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Halogen Bonding and Structural Modularity in 2,3,4- and 3,4,5-Trichlorophenol Published as part of the Crystal Growth & Design virtual special issue on Halogen Bonding in Crystal Engineering: Fundamentals and Applications Arijit Mukherjee and Gautam R. Desiraju* Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560 012, India
bS Supporting Information ABSTRACT: The crystal structure of 3,4,5-trichlorophenol contains hydrogen bonded domains that occur respectively in the structures of 4-chlorophenol and 3,5-dichlorophenol. Such modularity is also seen in 2,3,4-trichlorophenol. These structures, and those of the six isomeric dichlorophenols, illustrate the importance of halogen bonding as a structure determining interaction.
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ntermolecular interactions, of the type X 3 3 3 X and X 3 3 3 Y (X = Cl, Br, I; Y = N, O, F), formed by electrophilic halogen, have long been known, and their role in crystal packing has also been well investigated.1 More recently, their nomenclature as halogen bonds has been suggested,2 analogous to hydrogen bonds, because the role of the halogen atom in a halogen bond is somewhat equivalent to that of the hydrogen atom in a hydrogen bond. The relevance of this interaction in crystal engineering has also been alluded to over the years. Schmidt’s “chloro rule”, which goes back to 1971, states that polychlorosubstitution of an aromatic compound leads to the adoption of a crystal structure with a short axis of around 4 Å.3 A rationalization of this rule was given in 1986 by Sarma and Desiraju in terms of the Clδ+ 3 3 3 Clδ halogen bonds that are present in these structures.4 Not all Cl 3 3 3 Cl interactions are halogen bonds; it is only the type II interactions that can be modeled with electrophilic halogen.5 The six dichlorophenols furnish an interesting example of halogen bonding. Thomas and Desiraju analyzed these crystal structures in 1984.6 Three of them, the 2,3-, the 2,4-, and the 3,4isomer adopt 4 Å structures: the three others do not. The former compounds have short Cl 3 3 3 Cl interactions while the latter do not. There is a conflict here between close packing and directional interactions. The close packed structures do not generally have directional Cl 3 3 3 Cl interactions and adopt monoclinic space groups, which is the Kitaigorodskii default packing; the halogen bonded structures have trigonal or tetragonal symmetry.7 This early example showed that while deviations from close packing are generally only slight in most organic crystals, it is these small r 2011 American Chemical Society
deviations that allow one to design a crystal structure. Structural anisotropy is at the heart of crystal design strategies.8 In this communication, we extend the earlier analysis of the six dichlorophenols to two trichlorophenols and also report the crystal structures of some related cocrystals formed by these compounds. This work also reports new observations that pertain to the modularity of crystal packing, in other words the algorithms that relate molecular and crystal structure. In 3,4,5-trichlorophenol, there are two synthons I and II (Figure 1) that are connected to one another by a Cl 3 3 3 Cl contact which is as short as 3.352 Å (the variable temperature study is provided in the Supporting Information). Synthon I is a cooperative hydrogen bonded finite tetramer; these tetramers are themselves connected with Cl 3 3 3 Cl halogen bonds of 3.205 Å. Synthon II is made up of tetramers formed with OH 3 3 3 O and O 3 3 3 Cl interactions. The tetramers, however, form infinite ladder patterns that are connected with Cl 3 3 3 Cl contacts of 3.432 Å. All the Cl 3 3 3 Cl contacts in this structure are thus relatively short. Inspection of Figures 1c and 2 reveals that the synthon I patterns are reminiscent of the crystal structure of (the β form of) 4-chlorophenol. In other words, the Cl-atoms in the 3- and 5-positions are not involved in the assembly of these synthons. The 4-chloro substituent plays the same role as it does in 4-chlorophenol. It is almost as if the packing of this tetramer Received: June 21, 2011 Revised: August 1, 2011 Published: August 04, 2011 3735
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Figure 1. Crystal structure of 3,4,5-trichlorophenol: (a) tetramer synthons I connected with type I Cl 3 3 3 Cl interactions of 3.205 Å; (b) ladder Cl 3 3 3 Cl and O 3 3 3 Cl synthons II connected with type II Cl 3 3 3 Cl interactions of 3.432 Å; (c) linking of synthon I and II patterns with a Cl 3 3 3 Cl halogen bond of 3.352 Å.
