DOI: 10.1002/chem.201402533
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Recognition of N-Alkyl and N-Aryl Acetamides by N-Alkyl Ammonium Resorcinarene Chlorides N. Kodiah Beyeh,*[a] Altti Ala-Korpi,[a] Mario Cetina ,[a, b] Arto Valkonen ,[a, c] and Kari Rissanen*[a]
alkyl acetamide guests through intermolecular hydrogen bonds involving the carbonyl oxygen (C=O) atoms and the amide (NH) groups of the guests, the chloride anions (Cl ) and ammonium (NH2 + ) cations of the hosts, and also through CH···p interactions between the hosts and guests. The self-included and host–guest complexes were studied by single-crystal X-ray diffraction, NMR titration, and mass spectrometry.
Abstract: N-Alkyl ammonium resorcinarene chlorides are stabilized by an intricate array of intra- and intermolecular hydrogen bonds that leads to cavitand-like structures. Depending on the upper-rim substituents, self-inclusion was observed in solution and in the solid state. The self-inclusion can be disrupted at higher temperatures, whereas in the presence of small guests the self-included dimers spontaneously reorganize to 1:1 host–guest complexes. These host compounds show an interesting ability to bind a series of N-
Introduction
tubes[14,15] have been reported. The phenolic hydroxyl groups make the 2-position of the benzene ring suitable for electrophilic substitution. Attaching suitable functional groups to resorcinarenes while maintaining the concave nature increases their recognition potential. Thus, the recognition properties of resorcinarenes can be tuned, and hence the array of guest compounds that can be recognized by resorcinarenes extended.[2, 11] Mannich condensation is a common procedure for functionalizing resorcinarenes at the benzene ring.[16–19] Primary amines and resorcinarenes in the presence of an excess of formaldehyde react to form tetrabenzoxazines.[16–18] Under refluxing conditions in the presence of mineral acids, the ring opening of tetrabenzoxazines leads to the formation of N-alkyl ammonium resorcinarene salts.[17–19] The hydrogen bonds between the ammonium moieties and halides form strong circular hydrogen-bond seams (···H(R’)N + (R’’)H···X ···H(R’)N + (R’’)H···X ···)2, which are referred to as the hydrogen-bond analogues of cavitands,[17, 18] since they have similar shape and cavity size to covalent cavitands. The resorcinarene salts have larger and deeper cavities as well as different binding features than unfunctionalized resorcinarenes and can thus bind a greater variety of guests.[17–19] Unfunctionalized resorcinarenes have a pbasic cavity and can bind guests through cation···p, CH···p, and hydrophobic interactions.[1, 2, 5] In addition, the resorcinarene salts can, by means of the circular hydrogen-bond seam, interact with guests through hydrogen-bond interactions.[17, 18] Recently, the resorcinarene salts have been shown to also act as halogen-bond[20] acceptors to give deep-cavity cavitand-like compounds.[21] The combination of these properties makes the N-alkyl ammonium resorcinarene salts potentially suitable hosts for a multitude of structurally different guests such as amides. Amides are very common in nature and amply used in
Resorcinarenes are very versatile compounds that can act as host compounds or as building blocks.[1–3] The possibility of functionalizing resorcinarenes to give more sophisticated compounds by utilizing the hydroxyl groups, the phenyl rings, or the lower-rim substituents make resorcinarenes an interesting family of compounds in supramolecular chemistry.[4] This unique property has led to resorcinarenes being labeled as one of the pillars of supramolecular chemistry. Resorcinarenes exist in several conformations, of which the C4v conformation is one of the most common.[1, 2, 4] Intramolecular hydrogen bonds between adjacent phenolic hydroxyl groups help maintain the C4v conformation.[1, 2, 4] The C4v conformation of unfunctionalized resorcinarenes has a concave cavity suitable for binding a variety of guests through several weak interactions.[1, 5] Supramolecular assemblies such as 1:1 open inclusion complexes,[6, 7] dimeric[5, 8, 9] and hexameric[10–13] capsular assemblies, and nano[a] N. K. Beyeh, A. Ala-Korpi, M. Cetina , A. Valkonen , K. Rissanen Department of Chemistry, Nanoscience Center, University of Jyvskyl P.O. Box 35, 40014 Jyvskyl (Finland) Fax: (+) 358 14 2602501 E-mail: [email protected] [email protected] [b] M. Cetina Present address: University of Zagreb, Faculty of Textile Technology Department of Applied Chemistry Prilaz baruna, Filipovic´a 28a, 10000 Zagreb (Croatia) [c] A. Valkonen Present address: Department of Chemistry and Bioengineering Tampere University of Technology P.O. Box 541, 33101 Tampere (Finland) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201402533 or from the author. Chem. Eur. J. 2014, 20, 1 – 8
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Full Paper technological applications.[22] The amide bond (HN C=O) is quite rigid and easily formed.[22] The field of application of amides is very broad, and hence the quest for new amide receptors is an interesting and a continuously developing area of research.[22] The upper-rim substituents of the N-alkyl ammonium resorcinarene chlorides have a direct effect on both the cavity size and the complexation properties towards guest species. Herein, the structural elucidation of self-inclusion and guestbinding properties of N-propyl ammonium resorcinarene chlorides is presented. Self-inclusion was monitored at various temperatures and also in the presence of small guests. Furthermore, the complexation of a series of N-alkyl and N-aryl acetamide guests 3 a–d by resorcinarene salts 1 a,b was investigated in the solid state, in solution, and in the gas phase.
Figure 1. a) Ball-and-stick representation of self-inclusion dimer (1 a)2. Atoms of one self-included n-propyl chain and the nitrogen atom to which it is attached are presented in CPK style. Hydrogen atoms bonded to carbon atoms and five carbon atoms of the lower-rim hexyl groups are omitted for clarity. b) CPK plot of the dimer 1 a showing symmetrical disposition of cations that form the dimer. Chloroform molecules displaced outside the dimer and oxygen atoms of crystal-lattice water are omitted for clarity in both figures.
Results and Discussion N-Alkyl ammonium resorcinarene chlorides 1 a,b with flexible N-propyl and rigid cyclohexyl substituents were synthesized (Scheme 1). Formation of a very strong, circular, hydrogen-
cluded resorcinarene tetracations and six chloride anions. The dimer is additionally stabilized by C H···p interactions between hydrogen atoms of the terminal methyl group and the C8–C13 phenyl ring (Supporting Information, Table S1). The dimer is nearly symmetrical, that is, propyl and hexyl chains are approximately related by an inversion center (Figure 1 b). Unexpectedly when 1,4-dioxane was used as the crystallization solvent instead of chloroform, the self-included dimer was not formed, and instead 1:1 host–guest complex 2 c@1 a was obtained. Overall, three 1,4-dioxane (2 c_1–2 c_3) molecules interact with host 1 a through hydrogen bonds. Molecule 2 c_ 1 is situated deep and almost in the center of the cavity of 1 a (Figure 2), with the dioxane oxygen atoms located in the
Scheme 1. N-alkyl ammonium resorcinarene chlorides 1 a,b, small guests 2 a–c, and N-alkyl and N-aryl acetamides 3 a–d.
bonded cation/anion seam between the spherical chloride anions and the ammonium moieties results in an extended interior cavity that is suitable for the recognition of a variety of guest molecules.[17–19] The resorcinarene salts are generally symmetrical in solution, as verified by their relatively simple 1 H NMR spectra.
