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Crystals 2017, 7(9), 263; doi:10.3390/cryst7090263

Article
Substituent Effects on the Crystal Structures of Salts Prepared from (R)-2-Methoxy-2-(1-naphthyl)-propanoic Acid and (R)-1-Arylethylamines
Akio Ichikawa 1,*, Hiroshi Ono 2 and Yuji Mikata 3Orcid
1
Institute of Agrobiological Sciences, National Agriculture and Food Research Organization (NARO), Tsukuba 305-8634, Japan
2
Advanced Analysis Center, National Agriculture and Food Research Organization (NARO), Tsukuba 305-8642, Japan
3
Department of Chemistry, Biology, and Environmental Science, Faculty of Science, Nara Women’s University, Nara 630-8506, Japan
*
Correspondence: Tel.: +81-29-838-6267
Academic Editor: Dmitriy V Soldatov
Received: 26 July 2017 / Accepted: 22 August 2017 / Published: 28 August 2017

Abstract

:
The crystal structures of salts 69 prepared from (R)-2-methoxy-2-(1-naphthyl)propanoic acid [(R)-MαNP acid, (R)-1] and (R)-1-arylethylamines [salt 6, (R)-1-(4-methoxyphenyl)ethylamine∙(R)-1; salt 7, (R)-1-(4-fluorophenyl)ethylamine∙(R)-1; salt 8, (R)-1-(4-chlorophenyl)ethylamine∙(R)-1; and salt 9, (R)-1-(3-chlorophenyl)ethylamine∙(R)-1] were elucidated by X-ray crystallography. The solid-state associations and conformations of the MαNP salts were defined using the concepts of supramolecular- and planar chirality, respectively, and the crystal structures of salts 69 were interpreted as a three-step hierarchical assembly. The para-substituents of the (R)-1-arylethylammonium cations were found on sheet structures consisting of 21 columns. Thus, salts possessing smaller para-substituents, that is, salt 7 (p-F) and salt 9 (p-H), and larger para-substituents, that is, salt 6 (p-OMe) and salt 8 (p-Cl), crystallized in the space groups P21 and C2, respectively. Additionally, weak intermolecular interactions, that is, aromatic C–H···π, C–H···F, and C–H···O interactions, were examined in crystalline salts 69.
Keywords:
chiral recognition; crystal engineering; planar chirality; supramolecular chirality

1. Introduction

Stereochemistry is important in biofunctional molecules [1]. Therefore, methods that facilitate the elucidation of absolute configurations and the preparation of single enantiomers are highly desired [2]. Based on stereochemical studies of biofunctional molecules, we synthesized a chiral resolving agent, MαNP acid (acid 1, Figure 1) [3,4]. Acid 1 is superior to Mosher’s 3,3,3-trifluoro-2-methoxy-2-phenylpropanoic acid (MTPA, 2) [5] for the enantioresolution of secondary alcohols [2].
Goto et al. reported the enantioresolution of rac-1 via diastereomeric salt formation with (R)-3 [3]. In 2011, we examined the crystal structures of the less-soluble salt 4 [(R)-3∙(R)-1] and the more-soluble diastereomeric salt (R)-3∙(S)-1 by X-ray crystallography [6]. Those crystal structures revealed a chiral recognition mechanism during the enantioresolution process. With the less-soluble salt 4, the (R)-MαNP anion and the (R)-PEA cation form a close ion-pair via a methoxy-group-assisted salt bridge and aromatic C–H∙∙∙π interactions (Figure 2A). The close ion-pairs then join with the salt bridges to form 21 columns. Additionally, results have shown that intercolumnar aromatic C–H∙∙∙π interactions [7,8,9] are more effective with the less-soluble salt 4.
Recently, we introduced the concept of supramolecular chirality as a means of defining the association of close ion-pairs in the solid state [10]. Considering the virtual chiral center of the carboxylate and methoxy groups of the (R)-MαNP anion and the phenyl and ammonium groups of the (R)-PEA cation, the supramolecular chirality of salt 4 was assigned as supS (Figure 2B) [10].
Salts 4 and 5 [(R)-1-(p-tolyl)ethylamine∙(R)-1] yielded space groups P21 and C2, respectively [6,11]. This implied an effect of para-substitution of the PEA cation on the latter stage of hierarchical assembly [12,13].
This report describes substituent effects on the crystal structures of salts 69. The 4-methoxyphenyl- and 3-chlrorophenyl groups were fixed in the crystal lattice. Thus, the planar chirality [14] of the (R)-1-arylethylammonium cations was assigned in salts 6 and 9. The molecular packing of salts 69 was interpreted as the three-step hierarchical assembly [12,13].
A large number of agrochemicals and pharmaceuticals are halogenated compounds. In 2007, Müller et al. reported that ca. 20% of all pharmaceuticals, and even more agrochemicals (up to 30%), contained fluorine atoms [15]. The ratio of chlorinated drugs was next to the fluorinated drugs in all halogenated drugs [16]. However, the effects of halogen atoms, especially fluorine, are ambivalent. Organic crystals are now considered a type of supermolecule [7]. Therefore, the elucidation of substitution effects in organic crystals will contribute to an overall understanding of weak intermolecular interactions. The current study explores aromatic C–H···π, C–H···F, and C–H···O interactions in crystalline salts 69.
Crystal engineering of organic salts is important as a means of enantioresolution [17,18,19]. Investigations of crystal structures provide information on weak intermolecular interactions that are useful in the design of biofunctional molecules.

