1.2.3- Thiadiazolo pyrimidines rearrangement

Ab initio molecular orbital calculations on these systems have been confined to the 1,2,3-triazolo[4,5-d]pyrimidines (7), the so-called 8-azapurines , and references to this subject may be found in the previously mentioned review <86AHC(39)ii7>. In 1989, quantum mechanical perturbation methods have been used to study the activity of 8-azapurine nucleoside antibiotics in transcription processes <89Mi 7i3-oi>. The l,2,3-thiadiazolo[5,4-d]pyrimidine derivative (51), a rearrangement product of 8-aza-6-thioinosine, has been used in a molecular modeling study of the antitumor activity of sugar derivatives of pyrimidopyrimidines <89PNA(86)8242>. 

Rearrangement of the oxygen analogs of the above-mentioned thiadiazolo[3,4-r pyrimidines are of practical value because syntheses of 2-, 8-, and 9-substituted adenines are possible. The most useful reaction in this context is the synthesis of acyclovir (acycloguanosine 8, see Section 7.1.1.3.3.9.).i ... 

The previous reaction describes the synthesis of a novel class of heterocycles by the name of [l,2,3]thiadiazolo[4,5- /]-pyrimidines. Visibly, a redox process is involved, whereby the initial hydrazine derivative becomes an R-N=N-R system and, at the same time, the sulfur atom in thionyl chloride is converted to an azo-sulfide. The transfer of oxidaton level from sulfur—as sulfoxide—to the neighboring atom is a well documented process in sulfur chemistry that is called the Pummerer rearrangement. In essence, it involves the treatment of sulfoxides with an electrophile such as acetic anhydride to yield an a-acetoxy sulfide, according to the following sequence (see Scheme 26.1) ... 

Treatment of 3-(2-pyridylimino)-3f/-l, 2,4-thiadiazolo[4,3-a]pyrimidine (304 R=2-pyridyl) with either 10% ethanolic HC1 or NaOH resulted in the formation of 2-(2-pyridylimino)-2//-l,2,4-thiadiazolo[2,3-fl]pyrimidine (305 R=2-pyridyl), which was alternatively synthesized by the action of sul-furyl chloride on thiourea 306 (74JOC3783). Under similar conditions 5,7-dimethyl-3-(2,6-dimethyl-4-pyrimidylimino)-3//-l,2,4-thiadiazolo[4,3-c]py-rimidine (307) gave no rearranged products. Thus, it afforded 308 with HCI, whereas attempted rearrangement in NaOH gave a product which corre-... 

---