Reduced Quinazolines

Quinazolinones and thiones are not considered as hydro compounds in this section unless other double bonds in the rings are saturated. 4-Methylene-3,4-dihydroquinazolines, however, are included in this section. 

A new ring closure to quinazolines was found by allowing 2-benzoyl-5-nitroaniline to react with hexamine (hexamethylenetetramine), in the presence of ethyl a-bromoacetate, in a solvent. When the solvent was methanol, 

The red crystalline product, called isamic acid, from treatment of isatin with ammonia, was proved by Cornforth to be the spiro-1,2-dihydroquinazoline-4-carboxylic acid 66 (R = H). iV-Methylisatin provided the dimethyl derivative (66 R = Me). Isamic acid has an asymmetric carbon atom and is chiral. In an attempted optical resolution, its brucine salt gave 

Gatta and R. Landi Vittory, Cazz. Chim. Ital. 99, 715 (1969). 

2-(2-Pyridyl)-3-(N-2-picolylimino)-l,2-dihydroquinazolin-4-one formed stable complexes with Zn, Cd, Mn, Cu, Co, and Ni ions. Infrared (IR) studies indicated that the metals coordinated with two different conformations of this ligand. 

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Reduction of quinazoline with hydriodic acid gives 3,4-dihydro-quinazoline but this can be achieved more satisfactorily by catalytic means. With palladium-charcoal it was found possible to reduce quinazoline to 1,2,3,4-tetrahydroquinazoline. ... 

Hydrolysis of reduced quinazoline derivatives has also been performed, as demonstrated by the synthesis of enantiopure 2-aminocyclohexanecarboxylic acid 560 from octahydroquinazoline 559 <2004TA3545>. 

Prolonged reduction of quinazoline, 2-chloroquinazoline, 4-chloroquinazoline, and 4-phenyl-sulfanylquinazoline with lithium aluminum hydride results in ring cleavage and formation of diamines 2 in addition to the partially reduced quinazolines. ... 

When two fused six-membered rings (naphthalene analogues) are considered, possibilities become very numerous, partly on account of the reduced symmetry of naphthalene, compared with benzene, and also because of the larger number of positions available for substitution. Thus, there are two monoazanaphthalenes, quinoline (8) and isoquinoline (9), four benzodiazines [cinnoline (10), phthalazine (11), quinazoline (12) and quinoxaline(13)], with the two nitrogen atoms in the same ring, and six naphthyridines (e.g. (14), named and... 

Quinazoline [253-82-7] M 130.2, m 48.0-48.5 , b 120-121 /17-18mm, pK, -4.51 (aq H2SO4, anhydrous dication), pK 2.01 (anhydrous monocation), pK3 4.3 (equilibrium with 3,4-hydrated species), PK4 12.1 (hydrated anion). Purified by passage through an activated alumina column in benzene or pet ether (b 40-60°). Distd under reduced pressure, sublimed under vacuum and crystd from pet ether. [Armarego 7 Chem 1170 1961.]... 

The A -oxide reactions in quinazoline 3-oxide are, however, modified to a certain extent by the aforementioned properties. Thus, whereas it can be reduced to quinazoline with phosphorus trichloride or iron and ferrous sulfate in ethanol, reactions with alkali, acetic anhydride, and benzoyl chloride in the presence of cyanide result in ring fission (Scheme 4). 

It appears, therefore, that quatemization of the unsubstituted quinazoline nucleus is the exception and that steric factors probably cause the substituted derivatives to react at the 1-position. 8-Hydroxy-quinazoline is believed also to quatemize at the 3-position here the effect of the hydroxyl group would be to reduce any tendency towards reaction at the 1-position and it is interesting that a monoalcoholate is isolated in this case too. ... 

BuOK. (15.4 g, 0.139 mol) was added in portions to 6-chloro-2-(chloromethyl)-4-phenyl-l,2-dihydro-quinazoline 3-oxide (11a 42.2 g, 0.137 mol) in THF (700 mL), cooled in acetone/solid carbon dioxide, and the mixture was stirred for 4.5 h as it warmed to 20 C. It was filtered through Celite, the filtrate was evaporated under reduced pressure and the residue was recrystallized (benzene/hexane) to give the crude aziridinoquinazoline oxide 12a yield 22.Og (57%) mp 135-136.5 C. 

The 3.4-dihydro-17/,2//.6//-pyrimido[2,l - quinazolin-2-ones 198 are blood platelet reducing agents <1997EPP0778258>. 2-(2-Pyndazyl-amino)-6//-pyrimido[2,l-Z ]quinazolin-6-oncs have been claimed as protein... 

Besson and coworkers reported an original approach for the synthesis of the rare thiazolo-[5,4-/]-quinazoline 29 in six steps [15] from commercially available 2-amino-5-nitrobenzonitrile 22 (Scheme 8.11). The authors studied the transposition of four steps (ii, iii, vi, and vii) of the synthesis of thiazoloquinazoline 29 to microwave irradiation of solutions, with the same concentration of starting material and volume of solvent, and found that yields of the desired compounds were better than those obtained by conventional heating (Tab. 8.3). The overall time for the synthesis of 29 was considerably reduced and the overall yield was enhanced. 

Thiourea and related compounds like thioamides have been studied polaro-graphically in alcoholic buffered media. Being cathodically reduced, benzotri-azepine (22) undergoes a ring contraction affording the corresponding quinazoline (23) (Eq. 25) [194,195]. 

It was recently observed that a iplant, Adhatoda vasica, long used in Indian herbal medicine (the source of many therapeutic leads) for the relief of cough and respiratory tract congestion, did appear to reduce the quantity and viscosity of sputum. The plant was studied and its active alkaloid named vasicine. The tricyclic quinazoline structure (XXVIII) was then reduced to fragments and a series of derivatives prepared [350]. From these bromhexine (XXIX, Na 274, Bisolvon)... 

Quinazoline was reduced by hydrogen over platinum oxide to 3,4-dihydro-quinazoline [489], and by sodium borohydride in trifluoroacetic acid to 1,2-dihydroquinazoline [490]. 

It is an piperazinyl quinazoline effective in the management of hypertension. It is highly selective for receptors. It also reduces the venous return and cardiac output. It is used in essential hypertension, benign prostatic hypertrophy and in Raynaud s syndrome. Prazosin lowers blood pressure in human beings by relaxing both veins and resistance vessels but it dilates arterioles more than veins. 

Finally, the reduced 1,2,4-triazolo[5,1 -fc]quinazolin-9-ones (310) were prepared from 1,2,4-triazole precursors when 3-amino-l,2,4-triazole (309) was cyclocondensed with 2-ethoxycarbonylcyclohexanones (72MI1 890PP163). 

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