2. Results and Discussion

2.1. Preparation of Crystalline MαNP Salts

Single crystals of salts 69 were prepared from (R)-1 and (R)-1-arylethylamines with MeOH/CHCl3 and were analyzed using X-ray crystallography (Figure 1). Table 1 and Figure 3 show their crystallographic data and ORTEP diagrams, respectively. Salts 6 and 8 crystallized in the monoclinic space group C2 with four ion-pairs per unit cell, while salts 7 and 9 belonged to the space group P21 with two ion-pairs per unit cell. For salts possessing larger substituents, that is, salt 6 (p-OMe), salt 8 (p-Cl), and salt 9 (m-Cl), methanol molecules functioned as space-fillers [19], stabilizing the crystal lattice.

2.2. Crystal Conformations of MαNP Salts

The conformations of the MαNP anions in salts 69 were similar to the major conformations of MαNP esters (Table 2) [2,6]: (1) The carboxylate oxygen atom O1 was synperiplanar to the methoxy oxygen atom O3; (2) The methoxy carbon atom C4 was antiperiplanar to the carboxylate carbon atom C1; (3) The methyl carbon atom C3 was in the naphthyl plane. The 1-arylethylammonium cations of salts 69 also exhibited the conformations similar to those of PEA cations [20]; that is, the benzylic hydrogen atom H15 was almost in the phenyl plane.
The 3-chlorophenyl group of salt 9 was fixed in the solid state; thus, the conformation of the (R)-1-(3-chlorophenyl)ethylammonium cation was elucidated using the concept of planar chirality [14] (Figure 4A): (1) The nitrogen atom N1, selected as the pilot atom, was not in the phenyl plane itself but was attached to the benzylic carbon atom at the end of the phenyl plane; (2) Considering the Cahn–Ingold–Prelog rules on the priority of ortho-carbon atoms, the three adjacent, in-plane carbon atoms 13 were selected; (3) Viewed from the pilot atom N1, the carbon atoms 13 were positioned in an anticlockwise direction in crystalline salt 9. Therefore, the planar chirality of the (R)-1-(3-chlorophenyl)ethylammonium cation was assigned to plS.
In salt 6, the methoxy group of the (R)-1-(4-methoxyphenyl)ethylammonium cation is in the phenyl plane [15] (Figure 3). Considering the orientation of the methoxy group, the ortho-carbon atom 3 was selected so as to be syn to the methoxy group (Figure 4B). The three adjacent carbon atoms 13 were positioned in a clockwise direction in crystalline salt 6; thus, the planar chirality of the (R)-1-(4-methoxyphenyl)ethylammonium cation was assigned as plR. It should be noted that the planar chirality of the (R)-1-arylethylammonium cations in salts 6 and 9 is not genuine due to the unrestricted rotation of the C15–C17 bonds.

