Sequential Halogen Bonding with Ditopic Donors - ACS Publications

Article pubs.acs.org/crystal

Sequential Halogen Bonding with Ditopic Donors: σ‑Hole Evolutions upon Halogen Bond Formation Irène Nicolas, Frédéric Barrière, Olivier Jeannin, and Marc Fourmigué* Institut des Sciences Chimiques de Rennes, Université de Rennes 1, UMR CNRS 6226, Campus de Beaulieu 35042 Rennes, France S Supporting Information *

ABSTRACT: The halogen bonding ability of ditopic halogen bond donors can be assessed from the maximum value of the molecular surface electrostatic potential, called σ-hole, at the two halogen atoms. We show here that in N,N′-diodo-dimethylhydantoin (DIH), the halogen bonding (XB) ability of the two nitrogen-bound iodine atoms does not parallel the calculated σ-hole amplitude. The cocrystallization of DIH with a series of para-substituted pyridines, noted Py-R (R = pyrrolidinyl, NMe2, Me, H, CO2Me, CF3, CN), affords bis-adducts DIH·(Py-R)2 with the more electron-rich pyridines, while mono-adducts DIH·(Py-R) are favored with the more electron-poor pyridines (R = CO2Me, CF3, CN). Analysis of the structural characteristics of these mono- and bisadducts, combined with theoretical calculations, demonstrates that the formation of a first N−I···N′Py‑R XB deeply modifies the XB ability (and associated σ-hole) of the second uncoordinated iodine atom. Under these conditions, the latter might associate through I···O XB to the carbonyl oxygen atom of a neighboring mono-adduct in the crystal rather than to a second pyridine. These studies show that when working with polytopic XB donors, one should always consider the deactivation of the remaining halogen atoms following sequential XB formation.

■

pounds,27,28 etc. Competition cases29,30 when halogen bonding is faced with hydrogen bonding31,32 have been reported in many instances,33 highlighting the strength of the halogen bonding and the cases of orthogonal XB and HB in proteins.34 Besides such hydrogen bond vs. halogen competitions, an approach aiming at establishing a hierarchy between different halogen bond donors would also be highly desirable. It would complement analogous scales reported for XB acceptors, for example, with I2 as an XB donor.35,36 Some trends are already well identified both experimentally and theoretically such as (i) the strength of XB increases in the order F ≪ Cl < Br < I,37 (ii) the electron withdrawing nature of the substituent linked to the halogen plays an important role,38 and (iii) the sp hybridization of the carbon atoms bearing the halogen is favored, over sp2 and then sp3 hybridization. More recently, competitive cocrystallizations experiments of a selected set of XB donors with a variety of XB acceptors were performed by Aakeröy et al.1,39 on the basis that “(i) a pronounced σ-hole would produce a more effective XB donor and (ii) a better XB donor should be more efficient at forming cocrystal with a suitable XB acceptor.” For that purpose, these authors have compared the XB donor ability of (i) the bromo- and iodoethynyl molecules (IEIB and BEIB in Scheme 1a), and (ii) p-diiodo-, p-dibromoperfluorobenzene, and mixed bromo-iodo analogues (Scheme 1a). Although often hampered by iodine/bromine disorder, these studies confirmed the iodine

INTRODUCTION Hierarchy and competition are two terms used in chemistry to describe cases when reactivitytaken in a broad sense involves a ranking of different thermodynamically offered possibilities. This is found in competing chemical bond formation or dissociation, but also in supramolecular chemistry or crystal engineering.1 Such cases are often desirable as they provide easy tools (temperature, solvents, ...) to direct the outcome of a chemical reaction in one direction or the other within a limited energy range. In crystal engineering, weak intermolecular interactions often compete with others, leading for example to polymorphism,2,3 or to different stoichiometries4 in multicomponent systems.5,6 Some priority rules, or hierarchy of supramolecular synthons,7,8 however emerge as for example in hydrogen bond (HB) systems with multiple binding sites, where the strongest HB donor group links to the strongest HB acceptor, while the second-best HB donor will bind to the second-best HB acceptor.9,10 Such a rule is based on the assumption that electrostatic interactions essentially control the outcome of the Y−H···Z hydrogen bonding interactions between Y−H+δ and −δ Z. Because of its strength and directionality, halogen bonding (XB)11,12 is currently investigated as a hydrogen bond analogue,13 where the halogen atom acts as the electrophile. This interaction plays a crucial role in many areas of supramolecular chemistry and crystal engineering, such as anion receptors,14,15 organocatalysis,16,17 molecular conducting18,19 and magnetic materials,20,21 solid state polymerization,22,23 liquid crystals24,25 and gels,26 luminescent com© XXXX American Chemical Society

Received: February 29, 2016 Revised: March 31, 2016

A

DOI: 10.1021/acs.cgd.6b00333 Cryst. Growth Des. XXXX, XXX, XXX−XXX

Crystal Growth & Design

Article

bonding to one over the other iodine atom will be established. The ability of DIH to form halogen bonds with one or with two pyridines will be assessed. This approach intends to illustrate that the σ-hole amplitude is not sufficient by itself to fully rationalize the formation of halogen bonded systems, since the stability of the reaction products is intimately linked to the whole charge distribution within the halogen-bonded cocrystals.

Scheme 1

■

RESULTS AND DISCUSSION The DIH Molecule: Preliminary Theoretical Investigations. The DIH molecule bears two iodine atoms with different environments, with one imide-type and one amide-type nitrogen atoms. It is therefore interesting to first estimate the different abilities of the two N−I sites to take part into XB adducts. One can indeed anticipate, based on chemical intuition, that halogen bonding should be stronger with the N-iodoimide motif (Na−Ia in Scheme 2) rather than with the N-iodoamide motif (Nb−Ib in Scheme 2). Since halogen bonding is primarily electrostatic in nature,48,49 a measure of the halogen bond donor character can be given by the maximum value of the molecular surface electrostatic potential at the iodine atom (Vmax).50 Linear relationships have been established, for example, by Politzer et al. on acetone-bromoarene adducts,51 between the calculated halogen-bond energies and the Vmax values at bromine. Such linear correlations however only hold if they can be confirmed with an experimentally determined halogen bond energy. This was nicely addressed by Taylor et al.52 from the determination of association constants53 through 19F NMR titrations.54,55 Very satisfactory correlations were obtained provided that the molecular surface electrostatic potential is calculated with an appropriate level of theory. On the basis of the work of Taylor, we calculated the electrostatic potential of DIH with the same methods, that is, DFT-B3LYP/6-31+G** for all atoms except iodine and LANLdp for iodine (see details in SI).56,57 As shown in Figure 1, the maximum value of the molecular surface

