Benzoic acid acids, substituted

We now turn to substituent-sensitive tautomerism. Johnson and Rumon studied a series of solids derived by cocrystallizing substituted benzoic acids and substituted pyridines (108). Their IR evidence indicated, as expected, that when the benzoic acid is a strong acid and the pyridine a strong base, salts 50a are formed. For a weak acid and a weak base, hydrogen-bonded pairs of neutral molecules,... 

A more recent process involves the reaction of benzoic acid (or substituted benzoic acid) with urea at 220-240"C in the presence of a metallic catalyst,... 

In 1987, Toray Industries, Inc., announced the development of a new process for making aromatic nitriles which reportedly halved the production cost, reduced waste treatment requirements, and reduced production time by more than two-thirds, compared with the vapor-phase process used by most producers. The process involves the reaction of benzoic acid (or substituted benzoic acid) with urea at 220—240°C in the presence of a metallic catalyst (78). 

Linear enthalpy-entropy compensation is well known to physical organic chemists and has been the subject of controversy since the relationship was first discovered experimentally. We have discussed the complications elsewhere and will only note here that the linearity found by Beetlestone et al. is statistically reliable for most of their examples. The most extensively studied set of small-solute compensation processes in water are the ionizations of weak acids. When acids such as acetic acid or benzoic acid are substituted in their nonpolar parts to form homologous series, the standard enthalpies and entropies of ionization are found to demonstrate compensation behavior with 7], values in the 280-290°K range but only after extraction of all the contributions to these quantities from the electronic rearrangements using methods developed by Hepler and Ives and their coworkers. The obvious conclusion is that this behavior in small-solute processes is due to solvation effects and thus a manifestation of some property of water. As a result of the comparison of their data with these small-solute examples, Beetlestone et al. suggested that bulk water also plays an important role in the protein processes they studied. 

Liquid phase oxidation of benzoic acid and substituted benzoic acids (molten) to make phenols... 

It was relatively straightforward to prepare compounds whose structural and electronic characteristics could readily be varied. For example, substituted benzoic acids and substituted methyl benzoates are readily prepared. As a result it was relatively straightforward to study substituent effects on rates and equilibria by varying the nature of X (equations (1.1) and (1.2)). 

The structure of novobiocin (LVII) may be dissected into three fragments a substituted benzoic acid, a substituted coumarin, and a new sugar, noviose. Optical rotational data suggest that it is an a-glycosidei . The enolic group of the coumarin imparts acidic properties to the molecule. 

The use of microwave heating allows a reduction in the reaction times from many hours to a few minutes. However, the biaryl product is always accompanied by the arene generated from decarboxylation of the benzoic acid. Similarly, substituted benzoic acids react with aryl iodides in the presence of PdCl as the catalyst, BINAP as the ligand, and 3 equivalents of Ag CO as an additive in dimethylacetamide (DMA) (Scheme 22.40, path b) [56]. Unsymmetrical biaryls have been obtained in 58-90% yield by the reaction of aryl iodides with arene carboxyhc acids by use of a PdClj/AsPhj catalytic system in the presence of AgjCOj [57]. 

Benzoic acid and substituted benzoic acids are readily thallated by thallium(III) trifluoroacetate. Subsequent reaction with palladium chloride and simple alkenes, allylic or vinyl halides, or vinyl esters result in the formation of isocoumarins eg ... 

Goswami, S., Jana, S., Hazra, A., Fun, H.-K. and Chantrapromma, S., Non-covalent synthesis of ionic and molecular complexes of benzoic acid and substituted 2-aminopyrimidines by varying aryl/allq l substituents and their supramolecular chemistry, Supramol. Chem. 20 (5), 495-500 (2008). 

A similar substituent effect on p Tg is observed for substituted benzoic acids and substituted protonated anilines—that is, electron-withdrawing substituents increase acidity, whereas electron-donating substituents decrease acidity. 

