Acid chlorides, aromatic, reduction

Acid chlorides, reduction to aldehydes, 53, 55 Acid chlorides, aromatic, diazoketones from, 53, 37... 

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... 

Hydrogenation of double bonds, acid chlorides, aromatic nitro compounds, carbonyl groups, partial reduction of triple bonds, etc. 

Rearrangement reaction, 138 Reducing sugar, 992 Reduction, 229. 348 acid chlorides, 804 aldehydes, 609-610. 709 aldoses, 992 alkene, 229-232 alkyne, 268-270 amides, 815-816 arenediazonium salt, 943 aromatic compounds and, 579-580... 

The hrst step in the preparation of the antidepressant maprotiline (33-5) takes advantage of the acidity of anthrone protons for incorporation of the side chain. Thus treatment of (30-1) with ethyl acrylate and a relatively mild base leads to the Michael adduct saponihcation of the ester group gives the corresponding acid (33-1). The ketone group is then reduced by means of zinc and ammonium hydroxide. Dehydration of the hrst-formed alcohol under acidic conditions leads to the formation of fully aromatic anthracene (33-2). Diels-Alder addition of ethylene under high pressure leads to the addition across the 9,10 positions and the formation of the central 2,2,2-bicyclooctyl moiety (33-3). The hnal steps involve the construction of the typical antidepressant side chain. The acid in (33-3) is thus converted to an acid chloride and that function reacted with methylamine to form the amide (33-4). Reduction to a secondary amine completes the synthesis of (33-5) [33]. 

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. 

Reduction of add chlorides (8, 461).2 Acid chlorides can be selectively reduced to aldehydes by slightly less than 1 molar equivalent of NaBH4 in a mixture of DMF THF at - 70°. It is essential to minimize further reduction by quenching the reaction with a mixture of propionic acid-dilute HC1 and ethyl vinyl ether (caution H2 is evolved). Both aliphatic and aromatic aldehydes can be obtained in 80-95% yield. 

Aromatic acid chlorides are decarbonylated to aryl chlorides when they are heated to 300-360 C with palladium on carbon. The reaction proceeds by way of an aroylpalladium chloride, then to an arylpalla-dium chloride and finally through a reductive elimination to the aryl chloride. If the reaction is conducted in the presence of a reactive alkene under mild conditions the aroylpalladium chloride intermediate will sometimes acylate the alkene, as noted in Section 4.3.5.3.I. More usually, however, decarboxylation is more rapid than acylation, especially at higher temperatures (>100 C), and decarbonylation occurs. The... 

Bis(triphenylphosphine)copper(i) tetrahydroborate [(Ph3P)2CuBH4] has found use as a reagent for the reduction of aliphatic and aromatic acid chlorides to the corresponding aldehyde, and is an alternative to the standard Rosenmund procedure. This is illustrated in Expt 6.120. The reagent may be prepared by either of the following two methods both preparations should be conducted in an efficient fume cupboard as hydrogen is evolved. 

Acid chlorides can be selectively hydrogenated in the presence of a catalyst (palladium deposited on a carrier, which is usually barium sulphate but is occasionally charcoal). The reaction, which involves the hydrogenolysis of the carbon-halogen bond, is known as the Rosenmund reduction and has been widely used for the synthesis of aromatic and heterocyclic aldehydes. 

Reduction of carbonyl compounds.2 The reagent reduces aromatic and aliphatic ketones, aldehydes, and acid chlorides to alcohols in moderate to excellent yield in chloroform solution. The order of substrate reactivity is RCOCl>RCHO>R2CO. Only three of the eight hydrogens are transferred under the reaction conditions. 

As an example of carbometallation, the 1,4-carbosilylation product 218 is obtained by the reaction of dienes, disilanes and acid chlorides of aromatic and a,/i-unsaturatcd acids at 80 °C. The phenylpalladium 216 is formed by the oxidative addition of benzoyl chloride, followed by facile decarbonylation at 80 °C, and reacts with butadiene to generate the benzyl-7i-allylic complex 217. Then, transmetallation with the disilane and reductive elimination afford 4-silyl-2-butenylbenzene 218 [92], Regioselective carbomagnesation of isoprene with allylic magnesium bromide 219 catalysed by Cp2TiCl2 gives 220, which is useful for terpene synthesis [93,94],... 

Once an amino group has been introduced to an aromatic ring, it can be alkylated with an alkyl halide, acylated with an acid chloride or converted to a higher amine by reductive animation as already described for an alkylamine. 

The scope of catalytic hydrogenations continues to be extended to more difficult reductions. For example, a notoriously difficult reduction in organic synthesis is the direct conversion of carboxylic acids to the corresponding aldehydes. It is usually performed indirectly via conversion to the corresponding acid chloride and Rosenmund reduction of the latter over Pd/BaS04 [65]. Rhone-Poulenc [30] and Mitsubishi [66] have developed methods for the direct hydrogenation of aromatic, aliphatic and unsaturated carboxylic acids to the corresponding aldehydes, over a Ru/Sn alloy and zirconia or chromia catalysts, respectively, in the vapor phase (Fig. 1.18). 

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