Quinazoline alkoxy

Alkaline hydrolysis of 6-methoxy- 4-methoxycarbonyl-2-methyl-tbiopyrimidine leaves unaffected only the methylthio group which can then be hydrolyzed in acid. 9-Alkylthioacridines are hydrolyzed by acid less readily than the corresponding alkoxy compounds and more readily than alkylamino derivatives. Peculiarly, a better yield of the amine results from 4-thioxo than from 4-methylthio-quinazoline on heating with primary amines. Displacement in 2-methylthio-quinolinium and 3-methylthiopyridazinium compounds (137) proceeds readily with the carbanion of diethylmalonate or the zwitterion of 2-methylbenzothiazolinium derivatives. 

Kinetic studies have been carried out on the displacement reactions of various chloroazanaphthalenes with ethoxide ions and piperi-dine. - 2-Chloroquinoxaline is even more reactive than 2-chloro-quinazoline, thus demonstrating the powerfully electrophilic nature of the -carbon atoms in the quinoxaline nucleus. The ease of displacement of a-chlorine in the quinoxaline series is of preparative value thus, 2-alkoxy-, 2-amino-, - 2-raethylamino-, 2-dimethyl-amino-,2-benzylamino-, 2-mercapto-quinoxalines are all readily prepared from 2-chloroquinoxaline. The anions derived from substituted acetonitriles have also been used to displace chloride ion from 2-chloroquinoxaline, ... 

The reduction of quinazoline with lithium aluminum hydride gave a mixture of 1,2,3,4-tetrahydroquinazoline and Va-methyl- ,2-toluenediamine. 4-Aryloxy- and 4-alkoxy-quinazolines gave 1,2-di-hydro derivatives, while 2-chloro-4-phenyl- and 4-chloro-2-phenyl-quinazolines gave the corresponding 3,4-dihydroquinolines with reductive loss of halogen.1356... 

Quinazolines bearing a hydroxy, alkoxy, or amino group at position 5 or positions 5 and 8 can be oxidized by various oxidizing agents [e.g., ammonium cerium(IV) nitrate (CAN)] to give quinazoline-5,8-dioncs 1 with loss of aromaticity. 

Friedlander synthesis, 2, 444 Quinalphos as insecticide, 1, 196 Quinapyramine trypanocidal activity veterinary use, 1, 215 Quinazolinamines structure, 3, 67 1,2,4-triazoIes from, 5, 779 Quinazolin-4-amines sulfonylation, 3, 86 Quinazoline, 2-alkoxy-Hilbert-Johnson reaction, 3, 93 Quinazoline, 4-alkoxy-Hilbert-Johnson reaction, 3, 93 Quinazoline, 6-alkoxy-Hilbert-Johnson reaction, 3, 93 Quinazoline, 4-alkyl-synthesis, 3, 124 Quinazoline, 2-alkyIthio-synthesis, 3, 137 Quinazoline, 4-alkyIthio-synthesis, 3, 137... 

Other synthons for 1,3-dicarbonyl compounds that have been successfully applied include p-chloro-a,P-unsaturated ketones and aldehydes, P-dimethylamino-a,P-unsaturated ketones (easily obtained from ketones by reaction with DMFDMA), P-alkoxy-enones"" and vinyl-amidinium salts."" Alkynyl-ketones react with 5-alkyl-isothioureas, giving 2-alkylthio-pyrimidines" and propiolic acid reacts with urea to give uracil directly in about 50% yield. "" 1,3-Keto-esters with formamidine produce 4-pyrimidinones"" and C-substituted formamidines with ethyl cyanoacetate give 2-substituted-6-amino -pyrimidinones. In analogy, pyrimidines fused to other rings, for example as in quinazolines, can be made from ortho-aminonitriles " and in general, from P-enamino esters. ... 

The high electrophilic character of the 2- and 4-positions in quinazoline makes hydrolysis to oxo derivatives easy. The significantly higher reactivity in the 4-position simplifies stepwise substitutions. Both 2- and 4-chloro substituents can be hydrolyzed in alkaline or acid solution. Hydrolysis of 4-chloro derivatives by boiling water is complete in minutes. The reaction is acid catalyzed, and is faster than in dilute alkali. A water adduct is postulated as an intermediate (132). Both 2- and 4-alkoxy- or aryloxyquinazolines are readily hydrolyzed by HCl to the corresponding quinazolinones . 

Alkoxy derivatives in the electrophilic positions are readily available by nucleophilic substitution reactions as discussed for the oxo derivatives above. 2,4-Dialkoxyquinazolines can be prepared by boiling 2,4-dichloroquinazolines with two equivalents of alkali alkoxide in the appropriate alcohol. Mixed ethers (137) are possible because of the great difference in positional reactivity the first substitution is in the 4-position (136). 4-Chloro- and 2,4-dichloro-quinazoline very readily suffer alcoholysis in the 4-position with acid catalysis, presumably via 4-adduct formation as in the facile hydrolysis discussed above. 

Several general reports covered more than one type of diazine. For example, Cu(II) complexes of a diverse set of alkoxy diazine ligands were prepared, and their magnetic properties investigated. X-ray crystal structure determinations of many of these were included <04IC4278>. New sulfinylcinnolines, quinoxalines, quinazolines, and phthalazines were prepared from appropriate halobenzodiazines. These were converted to sulfanyl benzodiazines, which in turn... 

A mixture of o-hydrazinobenzoic acid hydrodiloride, ethyl 2-cyano-3-ethoxy-acrylate, ethanol, and water heated 10 min. on a steam bath, and allowed to stand overnight at room temp. ethyl pyrazolo[l,5-a]quinazolin-5(4H)-one-3-carboxylate. Y 85%. F. e., also with amino and cyano in place of alkoxy leaving groups, s. J. B. Wright, J. Heterocyclic Chem. 6, 947 (1969). 

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). 

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... 

Quinazoline methiodide, 29 Quinazoline 3-oxides, 31 Quinazoline-thiones, 31, 51 4-Quinazolone, 3-alkyl-, 31 Quindolines, 103, 134, 144, 146 Quindoline-11-carboxylic acid, 144 Quinindoline, 135, 144 Quinolines, alkoxy-, reactions of, 311 2-alkyl-, reaction with carbenes, 77 aza-effects in, 318 basicity of, 244, 245, 247, 288, 289... 

---