Reduction, of acid chlorides

Acid chlorides are extremely reactive compounds that are usually prepared for the single purpose of reacting them with another compound. They are prepared by the reaction of a carboxylic acid with thionyl chloride. The stoichiometry is the same as for the conversion of an alcohol to an alkyl halide using thionyl chloride (Section 15.3). 

Acid chlorides can be reduced to aldehydes either by catalytic hydrogenation or by reaction with a metal hydride. In both cases, the reagent and the reaction conditions are selected to avoid the further reduction of the aldehyde. The conversion of an acid chloride to an aldehyde can be carried out by the Rosenmund reduction, which uses hydrogen gas and a modified palladium catalyst. The palladium catalyst is altered to prevent further reduction of the aldehyde. To prepare the catalyst, the palladium is treated with quinoline, an aromatic heterocyclic amine, and is heated with sulfhr. 

Acid chlorides can also be converted to aldehydes with hthium tri(ferr-butoxy)aluminum hydride. The reagent is prepared by reacting lithium aluminum hydride with three equivalents of tert-huxy alcohol. 

The electron-withdrawing rerr-butoxy groups decrease the reactivity of the A1—H bond. As a result, hthium tri(rerr-butoxy)aluminum hydride displaces a chloride ion from an acyl chloride, but will not reduce the carbonyl group of the aldehyde. By contrast, lithium aluminum hydride reduces acyl 

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Reduction of Acid Chlorides to Aldehydes. Palladium catalysis of acid chlorides to produce aldehydes is known as the Rosenmund reduction and is an indirect method used in the synthesis of aldehydes from organic acids. 

The organosilane reduction of acid chlorides to aldehydes has been accomplished in high yields with the use of the pentacoordinated organosilane 60 (Eq. 137).107 This transformation has been reported to occur with tribenzylsilane and triethylsilane, but yields were not reported.285,286... 

Reduction of acid chlorides. In combination with TMEDA, Zn(BH4)2 reduces acid chlorides, RCOC1, to primary alcohols, RCH2OH, in 80-95% yield. 

Kinetic studies established that tetra-n-butylammonium borohydride in dichloromethane was a very effective reducing agent and that, by using stoichiometric amounts of the ammonium salt under homogeneous conditions, the relative case of reduction of various classes of carbonyl compounds was the same as that recorded for the sodium salt in a hydroxylic solvent, i.e. acid chlorides aldehydes > ketones esters. However, the reactivities, ranging from rapid reduction of acid chlorides at -780 C to incomplete reduction of esters at four days at 250 C, indicated the greater selectivity of the ammonium salts, compared with sodium borohydride [9], particularly as, under these conditions, conjugated C=C double bonds are not reduced. 

The facile homogeneous catalysed reduction of acid chlorides to alcohols has many advantages over reduction with sodium borohydride in hydroxylic solvents where rapid reaction of the acid chloride with the solvent can occur [10]. The procedure has been incorporated into a simple one-pot conversion of aroyl chlorides into the corresponding benzyl chlorides (Scheme 11.1) under liquidrliquid or solid-liquid two-phase conditions [11], The reduction of a limited number of aryl compounds was reported with ca. 70% overall yields, although poorer yields result from the reduction of 4-nitro-, 2-cyano- and 2,4-dichlorobenzoyl chlorides, and the reduction failed completely with terphthaloyl chloride and with its 2,3,5,6-tetrafluoro derivative [11]. 

Hydrogenation reduction of acid chloride to aldehyde using BaS04-poisoned palladium catalyst. Without poison, the resulting aldehyde may be further reduced to alcohol. 

Linear sweep voltammetry of ben2x yl chloride in acetonitrile containing tetra-ethylammonium fluoroborate shows Ep == -1.4 V vs. see and for heptanoyl chloride Ep = -2,2 V vs. see [169] The one-electron reduction of acid chlorides at these potentials is a source of carbonyl radicals. Reduction of benzoyl chloride at the peak... 

Aldehydes are prepared by the hydroboration-oxidation of alkynes (see Section 5.3.1) or selective oxidation of primary alcohols (see Section 5.7.9), and partial reduction of acid chlorides (see Section 5.7.21) and esters (see Section 5.7.22) or nitriles (see Section 5.7.23) with lithium tri-terr-butox-yaluminium hydride [LiAlH(0- Bu)3] and diisobutylaluminium hydride (DIBAH), respectively. 