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Self-inclusion and guest-binding studies
Figure 2. a) Ball-and-stick representation of host–guest complex 2 c@1 a. Atoms of deeply included 1,4-dioxane molecule are presented in CPK style. Hydrogen atoms bonded to carbon atoms that do not participate in intermolecular interactions and five carbon atoms of the lower rim hexyl groups are omitted for clarity. b) Top view of complex 2 c@1 a presented in CPK style, showing position of the 1,4-dioxane molecules. Oxygen atoms of disordered water molecules are omitted for clarity in both figures.
Compound 1 a crystallizes from chloroform as self-included dimer (1 a)2 (Figure 1) with two intermolecular N(NH2+) H···Cl hydrogen bonds formed between hydrogen atoms of the ammonium moiety of the included propyl chain and the chloride anion of the other half of the dimer (Figure 1 a and Supporting Information, Table S1). Thus, the dimer consists of two self-in-
cation–anion belt. Its position is primarily fixed by one N(NH2+) H···O(dioxane) hydrogen bond (Supporting Information, Table S2). Furthermore, 2 c_1 shows two intracomplex C H···Cl hydrogen bonds and two C H···p interactions to the C15–C20 and C1–C6 phenyl rings. Finally, the included 2 c_1 is
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Full Paper also linked to the adjacent, exo-cavity 2 c_2 by one C H···O hydrogen bond. The 2 c_2 molecule is situated on the top and slightly aside of the cavity, and 2 c_3 is completely outside the cavity. Both 2 c_2 and 2 c_3 are bound to the host 1 a by several types of intermolecular interactions: N(NH2+) H···O, C H···O, and C H···Cl hydrogen bonds (for a more detailed description, see the Supporting Information). Inclusion of 2 c_1 in the cavity strongly affects the conformation of the resorcinarene core, as a consequence of repulsion between the atoms of this molecule and atoms of the cation–anion belt (see Supporting Information). In the cyclohexyl analogue 1 b, self-inclusion and subsequent dimer formation are not possible due to the sterically very bulky cyclohexyl groups. Thus, 1 b crystallizes from chloroform/diethyl ether as a 2:1 host–guest complex with two chloroform molecules (CHCl3_1 and CHCl3_2) as guest (2 CHCl3@1 b) with overall occupancy of 0.5. Molecule CHCl3_ 1 is situated deep in the cavity slightly below the cation–anion belt (Figure 3 a) and is somewhat offset from the center of the
tron density, which was treated as a disordered MeCN molecule with 0.25 occupancy. The resorcinarene core is more distorted than in 2 CHCl3@1 b (see Supporting Information). The MeCN@1 b structure is illustrated in the Supporting Information (Figures S4 and S5). Single-crystal X-ray studies showed that N-propyl ammonium resorcinarene chloride 1 a self-assembles into tightly packed dimers in CHCl3. In the presence of 1,4-dioxane (2 c), the self-included dimer was disassembled and a host–guest complex was formed. 1H NMR spectroscopic studies in CDCl3 were carried out to probe the self-inclusion properties of the host 1 a. The temperature dependence and stability of the selfincluded dimer were investigated in a variable-temperature 1 H NMR study. At 273 K, significant complexation-induced shielding of the 1H NMR resonances corresponding to the protons of one N-propyl group encapsulated in the cavity of the resorcinarene second host was observed, which results in the shielding effects observed for the host (Figure 4).
Figure 3. Ball-and-stick representation of host–guest complex 2CHCl3@1 b, showing chloroform molecule in the upper position (a) and in the lower position (b). Atoms of chloroform molecules are presented in CPK style. Hydrogen atoms bonded to carbon atoms that do not participate in intermolecular interactions, five carbon atoms of the lower-rim hexyl groups, and water oxygen atoms are omitted for clarity in both figures.
Figure 4. Variable-temperature 1H NMR of 1 a in CDCl3 showing self-inclusion at low temperature. The self-inclusion dimer disassembles into monomeric species at higher temperatures. Stars correspond to signals resulting from the self-inclusion of the n-propyl groups.
cavity, while CHCl3_2 sits between cyclohexyl rings on top of CHCl3_1 (Figure 3b). As in 2 c@1 a, their positions are fixed by N(NH2+) H···Cl(CHCl3), C H···Cl(CHCl3), and C(CHCl3) H···Cl hydrogen bonds (Supporting Information, Table S3); for a more detailed description, see Supporting Information. 2 CHCl3@1 b also contains one water molecule (occupancy 0.25) situated between the hydrogen-bonded cation–anion seam and the seam formed by intramolecular O H···O hydrogen bonds (Supporting Information, Figure S3b). From dichloromethane/acetonitrile, 1 b crystallized as a formally 1:1 host–guest complex with disordered MeCN and CH2Cl2 molecules (MeCN@1 b). The cavity of 1 b is fully occupied with MeCN/CH2Cl2 in 90:10 occupancy ratio. The MeCN molecule is further disordered over two positions with equal occupancies. The upper part of the cavity, that is, the space between the cyclohexyl rings, is occupied by one CH2Cl2 molecule (total occupancy 0.5) in two equally occupied positions (25/25 %). The MeCN@1 b structure also shows exo-cavity elecChem. Eur. J. 2014, 20, 1 – 8
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Since the NH2 + moieties of the N-propyl chain interact with the hydrogen-bond seam, the OH and NH2 signals are also affected, as seen from the new signals between 7 and 9 ppm. These new signals slowly disappear with increasing temperature, which results in isolated monomeric species (Figure 4). The stability of the self-dimer was investigated further in a competition experiment with a slight excess of three different small guests:1-propanol (2 a), 1-butanol (2 b), and 1,4-dioxane (2 c) (Scheme 1) in CDCl3 at 303 K. In all cases, complexation-induced shielding of the 1H NMR resonances corresponding to the protons of the self-included N-propyl group disappeared, while new signals corresponding to the protons of the encapsulated guests were observed. A representative spectrum with 2 a is shown in Figure 5, and those with 2 b,c are shown in the Supporting Information.
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Figure 5. 1H NMR spectral changes observed on mixing 1 a and guest 2 a in CDCl3 at 303 K. Stars correspond to signals resulting from the self-inclusion of the n-propyl groups. Black dots correspond to signals resulting from encapsulation of 2 a.
