Amide interchange

Amide interchange reactions of the type represented by reaction 3 in Table 5.4 are known to occur more slowly than direct amidation nevertheless, reactions between high and low molecular weight polyamides result in a polymer of intermediate molecular weight. The polymer is initially a block copolymer of the two starting materials, but randomization is eventually produced. 

Copolymers. There are two forms of copolymers, block and random. A nylon block copolymer can be made by combining two or more homopolymers in the melt, by reaction of a preformed polymer with diacid or diamine monomer by reaction of a complex molecule, eg, a bisoxazolone, with a diamine to produce a wide range of multiple amide sequences along the chain and by reaction of a diisocyanate and a dicarboxybc acid (193). In all routes, the composition of the melt is a function of temperature and more so of time. Two homopolyamides in a moisture-equiUbrated molten state undergo amide interchange where amine ends react with the amide groups. 

As time progresses, the two homopolyamides in the melt form a block and eventually a random copolymer as a result of amide interchange (Fig. 

Altanserin (100) is a representative of the thiaquinazolinones. This serotonin antagonist is said to prevent gastric lesions. One method for preparation of this compound involves first preparation of isothiocyanate derivative 99, by reacting 4-fluorobenzoylpiperidine with 2-bromoethylamine and then converting the intermediate to the isothiocyanate with thionyl chloride and base. Condensation of 99 with methyl anthranilate (98) probably proceeds initially to a thiourea. Cyclization by ester-amide interchange leads to altanserin (100) [28]. 

American Society for Testing and Materials (ASTM), 242 Amic acid ammonium salt, polyimide cyclization via, 305 Amic acid formation, 301 Amidation reaction scheme, 151 Amide-amide interchange reaction, 158 Amide concentration, in polyamides, 139-141... 

Similar interchange processes may occur in other condensation polymers under suitable conditions. There is ample evidence in the literature on polyamides, and on monomeric amides as well, for the occurrence of the amine-amide interchange reaction (II)... 

Isoniazide, the hydrazide of pyridine-4-carboxylic acid, is still, well over half a century after its discovery, one of the mainstays for the treatment of tuberculosis. Widespread use led to the serendipitous discovery of its antidepressant activity. This latter activity is retained when pyridine is replaced by isoxazole. The requisite ester (45-4) is obtained in a single step by condensation of the diketo ester (45-1), obtained by aldol condensation of acetone with diethyl oxalate, with hydroxylamine. One explanation of the outcome of the reaction assumes the hrst step to consist of conjugate addition-elimination of hydroxylamine to the enolized diketone to afford (45-2) an intermediate probably in equilibrium with the enol form (45-3). An ester-amide interchange of the product with hydrazine then affords the corresponding hydrazide (45-5) reductive alkylation with benzaldehyde completes the synthesis of isocarboxazid (45-6) [47]. 

A somewhat different route is used to prepare an analogue that bears additional oxygen. The sequence, in this case, starts by base-catalyzed formylation of the hydro-cinnamic acid derivative (40-1) with ethyl formate. Condensation of the product (40-2) with guanidine in this case leads to a pyrimidone (40-3), with the cyclization involving an ester-amide interchange between guanidine and the ester. Reaction of... 

The success of the Gabriel synthesis depends on N-alkylation being favored over O-alkylation and SN2 being favored over E2. Polar, aprotic solvents such as methylsulfinylmethane, (CH3)2SO, are useful for the Gabriel synthesis. Hydrolysis of the alkylation product often is difficult and amide interchange (analogous to ester interchange, Section 18-7A) with hydrazine can be an effective way to free the amine from the imide. 

Structurally characterized heterobimetallic Ln/Al complexes bearing donor-functionalized dianionic diamido ligands of the types [NNN]2" and [NON]2- were obtained from [amide]- [alkyl] (Scheme 52) or [aluminate] [amide] interchange reactions (Scheme 53). 

Scheme 53 Generation of heteroleptic tetramethylaluminate complexes via [aluminate] [amide] interchange [223]...

Nylon copolymers can be obtained by heating a blend of two or more different nylons above the melting point so that amide interchange occurs. Initially, block copolymers are formed, but prolonged reaction leads to random copolymers. For example, a blend of nylon-6,6 and nylon-6,10 heated for 2 h gives a random copolymer (nylon-6,6-nylon-6,10) which is identical with a copolymer prepared directly from the mixed monomers. Other copolymers of this type are available commercially. 

Many commercial nylon copolymers are also formed by melt mixing different nylons. Amide interchange reactions occur at melt conditions. Atfirstblock copolymers form, but prolonged heating and stirring results in formation of random copolymers. Nylon copolymers are also prepared directly from mixed monomers. 

Undergoes amide interchange reactions (broadened by incorporation of multifunctional units)... 

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