Amino- aromatic carboxylic acids, reactions

Note The chromatogram zones exhibit a broad spectrum of colors [3, 12] that is very dependent on the duration and temperature of heating. Therefore the optimum reaction conditions must be determined empirically. With a few exceptions (ferulic, 4-amino-benzoic and cumarinic acids) aromatic carboxylic acids do not react [3]. The reagent in 80 ethanolic sulfuric acid is reported to be most sensitive for steroids [25]. 

Preparation of a-amino acid amides of aromatic amines (111) is easily conducted as a one-pot procedure by the modified Curtius reaction of aromatic carboxylic acids with DPPA, followed by reaction with iV-protected a-amino acids (equation 44). By this method, -t-butoxycarbonyl-L-leucine p-nitroanilide, which serves as a substrate for leucine aminopeptidase after deblocking of its r-butoxycar-bonyl group, has been efficiently prepared from p-nitrobenzoic acid and -r-butoxycarbonyl-L-leucine. 

Kamochi and Kudo have reported the use of the Sml2/THF-H20 system to reduce aromatic carboxylic acids to alcohols (Scheme 50). Furthermore, aromatic esters amides and nitriles were similarly reduced by this system in good yield [104]. As indicated above, reduction of carboxylic acids to primary alcohols is also effective with Sml2 in a THF-H20-NaOH mixture [105]. In contrast, without water these substrates remain unchanged. With the Sml2/THF-H20 system, pyridine was rapidly reduced to piperidine in similar reactions with pyridine derivatives bearing chloro, amino and cyano substituents, these functionalities were partly eliminated to afford pyridine or piperidine [107]. 

Aldehydes and Ketones from Carboxylic Acids. Reduction of the derived acylimidazole (2) with Lithium Aluminum Hydride achieves conversion of an aliphatic or aromatic carboxylic acid to an aldehyde (eq 6). DiisobutyUduminum Hydride has also been used, allowing preparation of a-acylamino aldehydes fromiV-protected amino acids. Similarly, reaction of... 

Aromatic carboxylic acids produce intense molecular ion peaks. The most important fragmentation pathway involves loss of OH to form the CeHsC O" (miz = 105), followed by loss of CO to form the ion (mIz = 77). In the mass spectrum of para-anisic acid (Fig. 8.71), loss of OH gives rise to a peak at miz =135. Further loss of CO from this ion gives rise to a peak at miz =107. Benzoic acids bearing ortho alkyl, hydroxy, or amino substituents undergo loss of water through a rearrangement reaction similar to that observed for orffto-substituted benzoate esters, as illustrated at the end of Section 8.8R. 

Electrophilic substitution of the ring hydrogen atom in 1,3,4-oxadiazoles is uncommon. In contrast, several reactions of electrophiles with C-linked substituents of 1,3,4-oxadiazole have been reported. 2,5-Diaryl-l,3,4-oxadiazoles are bromi-nated and nitrated on aryl substituents. Oxidation of 2,5-ditolyl-l,3,4-oxadiazole afforded the corresponding dialdehydes or dicarboxylic acids. 2-Methyl-5-phenyl-l,3,4-oxadiazole treated with butyllithium and then with isoamyl nitrite yielded the oxime of 5-phenyl-l,3,4-oxadiazol-2-carbaldehyde. 2-Chloromethyl-5-phenyl-l,3,4-oxadiazole under the action of sulfur and methyl iodide followed by amines affords the respective thioamides. 2-Chloromethyl-5-methyl-l,3,4-oxadia-zole and triethyl phosphite gave a product, which underwent a Wittig reation with aromatic aldehydes to form alkenes. Alkyl l,3,4-oxadiazole-2-carboxylates undergo typical reactions with ammonia, amines, and hydrazines to afford amides or hydrazides. It has been shown that 5-amino-l,3,4-oxadiazole-2-carboxylic acids and their esters decarboxylate. 

In the reactions of 4-amino-l-azadienes 295 with esters of glyoxylic acid, chemoselective cyclization occurred with displacement of the amino group NHR, and 2/7-1,3-oxazine-2-carboxylic acid derivatives 296 were formed in high yields instead of the corresponding 1,2-dihydropyrimidines usually obtained in the reactions of 295 with aliphatic or aromatic aldehydes (Equation 28) <1996T3095>. 

Aliphatic and aromatic carboxylic esters are also directly converted, in one step, to oxazolines using amino alcohols. As expected, harsh conditions are required for this transformation. Typically, the reaction is performed in refluxing xylene in the presence of catalytic quantities of a Lewis acid such as dibromo- " or dichloro-dimethylstannane. More recently, lanthanide chloride and samarium chloride have also been reported as useful catalysts for this one-pot transformation in refluxing toluene. Representative examples are shown in Table 8.2 (Scheme 8.2). ... 

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