1.2.4- Triazole 3-halo-, synthesis

Propiolaldehyde diethyl acetal has found numerous synthetic applications in the literature which may be briefly summarized. The compound has been utilized in the synthesis of unsaturated and polyunsaturated acetals and aldehydes by alkylation of metal-lated derivatives, " by Cadiot-Chodkiewicz coupling with halo acetylenes, " and by reaction with organocuprates. Syntheses of heterocyclic compounds including pyrazoles, isoxazoles, triazoles, and pyrimidines have employed this three-carbon building block. Propiolaldehyde diethyl acetal has also been put to use in the synthesis of such natural products as polyacetylenes " and steroids. ... 

The most widely used method for the ring closure to the title ring system is the reaction of a 3-mercapto-4-amino[l,2,4]triazole compound with an a-halo-oxo reagent. The particular realizations of these syntheses are summarized in Table 4. Comparison of the reference lists shows that reactions with phenacylhalogenides and analogues (entry 1) is by far the best method. Synthesis of altogether more than 150 derivatives are described in... 

Table 4 Synthesis of [1,2,4]triazolo[3,4-b]thiadiazines by reaction of 3-mercapto-4-amino[1,2,4]triazoles with a-halo-oxo reagent...

Scheme 1 One-pot synthesis of lmldazo[l,5-b][l,2,4]triazoles 8 from of a,a-dlsubstltuted a-halo carbonyl compounds 1 with potassium thiocyanate in acetic acid and monosubstituted hydrazines 3.

Triazoles can also be prepared from in situ formation of azides from halo compormds. For example, 1,4-disubstituted-1,2,3-triazoles 138 were obtained in excellent yields by a convenient one-pot procedure from a variety of aryl and alkyl iodides 136 and terminal alkynes 137 without isolation of potentially unstable organic azide intermediates 05SL2941>. Efficient one-pot synthesis of 1,2,3-triazoles from in situ formation of azides from benzyl and alkyl halides with alkynes has also been reported <05SL943>. 

---