Relative stability of isomeric carbocations with migrating groups in the neighboring positions

Abstract

The relative stabilities of isomeric 9,9-dimethyl-10-R-and 9-R-9,10-dimethylphenanthrenyl, as well as of 3-R-2,3-diphenylbutan-2-yl and 1-R-2-methyl-1,2-diphenylpropan-1-yl cations, were determined in terms of the density functional theory. The equilibrium isomer ratio was found to depend to an appreciable extent on steric requirements of the substituents.Data on the energy barriers to rearrangements of carbocations and relative stabilities of the initial and rearranged ions are necessary for the determination of structural and kinetic relations holding in cationoid rearrangements, in particular for the prediction of the direction of multistep isomerizations involving carbocationic intermediates [1]. Long-lived 9-R-9,10-dimethylphenanthrenyl cations are capable of undergoing degenerate rearrangement via 1,2-shift of the R substituent (Scheme 1) and are therefore convenient models for studying relative migration abilities of various atoms and groups [2][3][4][5][6][7][8][9][10][11][12].(α-I) is formed under the conditions ensuring "long life" of such cationic species. For the sake of simplicity, cations with the group R located in the β-and α-positions relative to the cationic center (Scheme 2), are referred to as β-and α-isomers, respectively. When R = H [6], Et [2], ClCH 2 [7], Cl 2 CH [5], CH 2 =C(Me) [11], Ph, p-MeC 6 H 4 , p-FC 6 H 4 , m-FC 6 H 4 , p-F 3 CC 6 H 4 , C 6 F 5 [3], O 2 N [7], the equilibrium is displaced toward β-isomer, whereas α-and β-isomeric carbocations with R = p-MeOC 6 H 4 [3], CH 2 =CH [10], trans-MeCH=C(Me) [11], cyclopropyl [12], and Cl [4] are characterized by comparable stabilities. Therefore, for most of the above listed migrating groups we succeeded in determining by dynamic NMR the rate of 1,2-shift, not being concerned about almost complete transformation of β-isomer I into α-isomer as a result of 1,2-shift of methyl group. In addition, in many cases we were able to synthesize precursors of carbocations in one step according to Scheme 3.

RM1 Semiempirical Model: Chemistry, Pharmaceutical Research, Molecular Biology and Materials Science

“…In this sense, RM1 semiempirical method was employed to evaluate various conformer possibilities of organic compounds that are formed during chemical reactions. [66][67][68][69]73,80,86,87,90,95,96 The energetic properties, such as enthalpy of formation, are very important in the conformer studies, as will be shown in the next section.…”

“…117 E n e r g e t i c p r o p e r t i e s o f o r g a n i c compounds 98,100,[107][108][109]112,113,116,[118][119][120][121][122] are very important to find the most favorable structure. As previously noted, RM1 semiempirical method was employed to evaluate conformer possibilities of organic compounds, such as: arylazo phosphate dimer; 87 (1R,2R,6S)-3-methyl-6-(1-methylethenyl)cyclohex-3-ene-1,2-diol; 86 isomeric carbocations 9,9-dimethyl-10-R-and 9-R-9,10-dimethylphenanthrenyl, as well as of 3-R-2,3-diphenylbutan-2-yl and 1-R-2-methyl-1,2-diphenylpropan-1-yl cations; 80 2,5-dihydropyridazine-4-carboxylate and 1,4-dihydropyridazine-3,5-dicarboxylate derivatives; 73 aurones synthesized by intramolecular cyclization of monobrominated (+)-usninic acid; 72 substituted cryptophane derivatives; 69 nitrogencontaining derivatives of (18α,19β)-19-hydroxy-2,3-secooleanane-2,3,28-trioic acid 28,19-lactone; 68 aryl and alkyl chlorophosphates; 67 spirocyclic nitroxides of 2,5-dihydroimidazole compounds; 66 lyoniresinol stereoisomers; 95 and 4-and 5-mono-and 4,5-disubstituted 3,3-diphenyl-3H-pyrazoles. 95 An interesting strategy to study conformational flexibility of small molecules, of importance in drug design, was reported by Forti et al 42 The reported strategy consisted in combining low-level methods such as RM1, to calculate the conformational minima and high-level techniques to calibrate their relative stabilities.…”

Long-lived 9-cyano-9,10-dimethylphenanthrenyl cation. Migration of cyano group in carbocations

“…However, in keeping with the data of [7], the calculation method used overestimates the stability of cations like III. Therefore, cation I was presumed to predominate in the equilibrium mixture.…”