Acid chlorides with organocadmium compounds

Reaction of acid chlorides with organocadmium compounds. Discussed in Sec. 19.7. 

Aliphatic ketones are readily prepared from the corresponding secondary alcohols, if these are available. More complicated aliphatic ketones can be prepared by the reaction of acid chlorides with organocadmium compounds. A... 

This method allows the preparation of ketones from acid chlorides containing other functional groups such as CO, CO2R, and CN, though some of these react slowly with organocadmium compounds under the conditions normally used. 

The main use of organocadmium compounds is for the preparation of ketones and keto-esters, and their special merit lies in the fact that they react vigorously with acid chlorides of all types but add sluggishly or not at all to multiple bonds (compare addition of Grignard reagents to carbonyl groups). Some t3rpical syntheses are ... 

The success of the last reaction depends upon the inertness of the ester carbonyl groups towards the organocadmium compound with its aid and the use of various ester acid chlorides, a carbon chain can be built up to any reasonable length whilst retaining a reactive functional group (the ester group) at one end of the chain. Experimental details are given for l-chloro-2-hexanone and propiophenone. The complete reaction (formation of ketones or keto-esters) can be carried out in one flask without isolation of intermediates, so that the preparation is really equivalent to one step. 

Many organocadmium compounds are known but few have been of commercial importance. Wanklyn first isolated diethyl cadmium in 1856. The properties of this and other dialkylcadmiums are listed in Table 4. In general, these materials are prepared by reaction of an anhydrous cadmium halide with a Grignard or alkyUithium reagent followed by distillation of the volatile material in an inert atmosphere or in vacuo. Only the liquid dimethyl compound is reasonably stable and then only when stored in a sealed tube. Dimethylcadmium is mildly pyrophoric in air and produces dense clouds of white, then brown, cadmium oxide smoke, which is highly toxic if breathed (45). When dropped into water, the liquid sinks in large droplets that decompose with a series of small explosive jerks and pops. For this reason, and particularly because of the low thermal stability, most dialkylcadmium materials are prepared and used in situ without separation, eg, in the conversion of acid chlorides to speciality ketones (qv) ... 

Grignard reagents derived from aryl bromides are readily prepared and may be converted into organocadmium compounds by treatment with cadmium chloride (cf. Section 5.8.4, p. 616). Reaction of an organocadmium with a carboxylic acid chloride constitutes a convenient synthesis of aryl alkyl ketones. 

Grignard reagents react with dry cadmium chloride to yield the corresponding organocadmium compounds, which react with acid chlorides to yield ketones ... 

Grignard reagents themselves react readily with acid chlorides, but the products are usually tertiary alcohols these presumably result from reaction of initially formed ketones with more Grignard reagent. (If tertiary alcohols are desired, they are better prepared from esters than from acid chlorides. Sec. 20.21.) Organocadmium compounds, being less reactive, do pot react with ketones. 

The comparatively low reactivity of organocadmium compounds not only makes the synthesis of ketones possible, but in addition widens the applicability of the method. Organocadmium compounds do not react with many of the functional groups with which the Grignard reagent does react —NO2, —< N, —CO—, —COOR, for example. Consequently, the presence of one of these groups in the acid chloride molecule does not interfere with the synthesis of a ketone (compare with Sec. 15.15). For example ... 

In this ketone synthesis, (1) the Grignard reagent reacts with cadmium chloride to yield an organocadmium compound, plus a magnesium dihalide. (2) The organocadmium is then reacted with an acid chloride to yield a ketone plus cadmium chloride. 

The most common application of organocadmium compounds has been in the preparation of ketones by reaction with acid chlorides. 

The use of organocadmium compounds, RjCd, lies in the fact that they react only with acid chlorides and no other carbonyl compounds. Thus, acid chlorides can be converted to ketones with no risk of further reaction. Organocadmium compounds are prepared (Equation 15.3) by reaction of cadmium chloride with a Grignard reagent, and the reactions only work well when R is aryl or primary alkyl. An example is provided in Figure 15.45. 

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