Oxazolidone product

See also Antibacterial oxazolidinones antibacterials, 3 8 binding sites in, 77 736 optically pure, 77 740 preparation and manufacture, 3 13-14 therapeutic utility, 3 18 world market for, 3 16t Oxazolidone products, 70 410 Oxichromic developers, dye images from, 79 287-288... 

Ingham describes two by-products isolated in these reactions, (a) arylene-mandeloamides (8) formed in the presence of water and (b) diazines (11) resulting from dimerization of the chloroimine. Reconsideration by Comforth and Comforth demonstrated that reaction of 5 with water actually produces oxazolidone 9/... 

In 212 cc of water are mixed 21.2 grams (0.112 mol) of N-(benzylidene)-3-amino-2-oxa-zolidone, 8.93 grams of concentrated sulfuric acid, and 30.1 grams (0.124 mol) of 5-ni-tro-2-furaldehyde diacetate. This mixture is heated to effect the hydrolysis of N-(benzy-lidene)-3-amino-2-oxazolidone, steam distillation of the benzaldehyde and hydrolysis of 5-nitro-2-furaldehyde diacetate. Approximately IV2 hours are required for this reaction to take place. When the bulk of the benzaldehyde has been removed, 50 cc of 99% isopropanol are added, the reaction mixture is refluxed a short time, and the crystals of N-(5-nitro-2-furfurylidene)-3-amino-2-oxazolidone are filtered from the hot suspension. The product is washed with water and isopropanol and dried a yield of 23.3 grams, 92.8% based on N-(benzylidene)-3-amino-2-oxazolidone of MP 254° to 256°C is obtained, according to U.S. Patent 2,759,931. 

A mixture of 24.1 g (0.10 mol) of 3-o-methoxyphenoxy-2-hydroxy-1 -propyl carbamate and 6.0 g (0.10 mol) of urea was heated rapidly to the temperature range of 180°C to 200°C, and maintained there for five hours. The reaction melt was poured into 50% ethyl alcohol, from which the product crystallized as a white solid. The crude yield was 18.3 g (82%) melting point 131.5°C to 137 t. Crystallization from water and 95% alcohol gave 9.0 g (40.3%) of pure 5-o-methoxyphenoxymethyl-2-oxazolidone melting point 141°Cto 143. This melting point was not depressed when the material was mixed with an authentic sample. In additional runs acetone was used Instead of ethyl alcohol with equivalent results. 

More recently, such vinyl cations generated by the alkaline decomposition of 3-nitroso-2-oxazolidones have been trapped by halogens to give vinyl halides as products (108). It has been suggested that unsaturated carbenes, RjC=C , may be the intermediates in the basic decomposition of 132 (109). Indeed, when 132 (Ri=R2=CH3, R3=H) was treated with lithium ethoxide in the... 

Usually, (Z)-boron enolates can be prepared by treating /V-acyl oxazolidones with di-K-butylboron triflate and triethylamine in CH2CI2 at 78°C, and the enolate then prepared can easily undergo aldol reaction at this temperature to give a, vy -aldol product with more than 99% diastereoselectivity (Scheme 3-4). In this example, the boron counterion plays an important role in the stereoselective aldol reaction. Triethylamine is more effective than di-wo-propylethyl amine in the enolization step. Changing boron to lithium leads to a drop in stereoselectivity. 

Due to these limitations Evans et al. focussed on the exploration of imide-derived enolates (165). They expected these systems to react stereoselective in carbon-carbon bond formation and that the derived imides might be readily hydrolized or reduced under the mild conditions required for the construction of complex products, One of the two chiral 2-oxazolidones (175) chosen for study by Evans et al.179) is derived from (S)-valine and was readily prepared from this inexpensive commercially available a-amino acid having an optical purity exceeding 99 %. The preparation of the related imide-derived enolate (165) is shown in the next scheme. Alkylation reactions employing (175) resulted in excellent diastereoface selection, as summarized in Table 4 179). 

The synthesis of a triptan with a chiral side chain begins by reduction of the carboxylic acid in chiral 4-nitrophenylalanine (15-1). The two-step procedure involves conversion of the acid to its ester by the acid chloride by successive reaction with thionyl chloride and then methanol. Treatment of the ester with sodium borohy-dride then afford the alanilol (15-2). Reaction of this last intermediate with phosgene closes the ring to afford the oxazolidone (15-3) the nitro group is then reduced to the aniline (15-4). The newly obtained amine is then converted to the hydrazine (15-5). Reaction of this product with the acetal from 3-chloropropionaldehyde followed by treatment of the hydrazone with acid affords the indole (15-6). The terminal halogen on the side chain is then replaced by an amine by successive displacement by means of sodium azide followed by catalytic reduction of the azide. The newly formed amine is then methylated by reductive alkylation with formaldehyde in the presence of sodium cyanoborohydride to afford zolmitriptan (15-7) [15]. 

Formation of ethylenimine by the pyrolysis of 2-oxazolidone has been claimed, 88 -3J The evidence is based on the isolation of polymeric products and is of doubtful validity. 

Chiral 3,3-disubstituted cyclopentanones. Taber et al have extended a synthesis of cyclopentanones by a rhodium catalyzed intramolecular C—H insertion (11,459) to a synthesis of (+ )-a-cuparenone (3), which contains a chiral quaternary center. Thus the chiral a-diazo-p-keto ester 1, prepared by alkylation of a chiral oxazolidone (11, 379-381) on treatment with Rh2(OAc)4 is converted into 2 in 67% yield. This product is converted in several steps into (+ )-3. 