Amide complexation The ability of N-alkyl ammonium resorcinarene chloride hosts 1 a,b to complex small guests 2 a–c that have hydrogen-bond donating and accepting groups as demonstrated above led to further studies of the properties of these host compounds in the complexation of a series of small amides. Amides have hydrogen-bond donating NH and accepting C=O groups and, with the correct size, act as suitable guests for the resorcinarene salt hosts. A series of N-alkyl and N-aryl acetamides were synthesized by a Schotten–Baumann[23, 24] reaction in which an acid chloride reacts with amines under basic conditions to give the corresponding amides. These amides were then studied as potential guests for the N-alkyl ammonium resorcinarene chloride hosts in solution and in the solid and gas phases. A series of 1H NMR titrations between hosts 1 a–b and amides 3 a–d was performed in CDCl3 solution at 303 K. Increasing amounts of the amides were added to a solution of resorcinarene host 1 a or 1 b. Complexation-induced shielding of the 1H NMR resonances corresponding to the guest protons was observed (Figure 6). The observed shifts result from the shielding effects of the aromatic rings and alkyl groups of the bowl-shaped host cavity on addition of the guests. The guest exchange is fast on the NMR timescale. Job plots[25–28] for resorcinarene hosts 1 a,b with amide guests 3 a–d showed 1:1 binding stoichiometry (see Supporting Information, Figures S17– S20). Subsequently, 1H NMR titrations of 1 a,b with amides 3 a–d were performed in CDCl3 at 303 K. The most intense shifts were observed for signals of the a-hydrogen atoms and the NCH3 or NCH2 hydrogen atoms of the amide guests. Taking into consideration the high shielding power of the aromatic rings of the resorcinarene skeleton, the highly shielded signals of the a-hydrogen atoms indicate that the methyl group of the guest (CH3C(O) ) sits deep in the cavity of the host (as evidenced by the X-ray studies). The signals of the amide methyl &
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Figure 6. Fitting of the 1H NMR data of the NCH3 groups of 3 a (a) and spectral changes (b) observed on the addition of amide 3 a to N-alkyl ammonium resorcinarene chloride 1 a in CDCl3 at 303 K.
group are therefore the most reasonable target to follow in calculating the binding constant of the amide guests. However, due to severe overlap in the range between 2.4 and 1 ppm, these signals could not be reliably followed in all cases. The NCH3 signals of 3 a, NCH2 signals of 3 b,c, and NPhH(a) signals of 3 d were reliably monitored. Binding constants (Figure 6 and Supporting Information) of the complexes were determined by using the EQNMR computer program[29] (Table 1).
Table 1. Binding constants K [m 1][a] for host 1 a,b with guests 3 a–d. Complex
K
Complex
K
3 a@1 a 3 a@1 b 3 c@1 a 3 c@1 b
46 3 147 12 244 11 631 55
3 b@1 a 3 b@1 b 3 d@1 a 3 d@1 b
104 10 311 21 351 13 443 46
[a] Obtained by monitoring the NCH3 (3 a), NCH2 (3 b,c), and NPhH(a) (3 d) signals of the guests in CDCl3 at 303 K.
The titration data show generally stronger binding of the amide guests by host 1 b (Table 1, see Supporting Information). This could be explained by the more rigid cyclohexyl groups of host 1 b providing a more fixed cavity to bind the guests and hence less competition with the solvents. With host 1 a in CDCl3, the amide guests also compete with the self-inclusion 4
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Full Paper process, which leads to lower binding constants of the amides. The size and nature of the guests has a marked impact on the binding constants. The strongest binding was observed for 3 c@1 b (631 m 1) and can be explained by a good fit between the host cavity and the size of the guest. Intermolecular hydrogen bonding is the major interaction responsible for the binding of the guests in the host cavity. Unambiguous proof of guest encapsulation and hence further confirmation of the binding mode of N-methyl acetamide (3 a) in the cavity of resorcinarene 1 b was provided by the Xray structure of 3 a@1 b (Figure 7). Single crystals of this host–
Figure 8. ESI mass spectrum of a mixture of resorcinarene 1 b and 3 d showing the 1:1 monomeric complex [3 d@1 b 4 HCl+H] + (m/z 1405). Inset: experimental and calculated isotope patterns of the monomeric complex.
ral abundances. A mixture of host 1 b and amide guest 3 d in the positive-ion mode resulted in a 1:1 complex [3 d@1 b 4 HCl+H] + (m/z 1405). Signals corresponding to the fragments of the resorcinarene hosts and assemblies attributed to unspecific binding were also observed. Analyses of samples containing combinations of resorcinarene hosts 1 a,b and amide guests 3 a–d (see Supporting Information) showed similar patterns to those in Figure 8.
Figure 7. a) Ball-and-stick representation of the host–guest complex of 3 a@1 b. Atoms of deeply included 3 a are presented in CPK style. Hydrogen atoms bonded to carbon atoms and five carbon atoms of the lower-rim hexyl groups are omitted for clarity. b) Top view of complex 3 a@1 b presented in CPK style, showing the position of 3 a and almost parallel disposition of the cyclohexyl rings.
Conclusion
guest complex were obtained by recrystallizing 1 b with 3 a from CHCl3/diethyl ether. Guest 3 a is located in the center of the cavity in the plane of the cation–anion belt, with the amide nitrogen and carbonyl oxygen atoms involved in N(amide) H···Cl and HN + H···O hydrogen bonding interactions (Supporting Information, Table S5). Simultaneously, the hydrogen atoms of the amide methyl group participate in C H···p interactions (for a more detailed description, see Supporting Information). Interestingly the cyclohexyl rings are almost parallel, as in the structure of 2 CHCl3@1 b (Figure 7b). As a consequence of inclusion of the amide, like in the case of 2 c@1 a, the resorcinarene core is distorted (see Supporting Information).
We have reported the inclusion properties of two N-alkyl ammonium resorcinarene chlorides, one with a flexible N-propyl group (1 a) and the other with a rigid cyclohexyl group (1 b). Host 1 a forms a self-included dimer in solution at and below room temperature, as determined by 1H NMR experiments and single-crystal X-ray crystallography. The X-ray structural study on 1 a shows that the dimer is formed by N H···Cl hydrogen bonds and C H···p interactions. At higher temperatures, dimeric host (1 a)2 disassembles into the monomers. The presence of suitable guests 2 a–c disrupts the self-inclusion process and results in 1:1 host–guest complexes. The guests are linked to the host by various interactions: strong N H··· Cl , N H···O, and N H···Cl hydrogen bonds, weaker C H···Cl , C H···Cl, and C H···O hydrogen bonds, and C H···p interactions. The C H···p interactions are absent from 2 CHCl3@1 b because the C H bond of the chloroform molecule lies in the plane of the cation–anion seam atoms and consequently does not interact with the phenyl rings. The spatial orientation and position of the encapsulated molecules are strongly influenced by the intermolecular interactions established between the guest and the resorcinarene salt host. Host compounds 1 a,b were shown to bind a series of N-alkyl- and N-aryl acetamides in solution, in the gas phase, and in the solid state. The X-ray structure of 3 a@1 b revealed the position of the amide and that it is bound in the cavity of the host mainly through strong N(amide) H···Cl and N(NH2+) H···O hydrogen bonds and by
Gas-phase studies Gas-phase complexation of amide guests 3 a–d by the N-alkyl ammonium resorcinarene chloride hosts 1 a,b was investigated by electrospray ionization (ESI) mass spectrometry. By using CHCl3/acetonitrile as spray solvent, the N-alkyl ammonium resorcinarene chlorides could be easily ionized and good-quality spectra recorded. For example, for 1 b in the positive-ion mode, progressive loss of hydrogen chloride resulted in signals corresponding to [1 b 3 HCl+H] + (m/z 1305), [1 b 4 HCl+H] + (m/z 1269), and [1 b 4 HCl+2 H]2 + (m/z 635) (Figure 8). The experimental isotope patterns agree with those simulated on the basis of natuChem. Eur. J. 2014, 20, 1 – 8
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Full Paper two C H···p interactions. The 1H NMR titration studies revealed that the cyclohexyl-armed host 1 b binds the amides slightly more strongly than the host 1 a with flexible n-propyl groups, as evidenced by the higher binding constants for 1 b. Mass spectrometric studies showed that the resorcinarene salts form 1:1 monomeric host–guest complexes in the gas phase, and corresponding results were observed in solution and in the solid state, too. This work shows how an N-alkyl ammonium resorcinarene chloride host, that is, a hydrogen-bonded analogue of a cavitand, is stable and has a suitable cavity to quite robustly bind amides in the solid state, in solution, and in the gas phase. In addition to presenting a new amide receptor, this work also contributes to our understanding of the complex nature of weak interactions in self-assembly and guestrecognition processes as one of the corner stones of supramolecular chemistry.
from The Cambridge Crystallographic www.ccdc.cam.ac.uk/data_request/cif.
