Lone pairs carboxyl derivatives

The condensation reactions described above are unique in yet another sense. The conversion of an amine, a basic residue, to a neutral imide occurs with the simultaneous creation of a carboxylic acid nearby. In one synthetic event, an amine acts as the template and is converted into a structure that is the complement of an amine in size, shape and functionality. In this manner the triacid 15 shows high selectivity toward the parent triamine in binding experiments. Complementarity in binding is self-evident. Cyclodextrins for example, provide a hydrophobic inner surface complementary to structures such as benzenes, adamantanes and ferrocenes having appropriate shapes and sizes 12) (cf. 1). Complementary functionality has been harder to arrange in macrocycles the lone pairs of the oxygens of crown ethers and the 7t-surfaces of the cyclo-phanes are relatively inert13). Catalytically useful functionality such as carboxylic acids and their derivatives are available for the first time within these new molecular clefts. 

This affinity for metals results not only from the structural organization of the new diacids but from stereoelectronic effects at carboxyl oxygen as well. The in-plane lone pairs of a carboxylate 18 differ in basicity by several orders of magnitude 16). Conventional chelating agents17> derived from carboxylic acids such as EDTA, 19a are constrained by their shape to involve the less basic anti lone pairs [Eq. (4)]. The new diacids are permitted the use of the more basic syn lone pairs in contact with the metal 19b. These systems represent a new type of chelate for highly selective recognition of divalent ions. 

The methoxide ion uses of its lone pairs of electrons to form a bond to the electrophilic carbonyl carbon of the acid chloride. Simultaneously, the relatively weak n bond of the carbonyl group breaks and both of the n electrons move onto the carbonyl oxygen to give it a third lone pair of electrons and a negative charge. This is exactly the same first step involved in nucleophilic addition to aldehydes and ketones. However, with an aldehyde or a ketone, the tetrahedral structure is the final product. With carboxylic acid derivatives, the lone pair of electrons on oxygen return to reform the carbonyl n bond (Step 2). As this happens, the C-Cl o bond breaks with both electrons moving onto the chlorine to form a chloride ion that departs the molecule. 

Amides differ from carboxylic acids and other acid derivatives in their reaction with Li A1H4 Instead of forming primary alcohols, amides are reduced to amines (Fig.P). The mechanism (Fig.Q) involves addition of the hydride ion to form an intermediate that is converted to an organoaluminium intermediate. The difference in this mechanism is the intervention of the nitrogen s lone pair of electrons. These are fed into the electrophilic centre to eliminate the oxygen that is then followed by the second hydride addition. 

We ve already discussed this sequence of reactivity in relation to acid derivatives in Chapters 12 and 14— make sure you understand the reason forthe ordering of ester > amide > carboxylate. Here we re adding on aldehyde (the most reactive, for steric reasons—it is the least hindered) and ketone (more reactive than esters because the carbonyl group is not stabilized by conjugation with a lone pair). 

The most common representatives of the L-C=Y class of electron sinks are the carboxyl derivatives with Y equal to oxygen. In basic media there is only one pathway the addition-elimination path, path Ad y + Ep (see Section 4.5.1). The leaving group should be a more stable anion than the nucleophile, or the reaction will reverse at the tetrahedral intermediate. A follow-up reaction of a second addition to the polarized multiple bond occasionally occurs. With lone pair sources a second addition is rare because the nucleophile is usually a relatively stable species the second tetrahedral intermediate tends to kick it back out (see Section 9.2). 

Medium Acidic. Sources The lone pairs on the carbonyl are the best source (much better than the lone pairs of the OH). Leaving groups Chloride. Sinks The best, SOCI2, is a Y-L. The carboxylic acid is both an acid and a carboxyl derivative sink, but the OH is a poor leaving group. Acidic Hs The carboxylic acid s OH. Bases None. Resonance forms By VSEPR SOCI2 is tetrahedral, often drawn with an expanded octet resonance form containing a d-p pi bond. 

Because the carbon-chlorine bond is so long—typically on the order of 180 pm for acyl chlorides—overlap between the 3p orbitals of chlorine and the tt orbital of the carbonyl gronp is poor. Conseqnently, there is little delocalization of the electron pairs of chlorine into the tt system. The carbonyl group of an acyl chloride feels the normal electron-withdrawing inductive effect of a chlorine substituent without a significant compensating electron-releasing effect dne to lone-pair donation by chlorine. This makes the carbonyl carbon of an acyl chloride more susceptible to attack by nucleophiles than that of other carboxylic acid derivatives. 

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