Establishing a Hierarchy of Halogen Bonding by Engineering Crystals without Disorder

It has been shown, using a foundation of new structural data, that the relative strength and capability of iodo- and bromo-based molecules to act as halogen-bond donors in a competitive supramolecular arena accurately reflect a ranking of halogen-bond donors based upon electrostatic molecular potentials. Furthermore, to obtain the critical structural information, a protocol (comprising a lowering of molecular symmetry and the addition of strong and directional hydrogen bonds) for engineering crystals without positional disorder was successfully developed

Modulating Supramolecular Reactivity Using Covalent “Switches” on a Pyrazole Platform

Systematic co-crystallizations of halogen- methyl- and nitro-substituted pyrazoles with a library of 20 aromatic carboxylic acids have been carried out using melt and solution-based experiments. The solids resulting from all reactions were screened using infrared spectroscopy in order to determine if a reaction (co-crystal or salt) had taken place. The halogenated pyrazoles, including their dimethyl analogues, gave a supramolecular yield of 55–70%. Replacing a halogen atom (R-X, X = Cl, Br, I) with a nitro (R-NO₂) group drops the success rate significantly to 10% due to the reduced charge on the basic nitrogen atom of the pyrazole. Eleven crystal structures were obtained: six were co-crystals and five were salts (including one hydrate). In all six co-crystals, dimeric pyrazole···acid assemblies were constructed via a combination of O–H---N­(pyz) and N–H---O hydrogen bonds corresponding to a 100% supramolecular yield. A variety of weaker halogen-bonds CN---I, I---I and X---O^– connect dimers into infinite one-dimensional chains. In contrast, the salts displayed a variety of stoichiometries and a much wider range of noncovalent interactions, although a charge-assisted N⁺-H---O^– hydrogen bond was present in all five structures. In general, the salts lack structural and stoichiometric predictability and stability as compared to the co-crystals. Furthermore, the overall electrostatic charge on the key binding sites on the pyrazole backbone can be modulated by using specific covalent switches, which in turn can increase (or decrease) the success rate for a reaction

Modulating Supramolecular Reactivity Using Covalent “Switches” on a Pyrazole Platform

Systematic co-crystallizations of halogen- methyl- and nitro-substituted pyrazoles with a library of 20 aromatic carboxylic acids have been carried out using melt and solution-based experiments. The solids resulting from all reactions were screened using infrared spectroscopy in order to determine if a reaction (co-crystal or salt) had taken place. The halogenated pyrazoles, including their dimethyl analogues, gave a supramolecular yield of 55–70%. Replacing a halogen atom (R-X, X = Cl, Br, I) with a nitro (R-NO₂) group drops the success rate significantly to 10% due to the reduced charge on the basic nitrogen atom of the pyrazole. Eleven crystal structures were obtained: six were co-crystals and five were salts (including one hydrate). In all six co-crystals, dimeric pyrazole···acid assemblies were constructed via a combination of O–H---N­(pyz) and N–H---O hydrogen bonds corresponding to a 100% supramolecular yield. A variety of weaker halogen-bonds CN---I, I---I and X---O^– connect dimers into infinite one-dimensional chains. In contrast, the salts displayed a variety of stoichiometries and a much wider range of noncovalent interactions, although a charge-assisted N⁺-H---O^– hydrogen bond was present in all five structures. In general, the salts lack structural and stoichiometric predictability and stability as compared to the co-crystals. Furthermore, the overall electrostatic charge on the key binding sites on the pyrazole backbone can be modulated by using specific covalent switches, which in turn can increase (or decrease) the success rate for a reaction

Avoiding “Synthon Crossover” in Crystal Engineering with Halogen Bonds and Hydrogen Bonds

A combination of halogen bonds and hydrogen bonds has been used for effective assembly of three co-crystals containing desired one-dimensional architectures where the interactions within each assembly can be modulated using tunable electrostatics. The central tecton in these structures, 2-aminopyrazine, can interact with suitable hydrogen-bond donors and halogen-bond donors simultaneously without any “synthon crossover”. When different 2-aminopyrazine-based molecules are co-crystallized with 1,4-diiodo-tetrafluorobenzene (DITFB), a N···I halogen bond is driving the co-crystal synthesis in each case, whereas the N–H···N/N···H–N homosynthon is responsible for creating infinite chains of alternating pyrazine and DITFB molecules in the three crystal structures. The importance of electrostatic and geometric complementarity for refining strategies for supramolecular synthesis is emphasized