Keywords: amides · host–guest systems recognition · resorcinarenes · self-assembly
NMR titrations Titration experiments were carried out in CDCl3 at 303 K on Bruker Avance DRX 500 MHz and 400 MHz spectrometers. Solutions of host 1 a,b were treated with various amounts of guests 3 a–d. After each addition, a 1H NMR spectrum was recorded. The true guest concentrations in the solution under study were determined by integration of the signals for the host versus the integration of the signals for guest protons. From the curvature of the titration curve, the binding constant was determined by using the EQNMR computer program.[29]
Mass spectrometry The mass spectrometric experiments were performed with a QSTAR Elite ESI-Q-TOF mass spectrometer equipped with an API 200 TurboIonSpray ESI source from AB Sciex (formerly MDS Sciex) in Concord, Ontario (Canada). All experiments were performed in positive polarization. The parameters of the ion source, ion optics, and quadrupole were optimized to get maximum abundance of the ions under study.
X-ray crystallography Data for (1 a)2 were collected at 170 K on an Agilent SuperNova diffractometer with Atlas detector by using mirror-monochromatized MoKa radiation (l = 0.71073 ). Data for 2 c@1 a, CHCl3@1 b, MeCN@1 b and 3 a@1 b were collected at 123 K on an Agilent SuperNova Dual diffractometer with Atlas detector by using mirrormonochromatized CuKa radiation (l = 1.54184 ). All details of data collection and reduction, as well as structure solution and refinement, are given in the Supporting Information. CCDC 990705 [(1 a)2], 990706 (2 c@1 a), 990707 (CHCl3@1 b), 990708 (MeCN@1 b) and 990709 (3 a@1 b) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge www.chemeurj.org
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[1] P. Timmerman, W. Verboom, D. N. Reinhoudt, Tetrahedron 1996, 52, 2663 – 2704. [2] V. Bçhmer, Angew. Chem. 1995, 107, 785 – 818; Angew. Chem. Int. Ed. Engl. 1995, 34, 713 – 745. [3] K. Rissanen, Angew. Chem. 2005, 117, 3718 – 3720; Angew. Chem. Int. Ed. 2005, 44, 3652 – 3654. [4] C. D. Gutsche, in Calixarenes: Monographs in Supramolecular Chemistry (Ed.: J. F. Stoddart), The Royal Society of Chemistry, Cambridge, UK, 2008, p. 282.. [5] N. K. Beyeh, K. Rissanen, Isr. J. Chem. 2011, 51, 769 – 780. [6] N. K. Beyeh, D. P. Weimann, L. Kaufmann, C. A. Schalley, K. Rissanen, Chem. Eur. J. 2012, 18, 5552 – 5557. [7] E. Kalenius, T. Keklinen, R. Neitola, K. Beyeh, K. Rissanen, P. Vainiotalo, Chem. Eur. J. 2008, 14, 5220 – 5228. [8] N. K. Beyeh, A. Valkonen, K. Rissanen, Supramol. Chem. 2009, 21, 142 – 148. [9] H. Mansikkamki, C. A. Schalley, M. Nissinen, K. Rissanen, New J. Chem. 2005, 29, 16 – 127. [10] L. Avram, Y. Cohen, J. Am. Chem. Soc. 2002, 124, 15148 – 15149. [11] M. M. Conn, J. J. Rebek, J. Am. Chem. Soc. 1997, 119, 1647 – 1668. [12] N. K. Beyeh, M. Kogej, A. hman, K. Rissanen, C. A. Schalley, Angew. Chem. Int. Ed. Angew. Chem., Int. Ed. 2006, 45, 5214 – 5218. [13] J. Kang, J. Rebek, Nature 1996, 382, 239 – 241. [14] H. Mansikkamki, M. Nissinen, K. Rissanen, Angew. Chem. 2004, 116, 1263 – 1266; Angew. Chem. Int. Ed. 2004, 43, 1243 – 1246. [15] H. Mansikkamki, S. Busi, M. Nissinen, A. hman, K. Rissanen, Chem. Eur. J. 2006, 12, 4289 – 4296. [16] K. Airola, V. Bçhmer, E. F. Paulus, K. Rissanen, C. Schmidt, I. Thondorf, W. Vogt, Tetrahedron 1997, 53, 10709 – 10724. [17] A. Shivanyuk, T. Spaniol, K. Rissanen, E. Kolehmainen, V. Bçhmer, Angew. Chem. 2000, 112, 3640 – 3643; Angew. Chem. Int. Ed. 2000, 39, 3497 – 3500. [18] N. K. Beyeh, M. Cetina, M. Lçfman, M. Luostarinen, A. Shivanyuk, K. Rissanen, Supramol. Chem. 2010, 22, 737 – 750. [19] N. K. Beyeh, M. Cetina, K. Rissanen, Cryst. Growth Des. 2012, 12, 4919 – 4926. [20] a) C. L. D. Gibb, B. C. Gibb, J. Am. Chem. Soc. 2004, 126, 11408 – 11409; b) K. Srinivasan, B. C. Gibb, Org. Lett. 2007, 9, 745 – 748. [21] N. K. Beyeh, M. Cetina, K. Rissanen, Chem. Commun. 2014, 50, 1959 – 1961. [22] J. Boonen, A. Bronselaer, J. Nielandt, L. Veryser, G. De Tr, B. De Spiegeleer, J. Ethnopharmacol. 2012, 142, 563 – 590. [23] C. Schotten, Ber. Dtsch. Chem. Ges. 1884, 17, 2544 – 2547. [24] E. Baumann, Ber. Dtsch. Chem. Ges. 1886, 19, 3218 – 3222. [25] K. A. Connors, in Binding Constants: The Measurements of Molecular Complex Stability, John Wiley & Sons, Madison, Wisconsin, USA, 1987, p. 432.
Resorcinarene hosts 1 a,b and amide guests 3 a–d were synthesized according to reported procedures.[16,18,30] Solvent guests 2 a–c were commercially available. Experimental details for the synthesis and characterization data of resorcinarene host 1 a,b and amide guests 3 a–d can be found in the Supporting Information.
