Quinazoline reactions

Acid- or base-catalyzed cyclization of 2-(1-amino-3-oxoalk-l-enyl)acetanilides 33 constitutes a relatively novel route to various 2,4-disubstituted quinazolines. Reaction of 33 with a base gives the quinazolines 34 directly, whereas treatment of 33 with acid affords quinazolines 35 which can be converted practically quantitatively into quinazolines 34 by treatment with base. 

Kotsuki and co-workers used amidines to synthesize 2-substituted quinazolines. Reaction of 2-fluoro-5-nitro-benzaldehyde with 4-bromo-benzyl amidine gave the corresponding quinazoline in modest yield. This approach was subsequently used by Kotsuki and co-workers to generate a number of 5-nitro- and 5-cyanoquinazolines in modest yields. 

While pursuing a program directed at new ligands for GABAa receptors, Jones and Chambers developed a rapid approach to C-5 substituted l,2,3-triazolo-[l,5-a]quinazolines. Reaction of 2-azidobenzoic acid (46) with an isoxazole acetonitrile 47 under classical Dimroth triazole synthesis conditions gave the desired core skeleton with a chemical handle for rapid derivitization. 

The use of oximes as nucleophiles can be quite perplexing in view of the fact that nitrogen or oxygen may react. Alkylation of hydroxylamines can therefore be a very complex process which is largely dependent on the steric factors associated with the educts. Reproducible and predictable results are obtained in intramolecular reactions between oximes and electrophilic carbon atoms. Amides, halides, nitriles, and ketones have been used as electrophiles, and various heterocycles such as quinazoline N-oxide, benzodiayepines, and isoxazoles have been obtained in excellent yields under appropriate reaction conditions. 

There is a scattered body of data in the literature on ordinary photochemical reactions in the pyrimidine and quinazoline series in most cases the mechanisms are unclear. For example, UV irradiation of 4-aminopyrimidine-5-carbonitrile (109 R=H) in methanolic hydrogen chloride gives the 2,6-dimethyl derivative (109 R = Me) in good yield the 5-aminomethyl analogue is made similarly (68T5861). Another random example is the irradiation of 4,6-diphenylpyrimidine 1-oxide in methanol to give 2-methoxy-4,6-diphenyl-pyrimidine, probably by addition of methanol to an intermediate oxaziridine (110) followed by dehydration (76JCS(P1)1202). 

The recorded use of metallo derivatives in the pyrimidine and quinazoline series is minimal. The best described pyrimidinyllithium compounds are those derived from 5-bromopyrimidines. Their reactions are illustrated in the following examples. Pyrimidin-5-yllithium (474 R = H) reacts with solid carbon dioxide under ether to give pyrimidine-5-carboxylic acid (475 R = H) in good yield (65ACS1741) 4,6-dimethoxy- (474 R = OMe),... 

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). 

Benzisoxazoles were obtained from quinazolin-3-ols in an ArF displacement activated by Mn02 (equation 62) (74JHC885). The 1,2-benzisoxazole was produced as a minor side product in the reaction of (563) with hydroxylamine (73MI41600). 

Quinazoline, 2,4-bis(/3-diethylaminoethoxy)-Hilbert-Johnson reaction, 3, 93 Quinazoline, 2-chloro-4-(p-chlorophenylthio)-synthesis, 3, 137 Quinazoline, 6,8-dichloro-chlorosulfonation, 3, 76 Quinazoline, dihydrosynthesis, 3, 108, 124 Quinazoline, 2,4-dimethyl-Mannich reactions, 3, 78 Quinazoline, 4-ethoxy-1-oxide... 

Quinazoline, 1,2,3,4-tetrahydro-synthesis, 3, 108, 124 Quinazoline, 5,6,7,8-tetrahydro-synthesis, 3, 116 Quinazoline alkaloids occurrence, 3, 148 Quinazolinecarbonitriles hydrolysisj 3, 83 Quinazoline-2-carbonitriles reactions... 

Quinazoline-2,4( 1 H,3H)-dione, 7-nitro-synthesis, 3, 110 Quinazolihediones mass spectra, 2, 22 polymers, 1, 298 Quinazoline-2,4( 1 H,3 H)-diones synthesis, 3, 106 O-trimethylsilylation, 3, 91 Quiriazolines addition reactions, 3, 73... 

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... 

The ionization constant of a typical heterocyclic compound (e.g., quinoline) designates the equilibrium involving a proton, a neutral molecule and its cation. With quinazoline, however, two distinct species (hydrated and anhydrous) are involved each of which is in equilibrium with its cation, and can be represented as in the reaction scheme, (7), (8), (3), and (4). 

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