Reduction, of acid chlorides with

Reduction of Acid Chlorides with Lithium Aluminum Hydride... 

Reduction of acid chlorides with tripropyltin hydride in the presence of the radical initiator di-t-butyl peroxide has also been shown to furnish alkanes in moderate yield (equation 73). Carboxylic acids can also be decarboxylated via carboselenoic acid esters with TBTH in the presence of of AIBN... 

This procedure and others mentioned are particularly valuable for the prepn. of aliphatic aldehydes whereas reduction of acid chlorides with Li-hydridotri-ferf-butoxoaluminate (s. Synth. Meth. 11, 135) is especially valuable for the prepn. of ar. aldehydes. F. e. s. H. G. Brown and A. Tsukamoto, Am. Soc. 83, 2016, 4549 (1961). 

Whereas platinum-catalysed reduction of acid chlorides with triethyl-silane gives aldehydes, Eaborn has shown that rhodium catalysis can give predominantly ketones. a-Ketophosphonate esters, readily available from the action of carboxylic acid chlorides on trialkyl phosphites, are reduced by sodium borohyffiride to the ester (123), which fragments to the... 

It may also be prepared by the reduction of phenyldiazonium chloride with the calculated amount of a solution of stannous chloride in hydrochloric acid, but the yield is not so high as that obtained by the above sulphite method ... 

Reduction is also observed in the reaction of acid chlorides with Grignard reagents Whitmore, F.C., Whitaker, J.S., Mosher, W.A., Brevick, O.N., Wheeler,... 

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. 

Reduction of mercuric chloride with oxalic acid is slow whereas reduction of KMn04 by oxalic acid is fast. When mixture of mercuric chloride and oxalic acid is treated with KMn04, both get reduced simultaneously. Reduction of KMn04 induces the reduction of mercuric chloride. 

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]. 

Reduction of sulfonyl chlorides with Zn and acid yields first sulfinic acids and then thiophenols. C,H,SOXl > C H,SO H """ > C,H,SH... 

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 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 acid halides with lithium tri-tert-butoxyaluminum hydride is an effective method for synthesis of amino aldehydes. Nonfunctionalized amino aldehydes 22 are readily prepared from respective reduction of the N-terminal Fmoc, Boc, or Z acid chlorides or fluorides 21 (Scheme 8, Table 9). This method afforded these aldehydes in about 60% yield with small differences in optical rotation as compared to literature values 11,33 48 54 55 ... 

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.

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

Reduction of sulfonyl chlorides with Zn and acid yields first sulfinic acids and then thiophenols. 

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>. 

Rosenmund reduction , i.e. catalytic hydrogenation, of acid chlorides with poisoned Pd-BaS04 (in the presence of sulfur and quinoline poison) afforded aldehyde. 

Hydroxyketones are versatile intermediates in the synthesis of pharmaceutical intermediates and heterocyclic molecules. a-Aryl hydroxyketones have been prepared by reaction of aryl aldehydes with 1,4-dioxane followed by reduction with lithium aluminum hydride (LAH) and by the selective LAH reduction of a-silyloxy a,P-unsaturated esters." WissneC has shown that treatment of acid chlorides with tris(trimethylsilyloxy)ethylene affords alkyl and aryl hydroxymethyl ketones. 1-Hydroxy-3-phenyl-2-propanone (3) has been generated by the osmium-catalyzed oxidation of phenylpropene and by the palladium-catalyzed rearrangement of phenyl epoxy alcohoP both in 62% yield. 

Reduction of Chromic Chloride, CrClj.—Wohler obtained metallic chromium by reduction of chromic chloride with potassium, while Fremy obtained the metal in a crystalline condition by passing sodium vapour over chromic chloride in an atmosphere of pure dry hydrogen. Wohler prepared similar crystals—minute octahedra— by fusion of chromic chloride with zinc under a layer of mixed sodium and potassium cHorides, and removal of the zinc from the alloy so formed by means of nitric acid. Metallic calcium reduces chromic chloride at a dull red heat without formation of an alloy. ... 

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