Quinazolinone is the building unit of nearly 150 naturally occurring alkaloids isolated from microorganisms, plants and animals [1]. It is a very important heterocycle exhibiting excellent pharmacological activities such as antimicrobial [2], antifungal [3], antitumor [4], anticancer [5], antiinflammatory [6], antidepressant [7] and anticonvulsant [8] activities. 3-Aryl-2-thioxo-2,3-dihydroquinazolin-4(1H)-one are a subclass quinazolinones having a wide range of applications including pharmacological and biological activities and important building blocks a variety of heterocycles [9]. Thus altanserin (3-(2-(4-(4-fluorobenzoyl)-l-piperidinyl)-ethyl)-2,3-dihydro-2-thioxo-1H-quinazolin-4-one) and nitroaltanserin are used as drugs for 5-HT2A receptor antagonists [10]. 2-Thioxo-1H-4-quinazolinones are also versatile intermediates for fused heterocycloquinazolines like 2-phenyl-5H-[1,3,4]thiadiazolo[2,3-b]quinazolin-5-one, 3-(4-bromo phenyl)-2H,6H-[1,3,4]thiadiazino- [2,3-b] quinazolin-6-one, 4-amino-2-phenyl-3a,4-dihydro-2H-thiazolo[3,2-a]quinazoline-1,5-dione and 2-phenyl-[1,3,4]thiadiazino[2,3-b] quinazoline-3,6(2H,4H)-diones [11]. Two approaches for the solution-phase parallel synthesis of 2-thioxoquinazolin-4-ones include the reaction of methyl anthranilates with isothiocyanates in refluxing pyridine or DMF and reacting 2-(methylcarboxy)-benzene isothiocyanates in isopropyl alcohol with different aliphatic amines or anilines [12]. Herein we report a convenient method for synthesis of these compounds by base catalyzed intramolecular nucleophilic cyclization of 1-aroyl-3-arylthioureas.

The reaction sequence leading to the formation of title heterocycle is outlined in Figure 1. The base catalyzed intramolecular nucleophilic cyclization of 1-(2-bromobenzoyl)-3-(2-fluorophenyl)thiourea (1) was achieved using sodium tertiary butoxide in the presence of dry DMF by heating at 70–80 °C for 3 h under nitrogen to afford (2) which was recrystallized from ethanol as colorless crystals.

IR spectral data of (2) shows the characteristic single broad N-H peak in the range 3265 cm⁻¹ and a sharp C=O peak at 1650 cm⁻¹ which are relatively at higher wave number compared to the parent thiourea; aromatic absorptions appear at 1603 cm⁻¹, while those for C-S and C-N at 1249 cm⁻¹ and 1136 cm^-1 respectively. ¹H-NMR shows characteristic broad singlet for N-H at δ 10.8 in addition to those due to aromatic protons at δ 6.55–8.3 ppm [13]. In ¹³C-NMR spectrum characteristic peaks for C=S appears downfield as compared to C=O in contrast to the trend in thioureas where the C=O resonates at relatively low field while the C=S resonates up field; thus C=S appears at δ 177, C=O appears at δ 168.9 and C-F couplings appear in the range ¹J_C-F = 247 Hz, ²J_C-F = 22–24 Hz, ³J_C-F = 6–14 Hz and ⁴J_C-F = 3.75 Hz.

There are two crystallographically independent molecules A and B per asymmetric unit which exhibit almost equal geometries. Both the fluorophenyl rings make dihedral angles of 86.3(1)° (A) and 82.6(1)° (B) with the corresponding quinazoline planes. C=O and S=O bond lengths of av. 1.231(4) and 1.666(4) Å, respectively, correspond well to those from CCDC reference JESWEK [14] with equal thioxo group (Figure 2).

In the crystal packing molecules A and B are linked to centrosymmetric AB-dimers (Figure 3) via intermolecular N-H…S hydrogen bonds N12-H…S2 (−x + 0.5, y + 0.5,z − 0.5) with N…S of 3.374(3) Å and N22-H…S1 (−x + 0.5, y − 0.5, z + 0.5) with N…S of 3.272(3) Å, resp.

Melting points were recorded using a digital Gallenkamp (SANYO) model MPD BM 3.5 apparatus and are uncorrected. ¹H NMR spectra were determined as CDCl₃ solutions at 300 MHz using a Bruker Mass Spectra (EI, 70 eV) on a GC-MS instrument. All compounds were purified by thick layer chromatography using silica gel from Merck.

Synthesis, characterization, crystal and molecular structure of a novel medicinally and synthetically important heterocycle have been described.