	−0.0025 (7)	0.0001 (8)	−0.0051 (8)
O4	0.0280 (10)	0.0227 (9)	0.0486 (12)	0.0002 (8)	0.0117 (9)	−0.0072 (8)
N1	0.0147 (10)	0.0212 (10)	0.0287 (11)	0.0010 (8)	−0.0011 (9)	−0.0044 (9)
C1	0.0195 (12)	0.0233 (12)	0.0263 (13)	−0.0004 (10)	−0.0001 (10)	−0.0031 (10)
C2	0.0202 (12)	0.0246 (12)	0.0246 (12)	0.0042 (10)	0.0031 (10)	−0.0036 (10)
C3	0.0278 (14)	0.0346 (14)	0.0304 (13)	0.0074 (12)	−0.0007 (11)	−0.0066 (12)
C4	0.0404 (16)	0.0419 (16)	0.0292 (14)	0.0167 (14)	−0.0002 (12)	0.0046 (12)
C5	0.0420 (16)	0.0315 (15)	0.0385 (16)	0.0098 (13)	0.0110 (13)	0.0094 (12)
C6	0.0316 (15)	0.0262 (13)	0.0402 (15)	0.0026 (12)	0.0074 (12)	0.0010 (12)
C7	0.0225 (12)	0.0235 (12)	0.0290 (13)	0.0040 (10)	0.0045 (10)	−0.0028 (10)
C8	0.0212 (12)	0.0236 (12)	0.0267 (13)	0.0007 (10)	0.0029 (10)	−0.0059 (10)
C9	0.0253 (14)	0.0266 (13)	0.0394 (15)	−0.0021 (11)	0.0021 (11)	−0.0098 (12)
C10	0.0307 (14)	0.0397 (16)	0.0336 (15)	0.0050 (12)	−0.0056 (12)	−0.0159 (13)
C11	0.0351 (15)	0.0360 (14)	0.0254 (13)	0.0116 (12)	−0.0032 (11)	−0.0072 (11)
C12	0.0311 (14)	0.0249 (12)	0.0258 (13)	0.0037 (11)	0.0039 (11)	−0.0036 (10)
C13	0.0204 (12)	0.0239 (12)	0.0243 (12)	0.0014 (10)	0.0038 (10)	−0.0044 (10)
C14	0.0199 (12)	0.0268 (13)	0.0279 (13)	−0.0010 (10)	−0.0042 (10)	−0.0063 (11)
C15	0.0209 (12)	0.0179 (11)	0.0251 (12)	−0.0031 (10)	0.0011 (10)	−0.0005 (10)
C16	0.0175 (11)	0.0203 (11)	0.0258 (12)	−0.0001 (9)	−0.0011 (10)	−0.0032 (10)
C17	0.0269 (12)	0.0220 (12)	0.0276 (13)	−0.0005 (10)	0.0043 (10)	−0.0026 (10)
C18	0.0222 (13)	0.0206 (11)	0.0261 (13)	0.0003 (10)	−0.0025 (10)	0.0025 (10)
C19	0.0382 (16)	0.0261 (13)	0.0300 (14)	0.0002 (12)	−0.0060 (12)	−0.0010 (11)

Geometric parameters (Å, º) top

O1—C15	1.224 (3)	C7—C8	1.469 (3)
O2—C14	1.452 (3)	C8—C9	1.392 (3)
O2—C15	1.350 (3)	C8—C13	1.402 (3)
O3—C18	1.216 (3)	C9—H9	0.9500
O4—H4	0.94 (4)	C9—C10	1.385 (4)
O4—C18	1.320 (3)	C10—H10	0.9500
N1—H1	0.88 (3)	C10—C11	1.384 (4)
N1—C15	1.340 (3)	C11—H11	0.9500
N1—C16	1.462 (3)	C11—C12	1.394 (4)
C1—H1A	1.0000	C12—H12	0.9500
C1—C2	1.519 (3)	C12—C13	1.386 (3)
C1—C13	1.520 (3)	C14—H14A	0.9900
C1—C14	1.523 (3)	C14—H14B	0.9900
C2—C3	1.389 (3)	C16—H16	1.0000
C2—C7	1.407 (3)	C16—C17	1.528 (3)
C3—H3	0.9500	C16—C19	1.521 (3)
C3—C4	1.391 (4)	C17—H17A	0.9900
C4—H4A	0.9500	C17—H17B	0.9900
C4—C5	1.385 (4)	C17—C18	1.492 (3)
C5—H5	0.9500	C19—H19A	0.9800
C5—C6	1.390 (4)	C19—H19B	0.9800
C6—H6	0.9500	C19—H19C	0.9800
C6—C7	1.387 (3)