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Esa Haapaniemi (JYU Jyvskyl) is acknowledged for help with NMR experiments. N.K.B., A.A., and K.R. gratefully acknowledge the Academy of Finland (N.K.B.: grant no. 258653, K.R.: grant no. 263256 and 265328) and the University of Jyvskyl for financial support. M.C. is grateful to Faculty of Textile Technology, University of Zagreb and K.R. for giving him an opportunity to work in his research group. A.V. gratefully acknowledges the University of Jyvskyl and the Tampere University of Technology for financial support.
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Full Paper [26] K. Hirose, J. Inclusion Phenom. Macrocyclic Chem. 2001, 39, 193 – 209. [27] K. Hirose, Determination of Binding Constants, in Analytical Methods in Supramolecular Chemistry (Ed.: C. A. Schalley), Wiley-VCH, Weinheim, Germany, 2006, pp. 17 – 54. [28] K. Hirose, Quantitative Analysis of Binding Properties. In Analytical Methods in Supramolecular Chemistry, Volume 1 & 2, Second Edition (Ed.: C. A. Schalley), Wiley-VCH, Weinheim, Germany, 2012, pp. 27 – 66. [29] M. J. Hynes, J. Chem. Soc. Dalton Trans. 1993, 311 – 312.
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[30] A. Shivanyuk, K. Rissanen, E. Kolehmainen, Chem. Commun. 2000, 1107 – 1108.
Received: March 10, 2014 Revised: && &&, 0000 Published online on && &&, 0000
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FULL PAPER & Resorcinarenes N. K. Beyeh,* A. Ala-Korpi, M. Cetina , A. Valkonen , K. Rissanen* && – && Recognition of N-Alkyl and N-Aryl Acetamides by N-Alkyl Ammonium Resorcinarene Chlorides
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Self-inclusion: N-Propyl ammonium resorcinarene chlorides form self-included dimers. Self-inclusion can be disrupted at higher temperatures, whereas in the presence of small guests the self-included dimers spontaneously reorganize to 1:1 host–guest complexes (see scheme).
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These hosts proved to be good receptors for a series of N-alkyl acetamides through strong intermolecular hydrogen bonds. Larger binding constants were observed for hosts with rigid upper rim substituents.
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& Resorcinarenes
Recognition of N-Alkyl and N-Aryl Acetamides by N-Alkyl Ammonium Resorcinarene Chlorides N. Kodiah Beyeh,*[a] Altti Ala-Korpi,[a] Mario Cetina ,[a, b] Arto Valkonen ,[a, c] and Kari Rissanen*[a]
alkyl acetamide guests through intermolecular hydrogen bonds involving the carbonyl oxygen (C=O) atoms and the amide (NH) groups of the guests, the chloride anions (Cl ) and ammonium (NH2 + ) cations of the hosts, and also through CH···p interactions between the hosts and guests. The self-included and host–guest complexes were studied by single-crystal X-ray diffraction, NMR titration, and mass spectrometry.
Abstract: N-Alkyl ammonium resorcinarene chlorides are stabilized by an intricate array of intra- and intermolecular hydrogen bonds that leads to cavitand-like structures. Depending on the upper-rim substituents, self-inclusion was observed in solution and in the solid state. The self-inclusion can be disrupted at higher temperatures, whereas in the presence of small guests the self-included dimers spontaneously reorganize to 1:1 host–guest complexes. These host compounds show an interesting ability to bind a series of N-
Introduction
tubes[14,15] have been reported. The phenolic hydroxyl groups make the 2-position of the benzene ring suitable for electrophilic substitution. Attaching suitable functional groups to resorcinarenes while maintaining the concave nature increases their recognition potential. Thus, the recognition properties of resorcinarenes can be tuned, and hence the array of guest compounds that can be recognized by resorcinarenes extended.[2, 11] Mannich condensation is a common procedure for functionalizing resorcinarenes at the benzene ring.[16–19] Primary amines and resorcinarenes in the presence of an excess of formaldehyde react to form tetrabenzoxazines.[16–18] Under refluxing conditions in the presence of mineral acids, the ring opening of tetrabenzoxazines leads to the formation of N-alkyl ammonium resorcinarene salts.[17–19] The hydrogen bonds between the ammonium moieties and halides form strong circular hydrogen-bond seams (···H(R’)N + (R’’)H···X ···H(R’)N + (R’’)H···X ···)2, which are referred to as the hydrogen-bond analogues of cavitands,[17, 18] since they have similar shape and cavity size to covalent cavitands. The resorcinarene salts have larger and deeper cavities as well as different binding features than unfunctionalized resorcinarenes and can thus bind a greater variety of guests.[17–19] Unfunctionalized resorcinarenes have a pbasic cavity and can bind guests through cation···p, CH···p, and hydrophobic interactions.[1, 2, 5] In addition, the resorcinarene salts can, by means of the circular hydrogen-bond seam, interact with guests through hydrogen-bond interactions.[17, 18] Recently, the resorcinarene salts have been shown to also act as halogen-bond[20] acceptors to give deep-cavity cavitand-like compounds.[21] The combination of these properties makes the N-alkyl ammonium resorcinarene salts potentially suitable hosts for a multitude of structurally different guests such as amides. Amides are very common in nature and amply used in
Resorcinarenes are very versatile compounds that can act as host compounds or as building blocks.[1–3] The possibility of functionalizing resorcinarenes to give more sophisticated compounds by utilizing the hydroxyl groups, the phenyl rings, or the lower-rim substituents make resorcinarenes an interesting family of compounds in supramolecular chemistry.[4] This unique property has led to resorcinarenes being labeled as one of the pillars of supramolecular chemistry. Resorcinarenes exist in several conformations, of which the C4v conformation is one of the most common.[1, 2, 4] Intramolecular hydrogen bonds between adjacent phenolic hydroxyl groups help maintain the C4v conformation.[1, 2, 4] The C4v conformation of unfunctionalized resorcinarenes has a concave cavity suitable for binding a variety of guests through several weak interactions.[1, 5] Supramolecular assemblies such as 1:1 open inclusion complexes,[6, 7] dimeric[5, 8, 9] and hexameric[10–13] capsular assemblies, and nano[a] N. K. Beyeh, A. Ala-Korpi, M. Cetina , A. Valkonen , K. Rissanen Department of Chemistry, Nanoscience Center, University of Jyvskyl P.O. Box 35, 40014 Jyvskyl (Finland) Fax: (+) 358 14 2602501 E-mail: [email protected] [email protected] [b] M. Cetina Present address: University of Zagreb, Faculty of Textile Technology Department of Applied Chemistry Prilaz baruna, Filipovic´a 28a, 10000 Zagreb (Croatia) [c] A. Valkonen Present address: Department of Chemistry and Bioengineering Tampere University of Technology P.O. Box 541, 33101 Tampere (Finland) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201402533 or from the author. Chem. Eur. J. 2014, 20, 1 – 8
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Full Paper technological applications.[22] The amide bond (HN C=O) is quite rigid and easily formed.[22] The field of application of amides is very broad, and hence the quest for new amide receptors is an interesting and a continuously developing area of research.[22] The upper-rim substituents of the N-alkyl ammonium resorcinarene chlorides have a direct effect on both the cavity size and the complexation properties towards guest species. Herein, the structural elucidation of self-inclusion and guestbinding properties of N-propyl ammonium resorcinarene chlorides is presented. Self-inclusion was monitored at various temperatures and also in the presence of small guests. Furthermore, the complexation of a series of N-alkyl and N-aryl acetamide guests 3 a–d by resorcinarene salts 1 a,b was investigated in the solid state, in solution, and in the gas phase.
