Paolo Mencarelli

Fast transimination in organic solvents in the absence of proton and metal catalysts. A key to imine metathesis catalyzed by primary amines under mild conditions

Amine–imine exchange reactions of sterically unhindered reactants were found to be surprisingly fast at room temperature in a variety of nonaqueous solvents in the absence of proton and metal catalysts. The reaction mechanism suggested by ab initio calculations in the gas phase involves nucleophilic addition to the CN bond in concert with proton transfer from the amine NH bond to the imine nitrogen via a highly imbalanced transition state. These very fast transimination reactions were utilized in the catalysis of imine metathesis. Imine metathesis, usually carried out in organic solvents at high temperature in the presence of metal catalysts, occurs smoothly at room temperature in the presence of primary amines under nonacidic conditions as a result of coupled transimination processes. Kinetic data fully consistent with the proposed reaction mechanism were obtained.

Determination of the rotational barrier of a chiral biphenyl: Comparison of theoretical and experimental data

Abstract The rotational barrier of chiral 2-carboxy-2′-methoxy-6-nitrobiphenyl has been evaluated both by density functional calculations, at the B3LYP/6-31G(d) and B3LYP/6-311+G(d,p) levels of theory, and by HF and post HF MP2 calculations at the 6-31G(d) level of theory. The DFT computed data, which seemed almost independent of the basis set used, are in good agreement with the values obtained from dynamic HPLC enantiomerization experiments and from the racemization rate constant of one of the enantiomers obtained by CD. The HF model seems to overestimate the barrier whereas the MP2 calculations confirm the DFT results.

Photosensitized Oxidation of Alkyl Phenyl Sulfoxides. C−S Bond Cleavage in Alkyl Phenyl Sulfoxide Radical Cations

The 3-cyano-N-methylquinolinium perchlorate (3-CN-NMQ(+)ClO4(-))-photosensitized oxidation of phenyl alkyl sulfoxides (PhSOCR1R2R3, 1, R1 = R2 = H, R3 = Ph; 2, R1 = H, R2 = Me, R3 = Ph; 3, R1 = R2 = Ph, R3 = H; 4, R1 = R2 = Me, R3 = Ph; 5, R1 = R2 = R3 = Me) has been investigated by steady-state irradiation and nanosecond laser flash photolysis (LFP) under nitrogen in MeCN. Steady-state photolysis showed the formation of products deriving from the heterolytic C-S bond cleavage in the sulfoxide radical cations (alcohols, R1R2R3COH, and acetamides, R1R2R3CNHCOCH3) accompanied by sulfur-containing products (phenyl benzenethiosulfinate, diphenyl disulfide, and phenyl benzenethiosulfonate). By laser irradiation, the formation of 3-CN-NMQ(*) (lambda(max) = 390 nm) and sulfoxide radical cations 1(*+) , 2(*+), and 5(*+) (lambda(max) = 550 nm) was observed within the laser pulse. The radical cations decayed by first-order kinetics with a process attributable to the heterolytic C-S bond cleavage leading to the sulfinyl radical and an alkyl carbocation. The radical cations 3(*+) and 4(*+) fragment too rapidly, decaying within the laser pulse. The absorption band of the cation Ph2CH(+) (lambda(max) = 440 nm) was observed with 3 while the absorption bands of 3-CN-NMQ(*) and PhSO(*) (lambda(max) = 460 nm) were observed just after the laser pulse in the LFP experiment with 4. No competitive beta-C-H bond cleavage has been observed in the radical cations from 1-3. The C-S bond cleavage rates were measured for 1(*+), 2(*+), and 5(*+). For 3(*+) and 4(*+), only a lower limit (ca. >3 x 10(7) s(-1)) could be given. Quantum yields (Phi) and fragmentation first-order rate constants (k) appear to depend on the structure of the alkyl group and on the bond dissociation free energy (BDFE) of the C-S bond of the radical cations determined by a thermochemical cycle using the C-S BDEs for the neutral sulfoxides 1-5 obtained by DFT calculations. Namely, Phi and k increase as the C-S BDFE becomes more negative, that is in the order 1 < 5 < 2 < 3, 4, which is also the stability order of the alkyl carbocations formed in the cleavage. An estimate of the difference in the C-S bond cleavage rate between sulfoxide and sulfide radical cations was possible by comparing the fragmentation rate of 5(*+) (1.4 x 10(6) s(-1)) with the upper limit (10(4) s(-1)) given for tert-butyl phenyl sulfide radical cation (Baciocchi, E.; Del Giacco, T.; Gerini, M. F.; Lanzalunga, O. Org. Lett. 2006, 8, 641-644). It turns out that sulfoxide radical cations undergo C-S bond breaking at a rate at least 2 orders of magnitude faster than that of corresponding sulfide radical cations.

Structure and C-S bond cleavage in aryl 1-methyl-1-arylethyl sulfide radical cations.

Steady state and laser flash photolysis (LFP) of a series of p-X-cumyl phenyl sulfides (4-X-C(6)H(4)C(CH(3))(2)SC(6)H(5): 1, X = Br; 2, X = H; 3, X = CH(3); 4, X = OCH(3)) and p-X-cumyl p-methoxyphenyl sulfides (4-X-C(6)H(4)C(CH(3))(2)SC(6)H(4)OCH(3): 5, X = H; 6, X = CH(3); 7, X = OCH(3)) has been carried out in the presence of N-methoxy phenanthridinium hexafluorophosphate (MeOP(+)PF(6)(-)) under nitrogen in MeCN. Steady state photolysis showed the formation of products deriving from the C-S bond cleavage in the radical cations 1(+•)-7(+•) (2-aryl-2-propanols and diaryl disulfides). Formation of 1(+•)-7(+•) was also demonstrated by LFP experiments evidencing the absorption bands of the radical cations 1(+•)-3(+•) (λ(max) = 530 nm) and 5(+•)-7(+•) (λ(max) = 570 nm) mainly localized in the arylsulfenyl group and radical cation 4(+•) (λ(max) = 410, 700 nm) probably mainly localized in the cumyl ring. The radical cations decayed by first-order kinetics with a process attributable to the C-S bond cleavage. On the basis of DFT calculations it has been suggested that the conformations most suitable for C-S bond cleavage in 1(+•)-4(+•) and 7(+•) are characterized by having the C-S bond almost collinear with the π system of the cumyl ring and by a significant charge and spin delocalization from the ArS ring to the cumyl ring. Such a delocalization is probably at the origin of the observation that the rates of C-S bond cleavage result in very little sensitivity to changes in the C-S bond dissociation free energy (BDFE). A quite large reorganization energy value (λ = 43.7 kcal mol(-1)) has been calculated for the C-S bond scission reaction in the radical cation. This value is much larger than that (λ = 12 kcal mol(-1)) found for the C-C bond cleavage in bicumyl radical cations, a reaction that also leads to cumyl carbocations.

Structural and solvent effects on the C-S bond cleavage in aryl triphenylmethyl sulfide radical cations.

Steady-state and laser flash photolysis (LFP) studies of a series of aryl triphenylmethyl sulfides [1, 3,4-(CH(3)O)(2)-C(6)H(3)SC(C(6)H(5))(3); 2, 4-CH(3)O-C(6)H(4)SC(C(6)H(5))(3); 3, 4-CH(3)-C(6)H(4)SC(C(6)H(5))(3); 4, C(6)H(5)SC(C(6)H(5))(3); and 5, 4-Br-C(6)H(4)SC(C(6)H(5))(3)] has been carried out in the presence of N-methoxyphenanthridinium hexafluorophosphate in CH(3)CN, CH(2)Cl(2), CH(2)Cl(2)/CH(3)CN, and CH(2)Cl(2)/CH(3)OH mixtures. Products deriving from the C-S bond cleavage in the radical cations 1(•+)-5(•+) have been observed in the steady-state photolysis experiments. Time-resolved LFP showed first-order decay of the radical cations accompanied by formation of the triphenylmethyl cation. A significant decrease of the C-S bond cleavage rate constants was observed by increasing the electron-donating power of the arylsulfenyl substituent, that is, by increasing the stability of the radical cations. DFT calculations showed that, in 2(•+) and 3(•+), charge and spin densities are mainly localized in the ArS group. In the TS of the C-S bond cleavage an increase of the positive charge in the trityl moiety and of the spin density on the ArS group is observed. The higher delocalization of the charge in the TS as compared to the initial state is probably at the origin of the observation that the C-S bond cleavage rates decrease by increasing the polarity of the solvent.