C15—O2—C14	115.19 (17)	C10—C11—C12	121.1 (2)
C18—O4—H4	110 (2)	C12—C11—H11	119.4
C15—N1—H1	117.4 (18)	C11—C12—H12	120.7
C15—N1—C16	120.36 (19)	C13—C12—C11	118.5 (2)
C16—N1—H1	117.6 (18)	C13—C12—H12	120.7
C2—C1—H1A	110.5	C8—C13—C1	110.4 (2)
C2—C1—C13	102.15 (19)	C12—C13—C1	129.2 (2)
C2—C1—C14	113.24 (19)	C12—C13—C8	120.4 (2)
C13—C1—H1A	110.5	O2—C14—C1	107.37 (19)
C13—C1—C14	109.72 (19)	O2—C14—H14A	110.2
C14—C1—H1A	110.5	O2—C14—H14B	110.2
C3—C2—C1	129.7 (2)	C1—C14—H14A	110.2
C3—C2—C7	119.9 (2)	C1—C14—H14B	110.2
C7—C2—C1	110.3 (2)	H14A—C14—H14B	108.5
C2—C3—H3	120.6	O1—C15—O2	123.3 (2)
C2—C3—C4	118.8 (3)	O1—C15—N1	125.1 (2)
C4—C3—H3	120.6	N1—C15—O2	111.6 (2)
C3—C4—H4A	119.4	N1—C16—H16	108.3
C5—C4—C3	121.1 (3)	N1—C16—C17	109.11 (19)
C5—C4—H4A	119.4	N1—C16—C19	110.34 (18)
C4—C5—H5	119.7	C17—C16—H16	108.3
C4—C5—C6	120.6 (3)	C19—C16—H16	108.3
C6—C5—H5	119.7	C19—C16—C17	112.4 (2)
C5—C6—H6	120.7	C16—C17—H17A	108.1
C7—C6—C5	118.7 (3)	C16—C17—H17B	108.1
C7—C6—H6	120.7	H17A—C17—H17B	107.3
C2—C7—C8	108.5 (2)	C18—C17—C16	116.76 (19)
C6—C7—C2	120.9 (2)	C18—C17—H17A	108.1
C6—C7—C8	130.6 (2)	C18—C17—H17B	108.1
C9—C8—C7	130.9 (2)	O3—C18—O4	123.5 (2)
C9—C8—C13	120.4 (2)	O3—C18—C17	123.0 (2)
C13—C8—C7	108.7 (2)	O4—C18—C17	113.4 (2)
C8—C9—H9	120.5	C16—C19—H19A	109.5
C10—C9—C8	118.9 (2)	C16—C19—H19B	109.5
C10—C9—H9	120.5	C16—C19—H19C	109.5
C9—C10—H10	119.7	H19A—C19—H19B	109.5
C11—C10—C9	120.5 (2)	H19A—C19—H19C	109.5
C11—C10—H10	119.7	H19B—C19—H19C	109.5
C10—C11—H11	119.4

