Carboxylic acids, derivatives and

Pyridine- and azine-carboxylic acids, as amino acids, exist partly as betaines (e.g. 679) in aqueous solution, but very dominantly as neutral molecules in ethanol which has a lower dielectric constant. 

Azinecarboxylic acids lose C02 significantly more easily than benzoic acid. Pyridinecarboxylic acids decarboxylate on heating with increasing ease in the order (3 y a. 2-Pyridazinecarboxylic acid gives pyrazine at 200°C, and 4,5-pyrimidinedicarboxylic acid forms the 5-mono-acid on vacuum distillation. Pyrone- and pyridone-carboxylic acids also decarboxylate relatively easily thus, chelidonic acid (680 Z = O) at 160°C over copper powder and chelidamic acid (680 Z=NH) at 260°C give (681 Z = 0, NH). 

The relatively easy decarboxylation of a- (682) and y-carboxylic acids is a result of inductive stabilization of intermediate ylides of type (683) (cf. Section 3.2.1.8.2). By carrying out the decarboxylation in the presence of aldehydes or ketones, products of type (684) are formed (Hammick Reaction). 

Pyridines with an a- or y-carboxymethyl group (e.g. 685) undergo facile decarboxylation by a zwitterion mechanism (685 — 688) somewhat similar to that for the decarboxylation of 3-keto acids (cf. Section 3.2.3.1.1). Carboxymethylpyridines often decarboxylate spontaneously on formation thus, hydrolysis of (689) gives (690). The corresponding 2- and 4-pyridone and 2- and 4-pyrone acids are somewhat more stable, e.g. (691) decarboxylates at 170°C. 3-Pyridineacetic acid shows no pronounced tendency to decarboxylate. 

Pyridine nitriles show normal reactions. However, with rather more electron-deficient rings, such as those in pyrimidine nitriles or pyridinium nitriles, nucleophilic displacement of the CN becomes possible (cf. 561 — 562, Section 3.2.3.1.2.i). The nucleophilic displacement of CN in cationic ring (692) by dimethylamine is important in the manufacture of 4-dimethylaminopyridine. 

Like aldehydes and ketones, the a-hydrogens of acid and acid derivatives are acidic and can be abstracted with base to generate the carban-ions, which can then react with various electrophiles such as halogens, aldehydes, ketones, unsaturated carbonyl compounds, and imines, to give the corresponding products. Many of these reactions can be performed in aqueous conditions. These have been covered in related chapters. 

Compared with aldehydes and ketones, carboxylic acids and their derivatives are less reactive toward reduction. Nevertheless, it is still possible to reduce various acid derivatives in aqueous conditions. Aromatic carboxylic acids, esters, amides, nitriles, and chlorides (and ketones and nitro compounds) were rapidly reduced by the Sml2-H20 system to the corresponding products at room temperature in good yields 

Comprehensive Organic Reactions in Aqueous Media, Second Edition, by Chao-Jun 

The formation of the dimeric product (227) in the furo[3,2-6]pyrrole series was observed under conditions of flash vacuum pyrolysis of the acid (215) and its ethyl ester 82CC360 . 

Substituted derivatives (83CCC1878,84MI701-01) and pentacyclic (238)-(241) and hexacyclic (242)-(245) polyaza systems were prepared analogously from intermediates (236) and (237). 

Selective hydrogenation of acids to aldehydes is very difficult under high pressure, because the product is, in general, more easily hydrogenated than the substrate over conventional catalysts. The key point of our research was how to fine-tune the properties of the catalyst in such a way that it becomes active and selective. 

The cuiTent process for producing aromatic and aliphatic aldehydes by direct hydrogenation of the corresponding carboxylic acids over Zr02 and Cr203 has been developed by the Mitsubishi Chemical Corporation. It has successfully commercialized the production of p-t-butylbenzaldehyde, m-phenoxybenzaldehyde, p-methylbenzaldehyde, 10-undecenal, and dodecanal by reduction of the corresponding acids. By use of this technology, ca. 2000 t y of aldehydes have been manufactured since 1988 [3]. 

