Azetidines and Aziridines

The complicating termination reactions, arising because of the increased basicity of sulphide residues on the polymer backbone, compared with that of cyclic sulphide monomers, do not occur in the analogous polymerisations of azetidines such as l,3,3 -trimethyl-azetidine, 

N-substituted aziridines are also readily polymerised by stable cation salts (117) to give substituted polyethyleneimines. 

In all cases initiation is fast and quantitative, and propagation seems to take place via cyclic quaternary ammonium ions 

Polymerisations of 8,9, and 10 were rapid but stopped at limited conversions owing to a termination process involving an intramolecular back-biting reaction, the tertiary amino groups on the polymer backbone being more 

In marked contrast to this behaviour, monomer 11, l-benzyl-2-methyl-aziridine, gives a relatively slow reaction with Et30+BF4. However, polymerisation is quantitative and all the indications are that the system is living . Why this would be so is difficult to explain. Electronic factors would seem to be elimi-minated since this monomer is intermediate as far as basicity is concerned. Presumably the explanation lies in the stereochemistry of the system since this particular monomer is the only carbon substituted species. Even more strangely, however, the closely related molecule l-benzyl-2-ethyl-aziridine is reported (141) to behave like 8,9, and 10 when treated with boron trifluoride. 

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On the other hand, other chiral dirhodium(II) tetracarboxylate catalysts based on azetidine- and aziridine-2-carboxylic acids have been prepared by Zwanenburg et al. and submitted to the cyclopropanation of styrene with... 

Triflates are also known to be excellent leaving groups and, therefore, can participate in substitution reactions to generate saturated heterocycles, such as azetidines and aziridines... 

Although the l-t-butyl-l-azabicyclo[1.1.0]butonium ion (10) should also be highly strained, it and other such derivatives have been implicated as intermediates upon solvolysis of azetidine and aziridine precursors. Gaertner claimed that (11) and (12) are among the least reactive / -aminoalkyl chlorides known, yet isomerization of (11) = (12) occurred in either carbon tetrachloride or acetonitrile. With nucleophiles present, both gave products of simple displacement, hydrolysis, and rearrangement. The rate constants for solvolysis (in 50% aqueous ethanol) of (11) and (12) were... 

The absolute configuration of 2-methyl-azetidines and -aziridines has been determined by application of the octant rule (+)-2-methylazetidine is suggested to be 2R). The absolute configuration of a number of azetidinones has been deduced from c.d. measurements. ... 

N-Inversion in azetidine and azetidin-2-one is rapid, even at —77 and -40 °C, respectively (B-73NMR144). Again, halo substituents on nitrogen drastically slow the inversion rate, so that Af-chloro-2-methylazetidine can be separated into two diastereomers (b-77SH(1)54). Substituent effects on N-inversion are much the same as in the aziridines Af-aryl and N- acyl... 

Polyamines can also be synthesized by cationic ring-opening polymerization of ethyleneimines (aziridines), trimethyleneimines (azetidines), and 2-oxazolines. 

Calculations at the MP2(Full)/6-31++G(d,p)//MP2(Full)/6-31+G(d) level of theory were used to investigate the SN reactions between ammonia and aziridine, aze-tidine, methylethylamine, and four fluorinated derivatives of aziridine.52 The results show that aziridine and azetidine have strain energies of 27.3 and 25.2 kcalmol-1, respectively, and that as a consequence they react 7.76 x 1023 and 2.30 x 1017 times faster with ammonia than does the methylene group of methylethylamine. However, even after subtracting the effect due to the release of ring strain, aziridine still reacts much faster than the other two substrates. This is because the electrostatic attraction of the charges in the product-like dipolar transition state are much greater for aziridine. 

A somewhat similar ring closure in which a nitrogen anion attacks a halogenated carbon center is obtained in the anodic oxidation of dimethyl Q -(it -tosylaminoalkyl) malonates in methanol containing KI in an undivided cell. Aziridines, azetidines, and pyrrolidines may be formed in good yield [63]. 

Aziridine and azetidine are stable, if volatile, members of the saturated nitrogen heterocycle family, and aziridine has some interesting chemistry of its own. Like pyrrolidine and piperidine, aziridine can be acylated by treatment with an acyl chloride, but the product is not stable. The ring opens with attack of chloride, a relatively poor nucleophile, and an open-chain secondary amide results. 

These species were directly observed by H-NMR spectroscopy in the polymerization of thietanes41), azetidines 10,42) and aziridines 19 For a few monomers polymerization is nearly living (many are slowly dying as described by Goethals 18)). These processes were applied in the preparation of block, graft, star-shaped, etc., polymers. 

Altihough many of the early examples of the carbonylation of heterocycles included reactions of tetrahydrofurans, oxetanes, and azetidines, the majority of recent work has focused on the reactions of epoxides and aziridines. At this point, the ring-expansive reactions of epoxides are more general than the reactions of aziridines and occur imder milder conditions. Prior to 1994, ring-expansive carbonylation of epoxides was restricted to a few substrates. The patent by Droit and Kragtwijk s in 1994 inspired further work on these t)rpes of carbonylations, and tiiis work led to dramatic improvements in reaction scope. 

R. erythropolis (previously R. rhodochrous) AJ270, which has been utilized in many enantioselective transformations of nitriles such as cyclopropane, oxirane, and aziridine analogs [10, 12], was recently proved to catalyze the enantioselective hydrolysis of azetidine-2-carbonitriles [13] and P-lactam carbonitriles also [14] (Figure 11.2). Carboxylic acids and carboxamides were also obtained with significant enantiomeric excesses from 3-hydroxy-4-aryloxybutanenitriles and 3-hydroxy-3-arylpropanenitriles (Figure 11.3) using R. rhodochrous ATCC BAA-870 [15], which is more elaborately discussed in Chapter 14. 

Four-membered Ring Nitrogen Heterocycles.— The synthesis of azetidine and its derivatives by akylation of an external or an internal amine is well known, and two more examples were reported in 1980. Interest in simple alkyl substituted azetidines now lies in studies on their stereo-preferences, and conversions to other important systems. That said, two photochemical investigations surprisingly turned up such systems as unexpected major products. Pete et while extending their work on 2-amino-cyclohex-2-enones examined the consequence of N-sulphonylation on their photochemical behaviour, and instead of getting aziridines as the principal products, they obtained azetidines (Scheme 35). These reactions were not as clean as the earlier ones, and aryl migration... 

The reaction of the vinylcyclopropanedicarboxylate 301 with amines affords an allylic amine via the 7r-allylpalladium complex 302[50]. Similarly, three-membered ring A -tosyl-2-(l,3-butadienyl)aziridine (303) and the four-mem-bered ring azetidine 304 can be rearranged to the five- and six-membered ring unsaturated cyclic amines[183]. 

Azetidine N shifts are similar to those of the aziridines. Unsubstituted azetidine has its N resonance (relative to anhydrous ammonia) at 25.3 p.p.m., and N-r-butylazetidine shows the signal at 52 p.p.m. (80JOC1277). 

Addition of trichloromethide ion to azirine (210) generates aziridine (230). When this aziridine was treated with base, cyclization and rearrangement occurred and the azetidine (233) was isolated (73JA2982). 

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