Figure 1. a) Ball-and-stick representation of self-inclusion dimer (1 a)2. Atoms of one self-included n-propyl chain and the nitrogen atom to which it is attached are presented in CPK style. Hydrogen atoms bonded to carbon atoms and five carbon atoms of the lower-rim hexyl groups are omitted for clarity. b) CPK plot of the dimer 1 a showing symmetrical disposition of cations that form the dimer. Chloroform molecules displaced outside the dimer and oxygen atoms of crystal-lattice water are omitted for clarity in both figures.
Results and Discussion N-Alkyl ammonium resorcinarene chlorides 1 a,b with flexible N-propyl and rigid cyclohexyl substituents were synthesized (Scheme 1). Formation of a very strong, circular, hydrogen-
cluded resorcinarene tetracations and six chloride anions. The dimer is additionally stabilized by C H···p interactions between hydrogen atoms of the terminal methyl group and the C8–C13 phenyl ring (Supporting Information, Table S1). The dimer is nearly symmetrical, that is, propyl and hexyl chains are approximately related by an inversion center (Figure 1 b). Unexpectedly when 1,4-dioxane was used as the crystallization solvent instead of chloroform, the self-included dimer was not formed, and instead 1:1 host–guest complex 2 c@1 a was obtained. Overall, three 1,4-dioxane (2 c_1–2 c_3) molecules interact with host 1 a through hydrogen bonds. Molecule 2 c_ 1 is situated deep and almost in the center of the cavity of 1 a (Figure 2), with the dioxane oxygen atoms located in the
Scheme 1. N-alkyl ammonium resorcinarene chlorides 1 a,b, small guests 2 a–c, and N-alkyl and N-aryl acetamides 3 a–d.
bonded cation/anion seam between the spherical chloride anions and the ammonium moieties results in an extended interior cavity that is suitable for the recognition of a variety of guest molecules.[17–19] The resorcinarene salts are generally symmetrical in solution, as verified by their relatively simple 1 H NMR spectra.
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Self-inclusion and guest-binding studies
Figure 2. a) Ball-and-stick representation of host–guest complex 2 c@1 a. Atoms of deeply included 1,4-dioxane molecule are presented in CPK style. Hydrogen atoms bonded to carbon atoms that do not participate in intermolecular interactions and five carbon atoms of the lower rim hexyl groups are omitted for clarity. b) Top view of complex 2 c@1 a presented in CPK style, showing position of the 1,4-dioxane molecules. Oxygen atoms of disordered water molecules are omitted for clarity in both figures.
Compound 1 a crystallizes from chloroform as self-included dimer (1 a)2 (Figure 1) with two intermolecular N(NH2+) H···Cl hydrogen bonds formed between hydrogen atoms of the ammonium moiety of the included propyl chain and the chloride anion of the other half of the dimer (Figure 1 a and Supporting Information, Table S1). Thus, the dimer consists of two self-in-
cation–anion belt. Its position is primarily fixed by one N(NH2+) H···O(dioxane) hydrogen bond (Supporting Information, Table S2). Furthermore, 2 c_1 shows two intracomplex C H···Cl hydrogen bonds and two C H···p interactions to the C15–C20 and C1–C6 phenyl rings. Finally, the included 2 c_1 is
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Full Paper also linked to the adjacent, exo-cavity 2 c_2 by one C H···O hydrogen bond. The 2 c_2 molecule is situated on the top and slightly aside of the cavity, and 2 c_3 is completely outside the cavity. Both 2 c_2 and 2 c_3 are bound to the host 1 a by several types of intermolecular interactions: N(NH2+) H···O, C H···O, and C H···Cl hydrogen bonds (for a more detailed description, see the Supporting Information). Inclusion of 2 c_1 in the cavity strongly affects the conformation of the resorcinarene core, as a consequence of repulsion between the atoms of this molecule and atoms of the cation–anion belt (see Supporting Information). In the cyclohexyl analogue 1 b, self-inclusion and subsequent dimer formation are not possible due to the sterically very bulky cyclohexyl groups. Thus, 1 b crystallizes from chloroform/diethyl ether as a 2:1 host–guest complex with two chloroform molecules (CHCl3_1 and CHCl3_2) as guest (2 CHCl3@1 b) with overall occupancy of 0.5. Molecule CHCl3_ 1 is situated deep in the cavity slightly below the cation–anion belt (Figure 3 a) and is somewhat offset from the center of the
tron density, which was treated as a disordered MeCN molecule with 0.25 occupancy. The resorcinarene core is more distorted than in 2 CHCl3@1 b (see Supporting Information). The MeCN@1 b structure is illustrated in the Supporting Information (Figures S4 and S5). Single-crystal X-ray studies showed that N-propyl ammonium resorcinarene chloride 1 a self-assembles into tightly packed dimers in CHCl3. In the presence of 1,4-dioxane (2 c), the self-included dimer was disassembled and a host–guest complex was formed. 1H NMR spectroscopic studies in CDCl3 were carried out to probe the self-inclusion properties of the host 1 a. The temperature dependence and stability of the selfincluded dimer were investigated in a variable-temperature 1 H NMR study. At 273 K, significant complexation-induced shielding of the 1H NMR resonances corresponding to the protons of one N-propyl group encapsulated in the cavity of the resorcinarene second host was observed, which results in the shielding effects observed for the host (Figure 4).
Figure 3. Ball-and-stick representation of host–guest complex 2CHCl3@1 b, showing chloroform molecule in the upper position (a) and in the lower position (b). Atoms of chloroform molecules are presented in CPK style. Hydrogen atoms bonded to carbon atoms that do not participate in intermolecular interactions, five carbon atoms of the lower-rim hexyl groups, and water oxygen atoms are omitted for clarity in both figures.
Figure 4. Variable-temperature 1H NMR of 1 a in CDCl3 showing self-inclusion at low temperature. The self-inclusion dimer disassembles into monomeric species at higher temperatures. Stars correspond to signals resulting from the self-inclusion of the n-propyl groups.
cavity, while CHCl3_2 sits between cyclohexyl rings on top of CHCl3_1 (Figure 3b). As in 2 c@1 a, their positions are fixed by N(NH2+) H···Cl(CHCl3), C H···Cl(CHCl3), and C(CHCl3) H···Cl hydrogen bonds (Supporting Information, Table S3); for a more detailed description, see Supporting Information. 2 CHCl3@1 b also contains one water molecule (occupancy 0.25) situated between the hydrogen-bonded cation–anion seam and the seam formed by intramolecular O H···O hydrogen bonds (Supporting Information, Figure S3b). From dichloromethane/acetonitrile, 1 b crystallized as a formally 1:1 host–guest complex with disordered MeCN and CH2Cl2 molecules (MeCN@1 b). The cavity of 1 b is fully occupied with MeCN/CH2Cl2 in 90:10 occupancy ratio. The MeCN molecule is further disordered over two positions with equal occupancies. The upper part of the cavity, that is, the space between the cyclohexyl rings, is occupied by one CH2Cl2 molecule (total occupancy 0.5) in two equally occupied positions (25/25 %). The MeCN@1 b structure also shows exo-cavity elecChem. Eur. J. 2014, 20, 1 – 8
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Since the NH2 + moieties of the N-propyl chain interact with the hydrogen-bond seam, the OH and NH2 signals are also affected, as seen from the new signals between 7 and 9 ppm. These new signals slowly disappear with increasing temperature, which results in isolated monomeric species (Figure 4). The stability of the self-dimer was investigated further in a competition experiment with a slight excess of three different small guests:1-propanol (2 a), 1-butanol (2 b), and 1,4-dioxane (2 c) (Scheme 1) in CDCl3 at 303 K. In all cases, complexation-induced shielding of the 1H NMR resonances corresponding to the protons of the self-included N-propyl group disappeared, while new signals corresponding to the protons of the encapsulated guests were observed. A representative spectrum with 2 a is shown in Figure 5, and those with 2 b,c are shown in the Supporting Information.