Alkyl carbon atoms attached in a position a, / , or y to a carboxy function give rise to tx, [1. and y effects which shift the carboxy carbon resonances by 10, 4 and — 1 ppm, respectively. This trend is illustrated by the 13C shift values collected for formic, acetic, propionic, and butyric acids among others in Table 4.34 [305-309], Further, carboxy carbons of x halo acids and dicarboxylic acids with closely spaced carboxy groups arc shielded relative to those of parent alkanoic acids (Table 4.34). On the other hand, the x, j3 and y carboxy increments Z, = hi(RCOon)- — krh) f°r the carbon shifts of an alkyl chain are 

Equilibration of carboxylic acid dimers and monomers in the sample solution depends on the extent to which the carboxy group is involved in hydrogen bonding with the solvent  

Therefore, solvent shifts of up to 4 ppm must be expected, as illustrated for acrylic acid in Table 4.36 [282], 

Dissociation of the carboxy proton causes deshieldings decreasing from the carboxy (4.7 ppm) to the y carbon (0.6 ppm) [305, 307] which are attributed to electric fields (Section 3.1.4.3). Intramolecular electric fields are also made responsible for the different sp2 carbon shifts in long-chain carboxylic acids [309]. 

The 13C chemical shift values for the a- and /1-carbons in a, //-unsaturated carboxylic acids can be calculated using the eqs. (4.10) [306]  

The substituted furo[3,2-3]indole-2-carbonitrile 228 with a fluorous tin azide (C6F]3CH2CH2)3SnN3) gave the corresponding tetrazole derivative 229 (Equation 4) 1999T8997 . 

The reactions of substituted furo[3,2- ]pyrrole-5-carbohydrazides with 5-arylfuran-2-carbaldehydes, 4,5-disubsti-tuted furan-2-carbaldehydes, and thiophene-2-carbaldehyde have been studied 2005CEC622 . The advantage of microwave (MW) irradiation on some of these reactions was reflected in the reduced reaction time and increased yields (Table 8). The series of substituted hydrazones 241-246 was obtained from these 

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Carboxylic acids and derivatives (including amides and nitriles). 

The next several chapters deal with the chemistry of various oxygen containing func tional groups The interplay of these important classes of compounds—alcohols ethers aldehydes ketones carboxylic acids and derivatives of carboxylic acids— IS fundamental to organic chemistry and biochemistry... 

Syntheses of Aliphatic Carboxylic Acids and Derivatives. Alkenes are carbonylated in the presence of acid catalysts at 75-100°C and under pressures of 60—90 MPa (600—900 atm) to give carboxyUc acids (186). 

The reaction is less selective than the related benzoylation reaction (/pMe = 30.2, cf. 626), thereby indicating a greater charge on the electrophile this is in complete agreement with the greater ease of nuclophilic substitution of sulphonic acids and derivatives compared to carboxylic acids and derivatives and may be rationalized from a consideration of resonance structures. The effect of substituents on the reactivity of the sulphonyl chloride follows from the effect of stabilizing the aryl-sulphonium ion formed in the ionisation step (81) or from the effect on the preequilibrium step (79). 

Nitrilases convert nitriles to the corresponding carboxylic acids and NH3 through a cysteine residue in the active site [50]. Because of their high enantio- and regio-selectivity, nitrilases are attractive as green catalysts for the synthesis of a variety of carboxylic acids and derivatives (Figure 1.10) [51,52]. Recently, a number of recombinant nitrilases have been cloned and characterized heterologously for synthetic applications [50,53,54]. 

The photolysis of carboxylic acids and derivatives as lactones, esters and anhydrides can yield decarboxylated products 253>. This reaction has been utilized in the synthesis of a-lactones from cyclic diacyl peroxides 254) (2.34) and in the synthesis of [2,2]paracyclophane by bis-decarboxylation of a lactone precursor (2.35) 255). This latter product was also obtained by photoinduced desulfurization of the analogous cyclic sulfide in the presence of triethyl phosphite 256). 

Scheme 1.34. Formation of acyl-zirconocene derivatives by carbonylation and their conversion into aldehydes, carboxylic acids, and derivatives thereof.

R. Taylor in "Chemistry of Carboxylic Acids and Derivatives" Suppl. 2, (Patai, Editor) Chapter 15, 860, Wiley, N.Y. (1979). 

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.)... 

You can use the unique spectroscopy of carboxylic acids and derivatives, described in the following list, to help you identify those compounds. 

Acrylic Acid Propenoic Acid Benzoic Acid Carboxylic Acids Carboxylic Acids and Derivatives Carboxylic Acids with Other Functional Groups Carboxylic Acids with Other Functional Groups Dichlorophenoxyacetic Acid 2,4-d Cesium... 

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