2.3. Three-Step Hierarchical Assembly

The molecular packing of salts 69 was interpreted as a three-step hierarchical assembly [12,13] (Figure 5):
  • Close ion-pairs joined with salt bridges to form 21 columns.
  • The 21 columns formed a sheet structure via homo-aromatic C–H∙∙∙π interactions between 1-naphthyl groups.
  • These sheet structures stacked to form the whole crystal.
The para-substituents of 1-arylethylammonium cations were positioned on the surface of sheet structures. Therefore, they were important in the latter stage of the hierarchical assembly. With salts possessing smaller para-substituents, such as salt 7 (p-F) and salt 9 (p-H), the sheet structures stacked in the same manner, yielding a space group P21. With larger para-substituents, such as those of salt 6 (p-OMe) and salt 8 (p-Cl), the sheet structures stacked in an offset manner, yielding a space group C2. In addition, the space between columns formed in salts possessing the larger substituents, that is, salts 6, 8, and 9, were filled with methanol molecules [19].

2.4. Associations of Close Ion-Pairs

The methoxy-group-assisted salt bridge and the aromatic C–H∙∙∙π interactions joined the close ion-pairs of salts 69 as supramolecular synthons (Figure 2A and Figure 3) [6]. Table 3 and Figure 6 show the geometrical parameters of salt bridges in close ion-pairs of salts 69.
Table 4 and Figure 7 show the interatomic distances H11∙∙∙C19 and H12∙∙∙C18 (dL and dM, respectively) and the interatomic angles C11–H11∙∙∙C19 and C12–H12∙∙∙C18 in the close ion-pairs of salts 69. These data suggest the presence of aromatic C–H∙∙∙π interactions [8]. It has been reported that the strength of these C–H∙∙∙π interactions depends on the substituent in the phenyl group [9].
Considering the virtual chiral center of the carboxylate and methoxy groups of the (R)-MαNP anion and the phenyl and ammonium groups of the (R)-1-arylethylammonium cation, each of the supramolecular chirality in the close ion-pairs of salts 69 was assigned as supS (Figure 2B and Figure 3). This class of organic salts prefers the supS association over the supR association [10].

2.5. Molecular Packing of MαNP Salts (1): Arrays of Columns

The close ion-pairs of salts 69 form 21 columns via salt bridges (Figure 8, Figure 9, Figure 10 and Figure 11) [6,11]. Salts 69 revealed a similar herringbone motif [7] to form sheet structures. Table 5 and Figure 12 show the geometrical parameters of the homo-aromatic C–H···π interactions between the naphthyl groups of (R)-MαNP anions in salts 69. Space-filling models revealed that para-substituents of the 1-arylethylammonium cations are positioned on the sheet structures (Figure S1).
For smaller para-substituents, that is, salts 4 [6], 9 (p-H) and 7 (p-F), the sheet structures stacked in the same manner to yield a space group P21 (Figure 5). For larger para-substituents, that is, salt 5 (p-Me) [11]; salt 6 (p-MeO), and salt 8 (p-Cl), the sheets stacked in an offset manner to yield a space group C2. These results indicate that the para-substituents defined the space groups of salts 49. The following factors are deemed important for the stability of the diastereomeric salts [17]: (1) hydrogen bonding to form 21 columns; (2) van der Waals interactions between the columns; and (3) intra- and intercolumnar C–H∙∙∙π interactions. As noted above, methanol molecules filled the space [19] between the columns in salts 6, 8, and 9.

