Acetone, enolization reaction

In the acetone enolization reaction the rate-determining step is the first one, namely the transfer of the proton from the acid to the acetone. By a principle which has already been discussed (p. 365) the rate-constant k for the reaction in presence of an acid HA, shows a parallelism with the equilibrium constant of the reaction... 

Other possible ambident nucleophiles include cyanii anion (CN ), methyl sulfinate anion (CH3SO2 ), ar acetone enolate (CH3COCH2 ). Identify the most electro rich atom(s) in each anion (based on charges alone), ar indicate the major product that should result from an S, reaction with methyl bromide at this atom(s). 

Reaction of the enatiopure aldehyde 2-800, obtained from the corresponding imine by enantioselective hydrogenation, with Meldrum s acid (2-801) and the enol ether 2-802a (E/Z= 1 1) in the presence of a catalytic amount of ethylene diammonium diacetate for 4h gave 2-805 in 90 % yield with a 1,3 induction of >24 1. As intermediates, the Knoevenagel product 2-803 and the primarily produced cycloadduct 2-804 can be supposed the latter loses C02 and acetone by reaction with water formed during the condensation step (Scheme 2.178). 

The anion of nitromethane is particularly reactive in S l reactions. Various kinds of tertiary nitro groups are replaced by a nitromethyl group on treatment with the anion of nitromethane (Section 7.1).49 2-Iodoadamantane reacts with the anion of nitromethane in the presence of acetone enolate (entrainment reaction) under irradiation of a 400-W UV lamp to give 2-ni-tromethyladamantane in 68% yield, (see Eq. 5.32).50a 1-Iodoadamantane also reacts with the anion of nitromethane in a similar way.50b... 

These heterocyclic compounds undergo many reactions which are similar to those of the acetone enolate. Thus, Claisen condensation and o-sulfonylation are exemplified by Scheme 57. 

Halothiophenes undergo photostimulated reaction with acetone enolate ion to form substitution products (76H(5j377). This is believed to occur by the radical-chain SrnI mechanism. The propagation steps are as follows ... 

Here ArX is the halothiophene and ArY the product. The nature of the initiation and termination steps is not known. Thus irradiation of 3-bromothiophene in liquid ammonia in presence of potassium acetone enolate gives the monothienylation product (492 51%) and the dithienylation product (493 25%). Instead of employing photostimulation, the reaction can be brought about in lower yields by dissolving sodium or potassium metal in the liquid ammonia solution. Here the corresponding alcohol is a side product. 

The vertical electron affinity (EA) of acetone is given as —1.51 eV by Jordan and Burrow386. Lifshitz, Wu and Tiernan387 determine—among other compounds—the excitation function and rate constants of the slow proton transfer reactions between acclone-Ih, acetone-Dg and other ketones. The acetone enolate anion has been produced in a CO2 laser induced alkane elimination from alkoxide anions by Brauman and collaborators388-390. These show, e.g. that the methane elimination from t-butoxide anion is a stepwise process ... 

For the acid-catalyzed ketone -> enol reaction of typical unhydrated ketones, AS appears to be close to the normal or collision theory value for a second-order reaction. For example, AS for the acid-catalyzed bromination of acetone is —12 e.u. (Rice and Kilpatrick, 1923). Since for normal keto-enol equilibria, AS0 is close to zero, the conclusion is that AS for the ketonization reaction would also be close to —12 e.u. 

The photoinitiated reaction of diethylphosphite ion with iodobenzene has been examined in different solvents [60]. The reaction of acetone enolate ion with 2-chloroquinoline, under the same irradiation times, suffers a strong dependence on solvent nature. Thus, the yield of substitution product decreases going from liquid ammonia (90%) to THF (82%), DMF (74%), dimethoxyethane (28%), diethyl ether (9%), or benzene (4%) [61]. For this reason, the reactions are usually performed in liquid ammonia or DMSO under irradiation. 

It is known that acetone enolate anion does not react with primary alkyl radicals, and that nitromethane anion is not capable of initiating the SRN1 reactions even under irradiation [99]. Thus, the photo stimulated reactions of 25 with nitromethane anion as nucleophile and acetone enolate anion as entrainment reagent (which enables SRN1 initiation but cannot compete with the coupling of the methylene radical with nitromethane anion after cyclization) render the cyclized products 26 (Sch. 25) [98]. 

