Fluorine effect displacement reaction

The small effect on reaction rates of the addition of crown ethers to the lower alcohols was also observed in the reaction of potassium acetate with 1-bromobutane in ethanol (Hirao et al., 1978a,b). The displacement of fluorine in either o-nitro- or p-nitro-fluorobenzene by a methoxy group, by reaction with potassium methoxide in methanol was hardly influenced by the presence of dicyclohexyl-18-crown-6 (Del Cima et al., 1973). Mariani et al. (1978), too,... 

In perchloryl fluoride (FCIO3) the fluorine is a soft acid. Formation of the C-F bond is observed when it is treated with carbanions. Thiolates are oxidized to disulfides by this reagent (92, 93). This latter reaction presumably involves sulfenyl fluoride intermediates. In contrast, alkoxide ions effect displacement at chlorine to afford perchlorate esters or further transformation products. 

There are only a few examples of displacement of a fluorine atom in a cross-coupling reaction. With tricarbonylchromium complexes of fluoroarenes as substrates, cross-coupling with both boronic acids and vinylstannanes has been realized. Interestingly, only PMe3 is effective as ligand in this reaction (89).2" See Section 9.6.3.4.10 for an example of the involvement of unactivated fluoroarenes in cross-coupling reactions. 

The alkylation reaction is limited to nitro-substituted arenes and heteroarenes and is highly chemoselec-tive nucleophilic displacement of activated halogens, including fluorine, was not observed. The regio-selectivity is determined by the bulkiness of the silicon reagent. With unhindered silyl derivatives a strong preference for ortho addition was observed, as in the example of equation (6). With bulkier reagents attack took place exclusively at the para position (Scheme 1). The success of this reaction, which could not be reproduced with alkali enolates, was attributed at least in part to the essentially nonbasic reaction conditions under which side processes due to base-induced reactions of nitroarenes can be effectively eliminated.12... 

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],... 

In contrast, fluorine or fluorocarbon groups directly attached to the reaction centre have a much more pronounced effect [4] for example, the hydrolytic displacement of chloride from PhCHFCl appears to be activated with respect to benzyl chloride [10], although the situation is complicated by concomitant SnI and Sn2 processes. 

The faster reaction of aryl fluorides is attributed to the very strong inductive effect of fluorine by withdrawing electrons it stabilizes the transition state of the first step of a reaction that will ultimately lead to its displacement. 

Cellulase was found to be effective in the synthesis of artificial cellulose in a single-step reaction by polycondensation of /J-D-cellobiosyl fluoride (Scheme 13).123 The polymerization is a repetition of the transglycosylation reaction, which became predominant over the hydrolysis reaction when the enzymatic polycondensation was carried out in a mixed solvent of acetonitrile/acetate buffer (5 1, pH 5). This synthesis is therefore kinetically controlled as well as equilibrium controlled. The fi configuration of the Cl fluorine atom is necessary to form a reactive intermediate leading to a / (1—4) product via a double displacement mechanism .124 Thus, this method provided the first successful in vitro synthesis of cellulose, the most abundant biomacromolecules on the earth, the synthesis of which had been unsolved for one-half a century.123... 

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