Ring-opening ammonolysis

Sulfuryl chloride is superior to chlorine for the chlorination of N-benzoyl-e-capro-lactam. The product on ring opening, ammonolysis, and hydrolysis is converted into DL-lysine in 73% overall yield from -caprolactam. 

Other methods of generating a-aminoketones in situ are common, if somewhat less general than the methods already described. 2-Nitrovinylpyrrolidine, which is readily available, yields 2,3-bis(3-aminopropyl)pyrazine on reduction and this almost certainly involves ring opening of the intermediate enamine to an a-aminoketone which then dimerizes under the reaction conditions (Scheme 59) (78TL2217). Nitroethylene derivatives have also served as a-aminoketone precursors via ammonolysis of the derived epoxides at elevated temperatures (Scheme 60) (76S53). Condensation of 1,1-disubstituted hydrazine derivatives with a-nitro-/3-ethoxyethylene derivatives has been used in the synthesis of l,4-dialkylamino-l,4-dihydropyrazines (Scheme 61) (77S136). 

A number of groups have attempted to develop the analogous reaction for cyclotri- and cyclotetrasilazanes. Ring opening polymerization represents an alternative to direct ammonolysis even though the cyclomer precursors are normally made by ammonolysis or aminolysis. 

The lactone 1 was subjected to ammonolysis by treatment at room temperature for 5 hours with ethanol saturated with ammonia in the expectation that simple ring opening would occur. The product was not, however, the expected amide instead, two products were formed, the amide 2 and (7 )-lactamide, in almost quantitative yield. An unstable intermediate could be isolated and was shown to serve as precursor to 2. 

The treatment of 5-phenyl-5-(3 -bromopropyl)barbituric acid (145) with ammonium hydroxide yields 3-phenyl-3-allophanyl-2-piperidon. The reaction begins with the ammonolysis of 145 and then the resultant primary amino function attaches to the C-6 or C-4 carbonyl group of the ring with ring opening to yield 146, which then hydrolyzes to 147.400 5-Phenyl- and 5-allyl-5-(2 -hydroxypropyl)barbituric acids undergo similar intramolecular isomerization and a-phenyl-a-allophany,l-y-valerolactones are formed, respectively.359,401-403... 

Attempted preparation of a frons-related 2-amino-3-thiol derivative from (93) by ammonolysis led, instead, to a polymerized product. Presumably, the sulfide ion formed as the ring opens is a better nucleophile than ammonia, and can attack the starting material. An alternative approach, through an episulfonium ion, was, however, successful for the preparation of 3-amino-2-thiol derivatives having the D-altro configura-tion. Methyl 2,3-anhydro-4,6-0-benzylidene-a-D-allopyranoside (68) was treated with sodium benzylthiolate, and the product was converted into the 3-methanesulfonate (95). The latter reacted with sodium azide to give the 3-azido-2-benzylthio derivative (97) with retention of configuration, presumably by way of the episulfonium ion (96). The product (97)... 

The ammonolysis of j3-thiolactones and other ring opening reactions proceed only by a sulfur-acyl ring opening mechanism, in contrast to the analogous reactions with j5-lactones where the ring opens by both alkyl and acyl mechanisms [19, 20]. 

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