Acetophenone, enolate

Acetophenone enolate and nitromethane anions have also been used successfully in alkyl substitution. 

The very small p- and m-values observed for the fast bromination of a-methoxystyrenes deserve comment since they are the smallest found for this electrophilic addition. The rates, almost but not quite diffusion-controlled, are amongst the highest. The sensitivity to polar effects of ring substituents is very attenuated but still significant that to resonance is nil. These unusually low p-values for a reaction leading to a benzylic carbocation are accompanied by a very small sensitivity to the solvent. All these data support a very early transition state for this olefin series. Accordingly, for the still more reactive acetophenone enols, the bromination of which is diffusion-controlled, the usual sensitivity to substituents is annulled. 

Lectka and co-workers found that cationic Cu phosphine complexes are efficient Lewis acids in the activation of a-imino esters (248). The Tol-BINAP was found to be the most effective ligand providing the adduct of acetophenone enol-... 

Reduction of co-bromoacetophenone in aprotic solvents leads to acetophenone enolate. This is trapped by reaction with a second molecule of substrate to yield... 

Since photoexcitation greatly enhances the reactivity of acetylenes, formation of the enol intermediate becomes faster than its rearrangement to ketone. As a result, the intermediate acetophenone enol in the hydration of phenylacetylene could be directly observed 42... 

In 1978, we observed that flash photolysis of butyrophenone produced acetophenone enol as a transient intermediate, which allowed us to determine the acidity constant KE of the enol from the pH-rate profile (section pH Rate Profiles ) of its decay in aqueous base.4 That work was a sideline of studies aimed at the characterization of biradical intermediates in Norrish Type II reactions and we had no intentions to pursue it any further. Enter Jerry Kresge, who had previously determined the ketonization kinetics of several enols using fast thermal methods for their generation. He immediately realized the potential of the photochemical approach to study keto enol equilibria and quickly convinced us that this technique should be further exploited. We were more than happy to follow suit and to cooperate with this distinguished, inspiring, and enthusing chemist and his cherished wife Yvonne Chiang, who sadly passed away in 2008. Over the years, this collaboration developed into an intimate friendship of our families. This chapter is an account of what has been achieved. Several reviews in this area appeared in the years up to 1998.5 10... 

Rate constants of ketonization of acetophenone enol along paths (a) and (b) have been be estimated using the Bronsted Equation (16).20 Those predicted for path (a) are orders of magnitude below the observed rate constant k c = 0.18 s 1, while those for path (b) were found to be in reasonable agreement with experiment. The concerted mechanism (c) does not satisfactorily account for structure-reactivity relationships observed in aqueous solution. It may, however, well be the dominant mechanism in aprotic solvents containing small amounts of water. 

Flash photolysis and laser flash photolysis are probably the most versatile of the methods in the above list they have been particularly useful in identifying very short-lived intermediates such as radicals, radical cations and anions, triplet states, carbenium ions and carbanions. They provide a wealth of structural, kinetic and thermodynamic information, and a simplified generic experimental arrangement of a system suitable for studying very fast and ultrafast processes is shown in Fig. 3.8. Examples of applications include the keton-isation of acetophenone enol in aqueous buffer solutions [35], kinetic and thermodynamic characterisation of the aminium radical cation and aminyl radical derived from N-phenyl-glycine [36] and phenylureas [37], and the first direct observation of a radical cation derived from an enol ether [38],... 

Dihydropyridine 129 has been shown to catalyze Michael reactions in aqueous cationic micelles of cetyltri-methylammonium bromide (Scheme 34) <2003CL1064>. In the micelles, dihydropyridine 129 ionizes to form an acetophenone enolate salt 130. The highly basic enolate deprotonates the Michael donor which then rapidly reacts with the Michael acceptor. The use of anionic surfactants did not promote Michael reactions, suggesting that the cationic micelles promote the dissociation of salt 130. 

