Of methylene groups to carbonyls

A possible mechanism of oxidation of methylene groups to carbonyl groups involves autoxidation (oxidation by molecular oxygen) at the benzylic position. Autoxidation of arylalkanes is a facile reaction with low activation energies for example, 6.0 kcal/mole for 1,1-diphenylethane and 13.3 kcal/mole for toluene. ... 

The oxidation of methylene groups to carbonyls is especially easy if the methylenes are flanked by two carbonyl groups. The methylene group in barbituric acid is oxidized to the keto group by chromium trioxide either directly [555] or after reaction with benzaldehyde [554] (equation 410). 

Selenium dioxide may be used for the oxidation of reactive methylene groups to carbonyl groups. An example is the oxidation of cyclohexanone to cyclohexane-1,2-dione (27). In the procedure, the reaction is carried out on camphor to give camphor... 

Selenium dioxide (SeOi) oxidation Selenium dioxide is an excellent oxidizing agent for the oxidation of allylic and benzylic C-H fragments to allylic or benzylic alcohol. It also oxidizes the aldehydes and ketones to 1,2-dicarbonyl compounds (i.e. oxidation of active methylene groups to carbonyl groups). 

Oxidations with chromic oxide encompass hydroxylation of methylene [544] and methine [544, 545, 546] groups conversion of methyl groups into formyl groups [539, 547, 548, 549] or carboxylic groups [550, 55i] and of methylene groups into carbonyls [275, 552, 553, 554, 555] oxidation of aromatic hydrocarbons [556, 557, 555] and phenols [559] to quinones, of primary halides to aldehydes [540], and of secondary halides to ketones [560, 561] epoxidation of alkenes [562, 563,564, and oxidation of alkenes to ketones [565, 566] and to carboxylic acids [567, 565, 569]. 

Sodium dichromate hydroxylates tertiary carbons [620] and oxidizes methylene groups to carbonyls [622, 623, 625, 626, 631] methyl and methylene groups, especially as side chains in aromatic compounds, to carboxylic groups [624, 632, 633, 634, 635] and benzene rings to quinones [630, 636, 637] or carboxylic acids [638]. The reagent is often used for the conversion of primary alcohols into aldehydes [629, 630, 639] or, less frequently, into carboxylic acids or their esters [640] of secondary alcohols into ketones [621, 629, 630, 641, 642, 643, 644] of phenylhydroxylamine into nitroso-benzene [645] and of alkylboranes into carbonyl compounds [646]. 

OXIDATION WITH p-NITROSODIMETHYLANILINE Oxidation of Activated Methylene Group to Carbonyl [986]... 

In addition to the utility of phosphonate anions and phosphorus ylides in the preparation of C-glycosides, a discussion of the related chemistry surrounding sulfur ylides is warranted. Unlike phosphorus ylides, sulfur ylides deliver methylene groups to carbonyls, thus forming epoxides. As shown in Scheme 7.44, Frechou et al. [152] exploited this chemistry in the formation... 

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... 

Riley oxidations. Oxidations of organic compounds with selenium dioxide, e.g., the oxidation of active methylene groups to carbonyl groups. 

Selenium dioxide, SeO, is ery poisonous (cf. p. I47), but is valuable particu larly for the oxidation of methylene ( CHs) groups to carbonyl ( CO) groups. 

The Knorr pyrrole synthesis involves the reaction between an a-amino ketone 1 and a second carbonyl compound 2, having a reactive a-methylene group, to give a pyrrole 3. The amine 1 is often generated in situ by reduction of an oximino group. 

In the presence of a very strong base, such as an alkyllithium, sodium or potassium hydride, sodium or potassium amide, or LDA, 1,3-dicarbonyl compounds can be converted to their dianions by two sequential deprotonations.79 For example, reaction of benzoylacetone with sodium amide leads first to the enolate generated by deprotonation at the more acidic methylene group between the two carbonyl groups. A second equivalent of base deprotonates the benzyl methylene group to give a dienediolate. 

Dibromoethane normally reacts with activated methylene groups to produce cyclopropyl derivatives [e.g. 25, 27], but not with 1,3-diphenylpropanone. Unlike the corresponding reaction of 1,3-dibromopropane with the ketone to form 2,6-diphenylcyclohexanone, 1,2-dibromoethane produces 2-benzylidene-3-phenyl-tetrahydrofuran and the isomeric 2-benzyl-3-phenyl-4,5-dihydrofuran via initial C-alkylation followed by ring closure onto the carbonyl oxygen atom (Scheme 6.2) [28],... 

