N-substituted lactam

A very mild and efficient synthesis of N-substituted -lactams uses the Mitsunobu reaction (see section 2.6.2) for the ring closure of seryl dipeptides protected at the terminal N as 4,5-diphenyloxazol-2(3f/)-one ( Ox ) derivatives (see section 2,6.3)... 

Similarly, only N-substituted lactams are formed readily by intramolecular Diels-Alder or ene reactions (Scheme 9.10). Lactams without a substituent on the nitrogen can either not be prepared, or require higher reaction temperatures or longer reaction times than the preparation of similar, N-substituted lactams. 

Cydizations proceeding via radicals are, apparently, better suited to the preparation of N-unsubstituted lactams (Scheme 9.11). Nevertheless, in this type of cydiza-tion also the formation of N-substituted lactams proceeds more rapidly and more cleanly. 

Finally, it should be noted that the investigations of Bredereck60,129 and Meerwein et al.130,131 on the preparation of lactam acetals have significantly widened the scope of utility of O-alkyl derivatives of lactams, and have extended some of the reactions of lactim ethers, discussed in this review, to N-substituted lactam acetals. 

Many authors have observed an acceleration of caprolactam polymerization in the presence of A-acetyl-e-caprolactam, isocyanates, thiolactones, organic sulphates, aromatic amides, benzyldioxime carbonate, arylenedicarbamoyllactams, phosphorus oxychlorides and phosphorus pen-tachloride. Activator effectiveness increases with growing substituent electronegativity in N-substituted lactams. 

Centres of this kind might even gain technical importance in the future because N-substituted lactam derivatives can only be polymerized by a cationic process. 

This undesirable side reaction is avoided in the polymerization of N-substituted lactams i.e., N-alkyl, N-aryl, or N-acyl lactams. Polymerization of N-substituted lactams proceeds differently, thus in the presence of hydrogen chloride the following sequence of reactions takes place [217]. 

Substitution at the nitrogen atom decreases the polymerizability of small and medium lactams much more than substitution at any other ring atom (see Section 3) and, therefore, only the highly strained four-, eight-and nine-membered N-substituted lactams have been polymerized so far [53,241—243] (Table 11). Because of the lack of a dissociatable hydrogen at the amide group, A/ -substituted lactams cannot form the chemically activated species required for the anionic polymerization, i.e. lactam anions and AT-acylated lactam an anionic propagation could proceed only... 

In the general case, electrolytic fluorination of N-substituted lactams in EtaN 3HF/MeCN or EtsN - 5HF electrolytes is a selective reaction that affects the carbon atom in the a position relative to the nitrogen atom of the lactam to form a monofluorination product in high yield (99IJC151). 

N-substituted lactams can generally not be polymerized. Some exceptions, however, are known when cationic mechanisms are employed and when strong carbo g lic or inorganic acids are used as initiators. In such cases the anions of the initiating acids, like Cr, react with the lactam cations to yield amino acid chlorides ... 

Only the more strained four-, eight-, and nine-membered N-substituted lactams have so far been... 

Only the more strained four-, eight- and nine-membered N-substituted lactams have so far been shown to be capable of polymerizations [113]. The 2,2-dimethylquinuclidone is highly strained and undergoes polymerizations at room temperature [127]. The propagation reaction of substituted lactams can be Ulustrated as follows [122] ... 

N-substituted 2-pyrrolidone and 2-piperidone cannot be obtained. N-substituted lactams are more or less easily polymerized through the cationic or acidolytic mechanism (Sections 4.14.5 and 4.14.6). 

As compared to the addolytic, aminolytic, and hydrolytic routes, entailing the same reactions involved for unsuhstituted lactams (excluding amidine formation), the polymerization initiated by protic acids, such as HCl, differs for the most part. The most relevant aspeas characterizing the cationic polymerization of N-substituted lactams are, as said already, the absence of the detrimental formation of amidines and a much simpler mechanism compared to that pertaining to N-unsubstituted lactams. 

The rate of disproportionation depends on several factors nature of counter ion and reaction medium, lactam ting size, substituents, and structure of the resulting linear monomeric unit. An N-substituted lactam, for instance, may react with the lactam anion with a rate significantly higher than that of the initial reaction [46], depending on the size and the electrophi-lidty of the substituent (e.g., N-benzoyl lactams are very reactive). As a consequence, specific types of N-substituted... 

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