Reactions of heterocycles with thiophosgene. Part VI. Reactions of tetrahydropyrazolo[1,5-c]quinazolines

Hull, Roy; Swain, Michael L.

doi:10.1039/p19760000653

Cited by 20 publications

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“…2-Bromo-3H-quinazolin-4-one 26 was prepared by an adapted literature procedure from 2-mercapto-3H-quinazolin-4-one 24. 34 Alkylations with activated halides, e.g. benzyl bromide, allyl bromide and methyl iodide were successful but alkylations with unactivated halides were very poor or failed.…”

Section: H-4-oxoquinazolin-2-yl Radical Cyclisationmentioning

confidence: 99%

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Radical reactions with 3H-quinazolin-4-ones: synthesis of deoxyvasicinone, mackinazolinone, luotonin A, rutaecarpine and tryptanthrin

et al. 2007

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Alkyl, aryl, heteroaryl and acyl radicals have been cyclised onto the 2-position of 3H-quinazolin-4-one. The side chains containing the radical precursors were attached to the nitrogen atom in the 3-position. The cyclisations take place by aromatic homolytic substitution hence retain the aromaticity of the 3H-quinazolin-4-one ring. The highest yields were obtained using hexamethylditin to facilitate cyclisation rather than reduction without cyclisation. The alkaloids deoxyvasicinone 2, mackinazolinone 3, tryptanthrin 4, luotonin A 5 and rutaecarpine 8 were synthesised by radical cyclisation onto 3H-quinazolin-4-one.The 3H-quinazolin-4-one ring system is important to the biological activity of both naturally occurring alkaloids, biosynthesised from anthranilic acid, and pharmaceuticals. The alkaloids include vasicinone 1 and deoxyvasicinone 2, 1 mackinazolinone 3, 2 tryptanthrin 4, 3 luotonins A 5, B 6 and E 7 4 and rutaecarpine 8. 5 3H-Quinazolin-4-one alkaloids have been recently reviewed. 6 All the 3H-quinazolin-4-one natural products have interesting biological activity and have therefore been extensively investigated for useful pharmaceutical activity. The 3H-quinazolin-4-one ring is regarded as a 'privileged structure' in combinatorial synthesis. 7 These are structures which represent molecules that are capable of binding at multiple sites with high affinity and facilitate more rapid discovery of useful medicinally active compounds. 7Our study involved the development of protocols involving radical cyclisation for the synthesis of polycyclic 3H-quinazolin-3-ones (Scheme 1). The protocols have also been used for the synthesis of novel polycyclic quinazolinones including the natural Department of Chemistry, Loughborough University, Loughborough, Leics, UK LE11 3TU. E-mail: g.w.weaver@lboro.ac.uk; Fax: 44(0) 1509 223925; Tel: 44(0) All of the above cyclisations are 'oxidative' i.e. the intermediate p-radicals are not reduced by triorganometal hydrides [e.g. tributyltin hydyride (Bu 3 SnH)] as normally observed for these reagents. The cyclisations proceed by aromatic homolytic substitution with abstraction of hydrogen in a rearomatisation process. Aromatic homolytic substitution has been recently reviewed 27 and the mechanism of Bu 3 SnH mediated 'oxidative' cyclisation elaborated. 28 The pyrimidin-4-one ring of the quinazolin-4-ones has some aromaticity and therefore aromatic homolytic substitution could be predicted, and was observed in our studies, as shown in Scheme 1 (9 to 11 via the p-radical 10). However, the lower aromaticity could favour reductive cyclisation in which the intermediate p-radical 10 is intercepted by reagents such as Bu 3 SnH. Our prediction that radical cyclisation onto the quinazolin-4-one ring would be 'oxidative' was supported by the 'oxidative' radical cyclisation onto related ring systems, e.g. pyrimidine-2,4-diones, 23,24This journal is

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Section: H-4-oxoquinazolin-2-yl Radical Cyclisationmentioning

confidence: 99%

“…Hexamethylditin. The general procedure for reactions using photolysis and hexamethylditin yielded 5,6-dihydroisoquino [ (20), 116 (46), 104 (30), 90 (34), 89 (62), 77 (85), 76 (97), 63 (53) and 39 (54). One CH signal was coincident or could not be detected.…”

Section: Cyclisation Reactions Of 3-[2-(bromophenyl)ethyl]-3h-quinazo...mentioning

confidence: 99%

Radical reactions with 3H-quinazolin-4-ones: synthesis of deoxyvasicinone, mackinazolinone, luotonin A, rutaecarpine and tryptanthrin

et al. 2007

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“…ESI-HRMS spectra were measured with an ion trap mass spectrometer. o -Isothiocyanato-( E )-cinnamaldehydes 1 were prepared according to literature procedures. , …”

Section: Methodsmentioning

confidence: 99%

Chemoselective Synthesis of Structurally Diverse 3,4-Dihydroquinazoline-2(1H)-thiones and 4H-Benzo[d][1,3]thiazines

Dong

Wei

et al. 2018

J. Org. Chem.

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An efficient, mild, and substrate/catalyst-controlled chemoselective reaction of o-isothiocyanato-(E)-cinnamaldehyde with amines has been established, producing three types of six-membered heterocycles: 2-(4H-benzo[d][1,3]thiazin-4-yl)acetaldehydes, 2-(2-thioxo-1,2,3,4-tetrahydroquinazolin-4-yl)acetaldehydes, and (E)-4-(2-methoxyvinyl)-4H-benzo[d][1,3]thiazines. The reaction scopes were quite broad and excellent yield was achieved. This method is extremely efficient and practical and can be conducted on a gram-scale with slightly inferior reactivity under catalyst-free conditions at low cost, making it an ideal alternative to existing methods.

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o ‐Isothiocyanato‐( E )‐Cinnamaldehyde

Farrand¹,

Hull²

2003

Organic Syntheses

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Reactions of heterocycles with thiophosgene. Part VI. Reactions of tetrahydropyrazolo[1,5-c]quinazolines

Cited by 20 publications

References 0 publications

Radical reactions with 3H-quinazolin-4-ones: synthesis of deoxyvasicinone, mackinazolinone, luotonin A, rutaecarpine and tryptanthrin

Radical reactions with 3H-quinazolin-4-ones: synthesis of deoxyvasicinone, mackinazolinone, luotonin A, rutaecarpine and tryptanthrin

Chemoselective Synthesis of Structurally Diverse 3,4-Dihydroquinazoline-2(1H)-thiones and 4H-Benzo[d][1,3]thiazines

o ‐Isothiocyanato‐( E )‐Cinnamaldehyde

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