Efficient Synthesis, SC-XRD, and Theoretical Studies of O-Benzenesulfonylated Pyrimidines: Role of Noncovalent Interaction Influence in Their Supramolecular Network.

Crystalline organic compounds, 2-amino-6-methylpyrimidin-4-yl benzenesulfonate (AMPBS) and 2,6-diaminopyrimidin-4-yl benzenesulfonate (DAPBS), were prepared via O-benzenesulfonylation of 2-amino-6-methylpyrimidin-4-ol 1 and 2,6-diaminopyrimidin-4-ol 2, respectively. The structural interpretations were achieved unambiguously by single-crystal X-ray diffraction (SC-XRD) analysis. The Hirshfeld surface study showed that C-H···O, N-H···N, and especially C-H···C hydrogen bond interactions are the key contributors to the intermolecular stabilization in the crystal. Density functional theory (DFT) studies were used to obtain a better understanding of natural bond orbitals (NBOs) and nonlinear optical (NLO) analysis for AMPBS and DAPBS at the B3LYP/6-311G(d,p) level. The time-dependent density functional theory (TD-DFT)/CAM-B3LYP/6-311G(d,p) level was employed for frontier molecular orbital analysis of both compounds. DFT-based vibrations for C-H, C=N, N-H, and stretching for C-C were found to be in good agreement with the experimental data. Overall, the theoretical findings were acquired in correspondence to the SC-XRD-based parameters. Intracharge transfer occurred in AMPBS and DAPBS compounds, which was evaluated through FMO activity. Global reactivity indices had been acquired utilizing energies of HOMO-LUMO orbitals. Overall, the theoretical findings related to AMPBS and DAPBS consist of promising correspondence to experimental findings. The theoretical-based study also exhibited that both AMPBS and DAPBS compounds contain promising NLO features.

Introduction

Pyrimidine, a six-membered hetero-aromatic nucleus with two atoms of nitrogen, is a part of remarkable chemical architectures having numerous valuable pharmacological activities.[1,2] Some of the pyrimidine-based compounds are found to have anticancer[3] and anti-HIV potential.[4] Also, abilities like protein kinase inhibition and antitubercular potential are reported for pyrimidine derivatives.[5,6] Additionally, pyrimidine-based molecules are also known for their anti-inflammatory and antiviral activities.[7] These compounds have also been used as antibacterial,[8] antifungal,[9] and antitumor[10] agents. Moreover, pyrimidine-based chemical architectures are cardiovascular[11] and diuretic agents[12] (some of the selected structures with their biological activities are mentioned in Figure ). Applications of pyrimidine-based compounds are not only limited to medicinal chemistry but also have various applications in chemical biology and theoretical chemistry.[13] These important building blocks can be found naturally and can be synthesized in the laboratory employing various synthetic methodologies.[14] Naturally, the pyrimidine core is also found in the central skeleton of the nucleic acids like thymine, cytosine, and uracil. Furthermore, it can be found in folic acid, riboflavin, barbituric acid, alkaloids, coffee, cocoa, co-enzymes, purines, and so forth.[14] Pyrimidines can be synthesized by condensation of acetamidine and ethyl acetoacetate[15,16] or from urea using the 1,3-dielectrophilic approach in the basic medium[17] or via decarboxylation followed by intramolecular cyclization.[18−20]

Figure 1

Selected diversely functionalized pyrimidine-based chemical architectures with their pharmacological potential.

Owing to the synthetic utility as precursors and intermediates for the successful accomplishment of various diversely functionalized biologically active scaffolds, the pyrimidines core has attracted considerable attention. In addition, a number of reports have highlighted that organic compounds have a significant nonlinear optical response (NO), consequently emerged as promising NLO materials.[21−25] Indeed, organic compounds provide a more suitable diversity of structures and larger environmental stability as compared to transition-metal organometallic compounds.[26] Organic compounds with a conjugative skeleton by p-orbital overlapping facilitate efficient electronic communication and CT transitions which led to large changes in their dipole moments.[27] Moreover, many NLO organic molecular systems were exclusively studied from the theoretical point of view.[28−30] Therefore, we are reporting the synthesis, single crystal analysis, and computational investigation of the O-4-acetylamino-benzenesulfonylated pyrimidines starting from 2-amino-6-methyl-pyrimidin-4-ol and 2,6-diamino-pyrimidin-4-ol.

Experimental Section

Chemistry

Chemicals used for the synthesis of targeted compounds were of top grade and were purchased from well-reputed chemical industries like Acros Chemicals, Sigma-Aldrich, and Fisher Scientific Ltd. Thin-layer chromatography (TLC) was carried out using precoated silica gel plates, and the result was displayed at 254 nm in ultraviolet and also by vaniline within H2SO4. For structural investigation of compounds, data were collected on a Bruker Kappa Apex-II diffractometer, having an X-rays tube containing molybdenum as a target, the monochromator made of graphite, and CCD for recording the intensity peaks. For data correction and data reduction, APEX-II and SAINT were used, respectively.[31] SHELXS97 was used for structure solution,[32] and SHELXL2014/6 was used for the refinement of the structure[33] to minimize the errors in the structure. For graphical representation of single-crystal structure results, ORTEP was used for graphical representation of the asymmetric unit,[34] PLATON[35] was used for exploring hydrogen bonding, and Mercury 4.0[36] was used for graphical representation of the π–π stacking interaction.

General Procedure

Preparation of Compound 3

To a round-bottom flask containing 2-amino-6-methylpyrimidin-4-ol (1.0 mmol, 1 equiv) in acetone (10 mL), K2CO3 (3.0 mmol, 3 equiv) and benzenesulfonyl chloride (1.3 mmol, 1.3 equiv) were added. The reaction was refluxed for 4 h, and on completion (monitored by TLC), the crude product was filtered and purified by column chromatography. The purified product was recrystallized from ethanol (Figure ).

