6- Bromo-1,2,4-triazolo pyrimidine

Condensation of 2-hydrazinopyrimidine (384) with an aromatic aldehyde formed the Schiff bases (386), which then cyclized with bromine to 6-bromo-l,2,4-triazolo[4,3-a]pyrimidine (383) and with carbon disulfide to 387 (92PS145). A similar cyclization was effected also on 384 to give 388 (68T2839 85FRP2549834), but the cyclization of 384 or 385 with carbon disulfide afforded 3-thiolo-l,2,4-triazolo[4,3-a]pyrimidin-7-ones 389 and 390, respectively. A small amount of the isomeric 3-thiolo-l, 2,4-triazolo[4,3-a]pyrimidin-5-one was isolated in the former case (68T2839). Reaction of 385 with benzaldehyde [67JCS(C)498] or p-chlorobenzaldehyde (90MI3) followed by oxidation with LTA in benzene afforded 391 (Scheme 73). 

The halogen metal exchange reaction between 7-bromo or 7-iodo-3-phenyltriazolopyrimidine 165 and butyllithium in iV,N,N, N -tetra-methylethylenediamine afforded the 7-lithio compound 166, whereas a similar reaction with the 7-chloro derivative 165 (R = H) gave the ring-fission product, 5-amino-l-phenyl-l//-l,2,3-triazole-4-carbonitrile 169 (91 CPB2793). Reaction of 166 with electrophiles such as benzaldehyde and ketones gave 170 and 167 respectively, together with 7,7 -bis[3-phenyl-3//-1,2,3-triazolo[4,5-d]pyrimidine] 168 (Scheme 34). 

A variety of 2-substituted [l,2,4]triazolo[l,5-c]pyrimidines were obtained when the 2-bromo derivative (Scheme 11) was treated with nucleophiles (65JCS3357). 

Using 5,7-dimethyl-[l,2,3]triazolo[l,5-fl]pyrimidine (214), Af-bromosuccinimide in chloroform yielded not the expected 3-bromo product (215), but 2-(a,a-dibromomethyl)-4,6-dimethylpyrimidine (216) and, in lesser amounts, 4,6-dimethylpyrimidine-2-carbal-dehyde diethyl acetal (217) (76JOC385). The latter product was due to ethanolysis of (216) by the trace amounts of ethanol in the solvent since, following its removal, (216) was the only product. Use of iV-chlorosuccinimide and iodine monochloride proceeded in the same way giving rise to (218) and (219), respectively. The mechanism for these transformations is illustrated in Scheme 12 and is postulated to involve a diazonium cation (76JOC385). 

Bromination of 5-hydroxy-7-methyl-l,2,4-triazolo[4,3-c]pyrimidine (96) led to the introduction of the bromo function into the only available site in the pyrimidine ring (C8 of 96) to afford 97 (60G1821) (Scheme 42). 

Scheme 61 Interaction of 6-bromo-[l,2,4]triazolo[4,3-a]pyrimidine 94 with alkylamines...

It has recently been found that the ANRORC mechanism is realized in the reaction of 6-bromo-[l, 2, 4]triazolo[4,3-a]pyrimidine 94 with aliphatic amines under microwave irradiation, thus affording Ai-alkyl-[l,2,4]triazolo[l,5-a] pyrimidin-7-amines 95 (Scheme 61) [129]. 

---