Aziridines nucleophilic substitution

The reactivity of the agent mechlorethamine (11.31, R = Me, Fig. 11.5) was investigated in buffer solution by means of NMR to monitor the formation of primary, secondary, and tertiary products [66], The reactive aziridin-ium derivative (11.32) mentioned above and resulting from intramolecular nucleophilic substitution was indeed observed and underwent hydrolysis first to the 2-hydroxyethyl derivative and then to A-methyl-2,2 -iminodi-ethanol. 

Bromoethylamine (11.133, R = Br, Fig. 11.18) is a potent nephrotoxin used to create an experimental model of nephropathy. Its mechanism of toxicity is postulated to involve perturbation of mitochondrial function, and its metabolism was investigated in a search for toxic metabolites. In rat plasma, 2-bromoethylamine was converted to aziridine (11.134), formed by intramolecular nucleophilic substitution and bromide elimination [155], Another major metabolite was oxazolidin-2-one (11.136). This peculiar metabolite resulted from the reaction of 2-bromoethylamine with endogenous carbonate to form carbamic acid 11.135, followed by cyclization-elimination to oxazoli-din-2-one. In aqueous media containing excess carbonate, the formation of... 

In contrast to the syntheses described above, which all start from cystine derivatives to form lanthionine, the lanthionine syntheses in this section all start from a protected cysteine as the nucleophilic precursor, which is then allowed to react with any of a variety of different substrates. These subsequent reactions are the Michael addition with dehydroalanine, the nucleophilic substitution of halo amino acids, or the ring-opening reaction of serine p-lactones and aziridines, respectively. However, it must be emphasized that the Michael... 

Most of the ring-opening reactions of aziridines may be formulated -.as nucleophilic substitution reactions, in which one of the oarbon- nitrogen bonds is broken and a new bond with carbon is formed. In this section, ring-opening reactions are classified ou the basis of the element which is joined to the carbon atom in the newly formed bond of the reaction product. ... 

Nitrogen-based nucleophiles continue to remain popular in ring-opening reactions of aziridines. a-Substituted-a-methoxycarbonyl-V-nosylaziridines were opened with a variety of functionalized amines to provide access to enantiopure a,a -disubstituted (3-lactam scaffolds for ditopic peptidomimetics <07OL101>. A related intramolecular regioselective 3,Y-aziridine ring opening with an a-amino functionality was reported in the synthesis of... 

Terminal epoxides of high enantiopurity are among the most important chiral building blocks in enantioselective synthesis, because they are easily opened through nucleophilic substitution reactions. Furthermore, this procedure can be scaled to industrial levels with low catalyst loading. Chiral metal salen complexes have also been successfully applied to the asymmetric hydroxylation of C H bonds, asymmetric oxidation of sulfides, asymmetric aziridination of alkenes, and the asymmetric alkylation of keto esters to name a few. 

Piperidine aziridine 143 was reacted with a number of simple alcohols to provide a mixture of two possible ring-opened products 144 and 145 (Equation 35) <2002TL5315>. It was found that in all cases, nucleophilic substitution with alcohols gave only ring opening at G-4 giving 144 in a ratio greater than 20 1. Addition at C-3 is blocked by the BF3 complex of the phosphoramide. 

Under thermal activation conditions, ester 161 reacts with benzylamine to give a mixture of a-amino-p,y-unsaturated ester 164 and amide 165, but under 1.1 GPa pressure ester 161 gives the spiro-aziridines 162 and 163 in high yield and good diastereoselectivity. These are part of an attractive class of compounds that are formed by hetero-Michael addition of amine onto the unsaturated ester 161, followed by intramolecular nucleophilic substitution of the bromine atom (Scheme 7.41). ... 

The 4-halogen atom in chloroquinazoline was displaced by aziridine, by amines (with derivatives of a-amino acids), and by fluorine (with KHF) more readily than a halogen atom at C-2. When a 4-fluorine atom was activated, as in hexafluoroquinazoline, it could be readily substituted by an amino or methoxy group. Nucleophilic substitution in the benzene ring of quinazoline was also possible. Hexachloroquinazoline gave hexafluoroquinazoline with anhydrous potassium fluoride, and the latter... 

Michael additions are rather sensitive to steric hindrance hence, an addition of a nucleophile to yS-disubstituted a, S-unsaturated esters is nearly impossible. On the other hand, the application of high pressure alleviates this limitation and even allows the formation of two adjacent quaternary centers. The reaction of methyl tert-butylcyclohexylidenebromoacetate (107) with benzylamine in refluxing methanol as described by Duhamel et al. gave a mixture of the ester 108a and the amide 108b (Scheme 8.26) [57]. At room temperature another reaction channel is opened which leads to the aziridines 109 and 110. In this reaction, a Michael addition first takes place and this is followed by an intramolecular nucleophilic substitution. At atmospheric pressure, however, a reaction time of 60 days was necessary to obtain an 82 % yield. In contrast, at 1.1 GPa the addition took less than 4 days and the diastereomeric ratio rose from 1 1.7 at ambient pressure to 1 10 at 1.1 GPa in favor of 110. 

Aziridines, like amines, are nucleophiles and react with electrophiles. A nucleophilic substitution on a saturated C-atom and a nucleophilic addition to an alkene bearing an acceptor group serve as examples ... 

Die postulierte Zwischenstufe (13) vermag die Bildung aller drei Pro-dukte zu erklaren (57). Das Aziridin entsteht demnach durch intramole-kulare nucleophile Substitution von Dimethylsulfoxyd durch den... 

Three-membered rings can be constmcted by several methods. Of rather general occurrence is the intramolecular nucleophilic substitution process depicted for oxiranes and aziridines in Scheme 10.6. Many compounds have been prepared by these methods. Phosphiranes are... 

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