Figure 2

General synthetic scheme for the o-benzenesulfonylation of hydroxypyrimidine.

Preparation of Compound 4

To a round-bottom flask containing 2,6-diaminopyrimidin-4-ol (1.0 mmol, 1 equiv) in acetone (10 mL), K2CO3 (3.0 mmol, 3 equiv) and benzenesulfonyl chloride (1.3 mmol, 1.3 equiv) were added. The reaction was refluxed for 4 h, and on completion (monitored by TLC), the crude product was filtered and purified by column chromatography. The purified product was recrystallized from ethanol (Figure ).

Computational Procedure

The overall quantum chemical calculations forbenzenesulphonate derivatives: 2-amino-6-methylpyrimidin-4-yl benzenesulfonate (AMPBS) and 2,6-Diaminopyrimidin-4-yl benzenesulfonate (DAPBS) were carried out with the help of DFT/TD-DFT by using the Gaussian 09 package.[37] The entitled compounds were optimized using single SC-XRD-based geometries at the B3LYP/311G(d,p) level.[38−40] The frequency analysis was also carried out at the same level for verification of stability related with optimized geometries. Moreover, NBO and NLO analyses were carried out at the aforementioned level. However, the FMO analysis was performed at the TD-DFT/CAM-B3LYP/6-311G(d,p) level to determine electronic properties of AMPBS and DAPBS. The input files were organized with the help of GaussView 5,[41] Avogadro,[42] Gauss Sum,[43] and Chemcraft[44] programs. Furthermore, the same software was applied for the interpretation of output files.

Results and Discussion

The crystallographic study of the title compound showed that AMPBS exists in the monoclinic form with the P21/n space group, whereas DAPBS also exists in the monoclinic form but have a different space group as P21/c. The detailed crystallographic data of AMPBS and DAPBS are listed in Table .

Table 1

Crystallographic Data of Studied Compounds

crystal data	AMPBS	DAPBS
CCDC	1983263	1983262
chemical formula	C11H11N3O3S	C10H10N4O3S
Mr	265.29	266.28
crystal system, space group	monoclinic, P21/n	monoclinic, P21/c
temperature (K)	296	296
a, b, c (Å)	11.7448 (7), 8.0506 (5),13.4238 (9)	12.299 (5),7.664 (3),13.196 (4)
α, β, γ (deg)	90, 103.357 (4), 90	90, 108.405 (18), 90
V (Å3)	1234.92 (14)	1180.2 (7)
Z	4	4
density (calculated)	1.427 Mg/m3	1.499 Mg/m3
F(000)	552	552
radiation type	Mo Kα	Mo Kα
wavelength (λ)	0.71073 Å	0.71073 Å
μ (mm–1)	0.27	0.28
crystal size (mm)	0.44 × 0.38 × 0.30	0.36 × 0.24 × 0.22
diffractometer	Bruker APEXII CCD diffractometer	Bruker APEXII CCD diffractometer
absorption correction	absorption correction: multi-scan (SADABS; Bruker, 2007)	absorption correction: multi-scan (SADABS; Bruker, 2007)
no. of measured, independent and observed [I > 2s(I)] reflections	7565, 2668, 2278	7106, 2563, 1654
Rint	0.039	0.072
theta range for data collection	2.626–26.999°	3.116–27.000°
index ranges	–15 ≤ h ≤ 13, –10 ≤ k ≤ 10, –17 ≤ l ≤ 15	–15 ≤ h ≤ 12, –9≤ k ≤ 9, –15 ≤ l ≤ 16
(sin θ/λ)max (Å–1)	0.639	0.639
R[F2> 2σ(F2)], wR(F2), S	0.038, 0.107, 1.07	0.051, 0.137, 1.03
no. of reflections	2668	2563
no. of parameters	170	163
Δρmax, Δρmin (e Å–3)	0.26, −0.32	0.29, −0.42

In 2-amino-6-methylpyrimidin-4-yl benzenesulfonate (Figure , Table ), the 2-amino-6-methylpyrimidin-4-ol group A (C1–C5/N1–N3/O1) and benzene ring B (C6–C11) are planar with a root-mean-square deviation of 0.0097 and 0.0044 Å, respectively. The dihedral angle between A/B is 82.55 (5)°. The sulfonyl group C (S1/O2/O3) is oriented at dihedral angles of 59.96(6)° and 52.67 (10)° with respect to group A and B, respectively. The molecules are connected with each other in the form of dimers through N–H···O and N–H···N interaction to form the R22(12) loop,[45] where NH is from the meta aniline part, N is from pyrimidine of another molecule, and O is from the sulfonate group. The dimers are interlinked through N–H···N and N–H···O interaction to complete the R22(12) loop, where NH is from the meta aniline part. An adjacent set of the bifurcated R32(8) loop is formed through N–H···N. N–H···O and C–H···O interaction, where CH is from the meta methyl part of the 2-amino-6-methylpyrimidin-4-ol group. These loops are shown in Figure and given in Table . In this way, molecules form an infinite one-dimensional polymeric network with a crystallographic base vector [0 1 0]. π–π stacking interactions are present between rings that help in further stabilization of the crystal structure.[46] There exists a face-to-face stacking interaction between pyrimidine rings that are strictly parallel to each other with a distance of 4.4208(9) Å between centroids (Figure ), corresponding to the ring offset of 2.746 Å connected with each other by a symmetry code (iv) 1 – x, −y, 1 – z, as given in Table . The benzene rings at (x, y, z) and (1 – x, 1 – y, z) are juxtaposed through the face-to-face stacking interaction with the intercentroid separation of 4.1477(13) Å, with a slippage of 2.090 Å. There also exists a multi π–π stacking interaction between the pyrimidine ring and benzene ring with an intercentroid distance of 3.9722(13) Å, corresponding to a ring off-set of 1.702 Å connected with each other by the symmetry code (vi) 1 – x, −y, −z. The C–H–Cg (1) interaction also exists that further stabilizes the crystal packing with a C–Cg (1) distance of 3.745(2) Å related with each other by the symmetry code (vi) 1 – x, −y, −z, where Cg1 is the centroid of the (C2–C4/N2/N3) ring (Figure ).

