Conversion into acid chlorides

Reactions of carboxylic acids (Section 21.3) (a) Conversion into acid chlorides... 

Conversion of Carboxylic Acids into Acid Chlorides... 

Conversion of Acid Chlorides into Alcohols Reduction Acid chlorides are reduced by LiAJH4 to yield primary alcohols. The reaction is of little practical value, however, because the parent carboxylic acids are generally more readily available and can themselves be reduced by L1AIH4 to yield alcohols. Reduction occurs via a typical nucleophilic acyl substitution mechanism in which a hydride ion (H -) adds to the carbonyl group, yielding a tetrahedral intermediate that expels Cl-. The net effect is a substitution of -Cl by -H to yield an aldehyde, which is then immediately reduced by UAIH4 in a second step to yield the primary alcohol. 

Recently, Oshima et al. developed the conversion of acid chlorides into the corresponding homoallylic alcohols catalyzed by in r(/ -prepared hydridozirconium allyl reagents (Scheme 41),147 147a The proposed mechanism suggests an initial hydride transfer from the zirconocene crotyl hydride species, in equlibrium with its Cp2Zr(l-alkene),147a to the acid chloride with subsequent allylation to afford the corresponding homoallylic alcohols. 

The acid chlorides have served as useful synthetic intermediates leading to ketones via the malonic acid synthesis and Friedel rafts reaction, thiadiazole acetic acid derivatives, and halo ketones via the Arndt Eistert synthesis and carbinols by hydride reduction <68AHC(9)107>. The dialkylcadmium conversion of acid chlorides into ketones fails in the 1,2,5-thiadiazole series. The major product is either a tertiary carbinol or the corresponding dehydration product, by virtue of the high reactivity of the intermediate ketone. 

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) ... 

General procedure for the one-pot conversion of acid chlorides into nitriles.173... 

An alternative procedure49 for effecting the conversion of acid chlorides into aldehydes is chemical reduction with bis(triphenylphosphine)copper(i) tetrahy-droborate (see also Section 5.7.4, p. 594). The procedure is illustrated by the synthesis of 3,4-dimethoxybenzaldehyde which is isolated as the 2,4-dinitro-phenylhydrazine derivative50 (cognate preparation in Expt 6.120). 

The conversion of carboxylic acids and SOCl2 into acid chlorides is frequently catalyzed by DMF. The mechanism of this catalysis is shown in Figure 6.11. It is likely that SOCI2 and DMF first react to give the Vilsmeier-Haack reagent A. It differs from the reactive interne-... 

Fig. 6.11. Mechanism of the DMF-catalyzed conversion of carboxylic acids and SOC into acid chlorides.

A key intermediate of the esterification in Figure 9.16 is the iminium ion F. It is identical to the iminium ion B in Figure 6.11, which represents the activated carboxylic acid in the DMF-catalyzed conversion of carboxylic acids into acid chlorides. Thus, the iminium ion F in Figure 9.16 is a potent acylating agent. As such, it reacts with the methoxide ion, a stoichiometric by-product of its formation reaction, via the tetrahedral intermediate C to furnish the corresponding carboxylic acid methyl ester and DMF. 

Germanium was determined in coal dust after conversion into the chloride [604] by treatment with hydrogen chloride at a high temperature on a mixture of coal powder and Chromosorb (1 1), wetted with sulphuric acid. The analysis of a sample of 1.5 g was reported having a sensitivity of 3.3 ppm of germanium with an error of 6%. 

These conversions of acids into acid chlorides complete all the methods we need to convert acids into any acid derivatives. You can convert acids directly to esters and now to acid chlorides, the most reactive of acid derivatives, and can make any other derivative from them. The chart below adds reactions to the reactivity order we met earlier. 

Now for some of the reactions you have seen in the last few chapters. Starting with carbonyl substitution reactions, the first example is the conversion of acid chlorides into esters. The simplest mechanism to understand is that involved when the anion of an alcohol (a metal alkoxide RO ) reacts with an acid chloride. The kinetics are bimolecular rate = fc[MeCOCl] [RO ]. The mechanism is the simple addition elimination process with a tetrahedral intermediate. 

In this context, zirconium chemistry could open up new prospects for developing deoxygenative approaches to cyclopropanes. The Zr-assisted variant of the Kulinkovich reaction has been reported (Scheme 4, Eq. 1) [10]. Cyclopropanols were also formed, as by-products in addition to homoallylic alcohols, from aliphatic acid chlorides (Eq. 2) [ 10]. The conversion of acid chlorides (and also esters in several cases) into the corresponding homoallylic alcohols... 

Rriiss 8 published in 1887 the first modem determinations of any value. The gold employed was carefully purified, special attention being devoted to the elimination of silver and the metals of the platinum group. In his analyses of auric chloride, an aqueous solution of that salt was first prepared. With one weighed portion of the solution the gold was estimated by reduction with sulphurous acid with another the chlorine was determined by conversion into silver chloride. Eight experiments gave the mean result... 

Conversion of Corboxytic Acids Into Acid Chlorides (ftCOjH ---- RCOCI)... 

Alkyl chlorides , acid chlorides (1,1247). The conversion of alcohols into alkyl chlorides and of adds into acid chlorides with (CsHslsP and CCU proceeds more rapidly when the phosphine is polymer supported. One factor contributing to the rate increase may be the close proximity of the phosphorus-containing residues. 

Ketones, The diversity of reagent structural types, the simplicity and mildness of experimental conditions, and the functional group selectivity and stereoselectivity of organocopper reagents suggest that these are generally the reagents of choice for conversion of acid chlorides into ketones. ... 

REACTIONS OF ACID CHLORIDES 1. Conversion into acids and derivatives. Discussed in Sec. 20.8. 

Conversion of acid chlorides into acid derivatives... 

---