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Crystal structure, Hirshfeld surface analysis and DFT calculations of 7-bromo-2,3-di­hydro­pyrrolo[2,1-b]quinazolin-9(1H)-one

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aUniversity of Geological Sciences, Olimlar street, 64, Mirzo Ulugbek district, Tashkent, Uzbekistan, bDepartment of Chemistry, National University of Uzbekistan named after Mirzo Ulugbek, Tashkent, Uzbekistan, cS. Yunusov Institute of Chemistry of Plant Substances, Academy of Sciences of Uzbekistan, Tashkent, Uzbekistan, and dDepartment of Organic Synthesis and Bioorganic Chemistry, Samarkand State University, Samarkand, Uzbekistan
*Correspondence e-mail: a_tojiboev@yahoo.com

Edited by M. Weil, Vienna University of Technology, Austria (Received 13 July 2022; accepted 2 August 2022; online 9 August 2022)

The mol­ecular structure of the title compound, C11H9BrN2O, is almost planar. The benzene and pyrimidine rings are essentially coplanar, with r.m.s. deviations of 0.0130 Å, and the largest displacement is for the flap atom of the di­hydro­pyrrole moiety [0.154 (7) Å]. Hirshfeld surface analyses revealed that the crystal packing is dominated by H⋯H, Br⋯H/H⋯Br and O⋯H/H⋯O inter­actions, and Br⋯Br inter­actions in the crystal structure are also observed. Theoretical calculations using density functional theory (DFT) with the B3LYP functional basis set gave numerical parameters for the frontier molecular orbitals.

1. Chemical context

Quinazolines are of significant inter­est for their various biological properties (Rajput et al., 2012[Rajput, R. & Mishra, A. P. (2012). Int. J. Pharm. Pharm. Sci. 4, 66-70.]; Ramesh et al., 2012[Ramesh, K., Karnakar, K. G., Satish, G., Reddy, K. H. V. & Nageswar, Y. V. D. (2012). Tetrahedron Lett. 53, 6095-6099.]; Khan et al., 2014[Khan, I., Ibrar, A. N., Abbas, N. & Saeed, A. (2014). Eur. J. Med. Chem. 76, 193-244.]; Ajani et al., 2016[Ajani, O. O., Audu, O. Y., Aderohunmu, D. V., Owolabi, F. E. & Olomieja, A. O. (2016). Am. J. Drug Discov. Dev, 7, 1-24.]). This class of compounds is considered as an attractive target for medicinal chemists, because quinazoline and its derivatives are the scaffold of several potent anti­tumor drugs, for example the well-known erlotinib and gefitinib (Sordella et al., 2004[Sordella, R., Bell, D. W., Haber, D. A. & Settleman, J. (2004). Science, 305, 1163-1167.]; Raymond et al., 2000[Raymond, E., Faivre, S. & Armand, J. P. (2000). Drugs, 60, 15-23.]). Besides these two drugs, the Food and Drug Administration (FDA) has approved some other quinazolines as effective anti­cancer drugs, viz. lapatinib and vandetanib. In general, the reported biological activities of quinazolines include anti­bacterial, anti-inflammatory, CNS depressant, anti­convulsant, anti­fungal, anti­malarial, anti­cancer properties, which make them inter­esting for the pharmaceutical industry (Ajani et al., 2015[Ajani, O. O., Isaac, J. T., Owoeye, T. F. & Akinsiku, A. A. (2015). Int. J. Biol. Chem. 9, 148-177.]).

