Fluorine aromatic, hydrolysis

The formation of ethyl cyano(pentafluorophenyl)acetate illustrates the intermolecular nucleophilic displacement of fluoride ion from an aromatic ring by a stabilized carbanion. The reaction proceeds readily as a result of the activation imparted by the electron-withdrawing fluorine atoms. The selective hydrolysis of a cyano ester to a nitrile has been described. (Pentafluorophenyl)acetonitrile has also been prepared by cyanide displacement on (pentafluorophenyl)methyl halides. However, this direct displacement is always aecompanied by an undesirable side reaetion to yield 15-20% of 2,3-bis(pentafluoro-phenyl)propionitrile. 

Another powerful approach to prepare a-amino acids bearing an aromatic or unsaturated side chain in /I (but also many other compounds) is based on the reactivity of 5-fluoro-4-trifluoromethyloxazole, a starting material easily accessible from hexafluoroacetone. The fluorine atom in the 5 position is easily displaced by an allylic or benzylic alcohol. Then, the obtained ethers spontaneously undergo a Claisen rearrangement to afford, after acidic hydrolysis, an a-trifluoromethyl amino acid... 

Arylcinnolin-4-amines 246 could be obtained from o-trifluoromethylphenyl hydrazones 245 via treatment with NaHMDS in THF at —78°C (Equation 60). The mechanism consists of quinine methide formation followed by electrocyclization and elimination of HF yielding 3-aryl-4-fluorocinnolines. Nucleophilic aromatic substitution of the fluorine atom with NaFlMDS gave, after basic hydrolysis, 3-arylcinnolin-4-amines 246 <1999TL5111>. 

Substitution of fluorine for halogen in aromatic and alkyl sulfonyl halides can be carried out with or without using a solvent. An aqueous system such as 70 % aqueous potassium fluoride is also used because the rate of hydrolysis is much slower than the rate of fluorination as reported for the conversion of methanesulfonyl chloride (1) to methanesulfonyl fluoride (2).23... 

The narrow fluorine resonance of "Ci BF " is quite in contrast to the fluorine absorption found for the product of Illinois 6 coal with BF3. At room temperature, we observe a 0.25 mT (=2.5 G) wide, dipolar-broadened, spectrum not indicative of translation freedom. In contrast to the weakly bound complexes of BF3 with aromatic hydrocarbons, we anticipate BF3 to react strongly with oxygen functionality in the coal, through hydration with water, hydrolysis with acids (13), and ether complex formation (14), to give fluorine absorption lines which are in the rigid lattice condition. 

Because of the presence of nitrogen in the aromatic ring, electrons in pyridine are distributed in such a way that their density is higher in positions 3 and 5 (the P-positions). In these positions, electrophilic substitutions such as halogenation, nitration, and sulfonation take place. On the contrary, positions 2, 4, and 6 (a- and y-positions, respectively) have lower electron density and are therefore centers for nucleophilic displacements such as hydrolysis or Chichibabin reaction. In the case of 3,5-dichlorotrifluoropyridine, hydroxide anion of potassium hydroxide attacks the a- and y-positions because, in addition to the effect of the pyridine nitrogen, fluorine atoms in these position facilitate nucleophilic reaction by decreasing the electron density at the carbon atoms to which they are bonded. In a rate-determining step, hydroxyl becomes attached to the carbon atoms linked to fluorine and converts the aromatic compound into a nonaromatic Meisenheimer complex (see Surprise 67). To restore the aromaticity, fluoride ion is ejected in a fast step, and hydroxy pyridines I and J are obtained as the products [58],... 

Nucleophilic aromatic substitution of the fluorine substituents by benzene-dithiolate sulfur atoms (step a), reduction of the nitro compound (step b), diazotization, reaction with KSaCOEt, alkaline hydrolysis, and acidification gave tpS4 H2 (step c). It could be purified via the [Ni(tpS4)]2 complex (Fig. 1), which is readily hydrolyzed with dilute hydrochloric acid to give pure tpS4 H2. 

The synthesis of one of the agents begins with nucleophilic aromatic displacement of bromine by cyanide in the highly fluorinated compound 78. Acid hydrolysis of the nitrile (79), followed by esterification of the newly formed acid, affords ester 80. Base-catalyzed condensation of the intermediate with diethyl malonate leads to the tricarbonyl derivative 81. 

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