Aryl aliphatic ketones, reactions

The procedure described is an example of a more general synthetic method for the direct conversion of ketones into cyanides. " The reaction has been carried out successfully with acyclic and cyclic aliphatic ketones, including numerous steroidal ketones and aryl-alkyl ketones. The conversion of diaryl or highly hindered ketones such as camphor and )3,j8-dimethyl-a-tetralone requires the use of a more polar solvent. The dimethoxyethane used in the present procedure should be replaced by dimethyl sulfoxide. ... 

Thus the triplet states of the two diastereomers react to yield different product distributions although this effect is far less marked for the triplet than for the singlet reaction, which is essentially stereospecific. The singlet reaction could be either concerted or due to an extremely shortlived biradical. Since the product distributions of the triple reaction of these two diastereomers are different, it is clear that cleavage must occur before complete equilibration. Thus the lifetime of the aliphatic ketone derived biradical must be considerably shorter than the corresponding biradical derived from an aryl ketone. 

Kinetic and thermodynamic parameters have been measured for the chlorination of simple aliphatic and aryl alkyl ketones in strong acid media by chloramine-B (sodium A-chlorobenzenesulfonamide). Catalysis of the monochlorination of acetaldehyde in anhydrous carbon tetrachloride by trichloroacetic acid, and by hydrogen chloride, are reported. IR and UV spectroscopy have been used to probe the reaction of acetaldehyde with trichloroacetic acid in carbon tetrachloride. " Two cyclic 1 1 intermediates have been identified, and are found to be in equilibrium. 

Cyano-substituted ethylenes react in a different way with aliphatic ketones. The orientation of photochemical cycloaddition (4.661 is the opposite of that found for electron-rich alkenes, and the reaction is highly stereoselective (4.69) in the early stages. These processes involve the formation and subsequent decay of an excited complex (exciplex) from the (n,n ) singlet state of the ketone and the alkene. Aryl ketones undergo intersystem crossing so efficiently that such a singlet-state reaction is rarely observed, but the reaction of a benzoate ester with an electron-rich alkene 14.70 rnay well be of this type, with the ester acting as electron-acceptor rather than electron-donor. 

For the reactions described so far in this section, the ketone substrates have lowest excited states that are (n.ii ) in character aliphatic ketones may react by way of the singlet or the triplet state, and aryl ketones normally through the triplet because intersystem crossing is very efficient. The efficiency of photochemical hydrogen abstraction from compounds such as alcohols or ethers is very much lower if the ketone has a lowest (Ji,n triplet state, as does I - or 2-acetylnaphthalene (CmH-COMe). However, all aryl ketones, regardless of whether their lowest triplet state is fn,Jt l or (Jt.Ji ), react photochemically with amines to give photoreduction or photoaddition products. A different mechanism operates (4.38), that begins... 

The versatility of 5-nitrosopyrimidines in pteridine syntheses was noticed by Pachter (64MI21603) during modification of the Timmis condensation between (262) and benzyl methyl ketone simple condensation leads to 4-amino-7-methyl-2,6-diphenylpteridine (264) but in the presence of cyanide ion 4,7-diamino-2,6-diphenylpteridine (265) is formed (equation 90). The mechanism of this reaction is still uncertain (63JOC1187) it may involve an oxidation of an intermediate hydroxylamine derivative, nitrone formation similar to the Krohnke reaction, or nucleophilic addition of the cyanide ion to the Schiff s base function (266) followed by cyclization to a 7-amino-5,6-dihydropteridine derivative (267), oxidation to a quinonoid-type product (268) and loss of the acyl group (equation 91). Extension of these principles to a-aryl- and a-alkyl-acetoacetonitriles omits the oxidation step and gives higher yields, and forms 6-alkyl-7-aminopteridines, which cannot be obtained directly from simple aliphatic ketones. 

