Ether and Acetal Derivatives

Transition-metal acetylacetonates promote the 2 - and 3-methylation of ribonucleosides using trimethylsulphonium hydroxide as the methylating reagent complexed ferric ion was particularly effective. Since iV-methylation is also suppressed, co-ordination of the met ion with the nitrogen of the bases may occur. 

The 2 - and 3 -0-methyl ethers of guanosine have been prepared by partial methylation of 5 -0-t-butyldiphenylmethyl guanosine with diazomethane in presence of tin(ll) chloride. 5 -0-Deuteriomethyl-2 -deoxyuridine has also been synthesized.  

Tetrahydrofuranyl ethers of thymidine and 2 -deoxycytidine have been prepared by acid-catalysed reaction of the nucleosides with 2,3 dihydrofuran mixtures of the 3 - and 5 -mono- and 3 5 -di-ethers were obtained. 3 -0-Tetra-hydrofuranyl-thymidine was also obtained by etherification of 5 -6 -palmitoyl thymidine followed by deacylation, and rat liver microsomes were found to convert the 3, 5 -diether selectively to the 5 -ether. The puramycin analogues (58) has been prepared from a 5 -blocked adenosine derivative. 

The 2 -0-t-butyldimethylsilyl protecting group in ribonucleosides is stable under a variety of conditions used to prepare ribonucleotides, including the chloro-phosphite coupling procedure, which was then used to prepare several 3 -phosphate esters of uridine. 

The synthesis of 5 -0-( 3-D-glucopyranosyluronic acid)-6-azauridine has been reported.  

Bis-chlorodi-isopropylsiloxane has been recommended as a reagent for forming 3, 5-disilyl derivatives of nucleosides, e.g., (67) 5-monomethoxytritylated nucleosides gave the corresponding 2, 3-cyclic ether, from which the trityl ether group could be selectively removed using toluene-p-sulphonic acid in dioxan. These reactions provide useful routes to 2 - or 5 -mono-substituted nucleos-sides.  

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Apart from 1,3,4-oxadiazole (b.p. 150°C), its lower alkyl derivatives and some dihydro compounds, 1,3,4-oxadiazoles are generally solids. In synthesis, the common method of purification is by crystallization of the crude reaction product. A few oxadiazoles, for example, alkyl ethers and acetates derived from 2,5-dihydro-2-hydroxy-2,5,5-trialkyl-l,3,4-oxadiazoles (cf. (38)), have been purified by distillation under reduced pressure. In some cases, chromatography over silica gel has been used. 

By using various trapping reagents, it has been deduced that the transannular fragmentation is rapidly reversible. The cyclization of the fragmented radical C is less favorable, and it is trapped at rates which exceed that for recyclization under most circumstances. " Radicals derived from ethers and acetals by hydrogen abstraction are subject to fragmentation, with formation of a ketone or ester, respectively. 

Trityl ethers and acetals of sucrose have generally been used as precursors for the synthesis of partially acylated derivatives of sucrose. Deacetalation of 3,4,3, 4 -tetra-0-acetyl-2,l 6,6 -di-0-(diphenylsilyl)sucrose (33) and 3,3, 4, 6 -tetra-0-acetyl-2,l 4,6-di-0-isopropylidenesucrose (35) with aqueous acetic acid for 25 min at 50° gave 3,4,3, 4 -tetra-0-acetylsucrose27 (34) and 3,3, 4, 6 -tetra-0-ace-tylsucrose32 (36), respectively. Synthesis of 2,3,4,3, 4 -penta-0-acetyl-... 

Cationic mechanisms are much more characteristic of the polymerization of oxygen heterocycles, both ethers and acetals. A wide variety of catalysts has been used, including protonic acids, such Lewis acids as boron trifluoride, phosphorus pentafluoride, stannic chloride, antimony pentachloride, titanium tetrachloride, zinc chloride, and ferric chloride, and salts of carbocations or tri-alkyloxonium ions having anions derived from Lewis acids. Some complex, coordination catalysts that appear to operate by a mechanism... 

The lower members of the homologous series of 1. Alcohols 2. Aldehydes 3. Ketones 4. Acids 5. Esters 6. Phenols 7. Anhydrides 8. Amines 9. Nitriles 10. Polyhydroxy phenols 1. Polybasic acids and hydro-oxy acids. 2. Glycols, poly-hydric alcohols, polyhydroxy aldehydes and ketones (sugars) 3. Some amides, ammo acids, di-and polyamino compounds, amino alcohols 4. Sulphonic acids 5. Sulphinic acids 6. Salts 1. Acids 2. Phenols 3. Imides 4. Some primary and secondary nitro compounds oximes 5. Mercaptans and thiophenols 6. Sulphonic acids, sulphinic acids, sulphuric acids, and sul-phonamides 7. Some diketones and (3-keto esters 1. Primary amines 2. Secondary aliphatic and aryl-alkyl amines 3. Aliphatic and some aryl-alkyl tertiary amines 4. Hydrazines 1. Unsaturated hydrocarbons 2. Some poly-alkylated aromatic hydrocarbons 3. Alcohols 4. Aldehydes 5. Ketones 6. Esters 7. Anhydrides 8. Ethers and acetals 9. Lactones 10. Acyl halides 1. Saturated aliphatic hydrocarbons Cyclic paraffin hydrocarbons 3. Aromatic hydrocarbons 4. Halogen derivatives of 1, 2 and 3 5. Diaryl ethers 1. Nitro compounds (tertiary) 2. Amides and derivatives of aldehydes and ketones 3. Nitriles 4. Negatively substituted amines 5. Nitroso, azo, hy-drazo, and other intermediate reduction products of nitro com-pounds 6. Sulphones, sul-phonamides of secondary amines, sulphides, sulphates and other Sulphur compounds... 

