Crystal structures of two new isocoumarin derivatives: 8-amino-6-methyl-3,4-diphenyl-1H-isochromen-1-one and 8-amino-3,4-diethyl-6-methyl-1H-isochromen-1-one

The crystal structures of two new isocoumarin derivatives, 8-amino-6-methyl-3,4-diphenyl-1H-isochromen-1-one and 8-amino-3,4-diethyl-6-methyl-1H-isochromen-1-one, are described. The intermolecular contacts in the crystals were analysed using Hirshfeld surface analysis and two-dimensional fingerprint plots.

The title compounds, 8-amino-6-methyl-3,4-diphenyl-1H-isochromen-1-one, C 22 H 17 NO 2 , (I), and 8-amino-3,4-diethyl-6-methyl-1H-isochromen-1-one, C 14 H 17 NO 2 , (II), are new isocoumarin derivatives in which the isochromene ring systems are planar. Compound II crystallizes with two independent molecules (A and B) in the asymmetric unit. In I, the two phenyl rings are inclined to each other by 56.41 (7) and to the mean plane of the 1Hisochromene ring system by 67.64 (6) and 44.92 (6) . In both compounds, there is an intramolecular N-HÁ Á ÁO hydrogen bond present forming an S(6) ring motif. In the crystal of I, molecules are linked by N-HÁ Á Á interactions, forming chains along the b-axis direction. A C-HÁ Á Á interaction links the chains to form layers parallel to (100). The layers are then linked by a second C-HÁ Á Á interaction, forming a three-dimensional structure. In the crystal of II, the two independent molecules (A and B) are linked by N-HÁ Á ÁO hydrogen bonds, forming -A-B-A-B-chains along the [101] direction. The chains are linked into ribbons by C-HÁ Á Á interactions involving inversion-related A molecules. The latter are linked by offsetinteractions [intercentroid distances vary from 3.506 (1) to 3.870 (2) Å ], forming a three-dimensional structure.

Chemical context
In recent years, there has been growing interest in the synthesis of natural products, since they are a tremendous and trustworthy source for the development of new drugs. The isocoumarin nucleus is a rich structural pattern in natural products (Barry, 1964) that are also constructive intermediates in the synthesis of a range of significant compounds, including some carbocyclic and heterocyclic compounds. Many isocoumarins show evidence of attention-grabbing biological properties and a number of pharmacological activities, such as antibacterial, antifungal, antitumor, anti-inflammatory, antiallergic anti-cancer, anti-virus and anti-HIV (Khan et al., 2010) activities. Isocoumarins are isolated in a enormous range of microorganisms, plants, insects and show significant biological activity, such the regulation of plant growth (Bianchi et al., 2004). Isocoumarins and their derivatives are secondary metabolites of an extensive range of microbial plant and insect sources and in the creation of other medicinal compounds (Manivel et al., 2008;Basvanag et al., 2009). Depending on their chemical composition and concentration, they can be active either as inhibitors or stimulators in these processes.
Isocoumarins and their derivatives (Ercole et al., 2009;Schnebel et al., 2003;Schmalle et al., 1982) have been reported that have a close resemblance as far as isochromane and its attached phenyl ring is considered. The synthesis and pharmacological and other properties of coumarin and isocoumarin derivatives have been studied intensely and reviewed (Jain et al., 2012;Pal et al., 2011). Against this background and in view of the importance of their natural occurrence, biological activities, pharmacological activities, medicinal activities and utility as synthetic intermediates, we have synthesized the title compounds, and report herein on their crystal structures.

Structural commentary
The molecular structure and conformation of compound I is illustrated in Fig. 1. It consists of a 1H-isochromen-1-one moiety substituted by two phenyl groups, an amino group and a methyl group. The molecular structures and conformations of the two independent molecules (A and B) of compound II are illustrated in Fig. 2. Both molecules consist of a 1H-isochromen-1-one moiety substituted by two ethyl groups, an amino group and a methyl group. The bond lengths and angles in the two independent molecules agree with each other within experimental error. The normal probability plot analyses (International Tables for X-ray Crystallography , 1974, Vol. IV, pp. 293-309) for both bond lengths and angles show that the differences between the two symmetry-independent molecules are of a statistical nature. For both compounds, the bond lengths and angles are close to those observed for a similar structure (Mayakrishnan et al., 2018). In both compounds, there is an intramolecular N-HÁ Á ÁO hydrogen bond present in each molecule forming an S(6) ring motif: see Table 1 and Fig. 1 for I, and Table 2 and Fig. 2 for II.
one ring system in each molecule (A and B) is also planar (r.m.s. deviations are 0.012 and 0.0321Å , respectively) and atoms O2A and O2B deviate from their respective mean planes by 0.052 (2) and 0.014 (2) Å , respectively.
In the crystal of II, the two independent molecules are linked by N-HÁ Á ÁO hydrogen bonds involving the amino H atom of molecule B and the keto and chromen group oxygen atoms, O1A and O2A, of molecule A, forming -A-B-A-Bchains along the [101] direction (see Table 2 and Fig. 5). The chains are linked by C-HÁ Á Á interactions involving inversion-related A molecules to form ribbons (Table 2   A partial view along the a axis of the crystal packing of I. The intramolecular hydrogen bond and the N-HÁ Á Á interaction (Table 1) are shown as dashed lines, and only the H atoms (grey balls) involved in the various interactions have been included.