over bromine preference, and the added strength provided by sp hybridization or aryl perfluorination. Another important point in that respect is also raised by the case of polyhalogenated symmetric di-, tri-, or tetratopic XB donors such as the prototypical diiodoacetylene, 1,4-diodoperfluorobenzene, symtriiodo-trifluoro-benzene, tetraiodoethylene, or tetrabromomethane (Scheme 1b). In most examples reported so far where these polytopic XB donors cocrystallize with Lewis bases, all halogen atoms are engaged in equivalent halogen bonding interactions. Early studies by van der Boom et al. have nevertheless stressed that polytopic XB donors can remain unsaturated. For example, the tritopic sym-triodo-trifluorobenzene links to only two pyridines,40 highlighting a weakening of the N···I interactions as more pyridine moieties coordinate to the iodinated molecule. On the other hand, the same tritopic XB donor is known to engage its three iodine atoms into XB interactions with halide anions (Cl−, Br−, I−), probably because of their stronger Lewis base character.41,42 A similar behavior was very recently reported with sym-triiodo-trinitrobenzene.43 These observations raise the question of a ranking of halogen bonding ability in polytopic XB donors, upon sequential XB formation. To address this point, we have considered N,N′-diiodohydantoin derivatives as models. These molecules act as potential ditopic XB donors, with two highly activated iodine atoms, each of them in a N−I bond, nevertheless with slightly different environments. Such compounds are easily obtained from hydantoins themselves, with a variety of alkyl and aryl substitution patterns at the 5 position. Within this series, 1,3diiodo-5,5-dimethylhydantoin (DIH, 1,3-diiodo-5,5-dimethylimidazolidine-2,4-dione, Scheme 2) is commercially available and used extensively as a powerful reagent44,45 for electrophilic iodinations.46,47 We have investigated here the ability of DIH to form halogen bonded adducts with pyridine derivatives of different Lewis base strength, from the weaker 4-cyanopyridine to the stronger 4-dimethylaminopyridine (DMAP) and 4-(Npyrrolidinyl)pyridine Lewis bases (Scheme 2). The preferential

Figure 1. Molecular electrostatic potential surface of DIH (B3LYP/631G**-LANLdp, Gaussian03) with maximum values at iodine atoms indicated. Red indicates negative charge density and blue positive charge density. The full scale range is ±0.05 au (Hartrees), i.e., ±31.4 kcal/mol. The red arrow indicates the orientation of the dipolar moment.

Scheme 2

electrostatic potential at imidic Ia, Vmax(Ia) equals +30.65 kcal/ mol, while it amounts to a slightly larger value (+31.34 kcal/mol) at the amidic iodine atom Ib. Both absolute values are notably larger than those obtained with the same method for other strong prototypical XB donors such as C6F5−I (+25.8 kcal/mol) or Ph− CC−I (24.6 kcal/mol),52 demonstrating the strong XB donor ability of such N-iodoimide (or amide)58 functional groups.59,60 It should be stressed at this point that these calculated values Vmax on both iodine atoms are sensitive to how the calculations are carried out. For example, changing the isovalue from 0.0004 B



Article

(used here) to 0.001 as reported elsewhere48,61 or changing the level of theory can modify the ordering between the amidic and imidic iodine atoms.62 Nevertheless, the striking point of these calculations is the very similar Vmax values at both imidic Ia, and amidic Ib iodine atoms, contrary to chemical intuition which would predict a larger Vmax on the imidic iodine atom. We reckon that this apparent “anomaly” finds its origin in the whole molecule polarization, as shown by its dipolar moment. The latter (2.72 D) is indeed essentially controlled by the two electronegative oxygen atoms of the carbonyl moieties, leading to an overall dipolar moment nearly collinear to the Na−Ia bond however oriented unfavorably for the polarization of the Na−Ia bond. In the following discussion, we would like to address in particular to which extent this σ-hole amplitude difference affects the formation of XB adducts with various pyridines. Crystal Growth. Different techniques were used to isolate DIH cocrystals with 4-substituted pyridines of varying Lewis base character. In most cases, the ditopic DIH halogen bond donor was mixed with an excess (3 equiv) of the substituted pyridine, and the solution was either slowly evaporated, or hexane vapors were condensed on the solution surface to induce crystallization. It follows that under these conditions, the DIH molecule is always in the presence of an excess of the chosen 4-substituted pyridine. Under these conditions, the bis-adducts DIH·(Py-R)2 were isolated in a crystalline form with R = NC4H8, NMe2, Me, and H, while with R = CF3 and CN, despite the excess pyridine, only the mono-adducts DIH·(Py-R) were isolated during the crystallization (Scheme 3). Stoichiometry was deduced from

Structural Properties. The four bis(adducts) crystallize in the monoclinic system, space group P21/n, except DIH·(Py)2 which is found in the polar space group Cc. In DIH·(PyNC4H8)2, two crystallographically independent molecules are found, which differ by the relative angles between the pyridine and DIH mean planes. In each of the four 1:2 co-crystals isolated with Py-NC4H8, Py-NMe2, PyMe, and pyridine, the pyridine derivatives are halogen bonded to the two iodine atoms (Figure 2). Relevant bond distances and angles for the XB interactions

Scheme 3. Different Bis- and Mono-Adducts Isolated with DIH and Various Pyridines

Figure 2. View of the bimolecular adducts in the cocrystals of DIH with (a) pyrrolidinopyridine (two crystallographically independent molecules), (b) 4-dimethylaminopyridine, (c) 4-picoline, and (d) pyridine.