2.6. Molecular Packing of MαNP Salts (2): Stacking of Sheet Structures

The interactions between sheet structures were examined in crystalline salts 7 and 9 (Figure 13 and Table 6). The sheet structures of salts 7 and 9 (Figure 9 and Figure 11, respectively) stacked in a space group P21. The interactions between p-fluorophenyl groups in crystalline salt 7 were similar to those of phenyl groups in crystalline salt 4 [6]. There were no intermolecular contacts shorter than the sum of the van der Waals radii between the sheet structures of salt 7. The aromatic hydrogen atom H18 of the p-fluorophenyl group was relatively close to the neighboring fluorine atom F1’. The interatomic distance between H18···F1’ was 2.61 Å (the van der Waals radii: aromatic H, 1.00 Å; F, 1.47 Å) while the interatomic angle C18–H18···F1’ was 118°. However, the C–H···F interaction is reportedly very weak [21]. Despite large differences in physical and chemical properties, the substitution of a fluorine atom for a hydrogen atom only marginally affected the molecular packing.
A clear homo-aromatic C–H···π interaction was observed between the m-chlorophenyl groups of salt 9 (Figure 13). The interatomic distance between the aromatic hydrogen atom H20’ and the centroid of the neighboring phenyl ring (Cg) was 2.72 Å while the interatomic angle C20’–H20’–Cg was 170°. Kinbara et al. reported that the para-chlorine substituent of the 1-(4-chlorophenyl)ethylammonium cation increases the positive charge of the meta-hydrogen atoms, effectively stabilizing the C–H···π interaction [18]. In contrast, the chlorine atom of salt 9 did not show any short contacts (e.g., Cl···Cl, Cl···O, or Cl···π interactions [22]). The same is true for the chlorine atom of salt 8 (see below).
Finally, interactions between sheet structures were examined in crystalline salts 6 and 8. Figure 14 shows the molecular packing of salts 6 and 8 viewed along the c-axis. The sheet structures, shown in Figure 8 and Figure 10, respectively, yielded a space group C2 with hetero-aromatic C–H···π interactions between sheets. The aromatic hydrogen atom H7 of the naphthyl group was positioned nearly on the edge of phenyl group in salts 6 and 8; the distances between H7 and the neighboring phenyl plane were 2.65 Å and 2.69 Å, respectively.
In salt 6, the p-methoxy group was located in the phenyl plane [15], giving an extended herringbone motif; the interatomic distance between hydrogen atom H23A’ and aromatic carbon atom C7 was 2.97 Å. The chlorine atom of salt 8 had no short contacts with neighboring molecules. Methanol molecules filled the space between sheet structures in salts 6 and 8 (Figure 14). The oxygen atom of methanol molecule formed an O–H···O hydrogen bond and a C–H···O interaction. In salt 6, the interatomic distances O2···O5 and H21’···O5 were 2.84 Å and 2.48 Å, respectively. In salt 8, the interatomic distances O2···O4 and H21’···O4 were 2.83 Å and 2.42 Å, respectively. In terms of crystal engineering, the p-methoxy group of salt 6 was isosteric with the p-chloro group of salt 8.

3. Conclusions

This study clarified the crystal structures of MαNP salts 69 prepared from (R)-1 and (R)-1-arylethylamines. Using the concepts of supramolecular chirality, the solid-state associations of close ion-pairs were elucidated as supS in all salts. In addition, the solid-state planar chirality of the (R)-1-(4-methoxyphenyl)ethylammonium cation of salt 6 and the (R)-1-(3-chlorophenyl)ethylammonium cation of salt 9 were assigned as plR and plS, respectively. It should be noted that these are not genuine planar chirality due to unrestricted rotations. The crystal structures of MαNP salts 69 were interpreted as three-step hierarchical assemblies. Para-substituents of phenyl groups were positioned on sheet structures consisting of 21 columns and thereby affected the sheet stacking. Smaller para-substituents, that is, salt 7 (p-F) and salt 9 (p-H), and larger para-substituents, that is, salt 6 (p-OMe) and salt 8 (p-Cl), yielded space groups P21 and C2, respectively. For MαNP salts, p-H and p-OMe groups were isosteric with p-F and p-Cl groups, respectively. The 3-chlorophenyl groups of salt 9 exhibited homo-aromatic C–H···π interactions. For (R)-1-arylethylamines with larger substituents, methanol molecules filled the space in the crystal lattice. These results provide information on supramolecular chemistry for the design and preparation of single-enantiomer biofunctional molecules.

4. Materials and Methods

4.1. X-ray Crystallography

The single crystals (salt 6, 0.300 × 0.100 × 0.060 mm; salt 7, 0.200 × 0.200 × 0.200 mm; salt 8, 0.550 × 0.150 × 0.100 mm; salt 9, 0.600 × 0.600 × 0.500 mm) were covered with paraffin oil and mounted on a glass fiber, respectively. All measurements were made on a Rigaku Mercury70 diffractometer using graphite monochromated Mo-Kα radiation, operating at 50 kV/40 mA. Data were processed on a PC using CrystalClear Software (Rigaku, Tokyo, Japan). Structures were solved using direct methods and refined by full-matrix least-squares methods on F2 (SHELXL-97). CCDC 1442523 (salt 6), CCDC 1442524 (salt 7), CCDC 1442525 (salt 8), and CCDC 1442526 (salt 9) contain the supplementary crystallographic data for this study, which can be obtained from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk. Each crystal was dried in vacuo overnight at 80 °C prior to elemental analysis.

