Quinazolin-4 -imines

Ethyl propiolate or DMAD and the quinazoline imine (452) give a complex mixture.431... 

Tetracyelie derivatives 215 formed exclusively from imines 213 on the action of TMSOTf, whereas in the presence of TiCl4 both l//-pyrido[l,2-c]quinazolin-6-ones 214, as a >9 1 mixture of a//3 ehloro epimers, and tetraeyelie derivatives 215 were obtained. Imine 213 (R = H) gave a 3 1... 

Antibacterial activity has also been observed with a variety of sulphameth-oxypyridazine derivatives like the imine obtained upon reaction of (95, R1 = MeO R2 = H) with 5-nitrofurfural [312], 2-aryl-3-nitrofurylacrylamides (105) [313], quinazoline-2,4-diones (106) [314], thiazolin-4-ones of type (107) [315] and with aldol condensation products of the latter [316], Sulpnonylpyridazmones (108, R1, R3 = alkyl, Ph R2 = substituted NH2, HO, RO) [273,274], trichloromethylchloropyridazines (109) [317] and 3-mer-captopyridazine 2-oxide derivatives [318, 319] have been claimed as antibacterial agents. 

Quinazolino[3,2-c]l,2,3-benzotriazin-8(7//)-imine (611) was prepared from 4-amino-2-(2-aminophenyl)quinazoline (609) by diazotization, followed by basilication of the resulting diazonium salt (610). The isomeric... 

UV, 1H, and 13C NMR investigations revealed that 5,7,8,9-tetrahydro and 1,2,3,4,5,7,8,9-octahydro tautomeric forms are predominant for 6-ethoxalyl derivatives 23 and 24, while the lower homologs, the pyrrolidino[2,l-Z>]-quinazolin-10-ones, exist in the enol-imine forms [89JCS(P2)1613]. 

C NMR data indicated the presence of a mobile formyl-enamine and enol-imine tautomeric mixture with the predominance of the former at 6-formyl-l,2,3,4,5,7,8,9-octahydro-ll//-pyrido[2,l-b]quinazolin-ll-ones (87JHC1045). 

Ab initio calculations indicate that in the gas phase the reaction of ketene inline and formaldehyde is concerted but asynchronous whereas in dichloromethane it is a two-step zwitterionic reaction.38 The 2 + 2-cycloadditions of keteniminium triflates with imines yields 2-azetidiniminium salts with cis stereoselectivity.39 The intramolecular 2 + 2-cycloaddition of ketenimines with imines (24) provides a novel synthesis of azeto[2,l-Z>]quinazolines (25) (Scheme 9).40... 

The reaction between ketenimines and imines was found to be much more difficult to accomplish [85, 86]. However, Alajarin et al. [87, 88] discovered that the intramolecular version of the reaction proceeded smoothly and several previously unknown azeto[2,l-b] quinazolines (91)] were proposed (Scheme 22). 

The reaction of imine 89 (R = OMe) with sterically less hindered primary alkylamines <1998JHC659> or arylamines <2002SL1423> unexpectedly gives quinazolines 90 or 91, respectively, in moderate to good yields (Scheme 10). 

Hexahydro-l-phenyl-3jFf-oxazolo[3,4-a]pyridin-3-imines (292) have antihypotensive and central nervous system stimulant activity which is stereochemically dependent. Most active is the (-)-trans form of the parent compound (292 R = H, Ar = Ph) (80MI42902). Useful stimulant activity for the central nervous system has also been claimed for 2,3,5,6-tetrahydro-7H-oxazolo[3,2-a]pyrimidin-7-ones (74GEP2253555) and quinazoline homo-logues (293) (74GEP2252122). 

A convenient synthesis of quinazolines has been reported, and has been applied to the synthesis of representative alkaloids of the quinazoline group (Scheme 5).27 The procedure depends on the formation of sulphinamide anhydrides (23) from the reaction of anthranilic acids with thionyl chloride and the generation in situ of the iminoketens (24). Addition of the latter to the imine (25) or to 2-piperidone, for example, afforded alkaloid (27). Arborine (26) was prepared similarly from N-methylanthranilic acid application of the method to the synthesis of rutecarpine is described in Chapter 11. 

Similar reactions of carbamates 22 with Grignard reagents in diethyl ether or tetrahydrofuran lead, without isolation of the imine and/or ketone intermediate, to 4-substituted quinazolin-2(l//)-ones 23, albeit in only 11% yield. 

The reaction of 5-(bromomethyl)tetrahydrofuran-2-imine hydrobromide (8), generated in situ from penl-4-enamine and bromine, with substituted anthranilic acids 7 affords 2-substiluted quinazolin-4(.3//)-ones 9 in satisfactory yields using mild conditions. ... 

Cyclization of 2-ureidobenzonitriles 3 is used very rarely for the preparation of quinazoline-2.4(1//,3//)-diones. Depending on the reaction conditions, the resulting quinazolin-4(3//)-imine can be isolated as such or it can be hydrolyzed to the corresponding 4-oxo compound 4. ... 

Quinazolin-2(l//)-ones 7 react readily with hydrophosphorous acid or with trialkyl phosphites to afford the corresponding quinazoline-4-phosphinic acids or dialkyl quinazoline-4-phospho-nates 8 in good yields. If an alkyl group is present in position 4 of the quinazolin-2(l//)-one, for the reaction with trialkyl phosphites additional activation of the imine bond is required to overcome steric constraints and the hydrochlorides of 4-alkylquinazolin-2(l/f)-ones react readily with trialkyl phosphites to give 8 in 77-98% yield. " ... 

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