Substituent effects ketones

Dubois and co-workers (119,410-415) characterized alkyl (R) substituent effects in simple and sterically congested alkanes, alkenes, carboxylic acid derivatives, ketones, amines, alcohols, and so on by the use of topological parameters XR ... 

Alkyl- and aryl-hydrazones of aldehydes and ketones readily peroxidise in solution and rearrange to azo hydroperoxides [1], some of which are explosively unstable [2], Dry samples of the p-bromo- and p-fluoro-hydroperoxybenzylazobenzenes, prepared by oxygenation of benzene solutions of the phenylhydrazones, exploded while on filter paper in the dark, initiated by vibration of the table or tapping the paper. Samples were later stored moist with benzene at —60°C to prevent explosion [3], A series of a-phenylazo hydroperoxides derived from the phenyl-or p-bromophcnyl-hydrazones of acetone, acetophenone or cyclohexanone, and useful for epoxidation of alkenes, are all explosive [4], The stability of several substituted phenylazo hydroperoxides was found to be strongly controlled by novel substituent effects [5],... 

However, the ready distortion of the ar-electron system provides an additional mechanism whereby the charge dispersal can reach the substituents. The greater substituent effects in ketones compared to the alcohols are therefore equally consistent with the loss of an oxygen nonbonding electron. Unsaturated substituents which can conjugate with the carbonyl double bond do not have the expected large effect in reducing... 

In fact, a similar intramolecular cyclisation was studied by Reusch [11] and he found a remarkable methyl substituent effect on the aldol equilibrium. Starting from the cis-decalones 25 (easily prepared from the Wieland-Miescher ketone), in which the angular methyl group prevents isomerisation to the more stable trans-decalone, it was found that other methyl groups may exert profound but less... 

Aldehydes are generally more reactive than ketones in nucleophiUc addition reactions due to steric and electronic reasons. Sterically, the presence of two relatively large substituents in ketones hinders the approach of nucleophile to carbonyl carbon than in aldehydes having only one such substituent. Electronically, aldehydes are more reactive than ketones because two alkyl groups reduce the electrophUicity of the carbonyl carbon more effectively than in former. 

Structures have been determined for [Fe(gmi)3](BF4)2 (gmi = MeN=CHCF[=NMe), the iron(II) tris-diazabutadiene-cage complex of (79) generated from cyclohexanedione rather than from biacetyl, and [Fe(apmi)3][Fe(CN)5(N0)] 4F[20, where apmi is the Schiff base from 2-acetylpyridine and methylamine. Rate constants for mer fac isomerization of [Fe(apmi)3] " were estimated indirectly from base hydrolysis kinetics, studied for this and other Schiff base complexes in methanol-water mixtures. The attenuation by the —CH2— spacer of substituent effects on rate constants for base hydrolysis of complexes [Fe(sb)3] has been assessed for pairs of Schiff base complexes derived from substituted benzylamines and their aniline analogues. It is generally believed that iron(II) Schiff base complexes are formed by a template mechanism on the Fe " ", but isolation of a precursor in which two molecules of Schiff base and one molecule of 2-acetylpyridine are coordinated to Fe + suggests that Schiff base formation in the presence of this ion probably occurs by attack of the amine at coordinated, and thereby activated, ketone rather than by a true template reaction. ... 

Methyl hydrazones of a wide range of aldehydes and ketones (380) undergo addition-cyclization to give 1,2,4,5-tetrazines (382) via 381 (216-219). Substituent effects on the ring-chain tautomerism between 381 and 382 were studied by NMR spectroscopy. 

The following discussion is divided into three subsections the ketone chromophore (Section 4.4,1.1.), for which configurational assignments are based on the effect of ring dissymmetry and substitution pattern on the rotatory power of the n-rt transition. For conjugated chro-mophores (Section 4.4.1.2.) it is both the helicity of the chromophore and the vicinal substituent effect that determines the rotatory power of the 71-71 transition. Finally, the versatile stereochemical method, exciton chirality method (Section 4.4.2.), is based on the chiral interaction between the electric dipoles of the allowed transitions in two or more chromophores. 

The rates of sodium borohydride reduction of the ketones (46) in propan-2-ol have been measured (78JCS(P2)1232). The strategy was to vary X keeping Y = H, and then to vary Y with X = H. This permitted direct comparisons to be made of transmission of substituent effects through the aromatic rings to the same reaction centre. It was concluded that the... 

Inclusion of the different ketones in Silicalite was achieved as described previously (14,15), using 2,2,4-trimethylpentane (isooctane) as a solvent for the ketones. In our study of substituent effects we have used 120 mg of ketone per gram of Silicalite in all inclusion attempts. The quantities used would yield samples in which up to 60% of the void volume of Silicalite (0.19 mL/g) could be occupied. The actual yields (and therefore the efficiency of inclusion) were determined by microanalysis, and the results are listed in Table I. 

In accord with the above, substituent effects in 2-arylcyclopropanone hemiketals indicate that initial conversion to the parent ketone takes place prior to a C2—C3 ring opening. 16> Although hemiketal-ketone equilibration is slow under neutral conditions, ketone formation and hence cleavage through 130 is accelerated in acid. 

Substrate substituent effects on activity and enantioselectivity have been investi- gated in the enzymatic reduction of aryl ketones, using 24 recombinant ketoreduc-tases.308... 

The ruthenium-catalyzed addition of C-H bonds in aromatic ketones to olefins can be applied to a variety of ketones, for example acetophenones, naphthyl ketones, and heteroaromatic ketones. Representative examples are shown in the Table 1. Terminal olefins such as vinylsilanes, allylsilanes, styrenes, tert-butylethy-lene, and 1-hexene are applicable to this C-H/olefin coupling reaction. Some internal olefins, for example cyclopentene and norbornene are effective in this alkylation. The reaction of 2-acetonaphthone 1 provides the 1-alkylation product 2 selectively. Alkylations of heteroaromatic ketones such as acyl thiophenes 3, acyl furans, and acyl pyrroles proceed with high yields. In the reaction of di- and tri-substitued aromatic ketones such as 4, which have two different ortho positions, C-C bond formation occurs at the less congested ortho position. Interestingly, in the reaction of m-methoxy- and m-fluoroacetophenones C-C bond formation occurs at the congested ortho position (2 -position). 

Fig. 9.1. Substituent effects on the equilibrium position of the addition reactions of H20 (Het = OH), alcohols (Het = OAlkyl) and the respective carbonyl compounds [Het = 0(-CR1R2-0) -H] to aldehydes and ketones (EWG, electron-withdrawing group).

The bottom line complements Figure 12.1 by adding the >Ky values of representative ketones. The comparison of E G reveals the same substituent effects that are familiar from the analogous aldehydes A-C the enol content is increased by alkyl substituents in the on-position, and even more so by aryl substituents in the a-position. The ketone H in Figure 12.1, the nonexistent isophenol has by far the highest propensity to enolization of all the carbonyl compounds shown. The reason, of course, is that the tautomeric enol, phenol, is favored because of its aromaticity and thus particularly efficient C=C double bond stabilization. 

It is well-known that the carbonyl triplets of aromatic ketones are efficiently deactivated by p-aryl [7a,32] or p-vinyl [33] groups. This quenching process requires a n,n triplet state and typically leads to triplet lifetimes of about 1 ns at room temperature and is rather insensitive to substituent effects. It is suggested that this quenching process involves charge transfer interactions [32a]. 

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