Benzilic acid synthesis

Benzilic acid rearrangement Benzoin reaction (condensation) Blanc chloromethylation reaction Bouveault-Blanc reduction Bucherer hydantoin synthesis Bucherer reaction Cannizzaro reaction Claisen aldoi condensation Claisen condensation Claisen-Schmidt reaction. Clemmensen reduction Darzens glycidic ester condensation Diazoamino-aminoazo rearrangement Dieckmann reaction Diels-Alder reaction Doebner reaction Erlenmeyer azlactone synthesis Fischer indole synthesis Fischer-Speior esterification Friedel-Crafts reaction... 

Hirschmann and co-workers have reported the synthesis of another A-nor analog of cortisone obtained from the benzilic acid rearrangement of a 2,3-diketo-A -steroid. 17a,20 20,21-Bismethylenedioxypregna-L4-diene-... 

An interesting one-step combined oxidation and benzilic acid rearrangement has been described by Holden and Kerwin in connection with the synthesis of C-norpregnanes from 3a,20yS-dihydroxy-5j9-pregnan-12-one (partial structure 85). 

The structure of 82 was established by alkaline ring cleavage to benzilic acid amide and by hydrogenolysis to (C6H5)2CH—CONH— COCfiHs. These reactions also served to eliminate 83 as the structure of the 169° compound. The other possible isomeric structure, (C6H5)2C(CN)0C0C6H5, which could have formed after 0-acylation, was ruled out by its independent synthesis from bromodiphenyl-acetonitrile and silver benzoate. 

Due to excellent yields, mild reaction conditions, and a fast reaction rate, the azolide method is well suited to the synthesis of isotopically labeled esters, even ones with very short half-lives, just as it is always useful for the esterification of sensitive carboxylic acids, alcohols, and phenols under mild conditions. An example is provided by the synthesis of [nC]-quinuclidinyl benzilate prepared from benzilic acid, CDI, and nC-labeled quinuclidinol.[147]... 

In this paper, we report on the synthesis and structural characterization of a series of related zwitterionic (molecular) spirocyclic X Si-silicates (mononuclear A, Si-silicon(IV) complexes) containing two bidentate l,2-diolato(2-) ligands derived from a-hydroxycarboxylic acids, such as glycolic acid, 2 methyllactic acid, benzilic acid, and citric acid. In addition, some analogous zwitterionic X Ge-germanates (mononuclear X Ge-germanium(rV) complexes) are described. Furthermore, we report on the synthesis and structural characterization of related zwitterionic x Si,X Si -disilicates (binuclear X Si-... 

Early workers [103] detected benzilic acid formed during the reduction of benzophenone in dimethylformamide in the presence of carbon dioxide. The carbon dioxide radical anion system is known to have E" = —2.2V (vs. SCE) [104] and will thus not be formed in preference to the ketone radical anion. Reaction occurs through trapping of aromatic carbonyl radical anions by carbon dioxide, and this has been developed into a convenient synthesis of aryllactic acids. The modern technological process uses constant current conditions. On a small scale, a divided cell with mercury cathode has been used to obtain benzilic acids from substituted benzophenones and carbon dioxide in 70-90% yields [105] and to convert 4-isopropylacetophenone to the corresponding phenyllactic acid in 85% yield [106]. On a technical scale, these reactions are best carried out in an undivided cell using a lead cathode and a sacrificial aluminum anode with dimethylformamide as solvent... 

Japp also found that benzilic acid gave a triphenyloxazolone product with benzonitrile," and later woik " demonstrated that this material was (55 Scheme 26). The internal nucleophile in this case is the carbonyl oxygen. More recently, extensions of this type of reaction have been applied to the synthesis of stericaUy hindered peptides." A further interesting oxazolone synthesisfrom (56) involves nucleophilic attack by the nitrile on a cyclopropenium intermediate and leading ultimately to formation of the spiro derivative (57 Scheme 27). 

H. Takeshita and co-workers devised a short synthesis of (+)-hinesol and (+)-agarospirol via a mild base-catalyzed retro-benzilic acid rearrangement of profo-[2+2] photocycloadducts to the desired spiro[4,5]decanedione framework. 

P.A. Grieco et al. accomplished the total synthesis of (+)-shinjudilactone and (+)-13-ep/-shinjudilactone via a benzilic acid-type rearrangement. The substrate was exposed to basic conditions and the two desired products were obtained as a 1 1 mixture. Interestingly, when the Cl position was methoxy substituted, the rearrangement failed to take place under a variety of acidic and basic conditions. 

Hatsui, T., Wang, J.-J., Takeshita, H. Synthetic photochemistry. LXVIl. A total synthesis of ( )-hinesol and ( )-agarospirol via retro-benzilic acid rearrangement. Bull. Chem. Soc. Jpn. 1995, 68, 2393-2399. 

A detailed Organic Synthesis procedure is available for the conversion of benzil into benzilic acid. It is advantageous to isolate the acid as its potassium salt, for this enables the removal of the more soluble potassium benzoate, which results from a competitive cleavage reaction. Benzilic acid is then obtained in 77-79% yield by acidifying an aqueous solution of potassium benzilate. Since benzil is usually obtained by the oxidation of benzoin, both this conversion and rearrangement can be performed in tandem by using alkaline sodium bromate. Thus, benzilic acid is obtained in 84-90% yield from benzaldehyde via benzoin. 

In addition to these reactions in which the carbanions are supplied from carbonyl compounds, we will discuss in this chapter Grignard reactions, the benzilic acid rearrangement, the benzoin condensation, and the Kolbe synthesis of hydroxy aromatic acids. These reactions illustrate the addition of other kinds of carbanions to carbonyl groups. The benzilic acid rearrangement is an example of the intramolecular addition of a group with its pair of electrons to a carbonyl carbon atom. 

Further examples and elimination types will undoubtedly be added to the hitherto known ones and it appears highly versatile that our classification system is not limited to complex eliminations, but also covers complex additions (e.g. the so called benzilic acid rearrangement 36a) in terms of a complex [l,2,3]-addition 170) of water to benzil) and complex substitutions. Thus, the well known technical camphor synthesis starting with a-pinene (Scheme 9) is the result of a sequence of a [l,2,3]-addition 170), [l,2,3]-elimination, (l,2,3]-addition, and finally saponification and oxidation. This appears to be a highly economic description of the underlying chemical processes. 

---