Derivatives ketones

Derivative Formation. Hydrogen peroxide is an important reagent in the manufacture of organic peroxides, including tert-huty hydroperoxide, benzoyl peroxide, peroxyacetic acid, esters such as tert-huty peroxyacetate, and ketone derivatives such as methyl ethyl ketone peroxide. These are used as polymerization catalysts, cross-linking agents, and oxidants (see Peroxides and peroxide compounds). 

Some unsaturated ketones derived from acetone can undergo base- or acid-catalyzed exothermic thermal decomposition at temperatures under 200°C. Experiments conducted under adiabatic conditions (2) indicate that mesityl oxide decomposes at 96°C in the presence of 5 wt % of aqueous sodium hydroxide (20%), and that phorone undergoes decomposition at 180°C in the presence of 1000 ppm iron. The decomposition products from these reactions are endothermic hydrolysis and cleavage back to acetone, and exothermic aldol reactions to heavy residues. 

Isophorone. Isophorone (3,5,5-trimethyl-2-cyclohexen-l-one) is a cycHc a,P-unsaturated ketone derived from the trimeri2ation of acetone. It has a light yellow color and a disagreeable camphoraceous odor. It has the tendency to discolor and form residues on prolonged storage. Isophorone is completely miscible with organic solvents, and other physical properties are Hsted ia Table 1. 

Methyl amyl ketone, derived from the crossed aldol condensation of -butyraldehyde and acetone, is used predominandy as a high soHds coatings solvent. It is also employed as a replacement for the very toxic 2-ethoxyethyl acetate [111 -15-9J. 

The basic carbohydrate molecule possesses an aldehyde or ketone group and a hydroxyl group on every carbon atom except the one involved in the carbonyl group. As a result, carbohydrates are defined as aldehyde or ketone derivatives of polyhydroxy alcohols and their reaction products. A look at the formula for glucose shows that it contains hydrogen and oxygen atoms in the ratio in which they are found in water. The name carbohydrate... 

One of the more important approaches to 1-azirines involves a similar base-induced cycloelimination reaction of a suitably functionalized ketone derivative (route c. Scheme 1). This reaction is analogous to route (b) (Scheme 1) used for the synthesis of aziridines wherein displacement of the leaving group at nitrogen is initiated by a -carbanionic center. An example of this cycloelimination involves the Neber rearrangement of oxime tosylate esters (357 X = OTs) to 1-azirines and subsequently to a-aminoketones (358) (71AHC-(13)45). The reaction has been demonstrated to be configurationally indiscriminate both syn and anti ketoxime tosylate esters afforded the same product mixture of a-aminoketones... 

A large variety of methods is applicable to the formation of isolated double bonds. This permits selection of reagents compatible with other functionality present. Alcohol dehydration, ester elimination and other nonreductive p eliminations are the most common methods. Reductive elimination of halo-hydrins, vic-dihalides, etc., and of a variety of ketone derivatives has also been used. 

A special application of heteroaromatic acylation via a modified Dakin-West reaction leads to a-fluoro ketone derivatives [50] (equation 30) Such fluoro ketones have been successfully used as enzyme inhibitors in modern bioorganic chemistry [5, 6]... 

Alkylation of enamino ketones occurs on oxygen, as would be expected from the site of protonation. Thus 4-N-pyrrolidino-3-penten-2-one (47) gave N-(2-ethoxy-2-penten-4-ylidene)-pyrrolidinium iodide (48) on alkylation with ethyl iodide (22), and the enamino ketones derived from 5,5-... 

The reaction of enamines with perfluoro olefins has also been reported (62). Dienamines have been reported to react with ethyl acrylate at C2 to give the alkylated a,j8-unsaturated ketone derivative. Thus the dienamine (44) gave 71 in 50 % yield on reaction with ethyl acrylate in dioxane for 40 hr (63). 

In the reaction with enamino ketones derived from dimedone (e.g., 49) p-toluenesulfonyl chloride gives the chloroiminium cation (138) isolated as the perchlorate. This indicates that initial O sulfonation is followed by addition of chloride ion and subsequent expulsion of tosylate (42) in a manner similar to the trichloroacetyl chloride reaction with 49 (Section IV.A). 

Other interesting synthetic applications of the ketone-derived enamine alkylation are found in the monomethylation of steroid enamines (249), extension of the benzylation reaction (250) to a ferrocene derivative (251), the use of a-bromoesters (252) and ketones (252) or their vinylogues (25J), in the syntheses of alantolactone (254-256), isoalantolactone (257), and with a bridged bis-enamine (258). The use of bifunctional alkylating agents is also seen in the introduction of an acetylenic substituent in the synthesis of the characteristic fragrant constituent of jasmine (259), the synthesis of macrocyclic ketolactones (260), the use of butyrolactone (261), and the intermolecular or intramolecular double alkylations of enamines with dihalides (262). 

From the addition reaetions of acrolein- to aldehyde-derived enamines, aminotetrahydropyrans have been obtained. On heating, these products rearranged to enaminoaldehydes in examples where the initial enamine was disubstituted (320,321). The addition of acrolein to ketone derived enamines has been applied to syntheses of heterocyclic and bridged bieyclic compounds (301,321-323). 

On the other hand y-pyrones or 1,3-diketones could be obtained from the reactions of ketone derived enamines with diketene 423-426). The addition of dimethyl ketene dimer to aldehyde or ketone derived enamines produced cyclohexanediones 425,426). 

The condensation of sulfonyl chlorides with enamines (452,453) derived from aldehydes and ketones has led to four-membered-ring sulfones, presumably through such intermediates (454-464). Open sulfonation products have also been obtained, particularly from ketone-derived enamines and from a-disubstituted sulfonyl chlorides. 

