Influence of Ring Size and 2-Methyl Substituent on Two Modes of Alkaline Cleavage of 2-Acylcyclanones. Acylations of Cycloheptanone and Cyclooctanone¹

Abstract

A semiquantitative study was made of the two possible modes of alkaline cleavage of the 2-acetyl derivatives of cyclopentanone, cyclohexanone, cycloheptanone, and cyclooctanone. 2-Acetylcyclopentanone underwent largely ring opening and 2-acetylcyclohexanone, mainly ring opening. However, only side chain cleavage was realized with 2-acetylcycloheptanone and 2-acetylcycloóctanone, Also, only side chain cleavage was observed with 2-benzoylcycloheptanone and 2-benzoylcyclooctanone. The 2-methyl derivatives of 2-acetylcyclopentanone and 2-acetylcyclohexanone underwent relatively less ring opening than the corresponding unsubstituted 2-acetylcyclanones. The boron fluoride-acid anhydride and the sodium amideacid chloride methods of acylation of ketones were extended to cycloheptanone and cyclooctanone.

Synthesis of carboxyalkylindolenines from 6-methyl-7-oxooctanoic acid

“…[13][14][15] The degree of methylation at position 2 of the ring depends on the alkylating agent and the reaction conditions. We methylated 2 acetylcyclo hexanone 16,17 (10) with MeI in the presence of aqueous NaOH 15 to give 2 acetyl 2 methylcyclohexanone (11) in 75% yield.…”

“…The organic extracts were combined, washed with 2 M NaOH (200 mL) and brine (100 mL), and dried with 6)). 13 C NMR (CDCl 3 ), δ: 16.29 (6 CH 3 ); 19.57 (2 CH 3 ); 24.73 (C(3)); 26.72 (C(4)); 28.08 (C(8)); 32.45 (C(5)); 33.92 (C(2)); 47.02 (C(6)); 179.55 (COOH); 213.09 (C(7)).…”

“…12 The multistep scheme includ ing the Claisen retrocondensation of various 2 acetylcy cloalkanones affords oxo acids 2. 13 It should be noted that the retrocondensation outcome is sensitive to the ring size and the reaction conditions. We developed a conve nient method for the synthesis of oxo acid 8 from cyclo hexanone (9) (Scheme 2).…”