Carboxylic acids acid chloride formation

Esterification, Amidation, and Acid Chloride Formation. Amino acids undergo these common reactions of the carboxyl group with due regard for the need for A/-protection. 

Reactions of the carboxyl group include salt and acid chloride formation, esterification, pyrolysis, reduction, and amide, nitrile, and amine formation. Salt formation occurs when the carboxyUc acid reacts with an alkaline substance (22)... 

The PCBM methyl ester can be used for coupling amine-containing ligands after removal of the methyl group and activation of the carboxylate using a number of different reaction strategies. Hummelen et al. (1995) successfully coupled cholestanol and histamine to the fuller-ene-PCBM derivative (after acid chloride formation) for use in fabrication of photodetectors and biological studies, respectively. For specific applications of PCBM-fullerenes, see Shaheen et al. (2001), Brabec et al. (2001), Yu et al. (1995), Mecher et al. (2002), Meijer et al. (2003), van Duren et al. (2004), and Anthopoulos et al. (2004). 

The chroman ring system is stable to organometallic reagents, for example in the formation of the tertiary alcohol (690) in high yield (63HCA650), and to the usual interconversion of carboxylic acid, acyl chloride, carboxamide and nitrile. 

Phosphorus trichloride and phosphorus pentachloride are also suitable reagents for acid chloride formation, but their use is largely restricted to aromatic carboxylic acids. (Section 6.14.1, p. 1073). 

Acid chloride formation from carboxylic acid, see under Carboxylic acid Addition, amine to acrylonitrile, 98, 118 bromine to methyl acrylate, 202 bromine to vinyl acetate, 102 chlorine to methyl acrylate, 202 chlorine to vinyl acetate, 147 HC1 to styrene, 77 HC1 and HBr to acrylonitrile, 82. ... 

From the mechanism of the acid chloride formation, one can see that it is the C-OH bond of the carboxylic acid that is broken to form the C-Cl bond. Subsequently, the C-Cl bond is cleaved to form the C-OR bond with the alcohol oxygen. 

Later, Venkataraman and Wagle <1979TL3037> reported the use of TCT as a useful reagent for the conversion of carboxylic acids into chlorides, esters, amides, and peptides the authors proposed the formation of the acyl chloride as shown in Scheme 44. 

Other reactions of carboxylic acids include the formation of esters and the reaction with phosphorus(V) chloride to form acyl halides. 

Variations of this reaction have been applied over the years, typically involving the condensation of 2-aminothiophenols with substituted carboxylic acids, acyl chlorides, aldehydes, and nitriles. Initially, the reaction involves the formation of an imine that cyclizes spontaneously and then oxidation to form benzothiazole. An application of this chemistry has been showcased in the synthesis of 2-(4-aminophenyl)benzothiazoles and the evaluation of their in vitro and in vivo activities against breast cancer cell lines, with compound a exhibiting the most potent growth inhibition. Unfortunately, there are limitations due to the difficulties met during the syntheses of readily oxidizable o-aminothiophenol-bearing substituents. 

Two-stage single-pot derivatization of carboxylic acids (with intermediate formation of chloroanhydrides with thionyl chloride followed by their conversion into amides) was recommended preferably for HPLC analysis, but the simplest dialkylamides and even anilides ° are volatile enough for GC analysis also (the mixture of PhaP and CCLt, instead of SOCI2, can be used in this reaction). Moreover, the same procedure is used for the synthesis of diastereomeric derivatives of enantiomeric carboxylic acids (see below) ... 

PROBLEM 17.54 Observe the Acid chloride formation animation. What is the shape of thionyl chloride What is the shape of the SO2 that is formed at the end of the reaction This reaction converts a carboxylic acid into a much more reactive acid chloride. Why does the energy diagram show the reaction as being exothermic ... 

As with polyesters, the amidation reaction of acid chlorides may be carried out in solution because of the enhanced reactivity of acid chlorides compared with carboxylic acids. A technique known as interfacial polymerization has been employed for the formation of polyamides and other step-growth polymers, including polyesters, polyurethanes, and polycarbonates. In this method the polymerization is carried out at the interface between two immiscible solutions, one of which contains one of the dissolved reactants, while the second monomer is dissolved in the other. Figure 5.7 shows a polyamide film forming at the interface between an aqueous solution of a diamine layered on a solution of a diacid chloride in an organic solvent. In this form interfacial polymerization is part of the standard repertoire of chemical demonstrations. It is sometimes called the nylon rope trick because of the filament of nylon produced by withdrawing the collapsed film. 

The chloride of triflic acid (trifluoromethanesulfonyl chloride) is an effective sulfonylating agent Like triflic anhydride, it usually reacts with alcohols and other nucleophiles with the formation of the corresponding derivatives of tnflic acid [69] However, in some reactions, it acts as a chlorinating reagent [98] The reactions of tnfluoromethanesulfonyl chloride with 1,3-dicarbonyl compounds or some carboxylic esters in the presence of a base result m the formation of chlonnated products in high yields (equation 49)... 

This tertiary ester was developed to reduce aspartimide and piperidide formation during the Fmoc-based peptide synthesis by increasing the steric bulk around the carboxyl carbon. A twofold improvement was achieved over the the standard Fbutyl ester. The Mpe ester is prepared from the acid chloride and the alcohol and can be cleaved under conditions similar to those used for the r-butyl ester. ... 

Reactions between A -(l-chloroalkyl)pyridinium chlorides 33 and amino acids in organic solvents have a low synthetic value because of the low solubility of the amine partner. A special protocol has been designed and tested in order to circumvent this drawback. Soon after the preparation of the salt, an aqueous solution of the amino acid was introduced in the reaction medium and the two-phase system obtained was heated under reflux for several hours. However, this was not too successful because sulfur dioxide, evolved during the preparation of the salt, was converted into sulfite that acted as an 5-nucleophile. As a result, A -(l-sulfonatoalkyl)pyridinium betaines such as 53 were obtained (Section IV,B,3) (97BSB383). To avoid the formation of such betaines, the salts 33 were isolated and reacted with an aqueous solution of L-cysteine (80) to afford thiazolidine-4-carboxylic acids hydrochlorides 81 (60-80% yields). 

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