4.2. Preparation of Salt 6

A mixture of (R)-1 (29.2 mg, 127 μmol) and (R)-1-(4-methoxyphenyl)ethylamine (21.7 mg, 144 μmol) was dissolved in CHCl3 and MeOH (0.5 mL and 1.5 mL, respectively). The solution was warmed in a water bath at 45 °C and concentrated to ca. 1 mL in vacuo. Then, the solution was allowed to stand at RT for 5 days to give colorless crystals of salt 6 (MeOH solvate; 13.7 mg, 34 μmol) in 27% yield.
(R)-1-(4-Methoxyphenyl)ethylammonium (R)-2-methoxy-2-(1-naphthyl)propanoate (6). Elemental analysis calculated (%) for C23.5H29NO4.5 (6·0.5MeOH): C 71.01, H 7.35, N 3.52; found: C 71.21, H 7.37, N 3.51.

4.3. Preparation of Salt 7

A mixture of (R)-1 (31.0 mg, 135 μmol) and (R)-1-(4-fluorophenyl)ethylamine (18.7 mg, 134 μmol) was dissolved in CHCl3 and MeOH (2 mL and 1 mL, respectively). Then, the solution was allowed to stand at RT for three days to give colorless crystals of salt 7 (32.6 mg, 88 μmol) in 66% yield.
(R)-1-(4-Fluorophenyl)ethylammonium (R)-2-methoxy-2-(1-naphthyl)propanoate (7). Elemental analysis calculated (%) for C22H24FNO3: C 71.53, H 6.55, N 3.79; found: C 71.52, H 6.22, N 3.72.

4.4. Preparation of Salt 8

A mixture of (R)-1 (31.5 mg, 137 μmol) and (R)-1-(4-chlorophenyl)ethylamine (32.7 mg, 210 μmol) was dissolved in CHCl3 and MeOH (0.5 mL and 1.5 mL, respectively). The solution was warmed in a water bath at 45 °C and allowed to stand at RT for two days to give crude crystals of salt 8. Recrystallization from CHCl3/MeOH (1mL and 0.5 mL, respectively) gave colorless crystals of salt 8 (MeOH solvate; 18.3 mg, 46 μmol) with a total yield of 33%.
(R)-1-(4-Chlorophenyl)ethylammonium (R)-2-methoxy-2-(1-naphthyl)propanoate (8). Elemental analysis calculated (%) for C22.5H26ClNO3.5 (8·0.5MeOH): C 67.24, H 6.52, N 3.49; found: C 67.55, H 6.28, N 3.53.

4.5. Preparation of Salt 9

A mixture of (R)-1 (29.9 mg, 130 μmol) and (R)-1-(3-chlorophenyl)ethylamine (25.9 mg, 166 μmol) was dissolved in CHCl3 and MeOH (1 mL and 2 mL, respectively). The solution was warmed in a water bath at 47 °C and allowed to stand at RT for 10 days to give colorless crystals of salt 9 (MeOH solvate; 33.1 mg, 79 μmol) in 61% yield.
(R)-1-(3-Chlorophenyl)ethylammonium (R)-2-methoxy-2-(1-naphthyl)propanoate (9). Elemental analysis calculated (%) for C22H24ClNO3: C 68.48, H 6.27, N 3.63; found: C 68.50, H 6.24, N 3.56.

Supplementary Materials

The following is available online at www.mdpi.com/2073-4352/7/9/263/s1, Figure S1: Top and side views of sheet structures in salts 69 shown in space-filling models.

Author Contributions

Akio Ichikawa designed and performed the experiments; Yuji Mikata obtained and analyzed the data of X-ray crystallography; Akio Ichikawa, Hiroshi Ono, and Yuji Mikata discussed the results.