[Scheme 1]

In this context, synthetic analogues of the tricyclic quin­azoline-9-one-7-bromo-2,3-di­hydro­pyrrolo­[2,1-b]quinazolin-9(1H)-one have been synthesized, amongst them the title compound with a bromine atom in position 7. In comparison with a reported literature procedure (Shakhidoyatov, 1983[Shakhidoyatov, Kh. M. (1983). Doctoral Dissertation, University of Moscow, Russia, p. 124.]), this compound is now obtained in higher yields (80–88%). For this purpose, condensation of 2-amino-5-brombenzoic acid with appropriate pyrrolidin-2-one was used whereas in the literature (Shakhidoyatov, 1983[Shakhidoyatov, Kh. M. (1983). Doctoral Dissertation, University of Moscow, Russia, p. 124.]), 2-amino-5-brombenzoic acid was added to the corresponding lactam mixture with a condensing agent (POCl3) at room temperature (293–298 K) and the reaction products separated by extraction after the reaction mixture was reduced to pH = 9–10 with NH4OH. As distinguished from the reported procedure, we carried out these reactions by cooling in an ice bath at a much lower temperature (273–275 K) and for a relatively longer period of time. The reaction products were finally separated by cold NH4OH at pH = 10–11. In general, the inter­actions of 7-bromo-2,3-di­hydro­pyrrolo­[2,1-b]quinazolin-9(1H)-one with aldehydes are well-studied (Abduraza­kov et al., 2007[Abdurazakov, A. Sh., Elmuradov, B. Zh. & Shakhidoyatov, Kh. M. (2007). Uzb. Khim. Zh. 6, 46-50.]).

Here, we report the mol­ecular and crystal structures as well as Hirshfeld surface analysis and the frontier mol­ecular orbitals calculated by density functional theory (DFT) with the B3LYP functional basis set.

2. Structural commentary

The mol­ecular structure of the title compound is shown in Fig. 1[link]. The mol­ecule is almost planar. In particular, the benzene and pyrimidine rings are essentially coplanar, with an r.m.s. deviations of 0.0130 Å from planarity. The remaining atoms of the di­hydro­pyrrole ring are slightly displaced from these planes, with deviations of −0.060 (5) Å for C1, −0.154 (7) Å for flap atom C2, and 0.060 (6) Å for C3. The acyclic C7—Br1 bond length 1.900 (3) Å is consistent with the data for other Br-substituted tricyclic quinazolinone derivatives (Mukarramov et al., 2009[Mukarramov, N. I., Okmanov, R. Ya., Utaeva, F. R., Turgunov, K. K., Tashkhodzhaev, B., Khakimova, Z. M. & Shakhidoyatov, Kh. M. (2009). Chem. Nat. Compd. 45, 854-858.]; Tozhiboev et al., 2007a[Tozhiboev, A. G., Tashkhodzhaev, B., Turgunov, K. K., Mukarramov, N. I. & Shakhidoyatov, Kh. M. (2007a). J. Struct. Chem. 48, 534-539.]; D'yakonov et al., 1992[D'yakonov, A. L., Telezhenetskaya, M. V. & Tashkodzhaev, B. (1992). Chem. Nat. Compd. 28, 200-206.]; Okmanov et al., 2009[Okmanov, R. Ya., Tozhiboev, A. G., Turgunov, K. K., Tashkhodzhaev, B., Mukarramov, N. I. & Shakhidoyatov, Kh. M. (2009). J. Struct. Chem. 50, 382-384.]; Pereira et al., 2005[Pereira, M. F., Picot, L., Guillon, J., Léger, J.-M., Jarry, C., Thiéry, V. & Besson, T. (2005). Tetrahedron Lett. 46, 3445-3447.]).

[Figure 1]
Figure 1
The mol­ecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level.