are collected in Table 1 and reveal some notable trends. First of all, we note that the shortest XB are systematically found at the imidic iodine atom Ia, while a slightly longer, but still very short, halogen bond is observed on amidic Ib. This comes in apparent contradiction with the maximum value of the molecular surface electrostatic potential in free DIH (see above). Within the series R = H, Me, NMe2, NC4H8, we note a systematic halogen bond strengthening, in accordance with the increasing Lewis base character of the pyridines. As mentioned above, 1:1 adducts were also isolated with PyCO2Me and Py-NC4H8. As shown in Figure 3, the pyridine is in both cases halogen bonded to the imidic N-iodo moiety. The other amidic iodine atom, however, does not remain passive, but engages in another halogen bond with the oxygen atom of a neighboring molecule, leading to the formation of chain-like motifs. This structural arrangement is further accompanied by a rather short (CPy−)H···O hydrogen bond, involving the α hydrogen atom of the pyridine. Relevant bond distances and angles for these intermolecular interactions are collected in Table

elemental analysis and 1H NMR, as well as single crystal X-ray diffraction for all compounds except DIH·(Py-CF3) and DIH· (PyCN) which did not crystallize properly. Besides, with R = CO2Me, single crystals could not be obtained, and an alternative solution diffusion procedure was used, with a long tube successively filled with solution of DIH, pure solvent, and finally the Py-CO2Me solution. Under those conditions, single crystals of a 1:1 phase, DIH·(Py-CO2Me) were also isolated. The latter diffusion strategy with Py-NMe2 also afforded a 1:1 adduct, DIH· (Py-NC4H8), in addition to the 1:2 adduct DIH·(Py-NC4H8)2 isolated with the first procedure (Scheme 3). In conclusion, it appears that the most electron-rich pyridines can easily afford bisadducts with DIH, while weaker Lewis bases such as Py-CO2Me, Py-CF3, and Py-CN crystallize into mono-adducts, despite the presence of the two activated iodine atoms in DIH. These observations show that the two iodine atoms are not equivalent and that a competition for the formation of mono- or bis-adducts takes place, depending on the Lewis base character of the pyridine. C



Article

Table 1. Relevant Distances and Angles for the Halogen Bonded Bimolecular Adducts in the Co-Crystals with DIHa

Py-NC4H8b Na−Ia (Å) Ia···Na′ (Å) Na−Ia···Na′ (deg) Na---Na′ (Å) RRa Nb−Ib (Å) Ib···Nb′ (Å) Nb−Ib···Ib′ (deg) Nb---Nb′ (Å) RRb

2.116(12) 2.391(11) 173.2(4) 4.500(17) 0.678 2.131(12) 2.438(12) 177.8(4) 4.569(18) 0.690

2.118(12) 2.385(12) 178.7(4) 4.502(18) 0.677 2.130(12) 2.478(14) 177.4(4) 4.607(19) 0.702

Py-NMe2

Py-CH3

Py

2.169(5) 2.349(6) 177.4(2) 4.517(8) 0.666 2.111(6) 2.488(6) 176.4(2) 4.597(9) 0.705

2.110(4) 2.457(5) 176.7(2) 4.565(7) 0.696 2.102(5) 2.464(5) 178.3(2) 4.566(7) 0.698

2.105(11) 2.456(12) 177.5(3) 4.56(2) 0.696 2.094(10) 2.532(10) 177.2(3) 4.624(14) 0.717

a The reduction ratio, RR, stands for the ratio of the observed I···N′Py distance over the sum (3.53 Å) of the van der Waals radii of I (1.98 Å) and N (1.55 Å). The nomenclature used is shown in the scheme. bTwo crystallographically independent molecules.

Table 2. Relevant Distances and Angles for the Halogen Bonded Mono-Adductsa

Na−Ia (Å) Ia···Na′ (Å) Na−Ia···Na′ (deg) Na---Na′ (Å) RRa Nb−Ib (Å) Ib···Ob (Å) Nb−Ib···Ob (deg) Nb---Ob (Å) RRb

Figure 3. View of the bimolecular halogen bonded adducts DIH···PyNC4H8 (a) and DIH·Py-CO2Me (b), further linked into chains through I···O halogen bonds (pink dotted lines) and H···O hydrogen bonds (turquoise dotted lines).

Py-NC4H8

Py-CO2Me

2.208(4) 2.294(4) 178.8(1) 4.502(6) 0.650 2.042(3) 2.692(3) 175.1(1) 4.730(5) 0.769

2.137(6) 2.398(6) 177.2(2) 4.534(9) 0.679 2.051(5) 2.720(4) 175.3(2) 4.768(7) 0.777

a

The reduction ratio, RR, stands for the ratio of the observed I···N′Py or I···Ob distance over the sum of the van der Waals radii of I (1.98 Å) and N (1.55 Å) or O (1.52 Å). The nomenclature used is shown in the scheme below.

2. As observed above, and following the Lewis base strength, we note a stronger N−I···N′ halogen bond with the pyrrolidinylsubstituted pyridine than with the ester substituted one. Halogen bonding to the oxygen atom also appears as a secondary and weaker interaction, as the associated reduction ratio (0.769, 0.777) largely exceeds that observed for the N−I···N′ primary interaction (0.650, 0.679), Table 2. At this stage, an interesting comparison can also be performed between the two p-pyrrolidinylpyridine derivatives, namely, the mono-adduct, NIH·(Py-NC4H8), and the bis-adduct, NIH·(PyNC4H8)2. As shown in Scheme 4, the halogen bond on the imidic Na−Ia moiety is much shorter in the mono-adduct than in the bisadduct. This clearly shows (i) that the most stable XB system is linked through imidic Na−Ia moiety, (ii) that once formed, the remaining amidic iodine atom Ib in the mono-adduct, is noticeably deactivated toward the formation of a second halogen bond and, (iii) that the carbonyl oxygen atoms can compete

Scheme 4

favorably with the pyridine nitrogen atom as halogen bond acceptor in these deactivated mono-adducts. In order to rationalize all the above experimental observations, we have D



Article

performed theoretical calculations on mono- and bis-adducts, at the level of theory mentioned above for isolated DIH, that is DFT with B3LYP/6-31+G**-LANLdp. These results are detailed below. Theoretical Calculations. We first describe the outcome of the calculations on the bis-adducts, where both iodine atoms in DIH are engaged in a halogen bond with a given pyridine. As shown in Table 3, we note the following evolutions. First of all,

Table 4. Calculated Halogen Bond Distances in Two MonoAdduct Model Compounds, Based on Halogen Bonding with Either I1 or I2a

Table 3. Calculated Bond Distances within the Bis-Adducts (in Å)a

a

pyridine

Na−Ia

Ia···Na′

Nb−Ib

Ib···Nb′

Py-CN Py-CF3 Py-CO2Me Py Py-Me Py-NMe2 Py-NC4H8

2.09 2.10 2.10 2.10 2.11 2.12 2.12

2.65 2.65 2.64 2.61 2.60 2.56 2.56

2.08 2.08 2.09 2.09 2.09 2.10 2.10

2.72 2.71 2.69 2.67 2.66 2.63 2.62

pyridine

Na−Ia (Å)

Ia···Na′ (Å)

