Acetals, unsaturated hydroxylation

Nickel on Mg oxide allows a rapid, smooth hydrogenation of allylic amines, at and unsaturated hydroxyl amine, 10, is selectively reduced to saturated hydroxylamine, 11, by hydrogenation over prereduced Pd-on-CaC03. The compound is totally reduced to methyl-n-heptylamine in acetic acid. 

The first few steps in an alternative scheme are analogous to those used to introduce a hydroxyl group at Cn in progestins in Chapter 6 (Scheme 6.18). Treatment of the 11 -oxopregnane (5-1) with acetic anhydride in the presence of mineral acids converts both ketones to their respective enol acetates the hydroxyl at C3 is also acetylated in the process (5-2) (Scheme 7.5). Oxidation of that intermediate converts the side chain unsaturation to an epoxide the enol ester in... 

Products of degradation products of photooxidation chain scissions, free radicals, carbonyl groups, acetic acid, sulfoacetic acid, benzoic acid, crosslinks, unsaturations, hydroxyl groups, sulfonic acid, SO ... 

I60C-Hydroxy Derivatives of Gorticoids and their Acetonides. The preparation of 16a-hydroxy-9a-fluoroprednisolone (48) from the 3,20-bisethylene ketal of hydrocortisone acetate (49) has been reported (73). The latter was dehydrated with thionyl chloride in pyridine to yield the 4,9(11),16-triene (50). The 16,17-unsaturated linkage was selectively hydroxylated with OsO /pyridine to yield the 16a,17a-diol (51), which was converted... 

Hydroxyl tion. Commercial lecithin can be hydroxylated at the unsaturated fatty acid chains by treatment with concentrated hydrogen peroxide and acids like lactic or acetic acid. 

Halogenation of the 7 position also proves compatible with good antiinflammatory activity. Construction of this compound, aclomethasone dipropionate (80), starts by introduction of the required unsaturation at the 6,7 position by dehydrogenation with DDQ (76). The highly hindered nature of the hydroxyl at position 17 requires that a roundabout scheme be used for formation of the corresponding ester. Thus treatment of 76 with ethyl orthoformate affords first the cyclic orthoformate This then rearranges to the 17 ester on exposure to acetic acid. Acylation of the 21 alcohol is accomplished in straightforward fashion with... 

N,O-acetal intermediate 172, y,<5-unsaturated amide 171. It is important to note that there is a correspondence between the stereochemistry at C-41 of the allylic alcohol substrate 173 and at C-37 of the amide product 171. Provided that the configuration of the hydroxyl-bearing carbon in 173 can be established as shown, then the subsequent suprafacial [3,3] sigmatropic rearrangement would ensure the stereospecific introduction of the C-37 side chain during the course of the Eschenmoser-Claisen rearrangement, stereochemistry is transferred from C-41 to C-37. Ketone 174, a potential intermediate for a synthesis of 173, could conceivably be fashioned in short order from epoxide 175. 

Sodium hydroxyalkanesulfonates may be determined in the presence of an unsaturated hydrocarbon, including sodium alkenesulfonate. The sulfonates are converted to the free sulfonic acids using a slight excess of 2,4-dinitrobenzene-sulfonic acid. The hydroxyl group of the sulfonic acid liberated is acetylated in ethyl acetate solution by a known excess of acetic anhydride. The unconsumed anhydride is hydrolyzed by a pyridine-water mixture and the acids titrated potentiometrically with standard sodium hydroxide solution. The hydroxy-alkanesulfonate content is calculated after correction for any traces of acidity or alkalinity in the original sample. 

