Quinazoline hydrochloride, hydrates

Quinazolines readily undergo addition of nucleophiles at the 3,4-doublc bond. The reversible covalent addition of water to the quinazoline cation has been described as covalent hydration.Quinazoline hydrochloride hydrate (3) and 3,4-dihydro-4-hydroxy-3-methyl-... 

Anhydrous quinazoline hydrochloride absorbs one molecule of water readily, and. the product is difficult to dehydrate completely even in a high vacuum at 60°. Infrared spectral data suggest that this water is covalently bound because of (o) the absence of several bands in the spectrum of the hydrate which are present in the spectrum of the anhydrous hydrochloride and (6) the presence of extra bands at 1474 and 1240 cm that have been attributed to C— H and O— H bending vibrations of the — CHOH group. 

Quinazoline is a solid which crystallizes in the form of leaflets from petroleum ether (mp 48-48.5 °C) and can be distilled without decomposition (bp 241 °C/764 Torr, 120-121 "C/17-18 Torr). It is steam-volatile and sublimes readily under vacuum. It is freely soluble in water giving an alkaline reaction and is also soluble in various organic solvents. Quinazoline hydrochloride monohydrate has a melting point of 127-128°C [cf. that of its picrate (mp 188-190°C)]. In aqueous solutions the cation of quinazoline undergoes reversible water addition across the N3 —C4 double bond. This phenomenon is known as covalent hydration".Quinazoline is stable in cold dilute acid and alkali solutions but it decomposes when these solutions... 

The anomalous behavior of quinazoline was first discovered by Albert et who made the surprising observation that 4-methyl-quinazoline 2.5) was a weaker base than quinazoline (pA 3.5). Mason then observed that the ultraviolet spectrum of the quinazoline cation was abnormal but that the spectrum of 4-methylquin-azoline was normal (see Fig. 2). These anomalies led to the suggestion that water adds covalently to the cation of quinazoline to give 12 (R = H). The occurrence and position of hydration were confirmed by a detailed study of the ultraviolet and infrared spectra of the anhydrous and hydrated hydrochlorides and by mild oxidation of the cation to 4(3 )-quinazolinone. Using the rapid-reaction technique (the continuous-flow method), the spectrum of the unstable... 

Cyano-3-methyl-5,6-dihydro-l//-pyrido[l,2-a]quinazoline-l,6-dione and its 5-substituted derivatives were prepared from 2-cyano-3-methylpyrido[l,2-a][3,l]benzoxazin-6-one with ammonium acetate at 200°C for 4 h, with hy-droxylamine hydrochloride and (thio)ureas in a boiling mixture of pyridine and ethanol for 4-7 h, with hydrazine hydrate, phenylhydrazide, primary aliphatic and (hetero)aromatic amines in boiling ethanol for 3-6 h (93CCC1953). 

The center of basicity in quinazoline itself is N3. Depending on the conditions, quinazoline can form a normal monocation, an abnormal monocation, and a dication. The normal cation 1 is formed in anhydrous solvents, e.g. in anhydrous diethyl ether where quinazoline can be converted into a hydrochloride which is very hygroscopic and readily forms a hydrate, or in... 

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