Figure 3

Ortep diagram of studied compounds with ellipsoids at the 50 % probability level with H atoms as small circles of arbitrary radii.

Figure 4

Packing diagram of studied molecules showing dimerization and interlinkage of dimers.

Table 2

Hydrogen-Bond Geometry (Å, °) for Studied Compounds

	D—H···A	D—H	H···A	D···A	D—H···A
AMPBSa	N1–H1A···O2i	0.78 (3)	2.34 (2)	2.9702 (19)	139 (2)
	N1–H1B···N2ii	1.00 (3)	2.16 (3)	3.123 (2)	159.4 (19)
	C5–H5B···O2iii	0.96	2.45	3.322 (2)	152
DAPBSb	N1–H1A···N2i	0.86	2.21	3.054 (3)	168
	N1–H1B···O1ii	0.86	2.54	3.322 (3)	151
	N4–H4A···N3iii	0.86	2.43	3.163 (3)	144
	N4–H4B···O3iv	0.86	2.20	3.018 (3)	159
	C3–H3···O3iv	0.93	2.59	3.324 (3)	136
	C6–H6···O2v	0.93	2.65	3.252 (4)	123

Symmetry codes of AMPBS: (i) −x + 1/2,y – 1/2, −z + 1/2; (ii)–x + 1/2, y + 1/2, −z + 1/2; (iii) x, y – 1, z.

Symmetry codes of DAPBS: (i) −x, −y – 1, −z; (ii) −x, y – 1/2, −z – 1/2; (iii) x, −y – 1/2, z + 1/2; (iv) x, −y + 1/2, z + 1/2; (v) −x + 1, −y, −z.

Table 3

Geometrical Parameters (Å) for π–π Stacking for the Studied Compounds

	Ring i–ja,b	Rcc	R1vd	R2ve	αf	βg	γh	slippage
AMPBS	Cg1···Cgiv	4.4208(9)	3.4649(6)	3.4648(6)	0.00(7)	38.4	38.4	2.746
	Cg···Cg2v	4.1477(13)	3.5830(9)	3.5830(9)	0.02(10)	30.3	30.3	2.090
	Cg2···Cg2v	3.9722(13)	–3.5889(9)	–3.5889(9)	0.02(10)	25.4	25.4	1.702
DAPBS	Cg1···Cg1vi	3.522(2)	–3.3536(13)	–3.3536(13)	0.00(15)	17.8	17.8	1.076
	Cg2···Cg2vi	3.922(3)	3.7116(14)	3.7116(14)	0.02(10)	18.8	18.8	1.266

Symmetry codes of AMPBS: (i) −x + 1/2, y – 1/2, −z + 1/2; (ii)–x + 1/2, y + 1/2,–z + 1/2; (iii) x, y – 1, z. (iv)1 – x, y, 1 – z (v) 1 – x, 1 – y, z (vi) 1 – x, −y, −z; symmetry codes of DAPBS: (vi) 1 – x, 1 – y, 1 – z (vii) 1 – x, 1 – y, z.

Cg1 and Cg2 are the centroids of (C2–C4/N2/N3) and (C6–C11) rings, representing pyrimidine and benzene rings, respectively.

Centroid–centroid distance between ring i and ring j.

Vertical distance from ring centroid i to ring j.

Vertical distance from ring centroid j to ring i.

Dihedral angle between the first ring mean plane and the second ring mean plane of the partner molecule.

Angle between the centroid of the first ring and the second ring.

Angle between the centroid of the first ring and the normal to the mean plane of the second ring of the partner molecule.

In 2,6-diaminopyrimidin-4-yl benzenesulfonate (Figure , Table ), 2-amino-6-methylpyrimidin-4-ol group A (C1–C4/N1–N4/O1) and benzene ring B (C5–C10) are planar with an rms deviation of 0.0220 and 0.0026 Å, respectively. The dihedral angle between A/B is 81.47 (8)°. The sulfonyl group C (S1/O2/O3) is oriented at 51.31(10) and 64.49 (14)° with group A and B, respectively. The molecules are connected with each other in a form of dimers to form the R22(8) loop through N–H···N bonding, where NH is from one of the amino groups of the 2-amino-6-methylpyrimidin-4-oland N is from the pyrimidine moiety. The dimers are interlinked through N–H···O bonding to form a set of bifurcated R22(12) loops where NH is from one of the amino groups of the 2-amino-6-methylpyrimidin-4-ol group and O is from the sulfonate group. The dimers are also interlinked by another set of the bifurcated R21(6) loop through N–H···O and C–H···O bonding, where CH is from the pyrimidine moiety. All these loops are shown in Figure and Table . In this way, the molecules form an infinite 2D network with base vector [0 1 0], [0 0, 1] in the crystallographic plane (1 0 0).

A π–π stacking interaction helps in further firmly establishing the crystal packing. The pyrimidine ring at the general position (−x, −y, −z) is involved in face-to-face stacking interaction with another pyrimidine ring present at the position (1 – x, 1 – y, 1 – z) with an intercentroid separation of 3.522(2) Å, corresponding to a ring off of 1.076 Å. There also exists a face–face stacking between the benzene rings related with each other by a symmetry code (1 – x, 1 – y, z) with a distance of 3.922(3) Å between the centroids of rings, with a slippage of 1.266 Å.

