Synthesis of 2-oxazolines

Scheme 15 Parallel synthesis of 2-oxazolines from carboxylic acids and aminoalcohols using PS-Mukaiyama reagent...

Sharma R, Vadivel SK, Duclos RI Jr et al (2009) Open vessel mode microwave-assisted synthesis of 2-oxazolines from carboxylic acids. Tetrahedron Lett 50 5780-5782... 

Crosignani S, Young AC et al (2004) Synthesis of 2-oxazolines mediated by N, M-diisopropylcarbodiimide. Tetrahedron Lett 45 9611-9615... 

Solubility insol H2O sol all common organic solvents. Preparative Methods ligand (1) and related C2-symmetric bisox-azolines are readily prepared from chiral p-amino alcohols using standard methods for the synthesis of 2-oxazolines. This is exemplified by the simple three-step procedure shown in eq 1, involving amide formation, conversion of... 

Ibata s group extensively investigated [3 + 2] cycloaddition reactions of 5-alkoxyoxazoles with aldehydes as a means of preparing precursors of p-hydroxy amino acids or 2-amino-l,3-diols. In particular, acid hydrolysis of cw-2-oxazoline-4-carboxylates produces the relatively inaccessible erythro-p-hydroxy amino acids. The authors studied the effects of solvent, temperature, Lewis acid, and aldehyde substituent on the product distribution and developed a synthesis of 2-oxazoline-4-carboxylates that is both cii-selective and enantioselective. 

Mohammadpoor-Baltork and colleagues also investigated the scope and generality of this catalytic system by the synthesis of 2-imidazolines (20) (Table 1.9, entries 1-6) and 2-thiazolines (21) (Table 1.9, entries 7-12). The reactions were carried out starting from different types of arylnitriles and ethylenediamine or 2-aminoethanethiol, respectively, under the same reaction conditions used in the synthesis of 2-oxazolines, obtaining the corresponding derivatives in good to excellent yields. 

Representative Examples of Synthesis of 2-Oxazolines and Bis-Oxazolines Catalyzed by Supported TPA under Solvent-Eree Conditions at 100°C... 

Synthesis of 2-oxazolines and bis-oxazolines from nitriles and ethanol amine was reported under conventional reflux or ultrasound irradiation using SSA as the catalyst (Schemes 5.19 and 5.20). 2-lmidazolines and Ins-imidazolines can also be obtained under similar conditions. Eventually, the synthesis of such heterocyclic compounds was found to be better using ultrasound (Mohammadpoor-Baltork et al., 2008). 

Microwave-assisted synthesis of 2-oxazolines from carboxylic acids using the open vessel technique has been reported (Sharma et al., 2009). This method involves direct condensation of carboxylic acids with excess 2-amino-2-methyl-l-propanol at 170 °C to give the corresponding 2-oxazolines in moderate to excellent yields. This also proved to be simple and efficient for the conversion of carboxylic acids into 2-oxazolines. 

In 1994, the same authors reported the synthesis of corresponding oxazolines tethered to sulfoxides by ortholithiation of the parent 2-phenyl oxazoline with butyllithium followed by addition of either (5)- or (/ )-/ -tolylmenthyl-sulfinate. Applied as ligands in the test reaetion, these diastereomerie ligands gave very different results, as shown in Seheme 1.25, thus demonstrating the... 

In their synthesis of spirocyclopropanated oxazolines (see Section 2.1), the de Meijere group obtained initially unexpected cyclobutene-annelated pyrimidones 2-569 by reaction of the cyclopropylidene derivative 2-567 with the amidines 2-568. In this fourfold anionic transformation a Michael addition takes place to furnish 2-570, which is followed by an isomerization affording cyclobutenecarboxylates 2-572 and a final lactamization (Scheme 2.128) [294]. 

