Oxazolidine-2,5-diones

More recently a whole series of derivatives with excellent fungicidal action has been discovered, in which the heterocyclic part is mostly pyrrolidine dione, oxazolidine dione or imidazolidine dione, while the analogous functional group is N-(3,5-dichlorophenyl) dicarboximide. 

Oxazolidine-4,5-dione, At-benzoyl-synthesis, 6, 231 Oxazolidinediones reactions, 6, 214 structure, 6, 179 Oxazolidine-2,4-diones as anticonvulsants, 1, 166 NMI 6, 181 reactions, 6, 214 s mthesis, 6, 231 OxazoIidine-2,5-diones crystal structure, 6, 185 reactions, 6, 214 polymers, 1, 307 s mthesis, 6, 231 Oxazolidine-4,5-diones synthesis, 6, 231 Oxazolidines... 

El fazepam (80) not only is a tranquilizer, but also stimulates feeding in satiated animals. One of several syntheses involves reaction of benzophenone derivative with a glycine equivalent masked as an oxazolidine-2,5-dione (79). ... 

The residue is dissolved in ether and the solution is washed with sodium chloride solution and then with a little sodium thiosulfate solution. The ethereal solution is dried over sodium sulfate and ether removed by distillation. A yield of 108 parts of 3,5,5-trimethyl-oxazolidine-2,4-dione is obtained having a melting point of 45° to 46°C with slight softening at 43°C. This represents a 75% theory yield on the ethyl o-hydroxy-iso-butyrate taken. The product may be further purified by dissolving the minimum quantity of dry ether and cooling to -10°C. The product so obtained melts sharply at 45.5° to 46.5°C, according to U.S. Patent 2,559,011. 

Kricheldorf HR, Greber G (1971) N-silylated amino acid N-carboxylic acid anhydrides (oxazolidine-2.5-diones). Chem Ber 104 3131... 

Heterocycles like l,4,2-dioxazole-5-ones and 3-hydroxy-l,3-oxazolidine-2,4-diones are formed from a 2-hydroxycarbohydroxamic acid and CDI in the following reactions [117]... 

The vast majority of compounds having the bisindole nucleus characteristic of the vinca structure with antitumor activity in experimental tumor systems bear a carboxyl function and a free tertiary hydroxyl group at C-3 of the vindoline moiety. The group of semisynthetic derivatives distinguished by the presence of a C-3 spiro-fused oxazolidine-l,3-dione are important exceptions to this generalization. 

Note 3 Propagation in chain polymerization usually occurs without the formation of small molecules. However, cases exist where a low molar-mass by-product is formed, as in the polymerization of oxazolidine-2,5-diones derived from amino acids (commonly termed amino acid A-carboxy anhydrides). When a low-molar-mass by-product is formed, the adjective condensative is recommended to give the term condensative chain polymerization. 

A-Carboxy-a-amino acid anhydrides, also referred to as 4-substituted oxazolidine-2,5-diones, Leuchs s anhydrides, or N-carboxyanhydrides (NCA), are polymerized by bases and transition metal complexes. Polymerization proceeds with simultaneous decarboxylation to produce a polyamide... 

The zinc alkoxides of syn- or /7-3-(/3-hydroxyacyl)oxazolidin-2-ones underwent stereoselective rearrangement under mild conditions to afford syn- or /7-3-(2-hydroxyethyl)tetrahydro-l,3-oxazine-2,4-diones in good yields. The procedure was utilized in the synthesis of ( )-trisubstituted 0 ,/3-unsaturated amides and acids <2005OBC2976, 2005SL1090>. 

An unusual type of dipolar cycloaddition is known to occur to 2//-dihydrooxazine 180 when it is treated with dimethylsulfoxonium methylide 181 (Scheme 16) <1994CPB739>. Ring contraction of the intermediate 182 results in formation of the oxazolidine-4,5-dione 183. 

