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.

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.

Strong mineral acids convert 1,1,1-trichloro-2-hydroxy-4-alkanones to 1,1,1-trichloro-2-alken-4-ones and 1,1,5-trichloro-1-alken-4-ones via an intramolecular chlorine shift from C-l to -5 of an enol allylic system. Alternatively, 1,1,1-trichloro-2-alken-4-ones may be synthesized from 1,1,I-trichloro-2-hydroxy-4-alkanones by acetylation and elimination of acetic acid or by nucleophilic substitution with thionyl chloride followed by dehydrohalogenation. The two diastereomeric 1,1,1-trichloro-2-hydroxy-3-methyl-4-hexanones do not epimerize during acetylation, and the erythro-acetate resists elimination of acetic acid. Pyrolysis of 2-(1-hydroxy-2,2,2-trichloroethyl-)cyclohexanone yields 2-(2,2-dich1orovinyl)-2-cyclohexenone while treatment of 1,1,1,7,7,7-hexachloro-2,6-dihydroxy-4-heptanone with strong acid leads to the formation of 1,1,1,7,7,7-hexachloro-23-heptadien-4-one.Des acides mineraux forts transforment les trichloro-l,l,l hydroxy-2 alcanones-4 en trichloro-l,l,l alcene-2 ones-4 et en trichloro-1,1,5 alcene-l ones4 par deplacement intramolCculaire du chlore du carbone en position 1 sur le carbone en position 5 d'un systeme enol allylique. Alternativement, les trichloro-l,l,l alcene-2 ones-4 peuvent Etre synthetises a partir des trichloro-l,l,l hydroxy-2 alcanones-4 soit par acitylation et elimination de l'acide acetique soit par substitution nucleophile avec le chlorure de thionyle suivie d'une dCshydrohalogenation. I1 n'y a pas Cpimerisation au cours de I'acktylation des deux trichloro-l,l,l hydroxy-2 methyl-3 hexanones-4 diasterc5oisomeres et I'acCtate erythro rCsiste a I'elimination de I'acide acetique. Le pyrolyse de la (hydroxy-1 trichlorobthyl-2,2,2)-2 cyclohexanone conduit a la (dichloro-2,2 vinyl)-2 cyclohexene-2 one tandis que le traitement de la hexachloro-l,l,l,-7,7,7 dihydroxy-2,6 heptanone-4 avec un acide fort n'amene pas la formation d'hexachloro-l,l,l,7,7,7 heptadikne-2,5 one-4.Canadian Journal of Chemistry, 49,2964 (1971) In the course of our studies of the acetatecatalyzed crossed aldol condensation of chloral with aliphatic ketones in acetic anhydride (1) or glacial acetic acid (2) we observed that this reaction is not accompanied by dehydration of the resulting 1,1,1-trichloro-2-hydroxy-4-alkanones. The low tendency of trichloromethyl-substituted P-ketols to eliminate water (3) parallels the inertness of trichloromethylcarbinols in substitution reactions (4, 5) which has been attributed to the strengthening of the 0-alkyl bond by the inductive electron-withdrawing effect of the three chlorine atoms attached to the adjacent carbon (6, 7). Since our attempts to effect the desired elimination reaction under mild neutral conditions using the recently recommended dicyclohexylcarbodiimide (8) in ether solution were not successful and since trichloromethylcarbinols are sensitive to strong base (9), we investigated the synthesis of the title compounds in neutral or acidic solution by three methods involving the conversion of the hydroxy group of the corresponding P-ketols to a better leaving g...

Die Ketole (I) gehen unter der Einwirkung von konz. Schwefelsäure in Eisessig bei 100°C (auch von p‐Toluolsulfonsäure in siedendem Benzol oder Toluol) in Gemische der Dehydratisierungsprodukte (II) (Anteil am Produktgemisch 5 bis 42%) mit den Umlagerungsprodukten (III) (bis zu 58%) über.

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