Pyrazole 3 -trimethylsilyl

In recent years, trimethylsilyl protection has often been used for the methine proton of the acetylenic group because of the mild reaction conditions for desilylation. As a rule, the starting pyrazole trimethylsilyl derivative is mixed up, at room temperature, with a 2 A aqueous solution of NaOH, potash, or methanol solution in ammonia. 

Azoles can form stable compounds in which metallic and metalloid atoms are linked to nitrogen. For example, pyrazoles and imidazoles Af-substituted by B, Si, P and Hg groups are made in this way. Imidazoles with a free NH group can be Af-trimethylsilylated and Af-cyanated (with cyanogen bromide). Imidazoles of low basicity can be Af-nitrated. 

Pyrazole, 1 -bis(dimethylamino)phosphino- H NMR, 5, 185 (B-73NMR165, B-75MI40402) Pyrazole, 3,5-bis(trifluoromethyl)-1 -trimethylsilyl-5, 213 <71JOM(27)185)... 

Ethynylpyrazole was obtained under similar conditions in 46% yield (88M253). There are other examples of the trimethylsilyl cleavage with aqueous solution of potassium hydroxide for l-(hetaryl)-4-(trimethylsilylethynyl)pyrazole derivatives (96EUP703234). 

Trimethylsilylethynylpyrazole was deprotected by treatment with tetrabutyl-ammonium fluoride (TBAF) to give monosubstituted acetylene in 90% yield. (96ADD193). The same conditions were used to cleave the trimethylsilyl group in l-tetrahydropyranyl-3-carboxyethyl-4-[2-(trimethylsilyl)ethynyl]pyrazole (96INP 9640704). 

Less success has been obtained with removable N-substituents, however, the trityl and THP derivatives of 4-bromopyrazole both giving low yields of products derived from reaction of the lithio derivatives with carbonyl compounds [62CB222 82ACS(B)101]. Magnesium metal has also been used to produce l-methyl-4-(trimethylsilyl)pyrazole by an in situ Grignard reaction on the analogous 4-bromo compound in HMPT (84JOC4687). 

Metalation of 2 with lithium diisopropylamide (LDA) generates diazo(trimethyl-silyl)methyl hthium (3), which reacts with a,p-unsaturated nitrile 36 and phenyl-sulfones (37) to form 3(or 5)-trimethylsilyl-l//-substituted pyrazole 4 that can be desilylated to furnish pyrazoles 5 (Scheme 8.3). 

Bis(diisopropylamino)thiophosphoryl-5-tosyl-4-trimethylsilyl-l//-pyrazole (65%) was isolated after treatment with Sg. 

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