Hydroxy aldehydes benzene

Hydrogenation is effected in a steel shaking autoclave with a copper insert of 500 ml capacity. The ketone or aldehyde (0.25 mole) and copper chromite catalyst (4g)184 are introduced. For hydroxy aldehydes, anhydrous methanol (100 ml) is also added, to prevent formation of resinous products. For aromatic ketones the initial pressure of hydrogen is 300-340 atm, but for hydroxy aldehydes and hydroxy ketones 220-240 atm suffice. When alcohol is used, the temperature is kept at 200-250° until the pressure remains constant when no alcohol is used, a temperature of 180-195° suffices for reduction to the hydrocarbon. When hydrogenation is complete, the mixture is washed from the vessel with methanol or benzene, filtered from the catalyst, and worked up as usual. 

Oxime ethers derived from hydroxy aldehydes, upon conversion to their phenyl thionocarbonate esters, undergo radical cyclizations resulting in the formation of carbocycles. For example, an oxime ether obtained from D-glucose is converted into its phenyl thionocarbonate ester at C-5 and, upon heating in benzene in the presence of tributyltin hydride, affords cyclopentanes in 93% yield as a 62 38 mixture of two diastereomers (eq 7). In general, only low to modest stereoselectivity between the newly formed stereocenters is observed in a number of substrates examined. 

Apparently the role of methanol is to intercept unstable species which otherwise tend to polymerize or rearrange. The methoxy peroxide (72) can be isolated in crystalline form if desired, but it is preferable to treat the methylene dichloride solution at 0° with zinc dust and acetic acid until the mixture shows a negative potassium iodide test. The resulting crude seco-aldehyde (73) is then cyclized to (74) by stirring with neutral alumina in benzene at room temperature for 3 hr. ° Wechter has recently reported a number of transformations of a 5yS-hydroxy-6yS-formyl-B-norpregnane prepared in 8% yield by photolysis and hydrolysis of a 5a-hydroxy-6 -azidopregnane. 

The intermediacy of dipolar species such as 186 has been demonstrated by reaction of enamines with 2-hydroxy-1-aldehydes of the aromatic series (129). The enamine (113) reacts in benzene solution at room temperature with 2-hydroxy-1-naphthaldehyde to give the crystalline adduct (188) in 91 % yield. Oxidation with chromium trioxide-pyridine of 188 gave 189 with p elimination of the morpholine moiety. Palladium on charcoal dehydrogenation of 189 gave the known 1,2-benzoxanthone (129). 

Besides simple alkyl-substituted sulfoxides, (a-chloroalkyl)sulfoxides have been used as reagents for diastereoselective addition reactions. Thus, a synthesis of enantiomerically pure 2-hydroxy carboxylates is based on the addition of (-)-l-[(l-chlorobutyl)sulfinyl]-4-methyl-benzene (10) to aldehydes433. The sulfoxide, optically pure with respect to the sulfoxide chirality but a mixture of diastereomers with respect to the a-sulfinyl carbon, can be readily deprotonated at — 55 °C. Subsequent addition to aldehydes afforded a mixture of the diastereomers 11A and 11B. Although the diastereoselectivity of the addition reaction is very low, the diastereomers are easily separated by flash chromatography. Thermal elimination of the sulfinyl group in refluxing xylene cleanly afforded the vinyl chlorides 12 A/12B in high chemical yield as a mixture of E- and Z-isomers. After ozonolysis in ethanol, followed by reductive workup, enantiomerically pure ethyl a-hydroxycarboxylates were obtained. 

Reformatsky reaction. Tetrahydropyranyl esters are recommended for use in Rcformatsky reactions. They are formed from a-bromo acids in quantitative yield In dry benzene without need of an acid catalyst and they arc readily hydrolyzed by dilute hydrochloric acid. The Reformatsky reaction is generally conducted in THF at a temperature below 10". The reaction is more rapid if the zinc is activated with a trace of HgCI2. Yields of -hydroxy acids arc generally 70-90% when aldehydes are used, hul usually somewhat lower with ketones. 

A closely related synthesis of /8-hydroxy esters is provided by the Refor-matsky reaction. This synthesis starts with an aldehyde or ketone, RCOR, and an a-bromo ester, such as ethyl bromoethanoate. Zinc in a nonhydroxylic solvent (usually benzene) transforms the bromo ester into an organozinc compound, which then adds to the aldehyde or ketone carbonyl. Hydrolysis produces the /3-hydroxy ester ... 

Other aromatic ketones undergo photocyclization to form oxygen heterocycles. Methyl o-benzyloxyphenylglyoxylate (400) is converted in high yield into a mixture of the isomers (401 and 402).415 The stereochemistry of the cyclization is both solvent- and temperature-dependent, the former isomer (401) being formed almost exclusively in nonpolar solvents such as heptane or benzene, and in each case an excited triplet appears to be involved. The related aldehyde, O-benzylsalicylaldehyde (403), is similarly converted into cis-2-phenyl-3-hydroxy-2,3-dihydrobenzofuran (404), but in much lower yield a second product may possibly be the tram isomer.410... 

In basic chemicals, nitrile hydratase and nitrilases have been most successful. Acrylamide from acrylonitrile is now a 30 000 tpy process. In a product tree starting from the addition of HCN to butadiene, nicotinamide (from 3-cyanopyridine, for animal feed), 5-cyanovaleramide (from adiponitrile, for herbicide precursor), and 4-cyanopentanoic acid (from 2-methylglutaronitrile, for l,5-dimethyl-2-piperidone solvent) have been developed. Both the enantioselective addition of HCN to aldehydes with oxynitrilase and the dihydroxylation of substituted benzenes with toluene (or naphthalene) dioxygenase, which are far superior to chemical routes, open up pathways to amino and hydroxy acids, amino alcohols, and diamines in the first case and alkaloids, prostaglandins, and carbohydrate derivatives in the second case. 

The formylation of phenols with the electron-rich olefin to give imidazolidin-2-yl-phenols is very selective and avoids mixtures of o- and p-isomers which are frequently obtained by methods commonly employed for the synthesis of phenolaldehydes. Para substitution of the cyclic aminal group in the phenol is preferred. If the p-position is blocked or sterically hindered, the reaction proceeds via the ortho- aminals to salicylaldehydes. Incorporation of more than one aldehyde group in the benzene nucleus is often achieved with hydroxy- and aminophenols. 

Aldol cyclization. Exposure of the hydroxy ketone 1 to excess potassium t-butoxide and benzophenone in refluxing benzene provides the o,/S-unsaturated ketone 2 directly/ This transformation involves a modified Oppenauer oxidation followed by aldol closure of the resulting keto aldehyde. The product serves as an intermediate in the synthesis of Elaeocarpus alkaloids. 

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