Reduction of acid chlorides to aldehydes. Two laboratories12 have published details for this reduction. One difficulty is the large quantities of reagent needed for preparative-scale reactions. For large-scale reductions the Rosenmund reaction is preferable. 

Reduction of aromatic azides. Aromatic azides can be reduced to anilines by this reagent in CHCl3 at 25°. The rate is accelerated by electron-withdrawing substituents but is reduced by electron-attracting groups. Even so, the presence of an azide group does not interfere with use of the reagent for reduction-of acid chlorides to aldehydes. 

Barium sulphate is frequently used as a support for the palladium (compare the Rosenmund reduction of acid chlorides, Section IV, 120) barium carbonate... 

The electrochemical reduction of acid chlorides takes a very different course when carried out in an undivided cell equipped with nickel cathode and anode79. The product is a symmetrical ketone (57) 57 is formed by a complex sequence involving both electrodes (Scheme 12). This is really a chemical reaction induced by a highly reactive form of nickel produced by dissolution of the anode and plated onto the cathode. We have already encountered similar chemistry involving highly reactive zinc (Section V.A.l). 

The catalytic reduction of carboxylic acid chlorides by the Rosenmund procedure may be used for the preparation of aliphatic aldehydes but its application is mainly for the synthesis of aromatic aldehydes (e.g. Expt 6.120). Alternative procedures for the chemical reduction of acid chlorides include reduction with... 

Fig.M. Reduction of acid chlorides, acid anhydrides, and esters with lithium aluminium hydride.

E. Mosettig, R. Mozingo, The Rosenmund Reduction of Acid Chlorides to Aldehydes, Org. React. 1948, 4, 362-377. 

Table 23 Reduction of acid chlorides to aldehydes. Reproduced with permission from Elsevier...

Aldehyde synthesis by reduction of acid chlorides (Section 18-10)... 

The reduction of acid chlorides may proceed at lower temperatures in the presence of a tertiary amine or sodium acetate. Peters and van Bekkum improved the method of Sakurai and Tanabe,260 using ethyldiisopropylamine, instead of A(7V-dimethylaniline, as a HC1 acceptor.261 Ethyldiisopropylamine had the advantage of forming an acetone soluble hydrochloride, and workup of the reaction mixture was easier when acetone was used as solvent. Reductions in the presence of these basic substances have been found to be especially effective when the acid chlorides are labile to decarbonylation. Examples of the use of base are shown in eqs. 13.139261 and 13.140.262 When the original procedure of the Rosenmund reduction was applied to 1 -/-bulylcyclohcxanc-carbonyl chloride, f-butylcyclohexanc was the sole product, compared to greater than 95% yield of the corresponding aldehyde in the presence of ethyldiisopropylamine or sodium acetate.261... 

The aldehyde intermediate can be isolated if a leas puwerfu] reducintt agent such as lithiu.ni trt>lerl but0xyalurniiiii3n hydride is ii. ed in place of LiAlH. This reagent, which is obtained by reaction of LiAlK with 3 cciuiv-alente of lerl-butyl alcohol, is particularly effective far carrying out the partial reduction of acid chlorides to aldehyde (Section 19.2>. 

Reduction of acid chlorides to aldehydes One of the most useful synthetic transformations in organic synthesis is the conversion of an acid chloride to the corresponding aldehyde without over-reduction to the alcohol. Until recently, this type of selective reduction was difficult to accomplish and was most frequently effected by catalytic hydrogenation (the Rosenmund reduction section 6.4.1). However, in the past few years, several novel reducing agents have been developed to accomplish the desired transformation. Among the reagents that are available for the partial reduction of acyl chlorides to aldehydes are bis(triphenylphosphine)cuprous borohydride , sodium or lithium tri-terf-butoxyaluminium hydride, complex copper cyanotrihydridoborate salts °, anionic iron carbonyl complexes and tri-n-butyltin hydride in the presence of tetrakis(triphenylphosphine)palladium(0). ... 

Reduction of acid chlorides. Sodium borohydride impregnated on alumina reduces acid chlorides to primary alcohols (equation I). 

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