Trifluoromethyl-substituted building block

Synthesis of partially fluorinated heterocycles from 4,4-bis(trifluoro-methyl)-substituted hetero-1,3-dienes via C—F bond activation and their application as trifluoromethyl-substituted building blocks 06H (69)569. 

Semicarbazide hydrochloride [705] and amidrazones [106] react with trifluoropyruvates to give six-membered heterocycles A variety of trifluoromethyl substituted heterocyclic systems is available, starting from the hydrate of trifluoropy-ruvicacid, a versatile 1,2-bielectrophilic building block (reaction type 2, equation 10) [107] (equation 24). 

Polyfluorinated target molecules are obtained when both building blocks are fluorinated and/or perfluoroalkylated. A typical example for this type of condensation is the synthesis of a tris(trifluoromethyl)-substituted 1,3,4-triazole from 3,5-bis(trifluoromethyl)benzhydrazide and trifluoroaceta-midine (78BRP1510647). 

Trifluoromethyl-substituted nitrones have been prepared [78JFC-(12)153 88JFC(39)39, 88MI2 89JHC381] and used as building blocks for five-membered ring synthesis (Scheme 66). 

BTF belongs to an important group of trifluoromethyl-substituted aromatic compounds, which have broad applications as intermediates or building blocks for crop protection chemicals, insecticides and pharmaceuticals, as well as dyes. Related higher boiling compounds that are produced in multimillion pound quantities include 4-chlorobenzotrifluoride (PCBTF) and 3,4 dichlorobenzotri-fluoride (3,4-DCBTF). 

Fluorinated 1,3-dicarbonyl reagents or their equivalents can be used as building blocks for the preparation of trifluoromethyl-substituted pyrazoles in a strategy similar to that used for the synthesis of ring-fluorinated pyrazoles. Trifluoroacetyl dihydrofuran and pyran (135 or 136), as well as trifluoro-4-ethoxy-3-butene-2-one... 

In contrast, there are many reports of trifluoromethyl- and other perfluoroalkyl-substituted tetrazoles prepared from fluorinated building blocks. For example, consistent with its high reactivity, trifluoroacetonitrile reacts exothermically with sodium azide to give sodium 5-trifluoromethyltetrazole 168 (Fig. 3.98). ... 

Bromothiazole 70 undergoes trifluoromethylation with fluoroform-derived CUCF3 under nuld conditions to furnish the desired trifluorometh-ylated product 71 in moderate yield (13JOC11126). These trifluoromethyl-substituted thiazoles could serve as versatile building blocks in medicinal chemistry research. 

In connection with trifluoromethyl chemistry, one has, from the synthetic point of view, to mention the large-scale preparation of numerous trifluo-romethoxypyridines. They can, via regioselective functionalization, provide large libraries of fluoro-substituted pyridine building blocks [260]. 

Nishiwaki T, Kikukawa H (1994) 3-Oxo-4,4,4-tiifluorobutyronitriles as building blocks of trifluoromethyl substituted heterocycles. 2. Heterocyclization to 3-aryl-4-trifluoromethyl-2//-l-benzopyran-2-ones under Hoesch reaction conditions. J Heterocycl Chem 31 889-892... 

Cyclocondensation of substituted biguanides 81 with methyl trifluoroacetate in the presence of catalytic amounts of sodium ethylate gave 2-amino-4-(substituted amino)-6-trifluoromethyl 5ym-ttiazines 82 (Scheme 35) [66-72], A rapid and efQcient synthesis under microwave irradiation has been developed for various substituted l.S.S-biazines that can serve as versatile building blocks for both supramolecular and medicinal chemistry [61, 73],... 

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