(a) Cg1 and Cg2 are the centroids of (C2–C4/N2/N3) and (C6–C11) rings, representing pyrimidine and benzene rings, respectively. (b) Centroid–centroid distance between ring i and ring j. (c) Vertical distance from ring centroid i to ring j. (d) Vertical distance from ring centroid j to ring i. (e) Dihedral angle between the first ring mean plane and the second ring mean plane of the partner molecule. (f) Angle between the centroid of the first ring and the second ring. (g) Angle between the centroid of the first ring and the normal to the mean plane of the second ring of the partner molecule. Furthermore, in order to explore intermolecular interactions in the crystal packing quantitative, HS analysis is performed on Crystal Explorer version 3.1.[47]Figure [AMPBS (a)] and Figure [DAPBS(a)] have different colors which indicate the strength of intermolecular interaction. The strongest, intermediate, and weak interactions are indicated by red, white, and blue color, respectively. Surfaces are constructed by an assumption that is the electron distribution around the atom is formulated as a summation of spherical atom electron densities.[48−58] In Figure [AMPBS(a)], the ring nitrogen of the 2-amino-6-methylpyrimidin-4-ol moiety that is the nearest to the methyl group, the amino group, and methyl group of 2-amino-6-methylpyrimidin-4-ol moiety and one of the oxygen atom of sulfonyl group are involved in strong interaction as shown in Figure [AMPBS(a)]. Amino groups, ring nitrogens, ring CH, and one of the oxygen atoms of the sulfonyl group are involved in strong interactions in compound DAPBS, as shown in Figure [DAPBS (a)]. In Figure [AMPBS (b) and 7 DAPBS (b)], the donors and acceptors are classified by blue and red spots on the HS, respectively. In both compounds, the amino group and one of the ring N atoms of the pyrimidine ring act as the donor while one of the O of sulfonyl groups acts as the acceptor.[13] The configuration of contiguous red and blue regions around the benzene and pyrimidine rings on the Hirshfeld surface mapped over the shape index indicates the presence of π–π stacking interaction, as shown in Figure [AMPBS (c) and 7 DAPBS (c)]. The large and flat green regions around the benzene and pyrimidine rings on the corresponding curved surface also confirms the presence of π–π stacking interactions, as shown in Figure [AMPBS (d) and 7 DAPBS (d)]. In order to find out the percentage contributions of different interatomic contacts, two-dimensional figure print plots are drawn. These plots can be utilized to measure the individual contributions of each intermolecular interaction involved in the crystal packing.[45−47,49−55] The strongest interaction is found among hydrogen atoms in both AMPBS and DAPBS. The strength of this interaction is 34.8 and 31.1% for AMPBS and DAPBS, respectively, and as given in Figure , respectively. The percentage contribution for other interatomic contacts for AMPBS is shown in Figure , whereas the percentage contribution for interatomic contacts other than the strongest contact for DAPBS is shown in Figure .

Figure 6

Hirshfeld surfaces of the title compound AMPBS mapped over (a) dnorm, (b) electrostatic potential, (c) shape index, and (d) curvedness in the ranges −0.367–1.500, −0.098–0.096, −1.000–1.000, −4.000–0.4000 au, respectively. (1 au of electron density 6.748 e Å–3).

Figure 7

Hirshfeld surfaces of the title compound DAPBS mapped over (a) dnorm, (b) electrostatic potential, (c) shape index, (d) curvedness in the ranges −0.442–1.459, −0.109–0.118, −1.000–1.000, −4.000–0.4000 au, respectively. (1 au of electron density 6.748 e Å–3).

Figure 8

Percentage contributions of interatomic contacts to the Hirshfeld surface for the title compounds.

The voids present in the crystal packing are a good indicator to find out how closely the molecules are packed with each other. The less percentage of voids indicates stronger crystal packing. These voids are calculated based on the sum of spherical atomic electron densities at the appropriate nuclear positions (procrystal electron density).[59] The crystal-void calculation (results under 0.002 a.u. isovalue) shows the void volume is of the order of 176.92[3] and 159.61 Å[3] of titled salts, respectively. The surface area is of the order of 507.34[2] and 469.49 Å[2] for titled salts, respectively. With the porosity, the calculated void volume of tilted salts is 14.3 and 13.5%, respectively. There are no large cavities. This analysis shows that the crystal packing is stronger in DAPBS as compared to the crystal packing in AMPBS (Figure ).

Figure 9

Voids showed (Wolff et al., 2012) in the crystal structure of title compounds.

Molecular Geometric Parameters

The geometry of the AMPBS and DAPBS was optimized using the B3LYP/6-311G(d,p) level. The obtained results are shown in Tables S1 and S2 (Supporting Information) for AMPBS and DAPBS, respectively. In AMPBS, the bond lengths of O–S as S1–O1, S1–O2, S1–O3, and S1–C6, determined through XRD, were found to be as 1.417, 1.417, 1.615, and 1.746 Å, while through DFT, they were found to be as 1.447, 1.448, 1.692, and 1.788 Å, respectively. The bond lengths between nitrogen and carbon atoms for N1–C1, N2–C1, N2–C2, N3–C1, and N3–C4 were measured through SC-XRD as 1.345, 1.338, 1.345, 1.351, and 1.311 Å, whereas the calculated values were found to be 1.363, 1.336, 1.341, 1.35, and 1.314 Å, respectively. The C–C bond lengths for C2–C3, C2–C5, C3–C4, C6–C7, C11–C10, C10–C9, C9–C8, and C8–C7 were found through XRD as 1.38, 1.493, 1.365, 1.383, 1.383, 1.371, 1.36, and 1.382 Å, while simulated values were measured as 1.391, 1.503, 1.395, 1.391, 1.391, 1.395, 1.394, and 1.392 Å, respectively. Similarly, in AMPBS, the bond angles in O–S–O: O1–S1-02, O1–S1–O3, and O2–S1–O3 were observed through single-crystal X-ray diffraction as 119.4, 101.4, and 109.3°, while through DFT, they were found to be as 122, 100.9, and 109.6°, respectively. The bond angles in O–S–C like O2–S1–C6, O2–S1–C6, O3–S1–C6, and S1–O3–C4 were determined through SC- XRD as 109.8, 110.5, 105.2, and 124.8°, whereas simulated values were determined as 108.7, 110.5, 103.2, and 124.7°, respectively. The bond angles of S–C–C: S1–C16–C11 and S1–C6–C1 through SC-XRD were found to be 118.4 and 119.3°, whereas the calculated values achieved were 118.5 and 119.3°, respectively.

