The use of selenium dioxide

Selenium dioxide was first employed in steroid dehydrogenation for the direct formation of 12-ketones in corticoid synthesis. This dehydroge- 

A constant problem in the use of selenium dioxide is the removal of selenium-containing contaminants in the above example it was found necessary to treat the product with chromic acid to remove materials which otherwise poisoned subsequent hydrogenation steps. 

Selenium dioxide can be used to introduce A -double bonds into 3-ketones in a similar fashion as DDQ, although it is not such a versatile reagent. 

Reactions with selenium dioxide appear to be sensitive to the medium employed. Refluxing t-butanol is the usual solvent, often with small amounts of acid present, although pyridine has been introduced with acid labile substrates. 

References to recent examples may be found in the reviews of Owyang and Walker. Selenium dioxide has been superseded in most instances by DDQ, which generally gives higher yields and fewer purification problems. 

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Reviews of the use of selenium dioxide in organic oxidations are written by R. P. Linstead, Annual Reports of the Chemical Society, 1937, page 238, and G. W, Watkins and C. W. Clarke, Chemical Rexnews, 36 (1945), 235. 

Allylic Alcohols. The direct allylic oxidation of alkenes by selenium dioxide has been discussed in a review of modern organoselenium chemistry. The use of selenium dioxide in pyridine" allows oxidation of allylic positions to be performed in the presence of acid-labile groups (acetals, THP ethers) that are normally at least partially cleaved by SeOa. 

With methyl-3-nitropyridine iV-oxides, use of selenium dioxide results in complete oxidative demethylation (80TL2433). In isoquinoline methyl groups at positions 1 and 3 are efficiently oxidized to the corresponding aldehyde with selenium dioxide. 

Nicotinic acid and nicotinamide, members of the vitamin B group and used as additives for flour and bread enrichment, and as animal feed additive among other applications, are made to the extent of 24 million pounds (nearly 11 million kilograms) per year throughout the world. Nicotinic acid (pyridine-3-caiboxylic acid), also called niacin, has many uses. See also Niacin. Nicotinic acid is made by the oxidation of 3-picolme or 2-mcthyl-5-cthylpyridine (the isocinchomcnc acid produced is partially deearboxylated). Alternatively, quinoline (the intermediate quinolinic acid) is partially deearboxylated with sulfuric add in the presence of selenium dioxide at about 300° C or with nitric acid, or by electrochemical oxidation. Nicotinic acid also can be made from 3-picoline by catalytic ammoxidation to 3-cyanopyridine, followed by hydrolysis. 

Commercial selenious acid (129 g., 1 mole) may be used in place of the mixture of selenium dioxide and water. 

A solution of 15 g 3,4,5-trimethoxy propiophenone in a little absolute alcohol is stirred in, under warming in a bath (of saturated chlorine calcium solution), alternating with larger pieces sodium and alcohol, whereby at least 75 g sodium and 600 ccm absolute alcohol is necessary. After the sodium disappears in the mixture, is diluted with water (2L), acidified with hydrochloric acid, the alcohol distilled and then extracted with ether. Evaporation of the ether leaves 9 g of Divarin dimethylether. Source Asahina 1936 For use of selenium dioxide to crack off para methoxy group see page 180 in Amphetamine Syntheses Industrial. 

Removal of selenium and selenious acid. Use of selenium dioxide or selenious acid as an oxidant is attended with the difficulty of freeing the reaction mixture of colloidal selenium and of excess oxidant. A procedure for the oxidation of paraldehyde to glyoxal and isolation of the product as the bis-bisulfite addition compound specifies use of lead acetate as more satisfactory for the removal of selenious acid than sulfur dioxide, provided that the solution is kept cool and a large excess is avoided. A... 

Oxidation. Use of selenium dioxide for the oxidation of reactive methylene groups to carbonyl groups was introduced by H. L. Riley, Morley, and Friend. A procedure developed by H. A. Riley and Gray for the preparation of phenyl-glyoxal calls for heating a solution of acetophenone in dioxane with either selenious acid, or equivalent amounts of selenium dioxide and water, and stirring the mixture... 

N-Methylsolasodine (282) was isolated from Solarium nigrum [634]. N-Hydroxysolasodine (283) was isolated from roots of Solanum robustum, and its structure determined using HRMS, one- and two-dimensional H and 13c NMR, and catalytic hydrogenation to the saturated derivative [635]. A-hydroxysolasodine was synthesized from solasodine by hydrogen peroxide oxidation in the presence of selenium dioxide [636],... 

Smith and Holm487 have reported the preparation of an unsaturated acid from an unsaturated aldehyde by use of hydrogen peroxide in the presence of selenium dioxide. 3-Chloropropionaldehyde is converted into 3-chloro-... 

One method for the a-iodination of ketones calls for the assistance of selenium dioxide. Heterocyclization. A new route to a-iodo boronic acids consists of iodoethe-rification. p-Iodobutenolides that are useful for carbon chain extension at the P-position (via Pd-catalyzed coupling) are readily accessible by iodolactonization of allenic acids ... 

Selenadiazoles 176, which are readily formed by the action of selenium dioxide on semicarbazones of a-methylene ketones , decompose thermally to acetylenes (equation 25)106 the Lalezari reaction, is widely applicable. Recent uses are illustrated by the synthesis of four medium-sized cycloalkadiynes cyclonona-l,5-diyne (177), cyclodeca-1,5-diyne (178), cycloundeca-l,5-diyne (179) and cycloundeca-l,6-diyne (180) (Scheme 5) . Strained cycloalkynes with additional double bonds, e.g. the cyclododeca-3,7,11-triene-l-yne 181, have also been obtained by the Lalezari method. Compound 181 isomerizes spontaneously to the bicyclic hydrocarbon 182 . ... 

A second new synthesis of squalene utilizes the observation that selenium dioxide oxidation of gem-dimethyl olefins or cis- and truns-allylic alcohols yields stereospecifically traus-aj3-unsaturated aldehydes. The olefin (4) or a mixture of cis- and truus-diols (5) were transformed by use of selenium dioxide, followed by reduction, into the truns-allylic diol (6). The corresponding bromide (7) was used to alkylate two moles of the ylide from trans-geranyltributylphosphonium bromide leading eventually to all-traus-squalene in 46% yield [from the diol (6)]. Protection of one of the p-alcohol groups of (6) as the tetrahydropyranyl ether opens the possibilities of unsymmetrical coupling and the introduction of specifically labelled fragments. 

The synthesis of 1,2,3-selenadiazoles by the action of selenium dioxide on semi-carbazones, and their pyrolysis to the corresponding acetylenes (see Vol. 2, p. 720 Vol. 3, p. 673) has been applied to several examples incorporating steroid, phenanthrenyl, fluorenyl, and naphthyl residues. The method may prove useful as a route to pharmacologically active 17-ethynyl-steroids. A large number of aryl-1,2,3-selenadiazoles as well as the three isomeric 4-[(2-, 3-, and 4-)pyridyl]-... 

Reactions of enamines with selenium dioxide gave low yields of enamino ketones (J8). Aromatization of cyclohexanone derived enamines eould be largely prevented by the use of aeetonitrile as solvent for the reaction. Even then, yields were eonsiderably below the limit of 50%, imposed by the generation of an equivalent of water. 

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