Physical Properties of Carboxylic Acid Derivatives

Name the following carboxylic acid derivatives, giving both a common name and an lUPAC name where possible. 

Boiling points of add derivatives plotted against their molecular weights. Alcohols and unbranched alkanes are included for comparison. 

The resonance picture of an amide shows its strongly polar nature. Hydrogen bonds and dipolar attractions stabilize the liquid phase, resulting in higher boiling points. 

Acid derivatives (esters, acid chlorides, anhydrides, nitriles, and amides) are soluble in common organic solvents such as alcohols, ethers, chlorinated alkanes, and aromatic hydrocarbons. Acid chlorides and anhydrides cannot be used in nucleophilic solvents such as water and alcohols, however, because they react with these solvents. Many of the smaller esters, amides, and nitriles are relatively soluble in water (Table 21-2) because of their high polarity and their ability to form hydrogen bonds with water. 

Esters, tertiary amides, and nitriles are frequently used as solvents for organic reactions because they provide a polar reaction medium without O—H or N—H groups that can donate protons or act as nucleophiles. Ethyl acetate is a moderately polar solvent with a boiling point of 77°C, convenient for easy evaporation from a reaction mixture. Acetonitrile, dimethylformamide (DMF), and dimethylacetamide (DMA) are highly polar solvents that solvate ions almost as well as water, but without the reactivity of O — H or N—H groups. These three solvents are miscible with water and are often used as solvent mixtures with water. 

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Structure and Nomenclature of Acid Derivatives 982 21-3 Physical Properties of Carboxylic Acid Derivatives 988 21-4 Spectroscopy of Carboxylic Acid Derivatives 991 21-5 Interconversion of Acid Derivatives by Nucleophilic Acyl Substitution 997... 

How these factors affect the physical properties of carboxylic acid derivatives is summarized in Table 22.3. 

Table 22.3 Physical Properties of Carboxylic Acid Derivatives...

Physical properties of carboxylic acids and derivatives include solubility, melting point, boiling point, and a few other characteristics. In this section we examine each class and discuss the most important physical properties. (In the upcoming section Considering the Acidity of Carboxylic Acids, we discuss the most important chemical property of Ccirboxylic acids — acidity.)... 

The physical properties of cyanoacetic acid [372-09-8] and two of its ester derivatives are listed in Table 11 (82). The parent acid is a strong organic acid with a dissociation constant at 25°C of 3.36 x 103. It is prepared by the reaction of chloroacetic acid with sodium cyanide. It is hygroscopic and highly soluble in alcohols and diethyl ether but insoluble in both aromatic and aliphatic hydrocarbons. It undergoes typical nitrile and acid reactions but the presence of the nitrile and the carboxylic acid on the same carbon cause the hydrogens on C-2 to be readily replaced. The resulting malonic acid derivative decarboxylates to a substituted acrylonitrile ... 

Nirmalakhandan, N.N., Speece, R.E. (1988) QSAR model for predicting Henry s constant. Environ. Sci. Technol. 22, 1349-1357. Nishimura, K., Nozaki, Y., Yoshimi, A., Nakamura, S., Kitagawa, M., Kakeya, N., Kitao, K. (1985) Studies on the promoting effect of carboxylic acid derivatives on the rectal absorption of beta-lactam antibiotics in rats. Chem. Pharm. Bull. 33(1), 282-291. OECD (1981) OECD Guidelines for Testing of Chemicals. Section 1 Physical-Chemical Properties. Organization for Economic Co-operation and Development. OECD, Paris. 

Relative Reactivities, Structures, and Spectra of Carboxylic Acid Derivatives Comparisons of physical properties. 

Tackling the names and forms of carboxylic acids and their derivatives Analyzing the physical properties of these compounds Assessing how they are synthesized Looking at their reactions... 

Several aliphatic carboxylic acids have been known for centuries, and their common names reflect their historical sources. Formic acid was extracted from ants formica in Latin. Acetic acid was isolated from vinegar, called acetum ( sour ) in Latin. Propionic acid was considered to be the first fatty acid, and the name is derived from the Greek protos pion ( first fat ). Butyric acid results from the oxidation of butyraldehyde, the principal flavor of butter butyrum in Latin. Caproic, caprylic, and capric acids are found in the skin secrehons of goats caper in Lahn. The names and physical properties of some carboxylic acids are listed in Table 20-1. 

Once characterized as a carboxylic acid, an unknown is identified as a particular acid on the usual basis of its physical properties and the physical properties of derivatives. The derivatives commonly used are amides (Secs. 20.11 and 23.6) and esters (Sec. 20.15). 

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. 

Table 1 Physical properties of selected mercapto carboxylic acids, esters, and derivatives... 

Carboxylic acid derivatives are soluble in solvents such as ethers, chloroalkanes, and aromatic hydrocarbons. Like alcohols and ethers, carbonyl compounds with fewer than four carbons are soluble in water. Tables of physical properties can be found in the Study Area of MasteringChemistry. 

Besides carboxylates, esters of other biologically relevant acids have been used to synthesize PEG-based polyesters. Physical properties of PEG-derived polycarbonates have been explored since the 1960s [74-78]. More recent studies have focused on the degradability and cell interactions of these materials, but the PEG contents were low (<25%) [80-83]. Water-soluble polymers with higher PEG fractions have been prepared, but no degradation data has been reported for these [160, 161]. PEGs with a single carbonate linker were solely mentioned in patent literature [79, 84]. 

In this chapter, we first introduce the system of naming carboxylic acids and then list some of their physical and spectroscopic characteristics. We then examine their acidity and basicity, two properties that are strongly influenced by the interaction between the electron-withdrawing carbonyl group and the hydroxy function. Methods for the preparation of the carboxy group are considered next, followed by a survey of its reactivity. Reactions of carboxylic acids will feature a new two-step substitution pathway, addition-elimination, for the replacement of the hydroxy group by other nucleophiles, such as halide, alkoxide, and amide. The chemistry of the carboxylic acid derivatives, which result from these transformations, is the subject of Chapter 20. 

Maleic and fiimaric acids have physical properties that differ due to the cis and trans configurations about the double bond. Aqueous dissociation constants and solubiUties of the two acids show variations attributable to geometric isomer effects. X-ray diffraction results for maleic acid (16) reveal an intramolecular hydrogen bond that accounts for both the ease of removal of the first carboxyl proton and the smaller dissociation constant for maleic acid compared to fumaric acid. Maleic acid isomerizes to fumaric acid with a derived heat of isomerization of —22.7 kJ/mol (—5.43 kcal/mol) (10). The activation energy for the conversion of maleic to fumaric acid is 66.1 kJ/mol (15.8 kcal/mol) (24). 

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