The N–C–N bond angles for N1–C1–N2, N1–C1–N3, and N2–C1–N3 were measured by SC-XRD as 118.4, 115.6, and 125.9°, while the calculated values of aforementioned bond angles were found to be 117.2, 116.4, and 126.4°, respectively. The bond angles in C–N–C as C1–N2–C2, N2–C2–C3, N2–C2–C5, C1–N3–C4, and N3–C4–C3 were measured by XRD to be 116.6, 121.7, 116.7, 114.2, and 126°, while the calculated bond angles were found as 116.7, 121.9, 116.3, 115.3, and 124.2°, respectively. The bond angles in C–C–C: C3–C2– C5, C11–C6–C7, C6–C7–C8, C10–C9–C8, and C9–C8–C7 were found to be 121.6, 122.2, 118.6, 120.2, and 120.2° by SC-XRD, whereas the calculated abovementioned bond angles were found as 121.8, 122.2, 118.6, 120.4, and 120.2°, respectively.

In DAPBS, the S–O bond lengths for S1–O1, S1–O2, S1–O3, and S1–C45 were measured as 1.602, 1.425, 1.422, and 1.754 Å by SC-XRD, while the calculated aforementioned bond lengths were found to be 1.691, 1.450, 1.450, and 1.792 Å, respectively. In a similar way, bond lengths between nitrogen and carbon atoms for N1–C1, N2–C1, N2–C2, N3–C1, N3–C4, and N4–C2 were measured by XRD and were found to be 1.337, 1.347, 1.343, 1.358, 1.327, and 1.340 Å, whereas the calculated aforementioned bond lengths were found to be 1.359, 1.338, 1.340, 1.346, 1.317, and 1.367 Å, respectively. The carbon and carbon bond lengths for C2–C3, C3–C4, C5–C6, C5–C10, C8–C7, C7–C8, C8–C9, and C9–C10 were measured as 1.416, 1.356, 1.389, 1.378, 1.378, 1.361, 1.378, and 1.385 Å by XRD, while the calculated values of the mentioned bond lengths were found as 1.406, 1.385, 1.392, 1.392, 1.392, 1.394, 1.394, and 1.392 Å, respectively. In DAPBS, the bond angles in O–S–O through DFT were observed as 109, 109.1, and 122.4° for O2–S1–03, O2–S1–O4, and O3–S1–O4, respectively. Both the DFT and XRD values of the bond angle are the same for O2–S1–O3 but different in O2–S1–O4 and O3–S1–O4. The bond angles in O–S–C were calculated through DFT as 109.1° for O3–S1–C13 and O4–S1–C13, but the experimental values of the abovementioned bond angles were different from DFT and were found to be 110 and 109°, respectively. Furthermore, the same simulated and experimental S–C–C bond angles values for S1–C12–C14 and S1–C13–C18 were found to be 118.9 and 119°, respectively. The N–C–N bond angles for N5–C9–N6, N5–C9–N7, N6–C9–N7, and N6–C10–N8 were measured by SC-XRD as 116.4, 117.4, 126.1, and 117.9°, whereas the calculated values were found to be 117.2, 116.3, 126.5, and 116.1°, respectively. The C–N–C bond angles for C9–N6–C10, N6–C10–C11, C9–N7–C12, and N7–C12–C11 were measured by SC-XRD as 116.9, 121.7, 113.4, and 127.5°, whereas the simulated values of the aforementioned bond angles were found to be 116.4, 122.3, 115, and 125.2°, respectively. The simulated C–C–C bond angles were observed to be 122.1, 118.6, 120.1, and 120.1° for the C14–C13–C18, C13–C14–C15, C14–C15–C16, and C16–C17–C18, respectively, through DFT, and the same values of bond angles are observed through XRD (Figure ).

Figure 10

Optimized bond lengths (Å) and bond angles (°) of AMPBS and DAPBS.

Natural Bonding Orbital Analysis

The NBO analysis provided an effective method to investigate charge transfer and intra- and intermolecular bonding interactions.[60] The bonding and antibonding interactions were described by the NBO analysis which were expressed by the second-order perturbation energy E(2), as could be seen in eq .[61−64]Here, E(2), qi,F(i.j), εj, and εi are stabilization energy, donor orbital occupancy, diagonal, and the off-diagonal NBO Frock matrix elements, respectively.[65,66] NBOs were performed using Gaussian 09 programme at the B3LYP 6-311G(d,p) level.[67,68] The hyper conjugative interactions of both compounds (AMPBS and DAPBS) are depicted in Tables S3 and S4. Among π → π* plausible electronic transitions, π(C11–C12) → π*(N9–C14) and π(C14–C15) → π*(N9–C17) revealed the highest magnitude of a stabilization energy of 38.30 and 43.30 kcal/mol in AMPBS and DAPBS, respectively, whereas the transitions, such as σ(O4–C14) → σ*(C12–C14) and σ(S1–C18) → σ*(C19–H20) were obtained with the lowest stabilization energy as 0.50 kcal/mol for AMPBS and DAPBS, respectively. These lowest energy values indicated weak interactions between the electron donor and acceptor.