N1—C16—C17—C18	−170.6 (2)	C9—C8—C13—C12	−1.4 (3)
C1—C2—C3—C4	−177.1 (2)	C9—C10—C11—C12	−1.9 (4)
C1—C2—C7—C6	176.9 (2)	C10—C11—C12—C13	1.0 (4)
C1—C2—C7—C8	−2.4 (3)	C11—C12—C13—C1	179.4 (2)
C2—C1—C13—C8	−0.7 (2)	C11—C12—C13—C8	0.7 (3)
C2—C1—C13—C12	−179.5 (2)	C13—C1—C2—C3	−179.9 (2)
C2—C1—C14—O2	−67.4 (3)	C13—C1—C2—C7	1.9 (2)
C2—C3—C4—C5	0.2 (4)	C13—C1—C14—O2	179.18 (18)
C2—C7—C8—C9	−178.4 (2)	C13—C8—C9—C10	0.5 (4)
C2—C7—C8—C13	1.9 (3)	C14—O2—C15—O1	−1.0 (3)
C3—C2—C7—C6	−1.5 (4)	C14—O2—C15—N1	−179.49 (19)
C3—C2—C7—C8	179.2 (2)	C14—C1—C2—C3	62.2 (3)
C3—C4—C5—C6	−0.8 (4)	C14—C1—C2—C7	−116.0 (2)
C4—C5—C6—C7	0.2 (4)	C14—C1—C13—C8	119.7 (2)
C5—C6—C7—C2	0.9 (4)	C14—C1—C13—C12	−59.1 (3)
C5—C6—C7—C8	−179.9 (2)	C15—O2—C14—C1	161.10 (18)
C6—C7—C8—C9	2.3 (4)	C15—N1—C16—C17	90.3 (3)
C6—C7—C8—C13	−177.3 (3)	C15—N1—C16—C19	−145.8 (2)
C7—C2—C3—C4	0.9 (4)	C16—N1—C15—O1	11.4 (4)
C7—C8—C9—C10	−179.0 (2)	C16—N1—C15—O2	−170.19 (18)
C7—C8—C13—C1	−0.7 (3)	C16—C17—C18—O3	−147.0 (2)
C7—C8—C13—C12	178.2 (2)	C16—C17—C18—O4	36.3 (3)
C8—C9—C10—C11	1.1 (4)	C19—C16—C17—C18	66.7 (3)
C9—C8—C13—C1	179.6 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O4—H4···O3ⁱ	0.94 (4)	1.72 (4)	2.656 (2)	177 (3)
N1—H1···O1ⁱⁱ	0.88 (3)	2.04 (3)	2.844 (3)	152 (2)

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

(2) top

Crystal data top

C₁₅H₁₃NO₂	D_x = 1.324 Mg m⁻³
M_r = 239.26	Cu Kα radiation, λ = 1.54178 Å
Orthorhombic, Pca2₁	Cell parameters from 6701 reflections
a = 15.3560 (3) Å	θ = 3.2–65.9°
b = 5.0400 (1) Å	µ = 0.71 mm⁻¹
c = 31.0254 (7) Å	T = 100 K
V = 2401.19 (9) Å³	Needle, colourless
Z = 8	0.25 × 0.03 × 0.01 mm
F(000) = 1008

Data collection top

Bruker D8 Venture Photon III diffractometer	3754 reflections with I > 2σ(I)
φ and ω scans	R_int = 0.051
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	θ_max = 66.8°, θ_min = 2.9°
T_min = 0.683, T_max = 0.753	h = −18→18
18874 measured reflections	k = −5→5
4069 independent reflections	l = −36→36

Refinement top

Refinement on F²	Hydrogen site location: mixed
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F² > 2σ(F²)] = 0.030	w = 1/[σ²(F_o²) + (0.0291P)² + 0.3089P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.068	(Δ/σ)_max < 0.001
S = 1.05	Δρ_max = 0.14 e Å⁻³
4069 reflections	Δρ_min = −0.16 e Å⁻³
341 parameters	Absolute structure: Flack x determined using 1617 quotients [(I⁺)-(I^-)]/[(I⁺)+(I^-)] (Parsons et al., 2013)
1 restraint	Absolute structure parameter: −0.26 (13)
Primary atom site location: dual