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Figure 5. 1H NMR spectral changes observed on mixing 1 a and guest 2 a in CDCl3 at 303 K. Stars correspond to signals resulting from the self-inclusion of the n-propyl groups. Black dots correspond to signals resulting from encapsulation of 2 a.
Amide complexation The ability of N-alkyl ammonium resorcinarene chloride hosts 1 a,b to complex small guests 2 a–c that have hydrogen-bond donating and accepting groups as demonstrated above led to further studies of the properties of these host compounds in the complexation of a series of small amides. Amides have hydrogen-bond donating NH and accepting C=O groups and, with the correct size, act as suitable guests for the resorcinarene salt hosts. A series of N-alkyl and N-aryl acetamides were synthesized by a Schotten–Baumann[23, 24] reaction in which an acid chloride reacts with amines under basic conditions to give the corresponding amides. These amides were then studied as potential guests for the N-alkyl ammonium resorcinarene chloride hosts in solution and in the solid and gas phases. A series of 1H NMR titrations between hosts 1 a–b and amides 3 a–d was performed in CDCl3 solution at 303 K. Increasing amounts of the amides were added to a solution of resorcinarene host 1 a or 1 b. Complexation-induced shielding of the 1H NMR resonances corresponding to the guest protons was observed (Figure 6). The observed shifts result from the shielding effects of the aromatic rings and alkyl groups of the bowl-shaped host cavity on addition of the guests. The guest exchange is fast on the NMR timescale. Job plots[25–28] for resorcinarene hosts 1 a,b with amide guests 3 a–d showed 1:1 binding stoichiometry (see Supporting Information, Figures S17– S20). Subsequently, 1H NMR titrations of 1 a,b with amides 3 a–d were performed in CDCl3 at 303 K. The most intense shifts were observed for signals of the a-hydrogen atoms and the NCH3 or NCH2 hydrogen atoms of the amide guests. Taking into consideration the high shielding power of the aromatic rings of the resorcinarene skeleton, the highly shielded signals of the a-hydrogen atoms indicate that the methyl group of the guest (CH3C(O) ) sits deep in the cavity of the host (as evidenced by the X-ray studies). The signals of the amide methyl &
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Figure 6. Fitting of the 1H NMR data of the NCH3 groups of 3 a (a) and spectral changes (b) observed on the addition of amide 3 a to N-alkyl ammonium resorcinarene chloride 1 a in CDCl3 at 303 K.
group are therefore the most reasonable target to follow in calculating the binding constant of the amide guests. However, due to severe overlap in the range between 2.4 and 1 ppm, these signals could not be reliably followed in all cases. The NCH3 signals of 3 a, NCH2 signals of 3 b,c, and NPhH(a) signals of 3 d were reliably monitored. Binding constants (Figure 6 and Supporting Information) of the complexes were determined by using the EQNMR computer program[29] (Table 1).
Table 1. Binding constants K [m 1][a] for host 1 a,b with guests 3 a–d. Complex
K
Complex
K
3 a@1 a 3 a@1 b 3 c@1 a 3 c@1 b
46 3 147 12 244 11 631 55
3 b@1 a 3 b@1 b 3 d@1 a 3 d@1 b
104 10 311 21 351 13 443 46
[a] Obtained by monitoring the NCH3 (3 a), NCH2 (3 b,c), and NPhH(a) (3 d) signals of the guests in CDCl3 at 303 K.
The titration data show generally stronger binding of the amide guests by host 1 b (Table 1, see Supporting Information). This could be explained by the more rigid cyclohexyl groups of host 1 b providing a more fixed cavity to bind the guests and hence less competition with the solvents. With host 1 a in CDCl3, the amide guests also compete with the self-inclusion 4
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Full Paper process, which leads to lower binding constants of the amides. The size and nature of the guests has a marked impact on the binding constants. The strongest binding was observed for 3 c@1 b (631 m 1) and can be explained by a good fit between the host cavity and the size of the guest. Intermolecular hydrogen bonding is the major interaction responsible for the binding of the guests in the host cavity. Unambiguous proof of guest encapsulation and hence further confirmation of the binding mode of N-methyl acetamide (3 a) in the cavity of resorcinarene 1 b was provided by the Xray structure of 3 a@1 b (Figure 7). Single crystals of this host–
Figure 8. ESI mass spectrum of a mixture of resorcinarene 1 b and 3 d showing the 1:1 monomeric complex [3 d@1 b 4 HCl+H] + (m/z 1405). Inset: experimental and calculated isotope patterns of the monomeric complex.
ral abundances. A mixture of host 1 b and amide guest 3 d in the positive-ion mode resulted in a 1:1 complex [3 d@1 b 4 HCl+H] + (m/z 1405). Signals corresponding to the fragments of the resorcinarene hosts and assemblies attributed to unspecific binding were also observed. Analyses of samples containing combinations of resorcinarene hosts 1 a,b and amide guests 3 a–d (see Supporting Information) showed similar patterns to those in Figure 8.
Figure 7. a) Ball-and-stick representation of the host–guest complex of 3 a@1 b. Atoms of deeply included 3 a are presented in CPK style. Hydrogen atoms bonded to carbon atoms and five carbon atoms of the lower-rim hexyl groups are omitted for clarity. b) Top view of complex 3 a@1 b presented in CPK style, showing the position of 3 a and almost parallel disposition of the cyclohexyl rings.
Conclusion
guest complex were obtained by recrystallizing 1 b with 3 a from CHCl3/diethyl ether. Guest 3 a is located in the center of the cavity in the plane of the cation–anion belt, with the amide nitrogen and carbonyl oxygen atoms involved in N(amide) H···Cl and HN + H···O hydrogen bonding interactions (Supporting Information, Table S5). Simultaneously, the hydrogen atoms of the amide methyl group participate in C H···p interactions (for a more detailed description, see Supporting Information). Interestingly the cyclohexyl rings are almost parallel, as in the structure of 2 CHCl3@1 b (Figure 7b). As a consequence of inclusion of the amide, like in the case of 2 c@1 a, the resorcinarene core is distorted (see Supporting Information).