Conflicts of Interest

The authors declare no conflict of interest.

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Figure 1. Structures of chiral resolving agents and MαNP salts. See refs. [6] and [11] for salt 4 (CCDC 801461) and salt 5 (CCDC 871216), respectively. (R)-MαNP represents the (R)-2-methoxy-2-(1-naphthyl)propanoate anion.
Figure 1. Structures of chiral resolving agents and MαNP salts. See refs. [6] and [11] for salt 4 (CCDC 801461) and salt 5 (CCDC 871216), respectively. (R)-MαNP represents the (R)-2-methoxy-2-(1-naphthyl)propanoate anion.
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Figure 2. (A) Chiral recognition and (B) supramolecular chirality in the close ion-pair of the less soluble MαNP salt 4 [6,10]. Assigned numbers indicate priority based on the Cahn–Ingold–Prelog rules. The symbol “supS” represents the left-handed supramolecular chirality.
Figure 2. (A) Chiral recognition and (B) supramolecular chirality in the close ion-pair of the less soluble MαNP salt 4 [6,10]. Assigned numbers indicate priority based on the Cahn–Ingold–Prelog rules. The symbol “supS” represents the left-handed supramolecular chirality.
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Figure 3. ORTEP diagrams of salts 69 with ellipsoids set at 50% probability. Crystals of salts 6, 8, and 9 were methanol solvates. The methanol molecules in salts 6 and 8 showed positional disorder. The atom labels for salt 6 were also used for the other salts except for the substituents and methanol molecules.
Figure 3. ORTEP diagrams of salts 69 with ellipsoids set at 50% probability. Crystals of salts 6, 8, and 9 were methanol solvates. The methanol molecules in salts 6 and 8 showed positional disorder. The atom labels for salt 6 were also used for the other salts except for the substituents and methanol molecules.
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Figure 4. Planar chirality of (R)-1-arylethylammonium cations in crystalline (A) salt 9 and (B) salt 6. The symbols “plS” and “plR” represent left- and right-handed planar chirality, respectively. In salt 6, higher priority was given to the ortho-carbon atom that is syn to the methoxy group.
Figure 4. Planar chirality of (R)-1-arylethylammonium cations in crystalline (A) salt 9 and (B) salt 6. The symbols “plS” and “plR” represent left- and right-handed planar chirality, respectively. In salt 6, higher priority was given to the ortho-carbon atom that is syn to the methoxy group.
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Figure 5. Three-step hierarchical assemblies of MαNP salts.
Figure 5. Three-step hierarchical assemblies of MαNP salts.
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Figure 6. Geometrical parameters of methoxy-group-assisted salt bridges and other salt bridges in salts 69.
Figure 6. Geometrical parameters of methoxy-group-assisted salt bridges and other salt bridges in salts 69.
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Figure 7. Geometrical parameters of hetero-aromatic C–H···π interactions in the close ion-pairs of salts 69.
Figure 7. Geometrical parameters of hetero-aromatic C–H···π interactions in the close ion-pairs of salts 69.
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Figure 8. Sheet structure in crystalline salt 6, consisting of 21 columns. The pale-blue lines show salt bridges and hydrogen bonds. See Table 3 for the interatomic distances d1d4.
Figure 8. Sheet structure in crystalline salt 6, consisting of 21 columns. The pale-blue lines show salt bridges and hydrogen bonds. See Table 3 for the interatomic distances d1d4.
