Pyrazoles by dealkylation of pyrazolium salts

Abstract

A rapid, convenient conversion of 1,2‐dimethylpyrazolium salts (1) to 1‐methylpyrazoles (2) is accomplished in piperidine or 3‐methylpiperidine at temperatures ≥ 106°. This demethylation represents a particularly useful procedure for the synthesis of 3‐ and 5‐substituted aminopyrazoles, which are not readily obtainable by other methods. The 50:50 mixture of piperidinopyrazole isomers 2b can be obtained directly by treating 3‐chloro‐1,2‐dimethyl‐5‐phenylpyrazolium iodide (3b) with piperidine in ethanol at 106°.

Regioselective Synthesis of Polysubstituted Pyrazoles and Isoxazoles

“…Dihydropyrazoles (pyrazolines) 5a − e can be further converted to trisubstituted pyrazoles 8a − e by treatment with a mild base in 81−94% yields. The structures of 8a , 8b , 8c, 8d , and 8e 5 were assigned by comparison with their literature spectroscopic data.…”

“…Colorless needles from methanol (51%), mp 129-130 °C; 1 H NMR δ 8.07-8.04 (d, J ) 7.8 Hz, 1H), 7.52-7.49 (m, 1H), 7.42-7.31 (m, 7H), 7.22-7.19 (m, 2H), 7.16-7.13 (m, 3H), 6.67 (d, J ) 9.8 Hz, 1H), 4.63 (d, J ) 9.7 Hz, 1H), 3.10 (s, 3H); 13 C NMR δ 146. 6,142.8,137.2,131.5,130.6,129.1,128.7,128.6,127.8,126.9,124.9,124.2,120.4,110.0,77.0,72.8,40.5. Anal.…”

Preparation and Chemistry of 3/5-Halogenopyrazoles

“…The same was found with 3/5-halogenopyrazolium substrates, which could also undergo concomitant dealkylation. 448,449 Concerning other 5-halogenopyrazoles this reaction is also easy, 449 especially if an electronattracting moiety is present on position 4. As shown in Scheme 31, inhibitors of the HIV reverse transcriptase were made from aldehyde-bearing substrates such as 319 to give the thioether 320.…”