Oxidation with manganese dioxide

Manganese dioxide is capable of oxidizing alcohols to ketones or aldehydes. The reaction proceeds via a radical intermediate (see below), producing MnO (which is Mn +) as the byproduct. Manganese dioxide is an important reagent in organic synthesis since it oxidizes primary and secondary alcohols to the aldehyde or ketone, respectively, in neutral media.This reaction was discovered by Ballet al when they precipitated manganese dioxide and used it to convert vitamin A (94) to retinal (95) in 80% yield. 49 

There are several ways to prepare this reagent, and its oxidizing power is strongly influenced by the method of preparation. 48 One of the more common methods involves precipitation of Mn02 from a warm aqueous 

Manganese dioxide oxidizes allylic and benzylic alcohols faster than primary saturated alcohols, but primary and secondary allylic alcohols react at about the same rate. This use of manganese dioxide is particularly important.i Oxidation of benzylic alcohols is also facile and a secondary benzylic alcohol is oxidized faster than a primary saturated alcohol. The secondary benzylic alcohol group in 102 was oxidized to give aryl ketone 103 (94% yield) in preference to reaction at the primary aliphatic hydroxyl. 

Allylic alcohols can react with Mn02 under certain conditions to give the conjugated acid or ester (in alcoholic solvents). When indole aldehyde (104) was treated with Mn02 in the presence of NaCN and methanol, for example, a 75% yield of methyl ester (105) was ohtained.i63 

The purpose of cyanide in this oxidation is to convert the conjugated aldehyde to a conjugated ester. In a related reaction using HCN, Corey showed that HCN/CN reacts with a conjugated aldehyde to form a cyanohydrin such as 106. Subsequent oxidation with Mn02 gave the cyanoketone, 107, which reacted with the alcoholic solvent (methanol) to give the methyl ester. 

Cinnamyl alcohol (5 g, 0.037 mol) is stirred for 30 min with a suspension of 50 g (0.57 mol) of active manganese dioxide (Procedure 7) in 250 mL of carbon tetrachloride. The mixture is filtered, and the filtrate is evaporated. The residue is treated with a solution of 7.5 g (0.067 mol) of semicarbazide hydrochloride and 9 g (0.066 mol) of sodium acetate trihydrate in aqueous ethanol. The mixture is heated to 60 °C and kept at room temperature for 2 h. The semicarbazone of cinnamaldehyde, mp 212-215 °C, is obtained in 71.5% yield. 

A solution of 1 g (0.0058 mol) of c/s-9,10-decalindiol in 50 mL of dichloro-methane is stirred at room temperature with 20 g of active manganese dioxide for 1 h. The mixture is filtered through Celite (diatomaceous earth), and the filtrate is evaporated in a rotary evaporator under vacuum generated by a water aspirator. 

The residue is distilled to give 0.9 g (90%) of 1,6-cyclodecanedione, mp 92-95 °C, on crystallization from acetone. 

---

Laudanosine contains four methoxyl groups. By exhaustive methyla-tion it yields trimethylamine and laudanosene (tetramethoxy-o-vinyl-stilbene), CH2=CH—C6H2(OCH3)2—CH=CH—C6H3(OCH3),. On oxidation with manganese dioxide and sulphuric acid it furnishes, in addition to the interesting by-product 2 3 6 7-tetramethoxy-9 10-dihydroanthracene, veratraldehyde and 4 5-dimethoxy-2 )3-methyl-... 

The alcohol 172 obtained by reaction of 86 with ethynyl magnesium bromide on oxidation with manganese dioxide gave the ketone 17361 Glaser coupling of the ketone 173 gave an equimolar mixture of the two acyclic diketones 170 and 174. 

Several total syntheses of antirhine (11) and 18,19-dihydroantirhine (14) have been developed during the last decade. Wenkert et al. (136) employed a facile route to ( )-18,19-dihydroantirhine, using lactone 196 as a key building block. Base-catalyzed condensation of methyl 4-methylnicotinate (193) with methyl oxalate, followed by hydrolysis, oxidative decarboxylation with alkaline hydrogen peroxide, and final esterification, resulted in methyl 4-(methoxycar-bonylmethyl)nicotinate (194). Condensation of 194 with acetaldehyde and subsequent reduction afforded nicotinic ester derivative 195, which was reduced with lithium aluminum hydride, and the diol product obtained was oxidized with manganese dioxide to yield the desired lactone 196. Alkylation of 196 with tryptophyl bromide (197) resulted in a pyridinium salt whose catalytic reduction... 

The diphenyl derivative 388, R = R = Ph, has an absorption band at 1495 cm S which has been assigned to the carbonyl group. This assignment could be questioned. The following chemical reactions of the compound 388, R = R = Ph, may be noted (a) Raney nickel desulfurization followed by oxidation with manganese dioxide yields dibenzyl ketone,(b) hydrazine yields 3,5-diphenyl-4-hydroxypyrazole (390), (c) phenylhydrazine yields PhCH2COCPh=NNHPh," (d)... 

Furthermore, Marshall et al. developed the extractable MBF tracer 7 -[ F] fluoro-6, 7 -dihydrorotenone (p F]FDHR) [72]. p F]FDHR is a derivative of the neutral and lipophilic lead compound rotenone that binds to the complex I of the mitochondrial electron transport chain [73-76]. It was prepared from 7 -tosyl-oxy-6, 7 -dihydroroten-12-ol (DHR-ol-OTos) in two steps. After nucleophilic substitution of DHR-ol-OTos with p F]fluoride, the intermediate was oxidized with manganese dioxide to yield the target compound [ F]FDHR (Fig. 11). 