Crystal Engineering with Iodoethynylnitrobenzenes: A Group of Highly Effective Halogen-Bond Donors

The benefits of employing a “double activation” strategy for promoting effective practical co-crystal synthesis through halogen bonding was explored in a systematic supramolecular synthetic study of iodoethynylnitrobenzenes. The positive electrostatic potential on the iodine atom was enhanced through a combination of an sp-hybridized carbon atom and one or more electron-withdrawing nitro groups. Three model compounds, 1-(iodoethynyl)-4-nitrobenzene (<b>4N-I</b>), 1-(iodoethynyl)-3-nitrobenzene (<b>3N-I</b>), and 1-(iodoethynyl)-3,5-dinitrobenzene (<b>3,5DN-I</b>) were synthesized and characterized, and calculated molecular electrostatic surface potential values on the halogen-bond donor site were about 20–40 kJ/mol higher than those observed for previously well-established halogen-bond donors. The ability of these molecules to drive co-crystal formation was evaluated through a total of 45 co-crystallization experiments with 15 different acceptor molecules. IR spectroscopic data for the resulting products showed that each reaction resulted in the formation of a co-crystal driven by either C–I···N or C–I···O halogen bonds. The bromo-compound analogues displayed a 60% success rate whereas the chloro-analogues did not yield any co-crystals, emphasizing the importance of the magnitude of the electrostatic aspects of halogen bonding for practical supramolecular synthesis. Ten new crystal structures are presented and the outcome (in terms of stoichiometry and connectivity) is largely predictable. A comparison of I···acceptor distances found in these structures with relevant data from the CSD shows that iodoethynylnitrobenzenes consistently give rise to a larger reduction of combined van der Waals radii (for C–I···acceptor) than do other well-known halogen bond donor moieties

Electrostatic Potential Differences and Halogen-Bond Selectivity

Molecular electrostatic potential based guidelines for selectivity of halogen-bond interactions were explored via systematic co-crystallizations of 9 perfluorinated halogen-bond donors and 12 ditopic acceptors presenting two binding sites with different electrostatic potentials. A total of 89 of the 108 reactions resulted in co-crystal formation (as indicated by IR spectroscopy), and 35 new crystal structures were obtained. Methanol was exclusively used as a solvent for crystal growth in order to avoid any potential solvent–solute bias throughout these experiments. The structures were organized into three different groups depending upon the specific nature of the observed halogen-bond connectivities in each case. The electrostatic potential difference between the two acceptor sites on each molecule was defined as the Δ<i>E</i> value. Group 1 comprised acceptor molecules with a Δ<i>E</i> value below 35 kJ/mol units, and in this category halogen bonding took place on both binding sites in all co-crystals (9/9). Ditopic acceptor molecules in Group 2 were characterized by a Δ<i>E</i> value in the 35–65 kJ/mol range, and in this group half the structures showed halogen bonding to the best acceptor (11/22) and half the structures showed halogen bonding to both binding sites (11/22). In Group 3 the Δ<i>E</i> value was >167 kJ/mol, and in all of the co-crystals found herein (7/7), the halogen-bond donor favored the best acceptor site. These results allow us to propose some tentative guidelines and rationales for halogen-bond preferences in competitive systems. If Δ<i>E</i> < 35 kJ/mol, the electrostatic potential difference is not large enough to allow the donor molecules to form halogen bonds of sufficiently different thermodynamic strength to result in any pronounced molecular recognition preference (typically both, or several acceptors are then engaged in halogen bonding). Upon the basis of data produced in this study, in combination with relevant structures from the Cambridge Structural Database, it seems reasonable to suggest that if the Δ<i>E</i> value between two geometrically accessible halogen-bond acceptor sites is greater than 75 kJ/mol, the thermodynamic advantage of forming halogen bonds to the best acceptor provides a strong enough driving force that the best donor consistently interacts with the best acceptor; intermolecular selectivity is the result. However, if the Δ<i>E</i> resides between these two proposed boundaries, the outcome is unpredictable, and other factors are then likely to be responsible for the path that a particular supramolecular reaction will follow

Establishing Supramolecular Control over Solid-State Architectures: A Simple Mix and Match Strategy

