Enol ethers 2- ethanol

The crude ketal from the Birch reduction is dissolved in a mixture of 700 ml ethyl acetate, 1260 ml absolute ethanol and 31.5 ml water. To this solution is added 198 ml of 0.01 Mp-toluenesulfonic acid in absolute ethanol. (Methanol cannot be substituted for the ethanol nor can denatured ethanol containing methanol be used. In the presence of methanol, the diethyl ketal forms the mixed methyl ethyl ketal at C-17 and this mixed ketal hydrolyzes at a much slower rate than does the diethyl ketal.) The mixture is stirred at room temperature under nitrogen for 10 min and 56 ml of 10% potassium bicarbonate solution is added to neutralize the toluenesulfonic acid. The organic solvents are removed in a rotary vacuum evaporator and water is added as the organic solvents distill. When all of the organic solvents have been distilled, the granular precipitate of 1,4-dihydroestrone 3- methyl ether is collected on a filter and washed well with cold water. The solid is sucked dry and is dissolved in 800 ml of methyl ethyl ketone. To this solution is added 1600 ml of 1 1 methanol-water mixture and the resulting mixture is cooled in an ice bath for 1 hr. The solid is collected, rinsed with cold methanol-water (1 1), air-dried, and finally dried in a vacuum oven at 60° yield, 71.5 g (81 % based on estrone methyl ether actually carried into the Birch reduction as the ketal) mp 139-141°, reported mp 141-141.5°. The material has an enol ether assay of 99%, a residual aromatics content of 0.6% and a 19-norandrost-5(10)-ene-3,17-dione content of 0.5% (from hydrolysis of the 3-enol ether). It contains less than 0.1 % of 17-ol and only a trace of ketal formed by addition of ethanol to the 3-enol ether. 

Steroidal 17-cyanohydrins are relatively stable towards chromium trioxide in acetic acid (thus permitting oxidation of a 3-hydroxyl group ) and towards ethyl orthoformate in ethanolic hydrogen chloride (thus permitting enol ether formation of a 3-keto-A system ). Sodium and K-propanol reduction produces the 17j -hydroxy steroid, presumably by formation of the 17-ketone prior to reduction. ... 

Sulfides are hydrogenolyzed usually by Ra-Ni.383-391 Phenyl and methylthio groups were removed by Ra-Ni (10 mmol Ni/mmol) refluxing in ethanol for 2 hours.392 A thio enol ether was desulfurized with Ra-Ni (100 mmol Ni/mmol) in MeOH at room temperature for 30 minutes.393 During the synthesis of 2-deoxy-p-gl y cos ides the removal of the arylthio group was achieved using Ra-Ni with no problem.394... 

If one compares the solvolyses of 2-bromo-l,l-diphenyl-4-(p-methoxyphenyl)-but-l-en-3-yne (57) and 4.4-diphenyl-1 -bromo-1 -(/ -mcthoxyphcny l)-buta-1,2,3-tricncs (58, X = Br) in aqueous ethanol (equation 21), the destabilization of the intermediate cation 59 by the large inductive effect of the triple bond as compared to its conjugative effect is evident42. Only in the case of 58 could the substitution product butatrienyl enol ether 60 be isolated in 40% yield, while it was only detected by UV and IR spectroscopy in the solvolysis product of 57. The faster observed reaction rate of 58 as compared to 57 was ascribed to a difference in their ground-state energies42. 

FIGURE 10 Isocratic CEC of erythromycin A and its impurities. Cationic column 30cm (effective length 20 cm) x 50 pm ID mobile phase 25% (v/v) acetonitrile and 25% (v/v) ethanol in 30mM phosphate buffer, pH 8.0 applied voltage — l5kV detection, 206 nm. Sample (I) N-demethylerythromycin A, (2) erythromycin C, (3) erythromycin A, (4) erythromycin B, (5) erythromycin enol ether. Mobility of EOF measured with DMSO, peof = 3-33 x 10 °m /sV. (Reprinted from reference 321, with permission.)... 

The required 1-oxa-l,3-diene precursor was synthesized according to the synthesis design (Scheme 8). Cycloadditon with enol ether furnished exclusively the endo-isomer. Raney nickel treatment in refluxing ethanol yielded in one step the desired tetrahydropyran derivative in a favorable 6 1 cis/trans ratio. Transformation into the lactone and ring closure with potassium tert.-butoxide afforded (+)-ramulosin. 

The enol ethers generated in situ by the addition of ethanol to l,4-pentadiyn-3-ones are cyclised to the 4/f-chalcogenopyran-4-ones on treatment with disodium chalcogenides (Scheme 40) <99JHC707>. The 2,6-diphenyl derivatives are useful catalysts for the Baylis-Hillman reaction <99TL3741>. 

