Relative rates of base-catalyzed enolization of methyl alkyl ketones in aqueous dioxane

In the presence of sodium acetate as catalyst, chloral hydrate undergoes a mixed aldol condensation with aliphatic and alicyclic ketones in acetic anhydride as solvent. Contrary to previous literature reports, reaction occurs at both the methyl and the methylene group in cr-position to the carbonyl group of butanone, to give a mixture of I, I, I-trichloro-2-hydroxy-4-hexanone (1) and I, 1 ,I-trichloro-2-hydroxy-3-methyl-4-pentanone (2a and 26, diastereomers). 3-Pentanone, cyclohexanone, and 4-methyl-2-pentanone yield 1,1,1-trichloro-2-hydroxy-3-methyl-4-hexanone (3a and 36, diastereomers), 2-(1-hydroxy-2,2,2-trichloroethyl-)cyclohexanone (4a and 46, diastereomers), and I,l,l-trichloro-2-hydroxy-6-methyl-4-heptanone (5), respectively. Compound 5 is the exclusive product formed from chloral hydrate and 4-methyl-2-pentanone since attack at the methylene group is sterically hindered. The low-melting diastereomers 2a, 3a, and 4a which have not been characterized before, exhibit strong intramolecular hydrogen bonding and have been assigned the threo configuration on the basis of nuclear magnetic resonance and molecular model studies.

Section: Cyclohexanone and Chloral Hydratesupporting

confidence: 91%

Chloral–ketone condensations in acetic anhydride. Reaction of chloral with butanone, 3-pentanone, cyclohexanone, and 4-methyl-2-pentanone

Kiehlmann¹,

Loo²

1969

“…Again the effect of a-bromine is to enhance &-reactivity by a factor near lo3. A steric effect is introduced in going from CH,COC(CH,), to BrCH2COC-(CH,), but that factor is known to be small compared to lo3 (20). The second and third entries of set 2 are sterically equivalent and Can.…”

Section: Resultsmentioning

confidence: 99%

“…For an enolate-like transition state that effect would have to be one of electron-withdrawal, contrary to the effect of para CH, on benzoic acid acidity. Because of this problem we suggested (20) that the transition state might be enol-like, at least for the more highly endothermic enolizations involving weak bases. However, this concerted mechanism, originally postulated by Swain (26) to account for a termolecular term in the kinetics of enolization of acetone (27,28) has little support as a general mechanism, although it may be important in carboxylic acid -carboxylate anion catalyst systems (29).…”

Section: Resultsmentioning

confidence: 99%

Effects of Bromine Substituents on Rates of Acetate-promoted Enolization of Ketones

Cox¹,

Warkentin²

1972

Self Cite

Effects of bromine substituents on rates of acetate-catalyzed bromination of ketones are reported. Approximate polar contributions to the rates were obtained, based on the approximation that the steric effects of bromine and methyl are identical. Such polar substituent effects are quite large at the a'-position of an a-bromo ketone, leading to the conclusion that the carbonyl group is much better than the methylene group in transmitting polar effects.Rate enhancements caused by a-bromine substituents are largely entropic in origin and rates correlate well with ionization constants of a-bromo acids. These results are interpreted as indicative of an enolatelike transition state for acetate-catalyzed enolization.Les effets des substituants brome sur les vitesses de bromation des cttones, catalysee par I'acttate, sont rapportts. Les contributions polaires approximatives aux vitesses sont obtenues, fondtes sur l'approximation que les effets stkriques du brome et du mCthyle sont identiques. De tels effets polaires de substituants sont tres accentues sur la position a' d'une a-bromo cktone permettant de conclure que le groupe carbonyle est de deux fois environ aussi bon que le groupe methylene, dans la transmission des effets polaires. Les accroissements de vitesse dOs aux substituants a bromes sont grandement d'origine entropique et les vitesses sont en relation avec les constantes d'ionisation des a-bromoacides. L'interprttation de ces rtsultats revele un ttat de transition du type enolate dans l'enolisation catalysee par I'acetate.