Special details top

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
O1	0.53087 (12)	0.7151 (3)	0.47451 (7)	0.0233 (4)
O2	0.42477 (11)	0.4384 (3)	0.45115 (6)	0.0198 (4)
N1	0.53609 (17)	0.2741 (4)	0.48787 (8)	0.0230 (5)
H1A	0.5141 (19)	0.123 (6)	0.4816 (10)	0.019 (7)*
H1B	0.589 (2)	0.295 (6)	0.5007 (11)	0.031 (8)*
C1	0.32636 (17)	0.5633 (5)	0.39449 (9)	0.0176 (6)
H1	0.293372	0.398198	0.401756	0.021*
C2	0.26475 (15)	0.7768 (5)	0.37850 (9)	0.0176 (5)
C3	0.19497 (17)	0.8955 (5)	0.39955 (9)	0.0226 (6)
H3	0.179526	0.844026	0.427999	0.027*
C4	0.14832 (17)	1.0913 (6)	0.37805 (11)	0.0263 (6)
H4	0.100259	1.173510	0.391963	0.032*
C5	0.17085 (18)	1.1689 (5)	0.33649 (9)	0.0248 (6)
H5	0.138392	1.303942	0.322415	0.030*
C6	0.24063 (19)	1.0499 (5)	0.31541 (10)	0.0221 (6)
H6	0.256156	1.102689	0.287037	0.027*
C7	0.28718 (16)	0.8528 (5)	0.33653 (9)	0.0176 (5)
C8	0.36178 (15)	0.6916 (5)	0.32254 (8)	0.0171 (5)
C9	0.40625 (17)	0.6884 (5)	0.28345 (9)	0.0212 (6)
H9	0.391122	0.808222	0.261028	0.025*
C10	0.4733 (2)	0.5061 (5)	0.27793 (11)	0.0251 (7)
H10	0.503783	0.499597	0.251306	0.030*
C11	0.49616 (17)	0.3337 (5)	0.31090 (10)	0.0237 (6)
H11	0.542294	0.210925	0.306624	0.028*
C12	0.45228 (17)	0.3385 (5)	0.35021 (9)	0.0205 (6)
H12	0.468555	0.221720	0.372863	0.025*
C13	0.38445 (19)	0.5168 (5)	0.35564 (10)	0.0170 (6)
C14	0.37677 (17)	0.6619 (5)	0.43372 (9)	0.0194 (5)
H14A	0.417409	0.805151	0.425237	0.023*
H14B	0.336087	0.732822	0.455632	0.023*
C15	0.50003 (18)	0.4899 (5)	0.47137 (9)	0.0165 (6)
O3	0.71790 (12)	0.3289 (3)	0.51774 (6)	0.0235 (4)
O4	0.81702 (12)	0.6052 (3)	0.54788 (6)	0.0203 (4)
N2	0.71138 (16)	0.7720 (4)	0.50730 (8)	0.0201 (5)
H2A	0.663 (2)	0.759 (5)	0.4946 (10)	0.019 (7)*
H2B	0.730 (2)	0.928 (7)	0.5147 (11)	0.033 (9)*
C16	0.91776 (18)	0.4654 (5)	0.60216 (9)	0.0182 (6)
H16	0.948852	0.635510	0.595949	0.022*
C17	0.98232 (16)	0.2503 (5)	0.61506 (9)	0.0187 (5)
C18	1.05075 (16)	0.1434 (5)	0.59156 (9)	0.0229 (6)
H18	1.062974	0.204782	0.563253	0.028*
C19	1.10103 (18)	−0.0548 (6)	0.61018 (11)	0.0282 (7)
H19	1.148311	−0.128562	0.594474	0.034*
C20	1.08324 (19)	−0.1464 (5)	0.65126 (11)	0.0300 (7)
H20	1.118190	−0.283160	0.663310	0.036*
C21	1.0147 (2)	−0.0408 (5)	0.67526 (10)	0.0248 (7)
H21	1.002632	−0.103184	0.703529	0.030*
C22	0.96431 (16)	0.1588 (5)	0.65662 (9)	0.0187 (5)
C23	0.88995 (16)	0.3076 (5)	0.67375 (8)	0.0183 (5)
C24	0.84808 (18)	0.2916 (6)	0.71340 (9)	0.0232 (6)
H24	0.865756	0.164739	0.734293	0.028*
C25	0.7798 (2)	0.4652 (6)	0.72182 (11)	0.0274 (7)
H25	0.751130	0.458980	0.748942	0.033*
C26	0.75307 (19)	0.6472 (5)	0.69102 (10)	0.0266 (6)
H26	0.706041	0.763484	0.697254	0.032*
C27	0.79414 (17)	0.6619 (5)	0.65113 (9)	0.0225 (6)
H27	0.775450	0.786606	0.630113	0.027*
C28	0.86269 (19)	0.4917 (5)	0.64261 (10)	0.0178 (6)
C29	0.86563 (17)	0.3768 (5)	0.56314 (9)	0.0186 (5)
H29A	0.905150	0.311282	0.540284	0.022*
H29B	0.825305	0.231754	0.571180	0.022*
