Crystal structure, Hirshfeld surface analysis, intermolecular interaction energies, energy frameworks and DFT calculations of 4-amino-1-(prop-2-yn-1-yl)pyrimidin-2(1H)-one

The molecular structure of the title compound comprises an essentially planar pyrimidine ring from which the propynyl group is rotated by 15.31 (4)°. In the crystal, a tri-periodic network is formed by N—H⋯O, N—H⋯N and C—H⋯O hydrogen-bonding and slipped π–π stacking interactions, leading to narrow channels extending parallel to the c axis.


Chemical context
Owing to their importance in the fields of pharmaceuticals, cytosine derivatives and their syntheses have been in the focus of chemists in recent years, in particular during the Covid pandemic period, for example with respect to the synthesis of Molnupiravir as an anti-viral drug (Sahoo & Subba Reddy, 2022).An alternative product identified as cytarabine, which also has been synthesized from cytosine, is a chemotherapy drug used to treat acute myeloid leukaemia (AML), acute lymphocytic leukaemia (ALL), chronic myeloid leukaemia (CML) and non-Hodgkin's lymphoma (Lamba, 2009;Gu ¨ngo ¨r et al., 2022).1-(Prop-2-ynyl)-4-amino-2-oxopyrimidine was synthesized as an intermediate for the purpose of preparing other products that may have biological activities (Chatzileontiadou et al., 2015).
In a continuation of our research work devoted to the study of N-alkylation reactions involving cytosine derivatives, we report herein on synthesis, molecular and crystal structures as well as Hirshfeld surface analysis, intermolecular interaction energies, energy frameworks and DFT-computational studies of the title compound (I), C 7 H 7 N 3 O.This cytosine derivative was obtained by an alkylation reaction of cytosine using an excess of propargyl bromide as an alkylating reagent under the conditions of phase-transfer catalysis (PTC).

Structural commentary
The asymmetric unit of (I) comprises one molecule and is shown in Fig. 1.The pyrimidine ring is essentially planar (r.m.s.d = 0.0055 A ˚).The plane defined by the propynyl group (N1/C5/C6/C7) is inclined to the pyrimidine plane by 15.31 (4) � .

Figure 1
The title molecule with labelling scheme and displacement ellipsoids drawn at the 50% probability level.

Figure 3
Packing of (I) viewed along the a axis with hydrogen bonds depicted as in Fig. 2. The �-� stacking interactions are depicted by orange dashed lines.

Figure 4
Packing viewed along the c axis with hydrogen bonds depicted as in Fig. 2, and with �-� stacking interactions as in Fig. 3.

Hirshfeld surface analysis
In order to visualize the intermolecular interactions in the crystal of (I), a Hirshfeld surface (HS) analysis (Hirshfeld, 1977;Spackman & Jayatilaka, 2009) was carried out by using CrystalExplorer (Spackman et al., 2021).In the HS plotted over d norm (Fig. 5), the white surface indicates contacts with distances equal to the sum of the van der Waals radii, and the red and blue colours indicate distances shorter (in close contact) or longer (distinct contacts) than the van der Waals radii, respectively (Venkatesan et al., 2016).The bright-red spots appearing near O1, N2 and hydrogen atom H3A indicate their roles as the respective donors and/or acceptors atoms for hydrogen bonding; they also appear as blue and red regions corresponding to positive and negative potentials on the HS mapped over electrostatic potential (Spackman et al., 2008;Jayatilaka et al., 2005) shown in Fig. 6.The blue regions indicate positive electrostatic potential (hydrogen-bond donors), while the red regions indicate negative electrostatic potential (hydrogen-bond acceptors).The shape-index of the HS is a tool to visualize �-� stacking interactions by the presence of adjacent red and blue triangles (Fig. 7).The overall two-dimensional fingerprint plot, Fig. 8a

Figure 5
View of the three-dimensional Hirshfeld surface of the title compound plotted over d norm in the range of À 0.4969 to 1.1244 a.u.

Figure 6
View of the three-dimensional Hirshfeld surface of the title compound plotted over electrostatic potential energy in the range À 0.0500 to 0.0500 a.u.using the STO-3 G basis set at the Hartree-Fock level of theory.
Hydrogen-bond donors and acceptors are shown as blue and red regions around the atoms, corresponding to positive and negative potentials, respectively.

Figure 7
Hirshfeld surface of the title compound plotted over shape-index.

Interaction energy calculations and energy frameworks
The intermolecular interaction energies were calculated using the CE-B3LYP/6-31G(d,p) energy model available in Crys-talExplorer (Spackman et al., 2021), where a cluster of molecules is generated by applying crystallographic symmetry operations with respect to a selected central molecule within the radius of 3.8 A ˚by default (Turner et al., 2014).The total intermolecular energy (E tot ) is the sum of electrostatic (E ele ), polarization (E pol ), dispersion (E dis ) and exchange-repulsion (E rep ) energies (Turner et al., 2015) with scale factors of 1.057, 0.740, 0.871 and 0.618, respectively (Mackenzie et al., 2017).Energy frameworks combine the calculation of intermolecular interaction energies with a graphical representation of their magnitude (Turner et al., 2015).Energies between molecular pairs are represented as cylinders joining the centroids of pairs of molecules with the cylinder radius proportional to the relative strength of the corresponding interaction energy.Energy frameworks were constructed for E ele (red cylinders), E dis (green cylinders) and E tot (blue cylinders) and are shown in Fig. 10a-c.The evaluation of the electrostatic, dispersion and total energy frameworks reveals that the stabilization is dominated by the electrostatic energy contribution in the crystal structure of (I).

