Pyrimidines and quinazolines

Six-membered heterocycles containing at least two heteroatoms 3.6.1. Pyrimidines and quinazolines 

---

The mass spectra of pyrimidines and quinazolines are generally simple and of no great interest, factors which account for the paucity of data available (B-71MS468). 

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),... 

Pyrimidines and quinazolines have not been very successful in the antihistamine field. However, thonzylamine (1041 R = OMe) is used in some countries, while its demethoxy-lated analogue, hetramine (1041 R = H), and the quinazoline HPT909 (1042) both have strong support in the literature (63JCS2256, 65AF613, 60MI21301). 

Alkylthio, arylthio, and thioxo. The thioxo group in pyrimidine-2,4-dithione can be displaced by amines, ammonia, and amine acetates, and this amination is specific for the 4-position in pyrimidines and quinazolines. 2-Substitution fails even when a 5-substituent (cf. 134) sterically prevents reaction of a secondary amine at the 4-position. Acid hydrolysis of pyrimidine-2,4-dithione is selective at the 4-position. 2-Amination of 2-thiobarbituric acid and its /S-methyl derivative has been reported. Under more basic conditions, anionization of thioxo compounds decreases the reactivity 2-thiouracil is less reactive toward hot alkali than is the iS-methyl analog. Hydrazine has been reported to replace (95°, 6 hr, 65% 3deld) the 2-thioxo group in 5-hexyl-6-methyl-2-thiouracil. Ortho and para mercapto- or thio- azines are actually in the thione form. ... 

Enolates can also add to activated pyrimidines and quinazolines as shown by the synthesis of 4-(3-oxindolyl)qui-nazolines 106 from resin-attached 4-alkylthioquinazolines 104 <1999TL3881>. 

Both pyrimidine and quinazoline derivatives have been investigated as ligands for palladium-mediated reactions. Examples of ligands prepared include the phosphine-free bipyrimidine 1181, which gave the isolable palladium dichloride catalyst 1182 <2001JOM(634)39>, and the chiral oxazolinyl-quinazoline BINAP analogs 1183 and 1184 <20060L5109>. 

---