Carboxylic acid derivatives identification

Mass spectrometry is one of the major techniques in the interdisciplinary field of proteomics. It provides a rapid, sensitive and reliable means of protein identification and structural determination, allowing for development in this newly baptised but yet classical field of biochemistry and biomedicine. The use of electrospray ionisation in conjunction with a tandem mass spectrometer (MS/MS) provides essential amino acid sequence information from the m/z values of the so-called b andy ions formed from cleavage of the amide bond of a protonated peptide. This reaction requires proton catalysis, and the mechanism is of interest in the present context, since it is closely related to the processes occurring in other protonated carboxylic acid derivatives. 

Esters are carboxylic acid derivatives, and the spectrum of ethyl acetate is shown in Figure 14.19D. The carbonyl absorption does not distinguish this compound from an aldehyde or a ketone, but there is the C-O absorption at about 1200 cm 1. Because this is in the fingerprint region, however, its position can be difficult to identify. This is clearly the case for methyl pentanoate, where the C-0 absorption can easily be missed or misidentified. Based only on the infrared, it may be difficult to distinguish an ester from an aliphatic aldehyde or ketone. If the formula is known, however (from mass spectrometry), the identification is easier because an ester has two oxygen atoms, whereas the aldehyde or ketone has only one. 

The signal for an aldehyde hydrogen typically appears between 8 9.5 and 8 10.1 in a H-NMR spectrum. Because almost nothing else absorbs in this region, it is very useful for identification. Hydrogens on an a-carbon (carbon directly adjacent to carbonyl) of an aldehyde or a ketone appear around 8 2.2 to 2.6. The carbonyl carbons of aldehydes and ketones have characteristic positions in the C-NMR between 8 180 and 8 215 (and can be distinguished from carboxylic acid derivatives, which absorb at a higher field). 

The high reactivity of chlorides is utilized for the preparation of carboxylic acid derivatives by first converting the acids to chlorides and then allowing them to react with amines or alcohols to give suitable derivatives. For the identification of acid chlorides, reactions described on p. 254 are employed. A simple method of preparation of amides from acid chlorides is illustrated by the preparation of stearoylamide. Other useful amines are aniline or p-toluidine the reaction of amines with chlorides is usually carried out by heating the components in an inert solvent (benzene). 

From the list of melting points of derivatives of halo acids given in Table 10 it is evident that for the identification of halo acids, amides, anilides and /7-toluides are suitable / -bromophenacyl esters were prepared only in a few cases. If satisfactory results cannot be obtained by the application of procedures given for the preparation of carboxylic acid derivatives (see p. 249), original literature should be consulted. Identification of aromatic, halo acids is easy because they are well-crystallized solids, and, in addition the preparation of derivatives, for example, p-bromophenacyl esters, causes no difficulty. 

Perspicamides A and B are rare examples of quinoline-2-carboxylic acid derivatives (cf trididemnic acids, see above). Isolated from the AustraUan species Botrylloides perspicuum, these derivatives have no particular biological activity (McKay, Carroll, and Quinn, 2005). Trididemnic acids and the perspicamides, however, are related to kinurenic add, an anti-excitotoxic and anticonvulsant that was isolated from the spedes Botryllus schlosserl with other polar derivatives, and this is their first identification in a marine organism (Usov et al, 2002). 

S2S. Street, H. V., Gas-liquid chromatography of submicrogram amounts of drugs. IV. Identification of barbiturates, hydantoins, amides, imides, carbamates, phenylbutazone, carboxylic acids and hydrazine derivatives by direct derivative fonnation within the gas chromatograph. J. Chromaiogr. 41, 358-366 (1969). 

Dinitrophenyl (DNP) derivatives are useful for the separation and the subsequent MS identification of amines [207]. Most of the derivatives give reasonably intense molecular ions and an ion at m/e 196, which is usually the base peak formed by a-alkyl fission. A similar TLC separation and MS identification is also possible by converting aliphatic amines into 4-nitroazobenzene4-carboxylic acid amides [208]. The molecular ions are relatively intense (the second most abundant ion) and the base peak corresponds in all cases to a fragment at m/e 254. 

The manufacture of the large variety of polyamides (commonly referred to as nylons) occurs through polycondensation of amino carboxylic acids (or functional derivatives of them, e.g. lactams) and from diamines and dicarboxylic acids. Labeling the amino groups with A and the carboxyl groups with B allows differentiation of the different chemical structures between the two types AB (from amino carboxylic acids) and AA-BB (from diamines and dicarboxylic acids). The number of C atoms in the monomers acts as a code number for the identification of the polyamides. The polycaprolactam manufactured from caprolactam (type AB) is then called polyamide 6 (PA 6). The number of carbon atoms in the diamine is given first for type AA-BB followed by the number of atoms in the dicarboxylic acid, e.g. PA 66 for polyhexamethylenedia-dipic amide from hexamethylenediamine and adipic acid. For copolymers the components are separated by a slash, e.g. PA 66/6 (90 10) is a copolymer composed of 90 parts PA 66 and 10 parts PA 6. 

Identification or proof of structure of an acid derivative involves the identification or proof of structure of the carboxylic acid formed upon hydrolysis (Sec. 18.21). In the case of an ester, the alcohol that is obtained is also identified (Sec. 16.11). (In the case of a substituted amide, Sec. 23.6. the amine obtained is identified, Sec. 23.19.)... 

In keeping with this method, several approaches have been developed to document methods and dose-response relationships for irritation in humans. This work suggests that, at least for nonreactive compounds such esters, aldehydes, ketones, alcohols, carboxylic acids, aromatic hydrocarbons, and pyridine, the percentage of vapor pressure saturation of a compound is a reasonable predictor of its irritant potency. Specific physical properties of molecules predict overall irritation potential. This work is based on the identification of irritant thresholds for homologous series of specific agents. Quantitative structure-activity relationships derived from such work suggests a reasonable model to explain mucosal irritation. 

Odor compounds may also be released from the plastic materials used in cars. The variety of plastics and possible chemical compounds is broad, which makes the identification of odor causing compounds an extremely comphcated task. An effective and rapid screening of VOCs and semi-VOCs from materials used in automobiles was developed by utihzing the SPME technique [28]. The low molecular weight compoimds extracted from five different automobile materials included different benzene derivatives, aldehydes, esters, biphenyls, phthalates, butylated hydroxytoluene, phenols, alcohols, styrene, triethylene-diamine, carboxylic acids and ketones. A considerable munber of VOCs and semi-VOCs were detected, indicating that more attention should be paid to the selection of materials and additives for automotive parts. 

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