Tertiary aziridination

The ring opening of tertiary aziridines is deactivated by the presence of an alkyl group attached to the nitrogen atom (Table 12, entry 13), whereas it is activated by the presence of... 

The amino function of the terminal tertiary aziridine reacts as a nucleophile with an azitidinium ion to produce a quaternary azitidinium ion. This will eventually react with an amine also producing a branched (tertiary amine) stmc-ture (Scheme 4). 

A. Ueno, Y. Kayaki, T. Ikariya, Cycloaddition of tertiary aziridines and carbon dioxide using a recyclable organocatalyst, 1,3-dl-tert-butylimidazolium-2-carboxylate a straightforward access to 3-subsfituted 2-oxazoKdones, Green Chem. 15 (2013) 425-430. 

The azidohydrins obtained by azide ion opening of epoxides, except for those possessing a tertiary hydroxy group, can be readily converted to azido mesylates on treatment with pyridine/methanesulfonyl chloride. Reduction and subsequent aziridine formation results upon reaction with hydrazine/ Raney nickel, lithium aluminum hydride, or sodium borohydride/cobalt(II)... 

The present authors have found that the preparation of 7V-acetyl aziridine derivates provides the most secure method of differentiating aziridines from primary amines which are alternate reaction products in a number of cases. The infrared spectra of the former derivatives show only a peak at 1690 cm" for a tertiary amide peaks at ca. 3440 and 1530 cm" indicative of a secondary amide are absent. Acetylation also shifts the aziridine ring protons to a lower field in the NMR by ca. 1 ppm relative to the parent aziridine. The A"-acetyl aziridines are hydrolyzed with 3% methanolic potassium hydroxide. " Published NMR spectra of several 16j5,17j -aziridines reveal resonance patterns resembling those of the respective epoxides. " ... 

Iron phthalocyanine is an efficient catalyst for intermolecular amination of saturated C-H bonds. With 1 mol% iron phthalocyanine and 1.5 equiv. PhlNTs, amination of benzylic, tertiary, and ally lie C-H bond have been achieved in good yields (Scheme 31). With cyclohexene as substrate, the allylic C-H bond amination product was obtained in 75% yield, and the aziridination product was found in minor amount (17% yield) [79]. 

The use of m-CPBA allows the formation of nitrones in the oxidation of tertiary amines. The resulting amines A-oxides are subject to either Cope or Meisenheimer rearrangements, providing formation of nitrones. Thus, the generated corresponding nitrones in the oxidation of bicyclic aziridines give nitrones as a result of a Meisenheimer rearrangement (Scheme 2.14) (93). 

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. 

In rats administered 2-bromoethylamine, urinary aziridine accounted for 15-45% of the dose. The carbamate 11.135 was not detected in urine, whereas oxazolidin-2-one and a tertiary metabolite, 5-hydroxy oxazolidin-2-one, accounted for 0 - 20% and 2 - 12% of the dose, respectively [156], The innocuity of oxazolidin-2-one led to the suggestion that either aziridine or 2-bromoethylamine itself is responsible for mitochondrial toxicity. These studies show that the nephrotoxic 2-haloethylamines undergo two competitive cyclizations with halide elimination, one probably a reaction of toxification, the other clearly a reaction of detoxification. 

Better reagents than lithium aluminum hydride alone are its alkoxy derivatives, especially di- and triethoxyaluminohydrides prepared in situ from lithium aluminum hydride and ethanol in ethereal solutions. The best of all, lithium triethoxyaluminohydride, gave higher yields than its trimethoxy and tris(/er/-butoxy) analogs. When an equimolar quantity of this reagent was added to an ethereal solution of a tertiary amide derived from dimethylamine, diethylamine, W-methylaniline, piperidine, pyrrolidine, aziridine or pyrrole, and the mixture was allowed to react at 0° for 1-1.5 hours aldehydes were isolated in 46-92% yields [95,1107], The reaction proved unsuccessful for the preparation of crotonaldehyde and cinnamaldehyde from the corresponding dimethyl amides [95]. 

As a result of our previous work on the scope and mechanism of tertiary amine nitrosation (X), we became interested in the behavior of N-alkylaziridines toward nitrous acid. Possible modes of reaction are illustrated in Scheme 1. The operation of either path A or C would be consistent with our previous studies of oxidative dealkylation of tertiary amines (1 ), while pathway B would be akin to the observed cheleotropic transformation of N-nitroso-aziridines (2). 

The acid-catalyzed hydrolysis of aziridines is usually of little preparative value. In certain instances such a reaction may represent the final step in the isomerization of a jB-anaino aloolhoJai8 a4D (Eq. d). Kinetic studies show that when a nitrogen-tertiary carbon bond is present in the axiridine, this bond is hydrolyzed in an 5 1-type reaction318 [Pg.282]

Many aziridines form picrates and other salts which are stable in the crystalline state. - 4 Attempts to rocrystallize such compounds frequently result in decomposition. The quaternary azjridinium salts (XLII) are somewhat more stable, and have been much studied in connexion with the reaction of the jU-chloroalkyl tertiary amines ( nitrogen mustards ). 

In the presence of a base, acid chlorides react readily with aziridines to give acylated aziridines (2,22,160—163). In the absence of a base, however, ring opening takes place and 2-chloroethylamides are obtained (2,164). Under suitable conditions acylated trialkylammonium salts of ethylenediamine can be prepared from acid chlorides, ethyleneimine, and tertiary amines (71). Acylated aziridines can be rearranged to 2-oxazolines by the action of heat, nucleophiles, or acids. The rearrangement of thioacylaziridines proceeds analogously (7,8,165—171). 

Tertiary amines have been shown to react with isocyanates in an analogous fashion to form ureas (41—43). Similarly, aziridines (three-membered rings containing nitrogen) are found to react with isocyanates to yield cyclic ureas. Tertiary amines have also been shown to form labile dipolar 1 1 adducts with isocyanates reminiscent of salt formation. In contrast, formaldehyde A/,Ai-acetal aminals form insertion products with sulfonyl isocyanates (44,45). 

The 2-iminothiazolidine obtained from 2-aminothiazoline and 2-phenyl-l-(p- toluenesul-fonyl)aziridine (261) readily underwent ring closure in the presence of concentrated H2S04 to give 6-phenyl-2,3,5,6-tetrahydroimidazo[2,l-Z>]t hi azole (262) (69JHC751). Similar C-N fissions of sulfonamides rather than the normal N—S fissions in strong acid have been observed when it is possible to generate either a tertiary or secondary aryl carbonium ion by such a fission (59CRV1077). 

V-acyl aziridines therefore behave like Weinreb amides (see p. 300), and stabilization of the tetrahedral intermediate by chelation may also play a role. Esters, of course, typically react twice with organolithiums to give tertiary alcohols. 

The tunneling frequency is expected to be much smaller when the inversion barrier becomes high and thick and when the reduced mass of the systems increases. In such cases (for instance, tertiary amines, aziridines. . .) the rate of tunneling is expected to add little to the rate... 

---