Aminocyclanols, I: Synthesis and Analgetic Activities of Some Aminobenzylcyclanols Derived from Menthone. Aminocyclanole, 1. Mitt.: Synthese und analgetische Wirkung einiger vom Menthon abgeleiteter Aminobenzylcyclanole

Simple and Effective Protocol for Claisen-Schmidt Condensation of Hindered Cyclic Ketones with Aromatic Aldehydes

“…Camphor (14) (Scheme 3), being a sterically hindered and low-reactive ketone, has been shown to be almost unable to react with aromatic aldehydes under the traditional protocol (see, e.g., Table 3, entry 1). 5,36,37 More effective approaches to the synthesis of 3-arylidenecamphors 15 described before are in fact variations of Haller's method, 36a and represent two-step procedure: camphor enolization with NaH, 5 Na, 36a,c t-BuOK, 36b NaNH 2 38a in a nonpolar solvent under reflux followed by the addition of an appropriate aldehyde. Haller's protocol 36a,c,38a provides the highest yields of compounds 15 (50-70%) known to date.…”

“…[10][11][12][21][22][23] Apparently, it sometimes results in applying the simplest and non-optimized procedure, 24,25 or even in repeated studies on the reaction optimization. 5 Applications of superbasic media to Claisen-Schmidt condensation 26,27 and to subsequent transformations of a,b-unsaturated ketones 28,29 were also reported.…”

“…However, a poor reactivity of 1 under common reaction conditions (alkali metal hydroxides or alkoxides in alcohol media 2 ) has been found ( Table 1, entries 1,2,12,14,31). 3 The use of stronger bases such as NaNH 2 3 or NaH 4,5 in low-polar solvents has not improved the result substantially, and moderate yields of 3a have been obtained at best (entries 3,4). 5 The acid-catalyzed reaction is complicated due to migration of the benzylidene double bond in cyclohexane ring (compounds 5a and 5b, Scheme 1), 6,7 and only in rare cases has acid catalysis been reported (entry 5).…”

“…3 The use of stronger bases such as NaNH 2 3 or NaH 4,5 in low-polar solvents has not improved the result substantially, and moderate yields of 3a have been obtained at best (entries 3,4). 5 The acid-catalyzed reaction is complicated due to migration of the benzylidene double bond in cyclohexane ring (compounds 5a and 5b, Scheme 1), 6,7 and only in rare cases has acid catalysis been reported (entry 5). 3 These obstacles have been successfully overcome by applying the so-called super-basic media 8 (the combination of an alkali hydroxide and a polar aprotic solvent).…”

Monoterpenoids

“…436), of which only the E isomer Michael reaction with secondary amines. Reduction 269 P-Hof the adducts using LiAlH, leads to amino alcohols which have been examined for their analgesic activities 437. The p-chlorobenzylidene compound 256 reacts with thiophenate ion to give the adduct 257 of high de.438 ( -)-Menthone toluene-p-sulfonylhydrazone 258 has been obtained in pure form for the first time, and has been found to epimerise to the isomenthyl derivative, which by contrast with the parent ketone is the more thermodynamically stable form, under acidic conditions 150 times more rapidly than menthone does 439.…”