With the help of robust principles of crystal engineering, it is possible to construct co-crystals where two or more different molecular entities coexist in the same crystalline lattice; the supramolecular assembly is driven by noncovalent interactions, most commonly by hydrogen bonds. We have synthesized two ditopic amide based ligands (<i>N</i>-(4-pyridin-2-yl)isonicotinamide) and (<i>N</i>-(3-pyridin-2-yl)nicotinamide) and systematically established their binding preferences when faced with aliphatic dicarboxylic acids with an odd and even number of carbon atoms. Each ligand was co-crystallized with four odd and four even-chain dicarboxylic acids, and 13/16 reactions produced crystals suitable for single-crystal structure determination. On the basis of these results, it is clear that carefully selected systems can be manipulated to produce assemblies in the solid state with very precise control over topology and dimensionality. These ligands can be made to produce either 0-D or 1-D architectures simply by fine-tuning the choice of co-crystallizing agent in the supramolecular synthesis. This mix-and-match strategy allows us to mimic the reliability and versatility of covalent synthesis, in terms of successfully preparing a target with predetermined connectivity and metrics

One-Pot Cascade Approach to Phen­anthridine-Fused Qui­nazo­linimi­niums from Heteroenyne-Allenes

A one-pot cascade method to obtain functionalized phen­anthri­dine-fused quinazoliniminiums from a variety of heteroenyne-allenes is described. This protocol involves formation of C–N and C–C bonds in a single step in the presence of a Lewis acid and trace water to afford pentacyclic title compounds in moderate to good yields

Structural Chemistry of Oximes

Oximes (RR′CN–OH) represent an important class of organic compounds with a wide range of practical applications, but a systematic examination of the structural chemistry of such compounds has so far not been carried out. Herein, we report a systematic analysis of intermolecular homomeric oxime···oxime interactions, and identify hydrogen-bond patterns for four major categories of oximes (R′ = −H, −CH₃, −NH₂, −CN), based on all available structural data in the CSD, complemented by six new relevant crystal structures. The structural behavior of oximes examined here, can be divided into four groups depending on which type of predominant oxime···oxime interactions they present in the solid-state: (i) O–H···N dimers (R₂²(6)), (ii) O–H···N catemers (C(3)), (iii) O–H···O catemers (C(2)), and (iv) oximes in which the R′ group accepts a hydrogen bond from the oxime moiety catemers (C(6)). The electronic and structural effects of the substituent (R′) on the resulting assembly has been explored in detail to rationalize the connection between molecular structure and supramolecular assembly

Synthesis, structure, magnetic properties and kinetics of formation of a cluster containing a {Cu₃(μ₃-OH)} core supported by a triazole-based ligand

<p>The trinuclear copper complex, [Cu₃(μ₃-OH)(CTMB)₃(NO₃)₂(CH₃CN)₂]·5CH₃CN·H₂O (<b>1</b>) {CTMB = cyclohexotriazole-3-(4-methoxybenzamide)}, has been prepared by mixing Cu(NO₃)₂·2.5H₂O and CHMBH {CHMBH = N,N′-cyclohexane-1,2-diylidene-bis(4-methoxybenzoylhydrazide)} in acetonitrile under ambient conditions. Compound <b>1</b> was characterized by IR and UV–visible spectroscopies as well as elemental analyses. X-ray crystallography shows that the cluster contains a {Cu₃(μ₃-OH)} core supported by three triazole-based Schiff base ligands. Each Cu is bound to the 2-N of one triazole ring and the 1-N of another. However, the coordination sphere of each Cu is different, one is five-coordinate and the other two are six-coordinate and bridged by a NO₃ group. The six-coordinate sites are different, one has a terminal NO₃ and the other a MeCN ligand. Magnetic measurements revealed the presence of isotropic and antisymmetric exchange between the copper(II) centers. The data were analyzed using the Hamiltonian containing isotropic exchange for an isosceles triangle together with antisymmetric exchange: <i>H</i> = –<i>J</i>₁(<i>S</i>₁<i>S</i>₂ + <i>S</i>₂<i>S</i>₃)−<i>J</i>₂<i>S</i>₁<i>S</i>₃ + <i>G</i>[<i>S</i>₁ × <i>S</i>₂ + <i>S</i>₂ × <i>S</i>₃ + <i>S</i>₃ × <i>S</i>₁]. Compound <b>1</b> exhibits strong antiferromagnetic coupling with <i>J</i>₁ = −180 and <i>J</i>₂ = −118 cm⁻¹ and antisymmetric exchange with <i>G</i>_z = 15 cm⁻¹. Stopped flow spectrophotometric studies show that the formation of <b>1</b> occurs in three distinct phases and the kinetics of each phase has been determined.</p