Carboxylic acids aliphatic, reduction

The carbonyl group is a reactive function and, although aromatic aldehydes are somewhat less reactive than their aliphatic counterparts, benzaldehydes have an extensive chemistry. Many reactions replicate those of aliphatic aldehydes, but are mentioned here for completeness. Thus, oxidation of the carbonyl group leads to carboxylic acids and reduction gives alcohols. The aldehyde group reacts with a range of N-nucleophiles (Scheme 6.9). Imines (Schiff bases) are formed with amines and hydrazones with hydrazines. Semicarbazide gives semicarbazones and hydroxylamine forms oximes. 

In summary, the reactivity of various functional groups toward Li 9-BBNH is classified into four broad categories [18] (1) rapid- or fast-reduction aldehyde, ketone, ester, lactone, acylchloride, acid anhydride, epoxide, disulfide, -alkyli-odide, and tosylate (2) slow-reduction tertiary amide, alkylbromide, and aromatic nitrile (3) sluggish-reduction carboxylic acid, aliphatic nitrile, primary amide, nitro and azoxy compounds, and secondary alkylbromide and tosylate (4) inert olefin, oxime, alkylchloride, sulfoxide, azo-compound, sulfide, sulfone, and sulfonic acid. 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

A related convenient and mild method for the preparation of aliphatic and aromatic aldehydes in high yield from carboxylic acids is the reductive cleavage of l-acyl-3-methylimidazole-2-thiones by tributylstannane. 

A selective, mild, and facile reduction of aromatic and aliphatic carboxylic acid imida-zolides to primary alcohols is described in reference [33]. The reaction proceeds in water, water/dioxane or water/tetrahydrofuran solution at room temperature with 2-5 molar equivalents of NaBH4 in about 1 h. 

Aliphatic carboxylic acids are difficult to reduce electroehemically. Reduction of a 10% oxalic acid in 10% H2SO4. at 15 °C at a mercury cathode (Refs. [494, 532] in Ref. [29]), a lead or amalgamated lead cathode (Ref. [495] in Ref. [29]) or at a sodium amalgam (Na(Hg) cathode (Ref. [497] in Ref. [29]) produces glyoxylic acid with a material yield of 88% and a current efficiency of 70%. The glyoxylic acid formed is stabilized by hydration [29]. 

Because of the highly negative reduction potentials ( —3.0 V vs. SCE) [32], the electroreduction of esters of aliphatic carboxylic acids to primary alcohols by direct electron transfer from the cathode is very difficult and the electrochemical Birch-type reduction of aliphatic esters in MeNH2 or liquid NH3 has not been reported until recently (Scheme 15) [33, 34]. This reaction is not a reduction by direct electron transfer from the cathode to the C=0 bonds of the ester but the reduction by a solvated electron. 

Appropriate activation of carboxyl groups enables reduction of aliphatic carboxylic acids to the corresponding aldehydes. The electroreduction of iminium salts prepared from aliphatic carboxyKc... 

Recently, the electrolysis of aliphatic carboxylic acids in an undivided cell and in the presence of triphenyl phosphine has been reported, which turned out to be one of the most reliable methods for the reduction of aliphatic carboxylic acids to the corresponding aldehydes (Scheme 26) [11, 52]. In this reaction. 

Scheme 25 Cathodic reduction of activated aliphatic carboxylic acids to aldehydes (R alkyl, yields 70-82%) and ketones (R benzyl, yields 66- 72%).

Scheme 26 Cathodic reduction of aliphatic carboxylic acids in the presence of triphenylphosphineto aldehydes R alkyl, aryl, yields 36 -100%.

Acetonitrile, 407 Acetophenone, 725,729,730 phenylhydrazone, 852 p-Acetotoluidide, 593, 605 Acetoxime, 343 Acetylacetone, 861, 862, 863 Acetylation, reductive, 749 Thiele, 749 Acetyl chloride, 367 2-Acetylcyciohexanone, 862, 864 Acetylene, 245, 897 reactions of, 245, 246 Acetylenic compounds, synthesis of, 467-469, 895-902 Acetylglycine, 909 Acetylmethylurea, 968, 969 Acetylsalicylio acid, 996 Acetyl-o-toluidide, 578 2-Acetylthiophene, 837 Acid anhydrides of aliphatic carboxylic acids, 371... 

The most common preparations of amines on insoluble supports include nucleophilic aliphatic and aromatic substitutions, Michael-type additions, and the reduction of imines, amides, nitro groups, and azides (Figure 10.1). Further methods include the addition of carbon nucleophiles to imines (e.g. the Mannich reaction) and oxidative degradation of carboxylic acids or amides. Linkers for primary, secondary, and tertiary amines are discussed in Sections 3.6, 3.7, and 3.8. 

HYDROGEN-I ON REDUCTION Aliphatic CarboxylIc Acids Not Containing Nitrogen... 

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... 

Benzyl and allyl alcohols are oxidized with iodosylbenzene 18 in refluxing dioxane to aldehydes [67]. Further oxidation of aldehydes to carboxylic acids does not take place. Aliphatic primary alcohols are not oxidized under the conditions. Ligand exchange of 18 with alcohols produces alkoxy-A3-iodanes, which result in reductive /3-elimination to give aldehydes [Eq. (33)]. 

Fig. 17.17. Sodium chlorite oxidation of aliphatic or aromatic aldehydes to form a carboxylic acid. The extra additive destroys the reduction product of the oxidant, i.e., sodium hypochlorite or hypochloric acid.

A large number of stable /e-organo tellurocarboxylates were prepared from tellurolates and aliphatic1,2 or aromatic2 carboxylic acid chlorides or aliphatic carboxylic acid anhydrides . The tellurolates were obtained by reduction of diorgano ditelluriums with sodium borohydride. 

In the aliphatic series the carboxylic acids furnish the principal material of electrolysis. This is due to the reactive-ness of their anions, which readily split off carbonic acid, thus affording manifold syntheses. In the aromatic series, however, the nitro-compounds are the more interesting, on account- of their easy rcducibility and the importance of their reduction products. The facts which give to electrochemical reduction pre-eminence over oxidation have already been explained in... 

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). 

Bis(N-inethylpiperazinyl)aluniinum hydride (li. This hydride was originally prepared from aluminum hydride and N-methylpiperazine, and was used to reduce carboxylic acids directly to aldehydes. It can be prepared more conveniently from lithium aluminum hydride and the amine. It is useful for reduction of aliphatic and aromatic acids to aldehydes (80-95% yield). Significantly, it reduces a,p-unsaturated acids to aldehydes without reduction of the double bond (70-80% yield). ... 

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