Crystal structure and Hirshfeld surface analysis of 2-(1H-indol-3-yl)ethanaminium acetate hemihydrate

The title molecular salt crystallized with four 2-(1H-indol-3-yl)ethanaminium cations and four acetate anions in the asymmetric unit, together with two water molecules of crystallization.


Chemical context
2-(1H-Indol-3-yl)ethanamine (tryptamine) is an alkaloid found in plants and fungi and is a possible intermediate in the biosynthetic pathway to the plant hormone indole-3-acetic acid (Takahashi, 1986). It is also found in trace amounts in the mammalian brain, possibly acting as a neuromodulator or neurotransmitter (Jones, 1982). As a relatively strong base (pK a = 10.2), it readily forms salts with a number of organic acids. There are seven known families of serotonin receptors which are tryptamine derivatives, and all of them are neurotransmitters. Hallucinogens all have a high affinity for certain serotonin receptor subtypes and the relative hallucinogenic potencies of various drugs can be gauged by their affinities for these receptors (Glennon et al., 1984;Nichols & Sanders-Bush, 2001;Johnson et al., 1987;Krebs-Thomson et al., 1998). The structures of many hallucinogens are similar to serotonin and have a tryptamine core. Indole analogues, especially of tryptamine derivatives, have been found to be polyamine site antagonists at the N-methyldaspartate receptor (Worthen et al., 2001). Indole and its derivatives are secondary metabolites that are present in most plants (such as unripe bananas, broccoli and cloves), almost all flower oils (jasmine and orange blossoms) and coal tar (Waseem & Mark, 2005;Lee et al., 2003). In the pharmaceutical field, it has been discovered that it has antimicrobial and anti-inflammatory properties (Mohammad & Moutaery, 2005). The title compound, namely 2-(1H-indol-3-yl)ethanaminium acetate hemihydrate, was synthesized and its crystal structure and Hirshfeld surface analysis are reported herein.

Supramolecular features
In the crystal, the cations and anions are liked by N-HÁ Á ÁO and C-HÁ Á ÁO hydrogen bonds, forming chains propagating along the b-axis direction ( Fig. 2  A view of the molecular structure of the title molecular salt, with the atom labelling. Displacement ellipsoids are drawn at the 30% probability level. The C-HÁ Á Á interactions linking an anion to a cation are shown as orange arrows (see Table 1). For clarity, the majority of the C-bound H atoms have been omitted.

Figure 2
A view along the a axis of the crystal packing of the title molecular salt. The N-HÁ Á ÁO and O-HÁ Á ÁO hydrogen bonds are shown as dashed lines (see Table 1). For clarity, the C-bound H atoms have been omitted. HÁ Á ÁO and N-HÁ Á ÁO water hydrogen bonds, forming layers lying parallel to the bc plane ( Fig. 2 and Table 1). Within the layers, there are a number of C-HÁ Á Á interactions present (Table 1).

Database survey
A search of the Cambridge Structural Database (CSD, Version 5.40, update November 2018;Groom et al., 2016) for 2-(1H-indol-3-yl)ethanamines yielded 42 hits for structures that include atomic coordinates. In 14 hits, the alkylaminium side chain has an extended conformation, with the absolute value of the N-C-C-C torsion angle varying from ca 169.69 in the thiophene-2-carboxylate salt (CSD refcode LACPUA;  to ca 179.44 in the (2S,3S)-hydrogen tartrate monohydrate salt (SOCMED; Koleva et al., 2009). In 28 hits, the alkylaminium side chain has a folded conformation as in the title cations. For example, in the diphenylacetate salt (WODVUG;  Two views of the overall Hirshfeld surface mapped over d norm for the title molecular salt. Table 1 Hydrogen-bond geometry (Å , ).

Synthesis and crystallization
The title compound was synthesized by the reaction of a 1:1 stoichiometric mixture of tryptamine (0.160 mg, Aldrich) and acetic acid (0.060 mg, Merck) in a hot methanolic solution (20 ml) with 10 ml of water. After warming for a few minutes over a water bath, the solution was cooled and kept at room temperature. Within a few days, colourless needle-like crystals, suitable for the X-ray analysis, were obtained (yield 65%).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. The water O-bound H atoms were located in a difference Fourier map and freely refined. The NH and NH 3 hydrogens were originally located in a difference Fourier map but for refinement, together with the C-bound H atoms, they were positioned geometrically and refined using a riding model, with N-H = 0.86-0.89 Å and C-H = 0.93-0.97 Å , and with U iso (H) = 1.5U eq (C,N) for methyl and aminium H atoms, and 1.2U eq (C,N) otherwise. The structure was refined as a two-component twin with twin law (021) The total two-dimensional fingerprint plot of the crystal and of the relative contributions of the atom pairs to the Hirshfeld surface.  Data collection: APEX3 (Bruker, 2016); cell refinement: SAINT (Bruker, 2016); data reduction: SAINT/XPREP (Bruker, 2016); program(s) used to solve structure: SHELXL2018 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018 (Sheldrick, 2015b); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: SHELXL2018 (Sheldrick, 2015b) and PLATON (Spek, 2009).  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. Refinement. Refined as a 2-component twin. BASF = 0.074 (1) Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )