Dicarbonyl compounds dehydrogenation

A mixture of 1,4-dioxane and water is often used as the solvent for the conversion of aldehydes and ketones by H2Se03 to a-dicarbonyl compounds in one step (Eq. 8.117).331 Dehydrogenation of carbonyl compounds with selenium dioxide generates the a, (i-unsaturated carbonyl compounds in aqueous acetic acid.332 Using water as the reaction medium, ketones can be transformed into a-iodo ketones upon treatment with sodium iodide, hydrogen peroxide, and an acid.333 Interestingly, a-iodo ketones can be also obtained from secondary alcohol through a metal-free tandem oxidation-iodination approach. 

The reaction of phenols with alicyclic 1,3-dicarbonyl compounds in phosphorus oxychloride or sulfuric acid also leads to 3,4-fused coumarins (40JA2405). Dehydrogenation to the dibenzopyranone occurs on heating with sulfur or with palladium-charcoal (73CB62). 

This is a reaction of a-amino acids, in which they are oxidised to the corresponding aldehyde, giving off carbon dioxide, and ammonia is transferred to other components of the system, very little being liberated as such. The reaction is initiated by compounds, such as a-dicarbonyl compounds and their vinylogues, or compounds which can give rise to them readily, such as reductones by dehydrogenation or imino analogues by hydrolysis. The reaction may therefore be represented as follows ... 

The condensation of a, dicarbonyl compounds (49) with aj3-diamino compounds (50), which proceeds through the dihydropyrazine (51), has been much used for the synthesis of alkyl- and arylpyrazines (52). These reactions are usually carried out in methanol, ethanol, or ether in the presence of sodium or potassium hydroxide. The dihydropyrazines may be isolated, or oxidized directly to the pyrazine. Dehydrogenating agents that have been employed include oxygen in aqueous alkali (329), air in the presence of potassium hydroxide (330), sodium amylate in amyl alcohol (330a), alcoholic ferric chloride (24), and copper chromite catalyst at 300° (331) (see also Section 1). Pyrazines prepared by this method and modifications described below are listed in Table II.8 (2, 6, 24, 60, 80,195, 329-382) and some additional data are provided in Sections VI. 1 A, VlII.lA(l), and IX.4A(1). 

Selenium dioxide, Se02 (mp 315 °C, sublimes), and selenious acid, H2Se03, which is obtained by the evaporation of an aqueous solution of Se02 [507, 50S], are very selective oxidants. They are capable of mild dehydrogenation to form double bonds [375] and can oxidize alkenes and acetylenes to vicinal dicarbonyl compounds [509, 510] and allylic ethers to aldehydes [511]. The most important applications are conversions of alkenes into allylic alcohols [5i2] of benzylic, methyl, or methylene groups into carbonyl groups [513, 514, 5i5] and of carbonyl compounds into a-... 

The spectrum of applications of potassium permanganate is very broad. This reagent is used for dehydrogenative coupling [570], hydrox-ylates tertiary carbons to form hydroxy compounds [550,831], hydroxylates double bonds to form vicinal diols [707, 296, 555, 577], oxidizes alkenes to a-diketones [560, 567], cleaves double bonds to form carbonyl compounds [840, 842, 552] or carboxylic acids [765, 841, 843, 845, 852, 869, 872, 873, 874], and converts acetylenes into dicarbonyl compounds [848, 856, 864] or carboxylic acids [843, 864], Aromatic rings are degraded to carboxylic acids [575, 576], and side chains in aromatic compounds are oxidized to ketones [566, 577] or carboxylic acids [503, 878, 879, 880, 881, 882, 555]. Primary alcohols [884] and aldehydes [749, 868, 555] are converted into carboxylic acids, secondary alcohols into ketones [749, 839, 844, 863, 865, 886, 887], ketones into keto acids [555, 559, 590] or acids [559, 597], ethers into esters [555], and amines into amides [854, 555] or imines [557], Aromatic amines are oxidized to nitro compounds [755, 559, 592], aliphatic nitro compounds to ketones [562, 567], sulfides to sulfones [846], selenides to selenones [525], and iodo compounds to iodoso compounds [595]. 