DFT calculations
Bond lengths and angles as well as energies of (I) in the gas phase were computed on basis of density functional theory (DFT) using the standard B3LYP functional and the 6-311G(d,p) basis-set (Becke, 1993) as implemented in GAUS-SIAN 09 (Frisch et al., 2009).

Figure 11
The energy band gap of (I).

Synthesis and crystallization
A mixture of cytosine (1.5 mmol) and potassium carbonate (K 2 CO 3 ) (3 mmol) was dissolved in 25 ml of dimethylformamide (DMF).The solution was stirred magnetically for 10 min., followed by addition of 0.01 equivalents of tetra-nbutylammonium bromide (TBAB) and 3 mmol of propargyl bromide.The mixture was stirred magnetically for 24 h.After filtration of the formed salts, the DMF was evaporated under reduced pressure.The residue obtained was purified by chromatography on a silica gel column.Single crystals of (I) suitable for X-ray diffraction were obtained by slow evaporation of an ethanol solution.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 4. H atoms attached to carbon atoms were placed in idealized positions and were included as riding contributions with isotropic displacement parameters 1.2-1.5 times those of the parent atoms.Those attached to nitrogen were placed in locations derived from a difference-Fourier map and refined with a distance of 0.90 (1) A ˚. Reflection 020 was affected by the beamstop and was omitted from the final refinement.(Bruker, 2020), SHELXT (Sheldrick, 2015a), SHELXL (Sheldrick, 2015b), DIAMOND (Brandenburg & Putz, 2012) and publCIF (Westrip, 2010).

Figure 12
The molecular fragment II used for the database search.

Special details
Experimental.The diffraction data were obtained from 8 sets of frames, each of width 0.5° in ω, collected with scan parameters determined by the "strategy" routine in APEX3.The scan time was 5 sec/frame.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.Refinement of F 2 against ALL reflections.The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 .The threshold expression of F 2 > 2sigma(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement.R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.H-atoms attached to carbon were placed in calculated positions (C-H = 0.95 -1.00 Å) and were included as riding contributions with isotropic displacement parameters 1.2 -1.5 times those of the attached atoms.Those attached to nitrogen were placed in locations derived from a difference map and refined with a DFIX 0.91 0.01 instruction.One reflection affected by the beamstop was omitted from the final refinement. Fractional

Figure 2 A
Figure 2 A portion of one ribbon viewed along the a axis with N-H� � �N, N-H� � �O and C-H� � �O hydrogen bonds depicted, respectively, by blue, violet and black dashed lines.
, and those delineated into H� � �H, H� � �C/C� � �H, H� � �O/O� � �H, H� � �N/ N� � �H, C� � �C, C� � �N/N� � �C, N� � �N, C� � �O/O� � �C and N� � �O/ O� � �N (McKinnon et al., 2007) are illustrated in Fig. 8b-j, together with their relative contributions to the Hirshfeld surface.The most important interaction originates from H� � �H contacts, contributing 36.2% to the overall crystal packing, which is reflected in Fig. 8b as widely scattered points of high density due to the large hydrogen content of the molecule with the tip at d e = d i = 1.20 A ˚.In the absence of C-H� � �� interactions, the H� � �C/C� � �H contacts, contributing 20.9% to the overall crystal packing, are shown in Fig. 8c with the tips at d e + d i = 2.57A ˚.The pair of characteristic wings in the fingerprint plot delineated into H� � �O/ O� � �H contacts (Fig. 8d) with a 17.8% contribution to the HS is viewed as a pair of spikes with the tips at d e + d i = 2.05 A ˚.The pair of characteristic wings in the fingerprint plot delineated into H� � �N/N� � �H contacts (Fig. 8e, 12.2% contribution to the HS) is viewed as a pair of spikes with the tips at d e + d i = 2.00 A ˚.The C� � �C contacts, contributing with 6.1% to the overall crystal packing, have a bullet-shaped distribution of points.They are shown in Fig.8fwith the tip at d e = d i = 1.61A ˚.The C� � �N/N� � �C contacts,which contribute 5.1% to the overall crystal packing, have a bat-shaped distribution of points (Fig.8g) with the tips at d e + d i = 3.28 A ˚. Finally, the N� � �N (Fig.8h), C� � �O/O� � �C (Fig.8i) and N� � �O/O� � �N (Fig.8j) contacts contribute 0.9%, 0.4% and 0.3%, respectively, to the HS.The functions d norm plotted onto the HS are shown for the H� � �H, H� � �C/C� � �H, H� � �O/O� � �H and H� � �N/ N� � �H interactions in Fig.9a-d.The HS analysis confirms the importance of H-atom contacts in establishing the packing and suggest that van der Waals interactions and hydrogen-bonding play the major roles in the crystal packing(Hathwar et al., 2015).
Figure 10The views of the energy frameworks for a cluster of molecules of the title compound showing (a) electrostatic energy, (b) dispersion energy and (c) total energy diagrams.The cylinder radii are proportional to the relative strength of the corresponding energies, adjusted to the same scale factor of 80 with a cut-off value of 5 kJ mol À 1 within 2�2�2 unit cells.

Table 3
Calculated energies and quantum-chemical parameters of (I).

Table 2
Comparison of selected X-ray and DFT bond lengths and angles (A ˚, � ).

Table 4
Experimental details.