As previously discussed, solvents that dissolve cellulose by derivatization may be employed for further functionahzation, e.g., esterification. Thus, cellulose has been dissolved in paraformaldehyde/DMSO and esterified, e.g., by acetic, butyric, and phthalic anhydride, as well as by unsaturated methacrylic and maleic anhydride, in the presence of pyridine, or an acetate catalyst. DS values from 0.2 to 2.0 were obtained, being higher, 2.5 for cellulose acetate. H and NMR spectroscopy have indicated that the hydroxyl group of the methy-lol chains are preferably esterified with the anhydrides. Treatment of celliflose with this solvent system, at 90 °C, with methylene diacetate or ethylene diacetate, in the presence of potassium acetate, led to cellulose acetate with a DS of 1.5. Interestingly, the reaction with acetyl chloride or activated acid is less convenient DMAc or DMF can be substituted for DMSO [215-219]. In another set of experiments, polymer with high o -celliflose content was esterified with trimethylacetic anhydride, 1,2,4-benzenetricarboylic anhydride, trimellitic anhydride, phthalic anhydride, and a pyridine catalyst. The esters were isolated after 8h of reaction at 80-100°C, or Ih at room temperature (trimellitic anhydride). These are versatile compounds with interesting elastomeric and thermoplastic properties, and can be cast as films and membranes [220]. 

After prolonged degassing of a large batch of PPG, analyses showed that its hydroxyl, unsaturation, and water contents were 0.97 meq/g, 0.033 meq/g, and 0.0035%, respectively. The hydroxyl content was determined by an acetylation method, carried out with acetic anhydride (10). The amounts of unsaturation and water were determined by the mecuric acetate and Karl Fischer methods (10), respectively. The obtained analytical results indicate that the number-average molecular weight of the dihydroxy material is 2062, provided its molecular weight is arbitrarily assumed to be twice that of the monohydroxy material, and that the mole fraction of the monohydroxy poly (propylene oxide) is 0.066. This value corresponds to a number-average functionality of 1.93 for the PPG. 

Other functional groups which have a heteroatom rather than a hydroxyl group capable of directing the hydrogenation include alkoxyl, alkoxycarbonyl, carboxylate, amide, carbamate, and sulfoxide. The alkoxy unit efficiently coordinates to cationic iridium or rhodium complexes, and high diastereoselectivity is induced in the reactions of cyclic substrates (Table 21.3, entries 11-13) [25, 28]. An acetal affords much lower selectivity than the corresponding unsaturated ketone (Table 21.3, entries 14 and 15) [25]. 

Olefination of the Aldehyde 178 using a stabilized Wittig reagent followed by protecting group chemistry at the lower branch and reduction of the a,p-unsaturated ester afforded the allylic alcohol 179 (Scheme 29). The allylic alcohol 179 was then converted into an allylic chloride and the hydroxyl function at the lower branch was deprotected and subsequently oxidized to provide the corresponding aldehyde 161 [42]. The aldehyde 161 was treated with trimethylsilyl cyanide to afford the cyanohydrin that was transformed into the cyano acetal 180. The decisive intramolecular alkylation was realized by treatment of the cyano acetal 180 with sodium bis(trimethylsi-lyl)amide. Subsequent treatment of the alkylated cyano acetal 182 with acid (to 183) and base afforded the bicyclo[9.3.0]tetradecane 184. 

DL-cordycepose it was obtained in two steps, namely, epoxidation to 55 and mild, acid hydrolysis of the epoxide 55. For the synthesis of 53, substrate 54 was first brominated to the 2-bromo compound 57, which was dehydrobrominated with lithium amide, to afford the unsaturated acetal 58. cis-Hydroxylation of 58 under typical conditions then afforded 53. 

The method is simple, and has the additional virtue of great versatility. The requisite ally lie alcohol can be prepared via the Favorskii reaction of a 20-ketopregnane, or via ethoxyacetylene addition to a 17-ketoandrostane. Additional functional groups may be present prior to these reactions or introduced into the A17(20)-compound later. An aromatic A-ring, A-ring unsaturated ketones and the 11 /1-hydroxyl group are all stable to the oxidative attack on the A17(20)-olefln, and the 21-acetate is not hydrolyzed during the reaction. 

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