Mast MA, Drever JI (1987) The effect of oxalate on the dissolution rates of oligoclase and tremolite. Geochim Cosmochim Acta 51 2559-2568 Matsui T, Ko HC, Hepler LG (1974) Thermodynamics of ionization of benzoic acid and substituted benzoic acids in relation to the Hammett equation. Can J Chem 52 2906-2911... 

Hammen equation A correlation between the structure and reactivity in the side chain derivatives of aromatic compounds. Its derivation follows from many comparisons between rate constants for various reactions and the equilibrium constants for other reactions, or other functions of molecules which can be measured (e g. the i.r. carbonyl group stretching frequency). For example the dissociation constants of a series of para substituted (O2N —, MeO —, Cl —, etc.) benzoic acids correlate with the rate constant k for the alkaline hydrolysis of para substituted benzyl chlorides. If log Kq is plotted against log k, the data fall on a straight line. Similar results are obtained for meta substituted derivatives but not for orthosubstituted derivatives. 

The logarithm of the equilibrium constant, K,. for the chemical equation shown in Figure 3-8a for a substituted benzoic acid can be related to the logarithm of the... 

Figure 3-8 a) The dissociation of substituted benzoic acids (X = substituent), and b) the hydrolysis of benzoic acid methyl esters. 

Methyl, ethyl, n-propyl, isopropyl, n-hutyl, benzyl, cyclohexyl esters of formic, acetic, oxalic, succinic, tartaric, citric, benzoic, salicylic (and other substituted benzoic acids), phthalic and cinnamic acids phenyl esters of acetic, benzoic and salicylic acids. 

The best-known equation of the type mentioned is, of course, Hammett s equation. It correlates, with considerable precision, rate and equilibrium constants for a large number of reactions occurring in the side chains of m- and p-substituted aromatic compounds, but fails badly for electrophilic substitution into the aromatic ring (except at wi-positions) and for certain reactions in side chains in which there is considerable mesomeric interaction between the side chain and the ring during the course of reaction. This failure arises because Hammett s original model reaction (the ionization of substituted benzoic acids) does not take account of the direct resonance interactions between a substituent and the site of reaction. This sort of interaction in the electrophilic substitutions of anisole is depicted in the following resonance structures, which show the transition state to be stabilized by direct resonance with the substituent ... 

On the other hand an alkyl side chain on a benzene nng is oxidized on being heated with chromic acid The product is benzoic acid or a substituted derivative of benzoic acid... 

A considerable body of data is available on the acidity of substituted benzoic acids Ben zoic acid Itself is a somewhat stronger acid than acetic acid Its carboxyl group is attached to an sp hybridized carbon and ionizes to a greater extent than one that is attached to an sp hybridized carbon Remember carbon becomes more electron withdrawing as its s character increases... 

Table 19 3 lists the ionization constants of some substituted benzoic acids The largest effects are observed when strongly electron withdrawing substituents are ortho to the carboxyl group An o nitro substituent for example increases the acidity of benzoic acid 100 fold Substituent effects are small at positions meta and para to the carboxyl group In those cases the values are clustered m the range 3 5-4 5... 

Substituent in XC6H4CO2H Acidity of Some Substituted Benzoic Acids pKa for different positions of substituent X ... 

As discussed earlier in Section lOC.l, ultraviolet, visible and infrared absorption bands result from the absorption of electromagnetic radiation by specific valence electrons or bonds. The energy at which the absorption occurs, as well as the intensity of the absorption, is determined by the chemical environment of the absorbing moiety. Eor example, benzene has several ultraviolet absorption bands due to 7t —> 71 transitions. The position and intensity of two of these bands, 203.5 nm (8 = 7400) and 254 nm (8 = 204), are very sensitive to substitution. Eor benzoic acid, in which a carboxylic acid group replaces one of the aromatic hydrogens, the... 

In this experiment a theoretical model is used to optimize the HPLC separation of substituted benzoic acids by adjusting the pH of the mobile phase. An empirical model is then used... 

R. M. Muir and C. Hansch, "Chemical Stmcture and Growth-Activity of Substituted Benzoic Acids," in Ref. 27. 

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