C30	0.74632 (18)	0.5541 (5)	0.52380 (9)	0.0164 (5)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0227 (10)	0.0147 (9)	0.0326 (11)	−0.0011 (7)	−0.0087 (8)	−0.0015 (8)
O2	0.0215 (10)	0.0167 (9)	0.0211 (10)	−0.0041 (7)	−0.0075 (8)	0.0043 (7)
N1	0.0222 (13)	0.0150 (12)	0.0318 (14)	−0.0029 (9)	−0.0085 (11)	0.0005 (10)
C1	0.0160 (14)	0.0192 (13)	0.0176 (14)	−0.0019 (11)	−0.0010 (11)	0.0023 (10)
C2	0.0145 (11)	0.0163 (12)	0.0220 (14)	−0.0035 (9)	−0.0055 (10)	−0.0027 (11)
C3	0.0177 (13)	0.0271 (14)	0.0231 (15)	−0.0014 (11)	−0.0005 (11)	−0.0039 (11)
C4	0.0146 (13)	0.0256 (14)	0.0388 (18)	0.0021 (11)	−0.0022 (12)	−0.0103 (14)
C5	0.0194 (13)	0.0216 (13)	0.0334 (16)	0.0018 (10)	−0.0108 (11)	−0.0008 (11)
C6	0.0236 (15)	0.0216 (13)	0.0212 (15)	−0.0006 (11)	−0.0047 (12)	0.0012 (11)
C7	0.0135 (12)	0.0169 (13)	0.0225 (14)	−0.0027 (9)	−0.0037 (10)	−0.0020 (10)
C8	0.0145 (12)	0.0159 (13)	0.0208 (14)	−0.0041 (10)	−0.0024 (10)	0.0004 (10)
C9	0.0209 (13)	0.0214 (13)	0.0213 (14)	−0.0013 (11)	0.0002 (11)	0.0037 (10)
C10	0.0197 (16)	0.0308 (16)	0.0248 (18)	−0.0006 (10)	0.0063 (13)	−0.0013 (12)
C11	0.0180 (13)	0.0226 (14)	0.0304 (16)	0.0019 (11)	0.0001 (11)	−0.0014 (11)
C12	0.0192 (13)	0.0186 (13)	0.0235 (15)	−0.0011 (10)	−0.0038 (11)	0.0018 (11)
C13	0.0157 (15)	0.0160 (13)	0.0194 (15)	−0.0034 (9)	−0.0047 (12)	−0.0014 (10)
C14	0.0200 (13)	0.0183 (13)	0.0199 (14)	0.0007 (9)	−0.0044 (11)	0.0033 (11)
C15	0.0160 (13)	0.0188 (13)	0.0149 (14)	0.0002 (9)	0.0005 (11)	−0.0020 (10)
O3	0.0211 (10)	0.0142 (9)	0.0351 (12)	−0.0008 (7)	−0.0083 (8)	−0.0002 (8)
O4	0.0226 (10)	0.0144 (9)	0.0239 (10)	−0.0017 (7)	−0.0079 (8)	0.0020 (8)
N2	0.0195 (12)	0.0145 (11)	0.0263 (13)	−0.0004 (9)	−0.0079 (10)	0.0012 (9)
C16	0.0163 (12)	0.0185 (13)	0.0198 (15)	−0.0012 (9)	−0.0030 (11)	0.0020 (11)
C17	0.0150 (11)	0.0190 (12)	0.0223 (14)	−0.0031 (9)	−0.0043 (10)	−0.0002 (10)
C18	0.0163 (12)	0.0278 (14)	0.0248 (15)	−0.0030 (10)	−0.0019 (11)	−0.0032 (11)
C19	0.0163 (14)	0.0311 (15)	0.0372 (18)	0.0008 (11)	−0.0036 (12)	−0.0071 (13)
C20	0.0256 (14)	0.0213 (14)	0.0432 (19)	0.0054 (11)	−0.0156 (14)	−0.0015 (12)
C21	0.0239 (16)	0.0251 (14)	0.0255 (16)	−0.0028 (11)	−0.0117 (13)	0.0028 (12)
C22	0.0183 (13)	0.0172 (12)	0.0205 (14)	−0.0033 (9)	−0.0056 (11)	−0.0008 (10)
C23	0.0183 (12)	0.0190 (13)	0.0176 (14)	−0.0053 (10)	−0.0044 (10)	0.0000 (10)
C24	0.0260 (14)	0.0268 (15)	0.0167 (13)	−0.0093 (11)	−0.0030 (10)	−0.0014 (11)
C25	0.0258 (17)	0.0327 (16)	0.0236 (18)	−0.0113 (12)	0.0054 (14)	−0.0104 (12)
C26	0.0208 (13)	0.0251 (15)	0.0340 (17)	−0.0021 (11)	0.0041 (12)	−0.0124 (12)
C27	0.0197 (13)	0.0202 (13)	0.0275 (15)	−0.0009 (10)	−0.0020 (12)	−0.0033 (11)
C28	0.0147 (14)	0.0186 (14)	0.0201 (16)	−0.0043 (9)	−0.0015 (12)	−0.0022 (10)
C29	0.0202 (13)	0.0166 (13)	0.0189 (13)	0.0030 (10)	−0.0025 (10)	0.0028 (10)
C30	0.0153 (13)	0.0197 (13)	0.0142 (14)	−0.0006 (10)	−0.0003 (11)	−0.0004 (11)