Asymmetric aikyiation of imide etiolates.1 The sodium enolates of 3 and 7 are alkylated with marked but opposite diastereoselectivity by alkyl halides. The selectivity is improved by an increase in the size of the electrophile, with methylation being the least stereoselective process. The asymmetric induction results from formation of (Z)-enolates (chelation) with the diastereoselectivity determined by the chirality of the C4-substituent on the oxazolidone ring (equations I and II). The products can be hydrolyzed to the free carboxylic acids or reduced by LiAlH4 to the corresponding primary alcohols and the unreduced oxazolidone (1 or 2). 

The formation of vinyl cations by deamination of vinyl amines in neutral media, is therefore not established and the possibility that a carbene intermediate is actually involved must be considered. Thus, the products of the alkaline decomposition of N-nitroso-oxazolidones 109 were earlier explained (Newman and Kutner, 1951 Newman and Weinberg, 1956) in terms of a mechanistic scheme involving vinyl cation intermediates (equation 19). Such a scheme has recently been... 

Diphenyl-BINOL-derived chiral aluminum reagents are prepared in situ by addition of Ethylaluminum Dichloride or Diethylaluminum Chloride to 3,3 -diphenyl-BINOL. These chiral aluminum reagents promote the enantioselective Diels-Alder reaction of cyclopentadiene with the oxazolidone dienophile (eq 14). Endo products are obtained with a high level of asymmetric induction (>90% ee) however, a stoichiometric amount of the Lewis acid is required. The preparation and use of a C3 symmetric BINOL-derived boronate has been reported (eq 15). BINOL-B(OAr)3 complexes have recently been developed for the asymmetric Diels-Alder reaction with imines (eq 16). ... 

The oxazolidone tosylate 101 with sodium hydride in benzene at 55°C gives the aziridine 102 (48%). This aziridine reacts with sodium p-cresolate in hexamethylphosphoramide to yield two products. Attack of the anion at C5 of the aziridine 102 forms the oxazinone 103, while attack at C6 leads to the oxazolidinone 104. 

The product anion (V) decarboxylates (18b) on acquiring a proton from an acid species present (e.g. the conjugate acid BH of the initiating base product in (6) or an NCA molecule). Formation of species such as (VI) diversifies the routes to polymerization. Thus (VI) is a primary base and can react by the mechanism already described with any oxazolidone-2,5-dione system present, including monomer (I) or a molecule of its own kind. These processes are indicated in (19a) and (19b), respectively. 

DMF may also participate in ring formation. Reduction of A-phenyl-2-bromoiso-butyramide in DMF gave, besides debrominated and dehydrobrominated products, 5,5-dimethyl-2-dimethylamino-3-phenyl-4-oxazolidone [145]. 

In order to overcome the problems associated with acid hydrolysis of amides of prolinol, the Evans research group has investigated the diastereoselectivity of the alkylation of imides derived from chiral 2-oxazolidones. Imide enolates are somewhat less nucleophilic than amide enolates, but they have the advantage that their diastereomeric alkylation products are easily separated and the imide linkage is cleaved with a variety of reagents under mild conditions. As shown in Scheme 64, alkylation of the chelated (Z)-enolate of the propionimide derived from (S)-valinol (135) with benzyl bromide occurred in high chemical yield and with high si-face diastereoselectivity. In addition to oxazolidones, imidazoli-diones have proved to be useful chiral auxiliaries for diastereoselective enolate alkylations. ... 

LiBr solubilized by Bu"3PO (or HMPA) was found to catalyze the formation of 2-oxazolidones from organic isocyanates and terminal alkene epoxides. The epoxide substituent appears at the 5-position of the product as shown in equation (122). This outcome is in keeping with rapid trapping by the isocyanate of the halohydrin salt formed by attack of bromide at the primary center. This interpretation requires that oxazolidone formation be faster than epoxide rearrangement data are not available to confirm this point. 

Chiral oxazolidones are readily prepared from carbamates of a-amino esters by reduction with NaBHa-Lil in refluxing THF. Note that imides (A-acyloxazolidinones) are reduced to alcohols, therefore the reduction represents a method for recovery of both chiral products and auxiliaries. ... 

The Reformatsky reaction has been known for over 100 years a-bromo esters, ketones and amides react with activated zinc dust to give zinc enolates, which can react with carbonyl compounds to give aldol-type products. Recent examples include the reactions with sterically crowded oxazolidone... 

Saturation of an equimolar mixture of aromatic aldehyde cyanohydrins and aromatic aldehydes in absolute ether at 0°C with dry hydrogen chloride results in the formation of 2,5-diaryloxazoles.114 116 The reaction often yields 2,5-diaryl-4-oxazolidones as by-products, and oxazolid-4-ones are the only products or major by-products if either of the starting materials is aliphatic. 

High threo selectivity in allyl transfer reactions giving n = 2 telomers has been observed using achiral oxazolidone acrylamides (Fig. 7). Selectivities as high as 93 7 in favor of threo products were obtained in pentane. Selectivity also appeared to depend on solvent polarity with higher selectivities in solvents of lesser polarity [7]. The n = 2 telomers from the allyl transfer reaction of cyclododecyl iodide and allyl stannane can be crystallized, and the X-ray crystal structure of the threo product... 

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