Conversion of 3-amino-4-arylamino-1H-isochromen-1-ones to 1-arylisochromeno[3,4-d][1,2,3]triazol-5(1H)-ones: synthesis, spectroscopic characterization and the structures of four products and one ring-opened derivative.

An efficient synthesis of 1-arylisochromeno[3,4-d][1,2,3]triazol-5(1H)-ones, involving the diazotization of 3-amino-4-arylamino-1H-isochromen-1-ones in weakly acidic solution, has been developed and the spectroscopic characterization and crystal structures of four examples are reported. The molecules of 1-phenylisochromeno[3,4-d][1,2,3]triazol-5(1H)-one, C15H9N3O2, (I), are linked into sheets by a combination of C-H...N and C-H...O hydrogen bonds, while the structures of 1-(2-methylphenyl)isochromeno[3,4-d][1,2,3]triazol-5(1H)-one, C16H11N3O2, (II), and 1-(3-chlorophenyl)isochromeno[3,4-d][1,2,3]triazol-5(1H)-one, C15H8ClN3O2, (III), each contain just one hydrogen bond which links the molecules into simple chains, which are further linked into sheets by π-stacking interactions in (II) but not in (III). In the structure of 1-(4-chlorophenyl)isochromeno[3,4-d][1,2,3]triazol-5(1H)-one, (IV), isomeric with (III), a combination of C-H...O and C-H...π(arene) hydrogen bonds links the molecules into sheets. When compound (II) was exposed to a strong acid in methanol, quantitative conversion occurred to give the ring-opened transesterification product methyl 2-[4-hydroxy-1-(2-methylphenyl)-1H-1,2,3-triazol-5-yl]benzoate, C17H15N3O3, (V), where the molecules are linked by paired O-H...O hydrogen bonds to form centrosymmetric dimers.


Introduction
Isocoumarins are an important building block in synthetic medicinal chemistry because they have shown interesting bioactivities, for example, as anticoagulants (Oweida et al., 1990), as herbicides (Zhang et al., 2016) and as insecticides (Qadeer et al., 2007). In order to gain access to compounds of this type in a straightforward way, a synthetic route has been developed using reactions between 2-formylbenzoic acid, hydrogen cyanide and anilines to yield N-aryldiaminoisocoumarins (Opatz & Ferenc, 2005). We have reported the structures of several compounds of this type (Vicentes et al., 2013) and, more recently using such compounds as precursors, we have developed the synthesis of a new heterocyclic system, namely fused imidazoloisocoumarins, as part of an exploration of possible synergies between the imidazole and isocoumarin pharmacophores (Rodríguez et al., 2017).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 1. All H atoms were located in difference maps. H atoms bonded to C atoms were subsequently treated as riding atoms in geometrically idealized positions, with C-H = 0.95 (alkenyl and aromatic) or 0.98 Å (CH 3 ) and with U iso (H) = kU eq (C), where k = 1.5 for the methyl groups, which were allowed to rotate but not to tilt, and 1.2 for all other H atoms bonded to C atoms. For the H atom bonded to an O atom in compound (V), the atomic coordinates were refined with U iso (H) = 1.5U eq (O), giving an O-H distance of 0.90 (2) Å . Several low-angle reflections which had been attenuated by the beam stop were omitted, i.e. 101 for (II) and 102 for (IV); in addition, one bad outlier reflection, i.e. 606, was omitted from the data set for (II) before the final refinements. For several of the refinements, the final analyses of variance showed unexpected values of K = [mean(F o 2 )/mean(F c 2 )] for the groups of the very weakest reflections. Thus, for (III) and (IV), respectively, À0.035 and À0.125 for 312 and 289 reflections in the F c /F c (max) ranges 0.000-0.008 and 0.000-0.010, and for (V), 3.550 for 339 reflections in the F c /F c (max) range 0.000-0.009; these values are probably statistical artefacts.

Results and discussion
The constitutions of compounds (I)-(V) were all fully established by a combination of high-resolution mass spectrometry (HRMS), IR spectrosopy and 1 H and 13 C NMR spectroscopy, further confirmed by the structure analyses reported here . The HRMS data for (I)-(IV) demonstrate the incorporation of an additional H atom, the IR data show the absence of an NH 2 absorption around 3400 cm À1 and the 1 H NMR spectra show the absence of signals around 4.5-5.0 arising from an amino group; these observations taken together confirm the conversion of the diamino precursors of type (A) (Scheme 1) into the triazolo products (I)-(IV), whose constitutions were fully confirmed by the detailed assignments of the 1 H and 13 C NMR spectra (see x2.1). Hence, the constitutions of (I)-(IV) show clearly that the anticipated triazolo ring formation has occurred, with the additional N atom arising from the diazotization process; similarly, the constitution of (V) confirms the occurrence of a ring-opening transesterification process.
Aside from the orientation of the 2-methyl and 3-chloro substituents in compounds (II) and (III), respectively, the conformations of compounds (I)-(IV) are fairly similar; the dihedral angles between the triazolo ring and the pendent ring (C11-C16) are 65.32 (5), 64.59 (4), 45.48 (8) and 52.32 (9) in (I)-(IV), respectively. The molecules thus exhibit no internal symmetry and so are conformationally chiral in the crystalline state; the centrosymmetric space groups (Table 1)  The molecular structure of compound (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.
all of (I)-(IV), the reference molecules were selected to have the same sign for the torsion angle N2-N1-C11-C12, or N2-N1-C11-C16 in the case of (III). A comparison of the conformation of ester (V) with that of its precursor (II) (Figs. The molecular structure of compound (III), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.

Figure 4
The molecular structure of compound (IV), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.

Figure 5
The molecular structure of compound (V), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.

