Oxidation with selenium dioxide

Ninhydrin (also named 1 2 3-triketoindane or 1 2 3-triketohydrindene hydrate) is prepared most simply from the inexpensive phthahc anhydride (I). The latter is condensed with acetic anhydride In the presence of potassium acetate to give phthalylacetlc acid (II) reaction of the latter with sodium methoxide in methanol yields 1 3-indanedionecarboxyhc acid, which is decomposed upon warming with dilute hydrochloric or sulphuric acid to indane-1 3-dione (or 1 3-diketohydrindene) (HI). Selenium dioxide oxidation of (III) afibrds indane-1 2 3-trione hydrate (ninhydrin) (IV). 

Furalazine, Acetylfuratrizine, Panfuran-S. Heating nitrovin in butanol or dimethylformamide at 100—130°C affords furalazine, 6-[2-(5-nitro-2-furanyl)ethenyl]-l,2,4-triazine-3-amine (34). An improved synthesis originates with 5-nitro-2-furancarboxaldehyde and acetone, proceeds through 4-(5-nitro-2-furanyl)-3-buten-2-one followed by a selenium dioxide oxidation to the pymvaldehyde hydrate, and subsequent reaction with aininoguariidine (35). Furalazine, acetylfuratrizine (36), and the A[-A/-bis(hydroxymethyl) derivative, Panfuran-S, formed from the parent compound and formaldehyde (37), are systemic antibacterial agents. 

Phenylsulfonyl)indole 330 was converted to a ketone by a set of standard reactions followed by the selenium dioxide oxidation of the resulting acetyl goup to the ketoaldehyde 332 (Scheme 101). Methylthiosemicarbazide hydroiodide reacted with 332 to the triazine 333 in 83% yield. As Diels-Alder reactions with 1 -pyrrolidinocyclohexene failed, 333 was first oxidized... 

Dimethylquinoxaline reacts with pyridine and iodine to form quinoxaline-2,3-bis(methylenepyridinium iodide) (55). Condensation of (55) with p-nitrosodimethylaniline in the presence of potassium carbonate yields the bis-(p-dimethylaminonitrone) (56) and this on acid hydrolysis gives quinoxaline 2,3-dialdehyde (57) in high over-all yield. The dialdehyde is also obtained by selenium dioxide oxidation of 2,3-dimethylquinoxaline. ... 

The preparation of Pans-1,2-cyclohexanediol by oxidation of cyclohexene with peroxyformic acid and subsequent hydrolysis of the diol monoformate has been described, and other methods for the preparation of both cis- and trans-l,2-cyclohexanediols were cited. Subsequently the trans diol has been prepared by oxidation of cyclohexene with various peroxy acids, with hydrogen peroxide and selenium dioxide, and with iodine and silver acetate by the Prevost reaction. Alternative methods for preparing the trans isomer are hydroboration of various enol derivatives of cyclohexanone and reduction of Pans-2-cyclohexen-l-ol epoxide with lithium aluminum hydride. cis-1,2-Cyclohexanediol has been prepared by cis hydroxylation of cyclohexene with various reagents or catalysts derived from osmium tetroxide, by solvolysis of Pans-2-halocyclohexanol esters in a manner similar to the Woodward-Prevost reaction, by reduction of cis-2-cyclohexen-l-ol epoxide with lithium aluminum hydride, and by oxymercuration of 2-cyclohexen-l-ol with mercury(II) trifluoro-acetate in the presence of ehloral and subsequent reduction. ... 

An alternative practical synthesis of triquinacene-2-carboxylic acid (as the dextrorotatory enantiomer) has l n described by Deslongchamps and Soucy Their protocol begins with hydroxy ketone 467 and passes via the 2-methyl derivative (Scheme XXXVIII). Selenium dioxide oxidation of the hydrocarbon provided the aldehyde which was further oxidized and then hydrolyzed to arrive at the add. 

Oxidation of 6-methylphenanthridines with potassium dichromate in acetic acid results in oxidative loss of the methyl group, the product being the phenanthridone (e.g. 67 Scheme 62) (61JCS3771). If a second methyl group is present it remains unchanged. Selenium dioxide oxidizes the 6-methyl group to the aldehyde. 

Solvent-free selenium dioxide oxidation of 5,6-diaminopyrimidin-4-one was reported to give the [l,2,5]selenadia-zolo[3,4-i/ pyrimidin-7-one <2004MI289> as shown in Scheme 76. The fused selenadiozole ring may be alternatively formed by reacting the diamine in Seheme 76 with H2Se03 <1996CHEC-II(7)489>. 

A chemical correlation of the (—)-methyl derivative 109 with the ( )-methylester 111 was possible by selenium dioxide oxidation of the former and subsequent silver... 

