Oxazolidine, formation

FIGURE 6.5 Transfer of acyl between the amino and hydroxyl groups of seryl. (A) Deprotonation of O-acylseryl- induces oxazolidine formation, which is followed by (B) rearrangement to A-acylseryl-. (C) Protonation of the carbonyl of A-acylseryl- by mineral acid results in dehydration to the oxazoline, which is followed by hydrolysis (D) at the double bond giving protonated O-acylseryl-. 

Fig. 8 3-Benzyl-oxazolidine formation from N-benzyIdiethanolamine by fragmentation and intramolecular alkoxylation [28].

Yamasaki et al. applied gas chromatography to the separation and quantitative analysis of the alkaloids in some Ephedra species collected around the Himalayas. A satisfactory separation of the alkaloids and quantitative determination of L-ephedrine and D-pseudoephedrine was achieved using oxazolidine formation with acetone. ... 

Aldehydes could also be attached to resin-bound serine or threonine through oxazolidine formation [81]. This linker has been used for the preparation of peptide aldehydes. The cleavage was performed with mild aqueous add at 60 °C. 

Reaction 15.14 is an equilibrium reaction and this equilibrium is pushed to the oxazolidine formation by the water elimination from the reaction system under vacuum distillation. This reaction is used in practice to trap the traces of water in some PU formulations which need a perfect anhydrous media, for example in PU elastomers [26]. By the addition of oxazolidines to these formulations reaction of these compounds with water takes place and the oxazolidine is transformed in an aminoalcohol which is in fact a chain extender generated in situ and an aldehyde or a ketone practically inert in the reactions involved in PU chemistry (reaction 15.15). 

This mechanism for oxazolidine formation is strongly supported by the following experimental evidence (6) ... 

Derivatives With Cumene Hydroperoxide. Oxazolidine Formation Via Addition of a-Aminomethyl Radicals to Formaldehyde," J. Org. Chem., 1483 (1983). 

Apparently, cyclization involves the formation of open-chain intermediates 342, 343, further closing up to imidazolidines 344 and oxazolidines 345 which eliminate the secondary amine, thus leading to imidazolines 346 and oxazolines 347. The latter exist in the solution exclusively in the enolic forms 348, 349 which are stabilized by conjugation and intramolecular hydrogen bonds. 

Key steps, as shown in Scheme 4-15, involve the formation of a urethane intermediate 37 by treating epoxide 36 with methyl isocyanate in the presence of sodium hydride. Intramolecular A-nucleophilic ring opening of oxirane affords oxazolidine 38. Subsequent treatment furnishes product 34. 

The Michael addition reaction of the serine-derived oxazolidine 326 with ethyl acrylate gave two products. The major product of the reaction was found to be the bicyclic compound 327, which was formed in 27% yield, accompanied by the unsaturated ester 328. The Dess-Martin oxidation of 327 resulted only in formation of the elimination product, the 7,7a-dihydro-177, 377-pyrrolo[l,2-r ]oxazole 328 (Scheme 46) <2001JOC7555>. 

Formation of enantio- and diastereoenriched l-aza-4-oxa-7-thiabicyclo[3.3.0]octan-8-ones 453a and 453b was accomplished by ring closure of acyl-substituted. Y-bcnzyl thiocarbamates 452 in presence of Amberlyst 15 and 1,3-propanedithiol via a rearrangement of the oxazolidine ring (Equation 213) <2000JPR828>. 

In carbohydrate chemistry, the most described method for the preparation of saccharidic thionocarbamates involves preliminary introduction of the amine function on a partially or non-protected saccharidic template. The condensation of amino sugars with carbon disulfide or thiophosgene leads to cyclization in 1,3-oxazolidine- or l,3-oxazine-2-thiones. This reaction involves the formation of an intermediate isothiocyanate, which reacts further with a 3- or y-located hydroxyl group. The viability and facility of this process depends on the saccharidic ring size and the inherent strain. Some major rules can be put into light from the cases studied 30... 

The reaction of 1,2-allenyl sulfones with (-(-ephedrine led to enantiomerically pure 1,3-oxazolidines 216 via the formation of a conjugated enamine and subsequent intramolecular Michael addition [115]. 

Enol ethers 268a-c reacted with N-tosy]-4-vinylidene-l,3-oxazolidin-2-ones to give bicyclic tetrahydropyridine derivatives 269a-c (Table 12.12). Methyl /Tmcthoxyacry-late afforded 269c without formation of the [2 + 2] adduct. 

Bromoethylamine (11.133, R = Br, Fig. 11.18) is a potent nephrotoxin used to create an experimental model of nephropathy. Its mechanism of toxicity is postulated to involve perturbation of mitochondrial function, and its metabolism was investigated in a search for toxic metabolites. In rat plasma, 2-bromoethylamine was converted to aziridine (11.134), formed by intramolecular nucleophilic substitution and bromide elimination [155], Another major metabolite was oxazolidin-2-one (11.136). This peculiar metabolite resulted from the reaction of 2-bromoethylamine with endogenous carbonate to form carbamic acid 11.135, followed by cyclization-elimination to oxazoli-din-2-one. In aqueous media containing excess carbonate, the formation of... 

Fig. 11.18. Cyclization-elimination reactions in the in vitro and in vivo metabolism of nephrotoxic 2-haloethylamines (11.133). Aziridine (11.134) formation is probably a reaction of tox-ification, whereas oxazolidin-2-one (11.136) is clearly a reaction of detoxification [155][156].

In studies not yet published (66), the A/-acyl-oxazolidine-2-one 62 has been found to exhibit exceptionally high levels of (Z)-enolization stereoselection with either amide bases (LDA, THF, -78°C) or boryl triflates [(n-C4H9)2BOTf, CH2CI2, -78°C] in the presence of diiso-propylethylamine (DPEA). Upon aldol condensation, the enolates 63a and 63b afford the aldolates 64 (Scheme 11), which react readily with nucleophiles at the carbonyl function (Table 22). As discussed earlier, the large preference for (Z)-enolate formation in this system can be attributed to allylic strain considerations (37)... 

Aryl or alkyl substituents on the exocyclic double bond st r the regioselec-tivity towards the formation of i oxazolidine-4-spirocyclopropanes 274-276 (Table 22, entries 1-3). A complete reversal of regioselectivity to 277-279 was observed in the reactions of methoxycarbonyl substituted methylenecyclo-... 

---