Design of co-crystals/salts of some Nitrogenous bases and some derivatives of thiophene carboxylic acids through a combination of hydrogen and halogen bonds

Abstract

Background: The utility of N-heterocyclic bases to obtain molecular complexes with carboxylic acids is well studied. Depending on the solid state interaction between the N-heterocyclic base and a carboxylic acid a variety of neutral or ionic synthons are observed. Meanwhile, pyridines and pyrimidines have been frequently chosen in the area of crystal engineering for their multipurpose functionality. HT (hetero trimers) and LHT (linear heterotetramers) are the well known synthons that are formed in the presence of pyrimidines and carboxylic acids.

Results: Fourteen crystals involving various substituted thiophene carboxylic acid derivatives and nitrogenous bases were prepared and characterized by using single crystal X-ray diffraction. The 14 crystals can further be divided into two groups [1a-7a], [8b-14b] based on the nature of the nitrogenous base. Carboxylic acid to pyridine proton transfer has occurred in 3 compounds of each group. In addition to the commonly occurring hydrogen bond based pyridine/carboxylic acid and pyrimidine/carboxylic acid synthons which is the reason for assembly of primary motifs, various other interactions like Cl…Cl, Cl…O, C-H…Cl, C-H…S add additional support in organizing these supermolecules into extended architectures. It is also interesting to note that in all the compounds π-π stacking occurs between the pyrimidine-pyrimidine or pyridine-pyridine or acid-acid moieties rather than acid-pyrimidine/pyridine.

Conclusions: In all the compounds (1a-14b) either neutral O-H…Npyridyl/pyrimidine or charge-assisted Npyridinium-H…Ocarboxylate hydrogen bonds are present. The HT (hetero trimers) and LHT (linear heterotetramers) are dominant in the crystal structures of the adducts containing N-heterocyclic bases with two proton acceptors (1a-7a). Similar type supramolecular ladders are observed in 5TPC44BIPY (8b), TPC44BIPY (9b), TPC44TMBP (11b). Among the seven compounds [8b-14b] the extended ligands are linear in all except for the TMBP (10b, 11b, 12b). The structure of each compound depends on the dihedral angle between the carboxyl group and the nitrogenous base. All these compounds indicate three main synthons that regularly occur, namely linear heterodimer (HD), heterotrimer (HT) and heterotetramer (LHT).

Keywords: 5-chlorothiophen-2-carboxylic acid; Bipyridine; Cocrystal; Halogen bonding; Pyrimidine; Salts.

Scheme 1

Supramolecular heterosynthons that can be formed between carboxylic acids heterocyclic nitrogen of the AMPY: (a) hetero trimer (HT) (Synthon type-I) (b) linear hetero tetramer (LHT) (Synthon type-II).

Scheme 2

Supramolecular hetero dimers that can be formed between carboxylic acids/carboxylate and heterocyclic nitrogen: (a) carboxylic acid-aromatic nitrogen with R₂²(7) synthon (Synthon type-III)(b) pyridinium-carboxylate with R₂²(7) synthon (Synthon type-IV)(c) carboxylic acid-aromatic nitrogen with single point heterosynthon (Synthon type-V)and (d) pyridinium-carboxylate with single point heterosynthon (Synthon type-VI) Supramolecular hetero dimers that can be formed between carboxylic acids/carboxylate and heterocyclic nitrogen: (a) carboxylic acid-aromatic nitrogen with R₂ ² (7) synthon (Synthon type-III)(b) pyridinium-carboxylate with R ₂ ² (7) synthon (Synthon type-IV)(c) carboxylic acid-aromatic nitrogen with single point heterosynthon (Synthon type-V)and (d) pyridinium-carboxylate with single point heterosynthon (Synthon type-VI).

Figure 1

(a-g) ORTEP views of compounds 1a-7a showing the atom-numbering scheme. Displacement ellipsoids drawn at 50% probability level for all non hydrogen atoms and H atoms are shown as small spheres of arbitrary radii.

Figure 2

(a-g) ORTEP views of compounds 8b-14b showing the atom-numbering scheme. Displacement ellipsoids drawn at 50% probability level for all non hydrogen atoms and H atoms are shown as small spheres of arbitrary radii.

Scheme 3

Molecular structures of components used in 1–14 Molecular structures of components used in 1–14.

Figure 3

(a) Formation of hexameric super molecule in (1a) by the N-H…O and C-H…O hydrogen bonds. (b) Hexameric super molecule of one plane (yellow) linked to the similar kind of hexameric super molecule in another plane (blue) linked by soft C-H…O hydrogen bonds (red dotted lines).

Figure 4

Formation of R ₂ ² (8) moieties in 2a and the formation of LHT.

Figure 5

(a) Formation of supramolecular chains connected by stacking interactions. (b) Wavy sheet formed through weak C-H···O interaction in TDCAMPY (3a).

Figure 6

(a) Base pairing chains in (4a), hydrogens involved in bonding are omitted for clarity. (b) the base pairing chains linked by Cl…π interactions.

Figure 7

(a): R₂²(9) motif in (5a) and the formation of tetrameric super molecule. (b) Adjacent tetrameric super molecules linked by Cl…π interactions between Cl of 5-TPC of one chain and phenyl ring of BA of another chain.

Figure 8

π-π stacking interaction observed between the 2NPY ⁺ pyridinium cations in (6a).

Figure 9

(a) Stacking interaction between the oppositely oriented consecutive acridine molecules in (7a). (b) Two of the adjacent chains cross-linked via intermolecular C—H···π interactions.

Figure 10

(a) Formation of ladder through O–H…N and Cl…O bonds in (8b) where 4-4bipy acts as rungs and 5-tpc as uprights. (b) The three molecule aggregates in 8b are further linked to similar neighboring aggregates through strong Cl…O interactions.

Figure 11

Formation of ladder through C-H…O hydrogen bonds in (9b).

Figure 12

(a) Formation of ladders by Cl…π interactions. (b) Supramolecular architectures formed in (10b).

Figure 13

(a) Formation of chain by π-π and C-H…π interactions (b) supramolecular network in (11b).

Figure 14

Formation of supramolecular chains (yellow, green) in (12b) by N-H…O and O-H…O interactions and these chains linked by stacking interactions between TDC rings (represented as spacefilled models).

Figure 15

R ₄ ⁴ (12) ring motif and bridging of the ring motifs by the bipiperazinium cations in (13b).

Figure 16

Two of the chains linked by π-π stacking interactions between the 5-TPC rings in (13b).

Figure 17

(a) A portion of the crystal packing of 14b showing hydrogen-bonding patterns with graph-set notations R₃²(9), R₂²(8). Dotted lines denote hydrogen bonds. H atoms non-involved in hydrogen-bonding omitted for clarity. (b) Hydrogen bonded network formed in (14b).

Figure 18

Plot of ΔpKa vs ΔDc-o for compounds. Blue (cytosine salt) red block (ampy salt) red box (ampy cocrystal) black (bipy cocrystal) green (44TMBP cocrystal).