Temperature cyclic acetal preparation

In a search for other cyclic acetals that would undergo quantitative ring opening even at room temperature we prepared the seven-membered ketene acetal, 2-methylene-l,3-dioxepane (V), which underwent essentially complete ring opening at room temperature. 

Though useful polymers can be made by these reactions, their low ceiling temperatures (see p. 599) and consequent tendency to undergo facile depolymerization by an unzipping mechanism pose serious limitations. To overcome this problem the technique of end-capping or end-blocking may be used. Thus poly-oxymethylene (polyacetal), an engineering plastic, prepared from the cyclic acetal... 

Cyclic acetals of ketoses are prepared most commonly from acetone or benzaldehyde formaldehyde, acetaldehyde, butanone, and cyclohexanone have been used occasionally. These carbonyl reagents are frequently used directly, although such derivatives as 2,2-di-methoxy- or 2,2-diethoxy -propane (acetone dialkyl acetals), or l,l-dimethoxyethane (acetaldehyde diethyl acetal), are often employed in experiments in which intermediate acetals are of interest,or in which the presence of water in the reaction mixture adversely affects the yield of products. A polymeric form of an aldehyde is the reagent to be preferred whenever the monomer is volatile for example, acetaldehyde is often used in the form of a trimer, paraldehyde, and formaldehyde is employed as formalin solution, as paraformaldehyde, or as polyoxymethylene. An excess of the carbonyl reagent is generally used as the solvent, and the condensation is usually effected at room temperature. 

It was not always recognized in the past that in order to make polymerization of some cyclic acetals feasible, the highest possible [M]o and the lowest possible temperature should be used. This led to some unsuccessful attempts to prepare... 

The most reliable method of preparing benzofuroxans is by decomposition of o-nitrophenyl azides. Decomposition can be achieved by irradiation, or more usually by pyrolysis temperatures between 100° and 1.50° are commonly used. Refluxing in glacial acetic acid is the recommended procedure for 4- or 5-sub-stituted 2-nitrophenyl azides, but with 3- or 6-substituted compounds higher boiling solvents are usually necessary. Quantitative studies on the reaction rate have been made, and a cyclic transition state invoked, an argument which has been used to account for the greater difficulty of decomposition of the 6-substituted 2-nitrophenyl azides. Substituent effects on the reaction rate have also been correlated with Hammett a constants, ... 

Selenoaldehydes 104, like thioaldehydes, have also been generated in situ from acetals and then directly trapped with dienes, thus offering a useful one-pot procedure for preparing cyclic seleno-compounds [103,104], The construction of a carbon-selenium double bond was achieved by reacting acetal derivatives with dimethylaluminum selenide (Equation 2.30). Cycloadditions of seleno aldehydes occur even at 0 °C. In these reactions, however, the carbon-selenium bond formed by the nucleophilic attack of the electronegative selenium atom in 105 to the aluminum-coordinated acetal carbon, may require a high reaction temperature [103], The cycloaddition with cyclopentadiene preferentially gave the kinetically favorable endo isomer. 

Ethanolic solutions of isopropylidene (azacycloalk-2-ylidene)malonates (1629) were boiled in the presence of sodium ethylate overnight to give ethyl (azacycloalk-2-ylidene)acetates (1630, XR = OEt) in 56-90% yields (83S195). Acrylates (1630, X = O) or acryl amides (1630, X = NEt) were also prepared when mixtures of cyclic esters (1629) and the respective alcohol or amine were heated for 30 min at a temperature 25°C higher than the decomposition point. The latter was sometimes carried out in acetone. 

Cyclic ketene acetals, which have utility as co-polymers with functional groups capable of cross-linking, etc., have been prepared by the elimination of HX from 2-halomethyl-l,3-dioxolanes. Milder conditions are used under phase-transfer conditions, compared with traditional procedures, which require a strong base and high temperatures. Solid liquid elimination reactions frequently use potassium f-butoxide [27], but acceptable yields have been achieved with potassium hydroxide and without loss of any chiral centres. The added dimension of sonication reduces reaction times and improves the yields [28, 29]. Microwave irradiation has also been used in the synthesis of methyleneacetals and dithioacetals [30] and yields are superior to those obtained with sonofication. 

Free radical polymerization of cyclic ketene acetals has been used for the synthesis of polyfy-butyrolactone), which cannot be prepared by the usual lactone route due to the stability of the five-membered ring. The polymerization of 2-methylene-l,3-dioxalane at high temperatures (above 120 °C) gave a high molecular mass polyester [59,79]. Only 50% of the rings opened when the polymerization was carried out at 60 °C, and this led to the formation of a random copolymer. The presence of methyl substituents at the 4- or 5-position facilitated the reaction. The free radical initiators generally used in such polymerizations are ferf-butyl hydroperoxide, ferf-butyl peroxide, or cumene hydroperoxide. The various steps involved are described in Scheme 5 [59]. 

