Para-substituted acetophenones

The procedure reported here provides a convenient method for the a-hydroxylation of ketones which form enolates under the reaction conditions. The reaction has been applied successfully to a series of para-substituted acetophenones, 1-phenyl-1-propanone, 3-pentanone, cyclopentanone, cyclohexanone, cycloheptanone, cyclododecanone, 2-methyl cyclohexanone, 2-norbornanone and benzalacetone. In the case of a steroidal example it was shown that a carbon-carbon double bond and a secondary hydroxyl group are not oxidized. A primary amino function, as in the case of p-aminoacetophenone, is not affected.5 Similarly, a tertiary amino ketone such as tropinone undergoes the a-hydroxy at ion reaction.5... 

We have prepared two series of oximes and studied their association by the cryosoopic method in benzene solution. The first series was derived from acetone oxime by substituting one of the methyl groups by ethyl, isopropyl, iert-butyl, cyolohexyl or phenyl. The seoond series consisted of para-substituted acetophenone oximes. 

For example, Palmer and Fry oxidized para-substituted acetophenones-1-14C as shown in Equation 6.71 and compared these rates of oxidation with the... 

First, it was observed that substrates of lower basicity were hydrosilated by Ph3SiH much more rapidly than substrates of higher basicity. Thus, for the substrates benzaldehyde, acetophenone and ethylbenzoate, observed turnover numbers were 19, 45 and 637 h 1, respectively, while the measured equilibrium constants for adduct formation of these substrates with B(C6F5)3 were 2.1 X 104, 1.1 X 103 and 1.9 X 102. A similar inverse correlation between turnover number and equilibrium constant was observed for a series of para-substituted acetophenone derivatives, where much faster hydrosilation rates were observed for substrates with strongly electron withdrawing groups in the para position. Clearly, if activation of the substrate via adduct formation is important in the hydrosilation reaction, the opposite correlation between TON and Keq should be observed. 

The Willgerodt-Kindler reaction was studied for a series of para substituted acetophenones with different amines in different solvents. 

The example shows a sequential approach to the study of discrete variations. The Willgerodt-Kindler reaction was studied with a set of para substituted acetophenones, see Schema 9. As the reaction failed with strong electron-withdrawing substituents, the study was limited to include donor, alkyl, and halogen substituents. 

Placing two methyl groups ortho to the carbonyl of acetophenone should twist the phenyl out of the C=0 plane. The extent to which this affects gas- and solution-phase basicities of a series of para-substituted acetophenones is reported. ... 

If we limit the study in a first run to include only para substituted acetophenones, a series of eight systems as defined by the design in Fig 16.8 would be sufficient to afford a first check of the scope and limitations of the reaction. This would correspond to the systems summarized in Table 16.6. These systems were tested experunentally.[12]... 

In the initial set of test compounds five para substituted acetophenones were selected (Y = H, Me, Cl, MeO, Me2N) to span a variation along the "substrate" axis in the reaction space. 

Irradiation of the octahydroinden-2-yl derivatives of acetophenone (279) in both solution and the solid state afforded cA-hexahydro-1 //-indene (280) and a para-substituted acetophenone 281 via a Norrish type II cleavage process (Scheme 6.120).957 The Yang photocyclization reaction was not observed. 

The procedure reported here provides a convenient method for the a-hydroxylation of ketones which form enolates under the reaction conditions. The reaction has been applied successfully to a series of para-substituted acetophenones, 1-phenyl-1-propanone, 3-pentanone, cyclopentanone, cyclohexanone, cycloheptanone, cyclododecannne, 2-methyl cyclohexanone, 2-... 

It could be established that the hydrolysis of 1,3-dithianes derived from para-substituted acetophenones (4) is promoted by silver ions. Kinetic study using a 10% (vAf) diox-ane/water solvent shows that, when [Ag+] <0.2 mol L , the P-NO2, —Cl, —H and —Me derivatives hydrolyze via rapidly formed 1 Ag" " 1 dithiane complexes, but that the p-MeO derivative forms an unreactive 1 1 complex and hydrolyses via a 2 Ag+ 1 dithiane complex. Comparison of the kinetic parameters with those available for analogous open-chain SyS-acetals reveals that cycBzation leads to a substantial (>10 -fold) overall loss of reactivity and that this loss arises both from a lowering of acetal basicity toward Ag+ and from a slower rate of hydrolysis of the 1 1 complex. The implications for hydrogen ion-catalyzed hydrolysis of cyclic acetals have been discussed, as have the reasons for the lower reactivity of the cyclic acetals. ... 

Table 1 Stereoelectronic effect on the olefination of para-substituted acetophenones and...

Computational enzyme-substrate docking studies carried out on a CRED from Sporoholomyces salmonicolor showed that residues Met 242 and Gin 245 were in close proximity to the para-substituent of acetophenones in the substrate binding site. Site-saturation mutagenesis of Met 242 or Gin 245 (replacing these residues with all 19 other possible amino acids) and double mutation of both Met 242 and Gin 245 were carried out to enhance the enzyme s enantioselectivity toward the reduction of para-substituted acetophenones. The enantiopreference was inverted from R)- to (S)-configuration for three Gin 245 mutants that were obtained. Preference for the formation of (S)-enantiomeric alcohols was shown for four Met 242 mutant enzymes when compared to the wild-type enzyme Gin 245 and Met 242/Gln 245 double variations inverted the enantiopreference and affected the enantiomeric purity of the product alcohols. Residues 242 and 245 also exerted an effect on the catalytic activity of this GRED [23]. 

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