O-protected cyclic or acyclic carbon frameworks. The choice of acetals or ethers as derivatives allows a systematic manipulation of diols and polyols. Kinetic control and a lesser affinity for protonation on sulfur compared with oxygen allows the transformation of cyclic hemiacetals into acyclic dialkyl dithioacetals. Acetal, ether, and dithioacetal derivatives are some of the pivotal intermediates needed to explore various applications of carbohydrates in synthesis. 

N. Moufid, Y. Chapleur, and P. Mayon, Radical cyclisation of some unsaturated carbohydrate-derived propargyl ethers and acetals, J. Chem. Soc. Perkin Trans, p. 999 (1992). 

This rapidly growing tool for structural studies in the field of carbohydrate chemistry has been the subject of excellent reviews and a book.880,381 Initial studies of carbohydrates by mass spectrometry were confined to the acetals, methyl ethers, and acetates of the common sugars, owing to limitations imposed by the involatility of samples of other derivatives. 

Radical cyclization of allylsiloxy derivatives 148 to l-oxa-2-silacycloheptanes 149 was achieved by treatment of 2-(allyldimethylsiloxy)-l,l-dibromoalkanes with Bun3SnH in the presence of a catalytic amount of triethylborane in benzene (Equation 27). An interesting stereochemical outcome was observed in the cyclization of 1-allyldimethylsi-loxy-2,2-dibromo-l-phenylpropane (R1 = H, Rz = Ph) which gave a stereoisomeric mixture of 2,2,6-trimethyl-7-phenyl-l-oxa-2-silacycloheptane (cisftrans = 87/13). These seven-membered cyclic silyl ethers and acetals were stable and could be isolated by silica-gel column chromatography <1997BCJ2255>. 

The intramolecular aldol reaction in the presence of a titanium Lewis acid is a viable means of preparation of cyclic compounds. The cyclization is most conveniently performed between an enol silyl ether and an acetal, because the former is a reactive enol derivative and is readily prepared by silylation of the corresponding ketone in the presence of the acetal moiety in the same molecule. Equation (12) exemplifies a substrate undergoing intramolecular ring closure mediated by TiCU [74]. The conversion of sugar derivatives to carbocycles (called the Perrier reaction [75,76]) has been reported to occur in the presence of a Lewis acid. This process involves the aldol reaction between the enol ether and acetal moieties in the same molecule promoted by a titanium salt, as illustrated in Eq. (13) [77]. The similar reaction of a different type of substrate was also reported [78]. 

The safety and pharmacological profiles of hypromellose acetate succinate are similar to those of other ether and ester derivatives of cellulose.All nonclinical studies reported in the literature identify no target organs for toxicity by hypromellose acetate succinate. It has also been reported that hypromellose acetate succinate does not alter fertility in rats, does not produce any developmental anomalies in rats and rabbits, and does not alter perinatal and postnatal development in rats when assessed up to 2500mg/kg. ... 

Cyclopropanols can be converted to various cyclopropyloxy derivatives (esters, e.g. acetates, ethers, e.g. methyl and ethyl ethers, and acetals, e.g. tetrahydropyran-2-yloxy derivatives) under the appropriate reaction conditions. In most cases the synthesis of cyclopropyl esters by the reaction between a cyclopropanol and an acid chloride (e.g. formation of 1 ) or acetic anhydride (e.g. formation of 2 ) have been reported. The yields were particularly good (84-95%) when acetic anhydride was used, although a drawback of the reaction can be byproduct formation. When a reactive moiety is attached to the cyclopropane ring in addition to the hydroxy group, other reactions can also occur m-l-(aminomethyl)-2,2-dimethyl-3-(2-methylprop-l-enyl)cyclopropanol (3) reacted with phosgene in benzene to give the corresponding carbamate l,l-dimethyl-2-(2-methylprop-l-enyl)-4-oxa-6-azaspiro[2.4]heptan-5-one (4) in 31% yield. ... 

The preparations of dextran, and certain ethers and esters of dextran have been the subjects of about fifteen recent patents. The dextran (of L. mesenteroides or dextraniczim) may be precipitated first from the culture by the addition of ethanol or acetone, or the culture itself may be treated directly with the appropriate halide and sodium hydroxide in either a single stage or a two-stage procedure. The benzyl ether of dextran, formed by the reaction of dextran with benzyl chloride and sodium hydroxide at 75-185° for three to ten hours, is soluble in acetone and other solvents, and may be used in lacquers. Mixed ether and ester derivatives of dextran, e. g., benzyl and phthalate or butyl and benzoate, have been used for forming films, coatings or molded products. A preparation of dextran acetate has also been patented. ... 

At the temperatures commonly used in mass spectroscopy, this method is only valuable for the identification of such derivatives of D-fructose as the methyl ethers and acetates, but permits differentiation of ketoses from aldoses. ... 

Esters, Ethers, and Related Derivatives of Alcohols.— Although acetylation with acetic anhydride-pyridine is one of most familiar reactions, the detailed mechanism does not seem to have been elucidated.Spectroscopic detection of the acetylpyridinium ion resulting from the equilibrium ... 

Radicals derived from ethers and acetals by hydrogen abstraction are subject to (3-scission, with formation of a ketone or ester, respectively. 

Retention Times of Per(trimethylsilyl) Ethers and Other Derivatives of Some Acetals of D-Fructose and D-Psicose... 

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