Acids and Nitriles

Preparing Carboxylic Acids Reactions of Carboxylic Acids An Overview 

The burning sensation produced by touching or eating chili peppers is due to capsaicin, a carboxylic 

Carboxylic acids, RCO2H, occupy a central place among carbonyl compounds. Not only are they valuable in themselves, they also serve as starting materials for preparing numerous carboxylic acid derivatives such as acid chlorides, esters, amides, and thioesters. In addition, carboxylic acids are present in the majority of biological pathways. 

Approximately 5 million metric tons of acetic acid is produced worldwide each year for a variety of purposes, including preparation of the vinyl acetate polymer used in paints and adhesives. About 20% of the acetic acid synthesized industrially is obtained by oxidation of acetaldehyde. Much of the remaining 80% is prepared by the rhodium-catalyzed reaction of methanol with carbon monoxide. 

Why This Chapter Carboxylic acids are present in many industrial processes and most biological pathways and are the starting materials from which other acyl derivatives are made. Thus, an understanding of their properties and reactions is fundamental to understanding organic chemistry. We ll look both at acids and at their close relatives, nitriles (RC = N), in this chapter and at carboxylic acid derivatives in the next chapter. 

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Online homework forthis chapter may be assigned in Organic OWL. 

General information about carboxylic acids and nitriles (Sections 20.1 - 20.4). 

Noncyclic carboxylic acids are named by replacing the -e of the corresponding alkane by -oic acid. 

Compounds that have a carboxylic acid bonded to a ring are named by using the suffix -carboxylic acid. 

Many carboxylic acids have historical, nonsystematic names. 

Simple nitriles are named by adding -nitrile to the alkane name. 

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Isocyanates are derivatives of isocyanic acid, HN=C=0, ia which alkyl or aryl groups, as weU as a host of other substrates, are direcdy linked to the NCO moiety via the nitrogen atom. StmcturaHy, isocyanates (imides of carbonic acid) are isomeric to cyanates, ROCMSI (nitriles of carbonic acid), and nitrile oxides, RCMSI—>0 (derivatives of carboxyUc acid). 

Isoxazoles substituted in the 3-position, but unsubstituted in the 5-position, react under more vigorous conditions to give acids and nitriles (Scheme 24). Anthranils unsubstituted in the 3-position are similarly converted into anthranilic acids by bases (Scheme 25) (67AHC(8)277). Attempted acylation of anthranils gives benzoxazine derivatives via a similar ring opening (Scheme 26) (67AHC(8)277). 

C. Wenti up and P. Kamhouris, N-Sulfides Dinitrogen Sulfide, Thiofulminic Acid and Nitrile Sulfides, Chem. Rev., 91, 363 (1991). 

Chromium (II) sulfate is capable of reducing a variety of functional groups under mild conditions 10). Of particular interest is its ability to reduce a,jS-unsaturated esters, acids, and nitriles to the corresponding saturated compounds. This capability is illustrated in the procedure by the reduction of diethyl fumarate. 

Interactive to use a web-based palette to predict products from a variety of reactions involving carboxylic acids and nitriles. 

Closely related to the carboxylic acids and nitriles discussed in the previous chapter are the carboxylic acid derivatives, compounds in which an acyl group is bonded to an electronegative atom or substituent that can net as a leaving group in a substitution reaction. Many kinds of acid derivatives are known, but we ll be concerned primarily with four of the more common ones acid halides, acid anhydrides, esters, and amides. Esters and amides are common in both laboratory and biological chemistry, while acid halides and acid anhydrides are used only in the laboratory. Thioesters and acyl phosphates are encountered primarily in biological chemistry. Note the structural similarity between acid anhydrides and acy) phosphates. 

Spectroscopy of Carboxylic Acids and Nitriles 770 Focus On. .. Vitamin C 772... 

Chromium(II) sulfate is a versatile reagent for the mild reduction of a variety of bonds. Thus aqueous dimethylformamide solutions of this reagent at room temperature couple benzylic halides, reduce aliphatic monohalides to alkanes, convert vicinal dihalides to olefins, convert geminal halides to carben-oids, reduce acetylenes to /raw5-olefins, and reduce a,j3-unsatu-rated esters, acids, and nitriles to the corresponding saturated derivatives. These conditions also reduce aldehydes to alcohols. The reduction of diethyl fumarate described in this preparation illustrates the mildness of the reaction conditions for the reduction of acetylenes and o ,j8-unsaturated esters, acids, and nitriles. 

Notably, nitrile-degrading enzymes (e.g. nitrilase that converts the CN group to carboxylic acid, and nitrile hydratase that produces an amide function) have been described, and they co-exist with aldoxime-degrading enzymes in bacteria (Reference 111 and references cited therein). Smdies in this area led to the proposal that the aldoxime-nitrile pathway, which is implemented in synthesis of drugs and fine chemicals, occurs as a natural enzymic pathway. It is of interest that the enzyme responsible for bacterial conversion of Af-hydroxy-L-phenylalanine to phenacetylaldoxime, an oxidative decarboxylation reaction, lacks heme or flavin groups which are found in plant or human enzymes that catalyze the same reaction. Its dependency on pyridoxal phosphate raised the possibility that similar systems may also be present in plants . 

The first stable perchlorates of 1,3-benzo-TA were isolated as dioxane complexes 205 in a reaction between 2-mercaptobenzoic acid and nitriles in the presence of 70% HC104 and acetic anhydride. Heating these complexes in acetic acid affords salts 206, which may be transformed into benzo-TA 56. Protonation of 56 initially gives cations 206, whose IR spectra show that they exist in an NH form (there is a strong bond at 1700-1730 cm"1) (85KGS562) (Scheme 74). 

Regarding ozonation processes, the treatment with ozone leads to halogen-free oxygenated compounds (except when bromide is present), mostly aldehydes, carboxylic acids, ketoacids, ketones, etc. [189]. The evolution of analytical techniques and their combined use have allowed some researchers to identify new ozone by-products. This is the case of the work of Richardson et al. [189,190] who combined mass spectrometry and infrared spectroscopy together with derivatization methods. These authors found numerous aldehydes, ketones, dicarbonyl compounds, carboxylic acids, aldo and keto acids, and nitriles from the ozonation of Mississippi River water with 2.7-3 mg L 1 of TOC and pH about 7.5. They also identified by-products from ozonated-chlorinated (with chlorine and chloramine) water. In these cases, they found haloalkanes, haloalkenes, halo aldehydes, haloketones, haloacids, brominated compounds due to the presence of bromide ion, etc. They observed a lower formation of halocompounds formed after ozone-chlorine or chloramine oxidations than after single chlorination or chlorami-nation, showing the beneficial effect of preozonation. 

Fig. 7.1 Survey of the mutual interconversion of carboxylic acid derivatives, especially primary amides of carboxylic acids, and nitriles.

Using tetrafluoroboric acid, several unsaturated acids and nitriles were thus made reactive and were converted into acetoxy lactones [3]. Tosyloxy-, phosphoryloxy-and iodomethyl lactones as well as cyclic ethers resulting from analogous neighbouring group participation will be discussed in connection with other hypervalent iodine reagents. 

N,S- and N,0,S-Heterocycles as precursors of N2S, thiofulminic acid, and nitrile sulfides 91CRV363. 

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