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Figure 9. Sheet structure in crystalline salt 7, consisting of 21 columns. The pale-blue lines show salt bridges and hydrogen bonds. See Table 3 for the interatomic distances d1d4.
Figure 9. Sheet structure in crystalline salt 7, consisting of 21 columns. The pale-blue lines show salt bridges and hydrogen bonds. See Table 3 for the interatomic distances d1d4.
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Figure 10. Sheet structure in crystalline salt 8, consisting of 21 columns. The pale-blue lines show salt bridges and hydrogen bonds. See Table 3 for the interatomic distances d1d4.
Figure 10. Sheet structure in crystalline salt 8, consisting of 21 columns. The pale-blue lines show salt bridges and hydrogen bonds. See Table 3 for the interatomic distances d1d4.
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Figure 11. Sheet structure in crystalline salt 9, consisting of 21 columns. The pale-blue lines show salt bridges and hydrogen bonds. See Table 3 for the interatomic distances d1d4.
Figure 11. Sheet structure in crystalline salt 9, consisting of 21 columns. The pale-blue lines show salt bridges and hydrogen bonds. See Table 3 for the interatomic distances d1d4.
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Figure 12. Geometrical parameters of the homo-aromatic C–H···π interactions between the naphthyl groups in salts 69. Centroids of benzene rings: CgX, C9–C14; CgY, C5–C6–C7–C8–C14–C–13.
Figure 12. Geometrical parameters of the homo-aromatic C–H···π interactions between the naphthyl groups in salts 69. Centroids of benzene rings: CgX, C9–C14; CgY, C5–C6–C7–C8–C14–C–13.
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Figure 13. Molecular packing of salts 4 and 7 viewed along the a-axis, and salt 9 viewed along the c-axis. Numbers without units represent interatomic distances (Å). Cg: centroid of the phenyl ring (C17–C22). Van der Waals radii: aromatic H, 1.00 Å; F, 1.47 Å; half-thickness of the benzene ring, 1.77 Å.
Figure 13. Molecular packing of salts 4 and 7 viewed along the a-axis, and salt 9 viewed along the c-axis. Numbers without units represent interatomic distances (Å). Cg: centroid of the phenyl ring (C17–C22). Van der Waals radii: aromatic H, 1.00 Å; F, 1.47 Å; half-thickness of the benzene ring, 1.77 Å.
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Figure 14. Molecular packing of salts 6 and 8 viewed along the c-axis. Numbers without units represent interatomic distances (Å). The pale-blue dotted lines indicate hydrogen bonds and salt bridges. Van der Waals radii: aromatic H, 1.00 Å; H, 1.20 Å; O, 1.52 Å; half-thickness of the benzene ring, 1.77 Å.
Figure 14. Molecular packing of salts 6 and 8 viewed along the c-axis. Numbers without units represent interatomic distances (Å). The pale-blue dotted lines indicate hydrogen bonds and salt bridges. Van der Waals radii: aromatic H, 1.00 Å; H, 1.20 Å; O, 1.52 Å; half-thickness of the benzene ring, 1.77 Å.
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Table 1. X-ray crystallographic data for salts 69.
Table 1. X-ray crystallographic data for salts 69.
Compound6 178 19 1
Molecular formulaC23.5H29NO4.5C22H24FNO3C22.5H26ClNO3.5C23H28ClNO4
Formula weight397.49369.43401.91417.93
Crystal systemmonoclinicmonoclinicmonoclinicmonoclinic
Space groupC2P21C2P21
Z4242
a24.026(8)11.8064(12)28.612(5)11.5676(10)
b6.790(2)6.7248(6)6.8078(9)6.8976(6)
c14.800(5)12.7444(11)14.856(3)14.2838(14)
β117.208(4)102.717(4)132.9310(16)109.467(3)
V32147.3(12)987.03(16)2118.7(6)1074.54(17)
