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The Diels–Alder Reaction of 4,6‐Dinitrobenzofuroxan with 1‐Trimethylsilyloxybuta‐1,3‐diene: A Case Example of a Stepwise Cycloaddition

The reaction of 4,6-dinitrobenzofuroxan (DNBF) with 1-trimethylsilyloxybuta-1,3-diene (8) is shown to afford a mixture of [2+4] diastereomeric cycloadducts (10, 11) through stepwise addition-cyclization pathways. Zwitterionic intermediate sigma-adduct 9, which is involved in the processes, has been successfully characterized by (1)H and (13)C NMR spectroscopy and UV/visible spectrophotometry in acetonitrile. A kinetic study has been carried out in this solvent that revealed that the rate of formation of 9 nicely fits the three-parameter equation log k=s(E+N) developed by Mayr to describe the feasibility of nucleophile-electrophile combinations. This significantly adds to the NMR spectroscopic evidence that the overall cycloadditions take place through a stepwise mechanism. The reaction has also been studied in dichloromethane and toluene. In these less polar solvents, the stability of 9 is not sufficient to allow direct characterization by spectroscopic methods, but a kinetic investigation supports the view that stepwise processes are still operating. An informative comparison of our reaction with previous interactions firmly identified as prototype stepwise cycloadditions is made on the basis of the global electrophilicity index, omega, defined by Parr within the density functional theory, and highlighted by Domingo et al. as a powerful tool for understanding Diels-Alder reactions.

The Ambident Reactivity of 2,4,6-Tris(trifluoromethanesulfonyl)anisole in Methanol: Using the SO2CF3 Group as a Tool to Reach the Superelectrophilic Dimension in σ-Complexation Processes

The kinetics of sigma complexation of 2,4,6-tris(trifluoromethanesulfonyl)anisole (7 d) have been investigated over a large pH range of 2-13.70 at T = 20 degrees C in methanol. Two competitive processes associated with the initial addition of MeO(-) at the unsubstituted 3-position of 7 d to give a 1,3-dimethoxy adduct (9 d-Me) and a subsequent and slow conversion of this species into a 1,1-dimethoxy isomer (8 d-Me) have been identified. Both adducts 8 d-Me and 9 d-Me are 10(5)-10(6) times more stable than the related adducts 8 a-Me and 9 a-Me of 2,4,6-trinitroanisole (7 a), a conventional reference aromatic electrophile in Meisenheimer complex chemistry. The high stability of 8 d-Me and 9 d-Me is shown to derive from greater rates of formation and lower rates of decomposition than previously determined for 8 a-Me and 9 a-Me, thereby emphasising the especially high activation of a benzene ring by SO(2)CF(3) group(s). Analysis of the collected rate and equilibrium data for sigma complexation in the anisole series 2,4,6-tris(SO(2)CF(3))-, 2,6-bis(SO(2)CF(3))-4-nitro-, 4-SO(2)CF(3)-2,6-dinitro- and 2,4,6-trinitro- supports the idea that the especially high capacity of resonance stabilisation of the negative charge of the adducts through an F(pi)-type (as defined in ref. 49) polarisation effect is a major factor that accounts for the strong activation provided by SO(2)CF(3) groups. A most significant result is the finding that the 1,1-dimethoxy adduct 8 d-Me is by far the most stable benzene sigma adduct so far reported. With a pK(a)(MeOH) value of 7.32, this adduct is formed exclusively through methanol addition up to pH approximately 10. This is consistent with the location of 7 d in the superelectrophilic region defined by pK(a)(MeOH) < or = 9.5-10.5. For comparison, the solvent contribution is negligible in the formation of the 1,3-isomer 9 d-Me, the pK(a)(MeOH) (10.59) of which is situated on the upper limit of the boundary. Taking advantage of the simple relationship linking pK(a) values for sigma complexation in methanol and water, a ranking of the triflone 7 d on the general thermodynamic scale constructed for Meisenheimer electrophiles in water is informative. An approximate calibration on the electrophilicity scale kinetically derived by Mayr et al. has also been made.

Facile access to regio- and stereoselective synthesis of highly functionalized spiro[indoline-3,2′-pyrrolidines] incorporating a pyrene moiety: experimental, photophysical and theoretical approach

The regio- and stereochemical polar [3 + 2] cycloaddition of azomethine ylides, which were generated in situ by the reaction of isatin and sarcosine or benzylamine, with (E)-3-aryl-1-(pyren-1-yl)prop-2-en-1-ones as dipolarophiles, was studied using experimental and theoretical methods. The chemical structures and relative configurations of all products have been fully established by 1D and 2D homonuclear and heteronuclear correlation NMR spectrometry. The effects of the electronic and steric factors of the reactions were discussed. The photophysical properties of the synthesized spiro[indoline-3,2′-pyrrolidin]-2-ones and 5′-phenyl-spiro[indoline-3,2′-pyrrolidin]-2-ones were studied. The mechanism of the reactions was investigated using global and local reactivity indices and frontier molecular orbital (FMO) analysis at the B3LYP/6-31G level of theory. The relationship between the electrophilicity index ω of the dipolarophiles and the Hammett constant σp has been studied. The theoretical scale of reactivity correctly explains the electrophilic activation/deactivation effects promoted by electron-withdrawing and electron-releasing substituents in the para-position of the dipolarophiles.

Sensitive Kinetic Spectrophotometric Determination of Cyclobenzaprine HCl in Pure Form and Pharmaceutical Formulations

Abstract A novel and highly selective kinetic spectrophotometric method was developed for the determination of cyclobenzaprine HCl. This method was based on monitoring the different kinetic characteristics of the reaction between the studied drug and potassium permanganate as an oxidizing agent in alkaline medium and the associated change in absorbance by time at λmax 605 nm. The experimental conditions such as the effects of KMnO4 concentration, amount of NaOH and sequence of addition were optimized. The stoichiometric ratio and the reaction mechanism between the drug and the oxidant were determined. Different kinetic methods such as the initial rate and the fixed time methods were utilized under the optimum conditions for construction the calibration curves for determination cyclobenzaprine HCl. Linear range of 2.0-10 μg mL-1 was established. The precision of the proposed method was satisfactory where the relative standard deviation (RSD) ≤ 1.89% and the error percent (Er %) was in range (-0.33-1.75%). The proposed method was successfully applied for determination of cyclobenzaprine HCl in a dosage form. The results were compared with some reported methods.