Nb−Ib (Å)

Ib···Nb′ (Å)

rel. Ib vs Ia destabilization (kcal/mol)

Py-CN Py-CF3 Py-CO2Me Py Py-Me Py-NMe2 Py-NC4H8

2.11 2.11 2.12 2.12 2.13 2.15 2.15

2.61 2.60 2.57 2.56 2.54 2.49 2.49

2.09 2.09 2.10 2.11 2.11 2.12 2.13

2.67 2.66 2.63 2.61 2.60 2.55 2.54

1.45 1.44 1.41 1.52 1.54 1.67 1.59

a

Relative destabilization: energy difference between the two monoadducts, for a given pyridine (see text).

pyridines considered show that the halogen bonded adduct on Ia is systematically more stable (by 1.5−1.6 kcal mol−1) than the halogen bonded adduct on Ib with the same pyridine. One can also note that in these more stable mono-adducts halogen bonded through Ia, the halogen bond distance is found to be strikingly shorter than the same halogen bond on Ia in the corresponding bis-adducts. This point was experimentally identified in the X-ray crystal structures of the mono- and bis adducts with Py-NC4H8 (see above). It demonstrates that the formation of the second halogen bond with Ib, and associated charge transfer, deactivates the first strongest halogen bond on Ia. This is a consequence of the charge distribution which takes places upon the formation of the first halogen bond. The last point we would like to address now derives from the experimental observation that the bis-adducts could be isolated only with pyridines of strong Lewis base character, while pyridines of poorer Lewis base character (Py-CN, Py-CF3, PyCO2Me) yielded mono-adducts only. In the two structurally characterized mono-adducts (with Py-CO2Me and Py-NC4H8), the second amidic iodine atom Ib is halogen bonded to a DIH carbonyl oxygen atom, rather than to Py-CO2Me itself. This indicates that in the mono-adducts, depending on the first coordinated pyridine, a competition takes place for the second iodine atom Ib between different halogen bond acceptors, namely, either the substituted pyridine or the DIH Ob oxygen atom. In Table 5, we have reported the calculated maximum values (both positive and negative) of the molecular surface electrostatic potential of the mono-adducts associated through Ia, in order to assess the evolution of the σ-hole on Ib in these monoadducts. A view of the pyridine adduct is shown in Figure 4. We note first that the σ-hole on Ib ranges between +18 and +25 kcal mol−1, while it was found at ∼31 kcal mol−1 in isolated DIH on both iodine atoms (see above), confirming this deactivation of the Ib atom following the first XB interaction with Ia. Larger σholes on Ib are actually found in those mono-adducts involving the weaker Lewis base pyridines, while maximum value of the molecular surface electrostatic potential on the oxygen atoms in the mono-adducts increases with the strongest Lewis base pyridines. As shown in Table 5 however, for a given monoadduct, the outcome of the competition for the different Lewis bases, namely, the two oxygen atoms of the mono-adduct itself,

The nomenclature used is shown in the scheme below.

the calculated XB distances slightly exceed (by ca. 0.15 Å) those experimentally observed. This point likely finds its origin in the chosen functional/basis set and in the fact that gas-phase calculations on isolated systems do not take into account the molecular environment in the crystal.60 In any case, our aim here is mainly a handy evaluation of the differences between the two iodine atoms in their halogen bonding ability rather than a very accurate N···I distance modeling. In that respect, we note that both the calculated Ia···Na′ and Ib···Nb′ halogen bonds get shorter with the most electron-rich pyridines, as indeed experimentally observed in the X-ray crystal structures when going from pyridine to 4-pyrrolidinopyridine (Py-NC4H8) (Table 1). The second noteworthy point is that the calculated halogen bond involving Ia is systematically found shorter than that calculated on Ib, confirming also the evolutions observed in the X-ray crystal structures of the bis-adducts (see Table 1). We know that, upon XB formation, a partial charge transfer occurs which would lead, for the extreme situations, to an N-iodo pyridinium cation halogen bonded to an imidate or amidate anion.60 The differences observed here between the two sites illustrate the better ability of the imidic group to delocalize the partial negative charge, when compared with the less electronegative amidic group. It demonstrates also that the estimation of the maximum value of the molecular surface electrostatic potential at the iodine atom (Vmax) is not sufficient to correctly predict the outcome of a competition between two different halogen atoms or two different halogen environments. Clearly, the charge distribution within the whole adduct plays a crucial role in the overall stability of the system. This latter point is also emphasized in the theoretical calculations performed on the two possible mono-adducts, where a given pyridine can be halogen bonded either to Ia or to Ib (Table 4). Indeed, the calculated maximum value of the molecular surface electrostatic potential on the isolated DIH molecule was found to be larger at the amidic Ib than at the imidic Ia. Calculations of the two possible adducts for the different E



Article

charged (Cl−) or neutral (NMe3) Lewis bases.63 The stronger halogen bonding found counterintuitively with the less electronegative substituents (X = I) was indeed ascribed to a dominant charge-transfer contribution originating from a lower energy C− I σ* antibonding orbital. In order to rationalize the inclination of the Ib iodine atom in the mono-adducts toward the formation of a second XB interaction, we have reported in Figure 6, for each pyridine Py−R, the energy levels of the antibonding N−I empty orbital (noted σ*N−I) of these mono-adducts, together with the pyridine’s occupied orbital associated with the nitrogen lone pair (noted σN). Note that the two relevant orbitals are not always the LUMO of DIH·(Py-R) or the HOMO of Py-R. The energy difference for each pair σ*N−I/σN amounts to 4.6−4.8 eV for the stronger Lewis base pyridines (R = H, Me, NMe2, NC4H8), while it exceeds 5.0 eV (5.00−5.34) for the weaker Lewis base pyridines (R = CO2Me, CF3, CN). It follows that the calculated energy gain associated with a charge transfer is indeed stronger with the electron-rich pyridines, as experimentally observed.

