Quinazolin-4 3H -ones

Comparative results have been obtained in the synthesis of 3H-quinazolin-4-one [100]. The fusion of anthranilic acid with formamide led to the formation of an o-amidine intermediate and usually proceeded by intramolecular cyclization (Eq. 15) ... 

The Niementowski synthesis of the 3H-quinazolin-4-one core was re-investigated by Besson and coworkers using microwave irradiation [96]. It enabled significant rate enhancements and good yields compared with conventional reaction conditions. 

Storelli, S., Verdijk, P., Verzijl, D., Timmerman, H van de Stolpe, A.C., Tensen, C.P., Smit, M.J., De Esch, I.J.P. et al. (2005) Synthesis and structure-activity relationship of 3-phenyl-3H-quinazolin-4-one derivatives as CXCR3 chemokine receptor antagonists. Bioorganic Medicinal Chemistry Letters. 15, 2910-2913. 

Rajan S G et al. [74] designed and S3mthesized a sequence of 2-(2,4-disubstituted-thiazole-5-yl)-3-aryl-3H-quinazoline-4-one 23 compounds. S3mthesized molecules were estimated for their inhibitory activity in the course of record factors, nuclear factor-kB (NF-kB) and activating factor (AP-1) interceded transcriptional activation in a cell line based in vitro assay as well as for their anti-inflammatory activity in vivo model of severe inflammation. 

Rajan S, Hardik G, Thaker M, Tony G, Kamala K. V. Design, synthesis and characterization of novel 2-(2,4-disubstituted-thiazole-5-yl)-3-aryl-3H-quinazoline-4-one derivatives as inhibitors of NF-kB and AP-1 mediated transcription activation and as potential anti-inflammatory agents, Eur. J. Med. Chem. 2009. p. 2184 - 2189. DOI 10.1016/i.ejmech.2008.10.031... 

A synthetic method for 2-alkoxy-3H-quinazolin-4-ones was reported by Ding et al. in 2004 [54], In this study, 12 novel 2-alkoxy-3H-quinazolin-4-ones were synthesized from carbodiimide, which was obtained from aza-Wittig reaction of iminophosphorane with aromatic isocynate (Scheme 13.13). 

Dabiri and Mostafa reported [57] a rapid, efficient, and one-pot procedure for the synthesis of mono- and di-substituted (3H)-quinazolin-4-ones in the presence of an AlClg/ZnClj mixture supported on siUca gel, under solvent-free eonditions or water. 

Alagarsamy V, Solomon VR, Dhanabal K (2007) Synthesis and pharmacological evaluation of some 3-phenyl-2-substituted-3H -quinazolin-4-one as analgesic, anti-inflammatory agents. Bioorg Med Chem 15 235-241... 

Nandy P, Vishalakshi MT, Bhat AR (2006) Synthesis and antitubercular activity of Mannich bases of2-methyl-3H-quinazolin-4-ones. Indian J Heterocycl Chem 15 293-294 Saravanan G, Alagarsamy V, Prakash CR (2010) Synthesis and evaluation of antioxidant aetivities of novel quinazoline derivatives. Int J Pharm Pharm Sci 2 83-86 Lakhan R, Singh OP, Singh-J RL (1987) Studies on 4 (3H)-quinazolinone derivatives as anti-malarials. J Indian Chem Soc 64 316-318... 

Ding MW, Yang SJ, Chen YF (2004) Synthesis and fungicidal activities of 2-alkoxy-3H-quinazolin-4-ones. Chin J Oig Chem 24 923 926... 

A number of 2-hydrazino-3-phenylquinazoHn-4(3H)-ones 27 prefer in DMSO-dj solution the imino form 27b (Scheme 5.21) following the tautomeric preferences of aminoguanidines [59]. 3-Hydrazino-3-phenyl-3H-quinazolin-4-one itself (28) is in the amino form. To assign the tautomers, 5( N) of N-1 has been employed because of the circa 100 ppm chemical shift difference [27b 5( N) 99.7-113.9 ppm 28 ... 

The carbanion derived from 3-(o-chlorophenyl)-2-methyl-3H-quinazolin-4-one cyclizes in liquid ammonia under irradiation to yield 6H-indolo[2,l-h]quinazolin-12-one 20 (60%) " ... 

The same authors have described a related Niementowski condensation for the preparation of 3H-nitroquinazolin-4-ones. Subsequent manipulation of this structure led to 8H-thiazolo[5,4-/ quinazolin-9-ones through a series of open-vessel microwave-assisted transformations, as indicated in Scheme 6.251 [205, 438]. 

A similar rapid microwave one-pot synthesis of substituted quinazolin-4-ones was also reported, which involved cyclocondensation af anthranilic acid, formic acid (or an orthoester) and an amine under solvent-free conditions (Scheme 3.37)61. A complimentary approach was adopted to synthesise 4-aminoquinazolines in very good yields, involving the reaction of aromatic nitrile compounds with 2-aminobenzonitrile in the presence of a catalytic amount ofbase (Scheme 3.38)62. The reactions were performed in a domestic microwave oven and required only a very short heating time. A microwave-assisted synthesis of a variety of new 3-substituted-2-alkyl-4-(3H)-quinazolinones using isatoic anhydride, 2-aminobenzimidazole and orthoesters has also been described (Scheme 3.38)63. 

An acetoxy moiety, present in a side chain in the position 9 on 7-oxo-lH,3H,7H-pyrido[3,2,l-zy][3,l]benzoxazine skeleton, was hydrolyzed under basic condition to yield a hydroxy derivative (07WOP2007/ 054296). Phtalimido, and benzyloxycarbonylamino (07JP2007131577) and ferf-butoxycarbonylamino groups (06WOP2006/050940, 06WOP2006/ 050943), present in a side chain on pyrido[3,2,l-zy][3,l]benzoxazin-7-one and pyrido[3,2,l-zy]quinazolin-4-one skeletons, were converted to an... 