Figure 2. Two segments in the 3,4,5-trichlorophenol structure (center) find counterparts in the structures of 3,5-dichlorophenol (left) and 4-chlorophenol (right).
module is “blind” to the 3- and 5-chloro substituents. Most interestingly, a complementary modularity is seen in the packing of synthon II units. Here, the construction of the synthon and its extension into the infinite ladder is almost like the molecular assembly in 3,5-dichlorophenol. In other words, the packing of this segment of the structure is “blind” to the 4-chloro substituent. Such functional group modularity is very rare in molecular crystals, but it can, in principle, be extremely useful as far as transferability of motifs is concerned. The pivotal role of the halogen bond in 3,4,5-trichlorophenol is seen in the manner in which synthon I and II modules are assembled. The connecting interaction, as mentioned above, is a Cl 3 3 3 Cl halogen bond of 3.352 Å. The composite I 3 3 3 II synthon may be termed a longrange synthon Aufbau module (LSAM), as defined by Ganguly and Desiraju.9 In the sense that a synthon is a crystallization precursor, we may speculate that both synthon I and synthon II have some independent existence in solution (as they must in the crystallization of 4-chlorophenol and 3,5-dichlorophenol,
respectively). The later stages of nucleation perhaps involve a coming together of these synthons via Cl 3 3 3 Cl halogen bonding. Such a model would imply that OH 3 3 3 O and O 3 3 3 Cl interactions are stronger than Cl 3 3 3 Cl interactions—a conclusion that is hardly disputable. In summary, the crystal structure of 3,4,5-trichlorophenol can be described as an amalgam of the crystal structures of 4-chlorophenol and 3,5-dichlorophenol. 2,3,4-Trichlorophenol crystallizes as a methanol solvate and also in a solvent free modification that is obtained from the solvate. Figure 3 shows the crystal structure of the solvate. There is a cooperative hydrogen bonded synthon III that is arranged around a 31 axis. Such an arrangement is seen in the structure of 2,3-dichlorophenol.6 Once again, we observe structural modularity. A rationalization for solvation may also be obtained. Figure 3 shows that the modularity between 2,3,4-trichlorophenol and 2,3-dichlorophenol renders the 4-chloro substituent in the former as vestigial. The stability of synthon III means that assembly of these synthons results in the creation of empty spaces that are occupied by (disordered) solvent. In 2,3-dichlorophenol, no empty spaces are created by assembly of the hydrogen bonded synthons and, accordingly, the structure is unsolvated. The methanol solvate of 2,3,4-trichlorophenol loses solvent after storage for two days. The solvent free crystal (Figure 4) is close packed and illustrates the packing versus interaction dichotomy.10 The structure does not have any OH 3 3 3 O hydrogen bonds, and this in itself is very unusual for a phenol.11 The structure gains in free energy from the packing rather than from directional interactions, there being a Cl 3 3 3 O contact of 3.324 Å which is of average length. It is probably the thermodynamic structure. Interestingly, both the MeOH solvate and the solvent free form have a 4 Å packing, an indication that halogen bonding is important in both structures. However, the structure in which the interactions are more important, the MeOH solvate, takes the higher hexagonal symmetry (R3) while the structure in which close packing is more important adopts the classical monoclinic symmetry (P21/n). We next carried out cocrystallization experiments to further probe the occurrence of modularity in this system. When 3736
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Figure 3. Equivalence of the crystal structures of 2,3-dichlorophenol and 2,3,4-trichlorophenol MeOH solvate. Notice that the principal hydrogen bonded synthon is the same in both structures.
Figure 5. Synthon equivalence in 4-chlorophenol and its 1:3 cocrystal with 3,4,5-trichlorophenol. Figure 4. Solvent free structure of 2,3,4-trichlorophenol. Notice the absence of OH 3 3 3 O hydrogen bonds.
4-chlorophenol and 3,4,5-trichlorophenol were taken together in MeCN, a 1:3 cocrystal was obtained. Analysis of this structure shows that while modularity is still carried over, the cocrystal resembles the R-form of 4-chlorophenol (Figure 5). Clearly, similar hydrogen bonded strands are present in solution prior to crystallization in all these cases, and the particular structure that is obtained will depend on exact experimental
conditions. These hydrogen bonded strands are the growth units in this system.12 2,3,4- and 3,4,5-trichlorophenol form a 1:9 binary crystal in space group P1 and Z0 = 4. There are four molecular sites in the asymmetric unit. On two of these are located ordered molecules of the 3,4,5-isomer. The two other sites have multiple occupancy of either an ordered 3,4,5-molecule (∼80%) or a disordered 2,3,4-molecule (∼20%). In other words, the asymmetric unit contains four molecules of 3,4,5-trichlorophenol and two molecules of 2,3,4-trichlorophenol and the disorder model implies 3737
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Figure 6. Ladder synthon as seen in 3,5-dichlorophenol and tetramer as seen in 4-chlorophenol are conjoined in the 9:1 binary crystal of 3,4,5trichlorophenol and 2,3,4-trichlorophenol. For clarity, the variable occupancy of 2,3,4-trichlorophenol molecules on two of the sites is not shown.