Oxidation of the sulfur- or selenium-bridged azepines (171 X=S or Se) with mercury(II) oxide in methanol yields ultimately the 4f/-azepine (68JCS(C)23ll) with hydrogen peroxide as oxidant, the sulfur compound furnishes the sulfoxide (171 X=SO). Selenium dioxide oxidation of 7,8-dimethyl-lf/-l-benzazepin-2-one affords the 2,3-dioxo derivative (173) that displays no evidence of enol tautomers or heteroaromaticity (7ici(L)1439). 

Methyl groups in the 2-, 4- or 6-position of pyrimidine are also more reactive. In addition to typical reactions such as condensation with benzaldehyde, selenium dioxide oxidation and halogenation, they can be converted into oximino groups by nitrous acid, and undergo Claisen condensation with (C02Et)2. In the reaction of 2,5-dimethylpyrimidine with benzaldehyde, only the electrophilic 2-methyl group reacts preferentially to yield the 2-styryl derivative (631). In quinazolines partial double bond fixation makes a methyl group in the 4-position more reactive than that in the 2-position. 

Scheme 2 shows Rapoport s synthesis [15]. The cinnamic acid derivative 3 prepared from m-methoxy benzaldehyde [20] was ethylated by diethyl sulfate to give ethyl cinnamate derivative 4, followed by Michael addition with ethyl cyanoacetate to afford compound 5. Compound 5 was converted to lactam 6 by the reduction of the cyano group and subsequent cyclization. Selective reduction of the lactam moiety of 6 was achieved by treatment with trimethy-loxonium fluorob orate followed by sodium borohydride reduction. Amine 8 was obtained by the reductive methylation of amine 7. Amine 8 was converted to compound 9 by methylene lactam rearrangement [21], followed by selenium dioxide oxidation to provide compound 10. Allylic rearrangement of compound 10 and subsequent hydrolysis gave compound 12. The construction of the decahydroisoquinoline structure began with compound 12,... 

Methylbenzoselenazole (28a) and chloral affords the alcohol (44). Hydrolysis of the latter yields j8-(2-benzoselenazolyl)acrylic acid (45) which can be oxidized to ben-zoselenazole-2-carbaldehyde (46) along with benzoselenazole-2-carboxylic acid (47 Scheme 16) (52JCS3197). Aldehyde (46) was obtained by selenium dioxide oxidation of (28a) (53CB888). 

In an alternative approach, good yields of tetraaryltetraazapentalenes (151) have been obtained by prolonged treatment of 3-benzoyl-4-arylazopyrazoles (152 R = COPh) with hot triethyl phosphite. This reaction may well occur via a carbene intermediate (152 R = CPh). In a similar cyclization selenium dioxide oxidation of the 3-benzylpyrazoles (152 R = CH2Ph) gives low yields of the heteropentalenes (151) (73CL455,74CL951). 

Selenium dioxide oxidizes CH3 to CHO (662 663) and this differentiates 2- and 4-methyls from 3-methyl, e.g., Scheme 85 <2003SC475>. Conversion of 2- and 3-alkylpyridines into chiral hydroxyalkyl derivatives can be achieved with the enzyme toluene dioxygenase from the mutant soil bacterium Pseudomonas putida in high ee <2002TA2201>. 

Selenium dioxide oxidation of isopulegol acetate (133 3R) and neoisopulegol acetate (133 35) is reported 223 allylic oxidation is consistent with the Sharpless mechanism but a different mechanism is proposed. 

Some 2-deoxy-analogues of rubrosterone have been reported.73 The synthesis commenced with a Bamford-Stevens reaction upon 3/3,17/3-diacetoxyandrost-5-en-7-one tosylhydrazone to yield the corresponding 5,7-diene. Successive chromic acid and selenium dioxide oxidation of this diene furnished the 2-deoxyrubrosterones (177 R1 = OAc, R2 = H, R3 = OH, X= 17/3-0Ac,H 5a-H) and (177 R = OAc, R2 = R3 = H, X = 17/3-OAc,H 5a-H) respectively. Alkaline hydrolysis of the latter derivative afforded an A-homo-B-nor-steroid (178). The rubrosterone (177 R1 = R2 = R3 = OH, X = O 5/3-H), which possesses antidiabetic activity, has been prepared by oxidative degradation of the cholestene (179), itself obtained from ecdy-sterone.74... 

The most useful application of 3 is its use in photochemical [2+2] cycloadditions with alkenes and alkynes at the carbon-carbon double bond to afford bicyclo[4.2.0]octane-2,5-diones and bicyclo[4.2.0]oct-7-ene-2,5-diones in good to excellent yield.6 Since selenium dioxide oxidation of the resulting adducts furnishes the corresponding 3-ene-2,5-diones, diketone 3 can be regarded as a 1,4-benzoquinone equivalent leading to [2+2] cycloadducts at the carbon-carbon double bond. 