When the 5-phenyltetrahydro-l,3-thiazine-2,4-dione 155 is treated with NaBH4, the thiazine ring fragments to produce (3 )-3-mercapto-3-phenylpropan-l-ol in 45% yield and the oxazolidin-2-ones 156 and 157 as a mixture of diastereomers (Equation 11) <2006TL1153>. 

The Knoevengal reaction has been an extremely versatile method to functionalize C-5. Literally hundreds of 5-alkenyl- and 5-alkyl-2,4-oxazolidinedione analogues have been prepared in this manner. Generally, 2-thio-2,4-oxazolidine-dione, 104, is used in these reactions although 179 has been used successfully as well. Some representative examples follow. 

Symmetrical piperazine-2,5-diones have been obtained in good yields by treating Leuchs anhydrides (l,3-oxazolidine-2,5-diones) with aziridine [70AG(E)162]. The reaction apparently proceeds through the formation of dipeptide aziridides (Scheme 5). 

The oxazolidine-2,5-dione heterocycle, perhaps better known as the N-carboxyanhydride of an amino acid, has been incorporated employing a modification of chloromethylated poly(styrene) (192) (76USP3985715). The reaction sequence involved utilization of a masked amino acid, ethyl acetamidocyanoacetate (205). The amino acid was liberated in a subsequent hydrolysis/decarboxylation step (Scheme 98). The cyclized, IV-carboxyanhydride-functional resins (206) were reported to be useful in solid phase peptide synthesis and as supports for enzyme immobilization. 

The N-carboxy-a-amino-acid anhydrides, referred to as Leuchs anhydrides, or briefly as NCA s, are well-defined, colourless, crystalline substances having sharp melting points when pure. The synthesis of the simplest member of this class of compounds, viz. oxazolidine-2,5-dione,... 

The thermal decarboxylation of NCA s involves the 2-carbonyl group of the oxazolidine-2,5-dione ring. This was proved (9) by labelling glycine NCA with C13 and examining the C13 content of the carbon dioxide evolved in thermal polymerisation. 

Isotope labelling again proved (21) that the decarboxylation involves only carbon 2 of the oxazolidine-2,5-dione, and studies of the kinetic isotope effect (22) demonstrated that this step is not the rate-determining in the overall process. Therefore, the rate of the overall reaction is determined either by (a) — the formation of the complex, or by (b), viz. by opening of the ring between atoms 1 and 5. This conclusion applies also to the "normal amine-propagated NCA polymerisation. 

An earlier series of experiments established useful synthetic transformations involving carboxylation of ketones and nitroalkanes to yield P-keto acids and a-nitro acids respectively (Scheme 94).362 363 The reagent is methylmagnesium carbonate and the intermediate (130) can be alkylated with concomitant decarboxylation to provide greater versatility. These reactions can also be extended to ketone functions in imidazoline- and oxazolidine-diones (Scheme 95).364,365... 

Chemical Name (/LS )-3-(3,5-dichlorophcnyl)-5-vinyl-l,3-oxazolidine-2,4-dione 3-(3,5-dichlorophenyl)-5-ethenyl-5-methyl-2,4-oxazolidinedione CAS Registry No 50471-44-8... 

Oxazolidine-2,5-diones (276) are the anhydrides of iV-carboxy-a-amino acids. They react with nucleophiles, such as water, alcohols or amines, to give unstable N-carboxy acids, esters or amides which lose carbon dioxide (equation 87). The products (277) are themselves nucleophilic reagents and may react with another molecule of the oxazolidinedione to yield a dipeptide (equation 88). The process may continue, leading to a polypeptide. Chiral oxazolidine-2,5-diones derived from optically active a-amino acids undergo stereospecific polymerization (72C501). 

Compounds with two oxo groups in the oxazolidine ring have been prepared. Thus, 3,4-dihydro-2(l//)-quinolinones react with oxalyl chloride to form 5H-oxazolo[3,2-a Quinoline-1,2-diones (260) (70M383). 

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