Aziridines Gabriel synthesis

Gabriel synthesis, 7, 33 aziridines, 7, 81-82 thiazoles, 6, 302 Galanthamine structure, 4, 548 Galbacin NMR, 4, 574 Gelatin hardeners for... 

The cyclization of (3-haloamines is the Gabriel synthesis of aziridines (B-83MI101-01, 84CHEC-(7)47). Imines with halogen-containing side chains on the nitrogen atom have been reductively cyclized via the (3-haloamines, as shown in Scheme 14 (94SL287). 

The synthesis of aziridines from /i-haloamines (Gabriel synthesis) is very general and has been used extensively. 

Cyclization. A kinetic study on the rates of jff-chloroethylamine cyclization to aziridines revealed the role of neighbouring aryl group participation, and led to the postulation of a reaction scheme which explains the salt effects, the activation parameters, and the changes in rates. The Gabriel synthesis has been applied to a-chloroamides in the presence of potassium t-butoxide to yield 3-(l-adamantyl)aziridinones (211) accompanied by a low yield of the... 

A related aziridine synthesis is the Gabriel reaction (a.k.a. Gabriel-Cromwell reaction), which involves an intramolecular Sn2 reaction of a P-amino halide. However, the reaction has become so common that the name Gabriel is not tightly related to the transformation. 

The Gabriel-Cromwell reaction is a convenient strategy for the synthesis of vinylaziridines. Treatment of 4,5-dibromopent-2-enoate 50 with primary amines 51 in the presence of DBU afforded the corresponding conjugated aziridines 52 in 63-80% yields (Scheme 2.16) [28]. The use of DBU has proven to be essential for the successful conversion. 

The Gabriel-Cromwell aziridine synthesis involves nucleophilic addition of a formal nitrene equivalent to a 2-haloacrylate or similar reagent [29]. Thus, there is an initial Michael addition, followed by protonation and 3-exo-tet ring-closure. Asymmetric variants of the reaction have been reported. N-(2-Bromo)acryloyl camphor-sultam, for example, reacts with a range of amines to give N-substituted (azir-idinyl)acylsultams (Scheme 4.23) [30]. 

The Gabriel-Cromwell reaction of amines with chiral c/., 3-unsaturated a-bromo carbonyl compounds was exploited for the synthesis of aziridine-2-carboxylic acid derivatives. 79 This procedure was optimized for a solid support synthesis in which the peptide resin was acylated with 2,3-dibromopropanoic acid active ester in the presence of 3 equivalents of NMM to produce directly on resin the a-bromoacrylamide for the addition of amines to produce the aziridine ring. 80 ... 

Further examples, noted too late for inclusion in Table 2, are the preparation of 1- and 2-arylaziridines by the Wenkcr synthesis,[Pg.537]

Much like with total synthesis, the Gabriel-Heine aziridine isomerization has not found widespread application within the medicinal chemistry community, despite its ability to efficiently generate a variety of azoles. DeWald and coworkers at Parke-Davis used the Gabriel-Heine reaction in the preparation of potential antipsychotics. Compound 27 was rearranged upon exposure to sodium iodide in acetone to provide compounds of type 28 in moderate to good yield, which were evaluated as nondopamine-binding antipsychotics. 

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