Methoxide converted a series of X-phenyl iV-(4-thiocarboxamidophenyl)carbamates (32 X = 4-MeO, 3-MeO, 4-C1, 3-C1, H) into methyl )V-(4-thiocarboxamidophenyl) carbamate (33) and the corresponding phenate via an E cB mechanism (Scheme 11). However, when a series of the corresponding aryl )V-(2-thiocarboxamidophenyl)car-bamates (34 R1 = H, R2 = 4-MeO, 3-MeO, 4-Me, 3-C1, 4-C1, 3-N02, H) were treated similarly, a rapid intramolecular cyclization occurred to give 4-thioxo-lH,3H-quinazolin-2-one (35 R1 = H) and the corresponding phenate (Scheme 12). All the... 

Methylquinazolin-4(3//)-one was obtained in over 62% yield by reacting the phosphorane (25) with sodium hydride in methyl cyanide. The phos-phorane was readily formed from anthranilamide and prop-2-ynyltriphenyl-phosphonium bromide. When anthranilamide was fused with benzoin and a trace of acid at 150°C, it gave 2-phenylquinazolin-4(3H)-one together with o-iV-(a-benzoyl benzyl)aminobenzamide. The latter was cyclized, with ethyl orthoformate, to l-(a-benzoylbenzyl)quinazolin-4-one. If anthranilamide and benzoin were boiled in benzene with azeotropic removal of water, then the Schiff base (26) was formed. This gave 2-phenylquinazolin-4(3Jf/)-one and benzoic acid on heating alone at 150°C or with ethyl orthoformate. The mechanism of this reaction is not clear unless a retro-benzoin condensation and oxidation are occurring. 

Further examples have appeared in which N-3 of quinazolin-4-one was exchanged with amino groups from amines. 6,8-Dichloroquinazolin-4(3H)-one reacted with amphetamine to generate 13% of 6,8-dichloro-3(l-methyl-2-phenylethyl)quinazolin-4-one and when it was treated with ethanolamine it produced 6,8-dichloro-3-2 -hydroxyethylquinazolin-4-one and 6-chloro-8-2 -hydroxyethylaminoquinazolin-4-one in 21% and 13% yields, respectively. " ... 

Quinazoline-2,4-diones, ° octahydroquinazoline-2,4-diones (herbicides), and 3-0-carbonate esters of quinazolin-4-ones (fungicides) were tested for agricultural purposes, and 2-phenyl-l,2-dihydroquinazolin-4(3H)-one had insecticidal activity with a possible use for controlling the... 

The preparation of quinazoline-2(and 4)-thiones follows those of the corresponding pyrimidines (67HC(24-1)270) but there is at least one special primary synthesis for quinazoline-4(3H)-thiones, illustrated by the reaction of o-aminobenzonitrile with thioacetic acid at 110 °C to give 2-methylquinazoline-4(3H)-thione in 90% yield (53JA675). 

Quinazolin-4(3H)-one, 3-phenyl-reduction, 3, 75 Quinazolinones polymers, 1, 298 reactions, 3, 89 structure, 3, 66-67 synthesis, 2, 96 3, 133 thiation, 3, 89 Quinazolin-4-oties 2,3-disubstituted Grimmel synthesis, 3, 109 mass spectra, 2, 22... 

A series of novel l-substituted-4-phenyl-l,2,3-triazolo(4,3-a)quinazolin-5(4H)-ones 1 were synthesized by the cyclization of 2-hydrazino-3-phenyl-quinazolin-4(3H) 2 with various one carbon donors. The starting material 2-hydrazino-3-phenylquinazolin-4(3H)-one 2, was synthesized from aniline 7 by a novel innovative route. When tested for their in vivo Hi-antihistaminic activity on conscious guinea pigs all the test compounds protected the animals from histamine-induced bronchospasm significantly, whereas the compound l-methyl-4-phenyl-l,2,3-triazolo(4,3-a)quinazolin-5(4H)-one lb (percentage protection 70.7%) was found to be equipotent with the reference standard chlorpheniramine maleate (percentage protection 71%). These compounds show negligible sedation (5%) when compared to the reference standard (26%). Hence they could serve as prototype molecules for future development [1,4,5]. 

The key intermediate 2-thioxo-3-phenylquinazohn-4(3H)-one was prepared by adding carbon disulfide and sodium hydroxide solution simultaneously to a vigorously stirred solution of aniline 7 in dimethylsulfoxide over 30 min stirring was then continued for an additional 30 min. Dimethylsulfate was added to the reaction mixture whilst stirring at 5-10°C after which it was stirred for another 2 h and then poured into ice water to obtain a soHd dithiocarbamic acid methylester 6. The compoimd 6 and methylanthranilate 5 when refluxed in ethanol for 18 h yielded the desired 2-thioxo-3-substituted quinazolin-4(3H)-one 4. The product obtained was cycUc and not an open chain thiourea 5a. It was confirmed by its value, high melting point, and its... 

The 2-methylthio-3-substituted quinazolin-4(3H)-one 3 was obtained by dissolving 4 in 2% alcoholic sodium hydroxide solution and methylating with dimethylsulfate whilst stirring at room temperature (yield 88%, m.p 124-126 C). The IR spectrum of 3 showed the disappearance of the amino (NH) and thioxo (CS) stretching signals of the starting materials. It showed a peak for carbonyl (CO) stretching at 1680 cm The NMR spectriun of com-... 

Rad-Moghadam, K. and Khajavi, M.S., One-pot synthesis of substituted quinazolin-4(3H)-ones under microwave irradiation,/. Chem. Res., 1998, 702-703. 

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