a β-structure is adopted. When the chloro substitution exists on both sides of this axis, a 4 Å structure is not adopted. The crystal structures of the dichloro- and trichlorophenols contain domains that are hydrogen bonded and halogen bonded. These regions are well insulated, and this could account for the high degree of structural modularity in this group of compounds. The existence of structural modularity in this family is evidence for the implication of stable supramolecular synthons in the crystallization process. Such observations also help one to understand a phenomenon such as synthon polymorphism that relies on the presence of multiple synthons in the crystallization solution.
’ ASSOCIATED CONTENT
bS Figure 7. (a) Binary crystal of 2,3,4- and 3,4,5-trichlorophenol; (b) bifurcated Cl 3 3 3 Cl contact; (c) type I interaction; (d) type II interaction.
that the overall stoichiometry is 9:1. The crystal packing is rather similar to that of pure 3,4,5-trichlorophenol, but unlike the latter, both the hydrogen bonded patterns (which are responsible for structural modularity in 3,4,5-trichlorophenol structure) are coupled together like Siamese twins (Figure 6). The role played by 2,3,4-trichlorophenol is difficult to assess, but it probably assumes some function in bringing the 3,4,5-trichlorophenol molecules together into a structure that is more compact. It would be fair to say that both these structures (native and binary crystal) belong to the same landscape.13 Many Cl 3 3 3 Cl contacts are observed in the binary crystal. Notable among them are the bifurcated arrangement involving Cl3, Cl9, and Cl12, the type I interaction Cl11 3 3 3 Cl11, and the type II interaction Cl9 3 3 3 Cl10 (Figure 7). Earlier generalizations, pertaining to the adoption or otherwise of a 4 Å β-structure in the dichlorophenols, also hold for the trichlorophenol structures in this paper. When all the chloro substitution occurs on the same side of the C1C4 axis,
Supporting Information. Details of the experimental procedure, tables containing crystallographic information, variable temperature study of 3,4,5-trichlorophenol, ORTEP diagrams, and cif data. This material is available free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION Corresponding Author
*E-mail:
[email protected]. Fax: (+91) 80-23602306. Telephone: (+91) 80-22933311.
’ ACKNOWLEDGMENT A.M. thanks CSIR for a JRF. G.R.D. thanks the DST for the award of a J. C. Bose fellowship. We thank the Rigaku Corporation, Tokyo, for their support through a generous loan of a RigakuMercury375R/M CCD (XtaLAB mini) diffractometer. ’ REFERENCES (1) Desiraju, G. R. Crystal Engineering: The Design of Organic Solids; Elsevier: Amsterdam, 1989; pp 175198. (2) Metrangolo, P.; Neukirch, H.; Pilati, T.; Resnati, G. Acc. Chem. Res. 2005, 38, 386–395. (3) Green, B. S.; Schmidt, G. M. J. Isr. Chem. Soc. Annu. Meet. Abstr. 1971, 190. 3738
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(4) Sarma, J. A. R. P.; Desiraju, G. R. Acc. Chem. Res. 1986, 19, 222–228. (5) Desiraju, G. R.; Parthasarathy, R. J. Am. Chem. Soc. 1989, 111, 8725–8726. (6) Thomas, N. W.; Desiraju, G. R. Chem. Phys. Lett. 1984, 110, 99–102. (7) Desiraju, G. R. Nature 2004, 431, 25. (8) Desiraju, G. R.; Vittal, J. J.; Ramanan, A. Crystal Engineering: A Text Book; World Scientific: Singapore, 2011. (9) Ganguly, P.; Desiraju, G. R. CrystEngComm 2010, 12, 817–833. (10) (a) Dey, A.; Desiraju, G. R. CrystEngComm 2006, 8, 477–481. (b) Desiraju, G. R. Angew. Chem., Int. Ed. 2007, 46, 8342–8346. (11) Brock, C. P.; Duncan, L. L. Chem. Mater. 1994, 6, 1307–1312. (12) Davey, R. J.; Dent, G.; Mughal, R. K.; Parveen, S. Cryst. Growth Des. 2006, 6, 1788–1796. (13) Mukherjee, A.; Grobelny, P.; Thakur, T. S.; Desiraju, G. R. Cryst. Growth Des. 2011, 11, 2637–2653.
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