“…The ketol as a function of time. variation in individual integrations is i 15%, a common observation in this type of rate measurements (15)(16)(17)(18).…”

Section: Rate Measurements Deuterium Exchangementioning

confidence: 87%

“…The value of kCHz/kCH3 > I for butanone is in line with that obtained by Warkentin and Cox (16) for the acetate-catalyzed deuterium exchange of butanone in aqueous solution. The high reactivity of the methylene protons of butanone has been explained by Warkentin and Barnett (15) as being due to a polar effect which overcomes the steric effect resulting in rate acceleration. For 2-heptanone our kCH7kCH3 z 1.00 is quite different from the value (kCH2/ kc", < 0.3) reported by Rappe and Sachs (17) for the sodium carbonate-catalyzed deuterium exchange in aqueous solution.…”

Section: Rates Of Deuterium Exchangementioning

confidence: 99%

Kinetic Study of the Acetate-catalyzed Aldol Reaction Between Chloral and Alkyl Methyl Ketones

Menon¹,

Kiehlmann²

1971

A kinetic study of the acetate-catalyzed crossed aldol reaction of chloral with butanone, 2-heptanone, and 4-methyl-2-pentanone, respectively, in glacial acetic acid at 60" has been carried out. A comparison of the condensation rates with those for the acetate-catalyzed deuterium exchange of the ketones in glacial acetic acid at 60' indicates that the carbon--carbon bond formation in the aldol reaction is the rate-determining step. The relative rate constants for the crossed aldol reaction and the deuterium exchange of the corresponding ketones are best interpreted in terms of steric rather than polar effects.On a entrepris une etude cinetique de la reaction aldolique catalysee par acetate, du chloral avec la butanone, I'heptanone-2, et la methyl-4 pentanone-2, respectivement dans I'acide acktique glacial a 60".Une comparaison des vitesses de condensation avec celles obtenues pour 1'6change de deutbium catalyse par adtate des cetones dans I'acide acetique glacial a 60" indique que la formation du lien carbonecarbone dans la reaction aldolique est 1'6tape dkterminante. Les constantes de vitesse relative pour la reaction aldolique et l'tchange de deuterium des cetones correspondantes sont mieux interpretees en termes d'effets steriques que polaires. Canadian Journal of Chemistry, 49, 3648 (1971)The mechanistic aspects of aldol reactions have been the subject of intensive studies by various investigators. The fundamental studies by Bonhoeffer and Walters (1) and Bell and Smith (2, 3) firmly established the two-step enolization-addition mechanism through kinetic and deuterium exchange experiments with acetaldehyde.Although the aldol reaction is catalyzed by acids and bases, the latter are more frequently employed. The base-catalyzed mechanism (4-6) may be described by eqs. 1 to 5. For the formation of aldols in concentrated solutions of acetaldehyde (7), propanal (8), and butanal (91, the proton abstraction step 1 is rate-limiting (k, < k,). On the other hand, the formation of the new carbon--carbon bond [2] is the ratelimiting step (k, > k,) in many aldol reactions involving ketones, for example the ethoxidecatalyzed condensation of aromatic aldehydes with acetophenones (lo), the formation of diacetone alcohol from acetone (3), the condensation of benzaldehyde and acetone (ll), and the condensation of formaldehyde with acetone (12).As a continuation of our interest in the crossed aldol reaction between chloral and alkyl methyl ketones in glacial acetic acid -acetate medium (13), we have now carried out a kinetic study of the aldol reaction of chloral with butanone, 2-heptanone, and 4-methyl-2-pentanone, respectively, in glacial acetic acid -acetate medium, as well as the deuteration of these ketones under conditions similar to the aldol reaction. A com~arison of these two sets of rate constants shouli settle, among other things, the question of the rate-limiting step in the crossed aldol reaction. Experimental ReagentsThe commercially available ketones were purified by fractional distillation. Pure anhydrous chlora...