2- aziridines reaction with thiols

This reaction is analogous to 10-7. It may be acid (including Lewis acids),base, or alumina catalyzed, occur with electrolysis, and may occur by either an SnI or Sn2 mechanism. Many of the P-hydroxy ethers produced in this way are valuable solvents, for example, diethylene glycol, Cellosolve, and so on. Reaction with thiols leads to hydroxy thioethers. Aziridines can similarly be converted to P-amino ethers. 

With Sulfur Nucleophiles N-Carboxy-protected aziridine-2-carboxylates react with thiols to give P-mercapto-ot-amino acid derivatives. The reaction is usually catalyzed by BF3 and the yields range from fair to excellent [15, 16, 108-111]. With N-unprotected 3-substituted aziridine-2-carboxylates, the ring-opening with thiols usually takes place with anti stereoselectivity, especially in the case of the C-3 aliphatic substituted substrates. In cases in which C-3 is aromatic, however, the stereoselectivity has been found to be a function of the substitution pattern on the aromatic ring 3-p-methoxy ph eri yl-su bs li In led aziridines 143a (Scheme 3.51) and... 

The aziridine aldehyde 56 undergoes a facile Baylis-Hillman reaction with methyl or ethyl acrylate, acrylonitrile, methyl vinyl ketone, and vinyl sulfone [60]. The adducts 57 were obtained as mixtures of syn- and anfz-diastereomers. The synthetic utility of the Baylis-Hillman adducts was also investigated. With acetic anhydride in pyridine an SN2 -type substitution of the initially formed allylic acetate by an acetoxy group takes place to give product 58. Nucleophilic reactions of this product with, e. g., morpholine, thiol/Et3N, or sodium azide in DMSO resulted in an apparent displacement of the acetoxy group. Tentatively, this result may be explained by invoking the initial formation of an ionic intermediate 59, which is then followed by the reaction with the nucleophile as shown in Scheme 43. 

EpisuMdes, which can be generated in situ in various ways, react similarly to give p-amino thiols, and aziridines react with amines to give 1,2-diamines (10-38). Triphenylphosphine similarly reacts with epoxides to give an intermediate that undergoes elimination to give alkenes (see the Wittig reaction, 16-44). 

Sodium enolates of ketones and disodium enediolates of substituted phenylacetic acids reacted with activated aziridines to afford 7-amido ketones and 7-amidobutyric acids, respectively (Scheme 72). Aziridine-2-carboxylic acid esters can be utilized as versatile precursors for amino acid derivatives. Although the product distribution resulting from the reaction of activated aziridine-2-carboxylates with amines depends on the structure of the reactants, the reactions with alcohols or thiols in the presence of acidic cabilysts generally gave the a-amino acid derivatives (Scheme 73). ° On the other hand, free 3-methyl-2-aziridinecarboxylic acids (168) reacted with thiophenol, cysteine and glutathione to afford P-amino acid derivatives with sulfur substituents at the a-position as the main product (Scheme 73). ... 

A number of catalysts have been used to promote ring opening of A-tosyl-aziridines, such as phospho-molybdic acid and silica gel, for azide, cyanide and alcohols " and tri-n-butylphosphine for thiols and amines. Opening with iodide occurs at room temperature with iodine and thiophenol in the presence of air. In the nucleophilic ring opening of A-tosyl-aziridines, silver ion catalysis facilitates reactions with electron-rich arenes or hetarenes. ... 

Like epoxides, aziridines engage in facile ring-opening reactions with a variety of nucleophiles, and this represents an entry into many functionalized amines. For example, the 3-trifluoromethylaziridine-2-carboxyIatc 159 undergoes efficient nucleophilic attack by chloride or thiols under acidic conditions to provide the protected amino esters 160 and 161, respectively, in high yield and as a single diastcreomer <01SL679>. 

An SN2-type ring-opening of N-activated aziridines 105 with a 2-bromobenzyl alcohol/thiol 106, followed by a copper-catalyzed intramolecular N-arylation reaction, afforded the corresponding tetrahydrobenzox(thi)azepines 107 in good yields (14JOC6468). 

Reactions between aziridine-2-carboxylic acids and thiols in aqueous solution have been explored by Hata and Watanabe [112]. The reactions occurred predominantly at C-2 instead of C-3 to afford 3-amino acids, with the reaction between 148 (Scheme 3.53) and thiophenol in 0.2 m sodium phosphate buffer at room tem-... 

The reaction of an aziridine with a thiol is highly specific at slightly alkaline pH values. In aqueous solution, the major side reaction is hydrolysis. 

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