We have reported the inclusion properties of two N-alkyl ammonium resorcinarene chlorides, one with a flexible N-propyl group (1 a) and the other with a rigid cyclohexyl group (1 b). Host 1 a forms a self-included dimer in solution at and below room temperature, as determined by 1H NMR experiments and single-crystal X-ray crystallography. The X-ray structural study on 1 a shows that the dimer is formed by N H···Cl hydrogen bonds and C H···p interactions. At higher temperatures, dimeric host (1 a)2 disassembles into the monomers. The presence of suitable guests 2 a–c disrupts the self-inclusion process and results in 1:1 host–guest complexes. The guests are linked to the host by various interactions: strong N H··· Cl , N H···O, and N H···Cl hydrogen bonds, weaker C H···Cl , C H···Cl, and C H···O hydrogen bonds, and C H···p interactions. The C H···p interactions are absent from 2 CHCl3@1 b because the C H bond of the chloroform molecule lies in the plane of the cation–anion seam atoms and consequently does not interact with the phenyl rings. The spatial orientation and position of the encapsulated molecules are strongly influenced by the intermolecular interactions established between the guest and the resorcinarene salt host. Host compounds 1 a,b were shown to bind a series of N-alkyl- and N-aryl acetamides in solution, in the gas phase, and in the solid state. The X-ray structure of 3 a@1 b revealed the position of the amide and that it is bound in the cavity of the host mainly through strong N(amide) H···Cl and N(NH2+) H···O hydrogen bonds and by
Gas-phase studies Gas-phase complexation of amide guests 3 a–d by the N-alkyl ammonium resorcinarene chloride hosts 1 a,b was investigated by electrospray ionization (ESI) mass spectrometry. By using CHCl3/acetonitrile as spray solvent, the N-alkyl ammonium resorcinarene chlorides could be easily ionized and good-quality spectra recorded. For example, for 1 b in the positive-ion mode, progressive loss of hydrogen chloride resulted in signals corresponding to [1 b 3 HCl+H] + (m/z 1305), [1 b 4 HCl+H] + (m/z 1269), and [1 b 4 HCl+2 H]2 + (m/z 635) (Figure 8). The experimental isotope patterns agree with those simulated on the basis of natuChem. Eur. J. 2014, 20, 1 – 8
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Full Paper two C H···p interactions. The 1H NMR titration studies revealed that the cyclohexyl-armed host 1 b binds the amides slightly more strongly than the host 1 a with flexible n-propyl groups, as evidenced by the higher binding constants for 1 b. Mass spectrometric studies showed that the resorcinarene salts form 1:1 monomeric host–guest complexes in the gas phase, and corresponding results were observed in solution and in the solid state, too. This work shows how an N-alkyl ammonium resorcinarene chloride host, that is, a hydrogen-bonded analogue of a cavitand, is stable and has a suitable cavity to quite robustly bind amides in the solid state, in solution, and in the gas phase. In addition to presenting a new amide receptor, this work also contributes to our understanding of the complex nature of weak interactions in self-assembly and guestrecognition processes as one of the corner stones of supramolecular chemistry.
from The Cambridge Crystallographic www.ccdc.cam.ac.uk/data_request/cif.
Keywords: amides · host–guest systems recognition · resorcinarenes · self-assembly
NMR titrations Titration experiments were carried out in CDCl3 at 303 K on Bruker Avance DRX 500 MHz and 400 MHz spectrometers. Solutions of host 1 a,b were treated with various amounts of guests 3 a–d. After each addition, a 1H NMR spectrum was recorded. The true guest concentrations in the solution under study were determined by integration of the signals for the host versus the integration of the signals for guest protons. From the curvature of the titration curve, the binding constant was determined by using the EQNMR computer program.[29]
Mass spectrometry The mass spectrometric experiments were performed with a QSTAR Elite ESI-Q-TOF mass spectrometer equipped with an API 200 TurboIonSpray ESI source from AB Sciex (formerly MDS Sciex) in Concord, Ontario (Canada). All experiments were performed in positive polarization. The parameters of the ion source, ion optics, and quadrupole were optimized to get maximum abundance of the ions under study.
X-ray crystallography Data for (1 a)2 were collected at 170 K on an Agilent SuperNova diffractometer with Atlas detector by using mirror-monochromatized MoKa radiation (l = 0.71073 ). Data for 2 c@1 a, CHCl3@1 b, MeCN@1 b and 3 a@1 b were collected at 123 K on an Agilent SuperNova Dual diffractometer with Atlas detector by using mirrormonochromatized CuKa radiation (l = 1.54184 ). All details of data collection and reduction, as well as structure solution and refinement, are given in the Supporting Information. CCDC 990705 [(1 a)2], 990706 (2 c@1 a), 990707 (CHCl3@1 b), 990708 (MeCN@1 b) and 990709 (3 a@1 b) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge www.chemeurj.org
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Resorcinarene hosts 1 a,b and amide guests 3 a–d were synthesized according to reported procedures.[16,18,30] Solvent guests 2 a–c were commercially available. Experimental details for the synthesis and characterization data of resorcinarene host 1 a,b and amide guests 3 a–d can be found in the Supporting Information.
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Esa Haapaniemi (JYU Jyvskyl) is acknowledged for help with NMR experiments. N.K.B., A.A., and K.R. gratefully acknowledge the Academy of Finland (N.K.B.: grant no. 258653, K.R.: grant no. 263256 and 265328) and the University of Jyvskyl for financial support. M.C. is grateful to Faculty of Textile Technology, University of Zagreb and K.R. for giving him an opportunity to work in his research group. A.V. gratefully acknowledges the University of Jyvskyl and the Tampere University of Technology for financial support.
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Full Paper [26] K. Hirose, J. Inclusion Phenom. Macrocyclic Chem. 2001, 39, 193 – 209. [27] K. Hirose, Determination of Binding Constants, in Analytical Methods in Supramolecular Chemistry (Ed.: C. A. Schalley), Wiley-VCH, Weinheim, Germany, 2006, pp. 17 – 54. [28] K. Hirose, Quantitative Analysis of Binding Properties. In Analytical Methods in Supramolecular Chemistry, Volume 1 & 2, Second Edition (Ed.: C. A. Schalley), Wiley-VCH, Weinheim, Germany, 2012, pp. 27 – 66. [29] M. J. Hynes, J. Chem. Soc. Dalton Trans. 1993, 311 – 312.
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[30] A. Shivanyuk, K. Rissanen, E. Kolehmainen, Chem. Commun. 2000, 1107 – 1108.
Received: March 10, 2014 Revised: && &&, 0000 Published online on && &&, 0000
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FULL PAPER & Resorcinarenes N. K. Beyeh,* A. Ala-Korpi, M. Cetina , A. Valkonen , K. Rissanen* && – && Recognition of N-Alkyl and N-Aryl Acetamides by N-Alkyl Ammonium Resorcinarene Chlorides
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Self-inclusion: N-Propyl ammonium resorcinarene chlorides form self-included dimers. Self-inclusion can be disrupted at higher temperatures, whereas in the presence of small guests the self-included dimers spontaneously reorganize to 1:1 host–guest complexes (see scheme).
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These hosts proved to be good receptors for a series of N-alkyl acetamides through strong intermolecular hydrogen bonds. Larger binding constants were observed for hosts with rigid upper rim substituents.
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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