Ketones, with Aryl aliphatic

The classical aldol addition commonly uses a basic catalyst. However, the condensation reaction of various ketones with aryl aldehydes under basic conditions in water gave the expected aldol products along with the dehydration compounds. The presence of surfactants led mainly to dehydration products, whereas the use of a water/dioxane two-phase system gave good yields of aldol products with reactive aliphatic aldehydes. 

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. ... 

The Schmidt reaction of ketones works best with aliphatic and alicyclic ketones alkyl aryl ketones and diaryl ketones are considerably less reactive. The reaction is only seldom applied to aldehydes as starting materials. The hydrazoic acid used as reagent is usually prepared in situ by treatment of sodium azide with sulfuric acid. Hydrazoic acid is highly toxic, and can detonate upon contact with hot laboratory equipment. 

Aldehydes and ketones are similar in their response to hydrogenation catalysis, and an ordering of catalyst activities usually applies to both functions. But the difference between aliphatic and aromatic carbonyls is marked, and preferred catalysts differ. In hydrogenation of aliphatic carbonyls, hydrogenolysis seldom occurs, unless special structural features are present, but with aryl carbonyls either reduction to the alcohol or loss of the hydroxy group can be achieved at will. 

Reduction of aryl alkyl ketones with 78 was quantitative and (- )-/V-meth-ylephedrine was recovered with no loss in rotatory power. High optical yields were obtained with linear aliphatic chains in the ketone, but branching a to the carbonyl group lowered the optical yields significantly. Reduction of aliphatic methyl ketones with 78 at 0°C gave (S)-carbinols in low optical yield (14 to 46%). 

When arylhydrazones of aldehydes or ketones are treated with a catalyst, elimination of ammonia takes place and an indole is formed, in the Fischer indole synthesis.515 Zinc chloride is the catalyst most frequently employed, but dozens of others, including other metal halides, proton and Lewis acids, and certain transition-metals have also been used. Arylhydrazones are easily prepared by the treatment of aldehydes or ketones with phenylhydrazine (6-2) or by aliphatic diazonium coupling (2-7). However, it is not necessary to isolate the arylhy-drazone. The aldehyde or ketone can be treated with a mixture of phenylhydrazine and the catalyst this is now common practice. In order to obtain an indole, the aldehyde or ketone must be of the form RCOCH2R (R = alkyl, aryl, or hydrogen). 

Alkyl aryl ketimines were reduced with up to 99% ee (Scheme 8) [24]. The high enantioselectivity was not affected by the E Z ratio of the imines. For example, a 1.8 1 E Z mixture of the N-propylimine of 4 -methoxy-3-methyIbuty-rophenone was converted to the desired product in 97% optical yield. Hydrosilylation of the N-propylimine of cyclohexyl methyl ketone with a substrate to Ti molar ratio of 2,000 1 was completed to give the product in 98% ee [24]. N-Benzylimine of 2-octanone, a simple aliphatic ketimine, was reduced with 69% optical yield. The reduction of W-benzyl-l-indanimine gave the corresponding amine in 92% ee (Scheme 9) [24]. 

Bis[4-methoxyphenyl] dicyanomethylidene tellurium did not react with benzaldehyde3. Dibutyl ethoxyearbonylmethylidene tellurium and aliphatic aldehydes, aromatic aldehydes, cycloalkanones, dialkyl ketones, alkyl aryl ketones, and diphenyl ketone combine to yield a,/ -unsa turated carboxylic acid esters predominantly in the ( )-form4. Dibutyl cyanomethylidene and dibutyl benzoylmethylidene tellurium react similarly with benzal-dehydes and ketones5. 

In principle, the synthesis can be realized as a one-pot process treatment of ketones with hydroxylamine in KOH-DMSO following interaction of the formed ketoximes with acetylene. Various pyrroles with alkyl, cycloalkyl, aryl and hetaryl substituents, as well as pyrroles condensed with aliphatic macrocycles, terpenic and steroid structures, together with their vinyl derivatives now become available. 

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. ... 

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. "... 

Aryl aldehydes condense with aliphatic aldehydes in the presence of benzoylfor-mate decarboxylase and thiamin diphosphate to give an a-hydroxy ketone with god enantioselectivity. ° ... 

Nevertheless, chemical reactions between imines and electrophilic reagents have revealed that imine-enamine tautomerization exists and that the enamine tautomers are the reactive species which undergo the reactions . For example, imines 12 prepared from aliphatic amines and a variety of ketones react with aryl azides to afford triazolines 14 in good yields, On heating or in the presence of catalytic amounts of an acid, triazolines 14 are converted to triazoles 15 in a process which may proceed via rearrangement and a deamination pathway (equation 4). Formation of 14 demonstrates clearly the existence of imine-enamine tautomerism during the reaction ... 

Photoreduction of aliphatic ketones may involve both singlet and triplet excited states, but the quantum yield for product formation via singlet is usually low because other competing processes, such as radical pair recombination, are involved. The rapid intersystem crossing (ISC) in aryl ketones (Section 2.1.6) allows triplet reactivity. Ketones with n,7t lowest triplets, having an unpaired electron localized in an n-orbital on oxygen, are far more reactive than those with k.k lowest triplets.863... 

Thorough kinetics studies of the chlorination of aliphatic, alicyclic, and arylalkyl ketones with CBT were carried out by Indian workers (82PIA921). Kinetic measurements were performed using aqueous acetic acid and the addition of HC104 and NaCl. In the presence of mineral acid the reaction is first order in ketone and acid and zero order in CBT. A large kinetic isotopic effect was observed (for acetone kHlkD = 6.6). Addition of chloride ion causes some changes in the reaction order they become first order in CBT, 0.6 in ketone, and 0.2 in chloride ion. The rate constant for chlorination of substituted acetophenones correlate with a constants for substituents in the aryl ring (p is -0.57). On the basis of these data the mechanism in the absence and in the presence of chloride ion was developed. 

Formaldehyde is an exception and is nearly completely hydrated in aqueous solution. Unhindered aliphatic aldehydes are approximately 50% hydrated in water. Aryl groups disfavor hydration by conjugative stabilization of the carbonyl group. Ketones are much less extensively hydrated than aldehydes. Aldehydes and ketones with highly electronegative substituents such as trichloroacetaldehyde and hexafluoroacetone are extensively hydrated. a-Dicarbonyl compounds, such as biacetyl and ethyl pyruvate, are also significantly hydrated. Table 7.4 gives the for a number of carbonyl compounds. Data on other compounds are available in Table 3.23. 

Dioxans - Several syntheses of this ring are notable. In a modification of the Prins reaction, self-condensation of aliphatic aldehydes with styrene has given 4-phenyl-1,3-dioxans [such as ( 195)] in which the alkyl group is in the equatorial position.203 Good yields of the 1,3-dioxin-4-ones (196 R1 and R2 alkyl or aryl) have been obtained by reaction of aldehydes or ketones with diketene and Aliquat 336 (MeN[ (CH2 bMe] 3C1). 20 Condensation of aryl aldehydes with the diol (197) also gave good yields of the... 

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