To liquid ammonia (25 mL) under argon contained in a three-necked flask fitted with a dry-ice condenser, acetone is added (4 mmol) along with one equivalent amount of t-BuOK. To the solution of the acetone enolate thus formed, 2-bromo-3,4,5-trimethoxybenzamide is added and the reaction mixture is irradiated in a photochemical reactor. The reaction is quenched by addition of NH4C1 (0.5 g) when all the substrate has been allowed to react. The ammonia is evaporated and slightly acidified water (50 mL... 

The absence of dimerization in S l reactions indicates that it is not an important termination step (equation 8), which may be related to the low concentration of the radical R in the chain reaction. However, 17% of the dimerization product 1, l -biadamantyl was found in the reaction of 1-iodoadamantane with the less reactive carbanionic nucleophiles, such as acetone enolate ion in DMSO22. Likewise, under appropriate experimental conditions, the dimerization product 4,4 -dicyanobiphenyl (39%) was the principal product of the termination step in the electrochemical induced reaction of 4-chloroben-zonitrile with 2-pyridinethiolate ions in liquid ammonia23. 

Kornblum and coworkers31a have determined the quantum yield for the ET substitution reactions of / -nitrocumyl chloride with azide ions (3.5) and quinuclidine (6000). Furthermore, by studying the wavelength dependence of the quantum yields, they have obtained evidence that photochemical initiation proceeds by means of a charge-transfer complex. Similar results have been obtained in the reaction of acetone enolate ion with Phi and PhBr in DMSO, whereas other mechanisms are in competition when Phi reacts with potassium diethyl phosphite3115. 

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... 

Several carbanions, such as acetone enolate or diethyl malonate ions, failed to react with neopentyl bromide in liquid ammonia under irradiation. In DM SO dehalogenation (100%) was the main reaction of 97 in the presence of the enolate ion of the acetone (27a) whereas with the enolate ion of acetophenone (27b) it gave the substitution product in 55% yield (equation 75). This reaction showed slight inhibition by p-DNB or TEMPO157. 

Under photostimulation, acetone enolate ion (27a) reacts with Phi in DMSO affording 124a (88%) and 125a (11%). The reaction with the enolate ion of acetophenone (27b) gives the substitution product 124b (68%) and 125b (13%) (equation 85)169. 

The photostimulated reaction of l-bromo-2,4,6-trimethylbenzene (a substrate with no o-hydrogen atoms in order to avoid the benzyne mechanism) with NH2 ions gave 1-amino-2,4,6-trimethylbenzene (70%) and the reduction product 1,3,5-trimethylbenzene (6%). This reaction did not occur in the dark221. By competition experiments of NH2 ions with Ph2P" ions toward 2,4,6-trimethylphenyl radicals, it was found that Ph2P ions are 6.4 times more reactive than NH2 ions221, whereas NH2 ions are twice more reactive than acetone enolate ions toward the same radical in liquid ammonia222. 

Ring closure reactions can be induced electrochemically in liquid ammonia. For instance, the reaction of o-iodoaniline with acetaldehyde enolate ion gives 95% yield of indole, and with acetone enolate ion 87% of 2-methylindole321. 

Another system which leads to ring closure reaction is o-halobenzoic acids. For instance, the reaction of o-iodobenzoate ion (288) with acetone enolate ion gives the substitution product 289, which leads to the isocoumarin 290 in acidic conditions, in high overall yield (80%) (equation 178)329. 

There is no photostimulated reaction of o-bromo-(327a) or o-iodothioanilides (327b) in DMSO with -BuOK or NaH, but in the presence of acetone enolate ion (27a), quantitative yields of benzothiazoles (329) were obtained in the reaction of 327b (equation 195)341. 

In the photostimulated reaction of substrates with two leaving groups in 0-position, such as 0-dibromobenzene and acetone enolate ion, a disubstitution product (330) is formed. In the basic reaction conditions it leads, by an aldol condensation, to a final mixture of two acetylmethyl indenes 331a and 331b in 64% yield (equation 196)342. 

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