In certain polyfluorinated cyclic compounds difiuoromethylene groups are hydrolyzed to carbonyl groups relatively easily.141 This is usually associated with the formation of cycloalkene intermediates, since the proximity of a C = C bond notably increases the reactivity of a difluoro-methylene group towards hydrolytic reactions. Thus, easy conversion of such groups to oxo groups has been observed in many cyclobutene derivatives. 2-Chloro-l,l,2-trifluoro-3-phenyl-cyclobutane is converted by potassium hydroxide into cyclobutene 1 and cyclobut-2-enone 2.141... 

The observation of DA and MVK in similar conditions point to a possible common intermediate. A working hypothesis may be outlined in reference to the analagous SeC>2 oxidation of methylene groups alpha to a carbonyl group (ref. 12). In this hypothesis the enolate anion of MEK becomes susceptible to attack by a surface V=0 species, with V in the 5+ or 4+ oxidation state, i.e.,... 

The Reduction Reactions. The object of the next three reactions (steps 4 to 6 in fig. 18.12a) is to reduce the 3-carbonyl group to a methylene group. The carbonyl is first reduced to a hydroxyl by 3-ketoacyl-ACP reductase. Next, the hydroxyl is removed by a dehydration reaction catalyzed by 3-hydroxyacyl-ACP dehydrase with the formation of a trans double bond. This double bond is reduced by NADPH catalyzed by 2,3-trans-enoyl-ACP reductase. Chemically, these reactions are nearly the same as the reverse of three steps in the j6-oxidation pathway except that the hydroxyl group is in the D-configuration for fatty acid synthesis and in the L-configuration for /3 oxidation (compare figs. 18.4a and 18.12a). Also remember that different cofactors, enzymes and cellular compartments are used in the reactions of fatty acid biosynthesis and degradation. 

Freshly prepared Mn02 is a useful reagent in organic chemistry and has been used in a large variety of oxidative transformations.311 These reactions involve the allylic oxidation of alkene to a,/3-unsaturated carbonyl compounds, the transformation of methylarenes to benzaldehyde and benzoic acid derivatives, the oxidation of secondary methylene groups to ketones, and the oxidation of alcohols to carbonyl compounds.311 The yields are generally fair to good. 

The attachment of a methyl or methylene group to a carbonyl group results in the C—H symmetric bending deformations becoming more intense and the bands appear at slightly lower frequency than normally. 

The 13C spectrum of crotonaldehyde (CH3 CH=CH CHO Fig. 3.52) provides a good example of the way in which the 13C chemical shift is determined both by the state of hybridisation of the carbon atom and the nature of the substituent. The four carbon atoms have markedly different chemical shifts. The methyl carbon appears at 3 17.1. It is shifted downfield slightly compared to the methyl carbon at the end of a chain of methylene groups as in 3-methylheptane (Fig. 3.41) and hex-l-ene (Fig. 3.51). The two alkenyl carbons appear at <5133.4 and 3 152.9. The effect of conjugation of the carbon-carbon double bond is that the (i-carbon is shifted further downfield. The carbon of the carbonyl group is sp2-hybridised and is directly bonded to an electronegative atom. It is shifted furthest downfield and appears at 3 192.2,... 

Approaches of type (i) include the Michael type addition of ester activated methylene groups to a,( -unsaturated carbonyls with subsequent cyclization to afford 277-pyran-2-ones <1984CHEC, 1996CHEC-II>. In this manner, 3-acylamino-277-pyran-2-ones are prepared by the reaction of (3-ethoxyvinyl ketones or P-(dimethylamino)vinyl ketones with iV-acylglycines (Scheme 138) <2005S1269, 2004HAC85>. 

Recently, the transition-metal-catalyzed addition of active methylene C-H bonds to electron-deficient olefins having a carbonyl, a nitrile, or a sulfonyl group has been extensively studied by several research groups. In particular, the asymmetric version of this type of catalytic reaction provides a new route to the enantioselective construction of quaternary carbon centers [88]. Another topic of recent interest is the catalytic addition of active methylene C-H bonds to acetylenes, allenes, conjugate ene-ynes, and nitrile C-N triple bonds. In this section, the ruthenium-catalyzed addition of C-H bonds in active methylene compounds to carbonyl groups and C-C multiple bonds is described. 

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