A concise synthetic pathway towards 5-substituted indolizidines

Energy Managements in the Chemical and Biochemical World, as It may be Understood from the Systems Chemistry Point of View

“…Note that the two set of values represent different scales, than the amidicity is a special section of the carbonylicity scale. Amidicity percentage for example is able to predict whether a transamidation reaction is taking place under the given conditions or not [10][11][12] and it can also point out the most reactive amide bond of a molecule. It was shown that carbonyl groups exhibiting a lower amidicity value are more reactive toward nucleophilic reagents (like amines) than carbonyl groups having a larger value.…”

“…To form amide 35, the acid reagent need to be activated somewhat, that is to be transformed to a more active carbonyl reagent (36) having lower carbonylicity value. In all of the activation methods, this high carbonylicity value of 31 are lowered significantly, consequently the reactivity of the acid is enhanced [10][11][12]. The most widely known amide forming reagent is the acyl chloride (R-I; 37 in Figure 18) exhibiting as low carbonylicity value as 23.7 %.…”

“…34) are shown to react readily with formamide (75, R-XI) and acetamide (35, R-XII) at RT or above, as used in the Traube synthesis. The formylation of benzylamine and Nmethylbenzylamine furnished by 75 proceeded very smoothly, however, in the case of 33, AlCl 3 was required in order to attain an acceptable rate, which is due to the high activation energy of the sterically hindered reaction center [10][11][12]. Compounds 78 and 82 represent mild acylating agents (Figure 22) taking part in transamidation reactions with amines (e.g.…”

“…The not too high ∆AM value may be one of the underlying reasons that these types of reactions are not often referred to in the literature. The reaction between 88 and 34 is very slow, even in the presence of AlCl 3 at high temperature, but it may be due to the larger steric hindrance of the carbonyl group in 82 [10][11][12]. The use of the amidicity change or the change in stabilization enthalpy leads to a thermodynamic selection rule, allowing for the reactions to be categorized as being either thermodynamically favorable or unfavorable.…”

“…Taking into consideration of all of these criteria, it seems nearly impossible to model even a simple acylation reaction. It was demonstrated earlier that the computation of one or a few, easily and quickly computable quantum mechanical (QM) descriptors, such as aromaticity [6][7][8][9], amidicity [10][11][12], carbonylicity, [13,14] olefinicity, [15][16][17] and others can predict properly and somewhat quantitatively certain reactivity and selectivity issues. The global and complex view of these descriptors was defined as the concept of systems chemistry [18], wherein molecules are described as strategically located functional components within molecular frameworks, 'valued' at more than their components' sum, acting in unison to effect efficient energy management.…”