Herein, we reported some other π → π* interactions in AMPBS such as π(N8–C10) → π*(C11–C12), π(N9–C14) → π*(N8–C10), π(C24–C26) → π*(C19–C28), π(C19–28) → π*(C20–C22), and π(C20–C22) → π*(C24–C26), yielding 34.49, 32.78, 24.97, 21.68, and 21.59 kcal/mol stabilization energies, respectively. On the other hand, in DAPBS the π → π* interactions were observed as π(N8–C13) → π*(C14–C15), π(N9–C17) → π*(N8–C13), π(C18–C27) → π*(C19–C21), π(C19–C21) → π*(C23–C25), and (C23–C25) → (C18–C27) that led to the stabilization energies of 35.90, 35.74, 21.46, 21.54, and 24.30 kcal/mol, respectively. Moreover, some of the σ → σ* interactions were observed as σ(N9–C10) → σ*(O4–C14), σ(C19–C28) → σ*(C19–C20), σ(C20–H21) → σ*(C19–C28), σ(C28–H29) → σ*(C19–C20), and σ(N5–H7) → σ*(N8–C10) with stabilization energies of 5.43, 5.16, 4.88, and 4.97 and 3.93 kcal/mol, respectively, in DAPBS. Furthermore, some other σ → σ* interactions were found to be σ(N9–C13) → σ*(O2–C17), σ(C18–C19) → σ*(C18–C27), σ(C19–C21) → σ*(S1–C18), σ(C25–C27) → σ*(S1–C18), and σ(C27–H28) → σ*(C18–C19) with stabilization energies of 5.30, 5.08, 4.40, 4.41, and 4.91 kcal/mol, respectively.

In AMPBS and DAPBS, the most prominent interactions in LP → σ* were seen as LP1(N5) → σ*(N8–C10) and afforded stabilization energies of 46.22 and 41.17 kcal/mol, respectively. The transition between the lone pair to antibonding orbitals signified the presence of hydrogen bonding in compounds.[69−74] Moreover, in AMPBS, some important transitions such as LP(2)(O2) → σ*(S1–C19), LP(3) (O2) → σ*(S1–O4), LP(2)(O4) → π*(N9–C14), and LP(O3) → σ*(S1–O4) were seen with stabilization 16.16, 31.95, 29.86, and 37.84 kcal/mol, respectively. In DAPBS, some significant transition LP → π* and LP → σ* were observed as LP(2)(O2) → π*(N9–C17), LP(1)(N5) → π*(N8–C13), LP(1)(N10) → π*(C14–C15), and LP(3)(O3) → σ*(S1–O2) with stabilization energies 29.13, 51.49, 41.17, and 37.14 kcal/mol, respectively. The above discussion led to the conclusion that charge transfer, extended conjugation, and hyperconjugative interactions were present in the title compounds.

Natural Population analysis

In AMPBS and DAPBS, the atomic charges based on natural population[75] were determined by adopting B3LYP/6-311G(d,p). NPA of the AMPBS showed (Figure S1) that some carbon and sulfur atoms were positively charged, whereas O2, O3, O4, N5, N8, N9, and C19 atoms were negatively charged. For DAPBS, some atoms like C and S1 were positively charged, while O2, O3, O4, N7, N8, N9, and C18 were negatively charged (Figure S1).

Vibrational Analysis

The B3LYP/6-311G(d,p) level was employed to determine the vibrational frequencies of compound AMPBS and DAPBS. The simulated results were found to have an excellent concurrence to the experimental results.

C–H Vibrations

The stretching (C–H) vibrational frequencies of aromatic and heteroaromatic were found as 3100–3000 cm–1.[76] The calculated absorption frequencies for the symmetric vibration of C–H in AMPBS and DAPBS were located at 3225–3210 and 3221–3210 cm–1, respectively. In AMPBS and DAPBS symmetric and asymmetric, calculated vibrational frequencies were found to be at 3194 and 3193 cm–1, respectively. The scissoring vibrations were located at 1626 cm–1 and 1202 in AMPBS, whereas in DAPBS, the same vibrations were observed at 1628 and 1201 cm–1 in the aromatic ring. C–H wagging vibrations in AMPBS were found at 1409, 1368, 1364, 754, 706, and 569 cm–1, showing a good agreement with the experimental data (Figures S2–S3 and Tables S5–S6). C–H twisting vibrations were located at 987–980 cm–1(DFT) and 949 cm–1 (Experimental). On the other hand, in DAPBS wagging vibrations were located at 765, 703, and 702 cm–1. The rocking vibrations in the benzene ring were found at 1103–1082 cm–1 (DFT), showing a good agreement with 1199–1016 cm–1 (experimental) values in AMPBS and DAPBS (Tables S5 and S6).

C–C Stretching Vibrations

The C=C absorption frequencies were found in the range of 1650–1400 cm–1.[77] In AMPBS, the C–C stretching vibrations in the benzene ring were located at 1631–1626 and 729 cm–1 by DFT. Similarly, in DAPBS, same carbon–carbon stretching vibrations appeared at 1628, 1015, and 746 cm–1 (DFT).

C–N Vibrational Bands

The vibrational frequencies of C=N are found in the range of 1382–1266 cm–1.[78] AMPBS symmetric C–N vibrations in pyrimidine were located at 1603, 1288, 1018, and 621 cm–1, whereas in DAPBS, C–N vibrations appeared at 1604, 1331, 631, and 566 cm–1, showing a good agreement with the experimental data (Figures S2–S3 and Tables S5–S6).

N–H Vibration

In AMPBS and DAPBS, N–H symmetric stretching vibrations of NH2 were located at 3605 and 3612 cm–1 (DFT), respectively, whereas the experimentally determined values were found at 3603 and 3653 cm–1, respectively. Furthermore, the simulated N–H scissoring vibrations were found as 1647 and 1651 cm–1, while the experimental values were found to be 1692 and 1688 cm–1 for AMPBS and DAPBS, respectively.