Table 5. Calculated Maximum Values (in kcal/mol) of the Molecular Surface Electrostatic Potential in the MonoAdducts Associated through Ia, (a) at the XB Donor Site on Ib (σ-hole), (b) at the XB Acceptors Oxygen Sites Oa and Ob, and (c) at the Pyridinic Nitrogen Atom of Isolated Pyridines

XB donor site monoadduct at Ia DIH DIH·(Py-CN) DIH·(Py-CF3) DIH·(PyCO2Me) DIH·(Py) DIH·(Py-Me) DIH·(PyNMe2) DIH·(PyNC4H8)

XB acceptor site

Vmax at Ib

Vmax at Oa

Vmax at Ob

Vmax at Nb′ atom in free pyridine

+31.34 +24.88 +24.08 +22.44

−31.30 −35.61 −36.62 −40.25

−27.48 −31.08 −32.20 −36.17

−21.71 −23.80 −27.91

+21.97 +20.79 +18.35

−38.98 −40.24 −42.95

−35.43 −36.17 −39.36

−30.52 −32.32 −36.93

+18.22

−43.51

−40.06

−38.16

■

CONCLUSION We have shown here that DIH acts as a powerful XB donor, while the XB ability of the two nitrogen-bound iodine atoms does not parallel the calculated σ-hole amplitude. The cocrystallization of DIH with a series of para-substituted pyridines, Py-R (R = pyrrolidinyl, NMe2, Me, H, CO2Me2, CF3, CN), affords bisadducts DIH·(Py-R)2 with the most electron-rich pyridines, while mono-adducts DIH·(Py-R) are favored with the most electron-poor pyridines (R = CO2Me, CF3, CN). Analysis of the structural characteristics of these mono- and bis-adducts, combined with theoretical calculations, demonstrates that the formation of a first N−I···N′Py‑R XB deeply modifies the XB ability (and associated σ-hole) of the second uncoordinated iodine atom. These studies show that when working with di-, tri-, or tetratopic XB donors, one should always consider the deactivation of the remaining halogen atoms following sequential XB formation.

Figure 4. Molecular electrostatic potential surface of the mono-adduct DIH·(Py) (B3LYP/6-31G**-LANLdp, Gaussian03) with extrema at iodine and oxygen atoms indicated. Red indicates negative charge density and blue positive charge density.

■

and the nitrogen atom of a potential second pyridine, cannot be simply anticipated from the comparison of the calculated maximum values of the molecular surface electrostatic potential on these acceptor sites. An additional way to address these differences is based on molecular orbital interactions. Indeed, the halogen bond, particularly when involving strong XB donors and acceptors, can be described by an overlap interaction between the occupied pyridine nitrogen lone pair orbital and an antibonding N−I empty orbital (Figure 5). The interaction is expected to be stronger when occupied, and empty levels are closer in energy. This point has been nicely demonstrated by Huber et al. in their analysis of the XB ability of X3C−I (X = F, Cl, Br, I) toward

EXPERIMENTAL SECTION

Synthesis and Crystal Growth. N,N′-Diiodo-5,5-dimethylhydantoin (DIH, also known as 1,3-diiodo-5,5-dimethyl-imidazolidine-2,4dione) was obtained from Aldrich and used without further purification. The different pyridines are also commercially available. The solvents used (dichloromethane, ethyl acetate, acetonitrile, dichloromethane, and chlorobenzene) were dried over basic alumina and filtered before use. DIH·(Py)2. DIH (15 mg, 3.95 × 10−5 mol) was dispersed in AcOEt (2 mL). Pyridine (10 μL, 11.8 × 10−5 mol) was added, leading to DIH solubilization. The solution was filtered to remove nondissolved particles and poured in a Durham tube (ø × h = 7.25 × 50 mm). Crystals were obtained by vapor diffusion method with hexane as precipitant. The sample was left at 2 °C during 8 days in the dark. White crystals were obtained. Mp 155 °C. 1H NMR (300 MHz, DMSO-d6) δ 8.58 (dt, J = 4.4, 1.7 Hz, 4H, HAr), 7.80 (tt, J = 7.5, 1.8 Hz, 2H, HAr), 7.39 (ddd, J = 7.6, 4.2, 1.5 Hz, 4H, HAr), 1.08 (s, 6H, CH3). Elem. Anal. Calcd for C15H16I2N4O2 (MW: 538.1279 g mol−1): C, 33.48; H, 3.00; N, 10.41%. Found: C, 33.46; H, 2.92; N, 10.30%. DIH·(Py-Me)2. As above by vapor diffusion method with hexane from DIH (15 mg, 3.95 × 10−5 mol) dispersed in CH2Cl2 (2 mL) and 4picoline (12 μL, 11.8 × 10−5 mol). White crystals. M.p.: 104 °C. 1H NMR (300 MHz, CDCl3) δ 8.44 (d, J = 6.4 Hz, 4H, HAr), 7.16 (d, J = 6.4 Hz, 4H, HAr), 2.40 (s, 6H, CH3), 1.26 (s, 6H, CH3). Elem. Anal. Calcd for C17H20I2N4O2 (MW: 566.1819 g mol−1): C, 36.06; H, 3.56; N, 9.90. Found: C, 36.20; H, 3.38; N, 9.60%.

Figure 5. Calculated LUMOs of both DIH and its pyridine adduct, DIH· (Py-H), showing the strong antibonding contribution on the N−I bonds before XB formation. F



Article

Figure 6. Energy diagram with the HOMO/HOMO−1 orbitals of the pyridines (Py-R) and the LUMO/LUMO+1 orbitals of the mono-adducts DIH· (Py-R). The main interaction associating the occupied σN orbital of the pyridines (nitrogen lone pair) with the antibonding σ*N−I orbital is marked with a double arrow and associated energy difference.

Table 6. Crystallographic Data formula FW (g mol−1) crystal color system space group a (Å) b (Å) c (Å) α (deg) β (deg) γ (deg) V (Å3) T (K) Z Dcalc (g·cm−1) μ (mm−1) total refls Abs corr Tmin, Tmax θmax (deg) uniq refls Rint uniq refls (I > 2σ(I)) R1 wR2 (all data) GOF res. dens. (e Å−3)

DIH·(Py)2

DIH·(Py-Me)2

DIH·(Py-NMe2)2

DIH·(Py-NC4H8)2

DIH·(Py-NC4H8)

DIH·(Py-CO2Me)

C15H16I2N4O2 538.12 colorless monoclinic Cc 5.8708(6) 31.685(3) 9.9257(9) 90.00 98.258(7) 90.00 1827.2(3) 150(2) 4 1.956 3.456 3185 multiscan 0.640, 0.933 25.02 2074 0.0293 2001 0.0342 0.0839 1.04 1.633, −0.809

C17H20I2N4O2 566.17 colorless monoclinic P21/n 5.9221(2) 34.1720(14) 10.2022(4) 90.00 98.1100(10) 90.00 2043.97(13) 150(2) 4 1.840 3.094 14750 multiscan 0.647, 0.781 27.51 4655 0.0367 3915 0.0327 0.0685 1.048 1.063, −0.696



