Carboxylic acid derivatives synthesis modifications

In the particular case in which the carbonyl group belongs to a carboxylic acid derivative, such as an ester (17) or an amide (18) (or other functional groups which may be converted into it by a FGI), then they may be disconnected according to the "orthoacetate-modification" of the retro-Claisen rearrangement (Schemes 7.7 and 7.8) developed mainly by Eschenmoser [7] and Ziegler [8], independently, in the synthesis of alkaloids, and Johnson in a very simple and yet highly stereoselective synthesis of squalene [9]. 

In the synthesis of specially substituted methylene diphosphines, made from secondary phosphines and carbonyl derivatives (7), a carbenium ion adjacent to trivalent phosphorus as the transition state has been discussed. The transfer of this reaction principle to primary phosphines and suitable carbonyl compound revealed a further pathway to derivatives of dicoordinated phosphorus (8). Aromatic phosphines react with carboxylic acid amide acetals under elimination of alcohol giving dialkylamino-alkylidene phosphines (Scheme 5). A modification of the synthesis... 

Of lesser relevance to this discussion are halogenation methods involving the modification of the carbon skeleton (synthesis and degradation). The Hunsdiecker reaction, as applied to certain heterocyclic acids, has had limited application for the synthesis of halogen derivatives. The preparation of 3-bromo-4,6-dimethyl-2-pyridone from the silver salt of the respective 3-carboxylic acid by treatment with bromine in carbon tetrachloride is a rare example of success.13 The interaction of carbenes with heterocycles also has been employed infrequently, but recent advances in carbene generation may reactivate this approach.14 The Ciamician-Dennstedt ring expansion of pyrrole to / -halopyridines is a case in point18 [Eq. (4)] ... 

Carbodiimides are the diimides derived from carbon dioxide, and they are extensively used in the formation of peptide amide bonds from carboxylic acids and amines. This reaction was utilized by the Nobel laureate Sheehan in the total synthesis of penicillin. He also was the first to use water soluble carbodiimides to crosslink gelatin. Khorana, another Nobel laureate, demonstrated that carbodiimides can also be used in the synthesis of nucleotides. Today, carbodiimides are used extensively in the synthesis and modification of proteins. Proteomics is the new frontier of chemical research. 

P-Keto esters (8, 313). Complete details are available for use of acyl derivatives of Meldrum s acid as precursors to fi-keto esters.1 A modification of this procedure has been used in a synthesis of thienamycin.2 The carboxylic acid group is activated by reaction with carbonyldiimidazole, and 4-dimethylaminopyridine is used as... 

A modification of the known Conrad-Limpach synthesis of quinolines, using anilino-methylenemalonates instead of j -anilinocrotonates, has long been known ° N-Aryl and N-heteroaryl derivatives of aminomethylene malonates are also very useful and fruitful synthons for formation of 4-aminoquinolines used as antimalarials (equation 215), of the anticoccidial 6,7-dialkoxy-4-hydroxyquinoline-3-carboxylates and of antibacterial nalidixic acid derivatives (equation 216). Each of these is an important group of pharmaceuticals, developed in the last twenty years. Because of its medicinal interest this route is widely used for synthesis of quinolines and pyridinofused heterocycles. The chemistry has been comprehensively reviewed in a recent monograph . Hence, no further details are given here. 

The aspects relevant to the use of rosin as such, or one of the derivatives arising from its appropriate chemical modification as monomer or comonomer [12-14], have to do with the synthesis of a variety of materials based on polycondensations and polyaddition reactions of structures bearing such moieties as primary amines, maleimides, epoxies, alkenyls and, of course, carboxylic acids. These polymers find applications in paper sizing, adhesion and tack, emulsification, coatings, drug delivery and printing inks. 

The second chirality source used in the synthesis of aminocyclopropane carboxylic acids was D-glyceraldehyde acetonide, which after Wittig-Homer-Emmons reaction provided the alkenes 61. Treatment with diazomethane and subsequent irradiation at low temperatures alforded the cyclopropanes 62, which were converted into several other derivatives by modification of the side chain (Scheme 11). Notably, the best results were obtained by irradiating in the presence of benzophenone as triplet sensitizer [33, 34]. Following a similar synthetic procedure allocoronamic acid 65 was prepared, which is one of the amino acids that can be processed by plant tissues and promises the possibility to control the enzymatic processes underlying plant growth and fruit ripening [35]. 

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