S–O Vibration

In AMPBS, S–O stretching vibrations in SO3 were located at 1158, 729, 664, and 569 cm–1 (DFT) and 1144, 777, 658, and 559 cm–1 (experimental), respectively. Similarly, in DAPBS, the same vibrations were computed as 746, 676, and 566 cm–1 (DFT) and 746, 686, and 561 (experimental), respectively (Figures S2, S3, and Tables S5, S6).

Frontier Molecular Orbital

Frontier molecular orbitals (FMOs) containing the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO), as well as the energy gap were considered to be very effective parameters in chemical quantum chemistry.[79,80] FMOs also delivered important information to determine molecular dynamics and describe the chemical transformations.[81] The HOMO and LUMO of compounds were helpful in determining various parameters such as optical, electronic properties, chemical reactivity, stability, intermolecular charge transfer, chemical hardness, softness, and electronegativity. The HOMO–LUMO energy gap of molecules played an important role in chemical reactions.[82,83] The HOMO–LUMO energy gaps of AMPBS and DAPBS were calculated at the TD/DFT/CAM-B3LYP/6-311G(d,p) level are and shown in Table .

Table 4

Computed Energies (E) of Title Compoundsa

AMPBS			DAPBS
MO(s)	energy	ΔE	MO(s)	energy	ΔE
HOMO	–6.496	4.871	HOMO	–6.043	4.598
LUMO	–1.625		LUMO	–1.445
HOMO – 1	–7.200	6.224	HOMO – 1	–6.936	6.027
LUMO + 1	–0.976		LUMO + 1	–0.909
HOMO – 2	–7.723	6.820	HOMO – 2	–7.074	6.936
LUMO + 2	–0.903		LUMO + 2	–0.138

E = energy, ΔE(eV) = ELUMO – EHOMO; units in eV.

The HOMO was labeled as an electron donor, whereas the LUMO was assigned as the electron acceptor. A deeper understanding of chemical reactivity could be gained by this electronic absorption corresponded to the transition from the ground to the first excited state, and it was mainly described by one electron excitation from the HOMO to the LUMO orbital.[84,85] The chemical stability could be understood by the energy gap between the HOMO and LUMO (ΔE = ELUMO – EHOMO). In both molecules, the electronic distribution could be observed in HOMO → LUMO, HOMO – 1 → LUMO + 1, and HOMO – 2 → LUMO + 2, as shown (Table ).The energy gaps from the HOMO to LUMO in AMPBS and DAPBS were determined as 4.871 and 4.598 eV, respectively. Moreover, in AMPBS and DAPBS, the energy gaps from HOMO – 1 → LUMO + 1 and HOMO – 2 → LUMO + 2 were found as 6.224, 6.027 and 6.820, 6.936 eV, respectively.

Table 5

Ionization Potential (I), Electron Affinity (A), Electronegativity (X), Global Hardness (η), Chemical Potential (μ), Global Electrophilicity (ω), and Global Softness (σ)a

compounds	I	A	X	η	μ	ω	σ
AMPBS	8.557	–0.170	4.194	4.194	–4.194	2.015	0.115
DAPBS	8.111	–0.370	3.870	4.240	–3.870	1.766	0.118

Units in eV.

The electron density of the HOMO concentrated on 4-methoxypyrimidine-2-amine but had a small effect on other two oxygen atoms in 2-amino-6-methylpyrimidin-4-yl benzenesulfonate. The concentration of the LUMO was revealed at methyl benzensulfonate but affected pyrimidine carbon atoms for AMPBS. The electron density of the HOMO was observed on methyl benzenesulfonate and a small effect on pyrimidine carbon atom, while the concentration of the LUMO was found at 2,6-diaminopyrimidine-4-yl methansulfonate except the sulfur atom for DAPBS. Accordingly, the lower ΔE illustrated that the DAPBS obsessed slightly strong potential for the transfer of electrons and better NLO properties than AMPBS (Figure ).

Figure 11

Frontier molecular orbitals of the entitled compounds, Units in eV.

Global Reactivity Parameters

The stability and reactivity of AMPBS and DAPBS were described by the HOMO–LUMO energies. The electronic affinity (A) and ionization potential (I) can be calculated using eqs and 3.where Ec = cation (energy after losing one electron); Eo = basal state energy (neutral); and EA = anion (energy after gaining one electron).

Koopmans’s theorem has been utilized to measure the chemical hardness (η) and electronegativity (χ) of the investigated molecules.

Electrophilicity (ω), electron-donating capability (ω−), and electron-accepting capability (ω+) of AMPBS and DAPBS are calculated using eqs –8.

The softness values of AMPBS and DAPBS are calculated using eq .

The results obtained from these calculations are presented in Table .

In AMPBS and DAPBS, it could be seen that electron affinity had much lower values than ionization potential. The electron affinity as well as ionization potential values for AMPBS were greater than DAPBS. The preceding results indicated that all investigated molecules were chemically hard with greater kinetic stability and electron-donating capability. The global hardness of AMPBS and DAPBS were found to be 4.194 and 4.240 eV, respectively. The molecule with greater chemical potential values could be considered to be less reactive, more stable, and vice versa. The chemical potential values of AMPBS and DAPBS were found to be −4.194 and −3.870 eV, respectively. The global softness values of AMPBS and DAPBS were found to be 0.115 and 0.118 eV, respectively. These values were found to be greater in magnitude as compared to their global hardness values. The global electrophilicity (ω) values of AMPBS and DAPBS were found to be 2.015 and 1.766 eV, respectively. The aforementioned results showed that both investigated molecules have greater kinetic stability (Figures , 9, and 12).

Figure 5

π–π stacking of compounds showing interaction between centroids of various rings with distance measured in Å.

Figure 12

Electrostatic potential mapping on the electron density (isovalue = 0.02) of the studied compounds.