C14H18I2N4O2 528.12 colorless triclinic P1̅ 8.0715(4) 8.5714(5) 14.5645(8) 106.043(3) 93.681(3) 104.064(3) 929.99(9) 150(2) 2 1.886 3.393 13543 multiscan 0.732, 0.952 25.078 3297 0.0278 2846 0.0205 0.0473 1.056 1.016, −0.503

C12H13I2N3O4 517.05 colorless triclinic P1̅ 5.9748(2) 8.1003(3) 16.9805(5) 94.451(2) 98.712(2) 95.897(2) 804.40(5) 150(2) 2 2.135 3.927 9065 multiscan 0.405, 0.961 27.52 3664 0.0436 3081 0.0362 0.0845 1.021 0.86, −0.88

DIH·(Py-NMe2)2. From DIH (15 mg, 3.95 × 10−5 mol) and 4dimethylaminopyridine (10 mg, 11.8 × 10−5 mol) in CH3CN (4 mL). The solution was left to evaporate during 8 days in the dark at room temperature. White crystals. Mp 163 °C. 1H NMR (300 MHz, CDCl3) δ 8.15 (dd, J = 5.5 and 1.5 Hz, 4H, HAr), 6.42 (dd, J = 5.3 and 1.5 Hz, 4H,

HAr), 3.05 (s, 12H, CH3), 1.25 (s, 6H, CH3). Elem. Anal. Calcd for C19H26I2N6O2 (MW: 624.2659 g mol−1): C, 36.06; H, 4.20; N, 13.46%. Found: C, 36.61; H, 4.17; N, 13.27%. DIH·(Py-NC4H8)2. DIH (15 mg, 3.95 × 10−5 mol) was dispersed in CH2Cl2 (2 mL). Addition of 4-pyrrolidino-pyridine (17.6 mg, 11.8 × G



Article

10−5 mol) completely solubilizes DIH. Solution was filtered to remove nondissolved particles and poured in a Durham tube. Crystals were obtained by vapor diffusion method with hexane. The sample was left to 2 °C during 8 days in the dark. Only a few white crystals were obtained. DIH·(Py-NC4H8). DIH (15 mg, 3.95 × 10−5 mol) was dissolved in acetonitrile (0.5 mL). Separately, 4-pyrrolidino-pyridine (17.6 mg, 11.8 × 10−5 mol) was taken in CH3CN (0.2 mL). In a long thin tube were carefully and successively poured the solution of DIH, pure CH3CN (3 mL), and the solution of 4-pyrrolidinopyridine. The sample was left during 8 days in the dark at room temperature. The crystals were formed by slow diffusion. 1H NMR (300 MHz, DMSO-d6) δ 8.08 (d, J = 7.0 Hz, 2H, HAr), 6.48 (d, J = 7.0 Hz, 2H, HAr), 3.33−3.25 (m, 4H, 2xCH2), 1.96 (d, J = 3.2 Hz, 4H, 2 × CH2), 1.06 (s, 6H, CH3). DIH·(Py-CO2Me). DIH (15 mg, 3.95 × 10−5 mol) was dissolved in CH3CN (0.5 mL). Separately, 4-methylisonicotinate (12 mL, 11.8 × 10−5 mol) was taken in CH3CN (0.2 mL). In a long thin tube were carefully and successively poured the solution of DIH, pure CH3CN (3 mL), and the solution of 4-methylisonicotinate. The sample was left during 8 days in the dark at room temperature. The crystals were formed by slow diffusion. Mp 196 °C. 1H NMR (300 MHz, DMSO-d6) δ 8.81 (dd, J = 4.5 and 1.7 Hz, 2H, HAr), 7.84 (dd, J = 4.3 and 1.5 Hz, 2H, HAr), 3.91 (s, 3H, COOCH3), 1.08 (s, 6H, 2 × CH3). Elem. Anal. Calcd for C12H13I2N3O4 (MW: 516.8995 g mol−1): C, 27.87; H, 2.53; N, 8.1. Found: C, 27.66; H, 2.60; N, 8.12%. DIH·(Py-CF3). DIH (15 mg, 3.95 × 10−5 mol) was dispersed in CH2Cl2 (2 mL). 4-Trifluoromethyl-pyridine (12 mL, 11.8 × 10−5 mol) was added and completely solubilizes DIH. The solution was filtered to remove nondissolved particles and poured in a Durham tube. Crystals were made by vapor diffusion method with hexane. The sample was left to 2 °C during 8 days in the dark. White crystals were obtained. Mp 212 °C. 1H NMR (300 MHz, DMSO-d6) δ 8.89 (d, J = 6.5 Hz, 2H, HAr), 7.79 (d, J = 6.5, 2H, HAr), 1.13 and 1.08 (s, 6H, 2 × CH3). Elem. Anal. Calcd for C11H10F3I2N3O2 (MW: 527.0241 g mol−1): C, 25.07; H, 1.91; N, 7.97%. Found: C, 24.76; H, 2.02; N, 7.78%. The crystals could not be properly analyzed by single crystal X-ray diffraction because of severe twinning. DIH·(Py-CN). DIH (15 mg, 3.95 × 10−5 mol) was dissolved in CH3CN (0.5 mL). Separately, 4-cyano-pyridine (10 mg, 11.8 × 10−5 mol) was dissolved in CH3CN (0.2 mL). In a long thin tube were carefully and successively poured the solution of DIH, pure CH3CN (3 mL) and the solution of 4-cyanopyridine. The sample was left during 8 days in the dark at room temperature. The crystals were formed by slow diffusion. Mp 195 °C. 1H NMR (300 MHz, DMSO-d6) δ 8.85 (d, J = 6.5 Hz, 2H, HAr), 7.86 (d, J = 6.5, 2H, HAr), 1.08 (s, 6H, 2xCH3). Elem. Anal. Calcd for C11H10I2N4O2 (MW: 484.0359 g mol−1): C, 27.30; H, 2.08; N, 11.58%. Found: C, 27.43; H, 2.21; N, 11.62%. X-ray Crystallography. X-ray crystal structure collections were performed on a Nonius FR590 diffratometer or on an APEXII BrukerAXS diffractometer equipped with a CCD camera and a graphitemonochromated Mo−Kα radiation source (λ = 0.71073 Å) at 150 K. Details of the structural analyses are summarized in Table 6. Absorption corrections were performed with SADABS. Structures were solved by direct methods using the SIR97 program64 and then refined with fullmatrix least-squares methods based on F2 (SHELXL-97)65 with the aid of the WINGX program.66 All non-hydrogen atoms were refined with anisotropic atomic displacement parameters. H atoms were finally included in their calculated positions. The structure of DIH·(Py-C4H8)2 is reported here despite some large density residues after the refinements. A first data reduction was performed considering the crystal as a single crystal. Refinement of the structure with this data set yielded rather large R factor values, and large difference density residues located close to the four independent iodine atoms. A more careful data analysis showed some doubled reflections indicating the presence of at least two domains, but with very close orientation. Accordingly, refinements based on a second data set obtained from TWINABS-1 (HKLF4 and HKLF5 format)67 were performed but yielded even higher R factors and difference density values. The R factor values and large difference density residues reported here may be therefore the consequence of this unresolved twining.