The formation of a-acetoxyketones by oxidation of enamines with thallic acetate has been studied in detail (27) and found to be of preparative value (80 % yields) particularly in five- and six-membered-ring ketone derivatives. Enamines of linear or seven-membered-ring ketones were oxidized also, but at very much slower rates. Enamines of aldehydes with a-hydrogen substituents underwent self-eondensations during the oxidation reactions. Lead tetraacetate was less satisfactory as an oxidizing agent. 

While carboxylate anions do not add to the imonium function of ketone derived enamines, such as morpholinocyclohexene, when these are combined with carboxylic acids (38), the addition of thiophenol or benzyl mercaptan leads to a-aminothioethers (509,510). 

From the reactions of sulfur and carbon disulfide with cyclic ketone-derived enamines (570-573) 3H-l,2-dithiole-3-thiones were obtained, whereas the addition of carbon disulfide to other enamines gave a-dithio-pyrones (574), through initial dimerization of the enamine. 

Nal, CeCl3 7H20, CH3CN, rt, 0.5-21 h, 84-96% yield. Chemoselective cleavage of ketone derivatives is observed in the presence of aldehyde derivatives, and enone ketals are cleaved in the presence of simple ketone ketals. 

Quazepam (88) has a highly fluorinated sidechain so as to make this tranquilizer resistant to dealkylation. It also incorporates a lipid-solubilizing 2-thione moiety. The synthesis begins with bi aryl ketone derivative by ] -al kylation with 2,2,2-trifluoroethyltriclate to give 86. 

The ketone derivatives of the pseudo-ionone are converted under similar conditions into ketone-derivatives of the ionone. The pure ionone corresponds to the formula CjjHjjO, it boils under a pressure of 12 mm. at a temperature of about 128° 0., its specific weight is 0-935, and its index of refraction mD = 1-507. 

Hydrogenation of epoxides lends itself well to both synthetic applications and mechanistic studies. The reaction is complex, for either carbon-oxygen bond may break with or without inversion of configuration, and the product may contain deoxygenated products (92,93) as well as ketones derived by isomerization (26). The reaction is especially sensitive to both catalyst and environment (74). 

Catalytic cyclopropanation of alkenes has been reported by the use of diazoalkanes and electron-rich olefins in the presence of catalytic amounts of pentacarbonyl(rj2-ris-cyclooctene)chromium [23a,b] (Scheme 6) and by treatment of conjugated ene-yne ketone derivatives with different alkyl- and donor-substituted alkenes in the presence of a catalytic amount of pentacarbon-ylchromium tetrahydrofuran complex [23c]. These [2S+1C] cycloaddition reactions catalysed by a Cr(0) complex proceed at room temperature and involve the formation of a non-heteroatom-stabilised carbene complex as intermediate. 

The mechanism for aldehyde-derived enamines involves a Michael-type 1,4-addition of the enamine to the alkenylcarbene complex to generate a zwit-terionic intermediate which evolves to the final product by cyclisation. On the other hand, ketone-derived enamines react through an initial 1,2-addition to the carbene carbon to generate a different zwitterionic intermediate. Then, a [l,2]-W(CO)5 shift-promoted ring closure produces a new intermediate which, after elimination of the metal moiety, furnishes the corresponding cyclopen-tene derivatives (Scheme 30). 

The most popular reagent for the formation of aldehyde and ketone derivatives is 2,4-dinitrophenylhydrazine which forms hydrazones containing strong chromophores. 

In a reaction very much like 16-19, oximes can be prepared by the addition of hydroxylatnine to aldehydes or ketones. Derivatives of hydroxylamine, for example, H2NOSO3H and H0N(S03Na)2, have also been used. For hindered ketones, such as hexamethylacetone, high pressures (e.g., 10,000 atm) may be necessary. " ... 

For other methods of fragmentation of an a,p-epoxy ketone derivatives, see Mac Alpine, G.A. Warkentin, J. Can. J. Chem., 1978, 56, 308, and references cited therein. 

The first synthesis of stable 3-hydroperoxy-sultams (24) which are a new class of sultam with oxidising properties, was reported. The synthesis involved oxidation of the isothiazolium salts (23) with hydrogen peroxide in acetic acid. Reduction of (24) with aqueous sodium bisulphite afforded the corresponding novel 3-hydroxysultams whereas thermolysis in ethanol resulted in the elimination of water to give 3-ketone derivatives, which are versatile as dieneophiles <96T783>. 

CARBOHYDRATES ARE ALDEHYDE OR KETONE DERIVATIVES OF POLYHYDRIC ALCOHOLS... 

On the basis of these results and Damiano s report [28], Darcel et al. described an iron-catalyzed hydration of terminal alkynes using catalytic amounts of iron(III) chloride (10 mol%). The reaction selectively leads to the corresponding methyl ketone derivatives (Scheme 11) [29]. Iron(II) species such as FeCl2 or Fe(OAc)2 were not able to promote the reaction, the starting phenylacetylene remained unchanged after several days at 75°C. 

Synthesis of 2-alkyl- or 2-aryl-substituted benzo[b]furans has been reported, involving a CuITMEDA complex which catalyzes the transformation of readily available ketone derivatives into the corresponding benzofurans in good-to-excellent yields in water (Eq. 6.13).29... 

Preparation of the requisite side chain starts by alkylation of ethyl acetoacetate with 1,3-dibromopen-tane the initially formed bromoketone (shown as the enol 97) undergoes O-alkylation under the reaction conditions to give the dihydropyran 98. Reaction of that masked hydroxy ketone derivative with hydrogen... 

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