Sultams ring opening

Reviews have appeared of theoretical studies on ring-opening of /3-lactams in both solution and in enzymatic media90 and of a comparison of the mechanisms of reactions of /3-lactams and /5-sultams, including their reactions with some serine enzymes.91... 

However, an ElcB-type process was reported as a novel mechanism for hydrolysis of a /3-sultam. In the case of the N-a -methoxycarbon y I /3-sultam, deprotonation of the acidic exocyclic hydrogen leads to the formation of a carbanion, which then undergoes a rate-limiting conversion to a ring-opened species with expulsion of a sulfinate anion. Then, hydrolysis of the imine species produces benzoyl formate as the principal product detected (Scheme 14) <2002CC772>. 

Intramolecular aziridinations of the olefinic sulfonamides 297, by means of the iminoiodane derivatives 298, have recently been demonstrated (Scheme 85) (OOOL2327). Ring-opening reactions of the bi- and tricyclic sultams 299, thus obtained, with selected nucleophiles were explored and provide access to functionalized cyclic sulfonamides. 

Sultams, e.g. (187)-(189), suffer hydrolysis by treatment with acid or alkali. The reaction opens the sultam ring (Scheme 78). With acids, the hydrolysis involves initial protonation of the nitrogen atom followed by nucleophilic attack by X". In alkaline hydrolysis, the reaction involves nucleophilic attack by OH and subsequent cleavage of the nitrogen-sulfur bond (Scheme 78). The order of reactivity of sultams towards hydrolysis is p>y>8. This is to be expected since it parallels the relative instability of the ring systems, where the four-membered ring is more reactive than the five and six-membered rings. 

Pummerer reaction. 4-Arenesulfinyl-P-sultams undergo Pummerer reaction which also triggers ring opening and loss of sulfur dioxide. a-Amino acid thiol esters are obtained. ... 

Ring Opening of Cycloadducts and Synthesis of Chiral Sultams. . 126... 

The sultone cycloadducts could be further manipulated by ring-opening with various nucleophiles, such as alcohols and amines, at the y-position [41]. When optically active (S)-(-)-a-methylbenzylamine reacted with the racemic sultone cycloadduct 76 in ethanol at room temperature, one of the diastereomeric ammonium sulfonates precipitated from the reaction mixture (Scheme 17). Although the absolute stereochemistry of 77 had not been determined, cyclization of optically pure 77 with phosphorus oxychloride gave an optically pure sultam 78. Formic acid debenzylation followed by base hydrolysis of the N-formyl group afforded the optically pure sultam 80 in good yield [40]. 

Aromatic sultams are generally resistant to ring opening under acid conditions. When l,8-naphthosultam-2,4-disulphonic acid is heated in a sealed tube with hydrochloric acid, the sultam ring is opened and elimination of the sulphonate groups occurs (equation 214)2. 

Similar ring-opening poly-addition of the bis-sultam monomer 147 occurs with aliphatic diamines (equation 241). Polysulphonamides have also been obtained from the corresponding bis-2,2 -disubstituted keto sultams (equation 242)295. 

In an analogous manner to lactam polymerization, a high-MW polyamide was obtained by Bliss and collaborators 76 in the ring-opening polymerization of propane sultam under phenoxide or Na hydride catalysis ... 

Modification of the naphthosultam group such as expansion or opening of the sultam ring lowers 5-HT2A receptor afihiity and selectivity. 

In addition to the alternating radical polymerization of substituted norbomenes with sulfur dioxide, we also attempted anionic ring-opening polymerization of sultams (cyclic sulfonamides), especially, camphorsultam (2, Scheme II). This synthetic scheme was supposed to incorporate a novel base-soluble sulfonamide functionality in the backbone along with a bicyclic stmcture in the case of camphorsultam. 

Since the critical step in the anionic ring-opening polymerization of propanesultam is the rapture of the ring of the co-catalyst, N- benzenesulfonylsultam (activated sultam), induced by the attack of the cyclic sulufonamide anion, we treated 7V-toluenesulfonyl camphorsultam with sodium methoxide, potassium -butoxide, and a preformed camphorsultam Na salt and analyzed the products by and NMR. In all the cases the NMR analysis suggested that the sulfonamide ring had been opened by the base. It is not clear at the moment why camphorsultam is reluctant to polymerize. 

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