A SQUEEZE procedure was used in the crystal structure of DIH·(PyNC4H8) to take into account an acetonitrile molecule, disordered on the (0, 1/2, 0) inversion center. X-ray crystallographic data in CIF format are available from CCDC 1456620: DIH·(Py)2, CCDC 1456621: DIH·(Py-NMe2)2, CCDC 1456622: DIH·(Py-Me) 2 , CCDC 1456623: DIH·(Py-NC 4 H8 ), CCDC 1456624: DIH·(Py-NC4H8)2 and CCDC 1456625: DIH·(PyCO2Me), respectively.

■

ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.cgd.6b00333. Details on the theoretical calculations and coordinates of optimized structures, cif files for the single crystal X-ray diffraction experiments (PDF) Accession Codes

CCDC 1456620−1456625 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing [email protected], or by contacting The Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

■

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS The authors thank the University Rennes 1 for financial support (to I.N.), the CINES CCRT for allocation of computing time (projects c2015087449 and c2016085032) and the CDIFX (Rennes, France) for access to X-ray facilities.

■

REFERENCES

(1) Aakeröy, C. B.; Baldrighi, M.; Desper, J.; Metrangolo, P.; Resnati, G. Chem.-Eur. J. 2013, 19, 16240−16247. (2) Moulton, B.; Zaworotko, M. J. Chem. Rev. 2001, 101, 1629−1658. (3) Aakeröy, C. B.; Seddon, K. R. Chem. Soc. Rev. 1993, 22, 397−407. (4) Aakeroy, C. B.; Salmon, D. J. CrystEngComm 2005, 7, 439−448. (5) Shan, N.; Zaworotko, M. J. Drug Discovery Today 2008, 13, 440− 446. (6) Fleischman, S. G.; Kuduva, S. S.; McMahon, J. A.; Moulton, B.; Bailey Walsh, R. D.; Rodriguez-Hornedo, N.; Zaworotko, M. J. Cryst. Growth Des. 2003, 3, 909−919. (7) Bis, J. A.; Vishweshwar, P.; Weyna, D.; Zaworotko, M. J. Mol. Pharmaceutics 2007, 4, 401−416. (8) Kavuru, P.; Aboarayes, D.; Arora, K. K.; Clarke, H. D.; Kennedy, A.; Marshall, L.; Ong, T. T.; Perman, J.; Pujari, T.; Wojtas, L.; Zaworotko, M. J. Cryst. Growth Des. 2010, 10, 3568−3584. (9) Etter, M. C. Acc. Chem. Res. 1990, 23, 120−126. (10) Aakeröy, C. B.; Epa, K. N.; Forbes, S.; Desper, J. CrystEngComm 2013, 15, 5946−5949. (11) Cavallo, G.; Metrangolo, P.; Milani, R.; Pilati, T.; Priimagi, A.; Resnati, G.; Terraneo, G. Chem. Rev. 2016, 116, 2478−2601. (12) Fourmigué, M. Curr. Opin. Solid State Mater. Sci. 2009, 13, 36−45. (13) Desiraju, G. R.; Ho, P. S.; Kloo, L.; Legon, A. C.; Marquardt, R.; Metrangolo, P.; Politzer, P.; Resnati, G.; Rissanen, K. Pure Appl. Chem. 2013, 85, 1711−1713. (14) Taylor, M. S. Top. Curr. Chem. 2014, 359, 27−48. (15) Vargas Jentzsch, A.; Matile, S. Top. Curr. Chem. 2015, 358, 205− 240. H



