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

1969 ◽  
Vol 47 (11) ◽  
pp. 2029-2037 ◽  
Author(s):  
Eberhard Kiehlmann ◽  
Pui-Wah Loo
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Acetic Anhydride ◽  
Sodium Acetate ◽  
Chloral Hydrate ◽  
Aldol Condensation ◽  
Molecular Model ◽  
Intramolecular Hydrogen Bonding ◽  
Model Studies ◽  
Intramolecular Hydrogen ◽  
Methylene Group

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 α-position to the carbonyl group of butanone, to give a mixture of 1,1,1-trichloro-2-hydroxy-4-hexanone (1) and 1,1,1-trichloro-2-hydroxy-3-methyl-4-pentanone (2a and 2b, diastereomers). 3-Pentanone, cyclohexanone, and 4-methyl-2-pentanoneyield 1,1,1-trichloro-2-hydroxy-3-methyl-4-hexanone (3a and 3b, diastereomers), 2-(1-hydroxy-2,2,2-trichloroethyl-) cyclohexanone (4a and 4b, diastereomers), and 1,1,1-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.

A carbon-13 nuclear magnetic resonance study of the basicities of aliphatic alcohols

1987 ◽  
Vol 65 (8) ◽  
pp. 1769-1774 ◽  
Author(s):  
Donald G. Lee ◽  
Kenneth J. Demchuk
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Free Energy ◽  
Hydrogen Bonding ◽  
Chemical Shifts ◽  
Intramolecular Hydrogen Bonding ◽  
Nuclear Magnetic Resonance Study ◽  
Slope Parameter ◽  
Magnetic Resonance Study ◽  
Linear Free Energy ◽  
Intramolecular Hydrogen

Carbon-13 nmr chemical shifts have been used to determine the basicity constants for nine alcohols. The method involves comparing the chemical shifts for carbon atoms adjacent to the site of protonation with those for carbon atoms in a more remote position. The differences in the chemical shifts (Δ values) at different acidities are then used to calculate basicity constants for the alcohols. The pKBH+ values, determined by use of the "X function" are as follows: ethanol −2.12, 1-propanol −2.12, 3-chloro-1-propanol −2.24, 2-chloroethanol −2.45, 2-bromoethanol −2.41, 2-nitroethanol −2.09, 2-methoxyethanol −1.93, 2-phenoxyethanol −1.87, and 2-propanol −2.06. The typical slope parameter, m*, is 0.17. Two linear free energy correlations are obtained: when the alcohols are considered to be a series of monosubstituted ethanols, the Hammett plot has a slope of 0.65; when they are considered to be a series of mono- and disubstituted methanols, the slope is 1.7. Alcohols bearing oxygen-containing substituents are more basic than predicted by about 0.5 pK units, presumably because their conjugate acids can be stabilized by intramolecular hydrogen bonding.

Orientation in the Crossed Aldol Condensation of Chloral with Unsymmetrical Aliphatic Ketones

1971 ◽  
Vol 49 (10) ◽  
pp. 1588-1597 ◽  
Author(s):  
Eberhard Kiehlmann ◽  
Pui-Wah Loo
Keyword(s):  
Acetic Acid ◽  
Sodium Acetate ◽  
Marked Effect ◽  
Aldol Condensation ◽  
Condensation Product ◽  
Reaction Conditions ◽  
Methyl Group ◽  
Aliphatic Ketones ◽  
Alkyl Groups ◽  
Methylene Group

The reactivity of a series of 14 aliphatic ketones in the crossed aldol condensation with chloral has been studied in glacial acetic acid and in dimethoxyethane. The reaction is irreversible and not accompanied by dehydration of the resulting 1,1,1-trichloro-3-hydroxy-4-alkanones. Except for butanone, condensation occurs preferentially at the least-hindered position of an unsymmetrical ketone. The α-methyl/α-methylene condensation product ratio obtained from ketones of the general formula RCH2COCH3 is higher in acetic acid than in dimethoxyethane as solvent when sodium acetate is used as catalyst. The steric size and chain length of the alkyl groups of methyl alkyl ketones have a marked effect on the reactivity of the α-methyl group toward chloral. Condensation at the α-methylene group results in the formation of diastereomeric ketols which epimerize under the preparative reaction conditions.

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