3. Supra­molecular features

In the crystal, mol­ecules participate in centrosymmetric halogen-bonding dimers with Br⋯Br inter­molecular contacts of 3.5961 (5) Å, which is shorter than the sum of van der Waals radii (Bondi et al., 1964[Bondi, A. (1964). J. Phys. Chem. 68, 441-451.]) of two bromine atoms (3.66 Å). The C7—Br⋯Br angle amounts to 166.70 (14)°. The mol­ecules also engage in weak C7—Br⋯Cg inter­actions, with Br⋯Cg1(2 − x, 1 − y, 1 − z) = 3.6428 (15) Å, forming a layered network (Fig. 2[link]). Additional ππ stacking (Fig. 3[link]) occurs between the aromatic rings of neighbouring mol­ecules, with the distance between the centroids Cg2⋯Cg2i being 3.9969 (14) Å [symmetry code: (i) 1 − x, 1 − y, 1 − z] and a ring slippage of 1.569 Å, and Cg2⋯Cg3ii being 3.7513 (16) Å [symmetry code: (ii) 2 − x, 1 − y, 1 − z] and a ring slippage of 1.194 Å. Both short inter­molecular contacts help to stack parallel mol­ecules along [100]. The resulting two-dimensional network extends parallel to (002), with neighbouring layers linked through C1—H1B⋯N4 short inter­molecular contacts, H1B⋯N4(x, [{1\over 2}] − y, [{1\over 2}] + z) = 2.73 Å, C1—H1B⋯N4(x, [{1\over 2}] − y, [{1\over 2}] + z) = 169°, to form the full three-dimensional structure (Fig. 4[link]).

[Figure 2]
Figure 2
The packing of the title compound in a view perpendicular to (002). Inter­molecular Br⋯Br contacts and C—Br⋯Cg1 are shown as red and green dashed lines, respectively. Cg1 is the centroid of the C1–C3/C3A/N10 ring.
[Figure 3]
Figure 3
The packing of the title compound in a view approximately along [001], showing stacking between adjacent mol­ecules in terms of Cg2⋯Cg2 (blue dashed lines) and Cg2⋯Cg3 (red dashed lines) inter­actions. Cg2 is the centroid (blue sphere) of the pyrimidine ring and Cg3 is the centroid (red sphere) of the benzene ring. H atoms are omitted for clarity.
[Figure 4]
Figure 4
Packing of the title compound along [100], with inter­molecular C—H⋯N contacts shown as light-blue dashed lines.

4. Hirshfeld surface analysis

In order to qu­antify the inter­molecular inter­actions in the crystal of the title compound, a Hirshfeld surface (HS) analysis (Spackman et al., 2009[Spackman, M. A. & Jayatilaka, D. (2009). CrystEngComm, 11, 19-32.]) was performed and associated two-dimensional fingerprint plots (McKinnon et al., 2007[McKinnon, J. J., Jayatilaka, D. & Spackman, M. A. (2007). Chem. Commun. pp. 3814-3816.]) were generated with the program CrystalExplorer (Spackman et al., 2021[Spackman, P. R., Turner, M. J., McKinnon, J. J., Wolff, S. K., Grimwood, D. J., Jayatilaka, D. & Spackman, M. A. (2021). J. Appl. Cryst. 54, 1006-1011.]). The HS mapped over dnorm is depicted in Fig. 5[link], which shows the most prominent inter­molecular inter­actions as red spots corresponding to the Br⋯Br, C—H⋯O and N—H⋯O contacts. The two-dimensional fingerprint plot for all contacts is given in Fig. 6[link]a. H⋯H contacts are responsible for the largest contribution (37.2%) to the Hirshfeld surface (Fig. 6[link]b). Besides these contacts, Br⋯H/H⋯Br (19.6%), O⋯H/H⋯O (11.3%), N⋯H/H⋯N (8.1%) and C⋯H/H⋯C (6.9%) inter­actions contribute significantly to the total Hirshfeld surface; their decomposed fingerprint plots are shown in Fig. 6[link]cf. The contributions of further contacts are only minor and amount to N⋯C/C⋯N (3.5%), O⋯C/C⋯O (2.0%), Br⋯C/C⋯Br (0.9%), Br⋯Br (0.8%), O⋯N/N⋯O (0.5%) and Br⋯N/N⋯Br (0.3%).

[Figure 5]
Figure 5
The Hirshfeld surface of the title compound mapped over dnorm, showing the close contacts.
[Figure 6]
Figure 6
A view of the two-dimensional fingerprint plots for the title compound, showing (a) all inter­actions, and delineated into (b) H⋯H, (c) Br⋯H/H⋯Br, (d) O⋯H/H⋯O, (e) N⋯H/H⋯N and (f) C⋯H/H⋯C inter­actions. The di and de values are the closest inter­nal and external distances (in A°) from given points on the Hirshfeld surface contacts.

