Ishikawa reagent

Secondary and tertiary alcohols react with the Ishikawa reagent to give the corresponding fluorides and, usually, considerable amounts of alkenes or ethers [57] (Table 5]... 

Fluormation of tertiary benzylic hydroxy esters with the Ishikawa reagent gives somewhat lower yields of fluorides because of the formation of dehydrated products, 2-aryl acrylates [87] (equation 54)... 

Both aliphatic and aromatic carboxylic acids are converted to their fluorides by FAR [78, 79, by the Ishikawa reagent [S/], and by fluoroaminosulfuranes such as DAST [128, 166] and its analogues [128]... 

Abbreviations IMP, 2,4,6-trimethylpyridinium fluoride FMPTs, 2-fluoro-l-methylpyridinium tosylate Ishikawa, Ishikawa reagent (Ref. 74) Mitsunobu, through Mitsunobu reaction (Ref. 80) NBS, A-bromosuccinimide Piv, pivaloyl and Py, pyridine. 

V,A -Diethyl-l.l,2,3,3,3-hexafluoropropanamine (10, Ishikawa reagent) is a mild fluorinating agent which can convert primary, secondary and tertiary alcohols (which do not easily form carbanions) to their corresponding fluorides (see Table 3). It can also readily fluorinate carboxylic acids to their corresponding acid fluorides. 

R= CH3S02 -O CH-CH-SCHEME 2. Conversion of CH2OH to CH2F with Ishikawa reagent. 

The stability of the Ishikawa reagent itself [(I) in Scheme 2] was examined in our reactive system screening tool (RSST) this equipment was used, since, by design, it allowed us to test the effects of heat in a pressure vessel. The reactor and contents were heated at a rate of l°C/min under a pressure of 200 psi. 

As seen in Figure 4, a small exotherm occurred over the temperature range 65-100°C, possibly coinciding with Ishikawa reagent (I) converting to the enam-ine (IT) and HF. 

FIGURE 4. Temperature rate versus temperature. Ishikawa reagent heated in the RSST at l°C/min with a 200 psia nitrogen atmosphere. 

The batch sheet for operation of the process was written to ensure that the correct amount of the alcohol intermediate (RCH2OH) was added to consume the Ishikawa reagent produced. 

In an analogous manner, geraniol (7) does not give the expected substitution of the hydroxy group by fluorine with the Ishikawa reagent (2) but. instead, the 2,3,3,3-tetrafluoropropanoic acid ester 8 of geraniol is isolated. 

Simple primary alcohols generally give high yields of the expected fluoro compounds when treated with the Yarovenko reagent, 2-chloro-Af,Af-diethyl-l,l,2-trifluorocthylamine (1). or the Ishikawa reagent, A, A-diethyl-l,l,2,3,3,3-hexafluoropropylamine (2) examples arc given in Tables 6 and 7. 

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