Carboxylic acid derivatives structures

What structural features are responsible for the reactivity order of carboxylic acid derivatives Like the other carbonyl containing compounds that we ve studied they all have a planar arrangement of bonds to the carbonyl group Thus all are about the same in offering relatively unhindered access to the approach of a nucleophile They differ m the degree to which the atom attached to the carbonyl group can stabilize the carbonyl group by electron donation... 

Section 20 2 The structure and reactivity of carboxylic acid derivatives depend on how well the atom bonded to the carbonyl group donates electrons to it... 

The NMR spectrum of this compound shows a diamagnetic ring current of the type expected in an aromatic system. X-ray crystal structures of 1 and its carboxylic acid derivative 2 are shown in Fig. 9.2. Both reveal a pattern of bond lengths very similar to that in naphthalene (see p. 534). ... 

FIGURE 20.1 Structure, reactivity, and carbonyl-group stabilization in carboxylic acid derivatives. Acyl chlorides are the most reactive, amides the least reactive. Acyl chlorides have the least stabilized carbonyl group, amides the most. Conversion of one class of compounds to another is feasible only in the direction that leads to a more stabilized carbonyl group that is, from more reactive to less reactive. 

As a general rule, nucleophilic addition reactions are characteristic only of aldehydes and ketones, not of carboxylic acid derivatives. The reason for the difference is structural. As discussed previously in A Preview of Carbonyl Compounds and shown in Figure 19.14, the tetrahedral intermediate produced by addition of a nucleophile to a carboxylic acid derivative can eliminate a leaving group, leading to a net nucleophilic acyl substitution reaction. The tetrahedral intermediate... 

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. 

The difference in behavior between aldehydes/ketones and carboxylic acic derivatives is a consequence of structure. Carboxylic acid derivatives have ai acyl carbon bonded to a group -Y that can leave as a stable anion. As soon a the tetrahedral intermediate is formed, the leaving group is expelled to general- a new carbonyl compound. Aldehydes and ketones have no such leaving grouj however, and therefore don t undergo substitution. 

Problem 21.6 The following structure represents a tetrahedral alkoxide ion intermediate formed by addition of a nucleophile to a carboxylic acid derivative. Identify the nucleophile, the leaving group, the starting acid derivative, and the ultimate product. 

Calixarenes, which are macrocyclic compounds, are one of the best building blocks to design molecular hosts in supramolecular chemistry [158]. Synthesis of calix[4]arenes, which have been adamantylated, has been reported [105, 109]. In calix[4]arenes, adamantane or its ester/carboxylic acid derivatives were introduced as substituents (Fig. 29). The purpose of this synthesis was to learn how to employ the flexible chemistry of adamantane in order to construct different kinds of molecular hosts. The X-ray structure analysis of p-(l-adamantyl)thiacalix[4]arene [109] demonstrated that it contained four CHCI3 molecules, one of which was located inside the host molecule cavity, and the host molecule assumed the cone-like conformational shape (Fig. 30). 

The reaction of cycloheptaamylose with diaryl carbonates and with diaryl methylphosphonates provides a system in which a carboxylic acid derivative can be directly compared with a structurally analogous organo-phosphorus compound (Brass and Bender, 1972). The alkaline hydrolysis of these materials proceeds in twro steps, each of which is associated with the appearance of one mole of phenol (Scheme Y). The relative rates of the two steps, however, are reversed. Whereas the alkaline hydrolysis of carbonate diesters proceeds with the release of two moles of phenol in a first-order process (kh > fca), the hydrolysis of methylphosphonate diesters proceeds with the release of only one mole of phenol to produce a relatively stable aryl methylphosphonate intermediate (fca > kb), In contrast, kinetically identical pathways are observed for the reaction of cycloheptaamylose with these different substrates—in both cases, two moles of phenol are released in a first-order process.3 Maximal catalytic rate constants for the appearance of phenol are presented in Table XI. Unlike the reaction of cycloheptaamylose with m- and with p-nitrophenyl methylphosphonate discussed earlier, the reaction of cycloheptaamylose with diaryl methylphosphonates... 

J. Nishikawa, K. Tori, 3-Substituent Effect and 3-Methylene Substituent Effect on the Structure-Reactivity Relationship of 7 beta-(Acylamino)-3-cephem-4-carboxylic Acid Derivatives Studied by Carbon-13 and IR Spectroscopies , J. Med. Chem. 1984, 27, 1657-1663. 

The downward systemic movement of ONCOL (structure given earlier), a new insecticide derived from carbofuran, has been observed (19). A significant amount of radioactivity was observed in the roots of cotton and bean plants treated topically at the base of bifoliate or trifoliated leaves with [carbamate carbonylONCOL. Downward movement of the radiolabeled material may be explained by hydrolytic degradation of the ethoxycarbonyl moiety in ONCOL to the carboxylic acid derivative, the acid function serving as a downward moving carrier. 

A method for enantioselective synthesis of carboxylic acid derivatives is based on alkylation of the enolates of /V-acyl oxazolidinones.59 The lithium enolates have the structures shown because of the tendency for the metal cation to form a chelate. 

In an extension to this work, treatment of the template with 5-hexynal under the standard dehydrating conditions furnished the cycloadduct 301 in good yield (68). However, structural analysis of both the product and the azabicyclo[3.3.0]octane-3-carboxylic acid, derived by hydrogenation of the double bond, followed by... 

The related /V-oxide (77) demonstrates pharmaceutical activity without structural modification, being used as a radiosensitizer to promote tumour regression during radiation therapy (B-80MI20904). Similarly, 4-acetamidopyridine 1-oxide (78) has been described as a neuromuscular stimulant (80MI20905). A carboxylic acid derivative (79) demonstrating anticancer activity independent of any radiation treatment has recently been reported (81JMC1181). 

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