Functional carboxylic acid

Hexafluoroacetone and certain perfluorinated or partially fluorinated ketones, aldehydes, and imines react with a-functionalized carboxylic acids (e.g., a-amino, a-At-methylamino [S3, 84], a-hydroxy [S5], and a-mercapto [Sd] acids) to give five-membered heterocyclic systems (equation 13). 

The transformation has a broad scope, and higher oligopeptides can easily be obtained using higher functionalized carboxylic acids and/or isocyanides as starting materials [19]. The only disadvantage is the modest diastereoselectivity of approximately 2 1. 

The last work pertaining to the discovery of new catalysts is perhaps the most novel approach to be reported thus far. In one of the earliest approaches taken toward catalyst development, Menger et al. (61) attempted to find catalysts for phosphate ester hydrolysis. A series of eight functionalized carboxylic acids were attached to polyallylamine in various combinations. Each of these polymers were then treated with one of three metals, Mg2+, Zn2+, or Fe3+. The different members of each library were identified by the relative percentages of each carboxylic acid attached to the polyamine. For example, one polymer possessed 15% Oct, 15% Imi, 15% Phe, and 5% Fe3+. There is no attempt to identify the location of the various carboxylic acids in a given polymer. This approach is novel since each system consists of an ensemble of different ligands with the carboxylic acids positioned in various locations. Each polymer within a given ratio of carboxylic acids consists of a combinatorial library of potential catalysts. 

Preparahon of functional carboxylic acid and aldehyde groups see below. 

Zircoaluminates (ZAs) constitute a unique class of bifunctional additives which are synthesized in accordance with a highly specific procedure [4-6] to produce stable covalent molecules. As shown below, the essential chemistry involves the reaction of two solid inorganic raw materials with a number of different functionalized carboxylic acids in the presence of selected solvents [reaction (2)]. 

This methodology has been extended by employing functionalized carboxylic acids and/or isocyanides in order to increase the diversity of the reaction products and to achieve an easy access to four- or five-unit peptide mimetics [28]. For example, tetrapeptide 36 was obtained in 59% overall yield (Scheme 2.14). 

Kulik et al. [205] focused their studies on the identification of chemical species formed during the treatment of polyolefins such as polyethylene or polypropylene by gaseous ozone or ozone in aqueous medium. Experimental conditions have a great influence on the nature of the obtained species. For example, peroxidic functions, carboxylic acids, and ketones have been identified, aldehydes being absent of the surface of the materials. It must be noted here the instability of the peroxidic species formed during the treatment... 

Fig. 2.27. Stereoselectivity due to neighboring group participation in the synthesis of a-functionalized carboxylic acids.

This reaction can be extended to unsaturated nitriles, eg, acrylonitrile, which can give trihalostannyl-functional carboxylic acids, esters, and amides by the proper choice of solvents and reaction conditions (156). 

In a similar way, other derivatives of diamines (S,S)-28 and (R,R)-29 were evaluated for their gelation properties. As an example, trans-(R,R) 1,2-bis(dodecy-lureido)cyclohexane and trans-(R,R)-1,2-bis(octadecylureido)cyclohexane can cause physical gelation in a wide variety of organic solvents [76]. As an extension of these studies, novel polymerizable organogelators based on tra s-(7 ,7 )-l,2-bis(ur-eido)cyclohexane derivatives have been reported [77]. In these molecules, the presence of methacrylate-functionalized carboxylic acid groups determines the... 

Some other capsules have been described in which both complimentary functions, carboxylic acids and nitrogen-containing aromatic rings, are respectively attached to the rims of two bowl-shaped molecules. Reinhoudt has prepared selfassembling, multi-hydrogen bonding molecular capsules in which a calix[4]arene substituted with four carboxylic functions at the upper rim interacts with a complimentary calix[4]arene with four pyridines attached to the lower rim. These capsules have been identified by H-NiMR, IR and VPO measurements but encapsulation properties have not been reported [106]. 

M. Viertelhaus, R. Hilfiker, F. Blatter, Piracetam co-crystals with OH-group functionalized carboxylic acids, Cryst. Growth Des. 9 (2009) 2220-2228. 

Titanium alkoxide is quite effective, presumably as an acid/base catalyst, at facilitating transesterification between esters and alcohols [511-513]. The reaction conditions are mild and relatively hindered alcohols can be used. Methyl phenylacetate has been transformed to other esters of relatively hindered alcohols under the influence of Ti(OEt)4 (Eq. 216) [514]. Ethyl (or methyl) esters of a variety of functionalized carboxylic acids could be converted into menthyl esters in good yields under titanium catalysis (Eq. 217) [514]. 

Carbonyl dichloride can be taken similarly to form acid anhydrides (equation 31). Via a mixed anhydride and in the presence of triethylamine, it is possible to prepare symmetrical anhydrides in high yield. ° °° A variation provides ethyl chloroformate as reagent.In a first step the carboxylic acid is ethoxycarbonylated in the presence of triethylamine and then reacted with free caiiioxylic acid to form the acid anhydride (equation 32). As the intermediate can be isolated, this is a good method of forming mixed anhydrides.In addition it seems to be particularly suitable for functionalized carboxylic acids such as hydroxy acids." Polymer-bound chloroformates may be advantageous in some cases. " " ... 

Transesterification. The alkyl group of carbamates can be exchanged using Ti(OPri) as catalyst. [Note that transesterification of common esters of functionalized carboxylic acids with hindered alcohols such as menthol, bomeol, and isopinocampheol in the presence of Ti(OEt) has been reported. ]... 

The next stage is to take the ester mixture and react the residual alcohol functions with a di- or higher functionality carboxylic acid such as phthalic... 

Although no experimental details have been reported as yet, these results offer new, interesting applications of asymmetric hydrocarboxylation in the stereoselective synthesis of chiral hetero-functionalized carboxylic acids. 

Trifluoroacetic and triflic anhydrides can be utilized to promote acylation of aromatics with carboxylic acids without any metal catalyst. Thus, the trifluoroacetic anhydride (TFAA)-promoted cycloacylation of conveniently functionalized carboxylic acids prepared from Baylis-Hillman adducts... 

Decarboxylation of a-heteroatom-functionalized carboxylic acids occurs smoothly using PhI(OAc)2 and I2 without the requirement for photolysis. When proline derivatives are employed for this reaction, the intermediate A,0-acetal may be treated with nucleophilic agents to give 2-substituted pyrrolidine products (eq 55). 

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