Geometric parameters (Å, º) top

O1—C15	1.234 (3)	O3—C30	1.230 (3)
O2—C14	1.450 (3)	O4—C29	1.451 (3)
O2—C15	1.340 (3)	O4—C30	1.343 (3)
N1—H1A	0.86 (3)	N2—H2A	0.85 (3)
N1—H1B	0.91 (3)	N2—H2B	0.87 (4)
N1—C15	1.323 (4)	N2—C30	1.325 (3)
C1—H1	1.0000	C16—H16	1.0000
C1—C2	1.516 (4)	C16—C17	1.523 (4)
C1—C13	1.518 (4)	C16—C28	1.519 (4)
C1—C14	1.526 (4)	C16—C29	1.518 (4)
C2—C3	1.390 (4)	C17—C18	1.388 (4)
C2—C7	1.400 (4)	C17—C22	1.397 (4)
C3—H3	0.9500	C18—H18	0.9500
C3—C4	1.390 (4)	C18—C19	1.389 (4)
C4—H4	0.9500	C19—H19	0.9500
C4—C5	1.391 (4)	C19—C20	1.383 (5)
C5—H5	0.9500	C20—H20	0.9500
C5—C6	1.391 (4)	C20—C21	1.395 (4)
C6—H6	0.9500	C21—H21	0.9500
C6—C7	1.388 (4)	C21—C22	1.395 (4)
C7—C8	1.470 (4)	C22—C23	1.466 (4)
C8—C9	1.392 (4)	C23—C24	1.390 (4)
C8—C13	1.397 (4)	C23—C28	1.403 (4)
C9—H9	0.9500	C24—H24	0.9500
C9—C10	1.391 (4)	C24—C25	1.391 (4)
C10—H10	0.9500	C25—H25	0.9500
C10—C11	1.387 (4)	C25—C26	1.387 (5)
C11—H11	0.9500	C26—H26	0.9500
C11—C12	1.394 (4)	C26—C27	1.391 (4)
C12—H12	0.9500	C27—H27	0.9500
C12—C13	1.386 (4)	C27—C28	1.383 (4)
C14—H14A	0.9900	C29—H29A	0.9900
C14—H14B	0.9900	C29—H29B	0.9900

