Oxazolines synthetic routes

Scheme 5. Synthetic routes used for the preparation of functional polymers containing pendant 2-oxazoline and bromobenzyl groups.

From this point on two synthetic routes could be followed compound 1J could be treated either to yield the oxazoline 1J2, or the a-halogeno sugar both being... 

This article surveys the research work on the synthesis and modification reactions of poly(ethyleneimine) as well as its applications to metal complexation processes. Poly-(ethyleneimine), one of the most simple heterochain polymers exists in the form of two different chemical structures one of them is branched, which is a commercially available and the other one linear which is synthesized by cationic polymerization of oxazoline monomers and subsequent hydrolysis of polyf(/V acylimino)cthylcne]. The most salient feature of poly(ethyleneimine) is the simultaneous presence of primary, secondary, and tertiary amino groups in the polymer chain which explains its basic properties and gives access to various modification reactions. A great number of synthetic routes to branched and linear poly(ethyleneimine)s and polymer-analogous reactions are described. In addition, the complexation of polyfethyleneimine) and its derivatives with metal ions is investigated. Homogeneous and heterogeneous metal separation and enrichment processes are reviewed. 

Differently substituted oxazolines are available through one of the synthetic routes listed below ... 

The synthetic route began with the synthesis of the bromide 147 by benzylation and ketalisation of the known aldehyde 146 (Scheme 20). Generation of the Grignard reagent followed by addition of chiral oxazoline 105 afforded the biaryls 148 and 149 in 64% yield and a ratio of 77 23 respectively along with 22% of the demethylated oxazoline 114. Quaterisation, base hydrolysis and reduction then gave the alcohol 150 which was converted into the acetamide 144 by... 

Oxazolines are versatile intermediates in the synthesis of jS-substituted serines which are of significant importance because of their utility in the synthesis of various antibiotics [132]. Thus, the serine moiety constitutes the primary core structure of antibiotics, such as hypeptin and leucinostatin. Ethyl isocyanoac-etate, a synthon for the formation of oxazolines, is relatively acidic and can be deprotonated by a variety of bases for coupling with aldehydes to afford oxazolines. However, the lack of diastereoselectivity of such reactions has rendered this synthetic route of limited use and as a result, alternate routes to the jS-hydroxy-a-amino acids have been developed which, however, are also not entirely satisfactory. 

A new simple synthetic route to 2,5-dihydrooxazoles 71 by cycloaddition of allyl azido ethers 70 via triazoUnes was shown by Hassner et al. [37]. Earlier, they demonstrated that cr-azido ethers can be easily prepared from aldehydes using an alcohol, hydrazoic acid and titanium tetracliloride as well as the fact that thermolysis of azido ethers in the absence of a double bond forms imi-dates [35,36]. Using the above mentioned facts, the allyl azido ethers 70 were synthesized in good yields employing an aldehyde, an allyl alcohol and HN3 in a 1 3 9 ratio in presence of a Ti catalyst (Scheme 12). Allyl azido ethers 70, on thermolysis in benzene, proved to be ideal substrates for the formation of 2,5-dihydrooxazoles 71 in 66-90% yield. To show that oxazolines are formed via triazolines and not via an independent nitrene pathway, thermolysis of 70 was followed by NMR in hexadeuteriobenzene at 70 °C. 

The development of a short synthetic route to the dihydropyran framework of zanamivir congeners was then achieved by coupling the Petasis three-component condensation to this novel iron(m)-promoted one-pot cascade of deprotection - C-C double bond isomerization -cyclization - oxazoline formation. The entire sequence could also be applied to aldehydes 44 and 47 to furnish, in a few steps, the corresponding alcohols 45 and 48 or amines 46 and 49 (Scheme 13). 

The aziridine-2-carboxaldehyde 56 can also serve as synthon for the synthesis of sphingosines, which are important biomembrane constituents [64]. One possible route involves the addition of an alanate to the aldehyde. In a later stage of this synthetic plan the aziridine can be opened, either via the intermediacy of an oxazoline or directly with dilute acid. Unfortunately, the reaction of aldehyde 56 with a vinylalanate has a poor diastereoselectivity of 3 2. Therefore, an alternative approach was considered, namely one involving the addition of a vinylzinc reagent to the aldehyde thereby employing our N-tritylaziridinediphenyl-methanol 51 as the chiral catalyst. Gratifyingly, only one diastereomer was obtained. Reductive removal of the trityl function, acetylation of the hydroxy... 

The enantiomers of the naturally occurring lignans, schizandrin (5) and isoschizandrin (6), have been prepared from oxazoline 10 in 11 steps with 0.7% and 5.5% overall yield, respectively. Although both natural products are accessible by this strategy, the reported synthetic approach is basically a route to isoschizandrin (6). Schizandrin (5) was obtained only as minor congener and a selective synthesis of 5 has not been accomplished by the authors. 

The synthetic strategy of Wipf [9] is quite different. He decides to prepare oligo(oxazolines) instead of oligo(thiazolines). Then a new multiple oxazoline thiazoline conversion is used. Wipf chooses the oxazoline route for two reasons. The first reason is a synthetic one oxazo-lines are easier to prepare than thiazolines. The second reason is a pharmacological one the ox-azolines obtained along this route may be interesting drug candidates. 

To decrease the number of operations, an obvious remedy is to redefine the route by using different starting materials that require fewer steps to produce the product. Another similar time-saving approach is to carry out more than one synthetic transformation in one step. For example, three double reactions were developed for the benzazepine 7 (Figure 2.9) hydrolysis of a nitrile and an oxazoline, reduction of an amide and an ester/lactone, and cyclization-demethylation [12], Such double reactions save considerable operating time and expenses on scale. 

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