5. Frontier mol­ecular orbitals

DFT was used to calculate the frontier mol­ecular orbitals (FMOs, Fig. 7[link]), which give important details of how a mol­ecule inter­acts with other species, for example in terms of mol­ecular reactivity and the ability of a mol­ecule to absorb light. From the highest occupied mol­ecular orbital (HOMO) electrons can be donated to the lowest unoccupied mol­ecular orbital (LUMO). Moreover, the energy of the HOMO is directly related to the ionization potential, while the LUMO energy is directly related to the electron affinity, and the resulting energy difference (or energy gap) between HOMO and LUMO gives information about the stability of a mol­ecule. In the case where the energy gap is small, the mol­ecule is highly polarizable and has a high chemical reactivity. By using the HOMO and LUMO energy values of a mol­ecule, its electronegativity (c), chemical hardness (h) and chemical softness (s) can be calculated as follows: c = (I + A)/2; h = (I - A)/2; s = 1/2h, where I and A are the ionization potential and electron affinity, respectively, where I = –EHOMO and A = –ELUMO (Pir et al., 2014[Pir, H., Günay, N., Avcı, D., Tamer, Ö., Tarcan, E. & Atalay, Y. (2014). Arab. J. Sci. Eng. 39, 5799-5814.]; Azizov et al., 2021[Azizov, Sh., Sharipov, M., Lim, J. M., Tawfik, S. M., Kattaev, N. & Lee, Y. I. (2021). J. Mass Spectrom. 56, e4611-e4620.]).

[Figure 7]
Figure 7
The frontier mol­ecular orbitals (HOMO-LUMO) and the resulting band gap of the title mol­ecule.

EHOMO and ELUMO, electronegativity (c), hardness (h), potential (m), electrophilicity (w) and softness (s) for the title mol­ecule were calculated at the DFT/B3LYP level using the 6-311++G(d,p) basis set (Table 1[link]). The values of h and s are significant for the evaluation of both reactivity and stability. The electron transition from the HOMO to the LUMO energy level is shown in Fig. 7[link]. The energy band gap [ΔE = ELUMO − EHOMO] of the mol­ecule is 4.8208 eV, the frontier mol­ecular orbital energies EHOMO and ELUMO being −6.4559 and −1.6351 eV, respectively. The high value of the band gap (4,8208 eV) indicates the relatively high stability of the title mol­ecule.

Table 1
Calculated parameters of the title mol­ecule calculated at the B3LYP/6–311++G(d,p) level

Parameters DFT/B3LYP
Total energy TE (a.u.) −3183.662028
EHOMO (eV) −6.4559
ELUMO (eV) −1.6351
Energy gap, ΔE (eV) 4.8208
Dipole moment, μ (Debye) 4.6478
Ionization potential, I (eV) 6.4559
Electron affinity, A 1.6351
Electronegativity, χ 4.0455
Hardness, η 2.4104
Electrophilicity index, ω 3.3949
Softness, σ 0.2074