Nonlinear Optical Property

Nonlinear optical (NLO) materials were used for designing optical switches, optical memory devices, communication technology, and signal processing. Molecules containing the pi-electron conjugated system could be considered as strong candidates for electronic, optical, and nonlinear optical (NLO) applications.[86] Electronic properties were responsible for the strength of the optical response which depended upon the polarizability and hyperpolarizability (linear and nonlinear responses). The polarizability and hyperpolarizability should be evaluated for the estimation of NLO properties of compound AMPBS and DAPBS. To examine the change in the π-conjugated linker, the polarizability values of the compound AMPBS and DAPBS are given in Table .

Table 6

Dipole Moment, Polarizability, and Major Contributing Tensors (a.u.) of the Studied Compounds

linear polarizability	AMPBS	DAPBS
αxx	186.259	218.583
αyy	169.937	152.48
αzz	135.028	120.139
αtotal(a.u)	163.7413	163.734

For AMPBS, the linear polarizability along x, y, and z directions were obtained as 186.259, 169.937, and 135.028 a.u., respectively, which resulted an α total value of 163.7413 a.u. For DAPBS, the linear polarizability along x, y, and z directions were calculated as 218.583, 152.48, and 120.139 a.u., respectively, which resulted an α total of 163.734 a.u. as shown (Table ). The second-order polarizability (βtotal) values of AMPBS and DAPBS were calculated as 159.106 and 157.044 a.u., respectively. The sum of all the tensors calculated for AMPBS and DAPBS are 159.106 and 157.044, respectively (Table ).The urea molecule is frequently applied as the standard molecule.[87] βtotal values for AMPBS and DAPBS obtained were greater in magnitude than the urea molecule (βtotal).[88] Polarizabilities and hyperpolarizabilities characterized the 228 response of a system in an applied electric field.[89] The dipole moment of AMPBS (5.0908) was greater than DAPBS (4.2825), as shown in Table . The second hyper polarizabilities of AMPBS and DAPBS were computed as −8.0464 and 0.3622 a.u., respectively (Table ).Both AMPBS and DAPBS are centrosymmetric crystals, so there may be no NLO response property at the crystal/bulk level. The orientation of Cartesian coordinates of entitled molecules can be seen in Figure S6.

Table 7

Computed First Hyperpolarizabilities (βtot) and Major Contributing Tensors (a.u.) of the Studied Compounds

hyper polarizability	AMPBS	DAPBS
βxxx	–133.307	–196.585
βxxy	161.270	–19.303
βxyy	81.246	261.062
βyyy	–54.850	70.796
βxxz	–63.007	–4.991
βyyz	84.481	–5.369
βxzz	–32.604	62.331
βyzz	–22.236	40.339
βzzz	83.691	–1.868
βtotal(a.u.)	159.106	157.044

Molecular Electrostatic Potential

The chemical and physical aspects of any chemical system could be explored with the help of the molecular electrostatic potential (MEP) plot. Usually, the MEP plot could be employed to comprehend the plausible electrophilic or nucleophilic attack at suitable sites on chemical structures. The MEP surface contains several standard colors likewise orange, red, yellow, blue, and green which revealed the magnitude of the electrostatic potential. The order of magnitude of electrostatic potential in the decreasing order were found to be blue > green > yellow > orange > red. The segment highlighted with the red color was engaged to communicate the negative potential value which could be supportive for the electrophilic attack. On the contrary, the nucleophile enticing site by the most positive potential could be displayed with blue color, as given in equation . In current study, the oxygen, nitrogen, and sulfur atoms of both compounds contain a negative potential which might be favorable atoms for electrophilic attack (Figure ).

The MEP was associated to the electron density and presented very suitable indices for determining electrophilic and nucleophilic reactions and interaction because of hydrogen bonding.[2,90]

Conclusions

In summary, the synthesis of 2-amino-6-methylpyrimidin-4-yl benzenesulfonate AMPBS and 2,6-diaminopyrimidin-4-yl benzenesulfonate DAPBS was achieved via O-benzenesulfonylation reaction. The structures of the synthesized compounds were verified using the X-ray crystallographic technique. The SC-XRD study revealed that AMPBS and DAPBS consist of crystal systems with space groups as monoclinic, P21/n, and monoclinic, P21/c, respectively. The XRD study disclosed that in addition to hydrogen bonding, structures of the titled molecules are stabilized by the C–H–Cg and π–π stacking interactions. The molecules form an infinite one-dimensional polymeric network in AMPBS, while in DAPBS, molecules form an infinite two-dimensional network. From the Hirshfeld analysis, in the fingerprint plots of the close contacts in our entitled molecules, the highest values were seen as: H···H (34.81%), H···O (28.16%), H···C (16.03%), and H···N (13.73%), while the lowest interaction was found as N···N (1%) for AMPBS. In DAPBS, the highest values of interactions were found to be as H···H (31.32%), H···O (30.60%), H···N (16.52%), H···C (12.08%), whereas the lowest value was calculated as N···N (0.21%), respectively. Furthermore, DFT-based vibrational frequencies were in outstanding concurrence with the experimental data. The NBO investigation revealed that AMPBS and DAPBS are involved in the intra molecular charge transfer; therefore, these compounds have greater stability because of hyperconjugation. The FMO analysis was used to determine chemical reactivities and charge-transfer properties at different sites in entitled molecules. The global hardness of AMPBS and DAPBS are found to be −4.194 and −3.870 eV, respectively, and the global softness values are found to be 0.115 and 0.118 eV, respectively. Moreover, the chemical potential values are found to be −4.194 and −3.870 eV for AMPBS and DAPBS, respectively. On the basis of chemical reactivity descriptors, it could be considered that investigated compounds are less reactive and more stable. MEP surfaces indicate electrophilic and nucleophilic attack shown by red and blue color, respectively. The βtotal values of AMPBS and DAPBS were calculated as 159.106 and 157.044 a.u., respectively. These findings indicate that NLO values of title compounds were observed to be higher as compared to the urea molecule, indicating the significant NLO character, and may have important contribution in the field of technology.