Article

(16) Walter, S. M.; Kniep, F.; Herdtweck, E.; Huber, S. M. Angew. Chem., Int. Ed. 2011, 50, 7187−7191. (17) Kniep, F.; Jungbauer, S. H.; Zhang, Q.; Walter, S. M.; Schindler, S.; Schnapperelle, I.; Herdtweck, E.; Huber, S. M. Angew. Chem., Int. Ed. 2013, 52, 7028−7032. (18) Brezgunova, M.; Shin, K. S.; Auban-Senzier, P.; Jeannin, O.; Fourmigué, M. Chem. Commun. 2010, 3226−3228. (19) Shin, K.-S.; Jeannin, O.; Brezgunova, M.; Dahaoui, S.; Aubert, E.; Espinosa, E.; Auban-Senzier, P.; Świetlik, R.; Frąckowiak, A.; Fourmigué, M. Dalton Trans. 2014, 43, 5280−5291. (20) Fourmigué, M.; Batail, P. Chem. Rev. 2004, 104, 5379−5418. (21) Fourmigué, M. Struct. Bonding (Berlin) 2008, 126, 181−207. (22) Jin, H.; Young, C. N.; Halada, G. P.; Phillips, B. L.; Goroff, N. S. Angew. Chem., Int. Ed. 2015, 54, 14690−14695. (23) Sun, A. W.; Lauher, J. W.; Goroff, N. S. Science 2006, 312, 1030− 1034. (24) Nguyen, H. L.; Horton, P. N.; Hursthouse, M. B.; Legon, A. C.; Bruce, D. W. J. Am. Chem. Soc. 2004, 126, 16−17. (25) Bruce, D. W. Struct. Bonding (Berlin) 2008, 126, 161−180. (26) Meazza, L.; Foster, J. A.; Fucke, K.; Metrangolo, P.; Resnati, G.; Steed, J. W. Nat. Chem. 2012, 5, 42−47. (27) Bolton, O.; Lee, K.; Kim, H.-J.; Lin, K. Y.; Kim, J. Nat. Chem. 2001, 3, 205−210 (b). (28) Zhu, W.; Zheng, R.; Zhen, Y.; Yu, Z.; Dong, H.; Fu, H.; Shi, Q.; Hu, W. J. Am. Chem. Soc. 2015, 137, 11038−11046. (29) Aakeröy, C. B.; Panikkattu, S.; Chopade, P. D.; Desper, J. CrystEngComm 2013, 15, 3125−3136. (30) Awwadi, F. F.; Taher, D.; Haddad, S. F.; Turnbull, M. M. Cryst. Growth Des. 2014, 14, 1961−1971. (31) Aakeröy, C. B.; Wijethunga, T. K.; Haj, M. A.; Desper, J.; Moore, C. CrystEngComm 2014, 16, 7218−7225. (32) Mínguez Espallargas, G.; Zordan, F.; Arroyo Marín, L.; Adams, H.; Shankland, K.; van de Streek, J.; Brammer, L. Chem. - Eur. J. 2009, 15, 7554−7568. (33) Shirman, T.; Boterashvili, M.; Orbach, M.; Freeman, D.; Shimon, L. J. W.; Lahav, M. E.; van der Boom, M. Cryst. Growth Des. 2015, 15, 4756−4759. (34) Voth, A. R.; Khuu, P.; Oishi, K.; Ho, P. S. Nat. Chem. 2009, 1, 74− 79. (35) Le Questel, J.-Y.; Laurence, C.; Graton, J. CrystEngComm 2013, 15, 3212−3221. (36) Laurence, C.; Graton, J.; Berthelot, M.; El Ghomari, M. J. Chem. Eur. J. 2011, 17, 10431−10444. (37) Legon, A. C. Angew. Chem., Int. Ed. 1999, 38, 2686−2714. (38) Präsang, C.; Whitwood, A. C.; Bruce, D. W. Cryst. Growth Des. 2009, 9, 5319−5326. (39) Aakeröy, C. B.; Chopade, P. D.; Desper, J. Cryst. Growth Des. 2013, 13, 4145−4150. (40) Lucassen, A. C. B.; Karton, A.; Leitus, G.; Shimon, L J. W.; Martin, J. M. L.; van der Boom, M. E. Cryst. Growth Des. 2007, 7, 386−392. (41) Metrangolo, P.; Meyer, F.; Pilati, T.; Resnati, G.; Terraneo, G. Chem. Commun. 2008, 1635−1637. (42) Triguero, S.; Llusar, R.; Polo, V.; Fourmigué, M. Cryst. Growth Des. 2008, 8, 2241−2247. (43) Goud, N. R.; Bolton, O.; Burgess, E. C.; Matzger, A. J. Cryst. Growth Des. 2016, 16, 1765−1771. (44) Orazi, O. O.; Corral, R. A.; Bertorello, H. E. J. Org. Chem. 1965, 30, 1101−1104. (45) Chaikovskii, V. K.; Filimonov, V. D.; Funk, A. A.; Skorokhodov, V. I.; Ogorodnikov, V. D. Russ. J. Org. Chem. 2007, 43, 1291−1296. (46) Iida, S.; Ohmura, R.; Togo, H. Tetrahedron 2009, 65, 6257−6262. (47) Jiang, X.; Sakthivel, S.; Kulbitski, K.; Nisnevich, G.; Gandelman, M. J. Am. Chem. Soc. 2014, 136, 9548−9551 and references therein.. (48) Politzer, P.; Murray, J. S.; Clark, T. Phys. Chem. Chem. Phys. 2010, 12, 7748−7757. ́ R.; (49) Lieffrig, J.; Jeannin, O.; Frąckowiak, A.; Olejniczak, I.; Swietlik, Dahaoui, S.; Aubert, E.; Espinosa, E.; Auban-Senzier, P.; Fourmigué, M. Chem. - Eur. J. 2013, 19, 14804−14813.

(50) Clark, T.; Hennemann, M.; Murray, J. S.; Politzer, P. J. Mol. Model. 2007, 13, 291−296. (51) Riley, K. E.; Murray, J. S.; Politzer, P.; Concha, M. C.; Hobza, P. J. Chem. Theory Comput. 2009, 5, 155−163. (52) Sarwar, M. G.; Dragisic, B.; Salsberg, L. J.; Gouliaras, C.; Taylor, M. S. J. Am. Chem. Soc. 2010, 132, 1646−1653. (53) Libri, S.; Jasim, N. A.; Perutz, R. N.; Brammer, L. J. Am. Chem. Soc. 2008, 130, 7842−7844. (54) Metrangolo, P.; Panzeri, W.; Recupero, F.; Resnati, G. J. Fluorine Chem. 2002, 114, 27−33. (55) Cabot, R.; Hunter, C. Chem. Commun. 2009, 2005−2007. (56) Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 270−283. (57) Check, C. E.; Faust, T. O.; Bailey, J. M.; Wright, B. J.; Gilbert, T. M.; Sunderlin, L. S. J. Phys. Chem. A 2001, 105, 8111−8116. (58) Troff, R. W.; Mäkelä, T.; Topic, F.; Valkonen, A.; Raatikainen, K.; Rissanen, K. Eur. J. Org. Chem. 2013, 2013, 1617−1637. (59) Puttreddy, R.; Jurček, O.; Bhowmik, S.; Mäkelä, T.; Rissanen, K. Chem. Commun. 2016, 52, 2338−2341. (60) Makhotkina, O.; Lieffrig, J.; Jeannin, O.; Fourmigué, M.; Aubert, E.; Espinosa, E. Cryst. Growth Des. 2015, 15, 3464−3473. (61) Bader, R. F. W.; Carroll, M. T.; Cheeseman, J. R.; Chang, C. J. Am. Chem. Soc. 1987, 109, 7968−7979. (62) We thank one of the referees for highlighting this point. (63) Huber, S. M.; Jimenez-Izal, E.; Ugalde, J. M.; Infante, I. Chem. Commun. 2012, 48, 7708−7710. (64) Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, G.; Giacovazzo, C.; Guagliardi, A.; Moliterni, A. G. G.; Polidori, G.; Spagna, R. J. Appl. Crystallogr. 1999, 32, 115−119. (65) Sheldrick, G. M. Acta Crystallogr., Sect. A: Found. Crystallogr. 2008, 64, 112−122. (66) Farrugia, L. J. J. Appl. Crystallogr. 1999, 32, 837−838. (67) Sheldrick, G. M. TWINABS, Ver. 2012/1, 2012.

I


Sequential Halogen Bonding with Ditopic Donors - ACS Publications

Recommend Documents