Azide addition to an active methylene compound in the presence of a base involves a triazoline intermediate that aromatizes to a triazole the reaction is a well-established route to 1//-triazoles6-8 bearing a 5-amino or hydroxy substituent and an aryl or carbonyl-containing function in the 4-position. The proposed triazoline intermediates have been detected in the reaction of azides with aliphatic ketones (see Scheme 64, Section Il,A,3,f). 

Sml2 can effectively promote the intermolecular reductive dimerisation of aldehydes or ketones giving rise to symmetrical diols.7 9 Generally, arylalde-hydes and aryl ketones couple within seconds in THF at room temperature. Aliphatic aldehydes and ketones react considerably more slowly several hours are required for the aldehydes, whereas for ketones reaction times of 24 h are usually needed. Nevertheless, these slower couplings can be greatly accelerated by the addition of additives such as HMPA.10... 

Many reactions are not affected by the presence of a nearby benzene ring yet others depend on the aromatic ring to promote the reaction. For example, the Clemmensen reduction is occasionally used to reduce aliphatic ketones to alkanes, but it works best reducing aryl ketones to alkylbenzenes. Several additional side-chain reactions show the effects of a nearby aromatic ring. 

Muratake et al. reported the intramolecular a-arylation of ketones [55,56]. Thus, polycyclic compounds are readily obtained from aromatic keto-bromides and keto-triflates (Eq. 16). Bromo-amides can give the corresponding cycliza-tion products (Eq. 17) [52]. Related intramolecular vinylation reactions to give aliphatic polycyclic compounds have also been reported (Eq. 18) [57,581. The intramolecular cyclization of aromatic halo-ketones under carbon monoxide, which proceeds by mechanism C, gives the corresponding a-acylated products (Eq.l9) [321. 

Esters have been prepared in 63-73% yields from several simple cycloalkyl and aryl alkyl ketones by reaction at room temperature with per-benzoic acid. The larger radical of the ketone appears as the alcohol fragment of the ester. Cyclic ketones are oxidized by potassium persulfate and sulfuric acid to esters from which o>-hydroxy aliphatic esters are obtained upon hydrolysis and reesterification. Peracetic acid in acetic anhydride converts salicylaldehyde to o-hydroxyphenyl formate (88%). ... 

The addition of hydrogen cyanide to carbonyl compounds gives a-hydroxy cyanides (cyanohydrin synthesis). The reaction is reversible, and the extent of the cyanohydrin formation depends upon the structure of the Carbonyl compound. The equilibrium highly favors the formation of aliphatic and alicyclic cyanohydrins however, aryl alkyl ketones react to a lesser extent, and diaryl ketones, not at all. The reaction may be accomplished by mixing the carbonyl compound with liquid hydrogen cyanide in the presence of a basic catalyst. The equilibrium... 

Many water-insoluble ketones, aliphatic, aryl aliphatic, and heterocyclic, respond favorably to treatment with ammonium formate or formamide to form with subsequent hydrolysis the primary amines. A typical procedure for the synthesis of a-phenylethylamine (66%) from acetophenone and ammonium formate has been applied to many other ketones (65-84%). Nuclear alkoxyl, halo, and nitro groups are not disturbed. The reaction with formamide as the reducing agent is catalyzed by ammonium formate, ammonium sulfate, or magnesium chloride. ... 

A Variety of ketones may be made using cadmium alkyls (50-70%). In the preparation of alkyl aryl ketones, reaction of the aliphatic rather than the aromatic anhydride is preferred. Keto acids result when phthalic anhydride or dimethylsuccinic anhydride (60-70%) is used. 

Aliphatic and aryl aliphatic amino ketones are made by the amination of the halogenated carbonyl compounds, - e.g., dimethylaminoacetone (74%), l-diethylamino-2-pentanone (79%), and a-methylaminopropio-phenone (57%). It is noteworthy that this system may undergo a rearrangement, viz., ArCOCH,Br+ (C,H,),NH— ArCHjCON(C,H5)a (45%). The reaction of a-halo ketones with arylamines is even more complex. Examples of the formation of a-aminoaldehydes by this method are few. However, the same results may be achieved by the amination of the halo acetals with subsequent hydrolysis. "... 

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