Fluorine reaction with hydrazones

In the reaction of hydrazones with bromine monofluoride (Table 3), the best yields of fluorinated compounds are obtained with bromine monofluoride generated from NBS, (HF) / pyridine (entries 1-3). No satisfactory results were obtained with A-iodosuccinimide. 

The reaction of hydrazones with elemental fluorine can also be used for the synthesis of gem-in ally difiuorinated compounds (Table 4). The procedure, however, can have severe limitations it is only applicable to aryl ketone hydrazones (no reaction is observed with the hydrazones of benzaldehyde, cyclohexanone, or cyclopentanone), and mixtures ofdi- and monolluorinated compounds are obtained. In some cases, monofiuorinated derivatives are the only reaction products (entries 4 and 5). 

Mono- and Difluorinated Compounds by the Reaction of Hydrazones with Elemental Fluorine General Procedure "... 

For experimental procedures for fluorinations with iodine monofluoridc and bromine trifluoride, sec the reactions of hydrazones (Section 1.1.9.1.). 

In addition, diazo compounds can be prepared from hydrazones upon reaction with various oxidizing reagents. Despite the satisfactory results obtained using this procedure, fluorination of hydrazones or oximes is actually a more efficient method as these derivatives are easier to handle than diazo compounds. 

Hydrazones can be converted into gc/n-difluorides upon reaction with either fluorine [245], bromine monofluoride (generated in situ) [246] or iodine monofluoride [247], and the reaction of diazoketones with fluorine results in similar transformations [248] (Figure 3.50). 

Radical cyclization continues to be one of the most popular radical reaction classes used in synthesis. By far the majority of published cyclization reactions are 5-exo in nature and this year is no exception. The rates of 5-exo cyclization reactions continue to be measured. For example, the rate constants for the 5-exo cyclizations of the 6,6-diphenylhex-5-enyl, 1-methyl-6,6-diphenylhex-5-enyl and the 1,1-dimethyl-6,6-diphenylhex-5-enyl radicals have been measured by laser flash photolysis studies and Arrhenius parameters determined. The relative rate constants for cyclization, and the reaction with PhSeH, were determined at 20 °C. At 20 °C the rates of the three primary, secondary and tertiary radicals with PhSeH were approximately (1.2 0.1) X 10 lmol s The rate constants for alkyl radicals calibrated by competition reactions with PhSeH and PhSH were found to be 30-40% smaller than previously reported and thus it was concluded that derived rate constants for some fast radical reactions may have to be adjusted accordingly. The rate constants for the 5-exo cyclization of secondary radicals on to hydrazones and oxime ethers have been determined. The fastest rate constants were observed for the IV-benzoylhydrazone acceptor. The rate constants were found to be approximately 800 times faster than for the corresponding 5-exo cyclization on to alkenes." Other work has measured the rate constants of cyclization of a range of fluorinated hex-5-enyl, hept-6-enyl, oct-7-enyl and non-8-enyl radicals. Not only were the rate constants measured but the regioselectivity of cyclization was compared with that for the aU-carbon homologues." The 6-exo cyclization of 1,1,2,2-tetrafluoro- and l,l,2,2,3,3,4,4-octafluorohept-6-enyl radicals were found to be approximately 10 times faster than those for the parent... 

The hydrazone (100-500 mg) was dissolved in anhyd MeOH (50mL). Dilute F2 gas (1 -5% in N2) was bubbled through the stirred, icc-cold solution until TLC showed that nearly all of the hydrazone had been consumed. The overall reaction time was 3-7 mill. The mixture developed an orange-red color which dissipated on further fluorination. After concentration of the mixture with a rotary evaporator, the flu-orinated components were analyzed by l0F NMR speciroscopy, followed by separation by HPLC or column chromatography. 

Electron-withdrawing groups promote anodic fluorination while electron-donating groups interfere with fluorination. In fact. bis(4-methoxyphenyl) ketone hydrazone does not give mono-fluorinated product at all, probably due to the low electrophilicity of the anodically generated benzylic cation intermediate, although the mechanism of the reaction is not clear. 

An unusual formation of indoles via a formal Fischer cyclizalion of A-pentafluorophenyl hydrazones 147 was discovered by Brooke. Generally, the Fischer reaction demands the ortto-position be unoccupied. However, in refluxing tetraline, hydrazones 147 were transformed into polyfluoroindoles accompanying with the loss of one ort/tn-fluorine. Hydrazones of acetophenone and cyclohexanone afforded the corresponding indoles 148 and 149 in 12 and 18 % yields respectively. In case of acetaldehyde hydrazone, only a minor amount of parent tetrafluoroindole 132 were isolated. The mechanism of the reaction has not be clarified [57]. 

The synthesis of fluorinated 1,2,3-thiadiazole was not widely investigated and is essentially related to the general scheme of the Hurd-Mori reaction [55], i.e. the treatment of hydrazone derivatives with thionyl chloride (Scheme 31). 

Hydrazone 1042 (prepared from 2-amino-l,l,l-trifluoro-3-phenylsulfonyl-2-propanol) is one more NNCC binucleophile for the synthesis of chain-fluorinated pyridazines (Scheme 222) [626], In this case, two-step reaction of 1042 with a-diketones is used, including acid-catalyzed hydrazone formation and base-... 

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