6. Database survey

A search in the Cambridge Structural Database (CSD, version 2022; Groom et al., 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]) gave four matches of mol­ecules containing the 2,3-di­hydro­pyrrolo­[2,1-b]quinazolin-9(1H)-one moiety with a similar conformation to that in the title structure: de­oxy­vasicinone (TEFGEQ; Turgunov et al., 1995[Turgunov, K. K., Tashkhodzhaev, B., Molchanov, L. V. & Aripov, K. N. (1995). Chem. Nat. Compd. 31, 714-718.]), de­oxy­vasicinonium chloride (TEFGIU; Turgunov et al., 1995[Turgunov, K. K., Tashkhodzhaev, B., Molchanov, L. V. & Aripov, K. N. (1995). Chem. Nat. Compd. 31, 714-718.]), bis­(de­oxy­vasicinonium) tetra­chlorido­cobaltate(II) (TEFGOA; Turgunov et al., 1995[Turgunov, K. K., Tashkhodzhaev, B., Molchanov, L. V. & Aripov, K. N. (1995). Chem. Nat. Compd. 31, 714-718.]) and 4-oxo-2,3-tetra­methyl­ene-3,4-di­hydro­quinazolinium 2,3-tetra­methyl­ene-3,4-di­hydro­quinazol-4-one hemikis(oxalate) oxalic acid solvate (TITGUZ; Tozhiboev et al., 2007b[Tozhiboev, A. G., Turgunov, K. K., Tashkhodzhaev, B. & Shakhidoyatov, Kh. M. (2007b). Chem. Nat. Compd. 43, 184-189.]). A search for compounds substituted in position 7 of 2,3-di­hydro­pyrrolo­[2,1-b]quinazolin-9(1H)-one moiety gave only two hits: N-(9-oxo-1,2,3,9-tetra­hydro­pyrrolo­[2,1-b]quinazolin-7-yl)propanamide sesquihydrate (GABJAX; Elmuradov et al., 2016[Elmuradov, B. Zh., Shakhidoyatov, Kh. M., Drager, G. & Butenschon, H. (2016). Eur. J. Org. Chem. pp. 483-492.]) and 3b-hy­droxy-7-meth­oxy-2,3-di­hydro­pyrrolo­[2,1-b]quinazolin-9(1H)-one mono­hydrate (HIHLIT; Magotra et al., 1996[Magotra, D. K., Gupta, V. K., Rajnikant, Goswami, K. N., Thappa, R. K. & Agarwal, S. G. (1996). Acta Cryst. C52, 1491-1493.]). Comparing the listed structures with that of the title compound gave analogous complanarities of the benzene and pyrimidine rings. In the case of structures TEFGEQ, GABJAX and HIHLIT they have also similarities regarding ππ stacking inter­actions.

7. Synthesis and crystallization

The reaction scheme to yield the title compound is shown in Fig. 8[link]. To a mixture of 4.32 g (20 mmol) 2-amino-5-bromo­benzoic acid and 2.72 g (32 mmol) pyrrolidin-2-one, 21.8 g (13 ml) (d = 1.675) (0.142 mol) of phospho­roxychloride were added dropwise over 1 h at 273–275 K. The reaction mixture was then heated at 368–371 K for 2 h, it was subsequently cooled and finally poured over ice. The temperature of the mixture was kept at around 273–275 K. When the reaction mixture was completely decomposed, it was brought to pH = 10–11 with 25%wt ammonium hydroxide solution. The light-yellow precipitate was filtered off, dried and recrystallized from methanol. The yield of the product was 4.35 g (82%), m.p. 431–433 K (literature, m.p. = 430–431 K; Shakhidoyatov, 1983[Shakhidoyatov, Kh. M. (1983). Doctoral Dissertation, University of Moscow, Russia, p. 124.]).

[Figure 8]
Figure 8
The reaction scheme of the title compound.

1H NMR (400 Mz, CDCl3, δ, ppm): 8.4 (1H, d, J = 2.4, H-8), 7.8 (1H, dd, J = 2.4, J = 8.8, H-6), 7.5 (1H, d, J = 8.8, H-5), 4.2 (2H, q, J = 7.2, H-1), 3.18 (2H, t, J = 7.6, H-3), 2.31 (2H, m, H-2).

8. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link]. H atoms attached to C were positioned geometrically, with C—H = 0.93 Å (for aromatic) or C—H = 0.97 Å (for methyl­ene H atoms), and were refined with Uiso(H) = 1.2Ueq(C).