Figure 2
The molecular structure of compound (II), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.
The supramolecular assembly in compounds (I)-(IV) is dominated by contacts of C-HÁ Á ÁN, C-HÁ Á ÁO and C-HÁ Á Á(arene) types (Table 2) and it is therefore worthwhile to specify the criteria under which such interactions are regarded here is structurally significant, or otherwise. Firstly, we discount all C-HÁ Á ÁN and C-HÁ Á ÁO contacts in which the D-HÁ Á ÁA angle is less than 140 , as the interaction energies associated with such contacts are likely to be extremely small (Wood et al., 2009). Secondly, we discount all contacts involving methyl C-H bonds; these are not only of low acidity, but methyl groups CH 3 -E are generally undergoing very fast rotation about the C-E bonds, even in the solid state (Riddell & Rogerson, 1996, 1997. In particular, for methyl groups bonded to aryl rings, as found in (II) and (V), the rotation of the methyl group relative to the ring is subject to a sixfold rotation barrier, known to be in general extremely low, typically just a few J mol À1 rather than the more typical magnitude of a few kJ mol À1 (Tannenbaum et al., 1956;Naylor & Wilson, 1957). Hence, there is just one significant intermolecular C-HÁ Á ÁX interaction in each of (II), (III) and (V), involving atoms C13, C16 and O24, respectively, as the donors, and two each in (I) and (IV), involving as the donors C8 and C12 in (I), and C7 and C8 in (IV).
The supramolecular assembly in compound (I) is mediated by two hydrogen bonds, one each of the C-HÁ Á ÁN and C-HÁ Á ÁO types (Table 2). Molecules which are related by an nglide plane are linked by the C-HÁ Á ÁN hydrogen bond to form a C(7) (Etter, 1990 Part of the crystal structure of compound (II), showing the formation of a hydrogen-bonded C(10) chain parallel to [010]. Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, H atoms not involved in the motifs shown have been omitted. Table 2 Hydrogen bonds and short intermolecular contacts (Å , ) for compounds (I)-(V).

Figure 6
Part of the crystal structure of compound (I), showing the formation of a hydrogen-bonded sheet of R 4 chain motifs generates a sheet lying parallel to (101) and built of R 4 4 (28) rings (Fig. 6). For compound (II), a single C-HÁ Á ÁO hydrogen bond links molecules which are related by a 2 1 screw axis to form a C(10) chain running parallel to the [010] direction (Fig. 7), and chains of this type are linked by twostacking interactions, both involving the fused carbocyclic ring, which together generate a -stacked chain running parallel to [100] (Fig. 8). The combination of these two motifs generates a sheet lying parallel to (001). There is again just one hydrogen bond in the structure of compound (III), this time of the C-HÁ Á ÁN type, linking molecules which are related by a c-glide plane to form a C(5) chain running parallel to the [001] direction ( Fig. 9), but here there are no direction-specific interactions between adjacent chains.
The assembly in compound (IV) is built from a combination of C-HÁ Á ÁO and C-HÁ Á Á(arene) hydrogen bonds ( Table 2). The C-HÁ Á ÁO hydrogen bond links molecules which are related by a c-glide plane to form a C(7) chain running parallel to the [001] direction (Fig. 10). By contrast, molecules which are related by a 2 1 screw axis are linked by the C-HÁ Á Á (arene) hydrogen bond to form a chain running parallel to the [010] direction (Fig. 11), and the combination of these two chain motifs generates a sheet lying parallel to (100).
Paired O-HÁ Á ÁO hydrogen bonds link inversion-related pairs of molecules of (V) to form a cyclic centrosymmetric R 2 2 (8) dimer (Fig. 12), but there are no direction-specific interactions between adjacent dimer units. Part of the crystal structure of compound (III), showing the formation of a hydrogen-bonded C(5) chain parallel to [001]. Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, H atoms not involved in the motif shown have been omitted.

Figure 10
Part of the crystal structure of compound (IV), showing the formation of a hydrogen-bonded C(7) chain parallel to [001]. Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, H atoms not involved in the motif shown have been omitted.
Thus, minor variations in the substituent on the pendent aryl ring in compounds (I)-(IV) are associated with significant changes in the pattern of supramolecular assembly. Whereas for the unsubstituted parent compound (I), the molecules are linked into hydrogen-bonded sheets by a combination of C-HÁ Á ÁN and C-HÁ Á ÁO hydrogen bonds, the sheet formation in 4-chloro derivative (IV) is based on a combination of C-HÁ Á ÁO and C-HÁ Á Á(arene) hydrogen bonds. In each of the methyl compound (II) and the 3-chloro compound (III), a single hydrogen bond, of the C-HÁ Á ÁO and C-HÁ Á ÁN types, respectively, links the molecules into simple chains; these chains form -stacked sheets in (II), but not in (III).
In summary, therefore, we have developed a simple and efficient route to new 1-arylisochromeno[3,4-d][1,2,3]triazol-5(1H)-ones, with full spectroscopic and structural characterization of four examples, which show that small changes in substituents are associated with substantial changes in the patterns of supramolecular aggregation, and we have demonstrated the necessity of using only a weak acid in the synthesis, along with the spectroscopic and structural characterization of a ring-opened derivative.

Figure 11
Part of the crystal structure of compound (IV), showing the formation of a hydrogen-bonded chain parallel to [010]. Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, H atoms not involved in the motif shown have been omitted.

Figure 12
Part of the crystal structure of compound (V), showing the formation of a centrosymmetric R 2 2 (8) dimer. Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, H atoms bonded to C atoms have all been omitted. Atoms marked with an asterisk (*) are at the symmetry position (Àx + 1, Ày + 1, Àz + 1).

1-(2-Methylphenyl)isochromeno[3,4-d][1,2,3]triazol-5(1H)-one (II)
Crystal data Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.