Two isostructural carbamates: the o-tolyl N-(pyridin-3-yl)carbamate and 2-bromophenyl N-(pyridin-3-yl)carbamate monohydrates

In the isostructural ortho-tolyl N-pyridinylcarbamate and ortho-bromophenyl N-pyridinylcarbamate monohydrates, the primary aggregation involves cyclic hydrogen bonding as (amide–water–pyridine)2 comprising amideN—H⋯O—Hwater⋯Npyridine interactions about inversion centres [as (14) rings]. The remaining H2O O—H donor and carbonyl O=C form a strong hydrogen bond. The participation of strong hydrogen-bonding donors and acceptors is maximized in short interactions, resulting in two-dimensional sheets.


Chemical context
Isomorphous crystals and isostructural compounds feature regularly in series of metalloorganic compounds, lanthanide derivatives as well as in halide-containing organics (RX, where X = F, Cl, Br, I and often including the methyl group, Me). Given the vast array of data available in the Cambridge Structural Database (CSD; Groom & Allen, 2014), the relative proportion of isostructural relationships between sets of crystal structures can readily be ascertained. As such, Oswald & Crichton (2009) have reported on the regularity with which chlorine (Cl) and methyl (Me) groups exhibit isostructurality based on analysis of pairs of compounds in the CSD (van de Streek & Motherwell, 2005), whereby an estimate of 25-30% of compound pairs are isostructural. In addition, Polito et al. (2008) have rationalized the differences and similarities between ortho-chloro and ortho-methylbenzoic acids, while the ability of bromines (as Br-C) as well as other halogens to form isostructural pairs/series with methyl groups is well documented (Capacci-Daniel et al., 2008).
These researchers have reported an elegant example of an isostructural series of 1,3-bis(meta-dihalophenyl)ureas (with halo = Cl, Br, I) that form isomorphous crystals in space group P2 1 2 1 2, (No. 18) and reported with mono-and di-tolyl analogues (Capacci-Daniel et al., 2008). The molecules associate via (N-H) 2 Á Á ÁO C interactions into 1D chains [R 1 6 (6) motif] and withstacking interactions and halogen contacts completing the aggregation. One can surmise that isostructural series in organic molecules are possible whereby 1-2 strong hydrogen bonds dominate the interactions and drive molecular association, despite often semi-effective cumulative competition from other interactions, whilst taking into account the effect of atom/group replacement (Groom & Allen, 2014).
Further examples in coordination chemistry include the halogen-substituted pseudoterpyridine Zn II homoleptic ISSN 2056-9890 mononuclear complexes that lack strong hydrogen bonding and with the packing relying on a subtle interplay of weaker interactions, where isostructurality is rare amongst the four (F/ Cl/Br/I) halogens (Dumitru et al., 2013). Another example is where the metal complexes (Co II , Ni II , Cu II , Zn II ) form an isostructural series when coordinated to a tetraarylazadipyromethene ligand (Palma et al., 2009). The interchangeability effects of C-H and C-F groups in series of isomeric fluorinated benzamides has been noted (Chopra & Guru Row, 2008;Donnelly et al., 2008) and for C-H/C-CH 3 (Mocilac et al., 2010). More recently, Gomes and co-workers have reported four N-(4-halophenyl)-4-oxo-4H-chromene-3carboxamides (halo = F/Cl/Br/I), where isostructural (F/Cl) and (Br/I) pairs are noted though all four compounds have similar supramolecular structures (Gomes et al., 2015).

Structural commentary
The carbamates synthesised from condensation reactions (shown in the scheme) as their methyl (CmoM) and bromoderivatives (CmoBr) crystallize as isostructural monohydrates. The differences between the unit-cell parameters (a, b, c, ) are < 1% for CmoM (I) and CmoBr (II). Both molecules have similar geometric data (bond lengths and angles) apart from the (ortho)C-CH 3 /Br bond-length differences and some interplanar data. The molecules have three primary torsion angles along the molecular backbone namely benzene C-C-O-C, C-O-C-N and C-N-C-C pyridine where the molecule can adopt one of several conformations in solution. In (I) and (II), both aromatic rings are twisted from co-planarity with the four-membered OCON non-H carbamate atom backbone. The CmoM C 6 ring is oriented at an angle of 87.83 (4) to the central carbamate moiety which lies at an angle of 25.79 (7) to the C 5 N ring; the corresponding data for CmoBr are 88.60 (11) and 26.67 (18) and highlighting the similarities in the two molecular structures. For comparison, we have previously reported an isomer grid of nine related methoxycarbamates (CxxOMe) (x = ortho-/meta-/para-) in order to compare their crystal structures and molecular models (Mocilac & Gallagher, 2013).
In the CxxOMe series (Mocilac & Gallagher, 2013), the primary interaction mode for all nine isomers is the amideÁ Á Ápyridine (as N-HÁ Á ÁN) and typically aggregating as catemers, dimers or trimers. However, there is no evidence for the familiar N-HÁ Á ÁO C (amideÁ Á Áamide) type hydrogen bonding (Mocilac & Gallagher, 2013). This is in comparison to a series of related benzamides/carboxamides containing one strong donor/two strong acceptors where competition arises resulting in the formation of either (i) N-HÁ Á ÁN or (ii) N-HÁ Á ÁO C hydrogen bonds as the primary strong interaction (Mocilac et al., 2010. In the title structures of CmoM ( Fig. 1) and CmoBr (Fig. 2), the presence of a water molecule in the asymmetric unit was unexpected (water typically assists in the decomposition of organic carbamates at room temperature) though it can be shown to confer additional stability on the structure by forming compact hydrogen View of the asymmetric unit of (I)ÁH 2 O, showing the atomic numbering schemes. Rotational disorder of the methyl group is depicted. Displacement ellipsoids are drawn at the 30% probability level.

