Ethers, Acetals, Ketals

Nearly every substitution of the aromatic ring has been tolerated for the cyclization step using thermal conditions, while acid-promoted conditions limited the functionality utilized. Substituents included halogens, esters, nitriles, nitro, thio-ethers, tertiary amines, alkyl, ethers, acetates, ketals, and amides. Primary and secondary amines are not well tolerated and poor yield resulted in the cyclization containing a free phenol. The Gould-Jacobs reaction has been applied to heterocycles attached and fused to the aniline. 

CH,o— — 7=C—0- Alcohols, ethers, acetals, ketals, carbonyl compounds, carboxylic acids, esters, phenols... 

Tetrahydropyranyl ethers, acetals, ketals and orthoesters. . . 129-131 Miscellaneous derivatives. 131... 

Mixtures of glycerol with other substances are often named as if they were derivatives of glycerol eg, boroglycetides (also called glyceryl borates) are mixtures of boric acid and glycerol. Derivatives, such as acetals, ketals, chlorohydrins, and ethers, can be prepared but are not made commercially, with the exception of polyglycerols. 

Several reports iu the Hterature describe the preparation and characterization of low, medium, and high vinyl polybutadienes (55—69). Each of these references used polar modifiers including chelating diamines, oxygenated ether compounds, acetals, ketals, and compounds of similar stmctures (56—64). 

The alkoxyl group OR is not a leaving group, so these compounds must be converted to the conjugate acids before they can be hydrolyzed. Although 100% sulfuric acid and other concentrated strong acids readily cleave simple ethers, the only acids used preparatively for this purpose are HBr and HI (10-71). However, acetals, ketals, and ortho esters are easily cleaved by dilute acids. These compounds are... 

Acetals, " ketals, and ortho esters react with Grignard reagents to give, respectively, ethers and acetals (or ketals). The latter can be hydrolyzed to aldehydes... 

Chiral acetals/ketals derived from either (R,R)- or (5,5 )-pentanediol have been shown to offer considerable advantages in the synthesis of secondary alcohols with high enantiomeric purity. The reaction of these acetals with a wide variety of carbon nucleophiles in the presence of a Lewis acid results in a highly diastereoselective cleavage of the acetal C-0 bond to give a /1-hydroxy ether, and the desired alcohols can then be obtained by subsequent degradation through simple oxidation elimination. Scheme 2-39 is an example in which H is used as a nucleophile.97... 

The hexitols form the typical derivatives of alcohols and glycols— esters, ethers, acetals and ketals, and metallic complexes. Because of the multiplicity of reactive groups and because of stereoisomerism, the number of theoretically possible derivatives of a given type is enormous. For example, D-mannitol on reacting with a mono reagent such as an etherifying agent or an acid, can form 35 different compounds ... 

An alternative method for dialkyl peroxide synthesis is the nucleophilic addition of an alkyl hydroperoxide to an alkene under acid catalysis reported by Davies and coworkers (Scheme 31, path B) ". A similar reaction is the nucleophilic addition of alkylhy-droperoxides to vinyl ethers under acid catalysis, producing perketals. Perketals can be deprotected under mild conditions (THF/water/acetic acid) and this hydroperoxide protection-deprotection sequence has been used by Dussault and Porter as a means for the resolution of racemic hydroperoxides (see also Section II.A.2) . In this respect more detailed studies were carried out with the perketals 75, which were prepared via reaction of alkyl hydroperoxides with vinyl ethers (Scheme 33). Weissermel and Lederer reported that in the presence of teri-butyl hypochlorite, a-chlorodialkyl peroxides can be formed in yields between 12% and 45% (Scheme 31, path C)". a-Alkoxydialkyl peroxides and diperoxyacetals were prepared by Rieche and coworkers via acid catalyzed reaction of one or two equivalents of alkyl hydroperoxides with acetals, ketals or aldehydes (Scheme 31, path D)" or by methylation of the corresponding a-alkoxy hydroperoxides with diazomethane (yields 11%, 27%)" . The diperoxyacetals 76 were isolated in yields ranging from 39 to 77%. 

Compatibility of asymmetric epoxidation with acetals, ketals, ethers, and esters has led to extensive use of allylic alcohols containing these groups in the synthesis of polyoxygenated natural products. One such synthetic approach is illustrated by the asymmetric epoxidation of 15, an allylic alcohol derived from (S)-glyceraldehyde acetonide [59,62]. In the epoxy alcohol (16) obtained from 15, each carbon of the five-carbon chain is oxygenated, and all stereochemistry has been controlled. The structural relationship of 16 to the pentoses is evident, and methods leading to these carbohydrates have been described [59,62a]. 

Dehydration of alcohols to ethers, acetals, and ketals Deloxan ASP, Amberlyst Selectivity enhancement Gray et al. (1999)... 

In order to circumvent such a drawback, there has been a recent focus on the design of cleavable lipids whose hydrolysis is catalyzed by the drop in pH.10 This approach exploits acid-labile chemical groups such as acetals, ketals, orthoesters, and vinyl ethers. Such functional groups... 

Advances in the Chemistry of Acetals, Ketals, and Ortho Esters. Bergstrom, R. G. In The Chemistry of Ethers, Crown Ethers, Hydroxyl Groups, and their Sulphur Analogues, Part 2. Patai, S., Ed, Wiley New York, 1980 Chapter 20. 

Oxidation of Ethers, Acetal and Ketal Derivatives. Haines, A. H.T Methods for the Oxidation of Organic Compounds Academic Press London, 1988 p 183. 

Deprotection of acetals. Acetals, ketals, and dioxolanes are converted to the carbonyl compounds by TiClj in ether, usually in yields of 75-90%. 

The diols (97) from asymmetric dil droxylation are easily converted to cyclic sii e esters (98) and thence to cyclic sulfate esters (99).This two-step process, reaction of the diol (97) with thionyl chloride followed by ruthenium tetroxide catalyzed oxidation, can be done in one pot if desired and transforms the relatively unreactive diol into an epoxide mimic, ue. the 1,2-cyclic sulfate (99), which is an excellent electrophile. A survey of reactions shows that cyclic sulfates can be opened by hydride, azide, fluoride, thiocyanide, carboxylate and nitrate ions. Benzylmagnesium chloride and thie anion of dimethyl malonate can also be used to open the cyclic sulfates. Opening by a nucleophile leads to formation of an intermediate 3-sidfate aiuon (100) which is easily hydrolyzed to a -hydroxy compound (101). Conditions for cat ytic acid hydrolysis have been developed that allow for selective removal of the sulfate ester in the presence of other acid sensitive groups such as acetals, ketals and silyl ethers. 

K platinum-on-asbestos catalyst at 290° is used in the conversion of t liethyl acetal to ethyl vinyl ether (42%). Ketals of the type C(OCHj)jCHj are readily split by heating with a small amount of p-I oluenesulfonic acid to yield substituted vinyl ethers of the type t lC(OCHj)=CHj (92%). In the presence of excess of a higher alcohol, fl OH, the olefinic ether corresponding to this alcohol, RC(OR )=CHj, is formed in high yield. Similarly, treatment of alkoxy ketals with acid I atalysts gives alkoxy dienes and dialkoxy olefins. ... 

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