3- Azetidinols

Carbowax 20M, polysiloxanes, and N-cyclo-3-azetidinol are the most widely used sutetances for the thermal degradation method [143,180,192-194]. In the case of the Carbowax treatment deactivation can be carried out in either of two ways. The column can be dynamically coated with a solution of Carbowax 20H in a volatile solvent, excess solvent evaporated with a stream of nitrogen, the column ends sealed and the column heated at about... 

Determination of relative configuration. Thus, if diastereomeric compounds form complexes with LSR, a number of nuclei differ in their relative orientation with respect to the lanthanide ion. A given nucleus in one diastereomer has different r and 8 values than the corresponding nucleus in the other so that a different LIS is experienced. Using this method, structures of diastereomers can be assigned. For example, the LIS of the phenyl protons is much larger in cw-l-cyclohexyl-2-phenyl-3-azetidinol than in the tram-iso-... 

Photochemical excitation of cyclic a-amino ketones (41 and 43) leads to the formation of bicyclic azetidines and azetidinols by abstraction of a hydrogen y to the ketone followed by cyclization. Production of (42) (72CC1108) and (44) (75TL2463) is believed to occur as a singlet state reaction. 

In contrast to alkylamines in general and methylamine in particular, BSMA and RSMA reacted with epichlorhydrin to give the corresponding azetidinol as the sole product in high yields after neutralization of the chlorohydrate primarily formed.224... 

Hill and his co-workers have studied the photoreactions of a-amino-ketones and have observed reactions dependent on the ring size of the heterocycle. Thus the ketone (52) afforded the azetidinol (53), a Norrish Type II product, as the major product. With the smaller ring compound (54), the... 

Scheme 1. Structures of synthetic 3-azetidinol [1] and the antibiotic charamin [2] from the freshwater green alga Chara globularis.

From our own work studies of synthetic 3-azetidinol [1], part of the structure of the antibacterial agent charamin (4-azoniaspiro[3,3]heptane-2,6-diol, 2) from the green characean alga Chara globularis (1), serve to illustrate the kind of data and instrumentation available in modem investigations. The crystal and molecular struc-... 

Scheme 13)177,178. Azetidinols (205) also undergo ring fission to afford the sul-phonamides (206) by a path involving N—C bond fission. The resultant biradical rearranges to the final products 206 by aryl migration, the efficiency of which is determined by the substitution on the aryl group179. 

The alternative fate, i.e. other than elimination of the 1,4-biradical formed by a Norrish Type II process, is the formation of cyclobutanols. Such is the outcome of the irradiation of the gibberellin derivative (64a) which yields the cyclobutanol (65). Treatment of this derivative with a tritium or deuterium donor affords the labelled derivative (64b).Azetidinols (66) are formed on irradiation of the ketones (67) in ethereal solution. The azetidinols (66) arise by way of the Norrish... 

The smallest ring size obtained by this route is four membered, as shown by the synthesis, in poor yield, of 4-azoniaspiro[3,3]heptan-2,6-diol (7) from an azetidinol and a chloroepoxide (Equation... 

However, when the lone pair on the amine is a part of a 7T-sy-stem (N-Acyl [8] [Vj l (U), N-Tosyl [1 ] or N-Phenyl [12 IJi.]) 3-azetidinols are obtained, via cyclization of an intermediate 1, 4-diradical, unless steric factors prevent the formation of the four-mem-bered ring (Figure 3b). 

As shown from the kinetic data earlier in this chapter, ring closure to four-membered azacarbocyclic rings (N-4 participation) is quite slow relative to ring closure to higher or lower homologs. Nevertheless, R2N-4 participation does occur. In fact, this mode of participation is shown to be more efficient than HO-3 participation in l-alkylamino-3-chloro-2-propanols as l-alkyl-3-azetidinols are the exclusive products [Eq. (26)]. ... 

Cyclization, The reaction of primary amines with epichlorhydrins remains a popular route to azetidinols, for example the antiviral agents (85). Aze-tidine-3-carboxylic acid, which X-my analysis shows to exist in the zwitterion... 

N-alkyl-3-azetidinols, obtained from epidilorohydrin and a primary amine, have been polymerized to low-molecular-weight hydroxy-substituted polyamines. Transesterification of an azetidinol with methyl acrylate or methacrylate leads to the corresponding azetidinyl esters which can be polymerized or copolymetized with other vinyl monomers to produce reactive, cross-linkable polymers (Scheme 18). 

Barluenga J, Baragana B, ConceUon JM. Synthetic application of 1-aminoalkyl chlromethyl ketones. Synthesis of enantiopure 3-azetidinols and aminoalkyl epoxides. 7. Org. Chem. 1997 62(17) 5974-5977. 

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