This study on the immobilization of glucose oxidase and the characterization of its activity has demonstrated that a bioactive interface material may be prepared from derivatized plasma polymerized films. UV/Visible spectrophotometric analysis indicated that washed GOx-PPNVP/PEUU (2.4 cm2) had activity approximately equivalent to that of 13.4 nM GOx in 50 mM sodium acetate with a specific activity of 32.0 U/mg at pH 5.1 and room temperature. A sandwich-type thin-layer electrochemical cell was also used to qualitatively demonstrate the activity of 13.4 nM glucose oxidase under the same conditions. A quantitatively low specific activity value of 4.34 U/mg was obtained for the same enzyme solution by monitoring the hydrogen peroxide oxidation current using cyclic voltammetry. Incorporation of GOx-PPNVP/PEUU into the thin-layer allowed for the detection of immobilized enzyme activity in 0.2 M sodium phosphate (pH 5.2) at room temperature. 

The situation is similar with cyclic boronates, which are prepared by the following procedure. Steroid (10 pmol) and the respective substituted boric acid (10 jumol) are dissolved in ethyl acetate (1 ml) and the mixture is allowed to stand for 5 min at room temperature. Under these conditions, 17,20-diols, 20,21-diols and 17,20,21-triols are converted completely into boronates. Cyclic boronate was mainly produced from 17,21-dihydroxy-20-ketone, but side-products also appeared, the formation of which could be suppressed by adding a 10% excess of the reagent [387—389]. Different substituents on the boron atom, such as methyl, n-butyl, tert.-butyl, cyclohexyl and phenyl, are interesting from the viewpoint of GC—MS application. They are further suitable for converting isolated hydroxyl groups into TMS or acetyl derivatives. 

CHAPTER 7 THE PREPARATION OF CYCLIC NITRAMINES Hazards Use great care when handling 99% nitric acid produces poisonous reddish-brown fumes of nitrogen oxides use maximum ventilation. Wear gloves when handling acetic anhydride, and glacial acetic acid both of which can produce skin irritation. Do not allow the reaction mixture temperature to rise above 50 Celsius. 

Esters have been prepared in 63-73% yields from several simple cycloalkyl and aryl alkyl ketones by reaction at room temperature with per-benzoic acid. The larger radical of the ketone appears as the alcohol fragment of the ester. Cyclic ketones are oxidized by potassium persulfate and sulfuric acid to esters from which o>-hydroxy aliphatic esters are obtained upon hydrolysis and reesterification. Peracetic acid in acetic anhydride converts salicylaldehyde to o-hydroxyphenyl formate (88%). ... 

Preparative Methods (i) preparation of racemic DPEN and its optical resolution Reaction of benzil and cyclohexanone in the presence of ammonium acetate and acetic acid at reflux temperature gives a cyclic bis-imine (1) (eq 1). Stereoselective reduction of the bis-imine with lithium in THF-liquid ammonia at —78 °C followed by addition of ethanol, then hydrolysis with hydrochloric acid and neutralization with sodium hydroxide produces the racemic diamine (2). Recrystallization of the l-tartaric acid salt from a 1 1 water-ethanol mixture followed by neutralization with sodium hydroxide, recrystallization from hexane results in (5,5)-DPEN (3) as colorless crystals. 

Further adaptations of the boranes has led to reagents which reduce carboxylic acids but afford thio-acetals rather than the aldehyde itself.Thus, with the thioborane (3 equation 1), aliphatic acids give 80-87% yields of thioacetals but aromatic acids respond less well in giving significant quantities of sulfides as well. Carboxylic acid esters are inert to this reagent but give sulfides if a Lewis acid is included. Similarly, the 1,3,2-dithiaborinane-dimethyl sulfide adduct (4 equation 2) affords cyclic dithioacetals in 70-90% isolated yields in the presence of SnCb. Aliphatic acids react in about 6 h at room temperature but aromatic acids need about 20 h and yields are somewhat poorer. This area has been reviewed.From a practical viewpoint, it should be noted that the dithiaborinane (4) requires a week for its preparation. 

In the presence of a palladium(O) catalyst, allyl acetates having hydroxy functions afford cyclic ethers. Thus, exposure of (117a)- 117c), 1 1 diastereomeric mixtures, to [(DBA)3Pd2]/CHCb-Ph3P at room temperature gives rise to the same cyclic ether (118) in 92-96% yields as a 9 1 isomeric mixture. No cy-clization products derived from the secondary alcohol serving as the nucleophile are detected (Scheme 49). By this procedure, five- to seven-membered cyclic ethers have been prepared. ... 

Alkylation of sodium 1-(alkoxycarbonyl)methyIphosphonates proceeds equally with acetates in THF from low to room temperature or in DME at reflux. The asymmetric allylic alkylation of the sodium diethyl l-(ethoxycarbonyl)methylphosphonate with 3-acetoxy-l,3-diphenyl-l-propene and cyclic allylic acetates in the presence of a chiral palladium catalyst, prepared from chiral phosphine and palladium acetate, in THF at room temperature proceeds in good yields (44-88%) and high ec s. ... 

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