Dcalculated/g·cm–31.2291.2431.2601.292
μ/mm−10.0840.0880.2050.206
2θmax54.954.954.954.9
Temperature/K123123123153
No. of reflections collected84517757831210,547
No. of reflections unique4857440946714876
Rint0.02920.01900.01340.0115
No. of parameters272248262268
Final R1 (I > 2(σ)I)) 20.06110.04020.05210.0336
wR2 (all data) 30.16200.09840.13700.0963
GOF1.1271.0771.0361.061
Flack parameter 41.7(15)1.1(7)−0.03(9)−0.02(4)
CCDC1,442,5231,442,5241,442,5251,442,526
1 Crystals of salts 6, 8, and 9 were methanol solvates. 2 R1 = (Σ||Fo| − |Fc||)/(Σ|Fo|). 3 wR2 = {[Σw(Fo2Fc2)2]/[Σw(Fo2)2]}1/2. 4 The Flack parameters for salts 6 and 7 have no physical meaning because the salts do not contain heavy atoms.
Table 2. Conformational parameters of salts 69.
Table 2. Conformational parameters of salts 69.
SaltSubstituentO1–C1–C2–O3 (°)C4–O3–C2–C1 (°)C3–C2–C5–C6 (°)N1–C15–C17–C22 (°)
6p-MeO–26.4(3)–178.0(3)–5.3(4)49.0(4)
7p-F–28.9(2)179.9(1)2.7(2)53.0(2)
8p-Cl–26.9(3)–179.3(2)–5.9(4)48.8(4)
9m-Cl–26.5(2)178.4(1)0.2(2)47.1(2)
Table 3. Geometrical parameters of methoxy-group-assisted salt bridges and other salt bridges in salts 69.
Table 3. Geometrical parameters of methoxy-group-assisted salt bridges and other salt bridges in salts 69.
SaltSubstituentd1 (Å) 1θ1 (°) 2d2 (Å) 1θ2 (°) 2d3 (Å) 1θ3 (°) 2d4 (Å) 1θ4 (°) 2
6p-MeO2.231272.051581.901621.96163
7p-F2.331252.021611.891661.90163
8p-Cl2.301201.981661.861691.98162
9m-Cl2.251282.061581.891611.98161
1 Interatomic distances: d1, H1A∙∙∙O3; d2, H1A∙∙∙O1; d3, H1B∙∙∙O1’; d4, H1C∙∙∙O2’. 2 Interatomic angles: θ1, N1–H1A ∙∙∙O3; θ2, N1–H1A ∙∙∙O1; θ3, N1– H1B ∙∙∙O1’; θ4, N1–H1C ∙∙∙O2’. Van der Waals radii: H, 1.20 Å; O, 1.52 Å.
Table 4. Geometrical parameters of hetero-aromatic C–H···π interactions in the close ion-pairs of salts 69.
Table 4. Geometrical parameters of hetero-aromatic C–H···π interactions in the close ion-pairs of salts 69.
SaltSubstituentdL (Å) 1dM (Å) 1C11–H11∙∙∙C19 (°)C12–H12∙∙∙C18 (°)
6p-MeO2.883.17138121
7p-F2.983.15141126
8p-Cl2.833.12136121
9m-Cl3.013.29136123
1 Interatomic distances: dL, H11∙∙∙C19; dM, H12∙∙∙C18. H11 and H12 are offset slightly from the phenyl rings. Van der Waals radii: aromatic H, 1.00 Å; half-thickness of the benzene ring, 1.77 Å.
Table 5. Geometrical parameters of the homo-aromatic C–H···π interactions between the naphthyl groups in salts 69 1.
Table 5. Geometrical parameters of the homo-aromatic C–H···π interactions between the naphthyl groups in salts 69 1.
SaltSubstituentH9···CgX (Å)H10···CgY (Å)C9–H9···CgX (°)C10–H10···CgY (°)
6p-MeO2.503.05145137
7p-F2.623.41155127
8p-Cl2.533.02145135
9m-Cl2.663.36155126
1 Centroids of benzene rings: CgX, C9–C14; CgY, C5–C6–C7–C8–C14–C–13. Van der Waals radii: aromatic H, 1.00 Å; half-thickness of the benzene ring, 1.77 Å.
Table 6. Interatomic distances and angles between the sheet structures of salts 6–9.
Table 6. Interatomic distances and angles between the sheet structures of salts 6–9.
SaltSubstituentInteratomic Distance(Å)Interatomic Angle(°)
6p-MeOH7···π’ 12.65
H7···Cg’ 23.30C7–H7···Cg’ 1174
H23A’···C72.97
O2···O52.84
H21’···O52.48C21’–H21’···O5138
7p-FH18···F1’2.61C18–H18···F1’118
8p-ClH7···π’ 12.69
H7···Cg’ 23.09C7–H7···Cg’ 1165
O2···O42.83
H21’···O42.42C21’–H21’···O4133
9m-ClH20’···Cg 22.72C20’–H20’···Cg170
H20’···π 12.67
1 The phenyl plane is defined by carbon atoms C17–C18–C19. 2 Cg: centroid of the phenyl ring (C17–C22). Van der Waals radii: aromatic H, 1.00 Å; H, 1.20 Å; O, 1.52 Å; F, 1.47 Å; half-thickness of the benzene ring, 1.77 Å.
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