C15—O2—C14	117.54 (19)	C30—O4—C29	116.43 (19)
H1A—N1—H1B	124 (3)	H2A—N2—H2B	119 (3)
C15—N1—H1A	119 (2)	C30—N2—H2A	118.4 (19)
C15—N1—H1B	116 (2)	C30—N2—H2B	121 (2)
C2—C1—H1	110.4	C17—C16—H16	110.5
C2—C1—C13	102.5 (2)	C28—C16—H16	110.5
C2—C1—C14	110.3 (2)	C28—C16—C17	102.0 (2)
C13—C1—H1	110.4	C29—C16—H16	110.5
C13—C1—C14	112.7 (2)	C29—C16—C17	110.1 (2)
C14—C1—H1	110.4	C29—C16—C28	113.0 (2)
C3—C2—C1	129.3 (3)	C18—C17—C16	129.1 (2)
C3—C2—C7	120.6 (2)	C18—C17—C22	120.4 (2)
C7—C2—C1	110.2 (2)	C22—C17—C16	110.4 (2)
C2—C3—H3	120.7	C17—C18—H18	120.6
C4—C3—C2	118.5 (3)	C17—C18—C19	118.8 (3)
C4—C3—H3	120.7	C19—C18—H18	120.6
C3—C4—H4	119.5	C18—C19—H19	119.5
C3—C4—C5	121.1 (3)	C20—C19—C18	120.9 (3)
C5—C4—H4	119.5	C20—C19—H19	119.5
C4—C5—H5	119.8	C19—C20—H20	119.6
C4—C5—C6	120.4 (3)	C19—C20—C21	120.9 (3)
C6—C5—H5	119.8	C21—C20—H20	119.6
C5—C6—H6	120.6	C20—C21—H21	120.9
C7—C6—C5	118.9 (3)	C22—C21—C20	118.2 (3)
C7—C6—H6	120.6	C22—C21—H21	120.9
C2—C7—C8	108.4 (2)	C17—C22—C23	108.7 (2)
C6—C7—C2	120.5 (2)	C21—C22—C17	120.7 (3)
C6—C7—C8	131.1 (3)	C21—C22—C23	130.6 (3)
C9—C8—C7	130.2 (2)	C24—C23—C22	130.6 (2)
C9—C8—C13	120.7 (2)	C24—C23—C28	120.6 (2)
C13—C8—C7	109.0 (2)	C28—C23—C22	108.7 (2)
C8—C9—H9	120.7	C23—C24—H24	120.7
C10—C9—C8	118.6 (3)	C23—C24—C25	118.6 (3)
C10—C9—H9	120.7	C25—C24—H24	120.7
C9—C10—H10	119.7	C24—C25—H25	119.7
C11—C10—C9	120.7 (3)	C26—C25—C24	120.7 (3)
C11—C10—H10	119.7	C26—C25—H25	119.7
C10—C11—H11	119.6	C25—C26—H26	119.5
C10—C11—C12	120.8 (2)	C25—C26—C27	121.0 (3)
C12—C11—H11	119.6	C27—C26—H26	119.5
C11—C12—H12	120.6	C26—C27—H27	120.6
C13—C12—C11	118.7 (3)	C28—C27—C26	118.8 (3)
C13—C12—H12	120.6	C28—C27—H27	120.6
C8—C13—C1	109.9 (2)	C23—C28—C16	110.2 (2)
C12—C13—C1	129.7 (3)	C27—C28—C16	129.5 (3)
C12—C13—C8	120.4 (3)	C27—C28—C23	120.4 (3)
O2—C14—C1	107.6 (2)	O4—C29—C16	107.33 (19)
O2—C14—H14A	110.2	O4—C29—H29A	110.2
O2—C14—H14B	110.2	O4—C29—H29B	110.2
C1—C14—H14A	110.2	C16—C29—H29A	110.2
C1—C14—H14B	110.2	C16—C29—H29B	110.2
H14A—C14—H14B	108.5	H29A—C29—H29B	108.5
O1—C15—O2	123.1 (2)	O3—C30—O4	123.3 (2)
O1—C15—N1	124.4 (3)	O3—C30—N2	124.2 (3)
N1—C15—O2	112.5 (2)	N2—C30—O4	112.5 (2)

