Electrooxidative C–H Functionalization of Heteroarenes. Thiocyanation of Pyrazolo[1,5‐a]pyrimidines

Abstract

Efficient electrooxidative C–H thiocyanation of both high and low reactive pyrazolo[1,5‐a]pyrimidines using a new system of complementary approaches has been developed. Advantages of this promising strategy are the undivided cell, mild conditions, and readily available reagents as well as feasible scaling up process and transformation of the synthesized aryl thiocyanates to new thiols. Also, target thiocyanates were found to have pronounced antifungal activity.

A New Method for the Synthesis of 3-Thiocyanatopyrazolo[1,5-a]pyrimidines

“…A similar situation was reported in refs [ 16 , 18 ], where several approaches to the efficient C–H (An) thiocyanation of substituted pyrazolo[1,5- a ]pyrimidines were first developed. Such structures are of big interest, because pyrazolo[1,5- a ]pyrimidine is one of the synthetic analogs of purine and a scaffold for many bioactive compounds [ 24 ].…”

“…Earlier, we realized several processes of anodic C–H thiocyanation of (hetero)arenes [ 14 , 15 , 16 , 17 , 18 ] as part of the development of the C–H (An) functionalization methodology. To obtain target products, a thiocyanate ion ( I )/(hetero)arene ( II ) mixture in MeCN was subjected to controlled potential electrolysis (CPE) at an anode potential (Е An ) equal to the oxidation peak potential (E p ox ) of SCN − ( Scheme 1 ) in an undivided cell equipped with Pt or glassy carbon (GC) electrodes.…”

“…Based on cyclic voltammetry (CV) data and depending on conditions, the Е An was 0.70–0.85 V (vs. SCE). Furthermore, that C–H (An) thiocyanation can be carried out at galvanostatic electrolysis (GE) [ 14 , 16 , 19 , 20 , 21 ].…”

“…To avoid polymerization, electrolysis can be carried out at low current densities for 1–3 days [ 21 ] or at low temperatures [ 23 ]. However, we found [ 14 ] that thiocyanation in MeCN is successfully realized even at room temperature for 2–4 h—probably due to the ability of MeCN to partially stabilize thiocyanogen I′ [ 16 ] .…”

“…On the other hand, it was shown [ 16 , 17 , 18 ] that CPE of an SCN − ( I )/(hetero)arene ( II ) mixture can be realized at E An = E p ox (Неt)ArH ( Scheme 2 ). The process can proceed according to the ECE mechanism [ 16 , 18 ] via the electrogeneration of the radical cation II′ , leading to the target product III in good yield. This is especially valuable when the previous process ( Scheme 1 ) was ineffective.…”