Table 2
Hydrogen-bond geometry (Å , ) for CmoBr. bonding and contributing to sheet formation. The retention of carbamate crystal structure integrity is observed over time (as measured in months).

Synthesis and crystallisation
Carbamate formation (CmoX; X = Me, Br): The simplest method of phenyl-N-pyridinyl-carbamate (CxxR) synthesis is a condensation reaction of aminopyridines with commercially available phenylchloroformates in the presence of base (Et 3 N) and solvent (CH 2 Cl 2 ). This is performed in an analogous fashion to the Schotten-Baumann reaction and can provide relatively pure products in high yields. However, when using 2-aminopyridines, additional double carbamates are formed where both of the N-H H atoms are replaced by formates. In order to minimize double carbamate formation for these derivatives, reactions are usually performed by mixing the reagents without solvent and base at lower temperature, followed by simple recrystallization.
Another viable route into carbamate chemistry is to use an agent that transforms phenols into the required chloroformate; however, a simpler and more straightforward method for carbamate synthesis is the Curtius rearrangement reaction (or Curtius reaction or degradation) involving the rearrangement of an acyl azide to an isocyanate. The acyl azide (in this case pyridinyl azide) can be formed from the carboxylic  Part of the crystal structure of (I) with the primary interactions as a hydrogen-bonded moiety of four carbamates surrounding two hydrogenbonded water molecules and with selected labels. The symmetry-related molecules with suffices *, #, $ are positioned at (1 À x, 2 À y, Àz), (1 À x, 1 2 + y, À 1 2 À z) and (x, 3 2 À y, 1 2 + z), respectively.

Figure 4
A packing diagram of the two-dimensional sheets and interlocking o-tolyl groups in CmoM (with aromatic C 6 H atoms removed for clarity). Atoms are drawn as spheres of an arbitrary size.

Figure 5
A packing diagram of CmoM as two-dimensional sheets as viewed orthogonal to the direction shown in Fig. 4. Atoms are drawn as spheres of an arbitrary size with all H atoms included.
acid by a suitable agent like diphenylphosphoryl azide. The acid can be easily converted to pyridinyl azides using diphenylphosphoryl azide and at higher temperature (343 K) in the presence of base. The pyridinyl azides rearrange into pyridinyl isocyanates and following reaction with a phenol, the required phenyl-N-pyridinyl-carbamate (CxxR) is generated. Reaction procedure: A mixture of isonicotinic acid (1.2877 g, 10.46 mmol), Et 3 N (1.46 ml, 10.46 mmol), and diphenylphosphoryl azide (2.258 ml, 10.46 mmol) was stirred for 1 h in 30 mL of dry acetonitrile at room temperature. The reaction mixture was carefully heated (water bath) to reflux for 1 h, then with 2-methylphenol or 2-bromophenol (10.46 mmol) added and the resulting solution heated at reflux temperatures for 7 h, gradually cooled and stirred overnight. If a white precipitate formed, it was filtered, washed with acetonitrile and dried (and usually found to be the pure product). The solvent was removed from the reaction mixture under reduced pressure, the residue dissolved in CH 2 Cl 2 , washed thrice with a solution of KHCO 3 and Na 2 CO 3 (pH = 9) and twice with brine/ammonium chloride (pH = 5). The organic fraction was removed in vacuo and the compound recrystallized from diethyl ether and CH 2 Cl 2 . If necessary, purification was accomplished by column chromatography using silica as the stationary phase and a mixture of CH 2 Cl 2 and methanol (8:1) as mobile phase. Both ComM (46% yield, m.p. range = 352-357 K) and ComBr (21% yield, m.p. range = 359.2-359.9 K) compounds were obtained using this method (Mocilac, 2012).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 4. The refinement of structures (I) and (II) were performed similarly. H atoms attached to C atoms were treated as riding using the SHELXL2014 (Sheldrick, 2015) defaults at 294 (1) K with C-H = 0.93 Å (aromatic) and U iso (H) = 1.2U eq (C) (aromatic). The methyl C-H = 0.96 Å (aliphatic) and U iso (H) = 1.5U eq (C). The amino N-H and water O-H H atoms were refined with isotropic displacement parameters in both structures (I) and (II). In (I) the methyl group H atoms were refined as disordered over two sets of sites with equal occupancies 60 apart. used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015). Extinction correction: SHELXL2014 (Sheldrick, 2015), Fc * =kFc[1+0.001xFc 2 λ 3 /sin(2θ)] -1/4 Extinction coefficient: 0.017 (2) Special details Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.