Table 2
Experimental details

Crystal data
Chemical formula C11H9BrN2O
Mr 265.11
Crystal system, space group Monoclinic, P21/c
Temperature (K) 296
a, b, c (Å) 7.5654 (3), 11.4972 (2), 12.1025 (3)
β (°) 105.583 (3)
V3) 1013.99 (5)
Z 4
Radiation type Cu Kα
μ (mm−1) 5.30
Crystal size (mm) 0.45 × 0.10 × 0.10
 
Data collection
Diffractometer XtaLAB Synergy, Single source at home/near, HyPix3000
Absorption correction Multi-scan (CrysAlis PRO; Rigaku OD, 2020[Rigaku OD (2020). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.])
Tmin, Tmax 0.400, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections 9036, 1959, 1770
Rint 0.035
(sin θ/λ)max−1) 0.615
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.036, 0.099, 1.08
No. of reflections 1959
No. of parameters 137
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.61, −0.56
Computer programs: CrysAlis PRO (Rigaku OD, 2020[Rigaku OD (2020). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]), SHELXS (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), SHELXL (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. A71, 3-8.]), PLATON (Spek, 2020[Spek, A. L. (2020). Acta Cryst. E76, 1-11.]) and publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

Supporting information


Computing details top

Data collection: CrysAlis PRO (Rigaku OD, 2020); cell refinement: CrysAlis PRO (Rigaku OD, 2020); data reduction: CrysAlis PRO (Rigaku OD, 2020); program(s) used to solve structure: SHELXS (Sheldrick, 2008); program(s) used to refine structure: SHELXL (Sheldrick, 2015); molecular graphics: PLATON (Spek, 2020); software used to prepare material for publication: publCIF (Westrip, 2010).

