Substitutions 2 benzoate

Production of cellulose esters from aromatic acids has not been commercialized because of unfavorable economics. These esters are usually prepared from highly reactive regenerated cellulose, and their physical properties do not differ markedly from cellulose esters prepared from the more readily available aHphatic acids. Benzoate esters have been prepared from regenerated cellulose with benzoyl chloride in pyridine—nitrobenzene (27) or benzene (28). These benzoate esters are soluble in common organic solvents such as acetone or chloroform. Benzoate esters, as well as the nitrochloro-, and methoxy-substituted benzoates, have been prepared from cellulose with the appropriate aromatic acid and chloroacetic anhydride as the impelling agent and magnesium perchlorate as the catalyst (29). 

Taft began the LFER attack on steric effects as part of his separation of electronic and steric effects in aliphatic compounds, which is discussed in Section 7.3. For our present purposes we abstract from that treatment the portion relevant to aromatic substrates. Hammett p values for alkaline ester hydrolysis are in the range +2.2 to +2.8, whereas for acid ester hydrolysis p is close to zero (see Table 7-2). Taft, therefore, concluded that electronic effects of substituents are much greater in the alkaline than in the acid series and. in fact, that they are negligible in the acid series. This left the steric effect alone controlling relative reactivity in the acid series. A steric substituent constant was defined [by analogy with the definition of cr in Eq. (7-22)] by Eq. (7-43), where k is the rate constant for acid-catalyzed hydrolysis of an orr/to-substituted benzoate ester and k is the corresponding rate constant for the on/to-methyl ester note that CH3, not H, is the reference substituent. ... 

Correlation analyses of this type have also been carried out in connection with the kinetics of the reaction of ortho-substituted benzoate ions with para-substituted phenacyl bromides164 and of ortho-substituted benzoate ions with ethyl bromoacetate165. In all cases it is possible to include 0-SO2Me among the basic set of well-behaved substituents. 

Taft RW Jr. Linear free-energy relationships from rates of esterification and hydrolysis of aliphatic and ortho-substituted benzoate esters. / Am Chem Soc 1952 74 2729-32. 

The application of di-arene dihydrodiols has been noted in Part 1 of this chapter, and it is sufficient to note here the application of a mutant of Alcaligenes eutrophus strain B9 that is blocked in the degradation of benzoate (and some halogenated benzoates). This produced the cA-l,2-dihydrodiol (Reiner and Hegeman 1971), and has been used as the source of ring B for the synthesis of a range of tetracyclines (Charest et al. 2005). A range of substituted c -dihydrodiols has been produced, and it has been shown that for 3-substituted benzoates both 3- and 5-substituted cA-dihydrodiols were formed (Reineke et al. 1978). 

It can be concluded from these observations that whereas benzoate produced by the carboxylation of phenols can be degraded, dehydroxylation with the formation of substituted benzoates may produce stable terminal metabolites. 

Thus we have already seen (p. 384) that the acid-catalysed hydrolysis of m- and p-substituted benzoate esters (42) is (with a p value of 0 03) essentially uninfluenced by any polar effect exerted by the substituent, X and this substituent is sufficiently far removed from the reaction centre to be clearly incapable of exerting any... 

Thus oxidation of both 6- and 7-substituted 3-amino-benzo-l,2,3-triazin-4-ones with lead tetraacetate in methanol produced a mixture of p- and m-substituted benzoates, clearly indicating that a symmetrical intermediate, i.e. benzocyclopropenone (166) was formed and underwent ring opening by attack of solvent121 ... 

Second-order rate constants A for the replacement of a ring-substituted benzoate group by hydroxide ion in a number of complexes (base hydrolysis) have been carefully determined at 25°C in 40% aqueous methanol ... 

H 2[Cu(maleate)2]4H jO j Cu"-2-furancarboxylate trihydrate A range of Cu"-substituted benzoates Cu"-saccharate, -lactobionate,... 

Kummert, R. Stumm,W. (1980) The surface complexation of organic acids on hydrous y-AI2O3. J. Colloid Interface Sd. 75 373—385 Rung, K.H. McBride, M.B. (1989) Adsorption of para-substituted benzoates on iron oxides. Soil Sd. Soc. Am. J. 53 1673-1678 Rung, K.H. McBride, M.B. (1989a) Coordination complexes of p-hydroxybenzoate on Ee-oxides. Clays Clay Min. 37 333-340 Kuntze, H. (1982) Iron clogging in soils and pipes. Analysis and treatment. DVWK Bull. 10. Parey, Hamburg, Berlin, 123 p. 

Appropriately, ortho-substituted benzoates eliminate ROH through the general ortho effect described above under aromatic acids. Thus, the base peak in the spectrum of methyl salicylate is m/z 120 this ion eliminates carbon monoxide to give a strong peak at m/z 92. 

Furthermore, one might expect that electron-withdrawing substituents on aromatic systems (e.g., positive a values) make the -electrons of the ring system less nucleophilic and thus the rate of attack of the electrophilic oxygen on that ring slower. This is consistent with observations on a series of substituted benzoates where steric factors do not dominate (Knackmuss, 1981) ... 

KINETIC DATA FOR THE ACID-CATALYZED HYDROLYSIS AND FORMATION OF SUBSTITUTED BENZOATE ESTERS... 

Slightly smaller p values are obtained with more polar solvents, where the medium is able to stabilize the transition state more effectively, and thus the response to the electronic effects of substituents is less critical. For the alkaline hydrolysis of the phenyl esters of substituted benzoates in 33% aqueous acetonitrile Kirsch et al.235 find p = 1.98. The value is not significantly different for more or less reactive leaving groups under the same conditions... 

When the substituent is more remote from the carboxyl group than in substituted benzoate esters, smaller values of p are to be expected. Thus, p — 1.21 for the alkaline hydrolysis of orf/io-substituted ethyl cinnamates, ArCH=CHCOOEt, in 87.8% aqueous ethanol at 30°C148 149. 

For more remote substitution p is expected to be smaller. Thus Hay and Porter-28 found p = 0.6 for the alkaline hydrolysis of the methyl esters of a-amino acids, RCH(NH2)COOCH.3 in water at 25°C. However, higher sensitivities are possible if the geometry of the system is such that the direct transmission of polar effects becomes more important. For example, Roberts and Moreland245 found that the effects of substituents in the 4 position of ethyl bicyclo-[2.2.2]octane-l-carboxylates (28) on the hydrolysis in 88% ethanol at 30°C are comparable to those observed for meta- anti para-substituted benzoates (p = 2.24), and a similar, though smaller, effect, is observed for methyl rrarts-4-substituted cyclohexanecarboxylates (29). 

In the 1950s Taft devised a method of extending linear free-energy relationships to aliphatic systems.16 He suggested that, since the electronic nature of substituents has little effect on the rate of acid-catalyzed hydrolysis of meta- or para-substituted benzoates (p values are near 0, see Table 2.3), the electronic nature of substituents will also have littie effect on acid-catalyzed hydrolysis of aliphatic esters. All rate changes due to substituents in the latter reactions are, therefore, probably due to steric factors.17 Taft defined Es, a steric substituent constant, by Equation 2.16... 

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