Figure 4
A view along the b axis of the crystal packing of I. The intramolecular hydrogen bonds and the N-HÁ Á Á and C-HÁ Á Á interactions (Table 1) are shown as dashed lines, and only the H atoms (grey balls) involved in the various interactions have been included.

Figure 5
A partial view of the crystal packing of II (molecule A blue, molecule B red). The intramolecular hydrogen bond (Table 2) and the C-HÁ Á Á interaction, involving atom H12A (blue ball), are shown as dashed lines, and only the H atoms involved in the various interactions have been included.

Figure 6
A view along the a axis of the crystal packing of II (molecule A blue, molecule B red; O and N atoms are shown as balls). The hydrogen bonds (Table 2) are shown as dashed lines, and only the H atoms involved in hydrogen bonding have been included. Table 2 Hydrogen-bond geometry (Å , ) for II.
The Hirshfeld surfaces of I and II mapped over d norm are given in Fig. 7, and the intermolecular contacts are illustrated in Fig. 8 for I and Fig. 9 for II. They are colour-mapped with the normalized contact distance, d norm , ranging from red (distances shorter than the sum of the van der Waals radii) through white to blue (distances longer than the sum of the van der Waals radii). The d norm surface was mapped over an arbitrary colour scale of À0.125 (red) to 1.528 (blue) for compound I and À0.178 (red) to 1.537 (blue) for compound II. The red spots on the surface indicate the intermolecular contacts involved in hydrogen bonding.

Synthesis and crystallization
Compound I: An oven-dried round-bottom 25 ml flask with a magnetic stirrer bar was charged with 7-methyl-2H-benzo[d]-[1,3]oxazine-2,4(1H)-dione (1.0 equiv), diphenylacetylene (1.2 equiv), [RhCp*Cl 2 ] 2 (3.0 mol %), Cu(OAc) (1.0 equiv) and dimethylformamide (5 ml). The flask was sealed using a Teflon-coated screw cap and the reaction was continuously heated at 383 K for 24 h. The mixture was then cooled to ambient temperature, diluted with 25 ml of ethyl acetate, filtered through a celite pad, and washed with 40-60 ml of ethyl acetate. The combined organic phases were concentrated under reduced pressure, and the residue was purified by column chromatography using silica gel which led to the desired product, compound I. Compound II: An oven-dried round-bottom 25 ml flask with a magnetic stirrer bar was charged with 7-methyl-2Hbenzo[d][1,3]oxazine-2,4(1H)-dione (1.0 equiv), hex-3-yne (1.2 equiv), [RhCp*Cl 2 ] 2 (3.0 mol %), Cu(OAc) (1.0 equiv) and dimethylformamide (5 ml). The flask was sealed using a Teflon-coated screw cap and the reaction was continuously heated at 383 K for 24 h. The mixture was then cooled to ambient temperature, diluted with 25 ml of ethyl acetate, then filtered through a celite pad and washed with 40-60 ml of ethyl acetate. The combined organic phases were concentrated under reduced pressure, and the residue was purified by column chromatography using silica gel, which led to the desired product, viz. compound II.
Colourless block-like crystals of compounds I and II were obtained by slow evaporation of solutions in ethanol.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. All H atoms were positioned geometrically, with N-H = 0.86 Å , C-H = 0.93-0.97 Å , and constrained to ride on their parent atoms with U iso (H) = 1.5U eq (C-methyl) and 1.2U eq (N, C) for other H atoms. The crystal of compound II diffracted extremely weakly beyond 20 in and the data set was restricted to a maximum angle of 23.8 .

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.

8-Amino-3,4-diethyl-6-methyl-1H-isochromen-1-one (II)
Crystal data where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.14 e Å −3 Δρ min = −0.25 e Å −3 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.