Selenium-mediated allylic oxidations producing allylic alcohols have been discussed above however, in some cases oxidation proceeds further to give the a, -unsaturated carbonyl compounds directly, or mixtures of alcoholic and ketonic products. That the regioselectivity observed in these allylic oxidation reactions closely resembles that found in classical selenium dioxide oxidations is in accord with initial formation of the intermediate allylic alcohol before in situ oxidation to the carbonyl compound. This process was studied by Rapoport and was explained mechanistically as an elimination of the intermediate allylic selenite ester via a cyclic transition state, analogous to Ssi (rather than 5n20 solvolysis (Scheme 21). Of the two possible transition states (78) and (79), the cyclic alternative (78) was preferred tecause oxidation exclusively yields trans aldehydes. 

Dihydropyridazines have not been prepared by direct cycliza-tions reductions of pyridazines and oxidations of reduced pyridazines are known. 3,6-Diphenylp3n idazine is reduced with sodium and ethanol to the 1,2-dihydro derivative and the 1,2-dicarbethoxy analog is formed in a selenium dioxide oxidation of the corresponding 1,2,3,6-tetrahydro compound. 1-Carbethoxy- or 1,2-dicarbethoxy-1,2-dihydropyridazine was obtained similarly from an alkali treatment of 1,2-dicarbethoxyhexahydropyridazine. l,2-Dihydro-3,6-diphenylpyridazine is unstable and oxidizes to the parent pyridazine in the presence of air or on attempted acetylation. ... 

Among oxi tions producing allylic alcohols or their derivatives the modem variants of selenium dioxide oxidations are by far the most popular. Systems based on metal acetates, particularly palladium tri-fluoroacetate, can be very useful and are receiving increasing attention but the Kharasch-Sosnovsky reaction, once very common for allylic oxidation, is now rarely used. Sensitized photooxidation with singlet oxygen, a very well-known procedure, is still somewhat unpredictable and has periu K received less consideration than it deserves. 

Selenium dioxide oxidation of alkenes with a hydrogen in an a-position involves the formation of the allyl selenic ester (X = OH) by an ene reaction. [2,3] Sigmatropic rearrangement of the allyl selenic ester to the selenium(II) ester and its hydrolysis also resulted in the formation of allylic alcohols. The oxidation of alkenes with selenium dioxide is covered in Section D.4.10. 

Allylic oxidation of olefins is a reaction of considerable value in organic synthesis [18] and selenium dioxide itself or in combination with other cooxidants remains a highly predictable and reliable reagent to perform these reactions. Thus, selenium dioxide oxidation of (Z)-tributyltin 1-alkenylcarba-mates 46 constitutes the first successful example of such a conversion ever reported with an element other than hydrogen [19]. Namely, it was found that with the allylic stannanes 46a or 46b oxidation occurred smoothly within 15 min to deliver in good yields the expected corresponding allylic alcohols 47a and 47b, respectively (Eqs. 6 and 7). 

Benzimidazole (but not 1-methylbenzimidazole) is oxidized by permanganate, dichromate or hydrogen peroxide to imidazole-4,5-dicarboxylic acid, while napth-[l,2-d]- and -[2,3-d]-imidazoles also form products in which the heterocyclic ring remains intact, hence demonstrating its stability to these conditions. With lead peroxide benzimidazole is subject to an unusual oxidation as it forms (101), also the reaction product of lead dioxide and 2,2 -bibenzimidazolyl. In dioxane, selenium dioxide oxidizes 2-methylbenzimidazole to o-hydroxyacetanilide (66RCR122). 

Most usual oxidizing agents act normally with imidazole aldehydes and ketones but l-benzylimidazole-2-carbaldehyde is reportedly somewhat resistant to selenium dioxide oxidation. Reduction of ketone functions under Clemmensen and Wolfi-Kischner conditions is usually successful. Zinc dust and acetic acid reduce acetyl groups to a mixture of secondary alcohol and ethyl borohydride gives the alcohol exclusively (B-76MI40701). 

I2 DMSO, " MeRe03/H202, " as well as by electrooxida-A ruthenium complex with a small amount of trifluoroacetic acid converts internal alkynes to the a-diketone. Ozone generally oxidizes triple-bond compounds to carboxyhc acids (19-9), but a-diketones are sometimes obtained instead. Selenium dioxide (Se02) with a small amount of H2SO4 oxidizes alkynes to a-diketones as well as arylacetylenes to a-keto acids (ArC=CH ArCOCOOH). " ... 

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