Edinburgh Research Explorer A 1 : 2 co-crystal of isonicotinamide and propionic acid

Isonicotin­amide has been shown to form many 1:1 co-crystals with monofunctional carboxyl­ic acids, but with propionic acid it forms a co-crystal containing two acid mol­ecules and one isonicotin­amide mol­ecule per formula unit, C6H6N2O·2C3H6O2. The crystal structure consists of `supermol­ecules' made up of of one isonicotin­amide mol­ecule and two acid mol­ecules, and the asymmetric unit contains two of these supermolecules. One of the acid mol­ecules is hydrogen bonded to the pyridine function, and the other to the amide function of the isonicotin­amide. Further N—H⋯O hydrogen bonds connect these supermol­ecules into chains which run along the [100] direction. The chains are linked into layers perpendicular to (010) by C—H⋯O and π-stacking interactions. The layers are then linked together by further C—H⋯O interactions.

Isonicotinamide has been shown to form many 1:1 co-crystals with monofunctional carboxylic acids, but with propionic acid it forms a co-crystal containing two acid molecules and one isonicotinamide molecule per formula unit, C 6 H 6 N 2 OÁ-2C 3 H 6 O 2 . The crystal structure consists of 'supermolecules' made up of of one isonicotinamide molecule and two acid molecules, and the asymmetric unit contains two of these supermolecules. One of the acid molecules is hydrogen bonded to the pyridine function, and the other to the amide function of the isonicotinamide. Further N-HÁ Á ÁO hydrogen bonds connect these supermolecules into chains which run along the [100] direction. The chains are linked into layers perpendicular to (010) by C-HÁ Á ÁO and %-stacking interactions. The layers are then linked together by further C-HÁ Á ÁO interactions.

Comment
Isonicotinamide has been shown to crystallize with carboxylic acids in a 1:1 stoichiometry to form a robust building block or 'supermolecule' consisting of two amide and two acid molecules, (I) (Aakerö y et al., 2002). When a saturated solution of isonicotinamide in warm propionic acid was allowed to cool, colourless crystalline laths were obtained. Single-crystal X-ray diffraction revealed these to be a co-crystal consisting of isonicotinamide and propionic acid in a 1:2 ratio, viz. (II).
Similar preparative routes with formic and acetic acids both yielded 1:1 co-crystals (Oswald, 2004). Attempts to prepare a 1:1 co-crystal with propionic acid failed. For example, a 1:1 mixture of propionic acid and isonicotinamide in ethanol yielded only crystals of (II); even in the presence of excess isonicotinamide, the only crystals obtained were isonicotinamide itself and (II).
The crystal structure of (II) consists of supermolecules comprising two acid and one isonicotinamide molecule. One acid forms an R 2 2 (8) motif with the amide moiety (Bernstein et al., 1995). Another acid molecule forms a hydrogen bond to the pyridine N atom, supported by a weaker C-HÁ Á ÁO hydrogen bond ( Fig. 1 and Table 1). There are two supermolecules in the asymmetric unit and, in the terminology of Aakerö y et al. (2002), both are in the trans-trans conformation.
The independent supermolecules hydrogen-bond together using the second amide donor and the carbonyl group from the propionic acid molecules located at the pyridine end of the supermolecules. This builds up a helical chain in which successive supermolecules are aligned approximately perpendicular to one another (Figs. 2-4; hydrogen-bond dimensions are listed in Table 1). The chains run along the a direction, and they comprise all the conventional N-HÁ Á ÁO and O-HÁ Á ÁO hydrogen bonds in the crystal structure (see Table 1); additional C-HÁ Á ÁO interactions (C5A-H5AÁ Á ÁO2U and C5B-H5BÁ Á ÁO2V) are also formed within the chains (Desiraju & Steiner, 1999).
Successive helical chains are distributed along the c direction at z = 1 4 , 3 4 , . . . , etc. (Fig. 5). Though there are no direct hydrogen-bonding interactions between neighbouring chains, weak C-HÁ Á ÁO interactions are formed between chains located one lattice-repeat away from each other (e.g. the red and blue chains in The two crystallographically independent supermolecules, with the atomic numbering. Displacement ellipsoids are drawn at the 30% probability level. Conventional hydrogen bonds are shown in heavy dashes and the HÁ Á ÁO distances span 1.78 (4)-1.96 (4) Å (see Table 1). The C-HÁ Á ÁO hydrogen bonds (shown as open dashes) are quite weak for this type of interaction (2.73 and 2.72 Å ).

Figure 2
Hydrogen-bonded chains in the crystal structure of (II). Hydrogen bonds link supermolecules into chains. This view is approximately along the direct lattice direction [100]. Hydrogen bonds are shown as dashed lines, weak C-HÁ Á ÁO hydrogen bonds are shown in turquoise.

Figure 3
Hydrogen-bonded chains in the crystal structure of (II). Successive supermolecules are approximately perpendicular to each other; this view is perpendicular to (001).

Figure 4
Hydrogen-bonded chains in the crystal structure of (II based on molecule B occur at z = 0, 1, . . . etc. Within the stacks, pairs of pyridine moieties are %-stacked across inversion centres (Fig. 7). The stacking distances are 3.34 and 3.33 Å for the A and B pyridine rings, respectively. Thus, layers are formed in the ac-plane by chains of hydrogen-bonded supermolecules linked by weak C-HÁ Á ÁO and %-stacking interactions. The layers are connected via C-HÁ Á ÁO hydrogen bonds involving pairs of C4T-H4T1Á Á ÁO2T and C4V-H4V1Á Á ÁO2S interactions disposed about inversion centres (Fig. 8).

Experimental
All materials were obtained from Aldrich and used as received. Isonicotinamide (0.50 g, 4.10 mmol) was dissolved in an excess of propionic acid (2.40 g, 32.43 mmol) and warmed until all the solid dissolved. The solution was cooled to room temperature, producing colourless laths.    Packing of hydrogen-bonded chains in the crystal structure of (II), forming a layer perpendicular to b*. As Fig. 5, but with the green molecule deleted to reveal C-HÁ Á ÁO hydrogen bonds formed between the blue and red chains shown in Fig. 5. C-HÁ Á ÁO hydrogen bonds within chains are shown in turquoise, those between chains are shown in magenta.

Figure 7
Packing of hydrogen-bonded chains in the crystal structure of (II), forming a layer perpendicular to [010]. Neighbouring chains are connected by %-stacking interactions. This figure shows two chains viewed along [001]. One chain is shown in ball-and-stick representation, the other as wireframe.