Carbanion from haloforms

Caron aldehyde ester was of great help particularly for the casual preparation of many chrysanthemic acid analogues for insecticidal research. Instead of triphenyl phosphine the trisdimethylamino phosphine may be apphed preferentially [247]. The production of caronaldehyde 755 by the route outUned above is still essential for the production of deltamethrin. Alternatively to the Wittig reaction, the dichlorome-thylene moiety may be introduced by reaction of carbenoids or carbanions from haloforms with the hemiketal 158 of free cis-caronaldehyde, (reaction scheme 100) [248, 249] and subsequently completed by dehalogenation processes. 

The ease of carbanion formation from haloforms (58) depends on the a halogen as I > Br > Cl > F. This same order is valid for haloethylenes (59) as evidenced by the rate of deuterium exchange. 

Intermediate carbenes are also involved in the alkylation by haloforms of carbanions derived from Schiff bases of a-ammo esters [126] or aminomalonates... 

The catalytic conditions (aqueous concentrated sodium hydroxide and tetraalkylammonium catalyst) are very useful in generating dihalo-carbenes from the corresponding haloforms. Dichlorocarbene thus generated reacts with alkenes to give high yields of dichlorocyclopropane derivatives,16 even in cases where other methods have failed,17 and with some hydrocarbons to yield dicholromethyl derivatives.18 Similar conditions are suited for the formation and reactions of dibromocar-benc,19 bromofluoro- and chlorofluorocarbene,20 and chlorothiophenoxy carbene,21 as well as the Michael addition of trichloromethyl carbanion to unsaturated nitriles, esters, and sulfones.22... 

Figure 11-9 illustrates the mechanism for the haloform reaction. The mechanism involves a repeated series of base attacks (removal of an a-hydrogen) followed by the reaction with the halogen until all three a-hydrogen atoms are replaced. Then the base attacks the carbonyl carbon to induce the loss of a carbanion Q.CXf. The highly reactive carbanion quickly attacks and removes the hydrogen from the carboxylic acid group. 

Base-catalysed H/D exchange experiments for a series of haloforms [80] (Table 4.10) demonstrate that carbanion formation is stabilised by halogen in the order 1 > Br > Cl > F. When these results are combined with acidity measurements which show that CF3H (pKa 31) is little more acidic than methane (pKa 40) [81], we can conclude that, in these systems, fluorine attached to a carbanion centre is stabilising with respect to hydrogen but destabilising compared with the effects of other halogens. Similar conclusions can be drawn from pKa measurements of a number of halobis(trifluoromethyl) methanes [82]. 

Information about the acidities or relative acidities of the haloforms has been obtained from kinetic studies under conditions where low concentrations of the carbanion are present and decomposition is unimportant. Extensive studies of this type have been carried out by Hine et al. [164]. Exchange of deuterium from CDX3 in aqueous buffer solutions (98)... 

In Na0H/H20, these trihalocarbonyl compounds react further because hydroxide addition can lead to elimination of the stabilized trihalocarbanion. After these addition-elimination steps, the carbanion can gain a proton from solvent or the carboxylic acid to form a molecule of a haloform, which is a common name for a trihalomethane (Fig. 19.38). Under these basic conditions the carboxylic acid will remain deprotonated. 

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