Structure of Carboxylic Acid Derivatives

This electron delocalization can be represented in resonance terms by contributions from the following resonance structures  

Electron release from the substituent stabilizes the carbonyl group and decreases its electrophilic character. The extent of this electron delocalization depends on the electron- 

CHAPTER TWENTY Carboxylic Acid Derivatives Nucleophilic Acyl Substitution 

FIGURE 20.2 The three cr bonds originating at the carbonyl carbon are coplanar. The p orbital of the carbonyl carbon, its oxygen, and the atom by which group X is attached to the acyl group overlap to form an extended tt system through which the tt electrons are delocalized. 

X = OH carboxylic acid X = Cl acyl chloride X = OCR acid anhydride 

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The extent of resonance can be observed directly in the structures of carboxylic acid derivatives. In the progression from acyl halides to esters and amides, the C-L bond becomes progressively shorter, owing to increased double-bond character (Table 20-1). The NMR spectra of amides reveal that rotation about this bond has become restricted. For example, W,N-dimethylformamide at room temperature exhibits two singlets for the two methyl groups, because rotation about the C-N bond is very slow on the NMR time scale. The evidence points to considerable tt overlap between the lone pair on nitrogen and the carbonyl carbon, as a result of the increased importance of the dipolar resonance form in amides. The measured barrier to this rotation is about 21 kcal moF (88 kJ moF ). 

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... 

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... 

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. 

Two widely used general methods of synthesizing 1,2,4-oxadiazoles embrace 95% of the practical preparations of these compounds the conversion of amidoximes5 by means of carboxylic acid derivatives to the cyclic structure [shown schematically as the combination of two skeletons (I)] and the cycloaddition of nitrile oxides6 to nitriles (II). The... 

Click Coached Tutorial Problems for more practice Drawing Structures of Carboxylic Acids and Derivatives from IUPAC Names. 

The structural analysis has been carried out right up to the recognition of molecular Level (i, 2). a-Chymotrypsin is poly(amino acid) consisting of 245 amino adds, having relatively deep grooves. It catalyzes the hydrolysis of carboxylic acid derivatives such as protein, simple amides, esters, etc. The active site is composed of aspartic add, Asp (102). .. histidine, His (57). .. serine, Ser (195), and the distances between Asp. .. His and His... Ser are 2.8 A and 3.0 A, respectively. Electronic structures of these moieties depend on the pH of the reaction system. In the range of pH > 7 at which a-chymotrypsin is active, —COO" of Asp attracts N4 proton in imidazolyl of His, and Nj in the imidazolyl of His attracts the proton in OH of Ser. It is called charge-relay system . 

Structure and Nomenclature of Acid Derivatives 982 21-3 Physical Properties of Carboxylic Acid Derivatives 988 21-4 Spectroscopy of Carboxylic Acid Derivatives 991 21-5 Interconversion of Acid Derivatives by Nucleophilic Acyl Substitution 997... 

Nitriles are compounds that contain a cyano group, C=N, bonded to an alkyl group. Nitriles have no carbonyl group, so they are structurally distinct from carboxylic acids and their derivatives. The carbon atom of the cyano group, however, has the same oxidation state as the carbonyl carbon of carboxylic acid derivatives, so there are certain parallels in their chemistry. 

Identification or proof of structure of an acid derivative involves the identification or proof of structure of the carboxylic acid formed upon hydrolysis (Sec. 18.21). In the case of an ester, the alcohol that is obtained is also identified (Sec. 16.11). (In the case of a substituted amide, Sec. 23.6. the amine obtained is identified, Sec. 23.19.)... 

S,S-dioxides, those authors applied spHt/pool methodology. TWo different series of compounds were prepared such as compounds 376 containing an amino acid group acylated at the nitrogen atom. According to strategy 1 shown in Scheme 90, a series of structurally diverse carboxylic acid derivatives were prepared from supported aldehyde 373 condensed with different protected amino acids in the presence of NaBH(OAc)3 to afford intermediate 374, which was then acylated affording 375. After hydrolysis of ester and reaction with bromo derivative 368 (R = H) in PTC conditions, compounds 376 were obtained. 

Structure and Nomenclature of Carboxylic Acid Derivatives A. Structure... 

At this point we want to consider the relative reactivity of carboxylic acid derivatives and other carbonyl compounds in general terms. We return to the subject in more detail in Chapter 7. Let us first examine some of the salient structural features of the carbonyl compounds. The strong polarity of the C=0 bond is the origin of its reactivity toward nucleophiles. The bond dipole of the C-X bond would be expected increase carbonyl reactivity as the group X becomes more electronegative. There is another powerful effect exerted by the group X, which is resonance electron donation. 

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