It is not customary to attempt the isolation of ketone or aldehyde intermediates (121) the formula serves merely as a reminder that once hydrolysis of the protecting enol ether or acetal occurs, the same type of structure is formed from any given dicarbonyl compound. Cyclization has been carried out in refluxing ethanolic picric acid or acetic anhydride with a few drops of sulfuric acid, but Hansen and Amstutz (63JOC393) offered excellent theoretical reasons for avoiding an excess of acid, and reported that best results (Table 3) can be obtained by refluxing the dry hydrobromide in acetic anhydride containing no sulfuric acid. 

The superfluous bromine is then removed by reduction with zinc in acetic acid (26-1). The 20 ketone is next protected against the strongly reducing conditions in the subsequent step by conversion to the ethylene glycol acetal (26-2). Birch reduction with lithium in liquid ammonia in the presence of ethanol proceeds as usual to the dihydrobenzene (26-3). Treatment of this last product with mineral acid serves to hydrolyze both the enol ether at the 3 position and the acetal at the... 

Another work of Duhamel and Ancel [59] related this synthesis of retinal via (3-ionylideneacetaldehyde. Condensation of methallyl-magnesium chloride with diethyl phenyl orthoformate (EtC CHOPh) led after bromination of the ene-acetal, deshydrohalogenation (NaOH 50%), ethanol elimination with hexamethyldisilazane (HMDS) and ISiMes, to the bromo-dienol ether. This latter was submitted to bromine lithium exchange and the lithio enol ether was then condensed with p ionylideneacetaldehyde to give retinal, Fig. (28). 

Eschenmoser s pyrone 38 on treatment with cyclopropenone ketal 39 in refluxing benzene afforded lactone 40 (73%). Lactone 40 on hydrolysis with acetic acid at 100°C afforded, after deprotection and decarboxylation, tropone 37 (70%). Introduction of the tropolonic hydroxyl group was achieved with hydrazine hydrate in ethanol, to give a mixture of deacetyl-colchiceinamides 41 (53%) and 42 (37%), followed by reaction with ethano-lic potassium hydroxide, which afforded tropolones 43 and 44, respectively. Tropolone 43 was converted to 44 which, therefore, became the major reaction product. Methylation of 44 gave a mixture of enol ether 18 and 45 which were separated by chromatography. 

Ethanol was used to make the enol ether 23 R = Et, the addition of the Grignard 25 was successful and the cycloaddition went in excellent yield.3... 

Seleno- and telluropyranones have been prepared by the reaction of l,4-pentadiyn-3-ones with disodium selenide or telluride (see CHEC-II(1996), section 5.11.2.2). The desired seleno- and telluropyranones 144 are, however, often minor products in the reaction with formation of dihydroselenophenes and -tellurophenes 145 as major by-products (Equation 55). Acetylenic enol ethers 146 appear to be important intermediates in the formation of the desired seleno- and telluropyranones (Scheme 17) <1999JHC707>. Initial treatment of the l,4-pentadiyn-3-ones with sodium ethoxide in ethanol affords the isomeric mixture of enol ethers in high yield and these can then be made to react with the disodium selenide or telluride affording the seleno- and telluropyranones in very good yield without formation of the dihydroselenophene or -tellurophene by-products. 

The alternative to this 0,0-acetal formation is the sequence of addition and El reaction. As a matter of fact, this is familiar from the transformation of alcohols with carbonyl compounds, but only occurs in some (very rare) cases. This is illustrated by Figure 9.31 using acid-catalyzed transformations of ethanol with two /3-diketones as an example. Here, enol ethers, namely 3-ethoxy-2-cyclopentene-l-one and 3-ethoxy-2-cyclohexene-l-one, respectively, are... 

TrimethylsiIyloxy)furan may be considered as a special silyl enol ether in its reaction with IOB.BF3, followed by addition of ethanol, ( -functionalization occurred, with formation of 5-ethoxy-2(5//)-furanone [32] ... 

An interesting reaction between the bis phenyl iodonium triflate of acetylene and the silyl enol ether of acetophenone afforded an allene (PhCOCH=C=C=CHCOPh, 84%) [6], Also, alkynyl iodonium tosylates and carbon monoxide in methanol or ethanol, with palladium catalysis, furnished alkyne carboxylates [53]. 

Hydrogenation of ketones over platinum metals in alcoholic solvents, especially in methanol and ethanol, may be accompanied by the formation of acetals (and also hemiacetals and enol ethers) in the presence of a mineral acid and may lead to the formation of ethers, together with the formation of alcohols and hydrocarbons 98-100 The reactions involved under these conditions are shown in Scheme 5.4 for cyclohexanone. At an equilibrium in acidic methanol, acetals are present predominantly over hemiacetals for most ketones.101... 

Lipkowitz et al. observed that the hydrogenation of cyclic enol ether 1 to 2 over a 10% Pd-C in ethanol was accompanied by the formation of bicyclic acetals of the formula 3, of which the endo isomer was hydrogenolyzed to give 2 much more rapidly... 

Enol esters are much more labile to hydrogenolysis than enol ethers. Thus, 1-acetoxy-cyclohexene and ethyl 3-acetoxycrotonate are almost quantitatively hydrogenolyzed over Adams platinum in ethanol or acetic acid (eqs. 13.46 and 13.47).91 92... 

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