Formation of the oxazoline reduced undesirable 18F-19F exchange and the desired product was rapidly (15s) isolated in good yield (45-55%) with a specific activity (1.1 GBq pmol-1) that was 20 times higher than that obtained when using direct debromination route. In another example, the synthesis of 2-deoxy-2-18F-fluoro-D-glucose [110] the high purity of the product and the improved specific activity is attributed to the short reaction times that are made possible via the use of micro-... 

Tundo and colleagues reported the synthesis of 4-oxazolin-2-one 110 by [3,3]-sigmatropic rearrangement of an enehydroxylamine derivative 109 resulting from the reaction of a ketoxime with dimethyl carbonate at high temperatures and in basic medium (equation 33). 

The designed set of 2-oxazoline monomers that was used for the synthesis of the triblock copolymers (MeOx, EtOx, PheOx, and NonOx) yielded polymers of different polarity [91], P(MeOx) and P(EtOx) are hydrophilic, whereas P(PheOx) and P(NonOx) are hydrophobic. All possible combinations of these four different monomers would result in 64 different structures. However, all polymers that would have two times the same block after each other were excluded since they do represent diblock copolymers. Additionally, some structures, which have NonOx as the first block and EtOx or MeOx as the second block, were excluded due to extensive side reactions. Consequently, 30 different triblock copolymers were synthesized, and they are listed in Table 13 with their corresponding structural characterization. 

Hoogenboom R, Fijten MWM, Paulus RM et al. (2006) Accelerated pressure synthesis and characterization of 2-oxazoline block copolymers. Polymer 47 75-84... 

Hoogenboom R, Fijten MWM, Schubert US (2004) Parallel kinetic investigation of 2-oxazoline polymerizations with different initiators as basis for designed copolymer synthesis. J Polym Sci Part A Polym Chem 42 1830-1840... 

Hoogenboom R, Wiesbrock F, Huang H et al. (2006) Microwave-assisted cationic ringopening polymerization of 2-oxazolines a powerful method for the synthesis of amphiphilic triblock copolymers. Macromolecules 39 4719-4725... 

The preparation of several glucofuran [2, l-t/] oxazolines 35 and 36 from reaction of 2-amino-2-deoxy-D-glucose 34 with HF has been described. Compounds 35a and 35b are formed when the reaction is carried out in formic acid, whereas the orthoesters 36a-c are formed when the reaction is carried out using anhydrides. Further reaction of 35 and 36 with methanol gives methyl glycosides. Thus, 35 and 36 may hnd use as potential glycosyl donors for the synthesis of 2-amino-2-deoxy sugars (Scheme 8.14). " ... 

Ferrocenoyl chloride (318), ethyl ferrocenecarboxylate (319), and cyanoferrocene (320) are all used as starting materials for the synthesis of 2-ferrocenyloxazolines (321) (Scheme 87). Chirality may be incorporated into the oxazoline ring, and these important chiral compounds have been used to prepare a great number of ferrocene derivatives that are used as catalysts in asymmetric synthesis." " ... 

A two-step synthesis of 1,4-disubstituted imidazoles (8) from TOSMIC (1) plus an aldehyde, followed by reaction with ammonia or a primary amine, proceeds via a 4-tosyloxazoline (11). The reaction sequence could be classified as 1,2 and 1,5 bond formation, 1,5 bond formation, or transformation of another heterocycle. There are, however, analogies to the aldimine reactions, and so the process is detailed at this stage. Certainly the synthesis is carried out in two steps often with isolation of the oxazoline (see also Chapter 6). Heating (11) with a saturated solution of methanolic ammonia gives a 4-substituted imidazole with methanolic methylamine a 1,4-disubstituted product is isolated as a single regioisomer (Scheme 4.2.4). Some of the oxazolines cannot be isolated as they are unstable oils which have to be heated immediately with the amino compound [12]. Related is the synthesis of 2-carbamoyl-4-(2 -deoxy- 0-D-ribofuranosyl)imidazole [13]. 

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