C1—C2—C3—C4	179.2 (3)	C16—C17—C18—C19	−179.5 (3)
C1—C2—C7—C6	−178.9 (2)	C16—C17—C22—C21	179.5 (2)
C1—C2—C7—C8	1.5 (3)	C16—C17—C22—C23	−1.2 (3)
C2—C1—C13—C8	2.8 (3)	C17—C16—C28—C23	−2.3 (3)
C2—C1—C13—C12	−178.2 (3)	C17—C16—C28—C27	178.2 (3)
C2—C1—C14—O2	171.9 (2)	C17—C16—C29—O4	−170.1 (2)
C2—C3—C4—C5	−0.4 (4)	C17—C18—C19—C20	0.4 (4)
C2—C7—C8—C9	178.4 (2)	C17—C22—C23—C24	−179.6 (2)
C2—C7—C8—C13	0.4 (3)	C17—C22—C23—C28	−0.3 (3)
C3—C2—C7—C6	0.6 (4)	C18—C17—C22—C21	0.1 (4)
C3—C2—C7—C8	−179.0 (2)	C18—C17—C22—C23	179.4 (2)
C3—C4—C5—C6	0.4 (4)	C18—C19—C20—C21	−0.5 (4)
C4—C5—C6—C7	0.1 (4)	C19—C20—C21—C22	0.3 (4)
C5—C6—C7—C2	−0.6 (4)	C20—C21—C22—C17	−0.1 (4)
C5—C6—C7—C8	179.0 (3)	C20—C21—C22—C23	−179.2 (3)
C6—C7—C8—C9	−1.2 (5)	C21—C22—C23—C24	−0.3 (5)
C6—C7—C8—C13	−179.2 (3)	C21—C22—C23—C28	178.9 (3)
C7—C2—C3—C4	−0.2 (4)	C22—C17—C18—C19	−0.2 (4)
C7—C8—C9—C10	−177.3 (3)	C22—C23—C24—C25	178.0 (3)
C7—C8—C13—C1	−2.1 (3)	C22—C23—C28—C16	1.7 (3)
C7—C8—C13—C12	178.8 (2)	C22—C23—C28—C27	−178.7 (2)
C8—C9—C10—C11	−0.9 (4)	C23—C24—C25—C26	1.1 (4)
C9—C8—C13—C1	179.7 (2)	C24—C23—C28—C16	−179.0 (2)
C9—C8—C13—C12	0.5 (4)	C24—C23—C28—C27	0.6 (4)
C9—C10—C11—C12	0.3 (4)	C24—C25—C26—C27	−0.4 (4)
C10—C11—C12—C13	0.8 (4)	C25—C26—C27—C28	−0.2 (4)
C11—C12—C13—C1	179.9 (3)	C26—C27—C28—C16	179.6 (3)
C11—C12—C13—C8	−1.2 (4)	C26—C27—C28—C23	0.1 (4)
C13—C1—C2—C3	178.0 (2)	C28—C16—C17—C18	−178.6 (3)
C13—C1—C2—C7	−2.6 (3)	C28—C16—C17—C22	2.1 (3)
C13—C1—C14—O2	−74.2 (3)	C28—C16—C29—O4	76.7 (3)
C13—C8—C9—C10	0.5 (4)	C28—C23—C24—C25	−1.2 (4)
C14—O2—C15—O1	−2.3 (4)	C29—O4—C30—O3	6.6 (4)
C14—O2—C15—N1	176.8 (2)	C29—O4—C30—N2	−173.0 (2)
C14—C1—C2—C3	−61.8 (3)	C29—C16—C17—C18	61.2 (3)
C14—C1—C2—C7	117.6 (2)	C29—C16—C17—C22	−118.1 (2)
C14—C1—C13—C8	−115.7 (2)	C29—C16—C28—C23	115.9 (2)
C14—C1—C13—C12	63.3 (4)	C29—C16—C28—C27	−63.7 (4)
C15—O2—C14—C1	150.3 (2)	C30—O4—C29—C16	−158.2 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1B···O3	0.91 (3)	2.06 (3)	2.955 (3)	169 (3)
N1—H1A···O1ⁱ	0.86 (3)	2.08 (3)	2.849 (3)	149 (3)
N2—H2A···O1	0.85 (3)	2.13 (3)	2.967 (3)	169 (3)
N2—H2B···O3ⁱⁱ	0.87 (4)	2.03 (4)	2.827 (3)	152 (3)

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

Summary of the percentages of intermolecular contacts contributed to the HSA surface of Fmoc-protected β-aminobutyric acid 1 top

Inside atom		Outside atom			Total contributions
	C	H	N	O
C	2.0	13.0	0.0	0.2	15.3
H	9.8	51.8	0.5	9.8	71.9
N	0.0	0.5	0.0	0.0	0.5
O	0.2	11.6	0.0	0.5	12.3
Total contributions	12.0	77.0	0.5	10.5

Summary of the percentages of intermolecular contacts contributed to the HSA surface of Fmoc carbamate 2 top

Inside atom		Outside atom			Total contributions
	C	H	N	O
C	2.6	17.9	0.0	0.1	20.7
H	13.6	51.9	1.2	4.9	71.6
N	0.0	1.2	0.0	0.2	1.4
O	0.1	5.5	0.1	0.6	6.4
Total contributions	16.3	76.6	1.3	5.8

Acknowledgements

MAM is grateful to his family for support of his PhD studies.

References

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research communications\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Synthesis, crystal structure and Hirshfeld surface analysis of Fmoc-β-amino butyric acid and Fmoc carbamate

1. Chemical context

2. Structural commentary

3. Supra­molecular features

4. Database survey

5. Hirshfeld surface analysis

6. Synthesis and crystallization

7. Refinement

Supporting information

Acknowledgements

References

research communications

3. Supramolecular features