Lactams, preparation from amide esters

Adducts (6) and (7) from amides and chlorophosphoric acid aiyl esters or dichlorophosphoric acid aryl esters respectively are well known. - The adducts are formed in a 1 1 ratio. They have been applied to the synthesis of mixed anhydrides from diarylphosphoric acids and carboxylic acids, as well as mixed substituted esters of pyrophosphoric acid. The adduct formation between primary or secondary carboxamides and dichlorophosphates has been used to prepare nitriles and isonitriles respectively. The adduct from DMF and phenyldichlorophosphate is a useful reagent for the preparation of carboxylic acid esters from the corresponding acids and alcohols, 3-lactams from imines and carboxylic acids," carboxylic acid anhydrides, carboxylic acid esters and thiol esters. Adducts of amides with ester amides or diamides of chlorophosphoric acid have been studied. ... 

In addition to step and chain polymerizations, another mode of polymerization is of importance. This is the ring-opening polymerization of cyclic monomers such as cyclic ethers, esters (lactones), amides (lactams), and siloxanes. Examples of commercially important types are given in Table 10.1. Of those listed, only the polyalkenes are composed solely of carbon chains. Those that have enjoyed the longest history of commercial exploitation are polyethers prepared from three-membered ring cyclic ethers (epoxides), polyamides from cyclic amides (lactams), and polysiloxanes from cyclic siloxanes. 

Spirofused (3-lactams related to 64 were prepared from 3-hydroxy-3-arylpropanamides after activation of the hydroxyl group by formation of a phosphate ester <97JOC6412>. A similarly easy cyclization occurred when the A-aryl amide 66 was treated with potassium carbonate <97TA739>. Radical induced 4-e.w-trig cyclizations of yV-vinyl-2-bromobutan-... 

Polymerization of cyclic ester amides with large rings (e.g., 11-, 13-, and 14-membered rings) has also been studied [6-8]. In addition, it is well known that random copolymers can be easily prepared from mixtures of lactones and lactams, and even several works have recently been focused on the preparation of block copolymers from these macrocycles [9-11]. 

Amide enolates undergo silylation at both carbon and oxygen, depending upon the chloride used. Silyl acetals, which can be prepared from aldehydes, give /5-amino esters, or /5-lactams with Schiff bases. Silyl substituents also play a stereoselective role in the synthesis of aldol type systems, and protect nitrone-aldehyde condensates in dipolar additions that produce isoxazolidines and isoxazolines. ... 

Not only the Pinner synthesis provides alkoxymethyleneiminium salts the action of chloroformic acid esters on primary or secondary amides or thioamides ° as well as on lactams is a versatile method to get these salts and from them the imino esters, e.g. (230 equation 125). Primary and secondary amides have been alkylated by several reagents and the iminium salts thus formed were converted to imino esters with the aid of bases. A collection of imino esters prepared by this method can be found in a review the more recent results listed in Table 5 demonstrate the scope of this procedure. 

An in situ method for the preparation of N-methyleneamines has been devised by Overman and Osawa for use in condensation reactions with enolates and organometallic reagents. These species, with the exception of very hindered N-methyleneamines, cannot be isolated in the condensed phase because they rapidly trimerize to hexahydro-l,3,5-triazines. In this in situ method, A -methyleneamines (230) are generated from N-(cyanomethyl)amines (228) by deprotonation with an equivalent of enolate to give an intermediate amide (229) which loses LiCN (equation 22). When two equivalents of enolate are present, addition to the N-methyleneamine occurs and 3-lactams (233) are obtained in 60-70% yield upon warming the reaction mixture to 25 C (Scheme 48 Table 26). Uncyclized 3-amino esters can be isolated if the reaction is quenched at lower temperature a possible cycloaddition mechanism is thus ruled out. It is not clear to what extent, if any, the reaction is limited to a,a-disubstituted enolates. N-Methyleneamines, like oxime ethers, are useful for the synthesis of 4-unsubstituted 3-lactams and should also have important applications in the synthesis of monobactam antibiotics. 

Asymmetric hydroxylation of etiolates. Davis and Chen1 have reviewed this reaction using in particular (R,R)- and (S,S)-2-phenylsulfonyl)-3-phcnyloxaziridene (1) and (camphorylsulfonyl)oxaziridine (2). Of these reagents, 1 and ( + )- and (—)-2, derived from (lR)-lO-camphorsulfonic acid, provide highest enantioselectivity and in addition are easy to prepare. They are effective for hydroxylatation of ketones, esters, /2-keto esters, amides, lactones, and lactams. 

S- and 7-Lactams can be prepared in high yield by cyclization of halogenocarboxylic acid amides with an anion exchanger as catalyst . Cyclic peptides can be easily obtained from active peptide esters with a high-molecular ester component ... 

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