In the presence of a catalytic amount of aluminum chloride, acetophenone (Formula A in Figure 12.5) and bromine react to give phenacyl bromide (F). In contrast, the same reactants and a stoichiometric amount of aluminum chloride yield mefa-bromoacetophenone (Section 5.2.1). This difference is due to the different ratios of substrate quantities in the respective product-determining step. The acetophenone enol (iso-A) is the substrate for the formation of phenacyl bromide, and the aluminum chloride/acetophenone complex D is the substrate in the reaction leading to meto-bromoacetophenone. The acetophenone enol derives from a bimolecular reaction between the complexed (D) and the free acetophenone (A). This access is blocked, though, as soon as the all of the acetophenone has been complexed to form D—which occurs if aluminum chloride is added in stoichiometric amounts. 

In photoinitiated reactions, the reactivity of the substrate-nucleophile pair can be modified by changing the solvent and the irradiation source. For instance iodobenzene does not react under irradiation (pyrex-filtered flask) with acetophenone enolate anion in liquid ammonia [21], but it does react in DMSO [22]. However, the reaction occurs in liquid ammonia by irradiation in an immersion well [23]. 

Acetone enolate ion did not react with 66, whereas pinacolone enolate ion reacted to give 18% of 67d145. However, good yields of the substitution product were obtained in the photostimulated reaction of 7-iodonorcarane (68) with acetophenone enolate ion in DM SO (87%). This reaction is inhibited by p-D NB and it is sluggish in the dark (equation... 

Even though the starting substrate 68 was a mixture ca 1 1 of the exo endo isomers, product 69 was formed in a 16-22 1 exo endo ratio, suggesting that the coupling reaction of the 7-norcaranyl radical with acetophenone enolate ion is quite selective. 

The relative reactivity of 97 and 1 - Adi in competition experiments toward acetophenone enolate ion as nucleophile was studied. 1-AdI is ca 4.9 times more reactive than 97. This result shows that despite the fact that 1-AdI is a strained structure compared with the flexible structure of 97, it reacts faster due to the stabilization of the radical intermediate which is greater for tertiary than for primary carbons157. 

The reaction of Phi with acetophenone enolate ion 27b in DMSO is catalysed by Sml2, giving 47% of the substitution product. On the other hand, PhCl and PhBr did not react, but 1-chloro and 1-bromo naphthalenes reacted with 27b and Sml2 to give 93% yield of the substitution product174. 

The percentage of product 279b was increased to 98% when the reaction was performed in DMSO. The product 2-phenylfuro[3,2-6]pyridine was obtained in 70% yield with acetophenone enolate ion in DMSO326. 

An accurate value of the acidity constant of acetophenone enol (10.34 0.05) has recently been reported by Haspra et al. (1979) who used a straightforward method which consists in producing enol [66] by Norrish type... 

Fig. 4 Determination of acetophenone enol acidity constant by flash spectroscopy. Enolate absorption (310 nm) as a function of pH (Haspra et al., 1979). (Reprinted by courtesy of Angewandte Chemie, Verlag Chemie, GmbH, Weinheim, Germany)...

In the gas phase, the reaction of ethyl cations, C2H , with the ambident 2,4-pentanedione (which is 92% enolized at 25 °C in the gas phase) leads predominantly (>95%) to alkylation at the hard oxygen site and not at the soft carbon atom, as predicted by the HSAB concept [662]. Accordingly, the gas-phase alkylation of the enolate ion of cyclohexanone gives only the O- and no C-alkylation product [848], and the gas-phase acylation of acetophenone enolate with trifluoroacetylchloride leads predominantly to the 0-acylation product (0/C ratio = 6.0) [849]. 

Haspra, P, Sutter, A., Wirz, J., Acidity of Acetophenone Enol in Aqueous Solution, Angew. Chem. Int. Ed. Engl. 1978, 18, 617 619. 

Chiang, Y., Kresge, A. J., Capponi, M., Wirz, J., Direct Observation of Acetophenone Enol Formed by Photohydration of Phenylacetylene, Helv. Chim. Acta 1986, 69, 1331 1332. 

The sequence shows an initiating step as nucleophilic attack by acetophenone enolate on the protonated diketone, however an equally plausible sequence, shown below, starts with the nucleophilic addition of the enohc hydroxyl of the diketone to protonated acetophenone. We show this alternative to emphasise the uncertainty of the detailed order of events in such multi-step syntheses. 

Poly(a-acetoxystyrene) is an acetophenone enol ester and its acidolysis involves the polymer backbone in contrast to the side chain deprotection discussed earlier (Fig. 30). Protonation of the side chain carbonyl oxygen results... 

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