7-Bromo-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one top
Crystal data top
C11H9BrN2OF(000) = 528
Mr = 265.11Dx = 1.737 Mg m3
Monoclinic, P21/cCu Kα radiation, λ = 1.54184 Å
a = 7.5654 (3) ÅCell parameters from 5905 reflections
b = 11.4972 (2) Åθ = 3.8–71.3°
c = 12.1025 (3) ŵ = 5.30 mm1
β = 105.583 (3)°T = 296 K
V = 1013.99 (5) Å3Prismatic, colourless
Z = 40.45 × 0.10 × 0.10 mm
Data collection top
XtaLAB Synergy, Single source at home/near, HyPix3000
diffractometer
1959 independent reflections
Radiation source: micro-focus sealed X-ray tube1770 reflections with I > 2σ(I)
Detector resolution: 10.0000 pixels mm-1Rint = 0.035
ω scansθmax = 71.5°, θmin = 5.4°
Absorption correction: multi-scan
(CrysAlisPro; Rigaku OD, 2020)
h = 99
Tmin = 0.400, Tmax = 1.000k = 1413
9036 measured reflectionsl = 1414
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.036 w = 1/[σ2(Fo2) + (0.0459P)2 + 0.6636P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.099(Δ/σ)max = 0.005
S = 1.08Δρmax = 0.61 e Å3
1959 reflectionsΔρmin = 0.56 e Å3
137 parametersExtinction correction: SHELXL-2018/3 (Sheldrick 2015), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
0 restraintsExtinction coefficient: 0.0045 (4)
Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
Br0.90737 (5)0.85845 (3)0.51410 (4)0.0772 (2)
O0.6024 (3)0.46212 (19)0.28785 (15)0.0704 (6)
C10.5525 (4)0.2291 (2)0.3474 (2)0.0524 (6)
H1A0.6157150.2178620.2882810.063*
H1B0.4241820.2452930.3111480.063*
C20.5725 (5)0.1238 (3)0.4234 (3)0.0646 (8)
H2A0.6608040.0700680.4066880.077*
H2B0.4557140.0840940.4111000.077*
C30.6385 (5)0.1665 (2)0.5467 (2)0.0573 (7)
H3A0.5412870.1605670.5848740.069*
H3B0.7428540.1213170.5892880.069*
C3A0.6916 (4)0.2907 (2)0.53807 (19)0.0428 (5)
N40.7726 (4)0.35675 (17)0.62262 (17)0.0503 (5)
C4A0.8027 (3)0.4710 (2)0.59434 (19)0.0424 (5)
C50.8937 (4)0.5471 (2)0.6820 (2)0.0569 (7)
H50.9327970.5199680.7570500.068*
C60.9258 (4)0.6610 (2)0.6588 (2)0.0554 (7)
H60.9861510.7108370.7173970.066*
C70.8667 (4)0.7005 (2)0.5464 (2)0.0490 (6)
C80.7793 (4)0.6286 (2)0.4582 (2)0.0486 (6)
H80.7420350.6564760.3833670.058*
C8A0.7471 (3)0.5135 (2)0.48227 (19)0.0403 (5)
C90.6560 (3)0.4355 (2)0.38867 (19)0.0451 (5)
N100.6368 (3)0.32406 (18)0.42522 (15)0.0405 (4)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Br0.0940 (3)0.0341 (2)0.1020 (4)0.00671 (14)0.0235 (2)0.00799 (14)
O0.1104 (17)0.0553 (12)0.0345 (9)0.0020 (11)0.0007 (10)0.0064 (8)
C10.0651 (16)0.0489 (15)0.0402 (12)0.0045 (12)0.0089 (11)0.0130 (11)
C20.090 (2)0.0478 (16)0.0519 (16)0.0179 (15)0.0121 (15)0.0119 (12)
C30.088 (2)0.0401 (13)0.0432 (13)0.0170 (13)0.0171 (13)0.0026 (11)
C3A0.0572 (14)0.0365 (12)0.0347 (11)0.0038 (10)0.0121 (10)0.0004 (9)
N40.0768 (15)0.0375 (12)0.0338 (10)0.0096 (9)0.0099 (10)0.0008 (8)
C4A0.0548 (13)0.0338 (12)0.0377 (11)0.0018 (10)0.0110 (10)0.0000 (9)
C50.0807 (19)0.0420 (14)0.0412 (12)0.0082 (13)0.0047 (12)0.0026 (11)
C60.0657 (16)0.0411 (13)0.0557 (15)0.0073 (12)0.0100 (13)0.0097 (11)
C70.0530 (14)0.0315 (12)0.0638 (15)0.0004 (10)0.0177 (12)0.0019 (11)
