Reduction of Acid Anhydrides

Reductions of anhydrides of monocarboxylic acids to alcohols are very rare but can be accomplished by complex hydrides [55, 99]. More frequent are reductions of cyclic anhydrides of dicarboxylic acids, which give lactones. Such reductions were carried out by catalytic hydrogenation, by complex hydrides and by metals. 

Hydrogenation of phthalic anhydride over copper chromite afforded 82.5% yield of the lactone, phthalide, and 9.8% of o-toluic acid resulting from hydrogenolysis of a carbon-oxygen bond [1015]. Homogeneous hydrogenation of a,a-dimethylsuccinic anhydride over tris(triphenylphos-phine)rhodium chloride gave 65% of a,a-dimethyl- and 7% of )S,)S-dimethyl-butyrolactone [1016]. 

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One study of the Et3SiH/TFA reduction of acid anhydrides reports the formation of one equivalent each of the alcohol and the trifluoroacetate ester of the acid (Eq. 139).287... 

Another procedure for obtaining a-aminoketones is by reduction of a-nitrosoketones in the presence of the required carboxylic acid. Acylaminoketones are prepared either by reacting acids with the chlorhydrate of a-aminoketones according to the method of Pictet and Gauss (41) or by the action of acid anhydrides upon a-amino acids (550). 

Trifluoroethanol was first prepared by the catalytic reduction of trifluoroacetic anhydride [407-25-0] (58). Other methods iaclude the catalytic hydrogeaatioa of trifluoroacetamide [354-38-1] (59), the lithium aluminum hydride reductioa of trifluoroacetyl chloride [354-32-5] (60) or of trifluoroacetic acid or its esters (61,62), and the acetolysis of 2-chloro-l,l,l-trifluoroethane [75-88-7] followed by hydrolysis (60). More recently, the hydrogenation of... 

Reduction of Cyclic Anhydrides to Lactones and Acid Derivatives to Alcohols... 

An alternative scheme to simultaneous formation of acetaldehyde and acetic anhydride could entail the carbonylation of methyl acetate to acetic anhydride which is subsequently reduced to acetaldehyde and acetic acid. The reaction of acetaldehyde with excess anhydride would form EDA. In fact, Fenton has described production of EDA by the reduction of acetic anhydride using both rhodium and palladium salts as catalysts when modified with triphenylphosphine (26). Two possible mechanisms for the reduction are postulated in equation 16. 

Thiophthalide (452) is the oxo form of l-hydroxybenzo[c]thiophene. It is a stable compound, being intermediate in oxidation level between o-xylene and phthalic acid. It can be formed from o-xylene by oxidation with a mixture of sulfur and water at high temperatures it can also be formed by reduction of phthalic anhydride with H2S + H2 (72AHC( 14)331). It reacts with vinyllithium to form a complex which on hydrolysis undergoes ring expansion to 4,5,6,7-tetrahydro-2//-benzo[c]thiepin-5-one (453), as shown in Scheme 154. 

Alternative methods for the synthesis of peptide aldehydes include reduction of acid halides, phenyl esters, thioesters, and anhydrides prepared from corresponding acids, isoxazolidides, and the hydrolysis of thiazolidine peptides 17,54-56 Enzymes such as thermolysin, subtilisin, and pronase E have proven valuable as effective semisynthetic alternatives 40,57 5 62 ... 

The reduction of a-amino mixed anhydrides with lithium tri-/ert-butoxyaluminum hydride in THF at —70 °C is a very efficient method for synthesis of amino aldehydes (Table 9). 551 Three approaches were taken for the reduction of a-amino mixed anhydrides. 55 The first approach reduced Boc-Ala-OC02Et with lithium tri-terf-butoxyaluminum hydride was unsuccessful due to intramolecular rearrangements that gave Boc-Ala-OEt in addition to the Boc-Ala-H. The second approach involved reduction of diphenylacetic anhydride derivatives, which were prepared from Boc amino acids and diphenyl ketene, gave a diphenylacetic acid byproduct that was very difficult to remove unless the aldehyde was converted into its semicarbazone and separated chromatographically yields were 51-69%. The last and... 

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

Lithium aluminum hydride reduces acids, acid chlorides, anhydrides, and esters to primary alcohols. (The reduction of acids was covered in Section 20-13.) Acid chlorides are more reactive than the other acid derivatives. Either lithium aluminum hydride or sodium borohydride converts acid chlorides to primary alcohols. 

The present procedure is based upon the method of Reissert. Phthalide has also been prepared by reduction of phthalic anhydride, and by bromination of o-toluic acid followed by hydrolysis. ... 

Acyclic acid anhydrides are reduced to produce primary alcohols using NaBH4 and its many deriva-tives.2 - In most cases, the reaction gives both the primary alcohol and the carboxylate salt (1 1). Whilst such monoreduction may be desirable in cyclic anhydride chemistry (vide infra), it is inefficient when acyclic anhydrides are reduced. Thus, B2H6 or LAH reductions are the preferred synthetic methods. The reductions of mixed anhydrides, for example carboxylic/diphenylphosphoric or carboxylic/car-bonic anhydrides, produce the primary alcohol from the acyl component. ... 

In certain cases, reduction of mixed anhydrides of unsaturated acid such as 3.169 by NaBH4 can be delicate [JUl]. NaBH4-CeCl3 in MeOH does not appear to be efficient, as the formation of the methyl ester hinders the reduction. The use of NaBH4-Sml3 in THF leads to the expected allylic alcohol (Figure 3.60). Some... 

BHj-McjS or amine-boranes induce the same reductions of acids to alcohols linear anhydrides are reduced by Ph2NH BH3 in THF to alcohols, while succinic and phthalic anhydrides remain intact [CUl]. 

Na2[Fe(CO)4] is also used as a reductant, especially for the preparation of unsymmetric aldehydes or ketones. Reduction of maleic anhydride by Na2pe(CO)4 gives maleinalde-hydic acid (eq (10)) [40]. 

Reduction of the anhydride gave 103 with complete regioselectivity in favour of the carbonyl next to the acetate but without stereoselectivity. This doesn t matter as treatment with acid initiated a rearrangement - cyclisation sequence giving a the alcohol 104 after hydrolysis of its formate. This time there is complete stereoselectivity in the creation of three new chiral centres. 

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