Synthesis of a ditopic cyclophane based on the cyclobutane ring by chalcone photocycloaddition

The intramolecular photocycloaddition of chalcones to give cyclobutanes has proven to be a fast and simple method to shrink a cyclophane ring to a tricyclic system, in order to prepare potential ditopic receptors. In particular, the chalcone 1, having dioxyethylene chains as spacers, is converted in high yield to the cyclobutane 2. NOESY spectroscopy indicates that the formation of 2 occurs by a head-to-head syn ring closure.

Discrimination of the enantiomers of new biphenylic derivatives in chiral micellar aggregates

The synthesis and characterization of two new chiral biphenylic derivatives is reported. The rotational barriers have been calculated on simpler homologues. The racemic mixtures of the two compounds have been used as probes of chirality for exploring the sites of chiral recognition in chiral micellar aggregates. Results suggest that one of the sites of chiral discrimination is the hydrophobic part of the aggregates, far from the stereogenic centres.

Structural Effects on the C–S Bond Cleavage in Aryl tert-Butyl Sulfoxide Radical Cations

The oxidation of a series of aryl tert-butyl sulfoxides (4-X-C6H4SOC(CH3)3: 1, X = OCH3; 2, X = CH3; 3, X = H; 4, X = Br) photosensitized by 3-cyano-N-methylquinolinium perchlorate (3-CN-NMQ(+)) has been investigated by steady-state irradiation and nanosecond laser flash photolysis (LFP) under nitrogen in MeCN. Products deriving from the C-S bond cleavage in the radical cations 1(+•)-4(+•) have been observed in the steady-state photolysis experiments. By laser irradiation, the formation of 3-CN-NMQ(•) (λ(max) = 390 nm) and 1(+•)-4(+•) (λ(max) = 500-620 nm) was observed. A first-order decay of the sulfoxide radical cations, attributable to C-S bond cleavage, was observed with fragmentation rate constants (k(f)) that decrease by increasing the electron donating power of the arylsulfinyl substituent from 1.8 × 10(6) s(-1) (4(+•)) to 2.3 × 10(5) s(-1) (1(+•)). DFT calculations showed that a significant fraction of the charge is delocalized in the tert-butyl group of the radical cations, thus explaining the small substituent effect on the C-S bond cleavage rate constants. Via application of the Marcus equation to the kinetic data, a very large value for the reorganization energy (λ = 62 kcal mol(-1)) has been calculated for the C-S bond scission reaction in 1(+•)-4(+•).

Template Effects and Kinetic Selection in the Self‐Assembly of Crown Ether Cyclobis(paraquat‐p‐phenylene) [2]Catenanes—Effect of the 1,4‐Dioxybenzene and 1,5‐Dioxynaphthalene Units

The template effects exerted by bis(p-phenylene)[34]crown-10 (3) and by 1,5-dinaphto[38]crown-10 (4) in the ring-closure reaction of the trication 2(3+) to yield the [2]catenanes 7(4+) and 8(4+) have been quantitatively evaluated in acetonitrile at 62 degrees C by UV/visible spectroscopy. The rate of ring closure of the trication 2(3+) dramatically increases in the presence of the templates 3 and 4, up to approximately 230 times at [3] approximately equals 0.1 molL(-1), and up to approximately 1,900 times at [4] approximately equals 0.01 molL(-1). The outcome of kinetic selection experiments, in which the two crown ethers compete for the incorporation into the catenane structure, has been discussed in the light of the obtained results. It has been shown that the product ratio of catenanes obeys the Curtin-Hammett principle only if the concentrations of the templates are equal and much greater than that of the substrate. Analysis of the rate profiles has shown that the 1,5-dioxynaphthalene unit, present in the template 4, has a greater affinity than the 1,4-dioxybenzene unit, present in the template 3, for the electron-deficient pyridinium rings present in both the transition-state and substrate structures. Ab initio calculations at the 3-21G and 6-31G(d) levels of theory indicate that the greater affinity of the 1,5-dioxynaphthalene unit cannot be explained on the basis of greater pi-pi stacking and [C-H...pi] interactions, but rather on the basis of the model of apolar complexation in which the solvent plays a major role.

Oxidative N-demethylation ofN,N-dimethylanilines catalysed by lignin peroxidase: a mechanisticinsight by a kinetic deuterium isotope effect study

Lignin peroxidase can catalyse the N-demethylation of N,N-dimethylanilines by an electron transfer mechanism, where the deprotonation of the intermediate radical cation is also an enzymatic process.