Bromides nucleophilic reactions

The dianions derived from furan- and thiophene-carboxylic acids by deprotonation with LDA have been reacted with various electrophiles (Scheme 64). The oxygen dianions reacted efficiently with aldehydes and ketones but not so efficiently with alkyl halides or epoxides. The sulfur dianions reacted with allyl bromide, a reaction which failed in the case of the dianions derived from furancarboxylic acids, and are therefore judged to be the softer nucleophiles (81JCS(Pl)1125,80TL505l). 

It occasionally happens that a reaction proceeds much faster or much slower than expected on the basis of electrical effects alone. In these cases, it can often be shown that steric effects are influencing the rate. For example, Table 9.2 lists relative rates for the Sn2 ethanolysis of certain alkyl halides (see p. 390). All these compounds are primary bromides the branching is on the second carbon, so that field-effect differences should be small. As Table 9.2 shows, the rate decreases with increasing P branching and reaches a very low value for neopentyl bromide. This reaction is known to involve an attack by the nucleophile from a position opposite to that of the bromine (see p. 390). The great decrease in rate can be attributed to steric hindrance, a sheer physical blockage to the attack of the nucleophile. Another example of steric hindrance is found in 2,6-disubstituted benzoic acids, which are difficult to esterify no matter what the resonance or field effects of the groups in the 2 or the 6 position. Similarly, once 2,6-disubstituted benzoic acids are esterified, the esters are difficult to hydrolyze. 

This hypothesis is satisfactory for nucleophilic reactions of cyanide and bromide ion in cationic micelles (Bunton et al., 1980a Bunton and Romsted, 1982) and of the hydronium ion in anionic micelles (Bunton et al., 1979). As predicted, the overall rate constant follows the uptake of the organic substrate and becomes constant once all the substrate is fully bound. Addition of the ionic reagent also has little effect upon the overall reaction rate, again as predicted. Under these conditions of complete substrate binding the first-order rate constant is given by (8), and, where comparisons have been made for reaction in a reactive-ion micelle and in solutions... 

A useful extension of the in situ anomerization process involves the employment of C-nucleophiles such as vinyl and allyl magnesium bromides. Grignard reactions to per-O-benzylated glycosyl iodides proceed stereoselectively when a strong nucleophile like allyl magnesium bromide is used, giving [1-C-allyl fucosides (95% P-only)... 

The ammonium catalyst can also influence the reaction path and higher yields of the desired product may result, as the side reactions are eliminated. In some cases, the structure of the quaternary ammonium cation may control the product ratio with potentially tautomeric systems as, for example, with the alkylation of 2-naph-thol under basic conditions. The use of tetramethylammonium bromide leads to predominant C-alkylation at the 1-position, as a result of the strong ion-pair binding of the hard quaternary ammonium cation with the hard oxy anion, whereas with the more bulky tetra-n-butylammonium bromide O-alkylation occurs, as the binding between the cation and the oxygen centre is weaker [11], Similar effects have been observed in the alkylation of methylene ketones [e.g. 12, 13]. The stereochemistry of the Darzen s reaction and of the base-initiated formation of cyclopropanes under two-phase conditions is influenced by the presence or absence of quaternary ammonium salts [e.g. 14], whereas chiral quaternary ammonium salts are capable of influencing the enantioselectivity of several nucleophilic reactions (Chapter 12). 

The mechanism for the reactions with phosphorus halides can be illustrated using phosphorus tribromide. Initial reaction between the alcohol and phosphorus tribromide leads to a trialkyl phosphite ester by successive displacements of bromide. The reaction stops at this stage if it is run in the presence of an amine which neutralizes the hydrogen bromide that is formed.9 If the hydrogen bromide is not neutralized the phosphite ester is protonated and each alkyl group is successively converted to the halide by nucleophilic substitution by bromide ion. The driving force for cleavage of the C—O bond is the... 

New 3-desoxyanthocyanidins have been prepared according to a Grignard reaction of some flavones with appropriate alkyl- and aryl-magnesium bromides. The reaction of 5,7-dihydroxyflavone (chrysin) with an excess of phenylmagnesium bromide in THF under reflux conditions, followed by hydrochloric acid hydrolysis, afforded 1 in Scheme 10.2. Flavylium salts bearing a substituent at the 4-position are important compounds since they are known to be less sensitive to nucleophiles, especially water, and they give only minor amounts of the colorless pseudobases. ... 

Scheme 7.4 Nucleophilic reaction between a bromide anion and a bromonium ion generates 1,2-dibromoalkanes.

Radical cations act both as electrophiles and one-electron oxidants toward nucleophiles (Eberson, 1975 Bard et al, 1976 Eberson et al., 1978a,b Evans and Blount, 1978) as shown in (6), and it is therefore important to find out which factors govern the competitition between these reaction modes. Evans and Blount (1978) measured rate constants and products for a number of [9,10-diphenylanthracene)+ /nucleophile reactions and found that iodide, rhodanide, bromide and cyanide undergo oxidation, whereas nucleophiles that are more difficult to oxidize form a C—Nu bond directly. Entry no. 13 of Table 15 shows non-bonded electron transfer to be feasible for these ions, and the reactions of [perylene]+ with iodide, rhodanide and bromide (entry no. 14) presumably can be classified in the same way. The reaction with chloride ion... 

Particularly useful is a synthetic approach utilizing the diazotization of 0-alkynylanilines 222 followed by cyclization of intermediate diazonium salts 223 (the Richter method) (Scheme 128) . In this reaction a nucleophile attacks the C(l) of the alkyne moiety in the diazonium intermediate 223, allowing substitution in the C(4) position of the cinnoline 224. Classically, water was used as the attacking species in the Richter reaction but more recently chloride and bromide nucleophiles have been successfully utilized <1995LA775, 2004T7983>. 

Protection of hydroxyl groups. Alcohols and phenols react with 1 and tri-ethylamine to form tetrahydro-2-furanyl (THF) ethers (85-98% yield). The reaction of acids with 1 results in THF esters. These derivatives are stable to base and nucleophilic reagents they are readily removed by acid-catalyzed hydrolysis or methanolysis. One synthetic application is conversion of the ethers into alkyl bromides by reaction with triphenyphosphine dibromide (1,1247-1248), a reaction that is faster than that with the free alcohols. 

Often it is useful to draw resonance forms for proposed intermediates because their existence is an indication of stability, which represents a driving force for the reaction. Removal of a proton from the OH group of the resonance hybrid of 2-9 and 2-10 is unlikely because bromide ion is an even weaker base than DMSO (the pK of HBr is -9). Therefore, it is expected that ring closure, by nucleophilic reaction with the cation, takes place before removal of the proton. 

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