C80.0595 (15)0.0385 (13)0.0476 (13)0.0059 (10)0.0142 (11)0.0086 (10)
C8A0.0473 (12)0.0363 (12)0.0375 (11)0.0042 (9)0.0116 (9)0.0011 (9)
C90.0571 (14)0.0407 (13)0.0354 (11)0.0060 (10)0.0090 (10)0.0027 (9)
N100.0515 (11)0.0373 (10)0.0317 (9)0.0017 (8)0.0093 (8)0.0033 (8)
Geometric parameters (Å, º) top
Br—C71.900 (3)C3A—N101.371 (3)
O—C91.217 (3)N4—C4A1.392 (3)
C1—N101.471 (3)C4A—C8A1.396 (3)
C1—C21.503 (4)C4A—C51.404 (3)
C1—H1A0.9700C5—C61.375 (4)
C1—H1B0.9700C5—H50.9300
C2—C31.522 (4)C6—C71.389 (4)
C2—H2A0.9700C6—H60.9300
C2—H2B0.9700C7—C81.371 (4)
C3—C3A1.494 (4)C8—C8A1.391 (3)
C3—H3A0.9700C8—H80.9300
C3—H3B0.9700C8A—C91.464 (3)
C3A—N41.290 (3)C9—N101.376 (3)
N10—C1—C2104.5 (2)N4—C4A—C5118.8 (2)
N10—C1—H1A110.8C8A—C4A—C5118.3 (2)
C2—C1—H1A110.8C6—C5—C4A121.1 (2)
N10—C1—H1B110.8C6—C5—H5119.4
C2—C1—H1B110.8C4A—C5—H5119.4
H1A—C1—H1B108.9C5—C6—C7118.9 (2)
C1—C2—C3107.0 (2)C5—C6—H6120.6
C1—C2—H2A110.3C7—C6—H6120.6
C3—C2—H2A110.3C8—C7—C6121.8 (2)
C1—C2—H2B110.3C8—C7—Br119.1 (2)
C3—C2—H2B110.3C6—C7—Br119.1 (2)
H2A—C2—H2B108.6C7—C8—C8A119.0 (2)
C3A—C3—C2105.3 (2)C7—C8—H8120.5
C3A—C3—H3A110.7C8A—C8—H8120.5
C2—C3—H3A110.7C8—C8A—C4A120.8 (2)
C3A—C3—H3B110.7C8—C8A—C9119.6 (2)
C2—C3—H3B110.7C4A—C8A—C9119.6 (2)
H3A—C3—H3B108.8O—C9—N10121.4 (2)
N4—C3A—N10125.3 (2)O—C9—C8A125.6 (2)
N4—C3A—C3125.9 (2)N10—C9—C8A112.97 (19)
N10—C3A—C3108.8 (2)C3A—N10—C9123.4 (2)
C3A—N4—C4A115.8 (2)C3A—N10—C1113.1 (2)
N4—C4A—C8A122.9 (2)C9—N10—C1123.41 (19)
N10—C1—C2—C39.8 (4)C5—C4A—C8A—C80.7 (4)
C1—C2—C3—C3A11.4 (4)N4—C4A—C8A—C91.2 (4)
C2—C3—C3A—N4172.4 (3)C5—C4A—C8A—C9178.5 (2)
C2—C3—C3A—N108.8 (3)C8—C8A—C9—O0.4 (4)
N10—C3A—N4—C4A0.9 (4)C4A—C8A—C9—O179.6 (3)
C3—C3A—N4—C4A177.8 (3)C8—C8A—C9—N10178.8 (2)
C3A—N4—C4A—C8A1.0 (4)C4A—C8A—C9—N100.3 (3)
C3A—N4—C4A—C5178.7 (3)N4—C3A—N10—C92.6 (4)
N4—C4A—C5—C6179.6 (3)C3—C3A—N10—C9176.2 (2)
C8A—C4A—C5—C60.7 (4)N4—C3A—N10—C1178.4 (3)
C4A—C5—C6—C70.0 (5)C3—C3A—N10—C12.7 (3)
C5—C6—C7—C80.7 (4)O—C9—N10—C3A178.6 (3)
C5—C6—C7—Br179.0 (2)C8A—C9—N10—C3A2.1 (3)
C6—C7—C8—C8A0.8 (4)O—C9—N10—C10.3 (4)
Br—C7—C8—C8A179.02 (19)C8A—C9—N10—C1179.0 (2)
C7—C8—C8A—C4A0.1 (4)C2—C1—N10—C3A4.5 (3)
C7—C8—C8A—C9179.2 (2)C2—C1—N10—C9176.5 (2)
N4—C4A—C8A—C8179.6 (2)
Calculated parameters of the title molecule calculated at the B3LYP/6-311++G(d,p) level top
ParametersDFT/B3LYP
Total energy TE (a.u.)-3183.662028
EHOMO (eV)-6.4559
ELUMO (eV)-1.6351
Energy gap, ΔE (eV)4.8208
Dipole moment, µ (Debye)4.6478
Ionization potential, I (eV)6.4559
Electron affinity, A1.6351
Electronegativity, χ4.0455
Hardness, η2.4104
Electrophilicity index, ω3.3949
Softness, σ0.2074
 

Acknowledgements

The authors thank the Institute of Bioorganic Chemistry of Academy Sciences of Uzbekistan, Tashkent, Uzbekistan for providing the single-crystal XRD facility.

Funding information

Funding for this research was provided by: the Ministry of Innovative Development of Uzbekistan (grant No. F-FA-2021-408 "Study of the laws of introducing of pharmacophore fragments into the mol­ecule on the basis of modern cross-coupling and heterocyclization reactions").

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