Dimethyl sulfoxide (DMSO), (CH3)2SO, is a versatile reagent for the oxidation of alcohols to carbonyl compounds under gentle conditions. In addition to the previously mentioned dehydrogenations, it is capable of other oxidations acetylenes to a-diketones [997], alkyl halides to aldehydes 998, 999], tosyl esters to aldehydes [1000], methylene groups adjacent to carbonyl groups to carbonyls [1001, 1002], a-halocarbonyl compounds to u-dicarbonyl compounds [1003,1004,1005], aldehydes to acids [1006], and phosphine sulfides and selenides to phosphine oxides [1007]. 

The oxidation of a secondary alcoholic group in the presence of primary alcoholic groups by Acetobacter suboxydans converts adonit into adonose [1041]. The treatment of androstenediol and dehydroandrosterone with yeast yields A -androstenedione [1088]. Steroidal hydroxy ketones are dehydrogenated to dicarbonyl compound with CorynebacteriUlh simplex [1056] (see equations 446 and 447). Examples of oxidations of secondary alcohols to ketones are shown in equations 265-268. 

The use of an otherwise saturated 1,5-dicarbonyl compound does not lead directly to an aromatic pyridine, though it is easy to dehydrogenate the dihydro-heterocycle. 

A great variety of methods is available for the ring synthesis of pyridines the most obvious approach is to construct a 1,5-dicarbonyl compound, preferably also having further unsaturation, and allow it to react with ammonia, when loss of two mole equivalents of water produces the pyridine. 1,4-Dihydropyridines, which can easily be dehydrogenated to the fully aromatic system, result from the interaction of saturated... 

Ammonia reacts with 1,5-dicarbonyl compounds to give 1,4-dihydropyridines, which are easily dehydrogenated to pyridines. With unsaturated 1,5-dicarbonyl compounds, or their equivalents (e.g. pyrylium ions), ammonia reacts to give pyridines directly. 

From an Aldehyde, Two Equivalents of a 1,3-Dicarbonyl Compound and Ammonia Symmetrical 1,4-dihydropyridines, which can be easily dehydrogenated, are produced from the interaction of ammonia, an aldehyde and two equivalents of a 1,3-dicarbonyl compound, which must have a central methylene. 

Each of the diazines can be constructed from an appropriate source of two nitrogens and a dicarbonyl compound. In the case of pyridazines, the nitrogen source is, of course, hydrazine and this in combination with 1,4-dicarbonyl compounds readily produces dihydro-pyridazines, which are very easily dehydrogenated to the aromatic heterocycle. Pyrimidines result from the interaction of a 1,3-dicarbonyl component and an amidine (as shown) or a urea (giving 2-pyrimidones) or a guanidine (giving 2-amino-pyrimidines), without the requirement for an oxidation step. 

The main synthetic route to cyclopentapyrazines involves formation of the six-membered ring by condensation of appropriate 1,2-diamines and a-dicarbonyl compounds. For example, reaction of diacetyl with cyclopentane-1,2-diamine yielded the tetrahydro compound 2, which was dehydrogenated to the dihydroderivative 3. Suitable dehydrogenation methods include heating under reflux in xylene with palladium on charcoal or heating to 300° over copper chromite. Condensation of ethylenediamine or 1,2-propanediamine with cyclopentanediones such as 8 afforded tetrahydro compounds of formula 9, which on dehydrogenation with copper chromite at 300° afforded the dihydro derivatives 10. As expected, mixtures of isomers are formed when appropriate unsymmetrical starting materials are used. 

The Hantzsch synthesis of pyridine is a method of considerable scope and flexibility. In a condensation of four components, two molecules of a p-dicarbonyl compound react with an aldehyde and ammonia giving 1,4-dihydropyridines 165 which can be dehydrogenated to pyridines 166 ... 

Quinoxalines are obtained by cyclocondensation of 1,2-diaminoarenes with 1,2-dicarbonyl compounds or with a-halocarbonyl compounds followed by dehydrogenation of the dihydroquinoxalines 19 ... 

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