The pyrimidine synthesis was therefore changed to the alkynyl ketone route as the appropriate precursors could be formed under much milder conditions. Thus, treatment of the chloro aldehyde 1002 with ethynyl Grignards or lithium species at low temperature, followed by mild oxidation with manganese dioxide, gave the desired chloro alkynyl ketones 1003, which could be successfully converted to the pyrimidine products 1004, by condensation with substituted guanidines, without displacement of the chlorine atom <2003X9001, 2005BMC5346>. 

The modified cephalosporin ceftobiprole (31-8), yet another compound that contains a double bond at the ring carbon, though in this case with a rather complex extended side chain, has shown activity in the clinic against some strains of multidrug resistant bacteria. The synthesis starts with the weU-precedented acylation of the cephalosporin (31-2), available in several steps from the commercially available 7-acetoxy cephalosporanic acid, with the activated thiadiazole carboxylic acid (31-1). The hydroxyl group in the product (31-3) is then oxidized with manganese dioxide to afford the corresponding aldehyde (31-4). This product is then condensed with the fcw-pyrrolidyl phosphonium salt (31-5), itself protected with the... 

Native urine should be protected from light and stored at -20°C until processed. Oxidized urine sample can be stored at room temperature, but light protection is still recommended. Two procedures for the oxidation of urine (and other samples) are used (1) oxidation with manganese dioxide (Mn02) under acidic conditions, and (2) oxidation with iodine (iodine/potassium iodide, I2/KI) under acidic and basic conditions. The Mn02 oxidation method is a routine method used to quantify total pterins (fully oxidized neopterin, monapterin, biopterin, primapterin, isoxanthopterin, and pterin) the I2/KI method is used according to Fukushima and Nixon [11] for the differential oxidation of pterins and quantification of BH4. Total biopterin represents the sum of BH4, BH2, and fully oxidized biopterin. Under acidic conditions BH4 and BH2 are oxidized to biopterin, while under basic conditions only BH2 is oxidized to... 

It has been claimed in a recent paper that oxidation with manganese dioxide, followed by rearrangement with alkaline zinc sulfite, gives better results and avoids the necessity of irradiating the products to insure rapid and total development of fluorescence.269... 

Arylazoarylimines (527), with a methyl or ethyl group ortho to the imine function (prepared by oxidation with manganese dioxide of arylaminohydrazones from anilines (525) and chlorohydrazones... 

L-Gulono-l,4-]actone (21) was converted383 into 1 by the procedure shown in Scheme 11. When 21 was treated with benzaldehyde-hy-drogen chloride, 74 was isolated in >65% yield.384 On oxidation with manganese dioxide, compound 74 gave 75 in 70-90% yield on hydrolysis with 70% acetic acid-water, 75 afforded 1 in 70% yield. That this is one of the few syntheses of 1 which does not have the cycliza-tion of 28 or 29 as its last step is noteworthy. Under different conditions of lysis, (methanolic hydrogen chloride), 75 is converted into 29, not 1. 

Catalytic reduction of thiopyrylium salts under forcing conditions yields tetrahy-drothiopyrans, but oxidation with manganese dioxide of the unsubstituted thiopyrylium cation (first obtained by Pettit [100]) affords thiophene-2-carbaldehyde in a reaction without analogy to pyrylium salts [101], Like a- and y-benzylic positions in pyrylium salts, methyl(ene) groups of alkyl substituents in thiopyrylium cations are usefully acidic and as such the corresponding anhydrobases may be trapped by various nucleophiles. 

The 1,2-disubstituted ferrocene (13) on treatment with hydrochloric acid gives 14 which can be oxidized with manganese dioxide to give 15.9... 

In the second, the use of diazopropane is avoided the alcohol (250) is converted to the pyrazole (251) by a two step sequence of reaction with hydrazine in acetic acid and then oxidation with manganese dioxide. Photolysis then leads cleanly to the cyclopropene, without any interference by cyclisation of an intermediate carbene to the alcohol group the product is hydrogenated directly, the conversion of (251) to (252) occurring in 94% yield. Elimination of the elements of water leads to m-chrysanthemic acid in good overall yield 175) ... 

Protopine has been isolated from Bocconia frutescens,110 Fumaria judaica,111 F. schleicheri,112 and Papaver bracteatum,146 cryptopine from F. schleicheri,112 and allocryptopine from B. frutescens110 and Zanthoxylum nitidum.141 The protopine ring-system has been prepared from tetrahydrobenzindenoazepines (75) by photo-oxidation to the amides (76) followed by reduction with lithium aluminium hydride and re-oxidation with manganese dioxide.148-150 The tetrahydrobenzindenoazepines have been prepared from A-chloroacetyl-/ -phenylethylamines (73) by cyclization to the lactam (74) followed by reaction with a benzyl bromide and phosphorus oxychloride. -Protopine (77 R R2 — CH2)148 and fagarine II (77 R1 = R2 = Me)149 have been synthesized in this way. 

The ferrous ion is traditionally re-oxidized with manganese dioxide or sodium chlorate, but Caro s acid has also been introduced for this application.263 Under these conditions, Caro s acid is more efficient than hydrogen peroxide. 

---