Reversible Addition Reactions to Other Groups

Intramolecular Reversible Addition Reactions to Other Groups 

Two monographs devoted entirely to cyclization reactions involving the intramolecular addition of C—H, O — H, S—H (85MI1), or N—H groups (87MI1) to the C=N bond have been published in Russian However, the main interest of the authors of these books was the synthetic utility of these intramolecular reactions. 

The hydroxy- amino-, or mercaptonitriles 94A (X = O, NR, SH) that have been isolated undergo cyclization to 94B readily—and, in most cases, irreversibly—on heating in polar solvents, in the presence of acidic or basic catalysts, or upon melting. The iminoheterocycles 94B often isomerize subsequently to amines 94C or 94D, shifting the double bond into the ring. Equilibria of the type 94A 94B have rarely been observed. 

A slowly reached (in 1 day) equilibrium 97A 97B was observed (86JOC2988) in solutions of (2-azaarylamino)methylenemalononitriles. The equilibrium state exhibits a very high dependence on the solvent used (Table XX), the equilibrium being strongly shifted toward the open-chain 

Ring-Chain Equilibrium and Rate Constants of /V-Isopropyl 2-Cyanobenzamide (95) and 2-Cyanobenzenesulfonamide (96)° 

Many examples of the intramolecular addition of hydroxy, amino, or mercapto groups to C=C or C=C bonds are known to lead to the formation of a heterocycle [64QR211 84JCS(P2)1259, 84JCS(P2)1269]. 

The structure of the isomer shown is that of the compound found in (CD3)2SO solution. 

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III. Intramolecular Reversible Addition Reactions to Other Groups. 54... 

Volume 66 of our serial consists of five chapters. Ring-chain tautomerism was covered in an authoritative monograph by Valters and Flitch, which appeared in 1985. Now Professor Valters (Latvia), together with Professor Fiilop and Dr. Korbonits (Hungary), has updated this monograph in two chapters for our serial. The first of these has already appeared in Volume 64. The second, covering intramolecular reversible addition reactions to C=N and other groups, constitutes the first chapter of this volume. 

To illustrate the theory, let us consider a chain with two functional groups —A and —B capable of reacting with each other in a reversible addition reaction. Let us assume, as usual, that the intermolecular equilibrium constant for the addition reaction of end groups —A and —B, K, is independent of the length of the chain to which they are attached. Initially we consider only the process of linear polymerization. As a result, if [MjJo is the initial concentration of monomer, when the equilibrium is reached. 

The effect of a substituent may be substantially modified by fast, concurrent, reversible addition of the nucleophile to an electrophilic center in the substituent. Ortho- and para-CS.0 and pam-CN groups have been found by Miller and co-workers to have a much reduced activating effect on the displacement of halogen in 2-nitrohaloben-zenes with methoxide ion [reversible formation of hemiacetal (143) and imido ester anions (144)] than with azide ion (less interaction) or thiocyanate (little, if any, interaction). Formation of 0-acyl derivatives of 0x0 derivatives or of A-oxides, hydrogen bonding to these moieties, and ionization of substituents are other examples of reversible and often relatively complete modifications under reaction conditions. If the interaction is irreversible, such as hydrolysis of a... 

Maleic acid is a linear four carbon molecule with carboxylate groups on both ends and a double bond between the central carbon atoms. The anhydride of maleic acid is a cyclic molecule containing five atoms. Although the reactivity of maleic anhydride is similar to other cyclic anhydrides, the products of maleylation are much more unstable toward hydrolysis, and the site of unsaturation lends itself to additional side reactions. Acylation products of amino groups with maleic anhydride are stable at neutral pH and above, but they readily hydrolyze at acid pH values around pH 3.5 (Butler et al., 1967). Maleylation of sulfhydryls and the phe-nolate of tyrosine are even more sensitive to hydrolysis. Thus, maleic anhydride is an excellent reversible blocker of amino groups to temporarily mask them from reactivity while another... 

Table 16-2 shows the most common anaplerotic reactions, all of which, in various tissues and organisms, convert either pyruvate or phosphoenolpyruvate to ox-aloacetate or malate. The most important anaplerotic reaction in mammalian liver and kidney is the reversible carboxylation of pyruvate by C02 to form oxaloacetate, catalyzed by pyruvate carboxylase. When the citric acid cycle is deficient in oxaloacetate or any other intermediates, pyruvate is carboxylated to produce more oxaloacetate. The enzymatic addition of a carboxyl group to pyruvate requires energy, which is supplied by ATP—the free energy required to attach a carboxyl group to pyruvate is about equal to the free energy available from ATP. 

While reductive animation of glutamate via glutamate synthase appears to be the major pathway for incorporation of nitrogen into amino groups, some direct animation of pyruvate and other 2-oxoacids in reactions analogous to that of glutamate dehydrogenase occurs in bacteria.105 106 Another bacterial enzyme catalyzes reversible addition of ammonia to fumarate to form aspartate (p. 685). 

The mechanism of this reaction, usually called the Cannizzaro reaction,4 combines many features of other processes studied in this chapter. The first step is reversible addition of hydroxide ion to the carbonyl group ... 

Consideration of the oxidation level reveals diat while one carbon is reduced (the one to which hydrogen adds), die other is oxidized (die one to which the oxygen adds). There is no net change in oxidation level of the alkene functional group. Likewise die reverse processes of these addition reactions, namely, elimination of HX from alkyl halides and dehydration of alcohols to give alkenes, are not redox processes. Additions of water to alkynes is analogous. In this case, however, the product is a ketone, the oxidation level of the ketone is seen to be the same as the alkyne, and so no net change in oxidation level has occurred. 

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